1.Intestinal barrier in chronic gut and liver diseases: Pathogenesis and therapeutic targets.
Yongxin ZHANG ; Yameng LIU ; Xinyu LIANG ; Yingquan WEN ; Jingjie ZHAO ; Yong HE ; Qing XIE ; Cen XIE
Acta Pharmaceutica Sinica B 2025;15(11):5515-5536
The intestinal barrier is the primary defense that separates the host from the external environment, possessing several crucial physiological functions, including nutrient digestion, absorption, and protection against potentially harmful dietary antigens and pathogenic microorganisms. Nevertheless, various factors, such as diet, medications, circadian rhythm disturbances, gut microbiota, microbial metabolites, and genetic predisposition, can disrupt the intestinal barrier. Such disruption may lead to bacterial translocation, subsequently triggering enterohepatic and systemic inflammation. Impaired intestinal barrier has been implicated in the pathogenesis of numerous diseases, particularly chronic gut and liver diseases. In this review, we will summarize the fundamental functions of intestinal barrier and discuss clinical correlations between intestinal barrier dysfunction and diseases such as colitis, colorectal cancer, and chronic liver diseases including metabolic dysfunction-associated steatohepatitis, alcohol-associated liver disease, and primary sclerosing cholangitis. Additionally, we will also highlight some potential therapeutic strategies aimed at restoring barrier integrity to improve disease management.
2.Comparative analysis of the correlation between different intestinal ultrasound score and endoscopic disease activity in Crohn's disease
Shijie SUN ; Meizheng DANG ; Jia LI ; Dantong ZHAO ; Yameng ZHENG ; Piyu LI ; Pintong HUANG
Chinese Journal of Ultrasonography 2025;34(2):167-172
Objective:To verify and compare the correlation and diagnostic efficacy of international bowel ultrasound segmental activity score(IBUS-SAS),bowel ultrasound score(BUSS),simple ultrasound score for Crohn's disease(SUS-CD),and simple ultrasound score(Simple-US)with endoscopic disease activity in Crohn's disease(CD)patients. To provide external validation of the diagnostic efficacy of intestinal ultrasound(IUS)score and theoretical basis for clinical selection of optimal IUS score.Methods:A total of 160 patients with clinical diagnosis of CD combined with IUS and intestinal endoscopy were retrospectively analyzed in the Second Affiliated Hospital of Zhejiang University School of Medicine from January 2022 to August 2024. IUS parameters were measured and scored with IBUS-SAS,SUS-CD,BUSS and Simple-US scores. Endoscopic SES-CD was used to evaluate intestinal disease activity in patients without history of intestinal resection,and Rutgeerts score was used to evaluate intestinal disease activity in patients with history of intestinal resection. Endoscopic remission in patients with CD was defined as SES-CD < 3 or Rutgeerts score i0 and i1,mild endoscopic disease activity was defined as 7 > SES-CD≥3 or Rutgeerts score = 2,moderate endoscopic disease activity was defined as 15 > SES-CD≥7 or Rutgeerts score i3,severe endoscopic disease activity was defined as SES-CD≥15 or Rutgeerts i4. The correlation and diagnostic efficacy of IBUS-SAS,SUS-CD,BUSS and Simple-US scores with endoscopic disease activity in patients with CD were compared and analyzed.Results:IUS scores including IBUS-SAS,SUS-CD,BUSS and Simple-US were significantly correlated with endoscopic intestinal disease activity,SES-CD and Rutgeerts scores in CD patients( r s = 0.706,0.492,0.502,0.526;0.825,0.581,0.584,0.603;0.541,0.434,0.437,0.467;all P<0.05). Among them,IBUS-SAS showed better correlation than the other three IUS scores. ROC curve showed that IBUS-SAS,SUS-CD,BUSS,and Simple-US had high predictive values for endoscopic disease activity and endoscopic disease moderate-severe activity in patients with CD(AUC = 0.886,0.748,0.730,0.756;all P<0.05). The diagnostic efficacy of IBUS-SAS on the presence of endoscopic disease activity in patients with CD was significantly higher than those of the other three IUS scores . Conclusions:IBUS-SAS,SUS-CD,BUSS and Simple-US are significantly correlated with the endoscopic results of on intestinal disease activity of CD,and have high predictive values for intestinal disease activity status,among which IBUS-SAS is superior to the other three IUS scores. It is recommended that IBUS-SAS be used first to evaluate intestinal disease activity in patients with CD.
