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Aims Members of the chromogranin family play a role in angiogenesis. One such biologically active peptide, generated through the processing of chromogranin A, is vasostatin-2. This study aimed at assessing the association of serum vasostatin-2 levels with coronary collateral vessels (CCV) in diabetic patients with chronic total occlusions (CTO) and the effects of vasostatin-2 on angiogenesis in diabetic mice with hindlimb or myocardial ischemia. Methods and results Serum levels of vasostatin-2 in 452 diabetic CTO patients were evaluated. The status of CCV was categorized according to the Rentrop score. Vasostatin-2 recombinant protein or phosphate-buffered saline were then injected intraperitoneally in diabetic mouse models of hindlimb or myocardial ischemia, followed by laser Doppler imaging and molecular biology examinations. The effects of vasostatin-2 were also ascertained in endothelial cells and macrophages, with mechanisms clarified using ribonucleic acid (RNA) sequencing. Serum levels of vasostatin-2 were significantly different and progressively higher across Rentrop score 0, 1, 2, and 3 groups (P < .001), with significantly lower levels in patients with poor CCV (Rentrop score 0 and 1) than in those with good CCV (Rentrop score 2 and 3) (P < .05). Vasostatin-2 significantly promoted angiogenesis in diabetic mice with hindlimb or myocardial ischemia. RNA-seq analyzes verified an angiotensin-converting enzyme 2 (ACE2)-mediated vasostatin-2-induction of angiogenesis in ischemic tissues. Conclusion Lower serum levels of vasostatin-2 are associated with poor CCV in diabetic CTO patients compared with patients with good CCV. Vasostatin-2 significantly promotes angiogenesis in diabetic mice with hindlimb or myocardial ischemia. Such effects are mediated by ACE2.

Backgrounds: Apolipoprotein (apo) B and apo A1 are major protein component of low-density lipoprotein and high-density lipoprotein particles, which are closely linked to lipid metabolism, atherosclerosis, and endothelial function. We sought to investigate whether circulating apoB/A1 ratio could serve as a potential metabolic risk factor for the progression of chronic heart failure (HF). Methods Serum levels of apo B and apo A1 were measured in 1299 consecutive patients with clinical symptoms of chronic HF. Left ventricular ejection fraction (EF) and E/e’ were determined by two-dimensional echocardiography and Doppler flow imaging using standard biplane technique. The relationship of apo B/A1 ratio to classification and etiology of HF was examined. Results Overall, apoB/A1 ratio was gradually decreased from HF with reduced EF (HFrEF), HF with mid-range reduced EF (HFmrEF), to HF with preserved EF (HFpEF), and correlated negatively with left ventricular EF (r=-0.162, p

Background Because of advances in medical treatments, a substantial proportion of patients with heart failure (HF) have experienced recovery of ejection fraction (EF), termed HF with recovered EF (HFrecEF). Insulin resistance (IR) is prevalent in HF and tightly related with prognosis. This study investigates the relationship between IR and the incidence of HFrecEF in patients who are nondiabetic. Methods and Results A total of 262 patients with HF with reduced EF (HFrEF) who were nondiabetic were consecutively enrolled. Patients were classified into HFrecEF (follow‐up EF>40% and ≥10% absolute increase) or otherwise persistent HFrEF based on repeat echocardiograms after 12 months. IR was estimated by an updated homeostasis model assessment for IR (HOMA2‐IR). The median HOMA2‐IR level was 1.05 (interquartile range [IQR], 0.67–1.63) in our cohort of patients with HF who were nondiabetic. During follow‐up, 121 (odds ratio [OR], 46.2% [95% CI 40.2–52.2]) patients developed HFrecEF. Compared with patients with HFrEF, patients with HFrecEF had significantly lower HOMA2‐IR levels (0.92 [IQR, 0.61–1.37] versus 1.14 [IQR, 0.75–1.78], P =0.007), especially in nonischemic HF. Log 2 ‐transformed HOMA2‐IR was inversely correlated to improvements in EF (Pearson's r =−0.25, P Conclusions This study reveals that IR is independently associated with compromised development of HFrecEF in patients who are nondiabetic.

Background. Left ventricular (LV) diastolic dysfunction (LVDD) is the defining feature of heart failure with preserved ejection fraction (HFpEF) and predicts subsequent incident heart failure (HF) and all-cause mortality. Mounting evidence reveals that cardiometabolic risk factors play critical roles in the development of LVDD. In this study, we sought to investigate the relation between serum uric acid (SUA) level and the progression of LVDD in apparently healthy patients. Methods. A total of 1082 apparently healthy subjects without diagnosed cardiovascular disease and LVDD were consecutively enrolled. SUA levels were measured, and repeat echocardiography and tissue Doppler imaging (TDI) were performed at baseline and during 1-year follow-up. Results. By dividing the study population based on quartiles of SUA, we found subjects in higher quartiles had greater increases in TDI-derived early diastolic velocity (e ′ ) and E (peak LV filling velocity)/e ′ ratios during 1-year follow-up. After multivariate adjustment, high SUA persisted to be an independent predictor for the subsequent worsening of LVDD (odds ratio: 1.351 [95% CI 1.125~1.625], per 100 μmol/L SUA). Subgroup analysis suggested that the association between SUA and LVDD development was more pronounced in subjects without other cardiometabolic risk factors involved. Factor analysis demonstrated that high SUA was the major cardiometabolic attribute in patients with LVDD progression. Conclusion. Our findings suggest that high SUA is an independent cardiometabolic risk factor for the progression of LVDD in apparently healthy subjects.

Coronary collateralization is substantially impaired in patients with type 2 diabetes and occlusive coronary artery disease, which leads to aggravated myocardial ischemia and a more dismal prognosis. In a diabetic setting, altered serum lipid profiles and profound glycoxidative modification of lipoprotein particles induce endothelial dysfunction, blunt endothelial progenitor cell response, and severely hamper growth and maturation of collateral vessels. The impact of dyslipidemia and lipid-lowering treatments on coronary collateral formation has become a topic of heightened interest. In this review, we summarized the association of triglyceride-based integrative indexes, hypercholesterolemia, increased Lp(a) with its glycoxidative modification, as well as quantity and quality abnormalities of high-density lipoprotein with impaired collateral formation. We also analyzed the influence of innovative lipid-modifying strategies on coronary collateral development. Therefore, clinical management of diabetic dyslipidemia should take into account of its effect on coronary collateralization in patients with occlusive coronary artery disease.

