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Purpose The objective of this study was to investigate the association of abnormal glycemic phenotypes with microvascular complications in type 2 diabetes patients. Participants and methods A total of 24,266 participants who were from the multicenter cross-sectional survey of China National HbA1c Surveillance System across China were included in the present study. Diabetes patients with abnormal glucose were divided into three groups according to phenotype: isolated fasting hyperglycemia (IFH), isolated postprandial hyperglycemia (IPH), or combined hyperglycemia (CH). The main outcomes were isolated diabetic retinopathy, isolated diabetic nephropathy, and combined diabetic retinopathy with nephropathy. Multivariate logistic regression was used to assess the association of abnormal glycemic phenotypes with microvascular complications. Results The CH phenotype had the highest prevalence of isolated diabetic retinopathy, isolated diabetic nephropathy and combined diabetic retinopathy with nephropathy, followed by IPH. Multivariate analysis showed that the CH phenotype was associated with the highest risk of isolated diabetic retinopathy (OR: 1.20, 95% CI: 1.02-1.41), isolated diabetic nephropathy (OR: 1.59, 95% CI: 1.27-2.01) and combined diabetic retinopathy with nephropathy (OR: 1.93, 95% CI: 1.44-2.59). More importantly, participants with IPH phenotype also showed significantly higher risks of isolated diabetic retinopathy (OR: 1.16, 95% CI: 1.05-1.28), isolated diabetic nephropathy (OR: 1.37, 95% CI: 1.09-1.37) and combined diabetic retinopathy with nephropathy (OR:1.64, 95% CI: 1.21-2.21) compared to the IFH phenotype. After stratifying by age, sex, diabetes duration and BMI, the higher risks of isolated diabetic retinopathy, isolated diabetic nephropathy and combined diabetic retinopathy with nephropathy were confirmed in IPH phenotype group, compared to the IFH phenotype group. Conclusion Diabetic patients with IPH phenotype had higher risks of isolated diabetic retinopathy, isolated diabetic nephropathy and combined diabetic retinopathy with nephropathy compared with the participants phenotype of IFH, but lower than the phenotype of CH.

BackgroundIt is unclear the role of longitudinal trajectory of serum uric acid (SUA) on the development of non-alcoholic fatty liver disease (NAFLD). We aimed to determine whether longitudinal SUA trajectories are associated with the risk of new-onset NAFLD.MethodsWe explored the relationship between SUA trajectories and NAFLD in a cohort including 3822 participants. Individual’s SUA trajectories from 2012 to 2014 were defined using group-based trajectory modeling analysis in four distinct patterns: trajectory 1 (n = 991, 25.93%), trajectory 2 (n = 1421, 37.18%), trajectory 3 (n = 1156, 30.22%), and trajectory 4 (n = 254, 6.67%). The logistic regression model was used to evaluate the association between SUA changing trajectories and subsequent NAFLD until 2016. Dose–response relationship between SUA changing trajectories and NAFLD risk was evaluated through the testing of trajectory groups as a continuous variable.ResultsThe 2-year incidence of NAFLD was 13.27%. Compared with trajectory 1, the adjusted odds risk for NAFLD development was in a dose–response relationship as follows: 1.27 (95% CI 0.91–1.78) for trajectory 2, 1.89 (95% CI 1.29–2.75) for trajectory 3, and 2.34 (95% CI 1.43–3.83) for trajectory 4. And this dose–response relationship was not affected by age, sex, and abdominal obesity.ConclusionsHigher SUA changing trajectory is a risk factor for NAFLD. This finding highlights the importance of paying attention to SUA changing trajectory on the detection and prevention of NAFLD.

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.

