A 63-year-old female with non-Hodgkin's lymphoma was treated with a chemotherapeutic regimen composed of rituximab, cyclophosphamide, doxorubicin, vincristine, prednisolone (R-CHOP). She was given  rituximab 600 mg plus 750 ml of 0.9% sodium chloride injection intravenous drip on the first day, at the same time treatments for hydration, alkalization, protecting visceral function, prevention of adverse reactions were given. On day 2, the patient developed an involuntary shaking limbs, a lower limbs weakness, a slightly slow reaction and an unsteady gait. MRI of the brain did not show any significant finding. On day 3, she had a fever, cognitive impairment and confusion. On day 4, the patient could not have independent feeding and defecation. Methyl prednisolone, drugs for improving microcirculation and rehydration therapy were applied. Two days later, the patient's consciousness restored. He can eat independently, defecate by himself, and his limbs and neuropsychological symptoms were relieved. Five days later, the symptoms were apparently   improved.

Two female patients, aged 61 and 48 years old, received a combined chemotherapy of irinotecan 200 mg and lonaplatin 50 mg for cervical cancer. Patient 1 developed diarrhea, grade IV arrest of bone marrow and septicemia, accompanied by septic shock on the ninth day after the second cycle of chemotherapy. Patient 2 developed diarrhea, grade IV arrest of bone marrow, accompanied by fever on the sixth day after the first cycle of chemotherapy, and then developed secondary septicemia. Antidiarrhea, anti-infection, and immune support treatment were given. Five days later, diarrhea was controlled. Ten days later for patient 1 and six days later for patients 2, white blood cell, hemoglobin and platelet count were within normal range. After twenty days for patient 1 and six days later for patients 2, septicemia was controlled.

The proton pump inhibitors (PPI) are widely used as the treatment of choice in acid-related diseases in clinic. Long term use of PPI may further induce abnormal absorption of nutrition (vitamin B12, calcium, iron, magnesium and other minerals), abnormal proliferation of gastrointestinal mucosa, infection, and abnormal bone metabolism (osteoporosis and bone fracture), and so on. Most studies on safety of long term use of PPI are retrospective cohorts or case-control studies. More prospective randomized controlled trials should be performed and good clinical evidences should be obtained for reasonable and safe use of PPI.

ObjectiveTo develop a list of potentially inappropriate medication (PIM) for the Chinese aged people and provide reference for prevention and reduce the medication risk of the aged people.MethodsBased on the PIM lists of the United States, Canada, Japan, France, Norway, Germany, South Korea and Austria, and combined with the data of serious adverse drug reactions (ADR) in the aged people collected from China National Center for ADR Monitoring, ADR monitoring center in the People′s Liberation Army, Beijing Center for ADR Monitoring and ADR data from Beijing 22 hospitals, we created a preliminary PIM list for the Chinese aged people. Using Delphi technique experts consultation was made for the initial list. Round 1 consultantation invited 32 experts, according to the expert advice to adjust the initial list, and form a revised list. Round 2 consultantation invited 38 experts, according to the expert advice to adjust revised list, and the final version of the PIM list formed. ResultsA total of 13-class 72 medications or medication classes were selected as the Chinese aged people PIM list, each medicine had 1-6 risk points. The list was divided according to the result of expert evaluation into 35 kinds of high risk medications and 37 kinds of low risk medications. In addition, according to the frequency of drug use, the medications were divided into A and B two categories, including 24 medications or medication classes as the preferred alert medications (A), 48 medications or medication classes as routinely alert medications (B).ConclusionPIM list for the Chinese aged people have been developed, which can be taken as reference to intervention and evaluation of China′s elderly medication.

ObjectiveTo analyze the clinical characteristics and risk factors of lansoprazole-induced microscopic colitis (MC).MethodsPubMed, Da-Yi medical search, CHKD and Wanfang databases were searched and articles related to MC induced by lansoprazole were collected. The patients′primary diseases, coexisting diseases, the dosage, the way of administration, combination drugs, latent period, clinical manifestations, colonoscopic findings, the treatment measures, and the outcomes were recorded and the clinical characteristics, the risk factors of MC induced by lansoprazole were analyzed.ResultsA total of 30 articles and 62 patients with MC induced by lansoprazole were retrieved. All articles were case reports and no randomized controlled trials were found. Of all the 62 patients, 22 were male (35.5%) and 40 were female (64.5%) with age from 36 to 92 years and the average age was (69±12) years; 57 patients (91.9%) were >50 years; 43 patients were with collagenous colitis (CC) (69.4%) , 18 patients (29%) were with lymphocytic colitis (LC), and one patient with LC changed into CC (1.6%). All patients were treated with oral lansoprazole. The latent period of MC induced by lansoprazole were 5d-6 years and within 1-6 months in 31 patients (60.8%) . The most common clinical manifestations were non-bloody watery diarrhea (3-10 times daily in 59 patients, >10 times daily in 3 patients). Intestinal mucosal screening was performed for all the patients and mild abnormalities or edema were observed in 37 patients, mucosal defect and mucosal laceration in 11 patients, epithelial collagen layer thickening, inflammatory cells infiltration in lamina propria, increased lymphocytes in intraepithelial spaces in 18 patients. High-risk drugs for drug-induced MC were combined use in 20 patients and the combination drugs in 13 patients were non steroidal anti-inflammatory drugs. Fifty-eight patients with mild or moderate drug-induced MC returned to normal after withdrawl of lansoprazole and treatment with omeprazole or rabeprazole sodium and 4 patients with severe drug-induced MC recovered after withdrawl of lansoprazole and treatment with glucocorticoids.ConclusionsThe clinical characteristics in patients with MC induced by lansoprazole are watery diarrhea, mild abnormality or edema of colon mucosa, and thickening in the epithelium of colonic mucosa in histopathology. Age, gender, and combined use of drugs may be related to occurrence of MC induced by lansoprazole.

As stated by article 12 of the Drug Administration Law of the People′s Republic of China, the state shall construct pharmacovigilance regulations to monitor, identify, assess, and control adverse drug reactions and other harmful events related to medication. Pharmacovigilance runs throughout the whole life cycle of drug from research and development to clinical use, and the core idea is to prevent and control medication risks and ensure the safety of patients and the general public. As the main places for drug consumption and the key participants in pharmacovigilance activities, the construction of pharmacovigilance system in health facilities is an important part in the construction of national pharmacovigilance regulations. At present, we are at the initial stage of the implementation of national pharmacovigilance regulations. In order to promote the establishment of pharmacovigilance system in health facilities, domestic pharmacovigilance monitoring institutions, relevant academic groups, medical colleges and universities, periodical offices, and social welfare organizations jointly initiate the compilation of Expert consensus on construction of pharmacovigilance system in health facilities by inviting experts and scholars in relevant fields to discuss, distinguish, and analyze the important concepts on adverse drug reactions/events, medication safety, pharmacovigilance, etc., in combination with cutting-edge developments. The consensus puts forward systematic principles and methods on establishing pharmacovigilance system, expecting to provide reference to health facilities in pharmacovigilance system establishment.

ObjectiveTo observe the adverse reactions of zoledronic acid in the treatment of osteoporosis combined with rheumatic diseases and analyze the potential risk factors.MethodsMedical record data of patients with rheumatic diseases and osteoporosis who were treated with zoledronic acid during hospitalization in Xuanwu Hospital of Capital Medical University from January 2011 to December 2014 were collected and a retrospective analysis was conducted. The patients were grouped according to the occurrence of adverse reactions and their demographic characteristics, types of rheumatic diseases and medication regimen of zoledronic acid were compared. The screened risk factors for adverse reactions were analyzed by multivariate logistic regression. The results were expressed by odds ratio (OR) and 95% confidence intervals (CI).ResultsA total of 120 patients were enrolled into the study. There were 41 males and 79 females. Their ages ranged from 23 to 85 years. Of 120 patients, 64 cases (53.3%) received first infusion of zoledronic acid, 66 cases (55.0%) received the treatment with corticosteroids during hospitalization, 58 cases (48.3%) were given antipyretic analgesics before infusion of zoledronic acid and 64 cases (53.3%) received sufficient hydration before and after the infusion; 49 (40.8%) of the 120 patients were reported to have adverse reactions. All adverse reactions were of acute phase responses, including fever in 32 (65.3%), flu-like symptoms in 21 (42.9%), headache in 17 (34.7%), fatigue in 12 (24.5%), myalgia in 10 (20.4%), arthralgia in 8 (16.3%), chills in 6 (12.2%), nausea in 5 (10.2%), vomiting in 4 (8.2%), and dry cough in 1 (2.0%). No severe adverse events occurred. The incidence of adverse reactions in initial infusion patients was significantly higher than that in non-initial infusion patients［51.6% (33/64) vs. 28.6% (16/56), P=0.011］. The incidence of adverse reactions in patients with  corticosteroid therapy was significantly lower than that in patients with no corticosteroid therapy［24.2% (16/66) vs. 61.1% (33/54), P<0.001］. The patients who were given sufficient hydration before and after the infusion also had significantly lower incidence of adverse reactions than those without sufficient hydration treatments［31.2% (20/64) vs. 51.8% (29/56), P=0.023］. Multivariate logistic regression analysis suggested that initial infusion was a risk factor for adverse reactions (OR=2.631, 95%CI: 1.132-6.116, P=0.025). However, oral corticosteroid and sufficient hydration treatments before and after the infusion were protective factors (OR=0.232, 95%CI: 0.102-0.526, P<0.001; OR=0.379, 95%CI: 0.164-0.874, P=0.023).ConclusionsAcute phase responses related to zoledronic acid are common in the treatment of patients with rheumatic diseases and osteoporosis. Iniaial infusion is closely associated with adverse reactions of zoledronic acid, but oral corticosteroid and sufficient hydration treatments before and after the infusion might decrease the incidence of adverse reactions.

A perfect pharmacovigilance database is the core pillar of pharmacovigilance activities. At present, the United States, Japan, Europe, and the World Health Organization have all established comparatively mature pharmacovigilance databases, which have played an important role in adverse drug reaction (ADR) monitoring, ADR signal mining, and post marketing re-evaluation of drugs. This paper summarizes the data sources, data accessibility, available elements, data quality control, and data utilization status of the 4 major databases mentioned above, so as to provide references for clinical pharmacovigilance activities and improvement of the construction of pharmacovigilance database in China.

ObjectiveTo analyze the characteristics of highly cited papers published in Adverse Drug Reactions Journal (our journal) during 2009 to 2013， understand the hot spots of subject development and demands of readers, and improve impact and quality of our journal. MethodsThe citation frequency of papers published in our journal from 2009 to 2013 was searched in China Academic Journal Network Publishing Database (as of April 30, 2015). Price law was used to determine the highly cited papers. The main statistical parameters included total citation frequency of papers published in our journal, average citation frequency of papers, citation frequency of highly cited papers, and average citation frequency of highly cited papers. The distribution of subjects of highly cited papers, regional distribution of authors, distribution of article types, and funding  sources were analyzed descriptively.ResultsA total of 1 052 articles were searched and 736 articles were entered into the study, including 147 original articles, 85 reviews, and 504 case reports. Of the 736 articles, 517 were cited (70.2%) and the total citation frequency was 2 170 times and average citation frequency of papers was 4 times. According to the Price law, the papers which were cited ≥5 times were considered as highly cited papers in our journal during the study period. The citation frequency of 138 highly cited papers was 1 388 times which accounted for 64.0% of total frequency (2  170 times) during the study period and average citation frequency of highly cited papers was 10 times. The subjects of highly cited 138 papers are relatively centered and the top 5 subjects were antimicrobial agents (44 papers, 31.9%), Chinese Medicine (22, 15.9%), cardiovascular system drugs (19, 13.8%), antineoplastic drugs (11, 8.0%), and endocrine system drugs (5, 3.6%); there were 87 papers (63.0%) distributed in Beijing and 51 papers (37.0%) distributed in other 17 provinces or municipality directly under the central government; 33 of the highly cited 138 papers were original articles (23.9%), 29 were reviews (21.0%), and 76 were case reports (55.1%), their citation frequency was 390, 354, and 643, respectively which accounted for 28.1%, 25.5% and 46.3% of total citation frequency 1 388 times, respectively, and the average citation frequency of original articles, reviews, or case reports were 12,12, and 9, respectively. There was 1 paper supported by National funds at top 20 highly cited papers.ConclusionsAs highly cited papers published in our journal, distribution of subjects and regions were relatively centered; distribution of authors were dispersive; reviews and case reports made more contributions; and average citation frequency of original articles and reviews was higher. It is valuable to understand the above mentioned characteristics to make measures for improvement of impact and quality of our journal.

Chemotherapy-induced peripheral neuropathy (CIPN) usually manifests as persistent pain and sensory abnormalities, and in severe cases, loss of vibration and joint position sensation, autonomic and motor dysfunction may occur, severely affecting patients′ quality of life. Mitochondrial dysfunction may be one of the mechanisms by which chemotherapeutic drugs induce peripheral neuropathy. Different mitochondrial dysfunction caused by different chemotherapy agents are reviewed from 5 aspects in this paper, including abnormal neuronal mitochondrial morphology, activation of mitochondrial permeability transition pore and its associated calcium imbalance, dysfunction of mitochondrial bioenergetics, oxidative stress, and abnormal axonal mitochondrial transport. Avoiding or improving mitochondrial dysfunction is the main strategy to prevent or mitigate CIPN.

A 76-year-old male patient with acute coronary syndrome received regularly aspirin (0.1 g once daily), clopidogrel (50 mg once daily), atorvastatin calcium (20 mg once daily), and isosorbide mononitrate (10 mg twice daily) by mouth after undergoing percutaneous coronary intervention. He suffered from left lumbago with gross hematuria after 2 months of treatments. Laboratory tests showed the following values：urine occult blood(+++)，235 red blood cells per microlitre and 17 red blood cells per high power field. Urinary system ultrasonography and renal function detection showed no abnormalities. Aspirin and clopidogel were withdrawn and the symptomatic treatments were given. Two days later, the patient′s urine recovered to normal，his left lumbago was alleviated, and the red blood cell in his urine was negative. Gene polymorphism detection of cytochrome P-450(CYP)2C19 showed that the patient carried CYP2C19*17(CT) allele and CYP2C19 enzyme had ultra rapid metabolism. Aspirin was given orally and the hematuria did not appear again.

Monoclonal antibody (mAb) drugs belong to protein drugs, which are characterized by high relative molecular weight, strong polarity, and limited transmembrane. Their pharmacokinetics have certain particularity and complexity, and problems such as large individual differences in therapeutic effects, diverse biological effects, and loss of therapeutic response exist in clinical application. The blood concentration of mAb drugs is affected by many factors including the number of receptors at the target site, the level of anti-drug antibody, and the interaction between drugs. Early monitoring is helpful to timely adjust the dose of mAb drugs, improve the efficacy, and avoid or reduce the occurrence of adverse reactions. Clinical monitoring should be actively carried out to improve the level of rational use of mAb drugs and the ability of early warning of adverse reactions, so as to reduce the drug-induced injury in patients.

Objective To explore the international research hotpots and development trend of therapeutic drug monitoring (TDM).　Methods Web of Science database was searched as of February 16, 2022, with search term of "therapeutic drug monitoring" or "drug monitoring". The research articles on TDM were collected and analyzed for the annual publication amount, countries, authors, and institutions. Citation burst was detected using CiteSpace software, and keywords-cluster was carried out by VOSviewer to visually show the research hotpots.　Results A total of 2-318 articles were included, and the first one was published in 1975. The United States published the largest amount of related articles and had the closest cooperation with other countries. University of Queensland in Australia was the institution with the most publications, and Roberts JA was the author with the most publications. A total of 10 citation bursts were detected, and 6 keywords-clusters related to TDM were found by cluster analysis method. Recent international research hotspots included TDM of biologics in patients with inflammatory bowel disease, TDM of anti-infective drugs in critically ill patients, and TDM of anti-tumor drugs.　Conclusions Referring to the international research hotspots, TDM should be carried out for more drugs, such as infliximab, adalimumab, and imatinib, etc., to provide personalized and precise medication care for patients and improve the safety of drug therapy.

A 45-year-old man with about 10 years of drug abuse history took 96 tablets of sodium valproate sustained-release (48 g) and about 20 capsules of ziprasidone hydrochloride (＞400 mg) by himself one time. He appeared comatous and had no response to being called, then he was sent to the hospital by his family members. He presented no autonomous respiration, hypotonia of the four limbs and neck (2 level) on admission. He received symptomatic supportive treatments including tracheal intubation and ventilator assisted breathing, gastric lavage, coloclyster, fluid infusion,  diuresis, and central nervous system stimulant, immediately. Two hours later, the patient awoke. Laboratory tests revealed the following results: arterial oxygen partial pressure (PaO2) 292 mmHg (1 mmHg=0.133 kPa), lactic acid 5.70 mmol/L, D-dimer 7.8 mg/L, plasma fibrinogen degradation product (FDP) 45 mg/L. Twenty-four hours later, laboratory tests revealed the following results:  PaO2  98 mmHg, lactic acid 1.7 mmol/L, D-dimer 2.2 mg/L, FDP 19 mg/L. The trachea cannula was removed. Forty-eight hours later, his consciousness returned to normal. He could finish the common action. But he still had the symptom of  drowsiness. Seven days later, the patient could answer questions accurately. His muscular tension returned to normal. He had light drowsiness occasionally.

Insulin switching is very common in the treatment of diabetes mellitus, which is an important link that affects the safe use of insulin. At present, insulin switching, including selection of different insulin products, dosage adjustment, and patient education has been explained in the guidelines issued by the United States, the United Kingdom, Canada, and China. Relevant information on insulin switching is various and scattered and there is a lack of systemicity and comprehensiveness. It is suggested to refer to the guidelines of other countries, fully analyze the clinical characteristics of diabetes mellitus in China, and base on the real-world research data to formulate a systematic insulin switching guideline in line with China′s national conditions, in which the selection of insulin products, dose adjustment, patient education, dietary advice, and blood glucose monitoring, etc. can be described in detail. In addition, strengthening patient tracking and medication monitoring is also a necessary mean to ensure the safety in insulin switching.

Objective To compare the pharmacokinetics and safety of single intravenous injection of the generic bevacizumab injection WBP264 and the original bevacizumab injection Avastin- in healthy male volunteers.　Methods The study was designed as a randomized, double-blind, single dose, parallel, and controlled phase I clinical trial. Healthy male volunteers who were recruited publicly were randomized into the trial group (intravenous infusion of WBP264) and the control group (intravenous infusion of Avastin-), and the dose was 3-mg/kg. Peripheral venous blood was collected within 30-minutes before administration, 45-minutes after onset of the administration, immediately after finishing the administration, 2.5, 3.5, 5.5, 9.5, 13.5, 24, 48-hours and on the 5th, 8th, 15th, 22nd, 29th, 36th, 43rd, 57th, 71st, 85th, and 99th days after the administration. The plasma concentration was measured by enzyme-linked immunosorbent assay, the plasma concentration-time curve and its semilogarithmic plot were plotted, and the pharmacokinetic parameters such as the area under the plasma concentration-time curve [including AUC from time zero to the time of the last quantifiable concentration (AUC0-t) and AUC from time zero to infinity (AUC0-∞)], peak concentration (Cmax), time to peak (Tmax), plasma elimination half-life (t1/2), clearance rate (CL), and apparent volume of distribution (Vd) were calculated. When the 90% confidence intervals (CI) of the geometric mean ratio of AUC0-t, AUC0-∞, and Cmax between the trial group and the control group were between 0.80-1.25, it indicated that pharmacokinetics of WBP264 and Avastin- were similar. The physical examination, vital signs detection, electrocardiogram, and laboratory tests were performed on the subjects, the occurrence of adverse events (AEs) and the severity classification were recorded, and correlation between the AEs and the trial drug was evaluated. The anti-drug antibody and its neutralizing antibody were detected before administration and on the 8th, 15th, 29th, 43rd, 71st, and 99th days after administration to evaluate the immunogenicity of the drug.　Results A total of 78-subjects were recruited, 39 in the trial group and 39 in the control group. In the trial group, 2 cases withdrew from the trial (1 case did not take the drug and 1 case withdrew for personal reason after taking the drug). Seventy-seven cases were in the safety analysis set and 76 cases in the pharmacokinetic analysis set. The differences in age, height, weight, and body mass index between the 2 groups were not significant (all P>0.05). The plasma concentration-time curves of bevacizumab between the trial group and the control group were similar. The geometric mean ratios (90%CI) of AUC0-t, AUC0-∞, and Cmax were 1.04 (0.98-1.10), 1.03 (0.98-1.10), and 1.09 (1.03-1.14), respectively. The differences in the incidence of overall AEs ［89.5% (34/38) vs. 87.2% (34/39)］ and the incidence of AEs possibly related to the trial drug ［86.8% (33/38) vs. 79.5% (31/39)］ between the trial group and the control group were not significant (all P>0.05). Only one case of AE in the trial group was grade 3 in severity and was assessed as being not related to the drug, and the rest were grade 1-2, with grade 1 AEs accounting for the vast majority. The difference in the positive rate of anti-drug antibody between the trial group and the control group was not significant ［10.5% (4/38) vs. 10.3% (4/39), P>0.05］. The neutralizing antibody test was negative in the patients with positive anti-drug antibody.　Conclusion The pharmacokinetics and safety of WBP264 and Avastin- are similar.

Allergic diseases have serious influence on human health and quality of life. Cytokines secreted by T-helper cell type 2 (Th2), such as interleukin (IL)-4 and IL-13, play a pivotal role in the pathogenesis of allergic diseases. By recognizing and binding to IL-4 and IL-13 receptors, dupilumab can block the signal transduction pathways of IL-4 and IL-13, inhibit Th2 inflammatory reaction, and thus play a therapeutic role in allergic diseases. At present, dupilumab has been on the market in many countries and regions around the world, yet with different indications approved, mainly including atopic dermatitis, moderate-to- severe eosinophilic asthma, chronic rhinosinusitis with nasal polyps, eosinophilic esophagitis, etc. In addition, this drug may also have better curative effect on IgE-mediated allergic reactions and other dermal diseases. Meanwhile, the safety profile of dupilumab is generally good and the common adverse reactions mainly include injection site reactions (pain, ecchymosis and swelling at the injection site), ocular diseases (conjunctivitis, keratitis, itchiness of eyes and dry eyes), oral herpes, headache, and other herpes simplex virus infections. In China, dupilumab has been approved for the treatment of moderate-to-severe atopic dermatitis in patients aged ≥6 years, showing good efficacy and no obvious safety problems.

There are risks in the use and management of perioperative analgesics, which may be caused by analgesic methods, individual patient factors, or medication errors. In order to reduce the risk in perioperative analgesics use and improve the level of safe drug use, Medication Safety Panel in China Core Group of International Network for the Rational Use of Drugs, Chinese Pharmacological Society Professional Committee of Drug-induced Diseases, Adverse Drug Reactions Journal Agency, Beijing Municipal Health Commission Clinical Safety Medication Working Group organize the domestic pharmacy experts and anesthesiology experts to formulate the guideline. The risks prevention and management measures of perioperative analgesics were described from 3 aspects including management, drugs, and special populations. The management- related risks include the risks during the formulation of analgesia plan, the risks in information/goods/drugs transmission, the risks in the use of intraoperative analgesics and analgesia pumps, which can be prevented by formulating rules and regulations, strengthening training, and improving information technology. Drug-related risks are inherent properties of drugs. Analgesics are classified into narcotic analgesics, antipyretic analgesics, and analgesic auxiliary drugs. Corresponding prevention strategies can be formulated according to the risk points of specific drugs. Special populations including the elderly, pregnant and lacta- ting women, and children, etc. have their own physiological and pharmacokinetic characteristics and countermeasures can be formulated according to specific conditions. Through comprehensive monitoring of perioperative analgesics use, the risk can be predicted, the circumvention plan can be formulated, and the pharmaceutical care can be implemented, so as to ensure the medication safety of patients. This guideline is applicable to all medical personnel who use and monitor perioperative analgesics.

ObjectiveTo explore the relationships between active systemic allergic reaction induced by breviscapine injection and the drug dose and the sensitization time.MethodsActive systemic allergic reaction in guinea pigs was used as experimental method. Forty-eight guinea pigs were divided into 6 groups according to random number table: breviscapine injection 1, 5, 25 and 50 mg/kg group (the breviscapine injection group 1, 2, 3, 4), 0.9% sodium chloride injection group (the negative control group) and bovine serum albumin (BSA) control group (the positive control group). Each group comprised 8 guinea pigs. Sensitization: the guinea pigs in group 1 to 4 were given the breviscapine injection  at doses of 1, 5, 25 and 50 mg/kg (0.5 ml) by intraperitoneal injection every other day for three times, respectively. The the guinea pigs in the negative control group and the positive control group were given 0.9% sodium chloride injection (0.5 ml) and bovine serum albumin (BSA) 20 mg/kg by intraperitoneal injection every other day for 3 times, respectively. Excitation: the sensitized guinea pigs in each group were divided into 2 subgroups, each subgroup comprised 4 guinea pigs. On the 14 and 21 days after the last sensitization, the guinea pigs in breviscapine 1 to 4 subgroups received 2 times of breviscapine injection intravenously (1.0 ml), respectively. The guinea pigs in the negative and the positive control subgroups  received 2 times of control articles intravenously, respectively. The symptoms of anaphylactic reaction (pilo-erection, shiver, scratching nose, sneeze, cough, vomiturition, cyanosis, dyspnea, urinary and fecal incontinence, instability of gait or tumble, convulsion or hyperspasmia, shock and death) were observed every day during the sensitization phase. The guinea pigs′ reactions which appeared in 30 min after intravenous injections were observed and the occurrence time of allergic symptoms/signs were recorded attentively. The anaphylactic reaction was determined according to the Chinese Pharmacopoeia′s allergic reaction test. ResultsThe guinea pigs in 6 groups did not show any allergic symptoms in the sensitization phase. Within 30 min in fourteenth days′ excitation,  2, 4, 4, 4 guinea pigs developed allergic reactions in the breviscapine 1 to 4 groups, respectively. But none of them were identified as allergic reaction. The 4 guinea pigs in the positive control group were judged to have positive allergic reaction. Within 30 min of 21 days′ excitation, 4、3、4、4 guinea pigs developed allergic reactions in the breviscapine 1 to 4 groups, respectively. Only one guinea pig in the breviscapine 4 group was identified as allergic reaction. The 4 guinea pigs in the positive control group were all judged positive allergic reaction. The guinea pigs in the negative control group did not develop any allergic reactions during the 2 times of excitation. The occurrence time of allergic reactions in the breviscapine groups (within 20 min after excitation) on 21 days′ excitation was shorter than those (within 25 min after excitation) occurred on 14 days′ excitation, but the difference was not statistically significant.ConclusionsThe active systemic allergic reactions induced by breviscapine injection are associated with drug dose and sensitization time. The larger dose and longer sensitization time can increase the risk of allergic reaction and shorten the latency of allergic reaction.

From March 2013 to December 2018, Japan, the United Kingdom, Canada, Australia, and China successively issued guidelines on therapeutic drug monitoring of voriconazole. It is recommended in guidelines at home and abroad that voriconazole should be given a loading dose, and the blood drug concentration of patients should be monitored on the third day; when adjusting the dose, adverse events occurrence or poor efficacy, increasing or stopping the drugs that may interact, and sequential administration, the blood drug concentration should be monitored again. The clinical characteristics of voricona- zole-related adverse events have been clearly defined. After adverse reactions occur during the treatment period, the drug can be stopped or reduced according to its severity. Voriconazole is not only the substrate of cytochrome P450 (CYP) 2C9, CYP2C19 and CYP3A4, but also an inhibitor of them. We should pay attention to the interaction between voriconazole and other drugs.  In the future, further research is needed to accumulate more evidence-based medical evidences for the use of the drug in different medication purposes, different diseases or different fungal infections, Child-Pugh grade C severe liver disease, and children <2 years old, so as to provide reference for clinical individualized treatment.

Iron deficiency is the most common cause of anemia. Intravenous iron is a common therapeutic drug for iron deficiency and iron deficiency anemia, which is commonly used in the treatment of anemia patients with chronic kidney disease, heart failure, inflammatory bowel disease, and cancer, as well as anemia patients in perioperative period and during pregnancy and lactation. In order to strengthen the rational use of intravenous iron and improve the pharmaceutical care level, the Chinese Pharmacological Society Professional Committee of Drug-induced Diseases and the Guangdong Pharmaceutical Association organized experts majoring in medicine, pharmacy, nursing, hospital mana- gement and other specialties to develop this consensus through discussing, retrieving domestic and foreign literature, and collecting evidence-based medical evidence. The differences among intravenous iron agents, clinical situations of applica- tion, and the safety issues are considered in the consensus, in order to provide the basis for the rational application and pharmaceutical care in clinic.

Objective To analyze the risk of diabetes mellitus related to immune checkpoint inhibitors (ICI).　Methods The adverse event (AE) reports on fulminant type 1 diabetes mellitus (FT1DM), type 1 diabetes mellitus (T1DM), diabetic ketoacidosis (DKA), which were related to duvalizumab, pabolizumab, nivolumab, and atezolizumab in the US FDA Adverse Event Reporting System from the first quarter of 2004 to the second quarter of 2021， were collected.The correlation between the 4 drugs and FT1DM, T1DM,and DKA were evaluated using proportional reporting odds ratio (PRR) method.AE with reports ≥3, PRR value≥2, and χ2≥4 were judged to have statistical correlations with drugs. The greater the PRR value, the stronger the correlation between AE and drugs and the stronger the risk signals.　Results A total of 1-468 AE reports on diabetes mellitus were collected, 53, 386, 957, and 72 of which were related toduvalizumab, pabolizumab, nivolumab, and atezolizumab, respectively. For duvalizumab, pabolizumab, nivolumab, and atezolizumab, the PRR reflecting the correlation with FT1DM were 21.97 (χ2=40.71), 71.50 (χ2=3-531.21), 294.30 (χ2=4-3915.75), and 33.58 (χ2=279.70), respectively; the PRR reflecting correlation with T1DM were 12.12 (χ2=162.08), 21.04 (χ2=3391.17), 20.99 (χ2=5816.11), and 9.71 (χ2=224.81), respectively; the PRR reflecting correlation with DKA were 6.93 (χ2=161.26), 4.78 (χ2=426.52), 6.82 (χ2=1797.15), and 3.04 (χ2=41.84), respectively. The 4 drugs were statistically correlated with their corresponding AE. The order of risk signal intensity for corresponding AE was FT1DM > T1DM > DKA. The order of risk signal intensity for FT1DM were nivolumab > pabolizumab > duvalizumab > atezolizumab, for T1DM were pabolizumab ≈ nivolumab > duvalizumab > atezolizumab, for DKA were duvalizumab ≈ nivolumab > pabolizumab > atezolizumab.　Conclusions Duvalizumab, pabolizumab, nivolumab, and atezolizumab all can cause diabetes mellitus. The risk signal intensity was the strongest for FT1DM, followed by T1DM and DKA in order.

 A small amount of commonly used and first-aid drugs stored in the inpatient wards can facilitate the temporary treatment of patients and save precious time for the treatment of critically ill patients. But there is a risk of medication errors in the link of drug storage in the inpatient wards. In order to strengthen the management of drug storage in the inpatient wards and reduce medication errors, experts in medicine, pharmacy, nursing, hospital management, and etc., were organized by Medication Safety Panel in China Core Group of International Network for the Rational Use of Drugs, Chinese Pharmacological Society Professional Committee of Drug-induced Diseases, and Adverse Drug Reactions Journal Agency, to formulate the guideline for prevention of medication errors in the link of drug storage in inpatient wards based on the Expert Consensus on Medication Error Management in China. The medication errors in the link of drug storage in the inpatient wards include improper storage of drugs, wrong drug specifications, wrong drug quantity, and wrong drug placement. The risk factors include management factors (unsound management system, no designated person or post management, or no regular inspections and supervision), process factors (no corresponding standard operation process, or only imperfect or unreasonable operation process), environmental factors (unqualified drug storage space and equipment, or no special labels), human factors (no training for personnel involved in drug use, or unreasonable staff arrangement), and drug factors (too many types and quantity of drugs in inpatient wards). The prevention strategies include technical strategies (enforcement and constraint management policies, implement of informatization and intelligence management, and formulation of standardized marks and processes, and establishment of standard catalog list and audit project list) and management strategies (establishment of management systems, provision of sufficient human resources, and enhancement of training).

Objective To explore the adverse reaction risk signals of perampanel-related psychia- tric disorders, and provide reference for the clinical safe application of perampanel.　Methods The US FDA Adverse Event Reporting System database was searched, and the adverse event (AE) reports on psy- chiatric disorders from the third quarter of 2012 to the third quarter of 2021, which judged perampanel as the primary suspect drug were collected. The expression of AE was standardized using the preferred term (PT) in the Medical Dictionary for Regulatory Activities. Data such as patient general condition and psychiatric AE outcomes was extracted from AE reports and was analyzed descriptively. Risk signal mining for psychiatric adverse reactions to perampanel was performed using the reporting odds ratio (ROR) method. The positive signal PT was set as that the number of AE reports was 3 and more and the lower limit of the 95% confidence interval (CI) of the ROR was greater than 1.　Results A total of 922 reports on psychiatric AE with perampanel as the primary suspect drug were collected. Of the 922 patients involved, 439 were male, 441 were female, and 42 were unknown in gender. Age were recorded in 676 patients, and the age was (38±19) years. AE outcomes were recorded in 807 patients, of which hospitalization/prolonged hospitalization, urgent treatment needs, life threatening, and death due to AE occurred respectively in 409 (44.4%), 316 (34.3%), 60 (6.5%) and 22 patients (2.4%). The 922 AEs involved 1-580 PTs, and 46 PTs were detected with positive signals by ROR method. The top 5 PTs mostly reported were aggression (286 AEs), irritability (128 AEs), suicidal ideation (110 AEs), suicide attempt (100 AEs), and anger (77 AEs). The top 5 PTs with strongest signal intensity (ROR value) were postictal psychosis (383.13), schizophreniform disorder (355.27), homicidal ideation (203.56), dissociative disorder (119.64) and delusional perception (108.34), among which dissociative disorder and postictal psychosis were AEs not recorded in the drug labels. In the 46 PTs with positive signal, 14 (30.4%) were not recorded in the drug labels, and the other 12 PTs were listed as sexually inappropriate behaviour (81.43), suspiciousness (65.20), disinhibition (32.72), impulsive behaviour (31.18), perso- nality change (22.56), abnormal behaviour (16.31), social avoidant behaviour (12.95), restlessness (6.15), bipolar disorder (5.23), affect lability (5.09), nightmare es (2.86), and fear (2.79).　Conclusion psychiatric adverse reaction is a common and serious adverse reaction of perampanel, which should be paid attention to clinically.

Objective To mine risk signals related to tafamidis, which was a rare disease drug and newly included in the medical insurance list.　Methods The drug-related adverse event (AE) reports from the 1st quarter of 2013 to the 2nd quarter of 2022 were searched based on the US FDA Adverse Event Reporting System and AE reports with tafamidis as the primary suspect drug were extracted. The report odds ratio (ROR) method and Bayesian confidence propagation neural network (BCPNN) method were used to detect the AE risk signals of tafamidis. A target AE with reports ≥3 and 95% confidence interval (CI) lower limit of ROR>1 was defined as a positive signal for ROR method and the larger the ROR and its lower limit of 95%CI, the stronger the signal strength. The information component (IC)-2SD>0 (SD is the standard deviation) was defined as a positive signal for BCPNN method, and the larger the IC-2SD value, the stronger the signal. According to the preferred system organ class (SOC) and preferred term (PT) from terminology of adverse drug reactions in Medical Dictionary for Regulatory Activities, AEs were counted and classified. The risk signal with positive detection results from both ROR and BCPNN methods was determined as the AE risk signal of tafamidis and analyzed. Results A total of 3-999 cases with tafamidis as the primary suspect drug were collected, including 2-942 males (73.6%), 688 females (17.2%), and 369 unknown cases (9.2%); 3-148 cases (78.7%) aged >65 years, 192 cases (4.8%) aged 18-65 years, 52 cases (1.3%) aged <18 years, and 607 cases (15.2%) were unknown; 1-064 patients were with cardiac amyloidosis, 872 patients with cardiac amyloidosis, 148 patients with peripheral nerve amyloidosis, and 176 with other diseases; 1-403 cases (35.1%) died. A total of 110 positive signals were screened with both ROR and BCPNN methods, involving 20 SOCs. The top 5 PTs of AE reports were dyspnea (338 cases), fatigue (301 cases), edema (167 cases), dizziness (111 cases), and fall (110 cases). The SOC involved were systemic lesions, neurological diseases, respiratory/thoracic and mediastinal diseases, examination, metabolic and nutritional diseases. The top 5 PTs (ROR and the 95%CI lower limit) were early feeling of fullness （28.07，11.64), lumbar spinal stenosis （26.73，15.15), aortectasia （24.36，9.11), hypoxia （22.64，10.15), and cervical radiculopathy （22.13，7.11). Four of the top 20 PTs in the AE reports were not recorded in the drug label, including dizziness, height loss, chest pain, and renal failure; 16 of the top 20 PTs in signal strength (ROR method) were not recorded in the drug label, including lumbar spinal stenosis, aortic dilatation, physical decline, cervical radiculopathy, height reduction, carotid artery disease, hyperlipidemia, orthopnea, peripheral vein disease, benign prostatic hyperplasia, carpal tunnel syndrome, emaciation, foreign body sensation in the throat, immune thrombocytopenia, positional dizziness, and aortic atherosclerosis.　Conclusion Through data mining, it is found that early feeling of fullness, lumbar spinal stenosis, aortic dilatation, physical decline, and cervical radiculopathy may be the common adverse events of tafamidis, some risk signals are not recorded in the drug label, which should be paid attention to during the clinical use.

A 77-year-old male patient with rheumatoid arthritis was given methotrexate 10-mg once a week, tripterygium glycosides 20-mg twice daily, and methylprednisolone 8-mg once daily orally. However, the patient confused the medication frequency of methotrexate with tripterygium glycosides and mistakenly took methotrexate 5-mg twice daily. After 4 days of medication (taking methotrexate 7 times, 35-mg in total), the patient developed severe oral ulcers, generalized rash, fever, cough, and expectoration. Laboratory tests showed white blood cell count 1.21×109/L, serum creatinine 288-μmol/L, γ-glutamyl- transferase 163-U/L, alanine transaminase 82-U/L, and alkaline phosphatase 235-U/L. After 6 days of medi- cation, laboratory tests showed white blood cell count 0.13×109/L, neutrophil count 0.01×109/L, serum creatinine 317-μmol/L, estimated glomerular filtration rate 18-ml/(min·1.73 m2), C-reactive protein 233.8-mg L, and procalcitonin 14.31-μg/L. The patient was diagnosed as having methotrexate poisoning, myelosuppres- sion, renal insufficiency, and pulmonary infection. All drugs were discontinued immediately. Blood perfusion, intravenous injection of calcium folinate, and symptomatic treatments such as anti-infection, elevation of white blood cells, blood transfusion, rehydration, and mouth care were given. However, the patient′s infection and myelosuppression continued to worsen, and he died of multiple organ failure 12 days later.

Objective To explore the application value of radioisotope tracer technology in clinical research of biological drugs.　Methods The pharmacokinetic properties of mepuzumab in healthy volunteers were evaluated by measuring the radioactive concentrations of iodine in blood and urine samples of 3 healthy volunteers at different time points within 14 days after intravenous infusion of 131I-labeled international class I new drug mepuzumab (Trial 1). Positron emission computed tomography (PET/CT) was performed on 6 healthy volunteers after intravenous injection of 68Ga-labeled nucleic acid aptamer Sgc8, and the standard uptake values of 68Ga-Sgc8 in different organs were measured to evaluate its biodistribution in healthy humans (Trial 2). Nine patients with suspected neuroendocrine tumors underwent single photon emission and X-ray computed tomography (SPECT/CT) 4 hours after intravenous injection of 99mTc-labeled octreotide to determine the radioactive uptake level in the regions of interest; the affinity and targeting of 99mTc- labeled octreotide to somatostatin receptor subtype 2 (SSTR2) were evaluated in combination with the immunohistochemical staining results of SSTR2 in patients′ biopsy tissues (Trial 3).　Results The 3 healthy volunteers included in Trial 1 were male, aged 28, 45, and 25 years respectively; the injection doses of 131I-labeled mepuzumab were 21.0, 25.9, and 17.6-mg, and the injection doses of radioactivity were 364, 420, and 304 MBq, respectively. Among the 6 healthy volunteers included in Trial 2, 3 were male and 3 were female, with an age of (46±11) years, ranging from 35 to 63 years. The dose of radioactivity injected was (80±7) MBq, ranging from 69 to 87 MBq. Among the 9 patients included in Trial 3, 5 were male and 4 were female, with an age of (54±10) years, ranging from 39 to 69 years. The dose of radioactivity injected was (777±74) MBq, ranging from 740 to 925 MBq. After intravenous infusion of 131I-labeled mepuzumab, the blood radioactivity concentration reached the peak 1.5-hours later. 131I-labeled mepuzumab mainly bound to blood cells, and its whole-blood clearance half-life was 420-hours. The urine radioactivity concentration reached the peak 16-24-hours after administration and then gradually decreased after 24-hours of administration. After intravenous injection of 68Ga-labeled Sgc8, the organs with strong to weak radioactive signals were bladder, kidney, heart, uterus, liver, spleen, gallbladder, large intestine and lung. Within 3 hours after drug administration, the clearance rate was fastest in heart, followed by uterus, kidney, and liver; the clearance rate was slower in spleen and gallbladder and were slowest in large intestine and lung. All of the 9 patients had abnormal radioactivity accumulation 4 hours after intravenous injection of 99mTc-labeled octreotide and the immunohistochemical staining results of biopsy tissues showed strong positive expression of SSTR2, indicating that 99mTc-labeled octreotide had good affinity and targeting to SSTR2. The safety evaluation showed that in Trail 1, one subject developed iodine-related hyperthyroidism one month after intravenously infusion of 131I-labeled mepuzumab, which returned to normal after 8 months of continuous monitoring without intervention. No adverse reactions occurred in other subjects.　Conclusions Radioisotope tracer tech- nology can noninvasively, dynamically, and visually evaluate the pharmacokinetics, biological distribution, and targeting of biological drugs in human body. It has good safety and great application value in the clinical evaluation of biological drugs.

Objective To understand the main adverse event (AE) related to denosumab and the risks and provide reference for the safe use of the drug in clinic.　Methods The AE reports on denosumab included in the US FDA Adverse Event Reporting System from the second quarter of 2010 to the first quarter of 2021 were collected, and the AE risk signals was explored using proportional reporting odds ratio (PRR) method. AEs with ≥3 reports, PRR value ≥2, and χ2≥4 were defined as positive risk signals. AEs were counted and classified using the preferred system organ class (SOC) and preferred term (PT) of Medical Dictionary for Regulatory Activities 24.0. The PTs of top 50 adverse event reports and signal intensity were selected and analyzed.　Results A total of 132-764 AE reports with denosumab as the primary suspected drug were collected, involving 5-571 PTs, and 641 positive risk signals were selected. After the second screening, the top 50 PTs in the number of AE reports and the top 50 PTs with great PRR values were obtained, and 93 PTs were included in the analysis after sifting out the repeated, involving 114-617 AE reports. The top 5 PTs in the number of AE reports were off-label use (28.7%, 32-863/114-617), death (14.2%, 16-230/114-617), osteonecrosis of the jaw (6.0%, 6-861/114-617), arthralgia (4.7%, 5-420/114-617), and limb pain (4.1%, 4-727/114-617). The top 5 PTs with the high signal intensity were giant-cell tumour of bone (PRR=402.7), malignant giant-cell tumour of bone (PRR=325.2), C-telopeptide increase (PRR=169.4), exostosis of jaw (PRR=163.2), and ionised calcium abnormal (PRR=158.1). The top 5 SOC involving AE reports were injury, poisoning and procedural complications (35.9%, 41-757/114-617), musculoskeletal and connective tissue disorders (32.7%, 37-455/114-617), general disorders and administration site conditions (18.2%, 20-814/114-617), surgical and medical procedures (4.1%, 4-744/114-617), and investigations (2.9%, 3-290/114-617). Forty-four PTs were not included in the drug instructions, of which 23 were related to the oral cavity.　Conclusions Denosumab AE with the most reports were off-label use and osteonecrosis of the jaw. The risk signals of osteonecrosis of the jaw and recurrence or deterioration of giant-cell tumor of bone was strong. Most of the AE risk signals that were not included in the instructions are oral problems.

A 25yearold male patient took about 60 tablets of phenobarbital and scopolamine hydrobromide by himself (each tablet contains 30mg phenobarbital and 0.2mg scopolamine hydrobromide). About 1 hour later, he developed coma with paroxysmal limb convulsions. Drug poisoning was diagnosed. The patient received gastric lavage, catharsis, and intravenous injection of midazolam 10mg for epilepsy. Six hours later, his heart rate was 53 beats/min, breathing rate was 11 times/min, and occasional convulsions and hematuria occurred. Laboratory tests showed indirect bilirubin 16.97μmol/L, total protein 54g/L, albumin 27.6g/L, and thrombin time 25.0s. Multiple organ injury was considered and blood purification treatment was given. One day later, the patient′s consciousness was restored, heart rate was 68 beats/min, breathing rate was 16 times/min, and no convulsion occurred. Laboratory tests showed indirect bilirubin 8.69μmol/L, total protein 54.7g/L, albumin 34.0g/L, and thrombin time 16.7s.

