ObjectiveTo investigate the effects of Shengui Jiangtang Formula on insulin resistance and glucose-lipid metabolism in spontaneous type 2 diabetic db/db mice based on the phosphatidylinositol 3-kinase （PI3K）/protein kinase B （Akt）/forkhead box protein O1 （FoxO1） signaling pathway， and to provide theoretical foundation for its clinical application through fundamental experiments. MethodsA randomized controlled design was employed in this study. Thirty spontaneous type 2 diabetic db/db mice meeting the inclusion criteria （fasting blood glucose >7.0 mmol·L^-1 and random blood glucose on a different day≥11.1 mmol·L^-1） were selected as the subjects. After stratified block randomization by body weight and blood glucose levels， they were randomly assigned to a model group， a metformin group， and a Shengui Jiangtang formula group， with n=10 per group. Ten db/m mice were used as the normal group. During the 5-week intervention， general indicators （including general condition， fasting blood glucose （FBG）， body weight， and food intake） were recorded weekly. An oral glucose tolerance test （OGTT） was performed at week 5. After 5 weeks， serum was collected to measure glucose-lipid metabolism parameters. Liver tissues were analyzed as follows： Histopathology was observed through hematoxylin and eosin （HE） staining， periodic acid-Schiff （PAS） staining， and Oil red O staining. The expression of proteins and genes related to the PI3K/Akt/FoxO1 signaling pathway was quantitatively analyzed using Western blotting （Western blot） and real-time quantitative polymerase chain reaction （Real-time PCR）. ResultsGeneral observations： The mice in the normal group were generally healthy， exhibited agile responses and had smooth and glossy fur. Compared with the normal group， the mice in the model group displayed typical symptoms of polydipsia， polyphagia， and polyuria， along with listlessness and rough fur. Their food intake， initial body weight， liver weight， and liver index were all significantly higher than those in the normal group （P<0.01）. After 5 weeks of drug intervention， neither the Shengui Jiangtang Formula group nor the metformin group significantly affected the food intake of the model mice. Compared with the model group， no statistically significant difference was observed in liver weight or liver index in the Shengui Jiangtang formula group. Serum biochemical indicators： Compared with the normal group， the model group showed significantly elevated levels of FBG， fasting insulin， homeostatic model assessment of insulin resistance （HOMA-IR）， glycosylated serum protein， and blood lipids. After drug intervention， compared with the model group， the Shengui Jiangtang formula group significantly reduced FBG in the model mice （P<0.01）. The blood glucose levels at all time points during the OGTT in the Shengui Jiangtang Formula group were lower than those in the model group， with statistically significant differences in the 0 min blood glucose and the area under the curve for glucose compared to the model group （P<0.05）. Furthermore， the formula significantly reduced fasting insulin levels， HOMA-IR， and glycosylated serum protein levels （P<0.05）. It also showed a tendency to decrease blood lipids， liver enzymes （aspartate aminotransferase， alanine aminotransferase）， and blood urea nitrogen levels， and a tendency to increase creatinine levels， although these differences were not statistically significant. Liver histomorphology： HE staining indicated that Shengui Jiangtang formula improved the morphological structure of hepatocytes and attenuated steatosis in diabetic mice. Liver PAS staining showed that it increased hepatic glycogen content and promoted hepatic glycogen synthesis in diabetic mice. Oil red O staining demonstrated that it reduced lipid deposition within hepatocytes. Western blot： Compared with the normal group， the model group showed decreased protein expression of PI3K， Akt， p-Akt， and p-FoxO1， and increased FoxO1 protein expression. Compared with the model group， both the metformin and Shengui Jiangtang Formula groups showed increased protein expression of PI3K， Akt， p-Akt， and p-FoxO1， and decreased FoxO1 protein expression. Real-time PCR： Compared with the normal group， the mRNA expression of PI3K and Akt was downregulated （P<0.05）， and the mRNA expression of FoxO1 was downregulated （P<0.05） in the model group. ConclusionShengui Jiangtang Formula can improve insulin resistance and glucose-lipid metabolic disorders in db/db mice. It alleviates hepatic steatosis， promotes hepatic glycogen synthesis， and reduces lipid deposition in these mice. The mechanism by which Shengui Jiangtang Formula improves insulin resistance may be associated with the PI3K/Akt/FoxO1 signaling pathway.

