Objective To explore the long-term efficacy and safety of gene therapy with pUDK- hepatocyte growth factor (pUDK-HGF) for rest pain and ulcers caused by critical limb ischemia.　Methods Long-term follow-up were conducted through outpatient and telephone on patients who completed the pUDK-HGF Phase Ⅱ randomized double-blind placebo-controlled trial. The occurrence of tumors was observed, and tumor markers detection, fundus examination, visual analogue scale (VAS), and lower limb CT angiography (CTA) were performed according to voluntary principle. The results were analyzed descri- ptively and statistically. Results A total of 53 patients were included in the analysis, of which 15 (28.3%) were in the placebo group and 38 (71.7%) were in the pUDK-HGF treatment group in the Phase Ⅱ clinical trial. The median follow-up time was 2.8 years, ranging from 1.7 to 3.5 years. During the follow-up period, no tumor was found in the 53 patients. Among the 38 patients in the pUDK-HGF treatment group, 18 underwent comprehensive examination and evaluation, including tumor markers, fundus and CTA examination, and patients with resting pain underwent VAS evaluation. Among them, 1 patient had transient mild elevation of carcinoembryonic antigen, and no abnormal tumor markers were found in the other 17 patients; no proliferative retinal vasculopathy was found in the fundus examination. At the end of the phase Ⅱ clinical trial (out-group), 3 were effective and 2 were ineffective of the 5 patients with rest pain; at the end of this follow-up period, 4 were evaluated as effectiveness and 1 as ineffectiveness according to CTA, and 5 were all evaluated as effectiveness according to VAS. Of the 13 patients with ulcer, 9 were evaluated as effectiveness and 4 were as ineffectiveness according to CTA at out-group; 10 were evaluated as effectiveness and 3 were as ineffectiveness at the end of this follow-up.　Conclusions pUDK-HGF had relatively good safety in the treatment of rest pain and ulcers caused by critical limb ischemia. No risk of carcinogenesis and proliferative retinal vasculopathy has been found, and the long-term efficacy of pUDK-HGF is good.

Objective To investigate the effect of intravenous application of furosemide on occurrence of cardiac surgery-associated acute kidney injury (CSA-AKI) in patients after cardiac surgery.　Methods The electronic medical records of patients undergoing cardiac surgery in Linyi People′s Hospital from January 2014 to December 2022 were collected and retrospectively analyzed. According to whether CSA-AKI occurred after surgery, the patients were divided into AKI group and non-AKI group and the clinical characteristics between the 2 groups were compared. Multivariate logistic regression was used to analyze the influencing factors of CSA-AKI, and the odds ratio (OR) and its 95% confidence interval (CI) were calculated.　Results A total of 2-633 patients were enrolled in the analysis, including 1-601 males (60.8%) and 1-032 females (39.2%). The age was (62.8±8.9) years, ranging from 18 to 85 years. Among the 2-633 patients, 491 (18.6%) developed CSA-AKI. Multivariate logistic regression analysis showed that after adjusting for factors such as the type of operation, intraoperative cardiopulmonary bypass, hypertension, diabetes mellitus, hypoalbuminemia, NYHA cardiac function class Ⅲ/Ⅳ, intraoperative/postoperative aortic balloon counterpulsation, preoperative serum creatinine level, operation duration, and the number of vasoactive drugs used after the operation, postoperative intravenous application of furosemide was still independently associated with the occurrence of CSA-AKI (OR=2.161, 95%CI: 1.720-2.715, P<0.001).　Conclusions The incidence of CSA-AKI in patients enrolled in this study was 18.6%. Intravenous use of furosemide after cardiac surgery can increase the risk of CSA-AKI.

Objective To explore the clinical characteristics of cardiotoxicity due to 5-hydroxytryptamine 3 receptor (5-HT3) antagonists.　Methods Relevant databases at home and abroad (up to June 20, 2023) were searched and case literature of cardiotoxicity induced by 5-HT3 receptor antagonist were collected. Relevant information of patients, medication status (drug name, usage and dosage, indication, combined drugs), occurrence of cardiotoxicity, evaluation of the association between 5-HT3 receptor antagonists and cardiotoxicity, intervention measures and outcomes were extracted and analyzed descriptively and statistically.　Results A total of 23 case reports, 22 in English and 1 in Chinese, were enrolled in the analysis. There were 26 patients, 6 males and 20 females, and the age ranged from 8 to 60 years, with an average of 40 years. The reasons for drug use were perioperative antiemesis in 19 patients, chemotherapy antiemesis in 2 patients, and other reasons in 5 patients. Ondansetron was used in 19 patients, dolasetron in 4 patients, granisetron, tropisetron and palonosetron in 1 patient each. Except for 1 patient with overdose by self-medication, the dosage in 25 patients was within the recommended range in labels. A total of 50 case time of cardiotoxicity occurred in 26 patients, mainly including tachycardia (12 cases), electrocardiogram (ECC) changes (11 cases), bradycardia (9 cases), cardiac arrest (1 case), and myocardial infarction (1 case), etc. Twenty-one patients experienced cardiotoxicity after initial medication, of which 8 occurred immedia- tely after the initial medication, 5 patients occurred after ≥2 times of medication. After the occurrence of cardiotoxicity, 26 patients stopped 5-HT3 receptor antagonists successively, of which 24-stopped the drug immedia- tely and received symptomatic treatments, 1 stopped the drug after 8 days of medication without other intervention, and 1 stopped the drug and received symptomatic treatment after the symptoms aggravated. After drug withdrawal and/or symptomatic treatments, the mentioned symptoms disappeared and ECC returned to normal in 25 patients. Of them, 22 patients had a recovery time of ≤48-hours, while the other 3 patients had their ECG returned to normal at 1 week, 2 weeks, and 2 months, respectively; one patient died due to ineffective treatment for ventricular fibrillation.　Conclusions The cardiotoxicity induced by 5-HT3 receptor antagonists mostly occurs after the initial medication, and mainly manifests as tachycardia, bradycardia, ECG changes, etc. Most patients have a good prognosis after timely drug withdrawal and symptomatic treatments, and in severe cases, it can lead to death.

Objective To explore the occurrence, clinical characteristics and influencing factors of hypoglycemia induced by somatostatin in patients with acute pancreatitis (AP).　Methods The electronic medical records of AP patients treated with somatostatin in Fuyang people′s Hospital from May 1, 2019 to September 10, 2023 were collected. Patients with hypoglycemia caused by somatostatin were screened out, and the clinical characteristics of these patients were retrospectively analyzed. Patients were divided into hypoglycemia group and non-hypoglycemia group according to whether somatostatin-related hypoglycemia occurred. The clinical characteristics in patients of the 2 groups were compared and the influencing factors of somatostatin related hypoglycemia were analyzed using multivariate logistic regression method. The effect sizes were the odds ratio (OR) and its 95% confidence interval (CI).　Results A total of 353 patients were included in the analysis and 33 patients were diagnosed with somatostatin-related hypoglycemia, with an incidence of 9.3%. Of the 33 patients, 22 (66.7%) were male and 11 (33.3%) were female, aged (52±20) years. Thirty-three patients experienced a total of 66-hypoglycemic events, of which 17 (51.5%) had multiple episodes (≥2). The median blood glucose of 66-hypoglycemic events was 2.7-mmol/L, ranging from 1.8 to 3.8-mmol/L. Fifty-six times of hypoglycemia occurred during somatostatin treatment in 30 patients (90.9%), with a median time of 3 (2, 4) days for the first occurrence of somatostatin, and 39.3% (22/56) and 21.4% (12/56) of hypoglycemia episodes occurred in the first half of the night (18:00 to 23:59) and the second half of the night (0:00 to 5:59), respectively. Ten times of hypoglycemia occurred 4-7 days after somatostatin withdrawal in 3 patients (9.1%). Multivariate logistic regression analysis showed that diabetes mellitus was an independent risk factor for the occurrence of somatostatin related hypoglycemia in patients with AP (OR=6.574, 95%CI: 1.911-22.430, P=0.003), while high serum total protein and parenteral nutrition support were protective factors (OR=0.940, 95%CI: 0.885-0.998,P=0.043; OR=0.405, 95%CI: 0.166-0.990, P=0.047).　Conclusions Patients with AP should be alert to the occurrence of hypoglycemia during somatostatin treatment and within 1 week after drug withdrawal, especially at night. Diabetes mellitus and low serum total protein were independent risk factors for the occurrence of somatostatin-related hypoglycemia in patients with AP, while parenteral nutrition support was a protective factor.

