Notch signaling plays a critical role in the maintenance of intestinal homeostasis. The aim of the present study was to investigate the role of Notch signaling in the apoptosis of intestinal epithelial cells after intestinal ischemia reperfusion (I/R) injury. Male C57BL/6 mice were subjected to sham operation or I/R injury. Intestinal tissue samples were collected at 12 h after reperfusion. TUNEL (terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick end labeling) staining showed that intestinal I/R injury induced significantly increased apoptosis of intestinal epithelial cells. Meanwhile, the mRNA expression of Jagged1, DLL1, Notch2, and Hes5, and protein expression of NICD2 and Hes5 were increased significantly after I/R injury in intestinal epithelial cells. In an in vitro IEC-6 culture model, flow cytometry analyses showed that inhibition of Notch signaling by γ-secretase inhibitor DAPT and the suppression of Hes5 expression using siRNA both significantly increased the apoptosis of IEC-6 cells under the condition of hypoxia/ reoxygenation (H/R). In conclusion, the Notch2/Hes5 signaling pathway was activated and involved in the regulation of intestinal epithelial cells apoptosis in intestinal I/R injury.

Objective: Existing studies on short-chain fatty acids (SCFAs) and colorectal cancer (CRC) yield contradictory conclusions and are limited to single ethnic groups or sample types. This study aimed to (1) quantify associations between total SCFAs/subtypes (acetate, propionate, butyrate) and CRC/advanced colorectal adenoma (A-CRA) risks; (2) identify modifiers (ethnicity, sample type, intervention); and (3) clarify SCFA–gut microbiota interaction mechanisms via integrative Bayesian meta-analysis and multi-ancestry data integration. Methods: We systematically searched PubMed, Embase, Cochrane Library, and Web of Science (inception to September 2025) using keywords: “Short-chain fatty acids”, “SCFAs”, “Colorectal cancer”, “CRC”, “Gut microbiota”, “Dietary fiber”, and “High-amylose maize starch butyrate”. Eligible studies included 14 peer-reviewed original studies (7 observational, cohort/case–control/cross-sectional; 7 RCTs) covering Europeans, Asians, and African Americans. Inclusion criteria: Quantitative SCFA data (total/≥3 subtypes), clear ethnic grouping, reported CRC/A-CRA risks or intervention outcomes. Exclusion criteria: Reviews, animal/in vitro studies, incomplete data, low-quality studies (Newcastle–Ottawa Scale [NOS] <6 for observational; high Cochrane risk for RCTs), or limited populations (single gender/rare genetics). A Bayesian hierarchical random-effects model quantified effect sizes (Odds Ratio [OR]/Mean Difference [MD], 95% credible intervals [CrI]), with heterogeneity analyzed via multi-ancestry stratification, intervention efficacy, and microbiota interaction analyses (Preferred Reporting Items for Systematic Reviews and Meta-Analyses [PRISMA] 2020; International Prospective Register of Systematic Reviews [PROSPERO]: CRD420251157250). Results: Total SCFAs were negatively associated with CRC (OR = 0.78, 95% CrI: 0.65–0.92) and A-CRA (OR = 0.72, 95% CrI: 0.59–0.87), with butyrate showing the strongest protective effect (CRC: OR = 0.63, 95% CrI: 0.51–0.77). Ethnic heterogeneity was significant: Europeans had the strongest protection (OR = 0.71), Asians had weaker protection (OR = 0.86), and African Americans had the lowest fecal SCFA levels and the highest CRC risk. Fecal SCFAs showed a stronger CRC association than serum/plasma SCFAs (OR = 0.73 vs. 0.85). High-Amylose Maize Starch Butyrate (HAMSB) outperformed traditional fiber in increasing fecal butyrate (MD = 4.2 mmol/L vs. 2.8 mmol/L), and high butyrate-producing bacteria (Clostridium, Roseburia) enhanced SCFA protection (OR = 0.52 in high-abundance groups). Conclusions: SCFAs (especially butyrate) protect against CRC and precancerous lesions, with effects modulated by ethnicity, sample type, and gut microbiota. High-Amylose Maize Starch Butyrate is a priority intervention for high-risk populations (e.g., familial adenomatous polyposis, FAP), and differentiated strategies are needed: 25–30 g/d dietary fiber for Europeans, 20–25 g/d for Asians, and probiotics (Clostridium) for African Americans. Future Perspectives: Expand data on underrepresented groups (African Americans, Latinos), unify SCFA detection methods, and conduct long-term RCTs to validate intervention efficacy and “genetics-microbiota-metabolism” crosstalk—critical for CRC precision prevention.

