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Background Obesity (waist circumference, body mass index (BMI)) and lifestyle factors (dietary habits, smoking, alcohol drinking, Sedentary behavior) have been associated with risk of benign prostatic hyperplasia (BPH) in observational studies, but whether these associations are causal is unclear. Methods We performed a univariable and multivariable Mendelian randomization study to evaluate these associations. Genetic instruments associated with exposures at the genome-wide significance level (P –8) were selected from corresponding genome-wide associations studies (n = 216,590 to 1,232,091 individuals). Summary-level data for BPH were obtained from the UK Biobank (14,126 cases and 169,762 non-cases) and FinnGen consortium (13,118 cases and 72,799 non-cases). Results from UK Biobank and FinnGen consortium were combined using fixed-effect meta-analysis. Results The combined odds ratios (ORs) of BPH were 1.24 (95% confidence interval (CI), 1.07–1.43, P = 0.0045), 1.08 (95% CI 1.01–1.17, P = 0.0175), 0.94 (95% CI 0.67–1.30, P = 0.6891), 1.29 (95% CI 0.88–1.89, P = 0.1922), 1.23 (95% CI 0.85–1.78, P = 0.2623), and 1.04 (95% CI 0.76–1.42, P = 0.8165) for one standard deviation (SD) increase in waist circumference, BMI, and relative carbohydrate, fat, protein and sugar intake, 1.05 (95% CI 0.92–1.20, P = 0.4581) for one SD increase in prevalence of smoking initiation, 1.10 (95% CI 0.96–1.26, P = 0.1725) and 0.84 (95% CI 0.69–1.02, P = 0.0741) for one SD increase of log-transformed smoking per day and drinks per week, and 1.31 (95% CI 1.08–1.58, P = 0.0051) for one SD increase in sedentary behavior. Genetically predicted waist circumference (OR = 1.26, 95% CI 1.11–1.43, P = 0.0004) and sedentary behavior (OR = 1.14, 95% CI 1.05–1.23, P = 0.0021) were associated with BPH after the adjustment of BMI. Conclusion This study supports independent causal roles of high waist circumference, BMI and sedentary behavior in BPH.

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.

Non-muscle invasive bladder cancer (NMIBC) is a major type of bladder cancer with a high incidence worldwide, resulting in a great disease burden. Treatment and surveillance are the most important part of NIMBC management. In 2018, we issued "Treatment and surveillance for non-muscle-invasive bladder cancer in China: an evidence-based clinical practice guideline". Since then, various studies on the treatment and surveillance of NMIBC have been published. There is a need to incorporate these materials and also to take into account the relatively limited medical resources in primary medical institutions in China. Developing a version of guideline which takes these two issues into account to promote the management of NMIBC is therefore indicated. We formed a working group of clinical experts and methodologists. Through questionnaire investigation of clinicians including primary medical institutions, 24 clinically concerned issues, involving transurethral resection of bladder tumor (TURBT), intravesical chemotherapy and intravesical immunotherapy of NMIBC, and follow-up and surveillance of the NMIBC patients, were determined for this guideline. Researches and recommendations on the management of NMIBC in databases, guideline development professional societies and monographs were referred to, and the European Association of Urology was used to assess the certainty of generated recommendations. Finally, we issued 29 statements, among which 22 were strong recommendations, and 7 were weak recommendations. These recommendations cover the topics of TURBT, postoperative chemotherapy after TURBT, Bacillus Calmette-Guérin (BCG) immunotherapy after TURBT, combination treatment of BCG and chemotherapy after TURBT, treatment of carcinoma in situ, radical cystectomy, treatment of NMIBC recurrence, and follow-up and surveillance. We hope these recommendations can help promote the treatment and surveillance of NMIBC in China, especially for the primary medical institutions.

Background To evaluate the utility of the process capability indices C p and C pk for assessing the quality control processes at chain laboratory facilities. Methods In April 2020, the minimum C p and C pk values for 33 assays of a laboratory chain with 19 facilities were collected for further analysis and a total of 627 datasets (C p and C pk) were compared. In addition, standard values for C p and C pk, defined as the lowest of the top 20%, were obtained for comparison and the indices were used to determine whether precision or trueness improvements were required for the corresponding assay. Results A total of 627 datasets of 33 assays from 19 laboratory facilities were collected for further analysis. Based on the C p results, 329 (52.5%), 211 (33.7%), 65 (10.3%), and 22 (3.5%) were rated as excellent, good, marginal, and poor, respectively. While the corresponding results for C pk were 300 (47.8%), 216 (34.4%), 79 (12.6%), and 32 (5.1%). In addition, it was noteworthy that eight (C p criteria) and six assays (C pk criteria) were rated as excellent or good at all 19 facilities. Comparison of the process capability indices at the Jinan KingMed Center with the standard values revealed that total protein, albumin, and urea showed trueness individual improvement, precision individual improvement, and precision common improvement, respectively, while the results of other assays were stable. Conclusion Process capability indices are useful for evaluating the quality control procedures in laboratory facilities and can help improve the precision and trueness of laboratory tests., When the quality control chart shows an abnormal trend, are you anxious to analyze the cause? If we rely solely on the laboratory Sigma analysis, the root cause of the anomalies will remain unknown. The introduction of new application indexes C p and C pk and comparative analysis between laboratories can solve the problem easily. By comparing with absolute standard, we can determine the key points to be improved. Meanwhile, the interlaboratory comparison can help us find the root causes of anomalies (the individual factor of one laboratory or the common factor of most laboratories) and determine whether improvement is needed and what kind of improvement measures to be taken. The widespread application of C p and C pk in the field of laboratory medicine can guarantee the quality of test results and make the QC process more standardized and practical.

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.