1.Traditional Chinese Medicine Regulates AMPK Signaling Pathway to Prevent and Treat Non-alcoholic Fatty Liver Disease: A Review
Lijuan DAN ; Shuanglan CHEN ; Tianyuan WANG ; Xiaojie YOU ; Xiuyan LI ; Hongfei SONG ; Dong WANG ; Jie MU ; Qiao LI
Chinese Journal of Experimental Traditional Medical Formulae 2026;32(14):133-143
Non-alcoholic fatty liver disease (NAFLD) is one of the most prevalent forms of liver diseases globally. Its progression can lead to cirrhosis and end-stage liver disease, and there is currently a lack of effective pharmacological treatments. Adenosine monophosphate-activated protein kinase (AMPK), as a regulatory hub for maintaining cellular energy homeostasis, can coordinate key cellular processes such as adipogenesis, glucose metabolism, and mitochondrial functions. Its activation exerts metabolic regulatory effects through pathways including inhibiting lipogenesis, enhancing mitochondrial β-oxidation, regulating inflammation and oxidative stress, and promoting autophagy. Accordingly, AMPK emerges as a potential target for the prevention and treatment of NAFLD. Traditional Chinese Medicine (TCM), with low toxicity, high accessibility, and multi-component, multi-target synergistic effects, has demonstrated unique value in NAFLD treatment, particularly showing notable advantages in regulating the AMPK signaling pathway. Sichuan is known as the treasure house of TCM, and the active components of its authentic medicinal materials such as Coptidis Rhizoma not only reflect regional characteristics in AMPK signaling regulation but also form a multi-level metabolic regulatory network through crosstalk with pathways such as sirtuin 1 (SIRT1) and peroxisome proliferator-activated receptor α (PPARα). They can achieve specific regulation by directly activating AMPK and modulating upstream and downstream targets, exerting prominent effects in ameliorating hepatic steatosis and inflammation. This study systematically reviews the research findings on TCM for the prevention and treatment of NAFLD over the past five years, elaborating the mechanisms by which TCM treats NAFLD through regulating the AMPK signaling pathway. It aims to provide new perspectives and references for clinical diagnosis and treatment, basic research, and drug development.
2.Mechanism of action of mitochondrial calcium uniporter complex in treatment of metabolic dysfunction-associated fatty liver disease
Xinyu ZHANG ; Lijuan DAN ; Xiaojie YOU ; Jie MU ; Hongfei SONG
Journal of Clinical Hepatology 2026;42(8):1952-1959
Metabolic dysfunction-associated fatty liver disease (MAFLD) is a chronic liver condition closely associated with dysregulated lipid metabolism, with the central pathological event of mitochondrial dysfunction in hepatocytes. The mitochondrial calcium uniporter (MCU) complex is a key molecular apparatus regulating mitochondrial calcium (mtCa2+) homeostasis, and mtCa2+ overload due to its dysfunction plays a critical role in the progression of MAFLD. This article systematically elaborates on the pathogenesis of MAFLD, with a particular focus on how the central signaling axis of “MCU complex dysfunction-mtCa2+ overload” drives the disease progression of MAFLD by disrupting energy metabolism, activating the adenosine monophosphate-activated protein kinase signaling pathway, triggering the NOD-like receptor protein 3 inflammasome, and inducing cell death. It also points out that traditional Chinese medicine can exert an interventional effect on multiple downstream pathways through various targets and has shown unique advantages and a significant potential in alleviating MAFLD by maintaining mitochondrial homeostasis and targeting the MCU complex, and therefore, it is expected to provide new strategies for the prevention and treatment of MAFLD.
