CRISPR/Cas12a trans-cleavage mediated photoelectrochemical biosensor based on zeolitic imidazolate framework-67 for ATP determination.

An efficient PEC biosensor is proposed for ATP detection based on exciton energy transfer from CdTe quantum dots (CdTe QDs) to Au nanoparticles (AuNPs), integrating CRISPR/Cas12a trans-cleavage activity and specific recognition of ZIF-67 to ATP. Exciton energy transfer between CdTe QDs and AuNPs system is firstly constructed as photoelectrochemical (PEC) sensing substrate. Then, the activator DNAs, used to activate CRISPR/Cas12a, are absorbed on the surface of ZIF-67. In the presence of ATP, the activator DNAs are released due to more efficient adsorption of ZIF-67 to ATP. The released activator DNA activates trans-cleavage activity of CRISPR/Cas12a to degrade ssDNA on the electrode, leading to the recovery of photocurrent due to the interrupted energy transfer. Benefiting from the specific recognition of ZIF-67 to ATP and CRISPR/Cas12a-modulated amplification strategy, the sensor is endowed with excellent specificity and high sensitivity.

Light-harvesting iridium (III) complex-sensitized NiO photocathode for photoelectrochemical bioanalysis.

A novel iridium (III) complex bearing boron dipyrromethene (Bodipy) as the light-harvesting antenna has been synthesized and is firstly employed as photosensitizer to assemble a dye-sensitized NiO photocathode. The assembled photocathode exhibits significantly improved photoelectrochemical (PEC) performance. Integrating the prepared photocathode with hybridization chain reaction (HCR)--based signal amplification strategy, a cathodic PEC biosensor is proposed for the detection of microRNA-133a (miRNA-133a). In the presence of the target, HCR is triggered to form long duplex concatamers on the photocathode, which allows numerous manganese porphyrins (MnPP) to bind in the dsDNA groove. With the help of H2O2, MnPP with peroxidase-like activity catalyzes 4--chloro-1-naphthol (4-CN) to produce benzo--4--chlorohexadienone (4-CD) precipitate on the electrode, leading to a significant decrease of photocurrent signal. The decreased photocurrent correlates linearly with the target concentration from 0.1 fM to 1 nM with a detection limit of 66.2 aM (S/N = 3). The proposed PEC strategy exhibits delightful selectivity, reproducibility and stability.

Machine-learning predictions for acute kidney injuries after coronary artery bypass grafting: a real-life muticenter retrospective cohort study.

BACKGROUND: Acute kidney injury (AKI) after coronary artery bypass grafting (CABG) surgery is associated with poor outcomes. The objective of this study was to apply a new machine learning (ML) method to establish prediction models of AKI after CABG. METHODS: A total of 2,780 patients from two medical centers in East China who underwent primary isolated CABG were enrolled. The dataset was randomly divided for model training (80%) and model testing (20%). Four ML models based on LightGBM, Support vector machine (SVM), Softmax and random forest (RF) algorithms respectively were established in Python. A total of 2,051 patients from two other medical centers were assigned to an external validation group to verify the performances of the ML prediction models. The models were evaluated using the area under the receiver operating characteristics curve (AUC), Hosmer-Lemeshow goodness-of-fit statistic, Bland-Altman plots, and decision curve analysis. The outcome of the LightGBM model was interpreted using SHapley Additive exPlanations (SHAP). RESULTS: The incidence of postoperative AKI in the modeling group was 13.4%. Similarly, the incidence of postoperative AKI of the two medical centers in the external validation group was 8.2% and 13.6% respectively. LightGBM performed the best in predicting, with an AUC of 0.8027 in internal validation group and 0.8798 and 0.7801 in the external validation group. The SHAP revealed the top 20 predictors of postoperative AKI ranked according to the importance, and the top three features on prediction were the serum creatinine in the first 24 h after operation, the last preoperative Scr level, and body surface area. CONCLUSION: This study provides a LightGBM predictive model that can make accurate predictions for AKI after CABG surgery. The LightGBM model shows good predictive ability in both internal and external validation. It can help cardiac surgeons identify high-risk patients who may experience AKI after CABG surgery.

