Background: Low bone mineral density (LBMD), including osteoporosis and low bone mass, has becoming a serious public health concern. We aimed to estimate the disease burden of LBMD and its related fractures in 204 countries and territories over the past 30 years.Methods: We collected detailed information and performed a secondary analysis for LBMD and its related fractures from the Global Burden of Disease Study 2019. Numbers and age-standardized rates related to LBMD of disability-adjusted life-years (DALYs) and deaths in 204 countries and territories were compared by age, gender, socio-demographic index (SDI), and location.Results: Global deaths and DALYs number attributable to LBMD increased from 207 367 and 8 588 936 in 1990 to 437 884 and 16 647 466 in 2019, with a raise of 111.16% and 93.82%, respectively. DALYs and deaths number of LBMD-related fractures increased 121.07% and 148.65% from 4 436 789 and 121248 in 1990 to 9 808 464 and 301 482 in 2019. In 2019, the five countries with the highest disease burden of DALYs number in LBMD-related fractures were India (2 510 288), China (1 839 375), United States of America (819 445), Japan (323 094), and Germany (297 944), accounting for 25.59%, 18.75%, 8.35%, 3.29%, and 3.04%. There was a quadratic correlation between socio-demographic index (SDI) and burden of LBMD-related fractures: DALYs rate was 179.985-420.435SDI+417.936SDI²(R^{2 =} 0.188, p<0.001); Deaths rate was 7.879-13.416SDI+8.839 SDI²(R^{2 =} 0.101, p<0.001).Conclusions: The global burden of DALYs and deaths associated with LBMD and its related fractures has increased significantly since 1990. There were differences in disease burden between regions and countries. These estimations could be useful in priority setting, policy-making, and resource allocation in osteoporosis prevention and treatment.

Cancer stem cells (CSCs) play a critical role in tumor development and progression and are involved in cancer metastasis. The role of reactive oxygen species (ROS) in CSCs and cancer metastasis remains controversial. The aim of the present study was to investigate the correlation between ROS level of CSCs and cancer metastasis and to explore the possible underlying molecular mechanisms. Four different cell lines were used to isolate tumor spheres and to analyze intrinsic properties of tumor sphere cells including proliferation, self-renewal potential, differentiation, drug-resistance and cancer metastasis in vitro and in vivo. ROS assays were used to detect the intracellular ROS level of tumor spheres cells. Gene expression analysis and western blot were used to investigate the underlying mechanisms of ROS in regulating cancer metastasis. Tumor spheres possessed the characteristic features of CSCs, and ROS-high tumor spheres (RH-TS) displayed elevated mitochondrial ROS level exclusively drove metastasis formation. The gene expression analysis showed elevated fatty acid β-oxidation, downregulation of epithelial marker upregulation of mesenchymal markers, and the activation of MAP kinase cascades. Furthermore, 14 up-regulated genes in RH-TS cells were associated with reduced overall survival of different cancer patients. Our findings demonstrate that CSCs characterized by elevated mitochondrial ROS level potentiate cancer metastasis. Mechanistically, elevated mitochondrial ROS via fatty acid β-oxidation, activates the MAPK cascades, resulting in the epithelial-mesenchymal transition (EMT) process of RH-TS cells, thereby potentiating caner invasion and metastasis. Therefore, targeting mitochondrial ROS might provide a promising approach to prevent and alleviate cancer metastasis induced by RH-TS cells.

Nonalcoholic fatty liver disease (NAFLD) is a major health threat around the world and is characterized by dysbiosis. Primary bile acids are synthesized in the liver and converted into secondary bile acids by gut microbiota. Recent studies support the role of bile acids in modulating dysbiosis and NAFLD, while the mechanisms are not well elucidated. Dysbiosis may alter the size and the composition of the bile acid pool, resulting in reduced signaling of bile acid receptors such as farnesoid X receptor (FXR) and Takeda G protein-coupled receptor 5 (TGR5). These receptors are essential in lipid and glucose metabolism, and impaired bile acid signaling may cause NAFLD. Bile acids also reciprocally regulate the gut microbiota directly via antibacterial activity and indirectly via FXR. Therefore, bile acid signaling is closely linked to dysbiosis and NAFLD. During the past decade, stimulation of bile acid receptors with their agonists has been extensively explored for the treatment of NAFLD in both animal models and clinical trials. Early evidence has suggested the potential of bile acid receptor agonists in NAFLD management, but their long-term safety and effectiveness need further clarification.

Objective: To analyze the trends in disease burden of diabetes-related chronic kidney disease (CKD) by year, age, gender and types of diabetes in China from 1990 to 2019. Methods: Data on prevalence, deaths and disability-adjusted life years (DALYs) for diabetes-related CKD were extracted from the Global Burden of Disease (GBD) 2019 study. Analyses were performed by year, age, gender and types of diabetes. Results: In China, the numbers of deaths and DALYs of diabetes-related CKD continuously increased but the age-standardized rates (per 100,000 population) decreased over 30 years, in which the numbers of deaths and DALYs attributable to type 1 diabetes mellitus (T1DM)-related CKD barely changed and the age-standardized rates decreased over the years; and the number of deaths and DALYs attributable to type 2 diabetes mellitus (T2DM)-related CKD continuously increased, but the age-standardized rates also decreased. In 2019, 76.03 (58.24-95.61) thousand deaths and 2.13 (1.65–2.67) million DALYs were attributable to diabetes-related CKD, of which, T2DM accounted for 83.32% and 77.0% respectively, and T1DM accounted for the rest. Increasing gender disparity was seen, with males being more heavily impacted. The burden of diabetes-related CKD varied among different age groups, with the numbers of deaths and DALYs attributable to T1DM-related CKD peaking between 45 and 54 years of age and T2DM-related CKD peaking between 75 and 79 years of age; and the crude rates of deaths and DALYs attributable to T1DM-related CKD peaking between 70 and 79 years of age and 40 to 54 years of age, respectively, and T2DM-related CKD peaking over 90 years of age. Among neighboring and G20 countries, the burden of diabetes-related CKD in China was relatively controlled reflected by the ranking of adjusted death and DALYs rates. Conclusions: The burden of diabetes-related CKD in China worsens and shows gender disparities and different age distribution. Greater efforts are needed to improve the health outcomes of these patients, especially among males.