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

Background: Circulating miRNAs have been identified as diagnostic biomarkers for esophageal squamous cell carcinoma (ESCC), but their efficacy in discovering early-stage ESCC is still unsatisfying. Esophageal squamous dysplasia (ESD) is the precursor lesion of ESCC. Notably, little is known about the role(s) of circulating miRNAs in identifying ESD. In this study, we, therefore, aimed to identify serum miRNAs as novel diagnostic markers for detecting ESD and ESCC. Methods: The genome-wide miRNA expression was profiled in 104 (52 ESCC and 52 controls) serum samples using microarray. Seven candidate miRNAs from the microarray assay were evaluated for their diagnostic performance in another cohort of 266 participants (96 ESCC, 92 ESD, and 78 healthy controls). Results: The serum levels of miR-16-5p, miR-197-5p, miR-451a, and miR-92a-3p were associated with ESCC; the biomarker based on the panel of these four miRNAs could efficiently distinguish patients with ESCC from the controls [AUC = 0.856; 95% confidence interval (CI), 0.794–0.905; P < 0.001]. The serum levels of miR-16-5p, miR-320c, miR-638, and miR-92a-3p were significantly higher in patients with ESD than in controls, and this four-miRNA signature could efficiently differentiate patients with ESD from the controls (AUC = 0.842; 95% CI, 0.778–0.893; P < 0.001). In addition, compared with serum carcinoembryonic antigen and carbohydrate antigen 199, miRNA-based panels had a better diagnostic performance in distinguishing patients with ESCC and ESD from healthy controls. Conclusions: Our study identified two novel panels of circulating miRNAs with high efficiency in detecting ESCC and ESD, suggesting that circulating miRNAs, in particular the combination of them, might serve as noninvasive biomarkers for the early detection of ESCC. Impact: This study suggests the feasibility of using circular miRNA-based blood tests to aid in the detection of ESD and ESCC.

Hypertrophic cardiomyopathy (HCM) is a complex inherited cardiovascular disease. The present study investigated the long noncoding (lnc)RNA/microRNA (mi)RNA/mRNA expression pattern of patients with HCM and aimed to identify key molecules involved in the development of this condition. An integrated strategy was conducted to identify differentially expressed miRNAs (DEmiRs), differentially expressed lncRNAs (DElncs) and differentially expressed genes (DEGs) based on the {"type":"entrez-geo","attrs":{"text":"GSE36961","term_id":"36961"}}GSE36961 (mRNA), {"type":"entrez-geo","attrs":{"text":"GSE36946","term_id":"36946"}}GSE36946 (miRNA), {"type":"entrez-geo","attrs":{"text":"GSE68316","term_id":"68316"}}GSE68316 (lncRNA/mRNA) and {"type":"entrez-geo","attrs":{"text":"GSE32453","term_id":"32453"}}GSE32453 (mRNA) expression profiles downloaded from the Gene Expression Omnibus datasets. Bioinformatics tools were employed to perform function and pathway enrichment analysis, protein-protein interaction, lncRNA-miRNA-mRNA and hub gene networks. Subsequently, DEGs were used as targets to predict drugs. The results indicated that a total of 2,234 DElncs (1,120 upregulated and 1,114 downregulated), 5 DEmiRs (2 upregulated and 3 downregulated) and 42 DEGs (35 upregulated and 7 downregulated) were identified in 4 microarray profiles. Gene ontology analysis revealed that DEGs were mainly involved in actin filament and stress fiber formation and in calcium ion binding, whereas Kyoto Encyclopedia of Genes and Genomes pathway analysis identified the hypoxia inducible factor-1, transforming growth factor-β and tumor necrosis factor signaling pathways as the main pathways involved in these processes. The hub genes were screened using cytoHubba. A total of 1,086 lncRNA-miRNA-mRNA interactions including 67 lncRNAs, 5 miRNAs and 25 mRNAs were mined in the present study based on prediction websites. Drug prediction indicated that the targeted drugs mainly included angiotensin converting enzyme inhibitors or β-blockers. A comprehensive bioinformatics analysis of the molecular regulatory lncRNA-miRNA-mRNA network was performed and potential therapeutic applications of drugs were predicted in HCM patients. The data may unravel the future molecular mechanism of HCM.

