Objective To explore the role and related mechanism of neutrophil membrane-coated poly(lactic-co-glycolic acid) (PLGA) nanoparticles (Neu-NP) in cardiac repair after acute myocardial ischemia-reperfusion (MI/R) injury in mice. Methods The male C57 mouse model of acute MI/R injury was established and randomly divided into three groups: PBS control group (injection of 200 μL PBS), NP treatment group (injection of 0.5 mg/mL NP 200 μL), and Neu-NP treatment group (injection of 0.5 mg/mL Neu-NP 200 μL). Neutrophil membranes were extracted and fused with PLGA nanoparticles to construct biomimetic Neu-NP. The in vivo homing ability of Neu-NP was assessed using ex vivo imaging technology in the MI/R injury model, and the expression levels of tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6) in the myocardium were measured using enzyme linked immunosorbent assay one day and three days after administration. Echocardiography was used to determine cardiac function indicators of MI/R injured mice 28 days post-administration. Immunofluorescence staining was used to observe angiogenesis repair and inflammatory cell infiltration in mouse heart tissue. Results Neu-NP, engineered by integrating neutrophil membranes with nanoparticles, inherited surface receptors (TNF-αR and IL-6R) and functioned as decoys for inflammatory targeting. Compared with the PBS control group and NP treatment group, the secretion levels of TNF-α and IL-6 in the damaged myocardium of the Neu-NP treatment group were significantly decreased one and three days after administration (P＜0.05); 28 days after administration, the cardiac ejection fraction in the Neu-NP treatment group was significantly higher than that in the other two groups (P＜0.05). Immunofluorescence staining indicated a significant increase in the proportion of angiogenesis in the myocardial infarction area and a significant reduction in inflammation cell infiltration (P＜0.05). Conclusions Neu-NP plays an important role in cardiac tissue repair after MI/R injury by alleviating inflammatory factors in the damaged area and promoting angiogenesis.

The promise of regeneration therapy for restoration of damaged myocardium after cardiac ischemic injury relies on targeted delivery of proliferative molecules into cardiomyocytes whose healing benefits are still limited owing to severe immune microenvironment due to local high concentration of proinflammatory cytokines. Optimal therapeutic strategies are therefore in urgent need to both modulate local immunity and deliver proliferative molecules. Here, we addressed this unmet need by developing neutrophil-mimic nanoparticles NM@miR, fabricated by coating hybrid neutrophil membranes with artificial lipids onto mesoporous silica nanoparticles (MSNs) loaded with microRNA-10b. The hybrid membrane could endow nanoparticles with strong capacity to migrate into inflammatory sites and neutralize proinflammatory cytokines and increase the delivery efficiency of microRNA-10b into adult mammalian cardiomyocytes (CMs) by fusing with cell membranes and leading to the release of MSNs-miR into cytosol. Upon NM@miR administration, this nanoparticle could home to the injured myocardium, restore the local immunity, and efficiently deliver microRNA-10b to cardiomyocytes, which could reduce the activation of Hippo-YAP pathway mediated by excessive cytokines and exert the best proliferative effect of miR-10b. This combination therapy could finally improve cardiac function and mitigate ventricular remodeling. Consequently, this work offers a combination strategy of immunity modulation and proliferative molecule delivery to boost cardiac regeneration after injury.

