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.

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.

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.

Objective To analyze and compare the reporting data of adverse events following immunization (AEFI) of influenza vaccines in Fujian Province from 2019 to 2023.　Methods Using the National Immunization Program Information Management System, the AEFI reports and vaccination data of influenza vaccines in Fujian Province from 2019 to 2023 were collected, and the reporting rates and clinical characteristics of AEFI of 6 types of influenza vaccines were compared. The 6 types of vaccines in the analysis were as follows: trivalent inactivated influenza vaccines (IIV3) for 6-35 months old people, IIV3 for ≥3 years old people, trivalent live attenuated nasal spray vaccine (LAIV3) for 3-17 years old people, quadrivalent inactivated influenza vaccines (IIV4) for 6-35 months old people, IIV4 for ≥6 months old people, and IIV4 for ≥3 years old people.　Results From 2019 to 2023, a total of 87 687.21 million doses of influenza vaccine were vaccinated in Fujian Province, and 510 cases of AEFI were reported, with a reporting rates of 5.82 per 100 000 doses. Among the 510 cases, 443 (86.86%) were general reactions, 56 (10.98%) were abnormal reactions, 1 (0.20%) was psychogenic reactions, and 10 (1.96%) were coincidence. There were no reports of vaccination accidents and vaccine quality accidents. The reporting rates of AEFI were relatively higher in 2019 and 2020 (18.38 and 18.00 per 100 000 doses, respectively), and lower in 2021, 2022 and 2023 (8.91, 10.68 and 2.30 per 100 000 doses, respectively); the differences were statistically significant (all P<0.05). The differences of reporting rates of AEFI between  IIV3 for 6 35 months old people and IIV4 for 6-35 months old people, the injectable vaccines and nasal spray vaccines were not statistically significant. However, the reporting rates of overall AEFI, general reactions and abnormal reactions of IIV3 for ≥3 years old people were all higher than those of IIV4 for ≥3 years old people (7.77 per 100 000 doses vs. 3.88 per 100 000 doses, 6.18 per 100 000 doses vs. 3.59 per 100 000 doses, 1.41 per 100 000 doses vs. 0.19 per 100 000 doses). The reporting rates of overall AEFI and general reaction of IIV3 for 6-35 months old people were both higher than those of IIV3 for ≥3 years old (16.47 per 100 000 doses vs. 7.77 per 100 000 doses, 13.05 per 100 000 doses vs. 6.18 per 100 000 doses), and the differences were statistially significant (all P<0.05). The reporting rates of general abnormal reactions of IIV4 for 6-35 months old and ≥ 6 months old people were both higher than those of IIV4 for ≥3 years old people (14.73 per 100 000 doses and 9.52 per 100 000 doses vs. 3.88 per 100 000 doses); the reporting rates of general reactions and abnormal reactions of IIV4 for ≥6 months old people were both higher than those of IIV4 for ≥3 years old people (12.94 per 100 000 doses vs. 3.59 per 100 000 doses, 1.34 per 100 000 doses vs. 0.19 per 100 000 doses), the dif- ferences were statistcially significant (all P<0.05). In terms of clinical features, the reporting rates of fever (37.6-38.5 ℃ and ≥ 38.5 ℃), local redness and swelling (diameter 2.6-5.0 cm), and local induration (diameter  ≤2.5 cm and 2.6-5.0 cm) after vaccination of IIV3 for ≥3 years old people were higher than those of IIV4  for ≥ 3 years old people (1.41 per 100 000 doses vs. 0.64 per 100 000 doses, 3.00 per 100 000 doses vs. 1.16 per 100 000 doses); the reporting rates of allergic rash and angioedema of IIV3 for ≥ 3 years old people were higher than those of IIV4 for ≥3 years old people (0.53 per 100 000 doses vs. 0.12 per 100 000 doses, 0.35 per 100 000 doses vs. 0); the differences were statistically significant (all P<0.016 7).　Conclusions The reporting rates of AEFI for influenza vaccines in Fujian Province from 2019 to 2023 was showing a downward trend. The AEFI was mainly general reactions. The reporting rates of AEFI were different among dif- ferent influenza vaccines, but the overall safety was good.

A 66-year-old female patient with multiple chronic diseases was on long-term treat- ment with digoxin, spironolactone, metoprolol, atorvastatin, dapagliflozin, and entecavir, with no abnormality platelet count (PLT). Due to hypertrophic obstructive cardiomyopathy and atrial fibrillation, digoxin was discontinued, and rivaroxaban 15 mg once daily orally was added to prevent thrombosis. Concurrently, furosemide, sacubitril valsartan, meglumine adenosine cyclophosphate, and silibinin was given for cardiac load reducement, blood pressure control and heart failure improvement, myocardial nutrition, and liver function improvement, respectively. After the initiation of this regimen, the patient′s PLT gradually decreased and was 51×10⁹/L on day 13. Drug-induced thrombocytopenia was considered, with rivaroxaban being the likely causative agent. Rivaroxaban was then switched to warfarin, methylprednisolone 40 mg was administered intravenously once, and the remaining medications were continued. The patient′s PLT gra- dually increased. On day 11 after discontinuing rivaroxaban, the PLT was 155×10⁹/L. At a 2-week follow- up, PLT of the patient was 169×10⁹/L.

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.

Objective To understand the influencing factors for cardio-cerebrovascular complications in patients with T2DM and construct a nomogram risk prediction.　Methods The study design was a prospective observational study, and the subjects were selected from hospitalized patients with T2DM admitted to Huangshan City People′s Hospital from May 2022 to April 2023. Data on patients' gender, age, body mass index, alcohol consumption, smoking status, family history of cardio-cerebrovascular diseases, insulin use, duration of diabetes, blood pressure, and routine laboratory test results were collected using the hospital electronic medical record system. At discharge, patients were assessed using the T2DM-Specific Medication Belief Scale (total score range: 10-50), Medication Literacy Assessment Scale (total score range: 0-7), and Morisky Medication Adherence Scale (total score range: 0-8). Patients were followed up by telephone for 6 months after discharge and divided into 2 groups based on the occurrence of cardio-cerebrovascular complications. Logistic regression analysis was performed using SPSS 26.0 software to identify influencing factors for cardio-cerebrovascular complications in T2DM patients. A nomogram prediction model was constructed using R 4.1.0 software, and internal validation of the model was conducted using the Bootstrap method.　Results A total of 294 T2DM patients were included in the analysis. The medication belief score was (32.6±5.6) score, the medication literacy score was (4.2±0.5) score, and the medication adherence score was (6.1±0.8) score. During the 6 month follow-up, a total of 43 patients (14.6%) experienced cardio- cerebrovascular complications, including of coronary heart disease (23 cases), heart failure (12 cases), and stroke (8 cases). Compared to patients without cardio-cerebrovascular complications, patients with complications had higher body mass index, glycosylated hemoglobin A1c (HbA1c), D-dimer, and uric acid levels, as well as lower medi- cation belief scores, medication literacy scores, and medication adherence scores (all P<0.05). Binary logistic regression analysis showed that HbA1c, D-dimer, uric acid, medication belief, medication literacy, and medication adherence were influencing factors for cardio-cerebrovascular complications in T2DM patients. Accordingly, a nomogram prediction model was established. Internal validation results of the model showed that the concordance index was 0.958, the area under the receiver operating characteristic curve was 0.824, and the calibration curve was close to the ideal curve.　Conclusions The current status of medication belief, medication literacy, and medication adherence in T2DM patients was not ideal. High levels of HbA1c, D-dimer, and uric acid, as well as poor medication belief, medication literacy, and medication adherence were risk factors for cardio-cerebrovascular complications in T2DM patients. The nomogram model, which integrated multiple influencing factors, had high value in predicting the risks.

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.