BACKGROUND:The mechanism of programmed death receptor-1(PD-1)effect on osteogenic differentiation of bone marrow mesenchymal stem cells in high glucose environment remains unclear. OBJECTIVE:To explore the effect of PD-1 on osteogenic differentiation of rat bone marrow mesenchymal stem cells in high glucose environment and its regulatory mechanism. METHODS:Rat bone marrow mesenchymal stem cells were randomly divided into normal glucose group(5.6 mmol/L),high glucose group(30 mmol/L),PD-1 overexpression group,PD-1 overexpression no-load group,PD-1 knockdown group,PD-1 knockdown no-load group,and PI3K/AKT pathway inhibitor group(PD-1 knockdown+5 μmol/L LY294002).Rat bone marrow mesenchymal stem cells were cultured in high glucose to simulate the diabetic environment in vitro.The mRNA expression of PD-1 and ligand PD-L1 and the mRNA expression of osteogenic markers Runx2 and OSX in rat bone marrow mesenchymal stem cells were detected by qRT-PCR.The osteogenic differentiation ability was observed by alkaline phosphatase staining and alizarin red staining.Cell proliferation was detected by CCK-8 assay.The protein expressions of PD-1,PD-L1,p-PI3K,and p-AKT were detected by western blot assay. RESULTS AND CONCLUSION:(1)The levels of PD-1 and PD-L1 were significantly increased in the high glucose environment in vitro,and the osteogenic differentiation ability of bone marrow mesenchymal stem cells was inhibited in the high glucose environment.(2)Knockdown of PD-1 expression could promote osteogenic differentiation of bone marrow mesenchymal stem cells,increase cell proliferation activity,and activate the PI3K/AKT pathway.(3)After addition of PI3K/AKT pathway inhibitor LY294002,the ability of bone marrow mesenchymal stem cells to differentiate into osteoblasts decreased.The results show that PD-1 is dependent on the PI3K/AKT signaling pathway to inhibit osteogenic differentiation of rat bone marrow mesenchymal stem cells under high glucose environment.

ObjectiveTo investigate the mechanism of liver injury induced by tripterygium glycosides tablets （TG） and the molecular mechanism of compound glycyrrhizin tablets （CG） in alleviating the abnormalities of cholesterol metabolism caused by TG via cholesterol metabolism. MethodsAccording to the body weights， male Sprague-Dawley （SD） rats were randomly grouped as follows： control （pure water）， low-dose TG （TG-L， 189.0 mg·kg^-1·d^-1）， high-dose TG （TG-H， 472.5 mg·kg^-1·d^-1）， TG-L+CG （189.0 mg·kg^-1·d^-1 TG + 20.25 mg·kg^-1·d^-1 CG）， and TG-H+CG （472.5 mg·kg^-1·d^-1 TG + 20.25 mg·kg^-1·d^-1 CG）， with 6 rats in each group. Rats were administrated with corresponding drugs once daily for 3 weeks. At the end of the last administration， the mRNA and protein levels of liver X receptor-alpha （LXR-α）， low-density lipoprotein receptor （LDLR）， adenosine triphosphate-binding cassette transporter A1 （ABCA1）， adenosine triphosphate-binding cassette transporter G1 （ABCG1）， 3-hydroxy-3-methylglutaryl coenzyme A reductase （HMGCR）， cholesterol 7α-hydroxylase （CYP7A1）， cholesterol 12α-hydroxylase （CYP8B1）， and sterol 27-hydroxylase （CYP27A1） in the liver tissue were determined by Real-time PCR and Western blotting， respectively. The level of 3-hydroxy-3-methylglutaryl coenzyme A reductase （HMG-CoAR）， a regulatory enzyme of cholesterol synthesis， was measured by enzyme-linked immunosorbent assay （ELISA）. HepG2 cells were used to observe the effect of TG on the cell proliferation in vitro. Specifically， HepG2 cells were grouped as follows： Low-dose TG （TG-l， 15 mg·L^-1）， medium-dose TG （TG-m， 45 mg·L^-1）， high-dose TG （TG-h， 135 mg·L^-1）， fenofibrate （FB， 10 μmol·L^-1）， CG extract， TG-h+FB （135 mg·L^-1 TG + 10 μmol·L^-1 FB）， TG-m+FB （45 mg·L^-1 TG + 10 μmol·L^-1 FB）， TG-l+FB （15 mg·L^-1 TG + 10 μmol·L^-1 FB）， TG-h+CG （135 mg·L^-1 TG + 60 μmol·L^-1 CG）， TG-m+CG （45 mg·L^-1 TG + 60 μmol·L^-1 CG）， and TG-l+CG （15 mg·L^-1 TG + 60 μmol·L^-1 CG）. The mRNA