Proteomics in Cardiovascular disease.

This study focuses on recent advances in proteomics and provides an up-to-date use of this technology in identifying cardiovascular disease (CVD) biomarkers. A total of eight electronic databases (PubMed, EMBASE, Web of Science, Cochrane Library, Wanfang, Vip, Sinomed, and CNKI) were searched and five were used for integrative analysis of sensitivity, specificity, positive likelihood ratio (PLR), negative likelihood ratio (NLR), diagnostic ratio (DOR) and 1 secondary indicator area under the curve (AUC). This systematic review and integrative analysis summarized potential biomarkers previously identified by proteomics. The integrative analysis suggested that proteomics technology had high clinical value in CVD diagnosis. The findings provided new possible directions for the prevention or diagnosis of CVD.

Identification of circular RNA hsa_circ_0034621 as a novel biomarker for carotid atherosclerosis and the potential function as a regulator of NLRP3 inflammasome.

BACKGROUND AND AIMS: NLRP3 inflammasome plays a key role in vascular inflammation and atherosclerosis. Circular RNAs (circRNAs) are involved in disease development by regulating gene expression, and have emerged as promising novel disease biomarkers. This study aimed to identify the NLRP3 inflammasome-associated circRNA biomarkers of carotid atherosclerosis. METHODS: Based on the differential expression profiles of circRNAs in patients with carotid artery plaque (CAP) and healthy controls, hsa_circ_0043621, hsa_circ_0051995, and hsa_circ_0123388 were screened and validated using real-time quantitative polymerase chain reaction (RT-qPCR). Potential circRNA-miRNA-mRNA interactions were explored using a luciferase assay. The biological roles of the validated circRNAs were investigated in human umbilical vein endothelial cells (HUVECs) using Western blotting, transwell, and CCK-8 assays. Clinical significance was assessed using receiver operating characteristic (ROC) curves and logistic regression analysis. RESULTS: The expression levels of all candidate circRNAs were significantly higher in patients with CAP than in controls (p<0.05), which was consistent with the results of the microarray analysis. Overexpression of hsa_circ_0043621 significantly increased the expression of NLRP3, induced migration of HUVECs, and inhibited cell proliferation. hsa_circ_0043621 demonstrated reasonable diagnostic accuracy for CAP detection and increased intima-media thickness (IMT). hsa_circ_0043621 upregulation was an independent predictor of an increased risk of CAP and increased IMT. CONCLUSIONS: hsa_circ_0043621 is a valuable circulating biomarker of carotid atherosclerosis and may contribute to its pathogenesis by regulating the NLRP3 inflammasome.

The role of m6A modification in type 2 diabetes: A systematic review and integrative analysis.

This study focuses on the latest developments in the studies of m6A modification and provides an up-to-date summary of the association between m6A modification and type 2 diabetes (T2D). The possible mechanisms of m6A related to T2D were summarized by literature review. The differentially expressed genes (DEGs) of m6A methylase in T2D were analyzed from 12 datasets in Gene Expression Omnibus (GEO). The associations between m6A level and T2D were explored in four electronic databases, including PubMed, EmBase, Web of Science and CNKI. Standard mean difference (SMD) and 95 % confidence interval (95 %CI) was calculated to assess the total effect in integrative analysis. Differential expression genes detected in at least three of six tissues were ZC3H13, YTHDC1/2, and IGF2BP2. LRPPRC were differentially expressed in five tissues except in arterial tissue. A total of 6 studies were included for integrative analysis. The mean m6A levels were significantly lower in T2D than those in normal controls (SMD = -1.35, 95 %CI: -2.58 to -0.11). This systematic review and integrative analysis summarize the previous studies on the association between m6A modification and T2D and the possible role of m6A modification in the progression of T2D, such as abnormal blood glucose, abnormal pancreatic ß-cell function, insulin resistance, and abnormal lipid metabolism. The integrative analysis showed that decreased level of m6A was associated with T2D. These findings provide new targets for early detection and treatment for T2D.

