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 compare the clinical efficacy and adverse events of chemoradiotherapy (CRT) combined with immunotherapy versus CRT alone in patients with locally recurrent esophageal squamous cell carcinoma (ESCC) after surgery.Methods:A total of 221 patients with postoperative locally recurrent ESCC who underwent CRT at the Affiliated Huai′an No. 1 People′s Hospital of Nanjing Medical University from January 2020 to December 2022 were retrospectively analyzed. Patients were divided into two groups according to treatment modality: the CRT group ( n=118) and the CRT plus immunotherapy group (combined group, n=103). Among the combined group, 39 patients received camrelizumab, 33 received sintilimab, and 31 received tislelizumab. Short-term efficacy, survival outcomes, and treatment-related adverse events were compared between the two groups. The Cox proportional hazards model was used to analyze prognostic factors for overall survival (OS). Results:No statistically significant differences were observed in baseline clinicopathological characteristics between the two groups. The objective response rate (ORR) in the combined group was 72.8%, significantly higher than 55.9% in the CRT group ( P=0.009). The 1- and 2-year OS rates in the CRT group were 68.6% and 41.5%, respectively, while the 1- and 2-year progression-free survival (PFS) rates were 56.8% and 30.5%, respectively. In the combined group, the 1- and 2-year OS rates were 84.5% and 55.3%, and the 1- and 2-year PFS rates were 67.0% and 42.7%, respectively. The differences in both OS and PFS between the two groups were statistically significant ( P=0.001 and 0.023, respectively). Multivariate analysis showed that Karnofsky performance status score of 70, TNM stage III, and CRT alone were independent risk factors for OS ( P=0.035, 0.031, and 0.002, respectively). The incidence of grade ≥3 adverse events did not differ significantly between the two groups ( P=0.550). A total of 85 grade 1-2 immune-related adverse events (irAEs) and 7 grade ≥3 irAEs occurred in 65 patients in the combined group. Subgroup analysis suggested that tislelizumab combined with CRT showed the most favorable efficacy and safety profile. Conclusion:For patients with locally recurrent ESCC after surgery, concurrent chemoradiotherapy combined with immunotherapy demonstrates promising efficacy with tolerable safety, and may offer a potential therapeutic advantage.

Objective To investigate whether successful percutaneous coronary intervention(PCI)could improve symptoms and quality of life(QOL)in left main disease and/or 3-vessel disease patients with diabetes.Methods Patients with left main disease and/or 3-vessel disease who underwent PCI in the First Affiliated Hospital of Air Force Medical University from April 2018 to May 2021 were consecutively enrolled and subdivided into 2 groups:diabetes and no diabetes.Detailed baseline characteristics,symptoms,including dyspnea and angina,assessed with the Rose dyspnea scale(RDS),Seattle angina questionnaire(SAQ),the European quality of life-5 dimensions(EQ-5D)and 12-item short-form health survey(SF-12)questionnaire respectively,procedural details,and 1 month and 1 year follow-up data were collected.Results Among 440 left main disease and/or 3-vessel disease patients,disease was present in 176(40.00％),who had more hypertension,peripheral artery disease,and LCX lesion(all P＜0.05).The incidence of major adverse cardiovascular events(MACE)and all-cause mortality were similar between the two groups(both P＞0.05)at 1 month follow-up,while all-cause mortality in diabetes patients was significantly higher than those without diabetes at 1 year follow-up(P=0.013).Low left ventricular ejection fraction was an independent risk factor for MACE and all-cause mortality at 1 month and 1 year follow-up after successful revascularization(all P＜0.05).Most importantly,symptoms,including dyspnea and angina,and QOL were markedly improved regardless of diabetes both at 1 month and 1 year follow-up(all P＜0.05).Diabetes patients showed improved dyspnea and QOL at similar degree to the non-diabetes patients(all P＞0.05)and a more significantly relieved angina(P=0.013).Additionally,the number of chronic total occlusion(CTO)per patient was identified as an independent risk factor of dyspnea(OR 0.723,95％CI 0.525～0.997,P=0.048)and angina relief(OR 0.686,95％CI 0.473～0.995,P=0.047),and the contrast volume(OR 0.995,95％CI 0.992～0.999,P=0.008)as an independent risk factor of QOL improvement in diabetic patients.Conclusions Successful PCI is beneficial for relieving symptoms and improving quality of life in patients with diabetes who have left main disease and/or 3-vessel disease.

