Background: s/Aims: Non-invasive models stratifying clinically significant portal hypertension (CSPH) are limited. Herein, we developed a new non-invasive model for predicting CSPH in patients with compensated cirrhosis and investigated whether carvedilol can prevent hepatic decompensation in patients with high-risk CSPH stratified using the new model. Methods: Non-invasive risk factors of CSPH were identified via systematic review and meta-analysis of studies involving patients with hepatic venous pressure gradient (HVPG). A new non-invasive model was validated for various performance aspects in three cohorts, i.e., a multicenter HVPG cohort, a follow-up cohort, and a carvediloltreating cohort. Results: In the meta-analysis with six studies (n=819), liver stiffness measurement and platelet count were identified as independent risk factors for CSPH and were used to develop the new “CSPH risk” model. In the HVPG cohort (n=151), the new model accurately predicted CSPH with cutoff values of 0 and –0.68 for ruling in and out CSPH, respectively. In the follow-up cohort (n=1,102), the cumulative incidences of decompensation events significantly differed using the cutoff values of <–0.68 (low-risk), –0.68 to 0 (medium-risk), and >0 (high-risk). In the carvediloltreated cohort, patients with high-risk CSPH treated with carvedilol (n=81) had lower rates of decompensation events than non-selective beta-blockers untreated patients with high-risk CSPH (n=613 before propensity score matching [PSM], n=162 after PSM). Conclusions Treatment with carvedilol significantly reduces the risk of hepatic decompensation in patients with high-risk CSPH stratified by the new model.

Background: s/Aims: Non-invasive models stratifying clinically significant portal hypertension (CSPH) are limited. Herein, we developed a new non-invasive model for predicting CSPH in patients with compensated cirrhosis and investigated whether carvedilol can prevent hepatic decompensation in patients with high-risk CSPH stratified using the new model. Methods: Non-invasive risk factors of CSPH were identified via systematic review and meta-analysis of studies involving patients with hepatic venous pressure gradient (HVPG). A new non-invasive model was validated for various performance aspects in three cohorts, i.e., a multicenter HVPG cohort, a follow-up cohort, and a carvediloltreating cohort. Results: In the meta-analysis with six studies (n=819), liver stiffness measurement and platelet count were identified as independent risk factors for CSPH and were used to develop the new “CSPH risk” model. In the HVPG cohort (n=151), the new model accurately predicted CSPH with cutoff values of 0 and –0.68 for ruling in and out CSPH, respectively. In the follow-up cohort (n=1,102), the cumulative incidences of decompensation events significantly differed using the cutoff values of <–0.68 (low-risk), –0.68 to 0 (medium-risk), and >0 (high-risk). In the carvediloltreated cohort, patients with high-risk CSPH treated with carvedilol (n=81) had lower rates of decompensation events than non-selective beta-blockers untreated patients with high-risk CSPH (n=613 before propensity score matching [PSM], n=162 after PSM). Conclusions Treatment with carvedilol significantly reduces the risk of hepatic decompensation in patients with high-risk CSPH stratified by the new model.

Background: s/Aims: Non-invasive models stratifying clinically significant portal hypertension (CSPH) are limited. Herein, we developed a new non-invasive model for predicting CSPH in patients with compensated cirrhosis and investigated whether carvedilol can prevent hepatic decompensation in patients with high-risk CSPH stratified using the new model. Methods: Non-invasive risk factors of CSPH were identified via systematic review and meta-analysis of studies involving patients with hepatic venous pressure gradient (HVPG). A new non-invasive model was validated for various performance aspects in three cohorts, i.e., a multicenter HVPG cohort, a follow-up cohort, and a carvediloltreating cohort. Results: In the meta-analysis with six studies (n=819), liver stiffness measurement and platelet count were identified as independent risk factors for CSPH and were used to develop the new “CSPH risk” model. In the HVPG cohort (n=151), the new model accurately predicted CSPH with cutoff values of 0 and –0.68 for ruling in and out CSPH, respectively. In the follow-up cohort (n=1,102), the cumulative incidences of decompensation events significantly differed using the cutoff values of <–0.68 (low-risk), –0.68 to 0 (medium-risk), and >0 (high-risk). In the carvediloltreated cohort, patients with high-risk CSPH treated with carvedilol (n=81) had lower rates of decompensation events than non-selective beta-blockers untreated patients with high-risk CSPH (n=613 before propensity score matching [PSM], n=162 after PSM). Conclusions Treatment with carvedilol significantly reduces the risk of hepatic decompensation in patients with high-risk CSPH stratified by the new model.

