Objective To examine the changing prevalence and antimicrobial resistance profiles of Burkholderia cepacia in 52 hospitals across China from 2015 to 2021.Methods A total of 9 261 strains of B.cepacia were collected from 52 hospitals between January 1,2015 and December 31,2021.Antimicrobial susceptibility of the strains was tested using Kirby-Bauer method or automated antimicrobial susceptibility testing systems according to a unified protocol.The results were interpreted according to the breakpoints released in the Clinical & Laboratory Standards Institute(CLSI)guidelines(2023 edition).Results A total of 9 261 strains of B.cepacia were isolated from all age groups,especially elderly patients.The proportion was 11.1％(1 032 strains)in children,significantly lower than the proportion in adults.About half(46.5％,4 310/9 261)of the strains were isolated from patients at least 60 years old and 42.3％(3 919/9 261)of the strains were isolated from young adults.Most isolates(71.1％)were isolated from sputum and respiratory secretions,followed by urine(10.7％)and blood samples(8.1％).B.cepacia isolates were highly susceptible to the five antimicrobial agents recommended in the CLSI M100 document(33rd edition,2023).B.cepacia isolates showed relatively higher resistance rates to meropenem and levofloxacin.However,the resistance rates to ceftazidime,trimethoprim-sulfamethoxazole,and minocycline remained below 8.1％.The percentage of B.cepacia strains resistant to levofloxacin was the highest compared to other antibiotics in any of the three age groups(from 12.4％in the patients＜18 years old to 20.6％in the patients aged 60 years or older).Conclusions B.cepacia is one of the clinically important non-fermenting gram-negative bacteria.Accurate and timely reporting of antimicrobial susceptibility test results and ongoing antimicrobial resistance surveillance are helpful for rational prescription of antimicrobial agents and proper prevention and control of nosocomial infections.

Focal segmental glomerulosclerosis(FSGS)is a critical glomerular disease characterized by a complex pathogenesis involving podocyte injury,genetic variations,and immune dysregulation.Podocyte injury plays a central role in FSGS development,encompassing abnormalities in cytoskeletal structure and dynamics,dysfunction of cell adhesion,activation of programmed cell death pathways,and oxidative stress.In recent years,advancements in molecular biology and genomic technologies have deepened the understanding of FSGS pathogenesis,with notable progress in podocyte biology,genetics,and signaling pathway regulation.Genetic factors contribute significantly to FSGS,with studies on monogenic mutations,epigenetic regulatory mechanisms,and non-genetic mechanisms such as the circulating factor hypothesis and immune dysregulation enriching the molecular pathology of FSGS.Based on these mechanistic insights,researchers are exploring precision therapeutic targets,including podocyte-protective strategies,anti-fibrotic and anti-inflammatory approaches,and gene-and biomarker-guided therapies,to improve treatment outcomes.This review summarizes recent advances in the pathogenesis of FSGS,aiming to provide a theoretical framework and new insights for precision diagnosis and targeted therapy of this disease.

Prescription optimization is a crucial aspect in the study of traditional Chinese medicine （TCM） compounds. In recent years， the introduction of mathematical methods， data mining techniques， and artificial neural networks has provided new tools for elucidating the compatibility rules of TCM compounds. The study of TCM compounds involves numerous variables， including the proportions of different herbs， the specific extraction parts of each ingredient， and the interactions among multiple components. These factors together create a complex nonlinear dose-effect relationship. In this context， it is essential to identify methods that suit the characteristics of TCM compounds and can leverage their advantages for effective application in new drug development. This paper provided a comprehensive review of the cutting-edge optimization experimental design methods applied in recent studies of TCM compound compatibilities. The key technical issues， such as the optimization of source material selection， dosage optimization of compatible herbs， and multi-objective optimization indicators， were discussed. Furthermore， the evaluation methods for component effects were summarized during the optimization process， so as to provide scientific and practical foundations for innovative research in TCM and the development of new drugs based on TCM compounds.

