Search

Background and aims Observational studies showed that coronavirus disease 2019 (COVID-19) attacks universally and its most menacing progression uniquely endangers the elderly with cardiovascular disease (CVD). The causal association between COVID-19 infection or its severity and susceptibility of atrial fibrillation (AF) remains unknown. Methods and results The bidirectional causal relations of COVID-19 (including COVID-19, hospitalized COVID-19 compared with not hospitalized COVID-19, hospitalized COVID-19 compared with population, and severe COVID-19) and AF are determined by using two-sample Mendelian randomization (MR) analysis. Genetically predicted severe COVID-19 was not significantly associated with risk of AF [odds ratio (OR), 1.037; 95% confidence interval (CI), 1.005-1.071; P = 0. 023, q = 0.115]. In addition, genetically predicted AF was also not causally associated with severe COVID-19 (OR, 0.993; 95% CI, 0.888-1.111; P = 0.905, q = 0.905). There was no evidence to support association between of genetically determined COVID-19 and risk of AF (OR, 1.111; 95% CI, 0.971-1.272; P = 0.127, q = 0.318), and vice versa (OR, 1.016; 95% CI, 0.976-1.058; P = 0.430, q = 0.851). Besides, no significant association was observed for hospitalized COVID-19 with AF. MR-Egger indicated no evidence of directional pleiotropy. Conclusion Overall, this MR study provides no clear support that COVID-19 is causally associated with the risk of AF.

ObjectivesOver the coming decades, China is expected to face the largest worldwide increase in dementia incidence. Mobile health (mHealth) may improve the accessibility of dementia prevention strategies, targeting lifestyle-related risk factors. Our aim is to explore the needs and views of Chinese older adults regarding healthy lifestyles to prevent cardiovascular disease (CVD) and dementia through mHealth, supporting the Prevention of Dementia using Mobile Phone Applications (PRODEMOS) study.DesignQualitative semi-structured interview study, using thematic analysis.SettingPrimary and secondary care in Beijing and Tai’an, China.ParticipantsOlder adults aged 55 and over without dementia with an increased dementia risk, possessing a smartphone. Participants were recruited through seven hospitals participating in the PRODEMOS study, purposively sampled on age, sex, living area and history of CVD and diabetes.ResultsWe performed 26 interviews with participants aged 55–86 years. Three main themes were identified: valuing a healthy lifestyle, sociocultural expectations and need for guidance. First, following a healthy lifestyle was generally deemed important. In addition to generic healthy behaviours, participants regarded certain specific Chinese lifestyle practices as important to prevent disease. Second, the sociocultural context played a crucial role, as an important motive to avoid disease was to limit the care burden put on family members. However, time-consuming family obligations and other social values could also impede healthy behaviours such as regular physical activity. Finally, there seemed to be a need for reliable and personalised lifestyle advice and for guidance from a health professional.ConclusionsThe Chinese older adults included in this study highly value a healthy lifestyle. They express a need for personalised lifestyle support in order to adopt healthy behaviours. Potentially, the PRODEMOS mHealth intervention can meet these needs through blended lifestyle support to improve risk factors for dementia and CVD.Trial registration numberISRCTN15986016; Pre-results.

Suboptimal health status (SHS) is a reversible stage between health and illness that is characterized by health complaints, low energy, general weakness, and chronic fatigue. The Suboptimal Health Status Questionnaire-25 (SHSQ-25) has been validated in three major populations (African, Asian, and Caucasian) and is internationally recognized as a reliable and robust tool for health estimation in general populations. This study focused on the development of K-SHSQ-25, a Korean version of the SHSQ-25, from its English version.The SHSQ-25 was translated from English to Korean according to international guidelines set forth by the World Health Organization (WHO) for health instrument translation between different languages. A subsequent cross-sectional survey involved 460 healthy South Korean participants (aged 18-83 years; 65.4% females) to answer the 25 questions focusing on the health perspectives of 5 domains, 1) fatigue, 2) cardiovascular health, 3) digestive tract, 4) immune system and 5) mental health. The K-SHSQ-25 was further validated using tests for reliability, internal consistency, exploratory factor analysis (EFA), and confirmatory factor analysis (CFA).The version of K-SHSQ-25 achieved linguistic, cultural, and conceptual equivalence to the English version. The intraclass correlation coefficient (ICC) of test-retest reliability for individual items ranged from 0.88 to 0.99. Reliability estimates based on internal consistency reached a Cronbach's α of 0.953; the Cronbach's α for each domain ranged from 0.76 to 0.94. Regarding construct validity, the EFA of the K-SHSQ-25 generally replicated the multidimensional structure (fatigue, cardiovascular, digestive, immune system, and mental health) and 25 questions. The CFA revealed that the root mean square error of approximation (RMSEA), goodness-of-fit index (GFI) and adjusted goodness of fit index (AGFI) were excellent (RMSEA = 0.0690.08, GFI = 0.9290.90, AGFI = 0.9070.90). The five domains of the K-SHSQ-25 showed significant correlations with each other (r = 0.59-0.81, P0.001). The cut-off point of K-SHSQ-25 for SHS was determined as an SHS score of 25. The prevalence of SHS in this study was 60.0% (276/460), with 47.8% (76/159) for males and 58.5% for females (176/301).Our results indicate that the Korean version of SHSQ-25, K-SHSQ-25, is a transcultural equivalent, robust, valid, and reliable assessment tool for evaluating SHS in the Korean-speaking population.

Background: Previous prospective studies highlighted aberrant immunoglobulin G (IgG) N-glycosylation as a risk factor for dementia [such as Alzheimer’s disease (AD) and vascular dementia (VaD)]. It is unclear whether this association is causal or explained by confounding or reverse causation. Objective: The aim is to examine the association of genetically predicted IgG N-glycosylation with dementia using 2-sample Mendelian randomization (MR). Methods: Independent genetic variants for IgG N-glycosylation traits were selected as instrument variables from published genome-wide association studies (GWAS) among individuals of European ancestry. We extracted their corresponding summary statistics from large-scale clinically diagnosed AD GWAS dataset and FinnGen biobank VaD GWAS dataset. The inverse variance weighted (IVW) was performed to calculate the effect estimates. Meanwhile, multiple sensitivity analyses were used to assess horizontal pleiotropy and outliers. Results: There were no associations of genetically predicted IgG N-glycosylation traits with the risk of AD and VaD using the IVW method (all Bonferroni corrected p > 0.0013). These estimates of four additional sensitivity analyses methods were consistent with the IVW estimates in terms of direction and magnitude. Additionally, the MR-PRESSO global test and the intercept of MR-Egger regression indicated no evidence of horizontal pleiotropy. Meanwhile, the heterogeneity test showed no significant heterogeneity using the Cochran Q statistic. The leave-one-out sensitivity analyses also did not detect any significant change. Conclusion: Our MR study did not support evidence for the hypothesis that IgG N-glycosylation level may be causally associated with the risk of dementia.

Age-related disease burdens increased over time, and whether plasma peptides can be used to accurately predict age in order to explain the variation in biological indicators remains inadequately understood. Here we first developed a biological age model based on plasma peptides in 1890 Chinese Han adults. Based on mass spectrometry, 84 peptides were detected with masses in the range of 0.6-10.0 kDa, and 13 of these peptides were identified as known amino acid sequences. Five of these thirteen plasma peptides, including fragments of apolipoprotein A-I (m/z 2883.99), fibrinogen alpha chain (m/z 3060.13), complement C3 (m/z 2190.59), complement C4-A (m/z 1898.21), and breast cancer type 2 susceptibility protein (m/z 1607.84) were finally included in the final model by performing a multivariate linear regression with stepwise selection. This biological age model accounted for 72.3% of the variation in chronological age. Furthermore, the linear correlation between the actual age and biological age was 0.851 (95% confidence interval: 0.836-0.864) and 0.842 (95% confidence interval: 0.810-0.869) in the training and validation sets, respectively. The biological age based on plasma peptides has potential positive effects on primary prevention, and its biological meaning warrants further investigation.

