Background
Several somatic mutation hotspots were recently identified in the TERT promoter region in human cancers. Large scale studies of these mutations in multiple tumor types are limited, in particular in Asian populations. This study aimed to: analyze TERT promoter mutations in multiple tumor types in a large Chinese patient cohort, investigate novel tumor types and assess the functional significance of the mutations.
Methods
TERT promoter mutation status was assessed by Sanger sequencing for 13 different tumor types and 799 tumor tissues from Chinese cancer patients. Thymic epithelial tumors, gastrointestinal leiomyoma, and gastric schwannoma were included, for which the TERT promoter has not been previously sequenced. Functional studies included TERT expression by RT-qPCR, telomerase activity by the TRAP assay, and promoter activity by the luciferase reporter assay.
Results
TERT promoter mutations were highly frequent in glioblastoma (83.9%), urothelial carcinoma (64.5%), oligodendroglioma (70.0%), medulloblastoma (33.3%), and hepatocellular carcinoma (31.4%). C228T and C250T were the most common mutations. In urothelial carcinoma, several novel rare mutations were identified. TERT promoter mutations were absent in GIST, thymic epithelial tumors, gastrointestinal leiomyoma, gastric schwannoma, cholangiocarcinoma, gastric and pancreatic cancer. TERT promoter mutations highly correlated with upregulated TERT mRNA expression and telomerase activity in adult gliomas. These mutations differentially enhanced the transcriptional activity of the TERT core promoter.
Conclusions
TERT promoter mutations are frequent in multiple tumor types and have similar distributions in Chinese cancer patients. The functional significance of these mutations reflect the importance to telomere maintenance and hence tumorigenesis, making them potential therapeutic targets.
BackgroundAlternative N-glycosylation has significant structural and functional consequences on immunoglobulin G (IgG) and can affect immune responses, acting as a switch between pro- and anti-inflammatory IgG functionality. Studies have demonstrated that IgG N-glycosylation is associated with ageing, body mass index, type 2 diabetes and hypertension.MethodsHerein, we have demonstrated patterns of IgG glycosylation that are associated with blood lipids in a cross-sectional study including 598 Han Chinese aged 20–68 years. The IgG glycome composition was analysed by ultra-performance liquid chromatography.ResultsBlood lipids were positively correlated with glycan peak GP6, whereas they were negatively correlated with GP18 (P < 0.05/57). The canonical correlation analysis indicated that initial N-glycan structures, including GP4, GP6, GP9-12, GP14, GP17, GP18 and GP23, were significantly correlated with blood lipids, including total cholesterol, total triglycerides (TG) and low-density lipoprotein (r = 0.390, P < 0.001). IgG glycans patterns were able to distinguish patients with dyslipidaemia from the controls, with an area under the curve of 0.692 (95% confidence interval 0.644–0.740).ConclusionsOur findings indicated that a possible association between blood lipids and the observed loss of galactose and sialic acid, as well as the addition of bisecting GlcNAcs, which might be related to the chronic inflammation accompanying with the development and procession of dyslipidaemia.Electronic supplementary materialThe online version of this article (10.1186/s12967-018-1616-2) contains supplementary material, which is available to authorized users.
ObjectiveA solid understanding of levels and trends of spending on cancer is important to evaluate whether our healthcare resources were wisely spent and to prioritize future resources for cancer treatment and prevention. However, studies on economic burden of cancers in China are scant and the results are inconsistent.MethodsThe Chinese hospital information database and nearly 350 million inpatient medical record data were used. As the ratios of cancer inpatient payments to total inpatient payments were mainly influenced by the grades and sites of hospitals, the estimates of payments of cancer inpatients in this study were stratified by hospital grades and provinces. Only the payments of cancer inpatients happened in grade 2, grade 3 and specialized cancer hospitals were included in the analyses. The total medical payments of cancers in China were estimated based on the ratios of outpatient payments to inpatient payments in specialized cancer hospitals.ResultsFrom 2011 to 2015, the payments of cancer inpatients in China have increased by 84.1% and the total inpatient payments reached 177.1 billion RMB in 2015, accounting for 4.3% of the total health expenditure in China. Based on the ratio of outpatient payments to inpatient payments, the total payments on cancer treatments in China were estimated to be 221.4 billion RMB in 2015. Among different cancer types, the highest payments were the treatment of trachea, bronchus and lung cancer. The major cancer inpatient payments (67.1% in 2015) spent in grade 3 general hospitals and this ratio increased continually from 2011 to 2015. The expenditure of cancer treatments also varies by region with the major expenditure in the eastern region of China.ConclusionsThis study estimated the total payments of cancer treatments in China and analyzed how the money was spent on cancer treatments in the recent 5 years, which would provide information for decision makings on the allocation of resources to service provisioning, prevention strategies, research funding, and assessing whether the economic burden of cancer is affordable to the governments.
BackgroundIn accordance with the People’s Republic of China’s (China) National Health Reform Plan of 2009, two of the nation’s leading hospitals, located in Beijing, have implemented electronic medical record (EMR) systems from different vendors.To inform future EMR adoption and policy in China, as well as informatics research in the US, this study compared the United State’s Hospital Meaningful Use (MU) Objectives (phase 1) objectives to the EMR functionality of two early hospital EMR adopters in China.MethodsAt both hospitals, the researchers observed a physician using the EMR and noted MU functionality that was seen and functionality that was not seen yet was available in the EMR. The information technology department was asked about the availability of functionality neither observed nor known to the physician.Results and conclusionsApproximately half the MU objectives were available in each EMR. Some differences between the EMRs in the study and MU objectives were attributed to operational differences between the health systems and the cultures in the two countries.
BackgroundPrevalence of acute myocardial infarction (AMI) is increasing in China, and AMI has become a major cause of mortality; however, information is very limited about the nationwide geographic and hospital variation in in‐hospital mortality (IHM) and the use of percutaneous coronary intervention (PCI) after AMI.Methods and ResultsFrom the Nationwide Hospital Discharge Database of China, we identified 242 866 adult admissions with AMI in 2015 from 1055 tertiary hospitals. We used multivariable logistic regressions to analyze the associations between geographic or hospital characteristics with IHM or PCI use. The national IHM rate was 4.71% (95% confidence interval, 4.62–4.79%). There was a greater risk of mortality in the Northeast (odds ratio [OR]: 1.86), West (OR: 1.73), South (OR: 1.32), and North (OR: 1.14) regions than in the East region of China. Non–teaching hospitals (OR: 1.18) and tertiary level B hospitals (OR: 1.06) were associated with higher IHM rates. The national PCI use rate was 45.3% (95% confidence interval, 45.1–45.5%). Compared with the East region of China, PCI use was lower in the Northeast (OR: 0.50), West (OR: 0.64), North (OR: 0.84), and South (OR: 0.88) regions. Non–teaching hospitals (OR: 0.83) and tertiary level B hospitals (OR: 0.55) were also associated with lower usage rates. There was a significant negative correlation between IHM and PCI use (r=−0.955), and IHM rates for patients with and without PCI both differed by geographic regions.ConclusionsThere were significant differences in IHM and PCI use among China's tertiary hospitals, linked to both geographic and hospital characteristics. More targeted intervention at national and regional levels is needed to improve access to effective health technologies and, eventually, outcomes following AMI.
This experiment has preliminarily confirmed urinary CD80 as a non-invasive diagnostic biomarker. It may have significant value in the diagnosis of MCD.
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