Objective To understand the clinical characteristics of rivaroxban- related adverse events (AE) in perioperative patients.　Methods The relevant databases at home and abroad (as of April 20, 2020) were searched and the case reports of AE associated with rivaroxban used during perioperative period were collected. Relevant information in patients (nationality, gender, age, medical history, application of rivaroxaban, combined drugs, and the occurrence, treatment, and outcome of AE, etc.) was extracted and analyzed descriptively.　Results A total of 42 case reports of AE caused by rivaroxban during perioperative period were collected, involving 46 patients from 11 countries. Of the 46 patients，25 (54.3%) were male and 21 (45.7%) were female with an age of 16-96 years. In terms of the reasons for medication, 34 patients used rivaroxban before operation for prevention of postoperative venous thrombosis, 7 used rivaroxban after operation for prevention atrial fibrillation, stroke, or systemic thrombosis after operation, 4 discontinued rivaroxban during perioperative period, and 1 did not explain the reason for using rivaroxban. Past medical history were described in 21 patients, including hypertension, hyperlipidemia, and diabetes, etc. Combined medication was described in 22 patients, including antibiotics, non-steroidal anti-inflammatory drugs, analgesics, cardiovascular and cerebrovascular drugs, etc. The onset time of AE was recorded in 31 patients, which was 2 hours to 2 months after medication and most within 1 month. AE associated with rivaroxban were bleeding in 29 patients, liver injury in 7 patients, anaphylaxis in 6 patients, kidney injury in 3 patients, thrombosis in 3 patients, thrombocythemia in 2 patients, thrombocytopenia, pulmonary embolism, acute attack of coronary atherosclerotic heart disease, and visual loss in 1 patient each. After the occurrence of AE, 31 patients were improved after rivaroxban withdrawn, switching to other anticoagulants, and receiving symptomatic treatment; 1 patient improved after changing concomitant medications as well as reducing the dose of rivaroxban; 2 patients did not stop the drug in time and developed new allergic reaction; 2 patients were improved after using rivaroxban again; 1 patient died of hemorrhagic shock due to gastrointestinal bleeding; 9 patients′ outcome were unknown. Among the 46 patients, 18-had medication errors, of which 16-had dose error and 2 had compatibility errors.　Conclusions Hemorrhage is the most common AE related to rivaroxban in the perioperative use of rivaroxban, which mainly occurs within 1 month after medication. The overall prognosis is good after rivaroxban withdrawal, switching to other anticoagulants, and symptomatic treatment. Medication error is one of the causes of AE related to rivaroxban in perioperative period.

Objective To systematically evaluate the occurrence of interstitial lung disease (ILD) in patients with non-small cell lung cancer (NSCLC) treated with epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKI).　Methods PubMed, Embase, The Cochrane Library, CNKI, WanFang, and VIP databases were searched up to April 30, 2022. Randomized controlled trials (RCT) about NSCLC treated with EGFR-TKI (8 kinds listed in China, including gefitinib, erlotinib, icotinib, afatinib, dacomitinib, osimertinib, almonertinib, and furmonertinib) compared with chemotherapy were collected. Patients was treated with EGFR-TKI monotherapy in the trial group and chemotherapy in the control group. The outcomes included the occurrence of ILD. RevMan 5.4-software was used for meta-analysis, and the effect sizes were odds ratio (OR) and the 95% confidence interval (CI).　Results A total of 15 RCT were entered in the analysis, including 6 about gefitinib, 5 about erlotinib, 2 about icotinib, and 2 about afatinib， involving 2-318 patients in the trial group and 1-975 in the control group. Meta-analysis showed that the overall incidence of ILD in the trial group were higher than that in the control group ［1.47% (34/2-318) vs. 0.51% (10/1-975), OR=2.44, P=0.004］; difference in incidences of ILD-related death between the 2 groups was not significant ［0.35% (8/2-318) vs. 0.05% (1/1-975), OR=3.29, P=0.07］. The severity of ILD was graded in 14 RCT, and the meta-analysis showed that the incidence of more than grade 3 ILD in the trial group was higher than that in the control group ［0.62%(13/2-089) vs. 0.11% (2/1-864), OR=2.60, P=0.04］. The overall incidences of ILD and the incidences of more than grade 3 ILD in the gefitinib group were higher than those in the corresponding control groups ［2.31%(27/1-167) vs. 0.71% (8/1-123), OR=2.88, P=0.004; 0.86% (7/1-167) vs. 0.09% (1/1-123), OR=3.98, P=0.03］. There was no significant difference in ILD occurrence between the trial group and the control group for afatinib and erlotinib (all P>0.05). No ILD occurred in the trail group or in the control group in RCT about icotinib.　Conclusions Compared with chemotherapy, NSCLC patients receiving EGFR-TKI, especially gefitinib, have higher risks of ILD and serious ILD. Therefore, clinical vigilance and monitoring should be strengthened.

Medication rationality index (MAI) scale sets up 10 items to evaluate the rationality of prescription medication, including indication, effectiveness, dosage, correct direction, practical direction, drug-drug interaction, drug-disease interaction, duplication, duration, and cost. MAI scale has good reliability, which can be used to evaluate the rationality of drug use and the non-essential drug use, the potential inappropriate medication in elderly patients, verify the reliability and effect of irrational drug use detection software, quantify clinical intervention measures, and predict adverse events and quality of life. Since MAI scale application involves subjective judgment, evaluators should be trained before use.

In 2022, a total of 22-868 cases of medication error (ME) from 315-hospitals in 26 provincial administrative regions were collected in the National Monitoring Network for Clinical Safe Medication. The number of hospitals reporting ME increased by 14.55% compared with that in 2021 (275-hospitals), and the number of reported ME cases increased by 16.76% compared with that in 2021 (19-585 cases). In 22-868 cases of ME reports, 155 (0.68%) were classified as grade A, 18-981 (83.00%) as grade B, 3-076 (13.45%) as grade C, 422 (1.85%) as grade D, 75 (0.33%) as grade E, 156 (0.68%) as grade F, 1 (<0.01%) as grade G, and 2 (0.01%) as grade H; no MEs of grade I occurred. Among the 22-713 patients involved in MEs of grade B to I, 12-668 (55.77%) were male and 10-045 (44.23%) were female; their ages were from 1 day to 102 years; 2-453 (10.80%) were children (<18 years old), 11-374 (50.08%) were young and middle-aged adults (≥18 to <60 years old), and 8-886 (39.12%) were elderly (≥60 years old). A total of 234 patients were involved in serious MEs (grade E-I), including 134 (57.27%) males and 100 (42.73%) females, aged from 4 days to 94 years, of which 37 (15.81%) were children, 83 (35.47%) were young and middle-aged adults, 114(48.72%) were elderly. The serious MEs (grade E-I) mainly occurred in the administration link ［74.36% (174/234)］. The 155 grade A MEs did not involve person who triggered the ME and place where ME occurred. Among the 22-713 grade B-I MEs, 17-102 (75.30%) were triggered by physicians, 4-072 (17.93%) by pharmacists, 764 (3.36%) by nurses, 461 (2.03%) by patients and their family members, and 314 (1.38%) by other persons; the proportion of MEs triggered by physicians increased year by year for 4 consecutive years; the triggers of serious MEs were mainly patients and their family members ［61.97% (145/234)］. Among these MEs, 9-238 (40.67%) occurred in clinics, 7-183 (31.63%) in hospital wards, 4-620 (20.34%) in pharmacies, 1-063 (4.68%) in pharmacy intravenous admixture services, 213 (0.94%) in the nurse stations, 321 (1.41%) in patients′ home, 6 (0.03%) in the community health service stations, and 69 (0.30%) in other places. Among the 234-severe MEs, 129 (55.13%) occurred in the patient′s home, and the proportions of MEs and serious MEs occurred in the home increased year by year for 4 consecutive years. The top 3 contents of ME were wrong drug class (4-285, 18.40%), wrong dosage (4-115, 17.67%), and wrong administration frequency (2-808, 12.06%). The top 3 persons who discovered the ME were pharmacists (17-575, 74.74%), patients and their family members (2-654, 11.29%), and physicians (1-752, 7.45%). The top 3 factors causing ME were lack of related pharmacologic knowledge (8-665, 31.94%), tiredness (4-249, 15.66%), and insufficient training of medical workers (3-502, 12.91%).

Objective:To investigate adverse effects associated with traditional Chinese medicines for clinical reference.Method:ADR reports of our hospital during1998-2001were analysed.Results:ADRs occured in several organs systems,mainly in skin and its appendages and cardiovascular system.Among more severe reactions were anaphylactic shock,laryngeal edema and dyspnea,probably caused by allergy.Conclusion:Traditional Chinese medicines should be used with more care owing to yearly increase of unwanted reactions.

Objective To explore the clinical characteristics of dabigatran etexilate-related serious adverse events(AE).　Methods Databases of CNKI, WanFang, PubMed, and Embase were searched as of October 31, 2020 and case reports on serious AE related to dabigatran etexilate were collected. Relevant information in patients (nationality, gender, age, weight, application of dabigatran etexilate, co-existing diseases and combined drugs, the occurrence, treatment and outcome of AE, etc.) was extracted and analyzed descriptively.　Results A total of 77 literature were included, involving 101 patients from 20 countries. There were 64 males (63.4%) and 37 females (36.6%), aged 56-94 years with the body weight of 38-193-kg. In terms of the reasons for medication, 87 were for prevention of stroke caused by atrial fibrillation, 12 were for the treatment of venous thromboembolism or for prevention of the possible venous thromboem- bolism, and the other 2 were not described. Co-existing diseases or past medical history were described in 88 patients, including hypertension, renal insufficiency, and type 2 diabetes mellitus, etc. Combined medication was described in 67 patients, of which drugs that might increase the risk of bleeding (non-steroidal anti-inflammatory drugs, clopidogrel, P-glycoprotein inhibitors, etc.) were used in 35 patients. Other combined drugs were antihypertensive drugs and hypoglycemic drugs, etc. Serious AE occurred from 2 minutes to 5 years after medication and 33 cases occurred within 1 month after the start of medication. Serious AE associated with dabigatran etexilate were bleeding in 81 patients (including gastrointestinal bleeding, intracerebral hemorrhage, coagulation disorder, etc.), kidney injury/renal failure in 8 patients, esophageal ulcer in 4 patients, liver injury in 2 patients, and thrombocytopenia, leukocyte fragmentation vasculitis, and severe cough with dyspnea in 1 patient respectively. The main measure taken after AE occurence was drug withdrawal. Those who were not improved after drug withdrawal were given symptomatic treatment, and hemodialysis were performed on those who fail to respond to the treatment. A total of 29 patients died and all of them had bleeding events. Among the 101 patients, 43-had medication errors, of which 33-had overdose, 6 had contraindications, and 4 had wrong administration methods.　Conclusions Serious AE related to dabigatran etexilate manifest mostly as bleeding in clinic and can occur from 2-minutes to 5 years after medication, which can lead to death in severe cases. Medication error is one of the important causes of serious AE related to dabigatran etexilate, so the label should be strictly followed when prescribing the drug and medi- cation guidance should be given to patients.

Immune effector cell-associated neurotoxicity syndrome （ICANS） is a common adverse reaction of chimeric antigen receptor T-cell （CAR-T） immunotherapy. Its mechanism is mainly related to the destruction of brain mural cells, increase of cytokine level, the inflammation mediated by natural killer cells, and the activation of endothelial cells. The main clinical manifestations of ICANS are aphasia, tremor, dysgraphia, drowsiness, and epilepsy. In severe cases, asphyxia, coma, or brain edema may occur, and sometimes it is even life-threatening. The factors affecting ICANS include age, peak value of CAR-T amplification, product type, and disease type, etc. American Society for Blood and Marrow Transplantation recommends symptomatic and supportive treatments for mild ICANS and hormonal shock therapy for severe cases.

A 67-year-old male patient received immunotherapy with intravenous infusion of sintili- mab 200-mg once every 3 weeks due to postoperative recurrence of liver cancer, and the efficacy and tolerance was good. After 12 doses of sintilimab treatment, the patient developed a bright red skin rashes on the chest, abdomen, and extremities with itching. Oral loratadine and topical halometasone cream were given, and the rashes were improved slightly. The rashes did not spread in the next 2 doses of sintilimab treatment. But after the 3rd dose of continuing sintilimab, the patient suddenly developed a large-area rashes all over the body, which rapidly developed into blisters, ulcers, accompanied by oozing blood and fluid on the skin, itching, and pain. Drug eruptions were diagnosed, which was considered to be induced by sintilimab. The drug was stopped. After 1 week of treatments with intravenous infusion of methylprednisolone 60-mg once daily, anti-allergy, anti-infection, mucosal protection, and skin care, the rashes were repeated. Then the dose of methylprednisolone was increased, the rashes were still not relieved 1 week later, and gastrointesting bleeding occurred. After liver cancer surgery, the patient was accompanied by hypoproteinemia, liver dysfunction, and long-term high-dose glucocorticoid use. Therefore, despite active treatment measures, the patient still died of ineffective rescue.

Objective To explore the adverse event (AE) risk signals of romiplostim, and provide reference for the safe use of the drug in clinic.　Methods The adverse event reports on romiplostim included in the US FDA Adverse Event Reporting System from the first quarter of 2008 to the second quarter of 2022 were collected. AEs were standardized using preferred term (PT) in the Medical Dictionary for Regulatory Activities. The general situation of patients and the outcome of AEs were extracted from the AE reports and analyzed descriptively and statistically. The AE risk signals of romiplostim was explored using the reporting odds ratio (ROR) method and the proportional reporting odds ratio (PRR) method. The positive signal PT was set as that the number of AE reports was 3 and more and the lower limit of the 95% confidence interval (CI) of the ROR and PRR were greater than 1.　Results A total of 12-222 AE reports with romiplostim as the primary suspected drug were collected. Among the 12-222 patients involved, 10-295-had gender records, including 4-818 males and 5-477 females; 3-789 patients with age records, ranging from 0 to 98 years, with an average age of 58 years; 5-919 patients with AE outcome records, the patient number of hospitalizations, death, life-threatening, disabling, and congenital malformation due to AEs were 3-092, 2-305, 363, 152, and 7, respectively. Twelve thousand two hundred and twenty-two AE reports involved 2-090 PTs，which occurred 20-639 times. Signal mining was performed on the top 100 PTs in the number of reports and 42 positive signals were detected. The top 5 PTs in the number of AE reports were decreased platelet count (PLT) (1-510 patients), lack of efficacy (1-488 patients), decreased efficacy (921 patients), abnormal PLT (857 patients), and death (853 patients). The PTs with signal intensity ranking in the top 5 were bone marrow reticulin fibrosis (ROR=631.43, PRR=341.43), abnormal bone marrow biopsy (ROR=202.73, PRR=159.36), abnormal platelet count (ROR=200.90, PRR=159.49), splenectomy (ROR=118.82, PRR=102.55) and thrombocytosis (ROR=84.66, PRR=76.14). There were 10 PTs not recorded in the drug instruction, whose signal intensity from high to low in the order were splenectomy, chronic lymphocytic leukemia, hemolysis, hospitalization, pleural effusion, sepsis, bone pain, off-label drug use, hemoglobin reduction, and migraine.　Conclusions Bone marrow reticulin fibrosis and abnormal platelet count, as well as the resulting bleeding and thrombotic complications, are the AEs that need to be monitored during the use of romiplostim. Among the 10 PTs not recorded in the drug instruction, pleural effusion and sepsis need to be noticed.

A 79-year-old man received an intravenous (IV) infusion of cefoperazone sodium and sulbactam sodium 1.5 g every 12 hours with concomitant use of levofloxacin 0.5 g once daily，doxofylline injection 0.2 g via pump twice daily, and an IV push of 45 mg ambroxol injection twice daily for acute exacerbation of chronic obstructive pulmonary disease. Levofloxacin was discontinued after 7 days of treatments ambroxol and doxofylline were discontinued after 13 days of treatments. Just after completion of the infusion of cefoperazone sodium and sulbactam sodium on day 16 of treatment, the patient suddenly experienced unconsciousness, convulsion of extremities, gnathospasmus, and eyes gazing rightwards, which lasted about one minute. An IV injection of methylprednisolone sodium succinate 40 mg was given immediately and 1 minute later, his consciousness restored and symptoms relieved. And then an IV injection of sodium valproate 400 mg and sodium valproate 30 mg/h via a pump were given. On day 17, 2 hours after completion of the infusion of cefoperazone sodium and sulbactam sodium, the symptoms mentioned above appeared again. An IV push of diazepam 5 mg and sodium valproate 80 mg/h were given and 2 minutes later, the symptoms alleviated gradually. Subsequently, cefoperazone sodium and sulbactam sodium was discontinued, an IV push of sodium valproate 400 mg once daily and an oral sodium valproate 0.5 g twice daily were given. After that, he didn′t experience epilepsy seizure again.

Objective To explore the effects of tenofovir alafenamide fumarate (TAF) and tenofovir disoproxil fumarate (TDF) on blood lipid.　Methods The relevant databases (up to August 31, 2021) were searched. The data of dyslipidemia in treatment of hepatitis B virus (HBV) or human immunodeficiency virus (HIV) infection with TAF (trial group) and TDF (control group) in randomized controlled trials (RCTs) were collected. Methodological quality was evaluated by bias risk assessment tool of Cochrane collaborative network, and the meta-analysis was conducted using RevMan 5.3-software. The effect value was the risk ratio (RR) and its 95% confidence interval (CI).　Results A total of 11 RCTs were enrolled in the analysis, including 4 on the treatment of hepatitis B (HBV subgroup) and 7 on the treatment of AIDS (HIV subgroup), and the methodological quality evaluation results showed low risk of bias for all. Eleven thousand eight hundred and eighty-eight patients were involved in the 11 RCTs, of which 6-273 were in the trial group and 5-615 in the control group. The results of meta-analysis showed that the incidences of increased low density lipoprotein cholesterol (LDL-C), total cholesterol (TC), and triglyceride (TG) with the severity of ≥3 grade were higher in the trial group than those in the control group and the differences of incidences in LDL-C and TC increase were significant between the 2 groups ［LDL-C: 2.9% (157/5-347) vs. 0.8% (37/4-727), RR=3.39, 95%CI: 2.35-4.89, P=0.001; TC: 0.7% (36/4-880) vs. 0.1% (6/4-397), RR=4.25, 95%CI: 1.91-9.45, P<0.001; TG: 0.5%（16/3-157） vs. 0.3%（8/3-102），RR=1.83，95%CI：0.81-4.15, P=0.140］. The changes of blood lipid after treatment were compared and the results showed that the increase of LDL-C was higher in the trial group (14.00-mg/dl) than that in the control group (4.00-mg/dl), and the difference was statistically significant (P=0.004).　Conclusion TAF can significantly increase the levels of LDL-C and TC in patients.

Iodinated contrast encephalopathy is a rare complication after angiography or interventional therapy with iodinated contrast medium (ICM), with an incidence of 0.13%-2.92%. Iodinated contrast encephalopathy usually occurs minutes to hours after the use of ICM. Its clinical manifestations are diverse, and transient cortical blindness is the most common. Most patients have a good prognosis and generally recover completely within 48-72-hours, while a few may have irreversible neurological damage. The pathogenesis of iodinated contrast encephalopathy is not clear, which may be related to high-dose exposure of ICM due to the damage of blood-brain barrier and the direct cytotoxicity of ICM. Previous history of chronic kidney disease and stroke are risk factors for iodinated contrast encephalopathy, and types of ICM and body parts of angiography or intervention may have different influence on it. After angiography or interventional treatment using ICM, whether patients have symptoms such as mental disorder, visual field defect, and epilepsy should be observed. Once suspicious symptoms appear, CT or magnetic resonance imaging should be completed in time to avoid delaying treatment.

An 81-year-old female patient with pulmonary infection was given cefoxitin 2 g by intravenous drip. After 1.5 hours of treatment, the patient self-medicated with compound glycyrrhiza oral solution 10 ml for cough. About 10 minutes later, she experienced chest tightness, dyspnea, facial flushing, hyperhidrosis, weakness of limbs and rash. Disulfiram reaction was considered. Intravenous dexamethasone 10 mg and continuous low flow oxygen were given. About 30 minutes later, the patient′s condition improved. After 2 hours, the symptoms disappeared.

Objective To explore the risk signals of edoxaban-related adverse reactions and provide reference for the clinical safety of edoxaban. Method The US FDA adverse Event Reporting System database was searched and the adverse event (AE) reports on edoxaban as the suspicious drug from the second quarter of 2011 to the first quarter of 2022 were collected. An AE with reports>3, 95% confidence interval (CI) lower limit of ROR>1, PRR>2, and χ2>4 was defined as a positive signal. AEs were counted and classified using the preferred term (PT) and system organ class of Medical Dictionary for Regulatory Activities 25.0. The PTs of top 50 in AE report amount and signal intensity were selected and analyzed.　Results A total of 4-113 AE reports on edoxaban as the suspicious drug were collected and 996 PTs were involved. After calculation using ROR and PRR methods, 158 positive risk signals were obtained, involving 1-898 AE reports. PTs of the top 50 in AE report amount and signal intensity were merged 89 PTs were selected after screening out duplicates, involving 1-468 AE reports. The top 5 PTs in report amount were dyspnea, anemia, atrial fibrillation, melena, and cardiac failure; the top 5 PTs in signal intensity were angiodysplasia, urogenital haemorrhage, cardiac amyloidosis, chorea, and ischaemic cerebral infarction/cardioac- tive drug level increased. Fourty-five PTs were not included in the drug labels. Of them, acute renal injury, renal impairment, and interstitial lung disease were with more AE reports and stronger signals.　Conclusions Bleeding-related events are still the key AEs that need to be monitored during the use of edoxaban. Edoxaban may also lead to renal injury and interstitial lung disease, which requires special attention.

Metoprolol and propafenone are commonly used drugs in cardiovascular diseases. Both drugs are metabolized by liver cytochrome P450 (CYP) 2D6. However, propafenone is not only a CYP2D6 substrate, but also a CYP2D6 inhibitor, which may interact with metoprolol and cause adverse reactions. This interaction also depends on CYP2D6 genotype. For patients with CYP2D6 phenotypes of poor metabolizer (PM) and intermediate metabolizer (IM), the combination with propafenone can increase plasma concentration of metoprolol due to the inhibition of propafenone on CYP2D6. Therefore, the combination of metoprolol and propafenone should be avoided as far as possible. For the patients who need the combined treatment with the 2 drugs, attention should be paid to the monitoring of blood pressure, heart rate, and electrocardiogram changes during medication. If possible, CYP2D6 genotype should be detected and the drug dose should be adjusted according to the test results.

Barcode technology is a kind of automatic recognition technology which is produced and developed in computer application and practice. Barcode technology has been widely used in drug purchase, management, dispensing, use and other aspects, and plays an important role in reducing human errors, improving work efficiency, and reducing medication errors in drug information check, information matching of drug and patient, and other important links. However, barcode technology can also lead to medication errors due to human operation, technical level, and other factors during application. In order to strengthen the prevention of medication errors related to the application of drug barcode technology in medical institutions, experts in pharmaceutical, nursing, informational, and management, who were organized by Medication Safety Panel in China Core Group of International Network for the Rational Use of Drugs, Chinese Pharmacological Society Professional Committee of Drug-induced Diseases, and Adverse Drug Reactions Journal Agency, formulate the guideline for prevention of medication errors in application of barcode technology in medical institutions after several argumentation based on the Expert Consensus on Medication Error Management in China. The medication errors related to drug barcode technology may occurred in links of drug storage and delivery, drug dispensing and distribution, intravenous drug admixture, inpatient drug administration, and etc. The risk factors include systematic factors (damaged barcode quality, poor barcode printing quality, scanning and printing equipment problems, packaging problems, system defects, and sharing difficulties of internal barcode information) and human factors (barcode information maintenance error, not timely information update, wrong pasted barcode, too little internal barcode information, operation error, and improper implementation). The prevention strategies for medication errors related to drug barcode application include technical strategies (including enforcement and constraint policies, automation and information, establishment of good checking system) and management strategies (including regulatory framework, environment and personnel). The guideline is formulated for all medical staff involved in the application and management of drug barcode technology in medical institutions.

 2020年3月3日，国家卫生健康委员会发布《新型冠状病毒肺炎诊疗方案（试行第七版）》，提出抗病毒药物治疗方案、中医中药治疗方案及免疫治疗等。临床一线专业人员如何依据患者的病理、生理状况和药物的药理特性选择药物以及治疗中需要监测的指标，亟需明确和权威的学术支持。为此，中国药师协会治疗药物监测药师分会等11个学术团体联合编写了“新型冠状病毒肺炎及常见合并症药物治疗与药学监护指引”，期望为一线医师、药师和护士提供参考。

近年,甘露醇静脉及口服给药的不良反多有报告,其中过敏反应较为常见,严重者可发生过敏性休克。还可致肾损害、心血管系统损害、肺水肿、中枢神经系统反应等严重不良反应,本文仅对近五年来甘露醇应用时有关不良反应的文献进行回顾,探讨导致不良反应的相关因素,以期引起临床工作者的注意。

Objective To explore the efficacy and safety of crisaborole ointment (crisaborole) treatment in children with atopic dermatitis (AD).　Methods PubMed, Embase, Medline, CNKI, Wanfang Medicine, VIP, and Chinese Medical Journal Databases were searched (up to March 2022) and the literature on randomized controlled trials (RCTs) and cohort studies of crisaborole treatment in children with AD was collected. The quality of RCTs and cohort studies was evaluated using the modified Jadad scale and Newcastle- Ottawa scale, respectively. Data on effective rate and incidence of adverse event in children treated with crisaborole were extracted. The meta-analysis of single proportions was performed with Stata 15-software.　Results A total of 8 studies (4 RCTs and 4 prospective cohort studies, respectively) were entered in the analysis, including 1-855 children (aged from 3 months to 17 years) treated with crisaborole. The 8 studies were all of high quality. The meta-analysis of single proportions showed that the effective rate of children with AD treated with crisaborole for 14-28 days was 46% ［95% confidence interval (CI): 32%-61%］, the incidence of adverse events during treatment was 28% (95%CI: 19%-38%), and the incidence of treatment discontinuation due to adverse events was 1% (95%CI: 0-2%). Most of the adverse events caused by crisaborole were local skin reactions, mainly characterized by local pain, itching, dermatitis, paresthesia, and local infection, etc. Seven of the 8 studies reported the pain at the application site, and the incidence of pain at the application site was 17% (95%CI: 11%-24%). Most adverse events were mild to moderate and could be alleviated without treatment. Serious adverse events occurred in 8 patients (0.4%), 7 of which were unrelated to the treatment drugs.　Conclusion Crisaborole has good efficacy and safety in the treatment of mild to moderate AD in children.

A 77-year-old female patient was given combined chemotherapy with paclitaxel for injection (albumin bound) and nedaplatin for ovarian malignant tumor with peritoneal metastasis. When paclitaxel for injection (albumin bound) 100-mg dissolved in 0.9% sodium chloride injection 250-ml was given intravenously for the first time, the infusion was not smooth and the drip rate was slow. After stopping infusion, the infusion device was checked and white flocculent sediment above the filter was found. Clinical pharmacists ruled out the possibility of precipitation caused by drug preparation and incompatibility contraindications, and found that the infusion device used by this patient was a precision one (the pore diameter of microporous filter was 5-μm). However, in the drug label of paclitaxel for injection (albumin bound), it was pointed out that "Use of filters with a pore size less than 15-μm may result in blockage of the filter and should not be used." On the second day, a general infusion device (filter with 20-μm pore size) was used for IV infusion of paclitaxel for injection (albumin bound) and the process was smooth and no blockage recurred.

A 74-year-old female patient received oral carbamazepine 0.1g thrice daily because of epilepsy after acute ischemic stroke. On the third day, the patient suddenly presented drowsiness which gradually aggravated to a state of mild coma within 30 minutes. The electrocardiogram showed that sick sinus syndrome and junctional rhythm with a heart rate of 34 beats per minute. The patient was diagnosed as Adams-Stokes syndrome which may be induced by carbamazepine. She was given an intravenous injection of atropine sulfate 0.5 mg immediately. Then atropine sulfate 1 mg in 5% glucose injection 500 ml was slowly given by intravenous drip. Two hours later, the patient regained consciousness. The electrocardiogram showed restoration of sinus rhythm with a heart rate of 48 beats per minute. Carbamazepine was withdrawn and disturbance of consciousness did not recur.

Benifits outweigh the risks for patients with autoimmune disease (AID) in remission period to be vaccinated with coronavirus disease 2019 (COVID-19) vaccines. The mRNA vaccines, inactivated vaccines, and recombinant protein subunit vaccines are safe for AID patients, whereas the safety of recombinant adenovirus vector-based vaccines is still uncertain. Some drugs for the treatment of AID may reduce the immune response of the body to the COVID-19 vaccines and affect the immune efficacy of the vaccine, which may be related to the timing of vaccination. Based on several published relevant guidelines and recommendations for the COVID-19 vaccines in AID patients, this article elaborates on vaccination problems to be paid attention to in patients with AID treated with different drugs.

Reactive metabolites is one of the main causes of drug-induced liver injury (DILI). After entering the body, some drugs can be metabolized by liver to generate drug reactive metabolites, which can deplete glutathione, and in turn bind to macromolecules such as proteins or nucleic acids in the body, alter biomacromolecule function, induce cellular oxidative stress and the body′s immune response, interfere with the body′s normal physiological function, and produce hepatotoxicity. Reactive metabolites mediated DILI may be not the action of one mechanism, but the combined effects of multiple mechanisms. This article reviews the production process of drug reactive metabolites, the mechanism of liver injury, and the means of prevention and treatment, providing an important reference for clinical safe drug use.

太尼透皮贴剂是一种新型强效镇痛透皮缓释给药剂型,使用方法简便,不良反应较低,止痛效果好,广泛用于癌性疼痛(CP)和非癌性疼痛(NCP)的治疗。常见的不良反应有便秘、恶心、呕吐和嗜睡等。但如果使用不当或过量,可造成呼吸抑制甚至死亡。因此,使用芬太尼透皮贴剂时应正确选择适应证,掌握个体用药剂量,避免严重不良反应的发生。

Intravitreal injection (IVI) is an administration technique that uses a syringe to deliver drugs into the vitreous cavity. Currently, multiple IVI drugs have been successively approved for the treatment of various fundus diseases, including antivascular endothelial growth factor drugs, intravitreal sustained- release glucocorticoid drugs, and so on. Meanwhile, there are many injection drugs off label used by IVI. At present, there is a lack of pharmaceutical care guidance documents for the clinical application of IVI drugs. To promote the development of pharmaceutical care for IVI drugs, Ophthalmic Pharmacy Professional Committee of Peking Safety Medicine Foundation, Medicine Therapy Management Working Committee of Chinese Pharmacists Association, and Clinical Pharmacy Branch of China International Exchange and Promotive Association for Medical and Health Care organized experts to formulate this consensus based on clinical practice experience and with reference to relevant domestic and foreign research data, guidelines, and literature. This consensus combs the characteristics of clinical application of IVI drugs, relevant pharmaceutical services before, during and after injection, and forms 26 recommendations for 5 clinical issues, which can be used by medical institutions at all levels to carry out pharmaceutical services of IVI drugs. The users are medical staff in medical institutions at all levels (including pharmacists, physicians, nurses, and other relevant staff), and the target population for application is mainly patients using IVI drugs.

A 38-year-old female patient with recurrence of breast cancer accompanied by liver metastasis received intravenous infusion of sintilimab 200-mg on the first day and 21 days was a cycle. Before the immunotherapy, her function of liver, kidney, and thyroid was normal. Three days after the medication, the patient developed rash and itching on skin of waist. After that, diffuse erythema and desquamation appeared on skin of her whole body and blisters appeared on both upper limbs and back. At the same time, she developed blurred vision, increased eye secretions, and foreign-body sensation. Laboratory tests showed alanine aminotransferase (ALT) 123-U/L, aspartate aminotransferase (AST) 342 UL, γ-Glutamyltransferase (γ-GT) 907-U/L, alkaline phosphatase (ALP) 424-U/L, serum creatinine (Scr) 95.6-μmol/L, uric acid 691.0-μmol/L, and thyroid-stimulating hormone (TSH) 20.87 mU/L. She was diagnosed with rash, hypothy- roidism, kidney injury, conjunctivitis, and liver injury, which were considered to be associated with sintilimab. After 16 days of symptomatic treatments such as IV infusions of methylprednisolone sodium succinate for injection and magnesium isoglycyrrhizinate injection, oral administration of levothyroxine sodium and Haikun Shenxi capsules (海昆肾喜胶囊), levofloxacin eye drops, and skin care, her rash was subsided, blisters were absorbed, and the discomfort in the eyes disappeared. Laboratory tests showed ALT 111 UL, AST 122-U/L, γ-GT 1-430-U/L, ALP 321-U/L, Scr 56.0-μmol/L, uric acid 243.0-μmol/L, and TSH 13.60 mU/L.

Signal detection of adverse drug reaction (ADR) is an important research method in post marketing pharmacovigilance. In recent years, the number of literature on ADR signal detection in China has increased significantly. However, there are still many problems in this kind of research, such as unclear understanding of the concept of ADR signal, unclear purpose of signal detection research, limited signal source, inadequate processing of data in detection, unduly single data mining algorithm, unduly short time period in data selection, and no processing and analysis on bias in signal detection. This paper provides some views on these common problems in order to improve the quality of ADR signal detection research in China.

本共识分别从新型冠状病毒肺炎疫情防控期间居家隔离药物治疗的必要性和意义、居家消毒剂的选择和合理应用、医院处方药的相关规定、长期居家药物治疗的管理等多个维度，为大众居家期间的合理用药提供指导和帮助。

A 69-year-old man was treated with adalimumab 80-mg subcutaneously for psoriasis for the first time. Two days later, the patient developed diffuse erythema with pruritus. Because the active stage of psoriasis was not excluded, adalimumab 40-mg subcutaneous injection was continued once a week for 4 times. The patient′s skin erythema and pruritus continued to worsen. After intravenous infusion of methylprednisolone sodium succinate 40-mg/d for 1 week, the systemic erythema and pruritus were slightly relieved, but the condition was repeated after stopping the drug. Urine routine and sediment analysis showed urinary occult blood (+++), 190 red blood cells/μl, urinary protein（+）, and serum creatinine 80-μmol/L. Renal biopsy and skin histopathology suggested IgA nephropathy and psoriasiform dermatitis, respectively. After consultation with dermatologists, erythroderma caused by deterioration of psoriasis was considered. Excluding other factors, it is considered that IgA nephropathy and erythroderma were probably induced by adalimumab. Methotrexate 10-mg per week was given orally and halometasone ointment was used externally. The skin damage in the patient was gradually improved. Hematuria and proteinuria were self-relieved slowly.At one-year of follow-up, the patient′s renal function and urine routine remained normal, and nephropathy and rash did not recur.

盐酸西布曲明是20世纪90年代后期开发的新型减肥药,其相关不良反应临床报道较少。本文综述了国内外对西布曲明安全性评价的有关文献,对该药的常见、少见不良反应,与其他药物的相互作用以及防治措施作一介绍,以供临床参考。

Objective: To discuss the characteristics and related factors of ciprofloxacin-induced anaphylactic shock, and provide reference for clinical safe drug use. Methods: The literature between January 1979 and December 2005 was retrieved from "Chinese Journal Full-text Database", "Chinese Science and Technology Journal Full-text Database", and "Wanfang Medicine Data China info", Eighty-one cases with ciprofloxacin-induced anaphylactic shock of 73 papers were collected and analyzed. Results: Of the 81 cases, 42(52.5%) were male, 38(47.5%) were female, and one case' sex was unknown; 62(76.5%) were intravenous infusion, and 19(23.5%) were oral administration; 78(96.3%) were recovered, 3(3.7%) were dead. The time to onsef of anaphylactic shock varied from 10 seconds after intravenous infusion of ciprofloxacin to 60 minutes in fifth day after successive treatment of intravenous infusion of ciprofloxacin. Of the cases, 24 had allergic history, 25 had no allergic history. The investigation showed that ciprofloxacin-induced anaphylactic shock was not rare, and it was occurred in almost all areas of the whole country from 1975 to 2005. Conclusion: Careful attention should be paid to the serious reaction of ciprofloxacin-induced anaphylactic shock in clinical practice to ensure safemedication use.

Objective To understand the occurrence and the clinical characteristics of meropenem- related central nervous system (CNS) adverse reactions.　Methods Using the hospital information system, the electronic medical records of patients who were hospitalized in the Department of Respiratory， the 305 Hospital of the People′s Liberation Army from January 2016 to December 2021 and received meropenem were collected. Medical records of patients who developed CNS symptoms after meropenem administration were screened and analyzed retrospectively. The data extracted from the medical records mainly included gender, age, infectious diseases, underlying diseases, renal function at admission ［serum creatinine, endogenous creatinine clearance (Ccr)］ in the patient, the application of meropenem (dose, whether dose was adjusted according to Ccr), and the occurrence (occurrence time, main clinical manifestations, etc.), treatment, and outcome of meropenem-related CNS adverse reaction. The incidence of meropenem-related CNS adverse reactions was calculated, and their clinical characteristics was descriptively analyzed.　Results A total of 636 patients used meropenem during the set period and 17 of them developed meropenem-related CNS adverse reactions, with an incidence of 2.7%. Among 17 patients, 10 were male and 7 were female, aged from 74 to 94 years with a median age of 86 years. Thirteen patients had pulmonary infection (one with urinary system infection) and 4 had acute exacerbation of chronic obstructive pulmonary disease (2 with type Ⅱ respiratory failure); 14 patients had combined renal insufficiency (10 of them had a Ccr <50-ml/min) and 5 had sequelae of cerebral infarction. Ten patients were with Ccr <50-ml/min and 3 of them did not adjust the dose of meropenem according to Ccr, resulting in excessive dosage. The time to onset of CNS symptoms in 17 patients ranged from 1 to 7 days after starting meropenem, with a median time of 3 days. Twelve patients presented mainly with psychiatric disorders (including delirium, agitation, hyperarousal, hallucinations, confusion and sleep reversal, etc.), and 5 with limb or orolingual convulsions. Meropenem was discontinued in all 17 patients after the onset of CNS symptoms and 5 of them were given symptomatic treatments. Symptoms were relieved after 1-7 days in all the patients, with a median time of 3 days.　Conclusions Meropenem- related CNS adverse reactions are more common in elderly patients and patients with renal insufficiency, respiratory failure, and a history of CNS diseases. The main manifestations are mental disorders and convulsions, which mostly occur within one week of drug use. Stopping meropenem in time and receiving appropriate symptomatic treatments contribute a good prognosis in patients.

Objective To analyze the influencing factors on the occurrence of acute kidney injury(AKI) in hospitalized patients treated with esomeprazole and to construct a risk prediction model to predictthe occurrence of esomeprazole‑associated AKI. Methods The study was designed as a retrospectivestudy. The subjects were selected from patients who were hospitalized in the First Affiliated Hospital of·405·药物不良反应杂志 2024 年7月第 26 卷第7期 ADRJ，July 2024, Vol. 26, No. 7Shandong First Medical University from January 2018 to December 2020 and received treatment withesomeprazole. The clinical data of patients, including basic information, operations, intervention measures,medication, and laboratory test results, was collected through the hospital′s electronic medical recordsystem. Patients were divided into AKI and non‑AKI groups according to the occurrence of esomeprazole‑associated AKI, and the clinical characteristics between the 2 groups were compared. The least absoluteshrinkage and selection operator (LASSO regression) was used to analyze the influencing factors ofesomeprazole‑associated AKI. Patients were randomly divided into the training set and the test set at a 8∶2ratio. Based on data in the training set, 5 machine learning algorithms were used to build esomeprazole‑asso‑ciated AKI prediction models, including logistic regression, random forest, gradient boosting machine(GBM), extreme gradient boosting, and light gradient boosting machine. Based on data in the test set, the per‑formance of 5 models was validated through the area under the receiver operating characteristic curve (AUC),sensitivity, specificity, and accuracy. Results A total of 5 436 patients were enrolled in the study, including 3 231 males and 2 205 females, with an age of 61(51, 70) years. Esomeprazole‑associated AKI occurredin 393 patients, with an incidence of 7.23%. The results of LASSO regression analysis identified 24 variablesclosely related to esomeprazole‑associated, such as hepatic insufficiency, chronic renal insufficiency, hypo‑proteinemia. Based on data in the training set (4 349 patients), the esomeprazole‑associated AKI risk predic‑tion models were constructed and their predictive performance was good (all AUC>0.900). The predictiveperformance validation was conducted using the data in the test set (1 087 patients), and the results showedthat the GBM model has the highest AUC (0.922) and relatively stable performance, with small differences invarious indicators between the training and the test sets. Conclusions The use of esomeprazole is signifi‑cantly associated with AKI, and the risk is influenced by factors such as baseline renal function, comorbidi‑ties, and combined medications. The risk prediction model based on GBM algorithm is helpful for earlyassessment of the risk of esomeprazole‑related AKI in clinical practice.

A 60-year-old male patient with lung cancer received IV infusions of toripalimab 200-mg, bevacizumab 500-mg, and pemetrexed 1 g (the treatment was given on day 1 and 21 days was a cycle) due to the progression of tumor after 26 months of first-line and second-line chemotherapy successively. His thyroid function was normal before treatment. After the second medication of toripalimab (on day 30 after the first medication), the patient developed symptoms such as increased heart rate, fear of heat, hyperhidrosis, and weight loss. The reexamination of thyroid function showed triiodothyronine (T3) 3.4-nmol/L, thyroxine (T4) 305.0-nmol/L, free triiodothyronine (FT3) 13.1-pmol/L, free thyroxine (FT4) 55.7-pmol/L, thyroid stimula- ting hormone (TSH) 0.02 mU/L, thyroglobulin (Tg) 32.7-μg/L, antithyroglobulin antibody (TgAb) 531.0 kU/L, antithyroid peroxidase antibody (TPOAb) 318.0 kU/L, and thyroid stimulating hormone receptor antibody (TRAb) 1.00-U/L. Hyperthyroidism was considered, anti-tumor treatment was suspended, and symptoms were improved after metoprolol treatment. Ninety-seven days after the first toripalimab treatment, the patient developed symptoms such as chills, dizziness, fatigue, eyelid edema, weight gain, etc. The laboratory tests showed  T3-0.3-nmol/L, T4-20-nmol/L, FT3-1.0-pmol/L, FT4-1.8-pmol/L, TSH>100.00 mU/L, and carcinoembryonic antigen 251-μg/L. Hypothyroidism was considered, but the tumor progressed, so the treatment of toripalimab was restarted and thyroxine was supplemented at the same time. The patient′s thyroid function was gradually improved and then remained normal. More than 13 months after the first medication of toripalimab, the laboratory tests showed T3-1.3-nmol/L, T4-137.0-nmol/L, FT3-3.8-pmol/L, FT4-21.1-pmol/L, TSH 6.03 mU/L, Tg 3.9-μg/L, TgAb 432.0 kU/L, and TPOAb 222.0 kU/L.

There are risks of medication error in the whole process of drug use and management in the operating room. The types of medication errors in operating room include prescription issuing/doctor′s order giving error, prescription/doctor′s order delivery error, drug dispensing error, labeling error, preparation error, drug application technology error, drug monitoring error, drug storage error, essential drug setting error, etc. The risk factors of medication errors in the operation room mainly exist in the links of prescription issuing and delivery, drug dispensing and distribution, drug administration and monitoring, drug management, etc. The prevention strategies of medication errors in operating room include technical strategies (mandatory and constraint strategies, implementation of automation and computerization, development of standardized identifiers and processes, establishment of audit project lists) and management strategies (recommending the management mode of operation pharmacy, increasing the support of clinical pharmacy, storing drugs in different areas in operation room, allocating human resources reasonably, standardizing management of drug maintenance, advocating safe drug use culture, and strengthening professional skills training based on post competency). This guideline is applicable to all personnel involved in the use and management of drugs in the operating room.

