1.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.
2.Akkermansia muciniphila-derived acetate activates the hepatic AMPK/SIRT1/PGC-1α axis to alleviate ferroptosis in metabolic-associated fatty liver disease.
Aoxiang ZHUGE ; Shengjie LI ; Shengyi HAN ; Yin YUAN ; Jian SHEN ; Wenrui WU ; Kaicen WANG ; Jiafeng XIA ; Qiangqiang WANG ; Yifeng GU ; Enguo CHEN ; Lanjuan LI
Acta Pharmaceutica Sinica B 2025;15(1):151-167
Emerging evidences have indicated the role of ferroptosis in the progression of metabolic-associated fatty liver disease (MAFLD); thus, inhibiting ferroptosis is a promising strategy for the development of MAFLD therapeutics. Recent studies have demonstrated the antioxidative effect of the gut commensal bacterium Akkermansia muciniphila (A. muc); however, whether it can alleviate ferroptosis remains unclear. The current study indicates A. muc intervention efficiently reversed high-fat high-fructose diet (HFHFD)-induced lipid peroxidation and ferroptosis in the liver. These beneficial effects were mediated by activation of the hepatic AMPK/SIRT1/PGC-1α axis, as evidenced by the finding that AMPK deficiency abrogated the amelioration of lipid peroxidation in vitro and in vivo. Furthermore, the short-chain fatty acids (SCFAs) were enriched upon A. muc treatment, and acetate was identified as a key activator of hepatic AMPK signalling. Mechanistically, microbiota-derived acetate was transported to the liver and metabolized to adenosine monophosphate (AMP), which triggered AMPK activation. Furthermore, a colonization assay in germ-free mice confirmed that A. muc mediated antiferroptotic effects in the absence of other microbes. These data indicated that A. muc exerts antiferroptotic effects against MAFLD, at least partially by producing acetate, which activates the hepatic AMPK/SIRT1/PGC-1α axis to alleviate ferroptosis via the inhibition of polyunsaturated fatty acid (PUFA) synthesis.
3.Study on the Salary Distribution Equity of Health Technicians in China
Mian XIA ; Min'gou WANG ; Shengjie YIN ; Shuai JIANG
Chinese Health Economics 2024;43(5):1-4,22
Objective:To explore deficiencies in the reform of China's health remuneration system through empirical data,provide data support and references for optimization of China's remuneration policy for health technicians.Methods:The Gini coefficient is calculated based on the data of CHIP to analyze the equity of salary distribution of health technicians in different regions and different genders.Results:Health technicians'income is rising and at a higher level in society.Eastern,urban,and male health technicians receive higher salary;income distribution gap across regions and female is increasing;income distribution in health industry is more even than most industry.Conclusion:It is needed to continue to push forward the reform of the health remuneration system,balance efficiency and equity,formulate income distribution scheme according to local conditions,strengthen attention and protection to the income distribution for female health technicians.
4.Evolutionary Game Analysis of the Implementation of the Annual Salary System for Principal Officials in Public Hospi-tals
Mian XIA ; Shengjie YIN ; Shuai JIANG ; Meili ZHANG
Chinese Health Economics 2024;43(5):5-8
Objective:It explores how to promote the effective implementation of the annual salary system in public hospital.Methods:On the basis of the existing annual salary system reform,through evolutionary game model,it analyzes the key factors that affect strategy selection of government and principal person in charge of hospitals during the implementation of the annual salary sys-tem.Results:In addition to the interaction between behavioral agents,the cost of government supervision,the internal and external pressure of social and administrative systems affect the strategic choice of government.The level and structure of annual salary,the difficulty degree of achieving performance goals and intensity of punishment affect the strategic choice of the main person in charge of hospital.Conclusion:In order to improve the implementation of the annual salary system,government should make a reasonable sala-ry scheme,improve the reward and punishment mechanism and reduce transaction costs.
5.Study on the Salary Distribution Equity of Health Technicians in China
Mian XIA ; Min'gou WANG ; Shengjie YIN ; Shuai JIANG
Chinese Health Economics 2024;43(5):1-4,22
Objective:To explore deficiencies in the reform of China's health remuneration system through empirical data,provide data support and references for optimization of China's remuneration policy for health technicians.Methods:The Gini coefficient is calculated based on the data of CHIP to analyze the equity of salary distribution of health technicians in different regions and different genders.Results:Health technicians'income is rising and at a higher level in society.Eastern,urban,and male health technicians receive higher salary;income distribution gap across regions and female is increasing;income distribution in health industry is more even than most industry.Conclusion:It is needed to continue to push forward the reform of the health remuneration system,balance efficiency and equity,formulate income distribution scheme according to local conditions,strengthen attention and protection to the income distribution for female health technicians.