Association of long-term triglyceride-glucose index patterns with the incidence of chronic kidney disease among non-diabetic population: evidence from a functional community cohort.

BACKGROUND: The triglyceride-glucose (TyG) index is a reliable surrogate marker of insulin resistance and previous studies have confirmed the association of TyG index with incident chronic kidney disease (CKD). However, the impact of longitudinal patterns of TyG index on CKD risk among non-diabetic population is still unknown. Therefore, this study aimed to investigate the association of longitudinal patterns of TyG index with incident CKD among non-diabetic population. METHODS: A total of 5484 non-diabetic participants who underwent one health examination per year from 2015 to 2017 were included in this prospective study. TyG index variability and cumulative TyG index were calculated to assess the longitudinal patterns of TyG index. Cox proportional hazard models were performed to estimate the association of TyG index variability or cumulative TyG index with incident CKD. RESULTS: During a median of 3.82 years follow-up, 879 participants developed CKD. Compared with participants in the lowest quartile, the hazard ratio (HR) and 95% confidence interval (CI) of incident CKD were 1.772 (95% CI: 1.453, 2.162) for the highest TyG index variability quartile and 2.091 (95% CI: 1.646, 2.655) for the highest cumulative TyG index quartile in the fully adjusted models. The best discrimination and reclassification improvement were observed after adding baseline TyG, TyG index variability and cumulative TyG index to the clinical risk model for CKD. CONCLUSIONS: Both TyG index variability and cumulative TyG index can independently predict incident CKD among non-diabetic population. Monitoring longitudinal patterns of TyG index may assist with prediction and prevention of incident CKD.

Association between systemic immune inflammatory/inflammatory response index and hypertension: A cohort study of functional community.

BACKGROUND AND AIMS: In prospective studies, there is limited evidence of the association between inflammation and hypertension. We aimed to explore the relationship between systemic immune inflammatory index (SII)/systemic inflammatory response index (SIRI) and hypertension in a prospective cohort study to identify the best inflammatory cell markers that predict hypertension. METHODS AND RESULTS: This study was conducted in a functional community cohort in Beijing. In 2015, a total of 6003 individuals without hypertension were recruited and followed up until 2021. Using a restriction cubic spline with baseline SII/SIRI as a continuous variable, the dose-response relationship between hypertension and SII/SIRI was explored. Logistic regression was used to analyze the correlation between hypertension and SII/SIRI trajectory groups. At a mean follow-up of 6 years, 970 participants developed hypertension. SII showed a significant nonlinear dose-response relationship with hypertension (P < 0.05). Higher SII/SIRI was associated with an increased risk of hypertension (SII: RR = 1.003, 95%CI: 1.001-1.004; SIRI: RR = 1.228, 95%CI: 1.015-1.486). Both SII and SIRI were more predictive in males than females (SII: 0.698 vs. 0.695; SIRI: 0.686 vs. 0.678). CONCLUSION: Both systemic immune inflammatory index (SII) and systemic inflammatory response Index (SIRI) independently increased the risk of hypertension, and both were effective inflammatory cell indicators that predict the risk of hypertension.

Association of household solid fuel use and long-term exposure to ambient air pollution with estimated 10-year high cardiovascular disease risk among postmenopausal women.

