Rabies is an acute lethal infectious disease caused by a lyssavirus infection. In 2018, the World Health Organization proposed a global strategic plan to end human rabies deaths by 2030. However, systematic studies on the global rabies disease burden and epidemiological trends are scarce. We extracted the disease burden and epidemiological data of rabies worldwide in the preceding 30 years from the Global Burden of Disease Study 2019 and performed a comprehensive analysis. In 2019, the incident cases of rabies worldwide were 14,075.51 (95% uncertainty interval: 6124.33-21,618.11), and the number of deaths was 13,743.44 (95% uncertainty interval: 6019.13-17,938.53), both of which were lower than that in 1990. With the improvement of the sociodemographic index, the incident cases, the number of deaths, age-standardized incidence rate, age-standardized incidence death rate, and disability-adjusted life years of rabies all showed downward trends. Adolescents and adults aged <50 years represented the majority of rabies cases worldwide. The global disease burden of rabies has declined over the past 30 years. Furthermore, the disease burden of rabies was closely related to the sociodemographic index level.

Background: Smoking is believed as one of the major risk factors resulting in a variety of non-communicable diseases, such as lung cancer and chronic respiratory diseases (CRDs). However, the global burden of CRDs attributed to smoking has not been systematically studied, particularly across different temporal and spatial scales. Methods: We conducted a systematic analysis of the Global Burden of CRDs and related risk factors using data from the Global Burden of Disease Study 2019. Incidence, death, risk factors, and other parameters such as estimated annual percentage change have been analyzed. We also compared various risk factors across regions, countries, and genders. Results: Globally, the incidence of CRDs and deaths cases have increased in the last 30 years, while the corresponding age-standardized incidence rate (ASIR) and death rate (ASDR) have declined. Smoking was the leading risk factor for the death of CRDs all over the world. However, in low and low-middle Socio-demographic Index (SDI) areas, particulate matter pollution was the main risk factor leading to death from CRDs, while smoking was ranked first among the major risk factors in areas with middle, middle-high, or high SDI. Globally, gender differences in morbidity and mortality from CRDs were observed. Males had slightly more cases and ASIR of chronic respiratory diseases than females over the last 30 years. However, the mortality cases and ASDR in males were significantly higher than that of females. Furthermore, the ASDR of all major risk factors, specially smoking, was higher in men than in women. Conclusions: CRDs were still major threats human health. The current study highlights the dominating roles of smoking for death risks resulting from CRDs, followed by PM pollution. Therefore, tobacco control and improving air quality are key to reducing deaths from CRDs.

Our research aimed to identify new therapeutic targets for Lung adenocarcinoma (LUAD), a major subtype of non-small cell lung cancer known for its low 5-year survival rate of 22%. By employing a comprehensive methodological approach, we analyzed bulk RNA sequencing data from 513 LUAD and 59 non-tumorous tissues, identifying 2,688 differentially expressed genes. Using Mendelian randomization (MR), we identified 74 genes with strong evidence for a causal effect on risk of LUAD. Survival analysis on these genes revealed significant differences in survival rates for 13 of them. Our pathway enrichment analysis highlighted their roles in immune response and cell communication, deepening our understanding. We also utilized single-cell RNA sequencing (scRNA-seq) to uncover cell type-specific gene expression patterns within LUAD, emphasizing the tumor microenvironment’s heterogeneity. Pseudotime analysis further assisted in assessing the heterogeneity of tumor cell populations. Additionally, protein-protein interaction (PPI) network analysis was conducted to evaluate the potential druggability of these identified genes. The culmination of our efforts led to the identification of five genes (tier 1) with the most compelling evidence, including SECISBP2L, PRCD, SMAD9, C2orf91, and HSD17B13, and eight genes (tier 2) with convincing evidence for their potential as therapeutic targets.

Background: Sepsis is a major contributor to global morbidity and mortality, affecting millions each year. Notwithstanding the decline in sepsis incidence and mortality over decades, gender disparities in sepsis outcomes persist, with research suggesting higher mortality rates in males.Methods: This retrospective study aims to delineate gender-specific clinical biomarker profiles impacting sepsis progression and mortality by examining sepsis cases and related clinical data from the past three years. Propensity score matching was used to select age-matched healthy controls for comparison.Results: Among 265 sepsis patients, a significantly higher proportion were male (60.8%, P<0.001). While mortality did not significantly differ by gender, deceased patients were significantly older (mean 69 vs 43 years, P=0.003), more likely to have hypertension (54% vs 25%, P=0.019), and had higher SOFA scores (mean ~10 vs 4, P<0.01) compared to survivors. Principal Component Analysis (PCA) showed clear separation between sepsis patients and healthy controls. 48 serum biomarkers were significantly altered in sepsis, with Triiodothyronine, Apolipoprotein A, and Serum cystatin C having the highest diagnostic value by ROC analysis. Gender-stratified comparisons identified male-specific (e.g. AFP, HDLC) and female-specific (e.g. Rheumatoid factor, Interleukin-6) diagnostic biomarkers. Deceased patients significantly differed from survivors, with 22 differentially expressed markers; Antithrombin, Prealbumin, HDL cholesterol, Urea nitrogen and Hydroxybutyrate had the highest diagnostic efficiency for mortality.Conclusion: These findings enhance our understanding of gender disparities in sepsis and may guide future therapeutic strategies. Further research is warranted to validate these biomarker profiles and investigate the molecular mechanisms underlying these gender differences in sepsis outcomes.