3.Screening and validation of diagnostic biomarkers in metabolic dysfunction-associated fatty liver disease based on data-independent acquisition quantitative proteomics
Hongfei SONG ; Lijuan DAN ; Xiuyan LI ; Xiaojie YOU ; Shengjie WU ; Haibo YIN ; Wenping LIU ; Qiao LI ; Jie MU
Journal of Clinical Hepatology 2026;42(9):2075-2085
ObjectiveTo screen for and validate key differentially expressed proteins in serum of patients with metabolic dysfunction‑associated fatty liver disease (MAFLD), and to provide a basis for identifying diagnostic biomarkers and developing intervention strategies for this disease. MethodsA total of 20 patients who were diagnosed with MAFLD in the third affiliated hospital of Chengdu University of Traditional Chinese Medicine from December 2024 to January 2025 were enrolled as MAFLD group, and 20 healthy controls were enrolled as HC group. Demographic data and serum biochemical parameters were collected from both groups. Data-independent acquisition (DIA) quantitative proteomics was used to measure the relative expression levels of serum proteins, and related methods were used to obtain significantly differentially expressed proteins, including the gene ontology functional enrichment analysis, the Kyoto Encyclopedia of Genes and Genomes pathway enrichment analysis, protein-protein interaction (PPI) network, Hub node interaction, and weighted gene co-expression network analysis (WGCNA). Rats were given a high-fat diet to establish a model of MAFLD, and randomly assigned to the control group and model group. Serum biochemical parameters and inflammatory factors were measured, liver histopathological changes were observed, and the protein expression levels of MER proto-oncogene tyrosine kinase (MERTK) and matrix metalloproteinase-9 (MMP-9) in liver tissue were verified. The independent-samples t test was used for comparison of normally distributed continuous data between groups, while the Mann-Whitney U test was used for comparison of non-normally distributed continuous data or data with heterogeneity of variance between groups; the chi-square test or the Fisher’s exact test was used for comparison of categorical data between groups. ResultsCompared with the HC group, the MAFLD group had significant increases in the serum levels of aspartate aminotransferase (t=-7.348, P<0.05), alanine aminotransferase (Z=5.088, P<0.05), alkaline phosphatase (t=-3.943, P<0.05), triglyceride (Z=2.070, P<0.05), and high-density lipoprotein cholesterol (t=3.867, P<0.05). A total of 3 559 proteins were identified by DIA serum proteomics, among which 160 differentially expressed proteins were mainly enriched in pathways including metabolic disorders, immune inflammatory response, and extracellular matrix remodeling. The PPI network and the Hub node analysis showed that serpin family E member 1, MMP-9, and intercellular cell adhesion molecule-1 were core regulatory proteins. WGCNA showed that the MEyellow module was significantly positively correlated with MAFLD phenotype (cor=0.55, P<0.001), which was functionally enriched in the efferocytosis pathway. MERTK (P<0.001) and MMP-9 (P<0.001) showed the most significant differential expression in this module. A rat model of MAFLD was successfully established using a high-fat diet, and compared with the control group, the model group had enlarged, yellowish, and greasy liver and disordered structure of hepatic lobules, hepatocyte fatty degeneration, and inflammatory cell infiltration based on HE staining, as well as massive lipid droplet deposition based on oil red O staining, while no obvious fibrous cords were observed in Masson staining. Compared with the control group, the model group had significant increases in the serum levels of aspartate aminotransferase (t=-5.148, P<0.05), alanine aminotransferase (t=-5.663, P<0.05), total bilirubin (t=-13.061, P<0.05), triglyceride (Z=-2.722, P<0.05), total cholesterol (t=3.588, P<0.05), and tumor necrosis factor-α (t=-16.741, P<0.05), as well as significant increases in the protein expression levels of MERTK (t=-11.448, P<0.001) and MMP-9 (t=-10.875, P<0.001) in liver tissue. ConclusionMMP-9 and MERTK are abnormally expressed in MAFLD and may be used as potential diagnostic biomarkers for this disease.
4.An excerpt of management of acute variceal bleeding: updated APASL guidelines (2025 edition)
Lijuan FENG ; Min WANG ; Guanhua ZHANG ; Yuhong SUO ; You DENG ; Fuliang HE ; Yu WANG ; Jidong JIA
Journal of Clinical Hepatology 2025;41(11):2252-2257
On August 31, 2025, the Asian Pacific Association for the Study of the Liver (APASL) updated and released management of acute variceal bleeding: updated APASL guidelines (2025 edition), which systematically elaborates on the definition, diagnosis, assessment, and treatment of acute variceal bleeding. This article gives an excerpt of the recommendations in this guideline.
