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Hyperlipidemia-induced retinal vascular dysfunction is a complex pathological process. circRNAs are important regulators of biological processes and disease progression. However, the expression pattern of circRNAs in hyperlipidemia-induced retinal vascular dysfunction remains unclear. Herein, we used a murine model of hyperlipidemia and identified 317 differentially expressed circRNAs between hyperlipidemic retinas and normolipidemic retinas by circRNA microarrays. GO analysis indicated that the host genes of dysregulated circRNAs were targeted to cell differentiation (ontology: biological process), cytoplasm (ontology: cellular component), and protein binding (ontology: molecular function). Pathway analysis revealed that circRNAs-mediated network was mostly enriched in focal adhesion signaling. Notably, circLDB1 was significantly up-regulated in the serum of coronary artery disease patients and aqueous humor of age-related macular degeneration patients. circLDB1 regulated endothelial cell viability, proliferation, and apoptosis in vitro. Thus, circRNAs are the promising targets for the prediction and diagnosis of hyperlipidemia-induced vascular diseases.

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.

Type 2 diabetes mellitus is one of the most common forms of the disease worldwide. Hyperglycemia and insulin resistance play key roles in type 2 diabetes mellitus. Renal glucose reabsorption is an essential feature in glycaemic control. Kidneys filter 160 g of glucose daily in healthy subjects under euglycaemic conditions. The expanding epidemic of diabetes leads to a prevalence of diabetes-related cardiovascular disorders, in particular, heart failure and renal dysfunction. Cellular glucose uptake is a fundamental process for homeostasis, growth, and metabolism. In humans, three families of glucose transporters have been identified, including the glucose facilitators GLUTs, the sodium-glucose cotransporter SGLTs, and the recently identified SWEETs. Structures of the major isoforms of all three families were studied. Sodium-glucose cotransporter (SGLT2) provides most of the capacity for renal glucose reabsorption in the early proximal tubule. A number of cardiovascular outcome trials in patients with type 2 diabetes have been studied with SGLT2 inhibitors reducing cardiovascular morbidity and mortality.:The current review article summarises these aspects and discusses possible mechanisms with SGLT2 inhibitors in protecting heart failure and renal dysfunction in diabetic patients. Through glucosuria, SGLT2 inhibitors reduce body weight and body fat, and shift substrate utilisation from carbohydrates to lipids and, possibly, ketone bodies. These pleiotropic effects of SGLT2 inhibitors are likely to have contributed to the results of the EMPA-REG OUTCOME trial in which the SGLT2 inhibitor, empagliflozin, slowed down the progression of chronic kidney disease and reduced major adverse cardiovascular events in high-risk individuals with type 2 diabetes. This review discusses the role of SGLT2 in the physiology and pathophysiology of renal glucose reabsorption and outlines the unexpected logic of inhibiting SGLT2 in the diabetic kidney.

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.

Yuying Gu,1,* Lingtong Shan,2,* Ban Liu,3,* Mengwei Lv,4 Xi Chen,4 Tao Yan,5 Yu Shi,4 Jiapeng Chen,6 Zhi Li,7 Yangyang Zhang4 1Department of Cardiology, Shanghai East Hospital, Tongji University School of Medicine, Shanghai, People’s Republic of China; 2Department of Thoracic Surgery, Sheyang County People’s Hospital, Yancheng, Jiangsu, People’s Republic of China; 3Department of Cardiology, Shanghai Tenth People’s Hospital, Tongji University School of Medicine, Shanghai, People’s Republic of China; 4Department of Cardiovascular Surgery, Shanghai East Hospital, Tongji University School of Medicine, Shanghai, People’s Republic of China; 5Department of Cardiovascular Surgery, Zhongshan Hospital, Fudan University, Shanghai, People’s Republic of China; 6Xinglin College, Nantong University, Nantong, Jiangsu, People’s Republic of China; 7Department of Cardiovascular Surgery, Jiangsu Province Hospital, The First Affiliated Hospital with Nanjing Medical University, Nanjing, Jiangsu, People’s Republic of China*These authors contributed equally to this workCorrespondence: Yangyang ZhangDepartment of Cardiovascular Surgery, Shanghai East Hospital, Tongji University School of Medicine, 150 Jimo Road, Shanghai, 200120, People’s Republic of ChinaTel +86 13818132320Email zhangyangyang_wy@vip.sina.comZhi LiDepartment of Cardiovascular Surgery, Jiangsu Province Hospital, The First Affiliated Hospital with Nanjing Medical University, Nanjing, Jiangsu, People’s Republic of ChinaTel +86 13770606815Email zhili_cths@163.comBackground: 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.Keywords: cardiac troponin T, coronary artery bypass grafting, myocardial injury

