With the widespread use of immune checkpoint inhibitors (ICIs) in cancer therapy, immune-related adverse events (irAEs) are receiving increasing attention. Among them, ICI-related pneumonitis (CIP) is more common. This article introduces the clinical features, disease classification, and treatment strategies, etc. of CIP, and suggests multidisciplinary cooperation to carried out whole-process management for patients receiving ICIs treatment, early detection, early diagnosis, and establish clear and effective prevention and early warning strategies to maximize the benefits of cancer patients.

To explore the characteristics and factors affecting the occurrence of renal injury in patients with abnormal biochemical indexes of renal function after the use of immune checkpoint inhibitors (ICIs), and to provide reference for selection of clinical treatment regimen.　Methods Patients who were treated with immune checkpoint inhibitors researched and developed independently in China including camrelizumab, sintilimab, tislelizumab， and toripalimab from March 1, 2021 to February 28, 2022 and showed estimated glomerular filtration rate (eGFR) <90-ml/(min·1.73 m2) and/or serum creatinine (Scr)>105-μmol/L were retrieved from the China Hospital Pharmacovigilance System. The clinical data including general information, anti-tumor treatment regimen, laboratory test results, and concomitant medications were collected. Patients were divided into kidney injury group and non-kidney injury group, and all the clinical characteristics were compared between the 2 groups, the influencing factors of kidney injury were analyzed using a binary logistic regression model, the odds ratio (OR) and its 95% confidence interval (CI) were calculated.　Results A total of 222 patients were entered in the analysis, including 170 males and 52 females, with a median age of 67 (36, 85) years. Of them, 144 patients were treated with carrilizumab, 38 with sindilizumab, 31 with tirelizumab, and 9 with treprolizumab; 29 patients (13.1%) developed kidney injury, including 26 cases of grade 1 and 3 cases of grade 2 renal injuries; the time of renal injury occurrence was 19-355 days after the first application of ICIs, and the median time was 108 days. After diagnosed of kidney injury, 13 out of 29 patients stopped ICIs, of which 6 had recovered kidney function and 7 had no improvement; 16 patients continued the ICIs treatment, of which 10 patients had recovered or improved kidney function and 6 had no improvement. The clinical characteristics of patients in the 2 groups were compared, and 10 variables including age, gender, baseline renal function, previous use of carboplatin, previous radiotherapy, combined chemotherapy containing cisplatin, combined paclitaxel chemotherapy, combined tyrosine kinase inhibitor (TKI) anti-vascular therapy, combined proton pump inhibitors, and combined radiotherapy were screened for the binary logistic regression analysis. The results showed that female (OR=3.046, 95%CI: 1.149-8.077), ≤65 years (OR=3.649, 95%CI: 1.435-9.274), combined TKI anti-vascular therapy (OR=4.773, 95%CI: 1.496-15.227), and combined radiotherapy (OR=8.655, 95%CI: 1.268-59.076) were independent risk factors for the development of kidney injury.　Conclusions The incidence of kidney injury in patients with eGFR <90-ml/(min·1.73 m2) and/or Scr >105-μmol/L after using ICIs is 13.1%. In these patients, female, ≤65 years, combined TKI anti-vascular therapy, and combined radiotherapy may be risk factors for the development of ICI-associated kidney injury.

Objective To explore the influencing factors of immune checkpoint inhibitor-related pneumonitis (CIP) in lung cancer patients caused by programmed cell death 1 receptor (PD-1)/programmed cell death ligand 1 (PD-L1) inhibitors.　Methods A retrospective analysis was conducted on clinical data of lung cancer patients treated with PD-1/PD-L1 inhibitors in the First Affiliated Hospital of Guangzhou Medical University from January 2018 to June 2022. Patients with CIP were included in the CIP group, and those who did not experience any immune-related adverse events during the same period were screened in a 1∶1 ratio and included in the control group. The clinical characteristics in patients of the 2 groups were compared and influencing factors of CIP were analyzed using binary logistic regression method. The effect sizes were the odds ratio (OR) and its 95% confidence interval (CI). Results A total of 246 patients (123 in the CIP group and 123 in the control group) were entered in the analysis, including 208 males and 38 females, aged (63±9) years with a range of 32 to 86 years. The diagnosis was non-small-cell lung cancer in 234 patients and small cell lung cancer in 12 patients. There were no statistically significant differences in age, gender, history of respiratory diseases, tumor histological types, TNM stages, and types of immune checkpoint inhibitors used in patients between the 2 groups (all P>0.05). Compared with the control group, patients in the CIP group had a lower body mass index ［(21.5±3.2) kg/m2 vs. (22.6±3.0) kg/m2, P=0.004］, higher proportion of patients with Eastern Cooperative Oncology Group Performance Scale (ECOG-PS) ≥2 points［39.0% (48/123) vs. 22.0% (27/123), P=0.004］, higher proportion of patients with a history of radiation therapy ［25.2% (31/123) vs. 13.8% (17/123), P=0.024］, and lower proportion of patients with combination therapy with chemotherapy/targeted drugs［82.9%(102/123) vs. 97.6%(120/123), P<0.001］. Before immunotherapy, the peripheral blood interleukin-1β and interferon-α were lower ［1.97 (1.04, 2.74) ng/L vs. 2.40 (1.75, 4.03) ng/L, P=0.021; 2.08 (0.89, 3.00) ng/L vs. 2.76 (1.97, 3.94) ng/L, P=0.012］, lymphocyte count was lower ［1.4(1.0, 1.8)×109/L vs. 1.5(1.2, 2.1)×109/L, P=0.030］, and the neutrophil-to-lymphocyte ratio was higher ［3.85 (2.50, 6.40) vs. 3.11 (2.25, 4.61), P=0.006］ in patients of the CIP group than those in the control group. The binary logistic regression analysis showed that baseline ECOG-PS ≥2 points (OR=3.400, 95%CI: 1.180-9.798, P=0.023) and combination of PD-1/PD-L1 inhibitors and chemotherapy/targeted therapy (OR=0.047, 95%CI: 0.005-0.454, P=0.008) were independent influencing factors for the occurrence of CIP.　Conclusion The ECOG-PS ≥ 2 points before immunotherapy is an influencing factor for CIP, and the combination with chemotherapy/targeted therapy may reduce the risk of developing CIP in patients treated with PD-1/PD-L1 inhibitors.

