The Application and Teaching Value of a Ventricular Septal Defect Canine Model Established by Transcatheter Puncture.

This study aimed to improve and further explore a ventricular septal defect (VSD) canine model on the basis of the transcatheter puncture method and to evaluate its application and teaching value.In order to lessen the complications of VSD closure, it is necessary to improve the currently available treatment devices using appropriate animal models.In this study, we used 16 healthy adult canines as our models. After anesthesia, the VSD puncture was performed, followed by balloon dilatation of the perforation. VSD was confirmed by angiography. The venous-artery orbit was established, and the VSD was then closed once the catheter and occluder were across the defect.Of the experimental canines, 14 of the 16 canines were successfully modeled, giving a success rate of 87.5%. The canines underwent an immediate creation of a venous-artery orbit for teaching practice and were implanted with an occluder during the procedure. After 4 weeks, 13 canines survived. As per our findings, most VSD types established by the puncture were perimembranous (10 of 13, 77%).The current model has a high success rate. The model can not only avoid the risk of infection and hemodynamic disorders associated with an open thoracotomy, but can also be effectively used in evaluating the impact of occluders. It can also directly measure the parameters of the devices during the procedure, thus having a very high experimental and teaching value.

Retracted: Upregulated microRNA-132 rescues cardiac fibrosis and restores cardiocyte proliferation in dilated cardiomyopathy through the phosphatase and tensin homolog-mediated PI3K/Akt signal transduction pathway.

Cardiac fibrosis is known to be present in dilated cardiomyopathy (DCM) and it predicts the occurrence of sudden death and congestive heart failure. The aim of our study is to investigate the expression of microRNA-132 (miR-132) and its effect on cardiocyte proliferation, apoptosis, and cardiac fibrosis by binding to phosphatase and tensin homolog (PTEN) through the phosphateidylinositol 3-kinase (PI3K)/protein kinase (Akt) signal transduction pathway in DCM rats. DCM rat models induced by doxorubicin were established and confirmed by an ultrasonic cardiogram. Epithelial cells were treated with inhibitors, activators, and small interfering RNAs to identify the mechanisms by which miR-132 controls cardiocyte activity and cardiac fibrosis. Angiotensin II (Ang II) and aldosterone (ALD) expressions were detected by an enzyme-linked immunosorbent assay. The relationship between PTEN and miR-132 was verified by a dual-luciferase reporter assay. Cell proliferation and apoptosis were tested by the MTT assay and flow cytometry. PTEN was determined to be the target gene of miR-132. Rat models of DCM exhibited a lower level of miR-132, PI3K, Akt, B-cell lymphoma 2, collagen I, and collagen III, but a higher level of PTEN, Bcl-2-associated X protein, and proliferating cell nuclear antigen as well as inflammatory response (Ang II and ALD), accompanied by declined cardiocyte proliferation and elevated apoptosis and cardiac fibrosis. Upregulated miR-132 or silenced PTEN activated the PI3K/Akt pathway, thus facilitating cardiocyte proliferation and repressing cardiocyte apoptosis and cardiac fibrosis, as well as inflammatory responses. Downregulated miR-132 reversed this tendency. These findings indicate that miR-132 activates the PI3K/Akt pathway by inhibiting PTEN expression, thus facilitating cardiocyte proliferation and inhibiting apoptosis and cardiac fibrosis in DCM rats.

Quantitative assessment of the influence of PSMA6 variant (rs1048990) on coronary artery disease risk.

The proteasome system is a proteolytic pathway that regulates the expression of genes involved in inflammation. Recently, an association of a functional sequence variation, -8C/G, in the human proteasome subunit a type 6 gene (PSMA6) with the susceptibility to coronary artery disease (CAD) was reported. After that, several validation studies have been conducted among various ethnic populations, but the results have been inconsistent. To investigate this inconsistency and derive a more precise estimation of the relationship, a meta-analysis of 15,991 cases and 16,784 controls from 10 case-control studies was performed. Potential sources of heterogeneity including ethnicity, sample size and HWE status of study were also assessed. In a combined analysis, the summary per-allele OR for CAD of the -8C/G polymorphism was 1.09 (95 % CI: 1.02-1.16; P = 0.006). In the subgroup analysis by ethnicity, significantly increased risks were found in East Asians for the polymorphism; while no significant associations were found among Caucasians and other ethnic population in all genetic models. When restricted to studies concerning myocardial infarction patients, significant associations were detected in all genetic models. Furthermore, significant difference of PSMA6 mRNA expression was found between genotypes. In conclusion, this meta-analysis suggests that G allele of PSMA6-8C/G polymorphism is a risk factor associated with increased CAD susceptibility, but these associations vary in different ethnic populations.

