Hippo pathway-manipulating neutrophil-mimic hybrid nanoparticles for cardiac ischemic injury via modulation of local immunity and cardiac regeneration

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.

Investigation of clinical application for severe segmental calcification by subtraction technique of coronary artery CT angiography / 复旦学报（医学版）

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.

Limited value of recovery phase-limited ST segment depression of treadmill exercise test / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>Clinical 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.</p><p><b>METHODS</b>Clinical, 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).</p><p><b>RESULTS</b>With 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).</p><p><b>CONCLUSION</b>The present study provides preliminary evidence that the diagnostic and prognostic value of recovery phaselimited ST segment depression of treadmill exercise test is limited.</p>

Investigation of Circulating Fractalkine and its Receptor CX3CR1 Levels in Patients With Chronic Congestive Heart Failure / 中国循环杂志

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 Conclusion: The circulating FKN l and its receptor CX3CR1 might be involved in pathogenesis of immune-inlfammatory pathogenesis in CHF patients.

Clinical characteristics of variant angina patients with or without fixed coronary stenosis / 中华全科医师杂志

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.

Clinical and functional features of patients with left main coronary artery stenosis / 中国医师进修杂志

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

Impact of severity of coronary lesion on left ventricular end diastolic pressure / 医学研究生学报

Objective: To investigate the impact of severity of coronary lesion on left ventricular end diastolic pressure(LVEDP) in patients with coronary artery disease(CAD). Methods: 683 cases of consecutive coronary angiography were adopted for study according to the criteria and grouped in terms of extent and severity of coronary lesion and AHA coronary arterial lesion score respectively. The LVEDP were measured ventriculographically. Results: Comparing with the accordant contrast group, LVEDP was slightly decreased without statistical significance in the single vessel group in the (25%-50%) stenosis group, and the (1-3) scores group; while slightly increased without statistical significance in the double vessel group in (26%-50%) and (51%-75%) stenosis groups and (4-6) scores and (7-9) scores groups. There was a significant increase in the triple vessel group, in the 100% stenosis group, and the ≥10 scores group(P

Clinical characteristics of acute myocardial infarction without angiographically coronary artery stenosis / 中国介入心脏病学杂志

Objective To study the risk factors and left ventricular function in acute myocardial infarction (AMI) patients without angiographically coronary artery stenosis, and elucidate the possible mechanisms. Methods 399 AMI patients of selective coronary angiography were divided into two groups in terms of severity of coronary lesion: the group without angiographically coronary artery stenosis (coronary artery diameter stenosis percentage less than 50%) and the group with angiographically coronary stenosis (coronary artery diameter stenosis percentage equal to or more than 50%). The risk factors and left ventricular function were compared between the two groups. Results 5.76% (23/399) cases showed no angiographically coronary artery stenosis, while 94.24% (376/399) cases showed angiographically coronary artery stenosis. Compared with the group with coronary stenosis, the group without angiographically coronary artery stenosis featured more in young people aged less than 40 (26.08% vs 6.12%, P0.05). Left ventricular end diastolic pressure (LVEDP) was lower in the group without angiographically coronary artery stenosis (12.53 mm?Hg?5.46 mm?Hg vs 18.75 mm?Hg?7.10 mm?Hg, P0.05). Conclusion AMI without angiographically coronary artery stenosis is not a rare phenomenon, to which attention should be paid. The group without angiographically coronary artery stenosis features a better left ventricular function, and its prevalence is higher in young patients and female. Both group share the same risk factors such as diabetes, hyparlipedemia and hypertension.