1.Autophagy-related gene expression in pulmonary fibrosis models:bioinformatic analysis and experimental validation
Kexin LIU ; Kaimin HAO ; Wenyue ZHUANG ; Zhengyi LI
Chinese Journal of Tissue Engineering Research 2026;30(5):1129-1138
BACKGROUND:The stress effect of autophagy on epithelial cells,fibroblasts and myofibroblasts is closely related to the formation process of pulmonary fibrosis.OBJECTIVE:To screen the genes related to autophagy in patients with pulmonary fibrosis,and explore their correlation with the prognosis of patients with pulmonary fibrosis,in order to provide a new target for clinical intervention in pulmonary fibrosis.METHODS:The gene expression profiling dataset downloaded from GSE70866 was used as a training set,differentially expressed genes between pulmonary fibrosis patients and normal healthy individuals was analyzed using the R language and intersected with autophagy-related genes to identify the differentially expressed genes with the most significant changes.Multiple analysis methods were used to identify key prognostic genes and construct genetic prognostic models.Patients with pulmonary fibrosis were divided into high-risk and low-risk groups according to their risk scores,and the validity of the prognostic model was verified using the Siena cohort and Leuven cohort validation sets.A cell model of pulmonary fibrosis was established by inducing HFL-1 cells(human embryonic lung fibroblasts)with transforming growth factor-β1,and an animal model of pulmonary fibrosis was established in mice by tracheal instillation of bleomycin to validate the expressions of prognostic genes.RESULTS AND CONCLUSION:(1)There were 2 650 differentially expressed genes between fibrotic tissue and normal tissue.Among them,34 genes related to autophagy showed significant expression changes.(2)Kaplan-Meier survival analysis curves for the Siena cohort and Leuven cohort validation sets showed significantly lower survival in the high-risk group than in the low-risk group.(3)Three autophagy genes related to prognosis were screened out:myelocytomatosis viral oncogene(MYC),C-C motif chemokine ligand 2(CCL2),and GABA type a receptor associated protein like 1(GABARAPL1).(4)Both in vivo and in vitro studies showed that compared with the control group,the expression levels of myelocytomatosis viral oncogene and C-C motif chemokine ligand 2 mRNA and protein were significantly higher in the lung fibrosis model group(P<0.01,P<0.05),while the expression levels of GABA type a receptor associated protein like 1 mRNA and protein were lower(P<0.001).To conclude,bioinformatics methods are used to analyze the expression of three autophagy-related genes in pulmonary fibrosis and their correlation with the prognosis of patients with pulmonary fibrosis.The constructed prognostic model has good predictive ability for the 1-,2-,and 3-year survival rates of patients with pulmonary fibrosis.Moreover,in vivo and in vitro models have been used to verify that myelocytomatosis viral oncogene and C-C motif chemokine ligand 2 are highly expressed in lung fibroblasts and tissues,and that GABA type a receptor associated protein like 1 is lowly expressed.
