Identification of macrophage differentiation related genes and subtypes linking atherosclerosis plaque processing and metabolic syndrome via integrated bulk and single-cell sequence analysis.

Metabolic syndrome(MS) is a separate risk factor for the advancement of atherosclerosis(AS) plaque but mechanism behind this remains unclear. There may be a significant role for the immune system in this process. This study aims to identify potential diagnostic genes in MS patients at a higher risk of developing and progressing to AS. Datasets were retrevied from gene expression omnibus(GEO) database and differentially expressed genes were identified. Hub genes, immune cell dysregulation and AS subtypes were identified using a conbination of muliple bioinformatic analysis, machine learning and consensus clustering. Diagnostic value of hub genes was estimated using a nomogram and ROC analysis. Finally, enrichment analysis, competing endogenous RNA(ceRNA) network, single-cell RNA(scRNA) sequencing analysis and drug-protein interaction prediction was constructed to identify the functional roles, potential regulators and distribution for hub genes. Four hub genes and two macrophage-related subtypes were identified. Their strong diagnostic value was validated and functional process were identified. ScRNA analysis identified the macrophage differentiation regulation function of F13A1. CeRNA network and drug-protein binding modes revealed the potential therapeutic method. Four immune-correlated hub genes(F13A1, MMRN1, SLCO2A1 and ZNF521) were identified with their diagnostic value being assesed, which F13A1 was found strong correlated with macrophage differentiation and could be potential diagnostic and therapeutic marker for AS progression in MS patients.

Native mitral valve fungal endocarditis caused by Aspergillus fumigatus: A case report.

INTRODUCTION: Aspergillus endocarditis is a rare fungal infection associated with a poor prognosis. Most cases of Aspergillus endocarditis involve prosthetic valves, with native valve involvement being rarely reported. CASE PRESENTATION: A 53-year-old asian female patient presented with fever, chills, dyspnea, generalized fatigue, and significant weight loss one month after undergoing left lower lobectomy for a pulmonary abscess. Echocardiogram showed a large mobile vegetation with a broad base on the anterior leaflet of the mitral valve, resembling atrial myxoma. Despite negative blood cultures, circulating DNA of Aspergillus fumigatus was detected by metagenome Next Generation Sequencing, prompting the initiation of empiric antifungal therapy with voriconazole. Emergency surgery, involving thorough debridement and mitral valve replacement, was successfully performed. Indefinite fungal suppression therapy with oral voriconazole is continued to mitigate the risk of recurrence. The patient survived with no signs of Aspergillus disease recurrence for four years. CLINICAL DISCUSSION: Diagnosis of Aspergillus endocarditis requires a high index of suspicion and is often delayed due to consistently negative results from blood cultures. Non-culture-based methods, particularly metagenome Next-Generation Sequencing, play a crucial role in early diagnosis and therapeutic decision-making. Surgical debridement and valve replacement are imperative for survival in cases of Aspergillus endocarditis. Voriconazole should be considered the primary fungicidal agent for its treatment. Moreover, lifelong fungal suppression therapy is strongly recommended for all survivors to ensure long-term survival and minimize the risk of recurrence. CONCLUSION: Despite grim prognosis associated with Aspergillus endocarditis, patients can attain long-term survival through meticulous surgical debridement and lifelong antifungal therapy.

Inflammatory indicator levels in patients undergoing aortic valve replacement via median sternotomy with preoperative anxiety and postoperative complications: a prospective cohort study.

OBJECTIVE: This study was performed to evaluate the association of preoperative anxiety with inflammatory indicators and postoperative complications in patients undergoing scheduled aortic valve replacement surgery. METHODS: A prospective cohort study was performed. The Hamilton Anxiety Scale was used to assess preoperative anxiety. The serum white blood cell (WBC) count and concentrations of C-reactive protein, interleukin (IL)-6, and IL-8 were measured 1 day preoperatively and 3 and 7 days postoperatively. Postoperative complications were also recorded. RESULTS: Seventy-three patients were included. The incidence of preoperative anxiety was 30.1% (22/73). The payment source was the only independent risk factor for preoperative anxiety. The incidence of postoperative complications was lowest in the mild anxiety group. The WBC count 3 days postoperatively was significantly lower in the mild than moderate-severe anxiety group. The IL-8 concentration 1 day preoperatively was highest in the no anxiety group. CONCLUSIONS: Mild preoperative anxiety might help to improve clinical outcomes. However, further investigations with more patients are warranted. Patients with different degrees of anxiety may have different levels of inflammatory cytokines.

