High Plasma Fibrinogen Level Elevates the Risk of Cardiac Complications Following Spontaneous Intracerebral Hemorrhage.

BACKGROUND: Cardiac complications are related to poor prognosis after spontaneous intracerebral hemorrhage (ICH). This study aims to predict the cardiac complications arising from small intracranial hematoma at ultraearly stage. METHODS: The data of this work were derived from the Risk Stratification and Minimally Invasive Surgery in Acute ICH Patients study (ClinicalTrials.gov Identifier: NCT03862729). This work included patients with ICH but without brain herniation, as confirmed by a brain computed tomography scan within 48 hours of symptom onset. Every Patient's information recorded at the emergent department, including clinical, laboratory, electrocardiogram, and medical records, was derived from the electronic data capture. Cardiac complications were defined as the occurrence of myocardial damage, arrhythmias, and ischemic electrocardiogram changes during hospitalization. Variables associated with cardiac complications were filtrated by univariate and multivariate regression analyses. Independent risk factors were used to form the early predictive model. The restricted cubic splines were employed to investigate the nonlinear associations in a more sophisticated and scholarly manner. RESULTS: A total of 587 ICH patients were enrolled in this work, including 72 patients who suffered from cardiac complications after ICH. Out of the 78 variables, 24 were found to be statistically significant in the univariate logistic regression analysis. These significant variables were then subjected to multivariate logistic regression analysis and utilized for constructing risk models. Multivariate logistic regression analysis showed high plasma fibrinogen (FIB) level [odds ratio (OR) per standard deviation (SD) 1.327, 95% confidence intervals (CI) 1.037-1.697; P = 0. 024)] and older age (OR per SD 1.777, 95% CI 1.344-2.349; P ＜0.001) were associated with a higher incidence of cardiac complications after ICH. High admission pulse rate (OR 0.620, 95% CI 0.451-0.853; P = 0. 003) was considered a protective factor for cardiac complications after ICH. In the restricted cubic spline regression model, FIB and cardiac complications following ICH were positively correlated and almost linearly (P for nonlinearity = 0.073). The reference point for FIB in predicting cardiac complications after ICH was 2.64 g/L. CONCLUSIONS: Emergent factors, including plasma FIB level, age, and pulse rate, might be independently associated with cardiac complications after ICH, which warrants attention in the context of treatment.

Thrombin Time is a Diagnostic Biomarker of Sudden Sensorineural Hearing Loss and Predicts the Prognosis.

OBJECTIVES: The aim of this study is to determine whether thrombin time (TT) could be used as diagnostic biomarkers and predict the prognosis for sudden sensorineural hearing loss (SSNHL). METHODS: Sixty-one patients diagnosed with SSNHL and 65 people who underwent physical examination were recruited. Data on the patient's background, clinical course, and laboratory findings were collected. SSNHL patients were divided into the effective and ineffective groups according to the hearing recovery from the treatment and were assessed by binary logistic regression. Receiver-operating characteristic (ROC) analysis was carried out for the best discriminating cutoff value of the biomarker with the corresponding sensitivity and specificity was calculated. RESULTS: The SSNHL group exhibited prolonged TT (19.11 ± 1.12 seconds) compared to the control group (17.58 ± 2.18 seconds, P < .001). Binary logistic regression analysis found a significant positive association between TT and SSNHL and was observed with an odds ratio (OR) 1.769 [95% confidence interval (CI) 1.344-2.330, P < .001] in the unadjusted model. Even after adjustment using the variables included in the multivariate models, TT was significantly predictive of SSNHL. A TT cutoff value of 17.65 seconds provides optimal separation between patients with SSNHL and controls in the ROC analysis [Area Under the Curve (AUC) 0.773, 95% CI 0.689-0.856; sensitivity, 0.918; and specificity, 0.569]. TT in the effective group of SSNHL patients was shorter (18.76 ± 1.06 seconds) than that in the ineffective group (19.43 ± 1.09 seconds, P = .018). The cutoff value of TT as progress predictors was 19.85 seconds. The TT < 19.85 seconds showed an effective rate 59.09% (26/44) higher than 17.65% (3/17) of TT ≥ 19.85 seconds. CONCLUSIONS: TT is a potential biomarker of SSNHL and is independently associated with the prognosis of patients with SSNHL.