2.Mechanisms by which aerobic and resistance exercises improve obesity-related cognitive impairment
Yu LIU ; Senlin LEI ; Jintao ZHOU ; Hui LIU ; Xianhui LI
Chinese Journal of Tissue Engineering Research 2026;30(5):1171-1183
BACKGROUND:Obesity is not only related to metabolic diseases such as diabetes and cardiovascular disease,but also closely related to the increased risk of cognitive decline,dementia and other neurodegenerative diseases.Studies have found that aerobic exercise and resistance exercise can help improve obesity-related cognitive impairment,but their therapeutic effects and related mechanisms of action are still unclear.OBJECTIVE:To explore the protective effects of aerobic and resistance exercises on the nervous center of obesity-related cognitive impairment mice.METHODS:Forty-eight 8-week-old C57BL/6J wild-type male mice were randomly divided into four groups:a control group was fed normally for 20 weeks;a high fat group was fed with high fat diet(60%fat energy)for 20 weeks;an aerobic exercise group was fed with 12 weeks of high-fat diet followed by 8 weeks of aerobic exercise;and a resistance exercise group was fed with 12 weeks of high-fat diet followed by 8 weeks of resistance exercise.After the exercise intervention,body mass was weighed,insulin tolerance and glucose tolerance were tested to evaluate insulin resistance,and cognitive function of mice in each group was detected by new object recognition experiment and Y-maze experiment.The morphology of hippocampal and cortical tissue cells was observed by hematoxylin-eosin staining.The mRNA relative expression levels of tumor necrosis factor-α and interleukin-6 were detected by real-time fluorescence quantitative PCR,and the protein expressions of Bax,Bcl-2,nuclear factor-κB,Cleaved Caspase-1,Caspase-3,synapsin 1 and brain-derived neurotrophic factor were detected by western blot.RESULTS AND CONCLUSION:(1)Compared with the control group,the body mass of mice increased in the high-fat group(P<0.05),accompanied by insulin resistance and cognitive dysfunction,the expression levels of nuclear factor-κB,Bax,Caspase-3,Cleaved Caspase-1 in the hippocampus were significantly increased(P<0.05),the expression levels of brain-derived neurotrophic factor,synapsin 1and Bcl-2 proteins were significantly decreased(P<0.05),Bcl-2/Bax ratio was significantly decreased(P<0.05),and the mRNA levels of inflammatory cytokines,tumor necrosis factor-α and interleukin-6,were significantly up-regulated(P<0.05).(2)Compared with the high-fat group,the above indexes were significantly improved in the aerobic exercise group(P<0.05),while in the resistance exercise group,the body mass of mice was significantly decreased,the levels of inflammatory cytokines tumor necrosis factor-α and interleukin-6 mRNA were significantly decreased(P<0.05),the protein expression of Caspase-3 was significantly decreased(P<0.05),and the protein expression of brain-derived neurotrophic factor was significantly up-regulated(P<0.05),but no significant changes were observed in the other indexes(P>0.05).In conclusion,long-term exercise can reduce insulin resistance,down-regulate the expression of nuclear factor-κB pathway,weaken inflammatory response,inhibit neuronal apoptosis and improve synaptic plasticity,resulting in neuroprotective effects,and effectively alleviate obesity-related cognitive dysfunction in obese mice.The therapeutic effect of aerobic exercise is superior to that of resistance exercise.
3.Schwann cells promote peripheral nerve regeneration:retrospect and prospect
Zhenyi FU ; Junhao LI ; Yating ZHANG ; Yunkai HE ; Junyu LIU ; Yunhao WEI ; Jiaxin LIU
Chinese Journal of Tissue Engineering Research 2026;30(5):1236-1246
BACKGROUND:Peripheral nerve axon rupture seriously affects patients' physical function and mental health.Microsurgery,nerve autograft,nerve allograft,fibrin glue and catheter technology are the main treatments for peripheral nerve injury,each of which has its own advantages and disadvantages,but the overall treatment effect is not satisfactory.Despite the clinical success of Schwann cells in promoting axonal regeneration,there are still many challenges in the treatment with Schwann cells,such as slow expansion of Schwann cells,immune rejection,and low survival rate of transplanted cells.OBJECTIVE:To summarize the role and mechanism of Schwann cells in promoting the regeneration of peripheral nerve axons,and the difficulties and challenges of Schwann cells in the process of nerve regeneration treatment.METHODS:PubMed,Medline,WanFang,VIP,and CNKI were searched by computer using the search terms of"Schwann cells,synaptic Schwann cell,macrophage,peripheral nerve axon rupture,Wallerian degeneration,Peripheral nerve axon regeneration,Central nervous system repair"in English and Chinese.Literature related to Schwann cell proliferation and differentiation,promotion of peripheral nerve regeneration,and clinical applications was retrieved from database inception to October 2024,and a total of 95 articles were finally included for review.RESULTS AND CONCLUSION:Schwann cells interact with macrophages,T cells and other cells,to initiate the regeneration process through signaling pathways,including Krox20/C-Jun,NRG-1/ErbB,Notch,MAPK,and PI3K/Akt/mTOR,synthesize and release nerve growth factors,and thus promote regeneration of the peripheral nervous system.Schwann cells have been experimentally demonstrated to have great potential in peripheral nerve repair and are expected to become the key target of therapeutic intervention.However,there are still problems such as difficulties in cell harvest and culture,as well as the occurrence of other diseases during the treatment process.