5.Application of automated assessment software in optimizing thrombectomy workflow for stroke
Xiaolan YAN ; Ya SHAO ; Li XIAO ; Qiutong YUAN ; Baoyi GUO ; Yuping YOU ; Lijuan WANG ; Zhengzhou YUAN
Journal of Xi'an Jiaotong University(Medical Sciences) 2025;46(6):910-915
Objective To investigate whether the application of automated software for computed tomography angiography(CTA)and computed tomography perfusion imaging(CTP)can improve in-hospital workflow for endovascular treatment(EVT)in acute ischemic stroke patients.Methods We included patients with acute ischemic stroke who received CTA and CTP evaluation followed by EVT through the stroke emergency pathway at the Affiliated Hospital of Southwest Medical University between January 1,2020 and December 30,2022.The patients were divided into two groups:control group and artificial intelligence(Al)group based on whether automated software was used for assessment.The control group consisted of patients who underwent manual post-processing of multimodal imaging before June 2021,while the AI group was composed of patients whose imaging was processed with automated software from July 2021 onwards.The primary outcome was door-to-puncture time(DPT),and the secondary outcome was the 90-day modified Rankin Scale(mRS)score.Results A total of 312 patients were included,with 145 in the control group and 167 in the AI group.The median age of all the patients was 68 years(range:58-74 years),and 55.4%(173 patients)were male.The median National Institutes of Health Stroke Scale(NIHSS)score at presentation was 16 scores(range:12-19 scores).The median DPT was reduced from 110 min(range:80-150 min)before the use of automated software to 95 min(range:65-125 min)after its implementation(P<0.001).However,there was no significant difference in the proportion of patients achieving functional independence(mRS score of 0-2)between the two groups(39.3%vs.41.3%,P=0.719).Conclusion The application of multimodal CT automated software improves the in-hospital workflow for acute ischemic stroke patients by reducing the time to EVT.However,the software did not significantly impact neurological functional outcomes as measured by the mRS.
6.Application of automated assessment software in optimizing thrombectomy workflow for stroke
Xiaolan YAN ; Ya SHAO ; Li XIAO ; Qiutong YUAN ; Baoyi GUO ; Yuping YOU ; Lijuan WANG ; Zhengzhou YUAN
Journal of Xi'an Jiaotong University(Medical Sciences) 2025;46(6):910-915
Objective To investigate whether the application of automated software for computed tomography angiography(CTA)and computed tomography perfusion imaging(CTP)can improve in-hospital workflow for endovascular treatment(EVT)in acute ischemic stroke patients.Methods We included patients with acute ischemic stroke who received CTA and CTP evaluation followed by EVT through the stroke emergency pathway at the Affiliated Hospital of Southwest Medical University between January 1,2020 and December 30,2022.The patients were divided into two groups:control group and artificial intelligence(Al)group based on whether automated software was used for assessment.The control group consisted of patients who underwent manual post-processing of multimodal imaging before June 2021,while the AI group was composed of patients whose imaging was processed with automated software from July 2021 onwards.The primary outcome was door-to-puncture time(DPT),and the secondary outcome was the 90-day modified Rankin Scale(mRS)score.Results A total of 312 patients were included,with 145 in the control group and 167 in the AI group.The median age of all the patients was 68 years(range:58-74 years),and 55.4%(173 patients)were male.The median National Institutes of Health Stroke Scale(NIHSS)score at presentation was 16 scores(range:12-19 scores).The median DPT was reduced from 110 min(range:80-150 min)before the use of automated software to 95 min(range:65-125 min)after its implementation(P<0.001).However,there was no significant difference in the proportion of patients achieving functional independence(mRS score of 0-2)between the two groups(39.3%vs.41.3%,P=0.719).Conclusion The application of multimodal CT automated software improves the in-hospital workflow for acute ischemic stroke patients by reducing the time to EVT.However,the software did not significantly impact neurological functional outcomes as measured by the mRS.
