Integrated analysis of differentially m6A modified and expressed lncRNAs for biomarker identification in coronary artery disease.

N6-methyladenosine (m6A) is the most prevalent internal RNA modification in mammals. However, limited research has been conducted on the role of m6A in coronary artery disease (CAD). We conducted methylated RNA immunoprecipitation sequencing and RNA sequencing to obtain a genome-wide profile of m6A-modified long noncoding RNAs (lncRNAs) in human coronary artery smooth muscle cells either exposed to oxidized low-density lipoprotein treatment or not, and the characteristics of the expression profiles were explored using Gene Ontology and Kyoto Encyclopedia of Genes and Genomes analyses. The predictive effects of seven selected lncRNAs on CAD were evaluated in peripheral blood mononuclear cells (PBMCs). The differentially m6A-modified and expressed lncRNAs related genes were predominantly enriched in small GTPase-mediated signal transduction, ErbB signaling, and Rap1 signaling. Additionally, the expression levels of uc003pes.1, ENST00000422847, and NR_110155 were significantly associated with CAD, with uc003pes.1 identified as an independent risk factor and NR_110155 as an independent protective factor for CAD. NR_110155 and uc003pes.1 in PBMCs have the potential to serve as biomarkers for predicting CAD.

Exploration and bioinformatic prediction for profile of mRNA bound to circular RNA BTBD7_hsa_circ_0000563 in coronary artery disease.

BACKGROUND: As a novel circRNA, BTBD7_hsa_circ_0000563 has not been fully investigated in coronary artery disease (CAD). Our aim is to reveal the possible functional role and regulatory pathway of BTBD7_hsa_circ_0000563 in CAD via exploring genes combined with BTBD7_hsa_circ_0000563. METHODS: A total of 45 peripheral blood mononuclear cell (PBMC) samples of CAD patients were enrolled. The ChIRP-RNAseq assay was performed to directly explore genes bound to BTBD7_hsa_circ_0000563. The Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis were conducted to reveal possible functions of these genes. The interaction network was constructed by the STRING database and the Cytoscape software. The Cytoscape software were used again to identify clusters and hub genes of genes bound to BTBD7_hsa_circ_0000563. The target miRNAs of hub genes were predicted via online databases. RESULTS: In this study, a total of 221 mRNAs directly bound to BTBD7_hsa_circ_0000563 were identified in PBMCs of CAD patients via ChIRP-RNAseq. The functional enrichment analysis revealed that these mRNAs may participate in translation and necroptosis. Moreover, the interaction network showed that there may be a close relationship between these mRNAs. Eight clusters can be further subdivided from the interaction network. RPS3 and RPSA were identified as hub genes and hsa-miR-493-5p was predicted to be the target miRNA of RPS3. CONCLUSIONS: BTBD7_hsa_circ_0000563 and mRNAs directly bound to it may influence the initiation and progression of CAD, among which RPS3 and RPSA may be hub genes. These findings may provide innovative ideas for further research on CAD.

Long non-coding RNA in coronary artery disease: the role of PDXDC1-AS1 and SFI1-AS1.

This study investigates the interaction between long non-coding RNAs (lncRNAs) and metabolic risk factors that contribute to coronary artery disease (CAD). A total transcriptome high throughput sequencing study was conducted on peripheral blood mononuclear cells from five patients with CAD and five healthy controls. Validation assay by qRT-PCR was conducted among 270 patients and 47 controls. Finally, to evaluate the lncRNAs' diagnostic value for CAD, the Spearman correlation test and receiver operating characteristic curve (ROC) analysis were utilized. Additionally, univariate and multivariate logistic regression along with crossover analyses were conducted to identify the interaction between lncRNA and environmental risk factors. A total of 2149 of 26,027 lncRNAs identified by RNA sequencing were differentially expressed in CAD patients compared to controls. Validation by qRT-PCR showed significantly different relative expression levels for lncRNAs PDXDC1-AS1, SFI1-AS1, RP13-143G15.3, DAPK1-IT1, PPIE-AS1, and RP11-362A1.1 between the two groups (all P<0.05). The area under the ROC values of PDXDC1-AS1 and SFI1-AS1 is 0.645 (sensitivity=0.443 and specificity=0.920) and 0.629 (sensitivity=0.571 and specificity=0.909), especially. Multivariate logistic regression analyses showed that lncRNAs PDXDC1-AS1 (OR=2.285, 95%CI=1.390-3.754, p=0.001) and SFI1-AS1 (OR=1.163, 95%CI=1.163-2.264, p=0.004) were protective factors against CAD. Under the additive model, cross-over analyses demonstrated significant interactions between lncRNAs PDXDC1-AS1 and smoking in relation to CAD risk (S=3.871, 95%CI=1.140-6.599). PDXDC1-AS1 and SFI1-AS1 were sensitive and specific biomarkers for CAD and exhibited synergistic effects with certain environmental factors. These results highlighted their potential use as CAD diagnostic biomarkers for future research.