Background Immunoglobulin G (IgG) N-glycans have been shown to be associated with the risk of type 2 diabetes (T2D) and its risk factors. However, whether these associations reflect causal effects remain unclear. Furthermore, the associations of IgG N-glycans and inflammation are not fully understood. Methods We examined the causal associations of IgG N-glycans with inflammation (C-reactive protein (CRP) and fibrinogen) and T2D using two-sample Mendelian randomization (MR) analysis in East Asian and European populations. Genetic variants from IgG N-glycan quantitative trait loci (QTL) data were used as instrumental variables. Two-sample MR was conducted for IgG N-glycans with inflammation (75,391 and 18,348 participants of CRP and fibrinogen in the East Asian population, 204,402 participants of CRP in the European population) and T2D risk (77,418 cases and 356,122 controls of East Asian ancestry, 81,412 cases and 370,832 controls of European ancestry). Results After correcting for multiple testing, in the East Asian population, genetically determined IgG N-glycans were associated with a higher risk of T2D, the odds ratios (ORs) were 1.009 for T2D per 1- standard deviation (SD) higher GP5, 95% CI = 1.003–1.015; P = 0.0019; and 1.013 for T2D per 1-SD higher GP13, 95% CI = 1.006–1.021; P = 0.0005. In the European population, genetically determined decreased GP9 was associated with T2D (OR = 0.899 per 1-SD lower GP9, 95% CI: 0.845–0.957). In addition, there was suggestive evidence that genetically determined IgG N-glycans were associated with CRP in both East Asian and European populations after correcting for multiple testing, but no associations were found between IgG N-glycans and fibrinogen. There was limited evidence of heterogeneity and pleiotropy bias. Conclusions Our results provided novel genetic evidence that IgG N-glycans are causally associated with T2D.

Observational studies, randomized controlled trials (RCTs), and Mendelian randomization (MR) studies have yielded inconsistent results on the associations of vitamin D concentrations with multiple health outcomes. In the present umbrella review we aimed to evaluate the effects of low vitamin D concentrations and vitamin D supplementation on multiple health outcomes. We summarized current evidence obtained from meta-analyses of observational studies that examined associations between vitamin D concentrations and multiple health outcomes, meta-analyses of RCTs that investigated the effect of vitamin D supplementation on multiple health outcomes, and MR studies that explored the causal associations of vitamin D concentrations with various diseases (international prospective register of systematic reviews PROSPERO registration number CRD42018091434). A total of 296 meta-analyses of observational studies comprising 111 unique outcomes, 139 meta-analyses of RCTs comprising 46 unique outcomes, and 73 MR studies comprising 43 unique outcomes were included in the present umbrella review. Twenty-eight disease outcomes were identified by both meta-analyses of observational studies and MR studies. Seventeen of these reported disease outcomes had consistent results, demonstrating that lower concentrations of vitamin D were associated with a higher risk for all-cause mortality, Alzheimer's disease, hypertension, schizophrenia, and type 2 diabetes. The combinations of consistent evidence obtained by meta-analyses of observational studies and MR studies together with meta-analyses of RCTs showed that vitamin D supplementation was associated with a decreased risk for all-cause mortality but not associated with the risk for Alzheimer's disease, hypertension, schizophrenia, or type 2 diabetes. The results indicated that vitamin D supplementation is a promising strategy with long-term preventive effects on multiple chronic diseases and thus has the potential to decrease all-cause mortality. However, the current vitamin D supplementation strategy might not be an efficient intervention approach for these diseases, suggesting that new strategies are highly needed to improve the intervention outcomes.

Genome-wide association studies (GWAS) have identified over 60 genetic loci associated with immunoglobulin G (IgG) N-glycosylation; however, the causal genes and their abundance in relevant tissues are uncertain. Leveraging data from GWAS summary statistics for 8,090 Europeans, and large-scale expression quantitative trait loci (eQTL) data from the genotype-tissue expression of 53 types of tissues (GTEx v7), we derived a linkage disequilibrium score for the specific expression of genes (LDSC-SEG) and conducted a transcriptome-wide association study (TWAS). We identified 55 gene associations whose predicted levels of expression were significantly associated with IgG N-glycosylation in 14 tissues. Three working scenarios, i.e., tissue-specific, pleiotropic, and coassociated, were observed for candidate genetic predisposition affecting IgG N-glycosylation traits. Furthermore, pathway enrichment showed several IgG N-glycosylation-related pathways, such as asparagine N-linked glycosylation, N-glycan biosynthesis and transport to the Golgi and subsequent modification. Through phenome-wide association studies (PheWAS), most genetic variants underlying TWAS hits were found to be correlated with health measures (height, waist-hip ratio, systolic blood pressure) and diseases, such as systemic lupus erythematosus, inflammatory bowel disease, and Parkinson’s disease, which are related to IgG N-glycosylation. Our study provides an atlas of genetic regulatory loci and their target genes within functionally relevant tissues, for further studies on the mechanisms of IgG N-glycosylation and its related diseases.

Suboptimal health status (SHS), a physical state between health and disease, is a subclinical and reversible stage of chronic disease. Previous studies have shown alterations in the intestinal microbiota in patients with some chronic diseases. This study aimed to investigate the association between SHS and intestinal microbiota in a case‐control study with 50 SHS individuals and 50 matched healthy controls. Intestinal microbiota was analysed by MiSeq 250PE. Alpha diversity of intestinal microbiota in SHS individuals was higher compared with that of healthy controls (Simpson index, W = 2238, P = .048). Beta diversity was different between SHS and healthy controls (P = .018). At the phylum level, the relative abundance of Verrucomicrobia was higher in the SHS group than that in the controls (W = 2201, P = .049). Compared with that of the control group, nine genera were significantly higher and five genera were lower in abundance in the SHS group (all P

Aberrant immunoglobulin G (IgG) N-glycosylation offers new prospects to detect changes in cell metabolism and by extension, for biomarker discovery in type 2 diabetes mellitus (T2DM). However, past studies did not analyze the individual IgG subclasses in relation to T2DM pathophysiology. We report here original findings through a comparison of the IgG subclass-specific fragment crystallizable (Fc) glycan biosignatures in 115 T2DM patients with 122 healthy controls within the Uyghur population in China. IgG Fc glycosylation profiles were analyzed using nano- liquid chromatography–mass spectrometry to exclude changes attributed to fragment antigen binding N- glycosylation. After correction for clinical covariates, 27 directly measured and 4 derived glycan traits of the IgG subclass-specific N- glycopeptides were significantly associated with T2DM. Furthermore, we observed in T2DM a decrease in bisecting N-acetylglucosamine of IgG2 and agalactosylation of IgG4, and an increase in sialylation of IgG4 and digalactosylation of IgG2. Classification model based on IgG subclass- specific N-glycan traits was able to distinguish patients with T2DM from controls with an area under the receiver operating characteristic curve of 0.927 (95% confidence interval 0.894–0.960, p < 0.001). In conclusion, a robust association between the IgG subclass-specific Fc N-glycomes and T2DM was observed in the Uyghur population sample in China, suggesting a potential for the IgG Fc glycosylation as a biomarker candidate for type 2 diabetes. The integration of glycomics with other system science biomarkers might offer further hope for innovation in diagnosis and treatment of T2DM in the future. Finally, it is noteworthy that “Population Glycomics” is an emerging approach to biomarker discovery for common complex diseases.

