Objective To conduct data mining of asthma-inducing medications in underage populations based on the U.S.Food and Drug Administration Adverse Event Reporting System(FAERS)database,so as to provide reference for the clinical application of related medications.Methods Adverse drug event(ADE)reports from the first quarter of 2013 to the fourth quarter of 2022 in the FAERS database were collected and screened for reports of asthma adverse events in the this population(under 18 years old),which were categorized into infants,toddlers,children,and adolescents according to different age groups,and were subjected to medication signal mining by using the reporting odds ratio method,the composite standardized method,and the information component method.Results A total of 1 915 reports were obtained after screening,involving 1 042(54.41％)males and 831(43.39％)females;the highest percentage of the reporting population was between 12 and under 18 years old,with a total of 762(39.79％);60.78％of the reports were reported by health professionals;and the results of the clinical referrals showed that serious adverse events occurred in 85.90％of the cases.306 suspected drugs were screened,52 drugs were determined to be valid signals,and 1 044 adverse events were reported,of which 16 drug inserts did not mention the risk of asthma,in order of elosulfatase alpha,canakinumab,tobramycin,vancomycin,ceftriaxone,cetirizine,phenylephrine,imiglucerase,cefuroxime,betamethasone,atropine,tadalafil,riscovastatin,cyclophosphamide,octreotide,and omeprazole.Conclusion The FAERS database was mined for adverse drug event signals and evaluated using the proportional disequilibrium method to identify 16 medicines that may trigger pharmacogenetic asthma and are not documented in the specification,which can be used to provide a good early warning for the clinic.At the same time,focusing on special populations,strengthening the assessment of lung function before medication and monitoring during and after medication,timely interventions were taken to reduce the harm of drug-derived adverse reactions and ensure the safe use of medication.

Objective Based on the U.S.Food and Drug Administration Adverse Event Reporting System(FAERS)database,data mining was conducted on hematological adverse events related to antibody drug conjugates(ADC),providing reference for the safe use of ADC drugs in clinical practice.Methods The report data from the third quarter of 2011 to the fourth quarter of 2022 were retrieved from the FAERS database.After data cleaning such as deduplication and name standardization,extract hematological adverse events related to ADC,and use report odds ratio method and the information component method for signal detection.Results A total of 101 610 adverse event reports were extracted,with 8 ADC drugs as the primary suspected drugs,and 5 768 ADC related hematological adverse event reports.Among them,3 423 cases of agranulocytosis were involved,and the signal intensity from strong to weak were sacituzumab govitecan(SG),gemtuzumab ozogamicin(GO),brentuximab vedotin(BV),polatuzumab vedotin(PV),enfortumab vedotin(EV),trastuzumab deruxtecan(TD),inotuzumab ozogamicin(IO)and ado-trastuzumab emtansine(TDM-1).There were 2 327 cases hematopoietic cell deficiency,with signals ranging from strong to weak were IO,SG,BV,EV,PV,TD,TDM-1,and GO.Report with clinical outcome of death of ADC drug related hematological adverse events included BV 179(16.84％),TDM-1 102(13.01％),TD 88(27.08％),GO 12(16.90％),IO 8(11.59％),EV 54(24.32％),PV 22(27.16％),and SG 84(21.05％).Adverse event time analysis showed that the number of events on the first day of TD,IO,and SG medication accounts for ≥ 40％of the total number of cases.The median time of hematological adverse events in TD,GO,IO,EV,PV,and SG was within one treatment course(21 days).Conclusion Attention should be paid to the risk of ADC drug-related hematological adverse event,during the clinical medication process,blood cell count changes should be closely monitored,and any abnormalities should be promptly diagnosed and treated.