The longitudinal association between glycated hemoglobin (HbA1c) and different courses of depressive symptoms is understudied. This study aimed to identify different trajectories of depressive symptoms and investigate the relation of HbA1c with the risk of increasing and high-stable depressive symptoms. In the China Health and Retirement Longitudinal Study, depressive symptoms were measured using the 10-item Center for Epidemiological Studies-Depression scale in three visits (years: 2011, 2013 and 2015) among 9804 participants (mean age 60.0 ± 9.0 years). Group-based trajectory modeling was used to identify trajectories of depressive symptoms. HbA1c was measured at baseline and categorized five groups according to the respective quintile. Multinomial logistic regression was fitted to examine this relationship. Four distinct trajectories of depressive symptoms were identified: low symptoms (n=6401, 65.29%); decreasing symptoms (n=1362, 13.89%); increasing symptoms (n=1452, 14.81%); and high symptoms (n=1452, 14.81%). Adjusting for demographic, health-related, and cognitive factors, the risk ratio (95% confidence interval) pertaining to the highest HbA1c (Quintile 5) for decreasing, increasing, and high symptoms of depression versus low symptoms was 1.01 (0.82-1.25), 1.12 (0.92-1.36), and 1.39 (1.04-1.86) compared with the lowest HbA1c (Quintile 1), respectively. We observed a J-shaped relationship between HbA1c and high depressive symptoms, with the lowest risk at a HbA1c concentration of 5.0%. In summary, in this large population-based cohort, high levels of glycated hemoglobin concentrations were associated with a higher risk of increasing and high-stable symptoms of depression.

Objectives: Hypertension and type 2 diabetes mellitus comorbidity (HDC) is common, which confers a higher risk of cardiovascular disease than the presence of either condition alone. Describing the underlying glycomic changes of immunoglobulin G (IgG) that predispose individuals to HDC may help develop novel protective immune-targeted and anti-inflammatory therapies. Therefore, we investigated glycosylation changes of IgG associated with HDC. Methods: The IgG N-glycan profiles of 883 plasma samples from the three northwestern Chinese Muslim ethnic minorities and the Han Chinese were analyzed by ultra-performance liquid chromatography instrument. Results: We found that 12 and six IgG N-glycan traits showed significant associations with HDC in the Chinese Muslim ethnic minorities and the Han Chinese, respectively, after adjustment for potential confounders and false discovery rate. Adding the IgG N-glycan traits to the baseline models, the area under the receiver operating characteristic curves (AUCs) of the combined models differentiating HDC from hypertension (HTN), type 2 diabetes mellitus (T2DM), and healthy individuals were 0.717, 0.747, and 0.786 in the pooled samples of Chinese Muslim ethnic minorities, and 0.828, 0.689, and 0.901 in the Han Chinese, respectively, showing improved discriminating performance than both the baseline models and the glycan-based models. Conclusion: Altered IgG N-glycan profiles were shown to associate with HDC, suggesting the involvement of inflammatory processes of IgG glycosylation. The alterations of IgG N-glycome, illustrated here for the first time in HDC, demonstrate a biomarker potential, which may shed light on future studies investigating their potential for monitoring or preventing the progression from HTN or T2DM towards HDC.

The study aims to identify clinical factors affecting tacrolimus blood trough concentration (C0) in myasthenia gravis (MG) patients and to optimize the initial dose of tacrolimus in MG treatment. A total of 103 MG patients participated in this study, and their clinical factors, medication regimens, C0 values and CYP3A5*3 polymorphisms were collected in detail. We used a linear mixed model to analyze the effect of multiple factors on the dosage-weighted C0 (C0:D) and performed subgroup analyses to investigate the consistency of correlations between influencing factors and the C0:D ratios. Among all factors, CYP3A5*3 polymorphism and age showed a strong positive correlation with C0:D ratios. The C0:D ratios (ng/ml·mg−1) were higher for CYP3A5*3/*3 than for CYP3A5*1 (mean difference: 1.038, 95% confidence interval [CI]: 0.820–1.256, P-value

