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.

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 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.

Chronic refractory wound (CRW) is one of the most challengeable issues in clinic due to complex pathogenesis, long course of disease and poor prognosis. Experts need to conduct systematic summary for the diagnosis and treatment of CRW due to complex pathogenesis and poor prognosis, and standard guidelines for the diagnosis and treatment of CRW should be created. The Guideline forthe diagnosis and treatment of chronic refractory wounds in orthopedic trauma patients ( version 2023) was created by the expert group organized by the Chinese Association of Orthopedic Surgeons, Chinese Orthopedic Association, Chinese Society of Traumatology, and Trauma Orthopedics and Multiple Traumatology Group of Emergency Resuscitation Committee of Chinese Medical Doctor Association after the clinical problems were chosen based on demand-driven principles and principles of evidence-based medicine. The guideline systematically elaborated CRW from aspects of the epidemiology, diagnosis, treatment, postoperative management, complication prevention and comorbidity management, and rehabilitation and health education, and 9 recommendations were finally proposed to provide a reliable clinical reference for the diagnosis and treatment of CRW.

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*

Public health emergencies have occurred frequently in recent years, with the characteristics of difficult rescue and a complex environment. Helicopter emergency medical service is an effective way to deal with catastrophic events. The service can effectively shorten the transfer time taken for patient transfer between hospitals, directly send patients to the hospitals that meet requirements for clinical treatment, and avoid the possible delayed treatment caused by a secondary transfer. Helicopter emergency medical service in China is still in its infancy, and there are various problems in the actual operation. Strict whole process quality management is needed to achieve the expected outcome. The paper reviews the current situation of helicopter rescue for critically ill patients in China and suggests a set of quality management schemes (including base construction, rescue equipment allocation, rescue personnel selection, rescue system construction, and on-site rescue procedure standardization). Findings from this paper hope to provide evidence for the development of aviation rescue in China. This study is innovative and scientific.

Objective:Using high-throughput transcriptome sequencing technology to study the differentially expressed genes (DEGs) and related regulatory signaling pathways involved in H1N1 influenza virus infection in primary human retinal pigment epithelial (RPE) cells.Methods:Primary human RPE cells were infected with H1N1 influenza virus for 2 h or 12 h, respectively. Taking H1N1 uninfected cells as a control group, total RNA was extracted, a library was constructed, and transcriptome sequencing was performed. DEGs were screened by DESeq2 software, and DEGs were analyzed by gene ontology (GO) and Kyoto encyclopedia of genes and genomes (KEGG) pathway.Results:Compared with the control group, a total of 1830 DEGs were identified in the 2 h H1N1 influenza virus infection group, and 2847 DEGs were identified in the 12 h infection group; 1213 DEGs were identified in the H1N1 influenza virus infection kinetics process (2 h: 12 h). The GO functional annotation analysis of DEGs in the H1N1 influenza virus infection group for 12 h showed that DEGs widely exist in a variety of cellular components and participate in various biological processes such as cellular processes, biological regulation, and metabolic processes. KEGG pathway enrichment analysis showed that DEGs were mainly enriched in the PI3K-Akt signaling pathway, MAPK signaling pathway, cancer MicroRNAs, and cytokine-cytokine receptor interactions in the 2 h H1N1 influenza virus infection group; in the 12 h H1N1 influenza virus infection group, DEGs were mainly enriched in PI3K-Akt signaling pathway, cancer MicroRNAs, AGE-RAGE signaling pathway and immune-inflammatory pathways; during the kinetics of H1N1 influenza virus infection (2 h: 12 h), DEGs were mainly enriched in cytokine-cytokine receptor interaction, TGF-β signaling pathway.Conclusions:Infection with H1N1 influenza virus leads to significant changes in the transcriptome of RPE cells. These data provide scientific reference for elucidating the molecular mechanism of eye infection by respiratory viruses such as influenza virus.