Diabetic nephropathy （DKD）， as a common microvascular complication of diabetes mellitus （DM）， is a major cause of end-stage renal disease （ESRD）. Its clinical manifestations include increased urinary protein excretion， thickening of the glomerular basement membrane， and renal tubulointerstitial fibrosis. The pathogenesis of DKD is complex and involves multiple factors， including disordered glucose metabolism， hemodynamic alterations， and oxidative stress. Although modern medical approaches can alleviate certain symptoms， they still have limitations such as insufficient therapeutic targeting and prominent adverse effects. The transforming growth factor-β/Smad （TGF-β/Smad） signaling pathway is not only a tissue fibrosis pathway that has attracted considerable attention in recent years， but also regulates multiple protein molecules， including the glomerular podocyte slit diaphragm protein Podocin， interleukin-1β （IL-1β）， and superoxide dismutase （SOD）， thereby participating in various pathological processes and ultimately mediating renal injury. Flavonoid compounds， owing to their sustained pharmacological effects， broad spectrum of action， and high safety profile， have become ideal candidates for targeted therapy research in DKD. Existing studies have shown that these compounds can exert inhibitory effects on renal fibrosis， alleviate inflammatory responses， protect podocytes， and reduce oxidative stress by regulating the interactions between the TGF-β/Smad signaling pathway and the aforementioned protein molecules， thereby maintaining renal structure and function， reducing proteinuria， and significantly improving DKD lesions. This review briefly outlines the composition and functions of the TGF-β/Smad signaling pathway， elucidates the mechanisms by which this pathway regulates DKD， and focuses on summarizing major studies from the past decade on flavonoid-based interventions in DKD through targeted inhibition of the TGF-β/Smad signaling pathway. Furthermore， it discusses the considerable therapeutic potential of flavonoids in the treatment of this disease， aiming to provide a scientific basis for future clinical prevention and treatment of DKD and to promote the development of targeted drugs.

Myelodysplastic syndrome (MDS), a myeloid tumor derived from the malignant clones of hematopoietic stem cells, has an annually increasing incidence. The contemporary research direction has shifted to analyzing the synergistic effect of immune surveillance collapse and abnormal bone marrow microenvironment in the pathological process of MDS. Against this backdrop, the immune checkpoint molecule TIM3 has emerged as a key target because of its persistently high expression on the surface of important immune cells such as T and NK cells. The abnormal activation of the TIM3 pathway is the mechanism by which solid tumors and hematological malignancies achieve immune escape and is a key hub in the formation of immune exhaustion phenotypes. This work integrates the original discoveries of our team with the latest international progress, systematically demonstrating the bidirectional regulatory network of TIM3 between the malignant clone proliferation of MDS and the immunosuppressive microenvironment. Integrating the evidence from emerging clinical trials allows us to consider the clinical significance of TIM3-targeted blocking for MDS, providing a transformative path to overcome the resistance of traditional treatments and marking a new chapter in the active immune reconstitution of MDS treatment.

OBJECTIVE To systematically evaluate the efficacy and safety of tislelizumab in the treatment of advanced non- small cell lung cancer （NSCLC）. METHODS Computerized searches were conducted in PubMed， Embase， the Cochrane Library， CNKI， Wanfang and other Chinese and English databases to collect randomized controlled trials （RCTs） on tislelizumab for advanced NSCLC. The search period was from the establishment of the databases to December 2024. After strictly screening the literature， extracting data and conducting quality evaluations in accordance with the inclusion and exclusion criteria， a meta-analysis was performed using RevMan 5.3 and Stata 16.0 software. RESULTS A total of 18 RCTs involving 2 337 patients were included， with 1 283 in the experimental group and 1 054 in the control group. The meta-analysis results showed that the objective response rate [RR＝1.61， 95%CI （1.48， 1.75）， P＜0.000 01]， disease control rate [RR＝1.21， 95%CI （1.13， 1.29）， P＜0.000 01]， progression free survival [HR＝0.55， 95%CI （0.45， 0.66）， P＜0.000 01]， and overall survival [HR＝0.78， 95%CI（0.62， 0.97）， P＝0.03] were significantly better in the experimental group than in the control group. There was no statistically significant difference in the incidence of adverse reactions between the two groups [RR＝1.00， 95%CI （0.73， 1.37）， P＝1.00]； among the common adverse reactions， only the incidence of liver function impairment was significantly higher in the experimental group than in the control group [RR＝1.30， 95%CI （1.10， 1.54）， P＜0.01]. CONCLUSIONS Tislelizumab in combination with chemotherapy or targeted drugs significantly improves the efficacy in patients with advanced NSCLC without increasing the risk of adverse reactions overall. However， liver function should be closely monitored during treatment.

BACKGROUND: Epidemiological data on chronic diarrhea in the Chinese population are lacking, and the association between obesity and chronic diarrhea in East Asian populations remains inconclusive. This study aimed to investigate the prevalence of chronic diarrhea and its association with obesity in a representative community-dwelling Chinese population. METHODS: This cross-sectional study was based on a multistage, randomized cluster sampling involving 3503 residents aged 20-69 years from representative urban and rural communities in Beijing. Chronic diarrhea was assessed using the Bristol Stool Form Scale (BSFS), and obesity was determined based on body mass index (BMI). Logistic regression analysis and restricted cubic splines were used to evaluate the relationship between obesity and chronic diarrhea. RESULTS: The standardized prevalence of chronic diarrhea in the study population was 12.88%. The average BMI was 24.67 kg/m 2 . Of all the participants, 35.17% (1232/3503) of participants were classified as overweight and 16.13% (565/3503) as obese. After adjustment for potential confounders, individuals with obesity had an increased risk of chronic diarrhea as compared to normal weight individuals (odds ratio = 1.58, 95% confidence interval: 1.20-2.06). A nonlinear association between BMI and the risk of chronic diarrhea was observed in community residents of males and the overall participant group ( P  = 0.026 and 0.017, respectively). CONCLUSIONS This study presents initial findings on the prevalence of chronic diarrhea among residents of Chinese communities while offering substantiated evidence regarding the significant association between obesity and chronic diarrhea. These findings offer a novel perspective on gastrointestinal health management.
Adult ; Aged ; Female ; Humans ; Male ; Middle Aged ; Young Adult ; Body Mass Index ; China/epidemiology* ; Chronic Disease/epidemiology* ; Cross-Sectional Studies ; Diarrhea/epidemiology* ; Obesity/complications* ; Prevalence ; East Asian People/statistics & numerical data*