Circular RNA ZBTB46 depletion alleviates the progression of Atherosclerosis by regulating the ubiquitination and degradation of hnRNPA2B1 via the AKT/mTOR pathway.

BACKGROUND: CircZBTB46 has been identified as being associated with the risk of coronary artery disease (CAD) and has the potential to be a diagnostic biomarker for CAD. However, the specific function and detailed mechanism of circZBTB46 in CAD are still unknown. METHODS: The expression levels and properties of circRNAs were examined using qRT‒PCR, RNA FISH, and subcellular localization analysis. ApoE-/- mice fed a high-fat diet were used to establish an atherosclerosis model. HE, Masson, and Oil Red O staining were used to analyze the morphological features of the plaque. CCK-8, Transwell, and wound healing assays, and flow cytometric analysis were used to evaluate cell proliferation, migration, and apoptosis. RNA pull-down, silver staining, mass spectrometry analysis, and RNA-binding protein immunoprecipitation (RIP) were performed to identify the interacting proteins of circZBTB46. RESULTS: CircZBTB46 is highly conserved and is significantly upregulated in atherosclerotic lesions. Functional studies revealed that knockdown of circZBTB46 significantly decreased the atherosclerotic plaque area, attenuating the progression of atherosclerosis. In addition, silencing circZBTB46 inhibited cell proliferation and migration and induced apoptosis. Mechanistically, circZBTB46 physically interacted with hnRNPA2B1 and suppressed its degradation, thereby regulating cell functions and the formation of aortic atherosclerotic plaques. Additionally, circZBTB46 was identified as a functional mediator of PTEN-dependent regulation of the AKT/mTOR signaling pathway and thus affected cell proliferation and migration and induced apoptosis. CONCLUSION: Our study provides the first direct evidence that circZBTB46 functions as an important regulatory molecule for CAD progression by interacting with hnRNPA2B1 and regulating the PTEN/AKT/mTOR pathway.

Identification of circular RNA BTBD7_hsa_circ_0000563 as a novel biomarker for coronary artery disease and the functional discovery of BTBD7_hsa_circ_0000563 based on peripheral blood mononuclear cells: a case control study.

BACKGROUND: BTBD7_hsa_circ_0000563 is a novel circRNA and contains conserved binding sites with RNA-binding proteins. However, BTBD7_hsa_circ_0000563 has not been fully studied in coronary artery disease (CAD). We aimed to clarify the diagnostic value and the possible functional role of BTBD7_hsa_circ_0000563 in CAD. METHODS: A total of 276 human peripheral blood mononuclear cell (PBMC) samples were employed. The circularization of BTBD7_hsa_circ_0000563 was verified via Sanger sequencing. The expression level of BTBD7_hsa_circ_0000563 in CAD samples and control individuals was analysed via qRT-PCR. The diagnostic potential of BTBD7_hsa_circ_0000563 was evaluated using Spearman's analysis, univariate and multivariable logistic regression analysis, and receiver-operator characteristic (ROC) curve analysis. ChIRP-MS was performed to directly explore the proteins bound to BTBD7_hsa_circ_0000563. Bioinformatic analysis was conducted to investigate the possible functions and interactions of proteins bound to BTBD7_hsa_circ_0000563. RESULTS: In the present study, BTBD7_hsa_circ_0000563 was verified as a circular RNA in the PBMCs of CAD patients. The expression level of BTBD7_hsa_circ_0000563 in the CAD group was significantly lower than that in the control group. The area under the ROC curve was 0.690. ChIRP-MS found seven proteins that were directly bound to BTBD7_hsa_circ_0000563. Bioinformatic analysis of these seven proteins showed that the mitophagy and DNA repair pathways were enriched. These proteins interacted with each other to a certain extent. CONCLUSION: BTBD7_hsa_circ_0000563 may be a novel biomarker for the diagnosis of CAD and may influence the initiation and progression of CAD. These studies may reveal new possibilities for the diagnosis and treatment of CAD.

