ObjectiveTo investigate the therapeutic effect and mechanism of Huatan Qushi Huoxue prescription on rats with metabolic dysfunction-associated steatohepatitis （MASH）. MethodsA total of 60 specific pathogen-free Sprague-Dawley rats were randomly divided into blank control group， model A group， model B group， Western medicine group （polyene phosphatidylcholine， 143.64 mg/kg）， high-dose Chinese medicine group （Huatan Qushi Huoxue prescription， 20.16 g/kg）， and middle-dose Chinese medicine group （Huatan Qushi Huoxue prescription， 10.08 g/kg）. All rats except those in the blank control group were given high-fat diet. Samples were collected from the model A group at week 8， and since week 12， the other groups were given the corresponding drug once a day for 8 consecutive weeks， with samples collected at week 20. Body weight， liver wet weight， and liver index were measured for all rats； the microplate method was used to measure the serum levels of alanine aminotransferase （ALT）， aspartate aminotransferase （AST）， total cholesterol （TC）， triglycerides （TG）， high-density lipoprotein cholesterol （HDL-C）， low-density lipoprotein cholesterol （LDL-C）， and free fatty acids （FFA）； ELISA was used to measure the serum levels of tumor necrosis factor-α （TNF-α）， interleukin-1β （IL-1β）， interleukin-6 （IL-6）， and soluble triggering receptor expressed on myeloid cells 2 （sTREM2）； HE staining and oil red O staining were performed to observe liver histopathological changes； immunofluorescence assay was used to measure CD68⁺TREM2⁺ cells in liver tissue and calculate the phagocytosis rate of macrophages； quantitative real-time PCR was used to measure the mRNA expression levels of sphingosine 1-phosphate （S1P）， sphingosine 1-phosphate receptor 1 （S1PR1）， a disintegrin and metalloproteinase 17 （ADAM17）， and triggering receptor expressed on myeloid cells 2 （TREM2） in liver tissue， and immunohistochemistry was used to measure the protein expression levels of S1P， S1PR1， ADAM17， and TREM2 in liver tissue. A one-way analysis of variance was used for comparison of normally distributed continuous data with homogeneity of variance between groups， and the least significant difference t-test was used for further comparison between two groups； the Welch’s test was used for comparison of normally distributed continuous data with heterogeneity of variance between groups， and the Tamhane’s test was used for further comparison between two groups. The Kruskal-Wallis H test was used for comparison of non-normally distributed continuous data between groups， and the Dunn’s test was used for further comparison between two groups. ResultsCompared with the blank control group， the model A group and the model B group had significant increases in body weight and liver wet weight， and the model B group had a significant increase in liver index （all P<0.05）. HE staining showed diffuse macrovesicular steatosis of liver tissue in the model A group and a large number of hepatocytes with ballooning degeneration in liver tissue in the model group B， with the presence of mixed inflammatory cell infiltration and mild perisinusoidal fibrosis in the lobules and the portal area. Compared with the blank control group， the model A group and the model B group had significant increases in NAS score and oil red O-positive area （all P<0.05）， and the model B group had significant increases in these two indicators than the model A group （both P<0.05）. Compared with the blank control group， the model A group and the model B group had significant increases in the serum levels of TC， TG， LDL-C， FFA， IL-1β， IL-6， and sTREM2 and a significant reduction in the serum level of HDL-C， and the model B group had significant increases in the serum levels of ALT， AST， and TNF-α （all P<0.05）； compared with the model A group， the model B group had significant increases in the serum levels of ALT， AST， TC， TG， FFA， TNF-α， IL-1β， IL-6， and sTREM2 and a significant reduction in the serum level of HDL-C （all P<0.05）. Immunofluorescence assay showed that compared with the blank control group， the model A group had a significant increase in the phagocytosis rate of macrophages （P<0.05）， while the model B group had a significantly lower phagocytosis rate of macrophages than the model A group （P<0.05）. Quantitative real-time PCR showed that compared with the blank control group， the model A group and the model B group had a significant increase in the mRNA expression level of TREM2， and the model B group had significant increases in the mRNA expression levels of S1P and S1PR1 （both P<0.05）； moreover， compared with the model A group， the model B group had significant increases in the mRNA expression levels of S1PR1 and TREM2 （both P<0.05）. Immunohistochemistry showed that compared with the blank control group， the model A group and the model B group had significant increases in the protein expression levels of S1P， S1PR1， and ADAM17， and the model A group had a significant increase in the protein expression level of TREM2 （all P<0.05）； compared with the model A group， the model B group had significant increases in the protein expression levels of S1P， S1PR1， and ADAM17 and a significant reduction in the protein expression level of TREM2 （all P<0.05）. Compared with the model B group， each medication group had significant reductions in body weight， liver wet weight， and liver index （all P<0.05）； each medication group had significant improvements in hepatic steatosis and inflammatory damage， with significant reductions in NAS score and oil red O-positive area （all P<0.05）； each medication group had significant reductions in the serum levels of ALT， AST， TC， TG， FFA， IL-1β， and IL-6 （all P<0.05） and a significant increase in the serum level of HDL-C （P<0.05）， and the high-dose Chinese medicine group had a significant reduction in the serum level of TNF-α （P<0.05）； each medication group had a significant increase in the phagocytosis rate of macrophages （all P<0.05）； the high- and middle-dose Chinese medicine groups had a significant reduction in the protein expression level of ADAM17， and the high-dose Chinese medicine group had a significant increase in the protein expression level of TREM2 （all P<0.05）. ConclusionHuatan Qushi Huoxue prescription improves lipid metabolism and inflammation in the liver of MASH rats by regulating hepatic macrophage phagocytosis.