Background The formation of advanced glycation end-products (AGEs) is a crucial risk factor for the pathogenesis of cardiovascular diseases in diabetes. We investigated whether N-epsilon-carboxymethyllysine (CML), a major form of AGEs in vivo, was associated with poor coronary collateral vessel (CCV) formation in patients with type 2 diabetes mellitus (T2DM) and chronic total occlusion (CTO) of coronary artery. Methods This study consisted of 242 T2DM patients with coronary angiographically documented CTO. Blood samples were obtained and demographic/clinical characteristics were documented. The coronary collateralization of these patients was defined according to Rentrop or Werner classification. Serum CML levels were evaluated using ELISA assay. Receiver operating characteristic curve and multivariable regression analysis were performed. Results 242 patients were categorized into poor CCV group or good CCV group (107 vs. 135 by the Rentrop classification or 193 vs. 49 by the Werner classification, respectively). Serum CML levels were significantly higher in poor CCV group than in good CCV group (110.0 ± 83.35 vs. 62.95 ± 58.83 ng/ml by the Rentrop classification and 94.75 ± 78.29 ng/ml vs. 40.37 ± 28.69 ng/ml by Werner classification, both P Conclusions This study suggests that higher serum CML level is associated with poor collateralization in T2DM patients with CTO.

Background: Due to advances in medical treatments, a substantial proportion of heart failure (HF) patients with reduced left ventricular ejection fraction (EF, HFrEF) have experienced partial or complete recovery of EF, termed HFrecEF, and markedly improved clinical outcomes. In the present study, we sought to investigate the relationship between glycemic control and the incidence of HFrecEF in patients with type 2 diabetes mellitus (T2DM).Methods: A total of 385 T2DM patients with HFrEF were consecutively enrolled. Follow-up echocardiogram was performed after 6 to 12 months, which classified patients into HFrecEF or persistent HFrEF. Clinical outcomes of cardiovascular (CV) death and HF rehospitalization were analyzed during a mean of 3.3 years follow-up. Results: T2DM patients with HFrecEF had significantly lower HbA1c level than those with persistent HFrEF (6.4% [IQR 5.8%~7.1%] vs. 6.8% [IQR 6.1%~7.8%], P=0.001), especially in HF of ischemic etiology. After multivariate adjustment, every 1% increase in HbA1c conferred a 21.3% (OR: 0.787 [95% CI 0.658~0.933]) lower likelihood of HFrecEF. Compared to patients with good glycemic control (HbA1c≤6%), those with poor glycemic control (HbA1c > 8%) had higher risk of CV death or HF rehospitalization (HR: 2.778 [95% CI 1.470~5.251]). T2DM Patients with HFrecEF exhibited significantly better clinical outcomes than those with persistent HFrEF.Conclusions: This study demonstrates that T2DM patients with uncontrolled HbA1c levels were associated with compromised development of HFrecEF and worse clinical outcomes.

Background: The formation of advanced glycation end-products (AGEs) is a crucial risk factor for the pathogenesis of cardiovascular diseases. We investigated whether N-e-carboxy-methyl-lysine (CML), a major form of AGEs in vivo, was associated with poor coronary collateral vessel (CCV) formation in patients with type 2 diabetes mellitus (T2DM) and chronic total occlusion (CTO) of coronary artery.Methods: This study consisted of 242 T2DM patients with angiographically documented CTO. Blood samples were obtained and demographic/clinical characteristics were documented. The collateralization of these patients was defined according to Rentrop score. Receiver operating characteristic (ROC) curve and multivariable regression analysis were performed.Results: 242 patients were categorized into poor CCV group (Rentrop score 0 and 1)(n = 107) and good CCV group (Rentrop score 2 and 3)(n = 135). Serum CML levels were significantly higher in poor CCV group (110.0 ± 83.35 ng/ml) than in good CCV group (62.95 ± 58.83 ng/ml, PConclusions: This study suggests that higher CML levels are associated to poor CCV in T2DM patients with CTO. Inhibition of AGEs including CML is a strategy in antagonizing poor CCV in diabetic patients.

Background: Due to advances in medical treatments, a substantial proportion of heart failure (HF) patients with reduced left ventricular ejection fraction (LVEF, HFrEF) have experienced partial or complete recovery of LVEF, termed HFrecEF, and markedly improved clinical outcomes. In the present study, we sought to investigate the relationship between glycemic control and the incidence of HFrecEF in patients with type 2 diabetes mellitus (T2DM).Methods: A total of 310 age- and sex-matched T2DM patients with HFrecEF and persistent HFrEF were retrospectively enrolled based on 12-month repeat echocardiograms. HFrecEF was defined as follow-up LVEF > 40% and absolute LVEF improvement ≥ 10% compared to the baseline. The relationship between HFrecEF and HbA1c levels was analyzed. Results: During the 12-month follow-up, LVEF recovered from 35.93% ± 5.62% to 51.11% ± 8.53% in the HFrecEF group (PP=0.238) in the HFrEF group. T2DM patients with HFrecEF had significantly lower HbA1c level than those with persistent HFrEF (6.4% [IQR 5.8%~7.1%] vs. 6.8% [IQR 6.3%~7.4%], PConclusions: This study demonstrates that HFrEF patients with T2DM are more likely to develop HFrecEF under optimal glycemic control valued by lower HbA1c level.

Background: Chromogranin B (CgB) is increased in heart failure and proportionate to disease severity. We investigated whether circulating CgB level is associated with left ventricular (LV) functional recovery potential after successful recanalization of chronic total occlusion (CTO).Methods: Serum levels of CgB were assayed in 53 patients with stable angina with LV functional recovery [an absolute increase in LV ejection fraction (EF) of ≥5%] and 53 age- and sex-matched non-recovery controls after successful recanalization of CTO during 12-month follow-up.Results: We found that CgB level was significantly lower in the recovery group than in the non-recovery group (593 [IQR 454–934] vs. 1,108 [IQR 696–2020] pg/ml, P < 0.001), and that it was inversely correlated with changes in LVEF (Spearman's r = −0.31, P = 0.001). Receiver operating characteristic (ROC) analysis showed that the area under the curve of CgB for predicting LVEF improvement was 0.76 (95% CI 0.664–0.856), and that the optimal cutoff value was 972.5 pg/ml. In multivariate analyses, after adjusting for confounding factors, high CgB level remained an independent determinant of impaired LV functional recovery after CTO recanalization. LV functional improvement appeared to be more responsive to CgB in patients with poor than with good coronary collaterals.Conclusions: Elevated circulating CgB level confers an increased risk of impaired LV functional recovery after successful recanalization of CTO in patients with stable coronary artery disease.

