ObjectiveTo investigate the role of the Toll-like receptor 4 （TLR4）/myeloid differentiation factor 88 （MyD88）/nuclear factor-κB （NF-κB） signaling pathway in intestinal mucosal barrier damage in ulcerative colitis， as well as the intervention mechanism of Shaoyaotang. MethodsSixty SD rats were allocated into a blank group， a model group， a mesalazine （0.42 g·kg^-1） group， and low-， medium-， and high-dose （11.1， 22.2， 44.4 g·kg^-1， respectively） Shaoyaotang groups. A model of ulcerative colitis was induced by 2，4，6-trinitrobenzenesulfonic acid （TNBS）. After successful modeling， rats were administrated with corresponding agents via gavage for 7 days. Changes in colon length and colon weight were observed. Hematoxylin-eosin staining was performed to examine the pathological changes of the colon， and immunohistochemistry was employed to detect the expression of the inflammatory cytokine interleukin-8 （IL-8）， cyclooxygenase-2 （COX-2）， junction adhesion molecule-1 （JAM-1）， and claudin-1 in the colon. Western blot analysis was performed to determine the protein levels of TLR4， MyD88， and NF-κB in the colon. ResultsCompared with the blank group， the model group showed elevated DAI score （P<0.01）， reduced colon length and colon weight （P<0.01）， down-regulated protein levels of JAM-1 and claudin-1 （P<0.01）， and up-regulated protein levels of IL-8， COX-2， TLR4， MyD88， and NF-κB p65 （P<0.01） in the colon tissue. Compared with the model group， each treatment group showed decreased DAI score （P<0.05， P<0.01）， increased colon length and colon weight （P<0.05， P<0.01）， up-regulated protein levels of JAM-1 and claudin-1 （P<0.01）， and down-regulated protein levels of IL-8， COX-2， TLR4， MyD88， and NF-κB p65 （P<0.01） in the colon tissue. ConclusionShaoyaotang alleviates intestinal inflammation and intestinal mucosal damage to protect intestinal barrier integrity by regulating the TLR4/MyD88/NF-κB signaling pathway.

Objective: To analyze the effects of blue light on the formation of kidney stones. Methods: A total of 40 rats were randomly divided into 4 groups：A，B，C，and D，with 10 rats in each group.Rats in groups C and D were administered with a mixture of 10 g/L ethylene glycol，20 g/L ammonium chloride，and 100 g/L calcium gluconate via gavage (2 mL per mouse)，while rats in groups A and B received an equal volume of physiological saline via gavage.From the second day after gavage，rats in groups A and C were subjected to twice-daily blue light irradiation (one hour per session) as an intervention，while rats in groups B and D were subjected to fluorescent lamp irradiation using the same method.After 4 weeks of intervention，the 24-hour urine samples were collected，and the rats were then euthanized for the collection of blood and kidney tissue samples.Serum levels of antidiuretic hormone (ADH)，urinary Ca ，and urinary oxalate (Oxa) were measured.Levels of malondialdehyde (MDA) and superoxide dismutase (SOD) in kidney tissues were detected using ELISA.Von Kossa staining was performed to observe pathological changes in kidney tissues and the presence of calcium salt crystals in the kidneys. Results: Compared with groups A and B，groups C and D showed higher accumulation of calcium salt crystals in renal tissues，as well as elevated levels of ADH，urinary Ca ，urinary Oxa，and MDA in renal tissues, additionally，the SOD level in renal tissues was lower (P<0.05).Compared with group D，group C exhibited higher accumulation of calcium salt crystals in renal tissues，along with increased levels of ADH，urinary Ca ，urinary Oxa，and MDA in renal tissues；conversely，the SOD level in renal tissues was lower (P<0.05). Conclusion: Blue light may increase the formation of kidney stones in rats by promoting the secretion of ADH in serum and oxidative stress in kidney tissues through the brain-kidney axis.

