OBJECTIVE To investigate the induction of apoptosis in hepatocellular carcinoma cells by polyphyllin 9 （PP9） through the regulation of the Fas/Fas ligand （FasL） signaling pathway， and its inhibitory effect on the growth of transplanted tumor in nude mice. METHODS Based on the screening of cell lines and intervention conditions， HepG2 cells were selected as the experimental subject to investigate the effects of 2 μmol/L and 4 μmol/L PP9 treatment on cell colony formation activity， apoptosis rate， as well as the protein expressions of Fas， FasL， cleaved caspase-8 and cleaved caspase-3. Additionally， Fas inhibitor KR- 33493 was introduced to investigate the underlying mechanism of PP9’s anti-hepatocellular carcinoma activity. Using HepG2 cell tumor-bearing nude mice model as the object， and 5-fluorouracil （20 mg/kg） as the positive control， the effects of 10 mg/kg PP9 on tumor volume， tumor mass， and the protein expressions of the nuclear proliferation-associated antigen Ki-67 and cleaved caspase-3 in tumor-bearing nude mice were investigated. RESULTS Compared with the control group， 2， 4 μmol/L PP9 significantly decreased the number of clones and the clone formation rate of cells， but significantly increased the apoptosis rate， the protein expressions of Fas， FasL， cleaved caspase-8 and cleaved caspase-3 （P＜0.05 or P＜0.01）. However， the combination of Fas inhibitor KR-33493 could significantly reverse the effect of PP9 on the up-regulation of proteins related to the Fas/FasL signaling pathway （P＜0.01）. Compared with the control group， the tumor volume （on day 27）， mass and protein expression of Ki- 67 in nude mice of the PP9 group were significantly decreased， while the protein expression of cleaved caspase-3 was significantly increased （P＜0.01）. CONCLUSIONS PP9 can induce apoptosis of HepG2 cells by activating the Fas/FasL signaling pathway. Meanwhile， PP9 can also effectively inhibit the growth of transplanted tumors in nude mice.

Objective : To investigate the role of enhancer of zeste homolog 2(EZH2)-trimethylated lysine 27 of histone H3(H3K27me3) axis in the dedifferentiation of thyroid cancer and its clinical value as a potential target for the treatment of anaplastic thyroid cancer(ATC). Methods : Immunohistochemical SP method was used to detect the expression of EZH2, H3K27me3, paired box gene 8(PAX8), thyroglobulin(TG) and thyroid transcription factor 1(TTF1) in ATC and papillary thyroid carcinoma(PTC) and their adjacent tissues. The relationship between EZH2 and thyroid differentiation markers(PAX8, TTF1, TG) was further analyzed by gene expression omnibus(GEO) database. ATC cell lines 8305C and BHT-101 were culturedin vitro. Real-time reverse transcription PCR(RT-qPCR) was used to detect the expression of thyroid differentiation markers(TTF1, PAX8) mRNA in ATC cell lines treated with EZH2 inhibitor(GSK126), and evaluate the potential therapeutic effect of GSK126in vitro. The effects of GSK126 and BRAF inhibitor vemurafenib on the proliferation of ATC cell lines were observed by cell proliferation assay. Results : The expression of EZH2 in ATC tissues was significantly higher than that in papillary thyroid carcinoma and adjacent tissues(P<0.05). The expression of H3K37me3 in ATC tissues was significantly lower than that in PTC tissues(P<0.05). EZH2 was negatively correlated with PAX8 and TG expression levels, but not with TTF1 expression level.In vitroexperiments, GSK126 could reverse the expression of thyroid differentiation markers PAX8 and TTF1 in ATC cell lines. GSK126 combined with BRAF inhibitor vemurafenib could significantly inhibit the growth of ATC cell lines. Conclusion The EZH2-H3K27me3 axis plays an important role in regulating thyroid specific markers, and the inhibition of EZH2 by small molecular compounds is a promising target for ATC treatment in the future.

