Ningxia Medical University

Colon cancer is a major subtype of colorectal cancer and one of the leading causes of cancer-related morbidity and mortality worldwide. Age is a well-established risk factor, yet the precise nature of its association with colon cancer risk – particularly potential nonlinear effects – remains underexplored in large population-based datasets. We conducted a cross-sectional analysis using data from 16,982 adults aged ≥ 18 years who participated in the 2011 to 2018 National Health and Nutrition Examination Survey. Colon cancer status was determined through self-reported medical history. Multivariable logistic regression models were used to assess the independent association between age and colon cancer prevalence, adjusting for sociodemographic, anthropometric, and behavioral covariates. Segmented regression was applied to evaluate potential nonlinear threshold effects. Among 16,982 participants, 117 (0.69%) reported a diagnosis of colon cancer. Age was significantly associated with colon cancer prevalence across all models (adjusted OR = 1.047 per year, 95% CI: 1.032–1.063, P < .001). Subgroup analyses confirmed consistent associations across strata of smoking, diabetes, and hypertension. Segmented regression identified a nonlinear relationship with a threshold at 59 years: below this age, risk increased modestly (OR = 1.030), but rose more steeply thereafter (OR = 1.080). This nationally representative study highlights a strong and nonlinear association between aging and colon cancer prevalence, with a significant risk acceleration after age 59. These findings support the need for age-informed screening strategies and underscore the importance of early intervention and prevention efforts targeted toward older adults.

Research suggests that lipid levels may be associated with suicide risk. However, the specific relationship between Apolipoprotein B and suicidal ideation remains unclear. The aim of this study was to investigate the association between ApoB levels and suicidal ideation and to further explore the causal relationship using Mendelian randomization. A cross-sectional study of 6520 U.S. adults was conducted using the 2011-2016 National Health and Nutrition Examination Survey (NHANES) dataset. Multiple logistic regression, smoothed curve fitting, stratified analyses, and interaction tests were used to reveal the relationship between ApoB levels and suicidal ideation. MR analyses were conducted using inverse variance weighting (IVW), GSMR, Maximum likelihood method, and cML-MA-BIC MR method. Sensitivity analyses included MR-Egger intercept test, MR-PRESSO global test, and leave-one-out (LOO) analysis. Multivariate logistic regression analysis showed that serum ApoB levels were positively associated with suicidal ideation, and the association remained significant even after multiple covariates (P = 0.0463). Subgroup analyses showed that the risk of suicidal ideation was significantly increased in the highest tertile (T3) of the population compared to the lowest tertile (T1) of ApoB levels (OR = 1.48, 95% CI: 1.04-2.12, P = 0.0312). In addition, the association between ApoB and suicidal ideation was more significant in the smoking subgroup (P interaction = 0.034). However, MR analysis failed to confirm a significant causal effect of ApoB levels on suicidal ideation (P > 0.05), and these results were robust to sensitivity analyses. The present study found a significant positive association between serum ApoB levels and suicidal ideation, especially among smokers. MR analysis failed to provide causal evidence of ApoB on suicidal ideation. More research is needed to clarify the potential role of ApoB in the development of suicidal ideation.

Neutrophil extracellular trap (NET) formation has been implicated in the pathogenesis of rheumatoid arthritis-associated interstitial lung disease (RA-ILD), yet the specific neutrophil subsets involved and the mechanisms remain incompletely understood. Here, we identified a significantly expanded population of microsomal glutathione S-transferase 2-high NET-releasing polymorphonuclear neutrophils (Mgst2hi PMNs) in the lungs, bronchoalveolar lavage fluid (BALF), and peripheral blood (PB) of zymosan A-induced interstitial pneumonia-arthritis mouse models. Pharmacologic inhibition of Mgst2 with coniferyl ferulate (CF) and genetic knockdown using an adeno-associated virus (AAV9)-delivered shRNA under the Cd11b promoter (AAV9-shRNA-Mgst2) markedly attenuated pulmonary progression by suppressing NET formation. Mechanistically, Mgst2 promoted NET release in neutrophil-differentiated HL-60 cells and primary human peripheral blood neutrophils from healthy donors through a NADPH oxidases 2 (NOX2)-dependent pathway. NETs derived from these cells induced transdifferentiation of primary human pulmonary microvascular pericytes into myofibroblasts by activating transforming growth factor-beta (TGF-β) pathway. Clinically, circulating Mgst2hi NET-releasing PMNs were significantly elevated in the PB of patients with RA-ILD. Of note, more abundant Mgst2hi PMNs were found in RA patients with nonspecific interstitial pneumonia (NSIP) than those with usual interstitial pneumonia (UIP), organizing pneumonia (OP) and other ILD patterns. Moreover, the proportion of circulating Mgst2hi PMNs positively correlated with RA-NSIP severity, as assessed by and mean lung vessel diameter (6 mm), fibrosis score, and vessel score. Collectively, these findings demonstrate a critical pathogenic role for Mgst2hi PMNs in RA-ILD and suggest their utility as a potential therapeutic target through modulation of NET formation.

Abstract Background Rheumatoid arthritis (RA) is a systemic autoimmune disease featured by persistent synovial inflammation and multi-organ injury, with T lymphocytes as the core driver of its pathological progression. However, the molecular mechanisms of abnormal T cell functional regulation and the exact biological targets of resveratrol (a natural immunomodulatory polyphenol) in RA synovial microenvironment remain unclear. This study aimed to construct a T cell-focused RA diagnostic classifier and identify resveratrol-modulated molecular targets via multi-omics integration. Methods We integrated scRNA-seq and bulk transcriptome data of RA synovial tissues to characterize T cell-specific gene expression, intersected resveratrol targets from pharmacological databases with RA-related differentially expressed genes, and performed systematic benchmarking of 10 machine learning algorithms to screen stable diagnostic gene signatures (validated in external cohorts). CIBERSORT quantified synovial immune cell infiltration, and molecular docking evaluated resveratrol-target protein binding interactions. Results Distinct T cell subsets with differential resveratrol target gene expression were identified in RA synovium. A 5-gene signature ( PTTG1 , NUSAP1 , PDE4D , ITGA4 , BIRC3 ) was screened, showing excellent diagnostic performance (training cohort AUC = 0.983; external cohorts GSE55457 AUC = 0.908, GSE77298 AUC = 0.902). Its expression was positively correlated with activated T cell and pro-inflammatory macrophage infiltration. Molecular docking revealed stable binding of resveratrol to the five target proteins (binding free energy: -5.5 to -8.0 kcal/mol). Conclusion We constructed a robust T cell-centered 5-gene signature for RA diagnosis, and these five genes are potential molecular targets of resveratrol in RA immunotherapy. This study provides a novel molecular basis and research direction for developing synovitis-targeted therapeutic strategies for RA.