Development and validation for multifactor prediction model of sudden sensorineural hearing loss.

Background: Sudden sensorineural hearing loss (SSNHL) is a global problem threatening human health. Early and rapid diagnosis contributes to effective treatment. However, there is a lack of effective SSNHL prediction models. Methods: A retrospective study of SSNHL patients from Fujian Geriatric Hospital (the development cohort with 77 participants) was conducted and data from First Hospital of Putian City (the validation cohort with 57 participants) from January 2018 to December 2021 were validated. Basic characteristics and the results of the conventional coagulation test (CCT) and the blood routine test (BRT) were then evaluated. Binary logistic regression was used to develop a prediction model to identify variables significantly associated with SSNHL, which were then included in the nomogram. The discrimination and calibration ability of the nomogram was evaluated by receiver operating characteristic (ROC), calibration plot, and decision curve analysis both in the development and validation cohorts. Delong's test was used to calculate the difference in ROC curves between the two cohorts. Results: Thrombin time (TT), red blood cell (RBC), and granulocyte-lymphocyte ratio (GLR) were found to be associated with the diagnosis of SSNHL. A prediction nomogram was constructed using these three predictors. The AUC in the development and validation cohorts was 0.871 (95% CI: 0.789-0.953) and 0.759 (95% CI: 0.635-0.883), respectively. Delong's test showed no significant difference in the ROC curves between the two groups (D = 1.482, p = 0.141). Conclusion: In this study, a multifactor prediction model for SSNHL was established and validated. The factors included in the model could be easily and quickly accessed, which could help physicians make early diagnosis and clinical treatment decisions.

Development and validation of a diagnostic model for AFP-negative hepatocellular carcinoma.

PURPOSE: AFP appears to be negative in about 30% of overall hepatocellular carcinoma (HCC). Our study aimed to develop a nomogram model to diagnose AFP-negative HCC (AFPN-HCC). PATIENTS AND METHODS: The training set included 294 AFPN-HCC patients, 159 healthy objects, 63 patients with chronic hepatitis B(CHB), and 64 patients with liver cirrhosis (LC). And the validation set enrolled 137 healthy controls objects, 47 CHB patients and 45 patients with LC. LASSO, univariate, and multivariable logistic regression analysis were performed to construct the model and then transformed into a visualized nomogram. The receiver operating characteristic (ROC) curves, the calibration curve, decision curve analysis (DCA), and clinical impact curve (CIC) were further used for validation. RESULTS: Four variables including age, PIVKA-II, platelet (PLT) counts, and prothrombin time (PT) were selected to establish the nomogram. The area under the curve (AUC) of the ROC to distinguish AFPN-HCC patients was 0.937(95% CI 0.892-0.938) in training set and 0.942(95% CI 0.921-0.963) in validation set. We also found that the model had high diagnostic value for small-size HCC (tumor size < 5 cm) (AUC = 0.886) and HBV surface antigen-positive AFPN-HCC (AUC = 0.883). CONCLUSIONS: Our model was effective for discrimination of AFPN-HCC from patients with benign liver diseases and healthy controls, and might be helpful for the diagnosis for AFPN-HCC.

Association between polyfluoroalkyl substances exposure and sex steroids in adolescents: The mediating role of serum albumin.