Objective:To investigate the effects and related mechanisms of long non-coding RNA (lncRNA) AC092295.2 expression on the proliferation and invasion abilities of endometrial cancer cells.Methods:The correlations between AC092295.2 expression level and overall survival (OS) and disease-free survival (DFS) of endometrial cancer patients (180 cases) were analyzed by cBioPortal database (updated in 2022). The miRNA with complementary nucleotide sequences to AC092295.2 was predicted by DIANA Tools sequencing tool. Real-time fluorescence quantitative polymerase chain reaction (qRT-PCR) was used to detect the relative expression of AC092295.2 in human immortalised endometrial epithelial cell line hEEC and human endometrial cancer cell lines (KLE, AN3CA, Ishikawa, HEC-1A). Ishikawa cells with the lowest expression level of AC092295.2 were selected and divided into AC092295.2 overexpression group and control group, which were transfected with pGEX-AC092295.2 plasmid and pGEX-NC plasmid, respectively. qRT-PCR was used to detect the relative expression levels of AC092295.2 and miRNA-200c-3p (miR-200c-3p) in the two groups of cells. Methyl thiazol tetrazolium (MTT) method was used to detect cell viability. Transwell assay was used to detect cell invasion ability. Western blotting was used to detect the expression of proteins related to PTEN-AKT pathway. The dual luciferase reporter gene assay was used to verify the targeting relationship between AC092295.2 and miR-200c-3p.Results:The analysis results of cBioPortal database showed that the OS and DFS of endometrial cancer patients with high expression of AC092295.2 were better than those of patients with low expression (both P < 0.001); the expression levels of AC092295.2 and miR-200c-3p in endometrial cancer tissues were negatively correlated ( r = -0.846, P < 0.001). The results of qRT-PCR detection showed that the relative expression levels of AC092295.2 in endometrial cancer cell lines KLE, AN3CA, Ishikawa, HEC-1A and immortalized endometrial epithelial cell line hEEC were 0.56±0.09, 0.68±0.06, 0.17±0.07, 0.49±0.12 and 0.99±0.11, respectively, and the difference was statistically significant ( F = 35.10, P < 0.001); the relative expression levels of AC092295.2 in Ishikawa cells in the AC092295.2 overexpression group and the control group were 8.92±1.78 and 1.06±0.39, respectively, and the difference was statistically significant ( t = 4.31, P = 0.005). MTT assay results showed that the cell viability of Ishikawa cells in the AC092295.2 overexpression group was lower than that in the control group on days 2, 3, 4, and 5 (all P < 0.05). Transwell assay results showed that the number of invasive Ishikawa cells in the AC092295.2 overexpression group and the control group were 73±4 and 135±14, respectively, and the difference was statistically significant ( t = 4.25, P = 0.005). Western blotting results showed that the relative expression level of phosphatase and tensin homolog (PTEN) protein in Ishikawa cells in the AC092295.2 overexpression group was higher than that in the control group, while the relative expression levels of phosphorylated protein kinase B (p-AKT), Yes associated protein (YAP), murine double mimute 2 (MDM2), and bcl-2-associated death-promoting factor (BAD) proteins were lower than those in the control group. Dual luciferase reporter gene assay and qRT-PCR verified that AC092295.2 targeted negative regulation of miR-200c-3p expression. Conclusions:AC092295.2 is lowly expressed in endometrial cancer cells. Overexpression of AC092295.2 can inhibit the proliferation and invasion abilities of endometrial cancer cells, and its mechanism may be related to the expression of miR-200c-3p-PTEN-AKT signaling pathway.

