Associations between postoperative cognitive dysfunction, serum interleukin-6 and postoperative delirium among patients after coronary artery bypass grafting: A mediation analysis.

BACKGROUND: POCD is a common complication among patients who underwent coronary artery bypass graft (CABG), it is linked to loss of independence and reduced quality of life. AIMS AND OBJECTIVES: To examine the association between postoperative cognitive dysfunction (POCD), postoperative delirium (POD) and interleukin-6 (IL-6). DESIGN: A prospective cohort study. METHODS: Patients who underwent elective isolated CABG were enrolled. POCD was assessed by a set of cognitive function tools. Delirium was assessed using the CAM-ICU. The logistic regression analyses were used to identify the predictive value of POD or IL-6 on POCD. The path analysis was used to analyse the relationship among POD, IL-6 and POCD. RESULTS: A total of 212 patients were enrolled, with 25.0% of patients developing POD and 32.5% developing POCD. The multiple logistic regression analysis revealed that patients with POD had a four-fold increased hazard of POCD (OR = 3.655), and patients with IL-6 ≥ 830.50 pg/mL at the 6th hours after surgery had a 5-fold increased risk of experiencing POCD (OR = 5.042). However, the mediation effect of POD between IL-6 and POCD was not statistically significant (ß = 0.059, p = .392). CONCLUSIONS: POD and IL-6 at the 6th hour after surgery (≥830.50 pg/mL) are two potent predictors for POCD, while POD did not play a mediation effect between IL-6 and POCD. RELEVANCE TO CLINICAL PRACTICE: Early identification of risk factors (e.g., delirium assessment and testing for serum IL-6 levels) by clinical nurses for POCD may contribute to the clinical practice for the targeted prevention nursing strategies.

Severe Burn Injury Significantly Alters the Gene Expression and m6A Methylation Tagging of mRNAs and lncRNAs in Human Skin.

N6-methyladenosine (m6A) modulates RNA metabolism and functions in cell differentiation, tissue development, and immune response. After acute burns, skin wounds are highly susceptible to infection and poor healing. However, our understanding of the effect of burn injuries on m6A methylation and their potential mechanism is still limited. Human m6A-mRNA&lncRNA Epitranscriptomic microarray was used to obtain comprehensive mRNA and lncRNA transcriptome m6A profiling and gene expression patterns after burn injuries in human skin tissue. Bioinformatic and functional analyses were conducted to find molecular functions. Microarray profiling showed that 65 mRNAs and 39 lncRNAs were significantly hypermethylated; 5492 mRNAs and 754 lncRNAs were significantly hypomethylated. Notably, 3989 hypomethylated mRNAs were down-expressed and inhibited many wound healing biological processes and pathways including in the protein catabolic process and supramolecular fiber organization pathway; 39 hypermethylated mRNAs were up-expressed and influenced the cell surface receptor signaling pathway and inflammatory response. Moreover, we validated that m6A regulators (METTL14, METTL16, ALKBH5, FMR1, and HNRNPC) were significantly downregulated after burn injury which may be responsible for the alteration of m6A modification and gene expression. In summary, we found that homeostasis in the skin was disrupted and m6A modification may be a potential mechanism affecting trauma infection and wound healing.

Myeloperoxidase in the pericardial fluid improves the performance of prediction rules for postoperative atrial fibrillation.

OBJECTIVES: After surgery, inflammation is a prominent factor influencing postoperative atrial fibrillation. Myeloperoxidase is a major contributor to inflammatory responses after surgical tissue damage. We evaluated whether myeloperoxidase is associated with postoperative atrial fibrillation clinically and in an animal model. METHODS: This prospective cohort study included patients undergoing isolated coronary artery bypass grafting. Myeloperoxidase concentrations in blood and pericardial fluid were determined at baseline and 6, 12, and 18 hours after coronary artery bypass grafting. Myeloperoxidase activity in blood, pericardial fluid, and atrium were also evaluated in a canine coronary artery bypass grafting model. Electrophysiologic, histologic, and immunohistochemistry analyses were performed to explore underlying mechanisms. RESULTS: Postoperative atrial fibrillation occurred in 45 of 137 patients (32.8%). Patients with postoperative atrial fibrillation had significantly higher serum and pericardial myeloperoxidase levels. Individual clinical and surgical factors had moderate predictive value (area under the curve, 0.760) for postoperative atrial fibrillation. Discrimination improved remarkably when myeloperoxidase was combined with other parameters (area under the curve, 0.901). Pericardial myeloperoxidase at 6 hours postoperatively was the strongest independent predictor of postoperative atrial fibrillation (odds ratio, 19.215). The rate of postoperative atrial fibrillation increased exponentially across pericardial myeloperoxidase grades. Compared with controls, coronary artery bypass grafting-treated dogs showed higher atrial fibrillation vulnerability and maintenance, shorter atrial effective refractory period, attenuated connexin 43 expression, and increased myocardial and pericardial myeloperoxidase activity. Connexin 43 expression and atrial effective refractory period were strongly negatively correlated with myocardial and pericardial myeloperoxidase activity. CONCLUSIONS: Myeloperoxidase is linked to postoperative atrial fibrillation, and the ability to predict postoperative atrial fibrillation was remarkably improved by adding pericardial myeloperoxidase. Myeloperoxidase-related atrial structural and electrical remodeling is a physiologic substrate for this arrhythmia.