Objective To investigate the occurrence and characteristics of adverse reactions of Xuesaitong preparations, mine its coagulation disorders/bleeding risk signals, and provide references for its safe and rational use in clinic.　Methods The reports of adverse drug reactions (ADR) caused by Xuesaitong preparations from August 2003 to August 2023 in the database of Shandong Provincial Center of Adverse Drug Reaction Monitoring were collected. ADR were counted and classified using the system organ class (SOC) and preferred term (PT) of Medical Dictionary for Regulatory Activities 26.1. Three methods, namely the reporting odds ratio (ROR), the proportional reporting ratio (PRR), and the comprehensive standard method of the Medicines and Healthcare Products Regulatory Agency (MHRA) of the United Kingdom, were used to detect the risk signals of coagulation disorders/bleeding in using Xuesaitong preparations.　Results A total of 17 015 reports of ADR related to Xuesaitong preparations were collected, involving 9 dosage forms, in which injection dosage form accounted for 95.50% (16 250/17 015). The median age of the patients was 62 years, 44.87% of the cases were 45-64 years and 42.90% of them were 65 years and above. There were 2 217 cases of severe ADR reports, accounting for 13.03% (2 217/17 015). A total of 18 SOCs were involved, the top 3 were skin and subcutaneous tissue diseases, systemic diseases and drug administration site reactions, and neurological diseases. A total of 54 PTs were not recorded in the instructions, among which 34 were severe. Ninety-three cases about coagulation disorders/bleeding (98 times) were reported, the top 3 PTs were hematuria ［24.49% (24/98)］, purpura ［11.22% (11/98)］, and epistaxis ［10.20% (10/98)］. Seven dosage forms of Xuesaitong preparations were involved, the top 3 were Xuesaitong for injection (freeze-dried) (48 cases, accounting for 51.61%), Xuesaitong injection (29 cases, accounting for 31.18%), and Xuesaitong tablets (8 cases, accounting for 8.60%). Among 93 reports of coagulation disorders/bleeding, there were 23 severe cases, accounting for 24.73%, which was significantly higher than that in other reports (12.97%), and the difference was statistically significant (P<0.001). Sixteen PTs about coagulation disorders/bleeding were not recorded in the instructions, among which 9 were severe. The proportion of cases with onset time longer than 7 days in ADRs about coagulation disorders/bleeding was higher than that in other ADRs [22.58%(21/93) vs. 7.43%(1 258/16 922), P<0.001]. The risk signals of coagulation disorders/bleeding were mined for Xuesaitong for injection (freeze-dried), Xuesaitong injection, Xuesaitong tablets, and Xuesaitong capsules, and the risk signal density of Xuesaitong tablets was the strongest.　Conclusions The ADRs of Xuesaitong preparations involve multiple systems and organs. Among them, Xuesaitong for injection (freeze-dried), Xuesaitong injection, Xuesaitong tablets, and Xuesaitong capsules have a strong association with coagulation disorders/bleeding risks, and the proportion of severe cases is relatively high. However, the relevant risk warning information is not included in the drug instructions of some manufacturers. Medication monitoring needs to be strengthened and timely intervention should be carried out in clinic.

Objective To mine the risk signals of adverse events (AEs) in mavacamten treatment for hypertrophic cardiomyopathy, and provide reference for safe use of the drug in clinic.　Methods AE reports on mavacamten from June 2022 to June 2024 were collected by searching US Food and Drug Adminis- tration Adverse Event Reporting System (FAERS) database. AEs were classified and standardized according to the system organ class (SOC) and preferred term (PT) of Medical Dictionary for Regulatory Activities version 26.1. Reporting odds ratio (ROR) method and comprehensive standard method of the UK Medicines and Healthcare Products Regulatory Agency (MHRA) were used to mine the AE risk signals. An AE that simultaneously met the criteria of ≥3 reports, lower limit of the 95% confidence interval (CI) of ROR >1, PRR ≥2, and χ2 ≥4 was defined as a risk signal. Descriptive statistical analysis on signals was performed.　Results A total of 1 041 AE reports were collected, involving 47 PTs and 12 SOCs. The top 10 risk signals based on the number of AE reports were dyspnea, dizziness, fatigue, atrial fibrillation, cardiac failure, palpitation, nasopharyngitis, chest pain, COVID-19, and weight increased. Except dizziness and heart failure, above AEs were not recorded in the label. The top 10 risks in signal intensity were acquired left ventricle outflow tract obstruction, transvalvular pressure gradient increased, cardiovascular symptom, echocardiogram abnormal, hypervolaemia, left ventricular failure, ejection fraction decreased, coronavirus infection, brain fog, and atrial fibrillation. Except cardiovascular symptom, left ventricular failure, and ejection fraction decreased, above AEs were not recorded in the label.　Conclusions The AE risk signals of mavacamten in the treatment for hypertrophic cardiomyopathy recorded in the label are mainly heart failure and ejection fraction decreased. Clinicians and pharmacists should also be vigilant against risk signals not recorded in the lakel, such as atrial fibrillation, fatigue, nasopharyngitis, coronavirus infection, and brain fog, etc.

Objective To evaluate the clinical safety of Fufang E‘jiao syrup and provide reference for its rational and safe clinical use.　Methods The literature involving Fufang E'jiao syrup in domestic and international databases, as well as the relevant clinical trials on ClinicalTrials.gov and the Chinese Clinical Trial Registry website were searched up to June 1, 2024. Those literature and clinical trials reporting drug adverse events were included, and the basic information about literature/clinical trials (title, publication year, study design, etc.), patients (age, gender, primary diseases, and dosage of Fufang E'jiao syrup), and adverse events (time of occurrence, clinical manifestations, and outcomes) was extracted. The adverse events were standardized and classified using the Medical Dictionary for Regulatory Activities version 25.0, and were also analyzed based on traditional Chinese medicine theory.　Results A total of 19 literature were included in the analysis, including 16 observational/experimental clinical studies, and 3 case reports. The 19 literature reported a total of 430 adverse events involving 398 patients, and the patients were mainly with malignant tumors and anemia. The 430 adverse events involved 11 system organ classes, which mainly included gastrointestinal disorders (260 events, 60.47%, with the most common symptom being dry mouth), respiratory, thoracic, and mediastinal disorders (119 events, 27.67%, with the most common symptom being dry throat), and skin and subcutaneous tissue disorders (16 events, 3.72%, with the most common symptom being mucosal ulcers). Based on traditional Chinese medicine theory, the 430 adverse events were mainly manifested as symptoms of indigestion (nausea, epigastric discomfort, and decreased appetite) and symptoms of “heat” (dry mouth and dry throat).　Conclusions Fufang E'jiao syrup has a relatively good overall safety profile, with the most common adverse events being symptoms of “heat” and gastrointestinal reactions. Patients should not use it blindly, and it should be used with syndrome differentiation in clinical practice.

With the increasing prevalence of chronic kidney disease (CKD) and the progress of renal replacement therapy, there were more and more patients with long-term hemodialysis (hemodialysis). Cardiovascular diseases were the leading cause of death among hemodialysis patients, and a lot of these patients needed to be treated with percutaneous coronary intervention (PCI). However, hemodialysis patients had higher risks of both bleeding and thrombotic events, which made it difficulty to select drugs and their dosages for post-PCI dual antiplatelet therapy in clinical practice, and the impacts of hemodialysis on dual antiplatelet therapy were still unclear. We reported a 65-year-old male patient with CKD, who was on long-term hemodialysis treatment and underwent PCI for acute non-ST segment elevation myocardial infarction. The patient was given dual antiplatelet therapy with aspirin and clopidogrel after the procedure, and on the fourth day after PCI (14 hours after restarting hemodialysis), he developed subacute stent thrombosis due to clopidogrel resistance, which was resolved after revascularization. Based on the treatment experience in this patient and review of relevant literature, we proposed recommendations on management of dual antiplatelet 

