1.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.
2.Association between serum creatinine/cystatin C ratio and nonalcoholic fatty liver disease in adults
Qizhen ZHANG ; Sutong LIU ; Lihui ZHANG ; Yajie GUAN ; Junjiao XU ; Wenxia ZHAO ; Minghao LIU
Journal of Clinical Hepatology 2025;41(6):1083-1089
ObjectiveTo investigate the association between serum creatinine/cystatin C ratio (CCR) and nonalcoholic fatty liver disease (NAFLD) based on the NHANES database, and to evaluate the potential significance of CCR as an indicator reflecting the metabolic status of the body. MethodsBased on the data from the NHANES database in 1999 — 2004, a total of 4 217 participants were enrolled and divided into NAFLD group with 1 726 participants and non-NAFLD group with 2 491 participants. CCR was compared between the two groups, and the association between CCR and NAFLD was analyzed. The Wilcoxon rank-sum test was used for comparison of continuous data between two groups, and the chi-square test was used for comparison of categorical data between two groups. The multivariate logistic regression model was used to investigate the association between CCR and NAFLD; CCR was divided into 4 groups based on quartiles, and odds ratio (OR) and 95% confidence interval (CI) in the regression model was calculated with the first quartile as reference. In addition, the restricted cubic spline analysis was used to investigate whether there was a non-linear relationship between CCR and NAFLD, and interaction items were introduced into the Logistic regression model to perform an interaction analysis. Subgroup analyses were performed based on the stratification of variables to investigate the difference in the association between CCR and NAFLD in different populations. ResultsThe non-NAFLD group had a significantly higher CCR than the NAFLD group (Z=-4.76,P<0.01). The Logistic regression analysis showed that in model 1 without adjustment of variables, CCR was negatively associated with NAFLD (OR=0.993,95%CI:0.989 — 0.996,P<0.01), and in model 3 with adjustment of all variables, CCR was still negatively associated with NAFLD (OR=0.986,95%CI:0.981 — 0.991,P<0.01). The analysis of CCR based on quartiles showed a significant association between the increase in CCR and the reduction in the risk of NAFLD. In model 3, compared with the individuals with the lowest quartile of CCR, the individuals with the highest quartile of CCR had a significantly lower risk of NAFLD (OR=0.426,95%CI:0.316 — 0.574,P<0.01). Further interaction and subgroup analyses showed that the interaction between CCR and age/sex had a statistical significance (Pinteraction<0.01 and Pinteraction=0.04). The subgroup analysis based on age showed a more significant association between CCR and NAFLD in the middle-aged population (≤60 years) (OR=0.982,95%CI:0.976 — 0.987), and the subgroup analysis based on sex showed a stronger association between CCR and NAFLD in women (OR=0.979,95%CI:0.972 — 0.986). ConclusionThis study shows a significant negative association between CCR and NAFLD, and such association is more significant in middle-aged individuals and women.
3.Role and clinical application prospect of epigenetics in lean nonalcoholic fatty liver disease
Junjiao XU ; Sutong LIU ; Qizhen ZHANG ; Yajie GUAN ; Beilei CUI ; Wenjing WU ; Minghao LIU
Journal of Clinical Hepatology 2025;41(6):1161-1166
Epigenetic mechanisms play a crucial role in the development and progression of nonalcoholic fatty liver disease (NAFLD), especially among lean individuals. The research on related epigenetic mechanisms has provided new clues and directions for revealing the underlying causes and treatment strategies of NAFLD. This article introduces the role of epigenetics in the development and progression of NAFLD among lean individuals in recent years, analyzes the latest research advances in the epigenetics of NAFLD in this population, and briefly describes the basic concepts of epigenetics, including DNA methylation, histone modifications, and non-coding RNA regulation. This article also discusses how epigenetic alterations impact the pathogenesis, disease progression, and treatment strategies of NAFLD in lean individuals.
4.Analysis of the short-and medium-term curative effect of TIPS approach combined with AngioJet thrombus aspiration technology treatment in acute portal vein thrombosis
Dongbin ZHANG ; Kewei ZHANG ; Danghui LU ; Weixiao LI ; Rutao XU ; Kun LI ; Kai LIANG ; Mingzhe CUI ; Junjiao DONG ; Mingge LI ; Shuiting ZHAI ; Tianxiao LI
Chinese Journal of Hepatology 2021;29(8):754-758
Objective:To evaluate the short- and medium-term clinical efficacy of TIPS approach combined with AngioJet thrombus aspiration technology treatment in acute portal vein thrombosis.Methods:63 cases with acute portal vein thrombosis treated in our center from May 2017 to July 2019 were studied retrospectively, including 49 males and 14 females, aged 35-61 (46 ± 5) years. TIPS approach (with/without) combined with Angiojet thrombus aspiration and gastroesophageal varices embolization was performed simultaneously according to the patient's condition. Regular follow-up for 3-33 (22 ± 3) months after surgery was used to observe the curative effect.Results:The technical success rate was 100%. Portal vein and superior mesenteric vein blood flow were returned to normal after the operation. Two cases of biliary tract injury were untreated. Simultaneously, two cases of intrahepatic arteriovenous fistula were treated with superselective arterial embolization. During the follow-up period, 47 cases (74.61%) had complete portal vein recanalization, 13 cases (20.63%) had partial recanalization, 3 cases (4.76%) had complete portal cavernoma, 7 cases (11.11%) had symptomatic hepatic encephalopathy, 1 case had received artificial liver treatment (1.59%), 1 case had peptic ulcer (11.11%), 6 cases (9.52%) had lost to follow-up, and there was no portal hypertension-related bleeding or death.Conclusion:TIPS approach combined with AngioJet thrombus aspiration technology is safe, effective and feasible in the treatment of acute portal vein thrombosis, and the short- and medium-term clinical effects are satisfactory.

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