Objective:To report the nationwide surveillance results of pathogenic profiles and antimicrobial resistance patterns of Gram-positive bloodstream infections in China in 2023.Methods:The clinical isolates of Gram-posttive bacteria from blood cultures were collected in member hospitals of National Bloodstream Infection Bacterial Resistant Investigation Collaborative System（BRICS）during January to December 2023. Antimicrobial susceptibility testing was performed using the dilution method recommended by the Clinical and Laboratory Standards Institute（CLSI）. Statistical analyses were conducted using WHONET 5.6 and SPSS 25.0 software.Results:A total of 4 385 Gram-positive bacterial isolates were obtained from 60 participating center. The top five pathogens were Staphylococcus aureus（ n=1 544，35.2%），coagulase-negative Staphylococci（ n=1 441，32.9%）， Enterococcus faecium（ n=574，13.1%）， Enterococcus faecalis（ n=385，8.8%），and α-hemolytic Streptococci（ n=187，4.3%）. The prevalence of methicillin-resistant Staphylococcus aureus（MRSA）and methicillin-resistant coagulase-negative Staphylococci（MRCNS）was 26.2%（405/1 544）and 69.8%（1 006/1 441），respectively. Notably，all Staphylococci remained susceptible to glycopeptide or daptomycin. Staphylococcus aureus demonstrated excellent susceptibility（>97.0%）to cephalobiol，rifampicin，trimethoprim-sulfamethoxazole，linezolid，minocycline，tigecycline，and eravacycline. No Enterococcus exhibiting resistance to linezolid were detected. Glycopeptide resistance was uncommon but more frequent in Enterococcus faecium（resistance to vancomycin and teicoplanin：both 1.7%）compared to Enterococcus faecalis（both 0.3%）. The detection rates of MRSA and MRCNS exhibited significant regional variations across the country（ χ2=17.674 and 148.650，respectively，both P<0.001）. No vancomycin-resistant Enterococci were detected in central China. Institutional comparison demonstrated higher prevalence of MRSA（ χ2=14.111， P<0.001）and MRCNS（ χ2=4.828， P=0.028）in provincial hospitals than that in municipal hospitals. Socioeconomic analysis identified elevated detection rates of both MRSA（ χ2=18.986， P<0.001）and MRCNS（ χ2=4.477， P=0.034）in less developed regions（per capita GDP

Objective:To report the results of bacterial resistant investigation collaborative system（BRICS）on the distribution and antimicrobial resistance profile of clinical Gram-negative bacteria isolates from bloodstream infections in China in 2023，and provide reference for clinical tretment of bloodstream infections and prevention and control of bacterial resistance.Methods:The clinical isolates of Gram-negative bacteria from blood cultures in member hospitals of BRICS were collected during January 2023 to December 2023. Antibiotic susceptibility tests were conducted by agar dilution or broth dilution methods recommended by Clinical and Laboratory Standards Institute（CLSI）. WHONET 5.6 and SPSS 25.0 were used to analyze the data.Results:During the study period，11 492 strains of Gram-negative bacteria were collected from 60 hospitals，of which 10 098（87.9%）were Enterobacterales and 1 394（12.1%）were non-fermentative bacteria. The top 5 bacterial species were Escherichia coli（50.0%）， Klebsiella pneumoniae（26.1%）， Pseudomonas aeruginosa（5.1%）， Acinetobacter baumannii complex（5.0%）and Enterobacter cloacae complex（4.1%）. The ESBL-producing rates in Escherichia coli， Klebsiella pneumoniae and Proteus mirablilis were 46.8%（2 685/5 741），18.3%（549/2 999）and 44.0%（77/175），respectively. The prevalence of carbapenem-resistant Escherichia coli（CREC）and carbapenem-resistant Klebsiella pneumoniae（CRKP）were 1.3%（76/5 741）and 15.0%（450/2 999）；32.9%（25/76）and 78.0%（351/450）of CREC and CRKP were sensitive to ceftazidime/avibactam combination，respectively. 94.7%（72/76）and 90.2%（406/450）of CREC and CRKP were sensitive to aztreonam/avibactam combination. Furthermore，57.9%（44/76）and 79.1%（356/450）were sensitive to imipenem/relebactam combination. The prevalence of carbapenem-resistant Acinetobacter baumannii（CRAB）complex was 64.6%（370/573），while more than 80.0% of CRAB complex was sensitive to tigecycline，eravacycline and polymyxin B. The prevalence of carbapenem-resistant Pseudomonas aeruginosa（CRPA）was 17.0%（99/581）. There were differences in the composition ratio of Gram-negative bacteria in bloodstream infections and the prevalence of important Gram-negative bacteria resistance among different regions in China，with statistically significant differences in the prevalence of CREC，CRKP，CRPA and CRAB complex（ χ2=10.6，28.6，10.8 and 19.3， P<0.05）. The prevalence of ESBL-producing Escherichia coli， CREC，CRAB complex and CRKP were higher in provincial hospitals than those in municipal hospitals（ χ2=12.5，9.8，12.7 and 57.8，all P<0.01）. Conclusions:Gram-negative bacteria are the main pathogens causing bloodstream infections in China，and Escherichia coli is ranked in the top，while the trend of Klebsiella pneumoniae increases continuously with time. CRKP infection shows a slow upward trend，CREC infecton maintains a low prevalence level，and CRAB complex infection continues to exhibit a high prevalence rate. The composition and resistance patterns of pathogens causing bloodstream infections vary to some extent across different regions and levels of hospitals in China.