How to Set Up Central Isolation Sites to Prevent Re-outbreaks From Imported Cases of COVID-19: The Experience of Shanghai, China.

As strict measures were taken, the coronavirus disease 2019 (COVID-19) epidemic has been gradually brought under control. As a port city, Shanghai's main problem has shifted from treating local cases to preventing foreign imports. To prevent the re-outbreak of COVID-19 caused by imported cases, the Shanghai government has set up central isolation sites for all people entering the country from abroad to be placed under medical observation. This report describes how to set up central isolation sites and run them effectively. We put isolation sites in transformed hotels, arranged personnel according to a huge data network, and set up specific procedures to manage guests. The epidemic situation in Shanghai has confirmed the feasibility and effectiveness of the methods that other jurisdictions can adapt for their use.

Significance of plasma free fatty acid level for assessing and diagnosing acute myocardial infarction.

Aim: To clarify the diagnostic value of the circulating free fatty acid (FFA) level for acute myocardial infarction (AMI) in coronary heart disease patients. Methods & results: A total of 1776 patients were screened by coronary angiography from October 2014 to February 2016. The plasma FFA level was significantly higher in coronary heart disease patients with lesions in three or more vessels than those with lesions in one or two vessels. Moreover, an elevated FFA level was identified as an independent risk factor for AMI on multivariate regression analysis and shown to be a sensitive and specific indicator for AMI diagnosis by receiver operating characteristic curve analysis. Conclusion: An elevated FFA level is an independent risk factor and independent diagnostic marker for AMI.

miR-93-5p-Containing Exosomes Treatment Attenuates Acute Myocardial Infarction-Induced Myocardial Damage.

Adipose-derived stromal cells (ADSCs) have been considered as an attractive therapeutic tool. Accumulating evidence indicates that the healing effects of ADSCs are mainly related to paracrine action rather than transdifferentiation. Data show that the expression of miR-93-5p has a cardio-protective effect after acute myocardial infarction (AMI). To identify whether miR-93-5p-encapsulating exosomes that form ADSCs have a better cardio-protective effect, we investigated the inflammatory factors and miR-30d-5p expression in clinical levels. A rat model of AMI and an in vitro model of hypoxic H9c2 cells were established to study the protective mechanism of miR-93-5p in ischemia-induced cardiac injury. The results show that the expression of inflammatory cytokines and miR-93-5p were increased following AMI in both patients and animal models. Moreover, treatment with ADSC-derived miR-93-5p-containing exosomes has a greater protective effect on infarction-induced myocardial damage than simple exosome processing. Furthermore, in vitro experiments confirmed that the expression of miR-93-5p can significantly suppress hypoxia-induced autophagy and inflammatory cytokine expression by targeting Atg7 and Toll-like receptor 4 (TLR4), respectively, and was confirmed with Atg7 or TLR4 overexpression. The results also show that autophagy activation can promote inflammatory cytokine expression indirectly. Taken together, these results suggest that the miR-93-5p-enhanced ADSC-derived exosomes prevent cardiac injury by inhibiting autophagy and the inflammatory response.

Outcomes after primary coronary intervention with drug-eluting stent implantation in diabetic patients with acute ST elevation myocardial infarction.

