Ulcerative colitis (UC) is an increasingly prevalent inflammatory condition affecting the intestinal mucosa, while nonspecific orbital inflammation (NSOI) is a common non-neoplastic orbital disorder. Exploring the molecular interplay between UC and NSOI may help physicians make earlier diagnoses and enhance treatment approaches. We analyzed gene expression datasets (GSE58331, GSE105149, GSE206285, and GSE179285) for UC and NSOI from the GEO database. Using WGCNA and differential expression analysis, we identified genes commonly altered in both diseases. GO enrichment, PPI networks, and transcription factor prediction were performed using Cytoscape plugins (cytoHubba and iRegulon). Machine learning techniques were employed to assess transcription factor activity and evaluate potential therapeutic targets among the hub genes. We conducted an association analysis using the TwoSampleMR package in R to explore potential causal relationships between NSOI and UC. A total of 85 intersecting genes between NSOI and UC were identified, and enrichment analyses revealed their roles in immune and inflammatory processes. Key biomarkers, including CXCL10, CXCR4, CXCL9, CD27, SELL, MMP9, CD79A, CD3E, GZMK, and CCL19, were highlighted, linking them to processes such as leukocyte migration, viral response, and monocyte differentiation. STAT1 was identified as a shared transcription factor influencing both diseases. Machine learning algorithms identified eight potential genes for diagnostic and therapeutic use, with CXCL10 emerging as a key player in the pathogenesis of NSOI and UC. CXCL10 likely regulates CXCR4, LCK, CCR7, and other genes involved in pathways such as cytokine-cytokine receptor interactions, HIV-1 infection, and Epstein-Barr virus infection. This study offers insights into the co-pathogenic mechanisms of UC and NSOI, providing a foundation for further mechanistic research and therapeutic development.

The role of immune cells in diabetic retinopathy (DR) is unclear. This study aims to assess the causal effect of various immune cells on DR by Mendelian randomization (MR). Immune cell datasets were acquired from European Bioinformatics Institute, and a DR dataset was acquired in FinnGen. Single nucleotide polymorphisms were screened stepwise according to the assumptions of association, independence, and exclusivity. Inverse variance weighted was used as the main method for MR analysis. MR-Egger was used to assess the horizontal pleiotropy of the results. Cochran Q and leave-one-out methods were respectively used for heterogeneity and sensitivity of the results. MR analysis identified 11 immune cell phenotypes associated with an increased genetic susceptibility to DR: T cell related phenotypes included CD4 on resting Treg, CD4/CD8br, CD28+ CD45RA− CD8dim AC, and CD28− CD25++ CD8br %T cell; NKT cell related phenotypes included CD8br NKT AC and CD3 on NKT; Dendritic cell related phenotypes included CD80 on plasmacytoid DC, CD62L+ plasmacytoid DC, and myeloid DC; The monocyte related phenotype was HLA DR on CD33br HLA DR+ CD14−; and the myeloid cell related phenotype was CD33− HLA DR− AC. No horizontal pleiotropy was observed ( P ≥ .05). Cochran Q showed no heterogeneity in the results except for CD8br NKT AC ( P < .001) and HLA DR on CD33br HLA DR+ CD14− ( P = .002). Sensitivity analysis showed the results were robust. The MR analysis revealed 11 immune cell phenotypes associated with an increased genetic susceptibility to DR. These findings provide a new perspective on the pathogenesis and drug development of DR.

Background: Glaucoma is the leading cause of irreversible blindness worldwide. The aim of this study was to evaluate the efficacy and safety of Fufang Xueshuantong Capsules (FFXST) in combination with conventional drugs in the treatment of glaucoma using meta-analysis and trial sequential analysis (TSA). Methods: Clinical trials of FFXST for glaucoma were identified in 8 databases until November 2022, and studies were included for meta-analysis and trial sequential analysis. Results: In terms of efficacy endpoints, meta-analysis showed that the combination group of FFXST significantly improved clinical effective rate (RR 1.29, 95% CI 1.20–1.39, P < .00001), visual function (MD 0.04, 95% CI 0.04–0.05, P < .00001), light sensitivity (MD 6.07, 95% CI 4.63–7.51, P < .00001), end-systolic blood flow velocity (MD 2.68, 95% CI 2.19–3.16, P < .00001) and end-diastolic blood flow velocity (MD 2.07, 95% CI 1.86–2.28, P < .00001), and significantly reduced total gray-scale value (MD −64.38, 95% CI −69.08 to −59.68, P < .00001) and defect of visual field (MD −3.40, 95% CI −4.11 to −2.69, P < .00001) compared with the conventional regimen group, while the pulsatility index and resistance index were comparable. The TSA indicated that these benefits were conclusive. In terms of safety endpoints, meta-analysis demonstrated that total drug-related adverse events in the combination group of FFXST were comparable to those in the conventional regimen group, with TSA showing that more studies are needed to validate the current results. Conclusion: FFXST may be a safety and effective supplementary strategy for the treatment of glaucoma, which is worthy of further research.