Objective To evaluate the efficacy, safety, and economy of meropenem in the treatment of infectious diseases by means of rapid health technology assessment.　Methods The relevant databases (up to October 6, 2021) were searched to collect the meta-analyses and economic studies on the comparison of efficacy, safety, and economy in the treatment of infectious diseases with meropenem and other antibiotics. The quality of meta-analysis and economic research were evaluated by the Quality Assessment Scale for Systematic Review and Health Economics Evaluation Reporting Standard, respectively. The outcome indicators of meta-analysis were efficacy (clinical cure rate, bacterial clearance rate) and incidence of adverse drug reaction (ADR), the effect indicators were relative risk (RR), odds ratio (OR), or risk difference (RD), and the 95% confidence interval (CI). The economic research indicators were incremental cost- effectiveness ratio and minimum cost. Qualitative description of the results enrolled in this study was conducted.　Results A total of 6 meta-analyses and 5 economic studies were enrolled in this study, all of which were of high quality. Efficacy: the clinical cure rate of meropenem in the treatment of febrile neutropenia were higher than those of β-lactam antibiotics alone and β-lactam antibiotics combined with aminoglycoside antibiotics, the differences were statistically significant ［55.6% (956/1-720) vs. 49.3% (888/1-798), OR=1.36, 95%CI: 1.18-1.56, P<0.01； 58.3% (429/735) vs. 54.1% (415/767), OR=1.24, 95%CI: 1.01-1.53, P=0.04］. The clinical cure rate of meropenem in the treatment of abdominal infection was higher than those of ceftazidime- avibactam combined with metronidazole, ceftolozane-tazobactam combined with metronidazole, and imipenem, and the differences were all statistically significant ［86.6% (581/671) vs. 82.6% (571/691), RD=-0.04, 95%CI: -0.08-0, P=0.03; 87.8% (388/442) vs. 83.1% (374/450), RD=-0.05, 95%CI: -0.10-0, P=0.04; 90.8% (1-791/1-972) vs. 87.6% (1-884/2-151), OR=1.52, 95%CI: 1. 23-1. 86, P<0.05］. The bacterial clearance rate of meropenem in the treatment of abdominal infection was higher than those of ceftazidime-avibactam combined with metronidazole, and imipenem, and the differences were all statistically significant ［89.8% (491/547） vs. 85.5% (430/503), RD=-0.04, 95%CI: -0.08-0, P=0.04; 87.0% (1-109/1-274) vs. 82.3% (1-054/1-278), OR=1.45, 95%CI: 1.15-1.80, P<0.05］. The differences of bacterial clearance rate in treatment of abdominal infection among meropenem, ceftolozane-tazobactam combined with metronidazole, and β-lactam antibiotics were not statistically significant (all P>0.05). Safety: the differences of incidence of ADR in treatments of febrile neutropenia and pneumonia among meropenem, β-lactam antibiotics alone, β-lactam anti- biotics combined with aminoglycoside antibiotics, and non-carbapenem antibiotics were not statistically significant (all P>0.05). Economy: ceftazidime-avibactam, ceftolozane-tazobactam, and imipenem had better cost- effectiveness advantages than meropenem in the treatment of abdominal infection, pneumonia, and febrile neutropenia.　Conclusions Meropenem has good efficacy in the treatment of febrile neutropenia and abdominal infection. There is no significant difference in safety between meropenem and other anti-biotics, but meropenem has no economic advantage.

Objective To investigate the occurrence and clinical characteristics of extremely severe tirofiban-induced thrombocytopenia (TIT).　Methods Patients who used tirofiban during hospitali- zation in Linyi people′s Hospital from March 2015 to September 2021 was screened through the hospital information system. The medical records of patients with extremely severe TIT after medication were collected and analyzed retrospectively. The patient data extracted from the medical records included gender, age, medication indication, comorbidities, tirofiban application, combined drugs, platelet count (PLT) before and after tirofiban use, thrombocytopenia onset time from the application of tirofiban, the time to minimum value of PLT from medication, and the clinical manifestations, intervention, and prognosis of TIT, etc.　Results A total of 10-354 inpatients who used tirofiban during the set period were entered, of which 20 (0.19%) had extremely severe TIT. Among the 20 patients, 16 were male and 4 were female, aged 39-84 years with an average age of 66 years, 12 of which were ≥65 years. The medication indications of tirofiban were acute myocardial infarction in 8 patients, cerebral infarction in 5 patients, unstable angina pectoris in 4 patients, and post-operation of coronary artery bypass grafting, transient ischemic attacks, and post-operation of coronary- stent implantation in 1 patient respectively. The comorbidities included hypertension in 13 patients, diabetes mellitus in 4 patients, cerebral infarction in 3 patients, and New York Heart Association (NYHA) greater than or equal to class Ⅲ heart failure in 3 patients. Tirofiban was administered by continuous intravenous pumping for 1-48-hours. The combined drugs included aspirin enteric-coated tablets, clopidogrel tablets, ticagrelor tablets, heparin, low molecular weight heparin, alteplase, and plasmin. Five patients had symptoms of chills and shivers within 1-6 hours after treatment, 7 had oral mucosal bleeding, epistaxis, gingival bleeding, skin ecchymosis, ecchymosis on venipuncture sites, tarry stool, or bloody stool within 1-7 days after treatment, and 10-had no clinical symptoms. The median time from tirofiban application to the onset of PLT decrease and to the minimum value of PLT ［(1-18)×109/L］ were 12 (6, 20) and 18 (12, 22) hours, respectively, and the 2 kinds of time above were consistent in 13 patients. Tirofiban was discontinued in all patients after the diagnosis of extremely severe TIT, and treatments with glucocorticoids, human immunoglobulin, and platelet infusion were given. PLT recovered to (100-258)×109/L after 3-17 days (median time 4 days) of treatments in 18 patients. The other 2 patients developed tarry stool and bloody stool 2 and 1 days after the diagnosis of TIT, respectively, followed by respiratory and cardiac arrest, and died.　Conclusions Extremely severe TIT has low incidence but urgent onset, which can lead to fatal bleeding events, and some patients may have no clinical symptoms. The prognosis is generally good after tirofiban withdrawal and receiving glucocorticoids and symptomatic treatments. However, it should be alert to the adverse consequences caused by secondary bleeding events.

Objective To evaluate the cardiovascular safety of febuxostat and allopurinol in patients with gout/hyperuricemia, and to explore the difference in cardiovascular safety between Asian and non-Asian patients.　Methods Randomized controlled trials (RCTs) and cohort studies of comparision of cardiovascular safety between febuxostat (the trial group) and allopurinol (the control group) in the treatment of gout/hyperuricemia were collected by searching related databases at home and abroad (up to October, 2021). The outcome indicators were the incidences of acute decompensated heart failure (ADHF), stroke, acute coronary syndrome (ACS), coronary revascularization, death from cardiovascular causes, and all-cause death. The Cochrane collaboration risk of bias risk tool and Newcastle Ottawa Scale were used to evaluate the quality of the RCTs and the cohort studies, respectively. RevMan 5.4-software was used for meta-analysis, and the effect sizes were relative risk (RR) and its 95% confidence interval (CI).　Results A total of 9 RCTs and 7 cohort studies were enrolled in the analysis and 385-700 patients were involved, including 123-565 in the trial group and 262-135 in the control group. The results of quality evaluation showed that there were 4 and 5 RCTs with low and uncertain bias risk in 9 RCTs, respectively; among the 7 cohort studies, 2 and 5 were of high and medium quality, respectively. The result of meta-analysis of RCTs showed that the incidence of ADHF in the trial group was significantly lower than that in the control group ［1.37% (77/5-620) vs. 2.21% (102/4-607), RR=0.74, 95%CI: 0.55-0.99, P=0.04］. The result of meta-analysis of cohort studies showed that the incidence of stroke in Asian patients in the trial group was lower than that in the control group ［0.87% (519/59-559) vs. 0.90% (810/89-836), RR=0.94, 95%CI: 0.75-1.17, P=0.58］; the incidence of stroke in non-Asian patients in the trial group was lower than that in the control group, and the difference was statistically significant ［1.49% (377/25-306) vs. 1.70% (1-305/76-864), RR=0.88, 95%CI: 0.78-0.98, P=0.02］; the incidence of cardiovascular death in Asian patients in the trial group was higher than that in the control group ［0.96% (473/49-373) vs. 0.68% (335/49-368), RR=1.41, 95%CI: 1.23-1.62, P<0.01］.　Conclusions The risk of ADHF caused by febuxostat is lower than that caused by allopurinol; the risk of stroke caused by febuxostat is lower than that caused by allopurinol in non-Asian patients; the risk of cardiovascular death caused by febuxostat is higher than that caused by allopurinol in Asian patients.

Antineoplastic agents; Acute kidney injury; Renal insufficiency; Guideline; Interpretation

Exposure to antineoplastics is a potential health threat. If improperly disposed, it will also cause environmental pollution, which is a medical safety issue worthy of attention. In order to improve the protection awareness of healthcare professionals exposed to antineoplastic drugs (medical personnels, drug transportation staffs, patients and their caregivers, etc.), standardize exposure protection operations, and reduce the risk and harm of occupational exposure, the Division of Therapeutic Drug Monitoring of Chinese Pharmacological Society, the Hospital Pharmacy Professional Committee of Chinese Pharmaceutical Association, the Oncology Society of Chinese Medical Association, the Nursing Branch of China International Exchange and Promotive Association for Medical and Healthcare, and Chinese Pharmacological Society Professional Committee of Drug-induced Diseases formulated the Management guidelines for preventing exposure to antineoplastics, which was published in the 1st issue of Chinese Journal of Cancer Research in 2023. The guideline was developed referring to the World Health Organization handbook for guideline develo- pment and other international methodologies and focused on the full-process management of antineoplastics in hospitals. Using the Delphi method, clinical questions and 14 recommendations were formulated. This paper interprets 14 recommendations, hoping to help promote the implementation of the guideline.

In 2021, a total of 19-585 cases of medication error (ME) from 275-hospitals in 28 provincial administrative regions were collected in the National Monitoring Network for Clinical Safe Medication. The number of hospitals reporting ME increased by 7.84% compared with that in 2020 (255-hospitals), and the number of reported ME cases increased by 23.57% compared with that in 2020 (15-849 cases). In 19-585 cases of ME reports, 278 (1.42%) were classified as grade A, 16-221 (82.82%) as grade B, 2-442 (12.47%) as grade C, 410 (2.09%) as grade D, 95 (0.49%) as grade E, 133 (0.68%) as grade F, 1 (<0.01%) as grade G, 4 (0.02%) as grade H, and 1 (<0.01%) as grade I. Among the 19-307 patients with ME of grade B to I, 10-528 (54.53%) were male and 8-779 (45.47%) were female; they aged from 1 day to 102 years, of which 2-236 (11.58%) were children (<18 years old), 9-794 (50.73%) were young and middle-aged people (≥18 to <60 years old), and 7-277 (37.69%) were elderly people (≥60 years old). A total of 234 patients were involved in serious MEs (grade E-I), including 129 (55.13%) males and 105 (44.87%) females, aged from 3 months to 99 years, of which 45 (19.23%) were children, 88 (37.61%) were young and middle-aged people, 101 (43.16%) were elderly people. Among the 16 patients with severe MEs caused by mistaken use of drugs, 14 were children, which was a double of the number in 2020 (7 in 2020); only 3 cases were reported for mistaken use of drugs in children from 2012 to 2019. The 278 grade A MEs did not involve person who triggered the ME and place where ME occurred. Among the 19-307 grade B-I MEs, 13-932 (72.16%) were triggered by physicians, 3-961 (20.52%) by pharmacists, 541 (2.80%) by nurses, 412 (2.13%) by patients and their family members, and 461 (2.39%) by other persons; the proportion of MEs triggered by physicians and patients and their family members increased year by year for 4 consecutive years (60.89%, 65.46%, and 68.05% in 2018, 2019, and 2020 by physicians, and 1.06%, 2.04%, and 2.08% in 2018, 2019, and 2020 by patients and their family members, respectively); 8-662 MEs (44.87%) occurred in clinics, 5-256 (27.22%) in hospital wards, 3-856 (19.97%) in pharmacies, 977 (5.06%) in pharmacy intravenous admixture services, 289 (1.50%) in the nurse stations, 239 (1.24%) in patients′ houses, 6 (0.03%) in the community health service stations, and 22 (0.11%) in other places; the proportion of ME occurred in clinics and at home increased year by year for 4 consecutive years (37.32%, 37.74%, and 43.24% in 2018, 2019, and 2020 in clinics, and 0.41%, 0.89%, and 1.02% in 2018, 2019, and 2020 at home, respectively). The top 3 contents of ME were wrong dosage, wrong drug class, and wrong administration frequency. The top 3 persons who discovered the ME were pharmacists, patients and their family members, and physicians. The top 3 factors causing ME were lack of related pharmacologic knowledge, tiredness, and insufficient training of medical workers.

Migraine is one of the most common disorders in neurological clinic.New advances in pathogenesis and drug therapy for migraine have been obtained in recent years.This paper presents the drug therapy for migraine including treatment of acute attacks and preventive therapy.The common drugs used to treat acute migraine attacks are nonsteroidal non-inflammatory drugs,triptans,ergot alkaloids,etc.And the drugs used for preventive therapy are tricycle antidepressants,anticonvulsants,β-blockers,calcium channel blockers,etc.This article reviews the therapeutic actions and potential adverse reactions of these drugs in order to benefit the safe and rational drug use in clinical practice.

Objective To explore the risk factors and the predicting value of early urinary tract infection in patients treated with tacrolimus (TAC)-containing immunosuppressive regimen after kidney transplantation.　Methods The medical records of patients who underwent allogeneic kidney transplantation in the Provincial Hospital Affiliated to Shandong First Medical University from January 1, 2015 to October 30, 2021 and received triple immunosuppressive regimen with TAC+mycophenolate mofetil+methylprednisolone were collected and analyzed retrospectively. Relevant clinical data of patients were extracted from the hospital information system. Patients were divided into infection group and non-infection group according to whether urinary tract infection occurred within 1 month after taking TAC and the clinical characteristics in patients between the 2 groups were compared. The risk factors of urinary tract infection were analyzed by binary logistic regression method, and the odds ratio (OR) and its 95% confidence interval (CI) were calculated. The receiver operating characteristic (ROC) curve was used to analyze the predicting value of risk factors on the risk of urinary tract infection.　Results A total of 256 patients were entered in the analysis, including 208 males and 48 females, aged 34 (29, 42) years with an range from 18 to 66 years, and the body mass index of these patients was 22.9 (20.4, 25.4) kg/m2, ranging from 13.9 to 34.4-kg/m2. There were 163 living donors from relatives and 93 cardiac dead organ donors (DCD). Among the 256 patients, 56-had urinary tract infection (asymptomatic bacteriuria in 32 patients and symptomatic urinary tract infection in 24 patients) after kidney transplantation with an incidence of 21.9%. The differences in gender, age, body weight, body mass index, primary disease, comorbidity disease, donor source, length of hospital stay after surgery, time of indwelling urinary tube and ureteral stent, postoperative complications, complicated infection in other parts of the body after surgery, laboratory test results and so on in patients between the 2 groups were not significant (all P>0.05). The trough plasma concentrations of TAC on the 7th, 14th, and 21st days after taking TAC in the infection group was higher than those in the non-infection group ［9.7 (8.4, 13.5) μg/L vs. 8.0 (6.3, 9.8) μg/L, P<0.001; 9.4 (7.6, 11.0) μg/L vs. 8.0 (6.3, 9.8) μg/L, P=0.002; 9.2 (7.6, 11.1) μg/L vs. 8.2 (6.3, 9.8) μg/L, P=0.002］. The binary logistic regression analysis showed that the high trough plasma concentrations of TAC on the 7th day after taking TAC (OR=1.815, 95%CI: 1.332-2.474, P<0.001) was an independent risk factor for urinary tract infection in the early stage after kidney transplantation. The ROC curve analysis results showed that the area under the ROC curve of TAC trough plasma concentration on the 7th day was 0.704 (95%CI: 0.626-0.782), with the cutoff value 8.35-μg/L, the sensitivity 76.8%, and the specificity 53.5%. The patients were divided into >8.35-μg/L group and ≤8.35-μg/L group according to this cutoff value, the incidences of urinary tract infection in the 2 groups were 31.4% (43/137) and 20.6% (13/119) respectively and the difference was statistically significant (χ2=15.603, P<0.001).　Conclusion High trough plasma concentration of TAC on the 7th day after taking TAC is an independent risk factor for urinary tract infection after kidney transplantation and the predicting value is 8.35-μg/L, which has certain predicting value for early urinary tract infection after kidney transplantation.

An 87-year-old female patient with hypertension was given 3 Suhuang Zhike capsules (0.45 g/capsule) for cough. Half an hour after medication, the patient suddenly developed limbs tremor, accompanied by palpitation and sweating. The symptoms lasted for about 10-minutes and relieved spontaneously. Her blood pressure was 145/79-mmHg. Her nervous system examination showed no abnormality; blood glucose, electrolyte, thyroid function, and liver and kidney function were all normal; and electroencephalogram and cranial computed tomography showed no obvious abnormality. Ephedrine in Suhuang Zhike capsules was considered to be related to her symptoms. The drug was stopped and oral alprazolam 0.4-mg was given twice daily. The symptoms of limbs tremor did not recur in the patient.

A 4 years and 7 months old boy was treated with IV infusions of azithromycin 0.16 g once daily and methylprednisolone sodium succinate 32-mg once daily and oral amoxicillin and clavulanate potassium for suspension 228.5-mg twice daily for bronchopneumonia complicated with multiple co-infections with mycoplasma, viruses, and bacteria. After 6 days of treatments, the boy′s symptoms were improved and his body temperature returned to normal. On the 7th day of treatments, the boy developed rash with itching, which subsided on the same day after symptomatic treatments. Amoxicillin and clavulanate potassium and azithromycin were discontinued, but the child still developed rash every time after IV infusion of methylprednisolone sodium succinate, which could subside later that day. After withdrawal of methylprednisolone sodium succinate, the boy′s rash did not recur.

A 56-year-old male patient with nasopharyngeal carcinoma had progressed disease after receiving radiotherapy, chemotherapy, and targeted therapy, etc. Then he received chemotherapy combined with immunotherapy (capecitabine and sintilimab). Before receiving the 3rd immunotherapy, no abnormality was found in the relevant examination in the patient. On the 3rd day of treatment, he developed cough, shortness of breath, and other symptoms, and chest CT imaging indicated inflammatory lesion of both lungs. The results of sputum culture, sputum smear examination, G test, GM test, and autoantibody examination were all negative. Infectious pneumonia and interstitial pneumonia with autoimmune features were excluded. The common respiratory adverse reaction to capecitabine was pharyngeal discomfort, and no large-scale pneumonia caused by capecitabine was reported. Therefore, it was considered to be immune- associated pneumonitis cause by sintilimab. Treatments such as intravenous injection of methylprednisolone, IV infusion of cefoperazone sodium and sulbactam sodium and moxifloxacin were given and the patient′s condition was improved. After that, methylprednisolone dose was gradually reduced, and then changed to oral prednisone. On the 10th day of oral prednisone, the symptom of shortness of breath worsened. Chest CT imaging indicated that the pneumonitis was more severe than before. Intravenous methylprednisolone was re-given but the condition was not improved.

The ocular adverse reactions of paclitaxels can involve the ocular surface, ocular appendages and intraocular tissue, with various clinical manifestations, such as dry eye, lacrimal duct obstruction, conjunctivitis, keratitis, macular edema, retinal injury, optic nerve injury, etc., which can lead to irreversible visual impairment. The mechanism of ocular adverse reactions is still unclear. In these adverse reactions, macular edema may be related to the dysfunction of retinal pigment epithelial cells and Müller cells caused by paclitaxel, and others may be related to the cytotoxicity of paclitaxels. Baseline eye examination should be performed prior to the use of paclitaxels, and new ocular symptoms should be closely monitored during the treatment. Ocular adverse reactions can be diagnosed definitively through routine ophthalmic examination. The main treatments are timely adjustment of drugs and symptomatic treatments.

There is a risk of drug abuse associated with opioid drugs. With the widespread use of opioid drugs in chronic pain, it is of great significance to carry out risk monitoring of opioid drug abuse in medical institutions. This article introduces the relevant terms of opioid drug abuse, summarizes the current situation of opioid drug abuse and the risk situation of drug abuse in medical institutions, introduces the moni- toring tools for opioid drug abuse risks and the issue of discontinuation of drug treatment, and puts forward suggestions for the problems on opioid drug abuse in medical institutions, providing a reference for medical institutions to establish a pharmacovigilance system for drug abuse suitable for national conditions and promote the safe use of opioid drugs.

Objective To explore the adverse reactions to sintilimab in patients with non-small cell lung cancer (NSCLC) and Hodgkin lymphoma (HL).　Methods The clinical data of all NSCLC and HL patients who were treated with sintilimab during hospitalization in the Fifth Medical Center of the PLA General Hospital from January 2019 to August 2020 were collected by searching Hospital Information System. The clinical data including patients′ basic information (gender, age, diagnosis), medication (initial treatment or retreatment with sintilimab, single and cumulative dose, combined medication), and occurrence of adverse reactions (involved organs or systems, clinical manifestations, occurrence time, intervention and outcome) were recorded and analyzed retrospectively. The correlation between sintilimab and adverse reactions and the grade of adverse reactions were evaluated according to Hand Book of Adverse Drug Reaction Reporting and Monitoring in China and the International Adverse Reaction Evaluation System of Cancer Chemotherapy Drugs.　Results A total of 90 patients were enrolled in the analysis, including 75 NSCLC patients and 15 HL patients, aged from 16 to 81 years with the median age of 63 years; 81 patients were initially treated with sintilimab and 9 were retreated. Eighty-eight patients received sintilimab 200-mg per cycle and 2 patient received 100-mg per cycle. The cumulative dose was 200, >200-1-000, and >1-000-mg in 39, 35, and 16 cases, respectively; 32 patients were treated with sintilimab alone and 58 were treated with sintilimab combined with other regimens. Fifty-three (58.9%) patients had adverse reactions, among which, 41 (45.6%) and 12 cases (13.3%) had grade 1-2 and ≥ grade 3 adverse reactions, respectively. The occurrence time was 1-242 days after treatment. Among the 53 patients, 37 were male and 16 were female, aged 28-80 years; 48 were with NSCLC and 5 with HL. The incidence of adverse reactions in NSCLC patients was significantly higher than that in HL patients ［64.0% (48/75) vs. 33.3% (5/15), χ2=4.856, P=0.028］. Forty- eight patients were initially treated and 5 were retreated. Fifty-two patients received sintilimab 200-mg per cycle and 1 patient received 100-mg per cycle. The cumulative dose was 200, >200-1 000, and >1000-mg in 16, 26, and 11 cases, respectively. The difference in the incidences of adverse reactions among patients with different cumulative doses was significant (χ2=9.21, P=0.01). Fourteen patients were treated with sintilimab alone and 39 patients were treated with sintilimab combined with other therapeutic regimens; the incidence of adverse reactions in patients with sintilimab combined with other therapeutic regimens was higher than that in patients with sintilimab monotherapy, and the difference was statistically significant ［66.1% (39/58) vs. 43.8% (14/32), χ2=4.701, P=0.03］. A total of 101 times of adverse reactions to sintilimab occurred in 53 patients (1, 2, 3, 4 and 5 kinds of adverse reactions occurred in 24, 16, 9, 2, and 2 patients, respectively), 52 times of them were recorded in the medical records, and 49 times were found by rechecking the results of laboratory and auxiliary tests; 1, 3, and 97 times of adverse reactions were evaluated as “certainly”,“probably”, and “possibly”, respectively. Eighty-nine times (88.1%) of adverse reactions were grade 1-2 and 12 times (11.9%) were equal to or greater than grade 3. Multiple systems or organs were involved in the adverse reactions including blood, hepatobiliary, gastrointestinal, endocrine, respiratory, skin and appendix, heart, skeletal muscle and connective tissue, urinary, and nervous systems, and those with the top 5 incidence rates were blood, hepatobiliary, gastrointestinal, endocrine, and respiratory system adverse reactions［24.4% (22/90), 15.6% (14/90), 14.4% (13/90), 12.2% (11/90), and 11.1% (10/90)］. Twelve patients stopped sintilimab due to adverse reactions, 4 were only closely monitored without special treatment, and 49 received one day to seven months of symptomatic treatments. Among the 53 patients, 8 were cured, 29 were improved, 6 were not improved, 9 were unknown, and 1 died.　Conclusions　Sintilimab could lead to adverse reactions in multiple systems or organs in patients with NSCLC and HL, such as blood, hepatobiliary, gastrointestinal, endocrine, respiratory, and skin and appendages. The incidence and grade of adverse reactions were lower than those documented in the drug label, and no new adverse reactions were detected.

A 78-year-old female patient with hypertension （196/93-mmHg） received a slow IV infusion of urapidil injection 100-mg diluted into 250-ml of 0.9% sodium chloride injection to reduce blood pressure. The infusion rate was controlled at 40 drops/min. If the blood pressure dropped to the target value, the drug would be stopped temporarily. The blood pressure dropped to 152/70-mmHg when urapidil injection was intravenously infused for 40-min (about 80-ml). Then the drug was stopped temporarily. The nurse on duty did not introduce the patient′s condition and the use of urapidil to the nurse who would take turn on duty. The successive nurse did not check the doctor′s order and mistakenly infused the remained urapidil  170-ml within 60-min (60 drops/min). Five minutes later, the patient developed dizziness, fatigue, and severe vomiting, and the blood pressure dropped to 136/66-mmHg. Rehydration treatment was given imme- diately. About 2 hours later, the patient′s blood pressure increased to 158/76-mmHg and the symptoms were relieved.

Objective To compare the efficacy and safety between the generic sertraline tablets, which was selected in the national centralized volume-based procurement of drugs (trade name: Weitating), and the original sertraline tablets (trade name: Levofloxacin) in the treatment for depressive disorder, and to provide a basis for promoting the rational use of the generic drugs.　Methods Real world study using retrospective mirror-image comparison was adopted. The outpatient data of patients who were prescribed sertraline tablets one year after the implementation of the national centralized volume-based  procurement policy in Beijing Anding Hospital, Capital Medical University were collected. The patients were divided into the generic drug group and the original drug group. After the propensity score matching, the daily dose of prescription, blood concentration of sertraline, and incidence of abnormal laboratory test items (prolactin, liver and kidney function, blood lipids, etc.) of patients in the 2 groups were analyzed.　Results A total of 13-659 patients with depression, generalized anxiety disorder, and obsessive-compulsive disorder were enrolled in the study, including 5-973 (43.73%) patients in the generic drug group and 7-686 (56.27%) patients in the original drug group. Among the 5-973 patients in the generic drug group, 2-167 (36.28%) were male and 3-806 (63.72%) were female, aged (34±18) years, ranging from 6 to 94 years. Among the 7-686 (56.27%) patients in the original drug group, 2-709 (35.24%) were male and 4-977 (64.75%) were female, aged (35±19) years, ranging from 6 to 95 years. The difference between the daily dose of sertraline in prescription in the generic drug group and the original drug group was statistically significant ［(161.00±46.58) mg vs. (166.34±43.67) mg, t=6.614, P<0.001］. The difference of blood concentration of sertraline in patients between the generic drug group and the original drug group was statistically significant ［(50.41±39.49) μg/L vs. (53.80±39.62) μg/L, t=2.616, P=0.009］. The differences in incidence of prolactin elevation and liver and kidney dysfunction between the 2 groups were not statistically significant (all P>0.05). The difference in the proportion of patients with high-density lipoprotein cholesterol lower than limit of the reference value between the generic drug group and the original drug group was statistically significant ［41.75% (734/1-758) vs. 38.28% (673/1-758), χ2=4.409, P=0.039］. The difference in the proportion of patients with low-density lipoprotein cholesterol higher than the upper limit of the reference value between the 2 groups was statistically significant ［41.75% (734/1-758) vs. 45.39% (798/1-758), χ2=4.738, P=0.032］.　Conclusion In this study, no clinically significant differences in efficacy and safety of the generic and original sertraline tablets were found.

A 50-year-old male patient grinded his self-purchased blister-beetle (Mylabris) body into powder and then made it into paste for large area external use on his body skin for psoriasis. A few minutes later, the patient developed erythema and blisters on the site of medication; a few hours later, the purplish-red patches and blisters spread throughout the body, epidermis relaxed and exfoliated, and symptoms of systemic poisoning appeared. One day later, the patient developed multiple organ failure, such as respiratory failure, liver injury, kidney injury, severe hypoproteinemia, and abnormal coagulation function. Epidermolysis bullosa induced by externally application of Mylabris was diagnosed, and treatments of high-doses of pulsetherapy methylprednisolone, intravenous infusions of human immunoglobulin and human albumin, bedside hemofiltration, ventilator-assisted ventilation, and etc. were given. However, the patient′s condition deteriorated rapidly and finally he died of multiple organ failure 12-hours later.

Objective: To investigate and analyse the situation of digoxin used in our hospital and the factors affecting on serum-digoxin concentration. Methods: Eight hundred and sixty-one data of serum-digoxin concentration were collected in our hospital in 2005. The relationship between serum-digoxin concentration and the factors including age ,sex, serum-creatine concentra-tion was analysed by multivariate regression analysis. Results: The serum-digoxin concentration was affected by the four factors of age, sex, serum- creatine concentration, and the dose (P≤0.05). The relationship between them were con= -0.474+0.750×dose+0.154×Scr+0.128×sex+0.003×age by multivariate regression analysis. Conclusion: Serum-digoxin concentration varies with individuals and is affected by many factors. As regards most patients, the dose of digoxin should not be over 0.125 mg daily. If the serum-creatine concentration exceed the normal range, it is likely to be renal dysfunction to the patient. In such a case, the dose of digoxin should be reduced. As regards women, the dose of digoxin should be carefully adjusted to avoid digoxin toxicity.

A 3-day and 16-hour old male newborn was treated with IV infusion of meropenem 0.136 g once per 12-h combined with vancomycin 0.05 g once per 12-hours for severe infection. The platelet (PLT) was 116×109/L before treatment and reduced to 7×109/L after 11-h of treatment. Apheresis platelet by intravenous infusion was added, and PLT was 32×109/L 3 days later.Clinical pharmacists remind doctors to pay attention to adverse reactions of vancomycin when participating in ward rounds, and monitor the blood concentration of vancomycin in time. The physicians considered that the thrombocytopenia might be related to severe infection, and methylprednisolone, human immunoglobulin, cryoprecipitated antihemophilic factors, apheresis platelet products and etc. were added. The PLT increased to a transient level of 121×109/L and then continued to decrease. After 8 days of treatment, the platelet PLT decreased to 30×109/L and the trough concentration of vancomycin was 27.0-mg/L. Thrombocytopenia caused by vancomycin was considered.The pharmacist recommended temporary discontinuation of vancomycin. Vancomycin was stopped, PLT was 174×109/L 5 days later.

A 52-year-old male patient with primary bronchogenic carcinoma received an IV infusion of sintilimab 200-mg on the first day, oral anlotinib capsules 12-mg once daily on day 1-14, and 3 weeks were a cycle. At the 3rd cycle of treatments, the laboratory tests showed thyroid stimulating hormone (TSH) 0.08 mU/L, and no intervention was given. At the 5th cycle, his free thyroxine (FT4) was 11.45-pmol/L and TSH was 8.19 mU/L, indicating hypothyroidism. The patient received levothyroxine sodium tablets 50-μg orally once daily. Fifty-six days later, his thyroid function returned to normal. On the 3rd day of the 8th cycle of treatments, the patient developed dry mouth, polydipsia, polyuria, nausea, and vomiting, and laboratory tests showed blood pH 7.02, β-hydroxybutyric acid 6.740-mmol/L, and random blood glucose 66.0-mmol/L, indicating diabetes ketoacidosis. Sintilimab and anlotinib were stopped and fluid replacement and insulin hypoglycemic therapy were given. Eleven days later, his ketone body turned negative, and the fasting blood glucose was 5.8-mmol/L. About 2 weeks later, the laboratory tests showed that hemoglobin A1c was 7.8%, the serum C-peptide levels on an empty stomach and 2 hours after breakfast both were less than 0.01-nmol/L, and the islet cell antibody, insulin autoantibody, glutamic acid decarboxylase antibody, and protein tyrosine phosphatase autoantibody were negative, which was consistent with the characteristics of fulminant type 1 diabetes (T1DM). On the morning of the 32nd day of sintilimab and anlotinib withdrawal, laboratory tests showed cortisol 50.7-nmol/L and adrenocorticotropic hormone (ACTH) 2.73-pmol/L, indicating hypoadreno- corticism. Treatment with glucocorticoid was given. It was considered that the patient was with  autoimmune polyendocrinopthy syndrome (APS) type II (hypothyroidism,fulminant T1DM,hypoadrenocorticism) caused by sintilimab. After 9 months of glucocorticoid treatment, cortisol was 16.6, 79.4, and 17.2-nmol/L at 8:00,16:00, and 24:00, respectively, and ACTH was 1.12-pmol/L. The patient still needed maintenance treatment with alternative hormone.

A 45-year-old male patient was treated with canagliflozin 100-mg once daily orally for type 2 diabetes mellitus due to poor blood sugar control. On the 4th day of medication, the patient developed slight abdominal distension and fatigue; on the 5th day, the patient felt nausea and general fatigue, and the color of urine became dark brown. The laboratory tests showed serum creatinine (Scr) 136-μmol/L, blood urea nitrogen (BUN) 9.7-mmol/L, urine protein (+), and urinary occult blood (++). Acute kidney injury induced by canagliflozin was considered. Canagliflozin was stopped, and acarbose 50-mg (before meal), 2 Haikun Shenxi capsules (海昆肾喜胶囊), and 3 Jinshuibao capsules (金水宝胶囊) orally thrice daily were given. After 2 days of drug withdrawal, the symptoms of nausea and fatigue disappeared, and the color of urine was normal. After 5 days of drug withdrawal, laboratory tests showed fasting blood glucose 5.6-mmol/L, Scr 112-μmol/L, BUN 8.5-mmol/L, urine protein (-), and urine occult blood (-). After 19 days of drug withdrawal, the patient′s renal function indexes were all within the normal range, and no discomfort symptoms recurred.

To explore the risk signals of letrozole related adverse reactions and provide reference for the clinical safety of letrozole.　Methods The risk signals related to letrozole in the adverse events (AEs) reports from the first quarter of 2009 to the first quarter of 2019 in the US FDA adverse event reporting system (FAERS) were mined using the reporting odds ratio (ROR) method and the proportional reporting odds ratio (PRR) method. An AE with reports>3 and 95% confidence interval (CI) lower limit of ROR and PRR>1 was defined as a positive signal. AEs were counted and classified using the preferred system organ class (SOC) and preferred term (PT) of Medical Dictionary for Regulatory Activities (MedDRA). The PTs of top 50 adverse event reports and signal strength were selected and analyzed.　Results From the first quarter of 2009 to the first quarter of 2019, a total of 31 743 AE reports with letrozole as the primary suspicious drug were reported in the FAERS database. Four hundred and eighty‑three AE risk signals with reports>3 and the 95%CI lower limit of ROR and PRR>1 were detected, involving 16 295 AE reports. After the second screening, PTs with the top 50 AE reports and those with the top 50 PTs ROR values were obtained. After screening out repeated PTs, 93 PTs were included in the analysis, involving 10 138 AE reports. The top 5 system organs in AE reports were neoplasms benign, malignant and unspecified (cysts and polyps) ［24.48%(2 482/10 138)］, musculoskeletal and connective tissue disorders ［21.78%(2 208/10 138)］, general disorders and administration site conditions ［17.04%(1 728/10 138)］, blood and lymphatic system disorders ［17.04%(1 728/10 138)］, and investigations ［5.47%(555/10138)］. There were 32 PTs not labelled in the drug instructions, and PTs with the top 5 signal strength were ovarian fibrosis［ROR=379.63, 95%CI lower limit: 120.87; PRR=278.66, 95%CI lower limit: 120.39］, ret gene mutation［ROR=379.63, 95%CI lower limit: 120.87; PRR=278.66, 95%CI lower limit: 120.39］, antisynthetase syndrome［ROR=208.84, 95%CI lower limit: 190.30）; PRR=174.20, 95%CI lower limit: 101.56］, hashimoto′s encephalopathy［ROR=164.85, 95%CI lower limit: 69.68; PRR=142.51, 95%CI lower limit: 67.74］, and bone marrow oedema syndrome ［ROR=122.82, 95%CI lower limit: 65.47; PRR=110.00, 95%CI lower limit: 64.34］.　Conclusions Through data mining, 32 adverse reaction risk signals were found, which were not labelled in the drug instructions. Of them, ovarian fibrosis, ret gene mutation, antisynthetase syndrome, Hashimoto′s encephalopathy, and bone marrow oedema syndrome had strong signals, which were worthy of clinical attention.

Conducting quality evaluation of adverse drug reaction（ADR） case report and obtaining accurate, objective and scientific data is related to the level and quality of the entire monitoring work, and is an important basis for drug regulatory departments to formulate safety regulatory measures. The research progress and application status of the methodology of quality evaluation of ADR reports abroad were investigated through literature search in this paper. It mainly includes 3 different evaluation methods (WHO quality evaluation method, clinical documentation tool, ADR report quality algorithm) from Uppsala Monitoring Centre, Netherlands and Australia. There are currently 2 versions of ADR report quality evaluation methods in China, which are included in the appendices of the 2005 and 2012 editions of the "Adverse Drug Reaction Reporting and Monitoring Work Manual". Different ADR report quality evaluation methods have different focus points, and it is necessary to develop a scientific evaluation method suitable to provide reference for the quality supervision and management of ADR in China.

A 56-year-old male patient received an IV infusion of methylprednisolone 500-mg/d, which was changed to oral prednisone 40-mg/d after 3 days, for thyroid associated ophthalmopathy. Calcium carbonate, calcitriol, alendronate sodium, and esomeprazole magnesium enteric-coated tablets were given orally to prevent hormone-related adverse reactions. The renal function of the patient was normal in the past, but continued to decline after 1 month of medication. And at the end of 3 months after medication, the lowest estimated glomerular filtration rate (eGFR) was 33.1-ml/(min·1.73 m2). Renal diseases and urinary tract obstruction were excluded by routine urine analysis and color Doppler ultrasound examination of the kidneys. Kidney injury caused by esomeprazole magnesium enteric-coated tablets was considered. Then the drug was replaced by famotidine and the other drugs were continued. After 9 days, the renal function of the patient gradually recovered, with the eGFR of 74.0 ml/(min·1.73 m2) at discharge.

Objective: To study the pathogenesis , prevention and management of the liver damage caused by tra-dional Chinese medicines on analysis of cases with liver damage. Methods: This article summarized 427 cases of liver damage caused by traditional Chinese medicines in the last fifteen years and surveyed incidence of liver damage caused by traditional Chinese medicines, distribution of primary diseases, and clinical characteristics. Results: Liver damage cases induced by traditional Chinese medicines were on the increase year by year , amounted to 32.6% in all cases of the drug-induced liver damage. Those traditional Chinese medicines used to treat osteoarthropathy, kidney diseases and skin diseases induced liver damage more often. Zhuanggu Guanjie Wan , Tripterygium wilfordii Hook. f., and Dioscorea bulbifera L. were the most major medicines inducing liver damage. The clinical characteristics and the pathogenesis of liver damage caused by different medicine were varient. Conclusion: Ratio...更多nal use of traditional Chinese medicines and study of their hepatotoxicity should be strengthened further in clinical practice .

Traditional Chinese medicine (TCM) is widely used in medical institutions in China. Because TCM is often regarded as "natural and non-toxic", the irrational use of TCM is more common, such as repeated medication, incompatibility, long-term prescription, inappropriate usage and dosage, and inapprop- riate drug combination. The development and application of TCM prescription pre-audit system is of great significance to the safety management of TCM, but the existing TCM decoction prescription audit system still has some defects and needs to be further improved. The safety of TCM can be further improved by setting up TCM clinical pharmacist post, and strengthening the monitoring of adverse reactions and the study of the interaction between TCM and western medicines. In medical institutions, the management measures of TCM safety should be constantly explored and the pharmaceutical service level of TCM should be improved to ensure the patient safety.

In recent years, club drugs are often abused by teens and young adults, The common club drugs are gamma- hydroxybutyrate, ktamime, MDMA, and flunitrazepam. This paper describes the acute toxic effects of the four drugs in order to be beneficial to the management of their poisoning in clinical practice.

氨基糖苷类抗生素具有抗菌谱广,对大多数革兰阴性(G-)杆菌引起的感染疗效确切等特点。但该类药物具有个体差异大、治疗指数窄等缺点,应用不当,可引起严重不良反应。本文参考近期文献从葡萄糖转运及其代谢、第二信使、微量元素和线粒体功能等方面就氨基糖苷类抗生素耳毒性的可能机制及临床处置作一综述。

A 69-year-old male patient with depression was treated with amfebutamone and mirtazapine for a long time. Because of poor control of symptoms, the treatment plan was adjusted to oral duloxetine (60-mg in the morning) and mirtazapine (15-mg at night). After 13 days of treatments, the patient developed high fever (41.0-℃) with disturbance of consciousness, followed by muscle rigidity and dyspnea. His heart rate was 180 beats/min and blood oxygen saturation was 0.84. Laboratory tests showed serum creatinine (Scr) 609-μmol/L, creatine kinase (CK) 7-102-U/L, myoglobin (MYO)>3-000-μg/L, aspartate aminotransferase (AST) 88-U/L， and total bilirubin (TBil) 33.7-μmol/L. ECG monitoring showed rapid atrial fibrillation. The patient was diagnosed with malignant syndrome caused by duloxetine after excluding infection and other conditions. Duloxetine and mirtazapine were stopped immediately, and symptomatic and supportive treatments including endotracheal intubation, hemofiltration, improvement of water-electrolyte balance, and hepatoprotection were given. On the 6th day of drug withdrawal, the patient′s temperature was 38.2-℃, the blood oxygen saturation was 0.96, muscle tone was improved, and muscle tremor disappeared. On the 16th day of drug withdrawal, the patient′s condition was obviously improved, the consciousness was clear, the temperature was normal, the call could be answered, and no limb convulsion and muscle tremor occurred. Laboratory tests showed Scr 116-μmol/L, CK 250-U/L, MYO 148-μg/L, AST 38-U/L, and TBil 21.4-μmol/L.

Objective To understand and analyze the occurrence of medication error (ME) on insulin preparations and its influencing factors and provide reference for the standard use of insulin preparations.　Methods The ME reports on insulin preparation-related MEs in the National Monitoring Network for Clinical Safe Medication (monitoring network) from May 6, 2015 to June 30, 2022, were collected and information of MEs including drugs involved, grading, error content, the persons who caused and found the errors, and the factors that triggered the errors were analyzed.　Results During the set period, a total of 2-215 ME reports from 193-hospitals in 26 provinces and municipalities in China were collected in the monitoring network. A total of 2-215 patients were involved, including 1-345 males (60.72%) and 870 females (39.28%), aged from 1 to 95 years, with an average age of (52±4） years. Two thousand one hundred and eighty-two MEs (98.51%) were mild and 33 (1.49%) were severe. The 2-215 ME reports involved 8 classes and 29 kinds of insulin, and a total of 2-263 times of ME content. The top 3 ME contents of insulin preparations were variety errors (40.70%, 921), interaction/compatibility errors (18.29%, 414), and dosage errors (9.06%, 205). Among the 2-215 MEs, 58.24% (1-290 MEs) were triggered by physicians, 28.26% (626 MEs) by pharmacists, 6.5% (144 MEs) by patients and their families, 5.6% (124 MEs) by nurses, and 1.40% (31 MEs) by others; 1-741 MEs (78.60%) were detected and intercepted in time, of which 75.70% (1-318) were found by pharmacists, 14.01% (244) by patients/family members, 7.76% (135) by nurses, and 2.53% (44) by physicians. The main factors that caused MEs were lack of knowledge (23.28%, 701), similar drug names (19.36%, 583), fatigue (14.51%, 437), etc.　Conclusions The contents of insulin preparations-related MEs mainly include variety error, interaction/compatibility error, and dosage error. MEs are mainly caused by physicians and mostly discovered and intercepted by pharmacists. Lack of knowledge, similar drug names, and fatigue are the major factors causing MEs.

Hyperthyroidism combined with abnormal liver function is a tricky problem in clinical diagnosis and treatment, which mainly includes hyperthyroidism-related liver injury, liver injury caused by antithyroid drugs (ATD), and other liver diseases associated with hyperthyroidism. Chinese Pharmacological Society Professional Committee of Drug-induced Diseases, Section of Clinical Toxicology of Chinese Society of Toxicology, and the Editorial Committee of Adverse Drug Reactions Journal organized relevant experts majoring in endocrinology, hepatology, and clinical pharmacy to jointly discuss and formulate this consensus based on a systematic review of relevant research progress at home and abroad, combined with the actual clinical situation in China. This consensus systematically expounds the epidemiology, pathogenesis, clinical characteristics, diagnosis and differential diagnosis, monitoring and treatment of hyperthyroidism with liver dysfunction, and puts forward recommendations for diagnosis and treatment, aiming to help clinicians make reasonable decisions in the prevention, diagnosis and treatment of hyperthyroidism combined with abnormal liver function, and improve the level of clinical diagnosis and treatment.

The rational application of analgesics to control postoperative pain is an important measure to improve the efficacy of surgical treatment and the quality of life and prognosis of patient.The multi-mode analgesia, preventive analgesia, and the perioperative goal-oriented whole process analgesia management were recommended to control postoperative pain in relevant guidelines at home and abroad. However, irrational use of modes of analgesia and/or analgesics is still common and some patients are not satisfied with postoperative pain management. It is of high clinical significance to provide patient education with analgesic method and drug use before operation, enhance the continued medical education about postopera- tive pain management for doctors in related clinical departments, set up acute pain service management group at the hospital level for improvement of the satisfaction of postoperative analgesia, rational use of analgesics, and the prognosis of patients.