Liver fibrosis is the core pathological stage of the progression of various chronic liver diseases to liver cirrhosis， and hepatic stellate cell （HSC） activation and the abnormal accumulation of collagen fibers are important processes for the development and progression of liver fibrosis. In recent years， studies have shown that HSC activation is regulated by the complex interactions between various organelles （including mitochondria， endoplasmic reticulum， Golgi apparatus， lysosome， and peroxisomes）， and such interactions affect the key cellular processes such as energy metabolism， protein synthesis and folding， reactive oxygen species balance， and autophagy， thereby participating in the progression of liver fibrosis. Meanwhile， traditional Chinese medicine and its active ingredients with multi-target synergistic effects have attracted wide attention. From the perspective of the interaction between organelles， this article systematically elaborates on the specific mechanism of such interactions in the progression of liver fibrosis and reviews how traditional Chinese medicine inhibits HSC activation and collagen production by regulating the function of these organelle and their interaction networks， thereby exerting an anti-liver fibrosis effect， in order to provide a theoretical basis for in-depth understanding of the pathological mechanism of liver fibrosis and the development of new traditional Chinese medicine intervention strategies.

Animal model research on spleen and stomach diseases in traditional Chinese medicine （TCM） is of great significance for elucidating the nature of diseases and syndromes and for revealing the mechanisms of action of Chinese herbal medicinals. At present， studies on classical TCM syndrome models of spleen and stomach diseases mainly focus on spleen deficiency syndrome， liver constraint syndrome， and damp-heat syndrome. Model construction is mostly based on the etiological and pathophysiological characteristics of syndrome， and model evaluation primarily involves macroscopic manifestations and physicochemical indicators. This paper summarizes the current research status of animal models integrating disease and syndrome for seven common spleen and stomach diseases， including chronic gastritis and gastric precancerous lesions， gastroesophageal reflux disease， functional dyspepsia， inflammatory bowel disease， irritable bowel syndrome， functional constipation， and functional diarrhea. The modeling methods and characteristics of disease-syndrome combined animal models for each disease are analyzed. It is proposed that future research on disease-syndrome integration in spleen and stomach diseases should move toward syste-matic， precise， and integrative development， and that interdisciplinary and cross-disciplinary research approaches should be adopted to enhance the predictive value and application efficiency of disease-syndrome combined animal models.

Metabolic dysfunction-associated fatty liver disease （MAFLD） is a chronic metabolic liver disorder with complex etiologies. Different clinical phenotypes of MAFLD （such as obesity， hyperlipidemia， type 2 diabetes mellitus， the postmenopausal state， and chronic hepatitis B） have different mechanisms of action in the development and progression of MAFLD， leading to high heterogeneity in its clinical progression and prognosis. This article systematically reviews the pathogeneses and clinical features of the above five clinical phenotypes of MAFLD and elaborates on the corresponding individualized diagnosis and treatment regimens integrating traditional Chinese medicine and Western medicine， in order to provide a reference for clinical practice and improve clinical diagnosis and treatment.