Objective To monitor the susceptibility of clinical isolates to antimicrobial agents in tertiary hospitals in major regions of China in 2022.Methods Clinical isolates from 58 hospitals in China were tested for antimicrobial susceptibility using a unified protocol based on disc diffusion method or automated testing systems.Results were interpreted using the 2022 Clinical &Laboratory Standards Institute(CLSI)breakpoints.Results A total of 318 013 clinical isolates were collected from January 1,2022 to December 31,2022,of which 29.5％were gram-positive and 70.5％were gram-negative.The prevalence of methicillin-resistant strains in Staphylococcus aureus,Staphylococcus epidermidis and other coagulase-negative Staphylococcus species(excluding Staphylococcus pseudintermedius and Staphylococcus schleiferi)was 28.3％,76.7％and 77.9％,respectively.Overall,94.0％of MRSA strains were susceptible to trimethoprim-sulfamethoxazole and 90.8％of MRSE strains were susceptible to rifampicin.No vancomycin-resistant strains were found.Enterococcus faecalis showed significantly lower resistance rates to most antimicrobial agents tested than Enterococcus faecium.A few vancomycin-resistant strains were identified in both E.faecalis and E.faecium.The prevalence of penicillin-susceptible Streptococcus pneumoniae was 94.2％in the isolates from children and 95.7％in the isolates from adults.The resistance rate to carbapenems was lower than 13.1％in most Enterobacterales species except for Klebsiella,21.7％-23.1％of which were resistant to carbapenems.Most Enterobacterales isolates were highly susceptible to tigecycline,colistin and polymyxin B,with resistance rates ranging from 0.1％to 13.3％.The prevalence of meropenem-resistant strains decreased from 23.5％in 2019 to 18.0％in 2022 in Pseudomonas aeruginosa,and decreased from 79.0％in 2019 to 72.5％in 2022 in Acinetobacter baumannii.Conclusions The resistance of clinical isolates to the commonly used antimicrobial agents is still increasing in tertiary hospitals.However,the prevalence of important carbapenem-resistant organisms such as carbapenem-resistant K.pneumoniae,P.aeruginosa,and A.baumannii showed a downward trend in recent years.This finding suggests that the strategy of combining antimicrobial resistance surveillance with multidisciplinary concerted action works well in curbing the spread of resistant bacteria.

Objective To monitor the antifungal resistance of clinical isolates of Candida spp.in the East China region.Methods MALDI-TOF MS or molecular methods were used to re-identify the strains collected from January 2018 to December 2022.Antifungal susceptibility testing was performed using the broth microdilution method.The susceptibility test results were interpreted according to the breakpoints of 2022 Clinical and Laboratory Standards Institute(CLSI)documents M27 M44s-Ed3 and M57s-Ed4.Results A total of 3 026 strains of Candida were collected,65.33％of which were isolated from sterile body sites,mainly from blood(38.86％)and pleural effusion/ascites(10.21％).The predominant species of Candida were Candida albicans(44.51％),followed by Candida parapsilosis complex(19.46％),Candida tropicalis(13.98％),Candida glabrata(10.34％),and other Candida species(0.79％).Candida albicans showed overall high susceptibility rates to the 10 antifungal drugs tested(the lowest rate being 93.62％).Only 2.97％of the strains showed dose-dependent susceptibility(SDD)to fluconazole.Candida parapsilosis complex had a SDD rate of 2.61％and a resistance rate of 9.42％to fluconazole,and susceptibility rates above 90％to other drugs.Candida glabrata had a SDD rate of 92.01％and a resistance rate of 7.99％to fluconazole,resistance rates of 32.27％and 48.24％to posaconazole and voriconazole non-wild-type strains(NWT),respectively,and susceptibility rates above 90％to other drugs.Candida tropicalis had resistance rates of 29.55％and 26.24％to fluconazole and voriconazole,respectively,resistance rates of 76.60％and 21.99％to posaconazole and echinocandins non-wild-type strains(NWT),and a resistance rate of 2.36％to echinocandins.Conclusions The prevalence and species distribution of Candida spp.in the East China region are consistent with previous domestic and international reports.Candida glabrata exhibits certain degree of resistance to fluconazole,while Candida tropicalis demonstrates higher resistance to triazole drugs.Additionally,echinocandins resistance has emerged in Candida albicans,Candida glabrata,Candida tropicalis,and Candida parapsilosis.

