Air Pollutants and Mortality Risk in Patients with Aortic Dissection: Evidence from a Clinical Cohort, Single-Cell Sequencing, and Proteomics.

We aimed to evaluate the association between air pollutants and mortality risk in patients with acute aortic dissection (AAD) in a longitudinal cohort and to explore the potential mechanisms of adverse prognosis induced by fine particulate matter (PM2.5). Air pollutants data, including PM2.5, PM10.0, nitrogen dioxide (NO2), carbon monoxide (CO), sulfur dioxide (SO2), and ozone (O3), were collected from official monitoring stations, and multivariable Cox regression models were applied. Single-cell sequencing and proteomics of aortic tissue were conducted to explore the potential mechanisms. In total, 1,267 patients with AAD were included. Exposure to higher concentrations of air pollutants was independently associated with an increased mortality risk. The high-PM2.5 group carried approximately 2 times increased mortality risk. There were linear associations of PM10, NO2, CO, and SO2 exposures with long-term mortality risk. Single-cell sequencing revealed an increase in mast cells in aortic tissue in the high-PM2.5 exposure group. Enrichment analysis of the differentially expressed genes identified the inflammatory response as one of the main pathways, with IL-17 and TNF signaling pathways being among the top pathways. Analysis of proteomics also identified these pathways. This study suggests that exposure to higher PM2.5, PM10, NO2, CO, and SO2 are associated with increased mortality risk in patients with AAD. PM2.5-related activation and degranulation of mast cells may be involved in this process.

Differentiating Origins of Outflow Tract Ventricular Arrhythmias: The Correction of Transitional Zone Index Is Not Superior to the Original One.

INTRODUCTION: Our team once proposed a correction of transitional zone index (CTZI) based on the transitional zone index (TZI) in view of achieving a more precise prediction of outflow tract ventricular arrhythmia (OTVA). The predictive accuracy of these two electrocardiogram (ECG) algorithms has not been validated and compared. The purpose of this study was to compare the predictive accuracy of TZI and CTZI in a much larger population with idiopathic OTVA. METHODS: The predictive accuracy of TZI and CTZI was compared in 695 individuals with idiopathic premature ventricular complex or ventricular tachycardia which exhibited a left bundle branch block pattern and inferior axis QRS morphology. Receiver operating characteristic curve analysis, decision curve analysis, and calibration curve were used to compare the predictive accuracy of TZI and CTZI. RESULTS: TZI and CTZI manifested the similar area under the curve. While a TZI of <0 predicted a left ventricular outflow tract (LVOT) origin with a high specificity of 88.2% but a low sensitivity of 67.1%, a CTZI of <0 yielded a high sensitivity of 84.3% but a low specificity of 59.5% in the overall analysis. Similar results were yielded in the sub-analysis of participants with a precordial transition occurring at lead V3. In the sub-analysis of participants with a TZI = 0, CTZI demonstrated a bit higher but not satisfactory predictive accuracy than TZI. CONCLUSION: Based on the scientific spirit of self-criticism and seeking truth from facts, our team disproves the correction of TZI proposed previously.

Abnormal adiposity indices are associated with an increased risk of diabetes in a non-obese Asian population.

OBJECTIVES: The aim of this study was to evaluate the association between adiposity indices and the risk of incident diabetes and to compare their predictive ability in non-obese healthy individuals. STUDY DESIGN: Population-based cohort study. METHODS: Data were taken from the NAGALA research study, which enrolled Japanese adults aged 18-79 years. Cox regression was used to evaluate the association between adiposity indices (including waist circumference [WC], waist-to-height ratio [WHtR], lipid accumulation product index [LAP], body roundness index [BRI], visceral adiposity index [VAI] and Chinese visceral adiposity index [CVAI]) and diabetes risk. The performance of the indices for predicting diabetes was explored using area under the receiver operating characteristic curve (AUC). A Chinese community-based population was used for validation. RESULTS: A total of 12,940 healthy Japanese individuals with normal body mass index and glycaemic levels were included and were followed up for a median of 6 years. Multivariable Cox models revealed a positive and significant association between all indices and incident diabetes, with the hazard ratios for the highest quartile of the indices ranging from 1.89 to 2.90 (all P-values < 0.01). A non-linear association between WC, BRI and VAI and a linear association between WHtR, LAP and CVAI and diabetes risk were observed. CVAI, VAI and LAP had comparable ability in predicting diabetes, with the highest AUC being 0.733 for CVAI. Data from 10,830 Chinese individuals confirmed these results. CONCLUSIONS: Adiposity indices are associated with incident diabetes in healthy non-obese individuals. Participants in the highest quartile of WC, WHtR, LAP, BRI, VAI and CVAI had an increased risk of developing diabetes.