4.Regeneration and repair of oral alveolar bone defects
Xinyue LIU ; Chunnian LI ; Yizhuo LI ; Shifang XU
Chinese Journal of Tissue Engineering Research 2026;30(5):1247-1259
BACKGROUND:Developing a material that promotes alveolar bone regeneration and has good properties is of great significance for the treatment of alveolar bone defects.OBJECTIVE:To summarize the research on alveolar bone defect regeneration and repair in the past 5 years,classify and introduce new materials and drugs,so as to grasp the latest progress in related fields.METHODS:"Alveolar bone,alveolar bone defect,alveolar bone regeneration,mechanism,biomaterials,nanoscaffolds,hydrogels,medications,anti-inflammatory drugs,simvastatin,metformin,traditional Chinese medicine,growth factor,stem cell"were used as search terms in Chinese and English for literature retrieval in CNKI and PubMed,respectively.A total of 117 articles were finally obtained for review and analysis.RESULTS AND CONCLUSION:The application of biomaterials provides a scaffold structure for alveolar bone regeneration and can also be used as a bone substitute to repair bone defects.Topical and systemic applications of Western and Chinese medicines can control inflammation and promote bone regeneration.Materials loaded with various growth factors have the effect of osteogenesis and can promote the repair of alveolar bone defects.In stem cell tissue engineering,the seed cells are osteogenic and fibrogenic,which can differentiate into osteoblasts to generate new bone.In recent years,research has been keen on the combination of the above to develop new,biocompatible,and slow-release drugs or materials to promote the regeneration and repair of alveolar bone defects.
5.Influencing factors on the prevalence of depressive symptoms among middle school students in Yunnan Province in 2023
Xiaodong MU ; Hong LIU ; Fan YANG ; Tunan LI ; Junyu NI ; Yunjuan YANG
Shanghai Journal of Preventive Medicine 2026;38(2):108-115
ObjectiveTo investigate the epidemiological characteristics and influencing factors of depressive symptoms among middle school (junior, senior, and vocational high school) students in Yunnan Province, China, and to inform evidence-based intervention strategies for adolescent mental health. MethodsA cross-sectional survey was conducted between October and November 2023 using stratified random cluster sampling. Students from eight counties (districts) across four prefectures (cities) in Yunnan Province were included. Depressive symptoms were assessed using the Center for Epidemiologic Studies Depression Scale (CES-D). Multivariate logistic regression analysis was performed to examine factors associated with depressive symptoms, with stratified analyses conducted by gender, educational stage, and ethnicity. ResultsA total of 4 672 questionnaires were distributed, with 4 670 valid questionnaires retrieved, yielding a valid response rate of 99.96%. The surveyed participants were predominantly female students (50.81%), junior high school students (49.13%), ethnic minorities (52.78%), and urban residents (79.29%). The mean CES-D score for middle school students in Yunnan Province was (15.31±10.83). Female students had a significantly higher mean score (16.63±11.41) than male students (13.95±10.02) (P<0.001). Senior high school students had a significantly higher mean score (16.61±10.61) compared to both junior high school students (14.74±11.45) and vocational high school students (13.10±7.71) (all pairwise comparisons P<0.001). The prevalence of depressive symptoms among middle school students in Yunnan Province was 28.18%. The prevalence was significantly higher in females (34.09%) than in males (22.07%). By school type, the detection rate was highest among senior high school students (33.39%), followed by junior high school students (26.29%) and vocational high school students (17.27%) (P<0.05). Multivariate logistic regression analysis showed that female gender (OR=2.16, 95%CI: 1.86‒2.50), being in junior high school (OR=2.43, 95%CI: 1.84‒3.20) or senior high school (OR=2.27, 95%CI: 1.73‒2.98), not living with parents (OR=1.24, 95%CI: 1.07‒1.44), irregular breakfast consumption (OR=1.52, 95%CI: 1.33‒1.75), lack of moderate-to-vigorous physical activity (MVPA) (OR=1.69, 95%CI: 1.37‒2.09), sleep duration ≤5 h per night (OR=2.52, 95%CI: 2.02‒3.14) or 6‒7 h per night (OR=1.47, 95%CI: 1.25‒1.73), smoking (OR=1.86, 95%CI: 1.56‒2.23), and alcohol consumption (OR=1.81, 95%CI: 1.54‒2.13) were positively associated with depressive symptoms. In contrast, screen time ≤1 h (OR=0.71, 95%CI: 0.59‒0.86) was negatively associated with depressive symptoms. Stratified analyses showed that female students not living with parents (OR=1.29, 95%CI: 1.06‒1.58), senior high school students (OR=1.51, 95%CI: 1.21‒1.88), and Han Chinese students (OR=1.37, 95%CI: 1.11‒1.69) were more likely to experience depressive symptoms. Han Chinese students who smoked were also more likely to have depressive symptoms (OR=1.72, 95%CI: 1.34‒2.21). In contrast, male students with screen time ≤1 h (OR=0.71, 95%CI: 0.53‒0.95) and ethnic minority students (OR=0.74, 95%CI: 0.58‒0.95) were less likely to experience depressive symptoms. Regardless of gender, irregular breakfast consumption, lack of MVPA, sleep duration less than 8 h per night, smoking, and alcohol consumption were all positively associated with depressive symptoms (P<0.05). Among both junior and senior high school students, irregular breakfast consumption, lack of MVPA, smoking, and alcohol consumption were positively associated with depressive symptoms (all P<0.05), while screen time ≤1 h was negatively associated with depressive symptoms (all P<0.05). For junior high school students, engaging in 1‒2 days of MVPA per week, screen time more than 2 h per day, and sleep duration 6‒7 h per night were all positively associated with depressive symptoms (all P<0.05). Among junior high, senior high, and vocational high school students, sleep duration ≤5 h per night was positively associated with depressive symptoms (P<0.05). For both Han Chinese and ethnic minority students, irregular breakfast consumption, lack of MVPA, sleep duration less than 8 h per night, and alcohol consumption were all positively associated with depressive symptoms (all P<0.05). ConclusionThe prevalence of depressive symptoms among middle school students in Yunnan Province is comparable to that in central China and higher than that in northern regions. Prevention and control efforts should prioritize female students and those in junior and senior high school stages. Universal improvements in lifestyle behaviors among middle school students, such as regular breakfast consumption, MVPA, sufficient sleep (≥8 h), and abstinence from smoking and alcohol. Particular attention should be given to limiting excessive screen time among junior high school students and addressing the mental health needs of females not living with their parents, senior high school students, and Han Chinese students.
6.Research advances in antiviral drugs for the treatment of hepatitis D virus infection
Yang LIU ; Yonghe QI ; Zhongmin ZHOU ; Jianhua SUI ; Wenhui LI
Journal of Clinical Hepatology 2026;42(2):278-285
Co-infection of hepatitis D virus (HDV) and hepatitis B virus (HBV) is the most severe form of viral hepatitis and is associated with accelerated progression of liver disease and a significant increase in the risk of liver cirrhosis and hepatocellular carcinoma. Nucleo(s)tide analogues for HBV treatment are ineffective against HDV infection, necessitating the urgent need for developing specific and effective antiviral therapies for HDV. In recent years, significant advances have been made in the research and development of specific antiviral drugs against HDV, including entry inhibitors targeting viral entry (Bulevirtide) and monoclonal antibody drugs (Libevitug), which bring ground-breaking advances in the treatment of HDV infection. This article briefly reviews the latest research advances in therapeutic drugs for HDV, introduces the mechanism of action and clinical research data of new drugs recently approved for the treatment of HDV, and discusses the challenges that need to be solved in the field of HDV treatment, in order to provide a reference for understanding the current status of hepatitis D treatment.