Objective To investigate the occurrence and clinical characteristics of immune-related adverse events (irAEs) caused by pembrolizumab （PEM） in elderly patients with advanced lung cancer.　Methods The subjects were selected from the elderly patients with advanced lung cancer who received PEM therapy (200-mg was given by intravenous infusion once every 21 days and 21 days was a cycle) in the Affiliated Hospital of Inner Mongolia Medical University from August 2020 to July 2022. The medical records of patients meeting the inclusion criteria were collected through the Hospital Electronic Medical Record Information System, the clinical data such as patients′ basic information, pathological type of lung cancer, clinical stage, whether or not combination with chemotherapy, the occurrence time of irAEs, clinical manifestations, intervention, and prognosis were recorded and analyzed retrospectively. The irAEs were graded according to the Common Terminology Criteria for Adverse Event (CTCAE) Version 5.0 developed by the National Cancer Institute of the United States.　Results A total of 100 patients were enrolled in the analysis, of which 22 (22%) patients developed irAEs. Among the 22 patients, 19 were male and 3 were female, aged from 61 to 90 years, including 15 lung squamous cell carcinomas and 7 lung adenocarcinomas. There were 4 patients with clinical stage Ⅲ and 18 patients with stage Ⅳ; one patient received PEM monotherapy and 21 patients received PEM combined with chemotherapy. A total of 28 cases of irAEs occurred in 22 patients (19 cases of 1 type of irAE, 1 case of 2, 3, and 4 types of irAE each), including 10 cases of skin irAEs (3 in grade 1, 3 in grade 2, and 4 in grade 3), 8 cases of immune-related pneumonitis (1 in grade 1, 7 in grade 2), 7 cases of irAEs involving the endocrine system (1 case of hypothyroidism in grade 1, 3 cases of hypothyroi- dism in grade 2, 1 case of adrenocortical dysfunction in grade 1, 1 case of hyperglycemia in grade 1, and 1 case of pituitary inflammation in grade 4), 2 cases of immune-associated hepatitis (1 in grade 1, 1 in grade 3), 1 case of ICI-related myocarditis in grade 3. The shortest occurrence time of the 28 cases of irAEs was on the day of initial medication, the longest was 20 days after the 17th cycle of medication, and 22 cases occurred between the 1st to 8th cycles of medication. After the occurrence of irAEs, 5 patients discontinued PEM and most received hormone and/or symptomatic treatment. Twenty patients were cured or self-healed, 1 partially recovered, and 1 was not improved.　Conclusions Elderly patients with advanced lung cancer who receive PEM may experience skin, lung, endocrine system, liver, and heart irAEs, mostly occurring between the 1st to 8th cycles of medication, mostly in grades 1 and 2. Discontinuation of medication and hormone and/or symptomatic treatment can lead to a better prognosis.

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.

It was a very common phenomenon that an original drug was replaced by a generic drug after its patent expires. In order to further verify the efficacy and safety of domestic generic drugs selected in the national centralized volume-based procurement, the National Healthcare Security Admini stration guided a number of medical institutions to carry out large-scale real-world studies on clinical efficacy and safety of generic drugs, involving drugs for treating cardiovascular and cerebrovascular diseases, neuropsychiatric diseases, chronic hepatitis B, and tumor, and anesthetics. More than 110 thousands patients were included in the study. Evidence from real world studies and randomized controlled trials can complement each other. Because of the diversity of data, the complexity of design, the high requirements of analytical methods, and the uncertainty of the interpretation of results in the real world studies, higher requirements for the safety and efficacy evaluation and regulatory decision-making of generic drugs are put forward. Possible recommendations to constantly promote the scientificalness and standardization of the production and use of real world evidence are as follows: further strengthen the informatization construction in medical institutions and promote the standardization and convenience in real world data use, improve the scientificalness of research design and data processing, explore and improve the real world evidence quality evaluation criteria, strengthen the awareness of data security and pay attention to the participants′ privacy protection, etc.

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.

Objective To compare the efficacy and safety of vildagliptin tablets (the generic drug) manufactured by Qilu Pharmaceutical Co., Ltd. and vildagliptin tablets (the original drug) manufactured by Novartis Pharmaceutical Co., Ltd. in the treatment of type 2 diabetes mellitus (T2DM) in third round of national centralized volume-based procurement.　Methods The study design was a multicenter retrospective cohort study. The study subjects were T2DM patients treated with vildagliptin tablets at the Outpatient Department of Zhuhai People′s Hospital, Zhongshan City People′s Hospital, Jiangmen Central Hospital, and General Hospital of Southern Theater Command of PLA from January 2020 to December 2021. Using the hospital electronic medical record system, medical records in outpatients who met the inclusion criteria were collected, and relevant clinical data were extracted. The patients were divided into generic drug group and original drug group. To exclude the interference of confounding factors, the propensity score matching method was used. The efficacy evaluation index was the magnitude of hemoglobin A1c (HbA1c) and fasting plasma glucose (FPG) reductions within one year after administration. Generalized linear regression model was used to analyze the influencing factors for the magnitude of HbA1c and FPG reduction. The safety evaluation index was the incidence of adverse events within one year of drug use.　Results A total of 4-511 patients with T2DM who were treated with vildagliptin tablets were collected from 4 hospitals, including 3-039 in the generic drug group and 1-472 in the original drug group. After treatment, the HbA1c and FPG in patients of the 2 groups decreased compared with those before treatment. The magnitude of HbA1c and FPG reductions in patients of the generic drug group were not significantly different from those in the original drug group ［0.50 (0.05, 2.30)% vs. 0.90 (-0.10, 1.70)%, Z=0.235, P=0.814; 0.59 (-0.40, 2.20) mmol/L vs. 1.00 (-0.61, 2.32) mmol/L, Z=0.421, P=0.674］. The results of generalized linear regression model analysis showed that the therapeutic drugs did not affect the magnitude of HbA1c and FPG reductions (P=0.627, P=0.478). Compared with the original drug group, the incidences of adverse events and hypoglycemia in the generic drug group were not statistically significant ［1.6‰ (5/3-039) vs. 2.7‰ (4/1-472), P=0.721; 0.7 ‰ (2/3-039) vs. 0.7 ‰ (1/1-472), P=1.000］.　Conclusion The efficacy and safety of generic vildagliptin tablets manufactured by Qilu Pharmaceutical Co., Ltd. were generally consistent with those of the original drug in the treatment of T2DM.

Objective To compare the efficacy and safety of ticagrelor tablets produced by Zhejiang Hisun Pharmaceutical Co., Ltd. (the generic drug) and ticagrelor tablets produced by AstraZeneca Pharmaceutical Co., Ltd. (the original drug) in antiplatelet therapy.　Methods The study design was a retrospective cohort study. The subjects were patients who underwent percutaneous coronary intervention (PCI) for acute coronary syndrome (ACS) and postoperative antiplatelet therapy with ticagrelor tablets at First Affiliated Hospital of Dalian Medical University during January 2020 to July 2021. Through the hospital electronic medical record system, relevant clinical data of patients (age, gender, comorbidities, blood lipid level on admission, PCI indications, antiplatelet treatment regimen, efficacy and safety assessment endpoint events within 12 months of treatment, etc.) were collected. The patients were divided into the generic drug group and the original drug group. To exclude confounders, propensity score matching (PSM) method was used. The efficacy evaluation index was the incidence of the primary endpoint events (cardiogenic death, stroke, target revascularization, recurrent infarction) and secondary endpoint events (all-cause mortality, peripheral artery occlusion, stent thrombosis, angina attacks) within 12 months of treatment. The safety evaluation index was the incidence of bleeding event within 12 months of treatment.　Results A total of 1-486 patients were included in this study, including 734 in the generic drug group and 752 in the original drug group. The proportion of women and unstable angina, and the level of high-density lipoprotein cholesterol were higher than those in the original drug group (all P<0.05). The proportion of patients with hyperlipidemia and ST-segment elevation myocardial infarction were lower than those in the original drug group (both P<0.05). After PSM, 690 patients were enrolled in the generic drug group and 690 patients in the original drug group (all P>0.05). No differences in the comparison of clinical features between the 2 groups was significant(all P>0.05). No differences in the incidences of primary endpoints, secondary endpoints, and bleeding events between the 2 groups was significant before and after PSM ［before PSM: 12.1%(89/734) vs. 10.9%(82/752), 10.8%(79/734) vs. 8.4%(63/752), 0.3%(2/734) vs. 0.5%(4/752)； after PSM: 12.6%(87/690) vs. 12.3%(85/690), 11.0%(76/690) vs. 8.3%(57/690), 0.3%(2/690) vs. 0.4%(3/690); all P>0.05］. No death occurred in patients of both groups. Bleeding is predominantly characterized by epistaxis and subcutaneous petechiae, which did not lead to interruption of antiplatelet therapy.　Conclusion The efficacy and safety of ticagrelor tablets produced by Zhejiang Hisun Pharmaceutical Co., Ltd. for antiplatelet therapy in ACS patients after PCI surgery were basically the same as those of the original drug.

