OBJECTIVE To study the improvement effect and mechanism of Tripterygium wilfordii multiglucoside （TWM） on nephrotic syndrome in rats. METHODS The nephrotic syndrome model was established by intravenous injection of adriamycin via the tail vein. The modeling rats were randomly divided into the model group （distilled water）， prednisone group （10 mg/kg）， and TWM high- and low-dose groups （10 and 5 mg/kg， respectively）. Additionally， blank group （distilled water） without model induction was established. Each group consisted of 9 rats. Rats in each group were administered the corresponding drugs or distilled water by gavage， once a day， for 6 consecutive weeks. The histopathological morphology of kidney tissues in rats was observed； the levels of 24-hour urinary protein （24 h-UTP） and serum biochemical indicators [albumin （ALB）， blood urea nitrogen （BUN）， serum creatinine （SCr）， cholesterol （CHOL）， and triglyceride （TG）] in rats were determined； the levels of oxidative stress indicators [superoxide dismutase （SOD）， malondialdehyde （MDA）] in kidney tissue of rats were determined； expressions of hypoxia-inducible factor-1α （HIF-1α）/microRNA-155-5p （miR-155-5p）/nuclear factor erythriod 2- related factor 2 （Nrf2） signaling pathway-related mRNA and protein in the renal tissues of rats were detected. RESULTS Compared with the blank group， the rats in the model group exhibited disordered renal tissue structure， with a small amount of glomerular necrosis and edema of the renal tubular epithelial cells. 24 h-UTP， serum levels of SCr， BUN， CHOL and TG， MDA content， mRNA and protein expressions of HIF-1α and Keap1 as well as the expression of miR-155-5p in renal tissues were increased significantly （ P ＜0.05）. Serum level of ALB， SOD level in renal tissue as well as mRNA and protein expressions of Nrf2 were decreased significantly （ P ＜0.05）. Compared with the model group， TWM high-dose and low-dose groups exhibited significant improvements in renal injury， with notable reversals in the levels of the above quantitative indicators （ P ＜0.05）. CONCLUSIONS TWM can alleviate oxidative stress-induced damage and thereby improve nephrotic syndrome in rats by regulating the HIF-1α/miR-155-5p/Nrf2 signaling pathway.

Organ transplantation is an effective alternative treatment for patients with end-stage organ failure. However, the shortage of donor organs has limited the widespread application of clinical transplantation. In recent years, breakthroughs in CRISPR-Cas9 gene editing technology have overcome the barrier of hyperacute rejection in xenotransplantation, offering a potential solution to the organ shortage crisis. Rejection remains a critical factor affecting graft survival. Antigen-presenting cells play a vital role in the initiation and progression of rejection and immune regulation in xenotransplantation. Therefore, in-depth investigation into the role of antigen-presenting cells in xenotransplantation is of great significance. This article summarizes the roles and therapeutic strategies of professional antigen-presenting cells, including macrophages, dendritic cells and B cells in xenotransplantation, aiming to provide insights for future research on immune regulation mechanisms in this field.