Type 2 diabetes mellitus (T2DM) is a common complex trait arising from interactions among multiple environmental, genomic, and postgenomic factors. We report here the first attempt to investigate the association between immunoglobulin G (IgG) N-glycan patterns, T2DM, and their clinical risk factors in an Australian population. N-glycosylation of proteins is one of the most frequently observed co- and post-translational modifications, reflecting, importantly, the real-time status of the interplay between the genomic and postgenomic factors. In a community-based case-control study, 849 participants (217 cases and 632 controls) were recruited from an urban community in Busselton, Western Australia. We applied the ultraperformance liquid chromatography method to analyze the composition of IgG N-glycans. We then conducted Spearman's correlation analyses to explore the association between glycan biomarker candidates and clinical risk factors. We performed area under the curve (AUC) analysis of the receiver operating characteristic curves by fivefold cross-validation for clinical risk factors, IgG glycans, and their combination. Two directly measured and four derived glycan peaks were significantly associated with T2DM, after correction for extensive clinical confounders and false discovery rate, thus suggesting that IgG N-glycan traits are highly correlated with T2DM clinical risk factors. Moreover, adding the IgG glycan profiles to fasting blood glucose in the logistic regression model increased the AUC from 0.799 to 0.859. The AUC for IgG glycans alone was 0.623 with a 95% confidence interval 0.580-0.666. In addition, our study provided new evidence of diversity in T2DM complex trait by IgG N-glycan stratification. Six IgG glycan traits were firmly associated with T2DM, which reflects an increased proinflammatory and biological aging status. In summary, our study reports novel associations between the IgG N-glycome and T2DM in an Australian population and the putative role of proinflammatory mechanisms. Furthermore, IgG N-glycomic alterations offer future prospects as inflammatory biomarker candidates for T2DM diagnosis, and monitoring of T2DM progression to cardiovascular disease or renal failure.

BACKGROUND AND PURPOSE Elevated C-reactive protein (CRP) is associated with an increased risk of ischaemic stroke (IS). However, the causality of this association is uncertain. The aim is to investigate whether genetically raised plasma CRP concentration levels are associated with IS on the basis of the Mendelian randomization method. METHODS Based on the National Center for Biotechnology Information single nucleotide polymorphism (SNP) database, the Chinese online genetic database as well as previously published studies, four CRP-associated SNP alleles (rs1130864, rs1205, rs876537 and rs3093059) with minor allele frequency ≥0.15 were selected and the concentration levels of CRP were measured in 378 first-ever IS patients and 613 healthy controls. RESULTS Three SNPs were chosen and used as instrumental variables. The adjusted odds ratios (ORs) [95% confidence interval (95% CI)] of IS per addition of the modelled allele were 1.07 (0.79-1.45) for rs876537, 0.99 (0.73-1.35) for rs1205 and 1.08 (0.71-1.65) for rs3093059. The OR (95% CI) of IS for plasma CRP ≥2.0 mg/l was 2.19 (1.06-4.53) compared with

IntroductionProfiles of high risk for future dementia are well understood and are likely to concern mostly those in low-income and middle-income countries and people at greater disadvantage in high-income countries. Approximately 30%–40% of dementia cases have been estimated to be attributed to modifiable risk factors, including hypertension, smoking and sedentary lifestyle. Tailored interventions targeting these risk factors can potentially prevent or delay the onset of dementia. Mobile health (mHealth) improves accessibility of such prevention strategies in hard-to-reach populations while at the same time tailoring such approaches. In the current study, we will investigate the effectiveness and implementation of a coach-supported mHealth intervention, targeting dementia risk factors, to reduce dementia risk.Methods and analysisThe prevention of dementia using mobile phone applications (PRODEMOS) randomised controlled trial will follow an effectiveness–implementation hybrid design, taking place in the UK and China. People are eligible if they are 55–75 years old, of low socioeconomic status (UK) or from the general population (China); have ≥2 dementia risk factors; and own a smartphone. 2400 participants will be randomised to either a coach-supported, interactive mHealth platform, facilitating self-management of dementia risk factors, or a static control platform. The intervention and follow-up period will be 18 months. The primary effectiveness outcome is change in the previously validated Cardiovascular Risk Factors, Ageing and Incidence of Dementia dementia risk score. The main secondary outcomes include improvement of individual risk factors and cost-effectiveness. Implementation outcomes include acceptability, adoption, feasibility and sustainability of the intervention.Ethics and disseminationThe PRODEMOS trial is sponsored in the UK by the University of Cambridge and is granted ethical approval by the London—Brighton and Sussex Research Ethics Committee (reference: 20/LO/01440). In China, the trial is approved by the medical ethics committees of Capital Medical University, Beijing Tiantan Hospital, Beijing Geriatric Hospital, Chinese People’s Liberation Army General Hospital, Taishan Medical University and Xuanwu Hospital. Results will be published in a peer-reviewed journal.Trial registration numberISRCTN15986016.

Prospective studies have shown that abnormally circulating cholesterol is associated with the risk of dementia. However, whether the association is causal or not remains unclear. We attempt to infer the causal association in a MR meta-analysis by using ApoE gene polymorphisms as instrument variables. Studies with dementia risk (27 studies) or circulating lipid levels (7 studies) were included, with totally 3136 dementia patients and 3103 healthy controls. The analyses showed that carriers of ε2 allele significantly were of decreased risk of AD (OR = 0.70; 95% CI: 0.58–0.84; P P P P P P P P

Background Many contradictory conclusions pertaining to the telomere length in peripheral leukocyte chromosomes as a potential biomarker for ischemic stroke (IS) risk have been reported by the various observational studies in previous years. This study aims to investigate whether the leukocyte telomere length is associated with an increased IS risk or not, based on the Mendelian randomization (MR) approach. Methods Based on the NHGRI-EBI GWAS Catalog database, the Chinese online genetic database as well as the previous published studies, twelve single nucleotide polymorphisms (SNPs) with minor allele frequency ≥ 0.05 were selected and the leukocyte telomere length was measured in 431 first-ever IS patients and 304 healthy controls (quantitative polymerase chain reaction). To explore linear and non-linear effect of telomere length on the IS risk, we preformed the linear MR analysis (the inverse-variance weighted method, the maximum likelihood method, and the mode-based estimation method), and the non-linear MR analysis (semiparametric method with three tests for non-linearity, including the quadratic test, Cochran’s Q test, and the fractional polynomial test). Results Two verified SNPs (rs11125529 and rs412658) were chosen as instrumental variables. In linear MR analysis, the adjusted odds ratios and 95% confidence intervals of IS for genetically predicted telomere lengths, based on the two SNPs, were 1.312 (0.979 to 1.759), 1.326 (0.932 to 1.888) and 1.226 (0.844 to 1.781) for the inverse-variance weighted method, the maximum likelihood method, and the mode-based estimation method, respectively. Three tests for nonlinearity failed to reject the null exactly, indicating that the relationship between telomere length and IS risk is unlikely to be non-linear. Conclusion This MR study based on individual data does not provide strong evidence for a positive linear or non-linear effect of telomere length on the IS risk.