and protein levels of LXR-α， ABCG1， LDLR， CYP7A1， CYP8B1， and CYP27A1 in HepG2 cells were determined by Real-time PCR and Western blotting， respectively. ResultsThe rat experiment showed that compared with the control group， the TG-H group showed down-regulated mRNA levels of CYP7A1， CYP8B1， and CYP27A1 in the liver tissue （P<0.05， P<0.01）， which were up-regulated by the application of CG （P<0.05， P<0.01）， and the TG-H+CG group showed up-regulated mRNA level of LDLR （P<0.01）. Compared with the control group， the TG-L and TG-H groups showed down-regulated protein levels of LDLR， CYP7A1， and CYP8B1 in the liver tissue （P<0.05， P<0.01）. In addition， the protein levels of ABCG1 and LXR-α were down-regulated in the TG-H and TG-L groups， respectively （P<0.05）. Compared with TG alone， TG+CG up-regulated the protein levels of ABCG1 and LDLR （P<0.05， P<0.01）， and the protein levels of CYP7A1 and CYP8B1 in the TG-H+CG group were up-regulated （P<0.05， P<0.01）. The cell experiment showed that compared with the control group， the TG-h group presented up-regulated mRNA level of LXR-α （P<0.01）， and the TG-m and TG-h groups showcased down-regulated mRNA levels of LDLR and CYP7A1 （P<0.01） and up-regulated mRNA level of CYP27A1 （P<0.01） in HepG2 cells. The combination of CG with TG restored the above changes （P<0.01）. Western blotting results showed that compared with the control group， the TG-m and TG-h groups showed down-regulated protein levels of LXR-α， ABCG1， LDLR， CYP7A1， CYP8B1， and CYP27A1 in HepG2 cells （P<0.01）. Compared with the TG-h group， the TG-h+CG group showed up-regulated protein level of LDLR （P<0.05）. Compared with the TG-m group， the TG-m+CG group showcased up-regulated protein levels of LDLR， ABCG1， CYP7A1， and CYP27A1 （P<0.05， P<0.01）. ConclusionThe administration of TG at 189.0， 472.5 mg·kg^-1 for 3 weeks could modulate the signaling pathways associated with cholesterol efflux， endocytosis， and cholesterol biotransformation in hepatocytes， leading to the accumulation of cholesterol and subsequent liver injury in rats. CG could ameliorate the liver injury induced by lipid metabolism disorders caused by TG by up-regulating the expression of LXR-α， LDLR， ABCG1， CYP7A1， CYP8B1， and CYP27A1 to promote cholesterol biotransformation.

ObjectiveNonalcoholic fatty liver disease （NAFLD） is a metabolic stress liver injury. Ferroptosis is involved in the occurrence and development of NAFLD. Exploring the efficacy and mechanism of schisandrin B in treating NAFLD facilitates the development of strategies for the prevention and treatment of NAFLD. MethodsThe molecular structure of schisandrin B was obtained by searching against PubChem， and the related targets were predicted by SwissTargetPrediction. The active ingredients and their targets were retrieved from the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform （TCMSP） and the high-throughput experiment- and reference-guide database of traditional Chinese medicine （HERB）. GeneCards and FerrDb were searched for the targets of NAFLD and ferroptosis. The common targets were taken as the core targets， and the protein-protein interaction network of the core targets was established. DAVID was used for gene ontology （GO） and Kyoto Encyclopedia of Genes and Genomes （KEGG） analyses. Finally， molecular docking was performed between schisandrin B and core targets， and the binding energy was calculated. C57BL/6 mice were fed with a methionine and choline-deficiency （MCD） diet for the modeling of NAFLD. Mice were randomized into normal， model， positive drug （essentiale）， and low- and high-dose schisandrin B groups. The body mass and liver index of mice were measured after drug administration. The levels of alanine aminotransferase （ALT） and aspartate aminotransferase （AST） in the serum and those of total cholesterol （TC）， triglyceride （TG）， malondialdehyde （MDA）， glutathione （GSH）， and Fe²⁺ in the liver homogenate were measured by