Modified unicaval drainage in reoperative isolated tricuspid valve repair via totally thoracoscopic approach.

AIM: The aim of this study was to investigate the feasibility, safety, and clinical effect of modified unicaval drainage for thoracoscopic reoperative isolated tricuspid valve repair, compared with conventional bicaval drainage. METHODS: A total of 45 consecutive cases of patients who underwent thoracoscopic reoperative isolated tricuspid valve repair on beating-heart were enrolled and divided into two groups according to the different venous drainage (Group A: modified unicaval drainage, Group B: conventional bicaval drainage). A retrospective analysis of perioperative data and clinical outcomes were performed and all the surviving cases were followed up. Re-evaluation of echocardiography and electrocardiogram was performed prior to discharge, and at first month, sixth month, and every year follow-up. RESULTS: The overall postoperative 30-day mortality was 4.5% in Group A and 8.7% in Group B. The postoperative tricuspid valve regurgitation grade of both groups decreased significantly from preoperative regurgitation grade, p < 0.001, without intergroup significant difference, p = 0.815. Follow-up duration ranged from 6 to 38 months, there was one death at 24 months in Group A, and another at 9 months in Group B, respectively. Nobody from both groups experienced reintervention for residual tricuspid regurgitation. No significant difference could be identified about the incidence of postoperative morbidities and follow-up adverse events. CONCLUSION: Both strategies of caval venous drainage can provide satisfactory exposure for thoracoscopic reoperative isolated tricuspid valve repair and equivalent favorable postoperative outcome. And the modified unicaval drainage group may even preserve the anesthetic time and decrease the risk of iatrogenic jugular injury, achieving a more simplified procedure with better cosmetic outcome.

Prediction value of pulmonary hypertension in newly identified left ventricular dysfunction among adult patients after patent ductus arteriosus closure.

The present study aimed to propose the pulmonary hypertension for predicting left ventricular dysfunction in adults after patent ductus arteriosus closure. A total of 183 patients (age ≥18 years) after patent ductus arteriosus occlusion were retrospectively collected in this study. In brief, pre-, post-procedure and short-term follow-up transthoracic echocardiography were performed. Simpson's method was used to measure the left ventricular ejection fraction (LVEF), and LVEF less than 50% after procedure was utilized as a criterion to identify left ventricular dysfunction. As a result, 36 (19.67%) patients developed newly identified left ventricular dysfunction. The rate of newly identified left ventricular dysfunction was significantly higher in moderate or severe pulmonary hypertension groups compared to the groups of mean pulmonary artery pressure (mPAP) <25 mmHg (P < .001). Logistic regression analysis showed that elevated mPAP ( ≥25 mmHg) was an independent predictive value for newly identified left ventricular dysfunction (OR = 3.584, 95%CI: 1.186-10.832, P = .024) after adjusting confounders. The ROC curve revealed a good discrimination power for predicting newly identified left ventricular dysfunction (AUC = 0.924, 95%CI: 0.885-0.963, P < .001). Taken together, newly identified left ventricular dysfunction after patent ductus arteriosus closure was prevalent in patients with elevated mPAP. The pre-procedure elevated mPAP is an independent risk factor for the prediction of the newly identified left ventricular dysfunction in adult patients undergoing percutaneous patent ductus arteriosus closure. It is feasible to propose a risk model for predicting post-procedure left ventricular dysfunction and a heart function monitoring in pulmonary hypertension patients.

Results of surgery on adults with functional single ventricle without prior cardiac surgery in childhood.