BACKGROUND: Polyfluoroalkyl substances (PFASs) are an emerging class of contaminants with endocrine disrupting hazards. The impact of PFASs exposure on sex steroids remain inconclusive. METHODS: This study used data from the 2013-2016 National Health and Nutrition Examination Survey (NHANES), including 525 adolescents aged 12-19. We explored the association between serum PFASs and sex steroids using multiple linear regression, weighted quantified sum (WQS) regression, and Bayesian kernel machine regression (BKMR). Mediation analyses were performed to assess whether serum albumin mediates the effects of PFASs on sex steroids. RESULTS: Single exposure to perfluorohexane sulfonic acid (PFHxS) or n-perfluorooctanoic acid (n-PFOA) was found to be inversely associated with sex hormone binding protein (SHBG) after adjustment for confounders. Results from both the WQS and BKMR models showed that mixed exposure to the five PFASs was negatively associated with SHBG and testosterone (TT) in all adolescents, while only in the WQS model, the mixed exposure to PFASs was negatively correlated with E2 and FAI in boys and negatively correlated with TT and SHBG in girls. Serum albumin was found to possibly mediate 9.7 % of the association between mixed PFAS exposure and TT, and 9.7 % of the association between mixed PFAS exposure and SHBG. CONCLUSION: Our study demonstrates a negative association between mixed exposure to PFASs and adolescent TT and SHBG levels, and suggests that albumin may merit further study as a potential target for PFAS harm reduction.

Quantitative hematoma heterogeneity associated with hematoma growth in patients with early intracerebral hemorrhage.

Background: Early hematoma growth is associated with poor functional outcomes in patients with intracerebral hemorrhage (ICH). We aimed to explore whether quantitative hematoma heterogeneity in non-contrast computed tomography (NCCT) can predict early hematoma growth. Methods: We used data from the Risk Stratification and Minimally Invasive Surgery in Acute Intracerebral Hemorrhage (Risa-MIS-ICH) trial. Our study included patients with ICH with a time to baseline NCCT <12 h and a follow-up CT duration <72 h. To get a Hounsfield unit histogram and the coefficient of variation (CV) of Hounsfield units (HUs), the hematoma was segmented by software using the auto-segmentation function. Quantitative hematoma heterogeneity is represented by the CV of hematoma HUs. Multivariate logistic regression was utilized to determine hematoma growth parameters. The discriminant score predictive value was assessed using the area under the ROC curve (AUC). The best cutoff was determined using ROC curves. Hematoma growth was defined as a follow-up CT hematoma volume increase of >6 mL or a hematoma volume increase of 33% compared with the baseline NCCT. Results: A total of 158 patients were enrolled in the study, of which 31 (19.6%) had hematoma growth. The multivariate logistic regression analysis revealed that time to initial baseline CT (P = 0.040, odds ratio [OR]: 0.824, 95 % confidence interval [CI]: 0.686-0.991), "heterogeneous" in the density category (P = 0.027, odds ratio [OR]: 5.950, 95 % confidence interval [CI]: 1.228-28.828), and CV of hematoma HUs (P = 0.018, OR: 1.301, 95 % CI: 1.047-1.617) were independent predictors of hematoma growth. By evaluating the receiver operating characteristic curve, the CV of hematoma HUs (AUC = 0.750) has a superior predictive value for hematoma growth than for heterogeneous density (AUC = 0.638). The CV of hematoma HUs had an 18% cutoff, with a specificity of 81.9 % and a sensitivity of 58.1 %. Conclusion: The CV of hematoma HUs can serve as a quantitative hematoma heterogeneity index that predicts hematoma growth in patients with early ICH independently.

Time Trend of Upper Gastrointestinal Cancer Incidence in China from 1990 to 2019 and Analysis Using an Age-Period-Cohort Model.