Immune checkpoint inhibitors (ICIs) play the role of anti-tumor by activating the immune system in human, but they can also cause immune-mediated liver injury, which is different from conventional drug-induced liver injury in the incidence, clinical manifestations, pathogenesis, and prognosis. The main pathogenesis is that ICIs block key nodes of negative regulation of the immune response, including cytotoxic T-lymphocyte-associated antigen 4 and programmed cell death 1 receptor/programmed cell death ligand 1. Liver-injury occurs when the immune system is overactivated and loses immune tolerance to the liver. Immune-mediated liver injury includes immune-mediated hepatitis and immune-mediated cholangitis. Histopathological examination of the liver shows damage in hepatocytes and bile ducts, accompanied by central venous dermatitis mostly and granulomatous lesions partially. After diagnosis of immune-mediated liver injury, treatment should be given based on the severity, and glucocorticoids or immunosuppressants are often necessary.

Rituximab is a human-mouse chimeric monoclonal antibody synthesized using genetic engineering technology and exert pharmacological effects by specifically binding to the transmembrane protein CD20 on the surface of B cells. The clinical therapeutic effect of rituximab is significant, but its pharmacological mechanism is complex, the pharmacokinetics/pharmacodynamics (PK/PD) presents as nonlinear models and is highly variable, which brings great variability and uncertainty to the effectiveness and safety of rituximab in clinic, so individualized therapy needs to be implemented to improve the rationality of medication. At present, rituximab has the basic conditions for therapeutic drug monitoring (TDM), such as detection technology of blood drug concentration, tumor biomarkers, and related genetic polymorphisms. Using these technologies, combined with comprehensive analysis of factors such as disease diagnosis, population specificity, route of administration, and drug interactions, the PK/PD model of rituximab can be constructed to predict the efficacy, toxicity, and drug resistance. It is of great significance for pharmacists to participate in the individualized rituximab treatment and carry out TDM, which can provide safer and more effective individualized treatment for patients.

An 87-year-old male patient was scheduled for electronic laryngoscopy examination due to pharyngeal discomfort. Before the examination, he was anesthetized locally with 10-ml dyclonine hydrochloride mucilage in his mouth and vomited out 5-minutes later. After spitting out the medicine, the patient developed shortness of breath, fatigue, and dyspnea suddenly 5-minutes later; cold sweat and syncope appeared 20-minutes later; his pulse oximeter oxygen saturation (SpO2) decreased to 0.50 and unconsciousness appeared 30-minutes later. Severe allergic reaction was diagnosed, which mainly manifested as acute respiratory failure and might be related to dyclonine hydrochloride mucilage. Endotracheal intubation and ventilator assisted ventilation were performed immediately, and anti-infection, expectorant, nutritional support, stable internal environment maintaining treatments were given at the same time. After 6 days′ treatments, the endotracheal intubation was removed and the nasal tube was used for oxygen inhalation. Then the SpO2 was 0.99 and the above-mentioned symptoms disappeared.

Objective To understand the current status of perioperative analgesics use and management in China.　Methods A questionnaire was self-designed with the content consisting of 4 dimensions (the basic information of the respondents, perioperative analgesics management, medical behaviors in perioperative analgesia, and understanding of analgesics-related knowledge) and 55 questions (8, 10, 22, and 15 questions under 4 dimensions, respectively). The questionnaire was sent through Wechat by the members of Chinese Pharmacological Society Professional Committee of Drug-induced Diseases and Anesthesiology Branch of the Chinese Medical Association. Anesthesiologists, surgeons/nurses and clinical pharmacists volunteered to participate in the survey and submitted in anonymous form directly. The investigation period was from August 1 to 31, 2020.　Results A total of 204 effective questionnaires were received from 45-hospitals in 19 provinces and cities, including 43 tertiary hospitals (95.6%) and 2 secondary hospitals (4.4%). Among the 204 respondents, 46 were surgeons (22.5%), 80 were anesthesiologists (39.2%), 32 were clinical pharmacists (15.7%), and 46 were surgical nurses (22.5%). Of the 45-hospitals where the respondents work, 35 (77.8%) had established regular communication mechanisms for perioperative pain management, and 22 (48.9%) arranged clinical pharmacist to assist the work of the physician in the clinical division. Among the 204 respondents, 76.5% (156 respondents) received knowledge training on analgesics once or twice a year; 60.3% (123 respondents) had found irrational use of perioperative analgesics in their daily work, and the top 3 problems were about drug selection ［74.0% (91/123)］, usage and dosage ［69.1% (85/123)］, and drug interactions ［46.3% (57/123)］; 37.3% (76 respondents) had found the problem of irrational use of the analgesia pump, and the top 3 problems were about the usage and dosage ［69.7% (53/76)］, drug selection ［67.1% (51/76)］, and contraindications ［36.8% (28/76)］. Only 13.7% (28/204) of the respondents had a score of ≥120 points (full score of 150 points) in the survey for understanding of knowledge about analgesics. There was 53.9% (110/204) of the respondents with a score of <90 points, including 50.0% (23/46) of the surgeons, 43.8% (35/80) of the anesthesiologists, 46.9% (15/32) of the clinical pharmacists, and 80.4% (37/46) of the surgical nurses. Only 4 of the 15 questions had a correct answer fill rate of >50%.　Conclusion Most of the hospitals surveyed have established relevant mechanisms for perioperative pain management, but there are still problems of irrational use of perioperative analgesics and analgesia pumps. About half of the surgeons, anesthesiologists, clinical pharmacists, and most of the surgical nurses have little understanding of knowledge about analgesics.

A 63-year-old male patient took tamsulosin hydrochloride sustained release capsules 0.2-mg daily and Qianliexin capsules 2 g thrice daily by himself for urinary urgency and urodynia. Twenty- five days later, he developed itchy skin, deep brown urine, nausea, fatigue, and loss of appetite. Laboratory tests showed alanine aminotransferase (ALT) 265-U/L, aspartate aminotransferase (AST) 163-U/L, total bilirubin (TBil) 155.1-μmol/L, direct bilirubin (DBil) 74.7-μmol/L, indirect bilirubin (IBil) 80.4-μmol/L, alkaline phosphatase (ALP) 261-U/L, and gamma-glutamyltransferase (γ-GT) 184-U/L. Liver biopsy showed the cholestatic liver injury. He was diagnosed as acute drug-induced liver injury, which might be related to the above 2 drugs. The above 2 drugs were stopped and oral ursodeoxycholic acid 250-mg thrice daily was given. On day 42 of drug withdrawal, laboratory tests showed ALT 368-U/L, AST 179-U/L,TBil 504.9-μmol/L, DBil 382.8-μmol/L, IBil 122.1-μmol/L, ALP 201-U/L, and γ-GT 58-U/L. On day 91 of drug withdrawal, laboratory tests showed ALT 78-U/L, AST 62-U/L, TBil 138.1-μmol/L, DBil 118.2-μmol/L, IBil 20.2-μmol/L, ALP 140 U/L, and γ-GT 31-U/L. The patient′s liver function returned to normal 135 days after drug withdrawal.

Objective To explore the occurrence of adverse reactions of empagliflozin in hospitalized patients with type 2 diabetes mellitus.　Methods Medical records of all patients who were treated with empagliflozin during hospitalization in China-Japan Friendship Hospital from May 1 to December 31, 2020 were collected through the hospital information system. According to the main adverse reactions indicated in the label of empagliflozin, the occurrence of urinary tract infection, hypoglycemia, and hypotension after the application of empagliflozin was retrospectively analyzed. According to the Handbook of Adverse Drug Reaction Reporting and Monitoring in China, the causality between drugs and adverse reactions was evaluated, and those adverse events that were certainly, probably, and possibly related to empagliflozin were judged as empagliflozin-related adverse reactions.　Results A total of 718 inpatients received empagliflozin treatment during the study period, including 517 males and 201 females, with age of (59±12) years. The doses of empagliflozin were all 10-mg orally once daily. The treatment time was (7±3) days and the length of hospital stay was (8±4) days. Among 718 patients, 17 (2.4%) experienced adverse reactions possibly related to empagliflozin, including 11 (1.5%) with urinary tract infection (all showing asympto-　matic bacteriuria), 4 (0.6%) with hypoglycemia, and 2 (0.3%) with hypotension. There were 8 males and 9 females among the 17 patients with adverse reactions, and the incidence of adverse reactions in females was significantly higher than that in males ［4.5% (9/201) vs. 1.5% (8/517), χ2=5.376, P=0.020］. Among the 11 patients with urinary tract infection, 4 were male, 7 were female, and the incidence of urinary tract infection in females was significantly higher than that in males ［3.5% (7/201) vs. 0.8% (4/517), χ2=7.040, P=0.008］. In the medical records of the 17 patients, the above-mentioned adverse reactions were all not documented as related to empagliflozin, and were all not reported as adverse drug reactions. Conclusions The adverse reactions related to empagliflozin in hospitalized patients with type 2 diabetes mellitus were urinary tract infection, hypoglycemia, and hypotension. The prevention of urinary tract infection should be strengthened, especially in female patients. The awareness of clinical medical staff on the adverse reactions of empagliflozin needs to be improved.

A 37-year-old female patient with psoriasis received subcutaneous injection of secukinumab 300-mg once a week. Four weeks later, it was changed to subcutaneous injection of 300-mg once every 4 weeks. Seventy-five days later, the patient developed abdominal pain, diarrhea, and fever. The patient had no previous intestinal disease and family history of inflammatory bowel disease. Ulcerative colitis (initial, whole colon, and severe type) was diagnosed by enteroscopy, which was considered to be related to secukinumab. After 2 days of anti-inflammatory treatment with glucocorticoid, the patient′s body tempera- ture returned to normal and the abdominal pain was alleviated； after 9 days, the patient only had a dull abdo- minal pain at night and no other discomfort occurred.

为了解非典型抗精神病药物引起锥体外系症状(EPS)的情况,利用Medline检索系统对已公开发表的临床随机对照试验与流行病学资料进行分析。非典型抗精神病药物间引起EPS的程度各有差异,有的与剂量相关,总体较经典的抗精神病药物发生率低,严重程度轻。但临床仍应重视锥体外系症状的预防与治疗问题。

Objective: To investigate the adverse reactions of cephalosporins. Methods: 148 cases with allergic shock were collected and analysed mostly through Chinese literature retrieval of 1986 - 2000 in addition to a few patients of our hospital. Results: The shock appeared immediately after the drug administration in 66 cases with a severe nature and death followed if the first aid delayed. Conclusion: The treatment of shock and the skin test of drug were discussed. More attention should be attached to the shock associated with cephalosporins.

The recommendations of Guideline for Emergency Management of Anaphylaxis  answered 15 clinical questions about diagnosis, preparation for treatment, treatment measures, and post-treatment management of anaphylaxis and a total of 26 recommendations were formed. In the recommendations, the quality of evidence was divided into 4 levels: high, moderate, low, and very low. And the strength of recommendation was divided into 2 levels: strong and weak. The strength of recommendations was mainly determined by weighing the advantages and disadvantages, instead of relying on the quality of evidence. Emergency management of anaphylaxis in clinical practice could be carried out with reference to the recommendations of this guideline.

A 17-year-old male patient received rituximab due to nephrotic syndrome. No obvious discomfort occurred during the first treatment (500-mg by intravenous infusion). After half a year, when the second treatment (300-mg by intravenous infusion) was given, the patient developed symptoms such as fatigue of limbs and inability to lift both lower limbs. Laboratory test showed blood potassium 2.37-mmol/L. Before treatment, the serum potassium was 4.16-mmol/l, and other laboratory test indicators were basically normal. Acute hypokalemia caused by rituximab was considered. Oral potassium chloride was given. On the 2nd day, the symptoms in the patient were relieved, the feeling of powerlessness disappeared, and the blood potassium was 3.06-mmol/L. On the 3rd day, the blood potassium was 4.34-mmol/L. the potassium supplement was stopped after 3 days of medication. The next day, the blood potassium was 4.70-mmol/l, and the patient′s limb weakness and discomfort symptoms disappeared. After that, the patient did not use rituximab again, and no hypokalemia recurred.

In 2019, a total of 15 056 cases of medication error (ME) from 234 hospitals in 24 provincial administrative regions were collected in the National Monitoring Network for Clinical Safe Medication. The number of hospitals reporting ME increased by 32.20% compared with that in 2018 (177 hospitals), and the number of reported cases increased by 28.02% compared with that in 2018 (11 761 cases). In 15 056 cases of ME reports, 52 (0.35%) were classified as grade A, 11 175 (74.22%) as grade B, 3 351 (22.26%) as grade C, 350 (2.32%) as grade D, 79 (0.52%) as grade E, 44 (0.29%) as grade F, 0 as grade G, 4 (0.03%) as grade H, and 1 (0.01%) as grade I. Among the 15 004 patients involved in ME of grade B‑I, 8 801 (58.66%)were male and 6 203 (41.34%) were female; the age of these patients ranged from 1 day to 103 years, 2 027 patients (13.51%) were <18 years old, 7 377 patients (49.17%) were ≥18 to <60 years old, and 5 600 patients (37.32%) were ≥60 years old. Serious MEs (grade E‑I) involved 128 patients, of whom 65 (50.78%) were aged over 60 years. The top 3 drugs involved in serious MEs were insulin glargine, methotrexate tablets, and warfarin tablets. The 52 cases of grade A MEs did not involve person who triggered the MEs and places where MEs occurred. In the 15 004 cases of grade B‑I MEs, 9 821 (65.46%) were triggered by physicians, 3 561 (23.73%) by pharmacists, 634 (4.23%) by nurses, 306 (2.04%) by patients and their family members, and 2.04% (4.54%) by other persons; the proportion of MEs triggered by physicians and patients and their family members were higher than those in 2018 (60.89% and 1.06%), respectively; 5 662 (37.74%) occurred in the clinics, 4 001 (26.67%) in hospital wards, 3 721 (24.80%) in the pharmacies, 1 084 (7.22%) in pharmacy intravenous admixture services, 224 (1.49%) in the nurse stations, 133 (0.89%) in patients′ houses, 4 (0.03%) in the community health service stations, and 175 (1.17%) in other places; the proportion of MEs in pharmacy intravenous admixture services and patients′ houses were higher than those in 2018 (5.52% and 0.41%), respectively. The top 3 contents of MEs were wrong drug class, wrong usage, and wrong single dose. The top 3 persons who discovered the MEs were pharmacists, nurses, and physicians. The top 3 factors cau- sing MEs were lack of related pharmacologic knowledge, tiredness, and insufficient training of medical workers.

A 78-year-old female patient was treated with orelabrutinib 100-mg once daily orally due to recurrence of lymphoma. On the 2nd day of treatment, the patient′s fecal occult blood was weakly positive. Three days later, fibrinogen was 0.61-g/L. After intravenous infusion of cryoprecipitated coagulation factor and frozen plasma, the fibrinogen level rose slightly. The patient did not follow the doctor′s advice and took orelabrutinib irregularly, and her fibrinogen level recovered to 1.71-g/L. After further regular treatment with orelabrutinib, her fibrinogen decreased to 0.74-g/L and irregular skin ecchymosis and bleeding spots appeared in the inner side skin of both lower limbs. The fibrinogen in the patient returned to 2.17-g/L after temporary suspension of orelabrutinib and receiving 2 times of intravenous infusion of cold precipitated coagulation factor 10 U, then decreased to 0.94 g/L after reuse of orelabrutinib, and finally recovered to 3.82-g/L after 3 times of intermittent infusion of cold precipitated coagulation factor. It is considered that the hypofibrinogenemia in the patient was caused by orelabrutinib.

An 83-year-old male patient received moxifloxacin hydrochloride (moxifloxacin) 400-mg once daily orally for acute attack of chronic obstructive pulmonary disease. He developed scattered red rashes, accompanied by itching, on his both lower limbs 5 hours after the first dose. Next day, the rashes involved skin on the trunk, and purpura appeared on the multiple skin below the knees. Laboratory tests showed platelet count (PLT) 1×109/L，and thrombocytopenia related to moxifloxacin was considered. Moxi- floxacin was stopped and the treatments including hemostasis, anti-allergy, regulation of immune function, and platelet transfusion were given. On day 2 of drug withdrawal, his PLT was 3×109/L, and on day 4 the PLT was 35×109/L. He was transferred to a superior hospital and received the therapy including anti-immune response, platelet-raising, and hemostasis for 5 days. Then his PLT increased to 244×109/L.

The incidence of pediatric anesthesia emergence delirium (ED) is high, and the potential harm is significant. It can be diagnosed through the pediatric anesthesia emergence delirium scale (PAED). The risk factors of pediatric anesthesia ED include personal, surgical, and anesthetic factors. The anesthesia ED in children can be effectively prevented by relieving preoperative anxiety, optimizing anesthetic strategies, and providing effective postoperative analgesia. Alpha 2 agonists (eg. dexmedetomidine), opioids (eg. fentanyl), propofol, and ketamine have both preventive and therapeutic effects on anesthesia ED in children.
【Key-words】 Delirium; Child; Anesthesia; Risk factors

Drug safety is always the primary concern in both the stage of new drug development and the post-marketing clinical application stage, and it is also the main reason for drug development failure and even post-marketing drug withdrawal. The physiologically-based pharmacokinetic (PBPK) model can not only routinely predict the human plasma pharmacokinetics, but also predict the concentration distribution of drugs in different tissues, which has become an important tool for predicting the adverse reactions of new drugs and has gradually attracted the attention of drug regulatory authorities. In this article, the latest progress and application of the PBPK model for predicting drug-induced nephrotoxicity, cardiotoxicity, and neurotoxicity are briefly reviewed to provide references for early prediction of adverse drug reactions in new drug development and rational clinical use of drugs.

本文根据近年来国内外有关呋塞米的不良反应的文献报道,概述了呋塞米的少见不良反应,有些不良反应比较严重,应予以重视。

A 72-year-old male patient received anti-infectious treatments with piperacillin sodium and tazobactam sodium, moxifloxacin, and posaconazole, and expectorant treatment with acetylcysteine for pulmonary infection after lung transplantation; original antirejection therapy with tacrolimus and mycophenolate mofetil was continued. Before treatments, serum creatinine was 98-μmol/L and blood urea nitrogen was 3.4-μmol/L. On the 5th day of treatments, the trough blood concentration of tacrolimus increased to 22.9-μg/L, serum creatinine increased to 497-μmol/L, and blood urea nitrogen increased to 17.91-mmol/L. During the consultation, the clinical pharmacists learned that the patient used posaconazole and tacrolimus in combination. They also understood that posaconazole could inhibit the activity of liver cytochrome P450 (CYP) 3A4, while tacrolimus was mainly metabolized by CYP3A4 by searching the literature. Then it is considered that the acute kidney injury caused by tacrolimus occurred due to the increase of blood concentration following the simultaneous application of tacrolimus and posaconazole. Clinical pharmacists recommended that posaconazole was replaced by caspofungin and the dose of tacrolimus was reduced. The clinician adopted the above recommendations and the patient was given continuous venous-venous hemofiltration meantime. Eight days later, the patient′s serum creatinine level gradually decreased to 334-μmol/L, blood urea nitrogen was 7.6-mmol/L, and urine volume was 200-ml. Then hemodialysis was performed 3 times a week; 1 month later, the patient′s serum creatinine was 115-μmol/L, and blood urea nitrogen was 7.2-mmol/L.

Objective;To evaluate the side-effects induced by clindamycin and its safety in clinical practice. Method:According to organ/system types recommended by WHO, the adverse reactions of clindamycin in 248 cases were classified. Results; 15 organs/systems were involved and the commonest ADRs were damages of skin and its appendages, digestive system, central and peripheral nervous system. Conclusion; Clindamycin should be used with caution in patients with a history of hypersensitivity. There is a potential danger of significant diarrhoea, hematuria and respiratory depression mainly because of drug interactions.

Objective To understand the risk signal of ocular adverse events (AE) related to mycophenolate mofetil (MMF) and to provide reference for the safe clinical use of this drug.　Methods The US FDA Adverse Event Reporting System database was searched, and the AE reports on MMF as the primary suspect drug from the 1st quarter of 2004 to the 3rd quarter of 2022 were collected. AEs were counted and classified using the preferred system organ class (SOC) and preferred term (PT) of Medical Dictionary for Regulatory Activities version 24.0, and ocular AEs were screened out. The ocular AE risk signals were explored using 3 frequency methods, including reporting odds ratio (ROR) method, proportional reporting ratio (PRR) method, and Bayesian confidence propagation neural network method, and the multi-item gamma-Possion shrinker (MGPS) method. The information of the ocular AE reports and AE risk signals of MMF were analyzed descriptively.　Results A total of 402 cases of ocular AE with MMF as the primary suspect drug were collected, which involved 402 patients, 31 PTs and 5 SOCs. The 402 AE cases were reported among 33 countries, 283 of which had clinical outcome records, including death in 32 cases (11.3%), disability or blindness in 142 cases (50.2%), life-threatening in 14 cases (4.9%), and hospitalization or prolonged hospitalization in 95 cases (33.6%). Results of the frequency method showed that all 31 PTs were risk signals, while the results of the MGPS method manifested that 22 PTs were risk signals. None of the 31 PTs were recorded in the drug labels. The top 5 PTs in the number of AE reports were blindness (136 cases), cytomegalovirus chorioretinitis (37 cases), uveitis (34 cases), endophthalmitis (29 cases), and necrotising retinitis (22 cases). The ranking of signal intensity showed by the 4 methods was similar. The top 5 PTs with the high signal intensity were orbital apex syndrome [ROR=55.84, PRR=55.83, information component (IC)=5.58, empirical Bayesian geometric mean (EBGM)=47.71], quadrantanopia (ROR=43.22, PRR=43.21, IC=5.26, EBGM=38.21), retinitis viral (ROR=40.13, PRR=40.13, IC=5.16, EBGM=35.78), optic discs blurred (ROR=40.13, PRR=40.13, IC=5.16, EBGM=35.78), and serpiginous choroiditis (ROR=31.07, PRR=31.07, IC=4.83, EBGM=28.41).　Conclusions The clinical manifestations of ocular AE during MMF treatment are diverse, and none of them are recorded in the drug label. The clinical outcomes are poor and can lead to blindness, which should be vigilant in clinical practice.

An 82-year-old female patient with severe osteoporosis received an IV infusion of zoledronic acid 5 mg after the right hip artificial femoral head replacement. About 4 hours after the end of IV infusion, the patient presented chill, fatigue, myalgia and high fever. About 6 hours later the patient occurred nausea and vomiting. About 14 hours later the patient developed dyspnea, convulsions, loss of consciousness, and tachycardia. The results of laboratory tests showed the following results: carbon dioxide-combining power (CO2-CP)14 mmol/L, B-type natriuretic peptide (BNP) 1374.07 ng/L, prothrombin time (PT) 20 s, activated partial thromboplastin time (APTT) 37 s , alanine aminotransferase (ALT) 269 U/L, aspartate aminotransferase (AST) 279 U/L, blood urea nitrogen (BUN) 34.6 nmol/L, serum creatinine (Scr) 273 μmol/L. She was diagnosed as respiratory failure, multiple organ failure due to zoledronic acid. She was transferred to ICU, and was given a tracheal intubation with ventilator assisted breathing, she received   symptomatic treatments including those to keep heart rate and blood pressure stable, to protect the functions of liver and kidney. On day 7 in ICU, the patient recovered consciousness. The laboratory tests showed the following results: ALT 135 U/L, AST 137 U/L, BUN 35.3 nmol/L, Scr 217 μmol/L, CK-MB 2.1 μg/L. On day 53 in ICU, her heart rate was 55-86 beats/min, respiration rate was 21-25 times/min, blood pressure was 102-122/51- 69 mmHg (1 mmHg= 0.133 kPa), pulse oxygen saturation was 0.97-1.00. The results of laboratory tests were: ALT 38 U/L, AST 45 U/L, BUN 7.1 nmol/L, Scr 60 μmol/L, CK-MB 1.19 μg/L, myoglobin 0.03 μg/L and BNP 401 ng /L. On day 85 in ICU, the patient regained spontaneous respiration.

Objective To compare the occurrence and clinical characteristics of hypersensitivity reactions induced by 3 non-ionic iodine contrast media (NICMs) during percutaneous coronary intervention (PCI). Methods The patients who developed hypersensitivity reactions in iopromide, iohexol, and iodixanol application during PCI were screened out from adverse drug reaction reports of Beijing Anzhen Hospital from January 1, 2013 to December 31, 2018 and the total number of patients who underwent the PCI during that period and received the above NICMs was obtained by searching the hospital information system. The overall incidences of hypersensitivity reactions and severe hypersensitivity reactions and incidences of those induced by each of the 3 NICMs were calculated and their clinical characteristics were analyzed.　Results The overall incidences of hypersensitivity reactions and severe hypersensitivity reactions induced by the 3 NICMs were 0.603% (422/69-955) and 0.024% (17/69-955). The incidences of hypersensitivity reactions induced by iohexol, iopromide, and iodixanol were 0.418% (109/26-097), 0.364% (83/22-787), and 1.092% (230/21-071), respectively; the incidences of severe hypersensitivity reactions were 0.023% (6/26-097), 0.039% (9/22-787), and 0.009% (2/21-071), respectively. Iodixanol had a higher incidence of hypersensitivity reactions than iopromide and iohexol (both P<0.001) but the lowest incidence of severe hypersensitivity reactions, which was significantly different from that of iopromide (P=0.047). Of the 422 patients who developed hypersensitivity reactions, 327 were male and 95 were female with an average age of 59 years (range: 27-101 years). The time of hypersensitivity reactions occurrence was recorded in 373 patients and time from NICMs injection to hypersensitivity reactions occurrence were 30-minutes to 90-hours with the median time of 5 hours; hypersensitivity reactions were immediate type (latency ≤1 hour) in 127 patients (34.0%) and delayed type (latency>1 hour) in 246 patients (66.0%). The hypersensitivity reactions induced by iopromide were mainly immediate type (79.5%, 62/78), while those induced by ioxamol were mainly delayed type (87.7%, 193/220). The proportion of patients with a previous history of allergy in the immediate type patients was significantly higher than that in the delayed type patients ［15.0% (15/100) vs. 7.1% (14/197), P=0.030］. The most common clinical manifestation of hypersensitivity reactions was rash ［78.0% (329/422)］. Among 17 cases of severe hypersensitivity reactions, 15 (88.2%) were anaphylactic shock, 1 was laryngeal edema, and 1 was dyspnea, all of which were immediate type. Hypersensitivity reactions were all improved after treatments, but PCI failed to be fully performed in 6 patients due to severe hypersensitivity reactions.　Conclusions The safety of 3 NICMs for PCI was good and the incidence of hypersensitivity reactions was low; the incidence of severe hypersensitivity reactions due to iopromide was the highest. Severe hypersensitivity reactions such as anaphylactic shock might affect the performance of PCI and caution should be given.

An 81-year-old male patient with bipedal blue toe syndrome received IV pumping of dexmedetomidine 0.2-mg dissolved in 0.9% sodium chloride injection 48-ml at the rate of 4-ml/h once daily because of severe pain in his left toe. The patient developed irritability and delirium about 6 hours after the 3rd IV pumping. The next day, the pain was relieved and dexmedetomidine was stopped. After drug withdrawal, the patient occasionally had delirium. Due to difficulty in falling asleep, the same dose of dexmedetomidine was given again on the 3rd day of drug withdrawal. The same dose of dexmedetomidine was given twice the next day and obvious delirium and irritability occurred 2-3 hours after drug administration of each time. Delirium was suspected to be related to dexmedetomidine. Dexmedetomidine was stopped again and replaced by tramadol and midazolam. On the 6th day of drug withdrawal, the patient′s consciousness turned clear, and no delirium recured.

Drug conditional approval refers to the accelerated approval and marketing of clinically urgently needed drugs with outstanding therapeutic value through the form of "approval first, verification later" before completing complete clinical trials. Since the 1990s, the United States, Canada, the European Union, Japan, Australia, and the United Kingdom have successively implemented drug conditional approval for marketing. In 2017, the application for conditional approval of drugs was implemented in China. In this paper, the pre-market conditions and requirements, post-market monitoring and supervision of drugs in China are compared with other countries/regions. Based on the comparison results, the possible optimization directions of China′s drug conditional approval system are summarized and explored.

Objective: To introduce renal failure by Mutong and the way of its prevention and treatment. Methods: 17 cases of the renal failure by Mutong in our hospital were collected to analyze the clinical characteristics and causes of the adverse reactions. Results: Mutong and the compound Mutong preparations probably caused renal failure after long-term administration and overdosage. Conclusion: Great care could be required of appropriate dosage, treatment course and correct indications in order to assure the efficacy and safe use of the drug.

The "Top 10 drug tips for the public in 2023" issued by the Chinese Pharmaceutical Association emphasizes the importance of drinking water correctly to the safety and efficacy of drugs. Each drug has an optimal amount of drinking water, and only the appropriate amount can ensure the efficacy and avoid adverse reactions. According to UpToDate clinical consultant, Micromedex, MCDEX evidence-based databases and the drug labels of the US FDA and the European Medicines Agency, a total of 164 drugs in 20 categories, including drugs for metabolism and endocrine system, anti-infective drugs, anti-tumor drugs, etc., were labeled with the recommendation of adequate water intake. Here we summarize the above-mentioned drugs and their recommended water intake. The common reasons to drink enough water include preventing esophageal and gastric injury, preventing kidney injury, preventing dehydration, water and electrolyte disorders, preventing constipation, reducing bladder toxicity, reducing radiation damage, and promoting stone discharge. In addition, different people have different requirements for the amount of water when taking medicine. Mastering the correct amount of water is conducive to controlling the disease and reducing the adverse drug events.

Objective To explore the effect of evolocumab on the risk of early intracranial hemor- rhage in patients with acute anterior circulation ischemic cerebral infarction.　Methods The medical records of patients with acute anterior circulation ischemic cerebral infarction who were admitted to Tianjin Huanhu Hospital within 48-hours of onset from January 2019 to September 2020 were collected and analyzed retrospectively. On the day of admission, all patients were given statin lipid-lowering therapy and the patients with fasting low density lipoprotein cholesterol (LDL-c) >3.37-mmol/L received combination therapy with statin and evolocumab. The patients who used statins alone were enrolled in the statins group and those with combined application of evolocumab were enrolled in the combination group. The situation of blood lipid level up to standard (LDL-c <1.70-mmol/L) and the occurrence of intracranial hemorrhage in the second week after admission were compared between the 2 groups. The patients were divided into bleeding group and non-bleeding group according to the occurrence of intracranial hemorrhage. The basic information, combined diseases, etiological classification of cerebral infarction, lipid-lowering program, National Institute of Health Stroke Scale (NIHSS) score on admission, blood pressure, blood lipid level, and blood lipid level in the second week of lipid-lowering treatment between the 2 groups were compared. The factors with P<0.05 were enrolled in the multivariate logistic regression analysis, odds ratio (OR) and its 95% confidence interval (CI) were calculated, and the risk factors of intracranial hemorrhage were analyzed.　Results A total of 437 patients were enrolled in the analysis, including 358 (81.9%) in the statins group and 79 (18.1%) in the combination group. The differences in basic information, combined diseases, etiological classification of cerebral infarction, lipid-lowering program, NIHSS score on admission, blood pressure, and other clinical features between the 2 groups were not statistically significant (all P>0.05). The baseline levels of total cholesterol (TC), triglyceride (TG), LDL-c, and high-density lipoprotein cholesterol (HDL-c) in the statins group were lower than those in the combination group (TC: P<0.001, TG: P<0.001, LDL-c: P=0.004, HDL-c: P=0.024). At the 2nd week of lipid-lowering treatment, the levels of LDL-c and TC in the statins group and the combination group were lower than those before treatment, but the differences of LDL-c and TC levels before and after treatment in the statins group were significantly lower than those in the combination group ［LDL-c: (0.66±0.91) mmol/L vs. (2.58±0.38) mmol/L, P<0.001; TC: (0.37±0.18) mmol/L vs. (1.94±0.44) mmol/L, P<0.001］. The rate of lipid level up to standard in the combination group was significantly higher than that in the statins group ［87.3% (69/79) vs. 9.7% (37/358), P<0.001］. The incidences of intracranial hemorrhage were 12.0% (43/358) in the statins group and 13.9% (11/79) in the combination group within 2 weeks after admission respectively. Multivariate logistic regression analysis showed that complication with atrial fibrillation (OR=3.054, 95%CI: 1.402-6.651, P=0.005), higher NIHSS score on admission (OR=3.431, 95%CI: 1.554-7.573, P=0.001), and etiological classificantion as cardiac embolism (OR=1.544, 95%CI: 1.047- 2.278, P=0.028) were independent risk factors for early intracranial hemorrhage. Conclusions The combination of statins and elouzumab has better lipid-lowering effect in patients with acute anterior circulation cerebral infarction. No correlation is found between evolocumab and early intracranial hemorrhage.

An 89-year-old female patient received escitalopram 10-mg once daily for depression. Three months later, the patient was admitted to hospital for sudden dizziness and a fall. Escitalopram was continued after the admission. On the 6th day of admission, the patient developed syncope again, transient ventricular tachycardia was found by electrocardiogram (ECG) monitoring, and the ECG showed the rate-corrected QT interval (QTc) 612-ms. Escitalopram was discontinued. However, the next day the patient developed ventricular tachycardia again, and the ECG showed Torsades de Pointes and QTc 727-ms. The serum potassium level was 2.84-mmol/L and the patient was given intravenous and oral potassium supplementation. On the 9th day of admission, the patient′s serum potassium level and ECG returned to normal, and the QTc was 487-ms. Escitalopram (with the same dose as before) was given again. The next 5 days, her QTc gradually extended to 506-ms, but serum potassium was normal. Escitalopram was discontinued again and the QTc shortened to 495-ms 2 days later. After 27 days of drug withdrawal, the ECG showed the QTc was 467-ms.

In 2020, a total of 15-849 cases of medication error (ME) from 255-hospitals in 24 provincial administrative regions were collected in the National Monitoring Network for Clinical Safe Medication. The number of hospitals reporting ME increased by 8.97% compared with that in 2019 (234-hospitals), and the number of reported ME cases increased by 5.27% compared with that in 2018 (15-056 cases). In 15-849 cases of ME reports, 54 (0.34%) were classified as grade A, 12-297 (77.59%) as grade B, 3-010 (18.99%) as grade C, 358 (2.26%) as grade D, 72 (0.45%) as grade E, 52 (0.33%) as grade F, 0 as grade G, 5 (0.03%) as grade H, and 1 (0.01%) as grade I. Among the 15-795 patients with ME of grade B to I, 9-347 (59.18%) were male and 6-448 (40.82%) were female, aged from 1 day to 101 years; 1-714 (10.85%) were children (<18 years old), 8-355 (52.90%) were middle aged patients (≥18 to <60 years old), and 5-726 (36.25%) were elderly patients (≥60 years old). Among the 130 patients with serious ME (grade E-I) that caused injury, 77 (59.23%) were male and 53 (40.77%) were female, aged from 4 months and 14 days to 94 years; 16(12.31%) were children, 46（35.38%） were middle aged patients, 68(52.31%) were elderly patients. Among the 9 patients with serious ME caused by mistaken use of drugs, 7 were children, accounting for 43.75% (7/16) of all children with serious ME. The 54 grade A MEs did not involve person who triggered the MEs and place where MEs occurred. Among the 15-795 grade B-I MEs, 10-748 (68.05%) were triggered by physicians, 3-797 (24.04%) by pharmacists, 578 (3.66%) by nurses, 329 (2.08%) by patients and their family members, and 343 (2.17%) by other persons; the proportion of MEs triggered by patients and their family members increased year by year for 3 consecutive years (1.06% and 2.04% in 2018 and 2019, respectively), and 49.23% (64/130) of severe ME were triggered by patients and their family members; 6-830 (43.24%) occurred in clinics, 3-808 (24.11%) in hospital wards, 3-776 (23.91%) in pharmacies, 985 (6.24%) in pharmacy intravenous admixture services, 220 (1.39%) in the nurse stations, 161 (1.02%) in patients′ houses, 2 (0.01%) in the community health service stations, and 13 (0.08%) in other places; the proportion of MEs occurred in clinics and patients′ houses increased year by year for 3 consecutive years (37.32% and 0.41% in 2018, 37.74% and 0.89% in 2019, respectively). The top 3 contents of MEs were wrong drug class, wrong usage, and wrong quantity. The top 3 persons who discovered the MEs were pharmacists, physicians, and nurses. The top 3 factors causing MEs were lack of related pharmacologic knowledge, tiredness, and insufficient training of medical workers.

他汀类药物(Statins),即3-羟-3甲-戊二酰-辅酶A(HMG-CoA)还原酶抑制剂(HMG-CoA reduc—tase inhibitors),是一种新型降血脂药物,通过竞争性抑制HMG-CoA还原酶,阻断甲羟戊酸代谢的中间产物及最终产物——胆固醇的合成,降低血浆总胆固醇和LDL胆固醇,并影响机体的免疫及炎症反应、血管内皮功能、血栓形成等病理生理过程。他汀类药物有降脂和非降脂两种效应,对于延缓动脉粥样硬化进展及恶化、减少急性冠脉事件和心血管病死率,发挥着重要的作用。此类药物大多在肠道吸收,肝脏代谢,少数可直接经肾脏排泄。临床试验表明,他汀类药物安全、有效,毒副作用少。随着他汀类药物在心血管病一、二级预防中的广泛应用,有必要系统地了解本类药物的临床药理作用和常见毒副作用,为此本文特作介绍。

A 54-year-old female patient was scheduled to undergo laparoscopic segmental resection for hepatic hemangioma. Thirty minutes before operation, an IV infusion of etimicin sulfate and sodium chloride injection 100-mg was given to prevent infection. After 2-minutes of medication, the patient developed general numbness, apathy, redness of the skin, cold sweating, and dyspnea. Her breath rate was 22 times per minute, heart rate was 110 beats per minute, blood pressure was 45/32-mmHg, and pulse oxygen saturation (SPO2) was undetectable. Anaphylactic shock due to etimicin was considered. Etimicin was discontinued immediately and treatments such as oxygen inhalation, epinephrine, methylprednisolone sodium succinate, norepinephrine, and intravenous volume expansion were administered. Twenty minutes later, the patient′s symptoms were basically relieved, with breath rate 18 times per minute, heart rate 88 times per minute, blood pressure 108/60-mmHg, and SPO2-0.99. Thirteen hours later, all symptoms disappeared.

Dexamethasidine (DEX) is an alpha-2 adrenoreceptor (α2-AR) agonist, which is not only used in the perioperative period, but also in outpatient examination or treatment. The characteristics and advantages of sedation and hypnosis with DEX are that patients can enter a state similar to natural sleep, which is not only beneficial to improve the sedation effect, but also easy to wake up, and there is little jaw relaxation and no obvious respiratory inhibition. The additional advantages of DEX lie in its function of anti-stress response and potential organ protection and its little influence on cognitive function. The main adverse reactions of DEX were temporary hypertension, hypotension, bradycardia, and so on. Another characteristic of DEX is the relatively slow disappearance of drug effect. Patients may have drowsiness and postural hypotension after operation. It must be noted that DEX cannot be used as an independent anesthetic in general anesthesia to act as the main analgesic and sedative, but only to play an auxiliary role, which depends on the reasonable use and dosage and is not "all" or "none". And the vital signs of patients must be closely monitored during the process of DEX application.

Objective To explore the clinical features of tacrolimus-associated posterior rever- sible encephalopathy syndrome (PRES) in patients after kidney transplantation.　Methods Relevant databases at home and abroad were searched as of August 2020, and case reports of tacrolimus-associated PRES after kidney transplantation were collected. Clinical information including patient′s basic characteristics, tacrolimus application (such as route of administration, dose, blood concentration, drug combination regimen, etc.), and the occurrence time, clinical manifestation, imaging characteristics, intervention measures, and outcomes of PRES were extracted and analyzed by descriptive statistical method.　Results A total of 16 patients were enrolled in the study, including 7 males and 9 females, aged from 7 to 54 years with a median age of 26 years. Of them, 6 patients were <18 years old and 10 patients were ≥18 years old. Among the 16 patients, 8 received intravenous administration and 8 oral administration. Thirteen patients had records of drug combination regimen and 1, 2, and 3 immunosuppressants were combined in 3, 8, and 2 patients, respectively. PRES occurred from 3 days to 3 months after renal transplantation and 10 patients (62.5%) occurred within 1 month after operation. Eleven of 13 patients who underwent tacrolimus plasma concentrations testing did not exceed the upper limit of the treatment window when PRES occurred. The main symptoms of PRES included convulsions/seizures-like seizures (in 11 patients), visual abnormalities (in 7 patients), persistent headache (in 6 patients), and coma or disturbance of consciousness (in 6 patients). CT and/or magnetic resonance imaging were performed in all 16 patients. Imaging features of cerebral edema or vasogenic cerebral edema were found in 15 patients and the lesions located mainly in occipital lobe (13 patients), parietal lobe (12 patients), and the frontal lobe (8 patients). After discontinuation or reduction of the tacrolimus dose and/or giving symptomatic and supportive treatments for 2-44 days (the median time of 9 days), symptoms subsided in all 16 patients and imaging examination showed cerebral edema, vasogenic cerebral edema, and other lesions subsided in 15 patients.　Conclusions Tacrolimus-associated PRES mostly occurred within 3 months after renal transplantation, which was not related to the route of administration or blood concentration of tacrolimus. The clinical manifestations of tacrolimus-associated PRES were similar to those caused by other factors. After discontinuation of tacrolimus, reduction of drug dose and/or administration of symptomatic treatment, most of the symptoms disappeared quickly and the imaging changes returned to normal.

Objective To explore the occurrence and clinical characteristics of thyroid dysfunction caused by camrelizumab.　Methods The subjects were selected from all malignant tumor patients who were treated with camrelizumab during hospitalization in Heping Hospital Affiliated to Changzhi Medical College from June 2020 to September 2021. The electronic medical records of patients who met the inclusion criteria were collected, and the general conditions, camrelizumab application, combined medication, and the thyroid function test results before and after the application of camrelizumab were collected. The causality between drugs and injuries in patients who developed thyroid dysfunction was assessed using Naranjo′s causality assessment scale. The clinical characteristics of thyroid dysfunction were analyzed based on the medical records that had evaluation results of "certainly" or "probably".　Results A total of 71 patients were included in the analysis, and 22 patients (31.0%) developed camrelizumab-related thyroid dysfunction (causality assessment results were all "probably"). When thyroid dysfunction was found for the first time, hypothyroidism and hyperthyroidism were diagnosed in 11 patients, respectively, and 3 patients with hyperthyroidism developed into hypothyroidism later. The incidences of hypothyroidism and hyperthyroidism were 19.7% and 11.3% respectively. Among the 22 patients, 15 were male and 7 were female, aged 47-78 years; 10 patients were with lung cancer, 4 with gastric cancer, 3 with esophageal cancer, 2 with liver cancer, 2 with breast cancer, and 1 with peritoneal omental mesothelioma; 3 patients were treated with camrelizumab monotherapy, and 19 were treated with camrelizumab combined with chemotherapy and/or targeted drug therapy. Thyroid dysfunction all occurred in the first to sixth cycles of camrelizumab treatment, of which 15 (68.2%) in the first to third cycles. Of the 11 patients with initial diagnose of hypothyroidism, 6 had no obvious symptoms, 5 had fatigue (1 was complicated with apathy), and 4 were subclinical hypothyroidism; the severity was grade 1 in 4 cases and grade 2 in 7 cases. None of the 11 patients with initial diagnose of hyperthyroidism had significant symptoms, and 5 of them had subclinical hyperthyroid. All of the 11 cases were grade 1 in severity, 3 developed into hypothyroidism after 3, 6, and 7 cycles of camrelizumab treatment, which was grade 2 in severity. None of the 22 patients discontinued camrelizumab. No intervention was given to the patients with grade 1 hypothyroidism and hyperthyroidism, of which 3 patients with hyperthyroidism returned to normal on their own and the remaining showed no obvious changes in their thyroid function. Ten patients with grade 2 hypothyroidism received thyroid hormone replacement therapy; thyroid function was normal in 2 patients, improved in 5 patients, and without obvious changes in 3 patients.　Conclusions Thyroid dysfunction is a very common adverse reaction of camrelizumab, which can present as both hypothyroidism and hyperthyroidism, and initial hyperthyroidism can evolve to hypothyroidism. Thyroid dysfunction was mostly grade 1-2 in severity and the drug does not need to be discontinued generally. Patients with grade 2 hypothyroidism should be given thyroid hormone replacement therapy.