Objective:We aimed to develop a novel visualized model based on nomogram to predict postoperative overall survival.Methods:This was a multicenter, retrospective, observational cohort study, including participants with histologically confirmed gastric and colorectal cancer who underwent radical surgery from 11 medical centers in China from August 1, 2015 to June 30, 2018. Baseline characteristics, histopathological data and nutritional status, as assessed using Nutrition Risk Screening 2002 (NRS 2002) score and the scored Patient-Generated Subjective Global Assessment, were collected. The least absolute shrinkage and selection operator regression and Cox regression were used to identify variables to be included in the predictive model. Internal and external validations were performed.Results:There were 681 and 127 patients in the training and validation cohorts, respectively. A total of 188 deaths were observed over a median follow-up period of 59 (range: 58 to 60) months. Two independent predictors of NRS 2002 and Tumor-Node-Metastasis (TNM) stage were identified and incorporated into the prediction nomogram model together with the factor of age. The model's concordance index for 1-, 3- and 5-year overall survival was 0.696, 0.724, and 0.738 in the training cohort and 0.801, 0.812, and 0.793 in the validation cohort, respectively.Conclusions:In this study, a new nomogram prediction model based on NRS 2002 score was developed and validated for predicting the overall postoperative survival of patients with gastric colorectal cancer. This model has good differentiation, calibration and clinical practicability in predicting the long-term survival rate of patients with gastrointestinal cancer after radical surgery.

The aim of this study was to clarify the genetic diversity and population history of Ixodes persulcatus in some ar-eas of Inner Mongolia in order to provide accurate data for effective vector control programs and reveal the transmission mecha-nism.Samples were collected in 10 areas of Inner Mongolia during the active tick season(April 2021-July 2023)using the flag-dragging and manual sampling methods.The 16S rRNA and COI gene were sequenced to clarify genetic diversity of I.per-sulcatus.The positivity rates for the COI gene and 16S rRNA were 90.00％and 98.33％respectively.Overall,18 and 15 haplotypes were identified for the COI gene and 16S rRNA,respectively,with a total haplotype diversity＞0.762 and total nucleotide diversity＜0.005.The Tajima's values and Fu's Fs were negative for significance.A nucleotide mismatch map was shown as a single peak.The genetic differentiation index FST of the population indicates a small degree of genetic differ-entiation of the population,while analysis of molecular vari-ance indicates that the variation within populations was greater than between populations.Phylogenetic tree and haplotype network plots showed confounding distributions between hap-lotypes.I.persulcatus from the Hinggan League and Hulun-buir regions can adapt to environmental changes and possess abundant genetic diversity.Genetic differentiation is mainly concentrated within the population and no geographical isolation was observed.

low-grade glioma(LGG)is a slow-growing primary brain tumor originating from glial cells.The overall prognosis of LGG is good but incurable.The vast majority of LGG will have relapses,and some even progress to high-grade glioma(HGG).The treatment of LGG is still controversial.The current treatment includes surgical resection,radiation therapy(RT),chemical treatment(CT),targeting and immunotherapy,but its effectiveness and safety need further clinical exploration.This article describes the treatment of LGG,including surgery,radiotherapy,chemotherapy,targeting and immunotherapy,in order to develop an individualized treatment plan and provide theoretical strategies for maximizing the survival time of patients and improving the prognosis of patients.