Characteristics of circular RNAs expression of peripheral blood mononuclear cells in humans with coronary artery disease.

Circular RNAs (circRNAs) function as promising biomarkers and therapeutic targets for coronary artery disease due to their high stability, covalently closed structure, and potential gene regulation. We aimed to identify the expression profile and role of circular RNAs (circRNAs) in coronary artery disease (CAD). We performed RNA sequence analysis of circRNAs in peripheral blood mononuclear cells of five patients with CAD and five controls. Bioinformatics analyses were adopted to explore biological functions of differentially expressed circRNAs. The miRanda and TargetScan tools were used to predict the microRNA (miRNA)-targeting interactions and to construct a triple network of differentially expressed gene-circRNA-miRNA-mRNA. In total, 13,160 downregulated and 12,905 upregulated circRNAs were identified in CAD. A gene ontology annotation analysis showed that genes in the network were involved in organelle organization, cell cycle, mitotic cycle, and cellular metabolic process. Parental genes of the 10 dysregulated circRNAs were involved in metabolism and protein modification, and these circRNAs might regulate gene expression associated with CAD via miRNA sponges. As potential competing endogenous RNAs (ceRNAs), dysregulated circRNAs may be involved in the pathogenesis of CAD, which provides new insights into the diagnosis and prognosis of coronary artery disease.

Analysis on the polymorphisms of site RS4977574, and RS1333045 in region 9p21 and the susceptibility of coronary heart disease in Chinese population.

BACKGROUND: Rs4977574 (A > G) and Rs1333045 (C > T) are both single nucleotide polymorphisms (SNPs) related with coronary artery disease, locating on chromosome 9p21.3. The study aimed to identify the correlation between rs4977574 and rs1333045 polymorphism genotypes and coronary heart disease (CHD) in a Chinese population. METHODS: Blood samples were collected from 855 subjects. A case-control study was used in this experiment, and 598 cases in the CHD group and 257 subjects in the control group were enrolled. Genotyping was identified by the Agena MassARRAY system. Statistical analysis was conducted by SPSS (Ver 16.0) and plink (Ver. 1.07, Shaun Purcell). Haplotype analysis was performed using Haploview software. RESULTS: Association analysis by plink indicated a significant difference in the allele distribution for single nucleotide polymorphisms between cases and controls (rs4977574 P = 0.003, rs1333045 P = 0.035). Fisher's exact test by plink proved that allele G may be associated with a higher risk of CHD (P = 0.003, odds ratio (OR) = 1.371) and the T allele was likely to reduce the risk of coronary events (P = 0.035, OR = 0.798). The serum levels of apolipoprotein A (ApoA) were higher in subjects with the AG + AA genotype of rs4977574 compared to those with the GG genotype (P = 0.028). In the dominant model of rs1333045, the levels of ApoA were higher and LDL levels were lower in the TC + TT genotype than in the CC genotype. CONCLUSIONS: The present study examined the association between the 9p21 chromosome rs4977574 and rs1333045 polymorphism genotypes and CHD in a population of Chinese patients. The G allele of rs4977574 and the C allele of rs1333045 are the susceptibility sites of CHD.

The effectiveness of quarantine of Wuhan city against the Corona Virus Disease 2019 (COVID-19): A well-mixed SEIR model analysis.

A novel coronavirus pneumonia, first identified in Wuhan City and referred to as COVID-19 by the World Health Organization, has been quickly spreading to other cities and countries. To control the epidemic, the Chinese government mandated a quarantine of the Wuhan city on January 23, 2020. To explore the effectiveness of the quarantine of the Wuhan city against this epidemic, transmission dynamics of COVID-19 have been estimated. A well-mixed "susceptible exposed infectious recovered" (SEIR) compartmental model was employed to describe the dynamics of the COVID-19 epidemic based on epidemiological characteristics of individuals, clinical progression of COVID-19, and quarantine intervention measures of the authority. Considering infected individuals as contagious during the latency period, the well-mixed SEIR model fitting results based on the assumed contact rate of latent individuals are within 6-18, which represented the possible impact of quarantine and isolation interventions on disease infections, whereas other parameter were suppose as unchanged under the current intervention. The present study shows that, by reducing the contact rate of latent individuals, interventions such as quarantine and isolation can effectively reduce the potential peak number of COVID-19 infections and delay the time of peak infection.