7.Efficacy and safety of Babaodan Capsule in patients with chronic hepatitis B virus infection comorbid with gallbladder polyps
Qianqian NIU ; Huan CHEN ; Ying ZHENG ; Chunyan GOU ; Chen XU ; Li LI ; Xinxin WANG ; Jianping LIU ; Zhaolan LIU ; Xiuhui LI
Journal of Clinical Hepatology 2026;42(2):304-311
ObjectiveTo investigate the efficacy and safety of Babaodan Capsule (BBD) in the treatment of patients with chronic hepatitis B virus (HBV) infection with damp-heat in the liver and gallbladder comorbid with gallbladder polyps. MethodsA randomized, double-blinded, placebo-controlled single-center trial was conducted among 120 patients with chronic HBV infection who were admitted to Beijing YouAn Hospital, Capital Medical University, from August 2020 to April 2023, and they were divided into treatment group (BBD) and control group (placebo), with 60 patients in each group. The course of treatment was 24 weeks, and follow-up assessments were conducted every 4 weeks. The primary outcome measures were the number and maximum diameter of gallbladder polyps (assessed by ultrasound), and the secondary outcome measures included traditional Chinese medicine (TCM) syndrome score, blood lipid levels, and liver function parameters. The independent-samples t test or the Wilcoxon rank-sum test was used for comparison of continuous data between two groups, and the chi-square test or the Fisher’s exact test was used for comparison of categorical data between two groups; the Wilcoxon rank-sum test was used for comparison of ranked data between two groups; the generalized estimating equation was used to analyze repeated measures data. ResultsAfter 8 weeks of treatment, the treatment group had a significantly smaller diameter of polyps and a significantly lower number of polyps than the control group (Z=-1.76 and -1.80, both P<0.05), and after 24 weeks of treatment, the treatment group had a significantly higher polyp reduction rate than the control group (30.51% vs 10.91%, P<0.05). The subgroup analysis showed that patients receiving combined antiviral therapy, male patients, patients with a diameter of polyps of <5 mm, and patients with multiple polyps tended to achieve significantly greater benefits. At week 8 of treatment, the treatment group had a significantly better TCM syndrome score than the control group (Z=-2.35, P<0.05); after treatment, compared with the control group, the treatment group had a significantly greater increase in high-density lipoprotein (Z=-1.85, P<0.05) and significantly lower levels of alanine aminotransferase (Z=-2.06, P <0.05), aspartate aminotransferase (Z=-2.13, P<0.05), total bilirubin (Z=-2.12, P<0.05), and direct bilirubin (Z=-3.09, P<0.05). No serious adverse events were reported in either group. ConclusionBBD can effectively reduce the size of gallbladder polyps, improve TCM syndrome score, and reduce the level of bilirubin in patients with chronic HBV infection with damp-heat in the liver and gallbladder, with a favorable safety profile, and it may be more suitable for patients receiving combined antiviral therapy and specific subgroups (male patients, patients with a diameter of polyps of <5 mm, and patients with multiple polyps.
8.Correlation between liver fibrosis degree and carotid plaque in patients with lean metabolic dysfunction-associated fatty liver disease
Shuai ZHANG ; Shoulu JIN ; Wanqing LI ; Xijing SHI ; Hao LIANG ; Hao DONG ; Dailong LU ; Ying ZHU ; Xiaoxing XIANG ; Jun LIU
Journal of Clinical Hepatology 2026;42(2):319-325
ObjectiveTo investigate the association between noninvasive liver fibrosis markers and carotid plaque (CP) in patients with lean metabolic dysfunction-associated fatty liver disease (MAFLD), and to provide a basis for screening high-risk populations. MethodsA total of 957 patients with lean MAFLD who underwent physical examination in Subei People’s Hospital from January 2021 to June 2023 was enrolled as the observation cohort, with the presence or absence of CP as the outcome, and fibrosis-4 (FIB-4) index and nonalcoholic fatty liver disease fibrosis score (NFS) were used to assess liver fibrosis degree. The independent-samples t test was used for comparison of normally distributed continuous data between two groups, and the Mann-Whitney U test was used for comparison of non-normally distributed continuous data between two groups; the chi-square test was used for comparison of categorical data between two groups. The multivariate logistic regression analysis, the restricted cubic spline analysis, the receiver operating characteristic curve, and the mediation effect analysis were used to