3.Real-time or dynamic non-invasive liver fibrosis testing for evaluating clinical prognoses and predicting chronic liver disease
Xinyu ZHAO ; Yameng SUN ; Yankun GAO ; Zhengzhao LU ; Cheng HUANG ; Yuanyuan KONG ; Jidong JIA ; Hong YOU
Chinese Journal of Hepatology 2025;33(10):945-949
Liver fibrosis is a key histologic marker of long-term outcome in chronic liver disease. Non-invasive tests (NITs) have been shown to have predictive value, but the superiority of "dynamic" versus "static" assessment remains controversial. This article systematically reviews the latest evidence to elucidate the association between longitudinal changes in NITs and hepatic adverse events and assess the incremental contribution of dynamic monitoring to the model. Additionally, it reveals that the dynamic monitoring of NITs is truly superior to single evaluation, but the evidence is limited and the heterogeneity is significant. Dynamic modeling approaches for NITs require a shift from traditional parameter estimation to time-series machine learning. Future studies should make breakthroughs in disease stratification, modeling method innovation, data quality improvement, and prediction ability assessment so as to promote the transition of NITs from "static risk label" to "dynamic individualized engine," which can truly serve clinical decision-making.
4.Predictive role of dynamic changes in liver stiffness measurement for liver-related endpoint events in chronic hepatitis B
Chenglin SUN ; Shuyan CHEN ; Xiaoning WU ; Jialing ZHOU ; Tongtong MENG ; Bingqiong WANG ; Xinyan ZHAO ; Xiaojuan OU ; Jidong JIA ; Yameng SUN ; Hong YOU
Chinese Journal of Hepatology 2025;33(10):993-1000
Objective:To investigate the role of dynamic changes in liver stiffness measurement (LSM) in predicting liver-related end-point events (LREs) occurrence in patients with chronic hepatitis B (CHB) with liver fibrosis during long-term antiviral therapy.Methods:Data were collected from CHB patients whose liver biopsy results showed Metavir fibrosis stage F2~F4 or clinically diagnosed cirrhosis. Entecavir antiviral therapy was mainly administered. Follow-up was conducted once every six months. Clinical data such as demographic information, blood routine tests, liver biochemical parameters, HBV virological and serological test results, and LSM were collected. Dynamic changes in LSM were categorized into four types based on LSM levels before treatment (0y) and following two years of antiviral therapy (2y) : (1) LSM 0y < 10 kPa and LSM 2y < 10 kPa, i.e., LSM persisted < 10 kPa; (2) LSM 0y < 10 kPa and LSM 2y ≥ 10 kPa, i.e., LSM increased to ≥ 10 kPa; (3) LSM 0y ≥ 10 kPa and LSM 2y < 10 kPa, i.e., LSM decreased to < 10 kPa; (4) LSM 0y ≥ 10 kPa and LSM 2y ≥ 10 kPa, i.e., LSM persisted ≥ 10 kPa. The predictive role of the dynamic changes of LSM in the occurrence of LREs was analyzed. The Wilcoxon rank-sum test was used for quantitative data. Fisher's exact test was used for categorical data. Multivariate analysis was performed using the Cox proportional hazards regression model. Survival curves were plotted and compared using the Kaplan-Meier. Results:A total of 713 CHB cases with liver fibrosis were included, among whom 512 had cirrhosis. The cumulative incidence of LREs following two years of antiviral therapy was low in patients with LSM 0y < 10 kPa during follow-up (all patients: LSM persisted < 10 kPa 1.6% vs. LSM increased to ≥ 10 kPa 