Traditional Chinese medicine （TCM） has long recognized metabolism-associated fatty liver disease （MASLD）. The Classic of Difficulties （Nan Jing） records that "the accumulation of the liver is called obese Qi". ZHANG Jingyue also stated， "People with spleen and stomach deficiency and weakness or imbalance often suffer from diseases of accumulation". According to syndrome differentiation of the Zang-fu organs， modern physicians generally believe that the key pathogenesis of MASLD lies in the deficiency of spleen and stomach functions. However， MASLD is a chronic and complex disease， and its pathological characteristics cannot be fully explained by a single Zang-Fu syndrome differentiation. The concepts of sweat pores and collateral vessels emerged as early as the Huangdi's Internal Classic （Huang Di Nei Jing）， and later TCM scholars， based on the idea that "sweat pore is the gateway of collateral vessels" proposed the concept of Xuanluo （sweat pores-collateral vessels）. Xuanluo refers to fine structures widely distributed throughout the human body， serving as hubs and channels that regulate the movement and distribution of Qi， blood， and body fluids. By linking the Zang-Fu organs with Xuanluo， a theoretical framework of Qi， blood， and body fluid circulation centered on the "spleen and stomach-Xuanluo" as a whole was established， providing a new perspective for analyzing the essential pathogenesis of MASLD. Combined with the mechanisms involved in the formation and progression of MASLD， the intrinsic correlations between TCM pathogenesis and modern microscopic mechanisms are further analyzed. Modern studies have shown that intestinal microbial dysbiosis and mitochondrial dysfunction are pathological mechanisms involved in the occurrence and development of MASLD， but few have discussed the two as an integrated system. Existing research has confirmed that intestinal microorganisms can affect mitochondrial energy metabolism and oxidative stress through their metabolites， leading to hepatic energy metabolism disorders， oxidative stress （OS）， and inflammation， thereby promoting MASLD progression. Focusing on the correspondence between the "spleen and stomach-Xuanluo" theory and the intestinal microorganism-mitochondrion micro-pathological mechanism， it is proposed that the spleen and stomach share similarities with intestinal microorganisms in the generation of Qi， blood， and body fluids as well as in the regulation of Qi movement， while Xuanluo and mitochondria have commonalities in energy regulation. Moreover， harmonizing the spleen and stomach to ensure unobstructed Xuanluo is the key to maintaining the normal interaction mechanism between intestinal microorganisms and mitochondria. Based on the correlation between the "spleen and stomach-Xuanluo" theory and the intestinal microorganism-mitochondrion interaction， this paper reveals that the essence of MASLD pathogenesis lies in spleen and stomach dysfunction， specifically， failure of the spleen to ascend the clear and failure of the stomach to descend the turbid， resulting in insufficient transformation of Qi and blood， impaired nourishment of Xuanluo， stagnation of Qi and blood， and the long-term formation of phlegm and blood stasis in the liver. Furthermore， it explores the preventive and therapeutic effects of tonifying the spleen and stomach， dredging Xuanluo and collaterals， unblocking the bowels， and regulating Qi in the treatment of MASLD， thereby providing new insights for its prevention and therapy.

