Impact of lipoprotein(a) level on cardiometabolic disease in the Chinese population: The CHCN-BTH Study.

BACKGROUND: The emergence of promising compounds to lower lipoprotein(a) [Lp(a)] has increased the need for a precise characterisation and comparability assessment of Lp(a)-associated cardiometabolic disease risk. This study aimed to evaluate the distribution of Lp(a) levels in a Chinese population and characterise the association with cardiometabolic diseases. METHODS: We assessed data from individuals from the Cohort Study on Chronic Diseases of the General Community Population in the Beijing-Tianjin-Hebei Region project. All Lp(a) measurements were performed in the same hospital. The cardiometabolic diseases considered were coronary heart disease (CHD), stroke, hypertension and type 2 diabetes (T2DM). RESULTS: A total of 25343 individuals were included in the study. The median level of Lp(a) was 11.9 mg/dl (IQR 5.9 to 23.7 mg/dl), and higher Lp(a) levels showed a significant concentration-dependent association with CHD risk. Individuals with Lp(a) levels lower than the 25th percentile were at increased risk of hypertension (OR: 1.15, 95% CI: 1.06-1.25) and T2DM (OR: 1.15, 95% CI: 1.03-1.28); however, Lp(a) levels were not significantly associated with stroke. The addition of Lp(a) levels to the prognostic model led to a marginal but significant C-index, integrated discrimination improvement and net reclassification improvement. CONCLUSIONS: In this large sample size study, we observed that elevated Lp(a) levels were significantly associated with CHD. Furthermore, we found that the lowest Lp(a) levels were also significantly associated with hypertension and T2DM. These results provide evidence for differential approaches to higher levels of Lp(a) in individuals with different cardiometabolic diseases.

Association of long-term exposure to ambient particulate pollution with stage 1 hypertension defined by the 2017 ACC/AHA Hypertension Guideline and cardiovascular disease: The CHCN-BTH cohort study.

BACKGROUND: Evidence regarding the effects of ambient air pollution on new stage 1 hypertension defined by the 2017 ACC/AHA Hypertension Guideline remains sparse. OBJECTIVES: To investigate the association of long-term exposure to ambient PM2.5 with stage 1 hypertension and to explore the mediating and modifying effects of PM2.5 on cardiovascular disease (CVD). METHODS: A total of 32,135 participants aged 18-80 years were recruited in 2017. The three-year (2014-2016) average PM2.5 concentrations were assessed by a spatial statistical model. Blood pressure (BP) was divided into four categories according to the 2017 ACC/AHA Hypertension Guideline: normal BP (SBP<120 mmHg and DBP<80 mmHg), elevated BP (SBP 120-129 mmHg and DBP<80 mmHg), stage 1 hypertension (SBP 130-139 mmHg or DBP 80-89 mmHg), and stage 2 hypertension (SBP≥140 mmHg or DBP≥90 mmHg or taking antihypertensive medications). The associations of PM2.5 with BP categories were estimated by two-level generalized linear mixed models. Analyses stratified by age, mediation and interaction analyses of PM2.5 and stage 1 hypertension with CVD were performed. RESULTS: We detected a positive significant association between long-term exposure to PM2.5 and stage 1 hypertension. Compared to normal BP, the OR was 1.05 (95% CI: 1.02, 1.08) per 10 µg/m3 increase in PM2.5. The association was stronger than that of elevated BP but weaker than that of stage 2 hypertension. Stage 1 hypertension only partially mediated the association between PM2.5 and CVD, and the mediation proportions ranged from 1.55% to 11.00%. However, it modified the association between PM2.5 and CVD, which was greater in participants with stage 1 hypertension (OR: 1.66; 95% CI: 1.43, 1.93) than in participants with normal BP (OR: 1.32; 95% CI: 1.11, 1.57), with Pinteraction<0.001. In the analysis stratified by age, the above associations were age-specific, and significant associations were only observed in the young and middle-aged (<60 years) groups. CONCLUSIONS: Long-term exposure to ambient PM2.5 was significantly associated with stage 1 hypertension. This earlier stage of hypertension may be a trigger BP range for adverse effects of air pollution in the development of hypertension and CVD, especially in young and middle-aged individuals.

Association of Lipoprotein (a) variants with risk of cardiovascular disease: a Mendelian randomization study.