In 2023, a total of 27 742 cases of medication error (ME) from 439 hospitals in 27 pro‑vincial administrative regions were collected in the National Monitoring Network for Clinical Safe Medica‑tion. Among them, 282 (1.02%) were classified as grade A, 22 452 (80.93%) as grade B, 4 239 (15.28%) asgrade C, 499 (1.80%) as grade D, 141 (0.51%) as grade E, 127 (0.46%) as grade F, 1 (<0.01%) as grade G,and 1 (<0.01%) as grade I; no MEs of grade H occurred. Among the 27 460 patients involved in MEs ofgrade B to I, 15 131 (55.10%) were male and 12 329 (44.23%) were female; their ages were from 1 day to103 years; 3 198 (11.65%) were children (<18 years old), 12 576 (45.80%) were young and middle‑agedadults (≥18 to <60 years old), and 11 686 (42.56%) were elderly (≥60 years old). The top 3 contents of MEwere wrong drug class (5 880 cases, 20.97%), wrong dosage (4 668 cases, 16.65%), and wrong administration·390·药物不良反应杂志 2024 年7月第 26 卷第7期 ADRJ，July 2024, Vol. 26, No. 7frequency (3 184 cases, 11.35%). A total of 270 patients were involved in severe MEs (grade E‑I), including140 (51.85%) males and 130 (48.15%) females, aged from 52 days to 94 years, of which 31 (11.48%) werechildren, 91 (33.70%) were young and middle‑aged adults, and 148 (54.82%) were elderly. The top 3 drugsinvolved were cefoperazone sodium and sulbactam sodium, metformin, and estazolam. One fatal ME wascaused by mistakenly orally taking Fufang Jingjie for fumigation and washing. Among the 27 460 gradeB‑I MEs, 19 655 (71.58%) were triggered by physicians, 5 688 (20.71%) by pharmacists, and few by nurses,patients and their family members, etc. These MEs mainly occurred in clinics (10 537 cases, 38.37%), inhospital wards (8 187 cases, 29.81%), and in pharmacies (6 470 cases, 23.56%). But among the 270 severeMEs, 121 (44.81%) occurred in the patient′s home. The top 3 persons who discovered the ME were phar‑macists (20 693 cases, 74.46%), patients and their family members (3 240 cases, 11.66%), and physicians(2 214 cases, 7.97%). The top 3 factors causing ME were lack of related pharmacologic knowledge (9 382cases, 28.3%), tiredness (5 974 cases, 18.05%), and insufficient training of medical workers (3 831 cases,11.58%). In view of MEs with high incidence or more severe in 2023, relevant risks should be paid attentionto, including misusing external drugs for internal use, ingestion of drug packaging by mistake, wrong doseconversion in children, ME in special dosing frequency, too fast infusion speed of enteral nutrition prepara‑tions and irritant intravenous preparations, interaction between montmorillonite powder and other drugs,hypernatremia caused by fosfomycin sodium, etc. In addition, strengthening the management of drug varietieswith frequent severe MEs and fatal MEs, as well as the popular science and safe drug use education forpatients, can help ensure the medication safety of patients.

A 31-year-old pregnant woman was treated with progesterone soft capsule 0.2 g vaginally twice daily and nadroparin calcium injection 4 100 U subcutaneously once daily due to threatened abortion at 23+1 weeks of menopause. On the 16th day of treatments, laboratory tests showed alanine aminotransferase (ALT) 766-U/L, aspartate aminotransferase (AST) 411-U/L, γ-glutamyl transferase (γ-GT) 98-U/L, alkaline phosphatase (ALP) 180-U/L, and total bile acid (TBA) 40.1-μmol/L. Liver injury caused by nadroparin calcium was considered. The drug was stopped and liver protective treatments were given. On the 21st day of nadroparin calcium withdrawal, the patient had inevitable abortion and delivered a dead baby through vagina. Laboratory tests showed ALT 83 U/l, AST 103 U/l, γ-GT 37-U/L, ALP 157-U/L, and TBA 42.0-μmol/L. Liver protective treatments were continued After 35 days of nadroparin calcium withdrawal, laboratory tests showed ALT 18-U/L, AST 15-U/L, γ-GT 33-U/L, ALP 156-U/L, and TBA 6.2-μmol/L.

通过检索Medline和中国医院数字图书馆数据库,对体内药物相互作用的发生率、发生机制、临床干预方法等内容进行综述,以期引起医务工作者的充分认识,减少药源性损害,提高临床治疗水平。

Objective: To investigate the clinical characteristics of antibacterials-induced neuropsychiatric symptoms in patients with chronic renal failure. Methods: Patients with chronic renal failure treated with antibacterials, during January 1999 and December 2001,were retrospectively analysed. Results: 12 patients with chronic renal failure developed antibacterials- induced neuropsychiatric symptoms, 6 males and 6 femals, with a mean age of 64.3±9.7 years. After receiving intravenous injection daily for 1-6 days, patients presented with progressive neuropsychiatric symptoms, including extra-pyramidal system symptoms, disorientation, depressed consciousness, even coma, or apathy, agitation, hallucination, and personality changes. The very common drug involved was cephalosporins, the others were penicillins, carbopenems, quinolones and isoniazid. After withdrawal of evil agents, the neuropsychiatric symptoms disappeared within a few days. Conclusion: Antibacterial agents can cause neuropsychiatric symptoms in patients with chronic renal failure. Physicians should be aware of these potentially dangerous neurotoxicity during performing anti-infection therapy and withdrawal of the drugs whenever the adverse effects occur.

Based on the potentially inappropriate medication (PIM) criteria in older adults of the United States, Canada, Japan, France, Norway, Germany, South Korea, Austria, Thailand and Chinese Taiwan, and combined with the severe adverse drug reaction (ADR) data in the elderly of China National Center for ADR Monitoring, ADR monitoring center in the Chinese People′ s Liberation Army，Beijing Center for ADR Monitoring and drug data of people over 60 years from Beijing 22 hospitals, 3 rounds of Delphi expert consultation were made to accomplish the final criteria. The criteria was divided into high risk and low risk medications according to the experts evaluation and divided into A and B alert categories according to DDDs. Finally, criteria of potentially inappropriate medications for older adults in China was formed, including medication risk and medication risk under morbid state. A sum of 13 categories 72 medications or medication classes were selected in medication risk part, for example, neurologic medication，psychotropic medication，antipyretic, analgesic and anti-inflammatory medication and cardiovascular medication. The 72 medications were divided into 28 kinds of high risk and 44 kinds of low risk medications. The 72 medications were also divided into 24 kinds of preferred alert medications(A) and 48 kinds of routinely alert medications(B)．PIM in the elderly under morbid state contained 44 medications or medication classes under 27 kinds of morbid states, in which 35 medications under 25 morbid states of preferred alert medications (A) and 9 medications under 9 morbid states of routinely alert medications (B).

Anticancer drugs are important causes of kidney injury in cancer patients. Once kidney injury occurs, it will affect anticancer therapy and patient prognosis. Thus, the Japanese Society of Nephro- logy, Japan Society of Clinical Oncology, Japanese Society of Medical Oncology, and Japanese Society of Nephrology and Pharmacotherapy have jointly formulated the Clinical Practice Guidelines for Management of Kidney Injury During Anticancer Drug Therapy 2022 and made a particular discussion on the prevention and management of anticancer drug-induced kidney injury. This article focuses on interpreting the management of kidney injury related to cytotoxic anticancer drugs, targeted therapies, and immune checkpoint inhibi-tors to more effectively guide clinical practice.

A 69-year-old male patient was treated with nivolumab combined with tegafur-gimeraci- loteracil potassium due to gastric adenocarcinoma with liver, pancreas, and abdominal lymph node metastasis after completing 4 cycles of chemotherapy with oxaliplatin and raltitrexed. Ten days later, the patient developed severe rashes all over the body, which was considered to be adverse skin reactions caused by nivolumab and tegafur-gimeracil-oteracil potassium. Then the 2 drugs were stopped and treatments with methylprednisolone and antiallergic drugs were given. The rashes were gradually improved, the dose of glucocorticoid was reduced gradually, and it was stopped at last. However, on the day of glucocorticoid withdrawal, the patient developed fever, chills, and severe respiratory failure. In combination with clinical treatment, laboratory test results, and imaging changes in the patient, it was considered to be immune-related pneumonitis caused by nivolumab. Methylprednisolone, anti-infection, and high-flow nasal cannula oxygen therapy were given. Four days later, the asthma symptoms in the patient were obviously improved, and 28 days later, the pulmonary CT showed the pneumonitis was markedly improved than before.

A 26-year-old male patient with type 2 diabetes mellitus was given liraglutide (0.6-mg/d) on the basis of insulin combined with metformin because of the poor therapeutic effect. Four days later, the dose of liraglutide was doubled and empagliflozin (10-mg orally, once daily) was added. The next day, the patient developed nausea, vomiting, and abdominal pain accompanied by elevated serum amylase and lipase (peak levels were 1-048-U/L and 26-U/L, respectively). Acute pancreatitis was diagnosed, all hypoglycemic drugs were discontinued, and fasting, gastrointestinal decompression, intravenous fluid infusion, continuous infusion of low-dose insulin, and symptomatic treatments with lansoprazole and somatostatin were given. Three days later, the patient′s symptoms were relieved, and serum amylase and lipase levels returned to normal. Ten days later, the hypoglycemic drug was changed to subcutaneous injection of insulin aspart 30 injection (24 U in the morning and 16 U in the evening) before meals and oral metformin 0.5 g thrice daily. His blood glucose was controlled and no symptoms of pancreatitis recurred. Therefore, it was considered that the patients′ pancreatitis might be related to the combined use of liraglutide and empagliflozin.

A 49-year-old male patient received transcutaneous transcatheter arterial chemoembolization and an IV infusion of camrelizumab 200-mg (on day 1 and 14 days was a cycle) due to liver cancer with intrahepatic metastasis, liver cirrhosis, splenomegaly, and ascites. On day 12 after the third IV infusion of camrelizumab, the patient developed fever, cough, and chest tightness. On day 34 after the third IV infusion of camrelizumab,chest CT showed ground glass exudation shadow in bilateral lungs. Immune-related pneumonitis and infection caused by camrelizumab was considered. High-dose methylprednisolone was given to inhibit immune reaction and cefoperazone sodium and sulbactam sodium was given to resist infection, supplemented with symptomatic and supportive treatments such as oxygen inhalation and expectorant. Eighteen days later, the patient′s body temperature returned to normal, chest tightness disappeared, but he coughed occasionally. Chest CT showed that the ground glass exudation shadow of bilateral lungs was narrowed on the scope.

A 23-year-old healthy male received subcutaneous injection of recombinant human granulocyte colony-stimulating factor injection (rhG-GSF) 600-μg once daily for 6 days before allogeneic hematopoietic stem cell transplantation as a donor. Before medication, there were no abnormalities in the patient′s coagulation markers, blood routine and biochemical tests, as well as electrocardiographic examination. Seven days after discontinuation of the drug, the patient developed sudden chest pain, sweating, and vomiting. Laboratory tests showed high sensitivity cardiac troponin T 3 144-ng/L, creatine kinase MB>300 μ G/L, myoglobin 505.6-μg/L, N-terminal pro-brain natriuretic peptido 1-138-ng/L, white blood cell count 17.7×109/L, platelet count 160×109/L. The electrocardiogram showed ST segment elevation myocardial infarction. A dual antiplatelet therapy of aspirin and ticagrelor was administered in conjunction with percutaneous transluminal coronary angioplasty. After surgery, anticoagulation, antiplatelet, and lipid-lowering treatments were given. On the 3rd day after surgery, the patient developed toe pain, fever, and a platelet count of 382×109/L, symptoms were gradually relieved after symptomatic treatment, but platelet count increased to 566×109/L. After consultation with hematologists and rheumatologists, combined with relevant laboratory test indicators, autoimmune and hematological system-related diseases were excluded. It was considered that coronary artery thrombosis and thrombocytosis may be related to the use of rhG-CSF, and platelet count gradually decreased to 275×109/L without special treatment. During the follow-up of 7 months, his platelet count was 235×109/L .

A 59-year-old male patient received SOX chemotherapy regimen (IV infusion of oxaliplatin injection 200-mg dissolved in 5% glucose injection 250-ml for 2 hours on the first day, oral tegafur, gimeracil and oteracil potassium 60-mg once daily on day 1-14, every 3 weeks was a cycle) for gastric cancer with multiple lymph nodes metastases. One week after the infusion of oxaliplatin during the third cycle, the patient suddenly developed deafness and blurred vision. The patient was diagnosed with sudden sensorineural deafness and acute optic neuritis after otorhinolaryngologist consultation. His sudden sensorineural deafness and acute optic neuritis were considered to be associated with oxaliplatin. Chemotherapy was discontinued and the patient was given neurotrophic and microcirculation-improving medications. One 1 week later, the patient′s vision gradually returned to normal, but the deafness persisted.

A 73-year-old female patient received monotherapy with pembrolizumab (IV infusion of 200-mg once every 3 weeks) for lung cancer with bone metastases. On day 12 after the 6th treatment with pembrolizumab, the patient developed severe nausea and vomiting. Laboratory tests showed random blood glucose 53.6-mmol/L and serum potassium 6.8-mmol/L. Blood gas analysis showed pH 7.3, partial pressure of carbon dioxide 19.5-mmHg, partial pressure of oxygen 15.6-mmHg, base excess -8.9-mmol/L, bicarbonate 9.5-mmol/L, lactic acid 2.5-mmol/L, and anionic gap 23.5-mmol/L. Blood ketone body test was positive. The patient had no previous history of diabetes mellitus， fulminant type 1 diabetes mellitus and ketoacidosis due to pembrolizumab were considered. Pembrolizumab were stopped and rehydration, hypoglycemia, acidosis correction, and other symptomatic treatments were given. Seven days later, her symptoms were improved partly. Laboratory tests showed fasting blood glucose 12.9-mmol/L and serum potassium 4.5-mmol/L. Blood gas analysis showed pH 7.5, bicarbonate 28.3-mmol/L, and base excess +5.7-mmol/L. Blood ketone body test was negative.

Objective To mine the risk signals of ipilimumab-related adverse events (AEs) and provide reference for the safe use in clinical practice.　Methods AE reports with ipilimumab as the primary suspect drug were collected from US FDA Adverse Event Reporting System database during March 1, 2011 to September 30, 2022. AEs were standardized and classified according to the preferred term (PT) and system organ class (SOC) in Medical Dictionary for Regulatory Activites version 26.0. The AE risk signals of ipilimumab were mined using reporting odds ratio (ROR) method. An AE with reports≥3, ROR≥2, 95% confidence interval (CI) lower limit of ROR>1 was defined as a risk signal. Risk signals were analyzed using descriptive method.　Results A total of 12-329 AE reports were entered in the analysis, involving 1-915 PTs. Two hundred and sixty-eight risk signals (PTs) were obtained using ROR method, involving 21 SOCs. The top 10 PTs in report number were diarrhea, colitis, rash, fever, hypophysitis, adrenal insufficiency, decreased appetite, hypothyroidism, liver disease, and dehydration， all of which were common AEs in the labels. The top 10 PTs in signal intensity were hypophysitis, lymphocytic hypophysitis, immune-mediated dermatitis, immune-mediated adrenal insufficiency, hypopituitarism, immune-mediated liver disease, adrenocorticotropic hormone deficiency, immune-mediated encephalitis, autoimmune colitis, and immune-mediated hyperthyroidism. The SOCs involved were endocrine system diseases, skin and subcutaneous tissue diseases, hepatobiliary system diseases, gastrointestinal system diseases, and nervous system diseases. A total of 36 PTs were not included in the labels, and the top 5 in signal intensity were intracranial tumor hemorrhage, radiation necrosis, malignant pleural effusion, pulmonary granuloma, and lichenoid keratosis.　Conclusions The main AEs of ipilimumab are diarrhea, colitis, rash, etc. In addition, ipilimumab might cause adverse reactions such as intracranial tumor hemorrhage, radiation necrosis, and malignant pleural effusion that are not recorded in label, which should be vigilant in clinical practice.

Objective To explore the causes of medical disputes related to drug-induced liver injury (DILI).　Methods The Excel data sheet of drug-related medical disputes provided by the Beijing Municipal People′s Mediation Committee for Medical Disputes were searched and data on solved cases of DILI-related medical disputes from 2013 to 2019 were collected. The distribution characteristics, related drugs, and causes of disputes in these cases were analyzed retrospectively.　Results A total of 30 cases of DILI-related medical disputes were entered. Among the 30 patients, 23 (76.7%) were female and 7 (23.3%) were male, the age ranged from 3 months to 66 years, and the median age was 37 years; 25 (83.3%) were outpatients and 5 (16.7%) were inpatients. The drugs causing liver injury were traditional Chinese medicine (decoction and/or Chinese patent drugs) in 20 patients (66.7%), western medicine in 6 patients (20.0%), traditional Chinese medicine combined with western medicine in 4 patients (13.3%). Among the hospitals involved, tertiary hospitals accounted for 80.0% (24/30) and specialized hospitals of traditional Chinese medicine accounted for 60.0% (18/30). Of the 30 cases, 19 (63.3%) were judged to be the responsibility of the hospitals and the causes of liver injury were medication defects/errors, in which 17 cases (89.5%) were the responsibility of doctors and 2 cases (10.5%) were of nurses. The main problems were lack of inquiry before medication, lack of monitoring during treatment, illegal prescription, and overdosage due to negligence.　Conclusion DILI-related medical disputes often occur in outpatient department, most of the drugs involved were traditional Chinese medicine, which may be related to the lack of understanding of hepatotoxi- city of traditional Chinese medicine in physicians (especially physicians in specialized hospitals of traditional Chinese medicine) and the neglect of management for Chinese medicine prescriptions.

A 60-year-old woman with connective tissue disease received  cyclosporine 300 mg once daily . On day 2 of adding cyclosporine, the patient  developed pharyngalgia. On day 3, she developed hematochezia, abdominal distension and abdominal pain. On day 14, she lost her vision of both eyes,  developed attacks of binoculus transient upper left gaze twice, a slight headache, and the elevated blood pressure (150/90 mmHg). Laboratory tests showed that the cyclosporine blood concentration was 372.4 μg/L. The results of cranial MRI showed bilateral frontal, parietal, occipital and temporal lobes symmetrical multiple patchy long T1, long T2 signals, the fluid attenuated inversion recovery sequence showed high signal, which suggested the vascular edema.  The patient was diagnosed as reversible posterior encephalopathy syndrome due to cyclosporine. Cyclosporine was stopped immediately. She received an IV infusion of methylprednisolone 40 mg once daily and other symptomatic supportive treatments including deprivation of body fluids, anti-epileptic, and blood pressure control, etc. On day 5 of treatment, her vision began to recover, but she had blurred vision and visual hallucinations. On day 7 of treatment, the degree of abdominal distension and abdominal pain was relieved, vision was recovered obviously, visual hallucination disappeared. Her blood pressure returned to normal (125/86 mmHg). The result of laboratory tests showed the cyclosporine blood concentration 139.2 μg/L. The result of MRI reexamination showed that the original focus disappeared.

Hyperprolactinemia is a common adverse effect of antipsychotic drugs. The clinical presentations of hyperprolactinemia are gynecomastia in men, and breast distending pain, galactorrhea, menstrual disturbance, sexual dysfunction, osteoporosis, and metabolic disturbance in women. The incidence of hyperprolactinemia is 25%-89%. The factors related to antipsychotic-induced hyperprolactinemia are gender, age, the type of antipsychotic drugs and dosage. The mechanism of antipsychotic-induced hyperprolactinemia may be related to blockade of dopamine D2 receptors on the anterior pituitary by antipsychotic drugs and reduction of dopamine inhibitory effect on prolactin secretion of prolactin cells, leading to prolactin elevation. Antipsychotic-induced hyperprolactinemia should be distinguished from hyperprolactinemia due to severe stress, depressive state, pregnancy, hypothyroidism, renal failure, pituitary tumor and ovarian disease. The treatment of antipsychotic-induced hyperprolactinemia includes discontinuing antipsychotic drugs, reducing antipsychotic drugs dosage, switching to a prolactin-sparing agent, prescribing a dopamine receptor agonist or Chinese herbal medicines, and using low-frequency repetitive transcranial magnetic stimulation.

本文综述了有关甘草酸类药物引起不良反应的报道,其不良反应主要是对内分泌系统的影响:如水、钠潴留,低钾血症,高血压,假性醛固酮增多症等。过敏反应较少,罕见的不良反应有胆汁性肝硬化、上消化道或牙龈出血、腹泻和精神症状。甘草酸类药物不良反应发生的主要机制与该药的肾上腺皮质激素样作用有关。α异构体甘草酸类药物甘利欣的安全性优于β异构体甘草酸类药物。

A 45-year-old male patient underwent craniotomy and biopsy for intracranial lesions. In order to prevent epilepsy, sodium valproate 800-mg dissolved in 0.9% sodium chloride injection 8-ml was injected intravenously after operation, and then the sodium valproate solution of this concentration was continuously pumped at a speed of 0.6-ml/h. One hour after administration, the serum lactate level of the patient increased gradually, reaching the highest level of 14.7-mmol/L, accompanied by metabolic acidosis and compensatory respiratory alkalosis, and with the lowest pH of 7.09 and the lowest base excess of -26.3. The patient fell into a coma. The hyperlactatemia and metabolic acidosis were considered to be related to sodium valproate. Sodium valproate was stopped, intravenous infusion of 5% sodium bicarbonate injection and blood purification were given at the same time. After 3 days, the lactate level of the patient returned to normal, metabolic acidosis was basically corrected, and his mind was clear.

A 47-year-old female patient received compound polyethylene glycol electrolytes powder (III) 4 bags (73.59 g/bag) dissolved in 4 L warm water in 16 divided doses to prepare for colonoscopy the next day. The patient took medicated warm water 2 L within 2 hours. She had loose stool and watery stool for more than 10 times within 1 hour after medication. The patient did not continue to take drugs because of the severe diarrhea. Fourteen hours after medication, the patient developed apathy, no response to voice stimuli, and involuntary movement of both upper limbs. Sixteen hours after medication, the patient developed unconsciousness and tetanic convulsion of limbs. Laboratory tests showed that serum sodium was 120-mmol/L and plasma osmolality was 258.22 mOsm. She was diagnosed with hyponatremia encephalopathy. Except polyethylene glycol electrolytes powder (III), the patient did not take any other drug. It was considered that hyponatremia encephalopathy was related to polyethylene glycol electrolytes powder (III). Symptomatic treatments such as sodium supplement and dehydration were given immediately. After 1 hour of treatment, the patient′s consciousness recovered; 8 hours later, her serum sodium was 142-mmol/L.

A 16-year-old female patient with acute T-cell leukemia was going to undergo allogeneic hematopoietic stem cell transplantation. Pretreatment chemotherapy was required before operation. In order to reduce the degree of adverse reactions during the chemotherapy, the patient received treatments with ondansetron, dexamethasone, and fosaprepitant dimeglumine. After intravenous injections of ondansetron 4-mg and dexamethasone 5-mg, fosaprepitant dimeglumine 150-mg dissolved in 0.9% sodium chloride injec- tion 150-ml was intravenously pumped at a speed of 300-ml/h. Five minutes later, the patient developed sweating, foreign body sensation in pharynx, dyspnea, periumbilical pain, and vomiting. Anaphylactic reaction caused by fosaprepitant dimeglumine was considered. The drug was stopped immediately and intravenous injection of dexamethasone 5-mg and oxygen inhalation were given. Twenty minutes later, her symptoms of dyspnea and abdominal pain were relieved. Fifty minutes later, the allergic symptoms disappeared.

A 51-year-old male patient received an operation treatment for paranasal sinusitis induced by radiotherapy and chemotherapy of nasopharyngeal carcinoma. One oxycodone and acetaminophen tablet (each tablet contains oxycodone hydrochloride 5-mg and acetaminophen 325-mg) was given orally thrice daily before and after the operation. Pregabalin 75-mg twice daily was added because of the poor analgesic effectiveness. During the treatment, oral oxycodone hydrochloride 10-mg was given once daily by his family members for 2 days. Two days after the addition of pregabalin, the patient developed mental disorders, such as delirium, irritability, involuntary convulsions of limbs, cognitive impairment, and disorientation. All above-mentioned analgesics were discontinued and dexmedetomidine was given for pain relief and sedation. Three days later, the mental state of the patient was improved, there was no obvious delirium, the discrimination and orientation returned to normal, and dexmetomidine was discontinued. There was an obvious time correlation between the occurrence and disappearance of mental disorders and the combination of analgesic drugs. Referring to the previous literature, it was considered that the mental disorders of the patient were caused by the interaction between oxycodone and pregabalin.

本文根据近年文献报告,对5种质子泵抑制剂的作用特点、药代动力学、不良反应及相互作用进行综合比较,为临床安全合理用药提供依据。

Vaccines have made great contributions to the prevention of infectious diseases, but vaccine hesitancy is widespread in the world. The reasons for vaccine hesitancy are complex, but the main reasons are the lack of public awareness of vaccine-preventable diseases and the lack of confidence in vaccine effectiveness and safety. In the context of the continuous spread of the coronavirus disease 2019 (COVID-19) epidemic, boosting public confidence and ensuring the orderly development of the vaccination work of COVID-19 vaccines and conventional vaccines are necessary to curb the resurgence of the COVID-19 epidemic and prevent the outbreak of various infectious diseases in China. Under the current situation, the main measures to deal with vaccine hesitancy are to play the role of health care institutions, improve public health literacy, normalize the public opinion orientation of the media platform, strengthen the supervision of vaccine clinical research and production, and do a good job in surveillance and compensation for adverse events following immunization.

Objective To investigate the risk factors of acute kidney injury (AKI) in patients with severe drug eruption.　Methods Clinical data including basic information (gender, age, body mass index), type of severe drug eruption, allergenic drugs, co-existing diseases, first laboratory findings after admission, renal function during hospitalization, etc. in patients with severe drug eruption admitted to Department of Dermatology, Guangdong Provincial People′s Hospital from January 2014 to December 2020 were collected and analyzed retrospectively. Patients were divided into AKI group and non-AKI group and the clinical data were compared between the 2 groups. The risk factors of AKI in patients with severe drug eruption were analyzed by a binary logistic regression model and the odds ratio (OR) and its 95% confidence interval (CI) were calculated.　Results A total of 91 patients were enrolled in the study, including 50 males and 41 females, aged 54 (40, 65) years with a range of 9-85 years. The drugs that induced severe drug eruptions were allopurinol in 48 patients, antiepileptic drugs in 23 patients, antibacterial drugs in 6 patients, and other drugs in 14 patients. There were 21 patients (AKI incidence: 23.1%) in the AKI group and 70 patients in the non-AKI group. The proportion of patients sensitized to antiepileptic drugs, baseline estimated glomerular filtration rate, levels of serum albumin and hemoglobin in the AKI group were lower than those in the non-AKI group ［0（0/21） vs. 32.9% (23/70), (70±12) ml/(min·1.73 m2) vs. (103±6) ml/(min·1.73 m2), 26(23, 30) g/L vs. 36(34, 38) g/L, (116±17) g/L vs. (129±15) g/L］, the proportions of patients sensitized to allopurinol, with diabetes mellitus, and with chronic kidney diseases, baseline serum urea nitrogen level, serum creatinine level, and proportion of urinary albumin positive patients were all higher than those in the non-AKI group ［81.0%(17/21) vs. 44.3%(31/70), 28.6%(6/21) vs. 7.1%(5/70), 28.6%(6/21) vs. 5.7%(4/70), 7.2（4.6, 12.2） mmol/L vs. 5.0（3.8，6.4）mmol/L, 103（63, 134）μmol/L vs. 67（56, 79）μmol/L, 47.6%(10/21) vs. 17.1%(12/70)］, and the differences were statistically significant (all P<0.05). Binary logistic regression analysis showed that allopurinol sensitization (OR=6.588, 95%CI: 1.006-43.123, P=0.049) was the independent risk factor for AKI in patients with severe drug eruption and serum albumin (OR=0.595, 95%CI: 0.471-0.752, P<0.001) was a protective factor.　Conclusions Allopurinol sensitization was the independent risk factor for AKI in patients with severe drug eruption. Patients with low serum albumin were more likely to develop AKI.

Objective : To analyse ADR induced by Fufang Danshen Zhusheye. Methods: 104 ADRs due to the drug were retrieved from Chinese Pharmaceutical Abstract for statistics by sex, age of patients, the time of its occurrence, and organ - system injury. Results and Conclusion : ADR appeared mostly in groups of 31 - 60 years old and more, involving anaphylaxis and injuries of various systems and organs.

Objective To analyze and evaluate the enhancement of anticoagulant effect of warfarin by herbal and dietary supplements (HDS) based on case report literature.　Methods The case reports on enhancement of anticoagulant effect of warfarin by HDS were selected by searching the relevant databases at home and abroad (up to October 10, 2021). The degree of enhancement of anticoagulant effect of warfarin by HDS was evaluated according to the increase of International Standardized Ratio and the occurrence of bleeding events in patients in the case reports. The reliability scoring standard of HDS-warfarin interaction was established according to the causatity evaluation results between HDS and enhancement of anticoagulant effect of warfarin, the number of case reports, and the other evidences (warnings issued by relevant national institutions, clinical studies, pharmacokinetic/pharmacodynamic studies, experimental animal studies, etc.) and the reliability of enhancement of anticoagulation effects of warfarin by HDS was evaluated. The reliability was evaluated as highly, relatively, possible, and suspicious reliable if the total score was ≥9, 6-8, 3-5, and
≤2 points, respectively.　Results A total of 41 case reports were enrolled in the analysis, involving 56 patients and 26 kinds of HDS. Five kinds of HDS increased the anticoagulant effect of warfarin slightly, including Chinese angelica (Radix Angelicae Sinensis), melilotus extract tablets, pumpkin seed, fish oil, and milk thistle; 6 kinds of HDS increased the anticoagulant effect of warfarin moderately, including ginger (Rhizoma Zingiberis Recens), mango, bee pollen, scarponon grape, Persian walnut, and grifola frondosa; and 15 kinds of HDS increased the anticoagulant effect of warfarin severely, including cranberry, danshen (Salvia miltiorrhiza), glycyrrhiza (Radix Glycyrrhizae), safflower (Flos Carthami), dandelion (Herba Taraxaci), Lyciumbar barum L., grapefruit, matricaria chamomilla, pomegranate juice, astaxanthin, Artemisia absinthiu, royal jelly, bilberry(Vaccinium vitis-idaea), red dates, and St. John′s wort (Hypericum perforatum L.). The reliability of enhancement of anticoagulant effect of warfarin was evaluated as highly reliable in 1 kind of HDS, namely cranberry (11 points), relatively reliable in 8 kinds of HDS, including danshen, glycyrrhiza, safflower, dandelion, Lycium barbarum L., grapefruit, matricaria chamomilla, and pomegranate juice (8, 7, 7, 7, 6, 6, and 6 points, respectively), possibly reliable in 12 kinds of HDS, including Chinese angelica, ginger, melilotus extract tablets, mango, astaxanthin capsules, bee pollen, Artemisia absinthium, royal jelly, scarponon grape, Persian walnut, bilberry, and grifola frondosa (5, 5, 5, 5, 4, 4, 4, 3, 3, 3, 3, and 3 points, respectively), and suspicious reliable in 5 kinds of HDS, including pumpkin seed, red dates, fish oil, milk thistle, and St. John′s wort (2, 2, 2, 0, and -1 points, respectively).　Conclusions The degree and reliability of enhancement of anticoagulant effect of warfarin by cranberry, danshen, glycyrrhiza, safflower, dandelion, Lycium barbarum L, grapefruit, matricaria chamomilla, and pomegranate juice are higher, which should be avoided during warfarin therapy.

Objective To explore the clinical characteristics of immune checkpoint inhibitor- related pneumonitis (CIP) caused by pembrolizumab.　Methods We reported a case of CIP caused by pembro- lizumab admitted in Peking Union Medical College Hospital and searched case reports on CIP caused by pembrolizumab in PubMed, Embase, ScienceDirect, CNKI, VIP, and Wanfang databases (as of October 1, 2019). The main clinical data (gender, age, primary diseases, use of pembrolizumab, combination drugs, time to onset of CIP, symptoms, imaging results, CIP grade, and treatment and outcome) in all reported cases were collected and analyzed.　Results A total of 33 patients were enrolled, including 23 males and 10 females, aged from 44 to 91 years with a median age of 64 years. The primary diseases in 11 cases were melanoma, in 9 cases were lung adenocarcinoma, in 4 cases were lymphoma, in 3 cases were colon cancer, and in 6 patients were esophageal cancer, breast cancer, nasopharyngeal cancer, pulmonary pleomorphic carcinoma, pulmonary large-cell neuroendocrine carcinoma, and lung squamous cell cancer, respectively. Thirty patients received pembrolizumab as monotherapy, 1 patient received combination therapy of pembrolizumab with carboplatin and pemetrexed, and 2 patients received pembrolizumab combined with radiation therapy. Time to onset of CIP in the 33 patients was 1 day at the shortest and 2 years at the longest with a median time of 12(4, 16) weeks. The symptoms of CIP mainly were dyspnea in 19 cases, cough and expectoration in 15 cases, and fever in 9 cases. The common radiological features were ground glass opacities in 17 cases, consolidations in 11 cases, and grid-like high-density shadow in 8 cases. After the diagnosis of CIP, all patients stopped using pembrolizumab. Twenty-nine patients were treated with glucocorticoids, 19 patients received antibacterial therapy, 2 patients received human immunoglobulin, 1 patient received infliximab, and 2 patients did not receive any intervention. Of the 30 patients with known clinical outcomes, 24 patients were improved and 6 died. Among the improved patients, 6 patients underwent rechallenge with pembrolizumab and 1 of them developed CIP again.　Conclusions The clinical symptoms and radiologic features of CIP caused by pembrolizumab are lack of specificity. Constant vigilance for the presences of fever and respiratory symptoms within 12 weeks after pembrolizumab treatment is required. The CIP in most patients can be improved after drug withdrawal and additional use of glucocorticoids, but the potential fatal risk of CIP is still need to be alert to.

A 53-year-old male patient received intramuscular injection of diclofenac sodium and lidocaine injection 2-ml for abdominal pain. After one hour of medication, the patient developed upper abdominal discomfort, chest tightness, shortness of breath, sweating, and slight cyanosis of lips. Oxygen inhalation was given immediately. Electrocardiogram monitoring showed blood pressure 105/60-mmHg, heart rate 125 beats/min, and blood oxygen saturation 0.75. His peripheral blood glucose could not be detected. Glucose supplement and hormone therapy were given immediately. About 30-minutes later, the patient developed unconsciousness, no pulsation of the main artery, and cardiac and respiratory arrest. Cardiopulmonary resuscitation and other treatment measures were given immediately. However, the patient did not return to spontaneous heartbeat and breathing and was declared dead. It was considered that the patient′s severe hypoglycemia might be related to diclofenac sodium and lidocaine.

Objective To investigate the clinical characteristics of pemphigoid caused by immune checkpoint inhibitors (ICIs).　Methods The relevant databases at home and abroad (up to October 15, 2021) were searched and the case reports on pemphigoid caused by ICIs were collected. The relevant information of patients (gender, age, tumor type, drug varieties of ICIs, incubation period of pemphigoid, main symptoms, distribution site of lesions, biopsy and immunological examination, treatment and outcome, etc.) were collected and analyzed descriptively.　Results A total of 82 relevant literature were included, involving 103 patients, 72 males and 31 females, aged 30-90 years, of which 82 (79.6%) were ≥60 years old. The primary diseases were melanoma in 45 cases (43.7%) and lung cancer in 29 cases (28.2%). The 103 patients involved 6 varieties of ICI, including programmed cell death 1 receptors ［pablizumab (47 cases, 45.6%), navulizumab (44 cases, 42.7%), and terepril (4 cases, 3.9%)］， and programmed cell death ligand 1 inhibitors ［atezumab (3 cases, 2.9%), duvalizumab (2 cases, 1.9%)], and CTLA-4 inhibitor ipimamab (3 cases, 2.9%). Eighty-four patients had a record of the time from the beginning of ICI to the occurrence (incubation period) of pemphigoid. The incubation period of pabolizumab was 3-850 days, of navulizumab was 21-790 days, and of terepril was 70-728 days. Among 103 patients, 88 (85.4%) were bullous pemphigoid, 8 (7.8%) were mucous pemphigoid, 4 (3.9%) were non bullous pemphigoid, and 1 (1.0%) was dyshidrosiform pemphigoid; the clinical manifestations were bullous and vesicular lesions in 98 cases (95.1%), rash in 51 cases (49.5%), and pruritus in 48 cases (45.6%). Nine four patients had skin biopsy results, 78 patients (83.0%) had eosinophil infiltration in the lesion site; immunological examination was performed in 92 cases (97.8%), of which 63 cases (68.5%) were IgG and C3 deposits. Thirty-five patients had pemphigoid associated antigen test records, BP180 was detected in 25 patients, and 24 patients (96%) were positive; BP180 and BP 230 were detected simultaneously in 8 cases, both were positive in 6 cases, and BP180 was positive and BP 230 was negative in the other 2 cases; BP-Ag2 was detected in 2 cases, all of them were positive. After treatment with glucocorticoid or immunosuppressant and/or withdrawal of ICIs, 86 (83.5%) of 103 patients were improved, and 6 were not; 8 cases died, of which 7 cases of pemphigoid were improved but died of other causes, and 1 case died of unreported causes; 9 cases did not report the outcome.　Conclusions ICIs can cause pemphigoid, and the incidence in the elderly is higher. The incubation period of pemphigoid varies from 3 days to more than 2 years. After glucocorticoid or immunosuppressant treatment and/or withdrawal of ICIs, most patients had good prognosis.

Objective To mine the risk signals of baloxavir marboxil-related adverse events (AEs) and provide reference for rational use in clinical practice.　Methods The report odds ratio (ROR) and proportional reporting ratio (PRR) methods were used to mine the risk signals of baloxavir marboxil-related AEs in the US Food and Drug Administration Adverse Event Reporting System (FAERS) from the 1st quarter of 2018 to the 4th quarter of 2022. The AE with reports ≥3 and 95% confidence interval (CI) lower limit of ROR or PRR>1 was defined as a risk signal. AEs were classified according to the system organ class (SOC) and preferred term (PT) of Medical Dictionary for Regulatory Activities (MedDRA) 25.1 for statistical analysis.　Results A total of 1-102 AE reports were retrieved, involving 1-102 patients， and 498 were serious AE. A total of 45 AE risk signals were obtained by ROR and PRR methods. The top 10 PTs in signal intensity were febrile seizures, ischemic colitis, bacterial pneumonitis, anaphylaxis, hemorrhagic cystitis, erythema multiforme, melena, anaphylactic shock, disseminated intravascular coagulation, and anaphylactic reaction. Of them, 26 PTs were not recorded in the labels, in which the top 10 PTs were febrile seizures, ischemic colitis, bacterial pneumonia, hemorrhagic cystitis, disseminated intravascular coagulation, altered mental status, fever, rhabdomyolysis, cyanosis, and facial paralysis. The top 5 SOCs that involved more PTs were nervous system disorders, gastrointestinal disorders, respiratory system diseases, psychiatric disorders, and blood and lymphatic system disorders. Among the 498-serious AEs, a total of 5 risk signals were mined, including infectious pneumonia, diarrhea, rhabdomyolysis, allergic reactions, and abnormal behavior.　Conclusion The attention should be paid to AEs not mentioned in the drug label in clinical application of baloxavir marboxil, such as febrile seizures, bacterial pneumonia, ischemic colitis, and hemorrhagic cystitis.

A 77-year-old female patient with pneumonia received an IV infusion of piperacillin sodium and tazobactam sodium 4.5 g dissolved in 0.9% sodium chloride injection 100 ml, 3 times daily. The patient′s WBC, RBC, Hb, and PLT levels were 2.0×109/L， 2.9×1012/L， 88 g/L， and 10×109/L, respectively before using the medicine. On day 4 of drug administration, her WBC, RBC, Hb and PLT were 2.0×109/L, 2.9×1012/L, 88 g/L, and 10×109/L, respectively. The result of  bone marrow smear showed decrease of nucleated cell, granulocyte series,  and  erythrocyte series′ hyperplasia. The proportion and morphology of  cells at different stages were approximately normal. She was diagnosed as acute myelosuppression associated with piperacillin sodium and tazobactam sodium. Piperacillin sodium and tazobactam sodium were stopped. On day 15 of drug withdrawal, her WBC, RBC, Hb and PLT were 4.8×109/L, 3.0×1012/L, 88 g/L, and 218×109/L, respectively.

A 73-year-old male patient with metastatic sarcomatoid carcinoma of lymph node received an IV infusion of tirelizumab 200-mg on day 1, and 3 weeks was 1 cycle. After 10 cycles of treatment, the patient developed dizziness, chest tightness, nausea, and vomiting. Laboratory tasts showed random blood glucose 99.1-mmol/L, serum creatinine (Scr) 260 μ mo/L, blood potassium 5.8-mmo/L, blood sodium 129-mmol/L, and blood osmotic pressure 368 mOsm/(kg·H2O). Blood gas analysis showed pH 7.1 and lactic acid 2.8-mmol/L. Ketoacidosis was considered and treatments such as rehydration, hypoglycemic with insulin, and electrolyte supplement were given. After 5 days of treatments, the patient′s symptoms were improved, and laboratory tests showed blood potassium 4.4-mmol/L, blood sodium 134-mmol/L, carbon dioxide binding capacity 17.0-mmol/L, and fasting C-peptide 0.02-nmol/L. Seven days later, laboratory tests showed fasting C-peptide 0 and 2 h post-prandial C-peptide 0. The patient was diagnosed with fulminant type 1 diabetes mellitus, which was considered to be related to tirelizumab. After 19 days of treatments, laboratory tests showed fasting blood glucose 5.8-mmol/L, blood glucose at 2 hours after meal 19-mmol/L, Scr 102-μmol/L, blood sodium 139-mmol/L, blood chlorine 108-mmol/L, and blood potassium 3.9-mmol/L.

A 16-year-old female patient received ethinylestradiol and cyproterone acetate tablets (1 tablet once daily for 21 days) for artificial menstrual cycle treatment due to irregular menstruation. On the 7th day of medication, the patient developed swelling of the distal right lower extremity, accompanied by pain, and slight limitation of movement, which did not attract attention. The drug was stopped 21 days later. On the 2nd day after drug withdrawal, the patient had vaginal withdrawal bleeding and blood expectoration occurred once on the same day. After 16 days of drug withdrawal, the swelling and pain of the right lower limb was aggravated. Ultrasound showed deep vein thrombosis in the right lower limb, and CT angiography of the pulmonary artery showed embolism in the right lower pulmonary artery. Deep vein thrombosis complicated with subacute pulmonary embolism were diagnosed. Enoxaparin sodium for anticoagulation and symptomatic treatments were given, the symptoms were improved 17 days later. Laboratory tests showed that the platelet count was 90×109/L, the anticardiolipin antibody IgG was 209 GPL/ml, and the platelet-related antibody was positive. Antiphospholipid syndrome was diagnosed. It was considered that the thrombosis was related to ethinylestradiol and cyproterone acetate tablets.

Objective To explore the efficacy and safety of fenofibrate combined with ursodeoxycholic acid (UDCA) in the treatment of primary biliary cholangitis (PBC) with poor biochemical response.　Methods The medical records of early PBC patients who were diagnosed with poor biochemical response to UDCA and treated with fenofibrate in Outpatient Department of the Liver Research Center of Beijing Friendship Hospital, Capital Medical University from January 2010 to January 2018 were collected and analyzed retrospectively, so as to evaluate the efficacy and safety of combination treatment. The combination treatment regimen consisted of fenofibrate and UDCA. The efficacy indicators were the efficacy rate and biochemical response rate. When the serum alkaline phosphatase (ALP) decreased to below the baseline value before treatment after 12 months of combination therapy, it was  defined as effectiveness, and when it decreased to <1.5 times of upper limit of normal (ULN), the biochemical response was achieved. The safety indicator was the incidence of adverse reactions (liver injury, kidney injury, etc.) related to fenofibrate.　Results A total of 42 patients were enrolled in the analysis, including 12 males and 30 females. The age was (53±10) years when fenofibrate was added and the duration of combination therapy was from 5 days to 34 months. The efficacy analysis of 34 patients with combined treatment showed that the average level of ALP decreased from the baseline value after 12 months of treatment, of which 10 patients (29.4%) fell to the reference value range, and the effective rate was 100%. The ALP was 235 (210, 326) U/L before treatment and decreased to 134 (104, 190) U/L after 12 months of treatment, with a statistically significant difference (P=0.001). Of the 34 patients, 25 (73.5%) achieved biochemical response. The ALP before treatment was 221 (198, 256) U/L and decreased to 125 (99, 143) U/L after 12 months of treatment, with a statistically significant difference (P=0.010). Of the 42 patients, 16 (38.1%) developed adverse reactions related to fenofibrate, including liver injury in 8 patients (19.0%, one case was complicated with hearthurn), kidney injury in 4 patients (9.5%), myalgia, facial edema, heartburn, headache, and skin itch with rash in 1 patient each (each 2.3%). Of the 8 patients with liver injury, 4 were mild, 1 was moderate, and 3 were severe; the mild cases were not intervened, and the alanine aminotransferase (ALT) returned to the baseline level after 2 months; in moderate and severe cases, ALT and total bilirubin returned to the baseline level after stopping fenofibrate and receiving liver protection treatment. Of the 4 patients with renal injury, the serum creatinine (Scr) in 2 patients returned to the baseline level after withdrawal of fenofibrate, in the other 2 patients it recovered to the reference value range spontaneously without drug withdrawal.　Conclusions Fenofibrate combination with UDCA is effective in the treatment of early PBC patients with poor biochemical response, the rate of biochemical response is 73.5%. The common adverse reactions of fenofibrate are liver injury and kidney injury. During the medication, the patients′ liver and kidney function should be closely monitored.