Objective To improve the skin toxicity management model of tumor targeted drugs based on evidence-based practice method and apply it to clinical practice.　Methods Using the evidence- based practice method of Joanna Briggs Institute, evidence of skin toxicity management of tumor targeted drugs was formed by searching relevant guidelines and evidence-based medical literature at home and abroad, and conducting interviews and surveys with nurses and patients. Based on the evidence and in consultation with evidence-based medicine, nursing and clinical experts, the evidence was transformed into management improvement plans, and the skin toxicity checklist and care checklist were developed. The improvement scheme was applied to clinical practice, the training of nurses was strengthened, the nursing process was standardized and improved, and various forms of health education were provided to patients. Patients with skin toxicity who received targeted drug therapy in the Department of Oncology of Anhui Cancer Hospital from May to August 2023 were collected. Implementation of various management indicators by nurses before and after management improvement were compared. The occurrence and severity of skin toxicity in patients were compared to verify the effect of the improvement.　Results A total of 35 tumor patients with skin toxicity to targeted drugs were entered, including 26 males and 9 females, with age (60±10) years. Compared with before, the implementation rate of the 5 indicators after the management improvement, including the evaluation of skin toxicity and risk factors by nurses using the common terminology criteria for adverse events version 5.0, the qualified status of related nursing documents, the health education of skin care, and regular follow-up of patients, were significantly increased (from 0-31.4% up to 80%-100%), the differences were statistically significant (all P<0.05). After improvement, the incidence and severity of skin rash, skin dryness, skin reaction of hands and feet, and paronychia were significantly reduced, the score of skin care knowledge questionnaire was significantly increased ［6.00(5.00, 8.00) vs. 8.00(7.00, 9.00), P=0.002］, and the dermatology life quality index was significantly decreased ［8.00(6.00, 9.00) vs. 6.00(5.00，8.00), P=0.033］. The differences in anxiety and depression scores were not statistically significant (both P>0.05).　Conclusion The skin toxicity management of targeted drugs based on JBI evidence-based practice method can standardize the clinical nursing practice of nurses, improve the severity of skin toxicity in tumor patients, and improve their quality of life.

Objective To investigate the risk of adverse event (AE) associated with inclisiran and to provide reference for the safe use in clinical practice.　Methods The AE reports in the US FDA Adverse Event Reporting System (FAERS) database from the 4th quarter of 2004 to the 2nd quarter of 2023 with inclisiran as the primary suspect drug were collected. AE was standardized and classified using the preferred terminology (PT) and the system organ class (SOC) of the Medical Dictionary for Regulatory Activities 26.0. AE risk signal mining was performed using the report odds ratio (ROR) method and the UK Medicines and Healthcare Products Regulatory Agency (MHRA) comprehensive standard method. PT that was considered as an AE risk signal in both methods were defined as AE risk signals ［ROR method: ≥3 reports  and the lower limit of the 95% confidence interval (CI) of the ROR>1; MHRA comprehensive standard method: ≥3 reports、PRR ≥2 and χ2≥4]. A descriptive statistical analysis was performed.　Results A total of 1 888 AE reports were collected with inclisiran as the primary suspect drug, involving 1-888 patients and 835 PTs. The AE was predominantly reported in the United States (88.7%, 1 675/1 888), and predominantly by the consumer (62.1%, 1 171/1 886); there were a total of 484 reports (25.6%) about serious AE. Excluding non-drug and indication-related PTs, 85 PTs (involving 15 SOCs) met the criteria in both the ROR method and the MHRA comprehensive standard method, and defined as AE risk signals. The top 5 PTs ranked by the number of reports were arthralgia (248 cases), injection site pain (237 cases), limb pain (170 cases), myalgia (158 cases), and diarrhea (132 cases); the top 5 PTs ranked by the signal intensity included bladder discomfort (ROR=28.87, PRR=28.85), injection site discomfort (ROR=24.48, PRR=24.40), sinus pain (ROR=23.20, PRR=23.19), injection site vesicles (ROR=17.63, PRR=17.61), and injection site rash (ROR=12.51, PRR=12.45). Among the top 20 PTs ranked according to the number of reports and signal intensity respectively, 8 and 13 PTs were not documented in domestic and international specifications, of which myalgia and hypoacusis had more reports and stronger signal intensity.　Conclusion The main AE  of inclisiran in the US FAERS database were injection site reactions, followed by musculoskeletal-related AEs (arthralgia, myalgia, and myospasm, etc.) and infection-related AEs (such as urinary tract infections and bronchitis), which require clinical attention.

Objective To actively monitor and analyze the safety of levofloxacin and sodium chloride injection produced by Guangzhou Green Cross Pharmaceutical Co., Ltd (generic drug). and levofloxacin and sodium chloride injection produced by Daiichi Sankyo (Beijing) Pharmaceutical Co., Ltd (original drug).　Methods The data in this study came from the adverse drug reaction reports on levofloxacin and sodium chloride injection voluntarily monitored and reported to the National Adverse Drug Reaction Monitoring System Database by the First Affiliated Hospital of Sun Yat-sen University, Guangdong Provincial People′s Hospital, and the First Affiliated Hospital of Ji'nan University from October 1, 2022, to September 30, 2023. The information on patients′ age, gender, medication use, primary disease, time from medication to the occurrence of adverse reactions, clinical manifestations, treatment and prognosis of adverse reactions, and the occurrence of serious adverse reactions were collected. The incidence of adverse reactions was calculated.　Results A total of 30 adverse reaction reports involving levofloxacin and sodium chloride injection were collected, involving 30 patients. In the generic drug group, there were 21 cases, including 8 males and 13 females, aged from 20 to 91 years with a median age of 43 years; 2 cases of serious adverse reactions were reported. In the original drug group, there were 9 cases, including 3 males and 6 females, aged from 20 to 96 years with a median age of 56 years; no serious adverse reactions were reported. In the generic drug group, a total of 36 adverse reactions occurred in 21 patients, while in the original drug group, a total of 13 adverse reactions occurred in 9 patients. These adverse reactions involved the skin and appendages, digestive system, nervous system, musculoskeletal system, urinary system, and medication site, with skin itching and rash being the most common allergic reactions (15 case time in the generic drug group, accounting for 41.7%; 6 case time in the original drug group, accounting for 46.2%). Two cases of serious adverse reactions occurred in the generic drug group, and both were anaphylactic shock. After discontinuation of the drug, switching to other antibiotics, and symptomatic treatments, 5 cases in the generic drug group were cured, 15 cases were improved, and 1 case was unknown. In the original research drug group, 2 cases were cured and 7 cases were improved. There were no deaths in either the generic or original drug groups. The incidence of adverse reactions in outpatients and/or inpatients in the generic drug group was 0.07% (21/29 557), while that in the original research drug group was 0.08% (9/10 686). There was no statistically significant difference between the 2 groups (χ2=0.183, P=0.669).　Conclusion The results of active monitoring show that there is no significant difference in safety between the generic and original drugs of levofloxacin and sodium chloride injection.

Old drugs are generally considered as drugs that have been on the market for many years and are well known by medical workers and the public. There are still many unsolved problems about the safety of older drugs. Some adverse reactions of old drugs may not be fully understood at present, the safety of their application in special populations still needs long-term monitoring, the study on mechanism of many adverse reactions of old drugs need to be strengthened, and most adverse reactions lack specific diagnostic biomarkers and effective prevention and treatment measures. The adverse reaction content in the old drug labels needs to be continuously improved, and many safety issues in drug application still require standardized expert consensus and guidance.

Objective To explore the adverse cardiac event risk signals in arsenical for injection, improve the clinical understanding of the cardiac toxicity of arsenical.　Methods The risk signals of adverse cardiac events associated with arsenical for injection were mined using 3 methods, including reporting odds ratio (ROR) method, proportional reporting ratio (PRR) method, and the Medicines and Healthcare Products Regulatory Agency (MHRA) comprehensive standard method based on data in Shandong Provincial Center of Adverse Drug Reaction Monitoring (Shandong data) in China from the first quarter of 2003 to the fourth quarter of 2022 and the data in US FDA Adverse Event Reporting System (FAERS) database from the fourth quarter of 2003 to the third quarter of 2023. The definition of risk signal in ROR and PRR method was the number of adverse event reports ≥3 and the lower limit of 95% confidence interval (CI) of ROR and PRR >1. The definition of risk signals in MHRA comprehensive standard method was the number of adverse event reports ≥3, PRR>2, and χ2>4.　Results There were a total of 358 reports on arsenical for injection in Shandong data, of which 275 (76.8%) were related to arsenious acid and sodium chloride injection, and 83 (23.2%) were related to arsenic trioxide for injection. Among the 358 reports, adverse cardiac reactions were reported in 25 reports (7.0%), and severe cases accounted for 28.0% (7/25). There were a total of 1-294 reports on ATO in FAERS, and adverse cardiac events were reported in 418 reports (32.3%), of which severe cases accounted for 62.2% (260/418). The signal mining results form 275 reports on arsenious acid and sodium chloride injection in Shandong data showed that QT interval prolonged, chest tightness, cardiopalmus, and palpitations were risk signals. Among them, the signal strength of QT interval prolonged was the strongest. A total of 35 adverse cardiac event signals were mined in FAERS data, of which the signal strength of QT interval prolonged and long QT syndrome were the strongest. In addition, the strength of 6 arrhythmia signals (bradyarrhythmia, supraventricular premature contraction, ventricular premature contraction, torsade de pointes, ventricular tachycardia, and atrioventricular block) and 6 cardiac organic lesion signals (pericarditis, endocarditis, pericardial effusion, myocarditis, mitral regurgitation, and cardiac enlargement) also ranked high.　Conclusions Arsenical for injection is strongly associated with cardiotoxicity, and the proportion of severe cases is relatively high. The cardiotoxicity mainly affects the QT interval, and can also manifest as various types of arrhythmias and some cardiac organic lesions. 