Background Associations between the frequency of social and intellectual activities and cognitive trajectories are understudied in Chinese middle-aged and older adults. We aimed to examine this association in a nationally representative longitudinal study. Methods The China Health and Retirement Longitudinal Study (CHARLS) is a nationally representative sample of Chinese middle-aged and older participants. The frequency of social and intellectual activities was measured at baseline. Interview-based cognitive assessments of orientation and attention, episodic memory, and visuospatial skills and the calculation of combined global scores were assessed every 2 years from 2011 to 2016. Cognitive aging trajectories over time were analyzed using group-based trajectory modeling, and the associations of the trajectory memberships with social and intellectual activities were analyzed using multinomial logistic regression. Odds ratios (OR) and 95% confidence intervals (CI) were reported. Results Among 8204 participants aged 50–75 years at baseline, trajectory analysis identified three longitudinal patterns of cognitive function based on the global cognitive scores: “persistently low trajectory” (n = 1550, 18.9%), “persistently moderate trajectory” (n = 3194, 38.9%), and “persistently high trajectory” (n = 3460, 42.2%). After adjustment for sociodemographic variables, lifestyles, geriatric symptoms, and health conditions, more frequent intellectual activities (OR 0.54, 95% CI 0.38–0.77) and social activities (OR 0.79, 95% CI 0.65–0.95) were both associated with a lower likelihood of being in the “persistently low trajectory” for global cognitive function. Conclusions These findings suggested that more frequent social and intellectual activities were associated with more favorable cognitive aging trajectories.

Background Some previous studies on different populations have yielded inconsistent findings with respect to the relationship between levels of high-density lipoprotein cholesterol (HDL-C) and future type 2 diabetes mellitus (T2DM) incidence. This study was designed to gain further insight into this relationship through a cohort study with a 25-year follow-up duration. Methods In total, 1462 individuals that were 55 years of age or older and were free of T2DM at baseline were enrolled in the present study. T2DM incidence among this study population was detected through self-reported diagnoses or the concentration of fasting plasma glucose. The data were derived from nine surveys conducted from 1992 to 2017. The correlation between HDL-C levels and the T2DM risk was assessed through Cox proportional-hazards model and proportional hazards model for the sub-distribution with time-dependent variables. Results Over the follow-up period, 120 participants were newly diagnosed with new-onset T2DM. When research participants were separated into four groups on the basis for quartiles of their levels of HDL-C measured at baseline, and incidence of diabetes declined with higher baseline HDL-C levels at 12.60, 9.70, 5.38, and 5.22 per 1000 person-years, respectively. Adjusted hazard ratios (HRs) were 0.98 (95% confidence interval [CI]: 0.62–1.55), 0.48 (95% CI: 0.27–0.85) and 0.44 (95% CI: 0.25–0.80) for individuals with HDL-C levels within the 1.15–1.39, 1.40–1.69, and ≥ 1.70 mmol/L ranges relative to participants with HDL-C levels P values were 0.0296, 0.0011, respectively, for 5- and 10-year risk of diabetes). Conclusions Levels of HDL-C were independently and negatively associated with the risk of the new-onset T2DM among middle-aged and elderly Chinese.

The temporal relationship between hyperuricemia and non-alcoholic fatty liver disease (NAFLD) is debatable. This study aimed to explore whether there exists a bidirectional or temporal relationship between them.A total of 11,585 participants were recruited from the Beijing Health Management Cohort during the period 2012-2016. We evaluated whether hyperuricemia was associated with NAFLD development (part I) and whether NAFLD was associated with hyperuricemia incidence (part II) using a logistic regression model. Further, the cross-lagged panel analysis model was used to simultaneously examine the bidirectional relationship between hepatic steatosis and serum uric acid (SUA) (part III). Subgroup and interaction analyses were also performed to assess whether other variables moderated those relationships.In part I, multiple logistic regression indicated that baseline hyperuricemia was associated with the development of NAFLD (OR = 1.5970, p 0.0001). In part II, multiple logistic regression showed that baseline NAFLD was not correlated with hyperuricemia incidence (OR = 0.8600, p = 0.1976). In part III, cross-lagged panel analyses indicated that the standard regression coefficient of baseline SUA to follow-up hepatic steatosis (0.1516) was significantly greater than the coefficient from the baseline hepatic steatosis to follow-up SUA (-0.0044) with p 0.0001 for the difference. This indicated a unidirectional relationship from baseline SUA to follow-up hepatic steatosis, suggesting hyperuricemia may precede NAFLD; and this relationship was not affected by age, sex, dyslipidemia, metabolism syndrome, diabetes but was moderated by abdominal obesity.This study demonstrated a unidirectional relationship from hyperuricemia to NAFLD incidence, and suggested that lowering SUA levels in hyperuricemia patients may prevent subsequent NAFLD.