investigate the association between liver fibrosis degree and CP. ResultsThe prevalence rate of CP was 36.6% in the lean MAFLD population. Compared with the non-CP group(n=607), the CP group (n=350) had a significantly higher proportion of male patients, a significantly higher proportion of patients with smoking/diabetes/hypertension, and significantly higher levels of age, creatinine, blood urea nitrogen, triglycerides, fasting blood glucose, aspartate aminotransferase, aspartate aminotransferase/alanine aminotransferase ratio, NFS, and FIB-4 index, as well as significantly lower levels of platelet count and albumin (all P<0.05). The multivariate logistic regression analysis showed that after adjustment for confounding factors, FIB-4 index (odds ratio[OR]=2.979, 95% confidence interval[CI]:2.141 — 4.219, P<0.001) and NFS (OR=1.747, 95%CI: 1.499 — 2.046, P<0.001) were positively correlated with CP. Both FIB-4 index and NFS had a good value in predicting CP. Hypertension had a significant indirect effect on the prevalence rate of CP through its impact on liver fibrosis markers, and its mediating effect accounted for 39.5% — 40.8% of the total effect (P<0.001). ConclusionIn patients with lean MAFLD, NFS and FIB-4 index are significantly positively correlated with the prevalence rate of CP, and they can be used as potential epidemiological predictive indicators. Liver fibrosis markers may play a mediating role in the association between hypertension and CP. Interventions targeting hypertension and liver fibrosis markers may help to prevent and delay the progression of CP.
9.Effect of Huatan Qushi Huoxue prescription on macrophage efferocytosis mediated by a disintegrin and metalloproteinase 17 and triggering receptor expressed on myeloid cells 2 in rats with metabolic dysfunction-associated steatohepatitis
Lihui ZHANG ; Sutong LIU ; Qing ZHAO ; Shanzheng LI ; Minghao LIU ; Wenxia ZHAO
Journal of Clinical Hepatology 2026;42(2):345-355
ObjectiveTo investigate the therapeutic effect and mechanism of Huatan Qushi Huoxue prescription on rats with metabolic dysfunction-associated steatohepatitis (MASH). MethodsA total of 60 specific pathogen-free Sprague-Dawley rats were randomly divided into blank control group, model A group, model B group, Western medicine group (polyene phosphatidylcholine, 143.64 mg/kg), high-dose Chinese medicine group (Huatan Qushi Huoxue prescription, 20.16 g/kg), and middle-dose Chinese medicine group (Huatan Qushi Huoxue prescription, 10.08 g/kg). All rats except those in the blank control group were given high-fat diet. Samples were collected from the model A group at week 8, and since week 12, the other groups were given the corresponding drug once a day for 8 consecutive weeks, with samples collected at week 20. Body weight, liver wet weight, and liver index were measured for all rats; the microplate method was used to measure the serum levels of alanine aminotransferase (ALT), aspartate aminotransferase (AST), total cholesterol (TC), triglycerides (TG), high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), and free fatty acids (FFA); ELISA was used to measure the serum levels of tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β), interleukin-6 (IL-6), and soluble triggering receptor expressed on myeloid cells 2 (sTREM2); HE staining and oil red O staining were performed to observe liver histopathological changes; immunofluorescence assay was used to measure CD68+TREM2+ cells in liver tissue and calculate the phagocytosis rate of macrophages; quantitative real-time PCR was used to measure the mRNA expression levels of sphingosine 1-phosphate (S1P), sphingosine 1-phosphate receptor 1 (S1PR1), a disintegrin and metalloproteinase 17 (ADAM17), and triggering receptor expressed on myeloid cells 2 (TREM2) in liver tissue, and immunohistochemistry was used to measure the protein expression levels of S1P, S1PR1, ADAM17, and TREM2 in liver tissue. A one-way analysis of variance was used for comparison of normally distributed continuous data with homogeneity of variance between groups, and the least significant difference t-test was used for further comparison between two groups; the Welch’s test was used for comparison of normally distributed continuous data with heterogeneity of variance between groups, and the Tamhane’s test was used for further comparison between two groups. The Kruskal-Wallis H test was used for comparison of non-normally distributed continuous data between groups, and the Dunn’s test was used for further comparison between two groups. ResultsCompared with the blank control group, the model A