OBJECTIVES: Patients with unoperated functional single ventricle (FSV) rarely survive into adulthood with good functional status and there are few reports about surgical results of adult patients with FSV. This study retrospectively reviews our experience with surgery in adult patients with FSV. METHODS: From January 2008 to September 2017, 65 adult patients with FSV underwent surgery in our hospital. Twenty underwent Blalock-Taussig shunt or bidirectional Glenn procedures in other hospitals prior, and four were lost to follow-up. Finally, 41 patients were included in this study. RESULTS: The early postoperative mortality was 7.3% (3/41). Postoperative systemic arterial oxygen saturation (SpO2 , 83.7% ± 4.8%) was significantly higher than preoperative SpO2 (77.9% ± 10.1%, P < .01). The mean follow-up time was 3.9 ± 3.1 years (range 1-11 years). There was only one case of late mortality and massive hemoptysis was the cause of death. Right ventricular morphology and severe atrioventricular valve regurgitation (AVVR) were the risk factors of postoperative death for patients with pulmonary stenosis(PS). There was no death case in patients who received Fontan procedure. In a follow-up, we found the grade of AVVR was reduced and the grade of heart function (New York Heart Association) was improved. CONCLUSIONS: Adult patients with FSV can also undergo surgery. The mortality was acceptable and late results were satisfactory. After surgery, oxygen saturations increased, grades of AVVR decreased and the heart functions improved. Right ventricular morphology and severe AVVR were risk factors for patients with PS.

Mitral valve replacement via minimally invasive totally thoracoscopic surgery versus traditional median sternotomy: a propensity score matched comparative study.

BACKGROUND: To compare surgical outcomes after mitral valve replacement via either minimally invasive thoracoscopic (MIs) or traditional median sternotomy (MS) surgery and determine the short- and mid-term clinical outcomes of the MI approach. METHODS: All patients who received either MIs (n=405) or MS (n=691) mitral valve replacement surgery at the Guangdong Cardiovascular Institute between January 2012 and July 2015 were analyzed for outcome differences due to surgical approach using propensity score matching. The best 202 matches from the MI group and the MS group were analyzed. The clinical data of the two groups were collected, including preoperative cardiac function, operative data, postoperative complications, and follow-up. RESULTS: A final total of 404 patients were included in this study after propensity score matching; the MIs group and the MS group each contained 202 patients. The two groups were similar in age, weight, pathological changes, and surgical approach. Compared with the MS group, the MIs group had a longer cardiopulmonary bypass time (P<0.001), aortic cross-clamping time (P<0.001), and total procedure time (P<0.001). There were no significant differences between the groups regarding in-hospital mortality, stroke, pneumonia, acute renal failure, arrhythmia, and chylothorax. The MS group had significantly more patients with poor wound healing than the MIs group (P=0.004). The MI group had a lower rate of transfusion (P=0.037), shorter ventilation time (P=0.041), shorter ICU stay (P=0.033), reduced chest tube drainage and length of chest tube stay (P<0.001), and shorter hospital stay (P<0.001). There was no significant difference between the groups in hospital re-admission for bleeding, but the total hospitalization cost was higher in the MIs group (P=0.002). The mean follow-up was 26.59±12.33 months, the 1-year postoperative survival rate was 98.86%, and the overall survival rate was 97.44%. Compared with the MS group, the MIs group recovered earlier (P<0.05), and returned to work or study earlier (P<0.05). More patients in the MIs group were satisfied with the wound (P<0.001). The MS group had a higher incidence of postoperative osteomyelitis than the MIs group (P=0.028). There were no significant differences between groups in rates of mortality, stroke, pacemaker, reoperation, or 36-item Short Form Health Survey score. CONCLUSIONS: Compared with the MS approach, the MIs method of mitral valve replacement has longer cardiopulmonary bypass time and aortic cross-clamp time; however, it does not increase the risk of mortality and complications. Furthermore, MIs causes less trauma, fewer transfusions, less wound infection, faster recovery, faster return to work or study, and greater satisfaction with the incision in the mid-term. MI cardiac surgery is safe, effective, and feasible.

