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Purpose: To evaluate the relationship between the serum calcitonin gene-related peptide (CGRP) level and severity of coronary stenosis. Methods: A total of 233 eligible patients who underwent coronary angiography were divided into two groups: a control and a coronary heart disease (CHD) group. The angiographic severity of coronary stenosis was evaluated by SYNTAX and Gensini scores. The incidence of major adverse cardiovascular events within two years was collected. Results: A negative correlation between serum CGRP levels and Gensini scores was observed in all patients (r=-0.352, p22) was 0.772 [95% confidence interval (CI): 0.673-0.870, p22 [odds ratio (OR) =5.819, 95% CI: 2.240-15.116; p64) (OR=4.943, 95% CI: 2.020-12.095; p

Background: Cutaneous squamous cell carcinoma (cSCC) is a malignant proliferation of cutaneous epithelium. Ferroptosis is a new type of cell death involved in cancer progression. M2 macrophage derived exosomes promote cancer proliferation and progression. We intended to investigate the role of M2 macrophages derived exosomes on ferroptosis in cSCC and explore the underlying mechanism. Methods: cSCC samples and adjacent normal tissues were obtained from cSCC patients. Exosomes were isolated from M2 macrophages differentiated from human mononuclear macrophage (THP-1) cells by flow cytometry. Cell viability, iron level, Malondialdehyde (MDA), Lipid ROS, mitochondrial superoxide, mitochondrial membrane potential (MMP) were detected for the validation of ferroptosis. RNAs and proteins were measured using RT-qPCR and western blot. Binding relationships between miR-451a and circ_TNFRSF21 or SLC7A11 were revealed by dual luciferase assay.Results: M2 macrophages were increased in cSCC tissues. M2 macrophages inhibited erastin-induced ferroptosis, which was reversed by exosome inhibitor GW4869. SLC7A11 was up-regulated in cSCC tissues. Erastin treatment reduced cell viability, increased the level of iron and Fe2+, upregulated MDA, lipid-ROS, mitochondrial superoxide, and declined MMP, which were reversed by M2 exosomes. Interestingly, circ_TNFRSF21 knockdown antagonized these effects of M2 exosomes. Circ_TNFRSF21 targeted miR-451a to regulate SLC7A11. Erastin-induced ferroptosis was promoted by miR-451a mimics, which was reversed after SLC7A11 overexpression. M2 exosomes inhibited erastin-induced ferroptosis in cSCC cells, which was antagonized by SLC7A11 downregulation or miR-451a upregulation. Conclusion: M2 macrophage exosomes inhibited ferroptosis in cSCC through circ_TNFRSF21/miR-451a/SLC7A11 axis. It is contributed to cSCC progression and may providing a novel target for therapy.

In recent years, the role of circular RNA in cancer cells has been studied broadly; however, the functional significance of circular RNA in the regulation of the tumor microenvironment (TME) is not fully understood. In this study, we aimed to reveal the role of circ_TNFRSF21 in M2 macrophage-induced cutaneous squamous cell carcinoma (cSCC) angiogenesis. Quantitative polymerase chain reaction and Western blotting were performed to determine the levels of the indicated genes. Direct binding between circ_TNFRSF21 and miR-3619-5p, miR-3619-5p, and ROCK2 was verified by dual-luciferase activity. The migration and invasion of human umbilical vein endothelial cells were evaluated by wound healing and transwell assays. Tube formation was performed to detect in vitro angiogenesis. Circ_TNFRSF21 and ROCK2 were upregulated in cSCC tissue, while miR-3619-5p was downregulated. Circ_TNFRSF21 negatively regulated the expression of miR-3619-5p, while miR-3619-5p negatively regulated the expression of ROCK2. miR-3619-5p suppressed tube formation by inhibiting ROCK signaling. M2 macrophages facilitated tube formation via the circ_TNFRSF21/miR-3619-5p/ROCK2 axis. Our present study revealed that circ_TNFRSF21 was elevated in M2 macrophages and mediated M2 macrophage-induced tube formation in vitro.

