OBJECTIVE To investigate the effects of galangin on rheumatoid arthritis （RA） in rats by regulating the Janus kinase 3 （JAK3）/signal transducer and activator of transcription 3 （STAT3） pathway. METHODS Fifty male SD rats were taken， and an emulsion composed of bovine type Ⅱ collagen and Freund’s complete adjuvant was injected subcutaneously to establish an induced arthritis model. The rats that were successfully modeled were randomly divided into model group， low， medium and high dose groups of galangin （1， 5， 15 mg/kg）， and methotrexate group （positive control， 2 mg/kg）， with 10 rats in each group. Another 10 normal rats were taken as the normal group. Starting from the 15th day of modeling， each group of rats was gavaged with the corresponding drug solution or normal saline containing 0.5% Tween 80 once a day for 28 consecutive days. The arthritis index （AI） scores and paw volume of rats were compared before and after gavage administration. Twenty-four hours after the last administration， the serum levels of interleukin-6 （IL-6）， tumor necrosis factor-α （TNF-α）， IL-4 and IL-10 were determined， the pathological changes in ankle joint synovial tissue were observed， and the protein expressions of UNC-51 like kinase 1 （ULK1）， Beclin-1， microtubule-associated protein 1 light chain 3 （LC3）， B cell lymphoma 2 （Bcl-2）， Bcl-2-associated X protein （Bax）， caspase-3， JAK3， phosphorylated JAK3 （p-JAK3）， STAT3 and phosphorylated STAT3 （p-STAT3） in the synovial tissue of the ankle joint were detected， as well as the fluorescence intensity of LC3-positive areas. RESULTS Compared with the model group， the pathological changes such as cellular proliferation of ankle joint synovial tissue and infiltration of inflammatory cells in rats of each administration group showed improvement. Moreover， their AI scores and paw pad volumes （on day 28 after gavage）， the levels of IL-6 and TNF-α， the protein expression of Bcl-2， and the phosphorylation levels of JAK3 and STAT3 were all significantly reduced （ P ＜0.05）. The levels of IL-4 and IL-10， the protein expressions of ULK1， Beclin-1， Bax， caspase-3 and LC3， as well as the fluorescence intensity of LC3-positive areas， were all significantly increased （ P ＜0.05）. Moreover， the effect of galangin was in a dose-dependent manner （ P ＜0.05）. CONCLUSIONS Galangin can induce sustained autophagy in synovial tissue cells of RA rats， promote cell apoptosis， inhibit synovial cell proliferation， and alleviate persistent inflammatory responses. The above anti-RA effects may be related to the inhibition of the JAK3/STAT3 pathway.

Metabolic associated fatty liver disease (MAFLD) is fundamentally driven by an imbalance in hepatic fatty-acid flux: the influx of fatty acids exceeds the liver’s capacity for disposal, resulting in excessive hepatic lipid accumulation, predominantly in the form of triglycerides (TGs). The occurrence and progression of MAFLD depend on disordered regulation across multiple metabolic steps, including fatty-acid uptake, de novo lipogenesis (DNL), fatty-acid oxidation (FAO), and very low-density lipoprotein (VLDL) export. Forkhead box protein O1 (FOXO1) is a key transcriptional regulator within the hepatic network coordinating glucose and lipid metabolism. Under metabolic stress and insulin resistance (IR), FOXO1 expression is frequently increased, whereas its inhibitory phosphorylation is reduced. These changes enhance FOXO1 nuclear localization and transcriptional activity, thereby reprogramming the expression of genes related to metabolism in the liver. Because hepatic lipid deposition is the central pathological feature of MAFLD, the functional status of FOXO1 directly influences hepatic lipid homeostasis. Growing evidence suggests that FOXO1 can exert bidirectional, environment-dependent effects on hepatic lipid accumulation; however, the molecular basis for this functional switch remains incompletely understood. This review systematically summarizes the biological functions and regulatory mechanisms of FOXO1 and its roles in hepatic lipid metabolism, with a particular focus on its crosstalk with insulin signaling. FOXO1 expression is shaped by RNA modifications and epigenetic regulation mediated by non-coding RNAs. Its transcriptional output is precisely governed by post-translational modifications—such as phosphorylation and acetylation—as well as by coordinated nucleocytoplasmic