Minimally invasive, multi-disciplinary approach for surgical management of a mediastinal congenital bronchogenic cyst in a 6-month-old infant.

We present a case of prenatal diagnosis of a mediastinal cyst by ultrasound, confirmed during infancy through computed tomography (CT) and magnetic resonance imaging (MRI). A 6-month-old male infant was admitted to the hospital. A mid-mediastinal cyst was detected through a province-wide fetal ultrasonography screening program. During the infancy stage, the CT scan and the MRI confirmed the finding of a mediastinal cyst. Based on the findings on prenatal ultrasonography and postnatal imaging studies (CT, MRI), a benign mediastinal cyst was suspected. The cyst was below the tracheal carina, and the patient developed symptoms of respiratory distress. Owing to the enlargement trend of the cyst, the respiratory distress it has caused, and the anxiety it caused to the patient's family, a multi-disciplinary conference reached the consensus that surgical resection is the treatment of choice and a carina-approach mediastinal lesion resection via video-assisted thoracoscopic surgery (VATS) was performed. The cyst was removed successfully. Although this report is of a single case and follow-up duration is not long enough, we nevertheless make the first move to improve the pattern to a feasible, reliable, and efficient one, which could be used to treat similar patients.

Assessing the impact of total extracorporeal circulation on hemodynamics in an ovine fetal model.

The present study aimed to evaluate the impact of total extracorporeal circulation on hemodynamics and placental function in an ovine fetal model. Mid-term ovine fetuses (n=6) underwent extracorporeal circulation (30 min), cardioplegic arrest (20 min) and monitoring (120 min). The ascending aorta and umbilical cords of the fetuses were occluded during the bypass and an extracorporeal membrane oxygenator was used as the oxygen source. Biventricular intracardiac pressures, echocardiographic data, blood gas levels and placental function variables were recorded, and statistical analysis was performed using the repeated-measure analysis of variance test. The data indicated that fetal heart rate and blood pressure at 30, 60, 90 and 120 min following the bypass were stable relative to pre-arrest baseline (pre-bypass) values (P>0.05). However, end diastolic pressures in the ovine right ventricles post-bypass were significantly increased at 30, 60, 90 and 120 min relative to pre-bypass pressures (P<0.05). The pulsatility index also increased at 30 min post-bypass relative to the pre-bypass score (0.91±0.06 vs. 0.61±0.14; P=0.007). The mean resistivity index at all time points post-bypass was consistent with the pre-bypass score (P>0.05), while the mean Tei index values for the left and right ventricles post-bypass were significantly higher at all time points relative to pre-bypass values (P<0.05). The pre-bypass fetal blood pH, SaO2, base excess and lactate values were maintained during arrest (P>0.05). Fetal hemodynamics and placental function additionally remained stable for up to 2 h upon reperfusion following total extracorporeal circulation and cardioplegic arrest. Collectively these data suggest that the reproducible ovine fetal model may be useful in the evaluation of fetal cardiac surgery.

iPSC-Derived Regulatory Dendritic Cells Inhibit Allograft Rejection by Generating Alloantigen-Specific Regulatory T Cells.

Regulatory dendritic cell (DCregs)-based immunotherapy is a potential therapeutic tool for transplant rejection. We generated DCregs from murine induced pluripotent stem cells (iPSCs), which could remain in a "stable immature stage" even under strong stimulation. Harnessing this characteristic, we hypothesized that iPS-DCregs worked as a negative vaccine to generate regulatory T cells (Tregs), and induced donor-specific allograft acceptance. We immunized naive CBA (H-2Kk) mice with B6 (H-2Kb) iPS-DCregs and found that Tregs (CD4+CD25+FOXP3+) significantly increased in CBA splenocytes. Moreover, immunized CBA recipients permanently accepted B6 cardiac grafts in a donor-specific pattern. We demonstrated mechanistically that donor-type iPS-DCregs triggered transforming growth factor ß1 secretion, under which the donor-antigen peptides directed naive CD4+ T cells to differentiate into donor-specific FOXP3+ Tregs instead of into effector T cells in vivo. These findings highlight the potential of iPS-DCregs as a key cell therapy resource in clinical transplantation.