ObjectiveTo investigate the influence of histone deacetylase 3 (HDAC3) on the occurrence, development of psoriasis-like inflammation in mice, and the relative immune mechanisms. MethodsHealthy C57BL/6 mice aged 6-8 weeks were selected and randomly divided into 3 groups: control group (Control), psoriasis model group (IMQ), and HDAC3 inhibitor RGFP966-treated psoriasis model group (IMQ+RGFP966). One day prior to the experiment, the back hair of the mice was shaved. After a one-day stabilization period, the mice in Control group was treated with an equal amount of vaseline, while the mice in IMQ group was treated with imiquimod (62.5 mg/d) applied topically on the back to establish a psoriasis-like inflammation model. The mice in IMQ+RGFP966 group received intervention with a high dose of the HDAC3-selective inhibitor RGFP966 (30 mg/kg) based on the psoriasis-like model. All groups were treated continuously for 5 d, during which psoriasis-like inflammation symptoms (scaling, erythema, skin thickness), body weight, and mental status were observed and recorded, with photographs taken for documentation. After euthanasia, hematoxylin-eosin (HE) staining was used to assess the effect of RGFP966 on the skin tissue structure of the mice, and skin thickness was measured. The mRNA and protein expression levels of HDAC3 in skin tissues were detected using reverse transcription real-time quantitative polymerase chain reaction (RT-qPCR) and Western blot (WB), respectively. Flow cytometry was employed to analyze neutrophils in peripheral blood and lymph nodes, CD4⁺ T lymphocytes, CD8⁺ T lymphocytes in peripheral blood, and IL-17A secretion by peripheral blood CD4⁺ T lymphocytes. Additionally, spleen CD4⁺ T lymphocyte expression of HDAC3, CCR6, CCR8, and IL-17A secretion levels were analyzed. Immunohistochemistry was used to detect the localization and expression levels of HDAC3, IL-17A, and IL-10 in skin tissues. ResultsCompared with the Control group, the IMQ group exhibited significant psoriasis-like inflammation, characterized by erythema, scaling, and skin wrinkling. Compared with the IMQ group, RGFP966 exacerbated psoriasis-like inflammatory symptoms, leading to increased hyperkeratosis. The psoriasis area and severity index (PASI) skin symptom scores were higher in the IMQ group than those in the Control group, and the scores were further elevated in the IMQ+RGFP966 group compared to the IMQ group. Skin thickness measurements showed a trend of IMQ+RGFP966>IMQ>Control. The numbers of neutrophils in the blood and lymph nodes increased sequentially in the Control, IMQ, and IMQ+RGFP966 groups, with a similar trend observed for CD4⁺ and CD8⁺ T lymphocytes in the blood. In skin tissues, compared with the Control group, the mRNA and protein levels of HDAC3 decreased in the IMQ group, but RGFP966 did not further reduce these expressions. HDAC3 was primarily located in the nucleus. Compared with the Control group, the nuclear HDAC3 content decreased in the skin tissues of the IMQ group, and RGFP966 further reduced nuclear HDAC3. Compared with the Control and IMQ groups, RGFP966 treatment decreased HDAC3 expression in splenic CD4⁺ and CD8⁺ T cells. RGFP966 treatment increased the expression of CCR6 and CCR8 in splenic CD4⁺ T cells and enhanced IL-17A secretion by peripheral blood and splenic CD4⁺ T lymphocytes. Additionally, compared with the IMQ group, RGFP966 reduced IL-10 protein levels and upregulated IL-17A expression in skin tissues. ConclusionRGFP966 exacerbates psoriatic-like inflammatory responses by inhibiting HDAC3, increasing the secretion of the cytokine IL-17A, and upregulating the expression of chemokines CCR8 and CCR6.