Objective To explore the adverse effects of maternal exposure to angiotensin receptor blockers (ARBs) during the second and third trimesters of pregnancy on the fetus/neonate.　Methods Rele- vant databases at home and abroad were searched (up to April 2024), and case reports of ARB exposure during the second and third trimesters of pregnancy were collected. Data such as patient age, ARB drugs exposed to and the gestational age, concomitant drugs, maternal amniotic fluid examination, and fetal/neonatal outcomes were extracted from the literature. Descriptive statistical analysis was conducted on the information of ARB exposure during pregnancy.　Results A total of 37 case reports were included, describing the outcomes of 55 fetuses/neonates (including a pair of twins) exposed to ARBs in utero during the second and third trimesters of pregnancy of 54 pregnant women. Six kinds of ARBs were involved in the 54 pregnant women, including valsartan (31.5%, in 17 women), candesartan (25.9%, in 14 women), losartan (22.2%, in 12 women), olmesartan (11.1%, in 6 women), telmisartan (5.6%, in 3 women), and irbesartan (3.7%, in 2 women); 49 women (90.7%) took above ARBs continuously form pre-pregnancy or the first trimester of pregnancy to the second and third trimesters of pregnancy, which were mostly prescribed by non-obstetricians (internal medicine or general practice). In the 54 pregnant women, 46 had amniotic fluid examination during pregnancy, of which 45 (97.8%) had oligohydramnios or absence of amniotic fluid; 4 voluntarily induced labor to terminate pregnancy, and 50 reported the natural outcome of pregnancy and had 51 fetuses/newborns, 15 (29.4%) of which died in utero or within 1 week after birth, and 36 (70.6%) of which were discharged alive. Among the newborns, 81.3% (39/48) were premature infants, and 74.4% (32/43) were low birth weight infants. In the 55 fetuses/newborns, 48 (87.3%) had varying degrees of disease and developmental defects. The most commonly involved organ or system was kidney ［72.7% (40/55)］, and the major pathological change was renal tubular dysplasia; the following injury was lung/respiratory diseases and dysplasia with an incidence of ［41.8% (23/55)］, which was the main cause of fetal/neonatal death. Subsequently, abnormal development of skull/brain and limbs/hands and feet, abnormal circulatory system, abnormal coagulation, retinopathy, etc. have also been reported.　Conclusion ARBs exposure during the second and third trimesters of pregnancy poses significant risks to the fetus/neonate, often leading to developmental defects of renal tubular, lung, skull/brain, and limbs, and even death.

Objective To investigate the implementation of boxed warning of drug labels in US Food and Drug Administration (FDA) from 2019 to 2024, and compared it with the relevant situations in China, in order to provide reference for the revision of drug labels and safe drug use.　Methods Data on boxed warning revisions in the US FDA "Drugs Safety Related Labeling Changes" Database from January 1, 2019 to December 31, 2024 were retrieved, and the revised contents were classified. The drug labels for newly marketed drugs in the United States during the same period were collected, the boxed warnings were recorded and summarized, and compared with the warning statements in drug labels of relevant drugs approved in China.　Results From 2019 to 2024, FDA revised boxed warnings in 209 drug labels. Among them, 22 items (10.53%) were newly added, 63 items (30.14%) were major updates, 115 items (55.02%) were minor updates, and 9 items (4.31%) were removed. A total of 293 new drugs were approved in the United States from 2019 to 2024, of which 69 (23.55%) had boxed warnings when they were approved, and 4 (1.37%) were added boxed warnings when they were revised in the labels. Up to December 31, 2024, 92 of the 293 new drugs had been approved in China. Compared with the labeling in the United States, some drugs lacked warning statements section in China, including zolpidem tartrate, dexzopiclone, zaleplon, montelukast sodium, denosumab, terlipressin, etc.　Conclusions The warning statements in some Chinese drug labels are inconsistent with the boxed warnings in the American drug labels. It is suggested that the revision of the boxed warning by US FDA should be regarded as one of the new sources of safety information to assess the risks of related drugs and determine whether it is necessary to revise the relevant drug labels in China.

Drug-induced neurological disorders (DINDs) refer to the central or peripheral nervous system disease caused by drugs. DINDs account for a large proportion of adverse drug reactions/events in China, and its onset is complex to some extent. Common DINDs include epilepsy, movement disorders, stroke, peripheral neuropathy, spinal cord injury, cognitive impairment and so on. Usually, DINDs have characters of gradual development and late-onset reactions, and it is difficult to associate their clinical manifestations with drugs, leading to misdiagnosis and poor prognosis in clinic. To reduce the neurotoxicity of drugs, multidisciplinary cooperation should be strengthened, and individualized treatment plans for high-risk people and closer monitoring should be implemented for timely identification and diagnose. At the same time, relevant researches on DINDs should be strengthened in the clinic to cope with the complexity and long-term prognosis challenges of the diseases.

Objective To detect adverse reaction risk signals of triazole antifungal agents and provide evidences for their safe use in clinic.　Methods Adverse reaction/event reports with fluconazole, itraconazole, voriconazole, posaconazole, or isavuconazonium as the primary suspect drug were collected from the data in National Adverse Drug Reaction Monitoring System of China reported by Shandong Province from January 2004 to June 2024 and the US Food and Drug Administration Adverse Event Reporting System (FAERS) database from the first quarter of 2004 to the second quarter of 2023. Adverse reaction/event terms were standardized using the preferred term (PT) and system organ class in Medical Dictionary for Regulatory Activities 24.0. Risk signals were detected using the reporting odds ratio (ROR) method and the Bayesian confidence propagation neural network (BCPNN) algorithm. A PT was defined as an adverse reaction risk signal if the number of reports was ≥3, the lower limit of the 95% confidence interval (CI) for ROR was >2, and the lower limit of the 95%CI for the information component (IC) was >0. Descriptive statistical analysis was performed.　Results A total of 3 988 reports with the above 5 antifungal drugs as the primary suspect drug were collected from data in National Adverse Drug Reaction Monitoring System of China reported by Shandong Province, 822 (20.6%) of which were serious cases. Voriconazole, fluconazole, itraconazole, posaconazole, and isavuconazonium was the primary suspect drug in 1 852, 1 395, 703, 27, and 11 cases among the 3 988 reports, and in 591 (31.9%), 149 (10.7%), 59 (8.4%), 18 (66.7%), and 5 (5/11) serious cases among the 822 serious case reports, respectively. A total of 20 066 reports with the above 5 drugs as the primary suspect drug were collected in FAERS database, 9 635 (48.0%) of which were serious cases. Voriconazole, fluconazole, itraconazole, posaconazole, and isavuconazonium was the primary suspect drug in 7 758, 6 180, 2 869, 1 796, and 1 463 cases among the 20 066 reports, and in 4 295 (55.4%), 2 806 (45.4%), 1 191 (41.5%), 828 (46.1%), and 515 (35.2%) serious cases among the 9 635 serious case reports, respectively. Based on the data reported by Shandong Province and in FAERS database, 18 and 207 risk signals of  adverse reaction not mentioned in the labels were identified, respectively, and 5 of them were identified in both databases, including fluconazole-induced renal impairment and voriconazole-induced oliguria, delirium, psychiatric disorders, and rhabdomyolysis. In the data reported by Shandong Province and in FAERS database, 13 and 189 reports of muscle-related disorders (rhabdomyolysis, myopathy, and myositis) were identified respectively, involving voriconazole (in 8 and 62 cases), itraconazole (in 4 and 74 cases), and flucona- zole (in 1 and 53 cases).　Conclusions Renal impairment induced by fluconazole and oliguria, delirium, psychiatric disorders, and rhabdomyolysis induced by voriconazole are risk signals of adverse reaction not mentioned in the labels for triazole antifungal agents. Voriconazole, itraconazole, and fluconazole may also cause muscle-related disorders, warranting vigilance in clinical practice.

Neutropenia is the most common hematological toxicity in chemotherapy for cancer patients. Granulocyte colony-stimulating factors (G-CSF) are currently the most commonly used symptomatic therapeutic drugs in clinical practice, playing a key role in ensuring adequate doses and on schedule in chemotherapy. As of December 2024, more than 80 specifications of G-CSF have been approved for market in China, which provides diverse options in clinical practice while also poses higher demands on standardized management of pharmaceutical services. Therefore, the Oncology Specialty Pharmacists Branch of the Chinese Pharmacists Association, in collaboration with the National Cancer Center and multidisciplinary experts nationwide, jointly formulated this guideline by integrating clinical evidence, relevant regulations on pharmaceutical affairs management, and pharmaceutical service practices. The development process involves systematic literature search, Delphi method, expert interviews, and discussions. The key pharmacological service points of G-CSF in cancer patients were systematically elaborated in this guideline, covering aspects such as indication management, dosage and administration, medication for special populations, combined medication strategies, economic evaluation, and adverse reaction monitoring, resulting in 22 recommendations. This guideline aims to provide a systematic and scientific reference for the rational use of G-CSF and related pharmaceutical services for cancer patients.