Objective To investigate the feasibility of subtraction coronary computed tomography angiography (Sub-CCTA) for the diagnosis of coronary heart disease in the segment with severe calcification.Methods A retrospective analysis was performed on 27 patients who underwent clinically indicated digital subtraction angiography (DSA) and CCTA using a 320-detector row CT.Compared with the results of DSA,sensitivity,specificity,positive predictive value,negative predictive value and accuracy of Con-CCTA and Sub-CCTA were calculated.The clinical diagnostic accuracy of the two imaging methods was evaluated using the receiver operating characteristic (ROC) curve.The stenosis of coronary segments was divided into four grades (Ⅰ,Ⅱ,Ⅲ,Ⅳ).Kappa coefficient was used to measure agreement between two imaging methods.Image quality of 4-scale grade scoring method was used and t test was conducted.Results A total of 52 segments with severe calcification were evaluated.The scores of image quality in Con-CCTA and Sub-CCTA were 2.8 ± 0.5 and 3.4 ± 0.7,respectively.There was significant difference between them (t =5.9,P ＜ 0.05).Compared with the result of DSA as the golden standard,the Kappa coefficients were 0.55 and 0.81 respectively in Con-CCTA and Sub-CCTA for the quantitative evaluation of the severe calcified segments.The sensitivity,specificity,positive predictive value and negative predictive value and accuracy of Con-CCTA were 81.0％,63.1％,63.1％,81.1％ and 70.8 ％;and for Sub-CCTA they were 90.5 ％,85.2％,82.1 ％,92.0％ and 87.5 ％ respectively.Compared with Con-CCTA,the area under the ROC curve of Con-CCTA and Sub-CCTA were 0.84 (95％CI:0.70-0.93) and 0.96 (95％ CI:0.86-1.00),respectively,and the difference was statistically significant (P =0.03).Conclusions Sub-CCTA can improve the diagnostic accuracy of coronary artery stenosis in severe calcified segment.Application of subtraction technique in CCTA can reduce or even eliminate the artifacts caused by severe calcified plaque,and has a good clinical application prospect.

Objective:The goal of this study was to analyze the clinical significance of relationship between myocardial collateral and the levels of hypoxia‐inducible factor 1‐alpha (HIF‐1α) and vascular endothelial growth factor A (VEGF‐A) in patients with coronary chronic total occlusion lesion .Methods:89 patients with coronary chronic total occlusion lesion confirmed by clin‐ical data and coronary angiography were identified .The levels of HIF‐1αand VEGF‐A were measured by ELISA ,and the rela‐tive expression of VEGF‐A of peripheral blood mononuclear cell (PBMC) were measured by real‐time PCR .The results were statistically analyzed by the statistical programme for social sciences (SPSS version 18 .0) and software SAS JMP 9 .0 .Results:Compared to Rentrop 0‐1 grade group (18/38 ,47 .4% ) ,Rentrop 2 (11/31 ,35 .5% ) and Rentrop 3 (3/20 ,15 .0% ) grade group had fewer diabetes mellitus .Rentrop 2 [(6 .67 ± 1 .41) mmol/L] and Rentrop 3 [(5 .48 ± 1 .26) mmol/L] grade group had low‐er fasting blood glucose than Rentrop 0‐1 grade group [(7 .24 ± 1 .39) mmol/L] .Rentrop 2 (12/31 ,38 .7% ) and Rentrop 3 (3/20 ,15 .0% ) grade group had fewer clinical heart failure (NYHA Ⅱ ~ Ⅳ grade) than Rentrop 0‐1 grade group (20/38 , 52 .6% ) .Rentrop 2 [(85 .5 ± 27 .7) pg/mL ,(139 .5 ± 42 .1) pg/mL] and Rentrop 3 [(103 .3 ± 30 .2) pg/mL ,(162 .6 ± 43 .3) pg/mL] grade group had higher levels of HIF‐1αand VEGF‐A than Rentrop 0‐1 grade group [(42 .0 ± 16 .1) pg/mL ,(76 .5 ± 32 .2) pg/mL] .Rentrop 2 (1 .31 ± 0 .46) and Rentrop 3 (1 .38 ± 0 .44) grade group had higher level of relative expression of VEGF‐A in PBMC than Rentrop 0‐1 grade group (1 .00 ± 0 .28) .Conclusions:Chronic and consistent ischemia and hypoxia in‐duced the increase of expression of HIF‐1αand VEGF‐A is important for establishment of coronary collateral ,increasing blood supply and improving the heart function and prognosis .

