Cancer is the second most common cause of death globally. Therefore, it is imperative to investigate cancer incidence, mortality rates, and disability-adjusted life years (DALYs) to enhance preventive measures and healthcare resource allocation. This study aimed to assess cancer burden and associated risk factors in 204 countries and territories between 1980 and 2021. We selected data on cancer incidence and mortality rates and associated risk factors from the global burden of disease (GBD) study tool for 204 countries and territories from 1990 to 2021 and 1980 to 2021. We estimated the age-standardized incidence (ASIR) and age-standardized deaths (ASDR) of 34 cancer types categorized as level 3 causes based on the GBD hierarchy. In 2021, cancer accounted for 14.57% (95% uncertainty interval: 13.65–15.28) of total deaths and 8.8% (7.99–9.67) of total DALYs in both sexes globally. ASIR and ASDR were 790.33 (694.43–893.01) and 116.49 (107.28–124.69), respectively. Additionally, females exhibited higher ASIR than males (923.44 versus 673.09), while males exhibited higher ASDR than females (145.69 versus 93.60). This indicates that policymakers should focus on the importance of gender equality in healthcare. Non-melanoma skin cancer exhibited the highest ASIR (74.10) in both sexes, while digestive cancers accounted for 39.29% of all cancer-related deaths, and Asia exhibited the heaviest cancer burden. In females, breast cancer exhibited the highest ASIR (46.40) and ASDR (14.55). In males, tracheal, bronchial, and lung cancer exhibited the highest ASIR (37.85) and ASDR (34.32), highlighting the urgent need for targeted tobacco control measures. Different cancers in various countries exhibit unique characteristics. Therefore, policymakers should formulate specific prevention and control strategies that reflect the cancer in their country. Tobacco was the primary level 2 risk factor for cancer DALYs in males. It accounted for 29.32% (25.32–33.14) of all cancer DALYs. Dietary risks, alcohol consumption, and air pollution accounted for 5.89% (2.01–10.73), 5.48% (4.83–6.11), and 4.30% (2.77–5.95) of male cancer DALYs, respectively. Therefore, policymakers should prioritize smoking regulation and other carcinogenic risks. Cancer is a significant public health concern globally. Understanding the common etiologies of different cancers is essential for developing effective control strategies and targeted interventions.

Background and aims: Previous study disclosed Fucosyltransferase 2 (Fut2) gene as a IBD risk locus. This study aimed to explore the mechanism of Fut2 in IBD susceptibility and to propose a new strategy for the treatment of IBD. Methods: Intestinal epithelium-specific Fut2 knockout (Fut2^△IEC) mice was used. Colitis was induced by dextran sulfate sodium (DSS). The composition and diversity of gut microbiota were assessed via 16S rRNA analysis and the metabolomic findings was obtained from mice feces via metabolite profiling. The fecal microbiota transplantation (FMT) experiment was performed to confirm the association of gut microbiota and LPC. WT mice were treated with Lysophosphatidylcholine (LPC) to verify its impact on colitis. Results: The expression of Fut2 and α-1,2-fucosylation in colonic tissues were decreased in patients with UC (UC vs. control, P = 0.036) and CD (CD vs. control, P = 0.031). When treated with DSS, in comparison to WT mice, more severe intestinal inflammation and destructive barrier functions in Fut2^△IEC mice was noted. Lower gut microbiota diversity was observed in Fut2^△IEC mice compared with WT mice (p < 0.001). When exposed to DSS, gut bacterial diversity and composition altered obviously in Fut2^△IEC mice and the fecal concentration of LPC was increased. FMT experiment revealed that mice received the fecal microbiota from Fut2^△IEC mice exhibited more severe colitis and higher fecal LPC concentration. Correlation analysis showed that the concentration of LPC was positively correlated with four bacteria—Escherichia, Bilophila, Enterorhabdus and Gordonibacter. Furthermore, LPC was proved to promote the release of pro-inflammatory cytokines and damage epithelial barrier in vitro and in vivo. Conclusion: Fut2 and α-1,2-fucosylation in colon were decreased not only in CD but also in UC patients. Gut microbiota in Fut2^△IEC mice is altered structurally and functionally, promoting generation of LPC which was proved to promote inflammation and damage epithelial barrier.

Background: The NLRP3 inflammasome activation is the molecular basis of Helicobacter pylori (Hp)-associated gastritis. Tripartite motif (TRIM) 31 is involved in diverse pathological events. However, whether TRIM31 plays a role in the activation of NLRP3 inflammasome in Hp infection is not clarified. Methods: A mouse model of chronic Hp infection was established, and the gastric tissues were subjected to the polymerase chain reaction, western blotting, histopathological analysis, and RNA sequencing. The mitochondrial membrane potential and ROS in the human gastric epithelium GES-1 cells with or without Hp infection were measured by flow cytometry. GES-1 cells with or without TRIM31 knockdown were transfected with mCherry-EGFP-LC3 adenovirus. After rapamycin and bafilomycin A1 stimulation, autophagy flux in the above primed GES-1 cells was assessed by laser confocal microscope. Lysosomal acidification and expression levels of cathepsin B and cathepsin D in GES-1 cells with Hp infection were measured. Results: NLRP3 inflammasome was activated in the gastric tissues of mice with chronic Hp infection in vivo and the GES-1 cells with Hp infection in vitro. TRIM31 was downregulated in Hp infection. TRIM31 negatively regulated the NLRP3 inflammasome activation. Enhanced ROS, impaired autophagy flux, and decreased expression of lysosomal cathepsin B and cathepsin D were observed in TRIM31-deficient GES-1 cells with Hp infection. In turn, inhibition of ROS led to the decreased expression of NLRP3 inflammasome. Conclusions: Together, our data identified that TRIM31 negatively regulated the activation of NLRP3 inflammasome in Hp-associated gastritis by affecting ROS and autophagy of gastric epithelial cells.