MicroRNA-34a targets regulator of calcineurin 1 to modulate endothelial inflammation after fetal cardiac bypass in goat placenta.

INTRODUCTION: Placental dysfunction characterized by vascular endothelial inflammation is one of the most notable responses to fetal cardiac bypass. Regulator of calcineurin 1 (RCAN1) is an important regulator of inflammatory responses. MicroRNAs (miRNAs) are essential post-transcriptional modulators of gene expression, and miRNA-34a (miR-34a) was showed to activate vascular endothelial inflammation. We hypothesized that miR-34a may be a key regulator of placental dysfunction after fetal cardiac bypass. METHODS: We evaluated miRNA expression in goat placentas via small RNA sequencing, quantitative real-time polymerase chain reaction (qRT-PCR) and in situ hybridization. Expression of miRNA target genes was determined via bioinformatics analyses and dual luciferase reporter assays. Furthermore, human umbilical vein endothelial cells (HUVECs) were transfected with miR-34a or a control sequence. The RCAN1, nuclear factor of activated T-cells (NFATC1) and nuclear factor kappa-B (NF-κB) levels in HUVECs and placentas were evaluated via Western blot and qRT-PCR. RESULTS: We demonstrated that miR-34a was highly enriched in goat placenta after cardiopulmonary bypass. Moreover, RCAN1 was identified as a novel direct target of miR-34a. Transfection of miR-34a led to decreased RCAN1 expression and increased NFATC1 and NF-κB expression in HUVECs. Conversely, inhibition of miR-34a rescued RCAN1 expression and reduced NFATC1 and NF-κB expression in HUVECs. CONCLUSIONS: We demonstrated a remarkable role of miR-34a as a regulator of NFATC1-associated placental inflammation through direct targeting of RCAN1. MiR-34a could serve as a novel therapeutic target for limiting the progression of placental inflammation after fetal cardiac bypass.

Echocardiographic Findings of an Anomalous Origin of the Left Coronary Artery in Children and Adolescents: Real or Fake?

An anomalous origin of the left coronary artery (LCA) is a relatively uncommon congenital heart defect that can lead to myocardial ischemia and sudden cardiac death. An LCA arising from the pulmonary artery and an LCA arising from the opposite sinus of Valsalva are the common types of anomalous origins of the LCA. Echocardiographic assessment of the coronary arteries is an important component of the routine cardiovascular evaluation, but echocardiographic "pseudo images" of LCA origination can be present in some patients. Detection of an anomalous origin of the LCA remains a challenge to sonographers.

Giant Left Ventricular Myxoma With Obstruction of the Left Ventricular Outflow Tract.

A rare case of giant left ventricular (LV) myxoma with obstruction of the left ventricular outflow tract (LVOT) was found incidentally on echocardiography in an asymptomatic 21-year-old woman. The tumor was successfully resected through transatrial septal access.

The protective effect of trimetazidine on myocardial ischemia/reperfusion injury through activating AMPK and ERK signaling pathway.