The aim of this study was to investigate the upper gastrointestinal cancer incidence trend in China from 1990 to 2019 with Joinpoint software and to evaluate the age effect, cohort effect, and period effect using the age-period-cohort model, with the data obtained from the Global Burden of Disease, Injuries, and Risk Factors Study. The crude incidence rate (CR) of upper gastrointestinal cancer in China increased from 41.48/100,000 in 1990 to 62.64/100,000 in 2019, and the average annual percent change (AAPC) was 1.42 (p < 0.05). The age-standardized incidence rate (ASIR) decreased from 50.77/100,000 to 37.42/100,000, and the AAPC was -1.12 (p < 0.05). The net drift was -0.83 (p < 0.05), and the local drifts in the 35-79 age groups of males and all age groups of females were less than 0 (p < 0.05). The age effect showed that the upper gastrointestinal cancer onset risk gradually increased with age, the period effect was fundamentally manifested as a downward trend in onset risk after 2000, and the cohort effect indicated the decreased onset risk of the overall birth cohort after 1926. The ASIR of upper gastrointestinal cancer in China from 1990 to 2019 showed a downward trend, and the onset risk indicated the age, period, and cohort effects.

Early Predictors of the Increase in Perihematomal Edema Volume After Intracerebral Hemorrhage: A Retrospective Analysis From the Risa-MIS-ICH Study.

Background and Purpose: Perihematomal edema (PHE) is associated with poor functional outcomes after intracerebral hemorrhage (ICH). Early identification of risk factors associated with PHE growth may allow for targeted therapeutic interventions. Methods: We used data contained in the risk stratification and minimally invasive surgery in acute intracerebral hemorrhage (Risa-MIS-ICH) patients: a prospective multicenter cohort study. Patients' clinical, laboratory, and radiological data within 24 h of admission were obtained from their medical records. The absolute increase in PHE volume from baseline to day 3 was defined as iPHE volume. Poor outcome was defined as modified Rankin Scale (mRS) of 4 to 6 at 90 days. Binary logistic regression was used to assess the relationship between iPHE volume and poor outcome. The receiver operating characteristic curve was used to find the best cutoff. Linear regression was used to identify variables associated with iPHE volume (ClinicalTrials.gov Identifier: NCT03862729). Results: One hundred ninety-seven patients were included in this study. iPHE volume was significantly associated with poor outcome [P = 0.003, odds ratio (OR) 1.049, 95% confidence interval (CI) 1.016-1.082] after adjustment for hematoma volume. The best cutoff point of iPHE volume was 7.98 mL with a specificity of 71.4% and a sensitivity of 47.5%. Diabetes mellitus (P = 0.043, ß = 7.66 95% CI 0.26-15.07), black hole sign (P = 0.002, ß = 18.93 95% CI 6.84-31.02), and initial ICH volume (P = 0.018, ß = 0.20 95% CI 0.03-0.37) were significantly associated with iPHE volume. After adjusting for hematoma expansion, the black hole sign could still independently predict the increase of PHE (P < 0.001, ß = 21.62 95% CI 10.10-33.15). Conclusions: An increase of PHE volume >7.98 mL from baseline to day 3 may lead to poor outcome. Patients with diabetes mellitus, black hole sign, and large initial hematoma volume result in more PHE growth, which should garner attention in the treatment.

Knockdown of lncRNA ENST00000609755.1 Confers Protection Against Early oxLDL-Induced Coronary Heart Disease.

Background: This study investigated the association between long non-coding RNAs (lncRNAs) and coronary heart disease (CHD) and further elucidated the potential biological roles of lncRNAs in CHD pathogenesis. Methods: A case-control study (590 patients and 590 controls) was conducted from February 2017 and March 2019 in Fuzhou, China. Environmental factors were investigated using questionnaires and physical examinations. Five representative lncRNAs were screened using lncRNA microarray (peripheral blood in 5 cases and 5 controls) and further verified by quantitative real-time polymerase chain reaction (peripheral blood leukocyte in 100 cases and 100 controls). Oxidized low-density lipoprotein (oxLDL) was used to induce a human coronary artery endothelial cell (HCAECs) injury model, and loss of function was used to elucidate the role of lncRNA ENST00000609755.1 (lnc-MICALL2-2) in oxLDL-induced HCAECs injury. Results: A total of 320 lncRNAs were found dysregulated in CHD patients (fold change> 2, p < 0.05). The results of a discovery microarray, population verification and HCAEC experiments suggested the lnc-MICALL2-2 is upregulated in CHD subjects and in an oxLDL-induced HCAECs injury model. Conversely, lnc-MICALL2-2 inhibition in vitro attenuated the effects of oxLDL on HCAECs morphology, proliferation, and apoptosis. Conclusion: Elevated expression of lnc-MICALL2-2 is an independent risk factor for CHD, and knockdown subsequently confers protection against early pathological processes of oxLDL-induced CHD.

