1.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.
2.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.
3.Modified Weijingtang Regulates Pyroptosis of Macrophages via Caspase-1/GSDMD Pathway
Dongfang SHANG ; Chenlu ZHAO ; Siying WANG ; Cheng ZHOU ; Minghao LIU ; Pingsheng ZHU ; Suping MA ; Wenxia ZHAO
Chinese Journal of Experimental Traditional Medical Formulae 2024;30(11):27-33
ObjectiveTo investigate the effect of modified Weijingtang on the pyroptosis of RAW264.7 macrophages via the cysteinyl aspartate-specific protease-1 (Caspase-1)/gasdermin D (GSDMD) pathway. MethodLipopolysaccharide (LPS) was used to induce pyroptosis of RAW264.7 cells. The blank group was treated with the blank serum, and the intervention groups were treated with the sera containing different doses of modified Weijingtang. After 24 h, the viability of cells in different groups was examined by the cell counting kit-8 (CCK-8). The pyroptosis and morphology of cells in each group were observed by a scanning electron microscope and a phase-contrast microscope, respectively. The mRNA and protein levels of nucleotide-binding oligomerization domain-like receptor protein 3 (NLRP3), Caspase-1, and GSDMD in each group were determined by real-time fluorescence quantitative polymerase chain reaction (Real-time PCR) and Western blot, respectively. The levels of interleukin (IL)-18 and IL-1β in each group were measured by enzyme-linked immunosorbent assay. ResultUnder the electron microscope, RAW264.7 cells presented the best morphology and structure in the blank group and obvious pyroptosis and leakage of cell contents in the model (LPS) group. Compared with the model group, the intervention groups showed reduced pyroptosis to varying degrees, and the high-dose group had the closest cell morphology and structure to the blank group. Under the optical microscope, RAW264.7 cells were spherical in the blank group and irregular with protrusions in the model group. Compared with the model group, the intervention groups showed improved cell morphology, and the cell morphology in the group with the dose of 20% was the closest to that in the blank group. The mRNA and protein levels of NLRP3, Caspase-1, and GSDMD in the model group were higher than those in the blank group (P<0.05). Compared with the model group, each intervention group showed down-regulated expression of the above indicators (P<0.05). Compared with the blank group, the model group presented elevated levels of IL-18 and IL-1β (P<0.05), which were lowered in the intervention (10%, 20%) groups (P<0.01). ConclusionModified Weijingtang inhibits the pyroptosis of macrophages by down-regulating the Caspase-1/GSDMD pathway and reducing the release of proinflammatory cytokines.
4.Mechanism of lipid metabolism mediated by hepatokines and adipokines in nonalcoholic fatty liver disease
Chenlu ZHAO ; Dongfang SHANG ; Cheng ZHOU ; Junhao SHI ; Wenxia ZHAO
Journal of Clinical Hepatology 2023;39(1):168-174
Nonalcoholic fatty liver disease (NAFLD) has been renamed as metabolic-associated fatty liver disease, and systemic metabolic dysfunction has become one of the concerns of this disease. NAFLD is a metabolic disease based on dyslipidemia in the liver, which is closely associated with adipose tissue. Hepatokines and adipokines secreted by the liver and adipose tissue play an important role in regulating liver lipid metabolism. This article summarizes the hepatokines and adipokines that can promote or inhibit lipid metabolism, focusing on the mechanism of lipid metabolism mediated by hepatokines and adipokines in NAFLD, so as to provides ideas and a theoretical basis for clinical prevention and treatment.
5.Influence of white fat browning on nonalcoholic fatty liver disease
Chenlu ZHAO ; Cheng ZHOU ; Dongfang SHANG ; Sutong LIU ; Junhao SHI ; Xiaojie WANG ; Wenxia ZHAO
Journal of Clinical Hepatology 2023;39(4):909-914
Nonalcoholic fatty liver disease (NAFLD) is a chronic liver disease in which a large amount of fat accumulates in hepatocytes due to lipid metabolism disorders. Conventional anti-inflammatory and transaminase-lowering treatment regimens often have an unsatisfactory therapeutic effect, and restoring the normal biosynthesis and metabolism of lipids is the key to the treatment of NAFLD. Studies have shown that brown adipose tissue can improve metabolic diseases by enhancing insulin sensitivity and regulating lipid metabolism, and the treatment of NAFLD by promoting white fat browning has attracted wide attention in the medical field. This article reviews the mechanism of white fat browning in improving NAFLD and summarizes the hepatokines that can promote white fat browning, so as to provide new ideas for the clinical treatment of NAFLD.