Background Alternative 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. Methods Herein, 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. Results Blood lipids were positively correlated with glycan peak GP6, whereas they were negatively correlated with GP18 (P

Male infertility is an important global health burden that can benefit from novel biomarkers and diagnostics innovation. Aberrant methylation of the imprinted genes H19 and SNRPN (small nuclear ribonucleoprotein polypeptide N) in sperm DNA has been implicated in abnormal sperm parameters and male infertility. However, whether certain methylation patterns of one or multiple CpG sites within an imprinted gene are pathological for multiple sperm defects remains poorly understood. To examine the diagnostic potential of certain methylation patterns of CpG sites for multiphenotype defects in human sperm, the sperm DNA methylation patterns of individual CpG sites within imprinting control regions (ICRs) of imprinted genes H19 and SNRPN were measured by bisulfite pyrosequencing in a Han Chinese population sample: 39 oligoasthenozoospermia (OA) patients, 36 asthenoteratozoospermia (AT) patients, and 50 normozoospermia (N) controls. A partial least squares discriminant analysis model was built with the CpG sites as independent variables. Among the 16 CpG sites screened, the methylation patterns of eight CpG sites within H19-ICR (CpG sites 1, 6-9, 12 and 15-16), and eight CpG sites within SNRPN-ICR (CpG sites 2, 5-6, 8-10, 13, and 16) correctly classified 74.4% and 72.0% of the samples in terms of male fertile status, respectively. Furthermore, by combination of these 16 selected CpG sites within ICRs of H19 and SNRPN, 88.0% of the samples could be successfully classified. Our study demonstrates that methylation profiles of CpG sites within ICRs of imprinted genes H19 and SNRPN may potentially serve as epigenomic biomarkers for assessment of infertility in men with multiple sperm defects. Further studies in independent population samples are called for diagnostic significance of methylation patterns of CpG sites within imprinted genes.

Background Glycosylation significantly affects protein structure and function and thus participates in multiple physiologic and pathologic processes. Studies demonstrated that immunoglobulin G (IgG) N-glycosylation associates with the risk factors of ischemic stroke (IS), such as aging, obesity, dyslipidemia, type 2 diabetes, and hypertension. Methods The study aimed to investigate the association between IgG N-glycosylation and IS in a Chinese population. IgG glycome composition in patients with IS (n = 78) and cerebral arterial stenosis (CAS) (n = 75) and controls (n = 77) were analyzed by ultra-performance liquid chromatography. Results Eleven initial glycans and 10 derived glycans in IgG glycome representing galactosylation, sialylation, and bisecting GlcNAc significantly differed between IS patients and CAS and healthy controls after controlling for gender, age, obesity, diabetes, hypertension, and dyslipidemia. Logistic regression models incorporating IgG glycan traits were able to distinguish IS from CAS (area under receiver–operator characteristic curves (AUC), 0.802; 95% confidence interval (CI), 0.732–0.872) and controls (AUC, 0.740; 95% CI, 0.661–0.819). The canonical correlation analysis indicated that initial N-glycan structures are significantly correlated with inflammation markers (r = 0.566, p

Suboptimal health status (SHS) is a physical state between health and illness, and previous studies suggested that SHS is associated with majority components of cardiovascular health metrics defined by American Heart Association (AHA). We investigated the association between SHS and cardiovascular health metrics in a cross-sectional analysis of China suboptimal health cohort study (COACS) consisting of 4313 participants (60.30% women) aged from 18 to 65 years old. The respective prevalence of SHS is 7.10%, 9.18%, 10.04% and 10.62% in the first, second, third and fourth quartiles of ideal cardiovascular health (CVH) metrics (P for trend = 0.012). Participants in the largest quartile of ideal CVH metrics show a lower likelihood of having optimal SHS score compared to those in the smallest quartile (odds ratio (OR), 0.43; 95% confidence interval (CI), 0.32–0.59), after adjusting for age, gender, marital status, alcohol consumption, income level and education. Four metrics (smoking, physical inactivity, poor dietary intake and ideal control of blood pressure are significantly correlated with the risk of SHS. The present study suggests that ideal CVH metrics are associated with a lower prevalence of SHS, and the combined evaluation of SHS and CVH metrics allows the risk classification of cardiovascular disease, and thus consequently contributes to the prevention of cardiovascular diseases.

Colon cancer patients have major unmet needs in terms of robust diagnostics and molecular biomarkers for personalized therapeutics. We have previously reported that human CAP10-like protein 46 kDa (hCLP46) is overexpressed in human acute myelogenous leukemia, T acute lymphoblastic leukemia, and leukemia cell lines. We extend this line of biomarker and diagnostic discovery research by investigating hCLP46 expression in colorectal cancer (CRC) tissues and examine the possibility of hCLP46 as a candidate biomarker for diagnosis and prognosis of CRC. Using a tissue microarray analysis approach, we found that hCLP46 is (1) overexpressed in 90 CRC tissues compared with 90 matched noncancerous tissues and (2) positively correlated with higher tumor-node-metastasis (TNM) stage, lymph node metastasis, and shorter survival time. Moreover, in vitro experiments demonstrated that downregulation of hCLP46 in CRC cells results in proliferation arrest and adhesion enhancement, while apoptosis is unchanged. Further transcriptome profile analysis corroborated that the adhesion pathway is related to hCLP46 downregulation. This report for the first time, to the best of our knowledge, demonstrates that hCLP46 promotes tumor malignancy in CRC cells. We suggest that hCLP46 is warranted for further research as a candidate biomarker for clinical phenotypes related to colon cancer.

Glycomics is a new subspecialty in omics systems sciences that offers significant promise for next-generation biomarkers on disease susceptibility, drug target discovery, and precision medicine. In this context, alternative immunoglobulin G (IgG)

Cardiovascular disease is a common complex trait that calls for next-generation biomarkers for precision diagnostics and therapeutics. The most common type of post-translational protein modification involves glycosylation. Glycans participate in key intercellular and intracellular functions, such as protein quality control, cell adhesion, cell-cell recognition, signal transduction, cell proliferation, and cell differentiation. In this context, immunoglobulin G (IgG)

The increasing prevalence of hyperuricemia has been recognized as an emerging public health concern in both developed and developing countries. Hyperuricemia is a metabolic condition characterized by an elevated serum uric acid, and associated with renal damage, diabetes, autoimmune disorders, and cardiovascular diseases. Although human genetic variation has been recognized as a factor, posttranslational cellular processes and glycan biomarkers have not been studied extensively for susceptibility to hyperuricemia. We evaluated whether immunoglobulin (Ig)G

Immunoglobulin G (IgG) is the most abundant serum antibody and is a key determinant of the humoral immune response. Its structural characteristics and effector functions are modulated through the attachment of various sugar moieties called glycans. IgG N-glycome patterns change with the age of individual and in different diseases. Variability of IgG glycosylation within a population is well studied and is affected by a combination of genetic and environmental factors. However, global inter-population differences in IgG glycosylation have never been properly addressed. Here we present population-specific N-glycosylation patterns of whole IgG, analysed in 5 different populations totalling 10,482 IgG glycomes, and of IgG’s fragment crystallisable region (Fc), analysed in 2,530 samples from 27 populations sampled across the world. We observed that country of residence associates with many N-glycan features and is a strong predictor of monogalactosylation variability. IgG galactosylation also strongly correlated with the development level of a country, defined by United Nations health and socioeconomic development indicators. We found that subjects from developing countries had low IgG galactosylation levels, characteristic for inflammation and ageing. Our results suggest that citizens of developing countries may be exposed to country-specific environmental factors that can cause low-grade chronic inflammation and the apparent increase in biological age.

Background Increased body fat may be associated with an increased risk of developing an underlying pro-inflammatory state, thus leading to greater risk of developing certain chronic conditions. Immunoglobulin G has the ability to exert both anti- and pro-inflammatory effects, and the N-glycosylation of the fragment crystallisable portion is involved in mediating this process. Body mass index, a rudimentary yet gold standard indication for body fat, has been shown to be associated with agalactosylated immunoglobulin G N-glycans. Aim We aimed to determine the association between increased body fat and the immunoglobulin G glycosylation features, comparing body mass index to other measures of body fat distribution. Methods We investigated a sample of 637 community-based 45–69 year olds, with mixed phenotypes, residing in Busselton, Western Australia. Body mass index and the waist-to-hip and waist-to-height ratios were calculated using anthropometry, while dual-energy x-ray absorptiometry was performed to gain an accurate measure of total and area specific body fat. Serum immunoglobulin GN-glycans were analysed by ultra-performance liquid chromatography. Results Twenty-two N-glycan peaks were found to be associated with at least one of the fat measures. While the previous association of body mass index to agalactosylated immunoglobulin G was replicated, measures of central adiposity explained the most variation in the immunoglobulin G glycome. Conclusion Central adiposity is associated with an increased pro-inflammatory fraction of immunoglobulin G, suggesting that the android/gynoid ratio or waist-to-height ratio instead be considered when controlling for adiposity in immunoglobulin G glycome biomarker studies.