Objective:To analyze the clinical characteristics of patients with immediate severe coronary artery spasm(CAS) af‐ter stent implantation .Methods:The clinical data of 6918 patients who received percutaneous coronary intervention(PCI) from Jan 2012 to Dec 2013 in Zhongshan Hospital ,Fudan University were retrospectively analyzed .And 102 patients with immediate severe CAS after stent implantation were identified and 204 age‐and gender‐matched patients without immediate severe CAS af‐ter stent implantation were selected as control subjects .The general information ,blood indexes ,number and length of stents in the two groups were compared .Results:Compared with the control group ,the ratios of males ,smoking and dyslipidemia were higher in CAS group (P<0 .05) .Patients with CAS had higher neutrophil count and higher level of high sensitive C‐reactive protein(P<0 .05) and received more and longer stents implantation than the control group(P<0 .05 or 0 .01) .Conclusions:Male patients and patients with history of smoking are prone to have immediate severe CAS after stent implantation .Moreover , patients with more and longer stents implantation are prone to have immediate severe CAS .Inflammation may play an important role in the development of CAS after stent implantation .

Objective:To explore the effects of medical support program on local diagnosis,treatment and prognosis of acute myocardial infarction(AMI).Methods:Department of Cardiology,Zhongshan Hospital,Fudan University launched medical support program for Fuyuan People′s Hospital in Mar 2010.A total of 103 AMI patients admitted to Fuyuan People′s Hospital during Mar 2010 and Apr 2014 were enrolled.And 5 1 patients admitted during Mar 2010 and Nov 2012 were allocated to group A,while 52 patients admitted during Dec 2012 and Apr 2014 were allocated to group B.The treatment strategy,hospital stay, medication and prognosis were compared between the two groups.Results:Among the 103 AMI patients,male smoking pro-portion was significantly higher than female one(P <0.05).Only 21 patients with ST segment elevation myocardial infarction (STEMI)arrived hospital within 12 h.The thrombolytic therapy rate of patients with STEMI in group B was higher than that in group A(P <0.05).The usage rate of adenosine diphosphate(ADP)receptor antagonist(clopidegrel)during hospitalization in group B was higher than that in group A (P <0.05 ).Only 57 patients were followed up.And only 1/3 of these patients re-ceived consecutive coronary angiography and percutaneous coronary intervention(PCI).After discharge from hospital,the pre-scription rates of ADP receptor antagonist,β-receptor blockers and angiotension converting enzyme inhibitor (ACEI)all de-creased obviously and there was no significant difference between the two groups(P >0.05).There was no significant difference regarding the incidence rates of endpoint events between the two groups(P >0.05).Conclusions:Medical support program im-proves the rates of diagnosis and standardized treatment of AMI during hospitalization.However,the delay before admission has not been shortened yet.Furthermore,there was no standardized secondary prevention and treatment after discharge.Thus,apart from improving the ability of diagnosis and treatment during hospitalization,more attention should be paid to the health education for patients and the training for primary medical staff,and enhance the regional cooperation.

BACKGROUNDClinical meaning of recovery phase limited ST segment depression of a treadmill exercise test is controversial. The aim of this study was to re-assess the diagnostic and prognostic value of ST segment depression during the recovery phase with the active phase of a treadmill exercise test in suspected coronary artery disease patients.

METHODSClinical, exercise and angiographic data were retrospectively collected from 602 patients in the study. Five hundred and seventy-six patients developed ST segment depression during the active phase of the treadmill exercise test (group 1) and 26 patients developed ST segment depression only during the recovery phase (group 2).

RESULTSWith similar major clinical features, the prevalence of significant coronary artery stenosis and average Gensini scores were lower in the recovery phase-limited depression patients (group 2 vs. group 1, 50.0% vs. 66.9%, P = 0.031 and group 2 vs. group 1, 1.5 vs. 8.5, P = 0.04). At a median follow up of 50.9 months for 22 group 2 and 34.8 months for 438 group 1 patients, the prevalence of total cardiac events was higher in group 1 than in group 2 patients (RR 1.60, 95% CI 1.00-2.54, P = 0.049).

