Objective To construct an aptamer-functionalized carboxylated graphene oxide(CGO)fluo-rescent sensor to achieve highly sensitive and specific detection of ketamine(KET)and its metabolite norketamine(NK)using an aptamer capable of simultaneously recognizing KET and NK.Methods A specific aptamer for simultaneous recognition of KET and NK was screened using graphene oxide-sys-tematic evolution of ligand by exponential enrichment(GO-SELEX)and molecular docking tech-niques.The aptamer,labeled with Cy5 fluorescence,was chemically conjugated to CGO to construct an aptamer-functionalized CGO fluorescent sensor.By optimizing detection conditions,including the mass concentration of CGO,aptamer concentration,reaction temperature,and incubation time,quantita-tive analysis of the target analytes was achieved using the ratio of fluorescence intensity changes be-fore and after target addition.The stability of the sensor in biological matrices was evaluated by moni-toring fluorescence intensity changes over incubation time in blank blood and urine,in comparison with the traditional physical adsorption-based CGO fluorescent sensor.Spiked recovery experiments in blank blood and urine were conducted to compare performance with that of HPLC-MS/MS.Results A specific aptamer A5 was selected and chemically conjugated with CGO to construct the aptamer-functionalized CGO fluorescent sensor.Under optimized conditions,the proposed fluorescent sensor ex-hibited a linear detection range of 1.0-5.0 ng/mL for KET,with a limit of detection(LOD)of 0.86 ng/mL;while for NK,the linear detection range was 1.0-5.0 ng/mL,with an LOD of 0.70 ng/mL.Com-pared with the CGO fluorescent sensor constructed via physical adsorption,this sensor demonstrated greater stability in blood and urine.The spiked recovery rates of KET and NK in blank blood and urine ranged from 81.50%to 110.03%,exhibiting detection performance comparable to that of HPLC-MS/MS.Conclusion The aptamer screening method offers a novel approach for selecting aptamers tar-geting drugs and their metabolites.The constructed aptamer-functionalized CGO fluorescent sensor pro-vides an efficient and reliable strategy for the high-performance detection of KET and NK.

Objective To establish a chromatography-tandem mass spectrometry method for detecting chlorfenapyr and its metabolite tralopyril in blood,and to investigate the toxicokinetics in rats.Methods Chlorfenapyr(8 mg/kg)was administered orally to rats,and blood samples were collected from rats'canthus vein at 5 min,15 min,30 min,1 h,3 h,6 h,12 h,24 h and 48 h after administration.The blood samples were extracted using 100 μL of 5%formic acid solution and 400 μL of acetonitrile.Chlorfena-pyr was qualitatively and quantitatively detected by triple quadrupole gas chromatography-tandem mass spectrometry(GC-MS/MS)and tralopyril was detected by triple quadrupole liquid chromatography-tandem mass spectrometry(LC-MS/MS).The DAS 3.0 software was used to fit the toxicokinetic equa-tions and calculate the toxicokinetic parameters.Results Chlorfenapyr was detectable from 5 min to 24 h with a peak time of 1 h.Tralopyril was detectable from 15 min to 48 h with a peak time of 3 h.The toxicokinetic process of chlorfenapyr in rat blood conformed to a first-order absorption one-compartment open model,with the toxicokinetic equation described as C=e-0.265t-e-0.175t.Tralopyril con-formed to the first-order absorption three-compartment model,and the toxicokinetic equation was C=47 361.069e-2.209t-35 404.962e-1.486t+11 956.363e-0.512t.In the equations,C stands for the concentration of the target substance in the blood,e is the natural constant(≈2.718 28),and t stands for time.Conclu-sion This study optimized the detection method for chlorfenapyr and its metabolite tralopyril in blood.The toxicokinetic equations and parameters of chlorfenapyr and tralopyril can provide a reference for the estimation of oral intake time of chlorfenapyr.

Aim To explore the mechanism of Yangxin decoction in the treatment of chronic heart failure(CHF)based on network pharmacology and animal ex-periments.Methods The database was used to screen Yangxin decoction,a network of"drug-compo-nent-disease-target"was established,and the obtained targets were enriched and analyzed.The CHF model of rats was replicated by abdominal aortic ligation.After the administration,the general condition,body weight and heart weight of the rats were observed,and the he-modynamic changes,echocardiography indicators and left ventricular mass index were measured.HE staining was used to observe the morphological changes of myo-cardial tissue.Serum IL-1 β,IL-18,TNF-α and BNP were detected by ELISA.The expressions of NLRP3,caspase-1,ASC and NF-κB p65 proteinswere detected by Western blot.Results Enrichment analysis showed that the potential regulatory pathways of Yangx-in decoction in the treatment of CHF involved NOD-like signaling pathway,NF-κB signaling pathway,etc.The results of animal experiments showed that the body weight,left ventricular diastolic diameter and left ven-tricular systolic diameter of the rats in the administra-tion group decreased(P＜0.05),the left ventricular mass index,ejection fraction and short axis narrowing rate increased(P＜0.05),the pathological morphology of myocardial tissue was reduced,and the levels of IL-1 β,IL-18,TNF-α,BNP,NLRP3,caspase-1,ASC and NF-κB p65 decreased(P＜0.05).Conclusions The mechanism of Yangxin decoction in the treatment of CHF rats may be related to inhibiting the activation of NLRP3 inflammasome signaling pathway and reduc-ing the inflammatory response.

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.