Visceral fat and its dynamic change are associated with renal damage: Evidence from two cohorts.

BACKGROUND AND AIMS: To evaluate the association of Chinese visceral adiposity index (CVAI) and its dynamic trends with risk of renal damage, and to compare its prediction performance with that of other obesity indices. METHODS AND RESULTS: A community-based population with 23 905 participants from Shantou city was included in the cross-sectional analysis. A total of 9,778 individuals from two separated cohort were included in the longitudinal portion. Five patterns of CVAI change were predefined (low-stable, decreasing, moderate, increasing, and persistent-high). Logistic and Cox regressions were used to evaluate the association between CVAI and renal damage. We explored potential mechanisms using the mediating effect method, and the prediction performance was determined by receiver operating characteristic curve analysis. Results from both cross-sectional and longitudinal data revealed a positive and linear association between CVAI and risk of renal damage. Pooled analysis of the two cohorts showed that per unit increase in Z score of CVAI induced 18% increased risk of renal damage (P = .008). Longitudinal trends of CVAI were also associated with renal damage, and the moderate, increasing, and persistent-high patterns showing a higher risk. Blood pressure and glucose had a mediating effect on renal damage induced by CVAI. Among several obesity indices, CVAI was the optimal for predicting renal damage. CONCLUSION: A higher level of immediate CVAI and longitudinal increasing and persistent-high patterns of CVAI were independently associated with increased risk of renal damage. Monitoring immediate level and long-term trend of CVAI may contribute to the prevention of renal damage.

Protocol update for late endothelial progenitor cells identified by double-positive staining.

Endothelial progenitor cells (EPCs), which are precursors of endothelial cells (ECs), have the capacity to circulate, proliferate and differentiate into mature ECs. EPCs are primarily identified by the uptake of 1,1-dioctadecyl-3,3,3,3-tetramethylindocarbocyanine-labelled acetylated low-density lipoprotein (Dil-acLDL) and the binding of fluorescein-isothiocyanate (FITC)-conjugated Ulex europaeus agglutinin lectin (FITC-UEA-I). However, the cytoplasm and nucleus are usually stained by FITC-UEA-I via a typical method to double-stain late EPCs. It is necessary to explore a new method to improve the quality of fluorescence photomicrographs of late EPCs stained with FITC-UEA-I. Here, we described an updated protocol for double-staining late EPCs with Dil-acLDL and FITC-UEA-I, with the cells more optimally stained with FITC-UEA-I.

Reference intervals for coagulation tests in adults with different ABO blood types.

INTRODUCTION: Coagulation tests are affected by many factors, such as age, race, and gestation. Although coagulation test results vary by ABO blood type, reference intervals of different ABO blood groups remain to be determined. This study aims to investigate the reference ranges of coagulation tests for different ABO blood groups in the Han population in South China. METHODS: A retrospective study was conducted in the First Affiliated Hospital of Shantou University Medical College. In all, 9600 individuals aged between 20 and 79 years were included. Coagulation tests, including prothrombin time (PT), international normalized ratio (INR), activated partial thromboplastin time (aPTT), thrombin time, and fibrinogen, were performed. RESULTS: There was a significant difference in PT, INR, and aPTT among ABO blood groups. PT and INR varied slightly between ABO blood groups. There was a higher aPTT value in individuals in the O blood group than in those in non-O blood groups, in both males and females across the included age range. No differences were found in thrombin time and fibrinogen between the ABO blood groups. CONCLUSION: The study provides reference data on coagulation tests from ABO blood groups in South China. The established reference intervals specific to ABO blood type, sex, and age may improve clinical decisions based on coagulation tests.