Background: Patients with type 2 diabetes are under substantially higher risk of in-stent restenosis (ISR) after coronary stent implantation. We sought to investigate whether visit-to-visit HbA1c variability is a potential predictor of ISR in diabetic patients after stent implantation.Methods: We consecutively enrolled type 2 diabetic patients who underwent successful elective percutaneous coronary intervention and performed follow-up coronary angiography after around 12 months. The incidence of ISR and its relationship with visit-to-visit HbA1c variability, expressed as coefficient of variation (CV), standard deviation (SD) and variability independent of the mean (VIM), were studied. Multivariable Cox proportional hazards models were constructed to analyze the predictive value of HbA1c variability for ISR.Results: From September 2014 to July 2018 in Ruijin Hospital, a total of 420 diabetic patients (688 lesions) after stent implantation were included in the final analysis. During a mean follow-up of 12.8±1.3 months, the incidence of ISR was 8.6%, which was significantly increased in patients with higher CV of HbA1c (P=0.001). The mean diameter stenosis (DS), net luminal loss and net luminal gain were 22.9±16.8%, 0.42±0.88 mm and 1.66±0.83 mm, respectively. Greater DS was observed in subjects with higher tertiles of CV of HbA1c (P1c≤7%) in the baseline. In multivariate analysis, HbA1c variability was independently associated with incidence of ISR after adjustment for traditional risk factors and mean HbA1c (HR: 3.00 [95% CI:1.14~7.92] for highest vs. lowest tertile). Inclusion of CV of HbA1c led to a better risk stratification accuracy. Assessing HbA1c variability by SD or VIM yielded similar findings. Conclusions: This study suggests that visit-to-visit HbA1c variability is an independent predictor of incidence of ISR in patients with type 2 diabetes after stent implantation.Trial registration: Trials number, NCT02089360; registered on March 17,2014.

Background:Patients with type 2 diabetes are under substantially higher risk of in-stent restenosis (ISR) after coronary stent implantation. We sought to investigate whether visit-to-visit glycemic variability is a potential predictor of ISR in diabetic patients after stent implantation.Methods:Type 2 diabetic patients underwent elective percutaneous coronary intervention were consecutively enrolled and 1-year follow-up coronary angiography was performed. The incidence of ISR and its relationship with visit-to-visit HbA1c variability, expressed as coefficient of variation (CV), standard deviation (SD) and variability independent of the mean (VIM), were studied. Multivariable Cox proportional hazards models were constructed to analyze the predictive value of glycemic variability for ISR.Results:From September 2014 to July 2018 in Ruijin Hospital, a total of 420 diabetic patients (688 lesions) after stent implantation were included in the final analysis. During a mean follow-up of 12.8 ± 1.3 months, the incidence of ISR was 8.6%, which was significantly increased in patients with higher CV of HbA1c (P = 0.001). The mean diameter stenosis (DS), net luminal loss and net luminal gain were 22.9 ± 16.8%, 0.42 ± 0.88 mm and 1.66 ± 0.83 mm, respectively. Greater DS was observed in subjects with higher tertiles of CV of HbA1c (P 1c ≤ 7%). In multivariate analysis, HbA1c variability was independently associated with incidence of ISR after adjustment for traditional risk factors and mean HbA1c (HR: 3.00 [95% CI:1.14 ~ 7.92] for highest vs. lowest tertile). Inclusion of CV of HbA1c led to a better risk stratification accuracy. Assessing glycemic variability by SD or VIM yielded similar findings.Conclusions:This study suggests that visit-to-visit HbA1c variability is an independent predictor of incidence of ISR in patients with type 2 diabetes after stent implantation.

Background Patients with type 2 diabetes are under substantially higher risk of in-stent restenosis (ISR) after coronary stent implantation. We sought to investigate whether visit-to-visit HbA1c variability is a potential predictor of ISR in diabetic patients after stent implantation. Methods We consecutively enrolled type 2 diabetic patients who underwent successful elective percutaneous coronary intervention and performed follow-up coronary angiography after around 12 months. The incidence of ISR and its relationship with visit-to-visit HbA1c variability, expressed as coefficient of variation (CV), standard deviation (SD) and variability independent of the mean (VIM), were studied. Multivariable Cox proportional hazards models were constructed to analyze the predictive value of HbA1c variability for ISR. Results From September 2014 to July 2018 in Ruijin Hospital, a total of 420 diabetic patients (688 lesions) after stent implantation were included in the final analysis. During a mean follow-up of 12.8 ± 1.3 months, the incidence of ISR was 8.6%, which was significantly increased in patients with higher CV of HbA1c (P = 0.001). The mean diameter stenosis (DS), net luminal loss and net luminal gain were 22.9 ± 16.8%, 0.42 ± 0.88 mm and 1.66 ± 0.83 mm, respectively. Greater DS was observed in subjects with higher tertiles of CV of HbA1c (P

Background. In recent years, serious injuries associated with extreme climate, earthquakes, terrorism, and other natural and man-made disasters have occurred frequently throughout the world. A surge in medical demand that extends beyond local medical surge capacity in mass casualty incidents following major disasters is common. Materials and Methods. We reviewed and analyzed emergency medical rescue efforts after major disasters in recent years to elaborate the precision strategy of augmenting medical surge capacity for disaster response. Results. Precision augmentation of medical surge capacity for disaster response can be achieved through several measures. These include (1) release of internal capacity through precision launching or through upgrading the levels of response, (2) precision support for medical surge capacity from external efforts, (3) centralized response, and (4) altering standards of care. We should adopt precision augmentation of medical surge capacity according to the specific situation. Conclusions. Augmentation of medical surge capacity as a basic strategy can be used to achieve effective disaster response. In disaster response, due to the complexity of disaster medical capacity amplification, it is important to select the appropriate medical capacity strategy accurately according to the actual disaster situation.

Purpose To assess the accuracy of magnetic resonance (MR) imaging-based differential diagnosis of hepatocellular carcinoma (HCC) and intrahepatic cholangiocarcinoma (ICC) in a cohort of patients with focal liver lesions and cirrhosis. Materials and Methods This study was institutional review board approved, and the requirement for informed consent was waived. Between January 2009 and December 2014, a cohort of cirrhotic patients, including 71 with ICC and 612 with HCC, underwent unenhanced T1- and T2-weighted MR imaging, gadolinium-based contrast material-enhanced dynamic phase imaging, and partial hepatectomy. Results of pathologic examinations were obtained for all patients. Clinical, radiologic, and pathologic results in these patients were analyzed and compared comprehensively. Differences in signal intensity on baseline and contrast material-enhanced images and dynamic enhancement patterns were evaluated and compared by using the χ(2) test or the Fisher exact test. Results The preoperative diagnoses of 517 of 683 lesions were confirmed pathologically. Five ICCs and 481 HCCs displayed contrast material washout in delayed phases (P < .001). Thirty-six ICCs and 23 HCCs displayed a progressive enhancement pattern (P < .001). Twenty-six ICCs and 63 HCCs displayed a stable enhancement pattern (P < .001). ICCs displayed significantly different enhancement patterns according to size (P = .022). Conclusion The accurate discrimination of small ICCs from HCCs in the setting of cirrhosis at MR imaging is difficult, as substantial proportions of ICCs and HCCs have similar enhancement patterns. Absence of contrast material washout at MR imaging is not a factor that prevents the misdiagnosis of HCC. (©) RSNA, 2016 Online supplemental material is available for this article.