Objective To explore the clinical characteristics of interstitial lung disease (ILD) caused by furazolidone.　Methods Clinical data of 7 patients with furazolidone-related ILD (hospital cases) hospitalized in the Department of Respiratory Medicine, Huazhong University of Science and Technology Union Shenzhen Hospital from April 1, 2022 to April 1, 2023 were collected and retrospectively analyzed， including patient basic information, medication treatments, and characteristics, treatment and outcomes of ILD. Relevant databases at home and abroad were searched, and case reports of furazolidone-related ILD (literature cases) were collected. The basic information of literature, involving patient information, indications and treatment doses of furazolidone, as well as the latentperiod, main symptoms, laboratory tests, and auxiliary examination related to ILD was descriptively analyzed.　Results Among the 7 hospital cases, 2 were males and 5 were females, with a median age of 34 years. All patients were treated with a bismuth quadruple therapy containing furazolidone (0.2 g, once daily) due to Helicobacter pylori (HP)-associated gastritis. The median time from taking medicine to the onset of clinical symptoms of interstitial lung disease was 10 days. All patients had fever, and 6 had respiratory symptoms (dry cough, dyspnea, chest pain, etc.). ILD changes were found in all patients in their chest imaging, and pleural effusion was also found in 1 patient. Seven patients had normal eosinophil counts, and 1 had mild hypoxemia. The severity of ILD was grade 2 in 6 patients and grade 3 in 1 patient. All 7 patients stopped using furazolidone, and 4 received glucocorticoids additionally. After the hospitalization of 3-10 days, all the 7 patients recovered. Eighteen literature cases of furazolidone-related ILD were retrieved, of which 15 were from China and 14 used furazolidone to treat HP infection. The time from taking medicine to the onset of clinical symptoms was 2-14 days, and the time was >7 days in 13 patients. Sixteen patients had fever, 14-had respiratory symptoms, and 1 had respiratory failure. The peripheral blood eosinophil count or percentage increased in 12 patients. All 18 patients stopped using furazolidone; 7 received glucocorticoids and 1 received ventilator assisted ventilation. All patients recovered or were improved. ILD recured in rechallenge with furazolidone in 2 patients, and 1 of them had a strong positive reaction to furazolidone in vitro lymphocyte transformation test.　Conclusions ILD is a rare adverse reaction of furazolidone, main manifests as fever and respiratory symptoms and mostly occurs 7 days after furazolidone treatment. Early detection and timely withdrawal of furazolidone generally lead to a good prognosis.

Objective To analyze the general rules and characteristics of adverse reactions of succinylated gelatin injection and provide reference for safe and rational clinical use.　Methods Adverse reaction reports related to succinylated gelatin injection in National Adverse Drug Reaction Monitoring System database from January 2004 to August 2021 were collected. Retrospective analysis of patients′ gender, age, primary disease, reason for drug use, combined drugs, and time of adverse reaction occurrence from drug use, clinical manifestations, severity and patient outcomes were performed, and classified statistics were performed according to systematic organ class (SOC) and preferred terms of Medical Dictionary for Regulatory Activities.　Results A total of 3-036 adverse reaction reports of succinylated gelatin injection were entered, including 710-serious cases (23.39%), and the top 5 SOCs involved diseases of the immune system, systemic diseases and various reactions at the administration site, skin and subcutaneous tissue diseases, vascular and lymphatic diseases, and respiratory/thoracic and mediastinal diseases. The main symptoms were anaphylactic shock, similar rapid severe allergic reaction, chills, fever, and other rapid severe allergic reactions. Among the 3-036 patients, 1-543 were cured, 1-480 were improved, 3 were not improved, 2 had sequelae, 2 died, and 6 had unknown results. The SOCs involved in adverse reactions and not recorded in labels included ocular organ diseases, various musculoskeletal and connective tissue diseases, metabolic and nutritional diseases, kidney and urinary system diseases, etc.　Conclusions The adverse reactions related to succinylated gelatin injection are mostly associated with anaphylaxis. Severe adverse reactions are consistent with the characteristics of rapid severe anaphylaxis, but there may be related risks not covered in labels.

Objective To understand the adverse event (AE) risk signal of doxycycline in children and provide reference for the safe use of the drug in clinic.　Methods AE reports of children with doxycycline as primary suspect drug were collected from the US FDA Adverse Event Reporting System (FAERS) database during the 1st quarter of 2004 to the 3rd quarter of 2023. AEs were standardized and classified according to the preferred term (PT) and system organ class (SOC) in Medical Dictionary for Regulatory Activities 26.1. The AE risk signals of doxycycline were mined using reporting odds ratio (ROR) method. An AE with reports ≥3 and the lower limit of the 95%CI of ROR >1 was defined as a risk signal. Descriptive analysis on the risk signals was performed.　Results A total of 637 AE reports related to doxycycline in children were collected, involving 107 PTs and 21 SOCs. The top 10 PTs in the number of reports (including juxtaposition) were vomiting, depression, dysphagia, Jarisch-Herxheimer reaction, cholangitis sclerosing, headache, colitis ulcerative, oesophageal ulcer, nausea, oesophagitis, and suicidal ideation. Among them, depression, Jarisch-Herxheimer reaction, cholangitis sclerosing, colitis ulcerative and suicidal ideation were not recorded in labels. The top 10 PTs in signal intensity were Jarisch-Herxheimer reaction, photoonycholysis, hypnopompic hallucination, oesophageal ulcer, oesophageal injury, hypnagogic hallucination, vitritis, onycholysis, cholangitis sclerosing, erosive oesophagitis. Among them, Jarisch-Herxheimer reaction, hypnopompic hallucination, hypnagogic hallucination, vitritis and cholangitis sclerosing were not recorded in labels. Psychiatric disorders were not covered by adverse reactions in the label.　Conclusions The main AEs of doxycycline in children are vomiting, dysphagia, oesophageal ulcer, nausea, oesophagitis, all of which are recorded in the drug label. In addition, doxycycline may also cause AEs that are not recorded in drug label, such as Jarisch-Herxheimer reaction, sclerosing cholangitis, ulcerative colitis, and psychiatric disorders.

Objective To explore the clinical characteristics of mirtazapine-related thrombocytopenia.　Methods The diagnosis and treatment of a patient with mirtazapine-related thrombocytopenia who was admitted to the Aerospace Center Hospital was reported, and the main clinical data (gender, age, indications of mirtazapine use, dosage of mirtazapine, combined medication, platelet count before and after medication, time from application of mirtazapine to thrombocytopenia occurrence, clinical treatment and prognosis, etc.) of the case and similar cases collected by searching relevant databases (up to August 31, 2023) were analyzed by descriptive statistic method.　Results A total of 9 patients were enrolled in the analysis, including 4 males and 5 females; the age ranged from 28 to 74 years, with a median age of 52 years. The indication of medication was depression in 8 patients, and 1 had no record. The daily dose of mirtazapine was 15-mg in 4 patients, 30-mg in 3 patients, and no record in 2 patients. Two patients were treated with mirtazapine alone, 6 patients were treated with mirtazapine combined with other drugs, and it was not recorded in 1 patient. The time from the application of mirtazapine to occurrence of thrombocytopenia in the 9 patients ranged from 2 to 28 days, with a median time of 8 days. The severity of thrombocytopenia was grade 1, 3, and 4 in 3, 3, and 2 patients, respectively; 1 patient had no relevant record. Of the 5 patients with severe thrombocytopenia, 3 developed bleeding, and 1 had skin ecchymosis. The results of drug-dependent antiplatelet antibody test in 2 patients were positive. Nine patients stopped mirtazapine treatment after diagnosis of thrombocytopenia, 6 patients did not receive special intervention, and 3 patients were given symptomatic treatments. After drug withdrawal for 2-43 days with the median time of 9 days, platelet counts returned to the reference range in 7 patients, platelet count increased in 1 patient, and platelet count was unknown but skin symptom was improved in 1 patient.　Conclusions Mirtazapine-related thrombocytopenia usually occurs within 10 days of treatments, which can be improved after drug withdrawal. It is suggested to monitor the blood routine before and after the application of mirtazapine.

Objective To analyze the spontaneous reports on adverse drug reaction (ADR) in a hospital and to mine the risk signals of drug that might be associated with cardiac and neurological ADRs in pregnant women.　Methods The ADR reports in the database of China Hospital Pharmacovigilance System reported by Fujian Maternal and Child Health Hospital from January 1st, 2000 to December 31st, 2022 was downloaded. ADR reports about pregnancy women were collected, and the proportions and clinical manifestations of ADRs classified as "cardiac disorders" and "nervous system disorders" according to systems and organs were analyzed by descriptive statistic method. Data mining was conducted on drugs that might be associated with cardiac disorders and nervous system disorders in ADR reports using the reporting odds ratio (ROR) method and Bayesian confidence propagation neural network (BCPNN) method. The definition of risk signals in ROR method was the number of adverse reaction/event reports on the target drug (a) ≥3, and the lower limit of the 95% confidence interval (CI) of ROR >1. The definition of risk signals in BCPNN method was the information component minus twice the standard deviation (IC-2SD) >0. When the calculation results of an adverse reaction/event was in accordance with above-mentioned conditions in both methods, a suspected drug risk signal was determined.　Results A total of 783 ADR reports about pregnancy women were included in the analysis. Ninety-four reports (12.0%) were about cardiac disorders, mainly manifested as palpitations; 121 reports (15.5%) were about nervous system disorders, mainly characterized by trembling and dizziness. These ADRs of cardiac disorders and nervous system disorders often occurred in the third trimester of pregnancy. Through the ROR and BCPNN methods, results showed that ritodrine hydrochloride injection (a=61, ROR=14.64, the lower limit of 95%CI=9.08; IC-2SD=1.36) and ritodrine hydrochloride tablets (a=24, ROR=8.34, the lower limit of 95%CI=4.64; IC-2SD=1.10) were risk signals of drug leading to cardiac disorders during pregnancy, while magnesium sulfate injection (a=37, ROR=6.66, the lower limit of 95%CI=4.10; IC-2SD=0.98) and ritodrine hydrochloride injection (a=45, ROR=3.72, the lower limit of 95%CI=2.44; IC-2SD=0.56) were risk signals of drug leading to nervous system disorders during pregnancy.　Conclusion Ritodrine and magnesium sulfate may be associated with cardiac and nervous system ADR in women during pregnancy, which should arouse clinical vigilance.