6.Evolutionary Game Analysis of the Implementation of the Annual Salary System for Principal Officials in Public Hospi-tals
Mian XIA ; Shengjie YIN ; Shuai JIANG ; Meili ZHANG
Chinese Health Economics 2024;43(5):5-8
Objective:It explores how to promote the effective implementation of the annual salary system in public hospital.Methods:On the basis of the existing annual salary system reform,through evolutionary game model,it analyzes the key factors that affect strategy selection of government and principal person in charge of hospitals during the implementation of the annual salary sys-tem.Results:In addition to the interaction between behavioral agents,the cost of government supervision,the internal and external pressure of social and administrative systems affect the strategic choice of government.The level and structure of annual salary,the difficulty degree of achieving performance goals and intensity of punishment affect the strategic choice of the main person in charge of hospital.Conclusion:In order to improve the implementation of the annual salary system,government should make a reasonable sala-ry scheme,improve the reward and punishment mechanism and reduce transaction costs.
7.Study on the Salary Distribution Equity of Health Technicians in China
Mian XIA ; Min'gou WANG ; Shengjie YIN ; Shuai JIANG
Chinese Health Economics 2024;43(5):1-4,22
Objective:To explore deficiencies in the reform of China's health remuneration system through empirical data,provide data support and references for optimization of China's remuneration policy for health technicians.Methods:The Gini coefficient is calculated based on the data of CHIP to analyze the equity of salary distribution of health technicians in different regions and different genders.Results:Health technicians'income is rising and at a higher level in society.Eastern,urban,and male health technicians receive higher salary;income distribution gap across regions and female is increasing;income distribution in health industry is more even than most industry.Conclusion:It is needed to continue to push forward the reform of the health remuneration system,balance efficiency and equity,formulate income distribution scheme according to local conditions,strengthen attention and protection to the income distribution for female health technicians.
8.Evolutionary Game Analysis of the Implementation of the Annual Salary System for Principal Officials in Public Hospi-tals
Mian XIA ; Shengjie YIN ; Shuai JIANG ; Meili ZHANG
Chinese Health Economics 2024;43(5):5-8
Objective:It explores how to promote the effective implementation of the annual salary system in public hospital.Methods:On the basis of the existing annual salary system reform,through evolutionary game model,it analyzes the key factors that affect strategy selection of government and principal person in charge of hospitals during the implementation of the annual salary sys-tem.Results:In addition to the interaction between behavioral agents,the cost of government supervision,the internal and external pressure of social and administrative systems affect the strategic choice of government.The level and structure of annual salary,the difficulty degree of achieving performance goals and intensity of punishment affect the strategic choice of the main person in charge of hospital.Conclusion:In order to improve the implementation of the annual salary system,government should make a reasonable sala-ry scheme,improve the reward and punishment mechanism and reduce transaction costs.
9.Study on the Salary Distribution Equity of Health Technicians in China
Mian XIA ; Min'gou WANG ; Shengjie YIN ; Shuai JIANG
Chinese Health Economics 2024;43(5):1-4,22
Objective:To explore deficiencies in the reform of China's health remuneration system through empirical data,provide data support and references for optimization of China's remuneration policy for health technicians.Methods:The Gini coefficient is calculated based on the data of CHIP to analyze the equity of salary distribution of health technicians in different regions and different genders.Results:Health technicians'income is rising and at a higher level in society.Eastern,urban,and male health technicians receive higher salary;income distribution gap across regions and female is increasing;income distribution in health industry is more even than most industry.Conclusion:It is needed to continue to push forward the reform of the health remuneration system,balance efficiency and equity,formulate income distribution scheme according to local conditions,strengthen attention and protection to the income distribution for female health technicians.
10.Evolutionary Game Analysis of the Implementation of the Annual Salary System for Principal Officials in Public Hospi-tals
Mian XIA ; Shengjie YIN ; Shuai JIANG ; Meili ZHANG
Chinese Health Economics 2024;43(5):5-8
Objective:It explores how to promote the effective implementation of the annual salary system in public hospital.Methods:On the basis of the existing annual salary system reform,through evolutionary game model,it analyzes the key factors that affect strategy selection of government and principal person in charge of hospitals during the implementation of the annual salary sys-tem.Results:In addition to the interaction between behavioral agents,the cost of government supervision,the internal and external pressure of social and administrative systems affect the strategic choice of government.The level and structure of annual salary,the difficulty degree of achieving performance goals and intensity of punishment affect the strategic choice of the main person in charge of hospital.Conclusion:In order to improve the implementation of the annual salary system,government should make a reasonable sala-ry scheme,improve the reward and punishment mechanism and reduce transaction costs.

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