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.

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.

Most patients with drug-induced liver injury (DILI) have a good prognosis. However, 11%-17% of the patients will suffer from chronic DILI, and 6%-10% will suffer from acute liver failure, even death or need for liver transplantation. In 2019, the incidence of DILI in China was 23.8/100-000 person year, which was far higher than that in western countries, so the study on DILI should not be ignored. This paper summarizes the hot issues in the field of DILI in recent years, mainly including the new diagnostic markers, the genetic susceptibility, the in vivo and in vitro models of idiosyncratic DILI, the diagnosis of chronic DILI, the treatment scheme, the prognosis model, the liver injury caused by immune checkpoint inhibitors, etc., in order to provide a reference for clinical workers in future research.

Objective To investigate the difference in clinical characteristics of drug-induced liver injury (DILI) between patients of different gender.　Methods Through the hospital electronic medical record system, clinical data of patients hospitalized because of DILI at Liver Research Center, Beijing Friendship Hospital, Capital Medical University from January 2005 to January 2021 were collected and retrospectively analyzed. The collected information included gender, age, body mass index, underlying diseases, medication, results of the first laboratory tests after admission, clinical manifestation and types of DILI, etc. The patients were divided into 2 groups according to gender and the clinical characteristics of DILI were compared. The factors affecting death/liver transplantation in DILI patients were analyzed by Cox regression method.　Results A total of 616 patients with DILI were entered, including 139 males (22.6%) and 477 females (77.4%). The median age was 56 (47, 64) years, ranging from 18 to 80 years. Drugs that caused DILI were traditional Chinese medicine and/or health care products (TCMHCP) in 345 patients (56.0%), western drugs in 148 patients (24.0%), and TCMHCP and western drugs in 123 patients (20.0%). Death/liver transplantation occurred in 42 patients (6.8%), including 3 liver transplantation, 19 death directly caused by the liver disease, and 20 death with causes other than liver disease. The incidences of dark urine and abdominal distension, severe liver injury, and death/liver transplantation in male patients were all higher than those in female patients, respectively ［71.9% (100/139) vs. 60.0% (286/477), P=0.010; 28.8% (40/139) vs. 18.7% (89/477), P=0.010; 46.8% (65/139) vs. 40.5% (193/477), P<0.001; 15.1% (21/477) vs. 4.4% (21/139), P<0.001］. Laboratory test results such as the white blood cell count, hemoglobin, total bilirubin, direct bilirubin, total bile acid, triglyceride, and low density lipoprotein cholesterol in male patients were all higher than those in female patients, while the levels of pre-albumin, immunoglobulin G, immunoglobulin M, and serum creatinine were lower (all P<0.05). Cox regression analysis showed that male, older age, low albumin, high total bile acid, high serum creatinine, and prolonged international normalized ratio (INR) were the independent influencing factors of death/liver transplantation in patients with DILI.　Conclusions Clinical manifestation are different in DILI patients of different gender hospitalized in the Liver Research Center, Beijing Friendshop Hospital, Capital Medical University. In male patients, cholestasis is more obvious, the disease condition is more serious, and death/liver transplantation is more common. Male patients and patients with older age, lower albumin, higher total bile acid, higher serum creatinine, and higher INR are more prone to death/liver transplantation, which should be paid attention to in clinic.

Objective To explore the occurrence of programmed cell death 1 receptor (PD-1)/programmed cell death ligand 1 （PD-L1） inhibitor-related liver injury and the influencing factors in patients with extrahepatic primary tumors.　Methods The electronic medical records of patients with extrahepatic primary tumors who were treated with PD-1/PD-L1 inhibitors in Zhongshan Hospital, Fudan University from January to July 2021 were collected and retrospectively analyzed. Patients with PD-1/PD-L1 inhibitor-related liver injury were screened out, and the occurrence time, clinical type, and severity of liver injury were statistically recorded and analyzed. Patients were divided into liver injury group and non-liver injury group according to whether liver injury occurred. Clinical characteristics including age, gender, type of primary tumor, underlying disease, liver metastasis, regimen of PD-1/PD-L1 inhibitor therapy, combined medication, and baseline liver and renal function were compared between the 2 groups. The influencing factors of liver injury were analyzed by multivariate logistic regression method, and the odds ratio (OR) and 95% confidence interval (CI) were calculated.　Results A total of 386 patients were included in the analysis and 29 patients had PD-1/PD-L1 inhibitor-related liver injury, with an incidence of 7.5%. Of the 29 patients, 25 were male and 4 were female, aged from 19 to 90 years. PD-1/PD-L1 inhibitors used were sintilimab, nivolumab, teriprizumab, pembrolizumab, tislelizumab, atezolizumab, camrelizumab, and durvalumab in 7, 5, 5, 4, 3, 3, 1, and 1 patient, respectively. The median time from drug use to the occurrence of liver injury was 44 (24, 112) days. The liver injury were typed as hepatocellular injury in 8 patients, cholestatic liver injury in 17 patients, and mixed type in 4 patients, and the severity was grade 1 in 19 patients, grade 2 in 7 patients, and grade 3 in 3 patients. After diagnosis of liver injury, all 29 patients were given symptomatic treatments, of which 24 patients discontinued PD-1/PD-L1 inhibitors; 21 patients had recovered liver function after 6-71 days, and 8 developed chronic hepatitis. Multivariate logistic regression analysis showed that hepatitis virus infection (OR=5.749, 95%CI: 1.337-24.719, P=0.019), hypertension (OR=5.345, 95%CI: 2.034-14.047, P=0.001), and baseline alkaline phosphatase (ALP) ≥125-U/L (OR=4.651, 95%CI: 1.728-12.521, P=0.002) were independent risk factors for PD-1/PD-L1 inhibitor-related liver injury.　Conclusions Liver injury is a common adverse reaction of PD-1/PD-L1 inhibitors, and cholestatic liver injury is the most common clinical type. Patients with hepatitis virus infection, hypertension, and elevated baseline ALP are at high risk for developing PD-1/PD-L1 inhibitor-associated liver injury.

