Influenza virus causes serious threat to human life and health. Due to the inherent high variability of influenza virus, clinically resistant mutant strains of currently approved anti-influenza virus drugs have emerged. Therefore, it is urgent to develop antiviral drugs with new targets or mechanisms of action. RNA-dependent RNA polymerase is directly responsible for viral RNA transcription and replication, and plays key roles in the viral life cycle, which is considered an important target of anti-influenza drug design. From the point of view of medicinal chemistry, this review summarizes current advances in diverse small-molecule inhibitors targeting influenza virus RNA-dependent RNA polymerase, hoping to provide valuable reference for development of novel antiviral drugs.

BACKGROUND:Chlorfenapyr is used to kill insects that are resistant to organophosphorus insecticides.Chlorfenapyr poisoning has a high mortality rate and is difficult to treat.This article aims to review the mechanisms,clinical presentations,and treatment strategies for chlorfenapyr poisoning. DATA RESOURCES:We conducted a review of the literature using PubMed,Web of Science,and SpringerLink from their beginnings to the end of October 2023.The inclusion criteria were systematic reviews,clinical guidelines,retrospective studies,and case reports on chlorfenapyr poisoning that focused on its mechanisms,clinical presentations,and treatment strategies.The references in the included studies were also examined to identify additional sources. RESULTS:We included 57 studies in this review.Chlorfenapyr can be degraded into tralopyril,which is more toxic and reduces energy production by inhibiting the conversion of adenosine diphosphate to adenosine triphosphate.High fever and altered mental status are characteristic clinical presentations of chlorfenapyr poisoning.Once it occurs,respiratory failure occurs immediately,ultimately leading to cardiac arrest and death.Chlorfenapyr poisoning is difficult to treat,and there is no specific antidote. CONCLUSION:Chlorfenapyr is a new pyrrole pesticide.Although it has been identified as a moderately toxic pesticide by the World Health Organization(WHO),the mortality rate of poisoned patients is extremely high.There is no specific antidote for chlorfenapyr poisoning.Therefore,based on the literature review,future efforts to explore rapid and effective detoxification methods,reconstitute intracellular oxidative phosphorylation couplings,identify early biomarkers of chlorfenapyr poisoning,and block the conversion of chlorfenapyr to tralopyril may be helpful for emergency physicians in the diagnosis and treatment of this disease.

Objective To explore the therapeutic mechanism of Modified Lugen Formula(Phragmitis Rhizoma,Cicadae Periostracum,Batryticatus Bombyx,Lonicerae Japonicae Flos,Glycyrrhiza,Menthae Haplocalycis Herba,Notopterygii Rhizoma et Radix,Puerariae Lobatae Radix,Bupleuri Radix)in treating influenza from the virus-host interaction interface.Methods The phytocompounds were first collected from the HERB database,and then potential active compounds were screened out by Lipinski's rules of five.The targets of active compounds were further predicted through the SwissTargetPrediction platform.Differentially expressed genes(DEGs)were determined from the human H1N1 influenza dataset GSE90732 available in the Gene Expression Omnibus database(GEO).H1N1-Homo sapiens-related protein-protein interactions(PPIs)were gathered from the Pathogen-Host Interaction Search Tool(PHISTO).The above mentioned bioinformatic datasets were integrated.Then a PPI network and a Formula-virus-host interaction network were constructed using Cytoscape.Functional enrichment analyses were performed by using R software.Finally,molecular docking was carried out to evaluate the binding activities between the key compounds and targets.Results A total of 1 252 active compounds,1 415 targets,951 influenza-related DEGs,and 10 142 H1N1-Homo sapiens-related PPIs were obtained.There were 72 intersection targets between the Modified Lugen Formula and influenza.Functional enrichment analyses showed that these targets are closely related to host defense and programmed cell death.The network topological analysis showed that active compounds in the Modified Lugen Formula,such as oleanolic acid,γ-undecalactone,and longispinogenin,regulate viral proteins M2,NA,NS1,and HA and/or the host factors HSP90AA1,NRAS,and ITGB1,thus exert therapeutic effect.Molecular docking results confirmed that these compounds had a good binding ability with the targets.Conclusion Multiple active ingredients in Modified Lugen Formula directly target influenza virus proteins and/or host factors,thereby play an anti-influenza role in multiple dimensions,including inhibiting virus replication,regulating host defense and cell death.This study provides a theoretical basis for further experimental analysis of the action mechanism of the Modified Lugen Formula in treating influenza.