This study aimed to explore the separate and joint effects of long-term ambient air pollution and household air pollution exposure on 10-year high cardiovascular disease (CVD) risk among postmenopausal women. A total of 4679 postmenopausal women from the China Health and Retirement Longitudinal Study (CHARLS) were included in this study. Information of fuel type was collected by standard questionnaires and use of solid fuel was considered as a proxy for household air pollution. Data of ambient air pollutants (PM1, PM2.5, PM10, SO2, NO2, CO, O3) were obtained from the ChinaHighAirPollutants (CHAP) datasets. Logistic regression models were performed to assess the separate and joint effects of long-term exposure to ambient air pollution and use of solid fuel on 10-year high CVD risk. We found use of solid fuel and its duration and ambient air pollutants (PM1, PM2.5, PM10, SO2, NO2) were all positively associated with 10-year high CVD risk among postmenopausal women (P < 0.05). Compared to those used clean fuel and exposed to low ambient air pollution levels, odds ratios (ORs) and 95% confidence intervals (CIs) for participants using solid fuels and exposed to high ambient air pollution levels (PM1, PM2.5, PM10, SO2, NO2, CO, O3) were 1.66 (1.35, 2.05), 1.66 (1.35, 2.04), 1.49 (1.22, 1.83), 1.28 (1.05, 1.57), 1.67 (1.34, 2.07), 1.28 (1.04, 1.57), 1.46 (1.18, 1.80), respectively. Moreover, significant additive interactions of solid fuel use with PM1 and PM2.5 on 10-year high CVD risk were observed, with approximately 18% and 23% of 10-year high risk of CVD attributable to the interaction. Overall, indoor and outdoor air pollution had separate and joint effects on 10-year high CVD risk among postmenopausal women. Therefore, simultaneously improving indoor and outdoor air quality are of great importance and could have a joint impact on prevention of CVD and improved health among postmenopausal women.

Association of phenotypic frailty and frailty index with type 2 diabetes and dyslipidemia in middle-aged and elderly Chinese: A longitudinal cohort study.

PURPOSE: Frailty, type 2 diabetes (T2D) and dyslipidemia are highly prevalent in middle-aged and elderly populations. However, evidence on the longitudinal association of frailty with T2D and dyslipidemia is limited. The aim of our study was to explore the cross-sectional and longitudinal effects of frailty levels on T2D and dyslipidemia in combination with phenotypic frailty and frailty index (FI). MATERIALS AND METHODS: Multivariate logistic regression model was used to explore the association of frailty status with T2D and dyslipidemia. Area under curve (AUC) of the receiver operating characteristic curve (ROC) to estimate the predictive values of phenotypic frailty and frailty index for T2D and dyslipidemia. In addition, depressive symptom was used as a mediating variable to examine whether it mediates the association between frailty and T2D or dyslipidemia. RESULTS: 10,203 and 9587 participants were chosen for the longitudinal association analysis of frailty with T2D and dyslipidemia. Frailty was associated with T2D (phenotypic frailty: OR=1.50, 95 %CI=1.03, 2.17; FI: OR=1.17, 95 %CI=1.08, 1.26) and dyslipidemia (phenotypic frailty: OR=1.56, 95 %CI=1.16, 2.10; FI: OR=1.17, 95 %CI=1.10, 1.25). Phenotypic frailty and frailty index significantly improved the risk discrimination of T2D and dyslipidemia (p<0.05). Depressive symptoms played a mediating role in the association between frailty and long-term T2D or dyslipidemia (p<0.05). CONCLUSION: Frailty had adverse effects on type 2 diabetes and dyslipidemia, with depressive symptoms acting as the mediator.

Association between hypertriglyceridemic-waist phenotype and circadian syndrome risk: a longitudinal cohort study.