shuttling. Notably, these regulatory patterns vary markedly across nutritional states, degrees of insulin resistance, and stages of disease. In the fed state, insulin/IGF-1 signaling activates the PI3K-AKT pathway, promoting the inhibitory phosphorylation of FOXO1 and facilitating additional modifications, including acetylation, methylation, and ubiquitination. Together, these events drive FOXO1 export from the nucleus and dampen its transcriptional activity, suppressing gluconeogenesis and constraining lipogenic programs. Conversely, during fasting or when insulin signaling is weakened, FOXO1 inhibition is relieved. FOXO1 accumulates in the nucleus, binds to DNA, and regulates the transcription of downstream target genes. Mechanistically, FOXO1 can aggravate hepatic lipid accumulation by activating genes involved in TG synthesis while repressing FAO-related pathways, thereby favoring storage over oxidation. However, under specific conditions, FOXO1 may also alleviate the hepatic lipid burden by promoting TG hydrolysis and enhancing VLDL secretion, thereby reducing the net hepatic lipid load. In addition, lipotoxic signals mediated by ceramides and diacylglycerols (Cer/DAG) activate atypical protein kinase C (aPKC), further exacerbating the disruption of the AKT-FOXO1 axis. This vicious cycle ultimately produces a metabolic paradox in which increased hepatic glucose output coexists with persistent, insulin-independent lipogenesis, accelerating MAFLD progression. Importantly, FOXO1 regulation is not uniform: during early metabolic overload, insulin-mediated suppression may remain effective, whereas in advanced insulin resistance, the loss of AKT control permits sustained FOXO1 activity. Such stage-dependent dynamics may help explain why FOXO1 can either promote steatosis or, in certain contexts, support programs that facilitate lipid turnover. Accordingly, interventions should be liver-specific and tuned to the disease stage, aiming to curb maladaptive FOXO1 signaling while preserving its capacity to promote triglyceride hydrolysis and VLDL secretion when advantageous. Overall, this review offers an important perspective on MAFLD pathogenesis, emphasizing FOXO1 as a potential therapeutic target and providing a theoretical basis for developing liver-specific, disease-course-dependent precision interventions.

BACKGROUND:The extracellular-regulated protein kinase 5(ERK5)signaling protein is essential for the survival of organisms,and resveratrol can promote osteoblast proliferation through various pathways.However,whether resveratrol can regulate osteoblast function through the ERK5 signaling protein needs further verification. OBJECTIVE:To explore the regulatory effect of ERK5 on the proliferation of MC3T3-E1 cells and related secreted proteins,and to further verify whether resveratrol can complete the above process by activating ERK5. METHODS:Mouse MC3T3-E1 preosteoblasts were treated with complete culture medium,XMD8-92(an ERK5 inhibitor),epidermal growth factor(an ERK5 activator),resveratrol alone,XMD8-92+EGF,and resveratrol+XMD8-92,respectively.Western blot assay was used to detect the expression of ERK5 and p-ERK5 proteins,proliferation-related proteins Cyclin D1,CDK4 and PCNA,and osteoblast-secreted proteins osteoprotegerin and receptor activator of nuclear factor-κB ligand in MC3T3-E1 cells of each group.The fluorescence intensity of ERK5,osteoprotegerin and receptor activator of nuclear factor-κB ligand in each group was detected by cell immunofluorescence staining,and cell proliferation was detected by EdU staining,respectively.The appropriate concentration and time of resveratrol intervention in MC3T3-E1 cells were determined by cell morphology observation and cell counting kit-8 assay. RESULTS AND CONCLUSION:The activation of ERK5 signaling protein could effectively promote the proliferation of MC3T3-E1 cells,up-regulate the osteoprotegerin/receptor activator of nuclear factor-κB ligand ratio.The appropriate concentration and time for resveratrol intervention in MC3T3-E1 cells was 5 μmol/L and 24 hours,respectively.Resveratrol could activate ERK5 signaling protein,thereby promoting osteoblast proliferation and up-regulating the osteoprotegerin/RANKL ratio.All these results indicate that resveratrol can promote the proliferation of MC3T3-E1 cells and up-regulate the osteoprotegerin/RANKL ratio by activating the ERK5 signaling protein.