Association between circular RNA expression content and severity of coronary atherosclerosis in human coronary artery.

BACKGROUND: Circular RNAs (circRNAs) may act as biomarkers of coronary artery disease (CAD). However, the relationship between expression characteristics of circRNAs and coronary atherosclerosis has not been fully explored. The aim of this study was to determine and characterize the circRNAs from human coronary artery. METHODS: The coronary artery segments were obtained from an 81-year-old male patient with sudden death of myocardial infarction at autopsy. The coronary stenosis and atherosclerosis were evaluated by hematoxylin and eosin (H&E) staining, and the circRNAs expression profile was characterized by RNA sequencing (RNA-seq). The differentially expressed circRNAs were validated by qRT-PCR. RESULTS: The analysis of H&E staining indicated that coronary atherosclerosis grade and extent in the LM was more serious than that in other coronary arteries. Twenty-seven circRNAs were selected for expression validation in coronary artery. CircRNAs corresponding cyclization sites of 3 circRNAs (hsa_circ_0016868, hsa_circ_0001364, hsa_circ_0006731) have been verified by Sanger sequencing. CONCLUSION: The 3 circRNAs are suggested to play a pathological role underlying the coronary arteries atherosclerosis and may serve as a valuable resource as diagnostic or therapeutic targets against CAD.

Quantitative proteomics reveals the regulatory networks of circular RNA BTBD7_hsa_circ_0000563 in human coronary artery.

BACKGROUND: BTBD7_hsa_circ_0000563, which is located on chromosome 14, contains conserved binding sites with miR-155/130a and RNA-binding proteins according to bioinformatic prediction. We investigated the association of BTBD7_hsa_circ_0000563 expression in coronary artery segments with atherosclerotic stenosis and identified the proteome-wide BTBD7_hsa_circ_0000563-regulated proteins in human coronary artery. METHODS: The atherosclerotic grade and extent in coronary artery segments were determined by hematoxylin and eosin staining. BTBD7_hsa_circ_0000563 expression in eight coronary artery segments from one patient was quantified by RT-qPCR assay. A proteomic approach was adopted to reveal significant differences in protein expression between among four groups differing in their BTBD7_hsa_circ_0000563 expression levels. RESULTS: The RT-qPCR assay revealed that coronary artery segments with severe atherosclerotic stenosis had significantly low BTBD7_hsa_circ_0000563 levels. The proteomic analysis identified 49 differentially expressed proteins among the segment groups with different BTBD7_hsa_circ_0000563 expression levels, of which 10 were downregulated and 39 were upregulated with increases in the BTBD7_hsa_circ_0000563 level. The 10 downregulated proteins were P61626 (LYSC_HUMAN), P02760 (AMBP_HUMAN), Q02985 (FHR3_HUMAN), P01701 (LV151_HUMAN), P06312(KV401_HUMAN), P01624 (KV315_HUMAN), P13671 (CO6_HUMAN), P01700(LV147_HUMAN), Q9Y287(ITM2B_HUMAN), and A0A075B6I0 (LV861_HUMAN). The top 10 upregulated proteins were Q92552 (RT27_HUMAN), Q9UJY1(HSPB8_HUMAN), Q9Y235(ABEC2_HUMAN), P19022 (CADH2_HUMAN), O43837(IDH3B_HUMAN), Q9H479(FN3K_HUMAN), Q9UM22(EPDR1_HUMAN), P48681(NEST_HUMAN), Q9NRP0(OSTC_HUMAN), and Q15628(TRADD_HUMAN). CONCLUSION: BTBD7_hsa_circ_0000563 is involved in the atherosclerotic changes in human coronary artery segments. Verification, mechanistic, and function studies are needed to confirm whether patients with coronary artery disease would benefit from such personalized medicine in the future.