Objective To investigate the distribution and antimicrobial resistance profiles of clinical isolates in Xi'an No.3 Hospital from 2019 to 2023.Methods Clinical isolates were collected from January 1,2019 to December 31,2023.Antimicrobial susceptibility testing was carried out according to a unified protocol of China Antimicrobial Resistance Surveillance Network using Kirby-Bauer method or automated systems.The data were interpreted according to the breakpoints released by the Clinical and Laboratory Standards Institute(CLSI)in 2023.Results A total of 6 621 clinical isolates were collected from 2019 to 2023,including 1 569(23.7％)strains of Gram-positive bacteria and 5 052(76.3％)strains of Gram-negative bacteria.The prevalence of methicillin-resistant S.aureus,S.epidermidis and other Staphylococcus species(except SS.pseudintermedius and S.schleiferi)was 39.0％,62.3％,and 74.4％,respectively.Methicillin-resistant strains showed much higher resistance rates to most of other antimicrobial agents than methicillin-sensitive strains.No Staphylococcus strains were found resistant to vancomycin or linezolid.E.faecium strains demonstrated much higher resistance rates to most antimicrobial agents tested than E.faecalis.The prevalence of linezolid-resistant E.faecalis and vancomycin-resistant E.faecium was 0.9％and 0.4％,respectively.The prevalence of penicillin-nonsusceptible strains(PISP+PRSP)was 5.8％in nonmeningitis S.pneumoniae isolates.The prevalence of ESBL-producing E.coli,K.pneumoniae,and P.mirabilis in Enterobacterales was 48.5％,37.8％,and 47.2％,respectively.Among Enterobacterales strains,K.pneumoniae had the highest resistance rate to imipenem(18.2％)and meropenem(17.9％).Other Enterobacterales were highly sensitive to carbapenems.The resistance rates of P.aeruginosa to imipenem and meropenem were 22.5％and 19.5％,respectively.The resistance rates of A.baumannii to imipenem and meropenem were 65.0％and 71.6％,respectively.Conclusions Antibiotic resistance is still serious in this hospital.Nearly half of the strains of E.coli,K.pneumoniae and P.mirabilis produced ESBLs.K.pneumoniae and A.baumannii showed high resistance rates to carbapenems.Antimicrobial resistance surveillance should be performed appropriately.Relevant departments need to strengthen cooperation to curb the spread of drug-resistant bacteria.

This study was aimed at investigating the effectiveness of various host nucleic acid removal and non-specific amplifica-tion techniques in animal tissue samples,to increase the accuracy of pathogen identification in tissue samples.Simulated samples were prepared with a mixture of mouse lung tissue homogenates and Klebsiella pneumoniae fluids,and processed with six host nucleic acid removal kits and three non-specific amplification techniques.The effectiveness of each method in removing host DNA and enriching nucleic acids of pathogenic microorganisms was evaluated through real-time fluorescence quantitative PCR and high-throughput se-quencing.For host nucleic acid removal techniques,the method of selective cleavage and quantitative degradation of host DNA(Com-plete5 kit)effectively decreased the host nucleic acid content in tissue samples and increased the relative abundance of pathogen nucleic acids.In contrast,the magnetic bead method for host DNA removal(Next microbiome DNA enrichment Kit kit)was less effec-tive.At lower pathogen concentrations(77 CFU/mL),the Vazyme kit was more effective than the other kits in removing host nucleic acids.Non-specific amplification techniques(MALBAC whole genome amplification,MDA isothermal amplification,and random primer amplification)were not applicable to tissue samples and were not effective in increasing the relative abundance of pathogen nucleic acids.Selective lysis and quantitative degradation of host DNA were suitable for processing tissue samples with high host back-ground and low pathogenic microorganism levels,whereas non-specific amplification methods were not applicable to tissue samples for pre-processing of macro-genome high-throughput sequencing.

Objective To investigate the diagnostic efficacy of targeted biopsy(TB)combined with ipsilateral hemiglandular systematic biopsy(SB)of the dominant lesion,so as to explore a novel reduced-core biopsy strategy.Methods A retrospective analysis was conducted on the clinical data of 299 patients treated in our hospital during Sep.1,2022,and Feb.28,2023,who had a Prostate Imaging Reporting and Data System(PI-RADS)score ≥3 and underwent combined TB and SB.The dominant lesion was defined as the lesion with the highest PI-RADS score on multi-parametric magnetic resonance imaging(mpMRI);in cases of identical scores,the largest was designated as the dominant.SB was categorized as ipsilateral(ipsi-SB)or contralateral(contra-SB)to the dominant lesion.The consistency in detecting clinically significant prostate cancer(csPCa)was compared between TB with ipsi-SB(TB+ipsi-SB),TB with contra-SB(TB+contra-SB),and TB with SB(TB+SB).Subgroup analyses were performed based on PI-RADS score,prostate-specific antigen(PSA)level,prostate volume(PV),and mpMRI lesion distribution to evaluate csPCa detection rates across different variables.Results TB+ipsi-SB demonstrated comparable detection rate to TB+SB(46.2％vs.46.8％).The K values for TB+ipsi-SB and TB+contra-SB relative to TB+SB were 0.987(95％CI:0.969-1.000,P＜0.01)and 0.933(95％CI:0.892-0.974,P＜0.01),respectively.Across all subgroups,TB+ipsi-SB showed the highest agreement with TB+SB.Notably,in subgroups with PI-RADS 3 and 5,PSA＞0-20 ng/mL,PV＜25 mL,bilateral or multiple mpMRI lesions,TB+ipsi-SB achieved complete concordance with TB+SB in csPCa detection[K=1.000(95％CI:1.000-1.000),P＜0.01].Conclusion For patients with PI-RADS score ≥3,TB+ipsi-SB exhibits near-perfect consistency with TB+SB in csPCa detection while requiring fewer biopsy cores.TB+ipsi-SB represents a promising refinement of the TB+SB approach.