Construct validity of the Suboptimal Health Status Questionnaire-25 in a Ghanaian population.

BACKGROUND: The Suboptimal Health Status Questionnaire-25 (SHS-Q-25) developed to measure Suboptimal Health Status has been used worldwide, but its construct validity has only been tested in the Chinese population. Applying Structural Equation Modelling, we investigate aspects of the construct validity of the SHS-Q-25 to determine the interactions between SHS subscales in a Ghanaian population. METHODS: The study involved healthy Ghanaian participants (n = 263; aged 20-80 years; 63% female), who responded to the SHSQ-25. In an exploratory factor and parallel analysis, the study extracted a new domain structure and compared to the established five-domain structure of SHSQ-25. A confirmatory factor analysis (CFA) was conducted and the fit of the model further discussed. Invariance analysis was carried out to establish the consistency of the instrument across multi-groups. RESULTS: The extracted domains were reliable with Cronbach's [Formula: see text] of 0.846, 0.820 and 0.864 respectively, for fatigue, immune-cardiovascular and cognitive. The CFA revealed that the model fit indices were excellent [Formula: see text]. The fit indices for the three-domain model were statistically superior to the five-domain model. There were, however, issues of insufficient discriminant validity as some average variance extracts were smaller than the corresponding maximum shared variance. The three-domain model was invariant for all constrained aspects of the structural model across age, which is an important risk factor for most chronic diseases. CONCLUSION: The validity tests suggest that the SHS-Q25 can measure SHS in a Ghanaian population. It can be recommended as a screening tool to early detect chronic diseases especially in developing countries where access to facilities is diminished.

Effect of n-3 polyunsaturated fatty acids on ischemic heart disease and cardiometabolic risk factors: a two-sample Mendelian randomization study.

BACKGROUND: The cardioprotective ability of n-3 polyunsaturated fatty acids (PUFAs) is controversial. Most studies suggest a specific role for PUFAs in cardioprotection from ischemic heart disease (IHD). However, few studies have used genetic biomarkers of n-3 PUFAs to examine their potential relationships with IHD. This study aimed to use Mendelian randomization to evaluate whether genetically-predicted n-3 PUFAs affect IHD and cardiometabolic risk factors (CRFs). METHODS: Genetic variants strongly (p < 5 × 10-8) and independently (r2 > 0.1) associated with n-3 PUFAs were derived from the CHARGE Consortium (including 8,866 subjects of European ancestry) and were used as instrumental variables (IVs) for evaluating the effect of n-3 PUFAs, including α-linolenic acid (ALA), docosapentaenoic acid (DPA), docosahexaenoic acid (DHA), and eicosapentaenoic acid (EPA). Data on the associations between the IVs and IHD, myocardial infarction, and CRFs (including diabetes, lipids, blood pressure, body mass index, and waist-to-hip ratio (WHR)) were obtained from the UK Biobank SOFT CAD GWAS with the CARDIoGRAMplusC4D 1000 Genomes-based GWAS (113,937 IHD cases and 339,115 controls), the Myocardial Infarction Genetics and CARDIoGRAM Exome consortia (42,335 MI cases and 78,240 controls), the DIAbetes Genetics Replication And Meta-analysis consortium (26,676 diabetes mellitus cases and 132,532 controls), the Global Lipids Genetics Consortium (n = 196,475), the International Consortium for Blood Pressure (n = 69,395), and the meta-analysis of GWAS for body fat distribution in the UK Biobank and Genetic Investigation of Anthropometric Traits (n = 694,649). RESULTS: Genetically-predicted higher ALA was associated with lower risk of IHD, type 2 diabetes (T2D), and lower serum lipids. The effect size per 0.05-unit increase (about 1 standard deviation) in plasma ALA level) was - 1.173 (95% confidence interval - 2.214 to - 0.133) for IHD. DPA and EPA had no association with IHD but were associated with a higher risk of T2D, higher levels of lipids or WHR. DHA had no association with IHD or CRFs. CONCLUSIONS: Our study suggests a benefit of ALA for IHD and its main risk factors. DHA, DPA, and EPA had no association with IHD but were partly associated with increasing cardiometabolic risk factors.