Objective:To develop a quality assessment index system for infection prevention and control in integrated medical and elderly care facilities, providing methods for assessing infection control quality and a theoretical basis for enhancing infection prevention and control capabilities.Methods:This study initially constructed a framework for the quality evaluation index system through literature reviews, work specifications and standards and expert interviews. The Delphi method was employed to conduct two rounds of consultations with 19 experts to evaluate the necessity, feasibility, stability, and sensitivity of the indicators. The expert′s active coefficient, authority coefficient, degree of consensus, and coordination were statistically analyzed. The indicators were revised based on expert opinions to finalize the evaluation index system. The weights of the evaluation dimensions were determined using the Analytic Hierarchy Process (AHP), while the weights of the indicators were determined using the proportional allocation method. Reliability was assessed via Cronbach′s α coefficient, and content validity was verified through the Content Validity Index ( CVI). Results:After two rounds of expert consultation, the expert positive coefficient, expert authority coefficient ( Cr) and expert coordination coefficient Kendall′s W was 100%, 0.992 and 0.634 ( P<0.001), indicating high expert authority, good concentration and coordination of opinions. The assessment index system for infection prevention and control quality in integrated medical and elderly care facilities was ultimately constructed, comprising three primary indicators, 18 secondary indicators and 68 tertiary indicators. Among the primary indicators, the process quality had the highest weight of 0.338. Within the process quality, the secondary indicators with the highest weights were infection control material allocation, hand hygiene quality and the management of cluster outbreaks. A total of 11 unique evaluation indicators for integrated medical and elderly care facilities were established, with the highest weighted indicator being the rate of standardized surveillance of infection-related risk factors. Reliability and validity analyses demonstrated that the overall Cronbach′s α coefficient of the system was 0.991, and the Scale-level Content Validity Index was 0.936, confirming good reliability and validity. Conclusion:The evaluation index system constructed in this study can serve as an effective assessment tool for the quantitative evaluation of infection control quality in integrated medical and elderly care facilities. Furthermore, it is recommended that the system undergo continuous optimization concerning its application.

Objective To summarize the changing prevalence of carbapenem resistance in Enterobacterales based on the data of CHINET Antimicrobial Resistance Surveillance Program from 2015 to 2021 for improving antimicrobial treatment in clinical practice.Methods Antimicrobial susceptibility testing was performed using a commercial automated susceptibility testing system according to the unified CHINET protocol.The results were interpreted according to the breakpoints of the Clinical & Laboratory Standards Institute(CLSI)M100 31st ed in 2021.Results Over the seven-year period(2015-2021),the overall prevalence of carbapenem-resistant Enterobacterales(CRE)was 9.43％(62 342/661 235).The prevalence of CRE strains in Klebsiella pneumoniae,Citrobacter freundii,and Enterobacter cloacae was 22.38％,9.73％,and 8.47％,respectively.The prevalence of CRE strains in Escherichia coli was 1.99％.A few CRE strains were also identified in Salmonella and Shigella.The CRE strains were mainly isolated from respiratory specimens(44.23±2.80)％,followed by blood(20.88±3.40)％and urine(18.40±3.45)％.Intensive care units(ICUs)were the major source of the CRE strains(27.43±5.20)％.CRE strains were resistant to all the β-lactam antibiotics tested and most non-β-lactam antimicrobial agents.The CRE strains were relatively susceptible to tigecycline and polymyxins with low resistance rates.Conclusions The prevalence of CRE strains was increasing from 2015 to 2021.CRE strains were highly resistant to most of the antibacterial drugs used in clinical practice.Clinicians should prescribe antimicrobial agents rationally.Hospitals should strengthen antibiotic stewardship in key clinical settings such as ICUs,and take effective infection control measures to curb CRE outbreak and epidemic in hospitals.

