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Aims To investigate secular trends in severe periodontitis incidence, prevalence and disability-adjusted life year (DALY) rates in China, India, Japan, South Korea and Thailand from 1990 to 2017. Materials and methods Data were obtained from the "Global Burden of Disease Study" 2017. The annual percentage change and average annual percentage change were calculated using Joinpoint regression analysis. The independent age, period and cohort effects were estimated by age-period-cohort analysis. Results From 1990 to 2017, the overall age-standardized incidence, prevalence and DALY rates increased in China, Japan and India, while decreasing in South Korea and Thailand. The highest incidence, prevalence and DALY rates were in India. By APC analysis, the age effect presented increase in 20-59 years in China, Japan and South Korea, 20-54 years in India and 20-64 years in Thailand; the period effect showed progressive increases in five countries, with the most significant increase shown in China; the cohort effect showed monotonic decreases with birth cohort in five countries. Conclusions Severe periodontitis poses a serious burden in Asian countries, especially China and India. We suggest raising people's awareness of periodontal health and providing professional interventions in these countries, especially for high-risk groups, such as younger people aged ≤65 years.

High heterogeneity has been reported among epidemiological studies exploring the relationship between metformin and the risk of gastric cancer. Immortal time bias might be one of the vital factors causing heterogeneity because of its widespread existence in pharmacological observational studies and it could severely exaggerate the drug's effectiveness. Immortal time bias could occur in an observational study if exposure status is determined based on a measurement or event that occurs after baseline. In this study, we aimed to assess whether immortal time bias is responsible for the false assumption that metformin reduces the risk of gastric cancer. We searched PubMed, Embase, Web of Science and Cochrane Library databases for relevant studies from the inception to August 9, 2020. The strength of the relationship was assessed using pooled relative risks (RRs) with corresponding 95% confidence intervals (95% CIs). Statistical analyses were carried out using a random-effects model. Pooled RR from 6 cohort studies with immortal time bias found a clear 33% reduced risk associated with metformin use (RR = 0.67, 95% CI = 0.59, 0.77; P < 0.001; I2 = 48.5%). However, pooled RR from 8 cohort studies without immortal time bias indicated no association between the use of metformin and gastric cancer risk (RR = 0.95, 95% CI = 0.85, 1.05; P = 0.317; I2 = 64.5%). From a univariate meta-regression model, the presence of immortal time bias was associated with a significant reduction of 29% in the effect estimate of metformin on gastric cancer risk (ratio of RR = 0.71, 95% CI = 0.58, 0.86; P = 0.002). This meta-analysis indicates that metformin use has no protective effect on gastric cancer risk. The relationship between metformin use and gastric cancer risk has been exaggerated as a result of the presence of immortal time bias. Further studies are required to confirm the results by controlling for immortal time bias based on appropriate study designs and statistical methods.

Backgrounds Glioma is the most fatal primary brain glioma in central nervous system mainly attributed to its high invasion. Prucalopride, a Serotonin-4 (5-HT4) receptor agonist, has been reported to regulate neurodevelopment. This study aimed to investigate the influence of the Prucalopride on glioma cells and unveil underlying mechanism. Methods In this study, glioma cells proliferation was evaluated by Cell counting kit-8 (CCK8). Wound healing and transwell assay were used to test cellular migration and invasion. Flow cytometry was utilized to determine cellular apoptosis rate. Apoptosis related markers, autophagy markers, and protein kinase B (AKT)-mammalian target of rapamycin (mTOR) pathway key molecules were detected using western blot assay. Results As a result, the proliferation, migration and invasiveness of glioma cells were impaired by Prucalopride treatment, the apoptosis rate of glioma cells was enhanced by Prucalopride stimulation, accompanied by the increased pro-apoptosis proteins Bax and Cleaved caspase-3 and decreased anti-apoptosis protein Bcl-2. Prucalopride significantly promoted autophagy by increased expression level of Beclin 1 and LC3-II, while decreased expression level of p62. Prucalopride administration resulted in obvious inhibitions of key molecules of AKT-mTOR pathway, including phosphorylated- (p-) AKT, p-mTOR and phosphorylated-ribosomal p70S6 kinase (p-P70S6K). Conclusions Taking together, these results indicate that Prucalopride may be likely to play an anti-tumor role in glioma cells, which suggests potential implications for glioma promising therapy alternation in the further clinics.