INTRODUCTION: Trimetazidine (TMZ) is an anti-anginal drug that has been widely used in Europe and Asia. The TMZ can optimize energy metabolism via inhibition of long-chain 3-ketoacyl CoA thiolase (3-KAT) in the heart, with subsequent decrease in fatty acid oxidation and stimulation of glucose oxidation. However, the mechanism by which TMZ aids in cardioprotection against ischemic injury has not been characterized. AMP-activated protein kinase (AMPK) is an energy sensor that controls ATP supply from substrate metabolism and protects heart from energy stress. TMZ changes the cardiac AMP/ATP ratio by modulating fatty acid oxidation, thereby triggering AMPK signaling cascade that contributes to the protection of the heart from ischemia/reperfusion (I/R) injury. METHODS: The mouse model of in vivo regional ischemia and reperfusion by the ligation of the left anterior descending coronary artery (LAD) was used for determination of myocardial infarction. The infarct size was compared between C57BL/6J WT mice and AMPK kinase dead (KD) transgenic mice with or without TMZ treatment. The ex vivo working heart perfusion system was used to monitor the effect of TMZ on glucose oxidation and fatty acid oxidation in the heart. RESULTS: TMZ treatment significantly stimulates cardiac AMPK and extracellular signal-regulated kinase (ERK) signaling pathways (p<0.05 vs. vehicle group). The administration of TMZ reduces myocardial infarction size in WT C57BL/6J hearts, the reduction of myocardial infarction size by TMZ in AMPK KD hearts was significantly impaired versus WT hearts (p<0.05). Intriguingly, the administration of ERK inhibitor, PD98059, to AMPK KD mice abolished the cardioprotection of TMZ against I/R injury. The ex vivo working heart perfusion data demonstrated that TMZ treatment significantly activates AMPK signaling and modulating the substrate metabolism by shifting fatty acid oxidation to glucose oxidation during reperfusion, leading to reduction of oxidative stress in the I/R hearts. Therefore, both AMPK and ERK signaling pathways mediate the cardioprotection of TMZ against ischemic injury. The metabolic benefits of TMZ for angina patients could be due to the activation of energy sensor AMPK in the heart by TMZ administration.

Bilateral subclavian vein sheaths for superior vena cava drainage during thoracoscopic repair of atrial septal defects: cosmetic outcomes, safety and effectiveness.

OBJECTIVE: To investigate the cosmetic outcomes, safety and effectiveness of using bilateral subclavian vein sheaths for superior vena cava drainage during thoracoscopic repair of atrial septal defects. METHODS: Sixty-one consecutive adults scheduled for thoracoscopic repair of atrial septal defects between July 2012 and June 2013 were randomized into two groups: one group underwent placement of a 16 Fr percutaneous superior vena cava cannula (n = 30) and the other group underwent placement of bilateral 8 Fr subclavian vein sheaths (n = 31) for superior vena cava drainage during peripheral cardiopulmonary bypass. The perioperative data, central venous pressure during cardiopulmonary bypass, complications and the patient satisfaction scale scores for the incisions were compared between the two groups. RESULTS: The theoretical cardiopulmonary bypass flow rate was reached without complications in all patients. The average central venous pressure during cardiopulmonary bypass was not significantly different between the two groups [(6.9 ± 3.1) mmHg vs. (7.0 ± 3.5) mmHg, p=0.92]. The patient satisfaction scale scores for the incisions were significantly higher in the patients who underwent placement of bilateral subclavian vein sheaths than in the patients who underwent placement of a percutaneous superior vena cava cannula [(2.81 ± 0.75) vs. (2.07 ± 0.74), p<0.001]. CONCLUSIONS: Placement of bilateral subclavian vein sheaths is a safe and effective alternative to placement of a percutaneous superior vena cava cannula for superior vena cava drainage during thoracoscopic repair of atrial septal defects and results in greater patient satisfaction with the cosmetic outcome.

[Analysis of environmental risk factors in congenital heart defects].