Hepatic ischemia-reperfusion injury (IRI) is a very complex pathological process that is often associated with liver trauma and surgery, especially liver transplantation surgery. Although endoplasmic reticulum stress (ERS) plays a role in this process, the posttranscriptional regulators and the underlying mechanisms are still unclear. Here, we report that the lncRNA AK054386 was increased in hepatic IRI models. Furthermore, AK054386 can act as a “competing endogenous RNA (ceRNA)” and regulate ERS-related factors by binding and sequestering miR-199, which was shown to inhibit ERS in our previous report. Increased expression of AK054386, which might be mediated by activated NF-κB, resulted in sustained ERS and increased cell apoptosis and death in hepatic IRI mouse and cellular models. In contrast, AK054386 inhibition had protective effects on these models. Our data indicate that AK054386 and miR-199 are critical players in hepatic IRI, and we broadened the scope regarding ceRNA mechanisms. We hope that our results will improve the understanding of hepatic IRI and may provide potential therapeutic targets.

In the present study, a hypoxia/reoxygenation (H/R) model of cardiomyocytes was established to investigate the effects of long non-coding RNA (LncRNA) Nuclear Enriched Abundant Transcript 1 (NEAT1) and microRNA (miR)-520a on H/R-induced cardiomyocyte apoptosis. Flow cytometry and terminal deoxynucleotidyl transferase dUTP nick end labeling staining were used to evaluate cell apoptosis. Luciferase activity assay was used to investigate whether miR-520a targets NEAT1. Results revealed that NEAT1 was significantly upregulated and miR-520a was downregulated in the ischemia/reperfusion myocardium and the cardiomyocytes that received H/R treatment. Further study demonstrated that knockdown of NEAT1 and overexpression of miR-520a serves a protective role against H/R-induced cardiomyocyte apoptosis. miR-520a directly targets NEAT1 and its expression level is negatively correlated with that of NEAT1. The findings suggested that NEAT1 and miR-520a may protect cardiomyocytes from apoptosis through regulating apoptotic proteins B-cell lymphoma 2 (Bcl-2) and Bcl-2-associated X protein, and altering cleaved caspase3 expression levels.

Background: Angiotensin type 1 receptor (AT 1 R) antagonists are extensively used for blood pressure control in elderly patients with hypertension. This study aimed to investigate the inhibitory effects of AT 1 R antagonist valsartan on platelet aggregation and the occurrence of cardio-cerebral thrombotic events in elderly patients with hypertension. Methods: Two-hundred and ten patients with hypertension and aged > 60 years were randomized to valsartan (n = 140) or amlodipine (n = 70) on admission. The primary endpoint was platelet aggregation rate (PAR) induced by arachidonic acid at discharge, and the secondary endpoint was the rate of thrombotic events including brain infarction and myocardial infarction during follow-up. Human aortic endothelial cells (HAECs) were stimulated by angiotensin II (Ang II, 100 nmol/L) with or without pretreatment of valsartan (100 nmol/L), and relative expression of cyclooxygenase-2 (COX-2) and thromboxane B 2 (TXB 2 ) and both p38 mitogen-activated protein kinase (p38MAPK) and nuclear factor-kB (NF-kB) activities were assessed. Statistical analyses were performed by GraphPad Prism 5.0 software (GraphPad Software, Inc., California, USA). Results: PAR was lower after treatment with valsartan (11.49 ± 0.69% vs. 18.71 ± 2.47%, P < 0.001), associated with more reduced plasma levels of COX-2 (76.94 ± 7.07 U/L vs. 116.4 ± 15.89 U/L, P < 0.001) and TXB 2 (1667 ± 56.50 pg/ml vs. 2207 ± 180.20 pg/ml) (all P < 0.001). Plasma COX-2 and TXB 2 levels correlated significantly with PAR in overall patients (r = 0.109, P < 0.001). During follow-up (median, 18 months), there was a significantly lower thrombotic event rate in patients treated with valsartan (14.3% vs. 32.8%, P = 0.002). Relative expression of COX-2 and secretion of TXB 2 with concordant phosphorylation of p38MAPK and NF-kB were increased in HAECs when stimulated by Ang II (100 nmol/L) but were significantly decreased by valsartan pretreatment (100 nmol/L). Conclusions: AT 1 R antagonist valsartan decreases platelet activity by attenuating COX-2/TXA 2 expression through p38MAPK and NF-kB pathways and reduces the occurrence of cardio-cerebral thrombotic events in elderly patients with hypertension.

Background Uptake of oxidized low-density lipoprotein (oxLDL) by macrophages is recognized as a crucial step in the development of atherosclerosis, whereas the precise molecular mechanisms involving it remain to be elucidated. Methods and results This study focused on determining the role of toll-like receptor 4 (TLR4) and Src kinase in macrophage lipid accumulation. oxLDL significantly enhanced Src kinase activity and intracellular lipid contents in RAW264.7 macrophages, whereas the small interference RNA-mediated knockdown of TLR4 and Src or chemical inhibition of Src activity blocked oxLDL-induced lipid accumulation. Immunoprecipitation and immunofluorescence studies demonstrated that TLR4 was associated with Src on the plasma membrane upon oxLDL stimulation. Conclusions The results of the present study suggest an essential role of TLR4-Src signaling in macrophages in the pathogenesis of atherosclerosis.

Objective: In this paper, we review the previous classic research paradigms of a mass casualty incident (MCI) systematically and reflect the medical response to the Wenchuan earthquake and Hangzhou bus fire, in order to outline and develop an improved research paradigm for MCI management. Methods: We searched PubMed, EMBASE, China Wanfang, and China Biology Medicine (CBM) databases for relevant studies. The following key words and medical subject headings were used: ‘mass casualty incident’, ‘MCI’, ‘research method’, ‘Wenchuan’, ‘earthquake’, ‘research paradigm’, ‘science of surge’, ‘surge’, ‘surge capacity’, and ‘vulnerability’. Searches were performed without year or language restriction. After searching the four literature databases using the above listed key words and medical subject headings, related articles containing research paradigms of MCI, 2008 Wenchuan earthquake, July 5 bus fire, and science of surge and vulnerability were independently included by two authors. Results: The current progresses on MCI management include new golden hour, damage control philosophy, chain of survival, and three links theory. In addition, there are three evaluation methods (medical severity index (MSI), potential injury creating event (PICE) classification, and disaster severity scale (DSS)), which can dynamically assess the MCI situations and decisions for MCI responses and can be made based on the results of such evaluations. However, the three methods only offer a retrospective evaluation of MCI and thus fail to develop a real-time assessment of MCI responses. Therefore, they cannot be used as practical guidance for decision-making during MCI. Although the theory of surge science has made great improvements, we found that a very important factor has been ignored—vulnerability, based on reflecting on the MCI response to the 2008 Wenchuan earthquake and July 5 bus fire in Hangzhou. Conclusions: This new paradigm breaks through the limitation of traditional research paradigms and will contribute to the development of a methodology for disaster research.

