The Global Burden of Disease attributable to low physical activity and its trends from 1990 to 2019: An analysis of the Global Burden of Disease study.

Introduction: Low physical activity (LPA) is associated with several major non-communicable diseases (NCDs) and premature mortality. In this study, we aimed to assess the global burden and trends in disease attributable to LPA (DALPA) from 1990 to 2019. Methods: Annual age-standardized disability-adjusted life years (DALYs) and death rates of DALPA [all-cause and five specific causes (ischaemic heart disease, diabetes mellitus, stroke, colon and rectal cancer, and breast cancer)] by sex, age, geographical region and social deprivation index (SDI) score from 1990 to 2019 were available from the Global Burden of Disease (GBD) study 2019. The estimated annual percentage changes (EAPCs) were calculated to quantify the changing trend. A generalized linear model (GLM) was used to explore the relationship between DALYs/death rates of DALPA and sociodemographic factors. Results: Globally, in 2019, the age-standardized DALYs and death rates of DALPA were 198.42/100,000 (95% UI: 108.16/100,000-360.32/100,000) and 11.10/100,000 (95% UI: 5.66/100,000-19.51/100,000), respectively. There were 15.74 million (8.51-28.61) DALYs and 0.83 million (0.43-1.47) deaths attributable to LPA. Overall, age-standardized DALYs and death rates presented significant downward trends with EAPCs [-0.68% (95% CI: -0.85- -0.50%) for DALYs and -1.00% (95% CI: -1.13- -0.86%) for deaths] from 1990 to 2019. However, age-standardized DALYs and death rates of diabetes mellitus attributable to LPA were substantially increased [EAPC: 0.76% (95% CI: 0.70-0.82%) for DALYs and 0.33% (95% CI: 0.21-0.51%) for deaths]. In the 15-49 age group, DALPA presented significant upward trends [EAPC: 0.74% (95% CI: 0.58-0.91%) for DALYs and 0.31% (95% CI: 0.1-0.51%) for deaths]. The GLM revealed that higher gross domestic product and current health expenditure (% of GDP) were negatively associated with DALYs and death rates of DALPA. Conclusion: Although global age-standardized DALYs and death rates of DALPA presented downward trends, they still cause a heavy burden worldwide. These rates showed upward trends in the diabetic and 15-49 age groups, which need more attention and health interventions.

Dextran Sulfate Inhibits Cell Proliferation and Induces Apoptosis by Regulating EZH2 in Gastric Carcinoma.

BACKGROUND: Gastric cancer (GC) is one of the most common gastrointestinal malignancies. According to reports, the enhancer of zeste homolog 2 (EZH2) exhibits carcinogenic function in a variety of cancers. Therefore, EZH2 may be a potential therapeutic target for the treatment of human cancer. Macromolecular Dextran Sulfate (DS) has been displayed to play a critical role in tumor inhibition. However, the molecular mechanism by which DS mediates this effect is unclear. OBJECTIVES: In this study, we explored the effects of DS on the proliferation and apoptosis of gastric cancer and the related mechanisms. Cell proliferation and counting assays, as well as cell colony formation assays, revealed that DS inhibited the proliferation and tumorigenesis of GC cells. Additionally, flow cytometry analysis displayed that DS blocked the cell cycle of GC cells in the G1/S phase and promoted their apoptosis. METHODS: Bioinformatics analyses, enzyme-linked immunosorbent assays, immunohistochemistry, and other methods were applied to measure the expression of EZH2 in human GC cells and tissues. RESULTS AND DISCUSSION: Further studies have shown that DS treatment can reduce the expression of proliferating cell nuclear antigen (PCNA) and increase the level of the ratio of Bax: Bcl-2 protein in GC cells. In addition, DS reduced EZH2 levels and increased CXXC finger protein 4 levels both in vitro and in vivo. In addition, down-regulation of EZH2 with EZH2 inhibitors reversed the inhibitory effect of DS on gastric cancer cells. CONCLUSION: Collectively, our work demonstrates that DS suppresses proliferation and promotes apoptosis of GC cells by regulating EZH2. Our study suggests that DS is a promising therapeutic compound for the treatment of GC.

Dextran Sulfate Effects EMT of Human Gastric Cancer Cells by Reducing HIF-1α/ TGF-ß.

The peritoneal implant metastasis is one of the main pathway and main cause for high mortality for gastric cancer metastasis. Researchs show that epithelial-mesenchymal transition (EMT) playing essential role in modulating gastric cancer metastasis, and the expression of hypoxia inducible factor-1α (HIF-1α) can promote EMT in tumor cells. This research aims to explore the influence and mechanism of Dextran Sulfate (DS) affecting EMT of human gastric cancer. In the present study, we found that DS can enter into the cytoplasm and function in it. Inhibition of HIF-1α or DS significantly inhibit the migration and invasion of human gastric cancer cells, and decrease the mRNA and protein expressions of HIF-1α, matrix metalloproteinase-2 (MMP-2), transforming growth factor-ß (TGF-ß), Twist and N-cadherin (N-cad), rise E-cadherin (E-cad) expression, DS with HIF-1α knockdown has a stronger effect. In vivo studies indicated that compared with using DS or HIF-1α knockdown alone, DS with HIF-1α knockdown can better suppress the volume and number of metastatic tumors, and reduce the mRNA and protein expressions of HIF-1α, MMP-2, TGF-ß, Twist and N-cad in metastatic tumor tissues of nude mice. We further demonstrated that the expression of HIF-1α, MMP-2, TGF-ß , Twist and N-cad were higher in well and poorly differentiated gastric cancer than paracancerous tissue, and poorly differentiated gastric cancer were even higher, while E-cad expression was opposite. Taken together, this study shows that DS can interfere the expression of HIF-1α, thereby inhibiting TGF-ß-mediated EMT of gastric cancer cells, and demonstrated a promising application of DS in gastric cancer therapy.

Effect of preoperative intraperitoneal injection of Sapylin in advanced gastric cancer.

BACKGROUND AND OBJECTIVE: Sapylin is one of the biological response modifiers. It has been used in the comprehensive treatment for advanced cancer, and its clinical efficacy has been proved. This study was to evaluate the effect of preoperative intraperitoneal injection of Sapylin in treatment of advanced gastric cancer. METHODS: Seventy-nine patients eligible for radical gastrectomy were randomly divided into the treatment group (Sapylin + mitomycin C, 40 patients) and the control group (mitomycin C alone, 39 patients). In the treatment group, 5 KE Sapylin was injected intraperitoneally 48 h before operation and 4 mg of mitomycin C was injected into peritoneal cavity before the closure of the peritoneum. In the control group, only 4 mg mitomycin C was injected into peritoneal cavity before the closure of the peritonium. RESULTS: There was no operative mortality or duodenal stump leakage in the two groups. Postoperative complications were anastomotic leakage (2.5%, 1/40) and incision rupture (2.5%, 1/40) in the treatment group, and incision rupture (2.6%, 1/39) in the control group, with no significant difference between the two groups (P > 0.05). The 3-year survival rate was significantly higher in the treatment group than in the control group (76.5% vs. 49.4%, P < 0.05). CONCLUSIONS: Preoperative intraperitoneal injection of Sapylin can raise the 3-year survival rate after radical gastrectomy , without increasing the incidence rate of operative complications. Preoperative intraperitoneal injection of Sapylin is therefore a valuable therapy for advanced gastric cancer in clinic.