BACKGROUND: There is a well-documented empirical relationship between lipoprotein (a) [Lp(a)] and cardiovascular disease (CVD); however, causal evidence, especially from the Chinese population, is lacking. Therefore, this study aims to estimate the causal association between variants in genes affecting Lp(a) concentrations and CVD in people of Han Chinese ethnicity. METHODS: Two-sample Mendelian randomization analysis was used to assess the causal effect of Lp(a) concentrations on the risk of CVD. Summary statistics for Lp(a) variants were obtained from 1256 individuals in the Cohort Study on Chronic Disease of Communities Natural Population in Beijing, Tianjin and Hebei. Data on associations between single-nucleotide polymorphisms (SNPs) and CVD were obtained from recently published genome-wide association studies. RESULTS: Thirteen SNPs associated with Lp(a) levels in the Han Chinese population were used as instrumental variables. Genetically elevated Lp(a) was inversely associated with the risk of atrial fibrillation [odds ratio (OR), 0.94; 95% confidence interval (95%CI), 0.901-0.987; P = 0.012)], the risk of arrhythmia (OR, 0.96; 95%CI, 0.941-0.990; P = 0.005), the left ventricular mass index (OR, 0.97; 95%CI, 0.949-1.000; P = 0.048), and the left ventricular internal dimension in diastole (OR, 0.97; 95%CI, 0.950-0.997; P = 0.028) according to the inverse-variance weighted method. No significant association was observed for congestive heart failure (OR, 0.99; 95% CI, 0.950-1.038; P = 0.766), ischemic stroke (OR, 1.01; 95%CI, 0.981-1.046; P = 0.422), and left ventricular internal dimension in systole (OR, 0.98; 95%CI, 0.960-1.009; P = 0.214). CONCLUSIONS: This study provided evidence that genetically elevated Lp(a) was inversely associated with atrial fibrillation, arrhythmia, the left ventricular mass index and the left ventricular internal dimension in diastole, but not with congestive heart failure, ischemic stroke, and the left ventricular internal dimension in systole in the Han Chinese population. Further research is needed to identify the mechanism underlying these results and determine whether genetically elevated Lp(a) increases the risk of coronary heart disease or other CVD subtypes.

Construction of a ceRNA coregulatory network and screening of hub biomarkers for salt-sensitive hypertension.

Salt-sensitive hypertension (SSH) is an independent risk factor for cardiovascular disease. The regulation of long non-coding RNAs, mRNAs and competing endogenous RNAs (ceRNAs) in the pathogenesis of SSH is uncertain. An RNA microarray was performed to discover SSH-associated differentially expressed lncRNAs (DElncRNAs) and mRNAs (DEmRNAs), and 296 DElncRNAs and 44 DEmRNAs were identified, and 247 DElncRNAs and 44 DEmRNAs among these RNAs were included in the coexpression network. The coregulatory network included 23 ceRNA loops, and six hub RNAs (lnc-ILK-8:1, lnc-OTX1-7:1, lnc-RCAN1-6:1, GIMAP8, SUV420H1 and PIGV) were identified for further population validation. The ceRNA correlations among lnc-OTX1-7:1, hsa-miR-361-5p and GIMAP8 were confirmed in SSH and SRH patients. A larger-sample validation confirmed that GIMAP8, SUV420H1 and PIGV were differentially expressed between the SSH and SRH groups. In addition, SUV420H1 was included in the SSH screening model, and the area under the curve of the model was 0.720 (95% CI: 0.624-0.816). Our study explored the transcriptome profiles of SSH and constructed a ceRNA network to help elucidate the mechanism of SSH. In addition, SUV420H1 was identified as a hub element that participates in SSH transcriptional regulation and as a potential biomarker for the early diagnosis of SSH.

Associations between ambient air pollution and mortality from all causes, pneumonia, and congenital heart diseases among children aged under 5 years in Beijing, China: A population-based time series study.