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 know the clinical characteristics of liver injury related to thalidomide and its analogs.　Methods The relevant databases at home and abroad (up to August 31, 2022) were searched and the case reports on thalidomide and its analogs-associated liver injury were collected. The patients′ gender, age, primary disease, drug use, occurrence of liver injury (onset time, clinical manifestations, liver function status, liver injury classification, etc.), treatment and outcome were recorded and descriptively analyzed.　Results A total of 18 patients were enrolled, including 11 males and 7 females, aged from 36 to 93 years with an average age of 60 years. The primary disease was multiple myeloma in 16 patients, plasma cell leukemia and myelodysplastic syndrome in 1 patient each. Thalidomide was used in 9 patients, lenalidomide in 6 patients and pomalidomide in 3 patients. The time from the beginning of medication to the occurrence of liver injury ranged from 4 to 232 days and it was ≤ 60 days in 15 patients. The classification of liver injury was hepatocellular type in 9 patients, cholestasis type in 7 patients, and unable to be determined due to lack of data in 2 patients. Different degrees of abnormal liver function appeared in 18 patients, mainly including elevated alanine aminotransferase and aspartate aminotransferase (in 16 patients), elevated total bilirubin (in 14 patients), and elevated alkaline phosphatase (in 12 patients). Clinical symptoms were recorded in 15 patients, including jaundice (in 13 cases), fatigue (in 7 cases) and nausea (in 4 cases). After diagnosis of liver injury, thalidomide or its analogues were discontinued in all 18 patients, and 4 cases received symptomatic and supportive therapy. Liver function in 13 patients was improved or returned to normal within 7 to 28 days after drug withdrawal, and 5 patients died (2 cases died of liver failure, 3 cases died of primary diseases or other complications).　Conclusions Thalidomide and its analogs associated liver injury mostly occurs within 2 months after drug administration and the clinical symptoms were similar to those caused by other drugs. After drug withdrawal, the liver function in most patients could be improved or return to normal, but a few may progress to liver failure and death.

Two patients (patient 1, a 49-year-old female; patient 2, a 51-year-old female) took Anshen Bunao liquid 10-ml twice daily orally by themselves because of poor sleep. None of the 2 patients had concomitant medications. Patient 1 and patient 2 developed fatigue and poor appetite after 7 and 10 days of Anshen Bunao liquid treatment, respectively. Laboratory tests showed that alanine aminotransferase (ALT), aspartate transaminase (AST), and alkaline phosphatase (ALP) were 1-147-U/L, 1-271-U/L, 215-U/L and 805-U/L, 333-U/L, 227-U/L, respectively. Then Anshen Bunao liquid was stopped and hepatoprotective therapy was given. Seven days later, symptoms of fatigue and poor appetite in the 2 patients were improved, amd laboratory tests showed that the levels of ALT, AST, ALP decreased to 222-U/L, 396-U/L, 122-U/L and 85-U/L, 23-U/L, 129-U/L, respectively. Patient 1 took Anshen Bunao liquid again. Two days later, she developed abdominal discomfort with vomiting, ALT was 409-U/L, and AST was 339-U/L. After stopping the drug and giving liver-protective treatments for nearly 4 months, ALT was 32-U/L, AST was 22-U/L, and ALP was 89-U/L. Patient 2 did not take the drug again. Re-examination after 138 days after discharge, ALT was 39-U/L, AST was 28-U/L, and ALP was 130-U/L.

A 77-year-old male patient received amiodarone 0.2 g twice daily orally for arrhy- thmia. After 15 months of amiodarone treatment, he developed some symptoms such as poor appetite, reduced diet, nausea and vomiting, and dysphagia. After 22 months of amiodarone treatment, laboratory tests showed white blood cell count 13.5×109/L, neutrophil 0.78, C-reactive protein 117.4-mg/L, erythrocyte sedimentation rate 32-mm/1 h, alanine aminotransferase (ALT) 286-U/L, aspartate aminotransferase (AST) 215-U/L, alkaline phosphatase (ALP) 107-U/L, γ-glutamyl transferase (γ-GT) 45-U/L, total bilirubin (TBil) 14.8-μmol/L, direct bilirubin 9.3-μmol/L, and albumin 30-g/L. After treatments with anti-infection, hepatoprotection, and albumin supplementation, the above symptoms were improved and amiodarone was continued. After 40 months of amiodarone treatment, laboratory tests showed ALT 87-U/L, AST 106 U/L, ALP 308-U/L, γ-GT 1-242 U/L, and TBil 11.2-μmol/L. According to the results of liver biopsy, it is suspected that the patient was alcoholic liver fibrosis. After excluding alcoholic liver disease, viral hepatitis, autoimmune liver disease, and tumors by imaging and liver biopsy, it was considered to be associated with long-term use of amiodarone. Amiodarone was withdrawn, but the patient died 3 months later because of ascites and jaundice.

A 75-year-old male patient with lung cancer received intravenous infusion of sintilimab 200-mg on day 1, 21 days as one cycle. Three days after the 5th cycles of treatment, the patient developed edema of lower limbs and yellowish skin on whole body. Laboratory tests showed alanine aminotransferase (ALT) 914-U/L, aspartate aminotransferase (AST) 622-U/L, alkaline phosphatase (ALP) 385-U/L, total bilirubin (TBil) 152.6-μmo1/L, direct bilirubin (DBil) 87.9-μmol/L, indirect bilirubin (IBil) 64.7-μmol/L and total bile acid (TBA) 25.8-μmol/L. The liver injury caused by other reasons was excluded by laboratory and auxiliary examination, and it was diagnosed as drug-induced liver injury, which was considered to be related to sintilimab. Drugs such as reduced glutathione, compound glycyrrhizin, ademetio- nine, polyene phosphatidylcholine, magnesium isoglycyrrhizinate, and ursodeoxycholic acid successively were given. The patient′s edema of lower limbs and yellowish skin gradually subsided. After 25 days of treatments, laboratory tests showed ALT 33-U/L, AST 33-U/L, ALP 92-U/L, TBil 18.2-μmol/L, DBil 5.2-μmol/L, IBil 13.0-μmol/L, and TBA 7.4-μmol/L.