This study was aimed at exploring novel auxiliary diagnostic biomarkers for brucellosis and their potential miR-NA-mRNA regulatory networks.High-throughput sequencing was used to compare miRNA expression differences in serum ex-osomes between patients with brucellosis and healthy controls.Subsequently,RT-qPCR was used to validate the expression of significantly upregulated exosomal miRNAs.The diagnostic value of these miRNAs was assessed with ROC curves,and bioin-formatics analyses were performed to investigate the potential roles of the miRNAs in brucellosis infection.The ROC curve a-nalysis indicated that the area under the curve for exosomal hsa-miR-11400(P＜0.05),hsa-miR-199a-5p(P＜0.05),and hsa-miR-148a-5p(P＜0.05)was 0.79,0.81,and 0.74,respectively.A total of 465 differentially expressed miRNAs and their tar-get genes were predicted,including 25 immune-related target genes,most of which were closely associated with cancer-related proteoglycans,NF-kappa B signaling pathways,and IL-17 signaling pathways.The constructed differentially expressed gene network indicated that the immune genes PLXNA2,IL17RA,PRKCA,CD22,ACVR1B,and CBL might be regulated by hsa-miR-199a-5p and hsa-miR-148a-5p.These findings suggest that exosomal miRNAs might serve as auxiliary diagnostic indicators for brucellosis.Our exosomal miRNA-mRNA regulatory network provides new insights into the pathogenesis and treatment of brucellosis.

As a type of endogenous small non-coding RNA， microRNA （miRNA） can regulate gene expression and thereby intervene against the development and progression of cardiovascular diseases， neurodegenerative diseases， metabolic diseases， and autoimmune diseases. The pathogenesis of cholestasis is complex and is mainly associated with the metabolism and transport of bile acids， oxidative stress， inflammatory response， and intestinal flora. Currently， ursodeoxycholic acid is the preferred drug for the clinical treatment of cholestasis， but it may cause adverse reactions and exhibit poor efficacy in some patients. Studies have shown that miRNA can intervene in the disease process of cholestasis through multiple mechanisms such as regulating bile acid metabolism and transport， alleviating oxidative stress， inhibiting inflammatory response， improving cholangiocyte proliferation， and regulating intestinal flora. It can be used as a new biomarker and action target for cholestasis， with high research potential and value. Therefore， this article summarizes the role and mechanisms of miRNA in regulating cholestasis in recent years， in order to provide a reference for further research on the prevention and treatment of cholestasis by targeting miRNA.

Objective:To identify the relevant factors for the first-course remission of acute myeloid leukemia (AML) and to develop a predictive model as well as assess its predictive capability.Methods:Clinical data of 749 patients newly diagnosed with AML admitted to the Department of Hematology, the First Affiliated Hospital, Zhejiang University, School of Medicine from January 1, 2019, to April 30, 2023, were collected and randomly divided into training and validation sets. Multivariate logistic regression analysis was conducted to determine variables associated with complete remission in the first course of induction therapy, and a predictive model was established based on these variables. The receiver operating characteristic (ROC) curve of the predictive model was plotted, and the area under the curve (AUC) was calculated.Results:The indicators predicting the first remission course included peripheral blood white blood cell count during onset, CBF::MYH11 fusion gene, CEBPA bZIP region mutation, myelodysplastic syndrome-related gene mutation, and induction chemotherapy regimen selection as independent factors for the first remission course. The model’s area under the training and validation curves was 0.738 (95% CI: 0.696-0.780) and 0.726 (95% CI: 0.650-0.801), respectively. The Hosmer-Lemeshow test results yielded P-values of 0.993 and 0.335, respectively. Conclusion:In this study, the developed model demonstrates a strong predictive capability for the efficacy of the first course of patients with AML, providing valuable guidance to clinicians in assessing patient prognosis and selecting appropriate treatment strategies.

