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.

ObjectiveTo investigate the value of different noninvasive diagnostic models in the diagnosis of esophageal and gastric varices since there is a high risk of esophageal and gastric varices in patients with compensated hepatitis B cirrhosis and significant portal hypertension， and to provide a basis for the early diagnosis of esophageal and gastric varices. MethodsA total of 108 patients with significant portal hypertension due to compensated hepatitis B cirrhosis who attended Guangdong Provincial Hospital of Traditional Chinese Medicine from November 2017 to November 2023 were enrolled， and according to the presence or absence of esophageal and gastric varices under gastroscopy， they were divided into esophageal and gastric varices group （GOV group） and non-esophageal and gastric varices group （NGOV group）. Related data were collected， including age， sex， imaging findings， and laboratory markers. The chi-square test was used for comparison of categorical data between groups； the least significant difference t-test was used for comparison of normally distributed continuous data between groups， and the Mann-Whitney U test was used for comparison of non-normally distributed continuous data between groups. The receiver operating characteristic （ROC） curve was plotted to evaluate the diagnostic value of five scoring models， i.e.， fibrosis-4 （FIB-4）， LOK index， LPRI， aspartate aminotransferase-to-platelet ratio index （APRI）， and aspartate aminotransferase/alanine aminotransferase ratio （AAR）. The binary logistic regression method was used to establish a combined model， and the area under the ROC curve （AUC） was compared between the combined model and each scoring model used alone. The Delong test was used to compare the AUC value between any two noninvasive diagnostic models. ResultsThere were 55 patients in the GOV group and 53 patients in the NGOV group. Compared with the NGOV group， the GOV group had a significantly higher age （52.64±1.44 years vs 47.96±1.68 years， t=0.453， P<0.05） and significantly lower levels of alanine aminotransferase ［42.00 （24.00 — 17.00） U/L vs 82.00 （46.00 — 271.00） U/L， Z=-3.065， P<0.05］， aspartate aminotransferase ［44.00 （32.00 — 96.00） U/L vs 62.00 （42.50 — 154.50） U/L，Z=-2.351， P<0.05］， and platelet count ［100.00 （69.00 — 120.00）×10⁹/L vs 119.00 （108.50 — 140.50）×10⁹/L， Z=-3.667， P<0.05］. The ROC curve analysis showed that FIB-4， LOK index， LPRI， and AAR used alone had an accuracy of 0.667， 0.681， 0.730， and 0.639， respectively， in the diagnosis of esophageal and gastric varices （all P<0.05）， and the positive diagnostic rates of GOV were 69.97%， 65.28%， 67.33%， and 58.86%， respectively， with no significant differences in AUC values （all P>0.05）， while APRI used alone had no diagnostic value （P>0.05）. A combined model （LAF） was established based on the binary logistic regression analysis and had an AUC of 0.805 and a positive diagnostic rate of GOV of 75.80%， with a significantly higher AUC than FIB-4， LOK index， LPRI， and AAR used alone （Z=-2.773，-2.479，-2.206， and-2.672， all P<0.05）. ConclusionFIB-4， LOK index， LPRI， and AAR have a similar diagnostic value for esophageal and gastric varices in patients with compensated hepatitis B cirrhosis and significant portal hypertension， and APRI alone has no diagnostic value. The combined model LAF had the best diagnostic efficacy， which provides a certain reference for clinical promotion and application.

