circFTO from M2 macrophage-derived small extracellular vesicles (sEV) enhances NSCLC malignancy by regulation miR-148a-3pPDK4 axis.

BACKGROUND: Accumulation studies found that tumor-associated macrophages (TAMs) are a predominant cell in tumor microenvironment (TME), which function essentially during tumor progression. By releasing bioactive molecules, including circRNA, small extracellular vesicles (sEV) modulate immune cell functions in the TME, thereby affecting non-small cell lung cancer (NSCLC) progression. Nevertheless, biology functions and molecular mechanisms of M2 macrophage-derived sEV circRNAs in NSCLC are unclear. METHODS: Cellular experiments were conducted to verify the M2 macrophage-derived sEV (M2-EV) roles in NSCLC. Differential circRNA expression in M0 and M2-EV was validated by RNA sequencing. circFTO expression in NSCLC patients and cells was investigated via real-time PCR and FISH. The biological mechanism of circFTO in NSCLC was validated by experiments. Our team isolated sEV from M2 macrophages (M2Ms) and found that M2-EV treatment promoted NSCLC CP, migration, and glycolysis. RESULTS: High-throughput sequencing found that circFTO was highly enriched in M2-EV. FISH and RT-qPCR confirmed that circFTO expression incremented in NSCLC tissues and cell lines. Clinical studies confirmed that high circFTO expression correlated negatively with NSCLC patient survival. Luciferase reporter analysis confirmed that miR-148a-3p and PDK4 were downstream targets of circFTO. circFTO knockdown inhibited NSCLC cell growth and metastasis in in vivo experiments. Downregulating miR-148a-3p or overexpressing PDK4 restored the malignancy of NSCLC, including proliferation, migration, and aerobic glycolysis after circFTO silencing. CONCLUSION: The study found that circFTO from M2-EV promoted NSCLC cell progression and glycolysis through miR-148a-3p/PDK4 axis. circFTO is a promising prognostic and diagnostic NSCLC biomarker and has the potential to be a candidate NSCLC therapy target.

The abnormal expression of circ-ARAP2 promotes ESCC progression through regulating miR-761/FOXM1 axis-mediated stemness and the endothelial-mesenchymal transition.

Circular RNAs (circRNAs) belong to a novel class of noncoding RNA that gained more attention in human cancer pathogenesis. The role of circRNA in esophageal squamous cell carcinoma (ESCC) is largely unclear. Present investigation was to characterize new circRNAs regulating ESCC progression and explore the regulatory mechanisms in ESCC. In this study, circRNAs differentially expressed in ESCC and adjacent normal tissues were characterized via high-throughput sequencing. Then the differentially expressed circRNA between ESCC and adjacent normal tissues were investigated using Rt-qPCR. The role of circ-ARAP2 expression on tumor progression were detected in both in vivo and in vitro. Luciferase reporter assays were used to identify the relationships among circ-ARAP2, microRNA (miR)-761 and the cell cycle regulator Forkhead Box M1 (FOXM1). The result of the expression profile analyses regarding human circRNAs in ESCC demonstrated that circ-ARAP2 was up-regulated significantly in both ESCC tissues and cell lines. Downregulation circ-ARAP2 suppressed ESCC proliferation, tumor growth and metastasis in both in vivo and in vitro. The data also suggested that miR-761 and FOXM1 were circ-ARAP2 downstream targets which were confirmed through luciferase reporter analysis. Overexpression of FOXM1 or inhibiting miR-761 restored ESCC cell proliferation and invasion ability after silencing circ-ARAP2. The study also found that circ-ARAP2 influenced the endothelial-mesenchymal transition (EMT) and cancer stem cells differently by regulating miR-761/FOXM1. In one word, the results demonstrated that abnormal circ-ARAP2 expression promoted ESCC progression by regulating miR-761/FOXM1 axis-mediated stemness and EMT.

ARHGAP24 inhibits cell proliferation and cell cycle progression and induces apoptosis of lung cancer via a STAT6-WWP2-p27 axis.