BACKGROUND: Previous studies have mainly focused on the associations between particulate matters and infant mortality. However, evidence regarding the associations between gaseous pollutants and mortality among children aged <5 years remains sparse. OBJECTIVES: The aim of this study was to investigate the associations between ambient air pollution and death among children aged <5 years in Beijing, China, and explore the impact of age, gender and specific causes of death on these associations. METHODS: Concentrations of ambient air pollution and the number of deaths among children aged <5 years in Beijing from January 2014 to September 2016 were extracted from authoritative electronic databases. The associations were estimated for a single-month lag from the current month up to the previous 5 months (lag0-lag5) and moving averages of the current and previous months (lag01-lag05) using generalized additive Poisson regression (adjusted for time trends, season, meteorological variables and holidays). Subgroup analyses related to age, gender and specific diseases were performed. Two-pollutant models were used to evaluate the possible role of single pollutants. RESULTS: Sulfur dioxide (SO2), nitrogen dioxide (NO2) and carbon monoxide (CO) demonstrated the strongest associations with death among children aged <5 years at lag0, and the estimates decreased or even turned negative with the increasing lag periods. For an interquartile range increase in SO2, NO2 and CO at lag0, the odds ratios (OR) were 1.332 (95% CI 1.152-1.539), 1.383 (95% CI 1.113-1.718) and 1.273 (95% CI 1.028-1.575). However, CO lost significance after adjusting for SO2 and NO2, and PM2.5 gained significance (OR 1.548, 95% CI 1.061-2.258) after adjusting for PM10. The ORs for SO2 and NO2 remained the most stable across all two-pollutant models. The associations for children aged 1-5 years were stronger than those reported for infants at lag0 but lower at the other lag months. The pollutant associations were stronger for congenital heart disease-related death than overall and pneumonia-related death. We did not find significant differences in terms of gender. CONCLUSION: Exposure to air pollution may increase the incidence of death among children aged <5 years. SO2 and NO2 may be the most stable pollutants reflecting associations between air pollution and death, deserving further attention. Children with congenital heart diseases are more susceptible to air pollution. Therefore, it is urgent to implement the clean air targets established by WHO and reduce the exposure of children to air pollution.

The effect of PM2.5 exposure on the mortality of patients with hepatocellular carcinoma in Tianjin, China.

Several studies have shown the effects of PM2.5 exposure on respiratory and cardiovascular systems. However, there is no cohort study evidence of adverse effects of PM2.5 exposure on survival in patients with hepatocellular carcinoma (HCC) in China. This study is aimed at evaluating this association. This cohort study included 1440 HCC patients treated at the Third Central Clinical College of Tianjin Medical University from September 2013 to December 2018. We collected patient information, including demographic data, medical history, lifestyle characteristics, and disease characteristics. Based on PM2.5 concentrations measured at monitoring stations, the inverse distance weighted (IDW) method was used to assess the individuals' exposure during their survival period. Survival status was analysed by the Kaplan-Meier method. Restricted cubic splines and Cox proportional hazards models were used to estimate the relationship between PM2.5 and mortality, and potential confounders were adjusted for. The mortality rate of HCC patients exposed to PM2.5 ≥ 58.56 µg/m3 was significantly higher than that of HCC patients living in environments with PM2.5 < 58.56 µg/m3 (79.0% vs 50.7%, P < 0.001). The restricted cubic spline model showed a linear relationship between the PM2.5 concentration and mortality risk (P overall-association < 0.0001 and P nonlinear-association = 0.3568). Cox regression analysis showed that after adjusting for confounding factors, for every 10-µg/m3 increase in atmospheric PM2.5, the risk of death for HCC patients increased by 44% [hazard ratio (HR) = 1.44, 95% confidence interval (CI) 1.34, 1.56; P < 0.001]. Compared with patients exposed to PM2.5 <58.56 µg/m3, those exposed to PM2.5 ≥ 58.56 µg/m3 had a 1.55-fold increased risk of death. Stratified analysis results showed that the effects of PM2.5 on HCC mortality were more significant in patients aged ≥60 years or patients living in central urban areas. We found that exposure to elevated PM2.5 after HCC diagnosis may affect survival, with a higher concentration corresponding to a greater effect.

Polymorphisms and Gene-Gene Interaction in AGER/IL6 Pathway Might Be Associated with Diabetic Ischemic Heart Disease.

Background: Although the genetic susceptibility to diabetes and ischemic heart disease (IHD) has been well demonstrated, studies aimed at exploring gene variations associated with diabetic IHD are still limited; Methods: Our study included 204 IHD cases who had been diagnosed with diabetes before the diagnosis of IHD and 882 healthy controls. Logistic regression was used to find the association of candidate SNPs and polygenic risk score (PRS) with diabetic IHD. The diagnostic accuracy was represented with AUC. Generalized multifactor dimensionality reduction (GMDR) was used to illustrate gene-gene interactions; Results: For IL6R rs4845625, the CT and TT genotypes were associated with a lower risk of diabetic IHD than the CC genotype (OR = 0.619, p = 0.033; OR = 0.542, p = 0.025, respectively). Haplotypes in the AGER gene (rs184003-rs1035798-rs2070600-rs1800624) and IL6R gene (rs7529229-rs4845625-rs4129267-rs7514452-rs4072391) were both significantly associated with diabetic IHD. PRS was associated with the disease (OR = 1.100, p = 0.005) after adjusting for covariates, and the AUC were 0.763 (p < 0.001). The GMDR analysis suggested that rs184003 and rs4845625 were the best interaction model after permutation testing (p = 0.001) with a cross-validation consistency of 10/10; Conclusions: SNPs and haplotypes in the AGER and IL6R genes and the interaction of rs184003 and rs4845625 were significantly associated with diabetic IHD.