Objective: To analyze the influence of stress and psychological resilience on the dietary behavior of middle school students so as to privide a basis for the development of policies and interventions aimed at improving middle school students dietary behavior. Methods: A total of 8 874 middle school students in Shanghai were surveyed using stratified cluster random sampling method from November 2019 to January 2020. The questionnaire included general information, dietary behavior, Perceived Stress Scale (PSS-10) and Connor-Davidson Resilience Scale (CD-RISC-10). Factor analysis was used to analyze the dietary behavior model. Logistic regression model was used to explore the correlation between stress, psychological resilience and dietary behavior in adolescents. Besides, a structural equation model was established to analyze the mediating effect of psychological resilience on stress and dietary behavior. Results: The total score of psychological resilience among middle school students was (27.99±9.83), and the total score of stress was (25.56±7.06). Factor analysis categorized dietary behavior into two types: the high energy dietary behavior and balanced dietary behavior. High energy dietary behavior exhibited statistically significant differences across genders and schooling stage ( χ 2=41.37, 204.03), while balanced dietary behavior showed statistically significant differences across schooling stage and socioeconomic status ( χ 2=130.23, 96.53) (all P <0.01). Logistic regression analysis showed that adolescents with moderate and high stress levels had an increased risks of high energy dietary behavior ( OR=1.25, 95%CI =1.12-1.39; OR=1.58, 95% CI = 1.39-1.79) and a reduced likelihood of reduced balanced dietary behavior ( OR=0.73, 95%CI =0.65-0.81; OR=0.53, 95%CI =0.47-0.60); adolescents with high levels of psychological resilience had a decreased risk of highenergy dietary behavior ( OR= 0.73 , 95%CI =0.65-0.83), and those with moderate and high resilience levels showed improved balanced dietary behavior ( OR= 1.45 , 95%CI =1.29-1.62; OR=2.50, 95%CI =2.21-2.84) (all P <0.01). The mediating effect of psychological resilience between stress and high energy dietary behavior or balanced dietary behavior accounted for 15.61% and 56.10% of the total effects, respectively. Conclusions Stress and psychological resilience are the influencing factors of dietary behavior in middle school students. Psychological resilience have a partial mediating effect between stress and high energy dietary behavior or balanced dietary behavior.