Association Between Circular RNAs and Intracranial Aneurysm Rupture Under the Synergistic Effect of Individual Environmental Factors.

Introduction: To study the association between specific circular RNAs and rupture of intracranial aneurysm. To explore its clinical diagnostic significance and synergistic effects with individual environmental influencing factors. Methods: Three hundred and forty seven cases and controls were included in this study. Multivariate analysis was used to explore the main individual environmental factors. Intracranial aneurysm rupture related circular RNAs screened based on sequencing was verified in peripheral blood by PCR. ROC curve, logistic regression model and fork analysis were used to study the association, diagnostic values, and synergistic effects of circular RNA with intracranial aneurysms and individual environmental factors. Results: Smoking, hair dyeing, sitting time ≥6 h/day, single animal oil intake and hypertension are the main risk factors for intracranial aneurysm rupture; People with higher education, sleeping time ≥7 h/day, tea drinking, diabetes, higher levels of (hemoglobin, low density lipoprotein, serum calcium, and apolipoprotein-A1) have a low risk of intracranial aneurysm rupture. Hsa_circ_0008433 and hsa_circ_0001946 are closely related to intracranial aneurysm rupture and have certain clinical diagnostic significance (AUC = 0.726; 95% CI: 0.668~0.784). Hsa_circ_0008433 (OR = 0.497, 95% CI: 0.338~0.731), hsa_circ_0001946 (OR = 0.682, 95% CI: 0.509~0.914) were independent epigenetic factors affecting intracranial aneurysm rupture, and have a multiplicative interaction with age (OR = 3.052, 95% CI: 1.006~9.258). Conclusions: Low expressions of hsa_circ_0008433 and hsa_circ_0001946 are risk factors for intracranial aneurysms rupture and have good clinical diagnostic value. There was a multiplicative interaction between epigenetic score and age. The older and the higher the epigenetic score was, the more likely to have intracranial aneurysm rupture.

Assessment of Internet Hospitals in China During the COVID-19 Pandemic: National Cross-Sectional Data Analysis Study.

BACKGROUND: Internet hospitals in China are being rapidly developed as an innovative approach to providing health services. The ongoing COVID-19 pandemic has triggered the development of internet hospitals that promote outpatient service delivery to the public via internet technologies. To date, no studies have assessed China's internet hospitals during the COVID-19 pandemic. OBJECTIVE: This study aimed to elucidate the characteristics of China's internet hospitals and assess the health service capacity of these hospitals. METHODS: Data on 711 internet hospitals were collected from official websites, the WeChat (Tencent Inc) platform, smartphone apps, and the Baidu search engine until July 16, 2020. RESULTS: As of July 16, 2020, 711 internet hospitals were developed in mainland China. More than half of these internet hospitals (421/711, 59.2%) were established during 2019 (206/711, 29%) and 2020 (215/711, 30.2%). Furthermore, about one-third (215/711, 30.2%) of internet hospitals were established at the beginning of 2020 as an emergency response to the COVID-19 epidemic. The 711 internet hospitals consisted of the following 3 types of hospitals: government-oriented (42/711, 5.91%), hospital-oriented (143/711, 20.11%), and enterprise-oriented internet hospitals (526/711, 73.98%). The vast majority of internet hospitals were traditional hospitals (526/711, 74%). Nearly 46.1% (221/711) of internet hospitals requested doctors to provide health services at a specific web clinic. Most patients (224/639, 35.1%) accessed outpatient services via WeChat. Internet hospitals' consulting methods included SMS text messaging consultations involving the use of graphics (552/570, 96.8%), video consultations (248/570, 43.5%), and telephone consultations (238/570, 41.8%). The median number of available web-based doctors was 43, and the median consultation fees of fever clinics and other outpatient clinics were ¥0 (US $0) per consultation and ¥6 (US $0.93) per consultation, respectively. Internet hospitals have provided various services during the COVID-19 pandemic, including medical prescription, drug delivery, and medical insurance services. CONCLUSIONS: The dramatic increase of internet hospitals in China has played an important role in the prevention and control of COVID-19. Internet hospitals provide different and convenient medical services for people in need.