biochemical assay kits. The pathological changes of the liver tissue were observed by hematoxylin-eosin （HE） and red oil O staining. Enzyme-linked immunosorbent assay was employed to determine the levels of interleukin （IL）-6， IL-1β， tumor necrosis factor （TNF）-α， and 4-hydroxynonenal （4-HNE） in the serum. Western blotting and real-time PCR were employed to determine the protein and mRNA levels， respectively， of solute carrier family 7 member 11 （SLC7A11）， solute carrier family 3 member 2 （SLC3A2）， glutathione peroxidase 4 （GPX4）， transferrin， and ferritin heavy chain （FTH） in the liver tissue. ResultsA total of 2 370， 2 547， and 1 451 targets of schisandrin B， NAFLD， and ferroptosis were obtained， in which 90 common targets were shared by the three. Enrichment analyses predicted 505 GO terms and 92 KEGG pathways. Molecular docking suggested that schizandrin B had strong binding affinity with the key targets of ferropstosis （SLC7A11 and SLC3A2）. Animal experiments showed that schizandrin B significantly decreased the liver index， lowered the levels of ALT， AST， TC， TG， IL-6， IL-1β， and TNF-α， alleviated hepatocyte ballooning and inflammatory cell infiltration， and reduced lipid accumulation in the liver of NAFLD mice. In addition， schisandrin B significantly lowered the levels of MDA， 4-HNE， and Fe²⁺， elevated the level of GSH， up-regulated the protein and mRNA levels of SLC7A11， SLC3A2， and GPX4， and down-regulated the protein and mRNA levels of transferrin in the liver tissue. ConclusionSchisandrin B can alleviate NAFLD by inhibiting ferroptosis in hepatocytes.

Objective To explore the accuracy of machine learning algorithms based on SHOX2 and RASSF1A methylation levels in predicting early-stage lung adenocarcinoma pathological types. Methods A retrospective analysis was conducted on formalin-fixed paraffin-embedded (FFPE) specimens from patients who underwent lung tumor resection surgery at Affiliated Hospital of Nantong University from January 2021 to January 2023. Based on the pathological classification of the tumors, patients were divided into three groups: a benign tumor/adenocarcinoma in situ (BT/AIS) group, a minimally invasive adenocarcinoma (MIA) group, and an invasive adenocarcinoma (IA) group. The methylation levels of SHOX2 and RASSF1A in FFPE specimens were measured using the LungMe kit through methylation-specific PCR (MS-PCR). Using the methylation levels of SHOX2 and RASSF1A as predictive variables, various machine learning algorithms (including logistic regression, XGBoost, random forest, and naive Bayes) were employed to predict different lung adenocarcinoma pathological types. Results A total of 272 patients were included. The average ages of patients in the BT/AIS, MIA, and IA groups were 57.97, 61.31, and 63.84 years, respectively. The proportions of female patients were 55.38%, 61.11%, and 61.36%, respectively. In the early-stage lung adenocarcinoma prediction model established based on SHOX2 and RASSF1A methylation levels, the random forest and XGBoost models performed well in predicting each pathological type. The C-statistics of the random forest model for the BT/AIS, MIA, and IA groups were 0.71, 0.72, and 0.78, respectively. The C-statistics of the XGBoost model for the BT/AIS, MIA, and IA groups were 0.70, 0.75, and 0.77, respectively. The naive Bayes model only showed robust performance in the IA group, with a C-statistic of 0.73, indicating some predictive ability. The logistic regression model performed the worst among all groups, showing no predictive ability for any group. Through decision curve analysis, the random forest model demonstrated higher net benefit in predicting BT/AIS and MIA pathological types, indicating its potential value in clinical application. Conclusion Machine learning algorithms based on SHOX2 and RASSF1A methylation levels have high accuracy in predicting early-stage lung adenocarcinoma pathological types.