Coronary Artery Diameter is Inversely Associated with the Severity of Coronary Lesions in Patients Undergoing Coronary Angiography.

BACKGROUND: The diameters of the coronary arteries have been suggested to be a potential predictor of coronary artery disease (CAD). However, whether the diameters of the coronary arteries are associated with the coronary lesion severity on angiography has not been determined. METHODS: One hundred sixty-seven consecutive adult patients (109 men and 58 women) aged 31-84 years who underwent coronary angiography for suspected or known CAD were enrolled. The known catheter tip diameter was used as the calibration to measure the diameters of coronary arteries, and the severity of coronary lesions was evaluated with the vessel score and Gensini score. RESULTS: In patients with a higher vessel score and Gensini score, the diameters of the left main (LM), left anterior descending (LAD), left circumflex (LCX), and right coronary arteries (RCA) were smaller (all p<0.05) than those in patients with lower scores. Multiple linear regression analysis indicated that the average coronary artery diameter was significantly associated with the Gensini score (ß=-0.444, p<0.00001). Moreover, the diameters of the coronary arteries were potential predictors of CAD, with areas under the receiver operating characteristic curves of 0.268 for average diameter (95% confidence interval [CI]: 0.183-0.353, p<0.00001), 0.356 for the LM diameter (95% CI: 0.266-0.445, p=0.005), 0.214 for the LAD diameter (95% CI: 0.136-0.291, p<0.00001), 0.366 for the LCX diameter (95% CI: 0.271-0.461, p=0.009), and 0.346 for the RCA diameter (95% CI: 0.245-0.447, p=0.003). CONCLUSION: The diameters of coronary arteries are inversely associated with the severity of CAD.

Predictive Effects of Circulating miR-221, miR-130a and miR-155 for Coronary Heart Disease: A Multi-Ethnic Study in China.

BACKGROUND: Differences in microRNA (miRNA) profiles between patients with and without coronary heart disease (CHD)have not been fully determined. The purpose of the study was to evaluate in a multi-ethnic population in China the predictive value of miRNAs previously suggested to have a role in CHD. SUBJECT AND METHOD: 932 participants were included, and plasma samples obtained. A quantitative reverse-transcription PCR(RT-qPCR) assay was conducted to confirm the concentration of plasma miRNAs. Circulating levels of miRNAs were quantified using the 2-Δct method. The severity of coronary atherosclerosis was evaluated via Gensini Scores. RESULT: The circulating levels of the nine proposed miRNAs were not different among the five main ethnicities examined (all p > 0.05). The Spearman correlation analyses indicated that miR-221 and miR-130a were negatively associated with the severity of CHD as indicated by Gensini Scores (r = -0.106, p = 0.001;r = -0.073, p = 0.026). Results of the univariate analysis showed that lower circulating miR-221 (OR, 1.663; 95 % CI, 1.255-2.202, p = <0.001), miR-155 (OR, 1.520; 95 % CI, 1.132-2.042, p = 0.005), and miR-130a (OR, 1.943; 95% CI, 1.410-2.678, p = <0.001) were potential risk factors for CHD. Moreover, miR-130a (OR, 2.405; 95 % CI, 1.691-3.421, p = <0.001) remained independently associated with the risk of CHD after adjusting for potential confounding factors. The analysis of the possible positive/negative associations between miR-221, miR-155 and miR-130awere conducted. A positive association between miR-130a and miR-155 was found (SI = 1.60, SIM = 1.21 and AP = 0.22), and in these groups, the proportion of CHD attributable to the interaction between miR-130a and miR-155 was as high as 22 %. A negative interaction was found between miR-221 and miR-130a (SI = 0.68, SIM = 0.60 and AP = 0.27). CONCLUSION: Plasma levels of miR-221, miR-130a and miR-155 decreased in patients with CHD, and miR-130a may be an independent predictor for CHD.

Factors Associated with Blood Pressure Variability Based on Ambulatory Blood Pressure Monitoring in Subjects with Hypertension in China.