Application of Metabolomics in Various Types of Diabetes.

Metabolomics is the analysis of numerous small molecules known as metabolites. Over the past few years, with the continuous development in metabolomics, it has been widely used in the detection, diagnosis, and treatment of diabetes and has demonstrated great benefits. At the same time, studies on diabetes and its complications have discovered the metabolic markers that are characteristic of diabetes. However, the pathogenesis of diabetes has yet to be clarified, as well as no complete cure. The mechanism of diabetes has not been completely elucidated, and its eradication treatment is not available. Thus, prevention of the onset of the disease and its treatment have become very important. In this review, we focused on the recent progress in the use of metabolites in diabetes and their complications, as well as understanding the impact of diabetes metabolites.

Alanine-Glyoxylate Aminotransferase Sustains Cancer Stemness Properties through the Upregulation of SOX2 and OCT4 in Hepatocellular Carcinoma Cells.

Liver cancer stem cells (LCSCs) are a small subset of oncogenic cells with a self-renewal ability and drug resistance, and they promote the recurrence and metastasis of hepatocellular carcinoma (HCC). However, the mechanisms regulating LCSCs have not been fully explored. By enriching LCSCs from spheroid cultures and performing transcriptomic analysis, we determined that alanine-glyoxylate aminotransferase (AGXT), which participates in the metabolism of serine and glycine, was significantly upregulated in spheroid cultures, and its function in LCSCs remains unknown. Through the exogenous overexpression or short hairpin RNA knockdown of AGXT in HCC cells, we observed that changes in the AGXT level did not affect the spheroid ability and population of LCSCs. The knockdown of AGXT in LCSCs reduced the number of spheroids and the population of LCSCs; this implies that AGXT is required for the maintenance of cancer stemness rather than as a driver of LCSCs. Mechanistically, AGXT may sustain the self-renewal potential of LCSCs by upregulating the expression of SRY-box transcription factor 2 (SOX2) and octamer-binding transcription factor 4 (OCT4), two well-known master regulators of cancer stemness. Taken together, our study demonstrates the role of AGXT in supporting LCSCs; thus, AGXT merits further exploration.

[Exercise preconditioning attenuates the lipid metabolic disorder induced by chronic high fat diet feeding in mice].

Mounting evidence has shown that exercise exerts extensive beneficial effects, including preventing and protecting against chronic diseases, through improving metabolism and other mechanisms. Recent studies have shown that exercise preconditioning affords significant cardioprotective effects. However, whether exercise preconditioning improves high fat diet (HFD)-induced obesity and lipid metabolic disorder remains unknown. The study was aimed to explore the effects of exercise preconditioning on HFD-induced obesity and lipid metabolic disorder in mice. 4-week-old C57BL/6 mice were subjected to swimming or sedentary control for 3 months, and then were fed with normal diet (ND) or HFD for 4 more months. The results showed that the blood glucose was decreased, and the glucose tolerance and grip strength were increased in exercised mice after training. Exercise preconditioning failed to improve HFD-induced body weight gain, but improved HFD-induced glucose intolerance. Exercise preconditioning showed no significant effects on both exercise capacity and physical activity in ND- and HFD-fed mice. HFD feeding increased total cholesterol and low density lipoprotein (LDL) levels in circulation, promoted subcutaneous fat and epididymal fat accumulation in mice. Exercise preconditioning increased circulating high density lipoprotein (HDL) and decreased circulating LDL, without affecting the subcutaneous fat and epididymal fat in HFD-fed mice. HFD feeding increased liver weight and hepatic total cholesterol contents, and dysregulated the expressions of several mitochondria function-related proteins in mice. These abnormalities were partially reversed by exercise preconditioning. Together, these results suggest that exercise preconditioning can partially reverse the HFD-induced lipid metabolic disorder and hepatic dysfunction, and these beneficial effects of exercise sustain for a period of time, even after exercise is discontinued.