Introduction No-reflow phenomenon (NRP) is one of the complications that mostly occur during percutaneous coronary intervention (PCI). In this study, we comprehensively examined the relationship between the model for end-stage liver disease-XI (MELD-XI) score and NRP. Moreover, we discussed whether the MELD-XI score could be considered as an accurate risk assessment score of patients with ST-segment elevation myocardial infarction (STEMI) who are candidates for PCI. Methods This retrospective study involved 693 patients with acute STEMI and who underwent an emergency PCI. They were divided into a normal reflow group or a no-reflow group on the basis of the flow rate of post-interventional thrombolysis in myocardial infarction. Univariate, multivariate logistic regression, and Cox regression analyses were performed to identify the independent predictors of NRP in both groups. Receiver operator characteristic (ROC) curves and Kaplan–Meier curves were plotted to estimate the predictive values of the MELD-XI score. Results MELD-XI score was found to be an independent indicator of NRP (odds ratio: 1.247, 95% CI: 1.144–1.360, P P P 9.78 (P Conclusion The MELD-XI score can be used to predict NRP and the 30-day prognosis in patients with STEMI who are candidates for primary PCI. It could be adopted as an inexpensive and a readily available tool for risk stratification.

Objectives The present study established criteria to differentiate simple from complex bifurcation lesions and compared 1-year outcomes stratified by lesion complexity after provisional stenting (PS) and 2-stent techniques using drug-eluting stents. Background Currently, no criterion can distinguish between simple and complex coronary bifurcation lesions. Comparisons of PS and 2-stent strategies stratified by lesion complexity have also not been reported previously. Methods Criteria of bifurcation complexity in 1,500 patients were externally tested in another 3,660 true bifurcation lesions after placement of drug-eluting stents. The primary endpoint was the occurrence of a major adverse cardiac event (MACE) at 12 months. The secondary endpoint was the rate of stent thrombosis (ST). Results Complex (n = 1,108) bifurcation lesions were associated with a higher 1-year rate of MACE (16.8%) compared with simple (n = 2,552) bifurcation lesions (8.9%) (p Conclusions Complex bifurcation lesions had higher rates of 1-year MACE and ST. The 2-stent and PS techniques were overall equivalent in 1-year MACE. However, 2-stent techniques for complex lesions elicited a lower rate of cardiac death and in-hospital MACE but higher rates of in-hospital ST and revascularization at 1 year for simple lesions.

IntroductionProvisional stenting (PS) for simple coronary bifurcation lesions is the mainstay of treatment. A systematic two-stent approach is widely used for complex bifurcation lesions (CBLs). However, a randomised comparison of PS and two-stent techniques for CBLs has never been studied. Accordingly, the present study is designed to elucidate the benefits of two-stent treatment over PS in patients with CBLs.Methods and analysisThis DEFINITION II study is a prospective, multinational, randomised, endpoint-driven trial to compare the benefits of the two-stent technique with PS for CBLs. A total of 660 patients with CBLs will be randomised in a 1:1 fashion to receive either PS or the two-stent technique. The primary endpoint is the rate of 12-month target lesion failure defined as the composite of cardiac death, target vessel myocardial infarction (MI) and clinically driven target lesion revascularisation. The major secondary endpoints include all causes of death, MI, target vessel revascularisation, in-stent restenosis, stroke and each individual component of the primary endpoints. The safety endpoint is the occurrence of definite or probable stent thrombosis.Ethics and disseminationThe study protocol and informed consent have been approved by the Institutional Review Board of Nanjing First Hospital, and accepted by each participating centre. Written informed consent was obtained from all enrolled patients. Findings of the study will be published in a peer-reviewed journal and disseminated at conferences.Trial registration numberNCT02284750; Pre-results.