The loss-of-function mutation of CETP affects HDLc levels but not ApoA1 in patients with acute myocardial infarction.

BACKGROUND AND AIMS: Loss of the cholesteryl ester transfer protein (CETP) function affects HDLc levels, but its effects on major HDL protein component ApoA1 are not well understood in patients with acute myocardial infarction (AMI). METHODS AND RESULTS: We investigated the effects of an East Asian loss-of-function variant (rs2303790; p.D442G) in CETP gene on HDLc and ApoA1 levels and its relationship with AMI. A total of 2327 AMI patients and 2615 age- and sex-matched controls from INTERHEART-China study were included. In controls, both levels of HDLc (1.24 vs. 1.04 mmol/L, P = 0.001) and ApoA1 (1.48 vs. 1.37 mmol/L, P = 0.042) were significantly higher in CETP variant G allele carriers compared to CETP wildtype D allele carriers. In AMI patients, levels of HDLc were significantly higher (1.14 vs. 1.01 mmol/L, P = 0.013) while levels of ApoA1 were not statistically difference (1.31 vs. 1.32 mmol/L, P = 0.468) in CETP variant group compared to CETP wildtype group. Moreover, CETP variant is associated with HDLc increase, but is not associated with AMI risk (P = 0.564), even after adjusting for age, sex, history of hypertension and diabetes, waist to hip ratio, smoking, total cholesterol, LDL cholesterol, triglycerides, physical activity, depression, alcohol, vegetables and fruit consumption. CONCLUSIONS: Loss of CETP function is associated with increased HDLc and ApoA1 levels in healthy subjects, and in AMI patients, it is associated with HDLc levels but not ApoA1 levels. The lack of association of CETP variant with AMI may be related to the inability to increase ApoA1 levels and warranted further studies.

The association between ECG criteria and Echo criteria for left ventricular hypertrophy in a general Chinese population.

BACKGROUND: Several ECG criteria have been widely used for diagnosis of left ventricular hypertrophy (LVH) in clinical practice. However, their performance in a general Chinese population is limited. METHODS AND RESULTS: A multi-stage, stratified cluster sampling across China was performed and 7415 representative Chinese adults aged 18-85 years were analyzed. ECG was collected by using GE MAC 5500 machine. The association between five ECG-LVH criteria (i.e., Peguero-Lo Presti, Cornell, Cornell product, Sokolow-Lyon and Sokolow-Lyon product) and echocardiographic LVH (Echo-LVH) was assessed by Pearson's correlation, diagnostic statistics like predictive values, and receiver operating characteristics (ROC) curve. We found that the prevalence of the Echo-LVH was 11% while ECG-LVH ranged from 3% to 27%. All ECG-LVH criteria had high negative predictive value (NPV) (89%) and specificity (73-96%) but low positive predictive value (PPV) (12-24%) and sensitivity (4-29%). The newly Peguero-Lo Presti criteria had higher sensitivity (29%) but lower specificity (73%) and accuracy (68%) compared with other criteria. Cornell product had the best diagnostic performance (AUC: 0.59), as well as the highest specificity (96%) and accuracy (86%) but lowest sensitivity (4%). Among single-lead components of ECG criteria, RaVL voltage and QRS duration performed relatively better than others. Hypertensive and older individuals had higher sensitivity but lower specificity and accuracy than their counterparts. CONCLUSION: ECG-LVH criteria had high NPV to detect Echo-LVH. Though with higher sensitivity, Peguero-Lo Presti criteria did not have better diagnostic performance to detect Echo-LVH. RaVL and QRS duration had stronger association with Echo-LVH among all single-lead components.

Evaluation of right myocardial performance index of in vitro fertilization fetuses and spontaneous pregnancy fetuses: a cross-sectional study.