Objective:To mine the risk signals of adverse events of limaprost and provide reference for safe use of the drug.Methods:US FDA Public Data Open Project (OpenFDA) platform was searched, and the adverse event (AE) reports on limaprost from January 1, 2004 to October 1, 2023 were collected. AEs were classified and standardized according to the system organ class (SOC) and preferred terms (PT) of Medical Dictionary for Regulatory Activities version 25.1. The reporting odds ratio (ROR) method was used to mine the risk signal of limaprost. An AE with reports ≥3, ROR ≥2 and the lower limit of the 95% confidence interval ( CI)>1 was defined as a risk signal, which was analyzed descriptively. Results:A total of 1 618 AE reports with limaprost as the primary suspect drug were collected, 69 risk signals were identified, involving 17 SOCs. Of the 69 PTs, 10 were recorded in the drug instructions including hepatic function abnormal, red blood cell count decreased, drug eruption, blood pressure decreased, liver disorder, platelet count decreased, anaemia, haemoglobin decreased, pyrexia, and decreased appetite. The other 59 risk signals were not recorded in the drug instructions. The top 10 PTs in signal intensity were scleroderma, tumour haemorrhage, brain natriuretic peptide increased, inappropriate antidiuretic hormone secretion, colitis microscopic, large intestine perforation, cardiac failure acute, depressive symptom, cardiac failure chronic, pulmonary alveolar haemorrhage. The risk signals with more than 10 reports were inappropriate antidiuretic hormone secretion, interstitial lung disease, renal impairment, cardiac failure, pneumonia, fall, etc.Conclusion:In addition to the AEs recorded in the instructions, limaprost may also cause serious adverse reactions such as tumour haemorrhage, brain natriuretic peptide increased, and inappropriate antidiuretic hormone secretion, which are not recorded in the instructions and have a poor prognosis.

ObjectiveTo investigate the efficacy， safety， and cost-effectiveness of endoscopic ultrasound （EUS）-guided coil placement combined with tissue adhesive injection in the treatment of gastric varices with spontaneous shunt. MethodsA retrospective analysis was performed for the patients with acute gastric variceal bleeding and spontaneous portosystemic shunt who were hospitalized and received balloon-occluded retrograde transvenous obliteration （BRTO） combined with endoscopic tissue adhesive injection or EUS-guided coil placement combined with tissue adhesive injection in Xiangyang Central Hospital from March 2019 to September 2022. The two surgical procedures were compared in terms of efficacy （technical success rate， 5-day rebleeding rate， 1-year rebleeding rate， and time to rebleeding）， safety （the incidence rate of ectopic embolism， the amount of tissue adhesive used， and the amount of lauromacrogol used）， and cost-effectiveness （hospital costs and length of hospital stay）. The t-test was used for comparison of normally distributed continuous data between two groups， and the Mann-Whitney U test was used for comparison of non-normally distributed continuous data between two groups. The Kaplan-Meier method was used to estimate the rebleeding. The chi-square test was used for comparison of categorical data between two groups. ResultsA total of 25 patients received successful EUS-guided coil placement and tissue adhesive injection， with a technical success rate of 100%， a median amount of 2.5 mL tissue adhesive used， a median amount of 11.0 mL lauromacrogol used， a mean length of hospital stay of 14.88±3.21 days， a mean hospital cost of 32 660.00±4 602.07 yuan， and a 5-day rebleeding rate of 0%； among these patients， 2 were lost to follow-up， and 23 patients with complete follow-up data had an incidence rate of ectopic embolism of 0% and a median time to rebleeding of 689 days. A total of 14 patients underwent modified BRTO combined with endoscopic tissue adhesive injection， with a technical success rate of 100%； a median amount of 5.0 mL tissue adhesive used during surgery， which was significantly higher than that used in EUS （U=39.000， P<0.001）； a median amount of 10.5 mL lauromacrogol used during surgery； a mean length of hospital stay of 15.38±4.94 days； a mean hospital cost of 57 583.47±18 955.40 yuan， which was significantly higher than that used in EUS （t=-6.310， P<0.001）； a 5-day rebleeding rate of 0%. No patient was lost to follow-up， and all 14 patients had an incidence rate of ectopic embolism of 0% and a median time to rebleeding of 244.50 days， with no significant difference between the two groups （χ²=1.448， P=0.229）. ConclusionEUS-guided coil placement combined with tissue adhesive injection is a relatively safe and effective technique for the treatment of gastric variceal bleeding and has a high technical success rate， a low incidence rate of serious adverse events， and similar efficacy to BRTO， with higher safety and cost-effectiveness.