Recently, circadian syndrome (CircS) has been proposed as a new predictor of cardiometabolic risk. We aimed to investigate the relationship between the hypertriglyceridemic-waist phenotype and its dynamic status with CircS in China. We conducted a two-stage study based on the China Health and Retirement Longitudinal Study (CHARLS) from 2011 to 2015. Multivariate logistic regression models in cross-sectional analysis and Cox proportional hazards regression models in longitudinal analysis were used to estimate the associations of hypertriglyceridemic-waist phenotypes with CircS and its components. We then applied multiple logistic regression analysis to evaluate the odds ratios (ORs) and 95% confidence intervals (CIs) for CircS risk by transformation into the hypertriglyceridemic-waist phenotype. A total of 9863 participants were included in the cross-sectional analysis and 3884 participants in the longitudinal analysis. Compared with normal waist circumference (WC) and normal triglyceride (TG) level (NWNT), CircS risk was increased with enlarged WC and high TG level (EWHT) (hazard ratio (HR) 3.87 [95% CI: 2.38, 5.39]). Similar results were observed in subgroup analyses by sex, age, smoking status, and drinking status. During follow-up, CircS risk was increased in group K (stable EWNT during follow-up) (OR 9.97 [95% CI: 6.41, 15.49]) compared with group A (stable NWNT during follow-up), while group L (baseline enlarged WC and normal TG level transformed to follow-up EWHT) had the highest risk of CircS (OR 116.07 [95% CI: 72.77, 185.14]). In conclusion, the hypertriglyceridemic-waist phenotype and its dynamic status were associated with the risk of developing CircS in Chinese adults.

Association of variability in metabolic parameters with the incidence of type 2 diabetes: evidence from a functional community cohort.

BACKGROUND: To investigate the association of variability in metabolic parameters such as total cholesterol concentrations (TC), uric acid (UA), body mass index (BMI), visceral adiposity index (VAI) and systolic blood pressure (SBP) with incident type 2 diabetes (T2D) and whether variability in these metabolic parameters has additive effects on the risk of T2D. METHODS: Based on the Beijing Functional Community Cohort, 4392 participants who underwent three health examinations (2015, 2016, and 2017) were followed up for incident T2D until the end of 2021. Variability in metabolic parameters from three health examinations were assessed using the coefficient of variation, standard deviation, variability independent of the mean, and average real variability. High variability was defined as the highest quartile of variability index. Participants were grouped according to the number of high-variability metabolic parameters. Cox proportional hazards models were performed to assess the hazard ratio (HR) and 95% confidence interval (CI) for incident T2D. RESULTS: During a median follow-up of 3.91 years, 249 cases of incident T2D were identified. High variability in TC, BMI, VAI and SBP was significantly associated with higher risks of incident T2D. As for UA, significant multiplicative interaction was found between variability in UA and variability in other four metabolic parameters for incident T2D. The risk of T2D significantly increased with the increasing numbers of high-variability metabolic parameters. Compared with the group with low variability for 5 parameters, the HR (95% CI) for participants with 1-2, 3, 4-5 high-variability metabolic parameters were 1.488 (1.051, 2.107), 2.036 (1.286, 3.222) and 3.017 (1.549, 5.877), respectively. Similar results were obtained in various sensitivity analyses. CONCLUSIONS: High variability of TC, BMI, VAI and SBP were independent predictors of incident T2D, respectively. There was a graded association between the number of high-variability metabolic parameters and incident T2D.

Occupational stress is associated with insulin resistance and incident type 2 diabetes: A prospective cohort study of functional community.

BACKGROUND: To exploit the association of occupational stress with the development of insulin resistance (IR) and type 2 diabetes (T2D) in a Chinese population-based cohort. METHODS: A total of 6109 participants from a functional community cohort in Beijing were enrolled in 2015 and followed up until 2021. Copenhagen Psychosocial Questionnaire (COPSOQ) were used to evaluate occupational stress. RESULTS: At baseline, increase values of all five scales of COPSOQ and total COPSOQ were significantly associated with IR. During an average 5.63 y follow-up, 732 individuals developed T2D. Increasing in values of "Demands at work", "Insecurity at work", "Job satisfaction" and total COPSOQ were significantly associated with incident T2D (P < 0.01). Mediation analysis showed that subjectively perceived occupational stress promoted T2D mainly by affecting plasma cortisol and the mediation effects of HOMA-IR, SBP, DBP, TG, Urea and UA were significant on the association between cortisol and incident T2D, with proportion mediated of 37.1%, 8.12%, 2.02%, 2.94%, 2.35% and 2.70%. CONCLUSION: Occupational stress was independently associated with the development of IR and T2D. IR, BP, TG, Urea and UA all partly mediated the association between occupational stress and incident T2D.