Background Sirolimus-eluting stents (SES) with a biodegradable polymer coating have demonstrated promising results but have not been compared to SES with a durable polymer in high-risk patients. We compared the efficacy of these 2 stent types in patients with acute myocardial infarction (STEMI). Methods One thousand one hundred ninety-two STEMI patients were randomized to receive SES coated with biodegradable (n = 596) or durable polymer (n = 596). The study end-point was the composite of major adverse cardiac events (MACE) including all-cause death, recurrent myocardial infarction (MI), or target lesion revascularization (TLR) at 1-year follow-up. Secondary end-points included individual components of primary end-point and stent thrombosis. Results Compared with durable polymer SES, the noninferiority of SES with biodegradable polymer coating was established by an absolute risk difference of 0.9% in the primary end-point (12.4% vs. 13.3%, P = 0.67) and an upper limit of one-sided 95% confidence interval (CI) of 2.96% (P for noninferiority = 0.001). Rate of death, recurrent MI, and TLR were 7.9% and 8.6% (HR: 0.92; 95% CI: 0.61–1.38, P = 0.67), 2.9% and 3.5% (HR: 0.80; 95% CI: 0.42–1.54, P = 0.51), and 2.0% and 3.2% (HR: 0.62; 95% CI: 0.30–1.30, P = 0.20) in the biodegradable polymer SES and durable polymer SES group at 1-year clinical follow-up, respectively. Despite similar rates of 30-day ARC definite/probable stent thrombosis, late stent thrombosis (stent thrombosis occurring beyond 30 days) was lower with biodegradable polymer SES (0.7% vs. 2.2%, P = 0.028). Conclusions In patients undergoing primary PCI for STEMI, the use of biodegradable polymer SES was associated with noninferior 1-year rates of MACE compared with durable polymer SES. (J Interven Cardiol 2014;27:131–141)

Objectives: This study sought to ascertain the relationship of 9p21 locus with: 1) angiographic coronary artery disease (CAD) burden; and 2) myocardial infarction (MI) in individuals with underlying CAD. Background: Chromosome 9p21 variants have been robustly associated with coronary heart disease, but questions remain on the mechanism of risk, specifically whether the locus contributes to coronary atheroma burden or plaque instability. Methods: We established a collaboration of 21 studies consisting of 33,673 subjects with information on both CAD (clinical or angiographic) and MI status along with 9p21 genotype. Tabular data are provided for each cohort on the presence and burden of angiographic CAD, MI cases with underlying CAD, and the diabetic status of all subjects. Results: We first confirmed an association between 9p21 and CAD with angiographically defined cases and control subjects (pooled odds ratio [OR]: 1.31, 95% confidence interval [CI]: 1.20 to 1.43). Among subjects with angiographic CAD (n = 20,987), random-effects model identified an association with multivessel CAD, compared with those with single-vessel disease (OR: 1.10, 95% CI: 1.04 to 1.17)/copy of risk allele). Genotypic models showed an OR of 1.15, 95% CI: 1.04 to 1.26 for heterozygous carrier and OR: 1.23, 95% CI: 1.08 to 1.39 for homozygous carrier. Finally, there was no significant association between 9p21 and prevalent MI when both cases (n = 17,791) and control subjects (n = 15,882) had underlying CAD (OR: 0.99, 95% CI: 0.95 to 1.03)/risk allele. Conclusions: The 9p21 locus shows convincing association with greater burden of CAD but not with MI in the presence of underlying CAD. This adds further weight to the hypothesis that 9p21 locus primarily mediates an atherosclerotic phenotype.

Objective— In a previous study, we established diabetic and nondiabetic minipig models with coronary artery in-stent restenosis (ISR). Mass spectrometry showed that high-mobility group box (HMGB) 2 level was higher in ISR than in non-ISR tissue from diabetic minipigs. We here investigated whether serum HMGB2 levels were related to ISR in coronary artery disease patients. The effect of HMGB2 was evaluated in mice with femoral artery wire injury and in human aortic smooth muscle cells. Approach and Results— From 2513 patients undergoing coronary artery intervention and follow-up angiography at ≈1 year, 262 patients were diagnosed with ISR, and 298 patients with no ISR were randomly included as controls. Serum HMGB2 levels were significantly higher in patients with ISR than in those without ISR and were associated with ISR severity. Multivariable logistic regression analysis showed that HMGB2 level was independently associated with ISR. In experiments, HMGB2 expression was increased in vascular tissue after injury. Perivascular HMGB2 administration promoted injury-induced neointimal hyperplasia in C57Bl/6 mice compared with in the control, whereas such pathophysiological features were attenuated in Hmgb2 –/– mice. Mechanistically, HMGB2 enhanced neointimal hyperplasia in mice and proliferation and migration in human aortic smooth muscle cells by inducing reactive oxygen species through increased p47phox phosphorylation. Knocking down p47phox, however, inhibited HMGB2-induced effects in human aortic smooth muscle cells. Finally, HMGB2-induced effects were significantly declined in receptor of advanced glycation end products knockdown or deficient cells, but not in Toll-like receptor 4 knockdown or deficient cells. Conclusions— Serum HMGB2 levels were associated with ISR in patients. HMGB2 promoted neointimal hyperplasia in mice with arterial wire injury through reactive oxygen species activation.

The regulation of inflammatory responses by innate immune receptors is recognized as a crucial step in the development of atherosclerosis, although the precise molecular mechanisms remain to be elucidated. This study focused on illustrating the roles of dendritic cell-specific intercellular adhesion molecule-3-grabbing non-integrin (DC-SIGN)- and Toll-like receptor 4 (TLR4)-regulated inflammatory responses in macrophages. We found that DC-SIGN expression levels were increased in macrophages of atherosclerotic plaques. Oxidized low-density lipoprotein (oxLDL) significantly enhanced DC-SIGN protein expression levels after a short-term exposure. Knockdown of DC-SIGN decreased expression and secretion of interleukin 1-β (IL1-β), monocyte chemo-attractant protein 1 (MCP-1), tumor necrosis factor-α (TNFα) and matrix metalloproteinase-9 (MMP-9). Immunofluorescence studies demonstrated that DC-SIGN and TLR4 co-localized in regions of the plaques. Moreover, DC-SIGN was co-expressed with TLR4 on the plasma membrane after oxLDL stimulation. The presence of an endogenous interaction and the results of the in vitro pull-down assays revealed that DC-SIGN binds directly with TLR4. We also present evidence that DC-SIGN mediates TLR4-regulated NFκB activation but not activation of p38 and JNK. Our results suggest an essential role of DC-SIGN/TLR4 signaling in macrophages in the pathogenesis of atherosclerosis.

