Objective: To investigate the expression and functional role of FK506 binding protein 10 (FKBP10) in oral squamous cell carcinoma (OSCC), and to provide a research basis for the estimated prognosis and targeted therapy of OSCC. Methods: A total of 284 OSCC samples and 19 normal samples were selected from the Cancer Genome Atlas (TCGA) database, and diagnostic analysis was performed to determine mRNA expression. Survival analysis for FKBP10 and OSCC was conducted on a gene expression profile interaction analysis website. Real-time fluorescence quantitative PCR and Western Blot were used to detect the mRNA and protein expression of FKBP10 in four OSCC cell lines and SAS and SCC9 cells transfected with siRNA. The cell proliferation ability of FKBP10-silenced cells was detected using the CCK8 method, and the cell cycle distribution and apoptosis were detected by flow cytometry. Cell migration and invasion ability were detected through wound healing and invasion experiments. The expression changes of total protein and phosphatidylinositol 3-kinase (PI3K)-serine/threonine kinase (AKT) after FKBP10 silencing were analyzed by proteomics and Western Blot. Results: According to the analysis of gene expression levels, the mRNA expression level of FKBP10 in OSCC was significantly higher than that in normal tissues (P < 0.001). In terms of diagnosis, the expression level of FKBP10 has unique diagnostic value for OSCC (P < 0.05). The survival analysis of FKBP10 and OSCC showed that a high expression of FKBP10 led to a decrease in patient survival and poor prognosis (P < 0.05). The expression of FKBP10 mRNA and protein in OSCC cell lines was higher than that in normal oral keratinocytes (P < 0.001). Silencing FKBP10 can reduce the proliferation, invasion, and migration ability of SAS and SCC9 (P < 0.001), and also block their cell cycle in the G0/G1 phase (P < 0.001), with a significant increase in apoptosis (P < 0.05). Protein mass spectrometry and Western blot analysis revealed that FKBP10 silencing significantly downregulated the expression of multiple proteins in the RAP1 signaling pathway, mainly RAP guanine nucleotide exchange factor 1 (RAPGEF1) (P < 0.05) and the phosphorylation of PI3K-AKT proteins (P < 0.05). Conclusion FKBP10 is highly expressed in OSCC, leading to poor prognosis for patients. Downregulated FKBP10 expression can inhibit the proliferation, migration, and invasion ability of OSCC cells, hinder cell cycle progression, and promote apoptosis via the RAP1-PI3K-AKT axis. FKBP10 is a potential therapeutic target and prognostic biomarker for OSCC.

Objective To investigate the independent risk factors affecting the prognosis of chronic active antibody-mediated rejection (caAMR) after kidney transplantation. Methods A retrospective analysis was conducted on 61 patients who underwent renal biopsy and were diagnosed with caAMR. The patients were divided into caAMR group (n=41) and caAMR+TCMR group (n=20) based on the presence or absence of concurrent acute T cell-mediated rejection (TCMR). The patients were followed up for 3 years. The value of 24-hour urinary protein and estimated glomerular filtration rate (eGFR) at the time of biopsy in predicting graft loss was assessed using receiver operating characteristic (ROC) curves. The independent risk factors affecting caAMR prognosis were analyzed using the LASSO-Cox regression model. The correlation between grouping, outcomes, and Banff scores was compared using Spearman rank correlation matrix analysis. Kaplan-Meier analysis was used to evaluate the renal allograft survival rates of each subgroup. Results The 3-year renal allograft survival rates for the caAMR group and the caAMR+TCMR group were 83% and 79%, respectively. The area under the ROC curve (AUC) for predicting 3-year renal allograft loss was 0.83 ［95% confidence interval (CI) 0.70-0.97］ for eGFR and 0.78 (95% CI 0.61-0.96) for 24-hour urinary protein at the time of biopsy. LASSO-Cox regression analysis and Kaplan-Meier analysis showed that eGFR≤25.23 mL/(min·1.73 m²) and the presence of donor-specific antibody (DSA) against human leukocyte antigen (HLA) class I might be independent risk factors affecting renal allograft prognosis, with hazard ratios of 7.67 (95% CI 2.18-27.02) and 5.13 (95% CI 1.33-19.80), respectively. A strong correlation was found between the Banff chronic lesion indicators of renal interstitial fibrosis and tubular atrophy (P<0.05). Conclusions The presence of HLA class I DSA and eGFR≤25.23 mL/(min·1.73 m²) at the time of biopsy may be independent risk factors affecting the prognosis of caAMR.