Identification of Metabolism-Related Proteins as Biomarkers of Insulin Resistance and Potential Mechanisms of m6A Modification.

BACKGROUND: Insulin resistance (IR) is a major contributing factor to the pathogenesis of metabolic syndrome and type 2 diabetes mellitus (T2D). Adipocyte metabolism is known to play a crucial role in IR. Therefore, the aims of this study were to identify metabolism-related proteins that could be used as potential biomarkers of IR and to investigate the role of N6-methyladenosine (m6A) modification in the pathogenesis of this condition. METHODS: RNA-seq data on human adipose tissue were retrieved from the Gene Expression Omnibus database. The differentially expressed genes of metabolism-related proteins (MP-DEGs) were screened using protein annotation databases. Biological function and pathway annotations of the MP-DEGs were performed through Gene Ontology and Kyoto Encyclopedia of Genes and Genomes pathway analyses. Key MP-DEGs were screened, and a protein-protein interaction (PPI) network was constructed using STRING, Cytoscape, MCODE, and CytoHubba. LASSO regression analysis was used to select primary hub genes, and their clinical performance was assessed using receiver operating characteristic (ROC) curves. The expression of key MP-DEGs and their relationship with m6A modification were further verified in adipose tissue samples collected from healthy individuals and patients with IR. RESULTS: In total, 69 MP-DEGs were screened and annotated to be enriched in pathways related to hormone metabolism, low-density lipoprotein particle and carboxylic acid transmembrane transporter activity, insulin signaling, and AMPK signaling. The MP-DEG PPI network comprised 69 nodes and 72 edges, from which 10 hub genes (FASN, GCK, FGR, FBP1, GYS2, PNPLA3, MOGAT1, SLC27A2, PNPLA3, and ELOVL6) were identified. FASN was chosen as the key gene because it had the highest maximal clique centrality (MCC) score. GCK, FBP1, and FGR were selected as primary genes by LASSO analysis. According to the ROC curves, GCK, FBP1, FGR, and FASN could be used as potential biomarkers to detect IR with good sensitivity and accuracy (AUC = 0.80, 95% CI: 0.67-0.94; AUC = 0.86, 95% CI: 0.74-0.94; AUC = 0.83, 95% CI: 0.64-0.92; AUC = 0.78, 95% CI: 0.64-0.92). The expression of FASN, GCK, FBP1, and FGR was significantly correlated with that of IGF2BP3, FTO, EIF3A, WTAP, METTL16, and LRPPRC (p < 0.05). In validation clinical samples, the FASN was moderately effective for detecting IR (AUC = 0.78, 95% CI: 0.69-0.80), and its expression was positively correlated with the methylation levels of FASN (r = 0.359, p = 0.001). CONCLUSION: Metabolism-related proteins play critical roles in IR. Moreover, FASN and GCK are potential biomarkers of IR and may be involved in the development of T2D via their m6A modification. These findings offer reliable biomarkers for the early detection of T2D and promising therapeutic targets.

Associations between long-term exposure to ambient fine particulate pollution with the decline of kidney function and hyperuricemia: a longitudinal cohort study.