Serum lipoprotein (a) associates with the risk of renal function damage in the CHCN-BTH Study: Cross-sectional and Mendelian randomization analyses.

Background: Evidence regarding the effects of lipoprotein (a) [lp(a)] and renal function remains unclear. The present study aimed to explore the causal association of serum lp(a) with renal function damage in Chinese general adults. Methods: A total of 25343 individuals with available lp(a) data were selected from the baseline survey of the Cohort Study on Chronic Disease of Communities Natural Population in Beijing, Tianjin, and Hebei (CHCN-BTH). Five renal function indexes [estimated glomerular filtration rate (eGFR), serum creatinine (Scr), blood urea nitrogen (BUN), uric acid (UA), high-sensitivity C-reactive protein(CRPHS)] were analyzed. The restricted cubic spline (RCS) method, logistic regression, and linear regression were used to test the dose-response association between lp(a) and renal function. Stratified analyses related to demographic characteristics and disease status were performed. Two-sample Mendelian randomization (MR) analysis was used to obtain the causal association of lp(a) and renal function indexes. Genotyping was accomplished by MassARRAY System. Results: Lp(a) levels were independently associated with four renal function indexes (eGFR, Scr, BUN, CRPHS). Individuals with a higher lp(a) level had a lower eGFR level, and the association with Scr estimated GFR was stronger in individuals with a lower lp(a) level (under 14 mg/dL). . The association was similar in individuals regardless of diabetes or hypertension. MR analysis confirmed the causal association of two renal function indexes (Scr and BUN). For MR analysis, each one unit higher lp(a) was associated with 7.4% higher Scr (P=0.031) in the inverse-variance weighted method. But a causal effect of genetically increased lp(a) level with increased eGFR level which contrasted with our observational results was observed. Conclusion: The observational and causal effect of lp(a) on Scr and BUN were founded, suggesting the role of lp(a) on the risk of renal function damage in general Chinese adults.

Polymorphisms of microRNAs are associated with salt sensitivity in a Han Chinese population: the EpiSS study.

The majority of single-nucleotide polymorphism (SNP) association studies of salt sensitivity (SS) have focused on SNPs in protein-coding genes rather than on SNPs in noncoding RNAs. This study attempted to identify the association between whole blood microRNA (miRNA)-related SNPs and the risk of SS in a Han Chinese population. A case-control study of 762 individuals was performed. A modified Sullivan's acute oral saline load and diuresis shrinkage test was used to assess SS. All SNPs were analysed by RT-PCR on a Sequenom Mass ARRAY Platform (Sequenom, San Diego, CA, USA). A genetic risk score (GRS) was used to evaluate the joint genetic effect. In total, 24 miRNA-related SNPs were genotyped, four of which (miR-1307-5p/rs11191676, miR-1307-5p/rs2292807, miR-145/rs41291957 and miR-4638-3p/rs6601178) were associated with both SS and salt sensitivity of blood pressure (SSBP) (p ≤ 0.05). MiR-382-5p/rs4906032 and miR-15b-5/rs10936201 were associated with SSBP. Weighted GRS showed that participants in the second, third and fourth quartiles had 1.760-fold (95% CI: 1.068-2.903), 2.450-fold (95% CI: 1.470-4.083) and 2.774-fold (95% CI: 1.680-4.582) increased risk of SS, respectively. Bioinformatics analysis indicated that these four SNP risk alleles may affect transcription factor binding and influence promoter activity. A total of six miRNA-related SNPs were found to be associated with SS or SSBP, and the presence of multiple risk alleles resulted in increased risk level.

Associations of long-term ambient air pollution and traffic-related pollution with blood pressure and hypertension defined by the different guidelines worldwide: the CHCN-BTH study.