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 mechanism by which hypoxia-inducible factor(HIF)-1α and circ-UBE2G1 mutually regulate and promote thyroid cancer(THCA)metastasis under hypoxic microenvironment.Methods The GEPIA database was used to analyze the expression characteristics and correlation between circ-UBE2G1 and HIF-1α in THCA.The relationship of circ-UBE2G1 and miR-330-3p with survival rate was analyzed using Kaplan-Meier survival curve.After THCA cells were exposed to hypoxia,HIF-1α was silenced by transfection to analyze its regulation for circ-UBE2G1 transcription.The targeting relationship between miR-330-3p and either circ-UBE2G1 or HIF-1α was verified by sequence prediction and dual luciferase reporter assay.The effects of HIF-1α overexpression and circ-UBE2G1 silencing on THCA cell migration and invasion were analyzed after corresponding transfections.A tumor-bearing nude mouse model was established by subcutaneous injection of THCA cells with HIF-1α overexpression and circ-UBE2G1 silencing,respectively.THCA tissues and adjacent normal samples were clinically collected to analyze the expression levels and correlations of circ-UBE2G1,miR-330-3p,and HIF-1α.Results Bioinformatics analysis showed that circ-UBE2G1 was positively correlated with HIF-1α(P<0.01),and its high expression was associated with a low survival rate in THCA patients(P=0.024).Inhibition of HIF-1α blocked the promotive effect of hypoxia on circ-UBE2G1(P<0.05).Silencing circ-UBE2G1 inhibited the migration and invasion of THCA cells(P<0.05),and reversed the promotive effect of HIF-1α on these processes(P<0.05).Dual luciferase reporter gene assay revealed that miR-330-3p targeted both circ-UBE2G1 and HIF-1α(P<0.05).Silencing circ-UBE2G1 led to increased levels of miR-330-3p(P<0.05),whereas increasing miR-330-3p inhibited the expression of HIF-1α(P<0.05).In clinical THCA samples,both circ-UBE2G1 and HIF-1α were increased and positively correlated(P<0.05),while miR-330-3p was lowly expressed and negatively correlated with both circ-UBE2G1 and HIF-1α(P<0.05).Conclusion Hypoxia promotes the transcription of circ-UBE2G1 by inducing HIF-1α expression,and circ-UBE2G1 promotes HIF-1α expression by targeting miR-330-3p,thereby promoting THCA metastasis.

OBJECTIVES: Stress urinary incontinence (SUI) is a common condition among women that severely impairs quality of life. Pelvic floor proprioceptive training (PFPT) has attracted increasing attention for its potential to enhance pelvic floor muscle function and alleviate SUI symptoms. This study aims to observe and compare the clinical efficacy of PFPT combined with electroacupuncture, electrical stimulation, and biofeedback therapy versus conventional therapy consisting of electroacupuncture, electrical stimulation, and biofeedback alone in women with SUI, and to explore the role of PFPT in improving symptom and functional outcomes. METHODS: In this randomized controlled trial, 72 women with mild to moderate SUI were recruited from the Department of Rehabilitation Medicine at Third Xiangya Hospital, Central South University, between December 2021 and October 2023. Participants were randomly assigned to an experimental group (n=36) or a control group (n=36). Both groups received health education. The control group underwent electroacupuncture combined with electrical stimulation and biofeedback therapy, while the experimental group additionally received PFPT 3 times per week for 4 weeks. The primary outcome was assessed using the International Consultation on Incontinence Questionnaire-Short Form (ICIQ-SF). Secondary outcomes included pelvic floor muscle strength, bladder neck mobility, and balance ability. The ICIQ-SF was reassessed at 1, 3, 6, and 12 months post-treatment. RESULTS: Both groups showed statistically significant improvements in all parameters after treatment (all P<0.05). However, there were no statistically significant differences between groups in most measures (all P>0.05). The experimental group demonstrated longer single-leg stance duration with eyes closed than the control group (left leg: P=0.026; right leg: P=0.006), with a significant increase from baseline (P<0.001). At 6 months post-treatment, the cure rate in the experimental group was significantly higher than that in the control group (P=0.037). CONCLUSIONS Conventional therapy effectively improves SUI symptoms, but adding PFPT provides notable additional benefits, including enhanced balance ability and sustained mid-term cure rates. These findings suggest that PFPT is a valuable adjunct to standard SUI management strategies.
Humans ; Female ; Urinary Incontinence, Stress/physiopathology* ; Pelvic Floor/physiopathology* ; Middle Aged ; Biofeedback, Psychology ; Adult ; Exercise Therapy/methods* ; Proprioception ; Electroacupuncture/methods* ; Quality of Life ; Electric Stimulation Therapy/methods* ; Treatment Outcome ; Combined Modality Therapy