Objective The co-incidence of esophageal cancer and coronary heart disease (CHD) is increasing in elderly patients. This study was carried out to analyze the efficiency and safety of simultaneous esophagectomy and cardiac surgery in a selected group of elderly patients. Methods Prospective database for coexistency of severe CHD and esophageal or esophageal-gastric junction cancer was firstly reviewed. Twenty-two patients undergoing combined surgical interventions, including first beating-heart coronary artery bypass grafting (off-pump CABG) and then esophagectomy, were involved as group A. Then, 44 patients undergoing isolated esophagectomy were selected as group B using the propensity score matching method. Data including clinic pathological characteristics and postoperative outcomes were investigated. Kaplan–Meier analysis was used. Results The surgical procedure was performed through left lateral thoracotomy in all patients, except one patient in group A who received median sternotomy and left lateral thoracotomy. The operation time and blood loss were both more in group A, as a result of two operations performed at one session. Patients in both groups were followed up from 1.3 to 78.3 months. No significant between-group was found in overall survival or relapse-free survival. Conclusion The risk of simultaneous esophagectomy and cardiac surgery is not high. Despite certain differences in clinical indicators between groups, the safety of simultaneous procedures in group A is evident. Trial registration ChiCTR 1800014498. Registered 17 January 2018 Electronic supplementary material The online version of this article (10.1186/s12957-018-1512-5) contains supplementary material, which is available to authorized users.

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; P0.001). The 10-year mortality for the groups was 13.2% (normal), 7.8% (overweight), and 12.7% (obese). The20-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.

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.

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.

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.

Low-density lipoprotein cholesterol (LDL-C) is a pivotal factor in atherosclerotic cardiovascular disease (ASCVD), the leading cause of worldwide mortality. The limitations of statin therapy require alternative treatment strategies to achieve target LDL-C level. Proprotein convertase subtilisin/kexin type 9 (PCSK9) plays an important role in LDLR recycling, consequently regulating plasma cholesterol levels. Monoclonal antibodies targeting PCSK9 increased expression of LDLRs at the cell surface and therefore decreased circulating LDL-C. PCSK9 inhibitors have shown great efficacy in reducing plasma LDL-C levels, which needs to inject once or twice monthly. Though SPIRE sponsors concern the immunogenicity and terminate trials early, FOURIER and ODYSSER OUTCOME trials improved the efficacy of PCSK9 inhibitors in LDL-C reduction. Inclisiran actually is a small interfering RNA (siRNA) developed to inhibit PCSK9 messenger RNA, leading to reduced concentrations of the PCSK9 protein and thereby lower concentrations of LDL-C. Inclisiran is a latest alternative treatment to cholesterol-lowering therapeutics. Twice injections of inclisiran durably reduced LDL-C levels over 1 year. siRNA therapeutics provided a simple, novel, and less frequent approach to LDL-C reduction in phase I and II trials, which may be used either as in combination with statin therapeutics or a stand-alone therapy in the future.

