Objective To evaluate the safety and efficacy of a self-developed micro-normothermic machine perfusion (NMP) system (micro-perfusion device) for preserving isolated porcine limbs. Methods Five healthy Landrace pigs were selected, and their left and right forelimbs were randomly divided into the NMP group and static cold storage (SCS) group. The NMP group was perfused with the self-developed micro-perfusion device and polymerized hemoglobin perfusate for 32 hours at normothermia, while the SCS group was preserved at 4 ℃. Hemodynamic parameters such as perfusion pressure and flow were monitored. The pH value, partial pressure of oxygen (PO₂), lactic acid (Lac), creatine kinase (CK) and lactate dehydrogenase (LDH) in the perfusate were measured. Hematoxylin-eosin staining was used to assess the muscle tissue structure, terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling was employed to evaluate muscle cell apoptosis, and immunohistochemistry staining was applied to detect the expressions of tumor necrosis factor (TNF)-α and interleukin (IL)-6. A mixed-effects model was used to analyze the effects of time and treatment methods on tissue structure, cell apoptosis and inflammatory factors. Results The device could stably maintain a perfusion pressure of (69±15) mmHg and a flow rate of (117±42) mL/min. The pH value and electrolytes of the perfusate were generally stable, with PO₂ maintained at a high level. Lac was maintained at 5.38(3.81, 6.45) mmol/L, while CK and LDH increased over time. After 32 hours of perfusion in the NMP group, both the myocyte spacing and apoptosis rate were better than those in the SCS group. Mixed-effects model analysis showed that there were statistically significant differences in the effects of NMP treatment and SCS treatment on myocyte spacing and apoptosis rate per unit time (both P < 0.05). There were no statistically significant differences in TNF-α and IL-6 between the two groups, and mixed-effects model analysis showed no statistically significant differences in the effects of NMP treatment and SCS treatment on TNF-α and IL-6 per unit time (both P > 0.05). Conclusions The micro-perfusion device used in this study may achieve 32-hour normothermic preservation in a porcine limb amputation model, maintain basic metabolism and ionic homeostasis, reduce muscle structural damage and cell apoptosis without inducing additional inflammatory responses. This technology is expected to significantly extend the time window for replantation of amputated limbs in disaster rescue and long-distance transportation, providing an important technical basis for clinical translation and subsequent replantation research.

OBJECTIVE To investigate the improvement effect and mechanism of processed Oxytropis falcata on renal fibrosis （RF） in rats. METHODS RF model was induced by adenine. After modeling， the rats were divided into the model group， positive control group （colchicine， 0.45 mg/kg）， and processed O. falcata low-， medium- and high-dose groups （0.5， 1， 2 g/kg）， respectively. Additionally， a blank group without modeling was set up， with 8 rats in each group. The positive control group and the various dosage groups of processed O. falcata were given the corresponding medicinal solutions intragastrically， while the blank group and model group were given equal volume of normal saline intragastrically， once daily for 28 consecutive days. The appearance and histopathological morphology of the rats’ kidneys were observed. Serum levels of renal function indexes [bl ood urea nitrogen （BUN）， creatinine （Cr） ] and inflammatory factors [interleukin-6 （IL-6） and tumor necrosis factor-α （TNF-α） ] in rats were detected. Protein expressions of fibronectin （FN）， α -smooth muscle actin （ α -SMA） and collagen type Ⅰ （Col-Ⅰ） in renal tissue of rats were determined. mRNA expressions of transforming growth factor-β 1 （TGF-β 1 ）， Smad3 and extracellular signal-regulated kinase 1/2 （ERK1/2） in renal tissues were measured. Protein expression of TGF-β 1 and phosphorylation levels of Smad3 and ERK1/2 in renal tissues were detected. RESULTS Compared with the blank group， the rats in the model group exhibited enlarged kidneys with pale color， rough and uneven surface. There was a significant infiltration of inflammatory cells and vacuolated cells in the renal tubules， along with marked proliferation of collagen fibers. Serum levels of BUN， Cr， IL-6 and TNF-α， protein expressions of α -SMA， Col-Ⅰ and FN in renal tissues， mRNA expressions of TGF-β 1 ， Smad3， ERK1 and ERK2 and protein expression of TGF-β 1 as well as phosphorylation levels of Smad3 and ERK1/2 in renal tissues were increased significantly （ P ＜0.05）. Compared with the model group， renal pathological changes of rats were alleviated in processed O. falcata groups， with reduced infiltration of inflammatory cells and proliferation of collagen fibers. The levels of the aforementioned quantitative indicators were all significantly reversed （ P ＜0.05）. CONCLUSIONS Processed O. falcata can improve renal function in RF rats， alleviate inflammatory responses， and reduce abnormal collagen fiber deposition. Its mechanism of action may be related to the inhibition of the activity of the TGF-β 1 /Smad signaling pathway.