Effects of peak time of myocardial injury biomarkers on mid-term outcomes of patients undergoing OPCABG.

BACKGROUND: With the development of cardiac surgery techniques, myocardial injury is gradually reduced, but cannot be completely avoided. Myocardial injury biomarkers (MIBs) can quickly and specifically reflect the degree of myocardial injury. Due to various reasons, there is no consensus on the specific values of MIBs in evaluating postoperative prognosis. This retrospective study was aimed to investigate the impact of MIBs on the mid-term prognosis of patients undergoing off-pump coronary artery bypass grafting (OPCABG). METHODS: Totally 564 patients undergoing OPCABG with normal courses were included. Cardiac troponin T (cTnT) and creatine kinase myocardial band (CK-MB) were assessed within 48 h before operation and at 6, 12, 24, 48, 72, 96 and 120 h after operation. Patients were grouped by peak values and peak time courses of MIBs. The profile of MIBs and clinical variables as well as their correlations with mid-term prognosis were analyzed by univariable and multivariable Cox regression models. RESULT: Continuous assessment showed that MIBs increased first (12 h after surgery) and then decreased. The peak cTnT and peak CK-MB occurred within 24 h after operation in 76.8% and 67.7% of the patients respectively. No significant correlation was found between CK-MB and mid-term mortality. Delayed cTnT peak (peak cTnT elevated after 24 h after operation) was correlated with lower creatinine clearance rate (69.36 ± 21.67 vs. 82.18 ± 25.17 ml/min/1.73 m2), body mass index (24.35 ± 2.58 vs. 25.27 ± 3.26 kg/m2), less arterial grafts (1.24 ± 0.77 vs. 1.45 ± 0.86), higher EuroSCORE II (2.22 ± 1.12 vs.1.72 ± 0.91) and mid-term mortality (26.5 vs.7.9%). Age (HR: 1.067, CI: 1.006-1.133), left ventricular ejection fraction (HR: 0.950, CI: 0.910-0.993), New York Heart Association score (HR: 1.839, CI: 1.159-2.917), total venous grafting (HR: 2.833, CI: 1.054-7.614) and cTnT peak occurrence within 24 h (HR: 0.362, CI: 0.196-0.668) were independent predictors of mid-term mortality. CONCLUSION: cTnT is a better indicator than CK-MB. The peak value and peak occurrence of cTnT are related to mid-term mortality in patients undergoing OPCABG, and the peak phases have stronger predictive ability. TRIAL REGISTRATION: Chinese Clinical Trial Registry, ChiCTR2000033850. Registered 14 June 2020, http://www.chictr.org.cn/edit.aspx?pid=55162&htm=4 .

The Effects of Obesity on Mortality Following Coronary Artery Bypass Graft Surgery: A Retrospective Study from a Single Center in China.

BACKGROUND Coronary artery bypass graft (CABG) surgery has become a routine surgical procedure for patients with occlusive coronary artery atherosclerosis. Worldwide, increasing levels of obesity are associated with ischemic heart disease and systemic comorbidities. This retrospective study from a single center in China aimed to investigate the effects of obesity on patient mortality following CABG surgery. MATERIAL AND METHODS Patients undergoing CABG (N=1471) were grouped according to body mass index (BMI) as normal weight (N=596), overweight (N=684), or obese (N=191). Baseline clinical characteristics and outcomes were recorded. Logistic regression analysis was performed for 30-day postoperative mortality. Kaplan-Meier survival curves were plotted, and Cox regression analysis investigated risk and protective factors for long-term mortality, with subgroup analysis for differences between on-pump and off-pump CABG groups. RESULTS The 30-day postoperative mortality was 5.0% in the normal-weight group, 1.3% in the overweight group, and 0% in the obese group. BMI was an independent protective factor for 30-day postoperative mortality (odds ratio=0.748; 95% confidence interval, 0.640-0.874; P<0.001). The 10-year mortality for the groups was 13.2% (normal), 7.8% (overweight), and 12.7% (obese). The >20-year mortality rates for the groups were 33.0% (normal), 41.5% (overweight), and 12.7% (obese). There was no significant correlation between BMI and long-term mortality. Being overweight had a protective effect against long-term mortality in the off-pump CABG subgroup. CONCLUSIONS An "obesity paradox" was identified in postoperative outcomes in patients following CABG surgery, with an increased BMI associated with reduced 30-day postoperative mortality. This association was more significant in the off-pump CABG group.