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.

Bruton's tyrosine kinase inhibitors (BTKi) are a class of novel small-molecule targeted antitumor drugs used to treat B-cell malignancies. However, safety issues associated with BTKi may lead to treatment interruption, compromising their efficacy. To promote the standardized management of safety in BTKi treatment, Evidence-Based Pharmacy Professional Committee of the Chinese Pharmaceutical Association, Hospital Pharmacy Professional Committee of the Chinese Pharmaceutical Association, Division of Therapeutic Drug Monitoring of Chinese Pharmacological Society, Expert Committee on Lymphoma of Chinese Society of Clinical Oncology, Expert Committee on Leukemia of Chinese Society of Clinical Oncology, Integrated Cancer Cardiology Branch of China Anti-Cancer Association, Hematology Branch of the Chinese Medical Association, and Hospital Pharmacy Professional Committee of the Cross-Straits Medicine Exchange Association formulated the Evidence-based Expert Consensus on the Clinical Management of Safety of Bruton′s Tyrosine Kinase Inhibitors (2024), which was published in the Chinese Journal of Cancer Research in June 2024. It covered 9 clinical issues in the following 3 domains: (1) the management of common adverse reactions of BTKi such as bleeding, cardiovascular events, hematological toxicity, infections, rashes, diarrhea, and arthralgia; (2) the management of drug-drug interactions; (3) management guidance for special populations. This consensus provides evidence-based recommendations for the safety management of BTKi medication in clinical practice. This article provides an interpretation and evidence summary of the consensus in Chinese, aiming to facilitate its implementation in China, enhance the safety management of BTKi treatment, and improve patient outcomes.

A 70-year-old female patient with tumor in the neck and body of the pancreas received 11 cycles of chemotherapy with paclitaxel and gemcitabine. Due to disease progression, she subsequently underwent chemotherapy of fluorouracil, calcium folinate, and irinotecan, combined with immunotherapy of serplulimab. After 28 days (only one session of immunotherapy), the patient developed drooping of the right upper eyelid and chest tightness, followed by pain in the middle and lower segments of the sternum and radiating pain to the throat, accompanied by speech difficulties, dysphagia, and chest tightness and wheezing. Laboratory tests indicated hypersensitive troponin T 0.551 μg/L, creatine kinase (CK) 3 426 U/L, CK-MB 176 μg/L, and myoglobin 1 702 μg/L. The imaging examination of head and neck ruled out intracranial lesions, while the electrocardiogram suggested myocardial damage. Immune-related myocarditis with myositis and/or myasthenia gravis overlap syndrome (IM3OS) induced by serplulimab was considered. Immunotherapy was temporarily halted, and treatments with methyprednisolone and human immunoglobulin were administered. Sixteen days later, clinical symptoms of IM3OS in the patient were improved, with laboratory tests showing hypersensitive troponin I 0.075 μg/L, CK 216 U/L, CK-MB 58 μg/L, and myoglobin 273 μg/L. Upon follow-up, the patient switched to monotherapy with irinotecan alone or combined with raltitrexed for cancer treatment, clinical symptoms of IM3OS did not recur, and no abnormalities were observed in myocardial injury markers or muscle enzymes.

Objective To analyze the occurrence and influencing factors of adverse reactions in patients with inflammatory bowel disease (IBD) during the long-term treatment with vedolizumab （VDZ）.　Methods The study was a retrospective observational design. The study subjects were selected from patients who long-termly used VDZ to treat moderate-to-severe active IBD in Tianjin Medical University General Hospital from February 1, 2021 to December 31, 2023. Clinical data of patients were collected through the hospital system of clinical pharmacy management, including general information, IBD condition, VDZ maintenance treatment plan, combination of drugs, laboratory test results, etc. The adverse reactions of VDZ were screened and their clinical manifestations, severity, intervention and outcomes were analyzed descriptively. The patients were divided into 2 groups according to whether VDZ adverse reactions occurred, and the differences in clinical data between them were compared; the influencing factors of adverse reactions were analyzed by multivariate logistic regression method.　Results A total of 142 patients were included in the study, including 81 males and 61 females, aged (37.6±6.4) years with a range from 18 to 57 years. There were 103 patients (72.5%) developed VDZ adverse reactions, which mainly involved skin (52 patients, account for 50.5%), digestive system (33 patients, account for 32.0%) and respiratory system (18 patients, account for 17.5%). All 103 patients did not stop VDZ treatment, and the adverse reaction symptoms disappeared or were relieved after symptomatic treatments. Compared with patients without VDZ adverse reactions, the age of patients with VDZ adverse reactions were higher [(39.5±5.4) years vs. (32.4±6.7) years], and the proportions of patients with chronic relapsing clinical type [65.0%(67/103） vs. 41.0%(16/39)], severe disease activity [60.2%(62/103） vs. 33.3%(13/39)], combined drug use [67.0%(69/103） vs. 46.2%(18/39)], and injecting VDZ once every 4 weeks during maintenance treatment [27.2%(28/103） vs. 10.3%(4/39)] in the group were larger, with statistical significance (all P<0.05). Multivariate logistic regression analysis showed that the chronic relapsing clinical type ［odds ratio (OR)=1.012, 95% confidence interval (CI): 1.001-1.028, P=0.002］, severe disease activity (OR=1.096, 95%CI: 1.010-1.158, P=0.040), combination drugs (OR=1.035, 95%CI: 1.003-1.122, P=0.041), VDZ maintenance therapy injection interval of 4 weeks (OR=1.014, 95%CI: 1.002-1.113, P=0.005) were the risk factors for VDZ adverse reactions.　Conclusions Among IBD patients receiving long-term treatment of VDZ, the incidence of adverse reactions of VDZ was 72.5%, mainly involving skin, digestive system and respiratory system. Symptomatic treatments could be given, and the prognosis was good. Patients with chronic relapsing clinical type, severe disease activity, com- bination therapy, and shorter VDZ maintenance injection interval were at higher risk of adverse reactions.

Sodium-glucose transporter 2 inhibitors (SGLT2i) are currently widely used as a class of hypoglycemic drugs. Due to their unique hypoglycemic mechanism and significant cardio-renal protective effect, SGLT2i have become one of the core drugs in the treatment of type 2 diabetes mellitus. However, in recent years, it has been found that SGLT2i can lead to increased serum creatinine and urea nitrogen in some patients, and the risk of kidney injury has gradually attracted clinical attention. How to effectively prevent and supervise the potential renal injury risk while giving full play to its therapeutic advantages has become an important topic in current clinical practice and drug safety management. Multi-dimensional prevention and supervision strategies should be adopted in clinical practice such as identifying high-risk populations based on the latest evidence, strictly screening patients, dynamically monitoring renal function, optimizing combination medication regimens, and achieving risk warning using biomarkers and artificial intelligence tools.

Objective To explore the clinical features of nivolumab-induced Stevens-Johnson syndrome/toxic epidermal necrolysis (SJS/TEN).　Methods Relevant databases at home and abroad (as of December 31, 2023) were searched to collect case reports of nivolumab-induced SJS/TEN, and the demographic characteristics, nivolumab application, combination drugs, clinical manifestations, intervention measures, and outcomes were extracted and analyzed descriptively and statistically.　Results A total of 27 case reports were included and 29 patients were enrolled in the study, including 18 males and 11 females. The age ranged from 45 to 86 years, with an average age of 67 years. The primary diseases were mainly melanoma, stomach cancer, and lung cancer. Twelve patients had records of nivolumab administration, and the dosage was within the recommended range in the labels; 13 patients had records of combination drugs, mainly other antineoplastic drugs, hypoglycemic drugs, antihypertensive drugs, lipid-regulating drugs, etc. The time from using nivolumab to the diagnosis of SJS/TEN was 7 d to 3 years, and 20 patients were <8 weeks. The clinical manifestations were mainly diffuse erythema, flaky skin peeling and erosion, mucosal involvement, etc. Sixteen patients had skin biopsy records, all of which met the histopathological characteristics of SJS/TEN. After the diagnosis of SJS/TEN, 17 patients discontinued nivolumab and received symptomatic treatments, of which 15 patients had improved skin symptoms, one patient had worsened skin symptoms, and one patient had no record of skin outcome; 12 patients had no record of whether or not discontinuing nivolumab, of which 8 patients had improved skin symptoms, 2 patients had worsened skin symptoms, one patient had no record of skin outcome, and one had no record of prognosis. One patient rechallenged nivolumab, severe SJS/TEN recurred. Thirteen of 29 patients died. Of them, 1 died due to cardiac arrest, 4 due to worsened skin rash, and 8 due to primary disease progression.　Conclusions SJS/TEN caused by nivolumab mostly occurs within 8 weeks of treatment, and the clinical manifestations were similar to those caused by other drugs. The mortality rate of nivolumab-induced SJS/TEN is high, and skin rash could be improved after withdrawal of nivolumab and symptomatic treatments.