BACKGROUND The co-existence of coronary heart disease (CHD) and lung cancer is increasing in an increasingly aging population. The aim of this study was to evaluate patient outcome from combined off-pump coronary artery bypass graft (CABG) surgery and lung resection in patients more than 50 years-of-age. MATERIAL AND METHODS A retrospective clinical study of 23 patients with a mean age of 70.2±8.4 years (range, 51-86 years) included 18 men and five women with CHD and lung cancer who underwent a single operation with combined off-pump CABG surgery and lung resection, for non-small cell lung cancer (NSCLC) (n=22) and small cell lung cancer (n=1). Surgical approaches included: median sternotomy in six patients; left lateral thoracotomy in nine patients; a median sternotomy in three patients; median sternotomy combined with thoracoscopic lobectomy in five patients. RESULTS In the retrospective study of 23 patients, there were no deaths and no new cases of myocardial infarction (MI) in the immediate perioperative period. During the follow-up period, six patients died from lung cancer metastasis or recurrence; one patient died of acute renal failure; and one patient died from the effects of chemotherapy. The remaining 15 patients underwent postoperative follow-up for between 3-79 months with no deaths and no new cases of MI. CONCLUSIONS For patients who are more than 50 years-of-age and who have CHD and lung cancer, a single combined operation that includes off-pump CABG and lung resection can be safe and effective.

Vascular dysfunction is a hallmark of ischemic, cancer, and inflammatory diseases, contributing to disease progression. Circular RNAs (circRNAs) are endogenous non-coding RNAs, which have been reported to be abnormally expressed in many human diseases. In this study, we used retinal vasculature to determine the role of circular RNA in vascular dysfunction. We revealed that cZNF609 was significantly up-regulated upon high glucose and hypoxia stress in vivo and in vitro. cZNF609 silencing decreased retinal vessel loss and suppressed pathological angiogenesis in vivo. cZNF609 silencing increased endothelial cell migration and tube formation, and protected endothelial cell against oxidative stress and hypoxia stress in vitro. By contrast, transgenic overexpression of cZNF609 showed an opposite effects. cZNF609 acted as an endogenous miR-615-5p sponge to sequester and inhibit miR-615-5p activity, which led to increased MEF2A expression. MEF2A overexpression could rescue cZNF609 silencing-mediated effects on endothelial cell migration, tube formation, and apoptosis. Moreover, dysregulated cZNF609 expression was detected in the clinical samples of the patients with diabetes, hypertension, and coronary artery disease. Intervention of cZNF609 expression is promising therapy for vascular dysfunction.

// Ban Liu 1,* , Chang Gu 2,* , Yuliang Wang 3,* , Xiaowei Wang 4 , Wen Ge 5 , Lingtong Shan 6 , Yujian Wei 6 , Xiaohan Xu 4 and Yangyang Zhang 7,8 1 Department of Cardiology, Shanghai Tenth People’s Hospital, Tongji University School of Medicine, Shanghai, China 2 Department of Thoracic Surgery, Shanghai Chest Hospital, Shanghai Jiao Tong University, Shanghai, China 3 School of Public Health, Nanjing Medical University, Nanjing, China 4 Department of Cardiovascular Surgery, The First Affiliated Hospital with Nanjing Medical University, Nanjing Medical University, Nanjing, China 5 Department of Cardiovascular Surgery, Shuguang Hospital, Affiliated to Shanghai University of TCM, Shanghai, China 6 The First Clinical Medical College of Nanjing Medical University, Nanjing, China 7 Department of Cardiovascular Surgery, East Hospital, Tongji University School of Medicine, Shanghai, China 8 Key Laboratory of Arrhythmias of the Ministry of Education of China, East Hospital, Tongji University School of Medicine, Shanghai, China * Ban Liu, Chang Gu, and Yuliang Wang contributed equally to this work Correspondence to: Yangyang Zhang, email: // Keywords : esophagectomy, off-pump coronary artery bypass grafting, coronary artery disease, simultaneous, outcome Received : November 22, 2016 Accepted : January 17, 2017 Published : January 26, 2017 Abstract Introduction: To analyze the outcomes of off-pump coronary artery bypass grafting (OPCABG) and esophagectomy simultaneously for patients with coronary artery disease (CAD) and coexisting esophageal cancer. Methods: Twenty-two patients with CAD and coexisting esophageal cancer underwent combined surgical interventions were subjected to the study. OPCABG was performed first, followed by esophagectomy. All the corresponding data including clinicopathological characteristics and postoperative outcomes were all investigated. Results: All the combined procedures were performed successfully. The average number of grafts was 2.36. Tumors were located at the middle third of the esophagus in 5 patients, at the lower third of the esophagus in 8 patients, at the esophageal gastric junction (EGJ) in 9 patients, respectively. The operations were carried out through a left lateral thoracotomy approach in 21 patients while a median sternotomy and left lateral thoracotomy approach was used in 1 patient for his condition rapidly worsened. Postoperatively, pneumonia occurred in 4 patients (18.2%). During the follow-up, three patients died of cancer metastasis /recurrence (6, 18, 37 months) and one died of pneumonia (1 month). The cumulative 5 years survival rate is 52.9%. Conclusions: The combined procedure of OPCABG and esophagectomy is a safe and effective treatment option for patients with severe CAD and esophageal cancer.