Evidence of associations between ambient fine particulate matter (PM2.5) and risks of decline of kidney function and hyperuricemia is limited. We aimed to investigate the associations between long-term exposure to PM2.5 with decline of kidney function and hyperuricemia in China. We conducted a two-stage study based on China Health and Retirement Longitudinal Study (CHARLS) from 2011 to 2015. Cox proportional hazard regression models and restricted cubic splines were used to evaluate the associations of PM2.5 with risks of decline of kidney function and hyperuricemia. Latent class trajectory models (LCTM) were used to identify trajectories of PM2.5 from 2011 to 2015 in the sensitivity analysis. A total of 9760 participants were included in baseline analysis, and 5902 participants were in follow-up analysis. PM2.5 was associated with the risks of decline of kidney function [hazard ratio (HR): 2.14; 95% confidence interval (CI): (1.03, 4.44)] and hyperuricemia [HR 1.40 (95% CI: 1.10, 1.79)] in the second quartile group versus the lowest quartile group of PM2.5. We also observed nonlinear relationships between PM2.5 and the risks of the decline of kidney function and hyperuricemia (Pnon-linear < 0.001). In sensitivity analysis, four trajectory groups were identified. "Maintaining a high PM2.5" [odds ratio (OR): 2.20; 95%CI: (1.78, 2.73)] and "moderately high starting PM2.5 then steadily decreased" [OR (95%CI): 5.15 (1.55, 16.13)] were associated with hyperuricemia risk, using "low starting PM2.5 then steadily decreased" trajectory as reference. In conclusion, improved air quality is essential for prevention of decline of kidney function and hyperuricemia.

Associations of waist-to-height ratio with the incidence of type 2 diabetes and mediation analysis: Two independent cohort studies.

AIM: To assess the relationship between waist-to-height ratio (WHtR) and the incidence of type 2 diabetes (T2D)/impaired fasting glucose (IFG) and to explore to what extent these associations are mediated by blood pressure, lipids and other indicators related to liver and kidney metabolism. MATERIALS AND METHODS: This study was based on a functional community cohort included 6109 participants which were divided into two sub-cohorts. One sub-cohort included participants with normal fasting glucose (n = 5563), another included IFG individuals at baseline (n = 546). Cox regression models were used to evaluate the relationships of WHtR with T2D/IFG. Four-year time-dependent receiver operating characteristic (ROC) curve and area under curve (AUC) were calculated to estimate the discriminatory power of WhtR and other anthropometric indices on T2D. Mediation analysis was performed to estimate which risk factors mediate the association between WHtR and T2D. RESULTS: Significant positive associations were found between WHtR and the incidence of T2D/IFG in both sub-cohort. WhtR was a useful predictor of T2D (P < 0.05). Mediation analysis showed that HOMA-IR (0.45 %), SBP (5.10 %), triglycerides (11.02 %), creatinine (9.36 %) and combined kidney indicators (17.48 %) partly mediated the effect of WHtR on T2D in men. For women, this association was partly mediated by SBP (13.86 %), HDL (24.54 %), ALT (6.29 %), UA (22.58 %) and combined kidney indicators (39.51 %). CONCLUSIONS: WHtR was an independent risk factor for the development of T2D and IFG. This association was partly mediated by HOMA-IR, SBP, lipids and other liver and kidney metabolism indicators.

The effects of short-term exposure to air pollution on mortality in Baotou, China, during 2015-2019.

Air pollution was considered one of the main causes linked to increased morbidity and mortality around the world. This study aimed to estimate the effect of air pollutants on daily death in Baotou city of Inner Mongolia. Daily deaths data were provided by Baotou Centers for Disease Control and Prevention for the years 2015-2019 (Baotou CDC). The air pollutants, PM2.5, PM10, NO2, SO2, CO and maximum 8-h average concentrations of O3, came from the eight environmental monitoring stations in Baotou city. Time-series plots were used to exploit the trend of air pollutants at calendar time. Generalized additive model was used to estimate the effect of air pollutants on daily death. Restricted cubic spline was employed to investigate non-line relationships between air pollutants and daily death. After adjusting the meteorological factors, non-accidental daily deaths were related to PM2.5 (ER = 0.074%) and PM10 (ER = 0.023%), respectively. In stratified analysis, population aged over 65 years and females were more sensitive to air pollutants exposure and warm season might make people more susceptible to air pollutants compared with cold season. PM2.5 and PM10 increase the risk of non-accidental and cardiovascular daily death, but not respiratory daily death.

Association of serum uric acid with the risk of developing hypertension: A prospective cohort study with mediation analysis.