Objective: To evaluate factors associated with myopic shift among primary school children. Methods: In a one-year prospective school-based study, 5052 children from ten schools were enrolled using a multi-stage random cluster approach. The baseline examination included non-cycloplegic auto-refractometry and questionnaire interview. Measurements were repeated at the follow-up. Results: Among 5052 students at baseline investigated, 4292 students (85.0%) returned for the follow-up examination. The mean refractive error (-1.13±1.57 diopters) had changed -0.52±0.73 diopters from the baseline to the follow-up examination. 2170 (51.0%) had a rate of significant myopic shift (significant myopic shift is defined as the change of spherical equivalent of the refraction ≤ -0.50D between the follow-up and baseline measures). We confirmed that common associated factors (older age, parental myopia, lower refractive status at baseline, shorter reading distance and lower frequency of outdoor activities during class recesses) were associated with greater shift towards myopia. After controlling for age, sex, region of habitation, parental myopia and refractive status at baseline, greater shift towards myopia was independently associated with distance from near-work (OR=1.48 , 95% CI=1.26-1.74, P

Suboptimal health status (SHS) has become a new public health challenge in China. This study investigated whether high SHS is associated with psychosocial stress, changes in cortisol level and/or glucocorticoid receptor (GR) isoform expression. Three-hundred eighty-six workers employed in three companies in Beijing were recruited. The SHS score was derived from data collection in the SHS questionnaire (SHSQ-25). The short standard version of the Copenhagen Psychosocial Questionnaire (COPSOQ) was used to assess job-related psychosocial stress. The mean value of the five scales of COPSOQ and distribution of plasma cortisol and mRNA expression of GRα/GRβ between the high level of SHS group and the low level of SHS group were compared using a general linear model procedure. Multiple linear regression analysis was used to analyze the effect of psychosocial stress on SHS. We identified three factors that were predictive of SHS, including "demands at work", "interpersonal relations and leadership" and "insecurity at work". Significantly higher levels of plasma cortisol and GRβ/GRα mRNA ratio were observed among the high SHS group. High level of SHS is associated with decreased mRNA expression of GRα. This study confirmed the association between chronic psychosocial stress and SHS, indicating that improving the psychosocial work environment may reduce SHS and then prevent chronic diseases effectively.

Hypertension results from the interaction of genetic and acquired factors. IgG occurs in the form of different subclasses, of which the effector functions show significant variation. The detailed differences between the glycosylation profiles of the individual IgG subclasses may be lost in a profiling method for total IgG N-glycosylation. In this study, subclass-specific IgG Fc glycosylation profile was investigated in the four northwestern Chinese minority populations, namely, Uygur (UIG), Kazak (KZK), Kirgiz (KGZ), and Tajik (TJK), composed of 274 hypertensive patients and 356 healthy controls. The results showed that ten directly measured IgG N-glycan traits (i.e., IgG1G0F, IgG2G0F, IgG2G1FN, IgG2G1FS, IgG2G2S, IgG4G0F, IgG4G1FS, IgG4G1S, IgG4G2FS, and IgG4G2N) representing galactosylation and sialylation are significantly associated with hypertension, with IgG4 consistently showing weaker associations of its sialylation, across the four ethnic groups. We observed a modest improvement on the AUC of ROC curve when the IgG Fc N-glycan traits are added into the glycan-based model (difference between AUCs, 0.044, 95% CI: 0.016–0.072, P = 0.002). The AUC of the diagnostic model indicated that the subclass-specific IgG Fc N-glycan profiles provide more information reinforcing current models utilizing age, gender, BMI, and ethnicity, and demonstrate the potential of subclass-specific IgG Fc N-glycosylation profiles to serve as a biomarker for hypertension. Further research is however required to determine the additive value of subclass-specific IgG Fc N-glycosylation on top of biomarkers, which are currently used.

Suboptimal health status (SHS) has been linked to cardiovascular risk factors, psychosocial stress, and unhealthy lifestyle. These factors also contribute to the shortening of telomere length (TL). A case-control study was conducted to examine the association between subjective health measures of SHS from the behavior perspective and also objective measures of TL at molecular level. SHS (cases = 294) was matched by age, sex, and body mass index with ideal health (controls = 294) using a propensity score matching method. Suboptimal health status questionnaire-25 (SHSQ-25) was used in the community-based health survey. A quantitative polymerase chain reaction was used to measure relative telomere length (RTL). Shorter RTL was found among the SHS group compared to the ideal health group (p 0.05). SHS was almost four times likely to be in the first quartile (odds ratio [OR] = 3.81; 95% confidence interval [CI] 2.21-6.56), almost thrice in second quartile (OR = 2.84; 95% CI 1.65-4.90), and almost twice likely to be in the third quartile (OR = 1.71; 95% CI 1.00-2.94) compared to the fourth quartile (the longest) of RTL after adjusting for socioeconomic, dietary intake, anthropometric, blood pressure, and biochemistry variables (p 0.05). Notably, SHS score was negatively correlated with RTL (r = -0.218, p 0.05). Our study confirms an association between SHS and short RTL. Combination of subjective (SHS) and objective (RTL) measures is a novel tool for health aging investigation. Therefore, SHSQ-25 could be used as a screening tool for measuring biological aging in low-income countries at community level where the expensive technique for RTL measurement is not applicable.

Background: Epidemiological studies observing inconsistent associations of telomere length (TL) with ischemic stroke (IS) are susceptible to bias according to reverse causation and residual confounding. We aimed to assess the causal association between TL, IS, and the subtypes of IS, including large artery stroke (LAS), small vessel stroke (SVS), and cardioembolic stroke (CES) by performing a series of two-sample Mendelian randomization (MR) approaches. Methods: Seven single nucleotide polymorphisms (SNPs) were involved as candidate instrumental variables (IVs), summarized from a genome-wide meta-analysis including 37,684 participants of European descent. We analyzed the largest ever genome-wide association studies of stroke in Europe from the MEGASTROKE collaboration with 40,585 stroke cases and 406,111 controls. The weighted median (WM), the penalized weighted median (PWM), the inverse variance weighted (IVW), the penalized inverse variance weighted (PIVW), the robust inverse variance weighted (RIVW), and the Mendelian randomization-Egger (MR-Egger) methods were conducted for the MR analysis to estimate a causal effect and detect the directional pleiotropy. Results: No significant association between genetically determined TL with overall IS, LAS, or CES were found (all p &gt, 0.05). SVS was associated with TL by the RIVW method (odds ratio (OR) = 0.72, 95% confidence interval (CI): 0.54&ndash, 0.97, p = 0.028), after excluding rs9420907, rs10936599, and rs2736100. Conclusions: By a series of causal inference approaches using SNPs as IVs, no strong evidence to support the causal effect of shorter TL on IS and its subtypes were found.