Objective To explore the safety of nirmatrelvir/ritonavir (Paxlovid) in the treatment of coronavirus disease 2019 (COVID-19).　Methods Medical records of adult patients with COVID-19 who were hospitalized and treated with Paxlovid in Beijing Ditan Hospital, Capital Medical University between March 23 and May 31, 2022 were collected through the hospital electronic medical record system. The occurrence (time of occurrence, clinical manifestations, severity, etc.) and outcomes of adverse reactions were analyzed retrospectively and the clinical characteristics of patients with or without adverse reactions were compared. Paxlovid was administered orally with nirmatrelvir 300-mg and ritonavir 100-mg every 12-hours for 5 consecutive days.　Results Three hundred and sixty-four patients were entered in the analy- sis, including 200 males (54.9%) and 164 females (45.1%), with a median age of 60 (19, 92) years. The incidence of adverse reactions of Paxlovid was 13.2% (48/364), and the adverse reactions occurred 1 to 7 days after taking Paxlovid. Among the 48 patients, 37 patients had digestive system symptoms (mainly manifested as diarrhea in 17 patients, bitter mouth in 14 patients, etc.), 7 patients had nervous system symptoms (dizziness in 5 patients, headache in 2 patients), 4 patients had respiratory system symptoms (pharyngalgia in 3 patients, pharyngeal itching in 1 patient), 2 patients had kidney injury, 1 patient had elevated blood uric acid, 1 patient had myalgia, and 1 patient had rash. Of them, 2 patients had digestive and neurological symptoms at the same time, 1 patient had digestive and respiratory symptoms at the same time, and 1 patient had digestive, neurological, and respiratory symptoms at the same time. The severity of adverse reactions was grade 1 in 33 patients (68.8%) and grade 2 in 15 patients (31.2%), and no serious adverse reactions of grade 3 and above occurred. All patients completed 5 days of treatment except 1 patient who discontinued the drug because of intolerance to grade 2 digestive symptoms (nausea and bitter mouth). There were no significant differences in gender, age, body mass index, smoking status, underlying diseases, and COVID-19 clinical classification between the patients with and without adverse reactions (all P>0.05).　Conclusions Paxlovid has a good safety in the treatment of COVID-19. The main adverse reaction is digestive system symptoms, mainly diarrhea and bitter mouth. Most of the symptoms are mild and the patient′s tolerance is good.

Objective To explore the safety of azivudine tablets in the treatment of moderate coronavirus disease 2019 (COVID-19).　Methods Clinical data of adult COVID-19 patients who were hospitalized and treated with azivudine tablets at Xinglin Branch, the First Affiliated Hospital of Xiamen University from August 18 to September 18, 2022 were collected. The incidence, clinical manifestations, severity， and outcome of adverse reactions during treatment were analyzed descriptively and statistically.　Results A total of 117 patients were entered in the analysis, including 68 males (58.1%) and 49 females (41.9%); the age ranged from 18 to 76 years, with a median age of 44 years. The course of COVID-19 before taking azivudine tablets ranged from 2 to 25 days, with an average time of 13 days. Azivudine tablets were applicated for 2-14 days with an average time of 8 days. Among 117 patients, 10 patients (8.5%) had adverse reactions during taking azivudine tablets, including 5 patients with gastrointestinal reactions (2 had nausea, 2 had diarrhea, and 1 had abdominal distension), 2 patients with liver dysfunction and 2 patients with dizziness, 1 patient with elevated serum triglyceride level, and 1 with fatigue. Of them, one patient had 2 times of adverse reactions, which manifested as dizziness and abdominal distension. All patients recovered after discontinuation of azivudine tablets and/or symptomatic treatments. The severity of adverse reactions was grade 1 in 7 patients and grade 2 in 3 patients, and no grade 3 and above serious adverse reactions occurred. All adverse reactions observed in the study had been recorded in the drug label, and no new adverse reactions were found.　Conclusions Azivudine tablets is safe and well tolerated in the treatment of moderate COVID-19. The common adverse reactions were gastrointestinal reactions, abnormal liver function, and dizziness.

Objective To explore the clinical characteristics of tenofovir disoproxil fumarate (TDF)-related Fanconi syndrome (FS) in patients with HIV infection/AIDS (HIV/AIDS).　Methods The medical records of patients with HIV/AIDS who were hospitalized in Yunnan Provincial Hospital of Infectious Diseases from December 2017 to February 2021, treated with antiretroviral therapy (ART) containing TDF, and diagnosed as FS were collected by searching hospital information system. Information such as gender, age, body weight, body mass index (BMI), ART treatment regimen and period, time of FS diagnosis, main clinical characteristics, results of laboratory test at admission and discharge, dual energy X-ray bone mineral density (BMD) test results, and interventions and outcomes were retrospectively analyzed.　Results A total of 16 HIV/AIDS patients were diagnosed with TDF-related FS in the setting period, including 6 patients with complete FS and 10 with incomplete FS. FS were accompanied with chronic hepatitis C, hypertension, liver cancer, or depression in 7 patients. Sixteen patients received ART containing TDF for a minimum of 20 months and a maximum of 168 months with an average time of 68 months. The initial symptoms of FS were bone pain, fatigue, nausea, anorexia, polydipsia, polyuria, weight loss, etc. The time from initial symptoms to diagnosis of FS was 2 weeks at least, 24 weeks at most, with an average time of 7 weeks. Laboratory test results were as follows: all 16 patients had positive urine glucose under normoglycemic conditions and 14 patients had positive urine protein; 11, 11, 4, and 4 patients had low urine phosphorus, hypocalciuria, hypokalemia, and hyponatruria, respectively; 13, 12, 8, and 7 patients had hypophosphatemia, hypokalemia, hypocalcemia, and hyponatremia, respectively; 11 patients had serum creatinine increase; 10 patients had serum uric acid decrease; 1 patient had serum uric acid increase. Dual energy X-ray BMD detection was performed in 15 patients, of which 2, 2, and 11 patients had normal, reduced, and osteoporotic BMD, respectively. After diagnosis of TDF-related FS, 16 patients stopped using TDF immediately. After replacement of ART protocol without TDF and symptomatic treatment for an average time of 29 days, the above symptoms were alleviated, and some laboratory test indicators returned to the reference value range. The prognosis was good.　Conclusions TDF-related FS mostly occurs within 68 months of drug use. The clinical symptoms of FS are nonspecific. Laboratory tests show that urine glucose is positive under normal blood glucose. Most of the patients have low blood phosphorus, low urine phosphorus, hypocalciuria, and osteoporosis. The prognosis is better after discontinuing TDF, replacing therapy with ART regimen without TDF, and giving symptomatic treatments.

At present, 3 drugs specially for coronavirus disease 2019-have conditional marketing authorization (CMA) in China, including molnupiravir, nirmatrelvir/ritonavir, and azvudine. The data of clinical efficacy and safety of these drugs are relatively insufficient. Molnupiravir is not the main inhibitor or inducer of drug metabolizing enzyme or transporter and is less likely to have drug interactions, which may be more beneficial to patients with chronic diseases needing long-term drug treatments. Ritonavir in Paxlovid is a strong inhibitor to the key drug metabolism enzyme---CYP3A4, and may interact with a variety of drugs such as drugs for arrhythmia, diabetes, nervous system diseases, etc., resulting in increased drug safety risks in the treatment of underlying diseases. The reproductive and genetic toxicity recorded in the drug label of azvudine is worrying. Joint efforts of our government, hospital managers, clinicians and pharmacists are necessary to achieve the safety management of the 3 drugs, including improving the relevant CMA management regulations, strengthening the efficacy and safety monitoring of these drugs, conducting real world clinical research, and monitoring the variation and drug resistance of the virus.

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.

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.