Objective To mine and analyze the signals of the adverse event (AE) of erenumab and provide reference for the safe application of the drug.　Methods The reports of AE from 2004 to the first quarter of 2023 were extracted from the US FDA Adverse Event Reporting System database, and the full data and data after 2018 were analyzed respectively. AEs were classified according to preferred term (PT) and the system organ class (SOC) of Medical Dictionary for Regulatory Activities (MedDRA) 23.0 version for statistical analysis. The reported odds ratio (ROR) method and Bayesian confidence progressive neural network (BCPNN) method were used to mine the AE risk signals.　Results A total of 38-348 AE reports with erenumab as the primary suspect drug were collected, involving 2-629 PTs. The number of risk signals screened by the ROR and BCPNN methods from the full data and data after 2018 was 99 and 115, respectively, involving 19 SOCs. Among them, the most frequently reported AEs were injection site reactions and constipation, which were consistent with the label. Among the top 30 PTs, 13 were not recorded in the label, including pineal cyst, postural tachycardia, positive histone antibody, spastic eye movements, fear of injection, post-concussion syndrome, Raynaud effect, psychogenic seizures, coronary artery dissection, premature menopause, trichorrhexis, collagen disease, and blepharospasm.　Conclusion In clinical application of erenumab, in addition to the adverse reactions recorded in the label, attention should also be paid to the adverse events mined in this study.

Along with the reforms of the assessment and approval regime for new drugs in China in recent years, independently researched and developed innovative drugs and conditionally approved drugs in China have been more and more. The pre-market clinical trials, assessment and approval system (especially the conditional approval system), and post-market monitoring and management of new drugs in China are still in a continuous improvement stage. Thus we need to specially pay attention to the safety of innovative drugs that independently developed in China and do a good job in post-marketing safety supervision. More evidence-based information for safe use of this type of medication in patients can be provided through the following aspects: strengthening the drug safety monitoring, conducting systematic evaluation of literature data, widely collecting drug safety data through high-quality real-world research, and conducting in-depth mining of information from drug safety reports.

Objective To explore the occurrence of immune-related adverse events (irAEs) and the relationship to efficacy of camrelizumab in treatment for patients with non-small cell lung cancer (NSCLC). Methods Clinical data of patients with NSCLC who received camrelizumab in at the Affiliated Hospital of Inner Mongolia Medical University from December 2020 to December 2022 were collected, and the efficacy of camrelizumab and the occurrence of irAEs were retrospectively analyzed. Patients were divided into irAEs group and non-irAEs group according to whether they developed irAEs. The objective response rate (ORR), disease control rate (DCR), and progression-free survival (PFS) of the 2 groups were compared. Results A total of 48 patients were entered in the analysis, including 41 males (85.4%) and 7 females (14.6%), with an age of (65.9±7.4) years; the median treatment cycle was 9 (6, 14); the overall ORR was 52.1% (25/48), the DCR was 83.3% (40/48), and the median PFS was 11 months. Among the 48 patients, 34 patients (70.8%) had 59 times of irAEs, of which 8 patients (16.7%) had at least one irAE of grade ≥3. The median time of irAEs occurrence was 5 (3, 7) treatment cycles. The irAEs with an incidence of >10% included reactive cutaneous capillary endothelial proliferation (RCCEP), thyroid injury, skin injury, lung injury, liver injury, and blood toxicity, with the incidences of 37.5% (18/48), 18.8 (9/48), 16.7% (8/48), 12.5% (6/48), 10.4% (5/48), and 10.4% (5/48), respectively. Compared with non-irAEs group, patients in the irAEs group had higher ORR and DCR ［64.7% (22/34) vs. 3/14, 91.2% (31/34) vs. 9/14］ and longer median PFS (12.0 months vs. 7.0 months, hazard ratio=0.418, 95% confidence interval: 0.193-0.905), and the differences were statistically significant (all P<0.05).　Conclusions The common irAEs of camrelizumab in treatment for patients with NSCLC was RCCEP, and fewer serious irAEs occurs. To a certain extent, patients who experience irAEs during camrelizumab treatment may predict a more pronounced therapeutic response.

Objective To explore the occurrence, influencing factors, and predictive biomarkers of immune-related adverse events (irAEs) in malignant tumor patients treated with tislelizumab.　Methods The electronic medical records of adult patients with malignant tumors, who received tislelizumab for at least one cycle from June 2020 to June 2023 at Shanghai Ninth People′s Hospital, Shanghai Jiao Tong University School of Medicine, were collected, and the occurrence and clinical characteristics of irAEs were retrospectively analyzed. Patients were divided into irAEs group and non-irAEs group according to whether they had irAEs. The clinical characteristics and detection value of biomarkers in patients of the 2 groups were compared. Multivariate logistic regression was used to analyze the risk factors of irAEs in patients. The receiver operating characteristic (ROC) curve was used to find the cutoff point of the biomarkers for predicting the irAEs.　Results A total of 107 patients were entered, including 81 males (75.7%) and 26 females (24.3%), aged (61±15) years. Among them, 25 patients (23.4%) were diagnosed with tislelizumab-related irAEs, of which 6 patients (5.6%) had irAEs with a severity of grade 3 and above. A total of 28 irAEs occurred in the 25 patients, including 9 cases of thyroid dysfunction, 4 cases of immune-related enteritis, 4 cases of rashes, 3 cases of immune-related pneumonitis, 3 cases of kidney injury, 3 cases of liver injury, 1 case of immune- related myositis, and 1 case of hypertension. The median treatment cycle from the start of tislelizumab to the occurrence of irAEs was 3 (1, 5) cycles. After discontinuation of tislelizumab and/or glucocorticoids and symptomatic treatments, all 25 patients were improved. No deaths occurred due to irAEs. The results of multivariate logistic regression analysis showed that a high neutrophil-to-lymphocyte ratio (NLP) at baseline was a protective factor for irAEs [odds ratio (OR)=0.453, 95% confidence interval (CI): 0.279-0.735, P=0.001], while a high platelet-to-lymphocyte ratio (PLR) at baseline was a risk factor (OR=1.006, 95%CI: 1.002- 1.011, P=0.008). The ROC curve analysis results showed that the cutoff points of NLR and PLR at baseline for predicting the occurrence of irAEs were 1.58 (sensitivity: 0.988; specificity: 0.644) and 159.40 (sensitivity: 0.800; specificity: 0.524), respectively.　Conclusions The incidence of irAEs in the tislelizumab treatment for adult malignant tumors was 23.4%. Thyroid dysfunction is most common and attentions should also be paid to immune-related enteritis, rashes, immune-related pneumonitis, kidney injury, and liver injury. Baseline levels of NLR and PLR may be biomarkers for predicting irAEs.

Objective To evaluate the efficacy and safety of hybutimibe in the treatment of hypercholesterolemia.　Methods Relevant databases and clinical trial registration websites at home and abroad were searched (up to March 27, 2023), and randomized controlled trials (RCTs) of hybutimibe in the treatment of hypercholesterolemia have been collected. Patients in the trial group were given hybutimibe with or without other hypolipidemic agents, and those in the control group were given placebo or other hypolipidemic agents as same as that in the trial group. The primary outcome in effectiveness was the change rate of low-density lipoprotein cholesterol (LDL-C). The primary outcomes in safety were incidences of overall adverse events (AEs), serious AEs (SAEs), the trial termination due to AEs, and trial drug-related AEs. The secondary outcome in safety was incidence of the major AE reported in ≥ 2 trials. Meta-analysis was performed using RevMan 5.4-software. The effect sizes of counting data were expressed by the relative risk (RR) and its 95% confidence interval (CI). The effect sizes of measurement data were expressed by mean difference (MD) and its 95%CI.　Results A total of 4 RCTs and 1-488 patients were entered in the analysis, including 952 patients in the trial group and 536 in the control group. The results of meta-analysis showed that at 8-12 weeks of treatment, the decrease rate of LDL-C in the trial group (hybutimibe 20 or 10-mg daily with or without atorvastatin 10-mg daily) was significantly greater than that in the control group (hybutimibe 20-mg daily: MD=-13.36%, 95%CI: -15.28% - -11.44%, P<0.001; hybutimibe 10-mg daily: MD=-10.80%, 95%CI: -14.90%- -6.71%, P<0.001); at 52 weeks of treatment, the average decrease rate (from baseline) of LDL-C in the trial group (hybutimibe 20 or 10-mg combined with atorvastatin 10-mg daily) was significantly greater than that in the control group with atorvastatin 10-mg daily monotherapy (-41.92% and -39.34% vs. -31.56%, all P<0.001); the incidences of overall AEs ［47.94% (338/705) vs. 49.75% (202/406)，RR=0.99, 95%CI: 0.87-1.12］, SAEs［2.64% (16/606) vs. 2.79% (10/358), RR=1.19, 95%CI: 0.53-2.66］, trial termination due to AEs［4.11% (29/705) vs. 4.68% (19/406), RR=0.67, 95%CI: 0.17-2.65］, and trial drug-related AEs ［12.38% (75/606) vs. 11.45% (41/358), RR=0.87, 95%CI: 0.37-2.06］ were similar between the 2 groups at 8-12 weeks of treatment (all P>0.05).　Conclusion Hybutimibe could effectively reduce LDL-C level in patients with hypercholesterolemia, with good medication safety.

