1.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.
2.Study on the mechanism of Huatan qushi huoxue formula in improving metabolic dysfunction-associated steatohepatitis by inhibiting macrophage pyroptosis
Yajie GUAN ; Qizhen ZHANG ; Junjiao XU ; Yijia SONG ; Dongfang SHANG ; Wenxia ZHAO ; Minghao LIU
China Pharmacy 2026;37(7):864-869
OBJECTIVE To focus on the classic NOD-like receptor protein 3 (NLRP3)/Caspase-1/gasdermin D (GSDMD) pyroptosis pathway and explore the mechanism by which Huatan qushi huoxue formula (HQHF) inhibits macrophage pyroptosis to ameliorate metabolic dysfunction-associated steatohepatitis (MASH). METHODS RAW264.7 cells were divided into 5 groups: Control group (10% blank serum), Model group [10% blank serum+5 μg/mL lipopolysaccharide (LPS)], HQHF-L group (2.5% drug-containing serum+7.5% blank serum+5 μg/mL LPS), HQHF-M group (5% drug-containing serum+5% blank serum+5 μg/mL LPS), and HQHF-H group (10% drug-containing serum+5 μg/mL LPS). After 24 h of routine culture post-administration, cells and supernatants were collected for assays. Cell morphology was observed via scanning electron microscopy and phase-contrast microscopy; localization and expression of gasdermin D-N (GSDMD-N) were observed by immunofluorescence. Interleukin-1β (IL-1β) and IL-18 contents in supernatants were detected by ELISA; mRNA and protein expressions of NLRP3, Caspase-1, and GSDMD were measured using real-time PCR and Western blot. RESULTS Compared with the Control group, the Model group showed typical pyroptotic morphology (cell membrane bulging and pore formation), increased aggregation and fluorescence intensity of GSDMD-N on the cell membrane ( P <0.05), significantly increased the contents of IL-1β and IL-18 in cell supernatants ( P <0.05), and significantly up-regulated mRNA and protein expressions of NLRP3, Caspase-1, and GSDMD in cells ( P <0.05). Compared with the Model group, the HQHF-L, HQHF-M and HQHF-H groups showed improved pyroptotic morphology, reduced membrane localization and significantly weakened fluorescence intensity of GSDMD-N ( P <0.05), significantly decreased the contents of IL-1β and IL-18 in cell supernatants ( P <0.05), and significantly down-regulated mRNA and protein expressions of NLRP3, Caspase-1, and GSDMD in cells ( P <0.05). CONCLUSIONS HQHF inhibits LPS-induced macrophage pyroptosis, and its mechanism of improving MASH may be associated with the suppression of the activation of the classical NLRP3/Caspase-1/GSDMD pyroptosis pathway.
3.Mechanism of action of organelle interactions in the progression of liver fibrosis and traditional Chinese medicine prevention and treatment strategies
Yuanyuan ZHENG ; Chenlu ZHAO ; Lihui ZHANG ; Sutong LIU ; Wenxia ZHAO
Journal of Clinical Hepatology 2026;42(3):711-717
Liver fibrosis is the core pathological stage of the progression of various chronic liver diseases to liver cirrhosis, and hepatic stellate cell (HSC) activation and the abnormal accumulation of collagen fibers are important processes for the development and progression of liver fibrosis. In recent years, studies have shown that HSC activation is regulated by the complex interactions between various organelles (including mitochondria, endoplasmic reticulum, Golgi apparatus, lysosome, and peroxisomes), and such interactions affect the key cellular processes such as energy metabolism, protein synthesis and folding, reactive oxygen species balance, and autophagy, thereby participating in the progression of liver fibrosis. Meanwhile, traditional Chinese medicine and its active ingredients with multi-target synergistic effects have attracted wide attention. From the perspective of the interaction between organelles, this article systematically elaborates on the specific mechanism of such interactions in the progression of liver fibrosis and reviews how traditional Chinese medicine inhibits HSC activation and collagen production by regulating the function of these organelle and their interaction networks, thereby exerting an anti-liver fibrosis effect, in order to provide a theoretical basis for in-depth understanding of the pathological mechanism of liver fibrosis and the development of new traditional Chinese medicine intervention strategies.