Objective To explore the differences on contraindication information for children in domestic and foreign drug instructions, and provide reference for improving the relevant information in Chinese drug insert sheets.　Methods Chinese drug insert sheets of chemicals and biological products contained in the China Pharmacopoeia 2020 and those of the western medicines in the 2023 China′s Basic Medical Insurance, Work-related Injury Insurance and Childbirth Insurance Drug Catalog were collected; drugs that were marked as contraindication for children were selected and relevant contraindication information in the Chinese drug insert sheets was collected. Instructions of the above-mentioned drugs approved by the U.S. Food and Drug Administration (English labels) were also collected, and the information on pediatric medication was reviewed and compared with the Chinese drug insert sheets.　Results A total of 222 drugs were labeled as contraindication for children in the Chinese drug insert sheets, of which 149 were available for their English labels; 123 drugs (17.5%) were not labeled as contraindication for children in English labels, and 26 (82.5%) were labeled. The 123 drugs that were not labeled as contraindication for children in the English labels included the following conditions: 58 were labeled as contraindication for children of some age in the Chinese drug insert sheets but not in the English labels, and relevant medication information was provided; 40 were labeled as contraindication for children of some age group in the Chinese drug insert sheets but was described as the effectiveness and safety of the use for children have not yet been determined for this age group in the English labels; 13 were labeled as contraindication for children in the Chinese drug insert sheets, but the medication information on children in the English labels was not clear or missing; 12 were labeled as contraindicated for children in Chinese drug insert sheets but not in the English labels, only expressed as not yet determined or not recommended for use, etc., with inconsistent age group. Among the 26 drugs labeled as contraindication for children in both Chinese and English instructions, the contraindication age group were the same in above 2 instructions for 20 drugs, and were inconsistent for the other 6 drugs; reasons for contraindication were described in both the 2 instructions for 17 drugs (13 were consistent, 4 were inconsistent), only in English labels for 8 drugs, and only in Chinese drug insert sheets for 1 drug.　Conclusions Many drugs are labeled as contraindication for children in Chinese drug insert sheets, but reasons for contraindication are rarely explained. Differences in children′s age in contraindications exist for some drugs between the Chinese drug insert sheets and English labels. The information on contraindications for children in Chinese drug insert sheets still needs to be further improved.

Glucagon- like peptide- 1 receptor agonists (GLP- 1RA) have been widely used in the treatment of type 2 diabetes mellitus (T2DM). However, the acceleration of heart rate caused by GLP- 1RA should not be ignored. In the general population and patients with diabetes, increased heart rate has an independent correlation with the incidence and mortality of cardiovascular diseases. In general, the long- acting GLP- 1RA seem to exert a greater effect in increasing heart rate, and the effect is dose- dependent and negatively correlated with baseline heart rate. The increase in heart rate caused by GLP- 1RA may be related to enhanced sympathetic nervous activity, reflex tachycardia as a response to vasodilation, etc. It is advisable to closely monitor the increased heart rate induced by GLP- 1RA in clinical practice, especially in patients with high- risk factors for cardiovascular disease. In case of elevated heart rate, the management begins with immediate discontinuation of the GLP- 1RA and symptomatic intervention should be given if necessary.

Objective To mine the drugs that may cause capillary leak syndrome (CLS), and evaluate the risk of CLS, and provide reference for safe and rational use of drugs in clinic.　Methods Adverse event (AE) reports with the preferred term "capillary leak syndrome" from the 1st quarter of 2004 to the 4th quarter of 2023 were collected by searching US Food and Drug Administration Adverse Event Reporting System (FEARS) database. Reporting odds radio (ROR) method and proportional reporting ratio (PRR) method were used to mine the AE risk signals. Drugs with report number ≥3, lower limit of the 95% confidence interval (CI) of ROR value >1, PRR ≥2, χ² ≥4 were grouped and classified according to the Anatomical Therapeutic Chemical Classification (ATC) system. The top 20 drugs in ROR values were selected, and a risk assessment for drugs potentially causing CLS was performed by reviewing drug labels, adverse reaction datasets, and relevant literature.　Results A total of 1 033 AE reports related to CLS were collected, involving 558 primary suspected drugs associated with CLS. The top 5 types of drugs that the most commonly causing CLS were antineoplastic and immunomodulating agents, systemic hormonal preparations, anti-infectives for systemic uses, cardiovascular system, and alimentary tract and metabolism. The risk assessment results showed that 13 drugs of the top 20 drugs in signal intensity (clofarabine, gemcitabine, interleukin-3, denileukin diftitox, dinutuximab, filgrastim, trabectedin, cytarabine, busulfan, docetaxel, trastuzumab, vildagliptin and melphalan) were high-risk drugs causing CLS, among which cytarabine, docetaxel, busulfan, trastuzumab, vildagliptin, and melphalan were not recorded to cause CLS in the labels. The other 7 drugs (asparaginase, fludarabine, amphotericin B, bosutinib, daunorubicin, ponatinib, and bleomycin) were low-risk drugs causing CLS.　Conclusions Thirteen drugs are high-risk drugs that may cause CLS, among which cytarabine, docetaxel, busulfan, trastuzumab, vildagliptin and melphalan are not recorded causing CLS in the labels. It is suggested that clinicians and pharmacists should be vigilant against high-risk drugs, especially those not recorded causing CLS in the labels.

Objective Based on the adverse drug event active surveillance and assessment system-Ⅱ (ADE-ASAS-Ⅱ) and the information of inpatients in the hospital information system (HIS), the automatic monitoring module of movement disorders was constructed and its application effect in the real- world study of drug-induced movement disorders (DIMDs) was explored.　Methods Literature reviews, case reports, spontaneous reports and medical records were collected, the keyword set was screened based on ADE-ASAS-Ⅱ system and text classification technology, and an automatic monitoring module was constructed. The information of hospitalized patients in Chinese PLA General Hospital （our hospital） was selected from October 10 to 16, 2022. The results of manual evaluation and the system alarm by the automatic monitoring module were compared, and the performance of the automatic monitoring module was evaluated and optimized through repeated machine learning. The medical record information of hospitalized patients who used sodium valproate throughout the year in our hospital in 2022 were collected, and the occurrence of movement disorders related to sodium valproate was analyzed using the automatic monitoring module.　Results A total of 4 918 hospitalized patients (146 with movement disorders) were collected, and the final setting conditions of the automatic monitoring module were determined, including inclusion criteria (43 text keywords, 3 diagnosis) and exclusion criteria (11 text and 20 document titles were omitted). Among the 1 138 hospitalized patients using sodium valproate in 2022, the incidence of DIMDs with tic and tremor as main clinical manifestations detected by automatic monitoring module was 1.67% (19/1 138).　Conclusion The automatic monitoring module of druginduced movement disorders based on machine learning and manual evaluation can be applied to explore the occurrence characteristics of DIMDs in the real world, and provide information for pharmacovigilance in clinic.

Adverse drug reaction (ADR) is an important problem in clinical diagnosis and treatment, and basic research related to ADR is essential. Exploring the mechanism of ADR through basic research can provide a theoretical basis for formulating effective prevention strategies and targeted treatment programs for ADR; many safety problems found in the process of clinical medication can be effectively verified and solved through basic research, such as the dose?response (toxicity) relationship of drugs and drug interactions; basic research related to drug toxicity is an indispensable key link in the process of drug research and development, and its research results are directly related to the safety of candidate compounds and the feasibility of clinical application. At present, there is a limited amount of literature on the basic research related to the mechanism of ADR in China. It is hoped that more researchers will pay attention to basic research related to ADR and drug safety, and promote the development of this field to a higher level.