Rho GTPase-activating proteins (RhoGAPs) have been reported to be of great importance in the initiation and development of many different cancers. However, their biological roles and regulatory mechanisms in lung cancer development and progression are poorly defined. Real-time PCR or western blotting analysis was used to detect Rho GTPase-activating protein 24 (ARHGAP24), WWP2, p27, p-STAT6 and STAT6 expression levels as well as the activity of RhoA and Rac1 in lung cancer. Cell proliferation, apoptosis and cell cycle were measured by CCK-8 and flow cytometry analysis. Tumor growth of lung cancer cells was measured using a nude mouse xenograft experiment model in vivo. The correlation between WWP2 and p27 was measured by co-immunoprecipitation and ubiquitination analysis. We found that ARHGAP24 expression was lower in lung cancer tissues collected from the The Cancer Genome Atlas and independent hospital database. Overexpression of ARHGAP24 significantly suppressed cell proliferation and the activity of RhoA and Rac1, induced cell apoptosis and arrested cell cycle at the G0-G1 phase. ARHGAP24 overexpression also inhibited tumor growth in nude mice, whereas knockdown of ARHGAP24 significantly promoted cell proliferation and WWP2 expression and inhibited cell cycle arrest at G1 phase through activating STAT6 signaling. ARHGAP24 overexpression inhibited WWP2 overexpression-induced cell proliferation, cell cycle progression and the decreased p27 expression. Moreover, WWP2 was found interacted with p27, and WWP2 overexpression promoted the ubiquitination of p27. In conclusion, our findings suggest that ARHGAP24 inhibits cell proliferation and cell cycle progression and induces cell apoptosis of lung cancer via a STAT6-WWP2-p27 axis.

MicroRNA-30e-5p suppresses non-small cell lung cancer tumorigenesis by regulating USP22-mediated Sirt1/JAK/STAT3 signaling.

MicroRNA-30e-5p (miR-30e-5p) is a tumor suppressor that is known to be downregulated in non-small cell lung cancer (NSCLC). However, how miR-30e-5p inhibits NSCLC tumorigenesis is not known. Ubiquitin-specific peptidase 22 (USP22) is upregulated in NSCLC and promotes tumorigenesis via a Sirt1-JAK-STAT3 pathway. In this study, we investigated whether miR-30e-5p inhibits tumor growth by targeting USP22 in NSCLC. Our results reveal that miR-30e-5p expression was correlated negatively with USP22 in NSCLC tissues. Luciferase reporter assays showed that miR-30e-5p negatively regulated USP22 expression by binding to a specific sequence in the 3'UTR. MiR-30e-5p overexpression and USP22 knockdown significantly inhibited tumor growth in vivo and induced cell cycle arrest and apoptosis in NSCLC cells in vitro. The effects of miR-30e-5p inhibition were prevented by USP22 knockdown. MiR-30e-5p inhibited SIRT1 expression and increased expression of p53 and the phosphorylated form of STAT3 (pSTAT3). Furthermore, miR-30e-5p prevented USP22-mediated regulation of SIRT1, pSTAT3, and p53 expression. Taken together, these findings suggest that miR-30e-5p suppresses NSCLC tumorigenesis by downregulatingUSP22-mediated Sirt1/JAK/STAT3 signaling. Our study has identified miR-30e-5p as a potential therapeutic target for the treatment of NSCLC.

Mid-term outcomes of individualized surgeries in patients with Ebstein's anomaly.

The variable anatomy of Ebstein's anomaly leads to its various surgical procedures. The long-term outcomes of different operations were not well established. Thirty-five patients with Ebstein's anomaly who underwent operations from 2006 to 2018 in our department were retrospectively reviewed. Individualized surgical plans were performed according to the preoperative echocardiography and surgeons' preference. Tricuspid repair, either Danielson's or Carpentier's technique, was the primary choice in patients who had sufficient tricuspid leaflets and adequate right ventricle, while tricuspid replacement was used when a reliable repair is not achievable. Additional bidirectional cavopulmonary shunt was performed in those who had unstable hemodynamics despite of high central venous pressure after separation from cardiopulmonary bypass. The perioperative and follow-up data were collected. The age was 26.9 (0.6-54) years [16 children (age < 14, and 19 adults (age ≥ 14)]. Preoperative tricuspid regurgitation was severe in 30, moderate in 4, and mild in the remaining 1 patient. Preoperative cardiac-associated malformations include 20 atrial septal defects, 2 ventricular septal defects, 2 pulmonary stenosis, and 1 sub aortic ridge, and these were operated simultaneously. Among all the surgical patients, 2 needed additional reoperation during the same admission, and ultimately, 29 patients had biventricular repair, including 21 tricuspid repair and 8 replacements. The other 6 patients had cavopulmonary connection and achieved 1.5 ventricular repair (3 tricuspid repair and 3 replacements). In all the 24 tricuspid repair patients, Danielson's procedure was used in 17, while Carpentier's technique was used in the other 7 patients. The average cardiopulmonary bypass time was 90 ± 28 min and cross-clamp time was 48 ± 24min. There were 2 perioperative deaths (5.7%) and no third-degree atrioventricular block. The postoperative in hospital stay was 13.7 ± 9.6 days. In the 33 survivors who were followed up at a median of 29.2 months, 6 patients had severe tricuspid regurgitation, and 2 of them underwent tricuspid replacement. The 5-year freedom from severe tricuspid dysfunction or reoperation was 78.5%, and no difference was found between children and adults, neither between different surgical choices. The surgeries of Ebstein's anomaly were variable, and individualized operation achieved reasonable short- and mid-term results. However, severe tricuspid regurgitation during the follow-up was not neglectable, and reoperation in such cases also achieved good outcomes. New repair strategy such as cone repair may be considered.