The present study evaluated the efficacy of switching from premixed insulin or an insulin analogue to insulin glargine plus oral antidiabetic drugs (OADs) in patients with type 2 diabetes mellitus (T2DM). The feasibility and suitability of the regimen to the patients was examined based on islet function. Patients with T2DM (n=30) treated with stable doses of premixed insulin or an insulin analogue for eight weeks were divided into two groups according to islet function. Group A had a 2 h of C peptide (2hCP)/fasting C peptide (FCP) ratio ≤3, whereas group B had a 2hCP/FCP ratio >3. Eight weeks following the switch to insulin glargine plus OADs, a significant decrease in fasting blood glucose (FBG), 2 h postprandial blood glucose (2hPBG) and glycosylated‑haemoglobin (HbA1c) were observed in the two groups, with effective rates of 75, 42.9 and 39.3%, respectively. A distinct reduction in the insulin dose was particularly evident in group B. There was a marked decrease in FBG in group A, more so than that observed in group B. By contrast, the decrease in HbA1c was more evident in group B following the switch. A larger number of patients in group B had HbA1c≤7.0%, compared with group A. No difference in the incidence of hypoglycaemia and change of body weight were observed. Following the switch to insulin glargine plus OADs, patients with T2DM demonstrated improved blood glucose control and reduced insulin dosage. The results revealed that this switch in regimen is more suitable for patients with T2DM with 2hCP/FCP>3 and that administration of insulin glargine plus OADs is more efficacious for patients with T2DM with increased FBG levels.

Background Selenoprotein S (SelS) is a transmembrane protein that is expressed in the liver, skeletal muscle, adipose tissue, pancreatic islets, kidney, and blood vessels. In addition to its transmembrane localization, SelS is also secreted from hepatoma HepG2 cells (but not L6 skeletal muscle cells, 3T3-L1 adipocytes, Min6 pancreatic β cells and human embryonic kidney 293 cells) and has been detected in the serum of some human subjects, with a detection rate of 31.1 %. These findings prove that serum SelS is secreted by hepatocytes. However, whether vascularly expressed SelS can be secreted has not been reported. Transmembrane SelS has been suggested to play different roles in the pathogenesis and progression of diabetes mellitus (DM) and atherosclerosis (AS), but the association of secreted SelS with DM and macroangiopathy remains unclear. Research design and methods Supernatants were collected from human umbilical vein endothelial cells (HUVECs), human aortic vascular smooth muscle cells (HA/VSMCs) and human hepatoma HepG2 cells that were untransfected or transfected with the indicated plasmid and concentrated for western blotting. Serum samples were collected from 158 human subjects with or without type 2 DM (T2DM) and/or AS. Serum SelS levels were measured using an enzyme-linked immunosorbent assay. Results Secreted SelS was only detected in the supernatants of hepatoma HepG2 cells. The SelS detection rate among the 158 human serum samples was 100 %, and the average SelS level was 64.81 ng/dl. The serum SelS level in the isolated DM subjects was lower than the level in the healthy control subjects (52.66 ± 20.53 vs 70.40 ± 21.38 ng/dl). The serum SelS levels in the DM complicated with SAS subjects (67.73 ± 21.41 ng/dl) and AS subjects (71.69 ± 27.00 ng/dl) were significantly increased compared with the serum SelS level in the isolated DM subjects. There was a positive interaction effect between T2DM and AS on the serum SelS level (P = 0.002). Spearman correlation analysis showed that the serum SelS level was negatively correlated with fasting plasma glucose. Conclusions Vascular endothelial and vascular smooth muscle cells could not secrete SelS. Serum SelS was primarily secreted by hepatocytes. SelS was universally detected in human serum samples, and the serum SelS level was associated with T2DM and its macrovascular complications. Thus, regulating liver and serum SelS levels might become a new strategy for the prevention and treatment of DM and its macrovascular complications. Electronic supplementary material The online version of this article (doi:10.1186/s12933-016-0388-3) contains supplementary material, which is available to authorized users.

Insulin therapy has been shown to contribute to extended glycemia remission in newly diagnosed patients with type 2 diabetes mellitus. This study investigated the effects of insulin treatment on pancreatic lipid content, and β-cell apoptosis and proliferation in glucose-intolerant rats to explore the protective role of insulin on β-cell function. A rat glucose-intolerant model was induced by streptozotocin and a high-fat diet. Plasma and pancreatic triglycerides, free fatty acids, and insulin were measured; and pancreatic β-cell cell apoptosis and proliferation were detected by a propidium iodide cell death assay and immunofluorescence for proliferating cell nuclear antigen. Relative β-cell area was determined by immunohistochemistry for insulin, whereas insulin production in pancreas was assessed by reverse transcriptase polymerase chain reaction. Islet β-cell secreting function was assessed by the index ΔI30/ΔG30. Glucose-intolerant rats had higher pancreatic lipid content, more islet β-cell apoptosis, lower β-cell proliferation, and reduced β-cell area in pancreas when compared with controls. Insulin therapy reduced blood glucose, inhibited pancreatic lipid accumulation and islet β-cell apoptosis, and increased β-cell proliferation and β-cell area in glucose-intolerant rats. Furthermore, impaired insulin secretion and insulin production in glucose-intolerant rats were improved by insulin therapy. Insulin can preserve β-cell function by protecting islets from glucotoxicity and lipotoxicity. It can also ameliorate β-cell area by enhancing β-cell proliferation and reducing β-cell apoptosis.