Decreased expression of RPL15 and RPL18 exacerbated the calcification of valve interstitial cells during aortic valve calcification.

Calcific aortic valve disease (CAVD) is the most common valvular heart disease, with an increasing prevalence due to an aging population. The pathobiology of CAVD is a multifaceted and actively regulated process, but the detailed mechanisms have not been elucidated. The present study aims to identify the differentially expressed genes (DEGs) in calcified aortic valve tissues, and to analyze the correlation between DEGs and clinical features in CAVD patients. The DEGs were screened by microarray in normal and CAVD groups (n = 2 for each group), and confirmed by quantitative real-time polymerase chain reaction in normal (n = 12) and calcified aortic valve tissues (n = 34). A total of 1048 DEGs were identified in calcified aortic valve tissues, including 227 upregulated mRNAs and 821 downregulated mRNAs. Based on multiple bioinformatic analyses, three 60S ribosomal subunit components (RPL15, RPL18, and RPL18A), and two 40S ribosomal subunit components (RPS15 and RPS21) were identified as the top 5 hub genes in the protein-protein interaction network of DEGs. The expression of RPL15 and RPL18 was also found significantly decreased in calcified aortic valve tissues (both p < .01), and negatively correlated with the osteogenic differentiation marker OPN in CAVD patients (both p < .01). Moreover, inhibition of RPL15 or RPL18 exacerbated the calcification of valve interstitial cells under osteogenic induction conditions. The present study proved that decreased expression of RPL15 and RPL18 was closely associated with aortic valve calcification, which provided valuable clues to find therapeutic targets for CAVD.

Four novel suture-sealing techniques to repair varying size paravalvular leaks.

BACKGROUND: Paravalvular leak (PVL) is a well-known complication of aortic valve replacement. Currently, there is no consensus on optimal intraoperative management of patients with mild-to-moderate or moderate PVL. TECHNIQUE: In this paper we present four novel surgical techniques, each combining suturing with sealing technique, to repair aortic PVLs, nullifying the need to replace the prosthesis. CONCLUSION: These techniques will offer cardiac surgeons new alternatives to the repair techniques currently used.

Small Cavity of Left Ventricle Does Not Affect Short-term Outcome in Patients with Rheumatic Mitral Valve Stenosis Undergoing Mitral Valve Replacement.

BACKGROUND: Small cavity left ventricle (SCLV) may affect the clinical outcomes of patients undergoing mitral valve replacement (MVR). This study aims to investigate the incidence of SCLV in patients with rheumatic mitral valve stenosis undergoing MVR and analyze its effect on short-term patient outcomes. METHODS: We retrospectively examined all consecutive patients with isolated or concomitant MVR for rheumatic mitral valve stenosis in our center from 2013 to 2018. SCLV was defined as end-diastolic volume index ≤ 50 ml/m2. After inclusion and exclusion, a total of 1,437 patients were analyzed. The baseline information was collected and compared between SCLV and non-SCLV patients. Multivariate logistic regression analysis was conducted to determine the effect of SCLV on early mortality. RESULTS: A total of 1,437 patients were included in the study. SCLV was detected in 13.57% of the patients. Compared with the non-SCLV group, patients with SCLV were smaller-sized and primarily female. There were no significant differences between SCLV and non-SCLV patients regarding major postoperative complications, nor were there incidence of prosthesis-patient mismatch. Logistic regression analysis showed that SCLV was not a risk factor for short-term mortality (P = 0.998). CONCLUSIONS: Our results demonstrated that SCLV was not associated with poorer early outcomes after MVR surgery in patients with rheumatic mitral valve stenosis.

microRNA-148a-3p inhibited the proliferation and epithelial-mesenchymal transition progression of non-small-cell lung cancer via modulating Ras/MAPK/Erk signaling.