Objective To compare the efficacy and safety of insulin degludec and insulin glargine U100 in patients with type 2 diabetes mellitus.　Methods This study was a retrospective cohort study. The subjects were patients with type 2 diabetes mellitus who were hospitalized in 13-3A-level general hospitals in Shandong Province from September 2018 to December 2021. According to the type of basal insulin used, the patients were divided into insulin degludec group and insulin glargine U100 group. The basic information and laboratory test results in patients in the 2 groups were collected, the differences of fasting blood glucose level and incidence of hypoglycemia between the 2 groups were compared. The patients with complete blood glucose monitoring data in the 2 groups were selected and their blood glucose fluctuations were compared.　Results A total of 1-152 patients were entered in the study, including 552 patients in the insulin degludec group and 600 patients in the insulin glargine U100 group. The difference in the basic conditions in patients in the 2 groups was not statistically significant (all P>0.05). After treatment, the fasting blood glucose levels in patients in the 2 groups were lower than those before treatment, with statistically significant differences ［10.2 (8.8, 12.5) mmol/L vs. 7.5 (6.6, 8.7) mmol/L, Z=-19.443, P<0.001; 10.0 (8.6, 11.7) mmol/L vs. 7.8 (6.6, 9.0) mmol/L, Z=-15.449, P<0.001］, but the difference in fasting blood glucose levels between the 2 groups after treatment was not statistically significant (Z=-1.427, P>0.05). The incidence of hypoglycemia in the insulin degludec group was lower than that in the insulin glargine U100 group ［1.09% (6/552) vs. 2.83% (17/600), Z=4.481, P=0.032］. The intraday blood glucose standard deviation, maximum blood glucose fluctuation range, postprandial blood glucose fluctuation range, and average blood glucose fluctuation range in patients with complete blood glucose monitoring data in the insulin degludec group were significantly lower than those in the insulin glargine U100 group ［(1.7±0.6) mmol/L vs. (2.4±1.0) mmol/L, (4.5±1.6) mmol/L vs. (6.7±2.9) mmol/L, (1.8±1.0) mmol/L vs. (3.3±1.2) mmol/L, (2.9±1.3) mmol/L vs. (4.6±2.1) mmol/L; all P<0.001］.　Conclusion The efficacy of insulin degludec in the treatment of type 2 diabetes mellitus is equivalent to that of insulin glargine U100, but the risk of hypoglycemia and blood glucose fluctuation is lower.

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

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

Objective To explore the clinical manifestation, treatments, and outcomes of immune checkpoint inhibitor (ICI)-induced immune-mediated liver injury (IMLI).　Methods The patients with ICI- related IMLI and hospitalized in the Department of Oncology, the Affiliated Hospital of Qingdao University from January 2018 to November 2022 were collected. The basic information, tumor treatments, clinical manifestation, treatments and outcomes of the patients with IMLI were retrospectively analyzed.　Results A total of 29 patients were included in the study, including 17 males (58.6%) and 12 females (41.4%), with a median age of 65 years. The median treatment cycle from the use of ICI to the occurrence of liver injury was 3 cycles, and the median time was 78 days. In patients with IMLI, 48.3% (14/29) had no obvious symptoms and 51.7% (15/29) had symptoms such as decreased appetite, nausea, abdominal distension, fatigue, fever and jaundice; 44.8% (13/29) were accompanied by other immune-related adverse events. The clinical classification of IMLI was hepatocellular type in 18 patients (62.1%), cholestasis type in 4 patients (13.8%), and mixed type in 7 patients (24.1%). According to the Common Terminology Criteria for Adverse Events (CTCAE) classification, severe liver injury (≥ grade 3) accounted for 86.2% (25/29), while according to the Chinese Diagnosis and Treatment Guideline on Drug-Induced Liver Injury (DILI guidelines) classification, severe liver injury (≥ grade 2) accounted for 34.5% (10/29). All 29 patients discontinued the treatment of ICIs after occurrence of IMLI, and 28 patients were treated with glucocorticoids, 7 of which were combined with mycophenolate mofetil and/or human immunoglobulin and artificial liver; 22 patients (75.9%) were improved. In the other 7 patients that did not recover, 4 discharged automatically, 2 died, and 1 could not be judged. ICI was rechallenged in 3 patients after liver function improvement, and IMLI did not recur.　Conclusions The IMLIs often occur 2 to 3 months after the start of ICI treatment, the most common clinical type is hepatocyte type, and the severity of clinical symptoms in patients vary from mild to severe. After discontinuing ICIs and receiving glucocorticoid treatments, most patients may have a good prognosis.

Objective To investigate the current status of polypharmacy among elderly outpatients with 4 types of chronic diseases such as hypertension, diabetes mellitus, coronary atherosclerotic heart disease, and cerebrovascular disease.　Methods A retrospective study was conducted on the drug use of elderly (≥65 years old) outpatients with hypertension, diabetes mellitus, coronary atherosclerotic heart disease, and cerebrovascular disease with data of Beijing Municipal Health Insurance Centre database from July 2017 to September 2017. The included patients had at least 1 of 4 types of chronic diseases. Polypharmacy was defined as ≥5 different types of medication at the first visit, and non-polypharmacy was defined as <5 types of medication. The number and severity of comorbidity were quantified using the Charlson Comorbidity Index (CCI), and the prognosis of patient was evaluated at 4 levels of 0, 1, 2, and ≥3 scores. The larger the value, the more severe the disease. Based on the Beers Criteria 2015, the potential inappropriate medication (PIM) was identified using the prescription review system of Puhua Health.　Results A total of 405-608 patients were included in this study, with a median age of 74 (65-107) years , and 204-219 patients (50.35%) were female. According to the type of medication used by patients, they were divided into polypharmacy group (113-594 cases, 28.01%) and non-polypharmacy group (292-014 cases, 71.99%). The CCI of the polypharmacy group was significantly higher than that of the non-polypharmacy group (P<0.001). The proportion of patients with 0, 1, 2, and ≥3 scores in the polypharmacy group was significantly higher than that of the non-polypharmacy group, and the differences were statistically significant (all P<0.001). In terms of comorbidity, the proportions of patients among the 4 types of chronic diseases were higher in the polypharmacy group than in the non-polypharmacy group (P<0.001). In terms of concomitant diseases, the proportion of patients with hyperlipidemia, cognitive impairment, heart failure, and osteoporosis in the polypharmacy group was higher than that in the non-polypharmacy group (all P<0.001). In terms of medical treatment behaviour, the median number of medical visits was higher in the polypharmacy group than in the non-polypharmacy group ［2(1,3) vs. 1(1,2), P<0.001］. In terms of evaluating the unsuitability of medication, the proportion of patients with PIM in the polypharmacy group was higher than that in the non-polypharmacy group, including repeated medication ［4.60% （5-227/113 594） vs. 1.64% (4-486/292 014）］, contraindications ［2.97% （3-376/113 594） vs. 1.13% (3-294/292 014)］, interactions ［6.51% （7-399/113 594） vs. 1.94% (5-658/292 014）］, and lack of indications ［22.39% （25-432/113 594） vs. 13.54% （39-543/292 014）］, and the differences were all significant (all P<0.001). In terms of drug use categories, the top 5 most commonly prescribed drugs in the polypharmacy group were HMG-CoA reductase inhibitors (68-318 cases, 60.14%), dihydropyridines (60-951 cases, 53.66%), angiotensin receptor antagonists（45-050 cases, 39.66%）, β-receptor blockers (25-675 cases, 22.60%) and sulfonylureas (16-023 cases, 14.11%).　Conclusions Polypharmacy is common in elderly patients with hypertension, diabetes mellitus, coronary artery disease, and cerebrovascular disease. The elderly patients with polypharmacy have a worse baseline status and more problems with PIM.