Effects of nurse-led multidisciplinary team management on cardiovascular hospitalization and quality of life in patients with atrial fibrillation: Randomized controlled trial.

BACKGROUND: Atrial fibrillation is globally the most common sustained cardiac arrhythmia which increases patient morbidity and mortality, dramatically influencing well-being. Despite substantial efforts, an optimal clinical pathway for chronic atrial fibrillation management has yet to be developed. In recent practice, a multidisciplinary team management has been recommended for patients with atrial fibrillation. However, experiments exploring nurse-led multidisciplinary team management in chronic atrial fibrillation management relative to standard clinical management are still sparse and limited. OBJECTIVE: To evaluate the effects of a nurse-led multidisciplinary team approach on cardiovascular hospitalization and death, and quality of life in patients with atrial fibrillation. DESIGN: Randomized controlled trial. SETTING: The Cardiology Department of a tertiary referral hospital in Beijing, China. PARTICIPANTS: Eligible patients diagnosed with atrial fibrillation who consented. METHODS: Subjects were randomly assigned into one of two Cardiology Units upon admission. Patients in the control group (n = 119) received usual care and those in the intervention group (n = 116) underwent a nurse-led multidisciplinary team approach. Follow-up lasted for 12 months. The primary endpoint was a composite of cardiovascular hospitalization and cardiovascular death. The secondary endpoint was the differences in the quality of life between the groups observed at 6 months and 12 months of follow-up, compared to the baseline data, as determined using a Chinese version of the Medical Outcome Study Short-Form 36 General Health Survey. RESULTS: Patients under intervention showed a fewer cardiovascular hospitalization (17 vs. 35, p = 0.006) than those receiving usual care. Discernible differences were also observed in rates of cardiovascular hospitalization between the two groups (hazard ratio: 2.115, 95% confidential interval: 1.228-3.643, log-rank = 6.746, p = 0.009). Quality of life was improved in both groups, but more so in the intervention group (scores, 588.0 ± 106.0 vs. 519.1 ± 120.7 at 6 months and 674.4 ± 53.4 vs. 584.1 ± 105.9 at 12 months; both p < 0.001). Repeated measures analysis of variance indicated that group-by-time and between-subjects effects in respect of patients' quality of life (F = 9.310, p < 0.01; F = 29.042, p < 0.01, respectively). No relationships were found with cardiovascular death. CONCLUSIONS: Nurse-led multidisciplinary team management reduces cardiovascular hospitalization and improves quality of life in patients with atrial fibrillation, suggesting that this innovative management approach should be implemented in clinical practice. REGISTRATION NUMBER: Chinese Clinical Trial Registry (ChiCTR1800018851).

Association of the serum uric acid to creatinine ratio with metabolic syndrome in the middle age and older population in China.

Background: Metabolic syndrome (MetS) has attracted great interest, with an increasing prevalence. Recent studies have shown that the serum uric acid-to-creatinine ratio (SUACr) might be an excellent biomarker for MetS risk prediction in diabetic patients and postmenopausal women. However, the relationship between SUACr and MetS in a middle-aged and older population remains unclear. Methods: A total of 1277 participants were included in this cross-sectional study. Logistic regression modelling was performed to assess the association between SUACr and MetS in the total population. The dose-response relationship of SUACr and MetS was further assessed by a restricted cubic spline model (RCS). Furthermore, to explore the relationships between the levels of SUACr and the number of metabolic components, analysis of covariance (ANCOVA) was applied. Results: The levels of SUACr were lower in the non-MetS participants (OR 1.60, 95% CI 1.36 to 1.89; P<0.001),. Positive and dose-response relationships were further confirmed by the RCS model. We also found that, with increased number of components, the SUACr tended to increase. Moreover, values of SUACr were strongly related to levels of triglycerides (TGs), body mass index (BMI), blood glucose levels, systolic blood pressure/diastolic blood pressure (SBP/DBP), and hypertension. In addition, the positive association between SUACr and MetS also occurred in those patients with normal uric acid levels. Conclusion: Elevated values of SUACr were strongly associated with an increased risk of MetS; this positive relationship remained in those individuals with normal uric acid levels.