The assessment of the generalization of the strict hypertension definition in the 2017 ACC/AHA Hypertension Guideline from environmental condition remains sparse. The aims of this study are to investigate and compare the associations of ambient air pollution and traffic-related pollution (TRP) with hypertension defined by the different criteria. A total of 32,135 participants were recruited from the baseline survey of the CHCN-BTH in 2017. We defined hypertension as SBP/DBP ≥ 140/90 mmHg according to the hypertension guidelines in China, Japan, Europe and ISH (traditional criteria) and defined as SBP/DBP ≥ 130/80 mmHg according to the 2017 ACC/AHA Hypertension Guideline (strict criteria). A two-level generalized linear mixed models were applied to investigate the associations of air pollutants (i.e. PM2.5, SO2, NO2) and TRP with blood pressure (BP) measures and hypertension. Stratified analyses and two-pollutant models were also performed. The stronger associations of air pollutants were found in the hypertension defined by the strict criteria than that defined by the traditional criteria. The ORs per an IQR increase in PM2.5 were 1.17 (95% CI: 1.09, 1.25) for the strict criteria and 1.14 (95% CI: 1.06, 1.23) for the traditional criteria. The similar conditions were also observed for TRP. The above results were robust in both stratified analyses and two-pollutant models. Our study assessed the significance of the hypertension defined by the strict criteria from environmental aspect and called attention to the more adverse effects of air pollution and TRP on the earlier stage of hypertension.

Long-term exposure to ambient nitrogen dioxide and ozone modifies systematic low-grade inflammation: The CHCN-BTH study.

The potential effect of long-term exposure to ambient air pollutants on low-grade systematic inflammation has seldom been evaluated taking indoor air pollution and self-protection behaviors on smog days into account. A total of 24,346 participants at baseline were included to conduct a cross-sectional study. The annual (2016) average pollutant concentrations were assessed by air monitoring stations for PM2.5, PM10, SO2, NO2, O3 and CO. Associations between annual ambient air pollution and low-grade systematic inflammation (hsCRP>3 mg/L) were estimated by generalized linear mixed models. Stratification analysis was also performed based on demographic characteristics, health-related behaviors and disease status. Annual ambient NO2 and O3 were all associated with low-grade systematic inflammation in single-pollutant models after adjusting for age, sex, blood lipids, blood pressure, lifestyle risk factors, cooking fuel, heating fuel and habits during smog days (NO2 per 10 µg/m3: OR = 1.057, P = 0.018; O3 per 10 µg/m3: OR = 0.953, P = 0.012). The 2-year and 3-year ozone concentrations were consistently associated with lower systematic inflammation (2-year O3 per 10 µg/m3: OR = 0.959, P = 0.004; 3-year O3 per 10 µg/m3: OR = 0.961, P = 0.014). In two-pollutant models, the estimated effects of annual NO2 and O3 on low-grade systematic inflammation remained stable. The effect size of annual pollutants on inflammation increased in participants without air-purifier usage (NO2 per 10 µg/m3: OR = 1.079, P = 0.009; O3 per 10 µg/m3: OR = 0.925, P = 0.001), while the association was null in the air-purifier usage group. Thus, long-term exposure to ambient NO2 and O3 was associated with low-grade systemic inflammation, and the results were generally stable after sensitivity analysis. The usage of air purifiers on smog days can modify the association between gaseous pollutants and systematic inflammation.

Discrepant acute effect of saline loading on blood pressure, urinary sodium and potassium according to salt intake level: EpiSS study.

Acute dietary salt intake may cause an elevation in blood pressure (BP). The study aimed to assess the acute effect of saline loading on BP in subjects with different levels of salt intake. This study is based on the baseline survey of systemic epidemiology of salt sensitivity study. The sodium excretion in the 24-hour urine was calculated for estimating the level of salt intake. Subjects were performed an acute oral saline loading test (1 L), and data of 2019 participants were included for analyses. Multivariate linear regression and stratified analyses were performed to identify associations between 24-hour urinary sodium (24hUNa) with BP changes. Due to saline loading, systolic BP (SBP), pulse pressure, and urinary sodium concentration were significantly increased, while diastolic BP, heart rate, and urinary potassium concentration were significantly decreased. The SBP increments were more significant in subjects with lower salt intake, normotensives, elders, males, smokers, and drinkers. There was a significant linear negative dose-response association between SBP increment with 24hUNa (ß = -0.901, 95% CI: -1.253, -0.548), especially in lower salt intake individuals (ß = -1.297, 95% CI: -2.338, -0.205) and hypertensive patients (ß = -1.502, 95% CI: -2.037, -0.967). After excluding patients who received antidiabetic or antihypertensive medicines, the effects of negative associations weakened but remained significantly. In conclusion, acute salt loading leads to an increment in SBP, and the increased SBP was negatively related with 24hUNa. This study indicated avoiding acute salt loading was important for escaping acute BP changes, especially in lower salt intake populations.