Objective To understand the status quo and problems of insulin application at home in patients with diabetes mellitus.　Methods Pharmacists in many hospitals across the country were organized to conduct a questionnaire survey on status quo of insulin application in patients with diabetic mellitus, so as to understand their insulin use, insulin injection behavior, insulin treatment adherence, glucose monitoring adherence, insulin preservation behavior, rate of up to target blood glucose, and the incidence of adverse reactions such as hypoglycemia. The questionnaire contained 50 questions, the accuracy rate of 21 questions related to insulin application norms was calculated, and the effect of insulin application behavior of patients on the efficacy and safety of insulin therapy was investigated.　Results Clinical pharmacists from 31-hospitals across the country participated in the questionnaire distribution and survey, and 240 valid questionnaires were returned. Among the 240 patients, 106 (44.2%) were male and 134 (55.8%) were female, aged (58±15) years; 210 (87.5%) had type 2 diabetes mellitus, 25 (10.4%) had type 1 diabetes mellitus, and 5 (2.1%) had other types; 151 (62.9%) patients were treated with one kind of insulin, 89 (37.1%) were treated with 2 kinds of insulin, and a total of 13 kinds of insulin were involved; 97.9% (235/240) of the patients had at least one wrong or irregular insulin use behavior, 75.0% (180/240) had at least one problem related to insulin treatment adherence, 70.4% (169/240) had poor glucose monitoring adherence, and 68.8% (165/240) had at least one irregular insulin preservation behavior. The rate of up to target blood glucose was only 13.8% (33/240), and the incidence of hypoglycemia was 55.8% (134/240). The total correct rates of answers to insulin use behavior and treatment adherence in patients with up to target blood glucose were significantly higher than those in patients without up to target blood glucose ［71.4% (57.1%, 81.0%) vs. 61.9% (52.4%, 71.4%), P=0.045; 77.8% (55.6%, 88.9%) vs. 66.7% (55.6%, 77.8%), P=0.023］, and differences in the correct rate of answers to insulin use behavior and each behavior between the patients with and without hypoglycemia were not statistically significant (all P>0.05).　Conclusions Insulin has a wide variety and similar drug names, which are easily confused, leading to medication errors. The incidence of irregular insulin injection behavior, treatment adherence, and insulin preservation behavior in patients is high, which may affect the rate of up to target blood glucose.

Objective To compare the efficacy and safety of continuous subcutaneous insulin analogues infusion (CSII) and multiple daily insulin analogues injection (MDII) in fracture patients with type 2 diabetes mellitus (T2MD) during the perioperative period.　Methods The medical data of patients with lower limb fracture complicated with T2MD in Beijing Jishuitan Hospital from 2017 to 2021 were collected by hospital information system and analyzed retrospectively. The medical data of patients extracted included gender, age, body weight, body mass index (BMI), fracture site, pain score and grading, time from fracture to admission, duration of T2MD, laboratory test results at admission, blood glucose control regimen and monitoring result after admission, and the adverse events. Patients were divided into CSII group and MDII group according to blood glucose control regimen during the perioperative period. The clinical features, time to reach target blood glucose range, insulin application, and adverse events in patients of the 2 groups were compared.　Results A total of 207 patients were enrolled in this study, including 90 males and 117 females, aged (61±15) years with BMI of (25.5±3.5) kg/m2. No significant differences were found in gender, age, BMI, fracture site, pain score and grading, time from fracture to admission, duration of T2MD, and laboratory test resurts at admission in patients between the 2 groups (all P>0.05). Patients in the CSII group had shorter time to reach target range of fasting blood glucose, 2-h postprandial blood glucose, and the both than those in the MDII group ［(48.7±30.2) h vs. (78.7±44.5) h, P=0.003; (66.8±31.5) h vs. (93.3±47.6) h, P=0.001; (68.4±30.5) h vs. (96.3±48.1) h, P<0.001］. The total daily dose and total pre-prandial dose of insulin per unit weight in patients when the fasting and 2-h postprandial glucose both reach the target range were less in the CSII group than those in the MDII group ［(0.67±0.20) U/kg vs. (0.73±0.17) U/kg, P=0.030; (0.34±0.10) U/kg vs. (0.38±0.09) U/kg, P=0.004］. In 207 patients, hypoglycemia occurred in 17 patients for 23 times with an overall incidence of 8.2%(17/207). The difference in the incidence of hypoglycemia was not significant between the 2 groups ［4.9%(5/102) vs. 11.4%(12/105), P=0.319］. None of the 5 patients with hypoglycemia in the CSII group had hypoglycemia for 2 times or more, while 4 of the 12 patients in the MDII group had 2 times of hypoglycemia and 1 had 3 times of hypoglycemia. Other adverse drug events included allergy, systemic edema, nodular hyperplasia of subcutaneous fat, and persistent bleeding at the injection site. Eight patients in the CSII group had other adverse events, including device failure in 5 patients, and using insulin pump during anesthesia, in magnetic field environment, and in humid environment in 3 patients respectively.　Conclusions CSII regimen is helpful for fracture patients with T2DM to achieve target blood glucose range earlier, and provides more ways and opportunities to correct hypoglycemia in patients. However, the insulin pump needs more professional maintenance in practice, so it has limitations to some extent in clinical application.

Immunosuppressants can be used to treat a variety of pediatric diseases. However, at present, the information on children′s drug use in drug labels are insufficient, the drug specifications and dosage forms are lacking, and off-label prescribing is more common. The pathophysiological status and drug metabolism characteristics in children are obviously different from those in adults, and the immune system is not yet mature, so the risk in drug use is higher than that in adults. It is necessary to find a balance between insufficient and excessive immunosuppression. However, it is difficult for infants to feed drugs, and children and adolescents have poor treatment compliance in the absence of guardian management, which may lead to reduced efficacy or treatment failure. It is necessary to strengthen the monitoring of adverse reactions and treatment drug monitoring of immunosuppressants therapy in children, and carry out research on pharmacogenomics to ensure the safety of immunosuppressants in children from multiple dimensions.

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.

Objective To explore the effect of drug metabolism gene polymorphisms on blood concentration and safety of tacrolimus (TAC) in children with refractory nephrotic syndrome (RNS).　Methods The study was designed as prospective observational clinical study. The subjects were selected from the children with RNS who were hospitalized in Department of Pediatrics, the First Affiliated Hospital of Zhengzhou University from September 1, 2018 to August 31, 2019 and planned to receive TAC (first application) at the basis of glucocorticoids treatment. Clinical research files were formed and clinical conditions within 6 months of TAC treatment were recorded in detail for all subjects. The peripheral venous blood of all children was collected on the 7th day after TAC application for TAC blood trough concentration detection, and the TAC dose was adjusted according to the results. Blood samples were collected at the right time during hospitalization and gene polymorphisms of adenosine triphosphate binding cassette transporter B1 (ABCB1), cytochrome P450 (CYP) 2C19, CYP3A4, CYP3A5 and nuclear receptor subfamily 1, group I, member 2 (NR1I2) were detected. Children who completed 6 months of TAC treatment and follow-up were included. According to the genotype detection results, children were divided into wild-type group, heterozygous mutant group, and homozygous mutant group and first dose-adjusted blood trough concentration (C/D) of TAC were compared; they were divided into mutation carrier group (including heterozygous mutation carriers and homozygous mutation carriers) and wild-type group and the incidence of adverse reactions were compared.　Results A total of 39 children were included in the analysis, including 24 males and 15 females, aged 3 to 13 years with a median age of 8 years. The comparison results of the first C/D of TAC among various genotype groups showed that the TAC C/D in children of CYP2C19-homozygous mutant (*2*2) group was higher than that of wild-type (*1*1) group ［3.65 (2.78, 7.43) μg/L vs. 1.53 (1.27, 3.33) μg/L, P=0.032］, TAC C/D in children of CYP3A5 homozygous mutant (*3*3) group was significantly higher than those of the wild-type (*1*1) group and heterozygous mutation (*1*3) group ［3.68 (3.05, 5.14) μg/L vs. 2.10 (0.77, 3.56) μg/L and 1.74 (1.47, 3.25) μg/L, P=0.046, P=0.009］, and no significant differences were found in TAC C/D among different genotypes in CYP3A4, ABCB1, or NR1I2 (all P>0.05). A total of 7 children had adverse reactions within 6 months of TAC treatment (Naranjo′s assessment scale, "probable" in 2 children and "possible" in 5 children), including infection, rash, hypertensive encephalopathy, and convulsions in 4, 1, 1, 1 child, respectively. The incidence of adverse reactions in ABCB1 mutation carrying children (CT and TT) was significantly higher than that in children of wild-type (CC) group ［30.4% (7/23) vs. 0 (0/16), P=0.033］.　Conclusion CYP2C19 and CYP3A5 gene polymorphisms have significant effects on TAC blood concentration, and ABCB1 gene polymorphisms have significant effects on the safety of TAC application, which should be noticed in clinic.