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 & aims Although evidence indicates that visceral adipose tissue is associated with nonalcoholic fatty liver disease (NAFLD), it is unclear whether the visceral adiposity index (VAI) can predict the onset of NAFLD. This study aimed to determine whether the VAI is an independent risk factor of NAFLD and whether there is a dose-response relationship. Methods We explored the relationship between VAI levels and NAFLD in a health check-up cohort established in 2012. There were 4809 subjects with baseline data and results from 4 follow-up examinations. The diagnosis of NAFLD was established by demonstration of increased hepatic echogenicity with ultrasound and exclusion of alcohol overconsumption with questionnaires. We divided the subjects into 4 groups according to baseline VAI levels and used the Cox hazard regression model to estimate NAFLD risk by VAI quartile at baseline by adjusting for potential confounding factors. A Kaplan-Meier survival analysis was used to compare the risk of NAFLD incidence among individuals in each VAI quartile. Results The 4-year cumulative incidence of NAFLD in this cohort was 13.9%. The hazard ratios (95% confidence intervals, 95% CI) for NAFLD in the second, third and fourth VAI quartiles compared with the first quartile were 1.42 (95% CI: 1.24-1.64), 1.73 (95% CI: 1.51-1.99) and 2.13(95% CI: 1.86-2.45) respectively. The Kaplan-Meier survival analysis suggested that higher VAI levels predict higher incidences of NAFLD in a dose-dependent relationship. Conclusions Our findings suggest that the VAI level is an independent risk factor of NAFLD and there is a dose-response relationship between VAI level and NAFLD risk.

Key Points Question Are depressive symptoms associated with incident cardiovascular disease among middle-aged and older Chinese adults? Findings In this cohort study of 12 417 Chinese adults, participants with depressive symptoms at baseline had higher incident rates of cardiovascular disease compared with those without such symptoms. Elevated depressive symptoms as a whole and 2 individual symptoms (restless sleep and loneliness) were significantly associated with increased risk of cardiovascular disease after adjusting for potential confounders. Meaning This study suggests that depressive symptoms, particularly restless sleep and loneliness, may be associated with incident cardiovascular disease among middle-aged and older Chinese adults., This cohort study examines the association between depressive symptoms and incident cardiovascular disease among middle-aged and older Chinese adults., Importance The prevalence of depressive symptoms among older adults has become an increasingly important public health priority. Elevated depressive symptoms are well documented among elderly people with cardiovascular disease (CVD), but studies conducted among Chinese adults are scarce. Objective To estimate the association between depressive symptoms and incident CVD among middle-aged and older Chinese adults. Design, Setting, and Participants The China Health and Retirement Longitudinal Study is an ongoing nationally representative prospective cohort study that was initiated in 2011. This cohort study included 12 417 middle-aged and older Chinese adults without heart disease and stroke at baseline. Statistical analysis was conducted from April 25, 2018, to December 13, 2018. Exposure Depressive symptoms were assessed using the validated 10-item of Center for Epidemiologic Studies Depression Scale. Main Outcomes and Measures Incident CVD (ie, self-reported physician-diagnosed heart disease and stroke combined) was followed-up from June 1, 2011, to June 31, 2015. The Center for Epidemiologic Studies Depression Scale total score ranges from 0 to 30, with a score of 12 or more indicating elevated depressive symptoms. Results Of the 12 417 participants (mean [SD] age at baseline, 58.40 [9.51] years), 6113 (49.2%) were men. During the 4 years of follow-up, 1088 incident CVD cases were identified. Elevated depressive symptoms were independently associated with an increased CVD risk (adjusted hazard ratio, 1.39; 95% CI, 1.22-1.58) after adjusting for age, sex, residence, marital status, educational level, smoking status, drinking status, systolic blood pressure, and body mass index; history of diabetes, hypertension, dyslipidemia, and chronic kidney disease; and use of hypertension medications, diabetes medications, and lipid-lowering therapy. Of the 10 individual depressive symptoms measured by the Center for Epidemiologic Studies Depression Scale, only 2 symptoms, restless sleep (adjusted hazard ratio, 1.21; 95% CI, 1.06-1.39) and loneliness (adjusted hazard ratio, 1.21; 95% CI, 1.02-1.44), were significantly associated with incident CVD. Conclusions and Relevance Elevated depressive symptoms overall and 2 individual symptoms (restless sleep and loneliness) were significantly associated with incident CVD among middle-aged and older Chinese adults.