Association study of hsa_circ_0001946, hsa-miR-7-5p and PARP1 in coronary atherosclerotic heart disease.

BACKGROUND: Our previous work identified an aberrant expression of hsa_circ_0001946 in coronary atherosclerotic heart disease (CHD). Here we aimed to verify the role of hsa_circ_0001946 as a biomarker for CHD, and explore the clues of its downstream regulation. METHODS: The hsa_circ_0001946 expression in CHD patients (n = 120) and controls (n = 120) were confirmed with qRT-PCR. CircBank and miRDB were used for target analysis in silico. Spearman correlation test was performed to infer potential interrelationships among the nucleic acid molecular biomarkers, and their predictive abilities were examined using receiver operating characteristic (ROC) curves. RESULTS: Hsa_circ_0001946 was validated to be significantly up-regulated in the peripheral blood mononuclear cells of CHD patients, and revealed as an independent indicator of increased CHD risk (odds ratio: 2.364; 95% confidence interval [CI]: 1.765-3.165) after adjusting for confounding factors. Hsa-miR-7-5p was found to own the largest number of binding sites in has_circ_0001946 sequence, and among its targets predicted, the poly ADP-ribose polymerase 1 (PARP1) has been implicated in the pathophysiology of CHD. Spearman analysis indicated negative correlations of hsa-miR-7-5p with hsa_circ_0001946 and PARP1, respectively; while hsa_circ_0001946 was positively correlated with PARP1. The prediction accuracy of hsa_circ_0001946 in CHD was evaluated, showing an area under the ROC curve of 0.897 (95% CI: 0.791-0.961), which could further increase to 0.957 (95% CI: 0.870-0.992) upon a combination of hsa-miR-7-5p and PARP1. CONCLUSION: The present work demonstrated the predictive power of hsa_circ_0001946, hsa-miR-7-5p and PARP1 as combined biomarkers for CHD, and suggests a regulatory axis they consisted might contribute to the CHD development.

Preliminary verification of lncRNA ENST00000609755.1 potential ceRNA regulatory network in coronary heart disease.

BACKGROUND: This study aims to explore the possible ceRNA regulatory network of lncRNA ENST00000609755.1 in CHD patients based on the population; reveal the possible regulatory mechanism of lncRNA ENST00000609755.1. METHOD: Microarray analysis were used to identify differentially expressed miRNA, and mRNA profiles between 5 CHD and 5 healthy controls. The lncRNA ENST00000609755.1-miRNA-mRNA ceRNA regulatory network was constructed with lncRNA ENST00000609755.1 as the core based on microarray data and related prediction software (RNAhybird, miRanda, miRWalk 2.0). Furthermore, qRT-PCR was used to verify the expression levels of miRNA and mRNA. t-test and pearson correlation analysis were used to compare the expression differences and correlations of lncRNA, miRNA and mRNA. The receiver operating characteristic (ROC) curve was used to determine the discriminative ability of lncRNA ENST00000609755.1 and its downstream targets. RESULTS: Totally 25 miRNAs and 953 mRNAs were differentially expressed between CHD and healthy control. The lncRNA ENST00000609755.1- miRNA- mRNA ceRNA regulatory network was constructed (5 miRNA and 58 mRNA). qRT-PCR results suggest that the expression of lncRNA ENST00000609755.1 and ELK1 were up-regulated in CHD group and positively correlated, the expression of miR-150 was down-regulated in CHD, which was negatively correlated with lncRNA ENST00000609755.1 and ELK1. The AUC was 0.777(95%CI, 0.659-0.895) when miRNA-150 and ELK1 was added, which was higher than that of lncRNA ENST00000609755.1 single indicator. CONCLUSION: LncRNA ENST00000609755.1, miR-150 and ELK1 may have a potential ceRNA regulatory network relationship which could be considered to have a good combined diagnostic value for CHD. Also, preliminarily reveal the possible mechanism of lncRNA ENST00000609755.1 involved in CHD.