Objective:To explore the therapeutic effect and mechanism of Baicalin(BG)on chronic migraine(CM)rats.Methods:CM rat model was established by intermittent subcutaneous injection of nitroglycerin.Rats were randomly grouped into con-trol group,chronic migraine group(CM group),low-dose and high-dose Baicalin groups(BG-L group,BG-H group),Baicalin+MIP-1α recombinant protein group(BG+MIP-1α group)and CCR1 inhibitor ZK811752 group(CCR1-ZK group),with 10 rats in each group.General behavior of rats were observed and scored;von Frey fiber optic pain gauge was applied to measure the mechanical pain threshold of rats;Nissl staining was applied to observe the neuronal structure of ventrolateral periaqueductal gray(vlPAG);ELISA was applied to detect levels of TNF-α and IL-1β;immunohistochemical method was applied to detect expressions of pain related pro-teins c-Fos and CGRP;Western blot was applied to detect expressions of MIP-1α and CCR1 proteins.Results:Compared with Control group,the body mass,mechanical pain threshold,and the number of Nissl bodies in vlPAG area of rats in CM group were obviously reduced,the general behavioral score,levels of TNF-α,IL-1β,and expressions of c-Fos,CGRP,MIP-1α and CCR1 were obviously increased(P<0.05);compared with CM group,the body mass,mechanical pain threshold,the number of Nissl bodies in vlPAG area of rats in BG-L group,BG-H group and CCR1-ZK group were obviously increased,the general behavioral score,levels of TNF-α,IL-1β,and expressions of c-Fos,CGRP,MIP-1α and CCR1 were obviously reduced(P<0.05);compared with BG-H group,the body mass,mechanical pain threshold,and the number of Nissl bodies in vlPAG area of rats in BG+MIP-1α group were obviously reduced,general behavioral score,levels of TNF-α,IL-1β,and expressions of c-Fos,CGRP,MIP-1α and CCR1 were obviously increased(P<0.05).Conclusion:Baicalin has certain therapeutic effect on chronic migraine rats,and its mechanism may be related to inhibiting the activation of MIP-1α/CCR1 signaling pathway.

Objective:To report the nationwide surveillance results of pathogenic profiles and antimicrobial resistance patterns of Gram-positive bloodstream infections in China in 2023.Methods:The clinical isolates of Gram-posttive bacteria from blood cultures were collected in member hospitals of National Bloodstream Infection Bacterial Resistant Investigation Collaborative System（BRICS）during January to December 2023. Antimicrobial susceptibility testing was performed using the dilution method recommended by the Clinical and Laboratory Standards Institute（CLSI）. Statistical analyses were conducted using WHONET 5.6 and SPSS 25.0 software.Results:A total of 4 385 Gram-positive bacterial isolates were obtained from 60 participating center. The top five pathogens were Staphylococcus aureus（ n=1 544，35.2%），coagulase-negative Staphylococci（ n=1 441，32.9%）， Enterococcus faecium（ n=574，13.1%）， Enterococcus faecalis（ n=385，8.8%），and α-hemolytic Streptococci（ n=187，4.3%）. The prevalence of methicillin-resistant Staphylococcus aureus（MRSA）and methicillin-resistant coagulase-negative Staphylococci（MRCNS）was 26.2%（405/1 544）and 69.8%（1 006/1 441），respectively. Notably，all Staphylococci remained susceptible to glycopeptide or daptomycin. Staphylococcus aureus demonstrated excellent susceptibility（>97.0%）to cephalobiol，rifampicin，trimethoprim-sulfamethoxazole，linezolid，minocycline，tigecycline，and eravacycline. No Enterococcus exhibiting resistance to linezolid were detected. Glycopeptide resistance was uncommon but more frequent in Enterococcus faecium（resistance to vancomycin and teicoplanin：both 1.7%）compared to Enterococcus faecalis（both 0.3%）. The detection rates of MRSA and MRCNS exhibited significant regional variations across the country（ χ2=17.674 and 148.650，respectively，both P<0.001）. No vancomycin-resistant Enterococci were detected in central China. Institutional comparison demonstrated higher prevalence of MRSA（ χ2=14.111， P<0.001）and MRCNS（ χ2=4.828， P=0.028）in provincial hospitals than that in municipal hospitals. Socioeconomic analysis identified elevated detection rates of both MRSA（ χ2=18.986， P<0.001）and MRCNS（ χ2=4.477， P=0.034）in less developed regions（per capita GDP