Background: Although lactate metabolism-related genes (LMRGs) have attracted attention for their effects on cancer immunity, little is known about their function in clear cell renal cell carcinoma (ccRCC). The aim of this study was to examine the cellular specificity of lactate metabolism and how it affected the first-line treatment outcomes in ccRCC.Methods: GSE159115 was used to examine the features of lactate metabolism at the single-cell level. Utilizing the transcriptome, methylation profile, and genomic data from TCGA-KIRC, a multi-omics study of LMRG expression characteristics was performed. A prognostic index based on a gene-pair algorithm was created to assess how LMRGs affected patients’ clinical outcomes. To simulate the relationship between the prognostic index and the frontline treatment, pRRophetic and Subclass Mapping were used. E-MTAB-1980, E-MTAB-3267, Checkmate, and Javelin-101 were used for external validation.Results: The variable expression of some LMRGs in ccRCC can be linked to variations in DNA copy number or promoter methylation levels. Lactate metabolism was active in tumor cells and vSMCs, and LDHA, MCT1, and MCT4 were substantially expressed in tumor cells, according to single-cell analysis. The high-risk patients would benefit from immune checkpoint blockade monotherapy (ICB) and ICB plus tyrosine kinase inhibitors (TKI) therapy, whereas the low-risk individuals responded to mTOR-targeted therapy.Conclusions: At the single-cell level, our investigation demonstrated the cellular specificity of lactate metabolism in ccRCC. We proposed that the lactate-related gene pair index might be utilized to identify frontline therapy responders in ccRCC patients as well as predict prognosis.

The efficacy of PD‐1 inhibitor pucotenlimab (HX008) in solid tumors exhibits heterogeneity. This study integrated data from 6 clinical trials (covering gastric/gastroesophageal junction cancer, triple‐negative breast cancer, melanoma, and dMMR/MSI‐H solid tumors) using Bayesian meta‐analysis, machine learning (optimal XGBoost AUC = 0.86), and network meta‐analysis to construct an integrated “efficacy‐prediction‐safety” framework. Bayesian analysis showed pucotenlimab significantly improved outcomes versus control (ORR OR = 4.82, 95% CrI: 3.65–6.38; PFS HR = 0.41, 0.32–0.52; OS HR = 0.37, 0.26–0.51). Subgroups revealed TNBC patients with gemcitabine/cisplatin achieved highest ORR (80.6%, 62.5%–92.6%), while mucosal melanoma showed lowest response (8.7%, 1.1%–28.0%). Combination therapy demonstrated superior efficacy to monotherapy (ORR OR: 5.91 vs. 2.35). Machine learning identified 4 efficacy biomarkers (KMT2D mutation, post‐treatment NLR decrease, PD‐L1 CPS ≥ 1, high eotaxin) and 3 irAE risk factors (baseline NLR ≥ 4, irinotecan combination, high VEGF). Network analysis recommended regimens: gemcitabine/cisplatin for TNBC (SUCRA = 95.7%), oxaliplatin/capecitabine for G/GEJ cancer (ORR = 60.0% vs. irinotecan 27.6%, HR = 0.45). The integrated model classified high‐benefit (≥ 3 points; ORR 78.2%) and low‐benefit (≤ 0 points; ORR 28.3%) groups, plus high‐risk (≤ −2 points; grade ≥ 3 irAEs 41.2%) and low‐risk (≥ 1 point; irAEs 3.5%) groups, validated by decision curve analysis. This defines precise application scenarios and provides an extensible analytical paradigm.

肠稳态是由包括肠上皮细胞在内的多种肠道成分、肠道内环境以及大量神经内分泌调控通路相互作用所构成的动态平衡状态. 近年来研究显示, 作为肠道神经系统(enteric nervous system, ENS)的核心, 肠胶质细胞(enteric glial cell, EGC)可能通过参与调控肠道运动、营养吸收与分泌、肠道免疫、肠道防御等多种肠道功能在肠稳态调节机制中发挥关键作用. 同时, 异常活化的EGC也可能是炎症性肠病、肠道感染、肠道功能紊乱等肠道疾病以及代谢性疾病、帕金森病等肠外疾病的重要致病因素. 本文就近年来EGC相关研究进展结合本课题组的研究工作进行简要综述, 以期推动国内在这一领域研究的进一步发展.