0%; cirrhosis subgroup: LSM persisted < 10 kPa 0% vs. LSM increased to ≥ 10 kPa 0%). The 5-year cumulative incidence of LREs following two years of antiviral treatment was significantly higher in patients with LSM0y ≥ 10 kPa than in those with LSM persisting ≥ 10 kPa and those with LSM decreasing to < 10 kPa during follow-up (all patients: LSM persisted ≥ 10 kPa 12.4% vs. LSM decreased to < 10 kPa 3.6%; cirrhosis subgroup: LSM persisted ≥ 10 kPa 12.6% vs. LSM decreased to < 10 kPa 4.3%). Patients with LSM persisting at ≥ 10 kPa had a significantly increased risk of LREs following two years of antiviral treatment compared with those whose LSM decreased to <10 kPa during follow-up after adjusting for age, gender, baseline body mass index, platelet count, and alanine aminotransferase (all patients, aHR=2.96, 95% CI: 1.41~6.24, P=0.005; cirrhosis subgroup, aHR=2.74, 95% CI:1.26~5.95, P=0.011). Conclusions:LSM<10 kPa before antiviral treatment had a lower risk of liver-related endpoint events following two years of treatment among CHB patients with liver fibrosis. LSM ≥10 kPa before antiviral treatment and LSM persisted ≥10 kPa two years following treatment had a significantly higher occurrence risk of liver-related endpoints than LSM<10 kPa following treatment among CHB patients with liver fibrosis.
5.Analysis of factors affecting fibrosis reversal in patients with metabolic associated steatohepatitis based on magnetic resonance elastography
Ziyi ZHANG ; Chenglin SUN ; Hao REN ; Dawei YANG ; Xinyu ZHAO ; Mengyang ZHANG ; Xiao HAN ; Jingjie ZHAO ; Qianyi WANG ; Yameng SUN ; Xinyan ZHAO ; Jidong JIA ; Zhenghan YANG ; Xiaofei TONG ; Hong YOU
Chinese Journal of Hepatology 2025;33(10):1001-1008
Objective:To dynamically assess liver fibrosis using magnetic resonance elastography (MRE) and explore factors associated with fibrosis reversal in patients with metabolic dysfunction-associated steatohepatitis (MASH).Methods:This study included data from patients diagnosed with MASH by liver biopsy who underwent at least two MRE examinations. Patients were divided into a fibrosis reversal group and a non-reversal group according to whether MRE values decreased by 20% during follow-up. Differences in clinical data between the groups were compared using analysis of variance, the Kruskal-Wallis test, and the chi-square test. Univariate and multivariate logistic regression analyses were used to explore independent risk factors for fibrosis reversal in MASH.Results:A total of 46 cases were included in this study (mean age 50.1±12.3 years, BMI 26.1±3.1 kg/m2). Among them, the reversal group accounted for 26.1%. The rate of decrease in MRI proton density fat fraction (PDFF) was significantly higher in the reversal group (-50.0% vs. -8.1%, P=0.001) than in the non-reversal group between the two MRE examinations. The reversal group showed a more significant change rate of decreases in fasting insulin (-37.3% vs. -3.6%, P=0.011), insulin resistance index (-38.6% vs. -6.5%, P=0.044), and ALP (-24.9% vs. 0, P=0.004). Multivariate logistic regression analysis indicated that the rate of change in MRI PDFF was an independent predictor of fibrosis reversal ( OR=0.96, 95% CI: 0.92-1.00, P=0.046). Conclusion:A decrease in MRI proton density fat fraction levels is independently associated with liver fibrosis reversal in MASH, suggesting that intervention targeting liver fat content may be an effective treatment strategy.