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To evaluate the capability of PET/CT images for differentiating the histologic subtypes of non-small cell lung cancer (NSCLC) and to identify the optimal model from radiomics-based machine learning/deep learning algorithms. In this study, 867 patients with adenocarcinoma (ADC) and 552 patients with squamous cell carcinoma (SCC) were retrospectively analysed. A stratified random sample of 283 patients (20%) was used as the testing set (173 ADC and 110 SCC); the remaining data were used as the training set. A total of 688 features were extracted from each outlined tumour region. Ten feature selection techniques, ten machine learning (ML) models and the VGG16 deep learning (DL) algorithm were evaluated to construct an optimal classification model for the differential diagnosis of ADC and SCC. Tenfold cross-validation and grid search technique were employed to evaluate and optimize the model hyperparameters on the training dataset. The area under the receiver operating characteristic curve (AUROC), accuracy, precision, sensitivity and specificity was used to evaluate the performance of the models on the test dataset. Fifty top-ranked subset features were selected by each feature selection technique for classification. The linear discriminant analysis (LDA) (AUROC, 0.863; accuracy, 0.794) and support vector machine (SVM) (AUROC, 0.863; accuracy, 0.792) classifiers, both of which coupled with the l2,1NR feature selection method, achieved optimal performance. The random forest (RF) classifier (AUROC, 0.824; accuracy, 0.775) and l2,1NR feature selection method (AUROC, 0.815; accuracy, 0.764) showed excellent average performance among the classifiers and feature selection methods employed in our study, respectively. Furthermore, the VGG16 DL algorithm (AUROC, 0.903; accuracy, 0.841) outperformed all conventional machine learning methods in combination with radiomics. Employing radiomic machine learning/deep learning algorithms could help radiologists to differentiate the histologic subtypes of NSCLC via PET/CT images.

AimsThis study aimed to examine the association of different anatomical forms of obesity with adipose tissue insulin resistance and to assess the diagnostic value and contribution of obesity to adipose tissue insulin resistance.MethodsThis cross-sectional study included a total of 499 subjects aged 50 years or over. Multivariate regression analysis was conducted to clarify the association of different forms of obesity with adipose tissue insulin resistance (calculated as fasting insulin level×fasting free fatty acids level). Receiver operating characteristic cure analyses were used to assess the diagnostic value of each anthropometric indicator for adipose tissue insulin resistance. Attributable risk per cent and population attributable risk per cent were calculated to assess the contribution of obesity to adipose tissue insulin resistance.ResultsAfter adjustment for potential confounders, we showed that anthropometric indicators were all positively associated with adipose tissue insulin resistance. In males, waist circumference (WC) was the strongest associated factor (OR, 3.43 (95% CI 2.03 to 5.82)) and indicator (area under the curve (AUC): 0.79) of adipose tissue insulin resistance among those indicators. Here, abdominal obesity (WC≥90 cm) accounted for 64.9% of adipose tissue insulin resistance in the abdominal obese males. Accordingly, body mass index (BMI) was the strongest associated factor (OR,3.08 (95% CI 2.04 to 4.66)) and indicator (AUC: 0.78) of adipose tissue insulin resistance in females. Here, general obesity of BMI≥25 kg/m2 accounted for 66.2% of the adipose tissue insulin resistance in the general obese females. We further demonstrated that adipose tissue insulin resistance was associated or trended to be associated with the metabolic diseases of cardiovascular disease, type 2 diabetes and fatty liver in subjects with normal BMI and WC.ConclusionsMaintaining WC in males and BMI in females to a normal range could be an important strategy to significantly reduce the occurrence of adipose tissue insulin resistance and the subsequent metabolic diseases.