To investigate the association of tag-SNPs and haplotype structures of the CIDEA gene with obesity in a Han Chinese population. Five single nucleotide polymorphisms (SNPs) (rs1154588/V115F, rs4796955/SNP1, rs8092502/SNP2, rs12962340/SNP3 and rs7230480/SNP4) in the CIDEA gene were genotyped in a case–control study. Genotyping was performed using the sequenom matrix-assisted laser desorption/ionization time-of-flight mass spectrometry iPLEX platform. There were significant differences between the obese and control groups in genotype distributions of V115F (P

Background: More than 60 genetic susceptibility loci associated with type 2 diabetes mellitus (T2DM) have been established in populations of Asian and European ancestry. Given ethnic differences and environmental factors, validation of the effects of genetic risk variants with reported associations identified by Genome-Wide Association Studies (GWASs) is essential. The study aims at evaluating the associations of T2DM with 29 single nucleotide polymorphisms (SNPs) from 19 candidate genes derived from GWASs in a northern Han Chinese population. Method: In this case-control study, 461 T2DM-diagnosed patients and 434 controls were recruited at the Jidong oil field hospital (Hebei, China) from January 2009 to October 2013. A cumulative genetic risk score (cGRS) was calculated by summation of the number of risk alleles, and a weight GRS (wGRS) was calculated as the sum of risk alleles at each locus multiplied by their effect sizes for T2DM, using the independent variants selected. Result: The allelic frequency of the “A” allele at rs17106184 (Fas-associated factor 1, FAF1) was significantly higher in the T2DM patients than that of the healthy controls (11.7% vs. 6.4%, p < 0.001). Individuals in the highestquartile of wGRS had an over three-fold increased risk for developing T2DM compared with those in the lowest quartile (odds ratio = 3.06, 95% CI = 1.92–4.88, p < 0.001) adjusted for age, sex, BMI, total cholesterol (TC), triglycerides (TG), low-density lipoprotein cholesterol (LDL-C), systolic blood pressure (SBP) and diastolic blood pressure (DBP). The results were similar when analyzed with the cGRS. Conclusions: We confirmed the association between rs17106184 (FAF1) and T2DM in a northern Han Chinese population. The GRS calculated based on T2DM susceptibility variants may be a useful tool for predicting the T2DM susceptibility.

Rheumatoid arthritis (RA), a systemic, chronic, and progressive inflammatory autoimmune disease, affects up to 1.0% of the world population doubling mortality rate of patients and is a major global health burden. Worrisomely, we lack robust diagnostics of RA and its remission status. Research with the next-generation biomarker technology platforms such as glycomics offers new promises in this context. We report here a clinical case-control study comprising 128 patients suffering from chronic RA (80.22% in remission, 19.78% active clinically) and 195 gender- and age-matched controls, with a view to the putative glycan biomarkers of RA as well as its activity or remission status in Han Chinese RA patients. Hydrophilic interaction liquid chromatography-ultra-performance liquid chromatography (HILIC-UPLC) was used for the analysis of IgG glycans. The regression model identified the glycans that predict RA status, while a receiver operating characteristic (ROC) curve analysis validated the sensitivity and prediction power. Among the total 24 glycan peaks (GP1-GP24), ROC analysis showed only GP1 prediction to be highly sensitive with an area under the curve (AUC) = 0.881. Even though GP21 and GP22 could predict active status among the RA cases (p 0.05), they had lower sensitivity of prediction with an AUC = 0.658. Taken together, these observations suggest that GP1 might have potential as a putative biomarker for RA in the Han Chinese population, while the change in IgG glycosylation shows association with the RA active and remission states. To the best of our knowledge, this is the first glycomics study with respect to disease activity and remission states in RA.

Background Suboptimal health status (SHS) is a physical state between health and disease, characterized by the perception of health complaints, general weakness, chronic fatigue and low energy levels. SHS is proposed by the ancient concept of traditional Chinese medicine (TCM) from the perspective of preservative, predictive and personalized (precision) medicine. We previously created the suboptimal health status questionnaire 25 (SHSQ-25), a novel instrument to measure SHS, validated in various populations. SHSQ-25 thus affords a window of opportunity for early detection and intervention, contributing to the reduction of chronic disease burdens. Methods/design To investigate the causative effect of SHS in non-communicable chronic diseases (NCD), we initiated the China suboptimal health cohort study (COACS), a longitudinal study starting from 2013. Phase I of the study involved a cross-sectional survey aimed at identifying the risk/protective factors associated with SHS; and Phase II: a longitudinal yearly follow-up study investigating how SHS contributes to the incidence and pattern of NCD. Results (1) Cross-sectional survey: in total, 4313 participants (53.8 % women) aged from 18 to 65 years were included in the cohort. The prevalence of SHS was 9.0 % using SHS score of 35 as threshold. Women showed a significantly higher prevalence of SHS (10.6 % in the female vs. 7.2 % in the male, P

Background Type 2 diabetes mellitus (T2DM) is a complex, pandemic disease contributing towards the global burden of health issues. To date, there are no simple clinical tests for the early detection of T2DM. Method To identify potential peptide biomarkers for such applications, 406 sera of T2DM patients (n = 206) and healthy controls (n = 200) were analyzed using MALDI-TOF MS with a cross-sectional case-control design. Result Six peptides (peaks m/z 1452.9, 1692.8, 1946.0, 2115.1, 2211.0 and 4053.6) were identified as candidate biomarkers for T2DM. A diagnostic model constructed with the 6 peptides was able to discriminate T2DM patients from healthy controls, with an accuracy of 82.20%, sensitivity of 82.50%, and specificity of 77.80% in the validation set. Peptide peaks m/z 1452.9 and 1692.8 were identified as fragments of the complement C3f, while peptide peaks m/z 1946.0, 2115.0, and 2211.0 were identified as the fragments of kininogen 1 isoform 1 precursor. Conclusion This study reinforces proteomic analyses as a potential technique for defining significant clinical peptide biomarkers, providing a simple and convenient diagnostic model for T2DM in clinical examination. This article is protected by copyright. All rights reserved

The outcome of human immunodeficiency virus (HIV)-1 infection and course to AIDS are variable among individuals. Both chemokine receptor 5 (CCR5) and CCR2 gene polymorphisms play essential roles in the susceptibility of HIV-1 infection. To investigate the main and epistatic effects of the CCR5 promoter and CCR2-V64I polymorphisms on HIV-1 infection in the Northern Han Chinese, subjects of 91 HIV-1-infected patients and 91 health controls were recruited. Single-nucleotide polymorphisms (SNPs) in the CCR5 promoter region and CCR2-V64I variants were genotyped. In the single-locus analysis, CCR5 58755-G and CCR5 59653-T alleles were significantly associated with HIV-1 infection (odds ratio [OR]=0.529, 95% confidence interval [CI]: 0.295-0.948; OR=1.710, 95% CI: 1.039-2.814). After adjustment with age and gender, subjects with the CCR5 59653-CT genotype showed the increased risk of HIV-1 infection compared with those with the wild-type CC genotype (adjusted OR=2.502; 95% CI: 1.332-4.698). No positive association was observed in other SNPs. Haplotype-based association analysis revealed that the haplotype TATGC was associated with the susceptibility to HIV-1 infection (p=0.003). Besides, we found the significant epistatic effects between the CCR5 58755-A/G and CCR5 59029-A/G polymorphisms associated with the lower risk of HIV-1 infection. In addition, we also identified the best three-factor interaction model, including the CCR5 58755-A/G, 59029-A/G, and CCR2-V64I polymorphisms, indicating that there were also strong gene-gene interactions between the CCR5 promoter and CCR2 polymorphisms on the susceptibility of HIV-1 infection. These findings contribute to understanding the genetic mechanism for the susceptibility of HIV-1 infection in Northern Han Chinese.

The study aims at evaluating the association between brain-derived neurotrophic factor (BDNF) gene polymorphisms and heroin-dependent patients in the Chinese population. Three polymorphisms of the BDNF-gene (rs10835210, rs16917234, and rs6265) in 486 heroin-dependent patients and in 226 healthy controls were genotyped for analyzing the association of these polymorphisms with age of onset of heroin dependence. We defined the healthy cases as "unknown phenotype" and used the endophenotype (behavior traits) to stratify the heroin dependents group on the basis of self-reporting traits for examining the association between BDNF polymorphisms (rs10835210, rs16917234, and rs6265) and heroin dependence.Allelic distributions of BDNF gene polymorphisms did not differ significantly between heroin-dependent patients and controls. However, we found that the AA carriers of BDNF rs6265 had an earlier onset of heroin dependence and a clearer tendency of family history of heroin-dependent than GG carriers after controlling behavior characteristics across rs6265 genotypes.Our findings suggested that the BDNF genetic polymorphism (rs6265) may have effects on the age of onset of heroin dependence among the Chinese population. The BDNF gene could contribute to vulnerabilities to heroin dependence.