OBJECTIVE: Peritoneal fibrosis (PF) is an adverse event that occurs during long-term peritoneal dialysis, significantly impairing treatment efficiency and adversely affecting patient outcomes. Astragaloside IV (AS-IV), a principal active component derived from Astragalus membranaceus (Fisch.) Bunge, has exhibited anti-inflammatory and antifibrotic effects in various settings. This study aims to investigate the potential therapeutic efficacy and mechanism of AS-IV in the treatment of PF. METHODS: The PF mouse model was established by intraperitoneal injection of 4.25% peritoneal dialysis fluid (100 mL/kg). The epithelial-mesenchymal transition (EMT) of HMrSV5 cells was induced by the addition of 10 ng/mL transforming growth factor β (TGF-β). The differentially expressed genes in HMrSV5 cells treated with AS-IV were screened using transcriptome sequencing analysis. The potential targets of AS-IV were screened using network pharmacology and analyzed using molecular docking and molecular dynamics simulations. RESULTS: Administration of AS-IV at doses of 20, 40, or 80 mg/kg effectively mitigated the increase in peritoneal thickness and the development of fibrosis in mice with PF. The expression of the fibrosis marker α-smooth muscle actin in the peritoneum was significantly decreased in AS-IV-treated mice. The treatment of AS-IV (10, 20, and 40 μmol/L) significantly delayed the EMT of HMrSV5 cells induced by TGF-β, as demonstrated by the decreased number of 5-ethynyl-2'-deoxyuridine-positive cells, reduced migrated area, and decreased expression of fibrosis markers. A total of 460 differentially expressed genes were detected in AS-IV-treated HMrSV5 cells through transcriptome sequencing, with notable enrichment in the phosphatidylinositol-4,5-bisphosphate 3-kinase (PI3K)-AKT serine/threonine kinase 1 (AKT) signaling pathway. The reduced levels of phosphorylated PI3K (p-PI3K) and p-AKT were detected in HMrSV5 cells with AS-IV treatment. Epidermal growth factor receptor (EGFR) was predicted as a direct target of AS-IV, exhibiting strong hydrogen bond interactions. The activation of the PI3K-AKT pathway by the compound 740Y-P, and the activation of the EGFR pathway by NSC 228155 each partially counteracted the inhibitory effect of AS-IV on the EMT of HMrSV5 cells. CONCLUSION AS-IV delayed the EMT process in peritoneal mesothelial cells and slowed the progression of PF, potentially serving as a therapeutic agent for the early prevention and treatment of PF. Please cite this article as: Huang Y, Chu CL, Qiu WH, Chen JY, Cao LX, Ji SY, Zhu B, Wang GK, Shen QQ. Astragaloside IV delayed the epithelial-mesenchymal transition in peritoneal fibrosis by inhibiting the activation of EGFR and PI3K-AKT pathways. J Integr Med. 2025; 23(6):694-705.