Aim To explore the role of zinc transporter 6(SLC30A6)on the proliferation,migration and inva-sion capabilities of hepatocellular carcinoma(HCC)cell line Huh7,and to identify potential traditional Chi-nese medicine(TCM)small-molecule inhibitors targe-ting SLC30A6 from the China Natural Products Data-base(CNPD)using virtual screening techniques.Methods The expression levels,clinical characteris-ticsand prognostic value of SLC30A6 in HCC were pre-dicted based on TCGA and ICGC datasets.SLC30A6 was knocked down in Huh7 cells using lentiviral trans-fection.The effects on cell proliferation,migration,and invasion were assessed using CCK-8,EdU,wound heal-ing,and Transwell assays.The regulation of HCC cancer stem cell markers(CD44,CD133,CD90)by SLC30A6 was also examined.Based on the CNPD,a docking-based virtual screening strategy was employed,including high-throughput virtual screening,standard precision virtual screening,and high-precision virtual screening,to identify the potential drug candidates with high specificity and favorable drug-likeness.Results SLC30A6 expression was upregulated in HCC tissues.Higher SLC30A6 levels were associated with advanced pathological stages,histological grades,alpha-fetopro-tein(AFP)levels,vascular invasion,and poor progno-sis in HCC patients.SLC30A6 knockdown significantly inhibited the proliferation,migration,and invasion of Huh7 cells and reduced the levels of HCC cancer stem cell markers.Virtual screening identified six potential TCM small-molecule inhibitors.Conclusions SLC30A6 can regulate the proliferation,migrationand invasion of HCC cells.SLC30A6 may serve as a poten-tial prognostic biomarker and therapeutic target for HCC.

Objective To observe the effects of electroacupuncture on IL-4/STAT6/SPDEF pathway-related protein expressions in model mice of ulcerative colitis(UC);To explore the mechanism of electroacupuncture improving the intestinal mucus barrier.Methods Totally 48 BALB/c mice were randomly divided into blank group(12 mice)and modeling group(36 mice).The UC models were established in the modeling group using 3%dextran sulfate sodium free drinking.After successful modeling,mice were further randomly divided into model group,electroacupuncture group and sulfasalazine(SASP)group,with 12 mice in each group.The electroacupuncture group received electroacupuncture at"Guanyuan","Tianshu","Zusanli"and"Shangjuxu"acupoints for 20 minutes per day,the SASP group was administered sulfasalazine enteric-coated tablet suspension(500 mg/kg)by gavage,the blank group received no intervention,the model group was only confined for continuous 7 days.The general conditions were observed and disease activity index(DAI)score were recorded,HE staining was used to observe the morphology of colonic tissue and evaluate the colonic mucosal damage index(CMDI)score,AB-PAS staining was used to observe the number of goblet cells in colonic tissue,and immunofluorescence staining was used to detect the expression of mucin 2(MUC2)protein in colonic tissue,ELISA was used to detect the contents of serum tumor necrosis factor-α(TNF-α)and γ interferon(IFN-γ),and Western blot was used to detect the protein expressions of interleukin(IL)-4,signal transducer and activator of transcription(STAT)6 and epithelial specific transcription factor(SPDEF)in colonic tissue.Results Compared with the blank group,the model group showed mucous stool,bloody stool,reduced intake of food and water,reduced body mass,increased DAI and CMDI scores(P<0.01),with intestinal villi shedding and necrosis,destruction of colonic crypt villi structure,accompanied by severe neutrophil infiltration,thinning of mucus layer,atrophy and reduction of goblet cells(P<0.01),the expression of MUC2 in colonic tissue significant decreased(P<0.01),the contents of TNF-α and INF-γ in serum significantly increased(P<0.01),while the protein expressions of IL-4,STAT6 and SPDEF in colonic tissue significantly decreased(P<0.01).Compared with the model group,both the electroacupuncture group and SASP group