Elevated serum uric acid (SUA) is associated with the incidence of hypertension, but whether relevant metabolic factors have mediating effects is not certain. Our study was based on a functional community cohort established in Beijing. In 2015, a total of 7482 individuals without hypertension were recruited and followed up until 2019. Multivariate logistic regression analysis was used to investigate the association between SUA and hypertension. Cross-lagged panel analysis and mediation analysis were used to explore the effects of metabolic factors on the association between SUA and incident hypertension. During the average 4-year follow-up, the cumulative incidence of hypertension was 10.9% (n = 580). SUA was an independent risk factor for hypertension, and the RRs (95% CI) for subjects with baseline SUA levels in quartile 2, quartile 3 and quartile 4 were 1.20 (0.88-1.63), 1.50 (1.10-2.05), and 1.57 (1.11-2.22) compared to those in quartile 1, respectively. The cross-lagged panel analysis showed that the increases in Cr, TG, LDL, ALT, AST and WBC occurred after SUA increased (P < 0.001). Among these factors, TG, WBC and ALT played an intermediary role in both men (TG: 14.76%; WBC: 11.61%; ALT: 15.93%) and women (TG: 14.55%; WBC: 8.55%; ALT: 6.89%). The elevated SUA concentration was an independent risk factor for hypertension in the Chinese population, and TG, WBC and ALT had important mediating effects on the association between SUA and hypertension.

Association between surrogate indicators of insulin resistance and risk of type 2 diabetes combined with hypertension among Chinese adults: two independent cohort studies.

BACKGROUND: Type 2 diabetes (T2D) combined with hypertension has a higher risk of developing cardiovascular diseases. This study aimed to investigate the relationships between the surrogate indicators of insulin resistance (TyG, TG/HDL, and Mets-IR) with the risk of T2D combined with hypertension. METHODS: This study is based on a functional community cohort from Beijing and the China Health and Retirement Longitudinal Study, comprising 4234 and 4658 participants respectively. Cox proportional hazards models and restricted cubic spline regression were performed to assess the link between TyG, TG/HDL, and Mets-IR with T2D combined with hypertension. The cross-lagged panel analysis and the mediation analysis were used to examine the temporal relationship between insulin resistance and obesity and their temporal relationship with follow-up T2D combined with hypertension. RESULTS: In multivariable-adjusted models, higher TyG was associated with a higher risk of developing T2D combined with hypertension, the hazard ratios (95% confidence interval) were 3.46 (2.43-4.93) and 2.02 (1.67-2.44), in two cohorts respectively. A similar positive association was shown for Mets-IR, the hazard ratios (95% confidence interval) were 1.04 (1.03-1.06) and 1.05 (1.03-1.07), in two cohorts respectively. However, the association between TG/HDL with T2D combined with hypertension was different in two cohorts. The restricted cubic spline regression showed a linear association between TyG and T2D combined with hypertension (P-nonlinear > 0.05). The cross-lagged path coefficient from baseline BMI to follow-up TyG index was significantly greater than the path coefficient from baseline TyG to follow-up BMI. TyG partially mediated the effect of BMI on the risk of T2D combined with hypertension and the percentage of mediated association was estimated at 41.58% and 48.41% in two cohorts, respectively. CONCLUSION: These findings indicated positive associations between TyG and Mets-IR with the risk of T2D combined with hypertension in two cohorts. In addition, BMI change may precede TyG index change, and the TyG index plays a mediating role in BMI induced T2D combined with hypertension.

Trend analysis and prediction of injury death in Xi'an city, China, 2005-2020.