Background Platelet parameters are important indicators of cardiovascular risk, and environmental pollutants such as polychlorinated biphenyls (PCBs) may impair platelet function through oxidative stress. Objective To investigate the differential effects of single and mixed exposure to PCBs on platelet parameters among individuals with normal glucose tolerance (NGT), impaired fasting glucose (IFG), and type 2 diabetes mellitus (T2DM), and to evaluate the potential modifying role of a healthy lifestyle. Methods This study included 2249 participants (including 707 with NGT, 759 with IFG, and 783 with T2DM). Plasma PCB concentrations were measured using triple quadrupole gaschromatography-tandem mass spectrometry. Generalized linear regression was used to assess the associations between individual PCB congeners and platelet parameters. Quantile g-computation (QGC) and Bayesian kernel machine regression (BKMR) models were used to evaluate the overall effects of PCBs mixture exposure on platelet parameters across different glycemic states, as well as its interaction with healthy lifestyle score (HLS). Results Generalized linear regression analyses showed significant differences in the effects of PCBs on platelet parameters across different glycemic states (P<0.05). After adjusting for confounders, PCBs mixture exposure was significantly associated with lower platelet counts (PLT) in individuals with NGT (b=−10.60, 95%CI: −16.48, −4.71) and IFG (b=−12.91, 95%CI: −18.90, −6.92), whereas no significant association was observed in individuals with T2DM (P=0.051). Mean platelet volume (MPV) and platelet-large cell ratio (P-LCR) increased significantly with higher PCBs exposure levels across all three groups (P<0.05). BKMR analysis showed a positive association between PCBs mixture exposure and P-LCR, with the strongest association observed in the NGT group. Furthermore, a significant interaction was observed between HLS and PCBs mixture exposure, and a higher HLS attenuated the effects of PCBs on P-LCR. Conclusion Glycemic glycemic states may modify the effects of PCBs on platelets. Individuals with NGT appear more sensitive to PCBs exposure, whereas the T2DM state may attenuate this effect. Moreover, healthy lifestyles, including not smoking, moderate alcohol consumption, maintaining moderate-to-high physical activity, a healthy diet, and an appropriate body mass index (BMI), may mitigate the adverse effects of most PCBs on platelet parameters.

Background Platelet parameters are important indicators of cardiovascular risk, and environmental pollutants such as polychlorinated biphenyls (PCBs) may impair platelet function through oxidative stress. Objective To investigate the differential effects of single and mixed exposure to PCBs on platelet parameters among individuals with normal glucose tolerance (NGT), impaired fasting glucose (IFG), and type 2 diabetes mellitus (T2DM), and to evaluate the potential modifying role of a healthy lifestyle. Methods This study included 2249 participants (including 707 with NGT, 759 with IFG, and 783 with T2DM). Plasma PCB concentrations were measured using triple quadrupole gaschromatography-tandem mass spectrometry. Generalized linear regression was used to assess the associations between individual PCB congeners and platelet parameters. Quantile g-computation (QGC) and Bayesian kernel machine regression (BKMR) models were used to evaluate the overall effects of PCBs mixture exposure on platelet parameters across different glycemic states, as well as its interaction with healthy lifestyle score (HLS). Results Generalized linear regression analyses showed significant differences in the effects of PCBs on platelet parameters across different glycemic states (P<0.05). After adjusting for confounders, PCBs mixture exposure was significantly associated with lower platelet counts (PLT) in individuals with NGT (b=−10.60, 95%CI: −16.48, −4.71) and IFG (b=−12.91, 95%CI: −18.90, −6.92), whereas no significant association was observed in individuals with T2DM (P=0.051). Mean platelet volume (MPV) and platelet-large cell ratio (P-LCR) increased significantly with higher PCBs exposure levels across all three groups (P<0.05). BKMR analysis showed a positive association between PCBs mixture exposure and P-LCR, with the strongest association observed in the NGT group. Furthermore, a significant interaction was observed between HLS and PCBs mixture exposure, and a higher HLS attenuated the effects of PCBs on P-LCR. Conclusion Glycemic glycemic states may modify the effects of PCBs on platelets. Individuals with NGT appear more sensitive to PCBs exposure, whereas the T2DM state may attenuate this effect. Moreover, healthy lifestyles, including not smoking, moderate alcohol consumption, maintaining moderate-to-high physical activity, a healthy diet, and an appropriate body mass index (BMI), may mitigate the adverse effects of most PCBs on platelet parameters.