Environmental and Genetic Determinants of Major Chronic Disease in Beijing-Tianjin-Hebei Region: Protocol for a Community-Based Cohort Study.

Introduction: Personal lifestyle and air pollution are potential risk factors for major non-communicable diseases (NCDs). However, these risk factors have experienced dramatic changes in the Beijing-Tianjin-Hebei (BTH) region in recent years, and few cohorts have focused on identifying risk factors for major NCDs in this specific region. The current study is a large, prospective, long-term, population-based cohort study that investigated environmental and genetic determinants of NCDs in BTH areas. The results of this study may provide scientific support for efforts to develop health recommendations for personalized prevention. Methods: About 36,000 participants 18 years or older would be obtained by multistage, stratified cluster sampling from five cities for the baseline assessment. Participants underwent seven examinations primarily targeting respiratory and circulatory system function and filled out questionnaires regarding lifestyle behavior, pollutant exposure, medical and family history, medication history, and psychological factors. Biochemistry indicators and inflammation markers were tested, and a biobank was established. Participants will be followed up every 2 years. Genetic determinants of NCDs will be demonstrated by using multiomics, and risk prediction models will be constructed using machine learning methods based on a multitude of environmental exposure, examination data, biomarkers, and psychosocial and behavioral assessments. Significant spatial and temporal differentiation is well-suited to demonstrating the health determinants of NCDs in the BTH region, which may facilitate public health strategies with respect to disease prevention and survivorship-related aspects.

A cilium-independent role for intraflagellar transport 88 in regulating angiogenesis.

Endothelial cilia are microtubule-based hair-like protrusions in the lumen ofblood vessels that function as fluid mechanosensors to regulate vascular hemodynamics.However, the functions of endothelial cilia in vascular development remain controversial. In this study, depletion of several key proteins responsible for ciliogenesis allows us to identify a cilium-independent role for intraflagellartransport88 (IFT88) in mammalian angiogenesis. Disruption of primary cilia by heat shock does not affect the angiogenic process. However, depletion of IFT88 significantly inhibits angiogenesis both in vitro and in vivo. IFT88 mediates angiogenesis by regulating the migration, polarization, proliferation, and oriented division of vascular endothelial cells. Further mechanistic studies demonstrate that IFT88 interacts with γ-tubulin and microtubule plus-end tracking proteins and promotes microtubule stability. Our findings indicate that IFT88 regulates angiogenesis through its actions in microtubule-based cellular processes, independent of its role in ciliogenesis.

Elevated lipoprotein(a) and risk of coronary heart disease according to different lipid profiles in the general Chinese community population: the CHCN-BTH study.

BACKGROUND: To evaluate the contributions of elevated lipoprotein(a) [Lp(a)] to the risk of coronary heart disease (CHD) in the general Chinese community population according to different lipid profiles. METHODS: We recruited individuals aged over 18 years from the baseline survey of the Cohort Study on Chronic Disease of Communities Natural Population in Beijing, Tianjin and Hebei (CHCN-BTH) using a stratified, multistage cluster sampling method. Data were collected through questionnaire surveys, anthropometric measures and laboratory tests. Restricted cubic spline (RCS) functions, multivariate logistic regression, sensitivity analyses and stratified analyses were used to evaluate the association between Lp(a) and CHD. RESULTS: A total of 25,343 participants were included, with 1,364 (5.38%) identified as having CHD. Elevated Lp(a) levels were linearly related to an increased risk of CHD (Poverall-association<0.0001 and Pnonlinear-association=0.8468). Multivariate logistic regression analysis indicated that subjects with Lp(a) ≥300 mg/L had a higher risk of CHD [OR (95% CI): 1.36 (1.17, 1.57)] than did individuals with Lp(a) <300 mg/L. Compared with individuals with Lp(a) <119.0 mg/L (<50th percentile), the ORs (95% CI) for CHD in the 51st-80th, 81st-95th and >95th percentiles were 1.07 (0.93, 1.23), 1.26 (1.07, 1.50) and 1.68 (1.30, 2.17), respectively (P for trend <0.0001). This association was also found among the subgroup of subjects without dyslipidemia, including those with normal total cholesterol (TC) (<6.2 mmol/L), triglycerides (TG) (<2.3 mmol/L), high-density lipoprotein cholesterol (HDL-C) (≥1.0 mmol/L) and low-density lipoprotein cholesterol (LDL-C) (<4.1 mmol/L). Elevated Lp(a) and dyslipidemia significantly contributed to a higher risk of CHD with synergistic effects. Stratified analyses showed that elevated Lp(a) concentrations were significantly associated with an increased risk of CHD in the subgroups of individuals who were noncurrent drinkers, overweight individuals, individuals with hypertension, individuals who engaged in moderate physical activity, those without diabetes mellitus and individuals in Beijing and Tianjin. CONCLUSIONS: Elevated Lp(a) concentrations were linearly associated with a higher risk of CHD in the general Chinese community population, especially in normolipidemic subjects. Both dyslipidemia and elevated Lp(a) independently or synergistically contributed to the risk of CHD. Our results suggest that more attention should be paid to the levels of Lp(a) in normolipidemic subjects, which may be an early predictor of CHD.

