Introduction: Nuclear receptor subfamily five group A member two (NR5A2) plays a key role in the development of many tumor types, while it is uncertain in cutaneous squamous cell carcinoma (cSCC). The aim of this work was to determine the role of NR5A2 in cSCC proliferation, and to determine whether NR5A2 mediates the effect of cisplatin in cSCC.Methods: We performed a systematic study of existing data and conducted a preliminary bioinformatics analysis of NR5A2 expression in cSCC using bioinformatics databases. Immunohistochemical staining was performed on cSCC tissues of seven patients to study NR5A2 expression. NR5A2 expression was examined in human keratin‐forming cells (HaCaT) and human cSCC cells (A431, Colo‐16, SCL‐1, SCL‐2, and HSC‐5). Stable A431 and SCL‐2 cell lines consisting of sh‐RNA‐NR5A2 were constructed to detect changes in cell proliferation, cell cycle, apoptosis, and to determine the key proteins in the Wnt/β‐catenin pathway. We also investigated changes in the effects of cisplatin on cSCC cells by CCK‐8, clone formation assay, and Flow apoptosis assay after NR5A2 knockdown.Results: NR5A2 showed enhanced expression in cSCC tissues than in healthy tissues. Downregulation of NR5A2 in cSCC cells led to the formation of a less malignant phenotype. In contrast, the proliferative capacity of the cSCC cells was enhanced posttreatment with RJW100, an NR5A2 agonist. Additionally, NR5A2 knockdown led to a decrease in the expression level of the proteins in the Wnt/β‐catenin pathway, and this inhibition was reversed by LiCl and recombinant antibody, Wnt3a. Moreover, NR5A2 knockdown resulted in diminished proliferative capacity and increased apoptotic cells after the addition of cisplatin.Conclusion: NR5A2 plays a crucial role in the progression of cSCC, and the Wnt/β‐catenin signaling pathway may be involved in the regulation of NR5A2‐mediated cSCC. Knockdown of NR5A2 enhanced both the proliferation inhibiting and apoptosis promoting effects of cisplatin on cSCC.

Inflammatory bowel disease (IBD) is a chronic and relapsing gastrointestinal disorder whose global disease burden continues to rise, making it a significant public health issue. In recent years, rapid socioeconomic development in East Asia has led to notable changes in lifestyle and dietary patterns, accompanied by dynamic shifts in the epidemiological characteristics of IBD. However, there remains a lack of systematic comparison and analysis of the long-term disease burden and evolutionary trends of IBD across five East Asian countries and regions: China, Japan, South Korea, North Korea, and Mongolia. Based on data from The Global Burden of Disease Study 2021 (GBD 2021), this study aims to comprehensively describe the trends in incidence, prevalence, mortality, and disability-adjusted life years (DALYs) of IBD in The region from 1990 to 2021, thereby providing a basis for differentiated prevention and control strategies. Descriptive analysis, Joinpoint regression, and age–period–cohort (APC) modeling were employed to examine epidemiological patterns and trends. Significant variations in IBD burden were observed across the region. China and South Korea experienced the most rapid increases in incidence and prevalence, exhibiting a profile of “high morbidity and low disability.” Japan demonstrated a stabilizing disease burden alongside a continuing decline in standardized mortality rates, reflecting its advanced healthcare system. North Korea and Mongolia currently have a relatively low overall burden; however, a notable rise in incidence among young Mongolians suggests an emerging risk of early-onset IBD. APC analysis further indicated complex influences from environmental factors, healthcare resource allocation, and lifestyle changes such as Westernized diets. The study proposes tailored prevention strategies: high-SDI countries should optimize geriatric care systems, medium-SDI countries should enhance preventive interventions for adolescents, and low-SDI countries should prioritize the establishment of primary screening networks. These findings provide a scientific basis for differentiated IBD prevention and control in East Asia and contribute to a deeper understanding of the epidemiological transition of chronic diseases.