BACKGROUND/AIMS: We examined the factors associated with blood pressure variability in a multi-ethnicity prospective study in China to gain more evidence to guide the prevention and management of hypertension through risk factor intervention. METHODS: A total of 318 consecutive adult subjects aged 29-94 years with suspected or known hypertension were enrolled in this study. Blood pressure variability measurements were based on ambulatory blood pressure monitoring. To measure short-term reading-to-reading blood pressure variability in this study, we used the standard deviation(SD) of the blood pressure to estimate the blood pressure variability. RESULTS: The SDs of the blood pressure in this study ranged from 5.425 to 32.25, with a median of 10.81 (quartile range, 8.90-12.46). No significant difference regarding the level distribution of blood pressure variability was found across the various ethnicities. Spearman correlation analyses indicated that the SD of blood pressure was positively correlated with DSBP (r=0.302, p=<0.001), NSBP (r=0.383, p=<0.001), NDBP (r=0.230, p=<0.001), and FBG (r=0.129, p=0.023) and was negatively correlated with triglyceride (r=-0.289, p=<0.001), CR (r=-0.242, p=<0.001), HDL-C (r=-0.230, p=<0.001), LDL-C (r=-0.186, p=0.001), and apolipoprotein B levels (r=-0.157, p=0.006). Multiple linear regression analysis indicated that triglycerides (ß=-0.217, p=<0.001), NSBP (ß=0.174, p=0.003), FBG (ß=0.128, p=0.024), DDBP (ß=-0.128, p=0.022), and apolipoprotein A (ß=-0.116, p=0.036) were significantly and independently associated with the blood pressure variability. CONCLUSIONS: In this study, blood pressure variability was significantly associated with not only blood pressure levels but also patient demographic, clinical and biochemical characteristics.

Synergistic Effect of Lipoprotein-Associated Phospholipase A2 with Classical Risk Factors on Coronary Heart Disease: A Multi-Ethnic Study in China.

AIMS: We evaluated the synergistic effect of lipoprotein-associated phospholipase A2 (Lp-PLA2) in association with classical risk factors in predicting coronary heart disease (CHD) and demonstrated the diagnostic value of Lp-PLA2 for predicting coronary stenotic lesions in subjects with CHD. METHODS: Blood samples were acquired from 911 consecutive adult subjects (662 males and 249 females) from 11 ethnic groups. Lp-PLA2 plasma levels were detected using a commercially available turbidimetric immunoassay (TIA). CHD in patients was confirmed using coronary angiography, and the severity of coronary atherosclerosis was assessed using the Gensini scoring system. RESULTS: A binary logistic regression was performed to analyse the relationships between Lp-PLA2 and other risk factors. A multivariate logistic regression analysis revealed that Lp-PLA2 levels were significantly associated with CHD (OR, 1.882; 95% CI, 1.369-2.587, p=0.000).The area under the receiver operating characteristic curve for Lp-PLA2 was 0.589 (95%CI, 0.549-0.629, p=0.000).The synergism between Lp-PLA2 and other risk factors was also investigated. The proportion of CHD attributable to the interaction between Lp-PLA2 and age was as high as 64%. CONCLUSIONS: Lp-PLA2 levels in human plasma were positively associated with the severity of CHD, and there was a clear positive interaction between Lp-PLA2 and classical risk factors in predicting CHD.

Meteorological parameters and the onset of chest pain in subjects with acute ST-elevation myocardial infarction: an eight-year, single-center study in China.

OBJECTIVE: The purpose of this study was to investigate the influence of weather on the occurrence of acute ST-elevation myocardial infarction in Chinese subjects. METHODS: Weather and climate data, as well as the occurrence of STEMI, were monitored at 2 am, 8 am, 2 pm, and 8 pm between 2003 and 2010. Generalized additive Poisson models were utilized to plot the numbers of patients with STEMI within 6 hour intervals against climatological variations, after accounting for the effects of the hour and season. RESULTS: The inclusion of meteorological conditions, including observed atmospheric pressure (hPa, hectopascal) variations during the previous three hours and temperature (°C, degrees Celsius), significantly affected the occurrence of STEMI, as measured every six hours. Compared with the 50th percentile of atmospheric pressure variations, the RRs (95% CI) for the first percentile, 10th percentile, 25th percentile, 75th percentile, 90th percentile, and 99th percentile of atmospheric pressure variation over lag 0 were 1.66 (1.36∼2.03), 1.47 (1.30∼1.67), 1.22 (1.12∼1.33), 1.16 (1.07∼1.25), 1.27 (1.13∼1.43), and 1.16 (0.92∼1.46), respectively. Compared to the 50th percentile of temperature, the RRs (95% CI) for the first percentile, 10th percentile, 25th percentile, 75th percentile, 90th percentile, and 99th percentile of temperature over lag 0 were 0.58 (0.40∼0.83), 0.60 (0.46∼0.78), 0.69 (0.57∼0.83), 1.33 (1.14∼1.56), 1.39 (1.13∼1.71), and 1.17 (0.84∼1.63), respectively. CONCLUSIONS: Based on the eight-year, single-center study, significant relationships were observed among the occurrence of STEMI and atmospheric pressure variations during the previous three hours and temperature after account for long-term time trends.