Son of sevenless (SOS) is one of the guanine nucleotide exchange factors that can regulate the mitogen-activated protein kinase/extracellular signal regulated kinase signal pathway via controlling the activation of Ras. microRNAs are key regulon of gene expression and would be treated as tumor biomarkers or therapeutic targets. In this study, we find that miR-148a-3p acts as a tumor-suppressor in the development and progression of non-small-cell lung cancer (NSCLC). miR-148a-3p inhibits NSCLC cells proliferation and epithelial-mesenchymal transition by reducing the expression of SOS2, which refers Ras activating. Our findings demonstrate that the miR-148a-3p may play a significant role in NSCLC including the kind of lung cancer with K-Ras gene mutation, and it exerted the tumor inhibitor function by targeting SOS2. Because of that, miR-148a-3p and SOS2 may be an efficient target in developing more useful therapies against NSCLC.

A new technique of managing paravalvular leak using a folding pericardium patch.

Paravalvular leakage (PVL) is one of the most well-recognised complications of prosthetic valve replacement. The size of the leakage is usually about one to two stitches. We would like to introduce a new technique to manage this complication by using a folding pericardium patch, which can surely overcome the disadvantage of second-time valve replacement. By now, we have applied this new technique to at least four cases, all of them worked well. Thus, we present our new technique that can be considered as a good alternative management of intraoperative PVLs, especially in aortic position.

Modified band annuloplasty technique for functional tricuspid regurgitation repair in patients with grossly dilated annuli: The three-suture junctional continuous suture band annuloplasty technique.

Functional tricuspid regurgitation (FTR) is the most common of all tricuspid dysfunctions. Ring annuloplasty is an effective treatment strategy for FTR. Currently, the most commonly used suture method for tricuspid ring annuloplasty is the interrupted U-shaped suture method. However, when tricuspid annuli are grossly dilated (septal segments > 60 mm), interrupted sutures are insufficient in avoiding the folding over of the annulus or the tearing of sutures. Therefore, we recommend a new band suture technique; namely, the three-suture junctional continuous suture band annuloplasty technique.

Surgical management of aorta-pulmonary vein fistulas.

We report two patients with aorta-pulmonary vein fistulas and discuss the surgical management of these congenital lesions.

Giant Left Atrial Appendage Aneurysm: Surgical Treatment to Prevent Potential Complications.

Left atrial appendage aneurysm (LAAA) is a rare anomaly, which predisposes to hazardous cardiovascular events. We present a rare case of a 26-year-old female with a giant left atrial appendage aneurysm. The left atrial appendage was incidentally detected during her pregnancy. Six months later after her parturition, the patient was referred to our department and successfully received surgical treatment prophylactically to prevent potential complications. To the best of our knowledge, only about 100 cases of LAAA have been reported.

Cardiac Papillary Fibroelastoma with Coronary Artery Anomaly: A Case Report.

Primary cardiac tumors are extremely rare with occurrence range of about 0.0017-0.28%. Papillary fibroelastoma is a benign cardiac neoplasms. Improvement in the early diagnosis has been made possible with the help of high-resolution imaging technology, such as transesophageal echocardiography, combined with ischemic or embolic complications which patients typically present with clinically. We herein present a 51-year-old female patient with a papillary fibroelastoma on the aortic cusp, with its origin from the left coronary sinus. Her only clinical manifestation was angina-like chest pain and syncope. Surgical resection with aortic valve replacement due to the defect as a result of the resected tumor was performed with the patient on cardiopulmonary bypass. The patient recovered uneventfully and was discharged.  A 2-year follow-up showed an intact valve without tumor recurrence.

A Giant Coronary Sinus Aneurysm with Secondary Vena Cava Aneurysms.

Coronary sinus aneurysm (CSA) is an extremely rare entity. Herein, we present an unusual case of an 18-year-old symptomatic female patient with a giant CSA. Secondary vena cava aneurysms were also manifested. The final diagnosis was confirmed by enhanced computed tomography (CT) and cardiac catheterization. As far as we know, it is the first case that such a giant CSA coexists with secondary vena cava aneurysms. Considering the complexity of postoperative reconstruction, we believe that heart transplantation may be the optimal way for treatment. The patient received anticoagulant due to the superior vena cava (SVC) thrombosis while waiting for a donor.

[Intraoperative autologous based blood conservation strategies in mitral valve replacement].