Impact of Preoperative Occult Renal Dysfunction on Early and Late Outcomes After Off-Pump Coronary Artery Bypass.

BACKGROUND: Renal dysfunction is independently associated with increased early and late mortality after coronary artery bypass graft (CABG) surgery. Off-pump CABG (OPCABG) avoids postoperative complications from the cardiopulmonary bypass, but it is unclear how it is impacted by occult renal dysfunction (ORD). This study aimed to investigate the effects of ORD on early and late outcomes after OPCABG. METHODS: This retrospective and observational cohort study reviewed data on 1,188 patients who underwent first isolated OPCABG with normal serum creatinine (SCr) levels. According to preoperative estimated creatinine clearance (eCrCl) by the Cockcroft-Gault formula, the patients were divided into an ORD group (n=260, eCrCl <60 mL/min/1.73 m2) and a control group (n=928, eCrCl ≥60 mL/min/1.73 m2). RESULTS: The ORD patients presented with older age, higher incidence of small body surface area, hypertension, low preoperative eCrCl, cerebrovascular accident, peripheral vascular disease, New York Heart Association (NYHA) Ⅲ, and high risk score. The prevalence of hospital mortality, postoperative acute kidney injury (AKI), peak postoperative SCr, and prolonged hospital stay were greater in the ORD patients than the control patients. Multivariable logistic regression analysis showed that the ORD patients were at significantly higher risk of postoperative AKI (OR, 2.702; 95% CI, 1.994-3.662) and in-hospital mortality (OR, 2.884; 95% CI, 1.293-6.432). Multivariate Cox proportional hazard models confirmed that ORD was significantly associated with high later mortality (HR, 2.847; 95% CI, 1.262-6.425). CONCLUSIONS: Occult renal dysfunction is an independent risk factor for postoperative AKI in-hospital and later mortality in patients undergoing OPCABG with normal SCr levels.

FTO regulates ocular angiogenesis via m6A-YTHDF2-dependent mechanism.

Pathological ocular angiogenesis commonly results in visual impairment or even blindness. Unveiling the mechanisms of pathological angiogenesis is critical to identify the regulators and develop effective targeted therapies. Here, we used corneal neovascularization (CNV) model to investigate the mechanism of pathological ocular angiogenesis. We show that N6-methyladenosine (m6A) mRNA demethylation mediated by fat mass- and obesity-associated protein (FTO) could regulate endothelial cell (EC) function and pathological angiogenesis during CNV. FTO levels are increased in neovascularized corneas and ECs under pathological conditions. In vitro silencing of FTO in ECs results in reduced cellular proliferation, migration, and tube formation under both basal and pathological conditions. Furthermore, FTO silencing attenuates suture-induced CNV in vivo. Mechanically, FTO silencing in ECs could increase m6A methylation levels in critical pro-angiogenic genes, such as FAK, leading to decreased RNA stability and increased RNA decay through m6A reader YTHDF2. Our study demonstrates that FTO regulates pathological ocular angiogenesis by controlling EC function in an m6A-YTHDF2-dependent manner.

Predictive ability of EuroSCORE II integrating cardiactroponin T in patients undergoing OPCABG.