A Prediction Rule Including Interleukin-6 in Pericardial Drainage Improves Prediction of New-Onset Atrial Fibrillation After Coronary Artery Bypass Grafting.

OBJECTIVE: To test the hypothesis that a prediction rule including levels of interleukin-6 in pericardial drainage (pdIL-6) would improve the discrimination in classifying patients undergoing coronary artery bypass grafting (CABG) into different postoperative atrial fibrillation (POAF) risk levels. DESIGN: Prospective cohort study. SETTING: A university-affiliated tertiary hospital. PARTICIPANTS: Patients undergoing CABG. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: We prospectively recruited patients who underwent CABG into derivation and validation cohorts. The independent predictors were identified in the derivation cohort using multiple logistic regression and tested in the validation cohort. The performance of the predictive model was tested using area under the receiver operating characteristic curve (AUC) in both cohorts. A prediction rule was created by assigning points to each predictor. Patients were classified in various risk levels according to their total risk scores. We enrolled 302 and 207 patients in the derivation and validation cohorts, respectively. Multiple logistic regression analysis identified six predictors: age ≥61 y, left atrial diameter ≥49 mm, right atrial diameter ≥45 mm, number of grafts ≥3, and serum uric acid ≥226 µmol/L and pdIL-6 levels ≥166 ng/mL at postoperative 12 h. The AUC of the model was 0.78 and 0.77 for the derivation and validation cohort, respectively, which was greatly increased by adding pdIL-6. Patients were stratified into low-risk, moderate-risk and high-risk groups. CONCLUSIONS: A POAF prediction rule including pdIL-6 had good performance for stratifying CABG patients into various risk groups for POAF. The inclusion of pdIL-6 resulted in clinically meaningful improvement in risk prediction.

Inclusion of interleukin-6 improved performance of postoperative delirium prediction for patients undergoing coronary artery bypass graft (POD-CABG): A derivation and validation study.

BACKGROUND: Patients undergoing coronary artery bypass graft (CABG) are at high risk for developing postoperative delirium (POD). A simple prediction rule may benefit patients from early identification of POD followed by adequate preventive strategies. The purpose of the current study was to develop and validate a POD prediction rule for patients undergoing CABG (POD-CABG), by considering all possible perioperative factors. METHODS: In this prospective cohort study, patients who underwent first elective isolated CABG were continuously enrolled from May 2014 to November 2015 in a tertiary hospital. Delirium was assessed using the Confusion Assessment Method for Intensive Care Unit. Patients' perioperative risk factors were collected through interviews and review of medical records. The area under receiver-operating characteristic curve (AUC) was used to assess the overall performance of the predictive rule. RESULTS: A total of 242 and 148 patients were enrolled in the derivation and validation cohorts, respectively. Multiple logistic regression analysis identified seven variables that were independently associated with POD: age (≥65 years), gender (female), history of myocardial infarction and diabetes mellitus, postoperative atrial fibrillation, the use of intra-aortic balloon pump, and serum interleukin-6 ≥478 pg/ml at 18 hours after surgery. The AUC of the POD-CABG was 0.84 (95% CI, 0.79-0.90) in the derivation cohort, and was 0.86 (95% CI, 0.80-0.91) after bootstrap resampling. The AUC was 0.81 (95% CI, 0.73-0.88) after the POD-CABG was applied to the validation cohort. CONCLUSIONS: The POD-CABG with inclusion of interleukin-6 demonstrated good performance in predicting POD.

An Intelligent Individualized Cardiovascular App for Risk Elimination (iCARE) for Individuals With Coronary Heart Disease: Development and Usability Testing Analysis.