Acquired cerebral amyloid angiopathy,as a cerebrovascular disease discovered in recent years,mainly spreads through iatrogenic factors.This paper focuses on acquired cerebral amyloid angiopathy and delves into the new applications and profound implications of the"toxins damaging brain collaterals"theory proposed by academician WANG Yongyan in stroke research.Starting from the perspective of"toxins damaging brain collaterals",it comprehensively analyzes the causes and pathological mechanisms of acquired cerebral amyloid angiopathy,emphasizing the importance of external toxins,latent toxins,and turbid toxins in understanding the pathogenesis of the disease.It reveals that"toxins damaging brain collaterals"is the core mechanism of acquired cerebral amyloid angiopathy.On this basis,it proposes a new connotation of"toxins damaging brain collaterals":first,"toxin"includes both internal and external toxins;second,the organic integration of"external wind theory"and"toxins damaging brain collaterals"guides the improvement of theoretical research,clinical treatment,and prevention strategies for stroke,and promotes a deeper understanding of the disease.This approach to understanding acquired cerebral amyloid angiopathy from the perspective of"toxins damaging brain collaterals"not only demonstrates the effective integration of traditional Chinese medicine theory and modern biomedical science,but also provides insights and references for the clinical diagnosis and treatment of the disease.

Objective To mine and analyze cutaneous adverse drug event(ADE)of eight antibody-drug conjugates(ADC),and to ensure the safe clinical use of ADC drugs.Methods The data was obtained from the U.S.Food and Drug Administration Adverse Event Reporting System(FAERS)for the period from the third quarter of 2011 to the fourth quarter of 2023.The cutaneous ADE associated with 8 eight ADC drugs were identified through the process of specification and standardization of nomenclature.The potential ADE signals were detected using the reporting odds ratio and Bayesian confidence propagation neural network methods.Results A total of 124 234 ADE reports were identified with the 8 ADC drugs as the first suspected drugs,including 5 184 reports of cutaneous ADEs adverse reactions,involving 3 225 patients.A total of 72 preferred term signals were detected for the 8 ADC drugs.The highest number of signals were detected for enfortumab vedotin,followed by ado-trastuzumab emtansine and brentuximab vedotin.Except for detrolizumab,the first-day incidence of cutaneous ADEs associated with the remaining 7 ADC drugs was less than 30％.The median time of occurrence for the 7 drugs,excluding brentuximab vedotin,was within one course of treatment(21 d).Conclusion The risks of cutaneous ADEs was variable with ADC drugs,occurs early in treatment and poses a potential life-threatening danger.Therefore,clinical vigilance and close monitoring of skin conditions are essential during ADC drug use.

Objective:To mine the risk signals of adverse events of limaprost and provide reference for safe use of the drug.Methods:US FDA Public Data Open Project (OpenFDA) platform was searched, and the adverse event (AE) reports on limaprost from January 1, 2004 to October 1, 2023 were collected. AEs were classified and standardized according to the system organ class (SOC) and preferred terms (PT) of Medical Dictionary for Regulatory Activities version 25.1. The reporting odds ratio (ROR) method was used to mine the risk signal of limaprost. An AE with reports ≥3, ROR ≥2 and the lower limit of the 95% confidence interval ( CI)>1 was defined as a risk signal, which was analyzed descriptively. Results:A total of 1 618 AE reports with limaprost as the primary suspect drug were collected, 69 risk signals were identified, involving 17 SOCs. Of the 69 PTs, 10 were recorded in the drug instructions including hepatic function abnormal, red blood cell count decreased, drug eruption, blood pressure decreased, liver disorder, platelet count decreased, anaemia, haemoglobin decreased, pyrexia, and decreased appetite. The other 59 risk signals were not recorded in the drug instructions. The top 10 PTs in signal intensity were scleroderma, tumour haemorrhage, brain natriuretic peptide increased, inappropriate antidiuretic hormone secretion, colitis microscopic, large intestine perforation, cardiac failure acute, depressive symptom, cardiac failure chronic, pulmonary alveolar haemorrhage. The risk signals with more than 10 reports were inappropriate antidiuretic hormone secretion, interstitial lung disease, renal impairment, cardiac failure, pneumonia, fall, etc.Conclusion:In addition to the AEs recorded in the instructions, limaprost may also cause serious adverse reactions such as tumour haemorrhage, brain natriuretic peptide increased, and inappropriate antidiuretic hormone secretion, which are not recorded in the instructions and have a poor prognosis.