ObjectiveTo investigate the effect and mechanism of Yishen Tongluo prescription in protecting mice from oxidative stress injury in diabetic kidney disease （DKD） via the nuclear factor erythroid 2-related factor 2 （Nrf2）/heme oxygenase-1 （HO-1）/NAD（P）H quinone oxidoreductase 1 （NQO1） signaling pathway. MethodsSpecific pathogen-free （SPF） male C57BL/6 mice were assigned into a control group （n=10） and a modeling group （n=50）. The DKD model was established by intraperitoneal injection of streptozotocin. The mice in the modeling group were randomized into a model group， a semaglutide （40 μg·kg^-1） group， and high-， medium-， and low-dose （18.2， 9.1， 4.55 g·kg^-1， respectively） Yishen Tongluo prescription groups， with 10 mice in each group. The treatment lasted for 12 weeks. Blood glucose and 24-h urine protein levels were measured， and the kidney index （KI） was calculated. Serum levels of creatinine （SCr）， blood urea nitrogen （BUN）， alanine aminotransferase （ALT）， and aspartate aminotransferase （AST） were assessed. The pathological changes in the renal tissue were evaluated by hematoxylin-eosin， periodic acid-Schiff， periodic acid-silver methenamine， and Masson’s trichrome staining. Enzyme-linked immunosorbent assay kits were used to measure the levels of β2-microglobulin （β2-MG）， neutrophil gelatinase-associated lipocalin （NGAL）， kidney injury molecule-1 （KIM-1）， liver fatty acid-binding protein （L-FABP）， nitric oxide synthase （NOS）， glutathione （GSH）， total antioxidant capacity （T-AOC）， and 8-hydroxy-2'-deoxyguanosine （8-OHdG）. Immunohistochemical staining was performed to examine the expression of Kelch-like ECH-associated protein 1 （Keap1） and malondialdehyde （MDA）. Real-time fluorescence quantitative polymerase chain reaction (Real-time PCR） and Western blot were employed to determine the mRNA and protein levels， respectively， of factors in the Nrf2/HO-1/NQO1 signaling pathway. ResultsCompared with the control group， the DKD model group showed rises in blood glucose， 24-h urine protein， KI， SCr， BUN， and ALT levels， along with glomerular hypertrophy， renal tubular dilation， thickened basement membrane， mesangial expansion， and collagen deposition. Additionally， the model group showed elevated levels of β2-MG， NGAL， KIM-1， L-FABP， NOS， and 8-OHdG， lowered levels of GSH and T-AOC， up-regulated expression of MDA and Keap1， and down-regulated expression of Nrf2， HO-1， NQO1， and glutamate-cysteine ligase catalytic subunit （GCLC） （P<0.05）. Compared with the model group， the semaglutide group and the medium- and high-dose Yishen Tongluo prescription groups showed reductions in blood glucose， 24-h urine protein， KI， SCr， BUN， and ALT levels， along with alleviated pathological injuries in the renal tissue. In addition， the three groups showed lowered levels of β2-MG， NGAL， KIM-1， L-FABP， NOS， and 8-OHdG， elevated levels of GSH and T-AOC， down-regulated expression of MDA and Keap1， and up-regulated expression of Nrf2， HO-1， NQO1， and GCLC （P<0.05）. ConclusionYishen Tongluo prescription exerts renoprotective effects in the mouse model of DKD by modulating the Nrf2/HO-1/NQO1 signaling pathway， mitigating oxidative stress， and reducing renal tubular injuries.

Objective: To investigate the mechanism of Yishen Tongluo Formula in ameliorating renal pyroptosis in diabetic nephropathy mice by regulating the toll-like receptor 4 (TLR4)/myeloid differentiation factor 88 (MyD88)/nuclear factor-κB (NF-κB) signaling pathway. Methods: Sixty C57BL/6 male mice were randomly divided into control (10 mice) and intervention groups (50 mice) using random number table method. The diabetes nephropathy model was established by intraperitoneally injecting streptozotocin(50 mg/kg). After modeling, the intervention group was further divided into model, semaglutide (40 μg/kg), and high-, medium-, and low-dose Yishen Tongluo Formula groups (15.6, 7.8, and 3.9 g/kg, respectively) using random number table method. The high-, medium-, and low-dose Yishen Tongluo Formula groups were administered corresponding doses of medication by gavage, the semaglutide group received a subcutaneous injection of semaglutide injection, and the control group and model groups were administered distilled water by gavage for 12 consecutive weeks. Random blood glucose levels of mice in each group were monitored, and the 24-h urinary protein content was measured using biochemical method every 4 weeks; after treatment, the serum creatinine and urea nitrogen levels were measured using biochemical method. The weight of the kidneys was measured, and the renal index was calculated. Hematoxylin and eosin, periodic acid-Schiff, periodic Schiff-methenamine, and Masson staining were used to observe the pathological