Objective To investigate the antimicrobial resistance of clinical isolates from elderly patients(≥65 years)in major medical institutions across China.Methods Bacterial strains were isolated from elderly patients in 52 hospitals participating in the CHINET Antimicrobial Resistance Surveillance Program during the period from 2015 to 2021.Antimicrobial susceptibility test was carried out by disk diffusion method and automated systems according to the same CHINET protocol.The data were interpreted in accordance with the breakpoints recommended by the Clinical and Laboratory Standards Institute(CLSI)in 2021.Results A total of 514 715 nonduplicate clinical isolates were collected from elderly patients in 52 hospitals from January 1,2015 to December 31,2021.The number of isolates accounted for 34.3％of the total number of clinical isolates from all patients.Overall,21.8％of the 514 715 strains were gram-positive bacteria,and 78.2％were gram-negative bacteria.Majority(90.9％)of the strains were isolated from inpatients.About 42.9％of the strains were isolated from respiratory specimens,and 22.9％were isolated from urine.More than half(60.7％)of the strains were isolated from male patients,and 39.3％isolated from females.About 51.1％of the strains were isolated from patients aged 65-＜75 years.The prevalence of methicillin-resistant strains(MRSA)was 38.8％in 32 190 strains of Staphylococcus aureus.No vancomycin-or linezolid-resistant strains were found.The resistance rate of E.faecalis to most antibiotics was significantly lower than that of Enterococcus faecium,but a few vancomycin-resistant strains(0.2％,1.5％)and linezolid-resistant strains(3.4％,0.3％)were found in E.faecalis and E.faecium.The prevalence of penicillin-susceptible S.pneumoniae(PSSP),penicillin-intermediate S.pneumoniae(PISP),and penicillin-resistant S.pneumoniae(PRSP)was 94.3％,4.0％,and 1.7％in nonmeningitis S.pneumoniae isolates.The resistance rates of Klebsiella spp.(Klebsiella pneumoniae 93.2％)to imipenem and meropenem were 20.9％and 22.3％,respectively.Other Enterobacterales species were highly sensitive to carbapenem antibiotics.Only 1.7％-7.8％of other Enterobacterales strains were resistant to carbapenems.The resistance rates of Acinetobacter spp.(Acinetobacter baumannii 90.6％)to imipenem and meropenem were 68.4％and 70.6％respectively,while 28.5％and 24.3％of P.aeruginosa strains were resistant to imipenem and meropenem,respectively.Conclusions The number of clinical isolates from elderly patients is increasing year by year,especially in the 65-＜75 age group.Respiratory tract isolates were more prevalent in male elderly patients,and urinary tract isolates were more prevalent in female elderly patients.Klebsiella isolates were increasingly resistant to multiple antimicrobial agents,especially carbapenems.Antimicrobial resistance surveillance is helpful for accurate empirical antimicrobial therapy in elderly patients.

Objective To understand the clinical characteristics of patients with Streptococcus anginosus group(SAG)pulmonary abscess and resistance of SAG.Methods 67 patients with pulmonary abscess admitted to a hos-pital from January 2018 to May 2022 were retrospectively analyzed,clinical data of patients with SAG pulmonary abscess were analyzed,and the minimum inhibitory concentration of antimicrobial agents to 18 SAG strains was de-tected by microbroth dilution method,the carriage of resistance genes and virulence genes of SAG were detected by high-throughput sequencing technology.Results Among 67 patients with pulmonary abscess,SAG accounted for 29.9％(20/67),out of which 2 were excluded due to bacterial inactivation,and 18 patients were included for fur-ther studies.18 patients with SAG pulmonary abscess were all community acquired,with an average age of(60.9±9.1)years.There were 13(72.2％)male patients,most patients(94.4％)complicated chronic pulmonary disease,with cough(94.4％)and expectoration(88.9％)as the initial symptoms,some patients(44.4％)had chest pain,and more than half(61.1％)didn't have fever.The proportion of neutrophils,erythrocyte sedimentation rate,and C-reactive protein were mostly elevated,while procalcitonin was normal.The resistance rate of 18 SAG strains to erythromycin,clindamycin,and tetracycline was＞65％,out of which 14 strains carried resistance gene ermB,13 strains carried resistance gene tetM,and 1 strain carried both resistance gene msrD and mefA.18 SAG strains were detected virulence gene psaA,out of which 3 strains were detected virulence gene nan A.Conclusion SAG is an im-portant pathogen that causes pulmonary abscess,and the patients'complications are mainly chronic pulmonary di-seases,with non-specific clinical manifestations;Most strains carry ermB and tetM genes,mediating resistance to macrolides,lincosamides,and tetracyclines.