showed improved mucous stool,bloody stool,increased body mass,decreased DAI and CMDI scores(P<0.05),the morphology of the intestinal epithelium was basically normal,the glandular structure has improved,there was a small amount of inflammatory cell infiltration and slight edema,the thickness of the mucus layer was restored,the atrophy reduced and number of goblet cells increased(P<0.05),the expression of MUC2 in colonic tissue significantly increased(P<0.05),while the contents of TNF-α and IFN-γ in serum significantly decreased(P<0.05),the expressions of IL-4,STAT6 and SPDEF protein in colonic tissue significantly increased(P<0.05).Conclusion Electroacupuncture can facilitate the repair of the intestinal mucus barrier and inhibit inflammation,potentially through the activation of IL-4/STAT6/SPDEF pathway-related protein expressions.

Objective To observe the effects of electroacupuncture on IL-4/STAT6/SPDEF pathway-related protein expressions in model mice of ulcerative colitis(UC);To explore the mechanism of electroacupuncture improving the intestinal mucus barrier.Methods Totally 48 BALB/c mice were randomly divided into blank group(12 mice)and modeling group(36 mice).The UC models were established in the modeling group using 3%dextran sulfate sodium free drinking.After successful modeling,mice were further randomly divided into model group,electroacupuncture group and sulfasalazine(SASP)group,with 12 mice in each group.The electroacupuncture group received electroacupuncture at"Guanyuan","Tianshu","Zusanli"and"Shangjuxu"acupoints for 20 minutes per day,the SASP group was administered sulfasalazine enteric-coated tablet suspension(500 mg/kg)by gavage,the blank group received no intervention,the model group was only confined for continuous 7 days.The general conditions were observed and disease activity index(DAI)score were recorded,HE staining was used to observe the morphology of colonic tissue and evaluate the colonic mucosal damage index(CMDI)score,AB-PAS staining was used to observe the number of goblet cells in colonic tissue,and immunofluorescence staining was used to detect the expression of mucin 2(MUC2)protein in colonic tissue,ELISA was used to detect the contents of serum tumor necrosis factor-α(TNF-α)and γ interferon(IFN-γ),and Western blot was used to detect the protein expressions of interleukin(IL)-4,signal transducer and activator of transcription(STAT)6 and epithelial specific transcription factor(SPDEF)in colonic tissue.Results Compared with the blank group,the model group showed mucous stool,bloody stool,reduced intake of food and water,reduced body mass,increased DAI and CMDI scores(P<0.01),with intestinal villi shedding and necrosis,destruction of colonic crypt villi structure,accompanied by severe neutrophil infiltration,thinning of mucus layer,atrophy and reduction of goblet cells(P<0.01),the expression of MUC2 in colonic tissue significant decreased(P<0.01),the contents of TNF-α and INF-γ in serum significantly increased(P<0.01),while the protein expressions of IL-4,STAT6 and SPDEF in colonic tissue significantly decreased(P<0.01).Compared with the model group,both the electroacupuncture group and SASP group showed improved mucous stool,bloody stool,increased body mass,decreased DAI and CMDI scores(P<0.05),the morphology of the intestinal epithelium was basically normal,the glandular structure has improved,there was a small amount of inflammatory cell infiltration and slight edema,the thickness of the mucus layer was restored,the atrophy reduced and number of goblet cells increased(P<0.05),the expression of MUC2 in colonic tissue significantly increased(P<0.05),while the contents of TNF-α and IFN-γ in serum significantly decreased(P<0.05),the expressions of IL-4,STAT6 and SPDEF protein in colonic tissue significantly increased(P<0.05).Conclusion Electroacupuncture can facilitate the repair of the intestinal mucus barrier and inhibit inflammation,potentially through the activation of IL-4/STAT6/SPDEF pathway-related protein expressions.