Hemoglobin A1c risk score for the prediction of coronary artery disease in subjects with angiographically diagnosed coronary atherosclerosis.

OBJECTIVE: To develop a risk score by incorporating Hemoglobin A1c(HbA1c) with traditional risk factors for the prediction of coronary artery disease (CAD) in Chinese subjects. METHODS: A total of 196 consecutive subjects (131 males and 65 females) aged 38-89 years who underwent coronary angiography were enrolled in this study. HbA1c risk score sheets for the prediction of CAD were developed using age, gender and HbA1c. A receiver-operating characteristic curve analysis was used to determine the optimum cut-off levels of the HbA1c risk score for predicting CAD. RESULTS: In the ROC curve analysis, the optimal cut-off value of the HbA1c score for predicting CAD was 5.1, with a sensitivity of 72.0% and a specificity of 75.5% (area under the curve 0.781, 95% confidence interval 0.709 to 0.854, p=0.000). CONCLUSIONS: The HbA1c score system is a simple and feasible method that can be used for the prediction of CAD. Large-scale studies are needed to further substantiate these results.

JAK2 V617F mutation and 46/1 haplotype in Chinese Budd-Chiari syndrome patients.

BACKGROUND AND AIM: The presence of JAK2V617F was reported to be associated with JAK2 46/1 haplotype, which was considered as an independent risk factor for Budd-Chiari syndrome (BCS) in Western countries. However, little is known in China. Therefore, the aim of this study was to determine whether the 46/1 haplotype is associated with such patients. METHODS: Patients with primary BCS and controls were consecutively admitted in our study from October 2009 to December 2012. The subjects were detected for the JAK2V617F mutation by allele-specific polymerase chain reaction (AS-PCR) and the JAK2 46/1 haplotype by real-time PCR. RESULTS: The prevalence of JAK2V617F mutation was 2.37% (7/295) in BCS patients, and 46/1 haplotype was overrepresented in JAK2V617F-positive BCS patients compared with controls (P < 0.01). The risk for the JAK2V617F-positive BCS with CC genotype was elevated compared with subjects presented TT genotype (OR = 13.4, 95%CI = 2.01-89.5) and non-CC genotype (OR = 15.0, 95%CI = 2.45-91.7). CONCLUSIONS: Our study showed that the presence of 46/1 haplotype increased the risk of JAK2V617F-positive BCS in China. In addition, low prevalence of JAK2V617F mutation in BCS patients suggested that myeloproliferative neoplasms (MPNs) should not be an etiological factor of BCS in China.

OLR1, PON1 and MTHFR gene polymorphisms, conventional risk factors and the severity of coronary atherosclerosis in a Chinese Han population.

AIMS: To explore the association between six single-nucleotide polymorphisms in OLR1, PON1, MTHFR gene and the angiographical characteristics of coronary atherosclerosis to determine if any of the conventional factors correlate with genetic polymorphisms in the advent of the disease. METHODS: We examined rs1801131, rs1801133, rs3736232, rs3736234, rs854563 and rs662 by TaqMan® SNP Genotyping Assays in 1075 subjects that underwent angiography. The angiographical characteristics of coronary atherosclerosis were defined by the Gensini Score system. RESULTS: The T allele of rs1801133 was associated with coronary atherosclerosis severity with the OR = 1.49, 95% CI = 1.04-2.14. In MTHFR gene, haplotype T-A was a susceptibility haplotype to coronary atherosclerosis (OR = 1.27, 95% CI = 1.06-1.51) whereas haplotype C-A had a protective effect (OR = 0.83, 95% CI = 0.70-0.99). In addition, several synergistic effects between rs1801133 and conventional risk factors such as diabetes and smoking were found. CONCLUSIONS: Collectively, the results demonstrate that the T allele of rs1801133 conferred an increased risk for coronary atherosclerosis. The MTHFR C-A haplotype was a protective haplotype, while T-A haplotype was a susceptibility haplotype. The presence of the T allele of rs1801133 increases the odds of coronary atherosclerosis severity when associated with conventional risk factors.