BACKGROUND: Whether the in vitro fertilization (IVF) has an effect on the cardiac function of the fetus is very important to evaluate the safety of the technique. The aim of this paper is to establish normal reference range for the fetal right myocardial performance index (RMPI), and compare the reference range between IVF fetuses and spontaneous pregnancy (SP) fetuses by automatic measurement of the RMPI. METHODS: Three hundred seventy-one spontaneous singleton pregnancies (the control group) and 39 singleton pregnancies conceived by IVF (the experimental group) were enrolled into the current study. An automatic measurement system was used to acquire the RMPI. The cardiac function of the two groups was compared by t-test. RESULTS: There was no significant difference in normal reference range of RMPI between IVF fetuses and SP fetuses (RMPI 0.42 ± 0.05 vs 0.43 ± 0.05). No strong correlation was also noted between RMPI with gestational age and heart rate. CONCLUSIONS: Normal reference ranges of RMPI of IVF fetuses and SP fetuses were established, and no significant difference between IVF fetuses and SP fetuses in RMPI was found. Thus, these findings may suggest that IVF has little impact on cardiac function of the fetus.

Non-O blood group is associated with lower risk of in-hospital mortality in non-surgically managed patients with type A aortic dissection.

BACKGROUND: The association between different ABO blood groups and mortality of aortic dissection (AD) remains controversial. This study aimed to examine whether different ABO blood groups affect the prognosis of AD. METHODS: Demographic and clinical data were collected from 877 patients diagnosed with AD from 2015 to 2019 in the First Affiliated Hospital of Shantou University Medical College. The association between in-hospital mortality of AD patients and ABO blood group was analyzed using Cox proportional hazards regression models. RESULTS: This retrograde cohort study demonstrated that for 877 patients, male gender, non-O blood group, Stanford type B AD (TBAD), higher presenting systolic and diastolic blood pressure, and being a recipient of aortic arch replacement surgery (surgery) or endovascular stent-graft implantation (stent-graft) were associated with decreased in-hospital mortality of AD. In Cox proportional hazards models, non-O blood group was associated with lower risk of early mortality regardless of adjustment (HR = 0.668, 95% confidence interval [CI] 0.473-0.944 before adjustment, HR = 0.662, 95% CI 0.468-0.935 after adjustment for age and sex, and HR = 0.641, 95% CI 0.453-0.906 after adjustment for AD types, SBP and surgery). Further analyses revealed that for patients diagnosed with type A AD (TAAD), non-O blood group renders a significant 34.3% decrease in the risk of in-hospital mortality compared with blood group O. Specifically, this difference in mortality risk was found among TAAD patients who did not undergo surgery (HR = 0.579, 95% CI 0.377-0.889), rather than those who did. There was no significant difference in early mortality for patients with TBAD, whether or not stent-grafts were implanted. CONCLUSIONS: Non-O blood type decreases the risk of in-hospital mortality, especially for TAAD, in AD patients without surgical intervention. More attention must be paid to blood type O TAAD patients without surgical interventions, and early surgical intervention may be an effective means to decrease in-hospital mortality of TAAD.

Epigallocatechin-3-gallate regulates mitofusin 2 expression through the peroxisome proliferator-activated receptor-γ coactivator-1α and estrogen-related receptor-α pathway.