Neuroinflammatory response runs through the pathological process of epilepsy, and the regulation of proinflammatory factors such as (tumor necrosis factor-α, TNF-α), (interleukin, IL)-1β, IL-6 and Toll-like receptors 4/nuclear factor-kappa B signaling pathways may help improve epilepsy symptoms. Traditional Chinese medicines with anti-epileptic effects can be mainly divided into the following 6 categories: Pinggan Xifeng drugs (平肝息风药, liver-calming and wind-extinguishing herbs), Qingre drugs (清热药, heat-clearing drugs), Huatan drugs (化痰药, phlegm-relieving drugs), Huoxue Huayu drugs (活血化瘀药, circulation-promoting and stasis-removing drugs), Buxu drugs (补虚药, tonifying drugs), and Kaijiao drugs (开窍药, consciousness-restoring drugs). The active ingredients contained in these traditional Chinese medicines can play a therapeutic role in epilepsy treatment by regulating the release of key proinflammatory factors and inflammatory signaling pathways. Adverse reactions caused by Chinese patent medicines involve a variety of factors, which can be summarized into the process of medicinal materials preparation, the principle of traditional Chinese medicine compatibility, the accuracy of dialectical treatment, individual differences, etc. When using anti-epileptic Chinese medicine in clinical practice, it should be flexibly applied according to specific conditions to achieve the goal of precise treatment.

A 58 year old female patient with anti synthetase syndrome received compound sulfa- methoxazole ［containing trimethoprim (TMP) 80 mg and sulfamethoxazole (SMZ) 0.4 g， SMZ- TMP］ 3 tablets thrice daily orally for the treatment of Pneumocystis jirovecii pneumonia. Before medication, the patient′s blood potassium was 3.3 mmol/L and blood chlorine was 116 mmol/L. Three days after SMZ-TMP treatment, the patient′s blood potassium was 5.7 mmol/L, blood chlorine was 114 mmol/L, blood pH was 7.3, urine pH was <5.5, blood chlorine was 114 mmol/L, and bicarbonate was 15 mmol/L. Hyperkalemia type renal tubular acidosis due to SMZ-TMP was considered. The dosage of SMZ-TMP was reduced to 2 tablets once daily orally. After 1 day of diuretic and potassium excretion treatments, the patient′s blood potassium levels returned to normal; after 2 days of the treatments, her blood chlorine was 109 mmol/L and bicarbonate was 17 mmol/L; after 3 days of the treatments, her chest CT showed emphysema in the neck and mediastinum. The dose of SMZ-TMP was changed to 3 tablets thrice daily orally, and at the same time intravenous infusion of ganciclovir 0.3 g twice daily was given. And again, her blood potassium increased and blood pH decreased. Sodium bicarbonate 1 g thrice daily orally was given to correct the acidosis. After adding SMZ-TMP for 2 days, SMZ-TMP dosage was reduced to 2 tablets once daily orally again. Seven days later, the patient′s vital signs were stable, her mediastinal emphysema was significantly improved, her blood potassium was 4.7 mmol/L, and blood pH was 7.4.

Objective To analyze the clinical characteristics of tigecycline-related adverse reactions and provide the basis for the safe and rational use of the drug.　Methods Adverse reaction reports with suspected drug as tigecycline from Beijing Adverse Drug Reaction Monitoring Center from January 1st, 2019 to June 30th, 2024 were collected. The adverse reaction reports were standardized using the preferred term (PT) and system organ class (SOC) in the Chinese updated edition (2015 version) of the World Health Organization Adverse Reaction Terminology. The patients′ general condition, tigecycline use, and adverse reaction occurrence (including latency, severity, treatment, outcome, and correlation evaluation) were descri- ptively and statistically analyzed.　Results A total of 408 tigecycline-related adverse reaction reports were entered, including 153 females (37.5%) and 255 males (62.5%). The age was (68±21) years, ranging from 2 to 99. The main reasons for tigecycline use were infections of lung, blood flow, skin and skin soft tissue, etc. The pathogens were mainly Klebsiella pneumoniae, Acinetobacter baumanii, Escherichia coli, etc. The usage and dosage of tigecycline in most patients were in line with the instructions. Four hundred and eight adverse event reports involved 11 SOCs and 580 PTs. The top 3 SOCs were gastrointestinal diseases (195 case times, 33.62%), vascular, bleeding and coagulation diseases (183 case times, 31.55%), and hepatobiliary diseases (142 case times, 24.48%). The main clinical manifestations were nausea, vomiting, diarrhea, etc. The main laboratory abnormalities were decreased plasma fibrinogen, decreased platelet count, increased alanine aminotransferase, increased aspartate aminotransferase, and increased bilirubin. There were 27 case times of adverse reactions that were not recorded in the instructions, mainly including leukopenia, abdominal distension, fever, dysbacteriosis, etc. The latency of adverse reactions ranged from 5 min to 65 days, with a median time of 5 days. The grade of adverse reactions was general in 379 patients (92.89%) and severe in 29 patients (7.11%). The top 3 SOCs involved in 53 case times of severe adverse reactions were hepatobiliary diseases (30 case times, 56.60%), vascular, bleeding and coagulation diseases (8 case times, 15.09%), and urinary tract diseases (4 case times, 7.55%), the main clinical manifestations were elevated liver enzymes, coagulation disorders, pancreatitis, etc. After the occurrence of adverse reactions, all patients stopped tigecycline, and received symptomatic treatments such as liver protection, intravenous infusion of human fibrinogen, intravenous infusion of platelets, and antidiarrheal therapy. Among 408 patients, 66 (16.18%) were cured, 297 (72.79%) were improved, 20 (4.90%) were not improved, and 25 cases′ outcome (6.13%) were unknown. The shortest time for recovery or improvement was 0.5 hour, the longest was 44 days, with a median time of 5 days. The correlation between tigecycline and adverse reactions was probable in 132 patients (32.35%), and possible in 276 patients (67.65%).　Conclusions Tigecycline-related adverse reactions involve multiple organ systems, mainly including gastrointestinal diseases, vascular, bleeding and coagu- lation diseases, and hepatobiliary diseases, etc. which can lead to severe adverse reactions such as acute pancreatitis and coagulation disorders. After drug withdrawal and symptomatic treatments, most patients had a good prognosis.

Objective To analyze the current preparation and usage situation of first-aid drugs in the rescue vehicles in children′s medical institutions, and provide references for optimizing the list of emergency drugs.　Methods First-aid drug lists in the rescue vehicles of 12 children′s medical institutions from 11 provinces and municipalities in China were collected through questionnaire surveys, and the drugs as well as their quantities were compared. The existing problems in the use of first-aid drugs in the 12 medical institutions were investigated by on-site interviews. The usage information of first-aid drugs in the rescue vehicles of the General Surgery and Cardiology Department of Shanxi Children′s Hospital from May 2022 to April 2023 was collected through the hospital information center, and usage frequency and dosage per patient of the drugs were calculated. Descriptive statistical analysis was conducted on the collected data.　Results The first-aid drug lists in 12 hospitals were various, including 7 to 22 kinds of drugs and invol- ving a total of 23 drugs. These mainly included vasoactive drugs, cardiotonic drugs, antiarrhythmic drugs, antiangina and anti-ischemic drugs for the heart, antispasmodic drugs, diuretics, dehydrating drugs, sedative-hypnotic drugs, and glucocorticoids, all of which were injections. The drugs that were included in all the lists of 12 hospitals were epinephrine, dopamine, dexamethasone, furosemide, and atropine. The drug lists of different rescue vehicles throughout the hospital were the same in 4 hospitals, while the lists varied among departments based on their specific clinical needs in the other 8 hospitals. None of the 12?hospitals had a first?aid drug usage manual. The on?site interview results showed that, the existing problems about drug prepa- ration and use in rescue vehicles mainly involved the following 6 aspects: drug types, quantities, labels, storage, procurement, and usage. In Shanxi Children′s Hospital, the types and quantities of first?aid drugs in rescue vehicles of General Surgery Department and Cardiology Department were the same. There were 6 and 9 kinds of drugs were used in the 2 departments during rescue operations, respectively. The drugs that were never used in either department included promethazine, lidocaine, diazepam, phenobarbital, raceanisodamine, sodium bicarbonate, atropine, glucose, and calcium gluconate.　Conclusions The phenomenon of unreasonable kinds and quantities of first?aid drugs in the rescue vehicles existed in the children′s medical institutions, and the drugs provided did not fully match the actual clinical needs. There was an urgent need for preparation guidelines and usage manuals of first?aid drugs that were suitable for children′s medical institutions to enhance the scientificity of drug supply and the correctness of usage.