Objective To characterize the changing species distribution and antibiotic resistance profiles of respiratory isolates in hospitals participating in the CHINET Antimicrobial Resistance Surveillance Program from 2015 to 2021.Methods Commercial automated antimicrobial susceptibility testing systems and disk diffusion method were used to test the susceptibility of respiratory bacterial isolates to antimicrobial agents following the standardized technical protocol established by the CHINET program.Results A total of 589 746 respiratory isolates were collected from 2015 to 2021.Overall,82.6％of the isolates were Gram-negative bacteria and 17.4％were Gram-positive bacteria.The bacterial isolates from outpatients and inpatients accounted for(6.0±0.9)％and(94.0±0.1)％,respectively.The top microorganisms were Klebsiella spp.,Acinetobacter spp.,Pseudomonas aeruginosa,Staphylococcus aureus,Haemophilus spp.,Stenotrophomonas maltophilia,Escherichia coli,and Streptococcus pneumoniae.Each microorganism was isolated from significantly more males than from females(P＜0.05).The overall prevalence of methicillin-resistant S.aureus(MRSA)was 39.9％.The prevalence of penicillin-resistant S.pneumoniae was 1.4％.The prevalence of extended-spectrum β-lactamase(ESBL)-producing E.coli and K.pneumoniae was 67.8％and 41.3％,respectively.The overall prevalence of carbapenem-resistant E.coli,K.pneumoniae,Enterobacter cloacae,Pseudomonas aeruginosa,and Acinetobacter baumannii was 3.7％,20.8％,9.4％,29.8％,and 73.3％,respectively.The prevalence of β-lactamase was 96.1％in Moraxella catarrhalis and 60.0％in Haemophilus influenzae.The H.influenzae isolates from children(＜18 years)showed significantly higher resistance rates to β-lactam antibiotics than the isolates from adults(P＜0.05).Conclusions Gram-negative bacteria are still predominant in respiratory isolates associated with serious antibiotic resistance.Antimicrobial resistance surveillance should be strengthened in clinical practice to support accurate etiological diagnosis and appropriate antimicrobial therapy based on antimicrobial susceptibility testing results.

Objective:To study the subacute oral toxic effect of p-chloro-m-xylphenol on rats and provide a basis for its safety evaluation.Methods:SPF-grade Wistar rats were randomly divided into 4 groups according to body weight stratification randomization, with 20 rats in each group, half male and half female. The set concentrations of the p-chloro-m-xylphenol dose groups were 11.25, 22.50, and 45.00 mg/kg·BW respectively, with an intragastric volume of 10 ml/kg·BW. The blank control group was given the same amount of distilled water. The rats were treated with intragastric administration for 30 days. After intraperitoneal injection of 50 mg/kg·BW pentobarbital sodium for anesthesia, bloodletting and death, the organs were separated and weighed. Blood was collected from the abdominal aorta to determine the hematological and serum biochemical indicators of the whole blood of rats. Multiple groups comparison was performed by one-way analysis of variance, and pairwise comparison between groups was performed by the least significant difference test or Dunnett-t3 test.Results:The kidney weight in the 45.00 mg/kg·BW dose group of female rats [ (1.59±0.11) g] was lower than that in the blank control group [ (1.71±0.12) g], and the difference was statistically significant ( P<0.05) . The percentage of monocytes in the 11.25 mg/kg·BW dose group of male rats [ (4.81±0.74) %] was lower than that in the blank control group [ (5.86±0.58) %], the red blood cell count [ (6.93±0.26) ×10 12/L] and hemoglobin [ (134.30±4.95) g/L] in the 22.50 mg/kg·BW dose group of female rats were both lower than those in the blank control group[ (7.48±0.26) ×10 12/L, (146.20±4.42) g/L], the percentage of eosinophils in the 11.25 mg/kg·BW dose group of female rats [ (2.46±0.86) %] was higher than that in the blank control group [ (1.66±0.41) %], and the differences were statistically significant ( P<0.05) . Conclusion:P-chloro-m-xylphenol may have toxic effects on the blood system of rats, and the kidneys may be the potential target organs for its toxicity.