[Initial experience of percutaneous coronary intervention guided by computed tomography coronary angiography derived roadmap and magnetic navigation system].

OBJECTIVE: To evaluate the feasibility, efficacy and safety of the percutaneous coronary intervention (PCI)guided by computed tomography (CT) coronary angiography derived roadmap and magnetic navigation system (MNS). METHODS: During June 2011 and May 2012, thirty consecutive patients receiving elective PCI were enrolled, coronary artery disease was primarily diagnosed by dual-source CT coronary angiography (DSCT-CA) at outpatient clinic and successively proved by coronary artery angiography in the hospital. Target vessels from pre-procedure DSCT-CA were transferred to the magnetic navigation system, and consequently edited, reconstructed, and projected onto the live fluoroscopic screen as roadmap. Parameters including characters of the target lesions, time, contrast volume, radiation dosage for guidewire crossing, and complications of the procedure were recorded. RESULTS: Thirty patients with 36 lesions were recruited and intervened by PCI. Among the target lesions, sixteen were classified as type A, 11 as type B1, 8 as type B2, 1 as type C. The average length of the target lesions was (22.0 ± 9.8) mm, and the average stenosis of the target lesions was (81.3 ± 10.3)%. Under the guidance of CT roadmap and MNS, 36 target lesions were crossed by the magnetic guidewires, with a lesion crossing ratio of 100%. The time of placement of the magnetic guidewires was 92.5 (56.6 - 131.3) seconds. The contrast volume and the radiation dosage for guidewire placement were 0.0 (0.0 - 3.0) ml and 235.0 (123.5 - 395.1) µGym(2)/36.5 (21.3 - 67.8) mGy, respectively. Guidewires were successfully placed in 21 (58.3%) lesions without contrast agent. All enrolled vessels were successfully treated, and there were no MNS associated complications. CONCLUSIONS: It is feasible, effective and safe to initiate PCI under the guidance of CT derived roadmap and MNS. This method might be helpful for the guidewire placement in the treatment of total occlusions.

Detailed profiling of m6A modified circRNAs and synergistic effects of circRNA and environmental risk factors for coronary artery disease.

The modification of N6-methyladenosine (m6A) modification is implicated in human diseases. However, considerable uncertainty is associated with the regulatory mechanisms of m6A circRNAs in coronary artery disease (CAD), which require further clarification. In this study, m6A-modified RNA immunoprecipitation sequencing (MeRIP-seq) was conducted to investigate m6A-modified circRNAs in human coronary artery smooth muscle cells (HCASMCs) and to identify potential biomarkers for CAD. A total of 830 and 331 up- and down-regulated m6A peaks, (corresponding to 463 and 243 up- and down-regulated circRNAs, respectively), were identified in HCASMCs in a pathological condition. Functional analysis suggested that these circRNAs appeared to participate in intracellular protein, histone deacetylase complex, ATP-dependent activity, autophagy, and AMPK signaling pathway. Four candidate circRNAs were selected for further evaluation in HCASMCs and human samples. The results suggested that hsa_circHECTD1 and hsa_circZBTB46 were significantly increased in patients with CAD (p-value = 0.039 and p-value = 0.014) and may act as potential diagnostic biomarkers of CAD. Furthermore, statistical results showed that hsa_circHECTD1 and hsa_circSEC62 were positively correlated with triglyceride (TG) (r = 0.213, p-value = 0.014) and Gensini Score (used to quantify the severity of CAD) (r = 0.349, p-value <0.001), respectively. Logistic regression revealed that hsa_circZBTB46 was strongly correlated with the incidence of CAD, and the synergistic effects of circRNAs and hypertension enhanced the risk of CAD. These results show that hsa_circHECTD1 and hsa_circZBTB46 may be new targets for further studies, and this study enhances our understanding of the effects of m6A-circRNAs on the pathogenesis of CAD.