Percutaneous device occlusion and minimally invasive surgical repair for perimembranous ventricular septal defect (pmVSD) are two typical methods to reduce the invasiveness of the conventional operation through a median sternotomy. However, few studies have compared them in terms of effectiveness and cost.Inpatients with isolated pmVSD who had undergone percutaneous device occlusion or minimally invasive surgical repair from June 2009 to June 2012 were reviewed for a comparative investigation between the two procedures.Procedure success was achieved in 80 percutaneous (93.0%) and in 113 surgical (98.3%) procedures (p=0.076). Percutaneous patients were older, with a smaller VSD size than surgical patients (16±11.7 vs 3.8±2.4 mm, p0.001; 4.0±1.2 vs 4.3±1.3 mm, p=0.034, respectively). Major complications occurred in 1 percutaneous (1.2%) and in 4 surgical (3.5%) procedures (p=0.602), and minor complications occurred in 27 percutaneous (33.3%) and in 37 surgical (32.2%) procedures (p=0.991). The surgical repair cost 31% less than the device occlusion (¥20,565±¥3,497 vs ¥29,795±¥2,643, p0.001), where most of the cost was attributed to the occluder in the amount of ¥19,500.Compared with device occlusion, minimally invasive surgical repair can provide comparable efficacy and complication rates. In addition, it is 31% cheaper than device occlusion. In low-income countries where health care resources are limited, medical resources must be judiciously allocated to the treatment that allows for effective treatment of the largest number of patients.

The optimal stenting strategy for the treatment of coronary bifurcation lesions (CBLs) remains uncertain. The present study observed technical feasibility and reliability, 9-month clinical and angiographic outcomes of the modified culotte stenting (MCS) in the treatment of CBLs with drug-eluting stents.A total of 34 consecutive patients with CBLs that required stenting the parent vessel (PV), the main branch (MB) and the side branch (SB) were included. All patients were first assigned to receive MCS for CBL interventions (per MCS), and might be switched to receive the double-kissing-crush stenting (DKS) in case of temporally acute branch occlusion (per protocol).The immediate angiographic or procedural success was achieved in 33/34 (97%) lesions (patients) per MCS, 34/34 (100%) lesions (patients) per protocol with 100% successful final balloon kissing. The long-term clinical success at 9 months was 94% per MCS and 94% per protocol, only 2 patients had reoccurrence of angina but none of them needed target lesion revascularization. There were no procedure-related biomarker elevation, no in-stent thrombosis peri-procedurally and at 9-month follow-up. Quantitative coronary angiography data at 9 months showed that in-stent (6%) or in-segment (6%) binary stenosis was infrequent, and minimal lumen diameter was significantly reduced but late lumen loss was acceptable with only (0.10 ± 0.14) mm for PV, (0.21 ± 0.23) mm for MB and (0.27 ± 0.32) mm for SB.MCS for treatment of CBLs that required dual-stent implantation was technically easier and safer, readily to complete final balloon kissing, and was associated with high immediate success and optimal 9-month outcomes.

Transcatheter Amplatzer occlusion of patent ductus artertiosus (PDA) has emerged as a minimally invasive alternative to surgical closure. The goal of this study was to compare long-term clinical outcomes between two procedures, especially on chronic residual shunt, late or very late procedure-related complications, and regression of pulmonary hypertension and left ventricular dilation.A total 255 patients having isolated PDA with a minimal diameter ofor= 4 mm treated from January 2000 to July 2003 were included in this study and have been followed up until July 2008. The patients were assigned to either the device or surgical closure group according to the patients' and/or their parents' preference. Baseline physical exams, chest roentgenography, electrocardiography, and echocardiography were performed preprocedure and at each follow-up.Seventy-two patients accepted the transcatheter procedure (Group-TC) and 183 underwent surgical operation (Group-SO) for PDA closure, both groups were similar in their demographics and preoperative clinical characteristics. There were no cardiac deaths and late complications such as infectious endocarditis and Amplatzer duct occluder (ADO) dislodge in either group. More acute procedure-related complications were recorded in Group-SO (13.7%) compared with Group-TC (1.4%) (P = 0.004). The recovery time was (8.7 +/- 2.3) days for the Group-SO and (1.3 +/- 0.5) days for the Group-TC (P0.001). The survival freedom from persistent residual shunt, defined as residual shunt that can not resolve automatically, was 91.3% for Group-SO and 98.6% for Group-TC (P = 0.037 by Log-rank test). There was no significant difference in regression of pulmonary hypertension and left ventricular dilation; neither survival freedom from pulmonary hypertension nor abnormal left ventricular end-diastolic volume index were significantly different between the surgical group and the Amplatzer group.Our study confirmed the long-term safety and efficacy of transcatheter Amplatzer occlusion. In comparison to the time-proven surgical closure, transcatheter Amplatzer occlusion was less invasive and associated with fewer complications and residual shunt, and as effective in the regression of pulmonary hypertension and left ventricular dilation.