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 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.

Objective The co-incidence of lung cancer and coronary artery disease (CAD) is increasing in patients of advanced age. This study was performed to demonstrate the efficiency and safety of simultaneous coronary artery bypass grafting and lung cancer surgery in a selected group of older patients. Methods Twenty patients with severe CAD and coexisting lung cancer underwent simultaneous surgical interventions (Group A), and 20 patients with lung cancer underwent an isolated lung cancer operation (Group B). In Group A, the combined operations were carried out through 2 incisions in 3 patients, a single incision in 14 patients, and median sternotomy for heart surgery and thoracoscopic lobectomy for lung cancer in 3 patients. The single-incision approach was used in all patients in Group B. Results The operation time was longer and the blood loss volume was larger in Group A than B. No significant between-group differences were found in the 5-year relapse-free survival rate or 5-year survival rate. Conclusions The simultaneous performance of lung cancer surgery and cardiac surgery was effective and evidently safe in Group A. This treatment approach enabled earlier lung cancer resection and avoidance of the eventual complications associated with further surgical procedures.

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.

Glaucoma is a progressive neurodegenerative disease, characterized by retinal ganglion cells (RGCs) and axon degeneration. The development of neuroprotective drug is required for improving the efficiency of glaucoma treatment. Eucommia ulmoides Oliv. has been used as a source of traditional medicine and as a beneficial health food. Lignans is one of the main bioactive components of Eucommia ulmoides. Here, we show that lignans protects RGCs against oxidative stress-induced injury in vitro. Moreover, lignans exerts neuroprotective effect on glaucoma-associated optic neuropathy in glaucomatous rats. Lignans treatment could improve oxidative stress response in RGCs and retinas of glaucomatous rats. Lignans plays an anti-oxidative stress role via the activation of AMPK signaling. This study provides evidence that lignans possesses protective effect on glaucoma-associated optic neuropathy. Lignans might be an alternative for the prevention and treatment of glaucomatous neurodegeneration.

Background/Aims: Advanced glycation end products (AGEs) could elicit oxidative stress, trigger and aggravate endothelium damage in several ischemic retinopathies including diabetic retinopathy (DR). The leaves of Eucommia ulmoides O., also referred to as Tu-chung or Du-zhong, have been used for the treatment of hypertension and diabetes, showing great antioxidant activity and anti-glycation activity. Lignans is one of the main bioactive components of Eucommia ulmoides. This study mainly investigated the effect of lignans treatment on AGEs-induced endothelium damage. Methods: MTT assay, Hoechst staining, and calcein-AM/ propidium iodide (PI) staining was conducted to determine the effect of lignans treatment on endothelial cell function in vitro. Retinal trypsin digestion, Evans blue assay, isolectin staining, and western blots were conducted to determine the effect of lignans treatment on retinal microvascular function in vivo. Western blot, protein immunoprecipitation (IP), MTT assays, and enzyme activity assay was conducted to detect the effect of ligans treatment on oxidative stress response. Results: Lignans protected retinal endothelial cell against AGEs-induced injury in vitro and diabetes-induced vascular dysfunction in vivo. Lignans treatment could regulate oxidative stress response in retinal endothelial cell line, retina, and liver. Moreover, we showed that NRF2/HO-1 signaling was critical for lignans-mediated oxidative stress regulation. Conclusion: Lignans treatment could protect against endothelial dysfunction in vivo and in vitro via regulating Nrf2/HO-1 signaling. Lignans might be developed as a promising drug for the treatment of diabetes-induced microvascular dysfunction.