BACKGROUND: Preoperative risk evaluation systems are significant and important to the allocation of medical resources and the communication between doctors and patients. The European System for Cardiac Operative Risk Evaluation II (EuroSCORE II) is widely used in clinical practice. Cardiac troponin T (cTnT) can specifically and accurately reflect myocardial injury. Whether EuroSCORE II can improve the predictive power after integrating with cTnT is still unclear. This study was a retrospective single center study designed to assess the predictive ability of EuroSCORE II integrated with cTnT for patients undergoing isolated off-pump coronary artery bypass grafting (OPCABG). METHODS: This retrospective and observational cohort study included 1887 patients who underwent first isolated OPCABG. cTnT was detected within 48 h before operation in each patient. According to myocardial injury, patients were divided by cTnT into 4 stages. A new risk evaluation system was created through logistic regression with EuroSCORE II and myocardial injury classification as covariates. Then the two risk evaluation systems were comparatively assessed by regression analysis, receiver operator characteristic curves, net reclassification index, Bland-Altman plots and decision curve analysis. RESULTS: There were 43 in-hospital deaths, with a mortality of 2.30% (43/1887). The logistic regression analysis showed that preoperative myocardial injury classification was a significant risk factor for in-hospital mortality in both total cohort (OR 1.491, 95%CI 1.049-2.119) and subsets (OR 1.761, 95%CI 1.102-2.814). The new risk evaluation system has higher calibration and discrimination power than EuroSCORE II, both for overall cohort and subsets. Especially, the new system has obvious advantages in discrimination power in the subset of acute myocardial infarction (AUC 0.813 vs. 0.772, 0.906 vs. 0.841, and 0.715 vs. 0.646, respectively). CONCLUSIONS: Both myocardial injury classification and EuroSCORE II are independent risk factors of in-hospital mortality in OPCABG patients. The new risk evaluation system has higher predictive ability than EuroSCORE II, especially in patients with a recent history of AMI.

Effectiveness of Saphenous Vein Y-Grafts in Patients Undergoing Off-Pump Complete Myocardial Revascularization.

BACKGROUND To evaluate perioperative and mid-term outcomes of saphenous vein Y-grafts in patients with multi-vessel coronary artery disease. MATERIAL AND METHODS Sixty patients who underwent off-pump coronary surgery with Y-graft between 2005 and 2016 were enrolled, including 38 patients with natural Y-graft. Sixty patients with multi-vessel lesions in the same period were randomly selected as a control group. RESULTS A total of 484 conduits were employed. The intraoperative variables were insignificantly different between groups, but Y-graft group compared with control group had more grafts (4.2±0.84 vs. 3.87±0.85) and anastomoses (6.30±1.39 vs. 5.62±1.15). No patient died during coronary artery bypass grafting and no episode of perioperative myocardial infarction was found. Follow-up duration lasted from 1 to 137 (40.0±27.7) months. No significant difference between Y-graft group and control group was found in Kaplan-Meier 3-year survival rate (93.4% vs. 88.0%) or 5-year survival rate (81.4% vs. 88.0%). CONCLUSIONS Saphenous vein Y-graft is a feasible and safe revascularization strategy for multi-vessel coronary artery disease patients and brings about satisfactory outcomes.

The Early Diagnostic Value of Procalcitonin in Pneumonia After Off-Pump Coronary Artery Bypass Grafting Surgery.