7.Role of spinal Leucine-rich Repeat Kinase 2 in neuropathic pain in rats
Xiang ZHONG ; Shengxi XIAO ; Lijuan YOU ; Yaohua WU ; Quanshui HAO
Chinese Journal of Anesthesiology 2024;44(9):1122-1126
Objective:To evaluate the role of spinal Leucine-rich Repeat Kinase 2 (LRRK2) in neuropathic pain in rats.Methods:Fifty SPF healthy male Sprague-Dawley rats, aged 6-7 weeks, weighing 210-245 g, were divided into 5 groups ( n=10 each) using a random number table method: control group (C group), neuropathic pain group (NP group), low dose GNE-7915 group (low-dose GNE-7915 group), medium-dose GNE-7915 group (medium-dose GNE-7915 group), and high-dose GNE-7915 group (high-dose GNE-7915 group). Neuropathic pain was induced by the spared nerve injury in anesthetized rats. At 7 days after developing the model, LRRK2 inhibitor GNE-7915 12.5, 25.0 and 50.0 mg/kg were intraperitoneally injected in low-, medium- and high-dose GNE-7915 groups, respectively. The mechanical paw withdrawal threshold (MWT) and thermal paw withdrawal latency (TWL) were measured before developing the model, at 7 days after developing the model, and at 4 h after injecting the inhibitor. After measurement of the pain threshold, the rats were sacrificed and the spinal cord tissues were taken for determination of the positive expression of ionized calcium-binding adapter molecule 1(Iba-1) (by immunofluorescence staining), contents of interleukin-1β (IL-1β), monocyte chemotactic protein-1 (MCP-1) and IL-18 (by enzyme-linked immunosorbent assay), positive expression of phosphorylated LRRK2 (p-LRRK2) (by immunofluorescence staining), and expression of LRRK2, IL-1β, MCP-1 and IL-18 (by immunoblotting). The ratio of p-LRRK2/LRRK2 was calculated. Results:Compared with C group, the MWT was significantly decreased, the TWL was shortened, the proportion of Iba-1 and p-LRRK2 positive cells in spinal cord tissues, contents of IL-1β, MCP-1 and IL-18, and p-LRRK2/LRRK2 ratio were increased, and the expression of IL-1β, MCP-1 and IL-18 proteins was up-regulated in NP group ( P<0.05). Compared with NP group, the MWT was significantly increased, the TWL was prolonged, the proportion of Iba-1 and p-LRRK2 positive cells in spinal cord tissues, contents of IL-1β, MCP-1 and IL-18, and p-LRRK2/LRRK2 ratio were decreased, and the expression of IL-1β, MCP-1 and IL-18 proteins was down-regulated in low-, medium- and high-dose GNE-7915 groups ( P<0.05). Conclusions:LRRK2 in the spinal cord may be involved in the pathophysiological mechanism of neuropathic pain by activating microglia and inducing inflammatory responses in rats.
8.Study on SIRT1-NLRP3 axis-mediated pyroptosis in the role of remifentanil against liver ischemia-reperfusion injury
Xiufang LI ; Quanshui HAO ; Xiong GAO ; Lijuan YOU ; Ling QIN ; Yaohua WU ; Xihua ZHANG
Organ Transplantation 2024;15(6):895-902
Objective To investigate the role and mechanism of silent information regulator 1(SIRT1)-NOD-like receptor protein 3(NLRP3)axis in the effect of remifentanil against ischemia-reperfusion injury(IRI)in rat livers.SD rats were randomly divided into sham operation group(sham group),IRI group,IRI+remifentanil pretreatment group(IRI+RPC group),IRI+SIRT1 inhibitor EX-527 group(IRI+EX-527 group)and IRI+RPC+EX-527 group,with 8 rats in each group.The levels of serum alanine aminotransferase(ALT),aspartate aminotransferase(AST),lactate dehydrogenase(LDH),interleukin(IL)-1β and IL-18 of rats in each group were detected.The liver tissue pathology was observed.The apoptosis rate of hepatocytes in rats was detected.The expressions of SIRT1,NLRP3,cleaved cysteinyl aspartate specific proteinase-1(Cleaved Caspase-1)and Gasdermin D(GSDMD)proteins in rat liver tissue were detected.Results Compared with the sham group,the liver tissue pathological score and hepatocyte apoptosis rate of rats in the IRI group were increased,the serum ALT,AST,LDH,IL-1β,and IL-18 levels were increased,the relative expression of SIRT1 protein in liver tissue was decreased,and the relative expression of NLRP3,Cleaved Caspase-1,and GSDMD proteins were increased(all P<0.05).Compared with the IRI group,the liver tissue pathological score and hepatocyte apoptosis rate of rats in the IRI+RPC group were decreased,the serum ALT,AST,LDH,IL-1β,and IL-18 levels were decreased,the relative expression of SIRT1 protein in liver tissue was increased,and the relative expression of NLRP3,Cleaved Caspase-1,and GSDMD proteins were decreased;the liver tissue pathological score and hepatocyte apoptosis rate of rats in the IRI+EX-527 group were increased,the ALT,AST,LDH,IL-1β,and IL-18 levels were increased,the relative expression of SIRT1 protein in liver tissue was decreased,and the relative expression of NLRP3,Cleaved Caspase-1,and GSDMD proteins were increased(all P<0.05).Compared with the IRI+RPC group,the liver tissue pathological score and hepatocyte apoptosis rate in the IRI+RPC+EX-527 group were increased,the levels of ALT,AST,LDH,IL-1β,and IL-18 were increased,the relative expression of SIRT1 protein in liver tissue was decreased,and the relative expression of NLRP3,Cleaved Caspase-1,and GSDMD proteins were increased(all P<0.05).Conclusions SIRT1 may participate in the regulation of remifentanil against rat liver IRI by inhibiting NLRP3 mediated cell pyroptosis.