CONCLUSIONThe present study provides preliminary evidence that the diagnostic and prognostic value of recovery phaselimited ST segment depression of treadmill exercise test is limited.

Coronary Angiography ; Coronary Artery Disease ; diagnosis ; Electrocardiography ; Exercise Test ; Female ; Humans ; Male ; Middle Aged ; Prognosis ; Retrospective Studies

Objective: To observe the changes of circulating fractalkine and its receptor CX3CR1 level in patients with chronic congestive heart failure (CHF).
Methods: Our work included 2 group, CHF group, n=55 patients and Control group, n=25 healthy subjects. Plasma level of soluble fractalkine (sFKN) was measured by ELISA, CX3CR1 in peripheral blood mononuclear cell was examined by lfow cytometry method. The relationship between sFKN and NT-proBNP was studied.
Results: Compared with Control group, CHF group had increased sFKN level, P=0.004, and the patients with NYHY III, IV were more than NYHY II, and CHF group also had the higher CX3CR1 expression (14.7 ± 8.1), P<0.05. The CX3CR1 level increased accordingly with NYHY classiifcation, as the patients with NYHY II, CX3CR1 was at (25.1 ± 12.4), P=0.03 compare with Control group;with NYHY III, CX3CR1 was at (37.3 ± 11.0) , P=0.04 compared with NYHY II;with NYHY IV, CX3CR1 was at (41.7 ± 11.1), P=0.009 compared with NYHY II. The circulating sFKN level was positively related to pro-BNP level (r=0.364, P<0.01).
Conclusion: The circulating FKN l and its receptor CX3CR1 might be involved in pathogenesis of immune-inlfammatory pathogenesis in CHF patients.

Seventy-one patients with variant angina (VA) admitted in the Cardiology Department from January 2003 to March 2011,were divided into non-stenosis group (stenosis ＜ 50％,n =43) and stenosis group (stenosis ≥50％,n =28) according to the degree of stenosis.The differences of the risk factors,clinical manifestations,electrocardiogram,echocardiogram and laboratory examinations between these two groups were compared.The average age of patients in stenosis group 58 ± 8 y was higher than that in non-stenosis group (52 ± 9 y,t =2.43,P =0.02).Other risk factors,including male gender,smoking,hypertension,diabetes mellitus and lipid disorder did not show any differences between the two groups.Percentage of patients with angina pectoris lasting less than 5 min was higher in stenosis group (x2 =5.98,P =0.02),while percentage of effort angina,seeking medical consultation ≤ 6 months of onset and hemodynamic disorders showed no difference.Laboratory examinations had no differences.It is difficult to determine whether the VA patient has fixed coronary stenosis by analyzing the risk factors,clinical manifestations and laboratory examinations; to determine the fixed coronary stenosis coronary angiography is necessary.

Objective To describe clinical and functional features of patients with left main coronary artery (LM) stenosis. Methods Significant stenosis was defined as ≥ 50%.One hundred and eighty-eight patients with LM stenosis and 200 patients with clinically suspected coronary heart disease (CHD) without LM stenosis were enrolled. Results (1) The incidence rate of LM stenosis was 5.59%.(2) Patients with LM stenosis all had risk factors.Furthermore,featured older age,higher incidence of angina pectoris,and the same incidence of myocardial infarction history when compared with the patients without LM stenosis.(3) The left ventricular ejection fraction was lower in patients with LM stenosis than that in patients without LM stenosis,and it was lower too in patients with isolated LM stenosis than in patients with LM stenosis accompanied by triple vessel stenosis.The left ventricular end diastolic pressure showed no significant difference among various groups. Conclusion Patients with LM stenosis feature older age,severe angina pectoris.Furthermore, most of them are accompanied by other vessel lesions.Most LM stenosis are located at the ostium and the crotch of LM is presented as stenosis