Objective:To investigate the interventional effect of Rhizoma Corydalis on mice with ulcerative colitis(UC)induced by dextran sulfate sodium(DSS),as well as the potential mechanism of Rhizoma Corydalis in the treatment of UC based on metabolomics and inflammation biomarkers.Methods:A mouse model of UC was established,and then the mice were divided into model group,high-dose group(1.517 g/kg crude drug),middle-dose group(0.986 g/kg crude drug),low-dose group(0.455 g/kg crude drug),and positive drug group(5-aminosalicylic acid at a dose of 718.8 mg/kg),while the mice without modeling were selected as normal group(0.9%NaCl by gavage).The mice in each group were administered for 7 consecutive days,and phenotypic parameters were dynamically moni-tored,such as body weight change,disease activity index(DAI),mean daily food intake,and daily water intake.The mice were sacri-ficed after 7 days to collect serum and colon tissue samples;ELISA was used to measure the serum levels of the proinflammatory fac-tors interleukin-6(IL-6),interleukin-17A(IL-17A),C-reactive protein(CRP),and tumor necrosis factor-α(TNF-α),and ultra-performance liquid chromatography-quadrupole time-of-flight mass spectrometry(UPLC-Q-TOF/MS)was used to perform the non-targeted metabolomics analysis and compare the differences in se-rum metabolite profiles between groups.The mice were selected for modeling and validation with the same method,and glutathione(GSH)was selected as the positive drug.Colon length and mucosal damage were assessed,and quantitative real-time PCR was used to measure the relative mRNA expression levels of the key genes in the glutathione synthesis pathway(γ-glutamylcysteine synthetase[γ-GCS]and oxidative stress regulators yap1p and skn7)and mito-chondrial GSH transporter protein(Slc25a39)in colonic tissue.Results:Rhizoma Corydalis significantly improved weight loss,DAI,and colon length in a dose-dependent manner in the model animals,and there were reductions in the serum levels of IL-6,CRP,and TNF-α,while it had no significant effect on IL-17A.The metabolomics analysis revealed 21 potential biomarkers associated with amino acid and lipid metabolism,which were significantly regulated by Rhizoma Corydalis.In the verification experiment,both Rhi-zoma Corydalis and GSH exerted a significant protective effect against colonic mucosal damage without affecting colon length.Rhizoma Corydalis upregulated the expression of genes associated with glutathione synthesis,especially γ-GCS,suggesting that Rhizoma Co-rydalis could enhance intestinal antioxidant defenses.Conclusion:Rhizoma Corydalis has a therapeutic potential in a mouse model of DSS-induced UC and can alleviate symptoms,reduce the serum levels of inflammatory markers,and regulate metabolic pathways,and upregulation of the genes associated with glutathione synthesis suggests that the drug can enhance intestinal antioxidant defenses.

Bronchial asthma(hereinafter referred to as asthma)is a common chronic respiratory disease with significant gender differences.Epidemiologic surveys show that both the incidence and severity of asthma are significantly higher in adult females than in males.It is now believed that gender differences in asthma may be related to sex hormones,and the airway effects of estrogen and progesterone on asthma pathophysiology have been extensively studied.However,the mechanism of androgens in asthma is not clear.In recent years,some new studies have found that androgens and androgen receptors can exert anti-inflammatory effects in asthma through immune cells;moreover,they can also decrease airway hyperresponsiveness,relax airway smooth muscle,and improve lung function.This article reviews the progress of androgens and androgen receptors in asthma to deepen our understanding of the relationship between sex hormones and asthma,providing more options for future asthma treatment.

OBJECTIVE To investigate the renal protective effect and mechanism of Shenbining granule on IgA nephropathy （IgAN） rats by regulating the CXC chemokine motif ligand 12 （CXCL12）/CXC chemokine receptor 4 （CXCR4）/signal transducer and activator of transcription 3 （STAT3） signaling pathway. METHODS A total of 60 rats were randomly assigned into blank group （n＝12） and modeling group （n＝48）. IgAN model of modeling group was induced by using bovine serum albumin， carbon tetrachloride and lipopolysaccharide， followed by model validation. Ultimately， a total of 55 rats （9 in the blank group， 46 in the modeling group） were included in the subsequent study. The rats in the modeling group were randomly divided into model group （n＝10）， prednisone acetate group [positive control group， 6.25 mg/（kg·d）， n＝12]， Shenbining granule low- and high-dose groups [4.17， 8.33 g/（kg·d）， n＝12]. They were given relevant medicine/distilled water intragastrically， once a day， for 4 consecutive weeks. After the last medication， biochemical indicators in the urine and serum of rats were measured， and pathological morphological changes in the renal tissues of rats were observed. IgA deposition in the renal tissues， as well as the mRNA expression levels of CXCL12， CXCR4 and STAT3， and the protein expression levels of CXCL12， CXCR4， STAT3 and phosphorylated STAT3 （p-STAT3） were detected. Additionally， the level of interleukin-6 （IL-6） in the renal tissue was measured. RESULTS Compared with the model group， the low-dose and high-dose Shenbining granule groups showed significantly decreased urinary red blood cell count， 24 h total urinary protein， blood urea nitrogen， serum creatinine， and alanine amino-transferase， along with increased Alb levels （P＜0.05）. Pathological damage in the renal tissues was alleviated， with reduced IgA deposition in the mesangial region （P＜0.05）； protein and mRNA expressions of CXCL12， CXCR4 and STAT3， as well as phosphorylation level of STAT3 protein and the IL-6 level， were significantly decreased in renal tissue （P＜0.05）. CONCLUSIONS Shenbining granule may exert its renal protective effects in IgAN rats by inhibiting the activation of the CXCL12/ CXCR4/STAT3 signaling pathway， downregulating the expression of inflammatory factors such as IL-6， alleviating renal inflammation， and thereby improving renal pathological damage.