Objective: Intestinal flora and metabolites are associated with multiple systemic diseases. Current approaches for acquiring information regarding microbiota/metabolites have limitations. We aimed to develop a precise magnetically controlled sampling capsule endoscope (MSCE) for the convenient, non-invasive and accurate acquisition of digestive bioinformation for disease diagnosis and evaluation. Design: The MSCE and surgery were both used for sampling both jejunal and ileal GI content in the control and antibiotic-induced diarrhoea groups. The GI content was then used for microbiome profiling and metabolomics profiling. Results: Compared with surgery, our data showed that the MSCE precisely acquired data regarding the intestinal flora and metabolites, which was effectively differentiated in different intestinal regions and disease models. Using MSCE, we detected a dramatic decrease in the abundance of Bacteroidetes, Patescibacteria and Actinobacteria and hippuric acid levels, as well as an increase in the abundance of Escherichia–Shigella and the 2-pyrrolidinone levels were detected in the antibiotic-induced diarrhoea model by MSCE. MSCE-mediated sampling revealed specific gut microbiota/metabolites including Enterococcus , Lachnospiraceae , acetyl-L-carnitine and succinic acid, which are related to metabolic diseases, cancers and nervous system disorders. Additionally, the MSCE exhibited good sealing characteristics with no contamination after sampling. Conclusions: We present a newly developed MSCE that can non-invasively and accurately acquire intestinal bioinformation via direct visualization under magnetic control, which may further aid in disease prevention, diagnosis, prognosis and treatment.

Liver cancer is a significant contributor to the global disease burden, of which hepatoblastomas are the most common liver tumors in children, with 90% of cases occurring within the first 5 years of life. It is important for pediatricians and subspecialists in pediatric gastroenterology and hepatology to have knowledge of the epidemiology and incidence trends of pediatric hepatic cancer, despite its rarity. In the present study, we first provide estimates of the incidence and mortality burden of hepatoblastoma and liver cancer from 2000 to 2021 in the childhood and adolescence. Liver cancer burden and its attributable risk factors were estimated using data from the Global Burden of Disease Study (GBD) 2021. Percentage change was estimated to show the trend of liver cancer estimates from 2000 to 2021. The age-standardized rate (ASR) and estimated annual percentage change (EAPC) were utilized for measuring hepatoblastomas incidence and deaths rate trends. In accordance with the GBD framework, 95% uncertainty intervals (UIs) for all estimates by averaging the data from 1000 draws, with the lower and upper bounds of the 95% UIs. Globally, from 2000 to 2021 in the age 5–19 years group, the incidence cases and deaths cases due to liver cancer decreased from 2449.2 (95% UI: 2235.9–2689.8) to 1692.9 (95% UI: 1482.0–1992.5) and 2248.5 (95% UI: 2053.7–2474.9) to 1516.6 (95% UI: 1322.1–1797.9), respectively. Meanwhile, from 2000 to 2021 in the age 20–24 years group, the incidence cases and deaths cases due to liver cancer decreased from 1453.5 (95% UI: 1327.8–1609.4) to 1285.1 (95% UI: 1159.2–1447.2) and 1432.3 (95% UI: 1307.6–1585.7) to 1195.5 (95% UI: 1066.1–1355.2), respectively. In addition, the prevalence of liver cancer decreased from 41.9% (95% UI: 18.7%–64.7%) to 26.4% (95% UI: 14.2%–39.1%) in the age 5–19 years group, and 46.6% (95% UI: 42.8%–51.5%) to 36.5% (95% UI: 33.1%–40.9%) in the age 20–24 years. From 2000 to 2021, in the age group of 5–19 years, the proportion of liver cancer incidence due to hepatitis B has decreased from 42.2% to 37.9%, while the proportion due to hepatitis C has increased from 1.1% to 1.6%. Additionally, there has been an increase in the proportion of NASH-induced liver cancer incidence from 5.2% to 9.4%, and alcohol use induced liver cancer incidence has also increased from 0.5% to 0.7% over the same period. Globally, from 2000 to 2021, the incidence cases and deaths cases due to hepatoblastoma decreased from 6131.8 (95% UI: 5234.8–6961.9) to 4045.6 (95% UI: 3250–4995.8) and 4059.2 (95% UI: 3494.5–4621.2) to 2416 (95% UI: 1940.2–3022.5), respectively. There was some variation in age-related sex-specific patterns, the highest number of hepatoblastoma incidence cases occurred in children between 2 and 4 years old and females in the age range of 12 months to 9 years had a higher number of new cases. Importantly, the incidence of hepatoblastoma was started to increase sharply after the age of 1 month. The results of the present study are significant for liver health policy and practice in childhood and adolescence. Differentiated intervention and outreach strategies based on age and gender would be necessary to reduce the impact of liver cancer. Early screening and interventions for hepatoblastoma is important especially in the population of under 9 years old. This study was supported by the 10.13039/501100012166 National Key R&D Program of China (grant numbers 2023YFC2307000), 10.13039/501100001809 National Natural Science Foundation of China [grant numbers 82170571 and 81974068], 10.13039/501100002858 China Postdoctoral Science Foundation (grant numbers 2023M741283).