Objective To understand the adverse event (AE) risk signals of 3 anti-disialoganglioside 2 (GD2) monoclonal antibodies, including dinutuximab, dinutuximab beta, and naxitamab, and to provide reference to clinical use.　Methods AE reports with dinutuximab, dinutuximab beta, and naxitamab as the primary and secondary suspect drug were collected from the US FDA Adverse Event Reporting System (FAERS) database during 2015 to the 2nd quarter of 2023. AEs were standardized and classified according to the preferred term (PT) and system organ classification (SOC) in the International Medical Terminology Dictionary, Version 25.0, and AE risk signals were mined using the reporting odds ratio (ROR) method and information component (IC) method. The AE reports information and AE risk signals of 3 GD2 monoclonal antibodies were descriptively analyzed. Results A total of 630 AE reports were collected, in which the 3 GD2 monoclonal antibodies were the primary and secondary suspect drugs, including 465 reports of dinutuximab, 61 reports of dinutuximab beta, and 104 reports of naxitamab, which involved 341, 24, and 125 PTs and mapped to 19, 2, and 12 SOCs, respectively. The AEs of the 3 GD2 monoclonal antibodies were associated with the occurrence of death, life-threatening, hospitalization, or prolonged hospitali- zation adverse outcomes. Signal mining using ROR and IC methods detected a total of 142, 3, and 30 AE risk signals, of which 73, 0, and 6 were not documented in the corresponding drug instructions, respectively. The top PTs in report number were fever for both dinutuximab and dinutuximab beta, and hypotension and pain for naxitamab; the top PTs in signal intensity were puncture site abscess, device related bacteraemia, and wheezing for dinutuximab, dinutuximab beta, and naxitamab, respectively. The overlapping AE risk signals for the 3 drugs were fever and pain, with dinutuximab having the strongest signal intensity for fever and naxitamab having the strongest signal intensity for pain. Among the top 30 PTs in report number, naxitamab had significantly more AE risk signals than dinutuximab in respiratory, thoracic, and mediastinal disorders, skin and subcutaneous tissue disorders, immune system disorders, and vascular disorders. For naxitamab, the PTs that differed from dinutuximab′s AE risk signals and were not documented in the naxitamab drug instructions were respiration abnormal, cyanosis, and metabolic acidosis.　Conclusions Fever, pain, and hypotension are common AEs for the 3 GD2 monoclonal antibodies. Naxitamab causes significant pain; respiration abnormal, cyanosis, and metabolic acidosis are AE risk signals specific to naxitamab and not documented in the drug instruction, which warrant clinical vigilance and prompt intervention.

Objective To explore the occurrence and clinical characteristics of liver injury caused by immune checkpoint inhibitors (ICI) in cancer patients.　Methods Medical records of cancer patients with normal liver function who used ICI during hospitalization in Beijing Friendship Hospital from January 2017 to December 2022 were collected, and those with liver injury related to ICI were screened out. The basic information of patients with ICI-related liver injury, treatment regime of ICI, concomitant medication, liver function before and after medication, intervention measures and outcomes were extracted, and the clinical characteristics of ICI-related liver injury were analyzed descriptively.　Results A total of 155 patients with solid tumors were treated with ICI within the set time, of which 15 (9.7%) were diagnosed with ICI-related liver injury. Among the 15 patients, there were 6 males and 9 females, with a median age of 59 (41, 76) years. The suspected drug causing liver injury was camrelizumab in 5 patients, sugemalimab in 2 patients, serplulimab in 2 patients, toripalimab in 2 patients, sintilimab in 2 patients, penpulimab in 1 patient, and cadonilimab in 1 patient. All 15 patients received combined medication, such as traditional chemotherapy drugs, receptor tyrosine kinases inhibitors, and/or other ICIs. The median time from suspected ICI administration to liver injury in 15 patients was 22 (4-64) days, and the liver injury occurred after the first cycle of ICI treatment in 9 patients. The medians of peak value of alanine aminotransferase and aspartate aminotransferase were 157 (15-508) U/L and 131 (77-696) U/L, respectively; the total bilirubin was more than 2 times of the upper limit of normal in 3 patients. The liver injury was classified as hepatocellular type in 6 patients, cholestasis type in 5 patients, and mixed type in 3 patients; the type was unable to be determined due to lack of data in 1 patient. Among the 15 patients, 8 had liver injury of grade 2 and 7 had liver injury of grade 3; the suspected medication were discontinued after liver injury occurrence in 9 patients and did not discontinue in 6 patients. Seven and 5 patients recovered or basically had normal liver function after 1-4 months, respectively among those who stopped and did not stop ICI; the liver function did not return to normal in the other 3 patients at 2 to 9 months of follow-up.　Conclusions ICI-related liver injury usually occurs after the first cycle of ICI treatment (within 1-2 months of medication), and the severity is mostly grade 2 or 3. The 3 clinical types of drug-induced liver injury (hepatocellular type, cholestatic type, and mixed type) are clinically visible. After the occurrence of liver injury, most patients have a good prognosis through timely discontinuation and/or treatments.

Objective To explore the adherence and its influencing factors of tegafur, gimeracil and oteracil potassium (S-1) treatment in patients with tumor-node-metastasis (TNM) stage Ⅲ gastric cancer after operation.　Methods Medical records of adult patients with stage Ⅲ gastric cancer after operation in the Second Affiliated Hospital of Nanjing University of Chinese Medicine from October 2018 to April 2022 and treated with oral S-1 were collected, and the S-1 adherence and its related factors in these patients were retrospectively analyzed according to their S-1 treatment information. Good adherence was defined as completing 8 cycles of S-1 treatment within 186 days (14 days of continuous medication and 7 days of discontinuation as 1 cycle). The patients were divided into good and poor S-1 adherence groups. Univariate and multivariate logistic regression analysis were performed to analyze the factors affecting S-1 adherence of patients.　Results A total of 148 patients were entered in the study, including 116 males (78.4%) and 32 females (21.6%), with a median age of 67 (27-85) years. Sixty-nine patients (46.6%) completed ≥ 8 cycles of S-1 treatment within the set time and had good adherence; 79 (53.4%) patients had poor adherence. The reasons for interruption or failure to complete treatments as scheduled in the 79 patients were serious adverse reactions in 30 (38.0%) patients, refusal to treat in 27 (34.2%) patients, and poor curative effect in 22 (27.8%) patients. Univariate and multivariate logistic regression analysis showed that lack of or partial understanding of the disease ［odds ratio (OR)=5.368, 95% confidence interval (CI): 1.488-19.370, P= 0.010; OR=3.393, 95%CI: 1.309-8.793, P=0.012］, gastric cancer with a course of less than 1 year (OR=10.214, 95%CI: 2.400-43.472, P=0.002), and TNM stage Ⅲa (OR=3.879, 95%CI: 1.522-9.886, P=0.005) were the independent influencing factors of poor adherence to S-1 treatment in patients with gastric cancer.　Conclusions Less than half of the gastric cancer patients with stage Ⅲ after operation had good adherence to S-1 treatment. Insufficient understanding of the disease, short duration of gastric cancer, and TNM stage Ⅲa were independent influencing factors for poor adherence to S-1 treatment in gastric cancer patients. Increasing patients′ understanding of the disease and strengthening patient education may be important strate- gies to improve S-1 treatment compliance.

Objective To systematically evaluate the efficacy and safety of ixazomib in patients with relapsed or refractory multiple myeloma (RRMM) in the real world.　Methods Relevant databases at home and abroad were searched (up to April 2022), and the literature on real-world studies of ixazomib in the treatment of RRMM was collected. The quality of the literature was evaluated with the methodological index for non-randomized studies (MINORS) scale. Data such as the effectiveness rate and incidence of adverse events in RRMM patients treated with ixazomib were extracted. The effectiveness indicators included the overall response rate (ORR), very good partial response or better (≥VGPR) rate and median progression-free survival (PFS). The safety indicators included the incidence of adverse events (AEs) and the rate of treatment termination due to AEs, etc. Stata 13.0-software was used for meta-analysis of single proportions, and the occurrence of major adverse events was analyzed by descriptive statistics.　Results A total of 12-studies were entered, including 1-006 patients. The quality evaluation results showed that all of the 12-studies were with high quality. The meta-analysis of single proportions showed that ORR of ixazomib in the treatment of RRMM was 65%［95% confidence interval (CI): 58%-72%］, ≥VGPR rate was 32% (95%CI: 25%-38%), the median PFS was 21.73 (95%CI: 14.37-29.08) months, the incidence of ≥ grade 3 AEs was 39% (95%CI: 24%-55%), and the incidence of treatment termination due to AEs was 6% (95%CI: 3%-10%). AEs with an incidence of ≥10% included neutropenia, thrombocytopenia, infection, anemia, diarrhea, fatigue, peripheral neuropathy, rashes, and bone pain.　Conclusion In the real world, the efficacy of ixazomib in the treatment of RRMM is lower than that in clinical trials, but the safety is similar.