BackgroundResident physicians represent a high-risk group for sleep disorders， exhibiting a significantly higher prevalence of such conditions compared with the general population， which severely impairs their physical and mental health. It is hypothesized that perceived stress negatively impacts sleep quality through psychological mechanisms， such as depleting self-control resources and triggering anxiety. However， this pathway warrants empirical validation. ObjectiveTo explore the mediating role of self-control and anxiety emotions in the association between perceived stress and sleep quality among resident physicians， and to elucidate the underlying psychological mechanisms， aiming at providing theoretical basis for developing targeted psychological interventions. MethodsA cross-sectional survey was conducted in April 2025. First- to third- year resident physicians at a hospital in Fuyang City were recruited as participants （n=372）. The Chinese Perceived Stress Scales （CPSS）， the Chinese version of the Dual-Mode of Self-Control Scale （DMSC-S）， the Pittsburgh Sleep Quality Index （PSQI）， and the Generalized Anxiety Disorder Scale-7 item （GAD-7） were used for group testing. The model 6 of the Process macro version 4.1 was ultilized to examine the mediating pathway of self-control and anxiety emotions between perceived stress and sleep quality. ResultsA total of 322 valid questionnaires were collected， yielding an effective responsive rate of 86.56%. Among the respondents， 146 （45.34%） reported poor sleep quality. The CPSS score and GAD-7 score of resident physicians were positively correlated with the PSQI score （r=0.727， 0.784， P<0.01）， while the DMSC-S score was negatively correlated with the PSQI score （r=-0.615， P<0.01）. Perceived stress directly and positively predicted poor sleep quality （B=0.124， P<0.01）， with the direct effect accounting for 31.39% of the total effect. Furthermore， perceived stress indirectly affected sleep quality through the independent mediating effects of self-control and anxiety emotions. The indirect effect values of 0.053 （95% CI： 0.019 - 0.091） and 0.192 （95% CI： 0.141 - 0.249）， accounting for 13.42% and 48.61% of the total effect， respectively. Perceived stress also impact sleep quality through the serial mediating effect of self-control and anxiety， with the indirect effect value of 0.026 （95% CI： 0.005 - 0.049）， accounting for 6.58% of the total effect. ConclusionThe perceived stress of resident physicians can influence sleep quality by impairing self-control， exacerbating anxiety， and through the serial mediation of both factors.

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 systematically evaluate the risk prediction models for postoperative pulmonary infection in patients with esophageal cancer, providing an objective basis for clinical selection and optimization of models. Methods A systematic search was conducted in Chinese and English databases such as VIP, Wanfang, CNKI, CBM, PubMed, Cochrane Library, Embase, and Web of Science for studies related to the risk prediction models of postoperative pulmonary infection in patients with esophageal cancer from the inception to September 30, 2024. The PROBAST tool was used to assess the quality of prognostic model research, and the RevMan 5.4 software was used for meta-analysis of predictive factors. Results A total of 17 articles were included, containing 26 pulmonary infection risk prediction models. The area under the receiver operating characteristic curve (AUC) ranged from 0.627 to 0.942, among which 21 models had good predictive performance (AUC>0.7). Quality assessment through the PROBAST tool revealed that all 17 articles had a high risk of bias. Meta-analysis results showed that common predictive factors for postoperative pulmonary infection in esophageal cancer included smoking history (OR=1.97), smoking index ≥200 (cigarettes-years) (OR=4.38), smoking index ≥400 (cigarettes-years) (OR=2.00), age (OR=1.27), comorbid diabetes (OR=2.13), comorbid emphysema or chronic obstructive pulmonary disease (OR=1.55), low plasma albumin levels (OR=1.17), prognostic nutritional index (OR=4.45), history of related lung diseases (OR=2.10), tumor location (OR=2.32), surgical approach (OR=2.21), operation time (OR=1.73), preoperative serum procalcitonin levels (OR=3.06), anastomotic leakage (OR=3.39), reduced forced expiratory volume in the first second/forced vital capacity ratio (OR=0.86), and hoarseness (OR=2.23). Conclusion At present, the risk prediction models for postoperative pulmonary infection in esophageal cancer are still in the stage of continuous development and optimization, and their research quality needs to be further improved. Future research can refer to the predictive factors summarized in this study based on meta-analysis, combined with clinical practice, to select appropriate methods to construct and validate the risk prediction models for postoperative pulmonary infection in esophageal cancer, thus providing early targeted preventive strategies for high-risk patients.