6.Comparative analysis of the correlation between different intestinal ultrasound score and endoscopic disease activity in Crohn's disease
Shijie SUN ; Meizheng DANG ; Jia LI ; Dantong ZHAO ; Yameng ZHENG ; Piyu LI ; Pintong HUANG
Chinese Journal of Ultrasonography 2025;34(2):167-172
Objective:To verify and compare the correlation and diagnostic efficacy of international bowel ultrasound segmental activity score(IBUS-SAS),bowel ultrasound score(BUSS),simple ultrasound score for Crohn's disease(SUS-CD),and simple ultrasound score(Simple-US)with endoscopic disease activity in Crohn's disease(CD)patients. To provide external validation of the diagnostic efficacy of intestinal ultrasound(IUS)score and theoretical basis for clinical selection of optimal IUS score.Methods:A total of 160 patients with clinical diagnosis of CD combined with IUS and intestinal endoscopy were retrospectively analyzed in the Second Affiliated Hospital of Zhejiang University School of Medicine from January 2022 to August 2024. IUS parameters were measured and scored with IBUS-SAS,SUS-CD,BUSS and Simple-US scores. Endoscopic SES-CD was used to evaluate intestinal disease activity in patients without history of intestinal resection,and Rutgeerts score was used to evaluate intestinal disease activity in patients with history of intestinal resection. Endoscopic remission in patients with CD was defined as SES-CD < 3 or Rutgeerts score i0 and i1,mild endoscopic disease activity was defined as 7 > SES-CD≥3 or Rutgeerts score = 2,moderate endoscopic disease activity was defined as 15 > SES-CD≥7 or Rutgeerts score i3,severe endoscopic disease activity was defined as SES-CD≥15 or Rutgeerts i4. The correlation and diagnostic efficacy of IBUS-SAS,SUS-CD,BUSS and Simple-US scores with endoscopic disease activity in patients with CD were compared and analyzed.Results:IUS scores including IBUS-SAS,SUS-CD,BUSS and Simple-US were significantly correlated with endoscopic intestinal disease activity,SES-CD and Rutgeerts scores in CD patients( r s = 0.706,0.492,0.502,0.526;0.825,0.581,0.584,0.603;0.541,0.434,0.437,0.467;all P<0.05). Among them,IBUS-SAS showed better correlation than the other three IUS scores. ROC curve showed that IBUS-SAS,SUS-CD,BUSS,and Simple-US had high predictive values for endoscopic disease activity and endoscopic disease moderate-severe activity in patients with CD(AUC = 0.886,0.748,0.730,0.756;all P<0.05). The diagnostic efficacy of IBUS-SAS on the presence of endoscopic disease activity in patients with CD was significantly higher than those of the other three IUS scores . Conclusions:IBUS-SAS,SUS-CD,BUSS and Simple-US are significantly correlated with the endoscopic results of on intestinal disease activity of CD,and have high predictive values for intestinal disease activity status,among which IBUS-SAS is superior to the other three IUS scores. It is recommended that IBUS-SAS be used first to evaluate intestinal disease activity in patients with CD.
7.Real-time or dynamic non-invasive liver fibrosis testing for evaluating clinical prognoses and predicting chronic liver disease
Xinyu ZHAO ; Yameng SUN ; Yankun GAO ; Zhengzhao LU ; Cheng HUANG ; Yuanyuan KONG ; Jidong JIA ; Hong YOU
Chinese Journal of Hepatology 2025;33(10):945-949
Liver fibrosis is a key histologic marker of long-term outcome in chronic liver disease. Non-invasive tests (NITs) have been shown to have predictive value, but the superiority of "dynamic" versus "static" assessment remains controversial. This article systematically reviews the latest evidence to elucidate the association between longitudinal changes in NITs and hepatic adverse events and assess the incremental contribution of dynamic monitoring to the model. Additionally, it reveals that the dynamic monitoring of NITs is truly superior to single evaluation, but the evidence is limited and the heterogeneity is significant. Dynamic modeling approaches for NITs require a shift from traditional parameter estimation to time-series machine learning. Future studies should make breakthroughs in disease stratification, modeling method innovation, data quality improvement, and prediction ability assessment so as to promote the transition of NITs from "static risk label" to "dynamic individualized engine," which can truly serve clinical decision-making.