Objective:To examine the perioperative safety of laparoscopic cholecystectomy in human immunodeficiency virus (HIV)-positive patients undergoing antiretroviral therapy.Methods:A retrospective cohort study method was employed to collect clinical data from 388 patients with gallstones who were admitted to Department of General Surgery of the Provincial Hospital of Anhui Medical University between January 2020 and December 2023. The cohort comprised 135 males and 253 females. For the purpose of analysis, the participants were divided into HIV-positive group ( n=25) and HIV-negative group ( n=363). The distinction between the two groups was based on whether the participants were co-infected with HIV. The clinical and pathological data pertaining to the two groups of patients, along with the intraoperative and postoperative data, were collated. The propensity score matching method was employed to control for confounding bias, and the data on anaesthesia methods, intraoperative blood loss, duration of surgery, necessity for conversion to laparotomy, postoperative complications, postoperative drainage volume, postoperative hospital stay, and total treatment costs were compared between the two groups. Measurement data with normal distribution were expressed as mean±standard deviation ( ± s) and compared using the t-test. Measurement data with skewed distribution were expressed as M( Q1, Q3) and compared using the rank-sum test. The Fisher exact probability method or the chi-square test was employed for the comparison of count data. Results:The two groups of general data were found to be statistically significant in terms of gender, preoperative red blood cells, neutrophils, alanine aminotransferase, and indirect bilirubin exhibited statistically significant differences( P<0.05). Following propensity score matching, a total of 59 cases were identified. Of these, 25 cases were observed in the HIV-positive group, while 34 cases were observed in the HIV-negative group. No statistically significant differences were observed between the two groups with respect to the general data ( P>0.05). No statistically significant difference was observed between the two groups in terms of anaesthesia method, intraoperative blood loss, duration of surgery, need for conversion to laparotomy, postoperative complication rate, postoperative drainage volume and postoperative hospital stay ( P>0.05). The total length of hospital stay and total hospital expenses in the HIV-positive group were 5.0 (3.0, 7.0) days and (14 829.3±4 852.8) yuan, respectively. HIV-negative group were 3.0 (2.0, 4.8) days and (10 762.3±1 850.3) yuan, respectively. The HIV-negative group had a significantly shorter hospital stay and lower hospital expenses, these differences were statistically significant ( P<0.05). There was no occupational exposure of medical personnel in the perioperative period among those with HIV. Conclusions:Laparoscopic cholecystectomy is a safe and feasible procedure for HIV-positive patients who are receiving antiretroviral therapy. Adherence to established protocols by healthcare personnel can mitigate the risk of occupational exposure.

Objective To investigate the risk factors for bronchopulmonary dysplasia(BPD)in twin preterm infants with a gestational age of<34 weeks,and to provide a basis for early identification of BPD in twin preterm infants in clinical practice.Methods A retrospective analysis was performed for the twin preterm infants with a gestational age of<34 weeks who were admitted to 22 hospitals nationwide from January 2018 to December 2020.According to their conditions,they were divided into group A(both twins had BPD),group B(only one twin had BPD),and group C(neither twin had BPD).The risk factors for BPD in twin preterm infants were analyzed.Further analysis was conducted on group B to investigate the postnatal risk factors for BPD within twins.Results A total of 904 pairs of twins with a gestational age of<34 weeks were included in this study.The multivariate logistic regression analysis showed that compared with group C,birth weight discordance of>25%between the twins was an independent risk factor for BPD in one of the twins(OR=3.370,95%CI:1.500-7.568,P<0.05),and high gestational age at birth was a protective factor against BPD(P<0.05).The conditional logistic regression analysis of group B showed that small-for-gestational-age(SGA)birth was an independent risk factor for BPD in individual twins(OR=5.017,95%CI:1.040-24.190,P<0.05).Conclusions The development of BPD in twin preterm infants is associated with gestational age,birth weight discordance between the twins,and SGA birth.