Objective·To explore the diagnostic,therapeutic,and prognostic value of metagenomics next-generation sequencing(mNGS)in patients with pneumonia-induced sepsis.Methods·This study consisted of a multicenter,prospective,non-randomized controlled trial and a diagnostic test.Patients with pneumonia-induced sepsis who were hospitalized in four hospitals across China were enrolled between March 2020 and October 2021.All patients met the Sepsis-3 criteria issued by the Society of Critical Care Medicine and the European Society of Intensive Care Medicine,as well as the clinical diagnostic standard of pneumonia.Enrolled patients were assigned based on their preference to either the conventional test-only group[receiving only conventional test(CMT)]or the combined mNGS test group(receiving CMT and mNGS concurrently).The primary outcome was the 7-day all-cause mortality rate,and secondary outcomes included the changes in SOFA and APACHE Ⅱ scores from baseline to day 7,28-day all-cause mortality rate,the composite endpoint of mechanical ventilation or death within 28 d,28 d ventilation-free days,28 d hospital-free days,and the average daily hospitalization cost.Propensity score matching was used to balance covariates between the two groups.Kaplan-Meier curves were plotted and Cox proportional hazards models were built to compare the risk of death between the two groups.Pathogen detection results from infection site samples in the combined mNGS test group were used for the diagnostic test.The clinically-adjudicated causative pathogens was used as the reference standard.The results of traditional pathogen detection and mNGS detection were compared respectively with the reference standard.The positive percent agreement,negative percent agreement,positive predictive value,and negative predictive value between the two methods and the reference standard were calculated.McNemar's χ2 test was used to evaluate the causative pathogen detection capabilities of the two methods.Results·A total of 533 patients were enrolled,of whom 311 opted for additional mNGS testing,while 222 received only conventional pathogenetic testing.In the non-randomized controlled trial,after propensity score matching to balance covariates,the 7-day all-cause mortality was lower in the combined mNGS test group compared to the conventional test-only group[4.8%vs 8.6%,HR 0.37(95%CI 0.15?0.91),P=0.031].Additionally,the 28-day ventilation-free days were increased in the combined mNGS test group(19.9 d vs 18.4 d,P=0.041).No significant difference was observed between the two groups in terms of 28-day all-cause mortality or the average daily hospitalization costs.In the diagnostic test,compared to the reference standard,the positive percent agreement of mNGS with the clinical composite judgment for causative pathogens was higher than that of CMT[91.9%(95%CI 87.7%?95.0%)vs 56.1%(95%CI 49.7%?62.4%),P<0.001].Conversely,the negative percent agreement of mNGS was lower than that of CMT[29.2%(95%CI 18.6%?41.8%)vs 69.2%95%CI 56.6%?80.1%),P<0.001].The negative predictive value of nNGS was higher than that of CMT[48.7%(95%CI 32.4%?65.2%)vs 29.4%(95%CI 22.3%?37.3%),P=0.001].Conclusion·In patients with pneumonia-induced sepsis,mNGS of infection site samples demonstrated a higher detection rate of causative pathogen compared to CMT.Furthermore,the combination of mNGS with CMT may help reduce the 7-day all-cause mortality,suggesting that mNGS has clinical value and potential for application in the management of sepsis caused by pulmonary infections.

BACKGROUND: The clinical impact of post-percutaneous coronary intervention (PCI) quantitative flow ratio (QFR) in patients treated with PCI for chronic total occlusion (CTO) was still undetermined. METHODS: All CTO vessels treated with successful anatomical PCI in patients from PANDA III trial were retrospectively measured for post-PCI QFR. The primary outcome was 2-year vessel-oriented composite endpoints (VOCEs, composite of target vessel-related cardiac death, target vessel-related myocardial infarction, and ischemia-driven target vessel revascularization). Receiver operator characteristic curve analysis was conducted to identify optimal cutoff value of post-PCI QFR for predicting the 2-year VOCEs, and all vessels were stratified by this optimal cutoff value. Cox proportional hazards models were employed to calculate the hazard ratio (HR) with 95% CI. RESULTS: Among 428 CTO vessels treated with PCI, 353 vessels (82.5%) were analyzable for post-PCI QFR. 31 VOCEs (8.7%) occurred at 2 years. Mean value of post-PCI QFR was 0.92 ± 0.13. Receiver operator characteristic curve analysis shown the optimal cutoff value of post-PCI QFR for predicting 2-year VOCEs was 0.91. The incidence of 2-year VOCEs in the vessel with post-PCI QFR < 0.91 (n = 91) was significantly higher compared with the vessels with post-PCI QFR ≥ 0.91 (n = 262) (22.0% vs. 4.2%, HR = 4.98, 95% CI: 2.32-10.70). CONCLUSIONS Higher post-PCI QFR values were associated with improved prognosis in the PCI practice for coronary CTO. Achieving functionally optimal PCI results (post-PCI QFR value ≥ 0.91) tends to get better prognosis for patients with CTO lesions.