Objective:To explore the application value of part-cut jejunal transection in digestive tract reconstruction of totally laparoscopic total gastrectomy.Methods:The propensity score matching and retrospective cohort study was conducted. The clinicopathological data of 112 patients with gastric cancer who underwent totally laparoscopic total gastrectomy in The Second Affiliated Hospital of Anhui Medical University from June 2018 to September 2022 were collected. There were 81 males and 31 females, aged (70±8)years. Among the 112 patients, 60 patients undergoing diges-tive tract reconstruction by Roux-en-Y anastomosis with part-cut jejunum were set as the part-cut group, and 52 patients undergoing digestive tract reconstruction by traditional Roux-en-Y anasto-mosis were set as the traditional group. Observation indicators: (1) propensity score matching status and comparison of clinical data of patients between the two groups after matching; (2) intraopera-tive and postoperative conditions; (3) follow-up. Comparison of measurement data with normal dis-tribution between groups was conducted using the independent sample t test. Comparison of count data between groups was conducted using the chi-square test or Fisher exact probability. Com-parison of ordinal data was conducted using the nonparametic rank sum test. Propensity score matching was performed using the 1∶1 nearest neighbor matching method, with the caliper value of 0.02. Results:(1) Propensity score matching status and comparison of clinical data of patients between the two groups after matching. Of the 112 patients, 90 patients were successfully matched, with 45 cases in each of the part-cut group and the traditional group. After propensity score matching, the elimination of body mass index, clinical TNM staging confounding bias ensured comparability. (2) Intraoperative and postoperative conditions. After propensity score matching, the total operation time and digestive tract reconstruction time of patients in the part-cut group were (217.0±15.1)minutes and (34.7±1.8)minutes, versus (252.6±21.9)minutes and (52.6±7.4)minutes in the traditional group, respectively, showing significant differences in the above indicators between the two groups ( t=?8.97, ?15.66, P<0.05). (3) Follow-up. After propensity score matching, 90 patients were followed up postoperatively for (47±15)months. During the follow-up, no patient in either group received secondary surgery, and there was no death. There were 3 cases and 10 cases of Roux stasis syndrome in the part-cut group and the traditional group, respectively, showing a significant difference between the two groups ( χ2=4.41, P<0.05). Conclusion:Compared with traditional Roux-en-Y anastomosis, the Roux-en-Y anastomosis with part-cut jejunum in totally laparoscopic total gastrectomy can signifi-cantly shorten the time for digestive tract reconstruction and reduce the incidence of postoperative Roux stasis syndrome.

Cardiovascular disease is the leading cause of death worldwide,with atherosclerosis(AS)-its core pathological manifestation-representing a multifactorial-driven chronic inflammatory disorder.The pathogenesis of AS involves intricate pathological mechanisms including dyslipidemia,inflammatory cascades,and plaque vulnerability,whose complexity necessitates animal models capable of accurately recapitulating specific pathological features.Genetically engineered murine models have emerged as pivotal tools for deciphering AS mechanisms,owing to their genetic manipulability,phenotypic traceability,and molecular conservation with human pathophysiology.This review provides a systematic overview of current methodologies for establishing AS mouse models,with particular emphasis on evaluating the pathological fidelity of dietary induction approaches,genetic modification strategies[notably apolipoprotein E(ApoE)-/-and low density lipoproteins receptor(LDLr)-/-models],and physical injury paradigms.

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.

Cardiovascular disease is the leading cause of death worldwide,with atherosclerosis(AS)-its core pathological manifestation-representing a multifactorial-driven chronic inflammatory disorder.The pathogenesis of AS involves intricate pathological mechanisms including dyslipidemia,inflammatory cascades,and plaque vulnerability,whose complexity necessitates animal models capable of accurately recapitulating specific pathological features.Genetically engineered murine models have emerged as pivotal tools for deciphering AS mechanisms,owing to their genetic manipulability,phenotypic traceability,and molecular conservation with human pathophysiology.This review provides a systematic overview of current methodologies for establishing AS mouse models,with particular emphasis on evaluating the pathological fidelity of dietary induction approaches,genetic modification strategies[notably apolipoprotein E(ApoE)-/-and low density lipoproteins receptor(LDLr)-/-models],and physical injury paradigms.

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.

OBJECTIVE To understand the drug resistance genes,virulence genes and molecular epidemiological characteristics of extensively drug-resistant hypervirulent Klebsiella pneumoniae(XDR-hvKP)strains causing hospital-associated infection.METHODS The clinical isolates of XDR-hvKP were collected from Tongling People's Hospital from Jul.2020 to Dec.2022.The strains were identified by matrix-assisted laser desorption ionization-time-of-flight(MALDI-TOF)mass spectrometry,the common drug resistance genes and virulence genes were an-alyzed by Sanger sequencing,the capsular serotypes were determined by wzi gene sequencing;the drug resistance genes,virulence genes and ST subtypes were observed by means of whole-genome sequencing(WGS)technique.RESULTS Totally 18 strains of XDR-hvKP were collected,55.56％(10/18)of which were isolated from blood specimens,and 61.11％(11/18)were isolated from critical care medicine department.Sanger sequen-cing analysis showed that all of the strains carried blaKPC-2 drug resistance gene;rmpA2(100.00％)and rmpA,i-roN,iutA(94.44％,17/18)were the major virulence genes carried by the strains.WGS analysis indicated that all of the 18 XDR-hvKP isolates carried multiple drug resistance genes such as blaKPC-2 carbapenemase and the viru-lence genes like capsule(rmpA/rmpA2),aerobacterin(iucABCD-iutA),Salmonella(iroN)and yersinin(ybt).All of the ST subtypes were ST 11,and all of the capsular serotypes were KL 64.CONCLUSIONS The ST11-KL64 type XDR-hvKP strains carry blaKPC-2;rmpA,rmpA2,iroN and iutA are the major virulence genes.It is necessary to strengthen the monitoring of key population of the key departments and make joint efforts of multiple departments to contain the transmission of the strains.