9.Clinical Efficacy and Effect on NLR of Tongfu Xiezhuo Enema in Treating Patients with Stage 3-4 CKD Based on Theory of Gut-kidney Axis
Yonghao SANG ; Liqun SONG ; Jie YUN ; Lijuan DAI ; Zeyang DIAO ; Yuanyuan DANG ; You XIONG
Chinese Journal of Experimental Traditional Medical Formulae 2024;30(21):227-233
ObjectiveTo observe the clinical efficacy of Tongfu Xiezhuo enema in treating stage 3-4 chronic kidney disease (CKD) and the effect of the therapy on the neutrophil-to-lymphocyte ratio (NLR) as an inflammation marker. MethodSixty patients diagnosed with stage 3-4 CKD who visited the Nephrology Department of the First Affiliated Hospital of Heilongjiang University of Chinese Medicine from December 2022 to June 2023 were included and randomly assigned into observation and control groups in a ratio of 1∶1. The control group received conventional therapy plus Shenkang suppositories, while the observation group received conventional therapy plus Tongfu Xiezhuo enema. After 8 weeks of treatment, the clinical efficacy was assessed based on the changes in traditional Chinese medicine (TCM) symptom scores, renal function indicators, and NLR. Result① Both groups showed decreases in TCM symptom scores after treatment (P<0.01), and the decreases were more significant in the observation group than in the control group (P<0.05). The total response rate of TCM symptoms in the observation group was 79.31% (23/29), which was higher than that (62.96%, 17/27) in the control group (Z=0.604,P<0.05). ② After treatment, the observation group showed declined serum levels of creatinine (SCr), blood urea nitrogen (BUN), and cystatin C (Cys C) and increased glomerular filtration rate (GFR) (P<0.01), and the control group showed lowered SCr level and increased GFR (P<0.05). The observation group had lower SCr level and higher GFR than the control group after treatment (P<0.05). The total response rate of renal function in the observation group was 79.31% (23/29), which was higher than that (55.56%, 15/27) in the control group (Z=1.127,P<0.01). ③ The NLR in the observation group decreased after treatment (P<0.05), and it was lower than that in the control group (P<0.05). ④ There were no significant differences in safety indicators between the two groups before and after treatment. ConclusionTongfu Xiezhuo enema ameliorated symptoms and improved renal function indicators in the patients with stage 3-4 CKD by reducing the NLR and inhibiting inflammation.
10.The association between sleep duration, obesity types and the risk of chronic diseases among occupational population in Shanghai City
Jianhua XUE ; Aijun YOU ; Jianguang TIAN ; Zhiyue XU ; Xiuyu WANG ; Lijuan YANG
China Occupational Medicine 2023;50(3):349-354
Objective To investigate the relationship between sleep duration and obesity, and the risk of common chronic diseases in the occupational population in Shanghai City. Methods A total of 18 775 occupational individuals were selected as the study subjects using convenience sampling method in Shanghai City. Data on personal lifestyle behaviors and medical examination results were collected. The relationship between sleep duration and different types of obesity with dyslipidemia, hyperuricemia, hypertension, and hyperglycemia was analyzed. Results The incidence of dyslipidemia, hyperuricemia, hypertension, and hyperglycemia among the study subjects was 24.9%, 16.2%, 11.5%, and 7.3%, respectively. The incidence of these four chronic diseases were higher in individuals with central obesity and suboptimal sleep compared to the control group (all P<0.01). Multivariate logistic regression analysis showed that suboptimal sleep combined with general obesity/overweight increased the risk of dyslipidemia, hyperuricemia, hypertension, and hyperglycemia in the study subjects [odds ratio (OR) were 2.40, 3.47, 3.30, and 2.79, respectively; all P<0.01], after adjusting for age, gender, education level, marital status, occupation type, labor intensity, smoking, and drinking. Suboptimal sleep combined with central obesity also potentially increased the risk of these four chronic diseases (OR were 2.25, 3.09, 3.09, and 2.98, respectively; all P<0.01). Conclusion The incidence of common chronic diseases is relatively high in the occupational population in Shanghai City. Suboptimal sleep combined with different types of obesity increases the risk of common chronic diseases.

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