Metabolic associated fatty liver disease （MAFLD） is a chronic liver disease with a rapidly increasing incidence rate worldwide， and its complex pathogenesis is closely associated with O-linked β-N-acetylglucosamine （O-GlcNAc） modification. As a dynamic and reversible post-translational modification of proteins， O-GlcNAc modification is mainly regulated by O-GlcNAc transferase and O-GlcNAcase. O-GlcNAc modification can drive hepatic steatosis， exacerbate insulin resistance， and impair mitochondrial function， thereby leading to the aggravation of metabolic disorders， promoting inflammation response， and driving the progression of MAFLD to metabolic associated steatohepatitis and hepatic fibrosis. This article systematically reviews the latest research advances in the role of O-GlcNAc modification in the development and progression of MAFLD， in order to provide theoretical support and research direction for a deeper understanding of the pathological mechanism of MAFLD and the development of effective therapeutic strategies.

ObjectiveTo investigate the potential targets of 2，5-dihydroxybenzoic acid （2，5-DHBA） in the treatment of metabolic dysfunction-associated fatty liver disease （MAFLD） and the molecular mechanism by which it regulates the phosphatidylinositol 3-kinase （PI3K）/protein kinase B （Akt） signaling pathway. MethodsA network pharmacology analysis was performed at first， and related databases were used to obtain the common action targets of 2，5-DHBA and MAFLD， followed by molecular docking and pathway enrichment analysis to predict the potential biological processes and signaling pathways regulated by these targets. Then mouse normal hepatocytes AML-12 were used for cell experiments， and CCK-8 assay was used to determine the three optimal intervention concentrations of 2，5-DHBA. AML-12 cells were divided into control group， model group （cells cultured in a medium containing 2 mmol/L free fatty acid ［FFA］ to establish a cell model of MAFLD）， and three 2，5-DHBA intervention groups （cells cultured with FFA and 2，5-DHBA at the three different concentrations of 1.25， 5， and 20 μmol/L， respectively）. Oil red O staining was used to observe intracellular lipid accumulation； the fluorescent probe DCFH-DA was used to measure the level of intracellular reactive oxygen species （ROS）； biochemical assays were used to measure the content of triglyceride （TG） and total cholesterol （TC）； quantitative real-time PCR and Western Blot were used to measure the expression levels of related genes and proteins. A one-way analysis of variance was used for comparison between multiple groups， and the Tukey’s test was used for further comparison between two groups. ResultsA total of 32 common targets were obtained for 2，5-DHBA and MAFLD. Within a concentration range of 1.25 — 20 μmol/L， 2，5-DHBA treatment， starting from the concentration of 2.5 μmol/L， increased the viability of AML-12 cells in a dose-dependent manner. The minimum effective concentration of 1.25 μmol/L， the intermediate gradient concentration of 5 μmol/L， and the maximum safe concentration within the effective range of 20 μmol/L were selected for low-， middle-， and high-dose intervention， respectively. Compared with the model group， 2，5-DHBA intervention at concentrations of 1.25， 5， and 20 μmol/L could significantly reduce lipid droplet accumulation in cells （all P<0.05）， and there were significant differences in TG and TC between the model group and the three intervention groups （all P<0.05）. Compared with the control group， the model group had a significant increase in ROS fluorescence intensity （P<0.05）， and compared with the model group， there was a dose-dependent reduction in intracellular ROS level after treatment with 5 μmol/L or 20 μmol/L 2，5-DHBA （P<0.05）. Compared with the model group， 2，5-DHBA treatment at concentrations of 5 and 20 μmol/L significantly downregulated the mRNA expression levels of the lipogenic genes SREBf1 and FASN and upregulated the mRNA expression levels of the key antioxidant gene Nrf2 and its downstream target gene HO-1 （all P<0.05）. Compared with the control group， the expression of p-PI3K/PI3K and p-Akt/Akt in the model group was significantly increased （all P<0.05）. Compared with the model group， the protein expression levels of p-PI3K/PI3K and p-Akt/Akt were significantly decreased after 5 μmol/L 2，5-DHBA treatment （P<0.05）. Compared with the control group， the expression levels of Nrf2 and HO-1 protein in the model group were significantly decreased （all P<0.05）. The protein levels of Nrf2 and HO-1 were significantly increased after treatment with 1.25 μmol/L 2，5-DHBA （P<0.05）. ConclusionNetwork pharmacology and cellular experiments confirm that 2，5-DHBA can alleviate lipid deposition and oxidative stress by regulating the PI3K/Akt signaling pathway， thereby exerting a therapeutic effect on MAFLD.