ObjectiveTo investigate the effect of schisanlactone E in ameliorating neuroinflammation and synaptic injury in APP/PS1 mice and to elucidate whether its mechanism is related to the regulation of helper T cell 17 （Th17）/regulatory T cell （Treg） immune balance. MethodsAPP/PS1 transgenic mice were assigned into model， low- and high-dose （2 mg·kg^-1·d^-1 and 4 mg·kg^-1·d^-1， respectively） schisanlactone E， and donepezil （1 mg·kg^-1·d^-1） groups. C57BL/6J mice were used as the control group. Each group received the corresponding drug by gavage for 30 days. Learning and memory abilities were assessed by the Morris water maze and novel object recognition tests. The percentages of Th17 and Treg cells in the peripheral blood were analyzed by flow cytometry. The mRNA levels of retinoid-related orphan receptor γt （RORγt）， interleukin （IL）-17A， forkhead box protein 3 （FoxP3）， and IL-4 in the hippocampus were determined by Real-time fluorescence quantitative polymerase chain reaction （Real-time PCR）. The synaptic ultrastructure in the hippocampus was observed by transmission electron microscopy. The protein levels of synapsin Ⅰ and postsynaptic density protein 95 （PSD95） in the hippocampus were measured by Western blot. Aβ aggregation and microglial activation in the hippocampus were observed by immunofluorescence staining. The mRNA levels of tumor necrosis factor （TNF）-α， IL-6， and IL-1β in the hippocampus were determined by Real-time PCR. ResultsCompared with the control group， the model group showed prolonged escape latency （P<0.05）， decreased time spent in the target quadrant， platform crossings， novel object exploration time， and percentage of novel object contact frequency （P<0.05， P<0.01）， increased Aβ aggregation in the hippocampal tissue （P<0.01）， an increased proportion of Th17 cells （P<0.05）， a decreased proportion of Treg cells （P<0.05）， and an increased Th17/Treg ratio （P<0.01） in the peripheral blood. Furthermore， the hippocampal tissue in the model group exhibited upregulated mRNA levels of RORγt and IL-17A （P<0.05， P<0.01）， downregulated mRNA levels of FoxP3 and IL-4 （P<0.01）， decreased synapses （P<0.05）， decreased PSD density， synaptic interface curvature， and active zone length （P<0.05， P<0.01）， and increased synaptic cleft width （P<0.05）， downregulated protein levels of Synapsin Ⅰ and PSD95 （P<0.01）， increased microglial activation （P<0.01）， and upregulated mRNA levels of TNF-α， IL-6， and IL-1β （P<0.05）. Compared with the model group， the high-dose schisanlactone E group and the donepezil group exhibited shortened escape latency and increased time in the target quadrant and platform crossings （P<0.05， P<0.01）. The schisanlactone E groups and the donepezil group showed increased novel object exploration time （P<0.05， P<0.01） and percentage of novel object contact frequency （P<0.05， P<0.01）， and reduced hippocampal Aβ aggregation （P<0.05， P<0.01）. The schisanlactone E groups showed a decreased proportion of Th17 cells （P<0.05） and an increased proportion of Treg cells （P<0.05） in the peripheral blood， and all treatment groups showed a decreased Th17/Treg ratio （P<0.05， P<0.01）. The high-dose schisanlactone E group showed a downregulated mRNA level of RORγt in the hippocampal tissue （P<0.05）， and all treatment groups showed a downregulated mRNA level of IL-17A （P<0.05， P<0.01）， and upregulated mRNA levels of FoxP3 and IL-4 （P<0.05， P<0.01）. The schisanlactone E groups and the donepezil group showed increased synapses， active zone length， synaptic interface curvature， and PSD density， decreased synaptic cleft width （P<0.05， P<0.01）， and upregulated protein levels of synapsin Ⅰ and PSD95 （P<0.05， P<0.01）. The high-dose schisanlactone E group and the donepezil group showed decreased microglial activation in the hippocampus （P<0.01）. The schisanlactone E groups and the donepezil group showed downregulated mRNA levels of TNF-α， IL-6， and IL-1β in the hippocampal tissue （P<0.05， P<0.01）. ConclusionSchisanlactone E significantly improves the cognitive function in APP/PS1 mice by regulating the Th17/Treg immune balance， inhibiting neuroinflammation， and ameliorating synaptic injury.