8.Predictive role of dynamic changes in liver stiffness measurement for liver-related endpoint events in chronic hepatitis B
Chenglin SUN ; Shuyan CHEN ; Xiaoning WU ; Jialing ZHOU ; Tongtong MENG ; Bingqiong WANG ; Xinyan ZHAO ; Xiaojuan OU ; Jidong JIA ; Yameng SUN ; Hong YOU
Chinese Journal of Hepatology 2025;33(10):993-1000
Objective:To investigate the role of dynamic changes in liver stiffness measurement (LSM) in predicting liver-related end-point events (LREs) occurrence in patients with chronic hepatitis B (CHB) with liver fibrosis during long-term antiviral therapy.Methods:Data were collected from CHB patients whose liver biopsy results showed Metavir fibrosis stage F2~F4 or clinically diagnosed cirrhosis. Entecavir antiviral therapy was mainly administered. Follow-up was conducted once every six months. Clinical data such as demographic information, blood routine tests, liver biochemical parameters, HBV virological and serological test results, and LSM were collected. Dynamic changes in LSM were categorized into four types based on LSM levels before treatment (0y) and following two years of antiviral therapy (2y) : (1) LSM 0y < 10 kPa and LSM 2y < 10 kPa, i.e., LSM persisted < 10 kPa; (2) LSM 0y < 10 kPa and LSM 2y ≥ 10 kPa, i.e., LSM increased to ≥ 10 kPa; (3) LSM 0y ≥ 10 kPa and LSM 2y < 10 kPa, i.e., LSM decreased to < 10 kPa; (4) LSM 0y ≥ 10 kPa and LSM 2y ≥ 10 kPa, i.e., LSM persisted ≥ 10 kPa. The predictive role of the dynamic changes of LSM in the occurrence of LREs was analyzed. The Wilcoxon rank-sum test was used for quantitative data. Fisher's exact test was used for categorical data. Multivariate analysis was performed using the Cox proportional hazards regression model. Survival curves were plotted and compared using the Kaplan-Meier. Results:A total of 713 CHB cases with liver fibrosis were included, among whom 512 had cirrhosis. The cumulative incidence of LREs following two years of antiviral therapy was low in patients with LSM 0y < 10 kPa during follow-up (all patients: LSM persisted < 10 kPa 1.6% vs. LSM increased to ≥ 10 kPa 0%; cirrhosis subgroup: LSM persisted < 10 kPa 0% vs. LSM increased to ≥ 10 kPa 0%). The 5-year cumulative incidence of LREs following two years of antiviral treatment was significantly higher in patients with LSM0y ≥ 10 kPa than in those with LSM persisting ≥ 10 kPa and those with LSM decreasing to < 10 kPa during follow-up (all patients: LSM persisted ≥ 10 kPa 12.4% vs. LSM decreased to < 10 kPa 3.6%; cirrhosis subgroup: LSM persisted ≥ 10 kPa 12.6% vs. LSM decreased to < 10 kPa 4.3%). Patients with LSM persisting at ≥ 10 kPa had a significantly increased risk of LREs following two years of antiviral treatment compared with those whose LSM decreased to <10 kPa during follow-up after adjusting for age, gender, baseline body mass index, platelet count, and alanine aminotransferase (all patients, aHR=2.96, 95% CI: 1.41~6.24, P=0.005; cirrhosis subgroup, aHR=2.74, 95% CI:1.26~5.95, P=0.011). Conclusions:LSM<10 kPa before antiviral treatment had a lower risk of liver-related endpoint events following two years of treatment among CHB patients with liver fibrosis. LSM ≥10 kPa before antiviral treatment and LSM persisted ≥10 kPa two years following treatment had a significantly higher occurrence risk of liver-related endpoints than LSM<10 kPa following treatment among CHB patients with liver fibrosis.