Objective:To analyze the distribution, drug resistance, and factors influencing pathogenic microorganisms in patients with hepatitis B virus-associated acute-on-chronic liver failure (HBV-ACLF) combined with intra-abdominal infection (IAI).Methods:A retrospective analysis was conducted on 282 cases with HBV-ACLF admitted to the Hepatobiliary Internal Medicine Department of Mengchao Hepatobiliary Hospital of Fujian Medical University from May 2019 to December 2022. Patients combined with IAI and positive pathogen culture were enrolled in the infection group (141 cases), and patients combined without IAI admitted during the same period were included in the non-infection group (141 cases). Patient's general clinical data, laboratory examination indicators, pathogen types, and drug sensitivity test results were collected. Logistic regression analysis was used for IAI occurrence risk factors in patients with HBV-ACLF.Results:A total of 204 pathogenic bacteria were detected in the infection group, including 115 strains of Gram-negative bacteria (56.37%), 74 strains of Gram-positive bacteria (36.28%), and 15 strains of fungi (7.35%). The most frequently detected bacterial genera were Escherichia coli (21.57%, 44/204), Klebsiella pneumoniae (12.25%, 25/204), Enterococcus faecium (6.37%, 13/204), Staphylococcus aureus (5.39%, 11/204), and Staphylococcus epidermidis (4.90%, 10/204). The results of drug sensitivity tests showed that the resistance rates of Escherichia coli and Klebsiella pneumoniae to levofloxacin and ciprofloxacin were over 50% (66.67%,26/39;61.54%,24/39)and 30% (34.79%,8/23;39.13%,9/23)respectively. The resistance rate of Pseudomonas aeruginosa to carbapenems ( meropenem and imipenem) was 60.00%. The resistance rates of Acinetobacter baumannii to meropenem and imipenem were 100% (4/4) and 50.00% (2/4) respectively. The resistance rates of Enterococcus faecium and Enterococcus faecalis to penicillin were 100% (13/13) and 33.33% (1/3) respectively. The resistance rates of Staphylococcus aureus to penicillin (77.78%,7/9) and oxacillin (33.33%, 3/9) were relatively high. The results of the multivariate unconditional logistic regression analysis showed that puncture and drainage ( OR=17.90, 95% CI: 7.94-43.42, P<0.001), procalcitonin ( OR=3.23, 95% CI: 1.56-8.98, P=0.012), C-reactive protein ( OR=1.05, 95% CI: 1.02-1.00, P=0.003), and age ( OR=1.06, 95% CI: 1.02-1.10, P=0.001) were independent risk factors for IAI in patients with HBV-ACLF. Conclusions:The pathogenic microorganisms were mainly enterobacteriaceae and enterococci with varying degrees of drug resistance in HBV-ACLF patients combined with IAI. Early-stage intervention is an effective measure to prevent the occurrence of increase of inflammatory indicators in patients with intra-abdominal infection with HBV-ACLF.

Objective:To analyze the distribution, drug resistance, and factors influencing pathogenic microorganisms in patients with hepatitis B virus-associated acute-on-chronic liver failure (HBV-ACLF) combined with intra-abdominal infection (IAI).Methods:A retrospective analysis was conducted on 282 cases with HBV-ACLF admitted to the Hepatobiliary Internal Medicine Department of Mengchao Hepatobiliary Hospital of Fujian Medical University from May 2019 to December 2022. Patients combined with IAI and positive pathogen culture were enrolled in the infection group (141 cases), and patients combined without IAI admitted during the same period were included in the non-infection group (141 cases). Patient's general clinical data, laboratory examination indicators, pathogen types, and drug sensitivity test results were collected. Logistic regression analysis was used for IAI occurrence risk factors in patients with HBV-ACLF.Results:A total of 204 pathogenic bacteria were detected in the infection group, including 115 strains of Gram-negative bacteria (56.37%), 74 strains of Gram-positive bacteria (36.28%), and 15 strains of fungi (7.35%). The most frequently detected bacterial genera were Escherichia coli (21.57%, 44/204), Klebsiella pneumoniae (12.25%, 25/204), Enterococcus faecium (6.37%, 13/204), Staphylococcus aureus (5.39%, 11/204), and Staphylococcus epidermidis (4.90%, 10/204). The results of drug sensitivity tests showed that the resistance rates of Escherichia coli and Klebsiella pneumoniae to levofloxacin and ciprofloxacin were over 50% (66.67%,26/39;61.54%,24/39)and 30% (34.79%,8/23;39.13%,9/23)respectively. The resistance rate of Pseudomonas aeruginosa to carbapenems ( meropenem and imipenem) was 60.00%. The resistance rates of Acinetobacter baumannii to meropenem and imipenem were 100% (4/4) and 50.00% (2/4) respectively. The resistance rates of Enterococcus faecium and Enterococcus faecalis to penicillin were 100% (13/13) and 33.33% (1/3) respectively. The resistance rates of Staphylococcus aureus to penicillin (77.78%,7/9) and oxacillin (33.33%, 3/9) were relatively high. The results of the multivariate unconditional logistic regression analysis showed that puncture and drainage ( OR=17.90, 95% CI: 7.94-43.42, P<0.001), procalcitonin ( OR=3.23, 95% CI: 1.56-8.98, P=0.012), C-reactive protein ( OR=1.05, 95% CI: 1.02-1.00, P=0.003), and age ( OR=1.06, 95% CI: 1.02-1.10, P=0.001) were independent risk factors for IAI in patients with HBV-ACLF. Conclusions:The pathogenic microorganisms were mainly enterobacteriaceae and enterococci with varying degrees of drug resistance in HBV-ACLF patients combined with IAI. Early-stage intervention is an effective measure to prevent the occurrence of increase of inflammatory indicators in patients with intra-abdominal infection with HBV-ACLF.