Association of chronic diseases with depression, anxiety and stress in Chinese general population: The CHCN-BTH cohort study.

Background Large-scale epidemiological surveys focusing on characteristic differences in psychological and physical health conditions in Chinese adults are lacking. Objective To investigate the association of noncommunicable chronic diseases (NCDs) with depression, anxiety and stress in the Chinese general population. Methods A total of 13784 participants were recruited from the baseline survey of the Cohort Study on Chronic Disease of Communities Natural Population in Beijing, Tianjin and Hebei (CHCN-BTH) from 2017 to 2019. Sociodemographic characteristics, lifestyle and NCDs were assessed via questionnaire. Stress, anxiety and depression were assessed by the Depression-Anxiety-Stress Scale (DASS-21). The relationship of NCDs with psychological symptoms was determined through logistic regression analysis. Results Multivariate logistic regression analysis revealed that the prevalence of stress (OR = 1.640; 95% CI: 1.381-1.949), anxiety (OR = 1.654; 95% CI: 1.490-1.837) and depression (OR = 1.460; 95% CI: 1.286-1.658) symptoms were all significantly higher in patients with NCDs. Multimorbidities were associated with a higher risk of stress (OR = 2.310; 95% CI: 1.820-2.931), anxiety (OR = 2.119; 95% CI: 1.844-2.436) and depression (OR = 2.785; 95% CI: 1.499-2.126) than single NCDs. A course of disease within 1 year or more than 5 years also was associated with a higher risk. Limitations The cross-sectional design could not examine the causal link between psychological symptoms and NCDs. Conclusion Psychological symptoms were more prevalent among individuals with NCDs in the Chinese general population. This study suggests that more attention should be paid to the mental health problems of patients with NCDs.

New Insights Into Functions of IQ67-Domain Proteins.

IQ67-domain (IQD) proteins, first identified in Arabidopsis and rice, are plant-specific calmodulin-binding proteins containing highly conserved motifs. They play a critical role in plant defenses, organ development and shape, and drought tolerance. Driven by comprehensive genome identification and analysis efforts, IQDs have now been characterized in several species and have been shown to act as microtubule-associated proteins, participating in microtubule-related signaling pathways. However, the precise molecular mechanisms underpinning their biological functions remain incompletely understood. Here we review current knowledge on how IQD family members are thought to regulate plant growth and development by affecting microtubule dynamics or participating in microtubule-related signaling pathways in different plant species and propose some new insights.

Identification of lncRNA-NR_104160 as a biomarker and construction of a lncRNA-related ceRNA network for essential hypertension.