Introduction: Circulating microRNAs (miRNAs) are promising molecular biomarkers for the early detection of esophageal squamous cell carcinoma (ESCC). We investigated the serum miRNA expression profiles from microarray-based technologies and evaluated the diagnostic value of serum miRNAs as potential biomarkers for ESCC by using feature selection algorithms.Methods: Serum miRNA expression profiles were obtained from 52 ESCC patients and 52 age- and sex-matched controls via performing a high-throughput microarray assay. Five representative feature selection algorithms including the false discovery rate procedure, family-wise error rate procedure, Lasso logistic regression, hybrid huberized support vector machine (SVM), and SVM using the squared-error loss with the elastic-net penalty were jointly carried out to select the significantly differentially expressed miRNAs based on the miRNA profiles.Results: Three miRNAs including miR-16-5p, miR-451a, and miR-574-5p were identified as the powerful biomarkers for the diagnosis of ESCC. The diagnostic accuracy of the combination of these three miRNAs was evaluated by using logistic regression and the SVM. The averages of the area under the receiver operating curve and classification accuracies based on different classifiers were more than 0.80 and 0.79, respectively. The cross-validation results suggested that the three-miRNA-based classifiers could clearly distinguish ESCC patients from healthy controls. Moreover, the classifying performance of the miRNA panel persisted in discriminating the healthy group from patients with ESCC stage I-II (AUC > 0.76) and patients with ESCC stage III-IV (AUC > 0.80).Conclusions: These results in this study have moved forward the identification of novel biomarkers for the diagnosis of ESCC.

Background Cognitive impairment may increase the risk of all‐cause and cardiovascular disease ( CVD ) mortality. This study examined the association between cognitive function and risk of all‐cause and CVD mortality among the elderly in Beijing, China. Methods and Results A total of 1996 participants aged ≥55 years at baseline were enrolled from the BLSA (Beijing Longitudinal Study of Aging). Cognitive function was assessed using the Mini‐Mental State Examination ( MMSE ), and participants were categorized as: HR ) and 95% confidence interval ( CI ) were reported. During a 20‐year follow‐up, 1122 (56.21%) participants died, 478 (42.60%) of whom died of CVD . Compared with MMSE scores of 28 to 30, participants with MMSE scores of hazard ratio, 2.14; 95% confidence interval, 1.59–2.87; P , 4.52; 95% confidence interval , 2.80–7.30, P MMSE score was associated with a 34% increased risk of all‐cause mortality and a 56% increased risk of CVD mortality. This relationship remained statistically significant after using the competing risk model to consider non‐ CVD death as a competing risk event. Conclusion Cognitive impairment measured by MMSE score was associated with elevated risk of all‐cause and CVD mortality among the elderly in Beijing, China.

Background Epidemiologic evidence on metabolically healthy obese (MHO) phenotype and cardiovascular diseases (CVD) risk remains controversial. Aims We aim to examine the relationship between MHO and risk of CVD among the Chinese population. Methods The China Health and Retirement Longitudinal Study is a prospective cohort study of 7849 participants aged ≥45 years without CVD at baseline. Metabolic health status was assessed based on blood pressure, triglycerides, high-density lipoprotein cholesterol, glycated hemoglobin, fasting glucose, and C-reactive protein. A cutoff point of body mass index of 24.0 kg/m2 was used to define over-weight/obesity (≥24.0 kg/m2) or normal weight ( Results During a mean 3.6 years of follow-up, 880 incident CVD events were recorded. 789 (10.05%) were identified MHO among 3321 (42.3%) obese individuals. Compared with metabolically healthy normal weight individuals, the multivariable adjusted IRR of CVD was 1.33 (95%CI: 1.19–1.49) for MHO, 1.29 (95%CI: 1.22–1.38) for metabolically unhealthy normal weight, and 1.61 (95%CI: 1.51–1.75) for metabolically unhealthy obese in the full adjusted model. Conclusions MHO individuals are associated with the increased risk of cardiovascular diseases among the Chinese population.