Objective:To evaluate the efficacy and safety of oliceridine for treatment of moderate to severe pain after surgery with general anesthesia in patients.Methods:The patients with moderate to severe pain (numeric pain rating scale ≥4) after abdominal surgery with general anesthesia from 14 hospitals between July 6, 2021 and November 9, 2021 were included in this study. The patients were assigned to either experiment group or control group using a random number table method. Experiment group received oliceridine, while control group received morphine, and both groups were treated with a loading dose plus patient-controlled analgesia and supplemental doses for 24 h. The primary efficacy endpoint was the drug response rate within 24 h after giving the loading dose. Secondary efficacy endpoints included early (within 1 h after giving the loading dose) drug response rates and use of rescue medication. Safety endpoints encompassed the development of respiratory depression and other adverse reactions during treatment.Results:After randomization, both the full analysis set and safety analysis set comprised 180 cases, with 92 in experiment group and 88 in control group. The per-protocol set included 170 cases, with 86 in experiment group and 84 in control group. There were no statistically significant differences between the two groups in 24-h drug response rates, rescue analgesia rates, respiratory depression, and incidence of other adverse reactions ( P>0.05). The analysis of full analysis set showed that the experiment group had a higher drug response rate at 5-30 min after giving the loading dose compared to control group ( P<0.05). The per-protocol set analysis indicated that experiment group had a higher drug response rate at 5-15 min after giving the loading dose than control group ( P<0.05). Conclusions:When used for treatment of moderate to severe pain after surgery with general anesthesia in patients, oliceridine provides comparable analgesic efficacy to morphine, with a faster onset.

Objective To observe the effect of electroacupuncture(EA)on the immune balance between helper T cell 17(Th 17)/regulatory T cells(Treg)in the spleens of mice with dextran sulfate sodium(DSS)-induced ulcerative colitis(UC)by modulating the interleukin-6(IL-6)/signal transducer and activator of transcription 3(STAT3)signaling pathway,and to explore part of the mechanism of EA on treating UC.Methods Male C57BL/6N mice were randomly divided into UC model group,EA group,and sham acupuncture(SA)group,with 10 mice in each group,and 10 mice in the blank control group.After establishing the UC model mice by DSS free-drinking method,bilateral"Tianshu(ST25)"and"Shangjiuxu(ST37)"were selected for EA or SA treatment for 20 min each time,with a total of 10 times.The general condition and disease activity index(DAI)of the mice in each group were observed,the pathological changes of colon tissue were observed by HE staining,the levels of IL-6,IL-10 and IL-17 in serum were detected by ELISA,and the protein expression levels of IL-6,STAT3,retinoic acid-related orphan receptor gamma t(RORγt)and Forkhead box protein P3(FoxP3)were detected by Western blot in the colon tissue.Results Compared with the blank group,mice in the model group had significantly higher DAI scores(P＜0.01),with colonic mucosal rupture and massive inflammatory cell infiltration.Significant increases were detected in serum IL-6 and IL-17 levels(P＜0.01),with significant reductions in IL-10 levels(P＜0.01).Significant increases were detected in the expression of IL-6,STAT3,and RORγt in colonic tissues(P＜0.01),with the decreased expression of FoxP3(P＜0.05).The percentage of Th17 cells in the spleen was increased and the percentage of Treg cells was decreased(P＜0.05).Compared with the model group,mice in the EA group had lower DAI scores(P＜0.05),with reduced colonic injury,decreased inflammatory infiltration.Decreased serum IL-6 and IL-17 levels,with increased IL-10 levels(P＜0.05)were detected.Significantly lower IL-6,STAT3,and RORγt expression in the colonic tissues(P＜0.01),and increased FoxP3 expression(P＜0.05)were detected,as well as the decreased percentage of Th17 cells and increased percentage of Treg cells in spleen(P＜0.05).However,the colonic injury of mice in the SA group did not show any improvement,and no statistical difference was observed in these indexes compared with the model group.Conclusion EA may exert a therapeutic effect on UC by down-regulating the IL-6/STAT3 signaling pathway and promoting the restoration of immune balance by Th17/Treg,thereby diminishing intestinal inflammation in UC mice.