[Objective] To compare the efficacy and safety of deglycerolized red blood cells (DRBC) and suspended red blood cells (SRBC) based on the propensity score matching (PSM) method, so as to provide evidence for the rational use of DRBC resources in clinical practice. [Methods] A total of 89 patients who received DRBC transfusion and 2 916 patients who received SRBC transfusion in our hospital from January 2023 to September 2024 were included. A 1∶1 nearest neighbor PSM was used to balance covariates such as gender, age, and body mass index (BMI). The changes of hemoglobin (Hb), red blood cell (RBC) count, hematocrit (HCT), and inflammatory markers such as white blood cell (WBC) count, neutrophil (NE) count, C-reactive protein (CRP), and Interleukin-6(IL-6) in the last 72 hours after transfusion were analyzed by SPSS 26.0 and R software to evaluate clinical efficacy and transfusion safety. [Results] The baseline of the two groups was balanced after PSM (P>0.05). There was no significant difference in the total effective rate between the DRBC group (80.9%) and the SRBC group (86.5%) (P>0.05). In the SRBC group, WBC (×10 /L) increased from 9.634±6.742 to 10.147±6.835, CRP (mg/dL) increased from 5.468±4.647 to 6.174±6.114, and IL-6(pg/mL) decreased from 213.733±587.191 to 157.255±552.626. In the DRBC group, WBC (×10 /L) decreased from 11.123±7.880 to 11.011±8.549, CRP (mg/dL) decreased from 5.729±4.761 to 5.326±4.466, and IL-6(pg/mL) decreased from 238.806±639.060 to 152.255±266.558. Compared with the before treatment, the differences between the SRBC group and DRBC group were not statistically significant (P>0.05). Among all patients included in the statistics, the overall incidence of transfusion adverse reactions was 0.205% (6/2 916) in the SRBC group, and no adverse reactions occurred in the DRBC group. The incidence in the SRBC group was higher than that in the DRBC group. [Conclusion] Based on PSM analysis, there was no significant difference in the efficacy and safety of DRBC transfusion compared with SRBC transfusion, which can provide evidence-based support for routine application.

ObjectiveTo observe the clinical effect of Xiaozhi Hugan capsules in treating patients with non-alcoholic steatohepatitis （NASH） combined with phlegm-dampness and blood stasis syndrome and its effects on serum interleukin-6 （IL-6） and monocyte chemoattractant protein-1 （MCP-1）. MethodsA total of 124 patients with NASH combined with phlegm-dampness and blood stasis syndrome who were admitted to the Department of Spleen， Stomach， and Hepatobiliary Diseases， the First Affiliated Hospital of Henan University of Chinese Medicine from July 2020 to December 2022 were selected. According to the random number table method， patients were randomly divided into an observation group （62 cases） and a control group （62 cases）. The treatment duration was 6 months. The observation group received Xiaozhi Hugan capsules orally， while the control group received polyene phosphatidylcholine capsules. The efficacy indicators included alanine aminotransferase （ALT）， aspartate aminotransferase （AST）， controlled attenuation parameter （CAP）， liver stiffness measurement （LSM）， traditional Chinese medicine （TCM） syndrome scores （discomfort/dull pain/distending pain in liver region， fatigue， etc.）， body mass index （BMI）， waist-to-height ratio （WHtR）， high-density lipoprotein cholesterol （HDL-C）， total cholesterol （TC）， triglycerides （TG）， homeostatic model assessment for insulin resistance （HOMA-IR） ［including fasting blood glucose （FBG） and fasting insulin level （INS）］， free fatty acids （FFA）， IL-6， and MCP-1. Adverse drug reactions were recorded. ResultsAfter treatment， the total effective rate in the observation group was 92.3% （48/52）， while that in the control group was 75.5% （39/49）. The total effective rate in the observation group was higher than that in the control group （χ²=5.339， P<0.05）. After treatment， the TCM syndrome scores in both groups were significantly reduced （P<0.05）， and the post-treatment scores in the observation group were better than those in the control group （P<0.05）. After treatment， the levels of ALT， AST， TC， FFA， fasting insulin （FINS）， HOMA-IR， MCP-1， IL-6， CAP， LSM， BMI， and WHtR were decreased （P<0.05） significantly in both groups， and the observation group showed superior improvement in the above indicators compared to the control group （P<0.05）. The observation group exhibited significant reductions in TG and FBG （P<0.05） and an increase in HDL-C （P<0.05）， while no significant changes were observed in the control group. The observation group was superior to the control group after treatment （P<0.05）. No severe adverse reactions occurred in either group during the treatment. ConclusionXiaozhi Hugan capsules have significant clinical efficacy in treating patients with NASH combined with phlegm-dampness and blood stasis syndrome. It reduces hepatic steatosis， lowers liver stiffness， inhibits the expression of serum inflammatory factors， and alleviates liver inflammation. No obvious adverse reactions occur， suggesting it is suitable for clinical application.