OBJECTIVES: To explore the mechanism of Shenqi Buzhong (SQBZ) Formula for alleviating mitochondrial dysfunction in a rat model of chronic obstructive pulmonary disease (COPD) in light of the AMPK/SIRT1/PGC-1α pathway. METHODS: Fifty male SD rat models of COPD, established by intratracheal lipopolysaccharide (LPS) instillation, exposure to cigarette smoke, and gavage of Senna leaf infusion, were randomized into 5 groups (n=10) for treatment with saline (model group), SQBZ Formula at low, moderate and high doses (3.08, 6.16 and 12.32 g/kg, respectively), or aminophylline (0.024 g/kg) by gavage for 4 weeks, with another 10 untreated rats as the control group. Pulmonary function of the rats were tested, and pathologies and ultrastructural changes of the lung tissues were examined using HE staining and transmission electron microscopy. The levels of SOD, ATP, MDA, and mitochondrial membrane potential in the lungs were detected using WST-1, colorimetric assay, TBA, and JC-1 methods. Flow cytometry was used to analyze ROS level in the lung tissues, and the protein expression levels of P-AMPKα, AMPKα, SIRTI, and PGC-1α were detected using Western blotting. RESULTS: The rat models of COPD showed significantly decreased lung function, severe histopathological injuries of the lungs, decreased pulmonary levels of SOD activity, ATP and mitochondrial membrane potential, increased levels of MDA and ROS, and decreased pulmonary expressions of P-AMPKα, SIRTI, and PGC-1α proteins. All these changes were significantly alleviated by treatment with SQBZ Formula and aminophylline, and the efficacy was comparable between high-dose SQBZ Formula group and aminophylline group. CONCLUSIONS SQBZ Formula ameliorates mitochondrial dysfunction in COPD rats possibly by activating the AMPK/SIRT1/PGC-1α pathway.
Animals ; Pulmonary Disease, Chronic Obstructive/drug therapy* ; Drugs, Chinese Herbal/therapeutic use* ; Sirtuin 1/metabolism* ; Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha ; Rats, Sprague-Dawley ; Male ; Rats ; AMP-Activated Protein Kinases/metabolism* ; Mitochondria/metabolism* ; Disease Models, Animal ; Signal Transduction/drug effects*