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.

Background: The vascular complications of diabetes mellitus are the major causes of morbidity and mortality among people with diabetes. Circular RNAs are a class of endogenous noncoding RNAs that regulate gene expression in eukaryotes. In this study, we investigated the role of circular RNA in retinal vascular dysfunction induced by diabetes mellitus. Methods: Quantitative polymerase chain reactions, Sanger sequencing, and Northern blots were conducted to detect circular HIPK3 (circHIPK3) expression pattern on diabetes mellitus–related stresses. MTT (3-[4,5-dimethythiazol-2-yl]-2,5-diphenyl tetrazolium bromide) assays, EdU (5-ethynyl-2′-deoxyuridine) incorporation assays, Transwell migration assays, and Matrigel assays were conducted to detect the role of circHIPK3 in retinal endothelial cell function in vitro. Retinal trypsin digestion, vascular permeability assays, and ELISA assays were conducted to detect the role of circHIPK3 in retinal vascular dysfunction in vivo. Bioinformatics analysis, luciferase activity assays, RNA pull-down assays, and in vitro studies were conducted to reveal the mechanism of circHIPK3-mediated retinal vascular dysfunction. Results: circHIPK3 expression was significantly upregulated in diabetic retinas and retinal endothelial cells following stressors related to diabetes mellitus. circHIPK3 silencing or overexpressing circHIPK3 changed retinal endothelial cell viability, proliferation, migration, and tube formation in vitro. circHIPK3 silencing in vivo alleviated retinal vascular dysfunction, as shown by decreased retinal acellular capillaries, vascular leakage, and inflammation. circHIPK3 acted as an endogenous miR-30a-3p sponge to sequester and inhibit miR-30a-3p activity, which led to increased vascular endothelial growth factor-C, FZD4, and WNT2 expression. Ectopic expression of miR-30a-3p mimicked the effect of circHIPK3 silencing on vascular endothelial phenotypes in vivo and in vitro. Conclusions: The circular RNA circHIPK3 plays a role in diabetic retinopathy by blocking miR-30a function, leading to increased endothelial proliferation and vascular dysfunction. These data suggest that circular RNA is a potential target to control diabetic proliferative retinopathy.

Aims: Apoptosis plays a critical role in cardiomyocyte loss during ischaemic heart injury. A detailed understanding of the mechanism involved has a substantial impact on the optimization and development of treatment strategies. Here, we report that the expression of SIRT4, a mitochondrial sirtuin, is markedly down-regulated in hypoxia-induced apoptosis of H9c2 cardiomyoblast cells. Methods and Results: SIRT4 interference significantly alters H9c2 cell viability, apoptotic cell number and caspase-3/7 activity. Furthermore, SIRT4 expression can affect the ratio of pro-caspase 9/caspase 9 or pro-caspase 3/caspase 3, an affect Bax translocation, which in turn alters the development of H9c2 cell apoptosis. Conclusion: These results suggest that SIRT4 is a key player in hypoxia-induced cardiomyocyte apoptosis, and that strategies based on its enhancement might be of benefit in the treatment of ischaemic heart disease.