6.Mechanism of ferroptosis in the formation of nonalcoholic fatty liver disease/nonalcoholic steatohepatitis
Minghao LIU ; Sutong LIU ; Lihui ZHANG ; Yajiao GU ; Dongfang SHANG ; Zhun XIAO ; Wenxia ZHAO
Journal of Clinical Hepatology 2022;38(5):1152-1155
Ferroptosis is a type of iron-dependent cell death driven by lipid peroxidation, and its mechanism is associated with iron homeostasis imbalance, lipid peroxidation, and slC7A11-GSH-GPX4 antioxidant system. Ferroptosis plays a key role in the development and progression of nonalcoholic fatty liver disease (NAFLD)/nonalcoholic steatohepatitis (NASH), and inhibition of ferroptosis can almost completely inhibit the development of NASH. This article reviews the research advances in the mechanism of ferroptosis and its role in NAFLD/NASH and proposes the research strategies and technical means for ferroptosis, so as to provide a reference for research on the mechanism of NAFLD/NASH.
7.Effect of Huatan Qushi Huoxue prescription on lipopolysaccharide-induced pyroptosis of macrophages
Minghao LIU ; Sutong LIU ; Dongfang SHANG ; Lihui ZHANG ; Yajiao GU ; Wenxia ZHAO
Journal of Clinical Hepatology 2022;38(9):2016-2019
Objective To investigate the effect of Huatan Qushi Huoxue prescription on lipopolysaccharide (LPS)-induced pyroptosis of RAW264.7 cells and its mechanism. Methods An in vitro cell model of LPS-induced activated RAW264.7 was established and divided into blank group, model group, high-, middle-, and low-dose Huatan Qushi Huoxue prescription groups, and control group. The corresponding drug-containing serum intervention was performed for 24 hours. A scanning electron microscope was used to observe cell morphology, and immunofluorescence assay was used to perform quantitative localization of GSDMD-N. Results The cells in the blank group were round and regular in shape with smooth surface, and those in the control group were swollen, with folds on the surface and gaps in the capsule, which were consistent with the morphology of cell pyroptosis. The cells in the control group had bubbles on the surface with obvious pseudopodia and pores in cell membrane, and those in the high-dose group were not swollen and had a rough surface with pseudopodia, with no obvious pores in cell membrane. The cells in the low- and middle-dose groups were swollen and had a rough surface of cell membrane with pores and pseudopodia. Immunofluorescence assay showed that compared with the blank group, the model group had a significant increase in the positive staining intensity of GSDMD-N, and compared with the model group, the control group and the Traditional Chinese medicine group had a reduction in the positive staining intensity of GSDMD-N. Conclusion Huatan Qushi Huoxue prescription can improve the pyroptosis of macrophages and reduce the expression of GSDMD-N.
8.Risk factors for cognitive impairment associated with nonalcoholic fatty liver disease
Cheng ZHOU ; Ran JIA ; Jingjing WEI ; Chenlu ZHAO ; Dongfang SHANG ; Wenxia ZHAO
Journal of Clinical Hepatology 2022;38(11):2592-2595
At present, non-alcoholic fatty liver disease (NAFLD) has become one of the most common chronic liver diseases in the world. Recent studies have shown that varying degrees of central nervous system dysfunction can occur during the progression of NAFLD, including cognitive impairment and emotional imbalance. This article summarizes the main risk factors for NAFLD-related cognitive impairment at different stages, so as to provide a basis and ideas for the early prevention and clinical treatment of this disease.