Objective To optimize a C57BL/6J mouse liver fibrosis model induced by different doses of carbon tetrachloride through imaging,molecular biology,and pathology method.Methods Thirty-six healthy C57BL/6J male mice were randomly divided into a control group,2 weeks,3 weeks,4 weeks,6 weeks,and 8 weeks groups(n=6)after adaptive feeding for 1 week.The control group was intraperitoneally injected with 0.2 mL olive oil three times a week,and the positive-control groups were intraperitoneally injected with 0.2 mL 20%CCl4-olive oil solution three times a week.Changes in the body weights of mice in each group were recorded.Liver stiffness was measured on days 15,22,29,43 and 57,and blood samples were collected,and cereal third alanine aminotransferase(ALT),aspartate aminotransferase(AST),hyaluronic acid(HA),laminin(LN),pro-typeⅢcollagen(PC-Ⅲ),and typeⅣcollagen(Ⅳ-C)content was measured.The liver tissues were stained with hematoxylin and eosin(HE),Masson,and Sirius red.The Metavir scoring system was used to evaluate the degree of liver fibrosis.Results Compared with the control group,mice in the positive-control groups were listless and tended to huddle together.In terms of body weight,the 4 weeks,6 weeks,and 8 weeks groups were significantly lighter than the control group,while the 2 weeks group mice were significantly heavier than the control group mice.Liver elastography showed a progressive increase in stiffness with increased administration time.The biochemical tests showed that,compared with the control group,the other groups'ALT and AST levels were significantly higher.With an increase in drug delivery time,the positive-control group's HA,LN,PC-Ⅲ and Ⅳ-C levels showed increasing trends.Pathological examination revealed that liver fibrosis was progressively aggravated with an increase in administration time.At 4 weeks,the pathological diagnosis was consistent with that of liver fibrosis,and there were signs of pseudolobule formation at 6 weeks.Pseudolobules were formed at 8 weeks,suggesting early cirrhosis.Conclusions A liver fibrosis model can be successfully established in C57BL/6J mice by intraperitoneal injection of 20%CCl4-olive oil solution three times a week for 4 consecutive weeks.The model has good stability,and the modeling method is rapid and can be used as an optimized scheme for the establishment of liver fibrosis models.

Objective To explore the effective chemical components of Fuzhenghuaxian decoction and its mechanism of action in the treatment of liver fibrosis based on UPLC-Q-TOF-MS combined with network pharmacology and experimental verification.Methods UPLC-Q-TOF-MS/MS technology was used to analyze the active components of Fuzhenghuaxian decoction.The potential targets and mechanisms of FZHXD were analyzed from the aspects of pharmacokinetics,target information,GO enrichment and KEGG Pathway.FZHXD was used to verify the key pathways and targets screened by network pharmacology in mice with liver fibrosis induced by carbon tetrachloride(CCl4),and further improve the accuracy of its prediction results.Results A total of 35 effective chemical components were identified,mainly saponins and organic acids.Through network pharmacology screening,669 drug targets,440 common targets,5 core targets and 11 key active ingredients were obtained.The main signal transduction pathways were predicted to be PI3K-Akt,FOXO,NF-κB signaling pathway,etc.In vivo experiments confirmed that FZHXD improved liver fibrosis in mice through PI3K/AKT,FOXO and NF-κB signaling pathways.Conclusion Fuzhenghuaxian decoction has the characteristics of multi-pathway and multi-target in anti-liver fibrosis by down-regulating PI3K,AKT,NF-κB and up-regulating FOXO.

Objective To explore the effective chemical components of Fuzhenghuaxian decoction and its mechanism of action in the treatment of liver fibrosis based on UPLC-Q-TOF-MS combined with network pharmacology and experimental verification.Methods UPLC-Q-TOF-MS/MS technology was used to analyze the active components of Fuzhenghuaxian decoction.The potential targets and mechanisms of FZHXD were analyzed from the aspects of pharmacokinetics,target information,GO enrichment and KEGG Pathway.FZHXD was used to verify the key pathways and targets screened by network pharmacology in mice with liver fibrosis induced by carbon tetrachloride(CCl4),and further improve the accuracy of its prediction results.Results A total of 35 effective chemical components were identified,mainly saponins and organic acids.Through network pharmacology screening,669 drug targets,440 common targets,5 core targets and 11 key active ingredients were obtained.The main signal transduction pathways were predicted to be PI3K-Akt,FOXO,NF-κB signaling pathway,etc.In vivo experiments confirmed that FZHXD improved liver fibrosis in mice through PI3K/AKT,FOXO and NF-κB signaling pathways.Conclusion Fuzhenghuaxian decoction has the characteristics of multi-pathway and multi-target in anti-liver fibrosis by down-regulating PI3K,AKT,NF-κB and up-regulating FOXO.