OBJECTIVES: To identify long noncoding RNAs (lncRNAs) and construct a competing endogenous RNA (ceRNA) network for essential hypertension. METHODS: An RNA microarray and two-step quantitative real-time PCR were applied to identify differentially expressed RNAs (DE-RNAs), and a luciferase assay was performed to explore the binding relationship between RNAs. A generalized linear model and logistic regression model were used to analyze the associations between different RNAs and of RNAs with hypertension. Receiver operating characteristic curve analysis was executed to evaluate the diagnostic performance. Bioinformatics analysis was applied for network construction. RESULTS: In total, 439 DE-RNAs (387 lncRNAs and 52 mRNAs) were identified in the microarray, and 71 'lncRNA-miRNA-mRNA' loops formed the ceRNA network. The first validation confirmed that five RNAs (NR_104160, lnc-GPR63-8:1, lnc-HPRT1-9:1, ID1 and RSL24D1) were significantly upregulated in hypertensives (P < 0.05). NR_104160 was significantly associated with hypertension (OR = 2.863, 95% CI: 1.143-7.172; P = 0.025) after adjusting for confounding factors. NR_104160 was included in the hypertension diagnostic model, with an area under the curve of 0.852 (95% CI: 0.761-0.944). In the second validation, NR_104160 showed a constant significant difference (P = 0.001). An elevated expression level of NR_104160 was associated with the expression of ID1 (ß = 0.2235, P = 0.005). Luciferase assays showed hsa-miR-101-3p stimulation significantly inhibited the reporter gene activation ability of the NR_104160 wild-type plasmid (P < 0.001). CONCLUSIONS: Our study constructed a ceRNA network to provide hypotheses regarding the mechanism of hypertension development. lncRNA-NR_104160 was identified as a hub element that participates in hypertension transcriptional regulation and as a potential biomarker.

Inflammatory cytokines and DNA methylation in healthy young adults exposure to fine particulate matter: A randomized, double-blind crossover trial of air filtration.

Benefits of indoor air filtration in heavily polluted areas are not fully understood. This study aims to examine whether short-term air filtration intervention could attenuate the hazards from acute exposure to fine particulate matter (PM2.5), and investigate the potential impact on inflammatory cytokines and DNA methylation. A randomized, double-blind crossover trial of true or sham indoor air filtration was conducted among 29 healthy young adults in Beijing, China. Each episode covered a typical air pollution wave, and 38 cytokines and DNAm of 20 genes were measured at 3 time points: pre-smog, during smog, and post-smog. Linear mixed-effect models were used to evaluate the associations. The indoor PM2.5 concentration with true filtration was 67.8 % lower than sham filtration (13.8 µg/m3vs. 42.8 µg/m3). Air filtration was significantly associated with the decreases in 9 cytokines, from 6.61 % to 21.24 %. PM2.5 exposure was significantly associated with elevated levels of 9 cytokines and changed methylation at 7 CpG sites. Notably, PM2.5 was significantly associated with GM-CSF, sCD40L, MCP-1, and FGF-2, as well as methylation in corresponding genes, but no mediation effect was observed. This trial suggested that indoor air filtration might attenuate the adverse effects of PM2.5 exposure through changing cytokines and DNAm.

Associations of long-term exposure to ambient air pollution with cardiac conduction abnormalities in Chinese adults: The CHCN-BTH cohort study.

BACKGROUND: Evidence regarding the effects of long-term and high-level ambient air pollution exposure on cardiac conduction systems remains sparse. OBJECTIVES: To investigate the associations of long-term exposure to air pollution and cardiac conduction abnormalities in Chinese adults and explore the susceptibility characteristics. METHODS: In 2017, a total of 27,047 participants aged 18-80 years were recruited from the baseline survey of the Cohort Study on Chronic Disease of Communities Natural Population in Beijing, Tianjin and Hebei (CHCN-BTH). The three year (2014-2016) average pollutant concentrations were assessed by a spatial statistical model for PM2.5 and air monitoring stations for PM10, SO2, NO2, O3 and CO. Residential proximity to a roadway was calculated by neighborhood analysis. Associations were estimated by two-level generalized linear mixed models. Stratified analyses related to demographic characteristics, health behaviors, and cardiometabolic risk factors were performed. Two-pollutant models were used to evaluate the possible role of single pollutants. RESULTS: We detected significant associations of long-term air pollutant exposure with increased heart rate (HR), QRS and QTc, such that an interquartile range increase in PM2.5 was associated with 3.63% (95% CI: 3.07%, 4.19%), 1.21% (95% CI: 0.83%, 1.60%), and 0.13% (95% CI: 0.07%, 0.18%) changes in HR, QRS and QTc, respectively. Compared to the other pollutants, the estimates of PM2.5 remained the most stable across all two-pollutant models. Similarly, significant associations were observed between living closer to a major roadway and higher HR, QRS and QTc. Stratified analyses showed generally greater association estimates in older people, males, smokers, alcohol drinkers, and those with obesity, hypertension and diabetes. CONCLUSIONS: Long-term exposure to ambient air pollution was associated with cardiac conduction abnormalities in Chinese adults, especially in older people, males, smokers, alcohol drinkers, and those with cardiometabolic risk factors. PM2.5 may be the most stable pollutant to reflect the associations.