Objective To investigate the effect of drug metabolism related gene polymorphism on the efficacy of clopidogrel in patients with acute coronary syndrome (ACS).　Methods The medical records and follow-up records of ACS patients, who were hospitalized in the People′s Hospital of Daxing District between 2017 and 2019, received standardized treatment with aspirin (100-mg/day)+clopidogrel (75-mg/day), and underwent testing for genetic polymorphisms related to clopidogrel absorption/metabolism, were collected. The patients were divided into thrombotic event group and non-thrombotic event group according to whether they experienced thrombotic events such as myocardial infarction, stent thrombosis, and cerebral infarction within 1 year of treatment. The age, gender, smoking history and drinking habits, underlying diseases, drug combination, and alleles related to clopidogrel absorption/metabolism in patients in the 2 groups were compared. The factors affecting the clinical efficacy of clopidogrel was analyzed using logistic regression model.　Results A total of 342 patients were included in the analysis, including 274 males and 68 females, aged (58±9) years; of them, 78 (22.8%) developed thrombotic events. The differences in age, gender, smoking history, drinking history, hypertension, diabetes mellitus, hyperlipidemia, percutaneous coronary intervention history, proportion of combined with calcium channel antagonists, cytochrome P450 (CYP) 2C19*3, paraoxonase-1 Q192R, and adenosine triphosphate binding cassette transporter B1 C3435T between the thrombotic event group and the non-thrombotic event group were not statistically significant (all P>0.05), but the body mass index (BMI), the proportion of CYP2C19*2 GG type and CYP2C19*17 CT type in patients in the thrombotic event group were lower than those in the non-thrombotic event group (all P<0.05), and the proportion of patients with proton pump inhibitor and CYP2C19*17 CC type in the thrombotic event group was higher than that in the non-thrombotic event group (all P<0.05). Multivariate logistic regression analysis showed that high BMI (OR=0.915, 95%CI: 0.847-0.989, P=0.026), CYP2C19*2 GG type (OR=0, 95%CI: 0-0.008, P<0.001), and GA type (OR=0.028, 95%CI: 0.003-0.296, P=0.003) were independent protective factors for thrombotic events after clopidogrel treatment; CYP2C19*17 CC type (OR=2-856.665, 95%CI: 87.337-93-436.810, P<0.001) was an independent risk factor for thrombotic events after clopidogrel treatment.　Conclusion CYP2C19*2 and CYP2C19*17 mutations are important factors affecting the efficacy of clopidogrel and the occurrence of thrombotic events after treatment in ACS patients.

Objective To understand the pre-warnings of drug dosage errors in medical advices in elderly inpatients with renal insufficiency by the prescription review system.　Methods The pre-warnings of drug dosage errors in medical advices in ≥65 years old inpatients with renal insufficiency by the prescription review system in Xinhua Hospital Affiliated to Shanghai Jiao Tong University Medical College from January 1, 2021 to December 31, 2021 were reviewed, and the reasons for the wrong pre-warnings were analyzed. In the correct pre-warnings, the drugs involved in dosage errors related to kidney and the types of errors were evaluated, and the departments related to the occurrence of errors and the acceptance of physicians for pre-warnings were analyzed.　Results A total of 511 medical advices on pre-warnings related to drug dose in ≥65 years old patients with renal insufficiency were included in the analysis. One hundred and eighty-three medical advices (35.8%) were evaluated as wrong pre-warnings, and 328 (64.2%) were correct pre-warnings. The medical advices with correct pre-warnings involved 25 kinds of drugs, of which the most involved drugs was antibacterial drugs ［57.62%(189/328)］; the second was cardiovascular system drugs ［24.70% (81/328)］, among which trimetazidine tablets was the most common. Among the correct pre-warnings, 315 (96.04%) were excessive dose, and 13 (3.96%) were insufficient dose. The most common error content of excessive dose was "excessive single dose and excessive daily dose" (53.33%, 168/315), followed by "high frequency, excessive daily dose" (41.59%, 131/315); the most common errors of insufficient dose was "low frequency, insufficient daily dose" (9/13). A total of 186 (56.7%) medical advices were corrected by physicians after accepting the pre-warnings, and 142 (43.3%) were not. The acceptance rate of surgeons for pre-warning of wrong orders was higher than that of physicians, with a statistically significant difference ［73.3%(96/131) vs. 45.7%(90/197), P<0.001］.　Conclusions The effect of pre-warnings from the prescription review system on dosage errors related to kidney is positive. It is necessary to further improve the accuracy of the prescription review system for the dosage errors related to kidney, improve the acceptance of clinicians, and ensure the safety of patients.

Objective To explore the clinical characteristics of rituximab-related progressive multifocal leukoencephalopathy (PML) in patients with rheumatoid arthritis (RA).　Methods The relevant domestic and international databases (as of November 2021) were searched and case reports on PML in RA patients treated with rituximab were collected. Clinical data such as gender, age, underlying disease, use of rituximab, combination drugs, time to onset of PML, clinical manifestations, results of ancillary examinations(imaging, cerebrospinal fluid), intervention and prognosis were extracted and analyzed descriptively.　Results A total of 10 patients were enrolled in the study, including 1 male and 9 females, aged from 51 to 83 years with an average of 66 years. All of the patients were suffering from moderate to severe RA, 9 of which had a disease duration of ≥3 years and 1 had no disease duration record. The usage and dosage of rituximab in the 10 patients were in accordance with the instructions, and all the patients received combined medication with conventional synthetic disease-modifying anti-rheumatic drugs or glucocorticoids. The time from the last dose of rituximab to the onset of PML was recorded in 9 patients, which were 2-8, 16, and 18 months in 7, 1, and 1 patient respectively, with a median time of 6 months. Clinical symptoms were recorded in 6 patients, mainly including ataxia, speech disorders, cognitive impairment, and focal sensory deficits, etc. Six patients had head magnetic resonance imaging, and all of the results were consistent with the imaging changes of PML. Four patients had cerebrospinal fluid anti-John Cunningham virus test, which were positive for viral DNA in 3 patients and negative in 1 patient (the patient was diagnosed with PML by brain tissue biopsy). After the diagnosis of PML, 1 patient received no intervention, 3 had no record of intervention measures, 5 were treated with mefloquine and mirtazapine alone or in combination (2 of which were combined with plasma exchange and 1 with glucocorticoids), and 1 was treated with mirtazapine and nitrofurantoin in combination. Seven patients died due to ineffective treatment, 2 survived but had severe neurological sequelae, and the final outcome of 1 patient was not reported.　Conclusions Rituximab-related PML mostly occurs 2 to 8 months after the last application of the drug, which has similar clinical manifestations and imaging to that due to other causes and usually aggravate progressively with a high mortality rate. The survivors may have severe neurological sequelae.