Epithelial-Mesenchymal Transition/drug effects* ; Animals ; Saponins/pharmacology* ; Triterpenes/pharmacology* ; Mice ; Peritoneal Fibrosis/pathology* ; Proto-Oncogene Proteins c-akt/metabolism* ; ErbB Receptors/metabolism* ; Phosphatidylinositol 3-Kinases/metabolism* ; Signal Transduction/drug effects* ; Male ; Humans ; Molecular Docking Simulation ; Cell Line ; Mice, Inbred C57BL

OBJECTIVE: High-altitude hypoxia exposure often damages hippocampus-dependent learning and memory. Nogo-A is an important axonal growth inhibitory factor. However, its function in high-altitude hypoxia and its mechanism of action remain unclear. METHODS: In an in vivo study, a low-pressure oxygen chamber was used to simulate high-altitude hypoxia, and genetic or pharmacological intervention was used to block the Nogo-A/NgR1 signaling pathway. Contextual fear conditioning and Morris water maze behavioral tests were used to assess learning and memory in rats, and synaptic damage in the hippocampus and changes in oxidative stress levels were observed. In vitro, SH-SY5Y cells were used to assess oxidative stress and mitochondrial function with or without Nogo-A knockdown in Oxygen Glucose-Deprivation/Reperfusion (OGD/R) models. RESULTS: Exposure to acute high-altitude hypoxia for 3 or 7 days impaired learning and memory in rats, triggered oxidative stress in the hippocampal tissue, and reduced the dendritic spine density of hippocampal neurons. Blocking the Nogo-A/NgR1 pathway ameliorated oxidative stress, synaptic damage, and the learning and memory impairment induced by high-altitude exposure. CONCLUSION: Our results demonstrate the detrimental role of Nogo-A protein in mediating learning and memory impairment under high-altitude hypoxia and suggest the potential of the Nogo-A/NgR1 signaling pathway as a crucial therapeutic target for alleviating learning and memory dysfunction induced by high-altitude exposure. GRAPHICAL ABSTRACT available in www.besjournal.com.
Animals ; Oxidative Stress ; Hippocampus/metabolism* ; Rats ; Nogo Proteins/genetics* ; Male ; Rats, Sprague-Dawley ; Hypoxia/metabolism* ; Altitude ; Synapses ; Humans ; Altitude Sickness/metabolism*

Systemic lupus erythematosus （SLE） may lead to secondary gynecological and obstetric disorders such as decreased ovarian reserve function， menstrual abnormalities， and adverse pregnancy outcomes. Based on "bi （痹） of both body and viscera" theory， this paper proposed that the core mechanism of SLE secondary gynecological and obstetric diseases lies in the mutual transformation between "body bi" and "viscera bi"， which together affect the uterus. Physiologically， uterus forms an internal-external network with the body and viscera through the meridians and blood vessels. Pathologically， when the healthy qi is deficient， nourishment of the body and viscera is impaired； when toxins and stasis accumulate， pathogenic factors disturb the uterus through the chong （冲） and ren （任） meri-dians. The resulting obstruction in the uterus can， in turn， manifest externally and aggravate damage to the body and viscera. Therefore， the pathogenesis of SLE secondary gynecological and obstetric diseases follows a dynamic trajectory of "body bi first， body bi affecting viscera， and then bi of both body and viscera". In treatment， the principle of harmonizing and balancing the healthy qi is emphasized. The main approach is to regulate the viscera， stabilize the body， and nourish the uterus， with the coordination of nourishing the viscera through the body， thereby achieving simultaneous treatment of both body and viscera. This highlights the guiding significance of the "bi of both body and viscera" theory in preventing and treating SLE secondary gynecological and obstetric diseases.