OBJECTIVE: To evaluate whether intraoperative autologous donation (IAD) can reduce perioperative blood transfusion for patients underwent mitral valve replacement (MVR). METHODS: A total of 318 patients received implementation of IAD from January 2011 to December 2013 were analyzed retrospectively, and compared with 517 patients of the previous 36-month period (from January 2008 to December 2012). The method of small-volume retrograde autologous priming, strict blood transfusion standard along with IAD together constituted a progressive blood-saving strategy. Statistical methods including Students' t-test, Pearson's χ(2) test, Kruskal-Wallis analysis and multivariate Logistic regression model were used for comparisons of the data. RESULTS: There were no significant difference between IAD group and non-IAD group considering preoperative patient demographics, characteristics and preoperative comorbidities. However, IAD group significantly reduced number of patients transfused with intra/post-operative packed red-blood cell (PRBC) (55(17.0%) vs. 215 (42.1%), χ(2)=53.0, P=0.000), and had significantly reduced postoperative chest tube output (150(380) ml vs. 700(660) ml, H=195.648, P=0.000), length of stay ((16±6) d vs. (20±8)d, t=9.60, P=0.000). But hematocrit were lower in IAD group (30%±5% vs.33%±4% at end of operation, t=7.76, P=0.000; 30%±4% vs. 32%±5% at discharge, P=0.000, t=3.86). Multivariate logistic aggression analysis revealed that age, IAD and smoking history were factors influencing the probability of intra or postoperative blood transfusion. CONCLUSION: Implementation of blood conservation strategies based on intraoperative autologous donation in mitral valve replacement surgery can significantly reduce intra/postoperative blood transfusion as well as postoperative complications.

Short-term and Long-term Postoperative Safety of Off-Pump versus On-Pump Coronary Artery Bypass Grafting for Coronary Heart Disease: A Meta-analysis for Randomized Controlled Trials.

OBJECTIVE: The aim was to compare the short-term (30 days after surgery) and long-term (over 6 months' follow-up) postoperative safety of off-pump and on-pump coronary artery bypass grafting (CABG) for patients with coronary heart disease (CHD). METHODS: Relevant randomized controlled trials (RCTs) were obtained from PubMed, Embase, Springer, Ovid, and Cochrane library up to July 2013. Odds ratios (ORs) with their 95% confidence intervals (CIs) were used to access effect sizes. RESULTS: Seven RCTs involving 9,128 patients were included. Results suggested no significant difference in all the short-term outcomes (mortality, OR = 0.90, 95% CI: 0.69 to 1.16, p = 0.41; myocardial infarction, OR = 0.95, 95% CI: 0.79 to 1.15, p = 0.61; stroke, OR = 0.78, 95% CI: 0.56 to 1.07, p = 0.12; renal failure, OR = 0.84, 95% CI: 0.60 to 1.18, p = 0.43; revascularization: OR = 1.95, 95% CI: 0.79 to 4.85, p = 0.15) and some long-term outcomes (mortality, OR = 1.02, 95% CI: 0.86 to 1.22, p = 0.81; myocardial infarction, OR = 0.86, 95% CI: 0.70 to 1.04, p = 0.12; stroke, OR = 0.89, 95% CI: 0.67 to 1.19, p = 0.44) between off-pump and on-pump CABG. However, off-pump CABG had a significantly higher revascularization rate (OR = 1.45; 95% CI: 1.02 to 2.06; p = 0.04) than on-pump CABG in long-term follow-up. CONCLUSION: Short-term postoperative safety was similar between off-pump and on-pump CABG. A high revascularization rate was the drawback of off-pump CABG for CHD patients in long-term follow-up.

A Giant Right Coronary Artery of Diffuse Ectasia Induced by a Right Ventricular Fistula.

Coronary artery fistula (CAF) is a rare entity. Sometimes it may associate with mild diffuse or segmental coronary ectasia. CAF with giant coronary artery is exceptionally rare. We present a unique case of a 49-year-old female patient with a giant right coronary artery of diffuse ectasia coexisting with a fistula draining into the right ventricle. To our best knowledge, CAF with diffuse coronary ectasia of such giant size has never been reported. The patient was treated successfully by resection of the dilated right coronary artery, fistula closure, and coronary artery bypass grafting.

Efficacy and potential microRNA mechanism for computed tomography-guided percutaneous radiofrequency ablation of primary lung cancer and lung metastasis from liver cancer.