BACKGROUND: Death and disability from coronary heart disease (CHD) can be largely reduced by improving risk factor management. However, adhering to evidence-based recommendations is challenging and requires interventions at the level of the patient, provider, and health system. OBJECTIVE: The aim of this study was to develop an Intelligent Individualized Cardiovascular App for Risk Elimination (iCARE) to facilitate adherence to health behaviors and preventive medications, and to test the usability of iCARE. METHODS: We developed iCARE based on a user-centered design approach, which included 4 phases: (1) function design, (2) iterative design, (3) expert inspections and walkthroughs of the prototypes, and (4) usability testing with end users. The usability testing of iCARE included 2 stages: stage I, which included a task analysis and a usability evaluation (January to March 2019) of the iCARE patient app using the modified Health Information Technology Usability Survey (Health-ITUES); and stage II (June 2020), which used the Health-ITUES among end users who used the app for 6 months. The end users were individuals with a confirmed diagnosis of CHD from 2 university-affiliated hospitals in Beijing, China. RESULTS: iCARE consists of a patient app, a care provider app, and a cloud platform. It has a set of algorithms that trigger tailored feedback and can send individualized interventions based on data from initial assessment and health monitoring via manual entry or wearable devices. For stage I usability testing, 88 hospitalized patients (72% [63/88] male; mean age 60 [SD 9.9] years) with CHD were included in the study. The mean score of the usability testing was 90.1 (interquartile range 83.3-99.0). Among enrolled participants, 90% (79/88) were satisfied with iCARE; 94% (83/88) and 82% (72/88) reported that iCARE was useful and easy to use, respectively. For stage II usability testing, 61 individuals with CHD (85% [52/61] male; mean age 53 [SD 8.2] years) who were from an intervention arm and used iCARE for at least six months were included. The mean total score on usability testing based on the questionnaire was 89.0 (interquartile distance: 77.0-99.5). Among enrolled participants, 89% (54/61) were satisfied with the use of iCARE, 93% (57/61) perceived it as useful, and 70% (43/61) as easy to use. CONCLUSIONS: This study developed an intelligent, individualized, evidence-based, and theory-driven app (iCARE) to improve patients' adherence to health behaviors and medication management. iCARE was identified to be highly acceptable, useful, and easy to use among individuals with a diagnosis of CHD. TRIAL REGISTRATION: Chinese Clinical Trial Registry ChiCTR-INR-16010242; https://tinyurl.com/2p8bkrew.

Individualized mobile health interventions for cardiovascular event prevention in patients with coronary heart disease: study protocol for the iCARE randomized controlled trial.

BACKGROUND: Mobile health-based individualized interventions have shown potential effects in managing cardiovascular risk factors. This study aims to assess whether or not mHealth based individualized interventions delivered by an Individualized Cardiovascular Application system for Risk Elimination (iCARE) could reduce the incidence of major cardiovascular events in individuals with coronary heart disease. METHODS: This study is a large-scale, multi-center, parallel-group, open-label, randomized controlled clinical trial. This study will be conducted from September 2019 to December 2025. A total of 2820 patients with coronary heart disease will be recruited from two clinical sites and equally randomized into three groups: the intervention group and two control groups. All participants will be informed of six-time points (at 1, 3, 6, 12, 24, and 36 months after discharge) for follow-up visits. Over a course of 36 months, patients who are randomized to the intervention arm will receive individualized interventions delivered by a fully functional iCARE that using various visualization methods such as comics, videos, pictures, text to provide individualized interventions in addition to standard care. Patients randomized to control group 1 will receive interventions delivered by a modified iCARE that only presented in text in addition to routine care. Control group 2 will only receive routine care. The primary outcome is the incidence of major cardiovascular events within 3 years of discharge. Main secondary outcomes include changes in health behaviors, medication adherence, and cardiovascular health score. DISCUSSION: If the iCARE trial indeed demonstrates positive effects on patients with coronary heart disease, it will provide empirical evidence for supporting secondary preventive care in this population. Results will inform the design of future research focused on mHealth-based, theory-driven, intelligent, and individualized interventions for cardiovascular risk management. TRIAL REGISTRATION: Trial registered 24th December 2016 with the Chinese Clinical Trial Registry (ChiCTR-INR-16010242). URL: http://www.chictr.org.cn/showproj.aspx?proj=17398 .

Mechanism of IL-6-related spontaneous atrial fibrillation after coronary artery grafting surgery: IL-6 knockout mouse study and human observation.