Objective:To report the results of bacterial resistant investigation collaborative system（BRICS）on the distribution and antimicrobial resistance profile of clinical Gram-negative bacteria isolates from bloodstream infections in China in 2023，and provide reference for clinical tretment of bloodstream infections and prevention and control of bacterial resistance.Methods:The clinical isolates of Gram-negative bacteria from blood cultures in member hospitals of BRICS were collected during January 2023 to December 2023. Antibiotic susceptibility tests were conducted by agar dilution or broth dilution methods recommended by Clinical and Laboratory Standards Institute（CLSI）. WHONET 5.6 and SPSS 25.0 were used to analyze the data.Results:During the study period，11 492 strains of Gram-negative bacteria were collected from 60 hospitals，of which 10 098（87.9%）were Enterobacterales and 1 394（12.1%）were non-fermentative bacteria. The top 5 bacterial species were Escherichia coli（50.0%）， Klebsiella pneumoniae（26.1%）， Pseudomonas aeruginosa（5.1%）， Acinetobacter baumannii complex（5.0%）and Enterobacter cloacae complex（4.1%）. The ESBL-producing rates in Escherichia coli， Klebsiella pneumoniae and Proteus mirablilis were 46.8%（2 685/5 741），18.3%（549/2 999）and 44.0%（77/175），respectively. The prevalence of carbapenem-resistant Escherichia coli（CREC）and carbapenem-resistant Klebsiella pneumoniae（CRKP）were 1.3%（76/5 741）and 15.0%（450/2 999）；32.9%（25/76）and 78.0%（351/450）of CREC and CRKP were sensitive to ceftazidime/avibactam combination，respectively. 94.7%（72/76）and 90.2%（406/450）of CREC and CRKP were sensitive to aztreonam/avibactam combination. Furthermore，57.9%（44/76）and 79.1%（356/450）were sensitive to imipenem/relebactam combination. The prevalence of carbapenem-resistant Acinetobacter baumannii（CRAB）complex was 64.6%（370/573），while more than 80.0% of CRAB complex was sensitive to tigecycline，eravacycline and polymyxin B. The prevalence of carbapenem-resistant Pseudomonas aeruginosa（CRPA）was 17.0%（99/581）. There were differences in the composition ratio of Gram-negative bacteria in bloodstream infections and the prevalence of important Gram-negative bacteria resistance among different regions in China，with statistically significant differences in the prevalence of CREC，CRKP，CRPA and CRAB complex（ χ2=10.6，28.6，10.8 and 19.3， P<0.05）. The prevalence of ESBL-producing Escherichia coli， CREC，CRAB complex and CRKP were higher in provincial hospitals than those in municipal hospitals（ χ2=12.5，9.8，12.7 and 57.8，all P<0.01）. Conclusions:Gram-negative bacteria are the main pathogens causing bloodstream infections in China，and Escherichia coli is ranked in the top，while the trend of Klebsiella pneumoniae increases continuously with time. CRKP infection shows a slow upward trend，CREC infecton maintains a low prevalence level，and CRAB complex infection continues to exhibit a high prevalence rate. The composition and resistance patterns of pathogens causing bloodstream infections vary to some extent across different regions and levels of hospitals in China.