BACKGROUND The incidence of early postoperative pneumonia (EPOP) after off-pump coronary artery bypass grafting surgery (CABG) is relatively high, but its diagnosis by traditional methods remains difficult, which could be deleterious to the prognosis. Moreover, few data exist regarding procalcitonin (PCT) in early diagnosis of pneumonia after off-pump CABG. Thus, this study was performed to evaluate the value of PCT in diagnosing EPOP after off-pump CABG. MATERIAL AND METHODS A total of 402 consecutive patients undergoing off-pump CABG were retrospectively enrolled. Forty-four patients were diagnosed with EPOP and 112 patients were diagnosed with systemic inflammatory response syndrome (SIRS). Chest roentgenogram, serum PCT, white blood cells, neutral granulocyte ratio, and daily maximum body temperature were recorded. The ability of PCT to diagnose EPOP was evaluated by receiver operating characteristic (ROC) analyses in comparison with traditional methods. Clinical net benefits were estimated via decision curve analysis (DCA). RESULTS PCT presented satisfying accuracy in diagnosing EPOP with a cutoff value of 1.585 ng/mL (area under the curve [AUC] 0.808, 95% confidence interval [CI] 0.724-0.891, sensitivity 73%, specificity 86%). PCT performed better in diagnosing EPOP among SIRS patients (AUC 0.868, 95% CI 0.748-0.988, sensitivity 85%, specificity 89%). DCA showed valuable clinical net benefits of PCT in diagnosing EPOP after off-pump CABG regardless of threshold selected. CONCLUSIONS PCT could be a diagnostic marker for EPOP after off-pump CABG. The optimal cutoff value for diagnosing EPOP was 1.585 ng/mL. The application of PCT in diagnosing EPOP in SIRS patients was also satisfying with a cutoff value of 1.775 ng/mL.

The clinical applications of ensemble machine learning based on the Bagging strategy for in-hospital mortality of coronary artery bypass grafting surgery.

Background: Machine learning (ML) has excelled after being introduced into the medical field. Ensemble ML models were able to integrate the advantages of several different ML models. This study compares the ensemble ML model's and EuroSCORE II's performance predicting in-hospital mortality in patients undergoing coronary artery bypass grafting surgery. Methods: The study included 4,764 patients from three heart centers between January 2007 and December 2021. Of these, 3812 patients were assigned to the modeling group, and 952 patients were assigned to the internal test group. Patients from other two heart center (1733 and 415 cases, respectively) constituted the external test group. The modeling set data are trained using each of the three ML strategies (XGBoost, CatBoost, and LightGBM), and the new model (XCL model) is constructed by integrating these three models through an ensemble ML strategy. Performance of different models in the three test groups comparative assessments were performed by calibration, discriminant, decision curve analysis, net reclassification index (NRI), integrated discriminant improvement (IDI), and Bland-Altman analysis. Results: In terms of discrimination, the XCL model performed the best with an impressive AUC value of 0.9145 in the internal validation group. The XCL model continued to perform best in both external test groups. The NRI and IDI suggested that the ML model showed positive improvements in all three test groups compared to EuroSCORE II. Conclusions: ML models, particularly the XCL model, outperformed EuroSCORE II in predicting in-hospital mortality for CABG patients, with better discrimination, calibration, and clinical utility.

A cathodic photoelectrochemical biosensor based on CRISPR/Cas12a trans-cleavage mediated p-n heterojunction quenching mode for microRNA determination.

In this study, a cathodic photoelectrochemical (PEC) bioanalysis for sensitive determination of microRNA (miRNA) has been constructed based on CRISPR/Cas12a trans-cleavage mediated [(C6)2Ir(dcbpy)]+PF6- (C6 represents coumarin-6 and dcbpy represents 4,4'-dicarboxyl-2,2'-bipyridine)-sensitized NiO photocathode and p-n heterojunction quenching mode. The [(C6)2Ir(dcbpy)]+PF6--sensitized NiO photocathode exhibits a stable and dramatically improved photocurrent signal due to highly effective photosensitization of [(C6)2Ir(dcbpy)]+ PF6-. Then Bi2S3 quantum dots (Bi2S3 QDs) is captured on the photocathode, resulting in markedly quenching of the photocurrent. When target miRNA is specifically recognized by the hairpin DNA to stimulate the trans-cleavage activity of CRISPR/Cas12a, leading to the leave of the Bi2S3 QDs. The photocurrent is gradually recovered with the increasing target concentration. Thus, the quantitative signal response to target is achieved. Benefiting from excellent performance of NiO photocathode, intense quenching effect of p-n heterojunction and accurate recognition ability of CRISPR/Cas12a, the cathodic PEC biosensor shows a wider linear range over 0.1 fM-10 nM, with a low detection limit of 36 aM. Also, the biosensor exhibits satisfying stability and selectivity.