4.Metabolic dysfunction-associated fatty liver disease with different clinical phenotypes: Pathogenesis and strategies for integrated traditional Chinese and Western medicine treatment
Wenxia ZHAO ; Lei GAO ; Xinju CHEN ; Yuanyuan ZHENG ; Sutong LIU ; Lihui ZHANG ; Qing ZHAO ; Chenlu ZHAO
Journal of Clinical Hepatology 2026;42(4):930-937
Metabolic dysfunction-associated fatty liver disease (MAFLD) is a chronic metabolic liver disorder with complex etiologies. Different clinical phenotypes of MAFLD (such as obesity, hyperlipidemia, type 2 diabetes mellitus, the postmenopausal state, and chronic hepatitis B) have different mechanisms of action in the development and progression of MAFLD, leading to high heterogeneity in its clinical progression and prognosis. This article systematically reviews the pathogeneses and clinical features of the above five clinical phenotypes of MAFLD and elaborates on the corresponding individualized diagnosis and treatment regimens integrating traditional Chinese medicine and Western medicine, in order to provide a reference for clinical practice and improve clinical diagnosis and treatment.
5.Relationship between physical activity and mental health in children with autism spectrum disorder: the mediating role of social response
Guanting DUAN ; Xue XIAO ; Huisheng HOU ; Yunqiao JIANG ; Yuge LIU ; Wenxia SHI
Chinese Journal of Rehabilitation Theory and Practice 2025;31(2):150-157
ObjectiveTo evaluate the levels of physical exercise, mental health and social response in children with autism spectrum disorder (ASD), and explore the mediating effect of social response on physical exercise and mental health. MethodsFrom September, 2019 to April, 2024, 211 children with ASD from three special education schools in Haidian District and Shijingshan District of Beijing were selected. They were assessed with general data questionnaire, Physical Activity Rating Scale (PARS-3), Chinese version of Psycho-Educational Profile (C-PEP) and Social Response Scale-Short Form (SRS-SF). The correlation among physical exercise, mental health and social response was analyzed. The mediating effect of social response on physical exercise and mental health was explored. ResultsThe average physical exercise level was (58.72±3.34), the average mental health level was (14.85±1.67), and the average social response level was (24.98±3.79). Physical exercise was positively correlated with mental health (r = 0.546, P < 0.05) and negatively correlated with social response (r = -0.298, P < 0.05). Mental health was negatively correlated with social response (r = -0.397, P < 0.05). Average monthly family income, parental relationship, repeated transcranial magnetic stimulation therapy, physical exercise, social response were the influencing factors of mental health (P < 0.05). Social response was intermediary between physical exercise and mental health, accounting for 14.56%. ConclusionThe mental health level of children with ASD is poor, and there are many influencing factors. Physical exercise can directly affect the mental health of children with ASD, and can also play an indirect role through social response.
6.Association of menopausal time and menopausal age with nonalcoholic fatty liver disease: An analysis based on a restricted cubic spline model
Chenlu ZHAO ; Suping MA ; Dongfang SHANG ; Sutong LIU ; Xiaoyan LIU ; Yuanyuan ZHENG ; Wenxia ZHAO
Journal of Clinical Hepatology 2025;41(2):247-253
ObjectiveTo investigate the association of menopausal time and menopausal age with the risk of nonalcoholic fatty liver disease (NAFLD), and to provide a basis for the early prevention and treatment of NAFLD in clinical practice. MethodsRelated data were collected from 373 postmenopausal women who attended the outpatient service of Department of Spleen, Stomach, Liver and Gallbladder Diseases, The First Affiliated Hospital of Henan University of Chinese Medicine, from January 2017 to December 2021, including general information, menopausal age, menopausal time, and presence or absence of NAFLD. The chi-square test was used for comparison of categorical data; the independent-samples t test was used for comparison of normally distributed continuous data between groups, and the Wilcoxon rank-sum test was used for comparison of non-normally distributed continuous data between groups. A Logistic regression analysis was used to calculate the association intensity and 95% confidence interval (95%CI) of menopausal time and menopausal age for the risk of NAFLD, and the restricted cubic spline (RCS) method was used to investigate the dose-response relationship between menopausal time/age and the risk of NAFLD. ResultsCompared with the women with normal menopause or late menopause, the women with early menopause had a higher prevalence rate of NAFLD and a higher degree of steatosis and fibrosis (all P<0.05). After adjustment for the confounding factors such as age and age of menarche, the risk of NAFLD in women with a menopausal time of >3 years was 4.80 (95%CI: 1.93 — 11.95, P=0.001) times that in women with a menopausal time of ≤3 years, and the risk of NAFLD in women with early or late menopause was 8.14 times (95%CI: 1.77 — 37.58, P=0.007) and 0.09 times (95%CI: 0.03 — 0.32, P<0.001), respectively, that in those with a normal menopausal age. There is a dose-response relationship between menopausal time/age and the risk of NAFLD. Menopausal time is positively correlated with the association intensity of NAFLD, while menopausal age is negatively correlated with the association intensity of NAFLD. ConclusionThe longer the menopause time and the earlier the menopause age, the ligher the risk of NAFLD.