Vascular remodeling is an important pathological feature of hypertension, leading to increased vascular resistance and reduced compliance. Endothelial cell (EC) and vascular smooth muscle cell (VSMC) dysfunction is involved in vascular remodeling. Long noncoding RNAs are potential regulators of EC and VSMC function. Herein, we determined whether long noncoding RNA–growth arrest–specific 5 (GAS5) is involved in hypertension-related vascular remodeling. We revealed that GAS5 knockdown aggravated hypertension-induced microvascular dysfunction as shown by increased retinal neovascularization and capillary leakage. GAS5 regulated the remodeling of arteries, including caudal arteries, carotid arteries, renal arteries, and thoracic arteries. GAS5 was mainly expressed in ECs and VSMCs, and its expression was significantly downregulated in hypertension. GAS5 knockdown affected endothelial activation, endothelial proliferation, VSMC phenotypic conversion, and EC-VSMC communication in vivo and in vitro. Mechanistically, GAS5 regulated EC and VSMC function through β-catenin signaling. This study identified GAS5 as a critical regulator in hypertension and demonstrated the potential of gene therapy and drug development for treating hypertension.

Microvascular dysfunction is an important characteristic of diabetic retinopathy. Long non-coding RNAs (lncRNAs) play important roles in diverse biological processes. In this study, we investigated the role of lncRNA-MEG3 in diabetes-related microvascular dysfunction. We show that MEG3 expression level is significantly down-regulated in the retinas of STZ-induced diabetic mice, and endothelial cells upon high glucose and oxidative stress. MEG3 knockdown aggravates retinal vessel dysfunction in vivo, as shown by serious capillary degeneration, and increased microvascular leakage and inflammation. MEG3 knockdown also regulates retinal endothelial cell proliferation, migration, and tube formation in vitro. The role of MEG3 in endothelial cell function is mainly mediated by the activation of PI3k/Akt signaling. MEG3 up-regulation may serve as a therapeutic strategy for treating diabetes-related microvascular complications.

HMG-CoA reductase inhibitors (statins) inhibit cholesterol biosynthesis, and also decrease the formation of isoprenoid intermediates required for the activation of Rho kinase (ROCK) pathway. ROCK pathway plays pivotal roles in cardiovascular diseases including arteriosclerosis. It has been implicated that inhibition of ROCK can reverse vascular dysfunction in humans with atherosclerosis. However, it is not clear whether statins, at doses used to lower cholesterol levels, inhibit ROCK activity in humans with atherosclerosis.We treated 40 subjects with stable atherosclerosis with rosuvastatin 10 mg/day, or rosuvastatin 40 mg/day for 28 days in a randomized, double-blinded study. We assessed the change in the lipid levels, C-reactive protein (CRP), ROCK activity, and flow-mediated dilation (FMD) of the brachial artery before and after statins therapy.Treatment with rosuvastatin 10 mg and 40 mg significantly reduced LDL cholesterol by 43.2% to 55.9% and increased FMD by 29.3% to 42.5% (p0.05 for both compared with baselines). Both doses inhibited ROCK activity (p0.05), and the extent of inhibition was greater with rosuvastatin 40 mg compared with 10 mg (p0.05). Only rosuvastatin 40 mg significantly reduced hsCRP (p0.05).There was no correlation between changes in ROCK activity and changes in low-density lipoprotein cholesterol (r=0.37, p0.05 vs. r=0.41, p0.05) among patients randomized to rosuvastatin 10 mg group or 40 mg group. There was a correlation between ROCK inhibition and change in FMD among patients with rosuvastatin 10 mg therapy (r=0.43, p0.05), and 40 mg therapy (r=0.54, p0.05). Correlation was found between changes in ROCK inhibition and changes in CRP in rosuvastatin 40 mg/day group (r=0.47, p0.05).These results demonstrate that high dose rosuvastatin exerts greater effects on LDL-C, ROCK activity, and CRP than low dose rosuvastatin. These findings provide clinical evidence that statins are effective in improving endothelium dysfunction by a cholesterol-independent mechanism in patients with atherosclerosis.