Preoperative prognostic nutritional index is an independent indicator for perioperative prognosis in coronary artery bypass grafting patients.

OBJECTIVES: The prognostic nutritional index is widely used for surgery prognosis, but the association between preoperative prognostic nutritional index and short-term prognosis for coronary artery bypass grafting surgery and the profiles of perioperative prognostic nutritional index remain unclear. METHODS: This study retrospectively enrolled a total of 879 adult patients undergoing coronary artery bypass grafting surgery in the Shanghai Chest Hospital from 2006 to 2022. The prognostic nutritional index was calculated based on serum albumin and peripheral lymphocyte count. In-hospital mortality, demographic characteristics, blood biochemistry parameters, cardiovascular medical history, and physical examination results were collected from the hospital information system. The propensity score matching method and multivariate logistic regression were used to detect the association between preoperative prognostic nutritional index and in-hospital mortality. RESULTS: Patients were divided into a high-prognostic nutritional index group (n = 500) and a low-prognostic nutritional index group (n = 379), using a cutoff value of 48.1 according to receiver operating characteristic curve analysis. The propensity score matching-adjusted mean prognostic nutritional index levels decreased from 48.35 before the operation to 34.04 an in ≤24 h after the operation and rebounded to 43.36 before discharge. High preoperative prognostic nutritional index was inversely associated with in-hospital mortality for coronary artery bypass grafting surgery (odds ratio = 0.86; 95% CI, 0.77-0.97) in propensity score matching-adjusted multivariate logistic regression. CONCLUSIONS: Preoperative prognostic nutritional index is an independent indicator for in-hospital mortality of for coronary artery bypass grafting surgery, and the variation trend of prognostic nutritional index during perioperation tends to be U-shaped.

Release Profile of Cardiac Troponin T and Risk Factors of Postoperative Myocardial Injury in Patients Undergoing CABG.

BACKGROUND: Cardiac troponin T (cTnT) is currently one of the important indicators for clinical diagnosis of myocardial injury, which is inevitable in cardiac surgery, especially coronary artery bypass grafting (CABG). Describing the release profile of cTnT and finding out the risk factors of postoperative myocardial injury (PMI) are of great significance. The purposes of this study are to explore the release profile of cTnT in patients undergoing CABG and to search for independent risk factors of PMI. METHODS: In this retrospective study, clinical data of CABG patients were collected. The cTnT was measured at 24 hours before and 6, 12, 24, 48, 72, 96 and 120 hours after operation separately. The release profiles and peak time of cTnT in total cohort and sub-cohorts were observed. Independent risk factors of PMI were explored via univariate and multivariate logistic regression analyses. RESULTS: In total, 2084 patients were enrolled, including 998 patients in a cTnT group and 1086 patients in a high-sensitive cTnT (hs-cTnT) group. PMI was recognized in 797 patients. In both groups, cTnT showed a trend of rising first and then falling within 120 hours after operation. The peak cTnT appeared within 12-24 hours after operation, while the peak hs-cTnT occurred mostly within 24-48 hours after operation. Univariate logistic analysis showed that body mass index (BMI), New York Heart Association (NYHA) classification, coronary artery disease (CAD) classification, cerebrovascular disease, left ventricular ejection fraction, number of diseased vessels, valvular disease, intra-aortic balloon pump (IABP) implantation, chronic obstructive pulmonary disease, pulmonary hypertension, previous percutaneous coronary intervention (PCI), BMI, bypass graft number, cardiopulmonary bypass, and preoperative cTnT were related risk factors. Multivariate logistic regression analysis showed that NYHA classification, CAD classification, valvular disease, IABP implantation, pulmonary hypertension, previous PCI, bypass graft number, cardiopulmonary bypass, and preoperative cTnT were independent risk factors of PMI. CONCLUSION: NYHA classification, CAD classification, valvular disease, IABP implantation, pulmonary hypertension, previous PCI, bypass graft number, cardiopulmonary bypass, and preoperative cTnT are independent risk factors of PMI in patients undergoing CABG.