As a kind of sirolimus-eluting stent (SES) made in China, Firebird SES is more effective than bare metal stent (BMS) and not inferior to Cypher SES for short coronary lesions in terms of reduction of restenosis and revascularization. However, Firebird SES does not show any benefits in patients with a very long coronary lesion (VLCL). The present study was undertaken to evaluate the safety and efficacy of Firebird SES for VLCL by comparison of Cypher SES and BMS.In this prospective, nonrandomized and comparative study, eligible patients with de novo coronary lesion (or = 30 mm) between January 2005 and June 2006 were allocated into Firebird SES group, Cypher SES group or BMS group. They were subjected to an angiographic follow-up of 6 months and a clinical follow-up of 12 months. The primary endpoints constitute the in-stent and in-segment restenosis rates at 6 months. The secondary endpoint was defined as a major adverse cardiovascular event (MACE) that was a 12-month combined endpoint of all-cause deaths, reinfarction or in-stent thrombosis, and target-lesion revascularization. The 12-month in-stent thrombosis was also evaluated to address the safety of Firebird SES implantation exceptionally.A total of 468 patients were assessed for eligibility. Of 113 patients who were finally included according to the prior inclusion and exclusion criteria, 39 (41 lesions) were treated with Firebird SES, 37 (39 lesions) with Cypher SES, and 37 (37 lesions) with BMS. There were no significant differences in the baseline characteristics between the three groups; but there were longer lesions, more frequent use of overlapping stent in the Firebird SES group and the Cypher SES group. Angiographic follow-up showed that the rates of binary stenosis were similar between the Firebird SES group and the Cypher SES group (in-segment: 14.6% vs 12.8%, relative risk (RR) 1.14, P = 0.81; in-stent: 9.8% vs 10.3%, RR 0.95, P = 0.94), and significantly lower than those in the BMS group (in-segment: vs. 36.1%, RR 0.41 or 0.36, P = 0.04 or 0.03, respectively; in-stent: vs 30.6%, RR 0.32 or 0.34, P = 0.03 or 0.04, respectively). The total MACE rate up to 12 months was also similar in both SES groups (7.7% vs 5.4%, P = 1.000), and significantly lower than that in the BMS group (27.0%, P = 0.034 or 0.024, respectively). The in-stent thrombosis rate in the follow-up period was 2.6% in the Firebird SES group, not higher in the Cypher SES and BMS groups (2.7% and 2.7%, respectively, P = 1.000).In the treatment of VLCL, Firebird SES would be safer and more effective than BMS. Firebird SES may be not inferior to Cypher SES in terms of restenosis and MACE.