Our previous study showed that epigallocatechin-3-gallate (EGCG) inhibition of human aortic smooth muscle cell (HASMC) proliferation might be mediated via upregulation of mitofusin 2 (Mfn-2). Studies on the mechanism of Mfn-2 inhibition of cell proliferation have mainly focused on downstream signaling. However, it is still not clear how upstream signaling molecules regulate Mfn-2. The promoter region of the Mfn-2 gene contains cis-acting elements of peroxisome proliferator-activated receptor-γ coactivator-1α (PGC-1α) and estrogen-related receptor-α (ERR-α), suggesting a possible link between EGCG, Mfn-2, and PGC-1α/ERR-α. However, the effect of EGCG on PGC-1α/ERR-α remains unknown. In this study, we investigated the role of PGC-1α/ERR-α in the regulation of Mfn-2 induced by EGCG and assessed the underlying mechanisms. The effects of EGCG on cell proliferation of cultured HASMCs were observed by a cell counting kit-8 (CCK8) and 5-ethynyl-2-deoxyuridine (EdU) incorporation assay. Mfn-2, PGC-1α, and ERR-α gene and protein levels were determined by quantitative real-time polymerase chain reaction (PCR) and Western blot analysis. PGC-1α gene-silencing (PGC-1α small interfering RNA [siRNA]) was achieved by RNA interference and Mfn-2 promoter and peroxisome proliferator response element (PPRE) functional activity was achieved by a luciferase transfection assay. The results showed that the ERR-α-specific antagonist XCT-790 and PGC-1α siRNA decreased the expression of Mfn-2, thus antagonizing the inhibition of HASMC proliferation induced by EGCG. EGCG enhanced Mfn-2 promoter (-352 to 459) activity, while XCT-790 and PGC-1α siRNA abrogated this effect. PGC-1α stimulating Mfn-2 expression was dependent on intact ERR-α binding in the Mfn-2 promoter. The transcriptional effect of PGC-1α on the Mfn-2 promoter required the integrity of the -432 to 459 region and supported that Mfn-2 was a key target gene of PGC-1α. These results imply that PGC-1α/ERR-α played important physiological roles in inhibiting the proliferation of HASMCs by modulating Mfn-2 gene expression. Hence, EGCG regulated Mfn-2 expression likely through the PGC-1α/ERR-α pathway.

Neutrophil-to-lymphocyte and platelet-to-lymphocyte ratio in Chinese Han population from Chaoshan region in South China.

BACKGROUND: Neutrophil-to-lymphocyte ratio (NLR) and platelet-to-lymphocyte ratio (PLR) are assumed to be prognostic factors in many diseases such as inflammatory diseases, cardiovascular diseases and cancer. However, NLR and PLR are race specific, it is important to determine the reference values of NLR and PLR in different races. The study aimed to investigate the reference range of NLR and PLR in Chinese Han population from Chaoshan region in South China. METHODS: A retrospective study was conducted in the First Affiliated Hospital of Shantou University Medical College in South China. Five thousand healthy adults aged 20-69 years were included. NLR and PLR were determined. RESULTS: Of 5000 healthy adults, 2500 men and 2500 women were included. The mean NLR and PLR across all ages for men and women were 1.59 ± 0.59, 92.88 ± 28.70, 1.62 ± 0.64 and 108.02 ± 32.99, respectively. The 95% reference range of NLR in normal male and female are 0.43~2.75 and 0.37~2.87, PLR are 36.63~149.13 and 43.36~172.68, respectively. The female had a higher NLR at age 30~49 than the male while the NLR at age 60~69 was higher in male than in female. The PLR was higher in female than in male. CONCLUSION: The study provides reference data on NLR and PLR from different age and sex groups in South China. NLR and PLR varied with age and sex.

Optimal blood pressure control for patients after thoracic endovascular aortic repair of type B aortic dissection.

BACKGROUND: Guidelines recommend tight systolic blood pressure (SBP) control for favorable outcomes of type B aortic dissection (BAD) but are still limited by the optimal cut-off value of SBP. The purpose of this study was to evaluate the optimal cut-off value of SBP in BAD patients after thoracic endovascular aortic repair (TEVAR). METHODS: From January 2011 to April 2017, 269 consecutive patients with BAD after TEVAR were included in the study. All patients were followed up according to a strict follow-up protocol. Cox regression analysis was used to examine the association between SBP at discharge and 90-day aortic related adverse events (ARAE). RESULTS: All 269 patients completed 90 days of follow-up, and the unadjusted ARAE-free rates at 90-day was 95.1 ± 1.3%. The cut-off value of SBP at discharge identified by receiver operator curve was 130 mmHg for 90-day ARAE. In multivariable models, binary SBP at discharge was significant associated with 90-day ARAE (HR 3.780; 95% CI 1.236-11.556; p = 0.020). Hybrid operation (OR 2.046; 95%CI 1.015-4.122; p = 0.045) and insertion of ≥2 stents (OR 2.950; 95%CI 1.172-7.426; p = 0.022) were demonstrated to be independently associated with poor SBP control (SBP > 130 mmHg) using Logistic analysis. CONCLUSIONS: The optimal cut-off value of SBP at discharge was 130 mmHg which can be used to predict short-term ARAE. Blood pressure in patients with hybrid operation and ≥ 2 stents should be given more focus.