changes in renal tissue. An enzyme-linked immunosorbent assay was used to detect urinary β2-microglobulin (β2-MG), neutrophil gelatinase-associated lipocalin (NGAL), and kidney injury molecule-1 (KIM-1) levels. Western blotting and real-time fluorescence PCR were used to detect the relative protein and mRNA expression levels of nucleotide-binding domain leucine-rich repeat and pyrin domain-containing receptor 3 (NLRP3), Caspase-1, gasdermin D (GSDMD), interleukin-1β (IL-1β), and interleukin-18 (IL-18) in renal tissue. Immunohistochemistry was used to detect the proportion of protein staining area of the TLR4, MyD88, and NF-κB in renal tissue. Results: Compared with the control group, the random blood glucose, 24-h urinary protein, serum creatinine, urea nitrogen, and renal index of the model group increased, and the urine β2-MG, NGAL, and KIM-1 levels increased. The relative protein and mRNA expression levels of NLRP3, Caspase-1, GSDMD, IL-1β, and IL-18 in renal tissue increased, and the proportion of TLR4, MyD88, and NF-κB protein positive staining areas increased (P<0.05). Pathological changes such as glomerular hypertrophy were observed in the renal tissue of the model group. Compared with the model group, the Yishen Tongluo Formula high-dose group showed a decrease in random blood glucose after 12 weeks of treatment (P<0.05). The Yishen Tongluo Formula high- and medium-dose groups showed a decrease in 24-h urinary protein, creatinine, urea nitrogen, and renal index, as well as decreased β2-MG, NGAL, and KIM-1 levels. NLRP3, Caspase-1, GSDMD, IL-1 β, and IL-18 relative protein and mRNA expression levels were also reduced, and the proportion of TLR4, MyD88, and NF-κB protein positive staining areas was reduced (P<0.05). Pathological damage to renal tissue was ameliorated. Conclusion Yishen Tongluo Formula may exert protective renal effects by inhibiting renal pyroptosis and alleviating tubular interstitial injury in diabetic nephropathy mice by regulating the TLR4/MyD88/NF-κB signaling pathway.

ObjectiveThis study aims to observe the effect of sinomenine （SIN） on fatty acid binding protein 4 （FABP4） in synovial tissue of rats with osteoarthritis （OA） and investigate the therapeutic mechanism of SIN on OA， further providing new ideas for the management of osteoarthritis by traditional Chinese medicine （TCM）. MethodsAn OA rat model was constructed and randomly divided into a control group， an OA group， an OA + SIN-L group （50 mg·kg^-1）， an OA + SIN-M （100 mg·kg^-1）， an OA + SIN-H （200 mg·kg^-1）， and an OA + prednisone （PDN） group （5 mg·kg^-1）. Following surgical modeling for three weeks， an appropriate medication was administered for four weeks. During modeling and administration， a hot plate test was performed to detect the pain and swelling of the knee joints of the rats. The periarticular tissue was collected for arthropathological observation at the end of drug administration. The expression of cleaved Caspase-3， B-cell lymphoma-2 （Bcl-2）， Bcl-2 associated X protein （Bax）， and FABP4 in the synovial tissue of rats was detected by Western blot and real-time quantitative polymerase chain reaction （Real-time PCR）， and the expression and distribution of FABP4 protein in the synovial membrane were detected by immunofluorescence. ResultsCompared with those in the control group， the levels of inflammatory factors and FABP4 in the serum of rats in the OA group were significantly increased （P<0.05， P<0.01）， and joint swelling was significantly elevated （P<0.01）. The thermal pain threshold was significantly reduced （P<0.01）， and the expression of FABP4 protein and the fluorescence intensity were significantly increased （P<0.01）. The synovial tissue exhibited significantly increased inflammatory infiltration， proliferated fibroblasts， and an elevated apoptotic index （P<0.05， P<0.01）. Compared with those in the OA group， the serum lipid metabolism indexes of rats in the SIN administration group gradually returned to normal （P<0.05， P<0.01）， while the levels of inflammatory factors and FABP4 in the serum of rats in the SIN-administered group were significantly reduced （P<0.05， P<0.01）， and joint swelling was significantly decreased （P<0.05， P<0.01）. The thermal pain threshold was significantly elevated （P<0.05， P<0.01）， and the expression of FABP4 protein and fluorescence intensity in the synovial tissue were significantly decreased （P<0.05， P<0.01）. The synovial tissue displayed significantly reduced inflammatory infiltration and a decreased apoptotic index （P<0.05， P<0.01）. ConclusionThe therapeutic effect of SIN on OA may be related to the down-regulation of FABP4 expression， reduction of apoptosis， and inhibition of inflammatory factor expression.