Background Dobutamine stress echocardiography has been proposed as a diagnostic tool to identify viable myocardium. How regional wall thickening responds to dobutamine in the ischemic or short-term hibernating myocardium has not been adequately defined. We hypothesized that regional wall thickening would improve initially and subsequently deteriorate with incremental doses of dobutamine in viable myocardial regions supplied by a stenotic coronary artery. This study was undertaken to determine whether this biphasic pattern of regional function characterizes the response of ischemic or hibernating myocardium to dobutamine and to explore the factors and mechanisms that determine this response. Methods and Results Twenty-six pigs in four groups were studied: a control group (n=5) to assess the response of myocardium perfused by nonstenotic coronary artery to incremental doses of dobutamine, and three experimental groups with a left anterior descending coronary artery stenosis producing acute myocardial ischemia (n=7), short-term myocardial hibernation for 90 minutes (n=7), and short-term hibernation for 24 hours (n=7) to determine the functional and metabolic response to dobutamine under these conditions. Regional coronary flow was reduced to 40% to 60% of baseline, with significant reductions of regional wall thickening as measured by two-dimensional echocardiography and sonomicrometers. An incremental dobutamine infusion from 2.5 to 25 μg · kg −1 · min −1 increased wall thickening and coronary flow without lactate production in the control group. In the other three groups, during the incremental dobutamine infusion, regional wall thickening improved initially, from 11.4±7.5% to 19.8±11.4%, P −1 · kg −1 but deteriorated subsequently to 5.0±5.8% at the maximal dose of dobutamine of 12.6±4.1 μg · min −1 · kg −1 . The initial improvement of regional wall thickening was associated with a small increase in regional coronary flow (from 0.53±0.18 to 0.68±0.25 mL · min −1 · g −1 myocardium, P P Conclusions A biphasic response of wall thickening to incremental dobutamine with initial improvement and subsequent deterioration is characteristic of ischemic or short-term hibernating myocardium. The initial low-dose dobutamine infusion improved wall thickening in the ischemic or hibernating myocardial region to a modest level. This initial modest improvement was transient and at the expense of metabolic deterioration of myocardial ischemia, so that at higher doses during prolonged dobutamine infusion, wall thickening deteriorated, lactate accumulated, and myocardial acidosis developed.

Objective Lifestyle interventions including exercise training have been shown to be a feasible option for the prevention and treatment of cardiovascular diseases. In this study, we investigated the effects of prior different intensities of exercise on infarct region and function and angiogenesis of the left ventricle (LV) in post-myocardial infarction (MI) rats, and further examined the expression of VEGF proteins in the left ventricle. Methods Male Sprague–Dawley rats were randomly assigned to six groups. The exercised rats underwent a daily 60-min treadmill exercise, 5 d/wk, for 6 wk. Different treadmill speeds were carried out in the high intensity exercise group (HIE-MI group, 30 m/min), moderate intensity exercise groups (MIE-Sh and MIE-MI groups, 21 m/min), low intensity exercise group (LIE-MI group, 12 m/min), respectively, whereas the untrained rats (Sed-Sh and Sed-MI groups) remained sedentary. At 6 wk, 24 h after the last treadmill exercise or the corresponding sedentary protocol, all rats underwent either acute MI (LIE-MI, MIE-MI, HIE-MI and Sed-MI groups) or sham MI operation (MIE-Sh and Sed-Sh groups). Then, all rats were sacrificed at 7d after recovery. Echocardiographic and haemodynamic measurements were performed at the end of the experimental protocol, and hearts were sampled for histological and molecular analysis. The infarct regions were analysed by using Masson9s trichrome staining; intramyocardial microvessels were detected by using Factor VIII-related antigen staining; and cardiac VEGF protein levels were determined by Western blotting analysis. Results Compared with Sed-Sh group, MIE-Sh group ameliorated left ventricular function and increased microvessels intensity, though the difference was not significant. Compared with Sed-MI group, MIE-MI and HIE-MI groups significantly reduced left ventricular infarct size, improved haemodynamic parameters, increased fractional shortening, scar thickness and microvessel density, but LIE-MI rats only had slight, and non-significant effect on these parameters. In addition, the differences between MIE-MI and HIE-MI rats were significant in haemodynamic parameters and microvessel density. Interestingly, compared with Sed-MI group, the exercised hearts displayed higher levels of VEGF protein in MIE-MI and HIE-MI groups. However, there was no significant difference between MIE-MI and HIE-MI groups. Conclusion Moderate intensity running exercise before acute MI improved LV function, reduced scar size, increased scar thickness and microvessel density in the post-MI rat. Additional higher intensity exercise could have little further effect. Low intensity exercise may be beneficial, but not sufficient to improve MI. Moderate and high intensity running upregulated the expression of VEGF protein, and contributed to the increased microvessels, which may partly benefit cardiac function after MI.