ObjectiveTo observe the clinical effect of Xiaozhi Hugan capsules in treating patients with non-alcoholic steatohepatitis （NASH） combined with phlegm-dampness and blood stasis syndrome and its effects on serum interleukin-6 （IL-6） and monocyte chemoattractant protein-1 （MCP-1）. MethodsA total of 124 patients with NASH combined with phlegm-dampness and blood stasis syndrome who were admitted to the Department of Spleen， Stomach， and Hepatobiliary Diseases， the First Affiliated Hospital of Henan University of Chinese Medicine from July 2020 to December 2022 were selected. According to the random number table method， patients were randomly divided into an observation group （62 cases） and a control group （62 cases）. The treatment duration was 6 months. The observation group received Xiaozhi Hugan capsules orally， while the control group received polyene phosphatidylcholine capsules. The efficacy indicators included alanine aminotransferase （ALT）， aspartate aminotransferase （AST）， controlled attenuation parameter （CAP）， liver stiffness measurement （LSM）， traditional Chinese medicine （TCM） syndrome scores （discomfort/dull pain/distending pain in liver region， fatigue， etc.）， body mass index （BMI）， waist-to-height ratio （WHtR）， high-density lipoprotein cholesterol （HDL-C）， total cholesterol （TC）， triglycerides （TG）， homeostatic model assessment for insulin resistance （HOMA-IR） ［including fasting blood glucose （FBG） and fasting insulin level （INS）］， free fatty acids （FFA）， IL-6， and MCP-1. Adverse drug reactions were recorded. ResultsAfter treatment， the total effective rate in the observation group was 92.3% （48/52）， while that in the control group was 75.5% （39/49）. The total effective rate in the observation group was higher than that in the control group （χ²=5.339， P<0.05）. After treatment， the TCM syndrome scores in both groups were significantly reduced （P<0.05）， and the post-treatment scores in the observation group were better than those in the control group （P<0.05）. After treatment， the levels of ALT， AST， TC， FFA， fasting insulin （FINS）， HOMA-IR， MCP-1， IL-6， CAP， LSM， BMI， and WHtR were decreased （P<0.05） significantly in both groups， and the observation group showed superior improvement in the above indicators compared to the control group （P<0.05）. The observation group exhibited significant reductions in TG and FBG （P<0.05） and an increase in HDL-C （P<0.05）， while no significant changes were observed in the control group. The observation group was superior to the control group after treatment （P<0.05）. No severe adverse reactions occurred in either group during the treatment. ConclusionXiaozhi Hugan capsules have significant clinical efficacy in treating patients with NASH combined with phlegm-dampness and blood stasis syndrome. It reduces hepatic steatosis， lowers liver stiffness， inhibits the expression of serum inflammatory factors， and alleviates liver inflammation. No obvious adverse reactions occur， suggesting it is suitable for clinical application.

Idiopathic pulmonary fibrosis (IPF) is a progressive disease lacking effective therapy. Metformin, an antidiabetic medication, has shown promising therapeutic properties in preclinical fibrosis models; however, its precise cellular targets and associated mechanisms in fibrosis resolution remain incompletely defined. Most research on metformin's effects has focused on mesenchymal and inflammatory responses with limited attention to epithelial cells. In this study, we utilized Sftpc lineage-traced and Fgfr2b conditional knockout mice, along with BMP2/PPARγ and AMPK inhibitors, to explore metformin's impact on alveolar epithelial cells in a bleomycin-induced pulmonary fibrosis model and cell culture. We found that metformin increased the proliferation and differentiation of alveolar type 2 (AT2) cells, particularly the recently identified injury-activated alveolar progenitors (IAAPs)-a subpopulation characterized by low SFTPC expression but enriched for PD-L1. Single-cell RNA sequencing revealed a reduction in apoptosis among mature AT2 cells. Interestingly, metformin's therapeutic effects were not significantly affected by BMP2 or PPARγ inhibition, which blocked the lipogenic differentiation of myofibroblasts. However, Fgfr2b deletion in Sftpc lineage cells significantly impaired metformin's ability to promote fibrosis resolution, a process linked to AMPK signaling. In conclusion, metformin alleviates fibrosis by directly activating AT2 cells, especially the IAAPs, through a mechanism that involves AMPK and FGFR2b signaling, but is largely independent of BMP2/PPARγ pathways.