Exploring the association of long noncoding RNA expression profiles with intracranial aneurysms, based on sequencing and related bioinformatics analysis.

BACKGROUND: The present study aims to investigate the complete long non-coding RNA (lncRNA) and messenger RNA (mRNA) expression profiles in Intracranial aneurysm (IA) patients and controls by RNA sequencing, which reveals the lncRNA with predictive value for IA risk. METHODS: The comprehensive lncRNA and mRNA expression profiles were detected by RNA-Seq in human IA walls and superficial temporal arteries (STAs), followed by bioinformatics analyses, such as GO analysis, KEGG pathway analysis, and CNC network construction. Subsequently, qRT-PCR was used to profile the expression levels of selected lncRNA (lncRNA ENST000000576153, lncRNA ENST00000607042, lncRNA ENST00000471220, lncRNA ENST00000478738, lncRNA MALAT1, lncRNA ENST00000508090 and lncRNA ENST00000579688) in 30 (small) or 130 (large) peripheral blood leukocytes, respectively. Multivariate logistic regression was utilized to analyze the effects of lncRNA on IA. Receiver operating characteristic (ROC) curve was further drawn to explore the value of lncRNA in predicting IA. RESULTS: Totally 900 up-regulated and 293 down-regulated lncRNAs, as well as 1297 up-regulated and 831 down-regulated mRNAs were discovered in sequencing. Enrichment analyses revealed that they were actively involved in immune/inflammatory response and cell adhesion/extracellular matrix. Co-expression analysis and further enrichment analyses showed that five candidate lncRNAs might participate in IA's inflammatory response. Besides, after controlling other conventional risk factors, multivariate logistic regression analysis disclosed that low expression of lncRNA ENST00000607042, lncRNA ENST00000471220, lncRNA ENST00000478738, lncRNA MALAT1 in peripheral blood leukocytes were independent risk factors for IA. LncRNA ENST00000607042 has superior diagnostic value for IA. CONCLUSIONS: This study reveals the complete lncRNAs expression profiles in IA. The inflammatory response was closely related to IA. Besides, lncRNA ENST00000607042 might be a novel biomarker for IA risk.

Development of a nomogram that predicts the risk for coronary atherosclerotic heart disease.

Studies seldom combine biological, behavioral and psychological factors to estimate coronary atherosclerotic heart disease (CHD) risk. Here, we evaluated the associations between these factors and CHD to develop a predictive nomogram to identify those at high risk of CHD. This case-control study included 4392 participants (1578 CHD cases and 2814 controls) in southeast China. Thirty-three biological, behavioral and psychological variables were evaluated. Following multivariate logistic regression analysis, which revealed eight risk factors associated with CHD, a predictive nomogram was developed based on a final model that included the three non-modifiable (sex, age and family history of CHD) and five modifiable (hypertension, hyperlipidemia, diabetes, recent experience of a major traumatic event, and anxiety) variables. The higher total nomogram score, the greater the CHD risk. Final model accuracy (as estimated from the area under the receiver operating characteristic curve) was 0.726 (95% confidence interval: 0.709-0.747). Validation analysis confirmed the high accuracy of the nomogram. High risk of CHD was associated with several biological, behavioral and psychological factors. We have thus developed an intuitive nomogram that could facilitate development of preliminary prevention strategies for CHD.