Objective: To analyse the causative drugs, clinical manifestations and precautions of liver damage. Methods: 111 reports of drug-induced liver damage were presented by clinical departments in the hospital from January 2000 to December 2003 and retrospectively reviewed. Results: In 111 cases there were 58 males and 53 females,with a mean age of 46.96 years(range 8-82). 77drugs were involved,mainly antibacterials (18/111 cases,accounting for 16.22%),hormones and other related substances(17/111,15.32%), drugs acting on the CNS ,traditional Chinese medicines and antineoplastics (12/111,10.81%). Classification of drug-induced liver damage was made: hepatocellular damage(40 cases,36.04%),cholestatic damage (43cases, 38.74%)and mixed type damage(28cases, 25.22%). Conclusion: Routine liver function test, early diagnosis, immediate discontinuance of the causative drug and timely treatment are the key to management of drug-induced liver damage.

A 48-year-old female patient received compound Congrong Yizhi capsules 1.2 g (4 capsules) orally thrice daily for memory decline. About 20 days later, the patient developed nausea, anorexia, yellow urine, and yellow staining of skin and sclera. Compound Congrong Yizhi capsules were discontinued. Seven days after drug withdrawal, laboratory tests showed that alanine aminotransferase (ALT) was 1-349-U/L, aspartate aminotransferase (AST) was 827-U/L, alkaline phosphatase (ALP) was 156-U/L, and total bilirubin (TBil) was 213.7-μmol/L. Liver injury induced by compound Congrong Yizhi capsules was considered. Reduced glutathione, compound glycyrrhizin, ademetionine 1,4-butanedisulfonate, and dexa- methasone were given. The patient′s appetite was gradually improved and jaundice gradually subsided. After 36 days of treatments, ALT was 26-U/L， AST was 30-U/L， ALP was 86-U/L， and TBil was 27.2-μmol/L. The liver injury of the patient was considered to be related to Radix Polygoni Multiflori Preparata (prepared fleeceflower root) in compound Congrong Yizhi capsules.

In 2024, a total of 27 309 cases of medication error (ME) from 484 hospitals in 27 provincial administrative regions were collected in the National Monitoring Network for Clinical Safe Medication. Among them, 279 (1.02%) were classified as grade A, 22 081 (80.86%) as grade B, 4 268 (15.63%) as grade C, 472 (1.73%) as grade D, 96 (0.35%) as grade E, 105 (0.38%) as grade F, 6 (0.02%) as grade H, and 2 (<0.01%) as grade I; no MEs of grade G occurred. Among the 27 030 patients involved in MEs of grade B to I, 15 124 (55.95%) were male and 11 906 (44.05%) were female; their ages were from 1 day to 104 years; 3 369 (12.46%) were children (<18 years old), 12 113 (44.81%) were young and middle-aged adults (≥18 to <60 years old), and 11 548 (42.72%) were elderly (≥60 years old). The top 3 contents of ME were wrong drug class (5 347 cases, 19.13%), wrong dosage (4 913 cases, 17.58%), and wrong administration frequency (3 429 cases, 12.27%). Among the 27 030 grade B-I MEs, the main person who triggered the event were physicians (18 703 cases, 69.19%) and pharmacists (6 343 cases, 23.47%). These MEs mainly occurred in clinics (11 009 cases, 40.73%), in hospital wards (7 393 cases, 27.35%), and in pharmacies (6 219 cases, 23.27%). The main persons who discovered the MEs were pharmacists (21 021 cases, 74.14%). The top 3 factors causing ME were lack of related pharmacologic knowledge (8 716 cases, 26.49%), tiredness (5 755 cases, 17.49%), and inexperienced skills (4 505 cases, 13.69%). A total of 209 patients were involved in severe MEs (grade E-I), including 133 (63.64%) males and 76 (36.36%) females, aged from 21 months to 94 years, of which 42 (20.10%) were children, 75 (35.88%) were young and middle-aged adults, and 92 (44.02%) were elderly. The top 3 diseases diagnosed in severe MEs were drug poisoning (41 cases, 19.62%), diabetes (34 cases, 16.27%), and hypertension (14 cases, 6.70%); the main person who triggered the MEs were patients and their families (135 cases, 64.59%); the MEs occurred mainly in patients′ houses (116 cases, 55.50%). Drug poisoning was mainly related to accidental ingestion by children, and MEs in patients with diabetes and hypertension were often related to issues on patient compliance. Based on the data of MEs in 2024, it was proposed to establish a better medication safety culture and improve the ME reporting situation in China, pay attention to the risks of misusing external drugs for internal use, children′s accidental ingestion and insulin-related MEs, strengthen the prevention of MEs related to look-alike sound-alike drugs, pay attention to the post administration management and the compliance education of home care for patients with chronic diseases, so as to improve the medication safety of patients in China.

A 75-year-old male patient with pulmonary infection received an IV infusion of piperacillin sodium and tazobactam sodium 4.5 g twice daily. Fifteen minutes after the first medication, the patient developed patches on the skin of both upper limbs with pruritus, chest tightness and suffocation. Physical examination showed heart rate 110 beats/min, breathing rate 26 breaths/min, blood pressure 196/118-mmHg, and oxygen saturation 0.85. Immediate-type hypersensitivity related to piperacillin sodium and tazobactam sodium was considered. The drug was discontinued and symptomatic treatments including glucocorticoids and antiasthma were given. Two hours later, the skin itching was alleviated, the color of erythema became lighter, and the symptoms of chest tightness and suffocation were relieved. Physical examination showed that the heart rate was 100 beats/min, the blood pressure was 150/90-mmHg, and the blood oxygen saturation was 0.90.

Objective To analyze the clinical characteristics of fatal cardiac adverse events associated with chloroquine, which was recommended for the antiviral treatment of novel coronavirus pneumonia, and provide reference for clinical safe drug use.　Methods The fatal cardiac adverse events associated with chloroquine were searched from the World Health Organization global database of individual case safety reports (VigiBase). The clinical characteristics of the individual cases with well-documented reports (VigiGrade completeness score ≥0.80 or with detailed original reports) were analyzed. The adverse events were coded using the systematic organ classification (SOC) and preferred term (PT) of Medical Dictionary for Regulatory Activities (MedDRA) version 22.1 of International Conference on Harmonization (ICH).　Results Up to 23 February 2020, a total of 45 reports of fatal heart injuries related to chloroquine were reported in VigiBase, which were from 16 countries. Of them, 30 reports were fully informative. Among the 30 reports, 20 cases developed fatal cardiac adverse events after a single large dose of chloroquine. Of them, 17 cases′ fatal cardiac adverse events were caused by overdose of chloroquine (15 cases were suicide or suspected suicide, and 2 children took chloroquine by mistake); 3 cases′ fatal cardiac adverse events were caused in clinical treatment; 18 cases showed arrhythmia and cardiac arrest; 6 cases showed prolonged QRS wave or QT interval; 6 cases were with hypokalemia, including 4 severe ones. Among the 30 reports, 10 cases deve- loped fatal cardiac adverse events after multiple administration of chloroquine, of which 4 cases were treated with chloroquine for 23 days to 2 months and died of heart failure, cardiac arrest or myocardial infarction; 6 cases were treated with chloroquine for 20 months to 29 years and all of them had cardiomyopathy, which were confirmed by endomyocardial biopsy to be caused by chloroquine in 3 cases.　Conclusion Cardiac toxicity was the primary cause of fatal adverse events caused by chloroquine; the main manifestation of single large dose of chloroquine was arrhythmia and the manifestation of multiple administration was cardiomyo- pathy.

本文对近年国内外发生的草药药害事件、草药不良反应的相关报道以及各国管理部门对此采取的相关措施进行了综合介绍。提出应切实加强对中药安全用药知识的宣传普及和不良反应的监测;规范中成药的说明书;做好中药质量的规范化、标准化工作。另外,应注意合理应用中成药,避免因其不正确应用或滥用而出现危害,影响中医药在国际上的声誉。

Objective To understand the usage status of high-alert medicines (HAM) for children in outpatient and emergency prescriptions and inpatient medication orders at department of pediatric.　Methods All outpatient and emergency prescriptions and inpatient medication orders in patients with an age of <18 years between July 1, 2016 and June 30, 2018 in Huairou Maternal and Child Health Hospital Affiliated to Beijing Obstetrics and Gynecology Hospital, Capital Medical University were collected. According to the List of High-Alert Medications for the Chinese Children, the use of HAM for children in prescriptions and medication orders was analyzed retrospectively.　Results A total of 297-968 prescriptions and medication orders were collected in the study, including 270-024 outpatient and emergency prescriptions (90.62%) and 27-944 inpatient medication orders (9.38%). There were 162-521 prescriptions (54.54%) involving male children and 135-447 (45.46%) involving female children with an age of (4±3) years, ranged 0-17 years. The number of drugs included in each prescription was (2±1), ranged 1-9. Of the 297-968 prescriptions and medication orders, 23-476 (7.88%) involved HAM for children. The proportion of prescriptions containing HAM for children in outpatient and emergency prescriptions was significantly higher than that in inpatient medication orders ［7.92% (21-381/270-024) vs. 7.50% (2-095/27-944), P=0.013］; the proportion of prescriptions and medication orders containing HAM for children in Surgery Department ［32.84% (1-220/3-715)］ was significantly higher than that in Medicine Department ［8.17% (22-043/269-777)］ and other departments ［0.87% (213/24-476)］, and the difference was statistically significant (all P<0.001). The 23-476 prescriptions involved 13 categories and 42 kinds of HAM for children and the total frequency of HAM for children was 26-084. The top 3 drug categories that most frequently used were traditional Chinese medicine injections (8-694, 33.33%), antipyretic analgesic and anti-inflammatory drugs (7-505, 28.77%), and anti-infective drugs (4-011, 15.38%); the top 10 HAM for children that most frequently used were paracetamol, Yanhuning injection (炎琥宁注射液), Xiyanping injection (喜炎平注射液), vitamin K1, vidarabine, tetanus antitoxin, penicillins, phenobarbital, promethazine injections, and heparin. Adverse events occurred in 9 children due to medication errors of HAM for children, which were all grade E, and the drugs involved were Xiyanping injection, paracetamol, and vitamin K1 injection.　Conclusions HAM for children was commonly used, among which the traditional Chinese medicine injection-related HAM was used more, and the proportion of prescriptions containing HAM for children was higher in departments of outpatient, emergency, and surgery. Medication errors related to HAM for children may lead to serious adverse events, so the management of HAM for children should be strengthened.

A 38-year-old female patient with thyroid nodule received Xingqi Sanjie cream 30 g orally twice daily for 4 treatment courses in total. Each treatment course was 1 month and the interval between the 2 courses was 14 days. On the 29th day of the 4th treatment course, the patient developed poor appetite, yellowish skin and sclera, and dark urine. Laboratory tests showed alanine aminotransferase (ALT) 3-201-U/L, aspartate aminotransferase (AST) 2-262-U/L, total bilirubin (TBil) 257.2-μmol/L, direct bilirubin (DBil) 186.9-μmol/L, and alkaline phosphatase (ALP) 159-U/L. Drug-induced liver injury (severe) was diagnosed, which was considered to be related to Xingqi Sanjie cream. The drug was stopped, and symptomatic and supportive treatments including hepatoprotection and rehydration were given. Twenty-two days later, the above symptoms in the patient were improved. Laboratory tests showed ALT 209-U/L, AST 117-U/L, TBil 92.7-μmol/L, DBil 63.2-μmol/L, and ALP 82-U/L. Fifty-one days later, the yellowish skin and sclera in the patient subsided, and the urine color returned to normal. Laboratory tests showed ALT 37-U/L, AST 22-U/L, TBil 30.3-μmol/L， DBil 14.7 μ mol/L, and ALP 58-U/L.

A 63-year-old male patient with hepatocellular carcinoma received sintilimab (200-mg by IV infusion on day 1, 21 days as one cycle) after surgery. After 3 cycles of treatment, the patient developed unclear speech, mental fatigue, drowsiness, and weight loss. Laboratory tests showed triiodothyronine (T3) 0.54-nmol/L, thyroxine (T4) 13.0-nmol/L, thyroid-stimulating hormone (TSH) 98.62 mU/L, free triiodothyronine (FT3) 0.43-pmol/ml, free thyroxine (FT4) 0.25-pmol/L, cortisol (Cor) (8:00) 6.1-nmol/L, adrenocorticotropic hormone (ACTH) (8:00) 0.22-pmol/L/L. He was diagnosed as having immune-related hypothyroidism and adrenal cortex hypofunction, which was caused by sintilimab. After 4 days of treatments with glucocorticoid, the above symptoms in the patient were improved, and levothyroxine was given. The dosage of glucocorticoids given to patients was gradually reduced.After 11 days of treatments with levothyroxine, the laboratory tests showed that the thyroid function returned to normal, and levothyroxine was stopped. Adrenal cortex function was still lower than normal ［Cor (8:00) 51.6-nmol/L，ACTH (8:00) 0.22-pmol/L］. Then prednisone acetate tablets 5-mg once daily orally were given continuously. At 8 months of follow-up, the adrenal cortex function in the patient remained low, and sintilimab was stopped forever.

A 55-year-old male patient with hepatic complex alveolar echinococcosis, who had a history of gout for more than 4 years, developed swelling and high skin temperature of feet when he waited for the result of remote consultation and prepared for optional right hemihepatectomy in the hospital. Laboratory tests showed that uric acid was 530-μmol/L and rheumatic factor was negative. Acute gout attack was considered. He was treated with oral colchicine 0.5-mg thrice daily. About 10-hours after the first administration, the patient developed urinary incontinence. According to the consultation results, it was considered that the urinary incontinence might be related to colchicine. Colchicine was stopped immediately. The symptoms of urinary incontinence disappeared 24-hours after drug withdrawal. The symptoms of urinary incontinence recurred after the patient took the drug again by himself. Urinary incontinence did not recur after the colchicine withdrawal again.

Objective;To observe the side-effects of thalidomide used for multiple myeloma. Method:Thalidomide-induced unwanted effects were analysed in 32 inpatients with multiple myeloma. Results; The occurrence rate of adverse reactions was 94% in all, 87.5% in alimentary system, 84.4% in neuropsychic system,and the others included sinus bradycardia, escape rhythm, drug fever, skin rashes, edema, etc. Conclusion; Thalidomide could cause gastro-intestinal and neuropsychic disturbances, which would disappear or relieve with discontinuation of administration or reduction of dose.

A 34-year-old female patient received an intramuscular injection of compound amionpyrine antipyrine barbitone injection for acute upper respiratory infection and fever. Eight hours after medication, the patient developed deep yellow urine followed by fatigue, anorexia, and yellowish skin. Laboratory tests showed alanine aminotransferase (ALT) 764-U/L, aspartate aminotransferase (AST) 211-U/L, alkaline phosphatase (ALP） 280-U/L, gamma-glutamyltransferase (γ-GT) 861-U/L, total bilirubin (TBil） 72.0-μmol/L, direct bilirubin (DBil） 61.3-μmol/L, and indirect bilirubin (IBil)10.7-μmol/L. The patient was diagnosed as having drug-induced liver injury, which might be related to compound amionpyrine antipyrine barbitone injection. Therapy with liver-protective drugs was given immediately. Sixteen days later, her jaundice subsided. The laboratory tests showed ALT 58-U/L, AST 34-U/L, ALP 237-U/L, γ-GT 345 U/L, TBil 26.0-μmol/L, and DBil 13.1-μmol/L.

A 64-year-old male patient with comminuted intertrochanteric fracture of right femur received subcutaneous injection of 4-100 U nadroparin calcium once daily for anticoagulant treatment due to pulmonary embolism and thrombosis of both lower limbs before operation. His platelet count (PLT) was 166×109/L before the treatment. After 5 days of treatment, the dose of nadroparin calcium was increased to 4-100 U once per 12-h. On the 8th day after the dose increase, the patient′s PLT increased to 800×109/L. Thrombocytosis was diagnosed, which was considered to be related to nadroparin calcium. The drug was stopped and replaced by rivaroxaban 20-mg once daily orally. Five days later, the patient′s PLT decreased to 590×109/L; 34 days later, PLT was 297×109/L.

A 67-year-old male patient with small cell lung cancer was given chemotherapy combined with immunotherapy (irinotecan+nedaplatin+tislelizumab), 21 days as a cycle. The patient′s cough was significantly improved without blood in sputum. After 2 cycles of treatment, chemotherapy and immunotherapy were suspended because of grade Ⅳ bone marrow suppression, and radiation therapy was changed. After the 29th radiotherapy, the patient developed paroxysmal cough and sputum with bloody, accompanied by shortness of breath and no fever. Blood gas analysis showed type Ⅰ respiratory failure. Chest computed tomography (CT) showed new pleural reticular vague shadows in both lungs, especially in the right lung. Radiotherapy was stopped and chemotherapy was restarted. The patient's cough and expectoration were improved, but the shortness of breath gradually aggravated. The interstitial pneumonia lesions involved both lungs rather than being localized, by which radiation pneumonitis were ruled out. Virus and atypical pathogen infection were excluded by etiology and imaging examination. Immune-related pneumoniatis complicated with infection caused by tislelizumab was considered. High-dose methylpre- dnisolone combined with gamma globulin and infliximab were given to inhibit immune response, mero- penem, moxifloxacin, voriconazole were given successively to prevent infection, and oxygen inhalation was given. The patient′s cough, expectoration, and shortness of breath disappeared, oxygenation index was improved, and chest CT showed that the range of interstitial changes in both lungs gradually reduced.

A 31-year-old male patient received moxifloxacin 400-mg orally once daily for pulmonary infection. After 9 days of treatment, the patient developed hemoptysis, hematochezia, and scattered petechia and ecchymosis on his body, with platelet count (PLT) 1×109/L. Thrombocytopenic purpura was diagnosed. Moxifloxacin were stopped and treatments such as hemostasis, recombinant human interleukin-11, and an IV infusion of concentrated platelets were given. Six days later, the patient′s petechia and ecchymosis disappeared and the PLT was 376×109/L. Bone marrow puncture result showed that it was immune thrombocytopenia.

Objective To understand the clinical characteristics of risperidone-induced rhabdomyolysis (RM).　Methods Risperidone-related RM case reports were collected by searching relevant databases at home and abroad as of February 2021, and the patients′ general conditions, disease conditions, medication use, RM occurrence ［time of occurrence, clinical symptoms, and serum creatine kinase (CK) level, etc.］, and treatment and outcome were recorded and descriptively analyzed.　Results A total of 16 patients were collected, including 14 males and 2 females, with age of 13-76 years. The primary diseases were schizophrenia in 11 patients, psychomotor agitation, obsessive-compulsive disorder, depressive syndrome with psychotic symptoms, depressive symptom cluster, and suspected psychotic symptoms in 1 case each. Among the 16 patients, 2 were treated with risperidone alone, and 14 were treated with risperidone combined with other drugs (6, 6, 5, 4, 3, and 1 with other antipsychotics, sedatives, antidepressants, statins, anticho- linergics, and cyclosporine, respectively, and 3, 7, 1, and 3 cases with 1, 2, 3, and 4 combination drugs, respectively). Except that the medication method was not described in 2 cases, risperidone was orally adminis- tered in 13 cases and injected in 1 case. Thirteen patients with oral risperidone had dosage descriptions, of which 12 cases′ dose met the requirements of the drug labels, and 1 case took risperidone 96-mg due to severe hallucinations induced by drug withdrawal after taking the drug with routine dose for 5 years. In addition to the patient with overdose of risperidone, the occurrence time of RM was described in 14 cases, which was 4 days to 2 years after risperidone, and 10 cases occurred within 4 to 15 days after risperidone use. The main clinical symptoms were muscle pain (10 cases), acute liver injury (8 cases), acute kidney injury (5 cases), muscle weakness (4 cases), fever (3 cases), tachycardia (3 cases), and acute tendon intermembrane space syndrome (3 cases). The CK level was 4-587 to 928-961-U/L with a median level of 27-355-U/L in the 16 patients with RM, and it was>15-000-U/L in 10 cases (62.5%). After RM occurred, risperidone was discontinued in 13 patients, continued in 2 patients, and used at reduced dose in 1 patient; 8 patients received hydration therapy, 3 received hemodialysis, 1 received organ support therapy, and 3 with acute compartment syndrome (ACS) were treated with fasciotomy. All 16 patients′ symptoms disappeared and CK levels returned to normal. Among them, the specific time of recovery were described in 12 patients. The time of symptom disappea- rance was 2-12 months and the time of CK level recovery was 7-56 days.　Conclusions Risperidone-related RM mostly occurs within 4-15 days after exposure to risperidone, which is mostly related to the combination with other drugs. The elevation of CK level is usually severe, which can be complicated by ACS. Symptoms could return to normal after risperidone was discontinued and/or symptomatic treatments are given.

A 49-year-old male patient with type 2 diabetes mellitus and diabetic nephropathy received long term use of retaglinide thrice daily orally, 1-mg in the morning, 2-mg in the afternoon and 1-mg in the evening. Because of the sudden acute cerebral infarction, clopidogrel was added, on the 4th day of the medication, the fasting blood glucose in the patient decreased to 2.6-mmol/L. It was considered that the interaction of clopidogrel and repaglinide caused the increase of repaglinide plasma concentration, which resulted in severe hypoglycemia in the patient. Clinical pharmacist suggested stopping repaglinide and using insulin. The physician reduced the dosage of repaglinide to twice daily, 1-mg in the morning and 0.5-mg in the afternoon, and after 3 days the patient′s fasting blood glucose fluctuated between 4.0 and 4.5-mmol/L. Since the patient had diabetes nephropathy and renal insufficiency, which might increase the risk of hypoglycemia, repaglinide was stopped, and insulin glutamine 3 U was injected subcutaneously before meals, at the same time blood glucose was closely monitored. Fasting blood glucose fluctuated between 4.9 and 5.4-mmol/L after insulin treatment.

目的 对利巴韦林和干扰素α的不良事件（AE）进行数据挖掘，为鉴别应用这两种药物治疗新型冠状病毒肺炎（新冠肺炎）过程中出现的临床症状/体征和实验室检查异常是药物引起还是疾病本身所致提供依据。　方法 根据文献及《新型冠状病毒肺炎诊疗方案（试行第五版）》中提到的新冠肺炎症状/体征及实验室检查异常结果选出本研究关注的AE。收集2004年1月1日至2019年12月31日美国FDA不良事件报告系统（FAERS）相关数据，采用报告比值比（ROR）法对利巴韦林和干扰素α进行数据挖掘。　结果 设定时段内FAERS数据库共收到7-582-463份药物相关的有效AE报告，其中利巴韦林31-775份，干扰素α 2-345份。分析结果显示，在呼吸系统、胸及纵隔疾病中可能与利巴韦林具有相关性的AE有鼻充血、咳嗽、喉疼痛、咽部水肿、咳痰和呼吸困难，可能与干扰素α具有相关性的AE有喉疼痛和咯血；在其他系统器官分类中可能与利巴韦林和干扰素α均具有相关性的AE包括发热、寒冷感、疲乏、恶心、呕吐、腹泻、头痛、关节痛、肌痛和皮疹。在实验室检查异常AE中，与利巴韦林相关的有白细胞计数降低、血小板计数降低、天冬氨酸转氨酶升高和丙氨酸转氨酶升高；与干扰素α相关的有白细胞计数降低、淋巴细胞计数降低、血小板计数降低、天冬氨酸转氨酶升高和丙氨酸转氨酶升高。　结论 利巴韦林和干扰素α相关AE中一部分与新冠肺炎的临床表现和实验室检查异常结果相似，临床实践中应当注意鉴别。

Enteral nutrition (EN) is defined as the administration of a nutrient solution orally or by means of a feeding tube with the purpose of contributing the supply of all or part of the body's nutrient requirements. EN preparations can be classified into three types: elemental type, non-elemental type, and module type. EN is usually given with feeding tube. Non-invasive tube includes nasogastric tube and nasointestinal tube, and invasive tube includes gastrostomy tube and enterostomy tube. Indications for EN include radical surgery in patients with upper alimentary tract or upper respiratory tract, tracheal intubation, esophageal stenosis, dysphagia, anorexia nervosa, largescale burning or trauma. Although considered safer than parenteral nutrition, enteral feeding is not of without complications. The common complications of EN were as follows: (1) mechanical complications such as obstructions of the feeding tube; (2) gastrointestinal complications are abdominal distension, nausea, vomiting, and diarrhea, and they can be reduced or avoided by using gastrointestinal pump or nasointestinal tube, reducing infusion speed, increasing nutrient solution temperature, and using gastrointestinal prokinetic drugs; (3) metabolic complications are mainly hyperglycaemia, and it can be treated with insulin; (4) infectious complications are mainly inhalation pneumonia caused by inhaling nutrient solution or regurgitation into the lungs presenting with sudden dyspnea, fever, increased heart rate. Attention should be paid to its gastric retention.

A 26-year-old woman received laser decolorization therapy for facial freckles. After the operation, compound arbutin cream 1 g once per night was applied on the face. She developed redness, swelling, and water blisters with desquamation on her face about 12-hours after the first application of the drug. She was diagnosed as having contact dermatitis, which was considered to be related to compound arbutin cream. Then the cream was withdrawn. She received prednisone acetate 20-mg orally once daily, levocetirizine 5-mg orally once per night, and local hydropathic compress with 3% boric acid lotion. Three days later, her facial redness, swelling, and desquamation were obviously improved, and most of the water blisters disappeared. At a one-week telephone follow-up, the patient′s water blisters disappeared.

Accumulation of drugs and its metabolites in the body occurs and risks of adverse drugreactions increase in renal insufficiency patients due to the renal function decline or delay of renal excretionand the pharmacokinetic changes related to the decline of renal function. Therefore, the dose of anticancerdrugs should be adjusted in tumor patients with renal dysfunction. The Japanese Society of Nephrology,JapanSociety of Clinical Oncology,Japanese Society ofMedical Oncology,and Japanese Society of Nephrologyand Pharmacotherapy have jointly formulated Clinical Practice Guidelines for Management of Kidney Injury During Anticancer Drug Therapy 2022, and specifically discusses the dose adjustment of anticancer drug forpatients with renal injury in the second chapter. This article focuses on the interpretation of the principle ofdrug dose adjustment for patients with renal insufficiency and suggestions for dose adjustment of platinumdrugs and fluorouracil drugs in this chapter.

A 56-year-old male patient with tuberculosis complicated by infection did not get better after treatment with moxifloxacin combined with rifampicin, isoniazid, ethambutol, and pyrazinamide. The invasive pulmonary aspergillosis was diagnosed by bronchoalveolar lavage fluid culture and detection of 1,3-beta-D-glucan, galactomannan antigen, and Aspergillus antibody. Moxifloxacin and anti-tuberculosis drugs were discontinued and an IV infusion of voriconazole (the dose was 300-mg once per 12-hours on the first day, the maintenance dose was 150-mg once per 12-hours) was given. On the 5th day of medication, the plasma concentration of voriconazole was zero. The consultation pharmacist considered that the voriconazole plasma concentration was related to rifampicin. The next day, the dose of voriconazole was adjusted to 200-mg once per 12-hours. Two days later, the plasma concentration of voriconazole was 1.3-mg/L. The patient′s cough and expectoration were relieved, but he still repeatedly developed high fever. On the 9th day of increase of voriconazole dose, intravenous infusion of methylprednisolone 40-mg once daily was given because connective tissue disease could not be excluded by consulting rheumatologists. The patient′s temperature returned to normal the next day and the plasma concentration of voriconazole was 3.0-mg/L. Clinical pharmacists and physicians reviewed the literature and reached a consensus: the induction effect of rifampicin on drug metabolizing enzymes in the body can last for 7-10 days or even longer after discontinuation of the drug, the monitoring of plasma concentration of voriconazole should be strengthened in patients treated with rifampicin sequential voriconazole, and the dose of voriconazole should be adjusted according to the plasma concentration until the induction effect of rifampicin on drug metabolizing enzymes completely disappears and the plasma concentration of voriconazole reaches a steady state.

Object iv e:To investigate kidney damage caused by low-dose of enteric-coated aspirin t ablets.Method:The outcomes of600patients tak ing aspirin(50～75mg dai ly)were retrospectively analysed from January1995to August2003in our h ospital.Results:Kid ney damage occurred in16of600cases.Its frequen cy wa s related to age of patients,dosage and treatment duration of aspirin.And imp aired renal function was returned to normal gradually when aspirin was withdrawn in them.Conclusion:Prolonged oral admi nist ration of aspirin in low-dose can cause kidney damage and ordinary exam ination of urine and renal function is suggested,especially for the elderly.

Ricin derived from castor beans is a potent toxin, the main machanism of its toxic effects to cells is to inhibit protein synthesis in cells and result in their death. People can be poisoned via different routes of exposure to ricin. The clinical presentations of ricin poisoning depend on the route of exposure and the dose received. The patients with severe ricin poisoning may develop multi-organ failure and death. So for no specific antidote exists for ricin. The toxin vaccine of ricin is being tried out on laboratory animal. Treatment for ricin poisoning is primarily supportive medical care to minimize the effects of the poisoning.

Minocycline is a semi-synthetic tetracycline antibiotic. In recent years, minocycline has been used in the treatment of chronic infections caused by multi-drug resistant bacteria and chronic diseases such as pemphigus and rheumatoid arthritis due to its lower incidence of bacterial resistance and good antibacterial effect. Long term use of oral minocycline can cause skin hyperpigmentation. According to the location, clinical features, and histopathological changes, minocycline-induced skin hyperpigmentation (MISH) is divided into 4 subtypes, but the definition of subtype 4 remains controversial. The incidence of MISH varies greatly in different studies, which may be closely related to factors such as patients′ underlying pathophysiological status, comorbid diseases, dose, and duration of treatment. For those patients who need to take minocycline for a long time, skin color should be observed. Once skin color changes were found, relevant examinations (e.g. skin biopsy) should be carried out in time to make a definite diagnosis as soon as possible. Patients with MISH should pay attention to sun protection. Reducing the dose or stopping minocycline is an effective strategy to improve MISH. Q-switched laser or picosecond laser is recommended to treat pigmentation which can not be recovered after drug withdrawal.

Oxaliplatin (OXA) is the third‑generation platinum antineoplastic agents, mainly used in the treatment of metastatic colorectal cancer. Sinusoidal obstruction syndrome (SOS) is a common and serious adverse reaction of OXA. The main clinical manifestations are splenomegaly, thrombocytopenia, abnormal liver function, and portal hypertension. The mechanism is closely related to OXA‑induced oxidative stress and inflammatory reactionsin the liver, which lead to injury of hepatic sinusoidal endothelial cells, and then lead to platelet aggregation and vascular obstruction in hepatic sinusoids. The occurrence of SOS is related to the accumulated dose and the treatment cycle of OXA. Splenomegaly is an independent predictor of OXA‑related SOS. Thrombocytopenia, elevated serum hyaluronic acid and aspartate aminotrans- ferase‑to‑platelet ratio index can also predict the occurrence of SOS. OXA should be used with caution in patients with chronic liver disease, especially in those with portal hypertension. Special attention should be paid to the occurrence of SOS during OXA treatment. For patients with symptoms of suspicious SOS, imaging examination should be performed in time. Early diagnosis and timely withdrawal of drugs are bene- ficial for the reversal of liver fibrosis, and the prognosis of patients with severe fibrosis is poor.

Drug-induced thrombocytopenia is defined as a platelet count lower than normal range(<100×10⁹/L) caused by a drug,resulting in bleeding and some related symptoms.Drug-induced thrombocytopenia includes at least three mechanisms such as marrow suppression,immunological and non-immunological thrombocytopenia.Drugs that have been more commonly reported to cause thrombocytopenia include cancer chemotherapy agents,heparin,quinidine,quinine,gold salts,valproic acid,and antibacterials.The incidence of thrombocytopenia induced by cancer chemotherapy agents is substantially higher than that caused by other types of drugs.Signs and symptoms associated with drug-induced thrombocytopenia are petechiae,ecchymosis,epistaxis,gingival bleeding.More significant bleeding such as gastrointestinal hemorrhage,hematauria,colporrhagia,and intracranial hemorrhage may occur.Treatment options for drug-induced thrombocytopenia include stopping the suspected causative agent;administering corticosteroids,immunog…更多lobulin or platelet transfusions;gold salt or arsenide-induced thrombocytopenia can be treated with IM dimercaprol to eliminate heavy metals.

A 64-year-old male patient with colon cancer received one cycle chemotherapy of oxaliplatin+capecitabine and 7 cycles of oxaliplatin+raltitrexed chemotherapy. There were no interstitial changes in chest CT before operation. After 8 cycles of chemotherapy, the patient deve- loped chest tightness and shortness of breath. Chest CT showed interstitial changes in bilateral lungs, which were considered to be related to oxaliplatin. After 31 days of treatments with drugs such as broad-spectrum antibiotics, glucocorticoids, acetylcysteine, and reduced glutathione, as well as noninvasive ventilator assisted ventilation, oxygen inhalation, and other symptomatic treatments, his symptoms of chest tightness and shortness of breath were relieved, and chest CT showed that interstitial lesions in the bilateral lungs were obviously relieved.

环境污染的加剧,导致过敏反应相应地增加,由此引伸对第2代组胺H1受体阻断药开发的日趋重视,新药不断上市,其作用强而持久,对中枢和植物神经系统的不良反应甚微,但部分药物对心脏的毒性却日益突出,过量或同时并用肝酶P450抑制剂偶可出现严重的心律失常(尖端扭转型室性心动过速)。为此,对其产生心脏毒性原因及合理应用问题进行探讨,以寻求应用时的防范措施。

Drug-induced liver injury (DILI) is caused by the direct toxicity of drugs and/or their metabolites or the body-specific heterogeneous response to drugs. Since 2019, the European Association for the Study of the Liver, the American College of Gastroenterology, and the Asia Pacific Association of Study of Liver have successively updated previously published guidelines on DILI. Based on the above 3 updated guidelines and in combination with Chinese Diagnosis and Treatment Guideline on Drug-Induced Liver Injury, the Guideline for Primary Care of Drug-Induced Liver Injury (2019), and the relevant literature at home and abroad in recent years, we review the progress on the diagnosis and treatment of DILI in this paper, aiming to help the diagnosis and treatment of DILI in clinic.

A 72-year-old male patient took colchicine 1-mg once daily orally by himself due to the acute attack of gouty arthritis. Thirty-two days later, the patient developed diarrhea. He increased the colchicine′s dose to 1-mg thrice daily orally by himself because of aggravation of arthritis pain. Then the patient′s diarrhea was worsened and muscle pain appeared. Laboratory tests showed white blood cell count (WBC) 2.5×109/L, platelet count (PLT) 76×109/L, alanine aminotransferase (ALT) 429-U/L, aspartate aminotransferase (AST) 595-U/L, γ-glutamyl transpeptidase（γ-GT) 375-U/L, alkaline phosphatase (ALP) 265-U/L, creatine kinase 2-300-U/L, lactate dehydrogenase (LDH) 777-U/L, serum creatinine (Scr) 299 μmol/L, urine occult blood (+++), and urine protein (++). Colchicine plasma concentration was 5.9-ng/ml and urine concentration was 81.8-ng/ml. Rhabdomyolysis and multiple organ dysfunction syndrome secondary to colchicine poisoning was considered. Colchicine was stopped, and the patient′s diarrhea was improved 2 days later. The patient also received symptomatic support therapy, plasma exchange, and bedside continuous renal replacement therapy for 6 times. After 23 days of drug withdrawal, symptom of muscle soreness was improved and the laboratory tests showed WBC 5.6×109/L, PLT 266×109/L, ALT 40-U/L, AST 19-U/L, γ-GT 135-U/L, ALP 133-U/L, creatine kinase 66-U/L, Scr 138-μmol/L, negative urine occult blood, and weakly positive urine protein.

本文阐述了血管紧张素转换酶抑制剂(AcEI)的作用机制、分类、药动学与临床应用,为合理选用ACEI提供参考。并参阅国内外相关文献,予以分析和归纳,对其作用特点及不良反应加以综述。ACEI是一类新型治疗高血压和充血性心衰的药物,合理选用,可以获得很好的治疗效果。

A 31-year-old female patient took ibuprofen sustained-release capsules (ibuprofen) 0.3 g by herself due to persistent dull pain in both sides of the waist during menstruation. Three hours later, she developed nausea and vomiting, weakness, and poor appetite. Laboratory tests showed serum creatinine 173-μmol/L, glomerular filtration rate 33-ml/(min·1.73 m2), urea 10.7-mmol/L, and uric acid 428-μmol/L. Ibuprofen-related acute kidney injury was considered. Then she received intravenous injection of methylprednisolone sodium succinate 20-mg once daily by micro injection pump and symptomatic treatments. After 14 days of treatments, her serum creatinine was 89-μmol/L, glomerular filtration rate 84.1-ml/(min·1.73 m2), and urea 8.0-mmol/L; after 21 days, her serum creatinine was 78-μmol/L, urea 3.9-mmol/L, and uric acid 313-μmol/L.

A 49-year-old male patient was treated with first-line and second-line chemotherapy regimens successively for 7 months because of Hodgkin′s lymphoma. However, the tumor failed to be well controlled. His treatment was changed to intravenous infusion of sintilimab 200-mg once every 21 days. His liver function was normal before treatment. After the second administration of sintilimab (on day 42 after the first medication), the patient developed chest distress, abdominal distension, poor appetite, and etc. Reexa- mination of liver function showed alanine aminotransferase (ALT) 1-590-U/L, aspartate aminotransferase (AST) 3-678-U/L, alkaline phosphatase (ALP) 468-U/L, gamma-glutamyl transferase (γ-GT) 399-U/L, total bilirubin (TBil) 50.1-μmol/L, and direct bilirubin (DBil) 26.8-μmol/L. Sintilimab was discontinued, but the patient′s jaundice was deteriorated. Intravenous infusion of methylprednisolone 150-mg once daily was given for 3 days, but the bilirubin reached the peak (TBil 152.6-μmol/L，DBil 109.2-μmol/L). Oral mycophenolate mofetil 0.5 g twice daily was added, the patient′s symptoms were gradually improved, and his liver function gradually recovered. After 6 days of combination use of methylprednisolone and mycophenolate mofetil, the laboratory tests showed ALT 63-U/L, AST 78-U/L, TBil 25.2-μmol/L, and DBil 12.9-μmol/L. Twenty-two dags later, his liver function returned to normal.

The prevalence of diabetes mellitus in China is rising year by year. Insulin is one of the important treatment means. However, insulin therapy still faced with the challenges of delayed initiation and intensive treatment, resulting in poor clinical blood glucose control. The potential risks of hypoglycemia, glycemic variability, treatment compliance, and other problems in insulin therapy make difficulties in clinic. Compared with currently used insulin, new insulin analogues have characteristics of longer action time and more stable pharmacokinetic/pharmacokinetic features, and can improve the safety of insulin treatment, glycemic variability, and patients′ treatment willingness and compliance in clinical application, thus provide good treatment options for safe, convenient, and stable control of blood glucose in diabetes patients.

A 41-year-old female patient received long-term treatment with metformin, glimepiride, sitagliptin, and acarbose for type 2 diabetes mellitus. Due to elevated blood-glucose, the hypoglycemic regimen was adjusted to metformin, acarbose, and dulaglutide (1.5-mg, subcutaneously injected once a week). After each injection of dulaglutide, the patient had severe anorexia but no intervention was given because that the patient could tolerate. Empagliflozin 10-mg orally once daily were added 3 days after the first injection and then the dose was adjusted to 10-mg next day. The day after the fourth injection, the patient developed dizziness, nausea, vomiting, general fatigue, etc. Laboratory tests showed blood glucose 20-mmol/L, arterial blood pH 7.22, partial pressure of carbon dioxide 22.1-mmHg, bicarbonate concentration 8.8-mmol/L, standard bicarbonate 12-mmol/L, total carbon dioxide content 10-mmol/L, ketone body in urine (+++), and urine sugar (++++). Diabetic ketoacidosis was diagnosed. Considering that severe anorexia after the application of dulaglutide caused serious insufficient carbohydrate intake and then empagliflozin- induced diabetic ketoacidosis was stimulated, the 2 drugs were discontinued and symptomatic and supportive treatments were given. Five days later, laboratory tests showed post-lunch blood glucose 10.1-mmol/L, ketone body in urine (+), negative urine sugar, and urine pH 5.5. Empagliflozin 5-mg once daily was added and laboratory tests showed carbon dioxide binding capacity of the blood 23.2-mmol/L, urine ketones (+++), urine sugar (++++), and uric acidity 5.0 four days later. The patient insisted on leaving the hospital. After discharge, she was treated with recombinant insulin glargine, acarbose, and empagliflozin. At 1 month of follow-up, symptoms of diabetic ketoacidosis did not recur.

鉴于20世纪末,我国出现俗称″冰毒(甲基苯丙胺)、摇头丸(亚甲二氧基甲基苯丙胺)和K粉(氯胺酮)″的毒品滥用问题。这些毒品被称为″新型毒品″,是相对鸦片、海洛因等传统毒品的一大类滥用毒品的称谓,同海洛因等传统阿片类毒品相比,此类毒品具有精神依赖性强,而身体依赖性相对弱的特点。现主要在娱乐场所被滥用,″新型毒品″滥用的群体广泛,不仅导致严重身心损害,也影响社会安定团结。本文主要介绍了全球范围滥用的几种″新型毒品″的药理学、毒理学作用特点和滥用导致的危害。

Objective To understand the problems of data mining in adverse drug reaction (ADR)/adverse event (AE) signal detection study in China.　Methods The literature on ADR/AE signal detection study in SinoMed, CNKI, WanFang Data and VIP databases were retrieved (up to May 30, 2022). The relevant content of the data mining in the literature was investiagted and evaluated from the following 4 dimensions and 9 items: (1) background data, including 1 item; (2) data preprocessing, including 4 items such as drug mapping, AE mapping, missing value processing, and data deduplication; (3) data mining algorithm (DMA), including 3 items such as DMA selection, DMA formula interpretation, and signal threshold; (4) interpretation of the results, including 1 item. According to the relevant specifications and technical requirements of data mining, the reporting/reporting error-free rate of the 4 dimensions and 9 items in the literature was taken as the overall quality evaluation index. Reporting/reporting error-free rate ≥60% was considered to be an excellent level of overall quality.　Results A total of 165 articles were included. On the background data dimension, the reporting/reporting error-free rate of using all the other drug data of the entire database in the literature was 35.2% (58/165), which did not reach an excellent level. On the data preprocessing dimension, the reporting/reporting error-free rates of drug mapping, AE mapping, missing value processing, and data deduplication in the literature were 22.4% (37/165), 73.9% (122/165), 10.3% (17/165), and 55.2% (91/165), respectively. The reporting/reporting error-free rate on this dimension was 40.5% (267/660), which did not reach the excellent level, only the rate of AE mapping reached the excellent level. On the DMA dimension, the reporting/reporting error-free rates of ≥2 DMA, DMA formula interpretation, and signal threshold in the literature were 63.6% (105/165), 78.2% (129/165), and 87.9% (145/165), respectively. The reporting/reporting error-free rate on this dimension was 76.6% (379/495), which reached an excellent level. The reporting/reporting error-free rate was 87.4% (144/165), reaching an excellent level. The signals were interpreted as "positive" or "negative" signals in 7 articles, and the meaning of signals were interpreted as causality in 14 articles. The overall reporting/reporting error-free rate in the 165 literature, analyzed from 9 items on 4 dimensions, was 57.1% (848/1-485), which did not reach the excellent level.　Conclusion The main problems in the domestic literature of ADR/AE signal detection study are the incomplete selection of background data and the lack of data preprocessing, suggesting that the further relevant studies in China should be improved on above 2 dimensions for better quality of ADR/AE signal detection research.

A 79-year-old male patient was given an IV infusion of piperacillin sodium and tazobactam sodium 4.5 g once every 8 hours for head injury complicated by Escherichia coli pneumonia. Before the treatment, his white blood cell count (WBC) was 10.20×109/L, red blood cell count (RBC) was 3.58×1012/L, hemoglobin (HB) was 101-g/L, and platelet count (PLT) was 202×109/L. On day 2 of medication, his blood cell count began to decrease, with the lowest values of WBC 2.96×109/L, RBC 2.40×1012/L, Hb 66-g/L, and PLT 128×109/L, respectively. It was misdiagnosed as gastrointestinal bleeding because of positive occult blood in gastric juice of the patient at the same time. However, the patient had no obvious melena, his gastric fluid occult blood did not match the development of anemia, and there was no evidence of hemolysis or hemorrhage at other sites. The relationship between the blood cell count decrease and piperacillin sodium and tazobactam sodium was considered. The drug was discontinued and the patient′s blood cell count returned to levels before treatment 3 days later.