7.Mechanism and Combination Therapy of Berberine in Treatment of Nonalcoholic Fatty liver Disease:A Review
Xiaojie WANG ; Heng ZHANG ; Sutong LIU ; Lihui ZHANG ; Wenxia ZHAO
Chinese Journal of Experimental Traditional Medical Formulae 2025;31(5):269-281
Nonalcoholic fatty liver disease(NAFLD) is the most common chronic liver disease in the world. Because of its complex pathogenesis, high clinical prevalence and large population, it poses a great threat and challenge to public health in the world. Therefore, active intervention measures are needed. Currently, western medicine is effective in reducing weight, reducing liver fat content, improving glucose-lipid metabolism and insulin resistance. However, for patients with NAFLD-related fibrosis and cirrhosis, there is still a lack of sufficient histological evidence to support its benefits, and randomized controlled trials are still needed to clarify. Lifestyle intervention is an important cornerstone for the treatment of NAFLD, but there are many problems such as poor implementation and low compliance of patients, and the clinical efficacy is not ideal. Traditional Chinese medicine(TCM) has the significant advantages of multiple pathways and multiple targets. Berberine, the active ingredient of TCM, can interfere with the production of NAFLD from multiple pathways, including increasing energy consumption, weight loss, improving glucose-lipid metabolism, improving insulin resistance, anti-inflammatory, anti-oxidation, regulating intestinal flora, restoring bile acid homeostasis, anti-fibrosis and so on, which can play a positive role in the treatment of NAFLD. At the same time, it was found that the combination of BBR with Chinese and western medicines had significant advantages in promoting drug absorption, improving oral bioavailability, increasing the highest biological distribution in the liver, enhancing the overall therapeutic effect of NAFLD, and reducing adverse drug reactions, which could provide reference for clinical medication.
8.Clinical Study on Treatment of Non-alcoholic Steatohepatitis Patients with Dyslipidemia by Dizhuo Huayu Prescription with Catgut Embedding Therapy
Xiaoyan LIU ; Dongfang SHANG ; Lihui ZHANG ; Chenlu ZHAO ; Siying WANG ; Huaxin CHEN ; Wenxia ZHAO
Chinese Journal of Experimental Traditional Medical Formulae 2025;31(20):152-159
ObjectiveTo observe the clinical efficacy and safety of Dizhuo Huayu prescription combined with catgut embedding therapy in patients with nonalcoholic steatohepatitis (NASH) and dyslipidemia and explore the effect of the combined therapy on inflammatory cytokines interleukin (IL)-18 and IL-1β. MethodsA total of 82 patients with NASH and dyslipidemia from the Gastroenterology Department of the First Affiliated Hospital of Henan University of Chinese Medicine were randomly divided into a control group and a treatment group, with 41 patients in each group. The control group received Polyene Polyenylphosphatidylcholine Capsules, while the treatment group received Dizhuo Huayu prescription granules combined with catgut embedding. The treatment duration was 24 weeks for both groups. At weeks 0, 12, and 24, the traditional Chinese medicine (TCM) syndrome score, body mass index (BMI), liver fat content assessed by Fibroscan (CAP value), the level of alanine transaminase (ALT), aspartate aminotransferase (AST), gamma-glutamyl transferase (GGT), total cholesterol (TC), triglyceride (TG), high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), and free fatty acid (FFA), and the expression of inflammatory cytokines IL-18 and IL-1β in serum were observed. Adverse reactions in both groups were recorded. ResultsA comparison of the comprehensive therapeutic effects between the two groups after 24 weeks of treatment revealed that the total effective rate was 62.16% (23/37) in the control group and 85.71% (30/35) in the treatment group, with a statistically significant difference (χ2 = 5.14, P<0.05). At weeks 12 and 24 after treatment, the TCM syndrome score, BMI, CAP value, TC, TG, LDL-C, and FFA were all significantly lower in both groups compared to pre-treatment levels, while the HDL-C level significantly increased (P<0.05). The effect was better at week 24 (P<0.05) than at week 12 (P<0.05), and the treatment group showed better outcomes than the control group at weeks 12 and 24 after treatment (P<0.05). After 24 weeks of treatment, both groups exhibited significant reductions in IL-18 and IL-1β levels (P<0.05). The treatment group demonstrated superior efficacy compared to the control group after treatment (P<0.05). Both groups experienced decreases in ALT, AST, and GGT levels after treatment (P<0.05). However, there were no statistically significant differences between the 12-week and 24-week post-treatment values within each group, nor were there significant differences between the two groups. No significant adverse reactions were observed in both groups. ConclusionThe Dizhuo Huayu prescription combined with catgut embedding therapy is safe and effective in treating patients with NASH and dyslipidemia, exhibiting hepatoprotective, anti-inflammatory, lipid-regulating, and weight-reducing effects.