Prescription sequence symmetry analysis (PSSA) is one of the important methods for post-marketing pharmacovigilance based on the real-world medical prescription databases. It can be used to detect prescription cascades and mine adverse drug reaction (ADR) signals, which has been verified by many studies. PSSA shows high specificity and medium sensitivity in identifying ADR. It can quantify the correlation or risks of ADR. It is easy to use and simple in algorithm, and it has good robustness to some non time-dependent confounding factors. However, the results may be affected by some human confounding factors and data quality. This paper reviews the principle, calculation method, application scope, and precaution of PSSA by reviewing related literature on PSSA domestically and abroad, in order to provide reference for pharmacovigilance in China.

Objective To understand the clinical characteristics of myelopathy induced by intrathecal chemotherapy of methotrexate (MTX) and/or cytarabine (Ara-C).　Methods Relevant databases at home and abroad (up to February 18, 2024) were searched and case reports of myelopathy induced by intrathecal chemotherapy of MTX and/or Ara-C were collected. The patients′ general situation (gender, age, primary disease, etc.), use of MTX and/or Ara-C, previous radiotherapy, and occurrence time, clinical manifestations, spinal magnetic resonance imaging (MRI) results, cerebrospinal fluid test results, treatments and outcomes of myelopathy were extracted and analyzed descriptively and statistically.　Results A total of 75 articles were enrolled, involving 104 patients, with 62 males, 35 females, and 7 unknown genders. Their ages ranged from 1 to 74 years, with a median age of 26 years. The primary diseases included hematological malignancy in 101 cases, and other solid tumors in 3 cases. Before the occurrence of myelopathy, 42 cases had central nervous system tumor infiltration. Seventy-three patients received intrathecal injection of MTX combined with Ara-C, 21 patients received single MTX therapy, 10 patients received single Ara-C therapy. The number of intrathecal injections ranged from 1 to 62, with a median of 5 injections. Twenty-nine patients had received radiotherapy before. When myelopathy occurred, the cumulative dose of MTX was 7.5-480.0 mg, with a median cumulative dose of 60.0 mg; the cumulative dose of Ara-C was 15 1 599 mg, with a median cumulative dose of 280 mg. The onset time of myelopathy was from immediately to 365 days after the last intrathecal injection, with a median time of 2 days. The main clinical manifestations were weakness of both lower limbs, urinary and fecal incontinence or retention, paresthesia, and paraplegia, etc. Fifty-three patients had spinal abnormality in MRI examination, 32 had abnormal cerebrospinal fluid protein quantity, intrathecal basic protein, or homocysteine. After the diagnosis of myelopathy, 86 patients were treated with drugs, radiotherapy, plasma exchange, and cerebrospinal fluid exchange, and 18 patients had no record of treatment situation. Therapeutic agents included glucocorticoids, B vitamins, folic acid, immunoglobulin, leucovorin, S-adenosylmethionine, and dextromethorphan. Of the 104 patients, 20 achieved complete remission, with a median remission time of 30 hours; 25 experienced partial remission, with a median duration of 120 days; 32 showed no significant improvement; 26 died; one patient′s prognosis and outcome were unknown.　Conclusions The median occurrence time of myelopathy induced by intrathecal injection of MTX and/or Ara-C is 2 days. The main clinical manifestations are bilateral lower extremity weakness, urinary and bowel incontinence or retention, paresthesia, and paraplegia, etc. Abnormal spinal in MRI examination, quantitative cerebrospinal fluid protein, intrathecal basic protein occurred in some patients. Intrathecal injection should be stopped immediately after diagnosis of myelopathy, and the treatments such as drug and cerebrospinal fluid replacement should be given. The clinical outcome of myelopathy induced by intrathecal MTX and/or Ara-C was poor.

Objective To understand the clinical characteristics of hypophysitis due to nivolumab and provide reference for the safe use of nivolumab in clinic.　Methods Relevant databases at home and abroad (up to May 31, 2024) were searched and case reports of hypophysitis caused by nivolumab were collected. Relevant information of patients (gender, age, primary disease), single and combined use of nivo- lumab, occurrence of hypophysitis, causality evaluation, intervention measures and outcomes were extracted and analyzed descriptively and statistically.　Results A total of 56 case reports, 53 in English and 3 in Chinese, were enrolled in the analysis, involving 59 patients, with 40 males and 19 females. Their ages ranged from 26 to 84 years, with an average age of 61 years. The primary diseases were malignant melanoma in 20 cases, renal cell carcinoma in 19 cases, lung cancer in 11 cases, glossopharyngeal cancer in 4 cases, esophageal cancer in 2 cases, and gastric cancer, colon cancer and pleural mesothelioma in 1 case each. Among the 59 patients, 33 were treated with nivolumab monotherapy, 24 with nivolumab and ipilimumab, 1 with nivolumab and anlotinib and 1 with nivolumab and platinum. The average time of hypophysitis caused by nivolumab alone was 25.6 weeks after treatment, and that caused by the combination therapy was 9.9 weeks after treatment. The main clinical manifestations of hypophysitis caused by nivolumab were fatigue, anorexia, headache, and nausea. Among the 59 patients, 56 patients discontinued nivolumab and received glucocorticoid, 20 of whom resumed nivolumab treatment after improvement of clinical symptoms; 3 patients′ situation was not described clearly. The outcomes of the 59 patients were as follows. Four were recovered, 46 were relieved, 2 patients′ pituitary function was not recovered, 4 died, 1 developed secondary autoimmune vasculitis, 1 developed secondary autoimmune hepatitis, and it was unknown in one patient.　Conclusions The average occurrence time of hypophysitis caused by nivolumab monotherapy is longer than that caused by combination therapy. The main clinical manifestations are fatigue, anorexia, headache, etc. After timely discontinuation of medication and symptomatic treatments with glucocorticoid, most patients have a good prognosis, but it can lead to death in severe cases.

Objective To analyze the characteristics of Fournier gangrene (FG) induced by sodium-glucose cotransporter 2 inhibitors (SGLT2i), and provide reference for clinical safe drug use.　Methods CNKI, Wanfang Med Online, VIP, PubMed, Web of Science and other databases (up to January 2024) were retrieved and clinical data on patients with FG associated with the 5 kinds of SGLT2i currently used in clinical practice in China were collected and descriptively analyzed, including gender, age, comorbidities, concomitant medications, onset time and clinical manifestations of SGLT2i-related FG, laboratory and imaging examination results, treatment and outcomes, etc.　Results A total of 15 documents were included in the analysis, involving 15 patients, with 12 males and 3 females. The age of these patients ranged from 34 to 72 years, with 11 cases being over 50 years. Dapagliflozin was used in 7 cases, empagliflozin in 6 cases, canagliflozin in 2 cases, and no related reports on ertugliflozin and henagliflozin were collected. The main clinical manifestations of the 15 patients were redness, swelling, pain, abscess or purulent discharge in perineum, scrotum and perianal, etc. The time from application of SGLT2i to onset of FG ranged from 1 month to 6 years. Wound secretion bacterial culture was performed in 10 patients, and the results were all positive, including 9 cases of bacterial infection and 1 case of mixed infection of bacteria and fungi. All 13 patients who underwent imaging examinations had imaging manifestations related to FG. SGLT2i were discontinued in all patients. After treatments with broad-spectrum antibiotics and surgery, 14 cases were improved and 1 case was cured.　Conclusions SGLT2i has the risk of causing FG, which is more common in males. The clinical use of SGLT2i should be monitored closely. Secretion culture and imaging examination are helpful for the diagnosis of FG. The patient′s prognosis is good after discontinuation of medication, symptomatic treatment, and surgery.

