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 investigate the expression and clinical significance of urinary C-X-C motif chemokine ligand 10(CXCL10)and C-X-C motif chemokine ligand 16(CXCL16)in patients with idiopathic membranous nephropathy(IMN).Methods:A total of 131 patients with IMN(IMN group)who were treated in Zhejiang Provincial Corps Hospital of the Chinese People's Armed Police Force from December 2020 to June 2022 were prospectively selected,131 healthy volunteers(control group)who underwent physical examination during the same period were selected.Patients with IMN were divided into stage Ⅰ group(25 cases),stage Ⅱ group(68 cases),stage Ⅲ group(22 cases)and stage Ⅳ group(16 cases)according to pathological staging,patients were divided into non-remission group(33 cases)and remission group(98 cases)based on the therapeutic efficacy after a 2-year follow-up.Urinary CXCL10 and CXCL16 levels were measured by enzyme-linked immunosorbent assay.Clinical data of patients with IMN were collected,The relationship between urinary CXCL10,CXCL16 levels and pathological staging in patients with IMN was analysied by Spearman/pearson correlation.Multivariate logistic regression analysis influencing factors on non-remission treatment in patients with IMN,and receiver operating characteristic(ROC)curves were used to assess the predictive value Of urinary CXCL10,CXCL16 levels for non-remission treatment in patients with IMN.Results:Urinary CXCL10 and CXCL16 levels in the IMN group were significantly higher than those in the control group(P＜0.05).Urinary CXCL10 and CXCL16 levels were the highest in stage Ⅳ group,urinary CXCL10 and CXCL16 levels in stage Ⅲ group were higher than those in stage Ⅱ group and stage Ⅰ group,and urinary CXCL10 and CXCL16 levels in stage Ⅱ group were higher than those in stage Ⅰ group(P＜0.05).Urinary CXCL10 and CXCL16 levels in patients with IMN were positively correlated with pathological staging,urinary CXCL10 were positively correlated with CXCL16(P＜0.05).Urinary CXCL10 and CXCL16 in non-remission group were higher than those in the remission group(P＜0.05).pathological staging Ⅲ～Ⅳ,elevated 24 h urine protein level,and elevated urinary CXCL10 and CXCL16 levels were independent risk factors for non-remission treatment in patients with IMN(P＜0.05).The areas under the curve(AUC)of urinary CXCL10 and CXCL16 levels for predicting non-remission treatment in patients with IMN alone and in combination were 0.783,0.785,and 0.875,respectively,the combined detection had the highest predictive efficacy(P＜0.05).Conclusion:Urinary CXCL10 and CXCL16 levels are elevated in patients with IMN,it is closely related to the pathological staging of patients and the therapeutic efficacy,the combined detection of urinary CXCL10 and CXCL16 has a high value in predicting the therapeutic efficacy in patients with IMN.

