Congenital birth defects (CBDs) present enormous challenges to global healthcare systems. These conditions severely impact patients' health and underscore issues related to socioeconomic development and healthcare accessibility and efficiency. Previous studies have been geographically limited and lacked comprehensive global analysis. This study provides global, regional, and national disability-adjusted life years (DALYs) data for four major congenital birth defects—congenital heart defects (CHD), neural tube defects (NTDs), digestive congenital anomalies (DCAs), and Down syndrome (DS) from 1990 to 2021, emphasizing health inequalities. The goal is to offer scientific evidence for optimizing resource allocation, focusing on high-burden populations, and reducing disease burden. This study systematically evaluated the global, regional, and national burden of CBDs and their changes from 1990 to 2021 using the Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2021. To conduct a more focused analysis, four specific CBDs were selected: CHD, NTDs, DCAs, and DS. DALYs were used as the metric, combined with the sociodemographic index (SDI). Analyses included the slope index of inequality and concentration index to measure health inequalities, frontier analysis to estimate achievable outcomes based on development levels, decomposition analysis to identify drivers of disease burden changes, Joinpoint regression analysis to assess temporal trends, and the Bayesian age-period-cohort (BAPC) model to predict future disease burden trends. Compared to 1990, the global burden of the CBDs in 2021 showed a downward trend. Males had a higher burden than females, with the highest burden observed in low-SDI regions. When examining CHD, NTDs, DCAs, and DS specifically, trends in burden changes varied across different CBDs at the global, regional, and national levels. Frontier analysis revealed potential for burden improvement in various countries and territories. Decomposition analysis highlighted differences in disease burden drivers across SDI regions, showing the greatest improvement observed in low-SDI regions. Joinpoint regression analysis indicated a downward trend in DALYs burden across SDI regions, and BAPC model predictions suggested that the burden of CBDs will continue to decline in the future. CBDs pose a major challenge to global public health. Despite an overall decline in disease burden, health inequalities remain prominent, particularly in countries and territories with lower levels of development. Future public health interventions should focus on countries and territories with low levels of development by optimizing healthcare resource allocation, improving basic health infrastructure, enhancing health education, and reducing disease burden inequalities. Global collaboration and data sharing are essential to promote a lifecycle management model for CBDs research and treatment, advancing global health development. This study was supported by the 10.13039/501100001809 National Natural Science Foundation of China (No. 82270310) and the 10.13039/501100013058 Jiangsu Provincial Key Research and Development Program (No. BE2023662).

Background: Nonmalignant upper gastrointestinal diseases, including peptic ulcer disease (PUD), gastritis and duodenitis (GD), and gastroesophageal reflux disease (GERD), significantly challenge global healthcare. These conditions not only impact patient health but also highlight socioeconomic development issues and healthcare system accessibility and efficiency. Utilizing the Global Burden of Disease database, this study aims to comprehensively assess the global burden of PUD, GD, and GERD, examining their association with the sociodemographic index (SDI). Methods: Employing data from the Global Burden of Disease 2019 database, this study analyzed the disability-adjusted life years for PUD, GD, and GERD. We integrated the SDI with the inequality slope index and concentration index for an international health inequality analysis, assessing disparities in the burden of these nonmalignant upper gastrointestinal diseases. Decomposition analysis was conducted to determine the effects of population growth, aging, and epidemiological change on disease burden. Frontier analysis was performed to identify potential improvement areas and disparities among countries by development status. Disease time trends were depicted using a Joinpoint regression model, and the Bayesian age-period-cohort model projected the disease burden up to 2030. Results: Between 1990 and 2019, the age-standardized disability-adjusted life years rates for nonmalignant upper gastrointestinal diseases declined. However, global geographic heterogeneity remained evident and closely linked to the SDI. Notably, low-SDI countries experienced higher disease burdens. Population growth and aging emerged as principal contributors to the increasing disease burden. Despite development levels, many countries have considerable potential for reducing the burden of these diseases. Furthermore, significant variations in the time trends of nonmalignant upper gastrointestinal diseases were observed among countries and regions with different SDI levels, a pattern expected to continue through 2030. Conclusion: Nonmalignant upper gastrointestinal diseases demonstrate notable heterogeneity across age, sex, and geography, with the disparities most marked in underdeveloped regions or countries. Consequently, it is imperative to focus research on policy development and to enact prevention and treatment strategies tailored to high-risk groups. This targeted approach is essential for effectively mitigating the disease burden.