Clinical observation and ex vivo studies have established a strong association between inflammation and postoperative atrial fibrillation (POAF). However, it is unclear whether the inflammatory phenotype is causally linked to this event or is an epiphenomenon, and it is not known which inflammatory meditators may increase susceptibility to POAF. The limitations of available animal models of spontaneous POAF (sPOAF) makes it difficult to select an experimental system. Here, we provide experimental and clinical evidence for mechanistic involvement of interleukin-6 (IL-6) in sPOAF. PHASE I: We established a mouse model of cardiac surgery with nonpaced sPOAF. IL-6 knockout mice were protected from sPOAF compared with wild-type mice. PHASE II: At 48 hours after surgery, the heart was separated into 6 regions and cultured. IL-6 was expressed in all regions, with highest abundance in the left atrium (LA). In PHASE III, we demonstrated that IL-6 in the LA elicited early profibrotic properties in atria via the pSTAT3/STAT3 signaling pathway and contributed to sPOAF. PHASE IV: In a translational prospective clinical study, we demonstrated that humans with POAF had a higher IL-6 concentration in pericardial drainage (PD). This study provides preliminary evidence of a causal relationship between IL-6 and POAF in a novel nonpaced sPOAF mouse model. IL-6 is a crucial prerequisite for eliciting profibrotic properties in cardiac myocytes via the pSTAT3 pathway during the early postoperative period, leading to an increased susceptibility to POAF. Measuring IL-6 in PD could be a new noninvasive biomarker for the clinical prediction of POAF.

Interleukin-6 Receptor Asp358 A>C Polymorphism Is Associated With Postoperative Atrial Fibrillation.

BACKGROUND: This study examined the associations of single-nucleotide polymorphisms in the interleukin-6 receptor gene (Asp358 A>C) and the interleukin-6 promoter (-174G>C and -597G>A) with interleukin-6 levels and postoperative atrial fibrillation (POAF) after coronary artery bypass grafting (CABG). METHODS: The study enrolled 371 Chinese Han patients who were undergoing CABG. Serum interleukin-6 levels were measured preoperatively and at 6, 12, and 18 hours postoperatively. Genotypes for the 3 polymorphisms were determined. RESULTS: Overall, POAF developed in 30.2% of patients. The CC genotype and C allele frequencies for the interleukin-6 receptor Asp358 A>C polymorphism were significantly higher in patients with POAF than in patients without POAF (P = .003), and the interleukin-6 levels were significantly higher in patients with the CC genotype compared with A allele carriers at 6, 12, and 18 hours in the overall cohort and at 12 and 18 hours in the POAF subgroup, but there were no significant differences in the non-POAF subgroup. However, the allele and genotype frequencies of the interleukin-6 -174G>C and -597G>A polymorphisms were similar among groups, and there were no differences in interleukin-6 levels at any time point between the C/A allele carriers and the patients with GG genotypes. Univariate analysis showed that the CC genotype for interleukin-6 receptor Asp358 A>C, age, and history of cerebrovascular disease were associated with POAF. Multivariable regression showed that the CC genotype was independently related to the development of POAF (odds ratio, 2.01; 95% confidence interval: 1.15 to 3.52; P = .014). CONCLUSIONS: The interleukin-6 receptor Asp358 A>C polymorphism may contribute to genetic susceptibility to POAF after CABG.

Blood microRNA 202-3p associates with the risk of essential hypertension by targeting soluble ST2.

MicroRNA (miR)-202-3p has attracted a great deal of attention in the fields of oncology, gynecology, and metabolic disorders. However, its role in cardiovascular diseases remains to be clarified. We previously found that disruption of miR-202-3p mediated regulation of expression of soluble (s)ST2, a decoy receptor for interleukin (IL)-33, promotes essential hypertension (EH). In the present study, we first measured miR-202-3p expression levels in the blood of 182 EH cases and 159 healthy controls using TaqMan assays. miR-202-3p levels were shown to be significantly higher in EH cases than controls (fold change = 3.58, P<0.001). Logistic regression analysis revealed that higher miR-202-3p expression was associated with an increased occurrence of EH (adjusted odds ratio (OR): 1.57; 95% confidence interval (CI), 1.36-1.82; P<0.001). Addition of miR-202-3p to traditional risk factors showed an additive prediction value for EH. Further functional experiments indicated that miR-202-3p could be induced by angiotensin II (Ang II) and inhibited by Ang II-triggered soluble ST2 (sST2) expression in a negative feedback manner. Moreover, blood miR-202-3p levels were negatively correlated with sST2 expression in vivo. Our study shows that blood miR-202-3p levels were significantly associated with the occurrence of EH. These findings indicate that miR-202-3p exerts a protective role against EH by antagonizing the induction of sST2 by Ang II.

α-Linolenic acid but not linolenic acid protects against hypertension: critical role of SIRT3 and autophagic flux.