BACKGROUND: Drug-eluting stent (DES) has been used widely for the treatment of patients with acute coronary syndrome with or without diabetes mellitus during percutaneous coronary intervention (PCI), but its long-term safety and efficacy in diabetic patients with acute ST elevation myocardial infarction (STEMI) remain uncertain. This study aimed to investigate the clinical outcomes after primary coronary intervention with DES implantation for diabetic patients with acute STEMI, compared with non-diabetic counterparts. METHODS: From December 2004 to March 2006, 56 consecutive diabetic patients (diabetic group) and 170 non-diabetic patients (non-diabetic group) with acute STEMI who underwent primary PCI with DES implantation in 3 hospitals were enrolled. Baseline clinical, angiographic, and procedural characteristics, as well as occurrence of major adverse cardiac event (MACE) including cardiac death, non-fatal recurrent myocardial infarction (re-MI) and target vessel revascularization (TVR) during hospitalization and one-year clinical follow-up were compared between the two groups. RESULTS: Patients in diabetic group were more hyperlipidemic (69.6% and 51.8%, P = 0.03) and had longer time delay from symptom onset to admission ((364 +/- 219) minutes and (309 +/- 223) minutes, P = 0.02) than those in non-diabetic group. The culprit vessel distribution, reference vessel diameter, and baseline TIMI flow grade were similar between the two groups, but multi-vessel disease was more common in diabetic than in non-diabetic group (82.1% and 51.2%, P < 0.001). Despite similar TIMI flow grades between the two groups after stenting, the occurrence of TIMI myocardial perfusion grade (TMPG) = 2 was lower in diabetic group (75.0% vs 88.8% in non-diabetic groups, P = 0.02). The MACE rate was similar during hospitalization between the two groups (5.4% vs 3.5%, P = 0.72), but it was significantly higher in diabetic group (16.1%) during one-year follow-up, as compared with non-diabetic group (6.5%, P = 0.03). The cumulative one-year MACE-free survival rate was significantly lower in diabetic than in non-diabetic group (78.6% vs 90.0%, P = 0.02). Angiographic stent thrombosis occurred in 5.4% and 1.2% of the patients in diabetic and non-diabetic group, respectively (P = 0.19). All of these patients experienced non-fatal myocardial infarction. CONCLUSIONS: Although the early clinical outcomes were similar in diabetic and non-diabetic patients with acute STEMI treated with DES implantation, the cumulative MACE-free survival at one-year follow-up was worse in diabetic than in non-diabetic patients. More effective diabetes-related managements may further improve the clinical outcomes of diabetic cohort suffering STEMI.

miR-26b-5p regulates hypoxia-induced phenotypic switching of vascular smooth muscle cells via the TGF-ß/Smad4 signaling pathway.

Hypoxia contributes to the phenotypic switch of vascular smooth muscle cells (VSMCs). Various microRNAs (miRNAs) participate in this process as post­transcriptional regulators, however the mechanism remains unclear. In the present study, mouse VSMCs (mVSMCs) harvested from aortas were cultured in normoxic and hypoxic conditions, and the mRNA levels of miR-26b-5p, desmin, H­caldesmon and smoothelin were quantified using reverse transcription­quantitative polymerase chain reaction. Following treatment with a miR­26b­5p antagonist (agomir) or non­targeting control (scramble), the cell areas of normoxic and hypoxic mVSMCs were analyzed by immunofluorescence staining. In addition, the protein expression levels of collagen Iα, Smad2/phosphorylated (p)­Smad2, Smad3/p­Smad3 and Smad4 were determined by western blotting. Potential miRNA26b­5p binding sequences in the 3'­untranslated region (UTR) of Smad4 were investigated, and the distribution of Smad4 in mVSMCs was visualized using immunofluorescence methods. Hypoxic mVSMCs exhibited a significant downregulation miR­26b­5p, upregulation of hypoxia inducible factor­1α mRNA and suppression of desmin, H­caldesmon and smoothelin mRNA levels. Additionally, miR­26b­5p agomir reduced the cell area and decreased collagen Iα expression levels in hypoxic mVSMCs compared with normoxic mVSMCs transfected with agomir, and the area was comparable with those of normoxic mVSMCs transfected with agomir or scramble. Furthermore, miR­26b­5p suppressed Smad4 expression in hypoxic mVSMCs, but did not change the expression levels of Smad2 and Smad3, p­Smad2 and p­Smad3, however p­Smad2 and p­Smad3 levels were upregulated in response to hypoxic stimuli. Additionally, the miR­26b­5p agomir caused weak immunoreactivity with Smad4 in hypoxic mVSMCs. The binding motif of miR­26b­5p in the Smad4 3'­UTR was identified as UACUUGA at position 978-984. These findings suggest that miR­26b­5p regulates hypoxia­induced phenotypic switching of VSMCs via the transforming growth factor ß/Smad4 signaling pathway.

miR-103 Regulates Oxidative Stress by Targeting the BCL2/Adenovirus E1B 19 kDa Interacting Protein 3 in HUVECs.