9.Analysis of factors affecting fibrosis reversal in patients with metabolic associated steatohepatitis based on magnetic resonance elastography
Ziyi ZHANG ; Chenglin SUN ; Hao REN ; Dawei YANG ; Xinyu ZHAO ; Mengyang ZHANG ; Xiao HAN ; Jingjie ZHAO ; Qianyi WANG ; Yameng SUN ; Xinyan ZHAO ; Jidong JIA ; Zhenghan YANG ; Xiaofei TONG ; Hong YOU
Chinese Journal of Hepatology 2025;33(10):1001-1008
Objective:To dynamically assess liver fibrosis using magnetic resonance elastography (MRE) and explore factors associated with fibrosis reversal in patients with metabolic dysfunction-associated steatohepatitis (MASH).Methods:This study included data from patients diagnosed with MASH by liver biopsy who underwent at least two MRE examinations. Patients were divided into a fibrosis reversal group and a non-reversal group according to whether MRE values decreased by 20% during follow-up. Differences in clinical data between the groups were compared using analysis of variance, the Kruskal-Wallis test, and the chi-square test. Univariate and multivariate logistic regression analyses were used to explore independent risk factors for fibrosis reversal in MASH.Results:A total of 46 cases were included in this study (mean age 50.1±12.3 years, BMI 26.1±3.1 kg/m2). Among them, the reversal group accounted for 26.1%. The rate of decrease in MRI proton density fat fraction (PDFF) was significantly higher in the reversal group (-50.0% vs. -8.1%, P=0.001) than in the non-reversal group between the two MRE examinations. The reversal group showed a more significant change rate of decreases in fasting insulin (-37.3% vs. -3.6%, P=0.011), insulin resistance index (-38.6% vs. -6.5%, P=0.044), and ALP (-24.9% vs. 0, P=0.004). Multivariate logistic regression analysis indicated that the rate of change in MRI PDFF was an independent predictor of fibrosis reversal ( OR=0.96, 95% CI: 0.92-1.00, P=0.046). Conclusion:A decrease in MRI proton density fat fraction levels is independently associated with liver fibrosis reversal in MASH, suggesting that intervention targeting liver fat content may be an effective treatment strategy.
10.Effect of nursing intervention on self-care ability and mood state of patients with hepatitis B under the framework of self-regulation theory
Li LI ; Yameng JI ; Juan REN ; Zhihe ZHAO ; Xiaolong CHEN
Chinese Journal of Modern Nursing 2024;30(23):3180-3185
Objective:To explore the effect of nursing intervention based on self-regulation theory on the self-care ability and mood state of patients with hepatitis B.Methods:From July 2021 to June 2023, a total of 126 patients with hepatitis B in the Department of Infectious Diseases in the First Affiliated Hospital of Zhengzhou University were selected as the research objects by the convenient sampling method. They were divided into the control group ( n=63) and the intervention group ( n=63) using the simple random number method. The control group received routine nursing intervention, while the intervention group received nursing intervention based on self-regulation theory based on routine nursing intervention. The intervention period was six months. Self-care ability, mood state, regular follow-up rate, medication compliance rate, and nursing satisfaction before and after intervention were compared between the two groups. Results:After six months of intervention, the score of the Exercise of Self-Care Agency Scale (ESCA) and the score of energy dimension in Profile of Mood states-short form (POMS-SF) in the intervention group were both higher than those in the control group? ( P<0.05), while scores of confusion, fatigue, anger, tension, and depression dimensions in POMS-SF were lower than those in the control group ( P<0.05). The intervention group's regular follow-up rate, medication compliance rate, and nursing satisfaction were all higher than those of the control group ( P<0.05) . Conclusions:Nursing intervention under the theoretical framework of self-regulation can improve the self-care ability of hepatitis B patients, their mood state, the regular follow-up rate, medication compliance rate, and nursing satisfaction.

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