DNA Methylation in Atrial Fibrillation and Its Potential Role in Precision Medicine.

Atrial fibrillation (AF), a common arrhythmia, can cause many serious consequences, including stroke and even death. The pathological mechanism of AF is very complicated. Epigenetic mechanisms, especially DNA methylation, contribute to the pathogenesis and maintenance of AF. DNA methylation is an important part of epigenetic and plays a significant role in human physiology and pathology. AF patients possess specific methylation sites (e.g., Pitx2c, RASSF1A, SURs, SERCA2a, and LINC00472), which have potential values of being biomarkers and underlie the diagnosis and prognosis of AF. These methylation sites can also benefit accurate treatment of AF. With deeper understanding into the epigenetic mechanisms of AF, the precision medicine for AF has also developed rapidly. In the future, DNA methylation omics and other research methods will be integrated to explore the epigenetic mechanisms in AF.

Identification of Regulatory circRNAs Involved in the Pathogenesis of Acute Myocardial Infarction.

BACKGROUND: Acute myocardial infarction (AMI) has high morbidity and mortality worldwide. However, the pathogenesis of AMI is still unclear, and the impact of circular RNAs (circRNAs) on AMI has rarely been recognized and needs to be explored. MATERIALS AND METHODS: The circRNA array was applied to investigate the expression level of circRNAs in the blood samples of coronary arteries of three AMI patients and three normal persons. Principal component analysis (PCA) and unsupervised clustering analysis were performed to reveal the distinguished expression patterns of circRNAs. The miRNA expression profiles of AMI patients were identified from a public dataset from the Gene Expression Omnibus (GEO) database (GSE31568). The miRNA binding sites on the circRNAs were predicted by miRanda. The miRNA enrichment analysis and annotation tool were used to explore the pathways that the dysregulated circRNAs may participate in. RESULTS: In total, 142 differentially expressed circRNAs, including 89 upregulated and 53 downregulated in AMI samples, were identified by the differential expression analysis. AMI patients had quite different circRNA expression profiles to those of normal controls. Functional characterization revealed that circRNAs that had the potential to regulate miRNAs were mainly involved in seven pathways, such as the Runt-related transcription factor-1 (RUNX1) expression and activity-related pathway. Specifically, hsa_circRNA_001654, hsa_circRNA_091761, hsa_circRNA_405624, and hsa_circRNA_406698 were predicted to sponge four miRNAs including hsa-miR-491-3p, hsa-miR-646, hsa-miR-603, and hsa-miR-922, thereby regulating RUNX1 expression or activity. CONCLUSION: We identified dysregulated blood circRNAs in the coronary arteries of AMI patients and predicted that four upregulated circRNAs were involved in the regulation of RUNX1 expression or activity through sponging four miRNAs.

Genome-wide screening of functional long noncoding RNAs in the epicardial adipose tissues of atrial fibrillation.

Atrial fibrillation (AF) is the most common arrhythmias, and patients with AF are facing increased risk of heart failure and ischemic stroke. However, the AF pathogenesis, especially the long noncoding RNAs (lncRNA)-related mechanism, has not been fully understood. In this study, we collected RNA sequencing data of the epicardial adipose tissues (EAT) from 6 AF and 6 sinus rhythm (SR) to identify the differentially expressed protein-coding genes (PCGs) and lncRNAs. Functionally, the differentially expressed PCGs were significantly enriched in bone development disease, chronic kidney failure, and kidney disease. Particularly, we found that homeobox (HOX) genes, especially the antisense RNAs, HOTAIRM1, HOXA-AS2 and HOXB-AS2, were significantly downregulated in EAT of AF. The biological function predictions for the dysregulated lncRNAs revealed that TNF signaling pathway was the most frequent pathway that the lncRNAs might participate in. In addition, SNHG16 and RP11-471B22.2 might participate in TGF-beta signaling and ECM-receptor interaction by interacting with the proteins involved in the pathways, respectively. Collectively, we provided some potentially pathogenic lncRNAs in AF, which might be useful for the related researchers to study their functionality and develop new therapeutics.