Objective To monitor the susceptibility of clinical isolates to antimicrobial agents in tertiary hospitals in major regions of China in 2022.Methods Clinical isolates from 58 hospitals in China were tested for antimicrobial susceptibility using a unified protocol based on disc diffusion method or automated testing systems.Results were interpreted using the 2022 Clinical &Laboratory Standards Institute(CLSI)breakpoints.Results A total of 318 013 clinical isolates were collected from January 1,2022 to December 31,2022,of which 29.5％were gram-positive and 70.5％were gram-negative.The prevalence of methicillin-resistant strains in Staphylococcus aureus,Staphylococcus epidermidis and other coagulase-negative Staphylococcus species(excluding Staphylococcus pseudintermedius and Staphylococcus schleiferi)was 28.3％,76.7％and 77.9％,respectively.Overall,94.0％of MRSA strains were susceptible to trimethoprim-sulfamethoxazole and 90.8％of MRSE strains were susceptible to rifampicin.No vancomycin-resistant strains were found.Enterococcus faecalis showed significantly lower resistance rates to most antimicrobial agents tested than Enterococcus faecium.A few vancomycin-resistant strains were identified in both E.faecalis and E.faecium.The prevalence of penicillin-susceptible Streptococcus pneumoniae was 94.2％in the isolates from children and 95.7％in the isolates from adults.The resistance rate to carbapenems was lower than 13.1％in most Enterobacterales species except for Klebsiella,21.7％-23.1％of which were resistant to carbapenems.Most Enterobacterales isolates were highly susceptible to tigecycline,colistin and polymyxin B,with resistance rates ranging from 0.1％to 13.3％.The prevalence of meropenem-resistant strains decreased from 23.5％in 2019 to 18.0％in 2022 in Pseudomonas aeruginosa,and decreased from 79.0％in 2019 to 72.5％in 2022 in Acinetobacter baumannii.Conclusions The resistance of clinical isolates to the commonly used antimicrobial agents is still increasing in tertiary hospitals.However,the prevalence of important carbapenem-resistant organisms such as carbapenem-resistant K.pneumoniae,P.aeruginosa,and A.baumannii showed a downward trend in recent years.This finding suggests that the strategy of combining antimicrobial resistance surveillance with multidisciplinary concerted action works well in curbing the spread of resistant bacteria.

BACKGROUND:Chlorfenapyr is used to kill insects that are resistant to organophosphorus insecticides.Chlorfenapyr poisoning has a high mortality rate and is difficult to treat.This article aims to review the mechanisms,clinical presentations,and treatment strategies for chlorfenapyr poisoning. DATA RESOURCES:We conducted a review of the literature using PubMed,Web of Science,and SpringerLink from their beginnings to the end of October 2023.The inclusion criteria were systematic reviews,clinical guidelines,retrospective studies,and case reports on chlorfenapyr poisoning that focused on its mechanisms,clinical presentations,and treatment strategies.The references in the included studies were also examined to identify additional sources. RESULTS:We included 57 studies in this review.Chlorfenapyr can be degraded into tralopyril,which is more toxic and reduces energy production by inhibiting the conversion of adenosine diphosphate to adenosine triphosphate.High fever and altered mental status are characteristic clinical presentations of chlorfenapyr poisoning.Once it occurs,respiratory failure occurs immediately,ultimately leading to cardiac arrest and death.Chlorfenapyr poisoning is difficult to treat,and there is no specific antidote. CONCLUSION:Chlorfenapyr is a new pyrrole pesticide.Although it has been identified as a moderately toxic pesticide by the World Health Organization(WHO),the mortality rate of poisoned patients is extremely high.There is no specific antidote for chlorfenapyr poisoning.Therefore,based on the literature review,future efforts to explore rapid and effective detoxification methods,reconstitute intracellular oxidative phosphorylation couplings,identify early biomarkers of chlorfenapyr poisoning,and block the conversion of chlorfenapyr to tralopyril may be helpful for emergency physicians in the diagnosis and treatment of this disease.