Objective To understand the application situation and role of prescription sequence symmetry analysis (PSSA) in pharmacovigilance.　Methods The relevant databases at home and abroad were searched (up to April 30, 2024), and the original articles using PSSA as the research method were collected. The basic information of the literature (first author, publication year, country, etc.), the purpose and main content of the study, the index drugs as well as the marker drugs or medical diagnoses involved in the adverse drug reactions (ADRs) were extracted. Descriptive statistical analysis was carried out.　Results A total of 66 articles were included in the analysis. The first article was published in 1996, the number of articles published in recent years has increased significantly, and those published after 2016 accounted for 68.2% (45/66). The top 3 countries in terms of published literature quantity were the United States, Denmark, and Japan. The index drugs most commonly studied were those for the cardiovascular system and the neuropsychiatric system, in 18 and 14 articles respectively. The drugs studied in 3 or more papers were hypolipidemic drugs, antihypertensive drugs, antipsychotics, antiepileptics, proton pump inhibitors, hypoglycemic drugs and anticoagulants. The targeted ADRs/diseases most studied were those about the neuropsy- chiatric system (in 13 studies), followed by those about the endocrine and metabolic system (in 12 studies). The research objective in 47 articles was to explore the association between index drugs and ADRs/diseases through PSSA. Finally, the associations between 21 ADRs and index drugs were identified in 24 articles, of which 9 were new ADRs not recorded in drug instructions; benefits or potential preventive and therapeutic effects of index drugs on certain diseases were found in 7 studies. Ten studies were conducted to explore ADR information of specific drugs or detect suspicious drugs that cause specific ADRs, and some correlation signals between drugs and ADRs that previously unknown were detected. Nine studies evaluated the prescribing cascades, including the use of antitussive drugs after ACEI, the prescribing cascades related to drug-induced lower urinary tract symptoms and edema, the prescription cascades of statins, and the prescribing cascade relic.　Conclusion PSSA is a useful method for identifying potential prescribing cascades and mining ADR signals using medical prescription databases, especially suitable for the safety monitoring of long-term medication for chronic diseases and the signal detection of ADR that causal relationships are difficult to determine.

A 38- year- old male patient with ankylosing spondylitis received subcutaneous injection of adalimumab 40 mg once every 2 weeks. After 21 months of medication, the patient developed fever, fatigue, swelling, and pain in the right neck lymph node and throat. Laboratory tests showed that the tuberculin test was strong positive, mycobacterium tuberculosis γ- interferon release test was 1  911.98  ng/L, and erythrocyte sedimentation rate was 27  mm/1 h. The biopsy of right neck lymph node showed granulomatous inflammation of the lymph node. The patient was diagnosed with cervical lymph node tuberculosis, which was considered to be related to adalimumab. The drug was stopped and anti-tuberculosis treatments were given. The next day, the patient′s temperature returned to normal. After 5 days, the swelling and pain of cervical lymph nodes and throat, and the fatigue were relieved gradually. After 45 days, the above symptoms in the patient disappeared.

Objective To investigate the awareness of medical staff on pharmacovigilance and the current situation of the construction of pharmacovigilance system in medical institutions.　Methods A self-designed questionnaire was sent to medical institutions in China through Professional Committee on Pharmacovigilance Research, China Society for Drug Regulation in the form of Wechat, and medical staff participated voluntarily. The contents of the questionnaire included 23 questions in 4 dimensions, including the basic information of the respondents, their understanding of the concept and regulations of pharmacovigilance, the management of pharmacovigilance, and the reporting and feedback of adverse drug reactions(ADRs)/events in their medical institutions. The survey time was from August 18, 2023 to October 18, 2023. The data from the questionnaire were analyzed descriptively.　Results The collected questionnaires were from medical institutions in 31 provinces, autonomous regions, and municipalities directly under the central government, with a total of over 100 questionnaires collected in each region. A total of 10 991 medical staff participated in the survey, including 5 504 pharmacists, 2 120 doctors, and 3 367 nurses. Among them, 10 131 (92.18%) respondents had heard of pharmacovigilance, 4 511 (41.04%) had participated in pharmacovigilance-related works, 9 368 respondents (86.41%) answered that the ADRs monitoring and management system had been established in medical institutions where they worked, 8 186 respondents (75.51%) answered that leading group for pharmacovigilance (including ADRs monitoring) had been set up in the medical institutions where they worked, 8 605 respondents (79.37%) answered that the pharmacovigilance works was managed by special personnel in the institutions where they worked, 7 859 (72.49%) answered that there were liaison officers in the clinical departments where they worked, 6 043 (55.74%) answered that the individuals would be rewarded for reporting ADRs, 4 809 （44.36%） answered that pharmacovigilance had been included in the daily works and assessment indicators of the departments, and 5 351 （49.36%） answered that reports of ADRs were reviewed by special personnel. Active reporting by medical staff was the main collection channel of ADRs, 3 391 (31.28%) answered they had actively captured ADRs from the hospital information system, and 7 728 (71.28%) answered they had reported ADRs through the hospital information system, 10 061 (92.81%) answered that the monitoring results of ADRs would be regularly fed back in the hospitals where they worked, and 6 239 (57.55%) answered that regular training on pharmacovigilance for all medical staff would be provided in the institutions where they worked.　Conclusions Medical staff have generally heard of pharmacovigilance and are aware of the national pharmacovigilance system, but they still have insufficient understanding of the concept and regulations of pharmacovigilance. The degree of participating in pharmacovigilance works of medical staff in different regions are different. The monitoring and management of ADRs could be paid attention to in the most medical institutions, but the degree of improvement of pharmacovigilance system in different levels of medical institutions is different.

Objective To systematically evaluate the incidence and risk factors of acute kidney injury (AKI) induced by vancomycin in pediatric patients.　Methods Databases of PubMed, Embase, The Cochrane Library, Web of Science, CNKI, Wanfang, VIP, Chinese Biomedical Database (CBM) were searched and articles about the risk factors of AKI induced by vancomycin in pediatric patients from inception to June 2024 were collected. Quality assessment was performed using the Newcastle-Ottawa Scale (NOS) for the included studies. Meta-analysis of the data for relevant exposure factors extracted from the included literature was conducted using Rev Man 5.4. The strength of association between the exposure factors and AKI was expressed using the odds ratio (OR) and its 95% confidence interval (CI).　Results A total of 13  studies were entered, involving 11 073 patients. Of them, 1 388 patients were in AKI group and 9 685 patients in non-AKI group. The incidence of AKI was 12.53%, ranging from 4.62% to 27.07%. The quality evaluation results showed that the 13 documents were all of high-quality (NOS score ≥7 points). Meta-analysis showed that admission to intensive care unit (ICU) （OR=2.39, 95%CI: 1.59-3.59, P<0.001）, vancomycin using time ≥7 d (OR=2.19, 95%CI: 1.44-3.34，P=0.003), vancomycin steady-state trough concentration ≥15 mg/L (OR=2.98, 95%CI: 2.22-4.01, P<0.001), combined with nephrotoxic drugs ≥2 kinds (OR=2.92, 95%CI=1.84-4.64, P<0.001), combined with piperacillin sodium and tazobactam sodium (OR=2.71, 95%CI: 1.72- 4.27, P<0.001), combined with carbapenem (OR=2.36, 95%CI: 1.36-4.10, P=0.002), combined with aminoglycosides (OR=1.78, 95%CI: 1.35-2.35, P<0.001), combined with loop diuretics (OR=3.16, 95%CI: 2.36- 4.23, P<0.001), combined with amphotericin B (OR=2.26, 95%CI: 1.35-3.79, P=0.002), combined with contrast medium (OR=2.34, 95%CI: 1.04-5.25, P=0.040), and combined with aciclovir (OR=1.74, 95%CI: 1.04-2.84, P=0.030) were all risk factors of AKI induced by vancomycin in pediatric patients.　Conclusions The incidence of vancomycin-related AKI in pediatric patients was 12.53%. Admission to ICU, vancomycin trough concentration ≥15 mg/L, medication time ≥7 d, and concomitant use of ≥2 nephrotoxic drugs and etc.were risk factors of vancomycin-related AKI.