Objective To investigate the incidence and types of patient-ventilator asynchrony(PVA)in mechanically ventilated patients within the intensive care unit(ICU),and to identify associated high-risk factors,thereby providing a basis for reducing PVA,enhancing mechanical ventilation efficiency,and refining ventilation strategies.Methods A prospective observational study was conducted among patients admitted to the general ICU of the Affiliated Hospital of Guizhou Medical University from October to December 2024 who were receiving mechanical ventilation.Inclusion criteria were as follows:age ≥18 years and mechanical ventilation duration ≥12 hours.Exclusion criteria included complete controlled mechanical ventilation,palliative care or do-not-resuscitate status,and lack of informed consent.Senior respiratory therapists performed daily bedside observations of ventilator waveforms for 10～15 minutes between 08:00 and 12:00.PVA was diagnosed based on pressure-time and flow-time waveforms,with the types of PVA being recorded.Demographic and clinical data,including age,sex,body mass index(BMI),primary diagnosis,comorbidities,APACHEⅡ score at ICU admission,blood gas analysis,ventila-tion mode and parameters,analgesia and sedation status,duration of mechanical ventilation,and length of ICU stay,were collected.The incidence and types of PVA during the observation period were analyzed.Univariate and multivariate logistic regression analyses were performed to identify high-risk factors for PVA.Clinical outcomes were compared between patients with and without PVA.Results A total of 105 patients and 453 episodes of assisted mechanical ventilation waveforms were analyzed.Among these,60.95％(64/105)experienced at least one episode of PVA.Of the 453 ventilation waveforms assessed,35.76％(162/453)demonstrated PVA.The types of PVA,ranked by incidence,were as follows:cycling mismatch(12.58％,57/453),double triggering(11.92％,54/453),ineffective triggering(9.49％,43/453),flow starvation(5.30％,24/453),and exhalation flow limitation(1.77％,8/453).The incidence of PVA varied significantly across different ventilation modes:45.7％in volume-assist/control ventilation(V-A/C),38.1％in pressure-assist/control ventilation(P-A/C),42.9％in synchronized intermittent mandatory ventilation(SIMV),and 16.7％in pressure support ventilation(PSV)(P<0.001).Multi-variate logistic regression analysis revealed that the mechanical ventilation mode[reference:PSV;V-A/C:OR=4.687,95％CI:2.140～10.263,P<0.001;P-A/C:OR=2.922,95％CI:1.489～5.734,P=0.002;SIMV:OR=4.682,95％CI:1.758～12.466,P=0.002]and actual respiratory rate(OR=1.07,95％CI:1.016～1.127,P=0.011)were significant high-risk factors for PVA.Patients with PVA had a significantly longer duration of mechanical ventilation[8.21(5.35,13.91)days vs.3.00(1.96,5.71)days,P<0.001]compared to those without PVA.Conclusions PVA is commonly observed in ICU patients receiving assisted invasive mechanical ventilation,with cycling mismatch,double triggering,and ineffective triggering being the most prevalent types.The incidence of PVA tends to be lower when using the PSV mode.Clinically,real-time monitoring of patient-ventilator synchrony via ventilator waveforms,along with the optimization of ventilator modes and parameters,should be employed to minimize the occurrence of PVA and enhance the efficiency of mechanical ventilation.

A mounting body of research suggests that circRNAs significantly contribute to the develop-ment of myocardial fibrosis.The microarray results of human circular RNA expression profile indicated that circHERC4_041 expression increased in the myocardium of patients with heart failure,RT-qPCR a-nalysis confirmed that the myocardial expression level of circHERC4_041 in individuals with heart failure were considerably elevated compared to that in healthy organ donors.Fluorescence in situ hybridization(FISH)confirmed that circHERC4_041 was abundant in the cytoplasm of human cardiomyocyte AC16.Overexpression of circHERC4_041 in mouse myocardial fibroblasts(mCFs)mediated by adenovirus in-hibited the expression of fibrosis-related proteins in mCFs.Experiments involving cell proliferation,wound healing,and Transwell assays demonstrated that overexpression of circHERC4_041 suppressed the growth and mobility of mCFs(P＜0.001).Sequence analysis results suggested that circHERC4_041 con-tains potential ribosome entry sequence(IRES)and open reading frame(ORF).Western blot confirmed that circHERC4_041 could translate the 516 amino acid HERC4-516aa protein,which was mainly located in the cytoplasm of the cell.Cell functional experiments confirmed that circHERC4_041 inhibited the fi-brotic phenotype of mCFs by specifically translating HERC4-516aa(P＜0.05).The specific interaction between HERC4-516aa and transglutaminase 2(TGM2)was confirmed by IP-MS screening and Co-IP i-dentification.Further results found that the degradation of TGM2 was promoted through proteasome path-way.The overexpression of TGM2 in mCFs facilitated by adenoviral vectors could counteract the suppres-sive effects of HERC4-516aa on the fibrotic phenotype of mCFs.Therefore,this study confirmed that the HERC4-516aa protein translated by circHERC4_041 can specifically bind to TGM2 to inhibit the fibrotic phenotype of myocardial fibroblasts.