Substantial evidence suggests that type 2 diabetes mellitus (T2DM) is a multi-factorial disease with a strong genetic component. A list of genetic susceptibility loci in populations of European and Asian ancestry has been established in the literature. Little is known on the inter-ethnic contribution of such established functional polymorphic variants. We performed a case-control study to explore the genetic susceptibility of 16 selected T2DM-related SNPs in a cohort of 102 Uyghur objects (51 cases and 51 controls). Three of the 16 SNPs showed significant association with T2DM in the Uyghur population. There were significant differences between the T2DM and control groups in frequencies of the risk allelic distributions of rs7754840 (CDKAL1) (p=0.014), rs864745 (JAZF1) (p=0.032), and rs35767 (IGF1) (p=0.044). Carriers of rs7754840-C, rs35767-A, and rs864745-C risk alleles had a 2.32-fold [OR (95% CI): 1.19-4.54], 2.06-fold [OR (95% CI): 1.02-4.17], 0.48-fold [OR (95% CI): 0.24-0.94] increased risk for T2DM, respectively. The cumulative risk allelic scores of these 16 SNPs differed significantly between the T2DM patients and the controls [17.1±8.1 vs. 15.4±7.3; OR (95%CI): 1.27(1.07-1.50), p=0.007]. This is the first study to evaluate genomic variation at 16 SNPs in respective T2DM candidate genes for the Uyghur population compared with other ethnic groups. The SNP rs7754840 in CDKAL1, rs864745 in JAZF1, and rs35767 in IGF1 might serve as potential susceptibility loci for T2DM in Uyghurs. We suggest a broader capture and study of the world populations, including who that are hitherto understudied, are essential for a comprehensive understanding of the genetic/genomic basis of T2DM.

Background: DNA methylation in sputum has been an attractive candidate biomarker for the non-invasive screening and detection of lung cancer. Materials and Methods: Databases including PubMed, Ovid, Cochrane library, Web of Science databases, Chinese Biological Medicine (CBM), Chinese National Knowledge Infrastructure (CNKI), Wanfang, Vip Databases and Google Scholar were searched to collect the diagnostic trials on aberrant DNA methylation in the screening and detection of lung cancer published until 1 December 2016. Indirect comparison meta-analysis was used to evaluate the diagnostic value of the included candidate genes. Results: The systematic literature search yielded a total of 33 studies including a total of 4801 subjects (2238 patients with lung cancer and 2563 controls) and covering 32 genes. We identified that methylated genes in sputum samples for the early screening and auxiliary detection of lung cancer yielded an overall sensitivity of 0.46 (0.41–0.50) and specificity of 0.83 (0.80–0.86). Combined indirect comparisons identified the superior gene of SOX17 (sensitivity: 0.84, specificity: 0.88), CDO1 (sensitivity: 0.78, specificity: 0.67), ZFP42 (sensitivity: 0.87, specificity: 0.63) and TAC1 (sensitivity: 0.86, specificity: 0.75). Conclusions: The present meta-analysis demonstrates that methylated SOX17, CDO1, ZFP42, TAC1, FAM19A4, FHIT, MGMT, p16, and RASSF1A are potential superior biomarkers for the screening and auxiliary detection of lung cancer.

Background Drug absorption, distribution, metabolism and excretion (ADME) contribute to the high heterogeneity of drug responses in humans. However, the same standard for drug dosage has been applied to all populations in China although genetic differences in ADME genes are expected to exist in different ethnic groups. In particular, the ethnic minorities in northwestern China with substantial ancestry contribution from Western Eurasian people might violate such a single unified standard. Methods In this study, we used Affymetrix SNP Array 6.0 to investigate the genetic diversity of 282 ADME genes in five northwestern Chinese minority populations, namely, Tajik, Uyghur, Kazakh, Kirgiz and Hui, and attempted to identify the highly differential SNPs and haplotypes and further explore their clinical implications. Results We found that genetic diversity of many ADME genes in the five minority groups was substantially different from those in the Han Chinese population. For instance, we identified 10 functional SNPs with substantial allele frequency differences, 14 functional SNPs with highly different heterozygous states and eight genes with significant haplotype differences between these admixed minority populations and the Han Chinese population. We further confirmed that these differences mainly resulted from the European gene flow, that is, this gene flow increased the genetic diversity in the admixed populations. Conclusions These results suggest that the ADME genes vary substantially among different Chinese ethnic groups. We suggest it could cause potential clinical risk if the same dosage of substances (eg, antitumour drugs) is used without considering population stratification.

Context : The Chinese government launched a comprehensive healthcare reform to tackle challenges to health equities. Medical education will become the key for successful healthcare reform. Purpose : We describe the current status of the Chinese medical degree system and its evolution over the last 80 years. Content : Progress has been uneven, historically punctuated most dramatically by the Cultural Revolution. There is a great regional disparity. Doctors with limited tertiary education may be licensed to practice, whereas medical graduates with advanced doctorates may have limited clinical skills. There are undefined relationships between competing tertiary training streams, the academic professional degree, and the clinical residency training programme (RTP). The perceived quality of training in both streams varies widely across China. As the degrees of master or doctor of academic medicine is seen as instrumental in career advancement, including employability in urban hospitals, attainment of this degree is sought after, yet is often unrelated to a role in health care, or is seen as superior to clinical experience. Meanwhile, the practical experience gained in some prestigious academic institutions is deprecated by the RTP and must be repeated before accreditation for clinical practice. This complexity is confusing both for students seeking the most appropriate training, and also for clinics, hospitals and universities seeking to recruit the most appropriate applicants. Conclusion : The future education reforms might include: 1) a domestic system of ‘credits’ that gives weight to quality clinical experience vs. academic publications in career advancement, enhanced harmonisation between the competing streams of the professional degree and the RTP, and promotion of mobility of staff between areas of excellence and areas of need; 2) International – a mutual professional and academic recognition between China and other countries by reference to the Bologna Accord, setting up a system of easily comparable and well-understood medical degrees. Keywords : medical degree; medical education; medical licensing; Bologna Accords; China (Published: 15 January 2014) Citation: Med Educ Online 2014, 19 : 23141 - http://dx.doi.org/10.3402/meo.v19.23141

Supplemental Digital Content is available in the text, As an important post-translation modifying process, glycosylation significantly affects the structure and function of immunoglobulin G (IgG) molecules and is essential in many steps of the inflammatory cascade. Studies have demonstrated the potential of using glycosylation features of IgG as a component of predictive biomarkers for chronological age in several European populations, whereas no study has been reported in Chinese. Herein, we report various patterns of changes in IgG glycosylation associated with age by analyzing IgG glycosylation in 701 community-based Han Chinese (244 males, 457 females; 23–68 years old). Eleven IgG glycans, including FA2B, A2G1, FA2[6]G1, FA2[3]G1, FA2[6]BG1, FA2[3]BG1, A2G2, A2BG2, FA2G2, FA2G2S1, and FA2G2S2, change considerably with age and specific combinations of these glycan features can explain 23.3% to 45.4% of the variance in chronological age in this population. This indicates that these combinations of glycan features provide more predictive information than other single markers of biological age such as telomere length. In addition, the clinical traits such as fasting plasma glucose and aspartate aminotransferase associated with biological age are strongly correlated with the combined glycan features. We conclude that IgG glycosylation appears to correlate with both chronological and biological ages, and thus its possible role in the aging process merits further study.