Objective:To investigate the preventive and therapeutic effects of iridoid glycosides from Boschniakia rossica(IGBR)on precancerous lesions of liver cancer in rats,and to clarify its possible mechanism.Methods:Thirty Wistar rats were selected and the precancerous liver lesion model was established using the modified Solt-Faber method.The rats were randomly divided into sham operation group,model group,and IGBR group,and there were 10 rats in each group.The morphology of liver tissue of the rats in various groups were observed;the liver weights,liver indexes and liver regeneration degrees of the rats in various groups were measured;HE staining was used to observe the pathomorphology of liver tissue of the rats in various groups;immunohistochemistry method was used to detect the expression of glutathione-S-transferase(GST)-Pi protein in liver tissue of the rats in various groups;colorimetric method was used to detect the activities of γ-glutamyl transpeptidase(γ-GT),catalase(CAT),superoxide dismutase(SOD),glutathione peroxidase(GSH-Px)and glutathione S-transferase(GST),and the level of malondialdehyde(MDA)in liver tissue and mitochondria of the rats in various groups;Western blotting method was used to detect the expression levels of α-smooth muscle actin(α-SMA),collagen type Ⅰ alpha 1 chain(ColⅠα1),matrix metalloproteinase(MMP)13,MMP2,tissue inhibitor of metalloproteinase(TIMP)1,TIMP2,transforming growth factor β1(TGF-β1),TGF-β1 receptor(TβR),mothers against decapentaplegic homolog(Smad)2/3,Smad4,and Smad7 proteins in liver tissue of the rats in various groups.Results:Compared with sham operation group,the liver weight,liver index and degree of liver regeneration of the rats in model group were increased(P<0.05);compared with model group,the liver weight and liver index of the rats in IGBR group showed a decreasing trend,but the difference was not statistically significant(P>0.05).The HE staining results showed that the liver lobule structure in sham operation group was intact and clear,with large hepatocytes,abundant eosinophilic cytoplasm,and hepatocytes arranged in single cords radiating from the central vein;there were irregular hepatic sinusoids between plates,with only a small amount of collagen fibers and inflammatory cell infiltration in the portal area,and no degeneration or necrosis of hepatocytes.In model group,the normal arrangement of hepatocytes disappeared,the liver lobule structure was disrupted,small cell hyperplasia(mainly oval cells)was observed in the portal area,with massive collagen deposition and significant fibrous tissue hyperplasia in the fibrous septum;hepatocytes showed extensive degenerative edema,hydropic degeneration or even ballooning degeneration and focal necrosis;basophilic hepatocytes formed proliferative areas with clear cytoplasm,centrally located nuclei and 1-2 prominent nucleoli;glassy hepatocytes with enlarged nuclei and pale transparent cytoplasm were also observed.In IGBR group,the liver lobule structure was basically preserved,with reduced inflammatory lesions,mild edema,and scattered spotty or focal necrosis;nuclear atypia and pathological mitotic figures or binucleation were observed.The immunohistochemistry results showed GST-Pi protein positive foci with brown-yellow cytoplasmic staining in round or oval nodules.The GST-Pi protein positive foci were observed in liver tissue of the rats in model group,indicating successful establishment of precancerous liver lesion model.The scattered GST-Pi protein positive foci were observed in IGBR group,which were significantly reduced compared with model group.Compared with sham operation group,the activity of γ-GT in liver tissue of the rats in model group was increased(P<0.05);compared with model group,the activity of γ-GT in liver tissue of the rats in IGBR group was decreased(P<0.05).Compared with sham operation group,the GST activity and MDA level in liver tissue and liver mitochondria of the rats in model group were increased(P<0.05),while the activities of SOD,CAT,and GSH-Px were decreased(P<0.05);compared with model group,the GST activity and MDA level in liver tissue and liver mitochondria of the rats in IGBR group were decreased(P<0.05),while the activities of SOD,CAT,and GSH-PX were increased(P<0.05).The Western blotting results showed that compared with sham operation group,the expression levels of α-SMA,ColⅠα1,TIMP1,and TIMP2 proteins in liver tissue of the rats in model group were increased(P<0.05),while the expression levels of MMP13 and MMP2 proteins were decreased(P<0.05),and the ratios of TIMP1/MMP13 and TIMP2/MMP2 were increased(P<0.05);compared with model group,the expression levels of α-SMA,ColⅠα1,and TIMP2 proteins in liver tissue of the rats in IGBR group were decreased(P<0.05),while the expression levels of MMP13 and MMP2 proteins were increased(P<0.05),and the ratios of TIMP1/MMP13 and TIMP2/MMP2 were decreased(P<0.05).Compared with sham operation group,the expression levels of TGF-β1 and Smad2/3 proteins in liver tissue of the rats in model group were increased(P<0.05);compared with model group,the expression levels of TGF-β1,Smad2/3 and Smad 4 proteins in liver tissue of the rats in IGBR group were decreased(P<0.05).Conclusion:IGBR can inhibit precancerous liver lesions and liver fibrosis in rats,and its mechanism may be related to enhancing the antioxidant capacity of liver tissue,inhibiting TGF-β/Smad signaling pathway and regulating TIMP/MMP balance.