ObjectiveTo observe the effect of aspirin curcumin ester （CA） on the activation and glucose metabolism reprogramming of the mouse microglia （BV2） model of inflammation induced by high glucose/β-amyloid （Aβ）_1-42， and to explore the potential mechanism of CA in reducing neuroinflammatory response in the brain. MethodsThe BV2 activation model was constructed by high glucose combined with Aβ_1-42 oligomers. BV2 cells were treated with Aβ_1-42 oligomers （10 μmol·L^-1） in a high glucose （50 mmol·L^-1） environment and allocated into normal， high glucose， Aβ， and high glucose + Aβ groups. The cell morphology of each group was observed under a bright field. Real-time fluorescence quantitative polymerase chain reaction （Real-time PCR） was adopted to assess the mRNA levels of inflammatory factors including tumor necrosis factor-α （TNF-α）， interleukin-6 （IL-6）， and interleukin-1β （IL-1β） as well as glycolysis-related glucose transporter type 1 （GLUT1）， hexokinase 2 （HK2）， phospofructokinase-2/fructose-2，6-bisphosphatase 3 （PFKFB3）， and pyruvate kinase M2 （PKM2）. To reveal the effects of CA on inflammatory response and glucose metabolism in BV2 cells exposed to high glucose/Aβ_1-42， this study established the BV2 cell model of inflammatory activation by high glucose and Aβ_1-42 oligomer intervention. The cells were allocated into normal， model （50 mmol·L^-1 glucose + 10 μmol·L^-1 Aβ_1-42）， CA （10 μmol·L^-1）， 2DG （0.2 mmol·L^-1）， and DADA （1 mmol·L^-1） groups. Cell counting kit-8 （CCK-8） was used to detect cell survival rate. The cell morphology of each group was observed under a bright field. The expression of inflammatory factors TNF-α， IL-6， and IL-1β and glycolysis-related key enzymes GLUT1， HK2， PFKFB3， and PKM2 at the mRNA level in each group was measured by real-time PCR. The protein levels of GLUT1， HK2， PFKFB3， and PKM2 were determined by Western blot. The glycolysis rate in each group was measured by seahorse. LC-MS was employed to identify the glucose metabolism intermediates. The morphology of mitochondria in cells was observed by electron microscopy. ResultsConstruction of the BV2 cell model： Compared with the normal group， the Aβ group and the high glucose + Aβ group showed more amoeboid-shaped cells and cell aggregation. The high glucose + Aβ group exhibited increased the mRNA levels of TNF-α， IL-1β， and IL-6 （P<0.05， P<0.01）， as well as those of key glycolytic enzymes GLUT1， HK2， PFKFB3， and PKM2 （P<0.01）. The Aβ group also showed significantly increased mRNA levels of PKM2 and PFKFB3 （P<0.01）. Effects of CA on the inflammatory response and glucose metabolism in BV2 cells exposed to high glucose/Aβ_1-42： Compared with the normal group， the model group exhibited amoeboid-shaped cells and cell aggregation， upregulated mRNA levels of TNF-α， IL-1β， IL-6， iNOS， GLUT1， HK2， PFKFB3， and PKM2 （P<0.01） and protein levels of GLUT1， HK2， and PFKFB3 （P<0.05， P<0.01）， an increased basal glycolysis rate （P<0.01）， a decreased compensatory glycolysis rate （P<0.01）， increased glycolytic intermediates and reduced TCA cycle intermediates. In addition， the mitochondria in the model group exhibited a decreased number （P<0.05）， impaired crista integrity （P<0.01）， an increased proportion of vacuolization （P<0.01）， and