Objective:To explore the effect of preoperative intensive functional training on the balance and functional recovery of patients with knee osteoarthritis (KOA) receiving total knee arthroplasty (TKA).Methods:Sixty KOA patients were randomly divided into an outpatient group, a home-based group and a control group, each of 20. Before their TKAs, both the outpatient and home-based groups underwent intensive functional training for 4 weeks, while the control group did nothing special. After the TKA, all received 4 weeks of standardized postoperative rehabilitation training. Before any training, after the 4 weeks of preoperative training and 4 weeks after the TKAs, all of the subjects performed the timed up and go test (TUGT), and their joint range of motion (ROM) was recorded. They also completed the 30-second chair stand strength test (30sCST), and the 6-minute walk exercise endurance test (6MWT). KOA osteoarthritis indices (WOMACs) were also recorded.Results:After the 4 weeks of preoperative training, significant differences were observed in the trajectory length, elliptical area and TUGT times of both the outpatient and home-based groups. Four weeks after the TKAs, significant differences were observed in all of the measurements in all three groups, but the results of the outpatient and home-based groups were significantly better than those of the control group, on average. After the 4 weeks of postoperative training, there were significant differences between the outpatient and home-based groups in terms of the average knee flexion angle, knee extension angle, 30sCST and 6MWT results. There were significant differences among the 3 groups in all of the measurements 4 weeks after the TKAs, with those of the two training groups showing significantly better results than the control group. The pain scores, stiffness scores, function scores and total WOMAC scores had improved significantly compared with the control group, but the average function and total WOMAC scores of the outpatient group (24.25±2.38) and (35.41±3.02) were then significantly superior to the home-based group′s averages.Conclusions:Intensive preoperative functional training conducted in an outpatient clinic or at home can significantly improve the balance, lower limb strength, exercise endurance and symptoms of KOA patients after TKA.

Objective:To investigate the effect of progressive resistance training on inflammatory markers, motor function and quality of life in the elderly after total knee arthroplasty (TKA).Methods:This study was a randomized controlled trial. A total of 46 elderly patients aged≥60 years who underwent total knee arthroplasty in the Affiliated Hospital 6 of Nantong University from January 2023 to June 2024 were selected and divided into experimental group and control group by computer random number method (23 cases in each group). The control group received routine rehabilitation management intervention, progressive resistance training was added to the experimental group on the basis of the control group, and all patients were intervened for 4 weeks. Interleukin-6 (IL-6), C-reactive protein (CRP), erythrocyte sedimentation rate (ESR), 30-Second Chair Stand Test (30sCST), Knee Society Score (KSS), and World Health Organization Quality of Life Scale-Brief Form Questionnaire (WHOQOL-BREF) scores were measured at 1 day before operation, 2 weeks and 4 weeks after operation, and were compared respectively.Results:At 2 and 4 weeks after operation, the levels of IL-6 [(22.44±2.17) and (9.91±1.41) pg/ml], CRP[(19.61±2.20) and (3.17±0.40) mg/L] and ESR[(44.85±3.78) and (28.28±3.31) mm/1 h] in the experimental group were significantly lower than those in control group [IL-6: (24.65±1.77) and (11.35±1.67) pg/ml, CRP: (23.24±2.69) and (4.15±0.45) mg/L and ESR: (48.54±3.66) and (34.60±2.98) mm/1 h](all P<0.05). At 2 and 4 weeks after operation, the 30sCST[(9.87±0.92) and (11.83±1.03) times], clinical scores of KSS[(48.44±3.13) and (71.09±3.30) points], functional scores of KSS[(40.44±3.96) and (69.35±4.07) points] in the experimental group were significantly higher than those in control group [30sCST: (9.30±0.70) and (10.52±0.79) times, clinical scores of KSS: (46.17±2.86) and (67.00±2.89) points, functional scores of KSS: (38.91±3.68) and (66.30±5.05) points](all P<0.05). At 2 weeks after operation, the scores of physical health, mental health and social relations in the WHOQOL-BREF of the experimental group [(16.96±1.02), (17.96±1.46) and (6.74±0.62) points], which were significantly higher than those in the control group [(16.09±1.08), (17.14±1.12), (6.44±0.51) points](all P<0.05). There was no significant difference in the environmental condition score between the two groups. At 4 weeks after operation, the scores of physical health, mental health, social relations and environmental conditions in WHOQOL-BREF of the experimental group [(22.09±1.81), (22.17±2.19), (12.09±1.28) and (33.91±2.26) points] were significantly higher than those in the control group [(19.65±1.80), (20.39±1.95), (10.17±1.30), (31.96±2.51) points] (all P<0.05). Conclusion:Progressive resistance training can effectively reduce the inflammatory response in the elderly after total knee arthroplasty, enhance lower limb muscle strength and knee joint function, and improve the quality of life.