Although dietary α-linolenic acid (ALA) or linolenic acid (LA) intake was reported to be epidemiologically associated with a lower prevalence of hypertension, recent clinical trials have yielded conflicting results. Comparable experimental evidence for the roles of these two different fatty acids is still lacking and the underlying mechanisms need to be further elucidated. Our data showed that ALA but not LA supplementation alleviated systolic blood pressure elevation and improved ACh-induced, endothelium-dependent vasodilation in both spontaneously hypertensive rats (SHRs) and AngII-induced hypertensive mice. In addition, SHRs displayed reduced vascular Sirtuin 3 (SIRT3) expression, subsequent superoxide dismutase 2 (SOD2) hyperacetylation and mitochondrial ROS overproduction, all of which were ameliorated by ALA but not LA supplementation. In primary cultured endothelial cells, ALA treatment directly inhibited SIRT3 reduction, SOD2 hyperacetylation, mitochondrial ROS overproduction and alleviated autophagic flux impairment induced by AngII plus TNFα treatment. However, these beneficial effects of ALA were completely blocked by silencing SIRT3. Restoration of autophagic flux by rapamycin also inhibited mitochondrial ROS overproduction in endothelial cells exposed to AngII plus TNFα. More interestingly, SIRT3 KO mice developed severe hypertension in response to a low dose of AngII infusion, while ALA supplementation lost its anti-hypertensive and endothelium-protective effects on these mice. Our findings suggest that ALA but not LA supplementation improves endothelial dysfunction and diminishes experimental hypertension by rescuing SIRT3 impairment to restore autophagic flux and mitochondrial redox balance in endothelial cells.

MiR-202-3p Inhibits Foam Cell Formation and is Associated with Coronary Heart Disease Risk in a Chinese Population.

A previous study and a gene-annotation enrichment analysis for potential targets of the microRNA miR-202-3p both suggest that this microRNA might be implicated in cardiovascular and metabolic diseases. In the present study, the role of miR-202-3p in the pathogenesis of coronary heart disease (CHD) was explored. We conduct a case-control study to detect the expression levels of miR-202-3p in peripheral blood cells and found that miR-202-3p expression was significantly higher in CHD cases than in controls (P < 0.001). miR-202-3p levels were negatively correlated with platelet distribution width (r = -0.348, P = 0.002) and mean platelet volume (r = -0.29, P = 0.01). Further functional analyses suggested that stimulation with oxidized low-density lipoprotein (ox-LDL) induced miR-202-3p expression, and that this microRNA suppressed the formation of ox-LDL-induced macrophage foam cells derived from THP-1 cells in a feedback manner. In addition, miR-202-3p overexpression modulated the expression of several key genes involved in foam cell formation, including that of ABCG4, NCEH1I, and SCARB2. In summary, miR-202-3p was associated with CHD, exerting a protective role against CHD by feedback suppression of ox-LDL-induced macrophage foam cell formation.

An audio-visual review model enhanced one-year retention of cardiopulmonary resuscitation skills and knowledge: A randomized controlled trial.

BACKGROUND: As the majority of out-of-hospital cardiac arrest occur at patients' homes, implementing high-quality cardiopulmonary resuscitation by family members is critical in improving patient outcomes. However, the survival rate remains low due to low bystander cardiopulmonary resuscitation rate and rapid skill deterioration in individuals who complete the training. OBJECTIVES: To evaluate the effectiveness of audio-visual review model and audio-visual-practice review model on cardiopulmonary resuscitation skill retention 12 months after training. DESIGN: A randomized, double-blind, placebo controlled, and three-arm parallel study. PARTICIPANTS: A total of 641 family members of patients at high risk of out-of-hospital cardiac arrest enrolled in the study and 448 participants completed the follow-up. METHODS: Family members from Beijing, China were recruited. All families underwent initial cardiopulmonary resuscitation training. Their cardiopulmonary resuscitation skill and knowledge were assessed immediately after training. Trainees who were rated "adequate skill and knowledge" were assigned randomly into one of three groups. The control group was given a cardiopulmonary resuscitation instruction booklet and a placebo-DVD without any reminders. Both audio-visual and audio-visual-practice groups were reinforced by a telephone reminder every 3 months. The audio-visual-practice group was also asked to simultaneously practice the skills while watching the instructional-DVD. The trainees' cardiopulmonary resuscitation skills and knowledge were re-assessed 12 months after training. RESULTS: The retention rates of cardiopulmonary resuscitation skills in both audio-visual-practice (N = 177) and audio-visual (N = 157) groups were higher than that in control group (N = 114) 12 months after training (all P-values  < 0.001). The cardiopulmonary resuscitation skill retention rate in audio-visual-practice group was higher than that in audio-visual group (49.7% vs 36.9%, P = 0.019), but no difference was found in intention-to-treat analysis (32.1% vs 27.1%, P = 0.230). Both audio-visual-practice and audio-visual groups had higher correct rates on all skill elements than that in control group (all P-values < 0.05). The cardiopulmonary resuscitation knowledge scores in both audio-visual-practice and audio-visual groups were higher than that in control group (all P-values < 0.001). However, no significant difference was found between audio-visual-practice and audio-visual groups (P = 0.243). CONCLUSIONS: Both audio-visual-practice and audio-visual review models demonstrated better long-term retention of cardiopulmonary resuscitation skills for families of people at higher risk of out-of-hospital cardiac arrest. (Registration number: chiCTR-TRC-12002149).