Background— Traditional reperfusion options for patients with acute ST-segment elevation myocardial infarction (STEMI) presenting to non-primary percutaneous coronary intervention (PPCI)-capable hospitals generally include onsite fibrinolytics or emergency transfer for PPCI. A third option, involving interventionalist transfer, was examined in the REVERSE-STEMI study. Methods and Results— A total of 334 patients with acute STEMI who presented to 5 referral hospitals with angiographic facilities but without interventionalists qualified for PPCI were randomized to receive PPCI with either an interventionalist- (n=165) or a patient-transfer (n=169) strategy. The primary end point of door-to-balloon (D2B) time and secondary end points of left ventricular ejection fraction and major adverse cardiac events (MACE) at 1-year clinical follow-up were compared between the 2 groups. Compared with the patient-transfer strategy, the interventionalist-transfer strategy resulted in a significantly shortened D2B time (median, 92 minutes versus 141 minutes; P P P P =0.019). Multivariate Cox proportional hazards modeling revealed that the interventionalist-transfer strategy was an independent factor for reduced risk of composite MACE (hazard ratio, 0.63; 95% CI, 0.45 to 0.88; P =0.003). Conclusions— The interventionalist-transfer strategy for PPCI may be effective in improving the care of patients with STEMI presenting to a non-PPCI-capable hospital, particularly in a congested cosmopolitan region where patient transfers could be prolonged. Clinical Trial Registration— URL: http://www.clinicaltrials.gov . Unique identifier: NCT00713557.

We sought to examine if polymorphisms in the promoter region of YKL-40 gene (CHI3L1) are associated with serum YKL-40 levels and coronary artery disease (CAD) in Chinese patients.Three single nucleotide polymorphisms (SNPs) (-329GA, rs10399931; -247CT, rs10399805; -131GC, rs4950928) in the CHI3L1 promoter were determined in 213 consecutive patients with angiographically documented CAD (luminal diameter stenosis ≥50%) and 248 normal controls. Coronary cumulative obstruction score and number of diseased vessels represent the severity of CAD. Serum YKL-40 levels were assessed using an ELISA kit.Patients with CAD had remarkably higher serum YKL-40 levels compared to controls (p0.001). There was no difference in the allele, genotype and haplotype distribution of these three SNPs between controls and CAD patients. The minor alleles of CHI3L1-329GA and -131GC were significantly associated with decreased serum YKL-40 levels in both controls (p = 0.001 and p0.001, respectively) and CAD patients (p = 0.007 and p0.001, respectively), whereas CHI3L1-247CT had no appreciable effect. None of these genetic variants and haplotypes was associated with severity of angiographic CAD.CHI3L1-329GA and -131GC polymorphisms are associated with serum YKL-40 levels, but not with the prevalence or severity of CAD.

This study aimed to characterize matrix metalloproteinases (MMPs) and their tissue inhibitors (TIMPs) in relation to changes in left ventricle (LV) geometry and function in a porcine model with streptozotocin (STZ)-induced diabetes. In 15 Chinese Guizhou minipigs with STZ-induced diabetes (diabetic group) and 15 age-matched normal controls (control group), Doppler tissue imaging was performed at 6 months of diabetes. Serum MMP-2, -9, TIMP-1, -4 and B-type natriuretic peptide (BNP) were determined. Expression of MMPs, TIMPs, urokinase type-plasminogen activator (uPA), its receptor (uPAR) and plasminogen activator inhibitor-1 (PAI-1) in aortic intima and LV myocardium was evaluated, with gelatinolytic activities of tissue MMP-2, -9 accessed by zymography. Left ventricle end-diastolic septum thickness (P < 0.05) and mass (P < 0.05) were increased, whereas peak systolic mitral annulus velocity (Sm, P < 0.001), LV systolic (P = 0.01) and diastolic strain (P < 0.001) were significantly decreased in diabetic group than in controls. Diabetic group showed higher expression of TIMP-1, -4 in aortic intima and LV myocardium (P < 0.01 or P < 0.05), with increased collagen content and elevated serum BNP level (P = 0.004) and lower gelatinolytic activities of tissue MMP-2, -9 (all P < 0.05). Semi-quantitative RT-PCR of those diabetic tissues revealed elevated mRNA levels of major TIMPs, uPA, uPAR and PAI-1. Reduction of serum MMP-2 and -9 levels was observed in diabetic group vs. control group (both P < 0.05). This study features elevated levels of TIMP-1, -4, uPA, uPAR and PAI-1, and decreased activities of MMP-2, -9 in aorta and myocardium in STZ-induced diabetic minipigs, indicating that MMP-TIMP dysregulation is associated with LV hypertrophy, cardiac dysfunction and increased cardiovascular fibrosis in diabetes.

We sought to investigate whether numbers and activity of circulating endothelial progenitor cells (EPCs) correlate with severity of coronary stenosis as well as cardiovascular risk factors in patients with stable coronary artery disease (CAD). Number of circulating EPCs was analyzed in 104 consecutive patients with proven or clinically suspected CAD. Adhesive and migratory activity was also determined. The number of EPCs was lower in patients with a single diseased coronary artery (Group II, n=35, p

Background: ApoA-IV is associated with HDL in plasma but a large portion circulates lipid free. It has been shown to possess anti-inflammatory and anti-atherosclerotic effects. Methods and Results: We isolated HDL from plasma of type 2 diabetic patients and healthy controls, and found that apoA-IV of HDL from diabetic patients was significantly glycated by using Western blot and mass spectrometry. The glycation levels of apoA-IV were higher in diabetic patients than in controls, and were associated with the severity of coronary artery disease. Immunohistochemically, glycation sites co-localized with apoA-IV in atherosclerotic plaques from diabetic patients. In cell and animal studies, in vitro glycated apoA-IV protein promoted inflammatory reactions in human aortic endothelial cells and atherogenesis in apoE-KO mice as compared with control, whereas apoA-IV exhibited anti-inflammatory and anti-atherogenic effects. The pro-inflammatory action of glycated apoA-IV was mediated by receptor for glycation end products in endothelial cells. In microarray analysis and verification in endothelial cells, glycated apoA-IV but not apoA-IV, enhanced the expression of nuclear receptor NR4A3 greatly. Glycated apoA-IV-induced inflammatory reaction and atherogenic effect was significantly attenuated in endothelial cell with siRNA-NR4A3, native endothelial cells and macrophages from NR4A3-KO mice and in NR4A3-KO mice. Co-localization of NR4A3 with CD31 was observed in atherosclerotic plaque from diabetic patients. Moreover, glycated apoA-IV but not apoA-IV induced trans-activation of NR4A3 to the promoter of adhesion molecules (VCAM-1, ICAM-1 and E-selectin). ESI-Q-TOF-MS identified several glycation sites including K78, K189 and K328 in apoA-IV from diabetic patients, but not in controls. Mutated apoA-IV proteins (m-apoA-IV-K78A/K189A/K328A) were made. In vitro glycated m-apoA-IV displayed significantly attenuated activation of NR4A3 in endothelial cells and atherogenesis in apoE-KO mice, as compared with glycated apoA-IV. Conclusion: Glycation of apoA-IV is associated with the severity of coronary artery disease in diabetic patients and glycated apoA-IV protein promotes atherogenesis through nuclear receptor NR4A3 mediation.

