Background: Neurological involvement and psychiatric manifestations have been documented in clinical cases of inflammatory bowel disease (IBD); however, the presence of a causal relationship remains elusive. The objective of this study is to investigate the modifications occurring in the cerebral cortex as a result of IBD.Methods: A compendium of data extracted from a genome-wide association study (GWAS) involving a maximum of 133,380 European subjects. A series of Mendelian random analyses were applied to exclude heterogeneity and pleiotropy, ensuring the stability of the results.Results: Neither IBDs nor inflammatory cytokines (IL-6/IL-6Rα) were found to have a significant causality with surface area (SA) and thickness (TH) at the global level. At the regional functional brain level, Crohn’s disease (CD) significantly decreased the TH of pars orbitalis (β=-0.003mm, Se=0.001mm, p_ivw =4.85×10^-4). IL-6 was observed to reduce the SA of middle temporal (β=-28.575mm², Se=6.482mm², p_ivw=1.04×10^-5) and increase the TH of fusiform (β=0.008mm, Se=0.002mm, p_ivw=8.86×10^-5) and pars opercularis (β=0.009mm, Se=0.002mm, p_ivw=2.34×10^-4). Furthermore, a causal relationship between IL-6Rα and an increase in the SA of superior frontal (β=21.132mm², Se=5.806mm², p_ivw=2.73×10^-4) and the TH of supramarginal (β=0.003mm, Se=0.0002mm, p_ivw=7.86×10^-37). All results passed sensitivity analysis and no heterogeneity and pleiotropy were detected.Conclusion: The correlation between IBD and changes in cerebral cortical structures implies the existence of a gut-brain axis at the organismal level. It is recommended that clinical patients with IBD prioritize long-term management of inflammation, as changes at the organismal level can lead to functional pathologies. Magnetic resonance imaging (MRI) may be considered as an additional screening option for IBD.

High levels of low-density lipoprotein cholesterol (LDL-C) have been associated with an augmented mortality of ischemic stroke. The yearly deaths and mortality data of IS-hLDL-C were derived from the global burden of disease 2019 dataset. The joinpoint, age-period-cohort and decomposition analysis were utilized to evaluate the long-term patterns in the disease burden of IS-hLDL-C, and the effects of population growth and aging. Globally, in 2019, 0.61 million ischemic stroke-related deaths were attributable to high LDL-C, with the highest death burden in the high-middle socio-demographic index (SDI) region. From 1990 to 2019, the age-standardized death rate (ASDR) for IS-hLDL-C exhibited a downward trend, with an average annual percentage change of -1.69 [95% confidence interval: −1.90, −1.48)]. The fastest decreasing trends in ASDR were experienced in the high SDI region. In 119 (58.33%) countries, aging increased the disease burden of hLDL-IS, and population growth increased the disease burden of IS-hLDL-C in 163 (79.90%) countries. The trend in disease burden of IS-hLDL-C exhibited variation across countries and regions, particularly in territories with high to middle high SDI. Aging in upper to middle-income countries and population growth in low to middle-income countries further offset endeavors to reduce the burden of ischemic stroke deaths.

Background: Previous observational studies have found that fistulas are common in Crohn’s disease (CD) and less common in ulcerative colitis (UC). However, some patients have a fistula before diagnosis. Based on retrospective analysis, it was not possible to determine whether there was a bi-directional causal relationship between inflammatory bowel disease (IBD) and fistulas. Methods: Data were extracted from the open GWAS database; 25,042 cases and 34,915 controls were included for IBD, and 6926 cases and 30,228 controls were included for fistula. Two-sample Mendelian randomization and multivariable Mendelian randomization were used in combination to determine the causal relationship between IBD and fistula. Results: Forward MR showed that IBD increased the risk of colonic or urogenital fistula (FISTULA) (OR: 1.09, 95% CI: 1.05 to 1.13, p = 1.22 × 10⁻⁶), mainly associated with fissure and fistula of the anal and rectal regions (FISSANAL) (OR:1.10, 95% CI:1.06 to 1.14, p = 6.12 × 10⁻⁸), but not with fistulas involving the female genital tract (FEMGENFISTUL) (OR:0.97, 95% CI: 0.85 to 1.11, p = 0.669). Furthermore, both UC and CD increased the risk of FISTULA. However, after adjusting by MVMR, only CD increased the risk of FISTULA (OR: 1.06, 95% CI: 1.02 to 1.11, p = 0.004), and UC did not increase the risk of FISTULA (OR: 1.01, 95% CI: 0.95 to 1.06, p = 0.838). Reverse MR showed that fistulas did not increase the risk of IBD. Conclusion: Our study confirms it is CD, rather than UC, that casually leads to an increased risk of fistula, but fistulas do not increase the risk of IBD.

The purpose of this retrospective cross-sectional study was to explore the clinical and pathogenic significance of vitamin D and its relationship with interferon-α (IFN-α) in Chinese patients with primary Sjögren’s syndrome (pSS). In our study, 32 pSS patients and 50 healthy controls were included. Serum vitamin D and IFN-α concentrations were determined by enzyme-linked immunosorbent assay (ELISA) and analyzed with the correlations of EULAR Sjögren’s Syndrome Disease Activity Index (ESSDAI). The multiple linear regression analysis of 25-OH vitamin D3 level with ESSDAI scores in pSS patients was also investigated. Serum 25-OH vitamin D3 significantly correlated in an inverse manner with ESSDAI scores (p < 0.001, r = −0.781) and IgG (p < 0.001, r = −0.64). Serum 25-OH vitamin D3 were only related to peripheral nervous system (PNS) domain deficiency. Further, serum IFN-α was positively correlated with ESSDAI, but negatively correlated with serum 25-OH vitamin D3. These results suggest an important role of vitamin D regulating disease activity in pSS patients and value of supplement vitamin D in pSS treatment.