Change in Serum Level of Interleukin 6 and Delirium After Coronary Artery Bypass Graft.

BACKGROUND: Serum level of interleukin 6 (IL-6) is known to be associated with postoperative delirium. However, no consensus has emerged on the postoperative time point at which IL-6 level may predict postoperative delirium after coronary artery bypass graft surgery. OBJECTIVES: To compare trends in IL-6 levels in patients with and without postoperative delirium and to examine the relationship between IL-6 levels at different times and postoperative delirium after coronary artery bypass graft. METHODS: A prospective cohort study of patients who underwent their first elective isolated coronary artery bypass graft between November 2013 and August 2015 at a cardiac intensive care unit in Beijing, China. Concentrations of IL-6 were measured before the operation and at the 6th, 12th, and 18th postoperative hours. Participants were assessed for postoperative delirium twice daily for 5 days. Univariate and multivariate logistic regression analyses were done to determine associations between IL-6 levels at different time points, postoperative changes in IL-6 levels, and the occurrence of postoperative delirium. RESULTS: Postoperative delirium was diagnosed in 85 of 266 patients (32%). Levels of IL-6 were significantly higher in patients with postoperative delirium than in patients without it at the 6th, 12th, and 18th postoperative hours (P = .03, .004, and .001, respectively). Change in IL-6 level (odds ratio, 2.97; 95% CI, 1.20-7.31; P = .02) and IL-6 level of 583 pg/mL or higher at the 18th postoperative hour (odds ratio, 5.20; 95% CI, 1.84-14.70; P = .002) were associated with higher incidence of postoperative delirium. CONCLUSION: Interleukin 6 level (≥ 583 pg/mL) at the 18th postoperative hour may serve as a potent predictor of postoperative delirium in coronary artery bypass graft patients.

Development of interventions for an intelligent and individualized mobile health care system to promote healthy diet and physical activity: using an intervention mapping framework.

BACKGROUND: The mortality of coronary heart disease can be largely reduced by modifying unhealthy lifestyles. However, the long-term effectiveness of interventions for modifying unhealthy diet and physical inactivity of patients with coronary heart disease remain unsatisfactory worldwide. This study aims to systematically design a set of theory-based and evidence-based, individualized, and intelligent interventions for promoting the adoption and maintenance of a healthy diet and physical activity level in patients with coronary heart disease. METHODS: The interventions will be delivered by a mobile health care system called Individualized, Intelligent and Integrated Cardiovascular Application for Risk Elimination. Three steps of the intervention mapping framework were used to systematically develop the interventions. Step 1: needs assessment, which was carried out by a literature review, in-depth interviews and focus group discussions. Step 2: development of objective matrix for diet and physical activity changes, based on the intersection of objectives and determinants from the Contemplation-Action-Maintenance behavior change model. Step 3: formulation of evidence-based methods and strategies, and practical applications, through a systematic review of existing literature, research team discussions, and consultation with multidisciplinary expert panels. RESULTS: Three needs relevant to content of the intervention, one need relevant to presentation modes of the intervention, and four needs relevant to functional features of the application were identified. The objective matrix includes three performance objectives, and 24 proximal performance objectives. The evidence-based and theory-based interventions include 31 strategies, 61 evidence-based methods, and 393 practical applications. CONCLUSIONS: This article describes the development of theory-based and evidence-based interventions of the mobile health care system for promoting the adoption and maintenance of a healthy diet and physical activity level in a structured format. The results will provide a theoretical and methodological basis to explore the application of intervention mapping in developing effective behavioral mobile health interventions for patients with coronary heart disease. TRIAL REGISTRATION: Chinese Clinical Trial Registry: ChiCTR-INR-16010242. Registered 24 December 2016. http://www.chictr.org.cn/index.aspx.