ObjectiveTo obtain the gene sequences of major histocompatibility complex (MHC ) Ⅱgenes of Wuzhishan pigs, analyze their genetic information, and explore the biological functions of their MHC system. MethodsSpleen samples were collected from 3 adult male Wuzhishan pigs. Primers were designed according to MHCⅡ gene sequences, and the coding sequences of Wuzhishan pig MHCⅡ genes were amplified by RT-PCR. Sanger sequencing was performed to determine the full-length sequences. Bioinformatics tools were employed to analyze the physicochemical properties, phylogenetic relationships, conserved motifs, structural domains, chromosomal localization, and syntenic relationships of these genes. ResultsEight MHCⅡ genes were identified in Wuzhishan pigs, designated as SLA-DRA, SLA-DQA, SLA-DQB, SLA-DRB, SLA-DOB, SLA-DMB, SLA-DMA and SLA-DOA. The full-length sequences of these genes were determined by Sanger sequencing and subsequently deposited in GenBank under accession numbers PQ182796, PQ182797, PQ182798, PQ182799, PQ182800, PQ182801, PQ182802, and PQ164779. Phylogenetic analysis showed that the six MHCⅡ genes of Wuzhishan pigs clustered separately from their counterparts in Duroc, Meishan, Large White, and Bama pigs, indicating distinct evolutionary trajectories. Bioinformatics analysis demonstrated that most MHC Ⅱ proteins were hydrophobic, with molecular weights ranging from 27 700 to 30 000 Da. Genes within the same subregion shared conserved motifs. Specifically, four MHCⅡ proteins encoded by SLA-DQB, SLA-DRB, SLA-DOB, and SLA-DMB contained the MHCⅡβ conserved domain, while those encoded by the genes SLA-DRA, SLA-DQA, SLA-DMA, and SLA-DOA contained the MHCⅡα conserved domain. The eight MHCⅡ genes were scattered along the long arm of chromosome 7 in the Wuzhishan pigs, exhibiting syntenic relationships with three human genes and five Duroc pig genes. ConclusionThe MHCⅡ genes of Wuzhishan pigs may possess a unique evolutionary origin.

ObjectiveTo obtain the gene sequences of major histocompatibility complex (MHC ) Ⅱgenes of Wuzhishan pigs, analyze their genetic information, and explore the biological functions of their MHC system. MethodsSpleen samples were collected from 3 adult male Wuzhishan pigs. Primers were designed according to MHCⅡ gene sequences, and the coding sequences of Wuzhishan pig MHCⅡ genes were amplified by RT-PCR. Sanger sequencing was performed to determine the full-length sequences. Bioinformatics tools were employed to analyze the physicochemical properties, phylogenetic relationships, conserved motifs, structural domains, chromosomal localization, and syntenic relationships of these genes. ResultsEight MHCⅡ genes were identified in Wuzhishan pigs, designated as SLA-DRA, SLA-DQA, SLA-DQB, SLA-DRB, SLA-DOB, SLA-DMB, SLA-DMA and SLA-DOA. The full-length sequences of these genes were determined by Sanger sequencing and subsequently deposited in GenBank under accession numbers PQ182796, PQ182797, PQ182798, PQ182799, PQ182800, PQ182801, PQ182802, and PQ164779. Phylogenetic analysis showed that the six MHCⅡ genes of Wuzhishan pigs clustered separately from their counterparts in Duroc, Meishan, Large White, and Bama pigs, indicating distinct evolutionary trajectories. Bioinformatics analysis demonstrated that most MHC Ⅱ proteins were hydrophobic, with molecular weights ranging from 27 700 to 30 000 Da. Genes within the same subregion shared conserved motifs. Specifically, four MHCⅡ proteins encoded by SLA-DQB, SLA-DRB, SLA-DOB, and SLA-DMB contained the MHCⅡβ conserved domain, while those encoded by the genes SLA-DRA, SLA-DQA, SLA-DMA, and SLA-DOA contained the MHCⅡα conserved domain. The eight MHCⅡ genes were scattered along the long arm of chromosome 7 in the Wuzhishan pigs, exhibiting syntenic relationships with three human genes and five Duroc pig genes. ConclusionThe MHCⅡ genes of Wuzhishan pigs may possess a unique evolutionary origin.