This study aims to analyze the screening results and epidemiological characteristics of prostate cancer (PCa) among elderly males in the rural areas of Songjiang, Shanghai City, through the implementation of a preliminary prostate-specific antigen (PSA) screening based on a community-linkage model, and to explore an effective screening approach. A retrospective observational study design was employed to collect data from residents who underwent PSA screening at Songjiang Hospital affiliated to Shanghai Jiao Tong University School of Medicine, in collaboration with multiple community health service centers in Songjiang District, Shanghai City, between June 2022 and June 2024, through free clinics and annual health examinations. Prostate biopsy was recommended for individuals with total PSA (tPSA) levels >10 ng/ml and those with 4 ng/ml≤tPSA≤10 ng/ml and abnormal free-to-total PSA (f/tPSA) ratios. Clinical characteristics of detected PCa patients were analyzed. Follow-up was conducted through phone calls and home visits by family doctors, coupled with enhanced health education. The results indicated that a total of 17 198 residents participated in the screening, among which 2 234 (12.99%) had tPSA levels between 4 ng/ml and 10 ng/ml, and 257 (1.49%) had tPSA levels >10 ng/ml. Ultimately, 417 residents underwent prostate biopsy, with 171 being diagnosed with PCa, yielding a positive biopsy rate of 41.00% and a PCa detection rate of 0.99%. The predominant pathological subtype among PCa patients was adenocarcinoma (168 cases, 98.24%). Of the 146 PCa patients who received treatment, the majority were classified as intermediate or high-risk (124 cases, 84.93%). Furthermore, with the optimization of the screening model, there was a significant increase in the proportion of subsequent outpatient visits. In conclusion, the community-linkage-based PSA screening model demonstrated high effectiveness in screening for PCa among elderly males in the rural areas of Songjiang, Shanghai City. Epidemiological findings revealed that PCa patients in this region are primarily composed of intermediate and high-risk groups, highlighting the need for intensified early screening and health education.

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.

Percutaneous coronary intervention(PCI)is the main treatment for coronary heart disease(CHD).is characterized by progressive lumen stenosis in the stent,which is related to the effect of PCI on vascular inflammation,platelet activation,smooth muscle cell proliferation and migration,and extracellular matrix remodeling caused by vascular mechanical injury.Endothelial cell(EC)growth can heal the vascular lining damaged by the stent and prevent thrombosis,while drug eluting stent(DES)implantation inhibits the proliferation of vascular smooth muscle cells(VSMC)while inhibiting the growth of all cells at the target lesion.At present,some studies have shown that some drugs developed around non-coding RNA and related epigenetic pathways can target and inhibit VSMC proliferation through scaffold delivery,without affecting vascular intimal reendothelialization and promoting vascular intimal healing.Therefore,this review reviews the research progress of non-coding RNA drug scaffolds development and related clinical trials to determine their feasibility in solving the problems related to the clinical application of DES.

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.

Aim To explore the mechanism of Yangxin decoction in the treatment of chronic heart failure(CHF)based on network pharmacology and animal ex-periments.Methods The database was used to screen Yangxin decoction,a network of"drug-compo-nent-disease-target"was established,and the obtained targets were enriched and analyzed.The CHF model of rats was replicated by abdominal aortic ligation.After the administration,the general condition,body weight and heart weight of the rats were observed,and the he-modynamic changes,echocardiography indicators and left ventricular mass index were measured.HE staining was used to observe the morphological changes of myo-cardial tissue.Serum IL-1 β,IL-18,TNF-α and BNP were detected by ELISA.The expressions of NLRP3,caspase-1,ASC and NF-κB p65 proteinswere detected by Western blot.Results Enrichment analysis showed that the potential regulatory pathways of Yangx-in decoction in the treatment of CHF involved NOD-like signaling pathway,NF-κB signaling pathway,etc.The results of animal experiments showed that the body weight,left ventricular diastolic diameter and left ven-tricular systolic diameter of the rats in the administra-tion group decreased(P＜0.05),the left ventricular mass index,ejection fraction and short axis narrowing rate increased(P＜0.05),the pathological morphology of myocardial tissue was reduced,and the levels of IL-1 β,IL-18,TNF-α,BNP,NLRP3,caspase-1,ASC and NF-κB p65 decreased(P＜0.05).Conclusions The mechanism of Yangxin decoction in the treatment of CHF rats may be related to inhibiting the activation of NLRP3 inflammasome signaling pathway and reduc-ing the inflammatory response.

Objective To investigate the safety and efficacy of the radial artery hemostatic device in trans-brachial coronary intervention,and assess its effectiveness.Methods A retrospective analysis was conducted on patients who underwent trans-brachial coronary intervention at Peking University International Hospital from January 1,2018 to December 31,2023.The patients were divided into the radial artery hemostatic device group(170 cases)and the conventional compression group(100 cases)based on the postoperative hemostasis method,and the incidence of complications and clinical characteristics were compared between the two groups.Results A total of 270 patients underwent trans-brachial coronary intervention,with 18 complications occurring.Among them,17 cases were hemorrhage around the puncture site(16 cases were mild and 1 case was severe)and 1 was transient median nerve injury.The overall complication rate was 6.7％,and the incidence of hemorrhage around the puncture site was 6.3％.The hemorrhage rate in the radial artery hemostatic device group was 5.9％,while that in the conventional compression group was 7.0％,with no statistically significant difference between the two groups(P=0.715).Multivariate regression analysis indicated that female was an independent risk factor for hemorrhage around the puncture site(OR 4.57,95％CI 1.40-14.96,P=0.012).With the accumulation of technology,the application of trans-brachial access and radial artery hemostatic devices increased year by year(both P＜0.010).Conclusions The radial artery hemostatic device effectively controls bleeding in trans-brachial coronary interventions and demonstrates satisfactory safety.Its simplicity and efficacy provide a new strategy for hemostatic management in percutaneous trans-brachial access,which may gradually become the new standard in the future.