Rho GTPase Activating Protein 24 (ARHGAP24) Silencing Promotes Lung Cancer Cell Migration and Invasion by Activating ß-Catenin Signaling.

BACKGROUND Rho GTPase activating protein (RhoGAPs) is an important negative regulator of the Rho signaling pathway that is involved in tumorigenesis in liver, colon, and renal cancer. However, the mechanism by which Rho GTPase activating protein 24 (ARHGAP24) regulates cell invasion and migration of lung cancer has not been fully explained. MATERIAL AND METHODS In this study, ARHGAP24 expression in lung cancer tissues and cell lines was measured by immunohistochemical and Western blot analysis. Transwell or wound healing analysis was performed to detect the cell migration and invasion of ARHGAP24 modulated A549 and NCI-H1975 cells with ß-catenin inhibitor XAV-939 (10 µM) treatment, and the expression of MMP9, VEGF, and ß-catenin protein was measured by Western blotting. RESULTS Our results showed that ARHGAP24 expression was downregulated in lung cancer tissues and cell lines. pLVX-Puro-ARHGAP24 transfection in A549 cells significantly inhibited cell invasion and migration, along with increased E-cadherin and decreased MMP9, VEGF, Vimentin, and ß-catenin protein expression. pLKO.1-ARHGAP24-shRNA transfection in NCI-H1975 cells significantly promoted cell invasion and migration, accompanied with decreased E-cadherin and increased MMP9, VEGF, and ß-catenin protein expression. Moreover, NCI-H1975 cells with XAV-939 treatment showed decreased cell invasion and migration when compared with pLKO.1-ARHGAP24-shRNA transfection. ARHGAP24 silencing promoted the transcriptional activity of ß-catenin in NCI-H1975 cells. CONCLUSIONS Our findings indicate that ARHGAP24 silencing promotes lung cancer cell migration and invasion through activating ß-catenin signaling.

Right minithoracotomy versus conventional median sternotomy for patients undergoing mitral valve surgery and Cox-maze IV ablation with entirely bipolar radiofrequency clamp.

Cox-maze IV ablation by bipolar radiofrequency clamp was considered to be only performed through median sternotomy (MS), but impossible through right minithoracotomy (RM). Now, we developed a novel technique of performing Cox-maze IV ablation entirely by bipolar clamp through RM. To compare the outcomes of RM or MS for patients undergoing mitral valve surgery and concomitant Cox-maze IV ablation with entirely bipolar clamp. All 152 patients underwent mitral valve surgery and concomitant Cox-maze IV ablation with bipolar clamp through RM (n = 69) or MS (n = 83) were analyzed for outcome differences. The etiology of mitral valve disease was rheumatic (n = 97) and degenerative (n = 55). All patients had long-standing persistent atrial fibrillation (AF). Diameter of left atrium ranged from 42 to 60 mm. All patients successfully underwent Cox-maze IV ablation by bipolar clamp. RM group had longer cardiopulmonary bypass time (130.3 ± 17.7 vs 115.3 ± 14.4 min; P < 0.001) and aortic cross-clamp time (91.8 ± 12.7 vs 74.6 ± 9.3 min; P < 0.001). But mechanical ventilation time (14.2 ± 6.6 vs 21.3 ± 9.0 h; P < 0.001) and hospital length of stay (9.3 ± 2.6 vs 11.7 ± 3.0 days; P < 0.001) were shorter in RM group. At discharge, the maintenance of normal sinus rhythm (NSR) was 94.2% in RM group and 95.1% in MS group (P = 1.000). Cumulative maintenance of NSR at 2 years postoperatively was 85.1 ± 5.8% in RM group and 88.6 ± 3.6% in MS group (P = 0.767). RM can achieve similar therapeutic effect to MS for patients undergoing mitral valve surgery and concomitant Cox-maze IV ablation with entirely bipolar clamp. In addition, patients through RM had faster recovery.

Stroke prevention following modified endoscopic ablation and appendectomy for atrial fibrillation.