9.Influenza virus infection of influenza-like illness at a sentinel hospital in Baoshan District of Shanghai from the monitoring year of 2015 to 2023
Yongdi HU ; Wenxia DOU ; Lunhui XIANG ; Ya GAO ; Xiaofeng LIU ; Fan HE
Shanghai Journal of Preventive Medicine 2025;37(7):606-610
ObjectiveTo investigate the influenza virus infection status of influenza-like illness (ILI) at a sentinel hospital in Baoshan District of Shanghai, to explore the seasonal patterns of influenza, so as to provide a scientific basis for influenza prevention and control in Baoshan District of Shanghai. MethodsSurveillance data and pathogenic testing results of ILI from the monitoring year of 2015 to 2023 were collected from the sentinel hospital to describe the seasonal epidemic characteristics of influenza in this district. ResultsThe proportion of ILI visits to sentinel hospital in Baoshan District of Shanghai showed an upward trend from 2015 to 2023 (Z=2.598, P=0.09). The positive rate of influenza virus in ILI was 20.43% (1 761/8 621), of which 14.17% were positive for influenza A virus, including 8.43% for influenza A/H3N2 and 5.74% for influenza A/H1N1. The positive rate of influenza B virus was 6.25%, of which the positive detection rate of influenza B/Victoria virus was 5.35%, while that of influenza B/Yamagata virus was 0.90%. Influenza B/Yamagata virus was not detected in 2019‒2023. The highest positivity rate was observed in the 5‒<15 years age group (25.57%). The positive rate of ILI was lower in males (19.90%) than that in females (20.90%). There were three patterns of influenza epidemic in the district: with year-round circulation in 2016‒2017 and 2021‒2022; with bimodal peaks in 2015‒2016, 2017‒2018 and 2022‒2023; and with one peak in 2018‒2019 and 2019‒2020. The positive rate of influenza virus exhibited seasonal variations, with influenza A virus predominated in summer and autumn. However, influenza B virus showed an increase in spring and winter. ConclusionThe influenza epidemic in Baoshan District, Shanghai exhibits diverse patterns with heterogeneous epidemiological characteristics across different age groups and seasons. Notably, children and adolescents aged 5‒<15 years constitute the key target population for influenza prevention and control. Enhanced surveillance and targeted control measures against influenza A/H3N2 lineage viruses are particularly warranted during summer and autumn seasons.
10.Study on the protective efect and mechanism of paeoniflorin on palmitic acid-induced HepG2 cells
Tong LIU ; Shanzheng LI ; Cheng ZHOU ; Sutong LIU ; Lihui ZHANG ; Wenxia ZHAO
Journal of Clinical Hepatology 2025;41(3):499-505
ObjectiveTo investigate the role and mechanism of action of paeoniflorin (PF) in protecting HepG2 cells induced by palmitic acid (PA). MethodsHepG2 cells were stimulated with PA at a concentration of 250 μmol/L to establish a NAFLD model. Compound C at a concentration of 10 μmol/L was used as an inhibitor, and PF at a concentration of 25 μmol/L was used for intervention. The experiment was divided into normal group (CON group) treated with complete culture medium, model group (MOD group) treated with PA, PF treatment group (MOD+PF group) treated with PA and PF, model+inhibitor group (MOD+COM group) treated with PA and Compound C, and model+inhibitor+PF group (MOD+COM+PF group) treated with PA, Compound C, and PF. Kits were used to measure lipid deposition indicators, liver function parameters, oxidative stress indicators, and inflammation indicators; oil red O staining was used to observe lipid deposition; Western Blot was used to measure the protein expression levels of AMPK, SIRT1, PGC-1α, mTOR, Beclin-1, LC3, and P62 in cells. The one-way analysis of variance was used for comparison of quantitative data between groups, while the Tukey’s test was used for comparison between two groups. ResultsCompared with the MOD group, PF improved the levels of TC and TG (P<0.05), reduced the levels of ALT, AST, CRP, TNF-α, IL-1β, and IL-6 (P<0.05), increased the activity of SOD and CAT and the level of GSH, and reduced the level of MDA in cells (all P<0.05). Oil red O staining showed that PF alleviated lipid deposition in cells. Western blot results showed that compared with the MOD group, PF increased the protein expression levels of p-AMPK, SIRT1, PGC-1α, LC3Ⅱ/LC3Ⅰ, and Beclin-1 and reduced the protein expression levels of p-mTOR and P62 (all P<0.05). ConclusionPF can inhibit PA-induced oxidative stress and inflammatory response in HepG2 cells, improve lipid deposition, and promote autophagy via the AMPK/SIRT1/PGC-1α/mTOR signaling pathway.

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