Objective To provide a basis for the selection of antiemetic regimen by establishing an artificial intelligence model for predicting chemotherapy-induced nausea and vomiting (CINV) in cancer patients receiving platinum-based chemotherapy with high emetic risk.　Methods The clinical information on cancer patients who received cisplatin or carboplatin with area under the blood concentration-time curve (AUC) ≥4 and registered in the Department of Oncology, Tianjin Medical University General Hospital from January 2018 to December 2022 was collected, including gender, age, history of alcohol consumption, history of vomiting in pregnancy, chemotherapy cycle, patient expects to have CINV, chemotherapeutic agents, antiemetic regimen, out-of-hospital antiemetic treatment, sleep of less than 7 hours on the night before chemotherapy, occurrence of CINV in the previous cycle, and creatinine clearance (Ccr). After pre-proces- sing, the data were randomly divided into the training set and the test set. The training set was used to construct the prediction model, and the test set was used to evaluate the prediction efficiency of the model. Three algorithms, gradient boosting decision tree (GBDT), random forest (RF), and logistic regression (LR), were used to build a prediction model and evaluate the model performance, respectively. The evaluation metrics included accuracy, sensitivity, recall, F1 value (the reconciled mean of sensitivity and recall), and area under the receiver operating characteristic curve (AUROC). Finally, Shapley Additive exPlanation (SHAP) was applied to analyze the interpretability of the clinical features with predictive significance.　Results A total of 698 patients, 439 males (62.9%) with a median age of 64 (21, 84) years, were included in this study and received a total of 1-654 cycles of chemotherapy. The chemotherapy regimen contained cisplatin in 364 cases with 864 cycles of chemotherapy, and carboplatin with AUC ≥4 in 361 cases with 790 cycles of chemotherapy. The number of treatment cycles in which neurokinin-1 receptor antagonist (NK-1 RA), 5-hydroxytryptamine-3 receptor antagonist (5-HT3 RA), and dexamethasone were selected as the antiemetic regimen was 1 347, and in those with the selection of 5-HT3 RA and dexamethasone was 307. The Spearman′s correlation analysis showed no strong correlation between the feature variables in the patients, and all of them could be used for model building. GBDT optimal hyperparameters n_estimators=500, max_depth=9; RF optimal hyperparameters max_depth=5; LR optimal hyperparameters penalty=L2. Three prediction models, GBDT, RF and LR, were established based on the optimal hyperparameter training data, respectively. The accuracy of GBDT model was 0.903, sensitivity was 0.882, recall was 0.903, F1 value was 0.883, and AUROC was 0.778±0.036 (95%CI: 0.739-0.814); the accuracy of RF model was 0.885, sensitivity was 0.861, recall was 0.885, F1 value was 0.870, and AUROC was 0.679±0.041 (95%CI: 0.636- 0.720); the LR model had an accuracy of 0.817, a sensitivity of 0.851, a recall of 0.817, an F1 value of 0.832, and an AUROC of 0.682±0.042 (95%CI: 0.639-0.723). Ccr, age, chemotherapy cycle, history of alcohol consumption, and patient expects to have CINV were the main features predicted by the model. The risk of CINV was negatively associated with Ccr, age, and chemotherapy cycle. And the risk of CINV was lower in patients with no history of drinking alcohol and patient expects to have CINV.　Conclusion The GBDT, RF, and LR models could all predict the risk of CINV in patients receiving platinum-based chemotherapy with high emetic risk, with the GBDT model having the best predictive effect.

The theme of World Patient Safety Day 2023 is "Engaging Patients for Patient Safety". Encouraging patients (including patients′ families, caregivers, etc.) to voice in medication safety is one of the important measures of medication safety management and pharmacovigilance, which conforms to the principles of ethics and science and is adapted to the development of society. It has been widely recognized in the world that patients participate in the safety monitoring in drug clinical trial, adverse drug reaction reporting， and information communicating and safety supervising of drug safety, and act as partners with doctors and drug regulatory agencies in drug safety. China should also attach importance to and address the obstacles in patient participation in management of medication safety, and accelerate the process of patient participation in management of medication safety.

Objective To explore the occurrence of rashes in healthy subjects caused by efavirenz in drug clinical trials.　Methods The occurrence of rashes related to efavirenz, which was used as an enzyme inducer, in healthy subjects in 2 clinical trials conducted by the Phase I Clinical Research Center of the Department of Pharmacy, Xuanwu Hospital, Capital Medical University (our hospital) in November 2020 and October 2021 was retrospectively analyzed. The relevant databases at home and abroad (up to November 30, 2022) were searched, and the literature, in which efavirenz was applied as trial drug or enzyme inducer in healthy subjects, were collected. The cases of efavirenz-related rashes reported in the literature were reviewed. The clinical characteristics of the cases in the literature and above 2 clinical trials in our hospital were summarized and analyzed by descriptive statistics.　Results A total of 40-healthy subjects were included in the 2 clinical trials, and 5 (12.5%) developed efavirenz-related rashes. The average time from taking the medicine to the appearance of rashes was 8 days. The initial symptom was skin itching. The rashes occurred mainly on the limbs and back, and mainly presented as maculopapular rashes, without other symptoms or laboratory abnormalities. Four subjects withdrew from the trial and the rashes subsided after 5-7 days of anti-allergic and symptomatic treatments; one subject was given calamine lotion for external use because of mild rashes, and continued to participate in the trial. His rashes subsided 17 days later (5 days after stopping efavirenz). Eighteen literature in which efavirenz was used as a trial drug or enzyme inducer in healthy subjects were retrieved. A total of 403-healthy subjects collected from 18 literature and our trials were included in the analysis. Of them, 19-subjects developed rashes, with a incidence of 4.7%. According to the daily dose of efavirenz, the incidence of rashes in the subjects of the 600-mg/d group was higher than that of the <600-mg/d group, but the difference was not statistically significant ［5.5% (18/329) vs. 1.4% (1/74), P=0.131］. According to the course of drug, the incidence of rashes was similar in subjects between the single dose group and the continuous dose group ［4.1% (4/97) vs. 4.9% (15/306), P=0.753］.　Conclusion Rashes are common adverse reactions in healthy subjects after taking efavirenz, which is generally mild and can subside after timely detection and treatment.

Objective To investigate the use of epinephrine in the treatment of anaphylaxis in the hospital.　Methods The adverse drug reaction (ADR) reports of anaphylaxis in National Center for ADR Monitoring of China reported by Suqian First People Hospital from August 12, 2016 to November 30, 2022 were retrospectively analyzed. Patients with anaphylaxis were divided into shock group and non-shock group according to whether they had shock. The basic information, organs and systems involved, and severity of anaphylaxis, epinephrine use, and outcomes in patients of the 2 groups were compared. The application of epinephrine in patients with anaphylaxis of different manifestations, and the rationality of the dose and route of epinephrine were analyzed and evaluated descriptively.　Results A total of 132 patients with anaphylaxis were entered in this study, including 62 males (47.0%) and 70 females (53.0%), with a median age of 53 years. There were 20 patients (15.2%) in the shock group and 112 patients in the non-shock group (84.8%). In comparison of the involving organs and systems in the anaphylaxis between the 2 groups, the cardiovascular system ［100% (20/20) vs. 17.9% (20/112)］, nervous system ［60.0% (12/20) vs. 28.6% (32/112)］, digestive system ［40.0% (8/20) vs. 15.2% (17/112)］, and urinary system ［15.0% (3/20) vs. 1.8% (2/112)］ were affected more often in patients of the shock group, while skin and mucosa were affected more often in patients of the non-shock group ［88.4% (99/112) vs. 60.0% (12/20)］. The differences were all statistically significant (all P<0.05). Only 21 (15.9%) of 132 patients with anaphylaxis used epinephrine in the treatment. The proportion of patients receiving epinephrine in the shock group was significantly higher than that in the non-shock group ［50.0% (10/20) vs. 9.8% (11/112), P<0.001］. Of the 21 patients who used epinephrine, 10 (47.6%) had excessive dose, and 11 (52.4%) received through subcutaneous injection, which was not recommended in the guidelines.　Conclusions In the emergency treatment of anaphylaxis in patients in the Suqian First People Hospital, the proportion of epinephrine use is low, and there are also situa- tions that the dosage and administration route are unreasonable. The awareness on the importance of rational use of epinephrine should be improved in medical staffs, and relevant training should be strengthened.

Objective To understand the current situation of skin tests before treatment with benzathine benzylpenicillin adviced by doctors of Dermatology Department on syphilis patients in China.　Methods A self-designed survey questionnaire was used, which included content of 3 aspects: basic information of the respondents (question 1), the time of the skin test in syphilis patients who were schedule to receive treatment with benzathine benzylpenicillin (question 2), and the issues and suggestions regarding the current skin test method of benzathine benzylpenicillin (question 3). Based on the Collaborative Study Group on Psychodermatology of the Psychosomatic Medicine Branch of the Chinese Medical Association, the survey was conducted through online questionnaires and domestic doctors of Dermatology Department participated voluntarily. The investigation period was from July 2, 2021 to August 16, 2021. The obtained information was analyzed descriptively.　Results A total of 366 electronic questionnaires were collected, of which 358 were confirmed to be valid, with a recovery rate of 97.8%. The 358 doctors of Dermatology Department were from 247 medical institutes in 20 provinces, 4 municipalities, and 4 autonomous regions across the country, including 129-3A-level first-class hospitals. The top 3 areas in number of respondents were Beijing (148 respondents, 41.3%), Yunnan province (42 respondents, 11.7%), and Henan province (25 respondents, 7%). Among the 358 doctors, 222 (62.0%) chose "conduct skin test weekly before injection of benzathine benzylpenicillin", 102 (28.5%) chose "in continuous injection, no further skin test is required for re-injection within 7 days", 33 (9.2%) chose "in continuous injection, no further skin test is required for re-injection within 72-hours", and 1 (0.3%) chose "other" and then added "further skin test is required after 48-hours of discontinuation". Compared with other medical institutions, there was a higher proportion of doctors (32.5%, 64/197) chose "in continuous injection, no further skin test is required for re-injection within 7 days" in hospitals of 3A-level first-class. Ninety one doctors (25.4%) answered question 3, all of whom believed that the current status of skin tests of benzathine benzylpenicillin had caused confusion in clinical treatment and some doctors provided suggestions such as developing standards for skin tests of benzathine benzylpenicillin and adding controlled trials.　Conclusions The skin test time window and operation have not been standardized in the treatment of syphilis with benzathine benzylpenicillin in China, which hinders the standar- dized treatment of syphilis. It is urgent to develop guidance documents for the skin test of benzathine benzylpenicillin.