OBJECTIVE: To explore the environmental risk factors of different categories of congenital heart defects (CHD) and provide evidence for further risk factors and prevention research of CHD phenotypes. METHODS: Data of Guangdong CHD Register Study from 2004 to 2012 were used. In the study, 3 038 CHD cases and 3 038 paired controls from 34 hospitals distributed in 17 cities were registered and related information were collected using uniform, and structured questionnaires. All the CHD phenotypes were coded according to the International Classification of Diseases 10th Revision (ICD-10) and classified into 6 categories according to their pathological features. Univariate analyses were adopted to filter potential risk factors for each category of CHD. Then multivariate conditional Logistic regression was used to calculate the odds ratios of the risk factors for each category of CHD. RESULTS: The risk factors for left-to-right shunt CHD included low (OR=2.63, 95%CI:2.04-3.39) or over birth weight (OR=2.21, 95%CI: 1.47-3.32), premature delivery (OR=1.95, 95%CI: 1.53-2.49), polyembryony (OR=1.99, 95%CI: 1.22-3.26), maternal low education, mother as factory worker (OR=1.62, 95%CI: 1.32-1.98), parity≥2 (OR=1.38, 95%CI: 1.13-1.69), maternal abnormal reproduction history (OR=2.29, 95%CI: 1.75-3.01), fever (OR=2.38, 95%CI: 1.26-4.48), virus infection (OR=1.80, 95%CI: 1.29-2.51), medicine usage (OR=1.73, 95%CI: 1.11-2.69), passive smoking (OR=1.69, 95%CI: 1.26-2.29), chemical agent contact (OR=8.71, 95%CI: 2.33-32.58), living in newly decorated houses (OR=2.56, 95%CI: 1.60-4.09) or room close to the main road (OR=1.40, 95%CI: 1.14-1.72) in the first 3 months of pregnancy and father as factory worker (OR=1.46, 95%CI: 1.23-1.73). The risk factors for pulmonary outflow tract obstruction CHD included low (OR=5.98, 95%CI: 2.88-12.44) or over birth weight (OR=6.56, 95%CI:1.19-36.26), maternal low education, parity≥2 (OR=2.08, 95%CI: 1.03-4.22), virus infection in the first 3 months of pregnancy (OR=4.30, 95%CI: 1.27-13.45). The risk factors for left ventricular outflow tract obstruction CHD included father as factory worker (OR=6.01, 95%CI:1.05-34.59). The risk factors for transposition of the great arteries included low birth weight (OR=12.93, 95%CI:1.14-146.26), maternal low education, mother as factory worker (OR=3.69, 95%CI:1.53-8.91). The risk factors for conditions with intra cardiac mixing of oxygenated and deoxygenated blood included parity=2 (OR=3.45, 95%CI: 1.42-8.38). The risk factors for other CHD included over birth weight (OR=4.87, 95%CI: 1.19-19.94), maternal abnormal reproduction history (OR=2.96, 95%CI: 1.14-7.68), virus infection (OR=4.92, 95%CI: 1.56-15.47), medicine usage (OR=4.90, 95%CI: 1.22-19.77) or passive smoking (OR=10.31, 95%CI: 1.25-85.05) in the first 3 months of pregnancy. CONCLUSION: The environmental risk factors were discrepant among different categories of CHD. Further risk factors study of CHD phenotypes should be performed specially. To prevent CHD, attention should be paid to the risk factors which are related to multi or complex categories of CHD.

MicroRNA-377 regulates mesenchymal stem cell-induced angiogenesis in ischemic hearts by targeting VEGF.

MicroRNAs have been appreciated in various cellular functions, including the regulation of angiogenesis. Mesenchymal-stem-cells (MSCs) transplanted to the MI heart improve cardiac function through paracrine-mediated angiogenesis. However, whether microRNAs regulate MSC induced angiogenesis remains to be clarified. Using microRNA microarray analysis, we identified a microRNA expression profile in hypoxia-treated MSCs and observed that among all dysregulated microRNAs, microRNA-377 was decreased the most significantly. We also validated that vascular endothelial growth factor (VEGF) is a target of microRNA-377 using dual-luciferase reporter assay and Western-blotting. Knockdown of endogenous microRNA-377 promoted tube formation in human umbilical vein endothelial cells. We then engineered rat MSCs with lentiviral vectors to either overexpress microRNA-377 (MSC miR-377) or knockdown microRNA-377 (MSC Anti-377) to investigate whether microRNA-377 regulated MSC-induced myocardial angiogenesis, using MSCs infected with lentiviral empty vector to serve as controls (MSC Null). Four weeks after implantation of the microRNA-engineered MSCs into the infarcted rat hearts, the vessel density was significantly increased in MSC Anti-377-hearts, and this was accompanied by reduced fibrosis and improved myocardial function as compared to controls. Adverse effects were observed in MSC miR-377-treated hearts, including reduced vessel density, impaired myocardial function, and increased fibrosis in comparison with MSC Null-group. These findings indicate that hypoxia-responsive microRNA-377 directly targets VEGF in MSCs, and knockdown of endogenous microRNA-377 promotes MSC-induced angiogenesis in the infarcted myocardium. Thus, microRNA-377 may serve as a novel therapeutic target for stem cell-based treatment of ischemic heart disease.