Background: Genome-wide association studies (GWAS) found that IGF2BP2 rs4402960 and rs1470579 polymorphisms were associated with type 2 diabetes mellitus (T2DM) risk. Many studies have replicated this association, but yielded inconsistent results. Materials and Methods: A case-control study consisting of 461 T2DM patients and 434 health controls was conducted to detect the genetic susceptibility of IGF2BP2 in a northern Han Chinese population. A meta-analysis was to evaluate the association more precisely in Asians. Results: In the case-control study, the carriers of TT genotype at rs4402960 had a higher T2DM risk than the G carriers (TG + GG) (adjusted odd ratio (AOR) = 1.962, 95% confidence interval (95% CI) = 1.065–3.612, p = 0.031]; CC carriers at rs1470579 were more susceptible to T2DM than A carriers (CA + AA) (AOR = 2.014, 95% CI = 1.114–3.642, p = 0.021). The meta-analysis containing 36 studies demonstrated that the two polymorphisms were associated with T2DM under the allele comparison, genetic models of dominant and recessive in Asians (p < 0.05). The rs4402960 polymorphisms were significantly associated with the T2DM risk after stratification by diagnostic criterion, size of sample and average age and BMI of cases, while there’re no consistent results for rs1470579. Conclusions: Our data suggests that IGF2BP2 polymorphisms are associated with T2DM in Asian populations.

Background Among the Chinese population of 1.3 billion, there are an estimated 93 million carriers of hepatitis B virus (HBV). Men who have sex with men (MSM) are at increased risk for HBV infection; however, the prevalence of HBV immunization and infection among Chinese MSM remains undetermined. Methods A cross-sectional survey of 1,114 eligible participants was conducted in Beijing, China. Multiple methods were used to recruit study participants. Demographic information and potential correlated factors were collected by questionnaire. Additionally, blood specimens were collected and tested for sexually transmitted infections and serologic markers of hepatitis B immunization and infection. Results Laboratory data were available for 1,111 participants (99.7%), the prevalence of hepatitis B immunization was 38.9%, and 26.5% had serologic markers of HBV infection. Multivariate analyses indicated that higher education level, smaller number of male sex partners in the past 12 months, reported diagnosis of sexually transmitted disease (STD), and history of blood donation were independently associated with HBV immunization. Absence of steady male sex partner(s) in the past 12 months, and reported diagnosis of STD were shown to be independently associated with HBV infection. MSM positive for HBV infection were more likely to have past or current syphilis infection. Conclusions Low prevalence of HBV immunization and high prevalence of HBV infection among Chinese MSM and a correlation between sexual risk factors and hepatitis B infection indicate that comprehensive preventative measures for HBV among MSM, including blood donor and HIV-STD clinic vaccination programs as well as targeted health education campaigns should be developed in China.

Highlights: {yields} Knock down of hCLP46 by RNAi impairs mammalian Notch signaling. {yields} hCLP46 affects neither cell surface Notch1 expression nor ligand-receptor binding. {yields} Knock down of hCLP46 inhibits U937 cell-growth by up-regulation of CDKN1B. -- Abstract: Human CAP10-like protein 46 kDa (hCLP46) is the homolog of Rumi, which is the first identified protein O-glucosyltransferase that modifies Notch receptor in Drosophila. Dysregulation of hCLP46 occurs in many hematologic diseases, but the role of hCLP46 remains unclear. Knockdown of hCLP46 by RNA interference resulted in decreased protein levels of endogenous Notch1, Notch intracellular domain (NICD) and Notch target gene Hes-1, suggesting the impairment of the Notch signaling. However, neither cell surface Notch expression nor ligand binding activities were affected. In addition, down-regulated expression of hCLP46 inhibited the proliferation of U937 cells, which was correlated with increased cyclin-dependent kinase inhibitor (CDKI) CDKN1B (p27) and decreased phosphorylation of retinoblastoma (RB) protein. We showed that lack of hCLP46 results in impaired ligand induced Notch activation in mammalian cell, and hCLP46 regulates the proliferation of U937 cell through CDKI-RB signaling pathway, which may be important for the pathogenesis of leukemia.

N-glycans play an essential role in biological process and are associated with age, gender, and body mass parameters in Caucasian populations, whereas no study has been reported in Chinese populations. To investigate the correlation between N-glycan structures and metabolic syndrome (MetS) components, we conducted a population-based study in 212 Chinese Han individuals. The replication study was performed on 520 unrelated individuals from a Croatian island Korčula. The most prominent observation was the consistent positive correlations between different forms of triantennary glycans and negative correlations between glycans containing core-fucose with MetS components including BMI, SBP, DBP, and fasting plasma glucose (FPG) simultaneously. Significant differences in a number of N-glycan traits were also detected between normal and abnormal groups of BMI, BP, and FPG, respectively. In the multivariate analysis, the level of monosialylated glycans (structure loadings = -0.776) was the most correlated with the MetS related risk factors, especially with SBP (structure loadings = 0.907). Results presented here are showing that variations in the composition of the N-glycome in human plasma could represent the alternations of human metabolism and could be potential biomarkers of MetS.

Schizophrenia has increasingly been considered a neurodevelopmental disorder, and the advancement of neuroimaging techniques and associated computational methods has enabled quantitative re-examination of this important theory on the pathogenesis of the disease. Inspired by previous findings from neonatal brains, we proposed that an increase in diffusion magnetic resonance imaging (dMRI) mean diffusivity (MD) should be observed in the cerebral cortex of schizophrenia patients compared with healthy controls, corresponding to lower tissue complexity and potentially a failure to reach cortical maturation. We tested this hypothesis using dMRI data from a Chinese Han population comprising patients from four different hospital sites. Utilizing data-driven methods based on the state-of-the-art tensor-based registration algorithm, significantly increased MD measurements were consistently observed in the cortex of schizophrenia patients across all four sites, despite differences in psychopathology, exposure to antipsychotic medication and scanners used for image acquisition. Specifically, we found increased MD in the limbic system of the schizophrenic brain, mainly involving the bilateral insular and prefrontal cortices. In light of the existing literature, we speculate that this may represent a neuroanatomical signature of the disorder, reflecting microstructural deficits due to developmental abnormalities. Our findings not only provide strong support to the abnormal neurodevelopment theory of schizophrenia, but also highlight an important neuroimaging endophenotype for monitoring the developmental trajectory of high-risk subjects of the disease, thereby facilitating early detection and prevention.

The KCNQ1 rs2237892 C→T gene polymorphism is reportedly associated with T2DM susceptibility, but various studies show conflicting results. To explore this association in the Asian population, a meta-analysis of 15,736 patients from 10 individual studies was performed. The pooled odds ratios (ORs) and their 95% confidence intervals (CIs) were evaluated using random-effect or fixed-effect models. A significant relationship between the KCNQ1 rs2237892 C→T gene polymorphism and T2DM was observed in the Asian population under the allelic (OR, 1.350; 95% CI, 1.240–1.480; P

It is critical to distinguish events that are temporarily associated with, but not caused by, vaccination from those caused by vaccination during mass immunization. We performed a literature search in China National Knowledge Infrastructure and Pubmed databases. The number of coincident events was calculated based on its incidence rate and periods after receipt of a dose of hypothesized vaccine. We included background incidences of Guillain-Barré syndrome, anaphylaxis, seizure, sudden adult death syndrome, sudden cardiac death, spontaneous abortion, and preterm labour or delivery. In a cohort of 10 million individuals, 7.71 cases of Guillain-Barré syndrome would be expected to occur within six weeks of vaccination as coincident background cases. Even for rare events, a large number of events can be expected in a short period because of the large population targeted for immunization. These findings may encourage health authorities to screen the safety of vaccines against unpredictable pathogens.