Objectives Delayed paraplegia developed postoperatively after thoracoabdominal aneurysm surgery is primarily associated with spinal cord ischemia/reperfusion injury. Our previous study suggested that spinal cord stimulation postconditioning protected the spinal cord from ischemia/reperfusion injury through microglia inhibition. In this study, we further investigated whether α7 nicotinic acetylcholine receptors were involved in the neuroprotective mechanism of spinal cord stimulation. Methods Rabbits were randomly assigned to sham, control, 2 Hz, α-bungarotoxin, and 2 Hz-α-bungarotoxin groups (n = 24/group). Transient spinal cord ischemia was performed on all rabbits except rabbits in the sham group. Rabbits in the control group received no further intervention, rabbits in the 2 Hz group were given 2 Hz spinal cord stimulation, rabbits in the α-bungarotoxin group received prescribed intrathecal α-bungarotoxin (α-bungarotoxin, a specific α7 nicotinic acetylcholine receptor antagonist) injections, and rabbits in the 2 Hz-α-bungarotoxin group received both α-bungarotoxin injections and 2 Hz spinal cord stimulation. Hind-limb neurologic function was assessed, and spinal cord histologic examination, terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling staining, and microglia staining were performed at 8 hours, 1 day, 3 days, and 7 days of reperfusion. Results Rabbits in the 2 Hz group had significantly better neurologic functions, more α-motor neurons, and lower terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling–positive neuron rates and microglia area/anterior horn area ratios (microglia area ratios) than the control group. The neurologic functions of the α-bungarotoxin group were significantly worse than those of the control group, whereas other results were not significantly different from the control group. The results of the 2 Hz-α-bungarotoxin group were insignificant to the control group except for the terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling–positive neuron rates, which were significantly lower than in the control group. Conclusions The neuroprotective effects of spinal cord stimulation postconditioning against spinal cord ischemia/reperfusion injury were partially mediated by activating α7 nicotinic acetylcholine receptors.

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.

Background Depressive symptoms tend to fluctuate over time. Data on the relationship between time-dependent depressive symptoms and the risk of cardiovascular and all-cause mortality among the elderly in China are lacking. Methods and results A prospective cohort of 1999 subjects aged ≥55 years were enrolled in the Beijing Longitudinal Study of Aging since 1992. Depressive symptoms were assessed at baseline (0 years) and after 2, 5, 8, and 12 years, defined as a score of ≥16 on the 20-item Center for Epidemiological Studies Depression Scale. Mortality status was obtained from the local death registry until December 31st, 2012. Hazard ratio (HR) for all-cause mortality and sub-distribution HR (SHR) for cardiovascular mortality were respectively deduced from time-dependent Cox and competing risk models. During 19,658 person-years of follow-up, 1127 (55.65%) deaths were recorded, of which 483 (23.85%) were attributable to cardiovascular inclinations. Baseline depressive symptoms were neither associated with all-cause mortality (adjusted HR: 1.12, 95% confident interval, CI: 0.94–1.33) nor cardiovascular mortality (adjusted SHR: 1.10, 95% CI: 0.82–1.46) after adjustment of potential cardiac-risk factors. When depressive symptoms were used as time-dependent variable updated from 1992 to 2004, the associations were significant for both all-cause mortality (adjusted HR: 1.48, 95% CI: 1.26–1.73) and cardiovascular mortality (adjusted SHR: 1.40, 95% CI: 1.08–1.82) in the full adjusted model. Conclusions Time-dependent depressive symptoms increased the risk of all-cause and cardiovascular mortality among the elderly in China.

Disability has become a critical issue among elderly populations, yet limited large-scale research related to this issue has been conducted in China, an aging society. This study explored sex and urban-rural differences in disability transitions and life expectancies among older adults in China. Data were collected from the Chinese Longitudinal Health Longevity Survey (CLHLS), which enrolled people aged 65 and older and was conducted in randomly selected counties and cities across 22 provinces in China. Disability was diagnosed based on basic activities of daily living (BADLs) and instrumental activities of daily living (IADLs). Several individual characteristics were assessed, including sociodemographic factors (age, sex and region, etc.) and health behaviors (currently smoking, currently drinking, etc.). Multistate models were applied to analyze the transition rates among 4 states: no disability, mild disability, severe disability and death. The transition rates from disabled states to the no-disability state were found to decrease markedly with age. The rates of recovery from mild disability in rural areas were higher than those in urban areas. Rural elderly individuals lived shorter lives than their urban counterparts, but they tended to live with better functional status, spending a larger fraction of their remaining life with less severe disability. Based on these findings, devoting more attention and resources to rural areas may help less severely disabled people recuperate and prevent severe disability. The study provides insights into health plan strategies to help guide the allocation of limited resources.