The theme of World Patient Safety Day 2022 is Medication Safety. Medication safety has become a hot issue in the field of life science research, and the adverse effects of drugs on the central nervous system have gradually attracted clinical attention. Common drug-induced neurological disorders include drug-induced epilepsy, drug-induced extrapyramidal disorders, drug-induced encephalopathy, drug-induced stroke, drug-induced visual impairment, drug-induced spinal cord injury, drug-induced sleep disorders, drug-induced cognitive dysfunction, drug-induced serotonin syndrome, and drug-induced peripheral neuropathy. The drugs that cause drug-induced neurological disorders mainly include antipsychotic drugs, antianxiety and antidepression drugs, anticonvulsant drugs, chemotherapy drugs, and some drugs for cardiovascular system diseases such as statins. The principles for treatment of suspected drug-induced neurological disorders include: (1) improving examination and clarifing diagnosis; (2) removing the causes and stopping or reducing the use of pathogenic drugs; (3) eliminating pathogenic drugs in the body; (4) giving symptomatic treatments and nutritional support.

Objective To analyze the occurrence of medication errors (MEs) and their influen- cing factors on proton pump inhibitors (PPIs) and to provide reference for the standard use of PPIs in clinic. Methods The ME reports on PPI-related MEs in the National Monitoring Network for Clinical Safe Medication (monitoring network) from January 1, 2020 to December 31, 2020, were collected and information of MEs including drugs involved, ME grading, error content, the persons who triggered and found the errors, and the factors that caused the errors were analyzed.　Results A total of 593 PPI-related ME reports from 97-hospitals in 21 provinces and municipalities in China were collected in the monitoring network in 2020. A total of 593 patients were involved, including 358 males (60.4%) and 235 females (39.6%), aged from 1 to 99 years old with an average age of 53.7 years. In the 593 MEs, there were 418 (70.5%), 167 (28.2%), 7 (1.2%), and 1 (0.2%) MEs were graded as grade B, C, D, and E, respectively; a total of 6 kinds of PPIs were involved and 649 times of ME occurred, of which 177 times (27.2%) were related to omeprazole, 143 (22.0%) to rabeprazole, 135 (20.8%) to esomeprazole, 123 (19.0%) to pantoprazole, 66 (10.2%) to lansoprazole, and 5 (0.8%) to ilaprazole. Among the 593 patients, the medication indications for PPIs included prevention of stress mucosal injury in 303 patients (51.1%), gastroesophageal reflux disease in 91 patients (15.3%), peptic ulcer in 64 patients (10.8%), upper gastrointestinal bleeding in 25 patients (4.2%), helicobacter pylori infection eradication in 6 patients (1.0%), and non-steroidal anti-inflammatory drug-related ulcers in 6 patients (1.0%). There were 103 patients (17.4%) received PPIs without appropriate indications and 5 patients (0.8%) with 2 indications at the same time. The 593 ME reports involved a total of 609 times of ME content, and the wrong indication (16.9%, 103/609) ranked the first, followed by the wrong drug class (16.3%, 99/609) and the wrong medication frequency (14.0%, 85/609). Among the 593 MEs, 75.1% (445 MEs) were triggered by physician, 20.7% (123 MEs) by pharmacists, 2.5% (15 MEs) by nurse, 0.7% (4 MEs) by patients/family members, and 1.0% (6 MEs) by others; 418 MEs (70.5%) were detected and intercepted in time, of which 87.6% (366/418) were found by pharmacists, 8.1% (34/418) by nurses, and 4.3% (18/418) by patients/family members. The factors that caused MEs occurred 659 times in total, mainly including lack of knowledge/insufficient training (accounting for 50.8%, 335/659), fatigue (accounting for 18.4%, 121/659), and look alike/sound alike (accounting for 9.1%, 60/659).　Conclusions The contents of PPIs-related MEs mainly include wrong indications, wrong drug class, and wrong medication frequency. MEs are mainly caused by physicians and mostly discovered and intercepted by pharmacists. Lack of knowledge/inadequate training is a major factor in causing MEs.

Objective To evaluate the preventive effect of angiotesion converting enzyme inhibitors (ACEI)/angiotensin receptor blockers (ARB) and beta-blockers against trastuzumab-related cardiotoxicity in patients with breast cancer.　Methods Databases of PubMed, Embase, and Web of Science and Clinical Trials.gov were searched (up to February 28, 2022) and randomized controlled trials (RCTs) on ACEI/ARB or beta-blockers in preventing trastuzumab-related cardiotoxicity in female breast cancer patients, who were treated with trastuzumab containing regimens and without underlying cardiac diseases, were collected. Patients in the trial group were given intervention measures of ACEI, ARB, or beta-blockers while those in the control group were given placebo or no intervention. The primary outcome indicator was the change of left ventricular ejection fraction (LVEF) from baseline, and the secondary outcome indicators were the incidence of cardiotoxic events, the incidence of trastuzumab discontinuation, and the change of blood pressure. Random effects model in Revman 5.4 was used for meta-analysis, the effect sizes of enumeration data were the relative risk (RR) and its 95% confidence interval (CI), and those of measurement data were the mean difference (MD) and its 95%CI.　Results A total of 4 RCTs and 844 patients were included in the analysis, including 520 patients in the trial group and 324 patients in the control group. The results of the meta-analysis showed that patients in the trial group treated with ACEI/ARB had a lower LVEF reduction (MD=1.37%, 95%CI: 0.49%-2.25%, P=0.002) and higher mean value of systolic blood pressure decrease (MD=-5.99-mmHg, 95%CI: -9.15--2.83-mmHg, P<0.001) than those in the control group; patients in the trial group treated with beta-blockers had a lower risk of trastuzumab discontinuation due to cardiotoxicity than those in the control group ［14.4% (27/187) vs. 26.6% (49/184), RR=0.55, 95%CI: 0.36-0.84, P=0.006］; other outcome indicators including the risk of cardiotoxic events in the patients of the trial group treated with ACEI/ARB or beta-blockers were not significantly different from those in the control group (all P>0.05).　Conclusion ACEI/ARB may have a certain preventive effect on trastuzumab-related LVEF reduction in breast cancer patients, but ACEI/ARB and beta-blockers could not reduce the risk of trastuzumab-related cardiotoxic events.

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.

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.

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.

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.