BACKGROUND: The aim of this study was to evaluate comparatively the effectiveness of computed tomography-guided percutaneous radiofrequency ablation (CT-PRFA) for primary non-small cell lung cancer (NSCLC) and lung metastases from hepatocellular carcinoma (HCC) and to explore the potential miRNA mechanisms for the efficacy of CT-PRFA. METHODS: 14 patients pathologically diagnosed with NSCLC and 12 patients with lung metastases from HCC were enrolled in the study and underwent CT-PRFA. Clinical outcomes were compiled on the basis of review of medical records, imaging follow-up reports, and any biopsy-proved residual or recurrent disease. Real-time RT-PCR was used to quantify the selected miRNAs known to be play key roles in lung cancer. RESULTS: A total of 21 tumors were treated with umbrella-tip electrodes and spiral-tip electrodes were used for the remaining 8 tumors. The median follow-up was 13.5 months (range, 3-30 months) and no patient was lost to follow-up. The rate of technique efficacy for primary tumors was ∼93% (13 of 14). Treatment was successful in 11 out of 12 (91.7%) lung metastases patients. Overall survival rate was 80.8% at 2 years, and cancer-specific survival rate was 100% at 2 years. The tumor-free survival was 69.2% at 1 year and 26.9% at 2 years. Before PRFA, tumor suppressor let-7a and miR-34a were downregulated whereas oncomiR miR-21 was upregulated in primary tumors, and let-7a and miR-126 levels were downregulated whereas oncomiRs miR-21, miR-155 and miR-17-5p/miR-20b levels were upregulated in secondary tumors. This abnormal expression was normalized by CT-PRFA. Most notably, CT-PRFA failed to normalize the deregulated miRNAs in the non-survivors. CONCLUSIONS: CT-PRFA is a effective treatment for primary NSCLCs and secondary lung tumors from HCC and the efficacy may be related to its ability to normalize deregulated expression of miRNAs: upregulating tumor suppressor miRNAs and downregulating oncomiRs.

MicroRNA-490-3p inhibits proliferation of A549 lung cancer cells by targeting CCND1.

MicroRNAs (miRNAs) are small non-coding RNAs that negatively regulate the translation of messenger RNAs by binding their 3'-untranslated region (3'UTR). In this study, we found that miR-490-3p is significantly down-regulated in A549 lung cancer cells compared with the normal bronchial epithelial cell line. To better characterize the role of miR-490-3p in A549 cells, we performed a gain-of-function analysis by transfecting the A549 cells with chemically synthesized miR-490-3P mimics. Overexpression of miR-490-3P evidently inhibits cell proliferation via G1-phase arrest. We also found that forced expression of miR-490-3P decreased both mRNA and protein levels of CCND1, which plays a key role in G1/S phase transition. In addition, the dual-luciferase reporter assays indicated that miR-490-3P directly targets CCND1 through binding its 3'UTR. These findings indicated miR-490-3P could be a potential suppressor of cellular proliferation.

Cardiac hypertrophy and dysfunction induced by overexpression of miR-214 in vivo.

BACKGROUND: An increasing number of studies have demonstrated the critical role of microRNAs in the pathogenesis of cardiac hypertrophy and dysfunction. This study evaluated whether miR-214 plays a pivotal role in the development of cardiac hypertrophy and heart failure. METHODS: In human tissues, miR-214 overexpression was determined to promote cardiac hypertrophy. We predicted miR-214 direct target by bioinformatics database and verifed it using luciferase dual reporting system. We silenced miR-214 using a specific antagomir in a pressure-overload mouse model of heart failure. RESULTS: Analysis of transgenic mice with cardiomyocyte-specific overexpression of miR-214 indicated that their hearts were 21% heavier than wild-type hearts and expressed several biochemical and functional markers consistent with dilated cardiomyopathy. These findings include enlarged left ventricular internal diameters, wall thinning, reduced ejection fraction, fractional shortening, and an increased fetal gene expression. The enhancer of zeste homolog 2 (EZH2) was confirmed as a direct target of miR-214 in cardiomyocytes. In vivo silencing of miR-214 using a specific antagomir rescued cardiac EZH2 expression and prevented cardiac hypertrophy and dysfunction. CONCLUSIONS: Taken together, these results suggest that miR-214 may induce pathologic cardiac hypertrophy in part by reducing EZH2 messenger RNA levels. MiR-214 may therefore be a potential therapeutic target for treating certain cardiac disease states.