Alteration of gut microbiota can affect chronic lung diseases, such as asthma and chronic obstructive pulmonary disease, through abnormal immune and inflammatory responses. Previous studies have shown a feasible connection between gut microbiota and bronchopulmonary dysplasia (BPD) in preterm infants. However, whether BPD can be ameliorated by restoring the gut microbiota remains unclear. In preterm infants with BPD, we found variance in the diversity and structure of gut microbiota. Similarly, BPD rats showed gut dysbiosis, characterized by a deficiency of Lactobacillus, which was abundant in normal rats. We therefore explored the effect and potential mechanism of action of a probiotic strain, Lactobacillus plantarum L168, in improving BPD. The BPD rats were treated with L. plantarum L168 by gavage for 2 weeks, and the effect was evaluated by lung histopathology, lung function, and serum inflammatory markers. Subsequently, we observed reduced lung injury and improved lung development in BPD rats exposed to L. plantarum L168. Further evaluation revealed that L. plantarum L168 improved intestinal permeability in BPD rats. Serum metabolomics showed altered inflammation-associated metabolites following L. plantarum L168 intervention, notably a marked increase in anti-inflammatory metabolites. In agreement with the metabolites analysis, RNA-seq analysis of the intestine and lung showed that inflammation and immune-related genes were down-regulated. Based on the information from RNA-seq, we validated that L. plantarum L168 might improve BPD relating to down-regulation of TLR4 /NF-κB /CCL4 pathway. Together, our findings suggest the potential of L. plantarum L168 to provide probiotic-based therapeutic strategies for BPD.

Gastric cancer (GC) is characterized by notable heterogeneity and the impact of molecular subtypes on treatment and prognosis. The role of programmed cell death (PCD) in cellular processes is critical, yet its specific function in GC is underexplored. This study applied multiomics approaches, integrating transcriptomic, epigenetic, and somatic mutation data, with consensus clustering algorithms to classify GC molecular subtypes and assess their biological and immunological features. A machine learning model was developed to create the Gastric Cancer Multi-Omics Programmed Cell Death Signature (GMPS), targeting PCD-related genes. We verified the expression of the GMPS hub genes using the RT-qPCR method. The prognostic influence of GMPS on GC was then evaluated. Single-cell analysis was performed to examine the heterogeneity of PCD characteristics in GC. Findings indicate that GMPS notably correlates with patient survival rates, tumor mutational burden (TMB), and copy number variations (CNV), demonstrating substantial prognostic predictive power. Moreover, GMPS is closely associated with the tumor microenvironment (TME) and immune therapy response. This research elucidates the molecular subtypes of GC, highlighting PCD’s critical role in prognosis assessment. The relationship between GMPS and immune therapy response, alongside gastric cancer’s microenvironmental features, provides insights for personalized treatment.

Alcohol use disorders (AUD), drug use disorders (DUD), interpersonal violence, and self-harm are a major public health concern globally, with high rates of disability, morbidity, and mortality associated with this. This study aims to estimate the disease burden, trends, projections, and disparities of AUD, DUD, interpersonal violence, and self-harm among all ages and sexes from 1990 to 2021. This study is a secondary analysis utilizing data from the Global Burden of Disease (GBD) 2021 in 204 countries and territories. The incidence, deaths, and disability-adjusted life years (DALYs), projection, and the inequality were estimated for AUD, DUD, interpersonal violence, and self-harm among all age and sex. In 2021, there were 55.78 (46.56–64.31) million new cases of AUD, 13.61 (11.63–15.67) million new cases of DUD, 29.40 (26.17–32.65) million new cases of interpersonal violence, 5.49 (4.6–6.5) million new cases of self-harm globally. By 2040, AUD is forecasted to be 51.98 (29-74.97) million, DUD will be 13.81 (9.23–18.39) million, 36.01 (15.25–56.78) million for interpersonal violence, and 10.55 (3.16–17.94) million for self-harm. In terms of gender and age distribution, males had higher incidence, mortality, and DALYs for AUD, DUD, and interpersonal violence compared to females. Females had higher incidence of self-harm, while males had higher mortality. By age group, individuals aged 15–49 bore the highest burden of DUD, interpersonal violence, and self-harm, while those aged 50–74 had the highest burden of AUD. The burden of these conditions is closely related to the socio-demographic index (SDI). High- and middle-high SDI regions had a heavier burden of AUD, DUD, and self-harm, while low- and middle-low SDI regions had a heavier burden of interpersonal violence. Additionally, from 1990 to 2021, health inequalities for AUD and self-harm decreased, while those for DUD and interpersonal violence increased. From 1990 to 2021, the disease burden of AUD, DUD, interpersonal violence, and self-harm exhibited specific patterns across different genders, age groups, and regions. Multilevel interventions should be initiated, with a focus on reducing inequalities through resource allocation and policy support.