Coronary-Heart-Disease-Associated Genetic Variant at the COL4A1/COL4A2 Locus Affects COL4A1/COL4A2 Expression, Vascular Cell Survival, Atherosclerotic Plaque Stability and Risk of Myocardial Infarction.

Genome-wide association studies have revealed an association between coronary heart disease (CHD) and genetic variation on chromosome 13q34, with the lead single nucleotide polymorphism rs4773144 residing in the COL4A2 gene in this genomic region. We investigated the functional effects of this genetic variant. Analyses of primary cultures of vascular smooth muscle cells (SMCs) and endothelial cells (ECs) from different individuals showed a difference between rs4773144 genotypes in COL4A2 and COL4A1 expression levels, being lowest in the G/G genotype, intermediate in A/G and highest in A/A. Chromatin immunoprecipitation followed by allelic imbalance assays of primary cultures of SMCs and ECs that were of the A/G genotype revealed that the G allele had lower transcriptional activity than the A allele. Electrophoretic mobility shift assays and luciferase reporter gene assays showed that a short DNA sequence encompassing the rs4773144 site interacted with a nuclear protein, with lower efficiency for the G allele, and that the G allele sequence had lower activity in driving reporter gene expression. Analyses of cultured SMCs from different individuals demonstrated that cells of the G/G genotype had higher apoptosis rates. Immunohistochemical and histological examinations of ex vivo atherosclerotic coronary arteries from different individuals disclosed that atherosclerotic plaques with the G/G genotype had lower collagen IV abundance and thinner fibrous cap, a hallmark of unstable, rupture-prone plaques. A study of a cohort of patients with angiographically documented coronary artery disease showed that patients of the G/G genotype had higher rates of myocardial infarction, a phenotype often caused by plaque rupture. These results indicate that the CHD-related genetic variant at the COL4A2 locus affects COL4A2/COL4A1 expression, SMC survival, and atherosclerotic plaque stability, providing a mechanistic explanation for the association between the genetic variant and CHD risk.

Integrative analysis of competing endogenous RNA networks reveals the functional lncRNAs in heart failure.

Heart failure has become one of the top causes of death worldwide. It is increasing evidence that lncRNAs play important roles in the pathology processes of multiple cardiovascular diseases. Additionally, lncRNAs can function as ceRNAs by sponging miRNAs to affect the expression level of mRNAs, implicating in numerous biological processes. However, the functional roles and regulatory mechanisms of lncRNAs in heart failure are still unclear. In our study, we constructed a heart failure-related lncRNA-mRNA network by integrating probe re-annotation pipeline and miRNA-target interactions. Firstly, some lncRNAs that had the central topological features were found in the heart failure-related lncRNA-mRNA network. Then, the lncRNA-associated functional modules were identified from the network, using bidirectional hierarchical clustering. Some lncRNAs that involved in modules were demonstrated to be enriched in many heart failure-related pathways. To investigate the role of lncRNA-associated ceRNA crosstalks in certain disease or physiological status, we further identified the lncRNA-associated dysregulated ceRNA interactions. And we also performed a random walk algorithm to identify more heart failure-related lncRNAs. All these lncRNAs were verified to show a strong diagnosis power for heart failure. These results will help us to understand the mechanism of lncRNAs in heart failure and provide novel lncRNAs as candidate diagnostic biomarkers or potential therapeutic targets.

An electrocardiographic diagnostic model for differentiating left from right ventricular outflow tract tachycardia origin.