Objective To explore the expression pattern and molecular function of ubiquitin-like containing PHD and RING finger domains 1(UHRF1)gene in soft tissue sarcoma(STS),as well as its correlation with clinical characteristics and prognosis of STS.Methods RNA data and related clinical data of 263 STS tissues were obtained from Cancer Genome Atlas(TCGA).Wilcoxon rank-sum test was used to analyze correlation between two groups of data;Spearman correlation coefficient analyzed the top 35 co-expressed genes positively and negatively correlated with UHRF1 expression in STS database,ggplot2 statistical package displayed co-expressed gene heatmap,Pearson correlation coefficient showed correlation between UHRF1 expression and expression of the top 10 genes in the heatmap;different UHRF1 gene expression groups in STS were analyzed using DESeq2 package,ggplot2 package was used to draw volcano plots,gene ontology(GO)and Kyoto Encyclopedia of Genes and Genomes(KEGG)enrichment analyzed differentially expressed genes(DEGs)and protein functions,ggplot2 package for visualization,and cluster Profiler package for statistical analysis;STRING web was used to establish PPI network of DEGs,and the MCC algorithm in CytoHubba of Cytoscape was used to analyze hub genes.Results In STS,UHRF1 gene was significantly correlated with its histological type(liposarcoma 22.2％,synovial sarcoma 3.8％,leiomyosarcoma 40.7％,malignant peripheral nerve sheath tumor 3.8％,myxofibrosarcoma 9.6％,pleomorphic sarcoma 19.9％,P=0.001),tumor necrosis(none 38.8％,focal necrosis 20.8％,moderate necrosis 33.8％,extensive necrosis 6.6％,P=0.010),and tumor metastasis(no metastasis 67％,metastasis 33％,P＜0.001).In different clinical subgroups(age,gender,histological type,residual tumor,tumor necrosis,tumor depth,margin status,tumor multifocality,radiotherapy),high expression of UHRF1 led to poor prognosis of overall survival(OS),disease-specific survival(DSS),and progression-free interval(PFI);Three prognostic factors above were simultaneously shortened in the following five subgroups:namely residual tumor R0 and R1,tumor necrosis extensive,focal and moderate,tumor depth deep,positive margin status,tumor without multifocality.Analysis of the top 10 co-expressed genes associated with UHRF1 expression revealed that the associated positive genes were PAGE5,LINC01425,LCEP3,SERPINB7,AC074031.1,LCE3A,LCE2A,PAGE2B,MYF5,and AC037486.1(P＜0.05);the associated negative genes were CDH19,CSN1S1,TAC3,AC103563.7,SAA1,CHST8,PRLHR,MIR202HG,IGHV1-24,and ART4(P＜0.05).A total of 3 029 DEGs of UHRF1 in STS were obtained with a threshold of|log2 fold-change(FC)|＞1.0 and adjusted P value＜0.05,in which 1 228 genes were up-regulated and 1 801 genes were down-regulated;GO enrichment analyed primary biological processes(BP),original cellular components(CC),and original molecular functions(MF),and KEGG enrichment analyed signaling pathways.A total of 343 DEGs including 133 up-regulated genes and 210 down-regulated genes,were obtained with a threshold of|log2 fold-change(FC)|＞2.0 and adjusted P value＜0.05.The top 10 hub genes were analyzed.The top 3 hub genes were GCG,SST and SHH,respectively.Conclusion UHRF1 is significantly correlated with histological type,tumor necrosis,metastasis,OS,DSS,and PFI events in STS.In co expressed genes model and molecular functions of related positive and negative genes involved in multiple biological processes;The network of differentially expressed genes and protein product interactions involved in mechanisms of occurrence and development of the disease,and provided new ideas for in-depth researches on STS.

Time rhythm and the immune system play crucial roles in the pathogenesis of allergic rhinitis.Traditional Chinese medicine(TCM)believes that the circulation of qi and blood in lung meridian follows the principle of"yang during the day,yin at night",which has a defensive function to protect the body from external pathogens.Qi stagnation in lung meridian and impaired qi and blood circulation can lead to the invasion of external pathogens,exacerbating allergic reactions,especially during the active period of the lung meridian,when the immune system is most sensitive to allergens.Based on this,this paper proposes the concept of"bidirectional regulation among meridian,time rhythm,and immune system",and in combination with TCM theory of midnight-noon and ebb-flow doctrine,analyzes the fluctuations of allergic rhinitis symptoms and the temporal changes of meridian qi and blood,and reveals the rhythmic relationship between meridian activity and immune response.This paper combines existing clinical and experimental studies to support this hypothesis,integrating the time dimension into traditional TCM syndrome differentiation and treatment,offering a more individualized treatment approach.This concept not only provides novel scientific evidence for TCM treatment of allergic rhinitis,but also offers theoretical support for optimizing treatment timing and intervention strategies.