OBJECTIVE To conduct data mining on drugs causing liver failure in underage populations based on the FDA Adverse Event Reporting System （FAERS） database， so as to provide reference for clinical use of related drugs. METHODS The data on reported adverse drug event （ADE） of liver failure in this population （under 18 years old） from the first quarter of 2013 to the third quarter of 2022 were retrieved from the FAERS database for mining and analysis； they were divided into infants（≤1 year old）， young children（＞1-＜6 years old）， children（6-＜12 years old） and adolescents（12-＜18 years old） according to the age. The reporting odds ratio （ROR）， proportional reporting ratio and Bayesian confidence propagation neural network of the proportional imbalance method were used to screen ADE signals. RESULTS A total of 1 051 ADE reports of liver failure were collected from the underage population involving 60 drugs. The highest incidence was found in adolescents （410 cases， 39.01%）， followed by young children （297 cases， 28.26%）. The instructions of 14 drugs did not mention hepatobiliary system injury and liver failure risk， including 31 cases of levetiracetam （2.95%），18 cases of metronidazole （1.71%）， 16 cases of each of topiramate and methylprednisolone （1.52% each）， 12 cases of dexamethasone （1.14%）， 11 cases of tisagenlecleucel （1.05%）， 10 cases of each of ferrous sulfate， metformin and busulfan （0.95% each）， 9 cases of propofol （0.86%）， 8 cases of onasemnogene abeparvovec （0.76%）， 5 cases of each of diphenhydramine and omeprazole （0.48% each）， 4 cases of sebeliesterase α （0.38%）， totaling 165 cases， accounting for 15.70% of the total reported cases. Metformin was contrary to the known liver safety， and E-mail：libingchemical@163.com metronidazole and levetiracetam were new risk signals， which caused more serious clinical outcomes. CONCLUSIONS Fourteen new pharmacovigilance signals which cause liver failure in the underage population are found in this study； the liver function of patients should be closely monitored when using these drugs. Among those drugs， metformin neither undergoes liver metabolism nor has been reported in the relevant literature， and the liver-related ADE caused by metformin deserves further attention. The clinical outcomes caused by metronidazole and levetiracetam are relatively serious and need to be given sufficient attention.

BACKGROUND: Dysfunction of the gap junction channel protein connexin 43 (Cx43) contributes to myocardial ischemia/reperfusion (I/R)-induced ventricular arrhythmias. Cx43 can be regulated by small ubiquitin-like modifier (SUMO) modification. Protein inhibitor of activated STAT Y (PIASy) is an E3 SUMO ligase for its target proteins. However, whether Cx43 is a target protein of PIASy and whether Cx43 SUMOylation plays a role in I/R-induced arrhythmias are largely unknown. METHODS: Male Sprague-Dawley rats were infected with PIASy short hairpin ribonucleic acid (shRNA) using recombinant adeno-associated virus subtype 9 (rAAV9). Two weeks later, the rats were subjected to 45 min of left coronary artery occlusion followed by 2 h reperfusion. Electrocardiogram was recorded to assess arrhythmias. Rat ventricular tissues were collected for molecular biological measurements. RESULTS: Following 45 min of ischemia, QRS duration and QTc intervals statistically significantly increased, but these values decreased after transfecting PIASy shRNA. PIASy downregulation ameliorated ventricular arrhythmias induced by myocardial I/R, as evidenced by the decreased incidence of ventricular tachycardia and ventricular fibrillation, and reduced arrythmia score. In addition, myocardial I/R statistically significantly induced PIASy expression and Cx43 SUMOylation, accompanied by reduced Cx43 phosphorylation and plakophilin 2 (PKP2) expression. Moreover, PIASy downregulation remarkably reduced Cx43 SUMOylation, accompanied by increased Cx43 phosphorylation and PKP2 expression after I/R. CONCLUSION PIASy downregulation inhibited Cx43 SUMOylation and increased PKP2 expression, thereby improving ventricular arrhythmias in ischemic/reperfused rats heart.
Rats ; Male ; Animals ; Myocardial Reperfusion Injury/metabolism* ; Connexin 43/genetics* ; Sumoylation ; Down-Regulation ; Rats, Sprague-Dawley ; Arrhythmias, Cardiac/drug therapy* ; Myocardial Ischemia/metabolism* ; RNA, Small Interfering/metabolism*

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