In recent years,the incidence rate of type 1 diabetes is on the rise.The causes of the disease are extremely complex,and the pathogenesis has not yet been fully clarified.Different types of studies have confirmed that the occurrence and evolution of type 1 diabetes is a typical process of polygene,multifactor,multi-stage and multi-channel,which is considered to be caused by the combined effect of genetic and environ-mental factors.At present,it is believed that environmental factors are related to the interaction of infection factors,diet factors,early exposure events,intestinal flora,immune factors,other factors and genetic factors.This article reviews the research on environmental factors of type 1 diabetes in recent years.

Objective To optimize the platelet enrichment method,and to analyze the concentration changes of key molecules in platelet-rich plasma(PRP)before and after activation,as well as the impact of its activated products on the proliferation of rat endothelial progenitor cells.Methods The tube double-centrifu-gation method was employed to optimize platelet enrichment,and the platelet count in the enriched PRP was measured.ELISA was used to detect the concentration changes of vascular endothelial growth factor(VEGF),endostatin(ES),and P-selectin(CD62P)in PRP before and after activation.The PRP was activated by using liquid nitrogen freeze-thaw method,and the effect of its activated products on the proliferation of rat endothelial progenitor cells was evaluated by using the methyl thiazolyl tetrazolium(MTT)assay.Results The optimal enrichment coefficient of platelets achieved by the double-centrifugation method was 4.63.After low-speed,long-duration double centrifugation,the platelet count was highest in the upper layer of the buffy coat.For PRP with a platelet count of 500× 109/L obtained by machine collection,the VEGF con-centrations before and after activation were(3 418.12±488.80)pg/mL and(4 530.04±308.30)pg/mL,re-spectively,the ES concentrations were(6 168.98±253.22)pg/mL and(6 594.65±82.47)pg/mL,respec-tively,the CD62P concentrations were(6 678.23±324.15)pg/mL and(17 630.53±746.24)pg/mL,respec-tively,statistically significant differences were observed in the above indicators before and after activation(P＜0.01).The activated PRP was diluted in a gradient manner by using a specialized culture medium for en-dothelial progenitor cells.MTT assay results indicated that,in the basal medium,the optimal volume fraction for promoting endothelial progenitor cell proliferation was 0.25％after 48 hours of culture;in the complete medium,the optimal volume fractions for promoting endothelial progenitor cell proliferation were 0.062 5％after 24 hours and 0.125％after 48 hours.Conclusion The concentrations of VEGF,ES,and CD62P in the optimized,enriched PRP exhibited significant changes before and after activation.The optimal volume fraction for promoting endothelial progenitor cell proliferation in the basal medium was 0.25％.

Immune checkpoint inhibitors (ICIs) have been approved for the treatment of a variety of solid tumors and hematological malignancies. Adverse reactions caused by ICIs have been gradually focused on. Cytomegalovirus (CMV) gastritis after ICIs treatment is relatively rare. Here we reported a case of advanced lung adenocarcinoma who experienced recurrent upper abdominal pain and vomiting after Pembrolizumab treatment. CMV gastritis was diagnosed through gastroscopy. The patient's symptoms improved after antiviral treatment. During the treatment of ICIs, attention should be paid to the differential diagnosis of upper abdominal pain symptoms, and vigilance should be maintained against CMV gastritis. It is difficult to differentiate CMV gastritis and immune-related gastritis judging from symptoms, and gastroscopy is important for differential diagnosis.
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Humans ; Adenocarcinoma of Lung/drug therapy* ; Cytomegalovirus/physiology* ; Cytomegalovirus Infections ; Gastritis/diagnosis* ; Immune Checkpoint Inhibitors/therapeutic use* ; Lung Neoplasms/drug therapy*

In current clinical practice, various dermal templates and skin substitutes are used to enhance wound healing. However, the role of wound commensal microbiome in regulating scaffold performance and the healing process remains unclear. In this study, we investigated the influence of both natural and synthetic scaffolds on the wound commensal microbiome and wound repair in three distinct models including diabetic wounds, burn injuries, and germ-free (GF) wounds. Remarkably, synthetic electrospun polycaprolactone (PCL) scaffolds were observed to positively promote microbiome diversity, leading to enhanced diabetic wound healing compared to the natural scaffolds Integra® (INT) and MatriDerm® (MAD). In contrast, both natural and synthetic scaffolds exhibited comparable effects on the diversity of the microbiome and the healing of burn injuries. In GF wounds with no detectable microorganisms, a reversed healing rate was noted showing natural scaffold (MAD) accelerated wound repair compared to the open or the synthetic scaffold (PCL) treatment. Furthermore, the response of the wound commensal microbiome to PCL scaffolds appears pivotal in promoting anti-inflammatory factors during diabetic wound healing. Our results emphasize that the wound commensal microbiome, mediated by different scaffolds plays an important role in the wound healing process.