This randomized, double-blind, parallel-design study compared the short-term effects of rosuvastatin and atorvastatin on serum lipids and markers of inflammation and endothelial function in patients with stable atherosclerosis. Patients received either 10 mg/day rosuvastatin ( n = 18) or 20 mg/day atorvastatin ( n = 18), orally, for 4 weeks. Serum lipids, high-sensitivity C-reactive protein (hsCRP), Rho-associated coiled-coil containing protein kinase (ROCK) activity and flow-mediated dilation (FMD) of the brachial artery were assessed before and after therapy. Both statins produced significant reductions in total cholesterol, low-density lipoprotein cholesterol (LDL-C), triglyceride and hsCRP levels, and significant increases in FMD. Both statins significantly reduced ROCK activity and inhibition was significantly greater with rosuvastatin. There was no correlation between ROCK activity and LDL-C level in either group. There was a significant correlation between ROCK activity and FMD for both statins, but no correlations between FMD and LDL-C or hsCRP levels. Short-term treatment with either rosuvastatin or atorvastatin inhibits ROCK activity independent of cholesterol reduction, and improves endothelium dysfunction in patients with atherosclerosis.

Background Familial hypercholesterolemia (FH), characterized by elevated plasma low-density lipoprotein-cholesterol (LDL-C) levels and premature coronary artery disease (CAD), remains mostly underdiagnosed and undertreated. We investigated the prevalence of clinical FH among Chinese patients with premature ST-segment-elevation myocardial infarction (STEMI) and one-year follow-up on their lipid management and cardiovascular events. Methods Four hundred and ninety-eight premature STEMI patients (363men) were enrolled. FH patients were identified using the Dutch Lipid Clinic Network Criteria. Lipid management and cardiovascular events in all patients were assessed. Results Nineteen patients (3.8%) were diagnosed as definite/probable FH, 211 (42.4%) as possible FH and 268 (53.8%) as unlikely FH. All patients were divided into two main groups: unlikely FH (0–2 points) and possible FH (≥3 points). Possible FH patients were younger (50.1 years vs. 53.5 years) with higher NT-proBNP level (3014.15 pg/mL vs. 2326.25 pg/mL), occurrence of multi-vessel CAD (37.4% vs. 18.3%), lower LVEF (47% vs. 49%) and more severe Killip classification (Class 3, 20.0% vs. 9.7%). Follow-up data were available for 203 patients from the possible FH group and 243 patients from the unlikely FH group. High intensity statin intake status (%) of possible FH vs. unlikely FH was as follows: 1) on admission: 4.8% vs. 0.4%; 2) at discharge: 10.4% vs. 1.6% and 3) at one year follow-up: 5.4% vs. 0.8%. A significantly low percentage of possible FH patients (18.7% vs. 51.4%) achieved target LDL-C levels. There were no significant differences in MACE defined as a composite of cardiogenic shock or Class IV heart failure, recurrent MI, cardiovascular-related rehospitalization, TLR and CV death between the two groups. However, the proportion of cardiogenic shock or Class IV heart failure was significantly higher in possible FH patients group (5.9% vs.1.2%). Conclusion Clinical diagnosis of possible FH is common in Chinese patients with premature STEMI. A low proportion of FH patients were prescribed high intensity statins. Despite aggressive cholesterol-lowering drugs, a significantly lower proportion of FH patients achieved LDL-C targets compared to unlikely FH patients. Possible FH patients were younger with a significantly higher occurrence of multi-vessel CAD and impaired cardiac function.