A mounting body of research suggests that circRNAs significantly contribute to the develop-ment of myocardial fibrosis.The microarray results of human circular RNA expression profile indicated that circHERC4_041 expression increased in the myocardium of patients with heart failure,RT-qPCR a-nalysis confirmed that the myocardial expression level of circHERC4_041 in individuals with heart failure were considerably elevated compared to that in healthy organ donors.Fluorescence in situ hybridization(FISH)confirmed that circHERC4_041 was abundant in the cytoplasm of human cardiomyocyte AC16.Overexpression of circHERC4_041 in mouse myocardial fibroblasts(mCFs)mediated by adenovirus in-hibited the expression of fibrosis-related proteins in mCFs.Experiments involving cell proliferation,wound healing,and Transwell assays demonstrated that overexpression of circHERC4_041 suppressed the growth and mobility of mCFs(P＜0.001).Sequence analysis results suggested that circHERC4_041 con-tains potential ribosome entry sequence(IRES)and open reading frame(ORF).Western blot confirmed that circHERC4_041 could translate the 516 amino acid HERC4-516aa protein,which was mainly located in the cytoplasm of the cell.Cell functional experiments confirmed that circHERC4_041 inhibited the fi-brotic phenotype of mCFs by specifically translating HERC4-516aa(P＜0.05).The specific interaction between HERC4-516aa and transglutaminase 2(TGM2)was confirmed by IP-MS screening and Co-IP i-dentification.Further results found that the degradation of TGM2 was promoted through proteasome path-way.The overexpression of TGM2 in mCFs facilitated by adenoviral vectors could counteract the suppres-sive effects of HERC4-516aa on the fibrotic phenotype of mCFs.Therefore,this study confirmed that the HERC4-516aa protein translated by circHERC4_041 can specifically bind to TGM2 to inhibit the fibrotic phenotype of myocardial fibroblasts.

Objective:To explore the clinical efficacy of Shexiang Baoxin pill in patients with unstable angina pectoris(UAP)and type 2 diabetes mellitus(T2DM)using meta-analysis.Methods:We searched the databases including Pubmed,Web of Science,EMbase,EBSCO,Cochrane,CBM,CNKI and Wanfang for randomized controlled trials(RCTs)about the therapeutic effect of Shexiang Baoxin pill on patients with UAP and T2DM from the establish-ment to January 20th,2023.RevMan 5.3 software was used to perform meta-analysis to investigate the effect of Shexiang Baoxin pill on angina improvement and blood glucose fluctuation in patients with UAP and T2DM.Results:Six eligible literatures were included,including 346 patients in Shexiang Baoxin pill group and control group respec-tively.The results of meta-analysis showed that compared to participants in control group,those in Shexiang Baox-in pill group had significantly higher clinical overall efficiency(OR=3.13,95％CI 2.01～4.89,P＜0.001),and significantly lower angina attack frequency(MD=-0.66,95％CI-0.79～-0.52,P＜0.001),duration of angi-na(MD=-3.10,95％CI-4.11～-2.09,P＜0.001),and 2-hour postprandial blood glucose(MD=-1.79,95％CI-2.00～-1.57,P＜0.001).Conclusion:Shexiang Baoxin pill could improve clinical overall efficiency,an-gina attack frequency and duration,and reduce 2-hour postprandial blood glucose in patients with unstable angina pectoris and type 2 diabetes mellitus.

Objective:To explore the clinical efficacy of Shexiang Baoxin pill in patients with unstable angina pectoris(UAP)and type 2 diabetes mellitus(T2DM)using meta-analysis.Methods:We searched the databases including Pubmed,Web of Science,EMbase,EBSCO,Cochrane,CBM,CNKI and Wanfang for randomized controlled trials(RCTs)about the therapeutic effect of Shexiang Baoxin pill on patients with UAP and T2DM from the establish-ment to January 20th,2023.RevMan 5.3 software was used to perform meta-analysis to investigate the effect of Shexiang Baoxin pill on angina improvement and blood glucose fluctuation in patients with UAP and T2DM.Results:Six eligible literatures were included,including 346 patients in Shexiang Baoxin pill group and control group respec-tively.The results of meta-analysis showed that compared to participants in control group,those in Shexiang Baox-in pill group had significantly higher clinical overall efficiency(OR=3.13,95％CI 2.01～4.89,P＜0.001),and significantly lower angina attack frequency(MD=-0.66,95％CI-0.79～-0.52,P＜0.001),duration of angi-na(MD=-3.10,95％CI-4.11～-2.09,P＜0.001),and 2-hour postprandial blood glucose(MD=-1.79,95％CI-2.00～-1.57,P＜0.001).Conclusion:Shexiang Baoxin pill could improve clinical overall efficiency,an-gina attack frequency and duration,and reduce 2-hour postprandial blood glucose in patients with unstable angina pectoris and type 2 diabetes mellitus.

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.