abnormal mitochondrial morphology. Compared with those in the model group， the number of amoeboid-shaped BV2 cells reduced in the CA and 2DG groups， while most BV2 cells in the DADA group became elongated spindle-shaped. All the three treatment groups showed downregulated mRNA levels of TNF-α， IL-1β， IL-6， GLUT1， HK2， PFKFB3， and PKM2 （P<0.05， P<0.01）， downregulated protein levels of GLUT1， HK2， and PFKFB3 （P<0.05， P<0.01）， and slow compensatory glycolysis and basal glycolysis （P<0.05， P<0.01）. Glycolytic intermediates were decreased and TCA cycle intermediates were increased in the CA and 2DG groups. Mitochondrial morphology largely returned to the normal level in all the three treatment groups， with an increase in mitochondrial number （P<0.05）， improved crista integrity （P<0.05， P<0.01）， and a decreased proportion of vacuolization （P<0.05）. ConclusionAβ_1-42 oligomers can activate BV2 cells and enhance glycolytic activity in the high glucose environment. CA can reduce the expression of inflammatory factors and inhibit the activation of BV2 cells by regulating the glucose metabolism reprogramming in BV2 cells.

ObjectiveTo investigate the effects of paeoniflorin （PF） on neuroinflammation and cognitive impairment in the rat model of Alzheimer's disease （AD） and to clarify whether its mechanism is associated with regulation of the Janus kinase 2 （JAK2）/signal transducer and activator of transcription 3 （STAT3） signaling pathway. MethodsGlycosides related to AD-associated neuroinflammation were screened through bibliometric analysis， and the potential targets of PF were predicted through network pharmacology and molecular docking. A rat model of AD was established by intraperitoneal injection of D-galactose （100 mg·kg^-1·d^-1）. Rats were assigned into a control group， a model group， a PF （200 mg·kg^-1） group， and a donepezil （0.5 mg·kg^-1·d^-1） group， and drugs were administered by gavage for 21 days. The learning and memory abilities were evaluated by the Morris water maze （MWM）. Hematoxylin-eosin （HE） staining and Nissl staining were performed to observe hippocampal neuronal morphology. The mRNA levels of inflammatory factors were determined by Real-time quantitative polymerase chain reaction （Real-time PCR）， and the protein levels of molecules in the JAK2/STAT3 signaling pathway were determined by Western blot. ResultsCompared with the control group， the model group showed prolonged escape latency and decreased platform crossings and time spent in the target quadrant （P<0.05， P<0.01）， accompanied by increased expression of interleukin-1β （IL-1β） and tumor necrosis factor-α （TNF-α）， as well as elevated ratios of phosphorylated （p）-JAK2/JAK2 and p-STAT3/STAT3 （P<0.01）. Compared with the model group， the PF group and donepezil group exhibited shortened escape latency and increased platform crossings and time spent in the target quadrant （P<0.05， P<0.01）， decreased expression levels of IL-1β and TNF-α， upregulated mRNA levels of interleukin-4 （IL-4） and interleukin-10 （IL-10）， and reduced ratios of p-JAK2/JAK2 and p-STAT3/STAT3 （P<0.05， P<0.01）. ConclusionPaeoniflorin can alleviate cognitive impairment and neuroinflammation in the rat model of AD by inhibiting the JAK2/STAT3 signaling pathway.