[Objective]To clarify the botanical origin of the exotic herb Poluode in Bencao Shiyi.[Methods]By consulting ancient,modern,domestic and foreign literature,the botanical origin of Poluode was demonstrated from the aspects of drug name,transmission route and origin distribution,plant morphological characteristics and medical efficacy.[Results]The names of Poluode and Uyghur medicine Baladu both originate from the Sanskrit word"bhallātaka",which is the Sanskrit name for Semecarpus anacardium L.f.(S.anacardium).S.anacardium and mainly distributed in India,which coincides with the origin of Poluode,and their morphological characteristics are consistent,with similar medical efficacy.[Conclusion]The botanical origin of Poluode is S.anacardium,and it is also one of the plant sources of Baladu,a Uyghur medicine.Clarifying the Chinese herbs in Bencao Shiyi and bringing back the lost Chinese herbs from history is not only inheritance and promotion of the"Zhejiang school of materia medica"masterpiece Bencao Shiyi,but also promotes the"sinicization"of foreign excellent medicinal resources and advances the high-quality development of traditional Chinese medicine.

Objective:This study aims to explore the current situation of scientific and technological achi evements transformation in district and county-level medical institutions, by analyzing 102 successfully transformed patents from a distric level III comprehensive hospital.Methods:Based on the hospital′s scientific and technological transformation registration data, this study comprehensively utilized patent databases and enterprise inquiry platforms, employing EXCEL and SPSS AU software for analysis.Results:Utility model patents predominate, primarily transformed through patent (application) right transfers, the average contract amount was 42 690 yuan and a relatively long transformation cycle. Female inventors and those under 50 years old account for a high proportion, with nurses being the most common first inventors of patents. Collaborating enterprises were mainly local hospitals, startups, as well as science and technology promotion and application service enterprises.Conclusions:District and county-level medical institutions face many challenges in transforming technological achievements. However, by deeply exploring clinical needs, developing differentiated training and support strategies, and focusing on key partner enterprises, it is possible to promote high-quality and sustainable technological achievement transformation.

Aim To reveal the mechanism of CIP4 homologs protein 1(RICH1)are involved in the regu-lation of myocardial fibrosis.Methods Mouse cardiac fibroblasts(MCFs)cells were treated with transforming growth factor-β(TGF-β1)to induce the formation of a myocardial fibrosis cell model;the level of the target protein was detected by Western blotting;and the RICH1 gene was detected by transfection of the cells with plasmid.The RICH1 gene was overexpressed(RICH 1 OE)using plasmid transfection;the RICH1 gene was silenced using siRNA fragment(siRICH1);and the expression levels of myocardial fibrosis marker genes,such as Col1 a1,Col3 a1,and Acta2,were de-tected using RT-qPCR.Results RICH1 was signifi-cantly down-regulated in TGF-β1-treated MCFs;the expression levels of myocardial fibrosis marker genes,such as Col1 a1,Col3a1,and Acta2,were down-regu-lated in the RICH1 OE+TGF-β1 group;and in the siRICH1+TGF-β1 group,myocardial fibrosis marker genes,such as Col1 a1,Col3a1 and Acta2 were up-regulated at the expression level;phosphorylated SMAD2(p-SMAD2)and phosphorylated SMAD3(p-SMAD3)levels were down-regulated in the siRICH1 OE+TGF-β1 group.p-SMAD2 and P-SMAD3 levels were upregulated in the siRICH1+TGF-β1 group.Conclusion RICH1 inhibits TGF-β1-induced myo-cardial fibrosis;RICH1 inhibits TGF-β1-induced myo-cardial fibrosis by negatively regulating the SMAD2/3 signaling pathway.