BACKGROUND: Injury is an important cause of death in China. In the present study, we systematically analyzed the epidemiological characteristics and trends of injury death in Xi'an residents from 2005 to 2020. METHODS: Data on injury deaths from 2005 to 2020 were obtained from the "Xi'an Center for Disease Control and Prevention", injury deaths were classified according to the International Classification Disease-10th Revision (ICD-10). The data were stratified by gender, age groups, injury types, and then overall and type-specific injury mortality rates were estimated. Joinpoint regression analysis was conducted to estimate annual percent change (APC). The grey interval predicting method was used to predict the future characteristics of injury deaths in Xi'an city. RESULTS: From 2005 to 2020, injury caused 32,596 deaths (5.79% of all deaths; 35.71/100000 population). Injury mortality rates were higher among males than females. Motor vehicle traffic accidents were the commonest injury type. The highest injury mortality rates were in those aged 85 years or older. Overall, Joinpoint regression analysis revealed that injury mortality had significantly (p < 0.05) decreasing trends. GM (1,1) model estimated that injury mortality will be on a declining curve. CONCLUSIONS: Motor vehicle traffic accidents, transport accidents other than motor vehicles, unintentional falls, suicide, and accidental poisoning are the main causes of injury. The injury death rate is projected to decline over the next decade.

Trends of cancer mortality in Xi'an City, China: 2005-2020.

PURPOSE: Describe and predict the malignant tumor deaths in Xi'an so as to provide evidence for the government to formulate the prevention and treatment plans. METHODS: Overall malignant tumor death in Xi'an in the past 16 years was described. The multi-decrease life table was used to calculate cumulative mortality risk by cause and life expectancy reduction years by cause of malignant tumors in 2020. The join point regression models were used to analyze the change trend of standard mortality of malignant tumors in Xi'an from 2005 to 2020. The appropriate gray models were selected to predict the death of malignant tumors in Xi'an in the next decade. RESULTS: The mortality of total malignant tumors in Xi'an showed that men are higher than women and the elderly are higher than other groups. As for 2020, lung cancer had the highest risk of death for both men and women, while leukemia had the highest life expectancy reduction years by cause. From 2005 to 2020, standardized mortality of majority malignant tumors showed downward trends, which were particularly obvious in recent years. The prediction results of several major malignant tumors showed that in the next decade, the mortality of most malignant tumors had downward trends, but combined with the increase of population in the future, the number of malignant tumor deaths in Xi'an will continue to increase. CONCLUSIONS: Malignant tumors in Xi'an have decreasing mortality trends in recent years, and effective measures to prevent and treat tumors should be strengthened in the future.

CircRNA hsa_circ_0071336 is associated with type 2 diabetes through targeting the miR-93-5p/GLUT4 axis.

Glucose transporter 4 (GLUT4) is a dominant regulator of whole-body glucose homeostasis. Accumulating evidence has shown that circular RNAs (circRNAs) play significant roles in the pathogenesis of disease. The aim of the present study was to identify the circRNA that can be used as a novel biomarker for type 2 diabetes (T2D) through regulating GLUT4. Based on previous microarray analysis comparing T2D cases and healthy controls, hsa_circ_0071336, which was predicted to be a regulator of GLUT4 by acting as a competitive endogenous RNAs (ceRNA) to sponge miR-93-5p, was selected for further validation. The clinical significance of circulating hsa_circ_0071336 was investigated in a large independent cohort. The results showed that circulating hsa_circ_0071336 was significantly downregulated in blood in T2D and had a high diagnostic accuracy for discriminating T2D and impaired fasting glucose (IFG) from healthy controls. Low expression of circ_0071336 was an independent predictor of T2D, IFG and insulin resistance. A luciferase reporter assay and western-blot analysis indicated that miR-93-5p was a direct target of hsa_circ_0071336, and miR-93-5p may negatively regulate the expression of GLUT4. The expression levels of hsa_circ_007136 were negatively related to miR-93-5p expression and positively correlated with the mRNA expression of GLUT4 in adipose tissues. In conclusion, hsa_circRNA_0071336 can be considered as a potential novel and stable biomarker for T2D and its early detection. hsa_circ_0071336 regulates the GLUT4 expression by sponging miR-93-5p and maybe involved in the pathogenesis of T2D. These findings may unveil new targets for the prevention, diagnosis and treatment of T2D.