Background: C1q/TNF-related protein (CTRP) 1 was initially identified as a paralog of adiponectin based on the similarity in C1q domain of these two proteins. However, vascular functions of CTRP1 remain largely undetermined. Here, we sought to investigate whether CTRP1 influences the pathogenesis of atherosclerosis. Methods and Results: We analyzed CTRP1 levels in sera of coronary artery disease (CAD) patients (n=451) and non-CAD controls (n=686), in coronary endarterectomy specimens (n=26) and non-atherosclerotic internal mammary arteries (n=32), and in peripheral blood mononuclear cells (PBMCs) from severe CAD patients (n=58) and non-CAD controls (n=25). CTRP1 levels were higher in sera, endarterectomy specimens and PBMCs from CAD patients compared with controls, and were related to CAD severity. Immunohistochemistry of human femoral arteries exhibited VE-cadherin loci-associated increased CTRP1 expression in atherosclerotic plaques. In cultured endothelial cells, CTRP1 stimulation resulted in reduced nitric oxide (NO) bioavailability and promotion of inflammatory reactions (increased production of inflammatory cytokines and induction of adhesion molecules). Intravital microscopy exhibited impaired endothelium-dependent arteriole dilation and enhanced leukocyte-endothelium interactions after injection of recombinant CTRP1, whereas improved arteriole dilation and decreased leukocyte-endothelium interactions were observed in CTRP1 knockout mice. Furthermore, we found that arginase 1 was significantly increased by CTRP1 in a dose-dependent fashion, thereby leading to eNOS-uncoupling and reactive oxygen species generation. Inhibition of arginase activity by synthetic chemicals markedly improved CTRP1-dependent endothelial dysfunction. Finally, intraperitoneal injection of recombinant CTRP1 promoted atherogenesis in apoE-/- mice. In contrast, proatherogenic effects were significantly attenuated in CTRP1-/-/apoE-/- double knockout mice. Conclusions: Our findings have demonstrated that CTRP1 is a pro-atherogenic adipokine, likely by modulating arginase 1 expression and enzyme activity. CTPP1 may represent a crucial therapeutic target in atherosclerosis.

Patients with hepatocellular carcinoma (HCC) experience poor prognosis and low survival rates. In this study, we explored the molecular mechanism of microRNA-147 (miR-147) in regulating human HCC. We firstly used quantitative RT-PCR (qRT-PCR) to compare the expression levels of miR-147 between 7 HCC and two normal liver cell lines, as well as 10 paired primary HCC tissues and their adjacent non-carcinoma tissues. We found miR-147 was down-regulated in both HCC cell lines and primary HCCs tissues. HCC cell lines HepG2 and HuH7 were transfected with lentiviral vector of miR-147 mimics. We found overexpressing miR-147 significantly inhibited HCC in vitro proliferation and migration, increased 5-FU chemosensitivity, and reduced in vivo tumorigenicity. Luciferase, qRT-PCR and western blot assays showed that HOXC6 was the downstream target of miR-147, and both gene and protein levels of HOXC6 were down-regulated by miR-147 in HCC cells. SiRNA mediated HOXC6 knockdown inhibited in vitro proliferation and migration, and increased 5-FU chemosensitivity in HCC. On the other hand, HOXC6 overexpression reversed the inhibitory effect of miR-147 on HCC in vitro proliferation. Therefore, our results suggest that miR-147 can modulates HCC development through the regulation on HOXC6.

We have identified Bombyx mori transformer-2 gene (Bmtra-2) cDNA by blasting the EST database of B. mori. It was expressed in the whole life of the male and female silkworm and was observed as a band of 1.3 kb by Northern blot analysis. By comparing corresponding ESTs to the Bmtra-2 DNA sequence, it was revealed that there were eight exons and seven introns, and all splice sites of exons/introns conformed to the GT/AG rule. Bmtra-2 pre-mRNA can produce multiple mRNAs encoding six distinct isoforms of BmTRA-2 protein using an alternative splicing pathway during processing. Six types of Bmtra-2 cDNA clones were identified by reverse transcription-polymerase chain reaction. All isoforms of BmTRA-2 protein contain two arginine/serine-rich domains and one RNA recognition motif, showing striking organizational similarity to Drosophila TRA-2 proteins.

Background Pulmonary embolism (PE) is a potentially life-threatening condition. Although computed tomography pulmonary angiography (CTPA) is the reference standard for diagnosis, its early diagnosis remains a challenge, and the concerns about the radiation exposures further limit the general use of CTPA. The primary aim of this meta-analysis was to evaluate the overall diagnostic accuracy of transthoracic lung ultrasound (TLS) in the diagnosis of PE. Methods PubMed, Web of science, OvidSP, ProQuest, EBSCO, Cochrane Library and Clinicaltrial.gov were searched systematically. The quality of included studies was assessed using the Quality Assessment of Diagnostic Accuracy Studies-2 tool. The sensitivity, specificity, positive likelihood ratio (PLR), negative likelihood ratio (NLR), diagnostic odds ratio (DOR) and hierarchical summary receiver operating characteristic (HSROC) curves were used to examine the TS performance. The Bayes analysis was used to calculate the post-test probability of PE. Publication bias was assessed with Deeks funnel plot. Results The results indicated that the sensitivity, specificity, PLR and NLR were 0.85 (95% confidence interval (CI), 0.78 to 0.90), and 0.83 (95% CI, 0.73 to 0.90). And the DOR and HSROC were 28.82 (95% CI, 17.60 to 47.21), 0.91(95% CI, 0.88, 0.93). Conclusions The present meta-analysis suggested that transthoracic lung ultrasonography is helpful in diagnosing pulmonary embolism. Although the application of transthoracic lung ultrasound may change some patients’ diagnostic processes, it is inappropriate to generally use transthoracic ultrasonography in diagnosing pulmonary embolism currently.

Eph receptor (Eph)‐ephrin signaling plays an important role in organ development and tissue regeneration. Bidirectional signaling of EphB4–ephrinB2 regulates cardiovascular development. To assess the role of EphB4–ephrinB2 signaling in cardiac lineage development, we utilized two GFP reporter systems in embryonic stem (ES) cells, in which the GFP transgenes were expressed in Nkx2.5+ cardiac progenitor cells and in α‐MHC+ cardiomyocytes, respectively. We found that both EphB4 and ephrinB2 were expressed in Nkx2.5‐GFP+ cardiac progenitor cells, but not in α‐MHC‐GFP+ cardiomyocytes during cardiac lineage differentiation of ES cells. An antagonist of EphB4, TNYL‐RAW peptides, that block the binding of EphB4 and ephrinB2, impaired cardiac lineage development in ES cells. Inhibition of EphB4–ephrinB2 signaling at different time points during ES cell differentiation demonstrated that the interaction of EphB4 and ephrinB2 was required for the early stage of cardiac lineage development. Forced expression of human full‐length EphB4 or intracellular domain‐truncated EphB4 in EphB4‐null ES cells was established to investigate the role of EphB4‐forward signaling in ES cells. Interestingly, while full‐length EphB4 was able to restore the cardiac lineage development in EphB4‐null ES cells, the truncated EphB4 that lacks the intracellular domain of tyrosine kinase and PDZ motif failed to rescue the defect of cardiomyocyte development, suggesting that EphB4 intracellular domain is essential for the development of cardiomyocytes. Our study provides evidence that receptor‐kinase‐dependent EphB4‐forward signaling plays a crucial role in the development of cardiac progenitor cells. J. Cell. Biochem. 116: 467–475, 2015. © 2014 The Authors. Journal of Cellular Biochemistry published by Wiley Periodicals, Inc.