Objective:To explore the effect of ginsenoside Rg1 on spermatogenic dysfunction in mice caused by diabetes and its mechanism of action.Methods:Eighteen male C57BL mice were randomly divided into control group, the model group and the ginsenoside Rg1 group by completely random method, with 6 mice in each group. Type 2 diabetes models were established in the model group and the ginsenoside Rg1 group by a high-fat diet combined with intraperitoneal injection of streptozotocin, while control group was injected with the same amount of normal saline. After successful modeling, control group was given a regular diet for 8 weeks, while the model group and ginsenoside Rg1 group were given a high-fat diet for 8 weeks. The ginsenoside Rg1 group was also treated with ginsenoside Rg1 medication. Reproductive hormone levels were detected by enzyme-linked immunosorbent assay test kits, and Western blotting was used to detect the expressions of apoptosis-related proteins (Bcl2 protein, Caspase-3 protein, Bax protein), autophagy-related proteins (P62, LC3Ⅰ, LC3Ⅱ, Beclin1), β-Catenin protein, mTOR protein, LAMP1 protein and transcription factor EB. The body weight, blood glucose levels, testicular index of mice in each group were compared, as well as the testicular injury status.Results:The body weight [(18.77±1.14) g], testosterone level [(141.07±8.47) ng/L], follicle-stimulating hormone level [(9.19±0.74) U/L], and luteinizing hormone level [(1 497.91±99.57) pg/L] of mice in the model group were significantly lower than those in the control [(31.57±2.35) g, P<0.001; (171.50±11.76) ng/L, P<0.001; (12.46±1.54) U/L, P<0.001; (1 807.29±92.76) pg/L, P<0.001]; fasting blood glucose level [(20.82±1.11) mmol/L], glycosylated hemoglobin (12.67%±1.03%), the testis index (0.65%±0.03%) were significantly higher than those in the control [(6.40±1.34) mmol/L, P<0.001; 5.17%±1.17%, P<0.001; 0.48%±0.04%, P<0.001]. Compared with the model group, the body weight [(22.62±0.92) g, P=0.023], testosterone level [(172.63±9.20) ng/L, P<0.001], follicle-stimulating hormone level [(12.37±1.15) U/L, P<0.001], and luteinizing hormone level [(1 847.80±108.80) pg/L, P<0.001] of mice in the ginsenoside Rg1 group increased significantly, fasting blood glucose level [(18.63±1.14) mmol/L, P=0.017], glycosylated hemoglobin (8.50%±1.05%, P<0.001) and testicular index (0.54%±0.02%, P<0.001) decreased significantly. Compared with the control, the expressions of P62 ( P=0.039), LC3Ⅱ/LC3Ⅰ( P<0.001), Beclin1 ( P=0.002) and mTOR ( P=0.036) in the testicular tissue of mice in the model group all increased, the expression of β-Catenin ( P<0.001), LAMP1 ( P=0.005), transcription factor EB ( P<0.001) all decreased. Compared with the model group, the expressions of autophagy-related proteins P62 ( P=0.048), LC3Ⅱ/LC3Ⅰ( P<0.001) , Beclin1 ( P=0.023) and mTOR ( P=0.005) in the ginsenoside Rg1 group all decreased, while the expression of β-Catenin ( P=0.001), LAMP1 ( P=0.011) and transcription factor EB ( P=0.022) all increased. Transmission electron microscopy detected a decrease in the number of autophagosomes in the testicles of mice in the model group, and it improved after drug intervention. The HE staining showed that the testes of mice in the model group exhibited phenotypes such as the shedding and disorganization of spermatogenic cells, while ginsenoside Rg1 was able to improve these phenotypes. Conclusion:Ginsenoside Rg1 can improve testicular injury caused by diabetes in mice by regulating autophagy.