Objective To investigate the distribution and antibiotic resistance profiles of clinical isolates in Beijing Children's Hospital,Capital Medical University from 2016 to 2022.Methods All the strains isolated from inpatients in Beijing Children's Hospital during the period from 2016 to 2022 were analyzed.Antimicrobial susceptibility test was conducted by Kirby-Bauer method or automated system.Results were interpreted according to the breakpoints recommended in the CLSI Ml00 2022 edition.Results A total of 24 904 isolates were analyzed,including Gram-positive bacteria(49.4％)and Gram-negative bacteria(50.6％).The top three Gram-positive bacteria were Staphylococcus aureus(15.6％),coagulase-negative Staphylococcus(14.0％),and Streptococcus pneumoniae(8.9％).The top three Gram-negative bacteria were Klebsiella spp.(8.6％),Pseudomonas aeruginosa(8.6％),and Haemophilus influenzae(8.1％).The prevalence of methicillin-resistant strains was 30.9％in SS.aureus(MRSA)and 82.7％in coagulase-negative Staphylococcus(MRCNS).The prevalence of PRSP was 75.0％(24/32)in meningitis isolates and 2.6％(57/2 195)in non-meningitis isolates.Five strains of E.faecium and 10 strains of E.faecalis were found resistant to linezolid.Two strains of E.faecium were resistant to vancomycin.The prevalence of extended-spectrum beta-lactamases(ESBLs)and carbapenem-resistant strains(CREco)in E.coli isolates was 69.0％and 9.7％,respectively.The prevalence of ESBLs and carbapenem-resistant strains(CRKpn)in K.pneumoniae isolates was 73.7％,and 37.2％,respectively.The prevalence of carbapenem-resistant strains was 21.9％in P.aeruginosa isolates and 59.3％in A.baumannii isolates.β-lactamase was detected in 68.3％of the H.influenzae isolates.Conclusions Antimicrobial resistance is still serious in children.It is necessary to strength the surveillance of bacterial resistance and use antibiotics rationally in order to curb the spread of drug-resistant strains.

Objective To understand the changing composition and antibiotic resistance of bacterial species in the clinical isolates from outpatient and emergency department(hereinafter referred to as outpatients)and inpatient children over time in various hospitals,and to provide laboratory evidence for rational antibiotic use.Methods The data on clinically isolated pathogenic bacteria and antimicrobial susceptibility of isolates from outpatients and inpatient children in the CHINET program from 2015 to 2021 were collected and analyzed.Results A total of 278 471 isolates were isolated from pediatric patients in the CHINET program from 2015 to 2021.About 17.1％of the strains were isolated from outpatients,primarily group A β-hemolytic Streptococcus,Escherichia coli,and Staphylococcus aureus.Most of the strains(82.9％)were isolated from inpatients,mainly SS.aureus,E.coli,and H.influenzae.The prevalence of methicillin-resistant S.aureus(MRSA)in outpatients(24.5％)was lower than that in inpatient children(31.5％).The MRSA isolates from outpatients showed lower resistance rates to the antibiotics tested than the strains isolated from inpatient children.The prevalence of vancomycin-resistant Enterococcus faecalis or E.faecium and penicillin-resistant S.pneumoniae was low in either outpatients or inpatient children.S.pneumoniae,β-hemolytic Streptococcus and S.viridans showed high resistance rates to erythromycin.The prevalence of erythromycin-resistant group A β-hemolytic Streptococcus was higher in outpatients than that in inpatient children.The prevalence of β-lactamase-producing H.influenzae showed an overall upward trend in children,but lower in outpatients(45.1％)than in inpatient children(59.4％).The prevalence of carbapenem-resistant Klebsiella pneumoniae(CRKpn),carbapenem-resistant Pseudomonas aeruginosa(CRPae)and carbapenem-resistant Acinetobacter baumannii(CRAba)was 14％,11.7％,47.8％in outpatients,but 24.2％,20.6％,and 52.8％in inpatient children,respectively.The prevalence of multidrug-resistant E.coli,K.pneumoniae,Proteus mirabilis,P.aeruginosa and A.baumannii strains was lower in outpatients than in inpatient children.The prevalence of fluoroquinolone-resistant E.coli,ESBLs-producing K.pneumoniae,ESBLs-producing P.mirabilis,carbapenem-resistant E.coli(CREco),CRKpn,and CRPae was lower in children in outpatients than in inpatient children,but the prevalence of CRAba in 2021 was higher than in inpatient children.Conclusions The distribution of clinical isolates from children is different between outpatients and inpatients.The prevalence of MRSA,ESBL,and CRO was higher in inpatient children than in outpatients.Antibiotics should be used rationally in clinical practice based on etiological diagnosis and antimicrobial susceptibility test results.Ongoing antimicrobial resistance surveillance and prevention and control of hospital infections are crucial to curbing bacterial resistance.