Objective To establish the Chinese version of Medication Appropriateness Index (MAI) and evaluate the appropriateness of medication in elderly inpatients on trial.　Methods According to Brislin′s translation model for cross-cultural research, the MAI was translated into Chinese through 4 steps: translation, back translation, cultural adaptation, and pre-survey. Using convenient sampling method, 300 elderly inpatients in the Department of Geriatrics, Nanjing Drum Tower Hospital from July to December 2019 were selected as the research subjects, and the Chinese version of MAI was used to evaluate the appropriateness of medication. Reliability of the Chinese version of MAI was evaluated using Cronbach′s α coefficient and intraclass correlation coefficient (ICC); the content validity and structural validity of the Chinese version of MAI were evaluated using 4-level scoring method and exploratory factor analysis, respectively. The appropriateness of medication in 300 elderly inpatients was evaluated by analyzing the MAI scores and the distribution of irrational items.　Results The Chinese version of MAI contained 10 items. The evaluation results of 300 elderly inpatients were statistically analyzed. The Cronbach′s α coefficient of the scale was 0.892 and the ICC of the scale was 0.876 when 20 patients were selected for re-testing 14 days later. The item-level content validity index (I-CVI) of the Chinese version of MAI was 0.86 to 1.00 and the scale-level content validity index/average (S-CVI/Ave) was 0.96. A total of 4 common factors were extracted by explo- ratory factor analysis, the cumulative variance contribution rate was 58.132%, and the factor loading of 8 items was more than 0.4. The evaluation results of appropriateness of medication showed that the average MAI score in 300 patients was 2.6, of which 198 patients did not score 0; inappropriate medication counted 66.00% and the average MAI score of each drug was 0.2. The top 3 items with more inappropriate medication were drug-disease/abnormal condition interaction (88 cases, 29.3%), duplication (69 cases, 23.0%), and incorrect dosage (67 cases, 22.3%).　Conclusions The Chinese version of MAI had good reliability and validity. The items with more inappropriate medication in elderly inpatients in the Department of Geriatrics, Nanjing Drum Tower Hospital were mainly drug-disease/abnormal condition interaction, duplication, and incorrect dose.

Objective To mine the risk signals of echinococcin antifungal drugs such as caspofungin-, micafungin-, and anidulafungin-related adverse events(AEs) and provide reference for their safe and rational use in clinical practice.　Methods AE reports of caspofungin, micafungin and anidulafungin from January 1, 2004 to June 30, 2021 were collected by searching the US FDA Adverse Event Reporting System database. AEs were classified and standardized according to the system organ class (SOC) and the preferred terms (PT) of Medical Dictionary for Regulatory Activities 25.0. Reported odds ratio (ROR) method was used to mine the AE risk signals of above mentioned 3 drugs. An AE with reports ≥3 and 95% confidence interval (CI) lower limit of ROR>1 was defined as a positive signal.　Results A total of 1-348 AE reports of caspofungin were collected, involving 73 PTs and 13 SOCs. The top 5 PTs in signal intensity were dilatation intrahepatic duct acquired, myoglobin urine present, retinitis, renal abscess, and hypoperfusion, all of which were new adverse reactions which were not recorded in the labels. A total of 837 AE reports of micafantine were collected, involving 39 PTs and 11 SOCs. The top 5 PTs in signal intensity were hepatoblastoma, leukaemoid reaction, blood creatine increase, acidosis, and skin necrosis all of which were new adverse reactions not recorded in the labels. A total of 202 AE reports of anidulafungin were collected, involving 22 PTs and 12 SOCs. The top 5 PTs in signal intensity were rectal obstruction, venous occlusive liver disease, anuria, supraventricular tachycardia, and acute respiratory distress syndrome. Except the acute respiratory distress syndrome, the other adverse reactions were new adverse reactions not recorded in the labels.　Conclusions The AEs of the 3 echinocandin antifungal drugs mined in this study are mostly new adverse reactions not recorded in the labels, involving liver and biliary system, blood and lymphatic system, kidney and urinary system diseases mainly, which should be vigilant in clinical practice.

With the rapid progress of cancer treatment, the treatment of chronic kidney disease (CKD) in cancer survivors has become more and more important in clinical practice. The Japanese Society of Nephrology, Japan Society of Clinical Oncology, Japanese Society of Medical Oncology, and Japanese Society of Nephrology and Pharmacotherapy have jointly formulated the Clinical Practice Guidelines for Management of Kidney Injury During Anticancer Drug Therapy 2022, in which the epidemiology, influencing factors, and treatment options of CKD in cancer survivors was comprehensively discussed. The above guideline emphasizes the complexity of managing CKD in cancer survivors from the perspective of clinical practice, and puts forward personalized treatment recommendations for this special population. This article interprets this chapter in the guideline in order to provide reference for clinicians.

With the application of immune checkpoint inhibitors (ICIs), the acute kidney injury (AKI) caused by ICIs has attracted increasingly extensive attention. The incidence of ICIs-induced AKI is 0.8%-29%, which can occur weeks or months after the first drug use or even after drug withdrawal. The typical renal histopathological features of AKI are acute tubulointerstitial nephritis, and glomerulopathy can also be seen. The risk factors include combined application of ICIs, the use of proton pump inhibitors, and having chronic kidney diseases, etc. After the diagnosis of AKI, it is necessary to decide whether to reduce the dose or stop using ICIs and start glucocorticoid treatment or add other immunosuppressive drugs accor- ding to the degree of disease and the specific situation of the patient. In case of level 3-4 AKI, ICIs shall be permanently discontinued.

Objective To explore the occurrence and characteristics of adverse reactions related to bevacizumab (Bev) in treatment of non-small cell lung cancer (NSCLC).　Methods The medical records of NSCLC patients treated with Bev in the Respiratory Department of Bozhou Hospital of Traditional Chinese Medicine from May 2019 to March 2021 were collected. Patients with Bev-related adverse reactions, which were judged by Naranjo scoring method, were selected. The relevant information in these patients was extracted from their medical records, and the occurrence and outcomes of the adverse reactions (incidence, time of occurrence, clinical manifestation, severity, etc.) were analyzed retrospectively. The dosing regimen of Bev was IV infusion of 7.5-mg/kg once per 21 days (1 cycle).　Results A total of 142 patients were included in the analysis, and 17 (12.0%), 20 (14.1%), 51 (35.9%), 35 (24.6%), and 19 (13.4%) patients received 1, 2, 3, 4, and 5 cycles of Bev treatment, respectively. All patients were treated with combination regimen with traditional chemotherapy drugs, including pemetrexed in 10 patients (7.0%), pemetrexed+carboplatin in 41 patients (28.9%), and pemetrexed+cisplatin in 91 (64.1%) patients, respectively. Among the 142 patients, 49 (34.5%) had adverse reactions, which were classified as grade 1, 2, 3, and 4 in severity in 18, 19, 6, 6 patients respectively, and the incidence of serious adverse reactions (≥ grade 3) was 8.5% (12/142). The clinical manifestations of adverse reactions included hematologic injury in 12 patients (8.5%; grade 1 in 4 and grade 2 in 8 patients), hypertension in 11 patients (7.7%; grade 1 in 4, grade 2 in 3, grade 3 in 2, and grade 4 in 2 patients), skin injury in 8 patients (5.6%; grade 2 in 5 and grade 3 in 3 patients), bleeding events in 6 patients (4.2%; grade 1 in 3, grade 3 in 1, and grade 4 in 2 patients), gastrointestinal reaction in 6 patients (4.2%; grade 1 in 3 and grade 2 in 3 patients), proteinuria in 3 patients (2.1%, grade 1), pulmonary embolism in 1 patient (0.7%, grade 4), gastric perforation in 1 patient (0.7%, grade 4), and alopecia in 1 patient (0.7%, grade 1). Bev was not discontinued in 37 patients who developed grade 1-2 adverse events, and 25 of them were given symptomatic treatments. Patients with grade ≥3 adverse reactions stopped Bev and received symptomatic treatments. All patients recovered or were improved.　Conclusions The common adverse reactions in Bev treatment for NSCLC include hematologic injury, hypertension, skin injury, bleeding events, gastrointestinal reaction, and proteinuria, most of which are of grade 1-2 in severity. Severe adverse effects such as pulmonary embolism and gastric perforation occurred occasionally. Patients with grade ≥ 3 adverse reactions have a good prognosis when Bev is discontinued and symptomatic treatments are given.

A 65-year-old man took 4 Lianhuaqingwen capsules thrice daily by himself for upper respiratory tract infection. The patient developed facial swelling and cervical lymphadenopathy after second treatment. Laboratory examination showed the following results: alanine aminotransferase (ALT) 219 U/L,  aspartate aminotransferase (AST) 106 U/L, gamma-glutamyl transpeptidase (γ-GT) 312 U/L, alkaline phosphatase (ALP) 223 U/L, total protein 65 g/L, albumin 33 g/L, albumin-globulin ratio (A/G) 1.02, total bilirubin (TBill) 14.4 μmol/L, direct bilirubin (DBil) 6.7 μmol/L, C-reactive protein (CRP) 110.4 mg/L. drug anaphylaxis and drug-induced liver injury were diagnosed. The patient was given IV infusions of polyene phosphatidylcholine 697.5 mg, reduced glutathione 2.4 g, magnesium isoglycyrrhizinate 150 mg, sodium thiosulfate 1.28 g and intramuscular injection of dexamethasone 5 mg once daily respectively. On day 6, the laboratory tests showed the following results: ALT 69 U/L, AST 19 U/L, γ-GT 275 U/L, ALP 191 U/L, total protein 56 g/L, albumin 24 g/L, A/G 0.76, TBil 16.6 μmol/L, DBil 8.5 μmol/L, CRP 148.2 mg/L。On day 16, the facial swelling disappeared. On day 21, the laboratory tests showed the following results: ALT 53 U/L, AST 36 U/L, γ-GT 155 U/L, ALP 149 U/L, total protein 76 g/L, albumin 32 g/L, A/G 0.71, TBil 6.1 μmol/L, DBil 3.1 μmol/L, CRP 89.5 mg/L.

Objective To analyze the clinical characteristics of pulmonary hypertension (PH) induced by dasatinib.　Methods The relevant databases at home and abroad (as of December 31, 2020) were searched and the case reports on PH induced by dasatinib were collected. Clinical information including patient′s basic characteristics, dasatinib dose, occurrence time of PH, clinical manifestations, interventions, and outcomes were collected and analyzed by descriptive statistical method.　Results A total of 25 patients from 24 case reports were enrolled in the study, including 16 males and 9 females, aged from 23 to 73 years with an average age of 50 years. There were 22 patients with chronic myeloid leukemia (CML) and 3 with acute lymphoblastic leukemia (ALL); the dose of dasatinib was 140-mg daily in 14 patients, 100-mg daily in 7 patients, 70-mg daily in 2 patients, and unknown in 2 patients. Time from dasatinib application to PH occurrence was 10 days to 144 months, with a median time of 37 months. The clinical symptoms included varying degrees of dyspnea in 24 patients, edema in 8 patients, hepatomegaly in 5 patients, jugular vein dilatation in 5 patients, cough in 3 patients,and chest tightness in 3 patients, chest pain in 2 patients, and fatigue in 1 patient. Pleural effusion and/or pericardial effusion were found in 20 patients by chest CT, chest X-ray or echocardiography. Cardiac function was graded as Ⅳ in 8 patients, Ⅲ in 9 patients, and Ⅱ in 4 patients according to WHO classification method, and the grade was unknown in 4 patients. Right cardiac catheterization and/or echocardiography showed elevated mean pulmonary artery pressure and/or systolic pulmonary artery pressure in 25 patients. Twenty-four patients stopped dasatinib following the doctor′s advice after the diagnosis of PH, of which 22 patients were treated with phosphodiesterase 5 inhibitor, endothelin receptor antagonist, diuretic, and glucocorticoid, and the other 2 patients were not given special intervention; one patient took dasatinib intermittently by himself. Nineteen patients were switched to other tyrosine kinase inhibitors. After discontinuation of dasatinib and giving symptomatic treatments for 1 week to 36 months (mean 7 months), 17 patients were improved, 7 were partially improved, and 1 had unknown outcome.　Conclusions Dasatinib-related PH was more common in patients with CML, occurred more in male patients, and had a median occurrence time of 37 months after drug administration. The main clinical manifestation was dyspnea, often complicated with pleural effusion or pericardial effusion. After dasatinib withdrawal and specific treatments, most patients could be improved.

A 15-year-old female patient with autoimmune encephalitis received methylpredniso- lone combined with plasma exchange and symptomatic treatments for convulsions, abnormal mental behavior, and involuntary facial and limb movements, including levetiracetam 0.5 g orally once per 12-hours, intramuscular injection of phenobarbital injection 0.1 g once per 6 hours, clonazepam 2-mg orally once per 8 hours, and gabapentin capsules 0.3 g orally once per 8 hours. Four days later, the dose of gabapentin was doubled; 7 days later, the patient had menstruation, but the amount of menstruation was very small; 10 days later, the patient developed lactation with serum prolactin 36.69-μg/L. Hyperprolactinemia was then diagnosed, which was considered to be related to gabapentin. Gabapentin was stopped and other drugs were continued. Six days later, the patient′s lactation disappeared and prolactin was 15.65-μg/L. In the following month, the patient′s menses returned to normal.

A 68-year-old male patient with severe active ulcerative colitis developed sleep disorder after using hormone pulse therapy. He received dexzopiclone 3-mg orally once a night to improve sleep. On the next day of medication, the patient developed ataxia symptoms such as dizziness, head drooping, and body skewing when walking, etc. The patient had a history of Parkinson′s syndrome and treatment effect of levodopa and benserazide hydrochloride was good. Dyskinesia caused by levodopa and benserazide hydrochloride were suspected. Then the drug was stopped and symptomatic treatments were given for 3 days, but his symptoms were not improved. After consultation with the neurologist, the patient was diagnosed as having ataxia, which was suspected to be related to dextrzopiclone. Four days after dextrzopiclone withdrawal, the patient′s symptoms were improved obviously. The patient resumed to use levodopa and benserazide hydrochloride before discharge and the ataxia symptoms above mentioned did not recur.

A 40-year-old female patient took ibuprofen dispersible tablets twice (0.4 g, 3-4 hours interval) by herself due to fever. One hour after the second medication, the patient developed nausea, vomiting, and small bleeding spots on skin. One day later, she developed yellowish skin and sclera. Three days later, her urine output decreased to 300-400-ml daily. Five days later, laboratory tests showed alanine aminotransferase (ALT) 3-531-U/L, aspartate aminotransferase (AST) 811-U/L, total bilirubin (TBil) 149.7-μmol/L, creatinine (Scr) 753-μmol/L, and uric acid (UA) 800-μmol/L. She was diagnosis as having severe liver injury and acute renal failure, which was considered to be associated with ibuprofen. After 6 days of treatments such as liver protection, continuous renal replacement therapy (CRRT), and fresh frozen plasma infusion, the patient′s yellowish skin and sclera were relieved and small bleeding points reduced. Laboratory tests showed ALT 513-U/L, AST 36-U/L, TBil 31.5-μmol/L, Scr 281-μmol/L, and UA 241-μmol/L. Her urine volume was 2-500-ml per day. After CRRT was stopped and liver-protective treatment was continued for 14 days, the yellowish skin subsided and the bleeding points disappeared. Laboratory tests showed ALT 55-U/L, AST 39-U/L, TBil 15.6-μmol/L, Scr 101-μmol/L, and UA 237-μmol/L, and her urine volume was 4-000-ml per day.

Objective To understand and analyze the occurrence of medication error (ME) on warfarin and their related factors in order to avoid or reduce adverse events.　Methods All ME reports in the National Monitoring Network for Clinical Safe Medication (monitoring network) from January 1, 2016 to December 31, 2020 were collected and warfarin ME reports were selected. The grading and contents of warfarin MEs, the persons who caused and found the errors, and the factors that triggered the errors were analyzed.　Results During the set period, a total of 59-987 ME reports from 30-hospitals in 13 provinces and municipalities in China were collected in the monitoring network, which included 149 ME reports (0.3%) of warfarin, involving 149 patients. Among the 149 patients, 94 were male (63.1%) and 55 were female (36.9%), aged 2-87 years. The indications of warfarin were atrial fibrillation in 78 patients, mechanical valve replacement in 47 patients, thrombosis in 10 patients, pulmonary embolism in 10 patients, and congenital heart defect in 4 patients. One hundred and thirty-two MEs (88.6%) were mild and 17 (11.4%) were severe, of which 1 caused patient death. Among the warfarin MEs, dose errors ranked the first, accounting for 29.5% (44/149), followed by medication frequency error (26.2%, 39/149) and wrong drug class (22.2%, 33/149). Among the 149 MEs, 102 (68.5%) were triggered by doctors, 25 (16.8%) were by pharmacists, and 22 (14.8%) were by patients/family members. In the 102 MEs triggered by doctors, 94 were intercepted by pharmacists or nurses and 8 were not intercepted, which were all severe MEs ［7 were drug selection errors (drugs were not selected based on drug interaction) and 1 were wrong dose］. In the 25 MEs triggered by pharmacists, 24 were intercepted by pharmacists, nurses, or patients/family members and 1 was not intercepted, which was dose error(severe); the patient involved in the severe ME was treated with combined anticoagulant therapy and no thromboembolic events occurred. In the 22 MEs caused by patients/family members, 14 were intercepted by doctors, nurses, or pharmacists and 8 were not intercepted, which were severe MEs, including 1 dose error (causing patient death), 2 frequency errors, and 5 drug class errors. A total of 132 MEs were found in time and successfully intercepted. Among the persons who found the MEs, 61 were pharmacists, accounting for 46.2%; 53 were nurses, accounting for 40.1%; 10 were doctors, accounting for 7.6%; 8 were patients/family members, accounting for 6.1%. The main factors causing MEs were lack of knowledge(accounting for 57.1%, 85/149), fatigue, misreading, and machine fault (accounting for 22.8%, 34/149), and unskilled technology (accounting for 13.4%, 20/149) in order.　Conclusions In the content of warfarin MEs, dose error ranks the first, and drug class errors and drug selection errors usually cause severe MEs. Pharmacists play an important role in discovering and intercepting the warfarin MEs. Lack of knowledge is the primary factor causing MEs.

Objective To establish a prescription pre⁃audit system based on the structureprocess⁃outcome (SPO) model in the the Affiliated Hospital of Qingdao University and explore its application effect. Methods Based on the structural dimension of SPO model, the organizational structure, pharmaceutical team, management system of pharmaceutical prescription audit, and audit environment of the prescription pre⁃audit system were established. Based on the process dimension of SPO model, the preaudit process, medication knowledge base, and audit rule base were established, quality monitoring and control were implemented, and relevant personnel training were conducted. Based on the outcome dimension of SPO model, the review rate, manual review rate, clinician acceptance rate of prescription review, reasonable rate of outpatient and emergency prescription comments, and intervention rate of inpatient medical order were verified after the prescription pre⁃audit system application. Results The prescription preaudit system was first launched in the main hospital area of the Affiliated Hospital of Qingdao University in March 2021, and achieved full coverage in all five hospital areas by May 2023. The review rates of outpatient and emergency prescriptions and inpatient medical orders had been increasing year by year from 2021 to 2023, and all reached more than 99% of the expected rates in 2023. Compared with 2021, the proportions of outpatient and emergency prescriptions and inpatient medical orders submitted to manual review decreased in 2023
[1.2% (112 206/9 509 430) vs. 2.9% (16 214/549 672), 2.9% (206 258/7 152 620) vs. 3.9% (147 679/3 814 929), the proportions of prescriptions that failed to be reviewed in time decreased [0.7% (62 382/9 509 430) vs. 1.4% (7 429/549 672), 0.3% (22 816/7 152 620) vs. 2.2% (83 303/3 814 929)], and the acceptance rates of outpatient and emergency prescription review and inpatient medical orders review by clinicians increased [76.1% (2 421/3 180) vs. 57.0% (339/595), 94.3% (1 000/1 060) vs. 70.7% (797/1 128)],
with statistically significant differences (all P<0.001). But there were still some prescriptions and orders that needed manual review but were not reviewed in time and finally missed review. Compared with 2021, the reasonable rates of outpatient and emergency prescription comments increased in 2023 [96.7% (924 558/956 252) vs. 92.2% (983 827/1 067 357), 98.7% (518 307/525 227) vs. 98.0% (181 296/185 069)], and the intervention rate of inpatient medical orders decreased [0.7% (196 522/26 751 992) vs. 0.9% (195 660/22 631 289)], with statistically significant differences (all P<0.001). Conclusions Applying the SPO model can improve the organization and management of the prescription pre⁃audit system, and ensure the smooth launch and safe operation of the system. After verification, the operating speed of the prescription pre⁃audit system and prescription review speed of pharmacists could basically meet the clinical needs, the indicators of rational drug use in the hospitals were improved, and the professional and technical ability of pharmacists were enhanced.

我国《新型冠状病毒肺炎诊疗方案（试行第六版）》在中医治疗中推荐了6个品种的口服中成药，包括藿香正气方（胶囊、丸、水、口服液）、金花清感颗粒、连花清瘟方（胶囊、颗粒）、疏风解毒方（胶囊、颗粒）、苏合香丸和安宫牛黄丸。其中藿香正气方、金花清感颗粒、连花清瘟方和疏风解毒方仅推荐在医学观察期使用，但也有用于新型冠状病毒肺炎轻型和普通型患者的报道；而苏合香丸和安宫牛黄丸则仅用于新型冠状病毒肺炎危重症患者。这6种口服中成药的安全性较好，很少有不良反应发生，但临床应用时应注意中医辨证、禁忌证、配伍禁忌，避免主治证型相似的药物叠加使用，加强不良反应的监测。

 A 26-year-old female patient took oral methimazole 20-mg twice daily due to hyperthyroidism. More than a month later, she developed spastic pain of limb muscles. Laboratory tests showed alanine aminotransferase (ALT) 45-U/L, aspartate aminotransferase (AST) 121-U/L, creatine kinase (CK) 6-090-U/L, and serum potassium 4.1-mmol/L. The dose of methimazole was reduced to 10-mg once daily, but the patient′s myalgia was not improved after 3 days. Adverse reactions due to methimazole were considered and therefore the drug was discontinued. Four days after drug withdrawal, the patient′s myalgia was obviously relieved, and laboratory tests showed ALT 36-U/L, AST 50-U/L, and CK 1-954-U/L. After 18 days of drug withdrawal, her myalgia disappeared, and the ALT, AST, and CK returned to normal.

A 60-year-old male patient was hospitalized due to acute attack of bronchial asthma and pneumonia and antitussive, antiasthmatic, and anti-inflammatory treatments was given. Then his symptoms were improved. Discharge medication included budesonide and formoterol fumarate powder for inhalation and montelukast sodium. On the 4th day of medication after discharge, the patient developed bilateral metatarsophalangeal joint pain with redness and swelling, abdominal distension, fatigue, and dark urine. Laboratory tests showed serum creatinine (Scr) 112-μmol/L, serum uric acid 228-μmoL/L, urine protein (+), and urine occult blood (++). Gout, rheumatoid arthritis, and other autoimmune diseases were excluded and the possibility of acute kidney injury and metatarsophalangeal joint pain related to montelukast sodium was considered. Montelukast sodium was discontinued, budesonide and formoterol fumarate powder for inhalation was continued, and symptomatic treatment was given at the same time. Seven days later, the pain of metatarsophalangeal joint was improved and the urine color returned to normal. Two weeks later, his Scr level returned to normal (75-μmol/L).

Objective To systematically evaluate cardiotoxicity of programmed cell death 1 receptor (PD-1)/programmed cell death ligand 1 (PD-L1) inhibitors.　Methods Clinical trials of PD-1/PD-L1 inhibitor alone or in combination with other treatments for tumors were collected by searching related databases at home and abroad (up to March 2, 2019). The methodological quality of studies was evaluated using the internationally accepted Cochrane collaboration′s risk of bias assessment tool. A meta-analysis was performed using RevMan 5.3 software to compare the incidences of cardiotoxicity between PD-1/PD-L1 inhibitors (trial group) and placebo or other antineoplastic agents(control group).　Results A total of 10 randomized controlled trials (RCTs) were enrolled, 9 of which were about PD-1 inhibitor alone or in combination with other antineoplastic agents, and 1 of which was about PD-L1 inhibitor monotherapy. There were a total of 5-291 patients, including 3-022 in the trial group and 2-269 in the control group. Evaluation of the methodological quality for studies showed that 4 RCTs were at high risk of bias and the other 6 were at low risk of bias. The meta-analysis showed that the incidence of cardiotoxicity in the trial group was significantly higher than that in the control group, and the difference was statistically significant［1.13% (34/3-022) vs. 0.22% (5/2-269), RR=2.38, 95%CI: 1.19-4.78, P=0.01］.　Conclusion PD-1/PD-L1 inhibitors have the risk of causing heart related adverse events, which should be paid attention to in clinical application.

随着人们生活水平的提高,已不满足于单纯的治疗药物,常服用一些抗衰老的保健药品,其中以中药因其“纯天然”的优势越来越受到青睐,一般认为中药药性平和,服用安全,纯中药制剂不会中毒,临床上常用的补益类中药有西洋参、灵芝、冬虫夏草、鹿茸、黄芪、何首乌、党参、白术、熟地、生地、当归、白芍、麦冬、丹参等,但这些补益类中草药在不同程度上都可产生不良反应。本文对近几年来几种补益类中草药的不良反应的国内文献作一介绍,通过病例说明补益药不是可以盲目服用,提倡合理使用补益类中草药。

A 62-year-old female patient with stomach cancer received an IV infusion of oxaliplatin and mannitol injection on day 1 and oral tegafur， gimeracil, and oteracil potassium on days 1-14 in a 21-day cycle after radical mastectomy. Pretreatment with dexamethasone and other drugs was given 3 hours before the infusion to alleviate possible adverse reactions. During the 1st cycle of chemotherapy, the patient had no other adverse reaction except nausea and fatigue, and no intervention was given. About 2 hours after oxaliplatin and mannitol injection in the 2nd cycle, the patient′s limbs were swollen and flushed, and red patches appeared on the skin. Then the erythema increased and merged into patches and her skin on the feet was desquamated. The above symptoms were improved after anti-allergic treatments. About 3 hours after oxaliplatin and mannitol injection in the 3rd cycle, the patient developed dyspnea, and systemic skin flushing and swelling accompanied by scratches. Then visible blisters on part of the skin appeared, which cracked at the flexion of the joints with exudate impregnation. The patient was given anti-allergic therapy such as prednisolone. Four days later, her skin on the whole body showed scaly desquamation, her hands and feet showed gloved desquamation, and she was diagnosed as having exfoliative dermatitis; 9 days later, her skin color became lighter and there was no new rash. Considering that exfoliative dermatitis was caused by oxaliplatin and mannitol injection, the chemotherapy regimen was switched to docetaxel (day 1) and tegafur, gimeracil, and oteracil potassium (days 1-14). The skin allergic reactions did not recur.

A 69-year-old female patient with diabetes mellitus was scheduled to undergo angiography of head because of acute cerebral infarction. When iopromide injection-370 was injected intravenously with a high-pressure syringe before operation, the contrast medium extravasated at the injection site of her right hand, resulting in severe subcutaneous hematoma, tissue necrosis, and infection. The maximum area of extravasation wound extended to 6.0-cm × 7.0-cm. Therapies such as local wet compress with cold 50% magnesium sulfate and dexamethasone, daily debridement and dressing change, and external application of hydrogel, silver containing hydrophilic foam, and hydrocolloid were given. On day 14 after extravasation, the necrotic tissue of the wound gradually fell off and the wound began to heal. Then the wound healed on day 35 after extravasation.

ObjectiveTo develop primary standard of potentially inappropriate medication (PIM) in Chinese aged people under morbid state and provide the basis and guide for clinical rational drug use in aged people.MethodsStandards of PIM in aged people under morbid state of the United States, Canada, Thailand, South Korea, and the Taiwan area of China were collected and, after summarizing, removing duplication, and integrating, the first round questionnaire was designed according to Delphi method to ask for the experts′ opinions. The experts′ feedback and suggestions were organized and the second round questionnaire was designed to ask for opinions again. Authoritative coefficient, positive coefficient, coordinate coefficient, mean score, and full mark rate were calculated. The selected drugs were respectively divided into grade A (frequency ≥ 3 000) and B (frequency < 3 000) standard according to medication frequency.ResultsThirty nine and 38 experts respectively took part in the 2 rounds of Delphi method investigations, who were selected from 23 grade Ⅲa hospitals in 11 provinces and 3 municipalities directly under the central government. These experts′ specialties involved 11 clinical medical specialties including neurology, psychiatry, cardiology, gastroenterology, endocrinology, urogenital epidemiology, gerontology, general medicine, pain medicine, dermatology, and respiratory medicine and 3 pharmacy specialties including clinical pharmacy, clinical pharmacology, and hospital pharmacy. After the 2 rounds of investigations, all of the authoritative coefficients of the experts were above 0.7, all of positive coefficients were 100%, and the first coordination coefficient were 0.17 and 0.21, respectively. Meanwhile, the mean scores were 3.65 and 3.94 and the means of full mark rates were 0.15 and 0.32, respectively. The first round investigation contained 188 points of drug-induced risks of 89 species (categories) of drugs under 31 kinds of morbid states and the second round investigation contained 74 points of drug-induced risks of 44 species (categories) of drugs kinds of morbid states. These indexes listed in the second round investigation were all enrolled the primary standard of PIM in Chinese aged people under morbid state. Grade A standard contained 62 points of drug-induced risks of 35 species (categories) of drugs under 25 kinds of morbid states, and grade B standard contained 12 points of drug-induced risks of 9 species (categories) of drugs under 9 kinds of morbid states.ConclusionsThe development of primary standard of PIM in Chinese aged people under morbid state has completed preliminarily. However, the standard still needs to be improved by clinical application to be used as a powerful tool for promoting rational drug use and lowering drug-induced risks of aged people.

A 76-year-old male patient with small cell lung cancer received EC (etoposide and carboplatin) chemotherapy combined with camrelizumab. On the 22th day of medication, the patient deve- loped chest tightness, shortness of breath, dyspnea, limb weakness, walking difficulty, etc. Laboratory tests revealed creatine kinase (CK) 1-210-U/L and CK-MB 63 U/L. The chemotherapy and immunotherapy were stopped, but the patient′s symptoms continued to worsen. Laboratory tests showed troponin T (TnT) 336-ng/L, CK 1-025-U/L, CK-MB 74-U/L, and N-terminal pro brain natriuretic peptide (NT-proBNP) 648-ng/L. The muscle magnetic resonance imaging (MRI) and electromyogram showed muscle injury and cardiac MRI showed left ventricular fibrosis. Then immune-related skeletal muscle and myocardial injury caused by camrelizumab was considered. The patient received an IV infusion of methylprednisolone sodium succinate for injection 100-mg once daily for 13 days. Then the patient′s fatigue symptoms were improved, the levels of CK and NT-proBNP decreased to the reference range, but the levels of TnT and CK-MB were 491-ng/L and 113-U/L, respectively. Therefore, an intravenous infusion of immunoglobulin 20 g once daily was given. Five days later, his dyspnea was improved, and TNT and CK-MB decreased to 201-ng/L and 59-U/L, respectively.

Objective To explore the clinical characteristics of anaphylaxis caused by gonado- relin in children in gonadotropin-releasing hormone (GnRH) stimulation test.　Methods The research subjects were children aged ≤14 years who experienced anaphylaxis using gonadorelin in the Chengdu Adverse Reaction Center database from January 1, 2015 to December 31, 2021. The purpose of medication was GnRH stimulation test. Through the hospital information system, the children′s basic information, usage of gonadorelin, occurrence of severe allergic reactions, and treatments and outcomes of anaphylaxis were collected and retrospectively analyzed.　Results A total of 14 cases of anaphylaxis in children caused by gonadorelin in the GnRH stimulation test were collected, including 3 males and 14 females, with an age of (9±2) years. All 14 cases were evaluated with a score of ≥5 using the Naranjo evaluation method. The dose of gonadorelin in the 14 children was (2.55±0.09) μg/kg and the drug was all given by intravenously injection; anaphylaxis occurred in 4 children during the first GnRH stimulation test and in 10 children during the second GnRH stimulation test. The time from medication to anaphylaxis occurence was (6.0±3.5) minutes. The symptoms of anaphylaxis in 14 children were systemic allergic reactions, involving various systems throughout the body. All children had 3 or more types of systemic damage. After anaphylaxis occurrence, gonadorelin was discontinued in all 14 patients; 5 received intramuscular injection of adrenaline, 5 received intravenous injection of adrenaline, 1 received intravenous injection of isoprenaline and intramuscular injection of adrenaline, and 3 received intravenous injection of dexamethasone only. After treatments, all children were improved.　Conclusions Anaphylaxis caused by gonadorelin in children is a rare but severe adverse reaction, and the drug may have a possibility of cross allergy with GnRH analogues. Therefore, when diagnosing and treating precocious puberty in children, medication should be given under monitoring conditions.

Anticancer drugs play an important role in the treatment for malignant tumors. The kidney function of patients has an important impact on the choice of anticancer drugs, the safety during treatments, and the prognosis of patients. All cancer patients should undergo comprehensive kidney function assessment before using anticancer drugs, so as to formulate an individualized anticancer regimen. The Japanese Society of Nephrology, Japan Society of Clinical Oncology, Japanese Society of Medical Oncology, and Japanese Society of Nephrology and Pharmacotherapy have formulated the Clinical Practice Guidelines for Management of Kidney Injury During Anticancer Drug Therapy 2022 and made special discussions and suggestions on the evaluation of kidney function of tumor patients before anticancer drug treatment. This article interprets this part in order to made a more comprehensive understanding on the occurrence and risk factors of kidney disease in cancer patients in the clinic. Paying attention to the kidney function assessment of cancer patients before anticancer drug treatment and mastering the correct assessment methods can help improve the kidney safety of cancer patients during treatments.

Objective To explore the occurrence and clinical characteristics of hyperprogression of metastatic malignant melanoma caused by toripalimab (JS001).　Methods The medical records of patients with metastatic malignant melanoma treated with JS001 alone or in combination with other antineoplastic agents between February 2018 and September 2019 in Department of Kidney Cancer and Melanoma of Beijng Cancer Hospital were collected. Patients displaying hyperprogression were screened into the case group, who were matched with those without hyperprogression evidence (the control group) in a 1/4 ratio according to baseline age, gender, Eastern Cooperative Oncology Group score, location of the primary lesion, and elevated level of lactate dehydrogenase (LDH). The clinical characteristics and prognosis of patients between the 2 groups were compared and the hyperprogression in the case group was analyzed descriptively.　Results A total of 130 patients with metastatic malignant melanoma who received JS001 alone or in combination with other antineoplastic agents were collected. Hyperprogression occurred in 8 patients (the case group), including 5 males and 3 females, aged (52.5±8.5) years. The incidence of hyperprogression was 6.15%. Thirty-two patients without displaying hyperprogression were matched as the control group according to the baseline characteristics of patients in the case group. Patients with metastatic lesions in more than 2 organs at baseline in the case group were significantly more than those in the control group (6/8 vs. 7/32, P=0.014); the LDH level of patients in the case group significantly increased after treatment than before ［(965±710) U/L vs. (264±64) U/L, P=0.025］; the progression-free survival and overall survival in patients were significantly lower than those of patients in the control group ［1.7 (95%CI: 1.4-2.0) months vs. 3.1 (95%CI: 2.7-3.5) months, P<0.001; 4.8 (95%CI: 0-11.2) months vs. 10.7 (95%CI: 10.4-10.9) months, P=0.031］.　Conclusions Patients with melanoma may experience hyperprogression in early stages of JS001 treatment. Patients with metastatic lesions in more than 2 organs before treatment are more likely to develop hyperprogression, and patients displaying hyperprogression have a poor prognosis. Serum LDH level monitoring can help detect tumor hyperprogression as early as possible.

A 61-year-old female patient underwent intestinal preparation before electronic colonoscopy. She took polyethylene glycol electrolytes powder (Ⅳ) in 6 times (dissolved content A 24 bags and B 24 bags in warm water 3-000-ml and then took 500-ml orally per 30-minutes). During the intestinal preparation, the patient′s urine output was about 4-500-ml, diarrhea occurred 8 times, and she vomited 2 times within 5.5-hours. The patient fell into a coma at 14:00 on the day, accompanied by limb convulsion and trismus. Laboratory tests showed that the serum sodium and potassium decreased from 140-mmol/L and 4.0-mmol/L to 120-mmol/L and 2.7-mmol/L before and after treatment, respectively. In addition, his chloride was 87.2-mmol/L and bicarbonate was 11.5-mmol/L. Blood gas analysis showed pH 7.29-mmHg, partial pressure of carbon dioxide 31-mmHg, partial pressure of oxygen 105-mmHg, and base excess -10.4-mmol/L. Metabolic acidosis was diagnosed. Head CT and MRI showed no abnormalities. Electrolyte disorder, metabolic acidosis, and hyponatremia encephalopathy due to hyponatremia caused by polyethylene glycol electrolytes powder (Ⅳ) was considered. Oxygen inhalation, continuous ECG monitoring, correction of electrolyte disorders, correction of acidosis, rehydration, and other symptomatic and supportive treatments were given immediately. After 4 hours of treatments, the vital signs of the patient were gradually stable but she was still in a coma. On the third day of treatments, the patient was conscious, her serum electrolytes returned to normal, and no seizures occurred.

治疗心血管病常用药物在医治躯体疾病的同时,可能影响病人的性生活质量,其中用于冠心病二级预防的药物尤为明显。本文综述了近年来治疗心血管病常用药物对性功能的影响、作用机制及防治方法。

A 68-year-old male patient with type 2 diabetes mellitus received saxagliptin, metformin, and voglibose for 10 months, voglibose was switched to acarbose due to poor blood glucose control firstly and then to empagliflozin (oral 10-mg thrice daily) 2 days later. Next day，compound tropicamide eye drops was used to mydriasis and 3 hours later (2 hours after the second administration of empagliflozin), the patient developed scattered red wheal like rash with pruritus on the chest and abdomen, followed by eyelid edema. Considering allergy to compound tropicamide eye drops, loratadine and cetirizine were given, the rash gradually subsided, but the skin pruritus increased. Diffuse red macules and papules, which faded from pressure, gradually appeared on his trunk and upper limbs. Allergic dermatitis caused by empagliflozin was considered after consulting the dermatologist, empagliflozin was discontinued, fexofenadine and calamine lotion were added, and the rash subsided. Due to the patient′s condition, empagliflozin was readministered 3 days later, and the patient experienced a skin allergic reaction again 9 days after the treatment. Empagliflozin was stopped again and the rash did not recur after anti-allergic treatment. It was considered that the patient′s skin allergic reaction was possibly related to empagliflozin.

Sodium-glucose transporter 2 inhibitors (SGLT2i) are novel oral hypoglycemic agents, which reduces blood glucose by inhibiting the reabsorption of glucose in the proximal convoluted tubule of the kidney and increasing the excretion of glucose to the urine. SGLT2i is effective in the treatment for diabetes mellitus, but there are also some safety problems. Diabetic ketoacidosis (DKA) is a serious adverse reaction of SGLT2i. SGLT2i could cause at least a 7-fold increase in developing DKA, approximately 70% of which are euglycemic DKA (euDKA). The risk factors for euDKA include insufficient insulin secretion cell reserve, type 1 diabetes mellitus, insulin reduction or discontinuation, hypovolemia, perioperative period, weight loss, and restricted feeding, etc. Because the increase of blood glucose in patients with euDKA is not obvious, the diagnosis is often delayed, so close attention should be paid to it. Safety medication training for SGLT2i should be strengthened to improve clinicians′ understanding of SGLT2i-related euDKA, so that they can strictly grasp the indications of medication and avoid the inducement of euDKA. Once euDKA occurs, clinicians can make early diagnosis and treatment. Pharmacists should be involved in the safety management of patients using SGLT2i to improve the safety in treatment.

A 32-year-old female patient received long-term use of paroxetine 40-mg/d orally for depression. Because of uncontrolled behavior, the patient took paroxetine about 1-000-mg at one time. About 24-hours after taking the medicine, the patient developed cough and expectoration, followed by dyspnea, and 2 days later, the patient became unconscious. The partial pressure of oxygen was 38-mmHg, and the partial pressure of carbon dioxide was 43-mmHg. Chest CT showed ground glass opacities in bilateral lungs, indicating interstitial pulmonary edema. Acute lung injury and respiratory failure were diagnosed. Then mechanical ventilation via a tracheal cannula, continuous intravenous pumping of methylprednisolone 160-mg/d, and symptomatic treatments such as anti-infection, fluid infusion, correction of acid-base imbalance were given. Her respiratory condition was gradually improved, and the partial pressure of oxygen gradually returned to normal; 5 days later, the ventilator was stopped and the tracheal tube was removed.

A 52-year-old male patient took one compound paracetamol and amantadine hydrochloride capsule （each capsule contains 250-mg acetaminophen, 100-mg amantadine hydrochloride, 2-mg chlorphenamine maleate, 10-mg artificial bezoar, and 15-mg caffeine） by himself for a cold. Half a day after the medication, the patient developed erythema with itching on the back. The next day the rash worsened and spread throughout the body, involving the mouth, eyes, and scrotal mucosa. Then the skin rash developed into big herpes with epidermal sloughing, and the area of skin damage reached to 90%, accompanied by mild liver injury and blood glucose rise. Epidermolysis bullosa type eruption was diagnosed. High-dose glucocorticoids, immunoglobulins, and symptomatic and supportive treatments were given and her skin lesions largely recovered 3 weeks later. The patient′s epidermolysis bullosa type eruption was consi- dered to be probably related to the acetaminophen in compound paracetamol and amantadine hydrochloride capsules.

 A 35-year-old female patient received metronidazole sustained release tablets 0.75 g once daily and cefuroxime axetil 0.25 g twice daily after hysteroscopy curettage for infection. Because of postoperative fever and cough, she took ibuprofen granules 0.2 g each time orally by herself. After 3 days of treatments with metronidazole sustained release tablets and cefuroxime axetil and 4 times of ibuprofen granules, the patient developed right upper abdominal pain and dark urine. On the next day, the patient′s right upper abdominal pain was aggravated progressively, she developed soy sauce-like urine and yellowish skin and sclera. Laboratory tests showed alanine aminotransferase (ALT) 403-U/L, aspartate aminotransferase (AST) 248-U/L, gamma glutamyl transpeptidase (γ-GT) 327-U/L, alkaline phosphatase (ALP) 58-U/L, total bilirubin (TBil) 72.5-μmol/L, and direct bilirubin (DBil) 41.5-μmol/L. Liver injury induced by concomitant use of metronidazole and ibuprofen was considered. Metronidazole and ibuprofen were stopped and liver-protective and symptomatic treatments were given. Cefuroxime axetil was continued. Three days later, the patient′s abdominal pain disappeared gradually, her urine color became lighter, the yellow staining of skin and sclera was alleviated, and the respiratory symptoms were improved. Nine days later, the reexamination of liver function showed ALT 88-U/L, AST 35-U/L, γ-GT 185-U/L, ALP 52-U/L, TBil 19.6-μmol/L, and DBil 9.7-μmol/L.

Since healthy volunteers usually have no expected direct clinical benefits in clinical trial, it is particularly important to fully assess the risks and carry out safety monitoring in all links of the trial in combination with their group characteristics. The risk points for healthy volunteers to participate in clinical trials lie in the aspects of trial drugs, clinical trial design, and trial implementation process. The safety and rights of healthy volunteers should be better protected by implementing the Good Pharmacovigilance Practices, improving the level of risk management, enhancing the transparency of clinical trial results, and carrying out relevant risk management research.

A 6-year-old girl received sinupret oral drops and mometasone furoate aqueous nasal spray for allergic rhinitis for more than 1 month, but her symptoms were not improved. Additional use of oral montelukast sodium chewable tablets 4-mg every night was given due to adenoid hypertrophy. After 7 days of montelukast sodium administration, the girl developed somnambulism once per week, which manifested as sitting up suddenly in the dream and lying down to sleep after 1-minute. Two months later, all drugs were stopped because the nasal symptoms were relieved and no sleepwalking occurred 1 week after drug withdrawal. More than a year later, the above 3 drugs were given by her parents due to the recurrence of rhinitis and the girl developed somnambulism again with worse symptoms 5 days later. After 2 weeks of continued medication, somnambulism continued to worsen. Montelukast sodium was stopped, symptoms of somnambulism were relieved 2 days later and disappeared 1 month later. Considering that somnambulism in the girl was an adverse reaction to montelukast sodium, it was replaced by oral loratadine 5-mg every night. At 3 months of telephone follow-up, the somnambulism did not occur in the girl.

Objective To construct a recommended list of high-alert medication (HAM) based on big data from medication error (ME) reports in China, providing reference for preventing and reducing HAM-related risks.　Methods The drugs involved in the serious ME reports of the National Monitoring Network for Clinical Safe Medication (Monitoring Network) were collected (as of December 31, 2023), and the candidate drugs were preliminarily determined referring to the HAM list of China 2023 (Chinese list) and the latest three lists of American Institute for Safe Medication Practices (ISMP). Candidate drugs that were included in both the Chinese list and ISMP lists, as well as those existed in the Chinese list but had never been included in the ISMP lists were included in the current list, and their risk levels followed the original risks in the Chinese list. Candidate drugs that existed in the Chinese list but had been excluded from the ISMP lists, and those existed in the ISMP lists but had not been included in the Chinese list were listed as suspected drugs. For the other candidate drugs, those did not meet the definition of HAM were excluded firstly, and those related to ME that had caused serious harm were listed as suspected drugs, according to the judicial cases on ME of China Judgements Online and PKULAW database. Two methods, including Delphi expert consultation and questionnaire survey, were used to determine whether the above suspected drugs were included in the HAM list and their risk levels.　Results A total of 138 drugs were obtained through the initial screening, 106 of which were directly included in the current list, and 32 of which were listed as drugs requiring further assessment. After 2 rounds of Delphi expert consultation by 18 experts and surveys with 136 valid questionnaires, 32 suspected drugs did not meet the inclusion criteria. Finally, a total of 106 drugs were included in the current list, including 51 A-class drugs in 9 categories, 33 B-class drugs in 9 categories, and 22 C-class drugs in 5 categories.　Conclusion Based on the big data of the ME reports in China, a HAM list is constructed, which is accurate and concise and better fits the actual clinical drug risks in China, helping to improve the drug safety management.