INTRODUCTION: Although several electrocardiographic (ECG) algorithms have been proposed for differentiating the origins of outflow tract ventricular arrhythmias, the most optimal one has not been agreed on. The purpose of this study was to establish an ECG diagnostic model based on the previous ECG algorithms. METHODS AND RESULTS: The following ECG diagnostic model, Y=-1.15×( TZ )-0.494×(V2S/V3R), was developed by standard 12-lead ECG algorithms in 488 patients with idiopathic premature ventricular contractions or ventricular tachycardia with a left bundle branch block pattern and inferior axis QRS morphology. Binary logistic regression analysis was performed to establish the ECG diagnostic model. The ECG diagnostic model consisted of two ECG algorithms-the transition zone (TZ) index and V2S/V3R index. The area under the curve by receiver operating characteristic curve analysis for the ECG diagnostic model was 0.88, with a cut-off value of ≥ -0.76 predicting a left ventricular outflow tract (LVOT) origin with a sensitivity of 82% and a specificity of 86%, which was higher than other ECG algorithms in this study. The predictive accuracy of the ECG diagnostic model was also the best among all ECG algorithms in patients with a lead V3 precordial transition. This model was tested prospectively in 207 patients with a sensitivity of 90%, a specificity of 87%, and Youden index of 0.77. CONCLUSIONS: A highly accurate ECG diagnostic model for correctly differentiating LVOT origin from right ventricular outflow tract origin was developed.

A Simple Scoring System for Quick, Accurate, and Reliable Early Diagnosis of Hand, Foot, and Mouth Disease.

BACKGROUND To construct an accurate, reliable, and simple scoring system of improving HFMD diagnosis. MATERIAL AND METHODS Based on the following 3 steps, a simple scoring diagnostic system was built: (1) we selected basic markers (age and sex), markers recommended in HFMD diagnosis guidelines, and significant biomarkers among severity groups found in a large dataset; (2) we used positive constituent ratio for determining scores of each marker; and (3) we applied receiving operating curve in an external dataset to determine the optimal cut-off score. RESULTS The selected markers were sex, age, fever, skin rashes, nervous system disorder, respiratory system disorder, digestive system disorder and cardiopulmonary complications, C-reactive-protein, White Blood Cell, Creatinine Kinase, Creatinine Kinase Isoenzyme, Gamma-Glutamyl Transpeptidase, Albumin, Globulin, Albumin/Globulin Ratio, Natrium, Chloride, Calcium, and Glucose. A simple scoring system with 3.9684 as the lower cut-off was constructed. The AUC was 0.918 (95% CI: 0.874-0.963, P<0.01). The sensitivity, specificity, and Youden Index, which were based on the validation dataset of 200 subjects (80 cases, 120 non-cases with skin rashes or fever), were 0.95, 0.90, and 0.85, respectively. CONCLUSIONS This simple scoring system is an effective method to diagnose HFMD.

Models for improved diagnosis of left ventricular hypertrophy based on conventional electrocardiographic criteria.

BACKGROUND: Electrocardiogram (ECG) is commonly used clinically due to convenience, but its accuracy is insufficient for left ventricular hypertrophy (LVH) diagnosis. In this study, we attempted to improve diagnostic accuracy of LVH by establishing models with ECG parameters. METHODS: Eighty hundred and twenty eight patients were recruited in the present study which were divided into groups according to gender, age and body mass index (BMI). The sensitivity, specificity, Youden index, positive predictive value, negative predictive value and accuracy were calculated using ultrasonic cardiogram criteria of LVH as the gold standard. Area under the curve was also calculated to assess the diagnostic accuracy of 22 conventional ECG criteria in different groups. Stepwise discriminant analyses were performed to establish models of ECG for LVH. RESULTS: The diagnostic accuracy of ECG11 (S V2 + R V5,6) and ECG12 (S V1,2 + R V5,6) was significantly higher than the other 20 criteria, while ECG15 (R V5/R V6) was lowest. The ECG12 sensitivity for males was 52.5%, for <60 years old was 44.2%, and for BMI <25 kg/m2 was 46.2%,higher than for females (27.5%), for ≧60 years old (35.7%), and for BMI ≧25 kg/m2(27.6%), respectively. The difference between genders was the most obvious. Based on these observations, the following models for males and females were established:[Formula: see text]and[Formula: see text]respectively. The sensitivities of the two new models were 71.4% and 75.8%, significantly higher than the22 conventional ECG criteria. CONCLUSION: Two models developed based on gender can be considered for use to investigate the preliminary assessment of the probability of LVH.