A comprehensive meta-analysis was performed to evaluate the comparative benefits of coronary artery bypass grafting (CABG) versus drug-eluting stents (DES) in patients with diabetes mellitus and severe coronary artery disease (CAD).A comprehensive literature search of PubMed, Embase, and ScienceDirect was undertaken. References cited with the papers were also checked to identify relevant articles.In all, four randomized controlled trials, two prospective registries, and 11 retrospective studies were identified for review. Pooled analysis demonstrated that DES was associated with lower all-cause mortality at Day 30. However, there was no significant difference between CABG and DES in mortality at 12 months and at maximum follow-up. Furthermore, DES was associated with lower overall and major adverse cardiac and cerebrovascular events (MACCE)-free survival, as well as a higher incidence of myocardial infarction and repeat revascularization. In contrast, CABG was associated with an increased risk of stroke.For patients with diabetes mellitus and severe CAD, CABG is superior to DES in that it significantly improves overall and MACCE-free survival and reduces the incidence of myocardial infarction and repeat revascularization in the long term, although it is associated with greater perioperative risk and a higher incidence of stroke. Therefore, CABG should remain the gold standard for these patients.

Objective: Renal dysfunction represents a risk factor for poor coronary collateral growth. We investigated whether Glomerular Filtration Rate (GFR) estimated with the cystatin C-based formula (GFRCYS) is superior to that with the creatinine-based abbreviated Modification of Diet in Renal Disease (GFRMDRD) and the Chronic Kidney Disease Epidemiology Collaboration (GFREPI) equations for evaluating coronary collateralization in type 2 diabetic patients with stable coronary artery disease. Methods: GFR was estimated with creatinine- and cystatin C- based equations in 302 diabetic and 127 nondiabetic patients with stable angina and angiographic total occlusion of at least one major coronary artery. The degree of collaterals supplying the distal aspect of a total occlusion from the contra-lateral vessel was graded as poor (Rentrop score of 0 or 1) or good collateralization (Rentrop score of 2 or 3). Results: In diabetic patients, GFRCYS correlated more closely with Rentrop score than GFRMDRD (Spearmen’s r=0.44 vs. Spearmen’s r=0.30, P=0.047) and GFREPI (Spearmen’s r=0.44 vs. Spearmen’s r=0.29, P=0.028), and area under the curve of GFRCYS was larger compared with that of GFRMDRD and GFREPI (0.78 vs. 0.68 and 0.66, P=0.001 and P

To evaluate whether glycation of high-density lipoprotein (HDL) increases cardiovascular risk in patients with type 2 diabetes mellitus by altering its anti-atherogenic property.Data cited in this review were obtained mainly from Pubmed and Medline in English from 2000 to 2013, with keywords "glycation", "HDL", and "atherosclerosis". Study selection Articles regarding glycation of HDL and its role in atherogenesis in both humans and experimental animal models were identified, retrieved and reviewed.Glycation alters the structure of HDL and its associated enzymes, resulting in an impairment of atheroprotective functionality and increased risks for cardiovascular events in type 2 diabetic patients.Glycation of HDL exerts a deleterious effect on the development of cardiovascular complications in diabetes.

To determine whether the prosthesis-patient mismatch has a deleterious impact on survival after mitral valve replacement.A comprehensive literature search of PubMed, Embase, and ScienceDirect was carried out. References and cited papers of relevant articles were also checked.All articles published after January 1980 was initially considered. Non-English and non-human studies, case reports, and reviews were excluded from the initial search. References and cited papers of relevant articles were also checked.A total of 8 retrospective cohort studies were identified for this review. The overall incidence of prosthesis-patient mismatch (1.3 to1.2 cm(2)/m(2)) after mitral valve replacement ranged from 3.7% to 85.9% (moderate prosthesis-patient mismatch (0.9 to 1.2 cm(2)/m(2)) in 37.4% to 69.5%, severe prosthesis-patient mismatch (0.9 cm(2)/m(2)) in 8.7% to 16.4%). Four studies demonstrated an association of prosthesis-patient mismatch with reduced long-term survival, but the other four studies found no significant deleterious impact of prosthesis-patient mismatch after mitral valve replacement. No definite conclusion could be derived from these conflicting results.Current evidence is insufficient to derive a definite conclusion whether mitral prosthesis-patient mismatch affects long-term survival because of the biases and confounding factors that interfere with late clinical outcomes. Goodquality prospective studies are warranted to evaluate the impact of mitral prosthesis-patient mismatch after mitral valve replacement in the future.

No randomized trial has been performed to compare the efficacy of an intracoronary bolus of tirofiban versus urokinase during primary percutaneous coronary intervention (PCI). We investigated whether the effects of adjunctive therapy with an intracoronary bolus of urokinase was noninferior to the effects of an intracoronary bolus of tirofiban in patients with ST-elevation myocardial infarction (STEMI) undergoing PCI.A total of 490 patients with acute STEMI undergoing primary PCI were randomized to an intracoronary bolus of tirofiban (10 µg/kg; n = 247) or urokinase (250 kU/20 ml; n = 243). Serum levels of P-selectin, von Willebrand factor (vWF), CD40 ligand (CD40L), and serum amyloid A (SAA) in the coronary sinus were measured before and after intracoronary drug administration. The primary endpoint was the rate of complete ( ≥ 70%) ST-segment resolution (STR) at 90 minutes after intervention, and the noninferiority margin was set to 15%.In the intention-to-treat analysis, complete STR was achieved in 54.4% of patients treated with an intracoronary bolus of urokinase and in 60.6% of those treated with an intracoronary bolus of tirofiban (adjusted difference: -7.0%; 95% confidence interval: -15.7% to 1.8%). The corrected TIMI frame count of the infarct-related artery was lower, left ventricular ejection fraction was higher, and the 6-month major adverse cardiac event-free survival tended to be better in the intracoronary tirofiban group. An intracoronary bolus of tirofiban resulted in lower levels of P-selectin, vWF, CD40L, and SAA in the coronary sinus compared with an intracoronary bolus of urokinase after primary PCI (P0.05).An intracoronary bolus of urokinase as an adjunct to primary PCI for acute STEMI is not equally effective to an intracoronary bolus of tirofiban with respect to improvement in myocardial reperfusion assessed by STR. This may be caused by less reduction in coronary circulatory platelet activation and inflammation.