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

Anaphylaxis is a severe, life-threatening, immediate, and systemic allergic reaction, and may lead to serious consequences due to delayed diagnose or improper treatment. Guidelines at home and abroad recommend epinephrine as a first-line treatment for anaphylaxis. But there are still some problems such as insufficient use, inappropriate administration route or dosage of epinephrine in the treatment of anaphylaxis in China. The timing (as early as possible), route (intramuscular injection is preferred), and dosage of epindphrine should strictly follow the recommendations of relevant guidlines. Epinephrine autoinjectors can win more rescue time for patients with anaphylaxis, and can be equipped and used after training by clinicians.

Objective To understand the current situation and problems of research design in adverse drug reaction (ADR) signal detection study in China.　Methods The literature on ADR signal detection study in SinoMed, CNKI, WanFang Data and VIP databases were retrieved (up to May 30, 2022). The research purpose, research direction (target drug, target ADR), source database of signals, target drug role, reference drug, signal detection algorithm, and bias control of the literature were analyzed descriptively one by one.　Results A total of 165 articles were included, of which 146 (88.5%) were published in core journals. From 2013 to 2022 (January to May, 2022), there were 4, 3, 2, 7, 8, 11, 20, 29, 55, and 26 relevant articles, respectively. Problems in these studies were as follows: research purposes were not clear in 6.7% (11/165) of the literature; target ADRs were selected as non targeted in 80.6% (133/165) of the literature; the domestic database was less utilized ［only 9.7% (16/165)］; did the selection range of the target drug role were not mentioned in 33.9% (56/165) of the literature; only a single algorithm for signal detection was used in 36.4% (60/165) of the literature; bias analysis was not conducted in 85.5% (141/165) of the literature.　Conclusions The domestic literature on ADR signal detection has problems of poor standardization in research design, such as unclear research purpose and direction, incomplete research items, etc. Chinese scholars should further improve the quality of research design while strengthening the research on ADR signal detection.

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

Objective To explore the neurological adverse events (AE) associated to brexucabtagene autoleucel (brexu-cel) and their risk of occurrence.　Methods Neurological AE reports related to brexu-cel were collected through the US FDA Adverse Event Reporting System database from July 1, 2020 to September 31, 2022. The AEs were classified and counted according to the system organ class (SOC) and preferred term (PT) of Medical Dictionary for Regulatory Activities (MedDRA) 24.1. The information component (IC) method and the reporting odds ratio (ROR) method were used to perform signal mining. AEs with ≥3 reports and a lower limit of 95% confidence interval (CI) for IC>0 or that for ROR>1 were defined as positive risk signals. The proportion of patients who suffered fatal outcomes after experiencing neurological AEs related to brexu-cel was analyzed.　Results A total of 1-960 neurological AE reports related to brexu-cel were collected, involving 559 patients and 22 PTs. Fifteen positive signals (PT) were detected by using the IC and ROR methods. The top 5 PTs in the number of AE reports were immune effector cell-associated neurotoxicity syndrome (153 reports), altered mental status (32 reports), encephalopathy (29 reports), tremor (27 reports), and aphasia (25 reports); the top 5 PTs with the high signal intensity were immune effector cell-associated neurotoxicity syndrome (IC=7.81, ROR=235.74), encephalopathy (IC=4.74, ROR=26.96), aphasia (IC=4.28, ROR=19.58), cerebral edema (IC=3.35, ROR=10.24), and incontinence (IC=3.04, ROR=8.22); incontinence (6 cases, IC=3.04, ROR=8.22) was not recorded in the drug instruction. Patients involved in 17 PTs, out of the 22 PTs, had fatal outcomes, and the proportion of deaths from immune effector cell-associated neurotoxi- city syndrome was 18% (28/153). The PTs with a proportion of patient deaths >50% were unresponsive to stimuli (80%, 4/5), brain oedema (75%, 6/8), cerebrovascular accident (67%, 2/3), lethargy (60%, 3/5), and seizure (57%, 4/7).　Conclusions Neurological AEs related to brexu-cel are common, of which incontinence is not yet recorded in the drug instruction. The clinical outcomes of some AEs (unrespontive to stimulus, brain oedema, and lethargy) are poor and should be closely monitored.

Objective To mine and compare the adverse event (AE) signals of allopurinol and febuxostat and provide reference for the rational and safe use of the 2 drugs in clinic.　Methods The AE reports on allopurinol and febuxostat from January 1, 2009 to December 31, 2021 were collected by searching the US Food and Drug Administration Public Data Open Project (openFDA) database. AEs were classified using preferred term (PT) and systemic organ class (SOC) of the International Medical Terminology Dictionary 25.0. The AE risk signals of allopurinol and febuxostat were mined using the reporting odds ratio (ROR) method. The number of AE reports ≥3 and the lower limit of the 95% confidence interval (CI) of the ROR>1 was defined as a positive signal. The new AE risk signals of allopurinol and febuxostat were screened according to the drug labels. The radar chart was drawn according to the number of allopurinol and febuxostat risk signals. The positive PT signals were descriptively and statistically analyzed.　Results The number of AE reports of allopurinol and febuxostat were 105-532 and 9-949, respectively. The analysis of the top 100 AE reports were as follows. There were 82 positive PT signals of allopurinol, involving 14 SOCs, and 61 AEs were not recorded in the drug labels; there were 86 positive PT signals of febuxostat, involving 18 SOCs, and 25 AEs were not recorded in the drug labels. The top 5 PTs in the signal strength of allopurinol were drug reaction with eosinophilia and systemic symptoms, end-stage renal disease, hypercalcemia, acute kidney injury, and chronic kidney disease; the top 5 PTs in the signal strength of febuxostat were enthesopathy, granu- loma skin, blood parathyroid hormone decreased, tenosynovitis and alanine aminotransferase abnormal. The 2 drugs had a total of 49 overlapping signals. More AE signals of allopurinol were detected in SOCs of meta- bolic and nutritional diseases, blood and lymphatic system diseases etc.; more AE signals of febuxostat were detected in SOCs of skin and subcutaneous tissue diseases, various musculoskeletal, and connective tissue diseases, etc.　Conclusions Allopurinol has a higher risk of causing AEs related to kidney and urinary system, blood and lymphatic system, and metabolic system, while febuxostat has a higher risk of causing AEs related to skin and subcutaneous tissue, musculoskeletal and connective tissue, and hepatobiliary system. It is suggested that patients with gout accompanied by renal insufficiency, urinary system diseases or blood disea- ses should be careful with allopurinol, and the patients with gout accompanied by liver dysfunction should be careful with febuxostat.

Objective To explore the risk signals of montelukast-related adverse events (AEs) in pediatric patients and provide reference for the safe use.　Methods AE reports of children with montelukast as the primary suspect drug from the first quarter of 2004 to the third quarter of 2022 were collected by searching the US FDA Adverse Event Reporting System database （FAERS）. AEs were standardized and classified according to the preferred terms (PT) and system organ class (SOC) of Medical Dictionary for Regulatory Activities 23.0. Proportional reporting odds ratio (PRR) method was used to mine the AE risk signals of montelukast. An AE with reports ≥3, PRR≥2, and χ2>4 was defined as a positive signal, which were analyzed using descriptive method.　Results A total of 5-179 AE reports were included in the analysis, involving 1-295 PTs, and 233 positive PTs were obtained by PRR method. The top 10 PTs in AE reports were aggres- sive behavior, anxiety, suicidal ideation, abnormal behavior, depression, anger, nightmares, insomnia, crying loudly and night terrors. Except crying loudly, all of them were adverse reactions recorded in the label. The top 10 PTs in signal intensity were sensory overload, arrhythmia, separation anxiety disorder, loneliness phobia, dust allergy, Mille-Fisher syndrome, eosinophilic granuloma complicated with polyangitis, personality disorder in children, night terrors and decreased platelet adhesion. Among them, abnormal heart rate, Mille-Fisher syndrome and decreased platelet adhesion were not recorded in the label. A total of 59 of the 233 positive PTs were not recorded in the label, involving 10 SOCs. The top 5 SOCs were social environment, mental illness, injury, poisoning and surgical complications, general conditions and administration site, and respiratory, thoracic and mediastinal diseases.　Conclusion The main AEs of pediatric patients receiving montelukast treatment in the US FAERS are aggressive behavior, anxiety, depression, insomnia, night terrors, etc., all of which are adverse reactions recorded in the label; adverse reactions not recorded in the drug label include abnormal heart rate, Miller-Fisher syndrome， and decreased platelet adhesion.