Oxidative stress plays a critical role in cardiovascular diseases. Salidroside, a glycoside from Rhodiola rosea, has been used as an antioxidative therapy for oxidative injury in cardiac diseases. However, the mechanism underlying its antioxidant effect needs to be elucidated. Treatment of HUVECs with H2O2 significantly decreased the expression of miR-103 in a dose- and time-dependent manner, whereas pretreatment with salidroside significantly inhibited this decrease. Subsequent analysis showed that overexpression of miR-103 abrogated cell activity and ROS production induced by H2O2. Bcl2/adenovirus E1B 19 kDa interacting protein 3 (BNIP3) was determined to be a novel miR-103 target in HUVECs. Interestingly, H2O2 treatment upregulated BNIP3 expression; in turn, this effect was inhibited by pretreatment with salidroside. Further studies confirmed that the knockdown of BNIP3 enhanced cell activity and suppressed the ROS production induced by H2O2. These results demonstrated for the first time that salidroside protects HUVECs in part by upregulating the expression of miR-103, which mediates BNIP3 downregulation and plays an important role in the cytoprotective actions.

Intensive-dose atorvastatin regimen halts progression of atherosclerotic plaques in new-onset unstable angina with borderline vulnerable plaque lesions.

To compare the therapeutic effects of intensive versus moderate dosage of atorvastatin regimens in new-onset unstable angina with borderline lesions, 100 patients were randomized to receive either 80 mg/d or 20 mg/d atorvastatin for 9 months. Clinical symptoms, lipid profiles, and coronary stenosis (evaluated by coronary angiography and intravascular ultrasound) were compared to their corresponding baselines within each group and between the 2 groups after 9 months of treatment. The results showed that (1) when compared to their corresponding baselines, both groups exhibited improvement in clinical symptoms, a significant decrease in total cholesterol, triglyceride, low-density lipoprotein cholesterol (LDL-C), and high-sensitivity C-reactive protein (hs-CRP; P < .01) and a significant increase in high-density lipoprotein cholesterol (HDL-C); (2) the improvement in clinical symptoms and the decrease in LDL-C and hs-CRP were significantly greater (P < .01) in the intensive-dose group than in the moderate-dose group; (3) the mean plaque volume did not progress in the intensive-dose group but increased significantly (P < .05) in the moderate-dose group. We conclude that compared to the moderate dose, the intensive-dose regimen significantly improves clinical symptoms, lowers LDL-C and hs-CRP, and halts the progression of borderline atherosclerotic plaques in patients with new-onset unstable angina.

Direct ambulance transport to catheterization laboratory reduces door-to-balloon time in patients with acute ST-segment elevation myocardial infarction undergoing primary percutaneous coronary intervention: the DIRECT-STEMI study.

BACKGROUND: Primary percutaneous coronary intervention (PCI) has been clearly identified as the first therapeutic option for patients with acute ST-segment elevation myocardial infarction (STEMI). The importance of reducing door-to-balloon (D2B) time has gained increased recognition. This study aimed to assess the feasibility, safety and efficacy of the strategy of direct ambulance transportation of patients with acute STEMI to catheterization lab to receive primary PCI. METHODS: The study population included 141 consecutive patients with chest pain and ST-segment elevation who were admitted to the catheterization laboratory directly by the ambulance and underwent primary PCI (DIRECT group). Another 145 patients with STEMI randomly selected from the PCI database, were served as control group (conventional group); they were transported to catheterization laboratory from emergency room (ER). The primary endpoint of D2B time, and secondary endpoint of in-hospital and 30-day major adverse cardiac events (MACE, including death, non-fatal reinfarction, and target vessel revascularization) were compared. RESULTS: Baseline and procedural characteristics between the two groups were comparable, except more patients in the DIRECT group presented TIMI 0-1 flow in culprit vessel at initial angiogram (80.1% and 73.8%, P = 0.04). Comparing to conventional group, the primary endpoint of D2B time was reduced ((54 ± 18) minutes and (112 ± 55) minutes, P < 0.0001) and the percentage of patients with D2B < 90 minutes was increased in the DIRECT group (96.9% and 27.0%, P < 0.0001). The success rate of primary PCI with stent implantation with final Thrombolysis in Myocardial Infarction (TIMI) 3 flow was significantly higher in the DIRECT group (93.8% and 85.2%, P = 0.03). Although no significant difference was found at 30-day MACE free survival rate between the two groups (95.0% and 89.0%, P = 0.06), a trend in improving survival status in the DIRECT group was demonstrated by Kaplan-Meier analysis. CONCLUSION: Direct ambulance transport of STEMI patients to the catheterization laboratory could significantly reduce D2B time and improve success rate of primary PCI and 30-day clinical outcomes.