OBJECTIVE To investigate the ameliorative effect of Weiling decoction on metabolic associated fatty liver disease （MAFLD） based on the gut-liver axis theory.METHODS Male C57BL/6J mice were divided into a blank group （ n ＝9） and a modeling group （ n ＝47）. The modeling group was fed a high-fat diet for 12 weeks to establish the MAFLD model. Forty-five modeled mice were randomly divided into a model group， a positive control group [metformin， 0.2 g/（kg·d）]， and Weiling decoction low-， medium-， and high-dose groups [6.17， 12.34， 24.68 g/（kg·d）， calculated as crude drug]， with 9 mice in each group. Mice in each group received intragastric administration of the corresponding drug solution or normal saline once daily for 4 consecutive weeks. After the last administration， the body weight， liver weight， and liver index were compared among groups； the levels of liver function indicators （alanine transaminase， aspartate transaminase）， lipid indicators （total cholesterol， triglycerides， low-density lipoprotein cholesterol， high-density lipoprotein cholesterol）， inflammatory indicators [tumor necrosis factor-α， interleukin-6 （IL-6）， IL-1β]， oxidative stress indicators （malondialdehyde， superoxide dismutase， glutathione peroxidase）， and intestinal barrier indicators [lipopolysaccharide （LPS）， diamine oxidase， D-lactic acid] were measured； hepatic pathological changes were observed； the expressions of tight junction proteins [zonula occludens-1 （ZO-1）， occludin] in jejunal tissue and proteins related to lipid metabolism [sterol regulatory element-binding protein-1 （SREBP-1）， fatty acid synthase （FASN）， peroxisome proliferator-activated receptor α （PPARα）] and inflammatory pathways [Toll-like receptor 4 （TLR4）， myeloid differentiation primary response protein 88 （MyD88）， nuclear factor-κB p65 （NF-κB p65）] in liver tissue were detected； and changes in gut microbiota were analyzed.RESULTS Compared with the model group， hepatic steatosis and inflammatory injury were significantly alleviated in all Weiling decoction dose groups； body weight （at week 16）， liver weight， liver index， and the levels of liver function indicators， lipid indicators， inflammation indicators， oxidative stress indicators， and intestinal barrier indicators were all generally improved （ P ＜0.05）. The expressions of SREBP-1， FASN， TLR4， and MyD88 and the phosphorylation level of NF-κB p65 in liver tissue were generally decreased or downregulated （ P ＜0.05）， while the expressions of ZO-1 and occludin in jejunal tissue and PPARα in liver tissue were generally increased or upregulated （ P ＜0.05）. Compared with the model group， the Observed species， Chao1， and Ace indices of gut microbiota in the Weiling decoction high-dose group were significantly increased （ P ＜0.05）， and the relative abundances of Verrucomicrobiota， Akkermansia ， etc. were significantly increased， while those of Actinomycetota， Alistipes ， Faecalibaculum ， etc. were significantly decreased （ P ＜0.05）.CONCLUSIONS Weiling decoction can ameliorate MAFLD， and its effect may be associated with regulating gut microbiota， repairing the intestinal mechanical barrier， reducing LPS translocation， thereby inhibiting the TLR4/MyD88/NF-κB inflammatory pathway， alleviating oxidative stress， and regulating SREBP-1/FASN and PPARα-mediated lipid metabolism.

Metabolic dysfunction-associated fatty liver disease （MAFLD） has become the leading chronic liver disease worldwide. As a classic food-medicine homologous Chinese herb， hawthorn fruit has the functions of promoting digestion to resolve food stagnation and activating blood circulation to resolve blood stasis. Modern pharmacological studies have shown that hawthorn fruit and its active components exert diverse pharmacological activities in regulating lipid metabolism， improving insulin resistance， inhibiting inflammatory response， delaying hepatic fibrosis， and protecting hepatocytes. These effects precisely match the “multiple-hit” pathological features of MAFLD， and thus hawthorn fruit shows significant advantages in the prevention and treatment of MAFLD. Drug pair combination is a key strategy in traditional Chinese medicine to enhance efficacy and reduce toxicity. In clinical practice， hawthorn fruit is often combined with Salvia miltiorrhiza， Alisma orientalis， cassia seed， and Poria cocos， and such combination adheres to the principle of “mutual reinforcement and assistance” to enhance efficacy and expand their application in different syndromes of MAFLD. This article systematically reviews the core pharmacological mechanisms of hawthorn fruit in intervening against MAFLD and the research advances in its classic drug combinations， in order to provide a scientific reference for the in-depth development of hawthorn fruit and its combinations and the precise clinical intervention of MAFLD.