BACKGROUND:Chlorfenapyr is used to kill insects that are resistant to organophosphorus insecticides.Chlorfenapyr poisoning has a high mortality rate and is difficult to treat.This article aims to review the mechanisms,clinical presentations,and treatment strategies for chlorfenapyr poisoning. DATA RESOURCES:We conducted a review of the literature using PubMed,Web of Science,and SpringerLink from their beginnings to the end of October 2023.The inclusion criteria were systematic reviews,clinical guidelines,retrospective studies,and case reports on chlorfenapyr poisoning that focused on its mechanisms,clinical presentations,and treatment strategies.The references in the included studies were also examined to identify additional sources. RESULTS:We included 57 studies in this review.Chlorfenapyr can be degraded into tralopyril,which is more toxic and reduces energy production by inhibiting the conversion of adenosine diphosphate to adenosine triphosphate.High fever and altered mental status are characteristic clinical presentations of chlorfenapyr poisoning.Once it occurs,respiratory failure occurs immediately,ultimately leading to cardiac arrest and death.Chlorfenapyr poisoning is difficult to treat,and there is no specific antidote. CONCLUSION:Chlorfenapyr is a new pyrrole pesticide.Although it has been identified as a moderately toxic pesticide by the World Health Organization(WHO),the mortality rate of poisoned patients is extremely high.There is no specific antidote for chlorfenapyr poisoning.Therefore,based on the literature review,future efforts to explore rapid and effective detoxification methods,reconstitute intracellular oxidative phosphorylation couplings,identify early biomarkers of chlorfenapyr poisoning,and block the conversion of chlorfenapyr to tralopyril may be helpful for emergency physicians in the diagnosis and treatment of this disease.

BACKGROUND:Chlorfenapyr is used to kill insects that are resistant to organophosphorus insecticides.Chlorfenapyr poisoning has a high mortality rate and is difficult to treat.This article aims to review the mechanisms,clinical presentations,and treatment strategies for chlorfenapyr poisoning. DATA RESOURCES:We conducted a review of the literature using PubMed,Web of Science,and SpringerLink from their beginnings to the end of October 2023.The inclusion criteria were systematic reviews,clinical guidelines,retrospective studies,and case reports on chlorfenapyr poisoning that focused on its mechanisms,clinical presentations,and treatment strategies.The references in the included studies were also examined to identify additional sources. RESULTS:We included 57 studies in this review.Chlorfenapyr can be degraded into tralopyril,which is more toxic and reduces energy production by inhibiting the conversion of adenosine diphosphate to adenosine triphosphate.High fever and altered mental status are characteristic clinical presentations of chlorfenapyr poisoning.Once it occurs,respiratory failure occurs immediately,ultimately leading to cardiac arrest and death.Chlorfenapyr poisoning is difficult to treat,and there is no specific antidote. CONCLUSION:Chlorfenapyr is a new pyrrole pesticide.Although it has been identified as a moderately toxic pesticide by the World Health Organization(WHO),the mortality rate of poisoned patients is extremely high.There is no specific antidote for chlorfenapyr poisoning.Therefore,based on the literature review,future efforts to explore rapid and effective detoxification methods,reconstitute intracellular oxidative phosphorylation couplings,identify early biomarkers of chlorfenapyr poisoning,and block the conversion of chlorfenapyr to tralopyril may be helpful for emergency physicians in the diagnosis and treatment of this disease.

BACKGROUND:Chlorfenapyr is used to kill insects that are resistant to organophosphorus insecticides.Chlorfenapyr poisoning has a high mortality rate and is difficult to treat.This article aims to review the mechanisms,clinical presentations,and treatment strategies for chlorfenapyr poisoning. DATA RESOURCES:We conducted a review of the literature using PubMed,Web of Science,and SpringerLink from their beginnings to the end of October 2023.The inclusion criteria were systematic reviews,clinical guidelines,retrospective studies,and case reports on chlorfenapyr poisoning that focused on its mechanisms,clinical presentations,and treatment strategies.The references in the included studies were also examined to identify additional sources. RESULTS:We included 57 studies in this review.Chlorfenapyr can be degraded into tralopyril,which is more toxic and reduces energy production by inhibiting the conversion of adenosine diphosphate to adenosine triphosphate.High fever and altered mental status are characteristic clinical presentations of chlorfenapyr poisoning.Once it occurs,respiratory failure occurs immediately,ultimately leading to cardiac arrest and death.Chlorfenapyr poisoning is difficult to treat,and there is no specific antidote. CONCLUSION:Chlorfenapyr is a new pyrrole pesticide.Although it has been identified as a moderately toxic pesticide by the World Health Organization(WHO),the mortality rate of poisoned patients is extremely high.There is no specific antidote for chlorfenapyr poisoning.Therefore,based on the literature review,future efforts to explore rapid and effective detoxification methods,reconstitute intracellular oxidative phosphorylation couplings,identify early biomarkers of chlorfenapyr poisoning,and block the conversion of chlorfenapyr to tralopyril may be helpful for emergency physicians in the diagnosis and treatment of this disease.