Mesenchymal stem cells attenuate rat graft-versus-host disease.

Mesenchymal stem cells (MSCs) derived from bone marrow are feasible for the exertion of a powerful immunoregulatory effect and thus shall hold a curative potency in T lymphocyte-dependent pathologies. This current article is intended to describe the method to investigate that MSCs might take advantage of regulation in graft-versus-host disease (GvHD), a major etiology of attack rate and lethality post allogeneic hematopoietic stem cell transplantation (HSCT). MSCs were isolated from Lewis rat bone morrow and cultured for 4 weeks. The purification of enriched conventional MSCs and macrophages was achieved by autoMACS. Using the limiting dilution method, MSCs were cloned and then expanded until more than 6 months. The cultured MSCs showed a typical spindle-shaped morphology and immunophenotypes, lack of CD45 and CD11b/c expression. MSCs are also known for their ability to differentiate into adipocytes. MSCs, like macrophages, exhibit the immunomodulatory propensity to inhibit T lymphocyte proliferation. Following the adoptive transfer, MSCs regulate systemic Lewis to (Lewis × DA) F1 rat GvHD. Meanwhile, the cloned MSCs surprisingly enhanced T cell proliferation in vitro and yielded no clinical benefit in regard to the incidence or severity of GvHD. This is in contradistinction to the immunosuppressive activities of MSCs as conventionally described. Hence, this rat GvHD model treated with MSCs has shown intriguing differences in the regulatory effects of lymphocyte proliferation and GvHD repression between short-term cultured conventional MSCs and cloned MSCs.

Alpha1 catalytic subunit of AMPK modulates contractile function of cardiomyocytes through phosphorylation of troponin I.

AIMS: The specific role of AMPKα1 or AMPKα2 in mediating cardiomyocyte contractile function remains elusive. The present study investigated how AMPK activation modulates the contractility of isolated cardiomyocytes. MAIN METHODS: Mechanical properties and intracellular Ca(2+) properties were measured in isolated cardiomyocytes. The stress signaling was evaluated using western blot and immunoprecipitation analysis. KEY FINDINGS: AMPK activator, A-769662 induced maximal velocity of shortening (+dL/dt) and relengthening (-dL/dt), peak height and peak shortening (PS) amplitude in both WT and AMPKα2 KO cardiomyocytes, but did not affect time-to-90% relengthening (TR90). AMPK KD cardiomyocytes demonstrated contractile dysfunction compared with cardiomyocytes from WT and AMPKα2 KO hearts. However, the rise of intracellular Ca(2+) levels as well as intracellular ATP levels has no significant difference among WT, AMPKα2 KO and AMPK KD groups with and without the presence of A-769662. Besides, WT, AMPKα2 KO and AMPK KD group displayed a phosphorylated AMPK and downstream acetyl-CoA carboxylase (ACC) phosphorylation. Interestingly, A-769662 also triggered troponin I (cTnI) phosphorylation at Ser(149) site which is related to contractility of cardiomyocytes. Furthermore, the immunoprecipitation analysis revealed that AMPKα1 of cardiomyocytes was phosphorylated by A-769662. SIGNIFICANCE: This is the first study illustrating that activation of AMPK plays a significant role in mediating the contractile function of cardiomyocytes using transgenic animal models. AMPK activator facilitates the contractility of cardiomyocytes via activating AMPKα1 catalytic subunit. The phosphorylation of cTnI by AMPK could be a factor attributing to the regulation of contractility of cardiomyocytes.