A female infant aged 7 months and 29 days received an IV infusion of ceftriaxone sodium for injection (ceftriaxone sodium) 0.5 g dissolved in 0.9% sodium chloride injection 100-ml once daily because of acute diarrhea, moderate dehydration, and myocardial injury. Symptomatic treatments such as maintaining water and electrolyte balance and nourishing myocardium were given at the same time. Her platelet count (PLT) was 269×109/L before treatment. On day 4 of treatments, the laboratory test showed that her PLT was 893×109/L. Infection-induced thrombocytosis was considered and ceftriaxone sodium was continued at the original dose. On day 6 of treatments, her PLT was 931×109/L; on day 8 of treatments, her PLT increased to 1-018×109/L. It was considered that the increase of PLT might be related to ceftriaxone sodium. Ceftriaxone sodium was stopped and anticoagulant therapy was given. Six days later, her PLT decreased to 359×109/L; 19 days later, the PLT decreased to 224×109/L.

A 29-year-old female patient took vitamins with minerals tablets (29) (each tablet contains 150-μg of iodine) for nearly one year because she was preparing for pregnancy. Abnormal thyroid function was found in pre-pregnancy examination. Her free thyroxine (FT4) was 23.2-pmol/L, free triiodothyronine (FT3) was 5.56-pmol/L, and thyroid stimulating hormone (TSH) was 0.10 mU/L. According to the doctor′s advice, she stopped taking vitamins with minerals tablets (29) immediately. Five days after discontinuation of the drug, her FT4 was 21.2-pmol/L, FT3 was 5.39-pmol/L, TSH was 0.08 mU/L, and thyrotropin receptor antibody was <0.3-U/L. The results of re-examination on day 59 after drug withdrawal showed FT4-16.35-pmol/L, FT3-4.97-pmol/L, and TSH 2.36 mU/L. It was considered that the patient′s thyroid dysfunction was caused by vitamins with minerals tablets (29).

An 83-year-old male patient received IV infusions of linezolid 600-mg once per 12-hours and imipenem and cilastatin sodium 1 g once per 8 hours for incisional wound infection after cervical spinal fusion. Three days later, imipenem and cilastatin sodium was stopped according to the drug sensitive test result and linezolid was continued. Two weeks after the use of linezolid, the patient developed dry mouth, and abnormal sensation of tongue; and 18 days later, he developed black tongue coating in the center of the tongue, which could not relieved after drinking a lot of water. After that, the tooth root blackened and the denture pigmented gradually. It was considered as black hairy tongue, which might be associated with linezolid. Linezolid was stopped and compound chlorhexidine gargle was given for gargling. Twelve days later, the patient′s tongue coating returned to normal, the symptoms of dry mouth and thirst disappeared, and the color of tooth root became lighter.

A 62-year-old female patient received oral aspirin enteric-coated tablets 100-mg once daily, clopidogrel hydrogen sulphate tables 75-mg once daily, metoprolol tartrate tablets 18.75-mg twice daily, and rosuvastatin calcium tablets 10-mg once daily after coronary artery stent implantation regularly according to the doctor′s instructions. Several days later, the patient developed edema of hands and feet from the distal end to the proximal end of the extremities, and he developed facial edema with rash and pruritus at the edema site. After 3 days of antiallergic treatment, there was no obvious regression of edema and new rash. After careful inquiry, the patient said that he always developed edema and increased rash symptoms about 2 hours after taking metoprolol tartrate tablets. After discontinuation of metoprolol tartrate tablets for 1 day, and other drugs were continued to be used, the patient′s edema and rash were relieved on the next day, and the above symptoms reappeared when the drug was used again according to the doctor′s instructions on the same day. When the drug was stopped again, the edema and rash were obviously improved the next day.After 2 days of discontinuation, the patient took metoprolol succinate sustained-release tablets at their own discretion, and still developed edema and rash. After discontinuation of metoprolol succinate sustained-release tablets, the edema and rash disappeared completely 10 days later.

Objective To understand the clinical characteristics of serotonin syndrome (SS) induced by combined use of linezolid and serotonergic drugs.　Methods Relevant databases at home and abroad as of February 2021 were searched and case reports of SS induced by linezolid combined with serotonergic drugs were collected. Clinical information including patients′ basic characteristics (gender, age, underlying disease, etc.), linezolid and serotonergic drugs application (medication reasons, usage and dosage, drug elution period, etc.), and the occurrence time, clinical manifestations, intervention measures, and outcomes of SS were extracted and analyzed by descriptive statistical method.　Results A total of 50 patients derived from 46 literature were enrolled in the study, including 23 males and 27 females. Of them, 49 patients were aged from 23 to 98 years, and one patient was 4 years old. The reasons for using serotonergic drugs were mental illness (36 patients), pain (8 patients), and Parkinson′s disease (2 patients), etc.; the reasons for using linezolid were staphylococcal infection (24 patients), enterococcal infection (13 patients), and empirical anti-infection treatments (11 patients), etc. Among the 50 patients, 48 were treated with serotonergic drugs and then with linezolid, and 2 were treated with linezolid and then with serotonergic drugs; the drug washout period was not recorded in 44 patients and not long enough in the other 6 patients; the serotonergic drugs were given orally in 40 patients and by intravenous infusion in 10 patients; 35 patients had usage and dosage records, which were all in line with the requirements of drug labels; 27, 16, 5, and 2 patients were treated with 1, 2, 3, and 4 kinds of serotonergic drugs respectively, and the drugs used mainly were selective serotonin reuptake inhibitors, serotonergic drugs and norepinephrine reuptake inhibitors, tricyclic antidepressants, and opioids, etc. Except the administration route of linezolid was not mentioned in 12 patients, it was given by intravenous infusion in 27 patients and orally in 11 patients. The frequency of medication met the requirements of drug labels in 49 patients, and the medication frequency of one child was lower than that specified in the drug labels. SS occurred 3 hours to 20 days after combined use of drugs, mostly 1 to 5 days. The clinical manifestations were mental state change, autonomic nerve dysfunction, and neuromuscular dysfunction in 45, 47, and 45 patients, respectively. After discontinuation of linezolid and/or serotonergic drugs and receiving symptomatic treatments for 2 hours to 9 days, 43 patients were improved, 1 patient died of cardiac arrest after SS occurrence, and 6 patients died of the primary diseases after the symptoms of SS were controlled.　Conclusions SS due to linezolid combined with serotonergic drugs mostly occurred 1 to 5 days after combined use of above 2 drugs, and the clinical manifestations were similar to SS induced by other reasons. After discontinuation of linezolid and serotonergic drugs and symptomatic and supportive treatments, the overall prognosis is acceptable, but serious SS can lead to death.

为提高毒鼠强中毒的诊治水平,本文介绍了毒鼠强的毒性、中毒机制、临床表现和救治研究进展,旨在增强人们对毒鼠强中毒的认识,提高抢救成功率,减少死亡和后遗症。

Smoking is one of major causes leading to death and more than five million people die from smoking each year worldwide. It has become a serious public health problem. Studies have been identified that there are more than 4000 compounds in tobacco and tobacco smoke. Among them at least 43 compounds are carcinogens. Regular smoking can cause a number of diseases like cancer, emphysema, heart disease, organ damage as well as dependence (addiction). The dependence is mainly caused by nicotine containing in tobacco. Most regular smoking are addicted to nicotine. So regular smokers stopping smoking may induce nicotine withdrawal symptoms including irritability, restlessness, dizziness, headache, difficulty sleeping, and inability to concentration. Most smokers who fail to succeed in quitting smoking is mainly related to the nicotine addiction. In view of this fact, a nicotine replacement therapy (NRT) was advanced. NRT is a way of getting nicotine slowly into the body without smoking. This help people not only to stop or reduce the symptoms of nicotine withdrawal, but also avoid the hazards from smoking. The results from the various studied have showed that NRT increase the rate of success in quitting smoking, and the risk for dependence to NRT product is small. NRT medicines are available as gums, patches, inhalers, sprays, and so on. All dosage forms of NRT medicines have adverse reactions. The severity of adverse reactions are generally mild, but their types differ across NRTs. The common adverse reactions are dizziness, headache, nausea, vomiting, and gastrointestinal discomfort. NRT can safely used for pationts with cardiovascular disease. NRT is not recommended for pregnant women, nursing mothers, and adolescents. In a word, nicotine replacement therapy is safe and effective in helping smokers stop using cigarettes. NRT products have been used in many countries worldwide as OTC. It is worthy of recommendation.

A 68-year-old male patient with advanced lung squamous cell carcinoma received intravenous infusion of pembrolizumab 200-mg once every 3 weeks. One week after the 4th IV infusion of pembrolizumab, the patient developed nausea and vomiting. Laboratory tests showed blood potassium 7.39-mmol/L, fasting blood glucose 28.1-mmol/L, β-hydroxybutyric acid 3.23-mmol/L, arterial blood pH 7.16, and bicarbonate 7.5-mmol/L. The patient was diagnosed as diabetic ketoacidosis, which was considered to be associated with pembrolizumab. After 8 days of treatments such as lowering blood sugar and correcting electrolyte disorder, his nausea and vomiting disappeared. Laboratory tests showed blood potassium 3.65-mmol/L, fasting blood glucose 7.5-mmol/L, β-hydroxybutyric acid 0.38-mmol/L, and bicarbonate 25.2-mmol/L.

Selective serotonin reuptake inhibitors (SSRIs) are a widely used newer class of antidepressants, which can treat different types of depression. The commonly used SSRIs are fluoxatine, paroxetine, sertraline, fluvoxamine, and citalopram. The SSRIs can cause various types of adverse reactions. The main adverse reactions are gastrointestinal disorders, withdrawal reactions, sexual disturbances, and syndrome of inappropriate secretion of antidiuretic hormone (SIADH), etc. SSRIs may increase the risk of suicidal thinking and behaviour in children and adolescents, but the issue remained controversial. The recent studies have suggested that exposure to SSRIs early in pregnancy appeared to be no increase in the risk of congenital malformations; however, exposure to SSRIs late in pregnancy may incresae the risk of pulmonary hypertension and withdrawal reactions of the newborn. In general, breastfeeding with SSRIs is regarded as safe because the amount of drug is very low in breast milk. But the possibility of longterm effects on development in the infant is unknown. As for the elderly, SSRIs may increase the risk of fracture. Adverse reactions resulting from interations of SSRIs with some drugs are given below. MAOIs: serotonin syndrome; diuretics: severe hyponatremia; anticoagulants: increased risk of bleeding; NSAIDs: increased risk of upper gastrointestinal bleeding; tryptophan: serotonin syndrome; astemizole, terfenadine: ventricular arrhythmias and Q-T interval prolongation; haloperidol, maprotiline: severe extrapyramidal symptoms; lithium increase in plasma lithium concentration and lithium toxicity. Overall, SSRIs have fewer adverse effects than tricyclic antidepressants, but the SSRIs do have characteristic adverse reactions of their own. Therefore, doctors should exercise caution when prescribing SSRIs to patients in clinical practice.

A 63-year-old female patient was treated with 30 Mugua pills and Zhuifeng Tougu pills 6 g twice daily for tenosynovitis. After taking the medicine for 10 days, the patient developed nausea and vomiting, which were aggravated gradually; after taking the medicine for 22 days, the patient had fever, nausea, retching, slight pain in the upper abdomen, systemic edema, skin pruritus, and poor spirit, appetite, and sleep. Laboratory tests showed alanine aminotransferase (ALT) 454-U/L, aspartate aminotransferase (AST) 946-U/L, alkaline phosphatase (ALP) 133-U/L, gamma glutamyltransferase (γ-GT) 170-U/L, direct bilirubin (DBil) 12.8-μmol/L, and glutamate dehydrogenase 17.3-U/L. Viral hepatitis and biliary obstruction were excluded by laboratory tests and imaging examination. Drug-induced liver injury was diagnosed, Mugua pills and Zhuifeng Tougu pills were stopped, and diisopropylamine dichloroacetate injection and compound glycyrrhizin tablets were given. Liver function was gradually improved in the patient and laboratory tests showed ALT 62-U/L, AST 49-U/L, γ-GT 38-U/L, and DBil 7.2-μmol/L 12 days later. The medication was adjusted to 3 compound glycyrrhizin tablets thrice daily for 2 weeks. After 4 weeks, laboratory tests showed ALT 31-U/L, AST 26-U/L, γ-GT 30-U/L, and DBil 5.0-μmol/L.

对乙酰氨基酚被认为具有较好的安全性而广泛用于感冒引起的发热、头痛以及各种疼痛的治疗。但其不良反应时有发生,并且大剂量使用易引起肝损害。因此,对乙酰氨基酚的安全性与合理使用问题有必要加以讨论。

我们将药物不良反应定义为“药物用于防治疾病而引起可以觉察到的有害的或不利的反应,这预示着继续给药会有危险,需要预防或特定治疗措施,或减少剂量,乃至停药”,这样一些反应现今以世界卫生组织不良反应术语(WHO-ART)进行报告,后者终将成为国际疾病分类(ICD)的一个组成部分。药物不良反应可分为6类(首字母记忆法):剂量相关型(Augmented,剂量增大),剂量无关型(Bizarre,异乎寻常),剂量相关和时间相关型(chronic,慢性),时间相关型(Delayed,迟发),停药型(End of use,终止使用),治疗失败型(Failure,失败)。时间关联,疾病类型,调查结果,再激发诸方面有助于确认可疑药物不良反应的因果关系。管理包括停药(如果可能的话),及对药物不良作用进行特殊治疗。可疑的药物不良反应应该报告,监测方法能够检出不良反应,并证实其因果关联。

Nucleoside/nucleotide analogues (NAs) which used to treat chronic hepatitis B and had been in the domestic market include adefovir dipivoxil (ADV), tenofovir (TDF), lamivudine ( LAM), telbivudine (LDT) and entecavir (ETV).  ADV and TDF have nephrotoxicity , LAM and ETV have a lesser effects on kidney function , and LDT has certain effect of improving kidney function. The diagnostic criteria of kidney injury due to NAs are serum creatinine (Scr) level higher than that of the baseline value (＞44.2 μmol/L) or serum phosphorus level lower than that of the baseline value (＜0.5 mmol/L) on two successive detections. The incidence rate of kidney injury due to ADV was higher than that due to TDF. The clinical manifestation of kidney injury due to ADV and TDF was Fanconi syndrome. The patient develops local or systemic osteodynia, osteoporosis, and amyasthenia, even limitation of activity and halisteresis in serious cases. The laboratory tests show increase in Scr, decrease in serum phosphorus and uric acid. The mechanisms of nephrotoxicity of ADV and TDF are related to injury of renal tubular epithelial cell mitochondria, change of renal tubular transport protein, and accumulation of drugs in proximal convoluted tubule. The nephrotoxicity of NAs are related to dosage, patients′ age, body weight, baseline level of estimated glomerular filtration rate (eGFR), primary disease, genetic factor, diet and drug. The patient who takes ADV or TDF for long term should monitor SCr, serum phosphorus, eGFR, uric acid, microalbuminuria，and glucose in urine regularly. ADV or TDF should be stopped timely in the case of appearance of symptom of kidney injury. The medication should be changed to LDT or ETV. Phosphorus compounds, vitamin D and calcium should be given.

A 69-year-old female patient received immunotherapy with intravenous infusion of sintilimab 200-mg once per 21 days because of recurrence of left lung adenocarcinoma after operation. The patient had no history of diabetes mellitus and blood sugar level was normal before treatment. Three days after the first intravenous infusion of sintilimab, the patient felt dry mouth and fatigue, 10 days later her symptoms were worsened, accompanied by nausea. Laboratory examination showed random blood glucose 27.0-mmol/L and hypoglycemic treatment was given. On the 29th day of intravenous infusion of sintilimab, oral glucose tolerance test showed that fasting, 1, 2 and 3 hours postprandial blood glucose levels were higher than those of the upper reference value, C-peptide and insulin were lower than those of the lower reference value, urine routine showed ketone bodies (±) and glucose (++++). Autoimmune diabetes mellitus caused by sintilimab was considered. After several adjustments, the hypoglycemic regimen was finally determined as recombinant human insulin injection 12 units subcutaneously before morning and evening meals, 14 units before lunch; albumin biosynthesis human insulin injection 12 units subcutaneously at bedtime. Five days later, the patient′s symptoms such as dry mouth, fatigue, and nausea disappeared, with fasting glucose 4.8-5.8-mmol/L and postprandial glucose 7.8-8.7-mmol/L. Urine routine examination showed negative ketone body and glucose.

A 53-year-old female patient received IV infusion of meropenem for injection 1.0 g once every 8 hours for urinary tract infection. Her platelet count (PLT) was 151×109/L before using meropenem. On the 9th day of meropenem treatment, the laboratory test showed PLT 577×109/L and on the 12th day, the patient′s infection was controlled but PLT increased to 829×109/L. The thrombocytosis related to meropenem was considered. Meropenem was stopped and replaced by IV infusion of piperacillin sodium and sulbactam sodium for injection 5 g dissolved in 100-ml of 0.9% sodium chloride injection once 8 hours. Three days later, the patient′s PLT decreased to 782×109/L; 23 days later, PLT was 272×109/L.

Objective To compare the clinical efficacy and safety of cefdinir dispersible tablets selected in the national centralized volume-based procurement (VBP) and the original drug cefdinir capsules.　Methods Clinical data of single-use cefdinir in outpatient of Xuanwu Hospital, Capital Medical University between January 1, 2020 and December 31, 2021 were collected through the hospital information system. The clinical data included gender, age, type of medical insurance, type of infection, application of cefdinir, whether to combine other antibacterial drugs, laboratory test results such as blood routine, C-reactive protein, liver and kidney function before and after cefdinir treatment, and adverse reaction report of cefdinir. After propensity score matching (PSM) of the age, sex, type of medical insurance, type of infection and whether to combine with other antibacterial drugs in the cefdinir dispersible tablets group selected in the VBP (VBP group) and the original cefdinir group (original group), the clinical application in patients in the 2 groups was compared to indirectly evaluate the efficacy of the 2 drugs. The white blood cell count, neutrophils percentage, and C-reactive protein levels before and after the use of cefdinir was compared to evaluate the efficacy. Adverse drug reaction report of cefdinir and liver and kidney function before and after the use of cefdinir were compared to evaluate the safety.　Results A total of 9-514 patients treated with cefdinir were entered, including 7-037 patients in the VBP group and 2-477 patients in the original group. After PSM, each group comprised 1-268 patients, the differences in gender, age, type of infection, and combination with other antibacterial drugs were not statistically significant (all P>0.05). The daily dose, course, and use density of cefdinir in the VBP group were lower than those in the original group［(0.30±0.04) g vs. (0.35±0.12) g, P<0.001; 8(4, 8) d vs. 10(8, 10) d, P<0.001; (3.96±1.70) g vs. (5.22±2.03) g, P<0.001］. The white blood cell count, neutrophils percentage, and C-reactive protein levels after the cefdinir application in patients in the VBP group were lower than those before the use of the cefdinir ［11.2(8.7, 13.8)×109 vs. 7.2(5.5, 9.9)×109, P<0.001; 80(74, 87)% vs. 66(56, 73)%, P<0.001; 23(10, 64) mg/L vs. 13(6, 44) mg/L, P=0.032］. No adverse drug reactions related to cefdinir were reported in the 2 groups. The differences in alanine aminotransferase, aspartate aminotransferase, blood creatinine, and urea nitrogen levels in patients between the 2 groups before and after use of cefdinir were not statistically significant (all P>0.05). The difference in aspartate aminotransferase before and after use of the cefdinir in the original group was statistically significant ［21(18, 23) U/L vs. 23(20, 29) U/L, P=0.040］, and the differences in alanine aminotransferase, blood creatinine, and urea nitrogen levels were not statistically significant (all P>0.05). The detection values of liver and kidney function in the 2 groups before and after use of the cefdinir were within the reference range.　Conclusion No significant differences were found in the clinical efficacy and safety between the VBP cefdinir dispersible tablets and the original cefdinir capsules.

Hepatic injury may induced by long-term use of total parenteral nutrition.The clinical presentations were elevated values of liver enzyme and bilirubin,cholestasis,fatty degeneration,and cirrhosis.The exact mechanism of TPN-induced hepatic injury is presently unknown;it may associated with the long-term fasting,imbalance of administered nutrients,and intestinal bacterial translocation.Balance of administered nutrients,use of cyclic infusion,early enteral feeding,and supplementation of some nutrients(such as choline and L-glutamine)may be beneficial to prevention and treatment of TPN-induced hepatic injury

Drug-induced liver injury (DILI) is a serious public health problem which can not be ignored. The mechanism of DILI include drug factors, immune mechanisms and individual factors. The traditional biological markers, such as alanine aminotransferase, aspartate transaminase, alkaline phosphatase, γ-glutamine transferase, total bilirubin, and total bile acid, lack sufficient sensitivity and specificity, so they often can not predict liver injury in the early course of the disease. MicroRNA-122, α- glutathione-S-transferase, 5′-nucleotidase, paraoxonase, purine nucleoside phosphorylase, malate dehydrogenase, and other new biological markers have higher sensitivity and specificity. Among them, microRNA-122 is expected to become a reliable new biological marker to predict hepatotoxicity because its specific, stable and sensitive expression in the liver tissue. Glutamate dehydrogenase, α-glutathione-S-transferase, arginase Ⅰand serum protein F are expected to become biological markers for hepatocellular injury. The 5′-nucleotidase has higher sensitivity and specificity than alkaline phosphatase and γ-glutamine transferase, and it is expected to become a biological marker for cholestasis. At present, these new biological markers of liver injury are still in the research stage and it will take time to get into the clinical use.

Three antiviral drugs, including interferon α (aerosol inhalation), lopinavir/ritonavir (oral medication), and ribavirin (intravenous infusion), are recommended by Diagnosis and Treatment of Novel Coronavirus Pneumonia (revised version, the 5th ed), which was issued by the National Health Commission of People′s Republic of China and National Administration of traditional Chinese Medicine. In addition, clinical trials on a new antiviral drug ---remdesivir which is not yet on the market has also been launched in China. Medication safety related data on treatment for infections of severe acute respiratory syndrome coronavirus, middle respiratory syndrome coronavirus, human immunodeficiency virus, lopinavir/ritonavir, and ribavirin, safety data of remdesivir in animal experiment, phase I clinical trials and clinical trials of treating Ebola virus infection, and preliminary reports of treatment in novel coronavirus pneumonia were briefly reviewed, aiming to provide evidence for clinical safety medication.

A 46 year old female patient with primary biliary cholangitis received Lanqin oral solution (蓝芩口服液) 10 ml orally thrice daily because of pharyngeal pain due to cold. About 20 minutes after taking the first dose of the drug, the patient suddenly felt general discomfort and numbness of mouth and tongue, followed by vomiting, sweating, pale complexion, dyspnea (27 times per minute), and hypotension (104/56 mmHg). Anaphylaxis induced by Lanqin oral solution was considered, the drug was discontinued and the liquid supplement to expand the blood volume and chlorphenamine maleate for anti allergy were given. One hour later, the patient′s symptoms disappeared and the blood pressure returned to 124/76 mmHg. The next day, the patient did not follow the doctor′s advice and took Lanqin oral liquid 10 ml again by herself. A few minutes later, she developed nausea and abdominal pain. The fluid infusion and symptomatic treatment were given immediately, and the symptoms disappeared 20 minutes later.

曲马多是一个应用比较广泛的中枢作用镇痛药,临床应用已近30年。它具有镇痛作用较强、依赖性相对较弱的特点。国际上对曲马多滥用及其不良反应的监测表明,曲马多滥用的发生率为2～3/10万。近年来,在我国部分地区发生曲马多流行性滥用。本文就曲马多的药理学特点,结合国际上对曲马多依赖性的评议以及我们此前的流行病学调查结果,对曲马多依赖性进行综述和分析。

Objective To mine the adverse event (AE) risk signals of semaglutide and liraglutide in weight management populations, and provide references for the safe use of these drugs in relevant patients.　Methods The reporting odds ratio (ROR) method, proportional reporting ratio (PRR) method, Bayesian confidence propagation neural network (BCPNN) method, and empirical Bayesian geometric mean (EBGM) method were used to mine the AE risk signals of semaglutide and liraglutide in weight management populations from the US Food and Drug Administration Adverse Event Reporting System (FAERS) database from the 1st quarter of 2010 to the 4th quarter of 2023. Adverse events that met the criteria of all 4 mining methods were considered as risk signals. The adverse events were classified and statistically analyzed using the system organ class (SOC) and preferred term (PT) of the 26.1 version of the Medical Dictionary for Regulatory Activities 26.1 version, and the identified risk signals were analyzed.　Results During the set period, 2 292 AE reports for semaglutide for weight management (excluding diabetes) and 2 973 for liraglutide were retrieved. The semaglutide-related AE reports involved 83 PTs, among which 57 were already recorded in the instructions and 26 were not. Among the 26 PTs not recorded in the labels, the top 5 PTs in terms of AE report numbers were increased appetite, hunger, panic attack, binge eating, and feeling cold; the top 5 PTs in terms of ROR values were lack of satiety, hunger-induced ketoacidosis, myoglobinuria, binge eating, and bulimia. The liraglutide-related AE reports involved 74 PTs, among which 60 were already recorded in the instructions and 14 were not. Among the 14 PTs not recorded in the labels, the top 5 PTs in terms of AE report numbers were weight gain, increased appetite, binge eating, weight fluctuation, and pancreatic cyst; the top 5 PTs in terms of ROR values were lack of satiety, binge eating, hepatic adenoma, increased appetite, and pancreatic cyst. Three PTs of severe AEs that were not recorded in the labels for semaglutide were identified, namely, olfactory abnormality, ketoacidosis, and panic attack. One PT of severe AE that was not recorded in the labels for liraglutide was identified, namely, metastatic pancreatic cancer.　Conclusion The AE risk signals of semaglutide and liraglutide in weight management include AEs not recorded in the labels, and some are even serious AEs, which need to be identified and prevented in clinical practice.

A 53-year-old male patient received subcutaneous injection of insulin aspart 30 injection 12 units twice daily and acarbose 50-mg orally thrice daily for 13 months because of type 2 diabetes mellitus, but the patient had poor glucose control. Oral glucose tolerance test showed that the fasting, 1-hour, 2-hour, and 3-hour postprandial blood glucose were 8.84, 17.94, 21.22, and 18.51-mmol/L respectively, insulin was 109.5 mU/L, C-peptide was 0.52-nmol/L, and insulin autoantibody was >175-U/ml. Exogenous insulin antibody syndrome was considered. Insulin aspart 30 injection was discontinued and replaced by metformin, pioglitazone, acarbose, and glimepiride orally. Thirteen days later, the patient′s fasting blood glucose decreased to 7.6-mmol/L. At 1 year of follow-up, the patient′s insulin autoantibody were negative in 3 tests. It is considered that the exogenous insulin antibody syndrome in the patient was caused by insulin aspart 30 injection.

A 48-year-old male patient with myocardial infarction received continuous intravenous pumping of propofol 1-2-mg/(kg· h) for 21 days due to delirium after cardiopulmonary resuscitation. On the 19th day after intravenous pumping of propofol, the patient developed high fever (the highest body temperature was 40.0-℃), decreased blood pressure (the lowest level was 90/60-mmHg), decreased urine volume (10-ml/h), and dark urine. The laboratory tests showed white blood cell count (WBC) 17.3×109/L, hemoglobin (Hb) 88-g/L, procalcitonin (PCT) 12.76-μg/L, cardiac troponin I (cTnI) 0.342-μg/L, serum creatinine (Scr) 239-μmol/L, creatine kinase (CK) 34-667-U/L, myoglobin (myo) 58-284-μg/L, lactic acid 2-mmol/L, and fungal (1-3)-β-D-glucan 457.9-ng/L. Candida albicans was identified from blood culture. The patient was diagnosed with propofol infusion syndrome and sepsis. Propofol was stopped immediately and replaced by continuous intravenous pumping of midazolam injection (5-mg/h). At the same time, treatments such as anti-infection and continuous bedside hemofiltration were given. After 3 days of treatments, the patient′s temperature dropped to within the normal range. After 7 days of treatments, laboratory tests showed WBC 5.6×109/L, Hb 95-g/L, PCT 0.12-μg/L, cTnI 0.023-μg/L, CK 43-U/L, myo 151-μg/L, Scr 78-μmol/L, and fungal (1-3)-β-D-glucan 88.9-ng/L. His urine volume was 90-100-ml/h.

Objective To understand the awareness and application status of drugs used with caution in myasthenia gravis (MG) patients.　Methods The list of drugs that should be used with caution in MG patients was formulated through discussion among pharmaceutical experts and neurology experts in Xuanwu Hospital, Capital Medical University, including 10 categories and more than 50 drugs like anti- infective drugs, cardiovascular drugs, sedative-hypnotics, statins, antiepileptics, antipsychotics, analgesics, anaesthetics, spasmolytics, and others. The questionnaire survey on knowledge of drugs used with caution was conducted in outpatients with MG in the Department of Neurology between January 2021 and February 2022 in Xuanwu Hospital, Capital Medical University. The contents of the questionnaire included the general demographic data of patients, the disease course and type of MG, comorbidities, drug utilization, awareness and application of drugs used with caution in MG patients, and accesses to relevant drug use knowledge. The questionnaire was distributed on-site after the patient ended the visit, and the patients were asked to participate voluntarily and answer and return the questionnaire on the spot. The participants were divided into the with and without relevant knowledge groups according to whether they were aware of drugs used with caution in MG patients, and the clinical characteristics of the patients in the 2 groups were compared. Multivariate logistic regression analysis was used to analyze the influencing factors of awareness of drugs used with caution, and the odds ratio (OR) and 95% confidence interval (CI) were calculated.　Results A total of 290 questionnaires were distributed and all of them were recovered. Among the 290 patients, 165 were male and 125 were female, and the disease course of MG ranged from 3 weeks to 360 months. The clinical subtypes were ocular MG in 179 patients and non-ocular MG in 111 patients. One or more chronic disease coexisted in 174 patients (60.0%), including hypertension, hyperlipidemia, diabetes mellitus, coronary atherosclerotic heart disease, immune system disease, anxiety/depression, etc. There were 248 patients (85.5%) who had received medications for MG. In the MG patients having access way to knowledge about drugs used with caution, there were 191 (92.7%), 26 (12.6%), 22 (10.7%), and 7 (3.4%) patients through the propagation by healthcare staff, bulletin boards/display boards in the hospital, networks, and books, respectively. There were 64.8% (188/290) of the patients knowing nothing about the drugs used with caution. After the diagnosis of MG, 110 patients had used the drugs that should be used with caution, and 7 (6.4%) had aggravated MG or adverse reactions later, of which 4 applied eye drops (quinolones and macrolides in 2 patients respectively). The independent influencing factors of low awareness of drugs used with caution were not receiving drugs for MG and not obtaining precautions in medication at the time of diagnosis (OR=6.811, 95%CI: 2.252-20.593, P=0.001; OR=5.615, 95%CI: 3.223-9.785, P<0.001).　Conclusion Patients with MG have low awareness of the drugs used with caution, and neurology staffs should take more effective measures to the patient education about drugs used with caution.

A 47-year-old male patient received irbesartan 225-mg orally once daily due to nephrotic syndrome. Three days later, the dose was changed to 300-mg once daily according to the doctor′s advice. His hemoglobin (Hb) was 153-g/L before irbesartan treatment. After 6 days of medication, the patient developed fatigue and weakness. Laboratory test showed that his Hb was 89-g/L. No laboratory test abnormality was found in serum creatinine, stool routine, and bone marrow puncture. After 13 days of medication, his Hb was 87-g/L. Moderate anemia related to irbesartan was diagnosed. Irbesartan was discontinued and IV infusion of methylprednisolone sodium succinate for injection 60-mg once daily and subcutaneous injection of erythropoietin 3-000 U thrice a week were given. Seven days later, the symptoms of fatigue and weakness were improved and laboratory test showed Hb 102-g/L. Twenty-seven days later, his Hb returned to 131-g/L.

A 41-year-old female patient received Rupixiao capsules 1.6 g thrice daily for hyperplasia of mammary glands. About 30 days later, the patient developed nausea, dark urine, and yellowish skin and sclera. After 20 days of continued treatment, her symptoms worsened, so she stopped using Rupixiao capsules by herself. After 10 days of drug withdrawal, her symptoms were not improved. The laboratory tests showed alanine aminotransferase (ALT) 1-234-U/L, aspartate aminotransferase (AST) 778-U/L, gamma-glutamyltransferase (γ-GT) 174-U/L, alkaline phosphatase (ALP) 156-U/L, total bilirubin (TBil) 78.7-μmol/L, and total bile acid (TBA) 45.4-μmol/L. After excluding liver injury caused by other reasons through laboratory and auxiliary examination, drug-induced liver injury was diagnosed, which was considered to be related to Rupixiao capsules. Drugs such as reduced glutathione, polyene phosphatidylcholine, compound glycyrrhizin, ademetionine 1,4-butanedisulfonate, and bicyclol were given. The patient′s symptoms of nausea, yellow urine, and jaundice gradually subsided. After 35 days of treatments, laboratory tests showed ALT 39-U/L, AST 43-U/L, γ-GT 57-U/L, ALP 85-U/L, TBil 17.3-μmol/L, and TBA 14.3-μmol/L.

Objective: To survey the adverse reactions caused by anti-infective drugs for their safe use in clinical practice. Method: ADR cases were analysed in Beijing Tongren Hospital during the last eight years. Results: 513 ADR cases were associated with 72 anti-infective drags, commonly aminoglycosides(114 cases, 22.22%), penicillins (107 cases, 20.86%), cephalosporins (97 cases, 18.91%) and quinolones(86 cases, 16.76%). Most of ADR were found in the skin and its appendages, nervous system and digestive system. Conclusion: Rational use of anti-infective drugs should be taken to decrease the occurrence of adverse reactions.

Vincristine is an antineoplastic agent for intravenous use only;inadvertent intrathecal administration of vincristine may cause severe neurologic damage,and often is fatal.The first fatal case of inadvertent intrathecal vincristine administration was reported by Schacht et al.in 1968.Since then,at least 20 deaths from inadvertent vincristine intrathecal administration are known to have occurred in the United States,Canada,the United Kingdom,Germany,Saudi Arabia,Singapore,Korea,and China.In published case reports,the patients developed rapid sensory and motor dysfunction followed by encephalopathy,coma,and death after inadvertent intvathecal administration of Vincristine.Early signs and symptoms were tremors,disorientation,nausea,and vomiting.The patients became unresponsive within one week.Ascending paralysis occurred in some patients.The time to death ranged from 7 to 83 days.If vincrrstine is mistakenly given by the intrathecal route,the following treatment should be initiated immedi…更多ately:removal of spinal fluid,flushing with sodium lactated Ringer' s injection and fresh frozen plasma diluted in sodium lactated Ringer' s injectiom,administration of glutamic acid,folic acid,vitamin B6 and so on.Reasons for inadvertent intrathecal vincristine administration can be the end-results of either a sigle medication error or a series of medication errors.Suggestions for preventing inadvertent intrathecal vincristine administration include vincristine should be labelled warning label on the syringe and outer wrap,stating "for intravenous use only—fatal if given intrathecally",vincristine should be prepared in a minibag for intraveous infusion rather than a syringe,the storage and delivery of vincristine should be separated from all medicines intended for intrathecal administration,and only specifically trained and designated oncology staff should prepare and administer vincristine.

Objective To know the clinical characteristics of liver injury related to levetiracetam (LEV).　Methods The relevant databases at home and abroad (up to August 31st, 2021) were searched and the case reports on LEV-associated liver injury were collected. Clinical information including patients′ basic characteristics, LEV application, concomitant medication, and occurrence, treatment, and outcome of liver injury, etc. were collected and analyzed by descriptive statistical method.　Results A total of 17 patients were enrolled in the study, including 9 males and 8 females, aged from 1 month to 76 years with an average age of 35 years. The primary disease was idiopathic epilepsy in 7 patients and secondary epilepsy in 10 patients. Five cases had comorbidities. Thirteen patients had drug dosage records, all of which were within the range recommended in the labels; 13 patients had concomitant medication. The time from LEV treatment to the occurrence of liver injury ranged from several hours to 5 months in 17 patients and it was ≤2 months in 14 patients. The classification of liver injury was hepatocellular type in 7 patients, cholestasis type in 1 patient, mixed type in 1 patient, and unable to be determined due to lack of relevant data in 8 patients. Clinical symptoms were recorded in 10 patients, including yellowish skin and sclera in 5 cases, fever in 4 cases, nausea in 2 cases, vomiting in 2 cases, and biliuria in 2 cases. LEV was discontinued in 14 patients, 4 of whom did not received other interventions and the liver function was improved or returned to normal 2 to 20 days after drug withdrawal; LEV was replaced with other antiepileptic drugs and/or sympto- matic treatments in 10 patients, 9 patients′ liver function were improved or returned to normal (the recovery time was 5-37 days in 5 patients and not recorded in 4 patients), 1 patient had normal liver function after liver transplantation, but the liver injury recurred after LEV use again and was improved after drug withdrawal. Two patients did not stop LEV, one underwent liver transplantation due to liver failure and hepatic encephalopathy, and the prognosis was unknown; the other one developed fulminant liver failure and died. One patient had no record of whether or not stopping LEV, and the liver function returned to normal after artificial liver support treatment.　Conclusions LEV-related liver injury mostly occurred within 2 months after drug administration. The clinical manifestations were similar to the liver injury caused by other drugs. Liver function usually was improved or returned to normal after the drug withdrawal. The patients who did not stop LEV had poor prognosis, and severe cases could lead to liver failure or death.

A 52-year-old male patient was given escitalopram 5-mg/d (gradually increased to 15-mg/d), trazodone 100-mg/d, and lorazepam 1-mg/d for depression. Increased salivary secretion occurred 3 days after taking the medicine. After 13 days of taking the medicine, she only took escitalopram and lorazepam due to lack of trazodone. After stopping trazodone for 3 days, the symptoms of increased salivary secretion disappeared. Trazodone 100-mg/d was added again later due to poor sleep and increased salivary secretion relapsed after 2 days of trazodone administration. Considering that the above symptoms were related to trazodone, the doctor ordered him to stop the drug and take escitalopram and lorazepam only. Three days later, the patient′s increased salivary secretion disappeared again. The patient′s depressive symptoms were relieved and increased salivary secretion did not recur at a 2-week follow-up.

Hepatitis C virus protease inhibitors (PIs) are one of the major categories that constitute directly acting antivirals (DAA) regimen in the treatment for hepatitis C. These drugs are mainly metabolized by liver cytochrome P450 and have potential hepatotoxicity. Population pharmacokinetic study data showed that the metabolism of PIs was slower in Asians than that in White/Caucasian subjects, and the results of clinical trials and real-world studies in Asians showed that these drugs had the risk of causing liver enzyme abnormalities and bilirubin elevations. Medical workers in our country should pay full attention to the potential risks of PIs in liver safety, and should not rely too much on safety data in Europe and America. The baseline liver disease severity should be accurately assessed before selecting the DAA regimen containing PIs and the risk of disease progression should be considered. PIs are contraindicated in patients with decompensated liver disease. For patients without cirrhosis or with compensated cirrhosis, the liver function should be closely monitored during the administration of PIs and the management of liver-related adverse events should be paid attention to.

Druginduced headaches refer to a headache caused either directly or indirectly by medications, which account for 5%～10% of the headaches. Mechanism of druginduced headaches is unclear. The comnon causes of drug-induced headaches are as follows: vasodilation, benign intracranial hypertension, aseptic meningitis, disulfiram-like reactions, and analgesic overuse. Clinical presentation of druginduced headaches may be accompanied by dizziness, nausea, vomiting, facial flushing, and decreased blood pressure, besides headache symptoms. The most common causative agents include NSAIDs, histamine H₂ receptor antagonists, calcium antagonists, and vasodilators. Care must be taken to distinguish a headache during drug therapy from a headache secondary to the primary disease. The symptoms of druginduced headaches may relieve after stopping the offending agents and receiving symptomatic therapy.

Objective To explore the characteristics and mechanism of Chinese herbs with fertility toxicity.　Methods Chinese herbs with reproductive toxicity, developmental toxicity and genetic toxicity were retrieved from Traditional Chinese Medicine System Toxicology Database. The property, taste, meridian tropism, toxicity classification and performance, and the toxic component and action target of each medicinal material were collected and descriptive statistical analysis was performed.　Results A total of 55 kinds of Chinese herbs with fertility toxicity were screened out. They were mostly warm ［20 (36.4%)］ or cold ［15 (27.3%)］ in property, and mostly bitter and pungent in taste ［bitter-pungent, bitter, and pungent accounted for 30.9% (17/55), 23.6% (13/55) and 18.2% (10/55)］. The channel tropisms were mainly liver, lung, spleen, and kidney ［58.2% (32/55), 38.2% (21/55), 38.2% (21/55) and 34.5% (19/55)］, and the main manifestations of its reproductive toxicity were reproductive function damage in males and females, abnormal embryonic growth and development and genetic/cytotoxicity, which might lead to reduced pregnancy rate, miscarriage, abnormal fetal growth and development, etc. There were 29 kinds of Chinese herbs with 35 known fertility toxic components. Among them, 30 toxic components had 11 known toxic targets. The more common toxic targets included thyroid hormone receptor beta, cytochrome P450 1A1, sex hormone-binding globulin and interleukin-1 beta.　Conclusions Chinese herbs with fertility toxicity are mostly warm or cold in property, and bitter and pungent in taste; their channel tropisms are mainly liver, lung, spleen and kidney; they mainly affect fertility and embryonic development by changing the body′s endocrine and interfering with sex hormone metabolism.

Objective To explore the factors influencing the severity and prognosis of vancomycin- associated acute kidney injury (AKI).　Methods Case reports on vancomycin-associated AKI were collected by searching the relevant databases home and abroad up to June 2020. Patients′ relevant information such as general condition, underlying diseases, infecting species, treatment of vancomycin, baseline serum creatinine (Scr), baseline estimated glomerular filtration rate (eGFR), time from medication to onset of AKI, Scr elevation rate, eGFR decline rate, management of AKI, and outcomes were recorded and descriptively analyzed. The influence factors of the rates of Scr elevation and eGFR decline in patients were analyzed using robust regression method and the influence factors of the prognosis of vancomycin-associated AKI were analyzed by comparing the main clinical features of patients with basic recovery and improvement of Scr level.　Results A total of 81 reports involving 109 patients were enrolled in the analysis, including 65 males and 44 females, aged from 1 to 84 years with a median age of 49 years, of which 20 were ≤15 years old and 61 (56.0%) suffered from underlying chronic diseases. The median daily dose of vancomycin was 2.00 (0.75, 6.00) g in 89 adult patients and 40.0 (10.3, 240.0) mg/kg in 20 pediatric patients. The median time from medication to onset of AKI was 7 (1, 135) days, and 80 (73.4%) occurred within 14 days after first medication. Seventy-five patients (68.8%) had concomitant use of drugs with potential nephrotoxicity. The median value of peak Scr was 408 (53, 1-000) μmol/L, and the median eGFR was 44.3 (4.2, 280.7) ml/(min·1.73 m2) after developing AKI. Steady-state trough concentration of vancomycin was recorded in 57 patients, which was 46.2 (11.8,284.0) mg/L before or at onset of AKI. Except 4 patients died and 1 patient was lost to follow-up, the Scr level basically recovered in 50 patients, were improved in 51 patients, and did not recover in 3 patients, which required continuous renal replacement therapy. Robust regression analysis showed that the trough concentration of vancomycin and the number of concomitant nephrotoxic drugs were significantly correlated with the rates of Scr elevation and eGFR decline after AKI (all P<0.05). The age and peak Scr in patients with basic recovery of renal function were significantly lower than those in patients with improved renal function (all P<0.001), while the lowest eGFR value was significantly higher(P=0.036).　Conclusions Patients with higher trough concentration of vancomycin and more nephrotoxic drugs would have greater elevation of Scr and the decline of eGFR. Older age, higher Scr peak value, and lower eGFR was associated with worse recovery of the renal function.

Acute kidney injury (AKI) is a common clinical critical illness. Several foreign studies showed that patients with drug-induced AKI accounted for 15%-27% of patients with AKI occurred during hospitalization and a domestic research showed that the proportion was 28.9%. The evaluation methods of causality assessment between drugs and AKI are experts judgement or global introspection, Karch & Lasagnar evaluation method, recommended standard for ADR monitoring center of Health Planning Commission of China, and Naranjo Adverse Drug Reaction Probability Scale(NADRPS), etc. The etiology of drug-induced AKI can be divided into 3 categories, including prerenal, renal, and postrenal. Predisposing factors include advanced age, diabetes, hypertension, chronic kidney disease, low serum albumin, etc. Prevention measures are avoiding and correcting all kinds of risk factors, selecting drugs of low toxicity or no toxicity to kidney, and if necessary early dialysis treatment should be given. Development and improvement of computer aided automatic alert system is very important in prevention, early diagnosis and early treatment of AKI.