Objective To investigate the changing antibiotic resistance profiles of E.coli isolated from patients in the 52 hospitals participating in the CHINET program from 2015 to 2021.Methods Antimicrobial susceptibility was tested for clinical isolates of E.coli according to the unified protocol of CHINET program.WHONET 5.6 and SPSS 20.0 software were used for data analysis.Results Atotal of 289 760 nonduplicate clinical strains ofE.coli were isolated from 2015 to 2021,mainly from urine samples(44.7±3.2)％.The proportion of E.coli strains isolated from urine samples was higher in females than in males(59.0％vs 29.5％).The proportion of E.coli strains isolated from respiratory tract and cerebrospinal fluid samples was significantly higher in children than in adults(16.7％vs 7.8％,0.8％vs 0.1％,both P＜0.05).The isolates from internal medicine department accounted for the largest proportion(28.9±2.8)％with an increasing trend over years.Overall,the prevalence of ESBLs-producing E.coli and carbapenem resistant E.coli(CREco)was 55.9％and 1.8％,respectively during the 7-year period.The prevalence of ESBLs-producing E.coli was the highest in tertiary hospitals each year from 2015 to 2021 compared to secondary hospitals.The prevalence of CREco was higher in children's hospitals compared to secondary and tertiary hospitals each year from 2015 to 2021.The prevalence of ESBLs-producing E.coli in tertiary hospitals and children's hospitals and the prevalence of CREco in children's hospitals showed a decreasing trend over the 7-year period.The prevalence of CREco in secondary and tertiary hospitals increased slowly.Antibiotic resistance rates changed slowly from 2015 to 2021.Carbapenem drugs(imipenem,meropenem)were the most active drugs amongβ-lactams against E.coli(resistance rate≤2.1％).The resistance rates of E.coli to β-lactam/β-lactam inhibitor combinations(piperacillin-tazobactam,cefoperazone-sulbactam),aminoglycosides(amikacin),nitrofurantoin and fosfomycin(for urinary isolates only)were all less than 10％.The resistance rate of E.coli strains to antibiotics varied with the level of hospitals and the departments where the strains were isolated,especially for cefazolin and ciprofloxacin,to which the resistance rate of E.coli strains from children in non-ICU departments was significantly lower than that of the strains isolated from other departments(P＜0.05).The E.coli isolates from ICU showed higher resistance rate to most antimicrobial agents tested(excluding tigecycline)than the strains isolated from other departments.The E.coli strains isolated from tertiary hospitals showed higher resistance rates to the antimicrobial agents tested(excluding tigecycline,polymyxin B,cefepime and carbapenems)than the strains from secondary hospitals and children's hospitals.Conclusions E.coli is an important pathogen causing clinical infection.More than half of the clinical isolates produced ESBL.The prevalence of CREco is increasing in secondary and tertiary hospitals over the 7-year period even though the overall prevalence is still low.This is an issue of concern.