group and the model B group had significant increases in body weight and liver wet weight, and the model B group had a significant increase in liver index (all P<0.05). HE staining showed diffuse macrovesicular steatosis of liver tissue in the model A group and a large number of hepatocytes with ballooning degeneration in liver tissue in the model group B, with the presence of mixed inflammatory cell infiltration and mild perisinusoidal fibrosis in the lobules and the portal area. Compared with the blank control group, the model A group and the model B group had significant increases in NAS score and oil red O-positive area (all P<0.05), and the model B group had significant increases in these two indicators than the model A group (both P<0.05). Compared with the blank control group, the model A group and the model B group had significant increases in the serum levels of TC, TG, LDL-C, FFA, IL-1β, IL-6, and sTREM2 and a significant reduction in the serum level of HDL-C, and the model B group had significant increases in the serum levels of ALT, AST, and TNF-α (all P<0.05); compared with the model A group, the model B group had significant increases in the serum levels of ALT, AST, TC, TG, FFA, TNF-α, IL-1β, IL-6, and sTREM2 and a significant reduction in the serum level of HDL-C (all P<0.05). Immunofluorescence assay showed that compared with the blank control group, the model A group had a significant increase in the phagocytosis rate of macrophages (P<0.05), while the model B group had a significantly lower phagocytosis rate of macrophages than the model A group (P<0.05). Quantitative real-time PCR showed that compared with the blank control group, the model A group and the model B group had a significant increase in the mRNA expression level of TREM2, and the model B group had significant increases in the mRNA expression levels of S1P and S1PR1 (both P<0.05); moreover, compared with the model A group, the model B group had significant increases in the mRNA expression levels of S1PR1 and TREM2 (both P<0.05). Immunohistochemistry showed that compared with the blank control group, the model A group and the model B group had significant increases in the protein expression levels of S1P, S1PR1, and ADAM17, and the model A group had a significant increase in the protein expression level of TREM2 (all P<0.05); compared with the model A group, the model B group had significant increases in the protein expression levels of S1P, S1PR1, and ADAM17 and a significant reduction in the protein expression level of TREM2 (all P<0.05). Compared with the model B group, each medication group had significant reductions in body weight, liver wet weight, and liver index (all P<0.05); each medication group had significant improvements in hepatic steatosis and inflammatory damage, with significant reductions in NAS score and oil red O-positive area (all P<0.05); each medication group had significant reductions in the serum levels of ALT, AST, TC, TG, FFA, IL-1β, and IL-6 (all P<0.05) and a significant increase in the serum level of HDL-C (P<0.05), and the high-dose Chinese medicine group had a significant reduction in the serum level of TNF-α (P<0.05); each medication group had a significant increase in the phagocytosis rate of macrophages (all P<0.05); the high- and middle-dose Chinese medicine groups had a significant reduction in the protein expression level of ADAM17, and the high-dose Chinese medicine group had a significant increase in the protein expression level of TREM2 (all P<0.05). ConclusionHuatan Qushi Huoxue prescription improves lipid metabolism and inflammation in the liver of MASH rats by regulating hepatic macrophage phagocytosis.
10.Mechanism of action of estrogen deficiency in autoimmune hepatitis via the intestinal barrier
Mingzhu SONG ; Ling LI ; Jinxia ZHU ; Shu ZHANG ; Guangwei LIU
Journal of Clinical Hepatology 2026;42(2):438-444
Autoimmune hepatitis (AIH) is an immune-mediated chronic liver inflammatory disease with unknown pathogenesis, and intestinal barrier dysfunction is considered an important factor. Meanwhile, there are sex and age differences in the incidence rate of AIH, suggesting that hormone may be involved in regulation. On this basis, this article focuses on the association between estrogen, intestinal barrier, and immune homeostasis, systematically reviews the evidence that estrogen deficiency disrupts intestinal barrier homeostasis, and further summarizes the potential mechanism of estrogen in regulating the development and progression of AIH via intestinal barrier.

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