9.Chinese Expert's Perspectives on Andrological Diseases Responding Specifically to Traditional Chinese Medicine
Yue-qing LI ; Hai-song LI ; Yong-zhang SUN ; Sheng LIN ; Bao-xing LIU ; Jia-you ZHAO ; Jian-wu SHEN ; Hong-ming LIU ; Jing-shang WANG ; Yuan TANG ; Shao-ming LIU ; Hai WANG ; Yu-tian ZHU ; Yong ZHU ; Yong YANG ; Xiao-xiao ZHANG ; Bin WANG
Chinese Journal of Experimental Traditional Medical Formulae 2021;27(12):182-188
In recent years, the incidence rate of andrological diseases has shown a significant growth trend. Considering the unavailability of a perfect theoretical system for andrology in traditional Chinese medicine (TCM) and the complex pathogenesis despite of the limited types of andrological diseases, it is necessary to improve the clinical efficacy of andrological diseases so as to satisfy the needs of patients. Therefore, the China Association of Chinese Medicine (CACM) organized the andrologists of TCM and western medicine and the outstanding young clinicians to discuss the andrological diseases responding specifically to TCM or integrated TCM and western medicine, such as chronic prostatitis, male infertility, benign prostatic hyperplasia, erectile dysfunction, and premature ejaculation, determine their diagnostic criteria in western medicine, and standardize the specifications for TCM diagnosis and treatment based on syndrome differentiation, thus formulating recognized and integrated diagnosis and treatment protocols. Apart from proposing suggestions on the treatment of such andrological diseases with TCM and western medicine, the experts have also figured out the andrological diseases responding specifically to TCM, the optimal intervention time of TCM and western medicine, and the suitable measures including surgery. The resulting consensus helps to better guide the formulation of accurate, personalized, and optimized treatment plans in clinical practice and improve the diagnosis and treatment effects of andrological diseases by giving full play to the advantages of TCM, which will in turn contribute to further innovation and development of TCM.
10.Association of gene mutations in the pre-C, C, and basic core promoter regions of hepatitis B virus with traditional Chinese medicine syndrome types
Dongfang SHANG ; Shilei WANG ; Wenxia ZHAO
Journal of Clinical Hepatology 2021;37(4):809-812
ObjectiveTo investigate the association of gene mutations in the pre-C, C, and basic core promoter (BCP) regions of hepatitis B virus (HBV) with traditional Chinese medicine (TCM) syndrome types in patients with chronic hepatitis B (CHB). MethodsA retrospective analysis was performed for the clinical data of CHB patients who were diagnosed and treated at the outpatient service and ward of Spleen, Stomach, and Hepatobiliary Department, The First Affiliated Hospital of Henan University of Chinese Medicine, from November 2014 to June 2018. Related clinical data were collected and recorded, including general information, HBV serological markers, HBV gene mutations, and information obtained by four TCM diagnostic methods. Syndrome differentiation and typing were performed for each patient with reference to the criteria for TCM syndrome differentiation of viral hepatitis, and the association of gene mutation in the pre-C, C, and BCP regions of HBV with TCM syndrome types was analyzed. The chi-square test was used for comparison of categorical data between groups, and the Kruskal-Wallis H test was used for comparison of continuous data between multiple or two groups. ResultsA total of 235 patients with CHB were enrolled, among whom 101 had internal retention of damp-heat, 88 had stagnation of liver Qi and spleen deficiency, 17 had blood stasis obstructing the collaterals, 19 had liver-kidney Yin deficiency, and 10 had spleen-kidney Yang deficiency. There were significant differences in sex, age, and course of disease between the patients with different TCM syndrome types (χ2=17.389, H=173.280, H=86.520, all P<0.01), and there was a significant difference in age between the CHB patients with gene mutations in the pre-C, C and BCP regions of HBV (H=30.150, P<0.001). There was a significant difference in the distribution of TCM syndrome types between the CHB patients with gene mutations in the pre-C, C and BCP regions of HBV (χ2=58.117, P<0.001), and internal retention of damp-heat and stagnation of liver Qi and spleen deficiency were major TCM syndrome types accounting for 80.43%. The patients with internal retention of damp-heat tended to have A1762T and G1764A mutations, and those with stagnation of liver Qi and spleen deficiency tended to have G1896A, A1762T, and G1764A mutations; G1764A mutation was often observed in the patients with blood stasis obstructing the collaterals or liver-kidney Yin deficiency, and I97L mutation was often observed in the patients with spleen-kidney Yang deficiency. ConclusionGene mutations in the pre-C, C, and BCP regions of HBV are associated with TCM syndrome types in CHB patients, and internal retention of damp-heat and stagnation of liver Qi and spleen deficiency are the most common TCM syndrome types. I97L mutation is often observed in patients with spleen-kidney Yang deficiency.

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