In mass spectrometry-based proteomics experiments,achieving high-throughput and efficientproteolytic digestion is crucial to ensure optimal protein cleavage and enhance the depth of protein identi-fication (including the number of identified proteins and the coverage of protein amino acid sequences) .Trypsin is the most widely used protease in mass spectrometry-based proteomics due to its ability to spe-cifically cleave the carboxyl terminus of arginine and lysine.However,it was found that Trypsin has some missed enzymatic efficiency for the cleavage of lysine residues.Therefore,in actual proteomics sample preparation,a combination of Trypsin and LysC will be used to ensure adequate cleavage of lysine resi-dues.Our study revealed that the commonly employed LysC-Trypsin tandem cleavage method exerts an impact on the enzymatic cleavage of protein samples by Trypsin due to the subsequent cleavage of Trypsin by initially added LysC.Consequently,we adjusted the order of LysC and Trypsin tandem digestion,with Trypsin cleavage being performed first followed by the addition of LysC to target any missed lysine resi-dues.We comprehensively compared and analyzed three distinct sequential digestion methods,namely Trypsin-Trypsin (T-T),LysC-Trypsin (L-T),and Trypsin-LysC (T-L),in terms of their effects on pro-tein sample preparation quality.The results demonstrated that the Trypsin-LysC sequential digestion ap-proach not only minimizes missed protein lysine/arginine cleavage sites without increasing experimental costs,at the same time yielding peptides with a moderate amino acid sequence length.The use of Tryp-sin-LysC digestion enhances the adsorption and separation of peptide samples in RP-HPLC,as well as improves the depth of protein detection and amino acid sequence coverage during tandem mass spectrome-try analysis.This research work offers a novel technical solution and serves as a valuable reference for proteome sample preparation.

Objective To analyze the composition of the aqueous extract of Polygonatum Cyrtonema Hua(PCHE)and evaluate its antitumor activity in vitro and in vivo.Our aim is to provide a theoretical basis for the further development and utilization of Polygonatum Cyrtonema Hua.Methods(1)PCHE was prepared by aqueous extraction,and the chemical composition of PCHE was analyzed by UPLC-Q-TOF/MS and phenol-sulfuric acid method.The inhibitory activity on tumor cells proliferation of PCHE was detected by CCK-8 assay.Cell cycle and apoptosis were detected by flow cytometry,and the expression of apoptosis-related proteins Bcl-2 and Bax was detected by Western Blot.The inhibitory activity of PCHE-containing serum on cell proliferation was detected.(2)A B16 tumor-bearing mice model was constructed and model mice were randomly divided into the model group(saline),the positive drug group(CTX:50 mg·kg-1),and PCHE low-,medium-,and high-dose groups(55.9,111.8,223.6 mg·kg-1),and treated by gavage for 7 days.Changes in body weight and tumor volume of mice were observed during the treatment period.The mice were executed after the treatment,and the histopathological changes of heart,liver,spleen,lung,kidney and tumor were observed by hematoxylin-eosin(HE)staining.The protein expression of Bcl-2 and Bax in tumor tissues was detected by immunohistochemistry(IHC).Results The polysaccharide content of PCHE reached(10.07±1.3)%,and the flavonoid content was(0.044±0.004)%,and thirty-nine components were detected by UPLC-Q-TOF/MS,which contained antitumor components such as flavonoids(baicalein,quercetin,luteolin and rutin),organic acids(ferulic acid)and polyphenols(gallic acid),etc.PCHE exhibited the inhibitory effects on Hela,A549,4T1,B16,MFC and HepG2 cells,among which the inhibitory effect on B16 cells was the most significant(P＜0.001),and PCHE induced cell cycle arrest at G0/G1 phase in B16 cells(P＜0.001).The results of double-staining flow cytometry and Western Blot showed that PCHE significantly promoted apoptosis of B16 cells,decreased the expression of Bcl-2,and promoted the expression of Bax(P＜0.01,P＜0.001).and PCHE constituents absorbed into blood also had an inhibitory effect on B16 cells(P＜0.001).In addition,the results of in vivo activity assay showed that different doses of PCHE could inhibit tumor growth,induce tumor cell necrosis,reduce Bcl-2 expression,and increase Bax expression compared with the model group.Conclusion The ingredients in PCHE are abundant.It contains a variety of antitumor active ingredients,which can inhibit tumor growth,induce tumor cell apoptosis,show strong anti-tumor effects and be worthy of in-depth study.