Multiple myeloma (MM) is a B lineage plasma cell malignancy which is essentially incurable.1 For the exploration of effective MM cures, immunotherapy, including dendritic cell (DC) based immunotherapy, has attracted significant interest recently due to its potentially superior efficacy and specificity.2 In fact, immunotherapy is considered the ideal treatment for cancer3 and it has therefore witnessed great progress in the past decades. However, a major problem that has hindered further progress in the area is immune tolerance. The spread of cancer within patients suggests that tumor cells can escape the surveillance of a patients’ immune system, which renders tumor-associated antigens (TAAs) poorly immunogenic. As a result, it is rather difficult to develop effective cancer vaccines using these natural antigens, and methods to improve the antigenicity of tumors or TAAs, and circumvent the immune tolerance are highly desirable. Recently, cell glycoenigeering has been established as a very useful technique for the modification of carbohydrate antigens on cell surfaces. For example, a number of N-acyl derivatives of N-acetyl-D-mannosamine (ManNAc), the physiological precursor of N-acetyl sialic acid (NeuNAC), have been successfully used in vitro and in vivo to glycoengineer numerous cells,4–6 including cancer cells.7,8 Cells treated with N-acyl-D-mannosamines can express on their surface artificial carbohydrates that contained unnatural N-acyl sialic acids. Studies have also shown that these unnatural sialyl carbohydrates are more immunogenic than their natural counterparts9–11 and monoclonal antibodies induced by these unnatural carbohydrate antigens were highly and specifically cytotoxic to the glycoengineered tumor cells.7 These results suggest that glycoengineering of cancer cells may well improve their immunological properties. Based on this hypothesis, we propose herein a novel strategy to circumvent immune tolerance to myeloma and to provoke antitumor cellular immunity that is critical for cancer immunotherapy. The basic concept is to first treat myeloma cells with an unnatural N-acyl-D-mannosamine to induce the expression of artificial carbohydrate antigens on cell surfaces, which is expected to render the tumor cells more antigenic. Next, the glycoengineered myeloma cells are fed to DCs allowing them to present the unnatural antigens expressed by the tumor cells. The neoantigen-loaded DCs can be used to stimulate an immune response in vitro or in vivo, which will be combined with glycoengineering of tumor cells to treat cancer. The main objectives of this work are to study whether DCs loaded with unnatural antigens expressed by glycoengineered myeloma can activate T-lymphocytes and induce cytotoxic T-lymphocyte (CTL) responses to MM.

The inward rectifier K(+) channel Kir2.1 mediates the potassium I(K1) current in the heart. It is encoded by KCNJ2 gene that has been linked to Andersen's syndrome. Recently, strong evidences showed that Kir2.1 channels were associated with mouse atrial fibrillation (AF), therefore we hypothesized that KCNJ2 was associated with familial AF. Thirty Chinese AF kindreds were evaluated for mutations in KCNJ2 gene. A valine-to-isoleucine mutation at position 93 (V93I) of Kir2.1 was found in all affected members in one kindred. This valine and its flanking sequence is highly conserved in Kir2.1 proteins among different species. Functional analysis of the V93I mutant demonstrated a gain-of-function consequence on the Kir2.1 current. This effect is opposed to the loss-of-function effect of previously reported mutations in Andersen's syndrome. Kir2.1 V93I mutation may play a role in initiating and/or maintaining AF by increasing the activity of the inward rectifier K(+) channel.

Background: SIRT5 is located in the mitochondria, and plays a crucial role in the regulation of metabolic process and cellular apoptosis. Cardiomyocytes are abundant in mitochondria. However, the role of SIRT5 in oxidative stress-induced apoptosis is still unknown in cardiomyocytes. Methods and Results: Western blots analysis revealed that SIRT5 is significantly down-regulated in cardiomyocytes upon oxidative stress. MTT assay, DAPI staining, and caspase 3/7 activity assay were used to estimate apoptosis development. The result suggested that compared with the wild-type group, SIRT5 knockdown results in a marked reduction in cell viability, and a significant increase in the number of apoptotic cells and the caspase 3/7 activity. Protein immunoprecipitation revealed a direct interaction between Bcl-Xl and SIRT5. Apoptosis assay and western blot anaylsis suggested that SIRT5 levels could affect the levels of Bcl-Xl expression, but have no effect on the apoptosis development in Bcl-Xl knockdown cells. Conclusion: This study reveals a novel role of SIRT5 in the regulation of oxidative stress-induced apoptosis in cardiomyocytes. Pharmacological interventions on SIRT5 expression may be useful in the treatment of oxidative stress-related cardiac injury.