Association of circular RNAs and environmental risk factors with coronary heart disease.

BACKGROUND: Coronary heart disease (CHD) is a complex disease caused by multi-factors and a major threat to human health. Circular RNAs (circRNAs) have critical roles in various biological processes and diseases. This study explores the independent role of circRNAs and their interaction with environmental factors in CHD. METHODS: A case-control study was conducted from March 2015 to September 2017 in Fuzhou, China. A total of 585 CHD patients and 585 gender- and age-matched healthy controls were enrolled. Questionnaire survey, health examination and molecular biology laboratory testing were conducted. Microarray technology and quantitative real-time polymerase chain reaction (PCR) were used to profile the expression levels of circRNAs. The area under the curve (AUC) of the receiver operating characteristic (ROC) was used to determine the diagnostic cut-offs. Multivariate logistic regression and multiplicative analysis were used to analyse the effects of environmental factors and hsa_circ_0008507, hsa_circ_0001946, hsa_circ_0000284 and hsa_circ_0125589 on CHD. RESULTS: The expression profile of circRNAs showed that 3423 circRNAs were differentially expressed at P < 0.05, but none pass multiple testing correction. qRT-PCR further confirmed the expression levels of hsa_circ_0008507, hsa_circ_0001946 and hsa_circ_0000284 in peripheral blood leukocytes in CHD cases were higher than those in non-CHD subjects (All p < 0.05). Hsa_circ_0008507 (OR = 1.29; 95% CI: 1.11-1.50), hsa_circ_0001946 (OR = 1.20; 95% CI: 1.01-1.42) and hsa_circ_0000284 (OR = 2.05; 95% CI: 1.32-3.19) were independent risk factors for CHD after controlling other common environmental risk factors. The AUC for hsa_circ_0008507, hsa_circ_0001946 and hsa_circ_0000284 was 0.75, 0.71 and 0.68, respectively. Compared with non-smoking individuals with low hsa_circ_0008507 expression, the smokers with high hsa_circ_0008507 expression showed the highest magnitude of OR in CHD risk. Additionally, a statistically significant multiplicative interaction was found between hsa_circ_0008507 and smoking for CHD. CONCLUSIONS: Hsa_circ_0008507, hsa_circ_0001946 and hsa_circ_0000284 were closely related to the occurrence and development of CHD. The combination of smoking and high hsa_circ_0008507 expression causes the occurrence and development of CHD.

Association of interleukin 4 -589T/C polymorphism with T(H)1 and T(H)2 bias and sepsis in Chinese major trauma patients.

BACKGROUND: Interleukin (IL)-4 is a pleiotropic cytokine, severed as an important component of the adaptive immune system, and implicated in the pathophysiology of sepsis. Data from other studies show that the -589T/C polymorphism in IL-4 promoter may alter IL-4 expression and susceptibility of inflammatory or autoimmune diseases. Whether this genetic variation is associated with sepsis susceptibility is unknown. The aim of this study was to search for the association of IL-4 -589T/C with the susceptibility to sepsis. METHODS: The polymorphism was genotyped among 308 severe trauma patients using restriction fragment length polymorphism polymerase chain reaction. The IL-4 and interferon-γ levels in the supernatants were determined with enzyme-linked immunosorbent assay. RESULTS: The IL-4/-589C allele was shown to be significantly associated with higher plasma IL-4 and lower interferon-γ production after lipopolysaccharide stimulation, indicating its effect on regulating T helper T(H)1/T(H)2 balance. Moreover, homozygosity and heterozygosity for the -589C were associated with an increased susceptibility of sepsis (p = 0.009; OR, 1.69; 95% confidence interval, 1.14-2.51). There was no relationship between the IL-4 -589T/C and multiple organ dysfunction scores in severe trauma patients. CONCLUSIONS: These results suggest that the IL-4 -589T/C polymorphism might affect T(H)1/T(H)2 balance and predispose trauma patients to susceptibility sepsis.