Background: The global prevalence and incidence of fungal skin diseases continue to rise due to population ageing, urbanisation and environmental changes, posing a significant public health challenge. These infections are particularly severe in immunocompromised individuals, potentially leading to deep‐seated infections and life‐threatening complications. However, comprehensive data on the global burden of fungal skin diseases remain limited, especially in low‐ and middle‐income countries (LMICs) with constrained resources. Methods: Using Global Burden of Disease (GBD) data from 1990 to 2021, this study analysed trends in incidence, prevalence and disability‐adjusted life years (DALYs) across 204 countries and territories. Joinpoint regression was employed to identify temporal trend changes, while the Age‐Period‐Cohort (APC) model was used to disentangle age, period and cohort effects. Additionally, the Bayesian Age‐Period‐Cohort (BAPC) model was applied to project disease burden from 2022 to 2036. Results: In 2021, the global age‐standardised incidence rate (ASIR) was 21,668.4 per 100,000 population, showing a slight increase compared to 1990 (Estimated annual percentage change [EAPC] = 0.11). The burden exhibited marked disparities by Socio‐demographic Index (SDI): low‐SDI countries had the highest ASIR and DALYs (e.g., Ethiopia's ASIR reached 45,535.04 per 100,000), whereas high‐SDI countries demonstrated a declining trend. Joinpoint regression revealed pronounced fluctuations in low‐SDI nations, contrasting with sustained declines in high‐SDI regions. APC analysis indicated elevated risks among older populations and younger birth cohorts. BAPC projections suggested a continued rise in global incidence by 2030, with females likely facing a higher burden than males. Conclusion: The burden of fungal skin diseases is closely linked to socioeconomic development, with resource‐limited regions bearing the highest risks. The projected upward trend underscores the urgent need for targeted public health interventions, particularly in strengthening prevention and management systems in low‐SDI countries. This study provides critical evidence to inform global strategies for mitigating the impact of fungal skin diseases.

Nuclear receptor subfamily 5 group A member 2 (NR5A2) is known to be a key regulator in the development of a variety of tumor types. However, it is still uncertain how NR5A2 affects cutaneous squamous cell carcinoma (cSCC). The aim of this work, therefore, was to determine the function of NR5A2 in cSCC proliferation, cell cycling, cell migration, and invasion. In this study, based on a systematic study of previous data, we conducted a preliminary exploration of NR5A2 expression in cSCC using bioinformatics databases. Immunohistochemical staining for NR5A2 expression was then performed in cSCC tissues and healthy tissues from 7 patients. NR5A2 expression was also examined in human keratin-forming cells (HaCaT) and human cSCC cell lines (A431, Colo-16, SCL-1, and SCL-2). A stable A431 cell line consisting of sh-RNA-NR5A2 was created to detect changes in cell proliferation, cell cycle, clonogenic ability, and the key proteins about the Wnt/β-catenin pathway. The results illustrated that NR5A2 showed enhanced expressed in cSCC tissues than in healthy adjacent tissues and was more robustly expression in Colo-16, A431, SCL-1, and SCL-2 cells versus HaCaT cells. Downregulation of NR5A2 expression in cSCC cells led to a less malignant phenotype. NR5A2 knockdown decreased the expression of proteins in the Wnt/β-catenin, and this inhibition could be reversed by the Wnt signaling pathway agonist LiCl. In conclusion, NR5A2 appears to encourage the development and metastasis of cSCC by Wnt/β-catenin pathway.

Objective: Thyroid cancer incidence has risen steadily, and elevated body mass index (BMI) is a modifiable risk factor for it. We assessed the disease burden of high BMI-attributable thyroid cancer across the BRICS countries (Brazil, Russia, India, China, and South Africa), which have undergone rapid lifestyle transitions, and characterized temporal, age, period, and birth-cohort patterns from 1990 to 2021. Methods: In this cross-sectional, population-based secondary analysis, we used modelled attributable-burden estimates from the Global Burden of Disease Study 2021 (GBD 2021) to evaluate spatiotemporal trends in disability-adjusted life years (DALYs; the primary endpoint) and mortality attributable to high BMI-related thyroid cancer from 1990 to 2021, applying descriptive analyses, Joinpoint regression, and age–period–cohort (APC) modeling. Results: In 2021, Russia exhibited the highest age-standardized DALYs rate (ASDR) (2.09 per 100,000 population), followed by South Africa and Brazil, while China and India demonstrated the lowest burden. Although women bore more DALYs overall, men showed more pronounced increasing trends, particularly in China (annual percentage change [AAPC]: 2.31% in men vs. -0.35% in women). DALY rates rose with age in all five countries. Period effects showed sustained increases in China and India but declining trends in Russia. Cohort effects indicated elevated risk among younger birth cohorts in China and India (relative risk [RR] >1.7 for 1997 birth cohort), contrasting with stable or decreasing patterns in Russia and Brazil. Conclusions: Cross-national and sex-specific disparities exist in the high BMI-attributable thyroid cancer burden among BRICS nations. The pronounced increase among Chinese and Indian male populations and younger birth cohorts highlights the potential value of enhanced public-health investment in obesity prevention, risk-based assessment of thyroid disease, and improved surveillance of high-risk populations, rather than population-wide thyroid cancer screening.