Background: Inflammatory bowel disease (IBD) represents a growing global health challenge, necessitating a systematic evaluation of its epidemiological trends and sociodemographic disparities. Methods: Using Global Burden of Disease 2021 data, we quantified IBD burden (incidence, mortality, prevalence, disability-adjusted life years [DALYs], years lived with disability [YLDs], and years of life lost [YLLs]) across 204 countries and territories from 1990 to 2021, and projected trends to 2050, evaluating associations with Sociodemographic Index (SDI) and sex disparities. Results: Between 1990 and 2021, global crude counts of incident cases, deaths, prevalence, DALYs, YLDs, YLLs increased by 88.3%, 98.1%, 76.5%, 59.2%, 75.1%, and 50.8%, respectively. However, age-standardized rates (ASRs) of mortality, prevalence, DALYs, YLDs, and YLLs declined by 13.0%, 6.5%, 16.1%, 6.6%, and 21.0%, respectively, contrasting with a modest rise in age-standardized incidence rates (ASIR, 5.5%). The average annual percentage changes (AAPCs) of Incidence, Mortality, Prevalence, DALYs, YLDs, and YLLs were 0.1582, -0.4885, -0.2223, -0.5704, -0.2237, -0.7686, respectively. Projections to 2050 indicate continued reductions in ASRs across all metrics. High and middle-high SDI regions retained the highest absolute burdens, yet low to middle-SDI regions exhibited the steepest escalation in crude incidence and prevalence, correlating strongly with rising SDI (Spearman’s ρ=0.599 for incidence). Females showed a bimodal pattern, with higher disability and prevalence in both mid-life and very old age groups. Conclusions: High-SDI regions remain IBD epicenters, but accelerating burdens in low- and middle-SDI areas demand context-specific interventions. Persistent sex/age disparities necessitate tailored healthcare strategies to address the evolving global burden.

Background Observational studies have shown that patients with primary biliary cholangitis (PBC) have a higher incidence of extrahepatic autoimmune diseases (EHAIDs) than healthy individuals. However, whether this correlation is causal remains unclear. Methods Genetic instrumental variables associated with PBC and 7 EHAIDs were derived from published genome-wide association studies (GWAS) of European ancestry. A bidirectional two-sample Mendelian randomization (MR) analysis was used to determine the causal relationship between PBC and EHAIDs. Result We found that PBC can increase the susceptibility to type 1 diabetes (TD1), autoimmune hyperthyroidism (AITD), systemic lupus erythematosus (SLE), ankylosing spondylitis (AS), Psoriasis and Sarcoidosis with IVW odds ratio (OR) of 1.35 (95% CI: 1.28 ~ 1.43, p = 1.76×10 − 28), 1.19 (95% CI: 1.09 ~ 1.30, p = 0.00014),1.48 (95% CI: 1.36 ~ 1.61, p = 2.43×10 − 19), 1.13 (95% CI: 1.04 ~ 1.22, p = 0.0030), 1.09 (95% CI: 1.05 ~ 1.14, p = 4.50×10 − 5) and 1.11(95% CI: 1.03 ~ 1.19, p = 0.0064) respectively. Using reverse MR analysis, we also found that TD1 can increase the susceptibility to PBC, with IVW OR of 1.29 (95% CI: 1.19 ~ 1.41, p = 1.77×10 − 9). Conclusion PBC and TD1 may be causally related to each other. PBC can increase the susceptibility to AITD, SLE, AS, Psoriasis and Sarcoidosis. It reminds us that we should pay attention to screening for these EHAIDs in clinical PBC patients to improve the patient's survival rate and quality of life.

Hepatocellular carcinoma (HCC) is a prevalent global malignancy characterized by a high incidence and poor prognosis. Current diagnostic and therapeutic modalities are insufficient to meet the demands for effective HCC diagnosis and management. Cuproptosis represents a novel mechanism of cellular death, which may offer new avenues for drug research in oncology. We employed the Summary-data-based Mendelian Randomization (SMR) method alongside gene intersection analyses related to Cuproptosis, identifying SIRT2 as the target gene. Single-cell RNA sequencing (scRNA-seq) and spatial transcriptome sequencing (stRNA-seq) were conducted to investigate the role of SIRT2 in HCC. Subsequently, we analyzed the differentially expressed genes of SIRT2 + malignant cell (SIRT2 + Mali) using a Deep Learning Survival Neural Network (deepsurv), leading to the construction of a prognosis model. The protein interactions between SIRT2 and the key genes involved in the model were assessed. Finally, RNA sequencing (RNA-seq) analysis was performed, encompassing gene correlation analysis, immune checkpoint analysis, GO, GSEA, and KEGG enrichment analysis, immune cell infiltration, clinical characteristics analysis and drug sensitivity analysis. SIRT2 was identified as a gene positively correlated with HCC risk through SMR analysis. The scRNA-seq analysis revealed that, compared to SIRT2- malignant cell (SIRT2- Mali), SIRT2 + Mali exhibited stronger interactions with cancer-associated fibroblasts (CAF), tumor-associated macrophages (TAM), and tumor-associated endothelial cells (TEC), participating in more diverse metabolic pathways. The stRNA-seq analysis indicated a robust spatial correlation of SIRT2 + Mali with CAF, TAM, and TEC. The deepsurv prognostic model demonstrated that the survival rate of patients with elevated risk scores was significantly lower than that of those with low risk scores. RNA-seq analysis confirmed a positive correlation between SIRT2 and various immune checkpoint genes. Immune cell infiltration analyses indicated higher abundance scores of monocytic lineage, endothelial cells, and fibroblasts in the SIRT2 high expression group compared to the SIRT2 low expression group. The expression of SIRT2 was associated with gender, T classification, and Stage. SIRT2 is posited as a pathogenic gene for HCC. It may facilitate the growth and invasion of HCC via multiple mechanisms, including Cuproptosis, tumor microenvironment modulation, metabolic pathway alteration, and immune checkpoint activation. SIRT2 presents as a potential biomarker for HCC and may serve as a novel therapeutic target for its treatment.