Therapeutic effect of Sanhua decoction on rats with middle cerebral artery occlusion and the associated changes in gut microbiota and short-chain fatty acids.

Sanhua decoction (SHD), a traditional prescription, has long been used in treating ischemic stroke (IS). However, the therapeutic effect of SHD and the associated changes in gut microbiota and short-chain fatty acids (SCFAs) are uncertain. In this study, a rat model of IS was established by the middle cerebral artery occlusion (MCAO). By evaluating the cerebral infarct area and brain tissue pathology, it was found that SHD ameliorated IS-related symptoms in MCAO rats. Using 16S rRNA gene sequencing, we found that SHD reduced abnormally elevated Lactobacillus and opportunistic pathogens such as Desulfovibrio, but increased some beneficial bacteria that produce SCFAs, including Clostridia, Lachnospiraceae, Ruminococcaceae, and Coprococcus. KEGG analysis revealed that SHD regulates several pathways, including D-arginine and D-ornithine metabolism, polyketide sugar unit biosynthesis, and cyanoamino acid metabolism, which are significantly altered in MCAO rats. By gas chromatography-mass spectrometry detection of SCFAs, we found that fecal acetic acid, valeric acid, and caproic acid were significantly increased in MCAO rats, whereas propionic acid and isobutyric acid were decreased. SHD reversed the changes in acetic acid and propionic acid in the model rats and significantly increased fecal butyric acid. In addition, MCAO rats had significantly higher serum levels of acetic acid, butyric acid, isovaleric acid, and valeric acid, and lower levels of caproic acid. Altered serum levels of butyric acid, isovaleric acid, valeric acid, and caproic acid were restored, and the level of isobutyric acid was reduced after SHD administration. Spearman analysis revealed that cerebral infarct area had a strong correlation with Bifidobacterium, Desulfovibrio, Lachnospiraceae, Lactobacillus, acetic acid, valeric acid, and caproic acid. Overall, this study demonstrates for the first time that the effect of SHD on IS may be related to gut microbiota and SCFAs, providing a potential scientific explanation for the ameliorative effect of SHD on IS.

MicroRNA-214 provokes cardiac hypertrophy via repression of EZH2.

Micro RNAs are small, non-coding RNA molecules that regulate gene expression via either translational inhibition or mRNA degredation. Enhancer of zeste homolog 2 (EZH2)-mediated hypertrophic signaling is a major regulatory response to hypertrophic stimuli. In this study, we constructed AAC rat models and PE-induced hypertrophic cardiomyocytes. We demonstrated that miR-214 relative levels were upregulated, whereas EZH2 was downregulated in both vivo and vitro models. Further, one conserved base-pairing site in the EZH2 3'-untranslated region (UTR) was verified. Mutation of the site in the EZH2 3'-UTR completely blocked the negative effect of miR-214 on EZH2, suggesting that EZH2 is a direct target for miR-214 regulation. Using a gain-of-function approach, incorporating the lentivirus constructed miR-214 and its sponge, we demonstrated that miR-214 significantly regulated endogenous levels of EZH2 gene expression; whereas, changes in the expression of the Sine oculis homeobox homolog gene were induced by an adrenergic receptor agonist in the AAC rat model. Having made this study it is possible to conclude that the negative regulation of EZH2 expression contributed to miR-214-mediated cardiac hypertrophy.

One-stage complete removal of intracardiac leiomyomatosis without cardiac arrest.

We present here a woman with an intracardiac leiomyoma originating from uterine leiomyomatosis. The tumor was completely removed in a one-stage procedure using cardiopulmonary bypass without cardiac arrest. Most one-stage operations were performed with total circulation arrest; however, using of on-pump beating-heart technique when removing the intracardiac mass has seldom been reported in detail. The patient was asymptomatic with no evidence of recurrence on 13-month follow-up.