Prognostic Values of Three Equations in Estimating Glomerular Filtration Rates of Patients Undergoing Off-Pump Coronary Artery Bypass Grafting.

BACKGROUND: Renal dysfunction is independently associated with both short-term and long-term mortality after coronary artery bypass grafting (CABG). The estimated glomerular filtration rate (eGFR) is a convenient and effective indicator of renal function. However, the ability of eGFR calculated by various equations to predict the outcomes of patients undergoing off-pump CABG (OPCABG) is still unclear. This study was aimed to compare the predictive ability of in-hospital and long-term mortality in three equations of estimating renal functions after OPCABG. METHODS: Totally, 1362 patients undergoing OPCABG were retrospectively reviewed. Preoperative and postoperative serum creatinine (Scr) levels were detected. The renal function was evaluated by the Cockcroft-Gault (CG) equation, the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equation, and the full-age spectrum (FAS) equation. The endpoints were in-hospital and long-term all-cause mortality rates. Receiver operating characteristic curves, net reclassification index, decision curve analysis (DCA), multivariable logistic model, and Cox regression model were used for comparisons. RESULTS: The CG equation had the significantly highest discriminatory power to predict in-hospital mortality (area under the curve=0.815). Valuable clinical net benefits of the CG equation were greater than the other two equations regardless of before or after operation by DCA. Multivariable logistic and Cox regression analysis illustrated that the eGFR calculated by the CG equation was a significant independent risk factor of both in-hospital mortality (odds ratio=3.390) and long-term mortality (hazard ratio=1.553). CONCLUSION: The CG equation outperformed the FAS and CKD-EPI equations in predicting the mortality of patients after OPCABG. Postoperative renal function was more efficiently predicted compared with the preoperative one.

The Joint Analysis of Multi-Omics Data Revealed the Methylation-Expression Regulations in Atrial Fibrillation.

Atrial fibrillation (AF) is one of the most prevalent heart rhythm disorder. The causes of AF include age, male sex, diabetes, hypertension, valve disease, and systolic/diastolic dysfunction. But on molecular level, its mechanisms are largely unknown. In this study, we collected 10 patients with persistent atrial fibrillation, 10 patients with paroxymal atrial fibrillation and 10 healthy individuals and did Methylation EPICBead Chip and RNA sequencing. By analyzing the methylation and gene expression data using machine learning based feature selection method Boruta, we identified the key genes that were strongly associated with AF and found their interconnections. The results suggested that the methylation of KIF15 may regulate the expression of PSMC3, TINAG, and NUDT6. The identified AF associated methylation-expression regulations may help understand the molecular mechanisms of AF from a multi-omics perspective.

Proteomic Analysis of Atrial Appendages Revealed the Pathophysiological Changes of Atrial Fibrillation.

Atrial fibrillation (AF), known as the most common arrhythmia in the developed world, affects 1.5-2.0% of the population. Numerous basic studies have been carried out to identify the roles of electric and structural remodeling in the pathophysiological changes of AF, but more explorations are required to further understand the mechanisms of AF development. Proteomics enables researchers to identify protein alterations responsible for the pathological developing progresses of diseases. Compared to the genome, the proteome is closely related to the disease phenotype and can better manifest the progression of diseases. In this study, AF patients proteomically analyzed to identify possible mechanisms. Totally 20 patients undergoing cardiac surgery (10 with paroxysmal AF and 10 with persistent AF) and 10 healthy subjects were recruited. The differentially expressed proteins identified here included AKR1A1, LYZ, H2AFY, DDAH1, FGA, FGB, LAMB1, LAMC1, MYL2, MYBPC3, MYL5, MYH10, HNRNPU, DKK3, COPS7A, YWHAQ, and PAICS. These proteins were mainly involved in the development of structural remodeling. The differently expressed proteins may provide a new perspective for the pathological process of AF, and may enable useful targets for drug interference. Nevertheless, more research in terms of multi-omics is required to investigate possible implicated molecular pathways of AF development.