We reported the results of stroke prevention following modified endoscopic procedure for atrial fibrillation. 82 patients underwent modified endoscopic procedure for atrial fibrillation (AF), in whom 47 had paroxysmal, 28 had persistent, and 7 had long-standing atrial fibrillation. CHA2DS2VASC median score was 3 (range from 0 to 8). The procedure was performed on the beating heart, through 3 ports on the left chest wall. Pulmonary vein isolation and ablation of the left atrium were achieved by bipolar radiofrequency ablation. Left atrial appendage (LAA) was excluded by stapler. Brain CT, cardiac CT and 24-h Holter monitoring were performed following the procedure. The procedure was successfully completed for all patients. The mean duration was 122 ± 40.1 min. LAA was excluded after appendectomy and checked by intraoperative transesophageal echocardiography. The mean follow-up duration was 24.3 ± 3.5 months. No patients showed signs and symptoms of transient ischemic attack or stroke. No new positive findings were demonstrated by recurring brain CT scan performed after the procedure. Cardiac CT confirmed the absence of LAA and thrombosis in the left atrium. 87.8 % (72/82) of all patients were in sinus rhythm. Our results demonstrate that the modified endoscopic procedure is a safe, effective, and appropriate treatment for AF, which restores sinus rhythm and may be associated with the prevention of AF-related stroke.

One-stage surgical treatment for Cantrell syndrome without repairing the left ventricular diverticulum: a case report.

Cantrell syndrome includes the defects of the heart, pericardium, diaphragm, abdominal wall, and sternum. The operative mortality is usually high. We report here a one-stage surgical correction in a case of Cantrell syndrome with left ventricular diverticulum.

Prognostic significance of overexpressed matrix metalloproteinase-2, mouse-double minute: 2 homolog and epidermal growth factor receptor in non-small cell lung cancer.

PURPOSE: To evaluate the rate of overexpression of matrix metalloproteinase-2 (MMP2), mouse double minute 2 homolog (MDM2) and epidermal growth factor receptor (EGFR) in patients with non-small cell lung cancer (NSCLC), and evaluate their correlation with clinicopathological parameters and prognosis. METHODS: This was a prospective cohort study conducted from 2003 to 2008 among 184 NSCLC patients who underwent tumor resection. Each patient's clinical history and tumor characteristics were obtained from histopathology reports and medical records. EGFR, MDM2 and MMP2 expression were assessed by immunohistochemical (IHC) staining of the tissue specimens. RESULTS: MDM2 overexpression was observed in 70 (38%) of the patients studied, and was significantly higher in younger patients (p=0.01). Only 46 (25%) of patients had overexpression of MMP2. EGFR positive staining occurred in 105 (57%percnt;) of the evaluated tumor specimens and was more frequent in specimens with squamous cell carcinoma (p<0.001), the elderly (p<0.001), and in smokers (p<0.001). Independent risk factors for mortality were older age (adjusted odds ratio/aOR 1.3=), being a smoker (aOR 10), having stage II disease (aOR 10.8) or stage III/IV disease (aOR 28.3), expression of EGFR (aOR 5.9) and MMP2 (aOR 4.1). However, the expression of MDM2 independently predicted a reduced risk of death (aOR 0.3). CONCLUSION: Overexpression of MMP2 and EGFR were independent risk factors for mortality in NSCLC patients, while overexpression of MDM2 independently predicted a reduced risk of death.

Pyruvate kinase M2 interacts with DNA damage-binding protein 2 and reduces cell survival upon UV irradiation.

Pyruvate Kinase M2 (PKM2) is highly expressed in many solid tumors and associated with metabolism reprogramming and proliferation of tumors. Here, we report that PKM2 can bind to DNA Damage-Binding Protein 2 (DDB2), which is necessary for global nucleotide excision repair of UV induced DNA damage. The binding is promoted by UV irradiation and K433 acetylation of PKM2. Over expression of PKM2 facilitates phosphorylation of DDB2 and impairs DDB2-DDB1 binding. Furthermore, knocking down of PKM2 increases cell survival upon UV irradiation, while over expression of PKM2 reduces cell survival and over expression of DDB2-DDB1 reverts this effect. These results reveal a previously unknown regulation of PKM2 on DDB2 and provide a possible mechanism for UV induced tumorigenesis.

MicroRNA-27b plays a role in pulmonary arterial hypertension by modulating peroxisome proliferator-activated receptor γ dependent Hsp90-eNOS signaling and nitric oxide production.

Pulmonary artery endothelial dysfunction is associated with pulmonary arterial hypertension (PAH). Based on recent studies showing that microRNA (miR)-27b is aberrantly expressed in PAH, we hypothesized that miR-27b may contribute to pulmonary endothelial dysfunction and vascular remodeling in PAH. The effect of miR-27b on pulmonary endothelial dysfunction and the underlying mechanism were investigated in human pulmonary artery endothelial cells (HPAECs) in vitro and in a monocrotaline (MCT)-induced model of PAH in vivo. miR-27b expression was upregulated in MCT-induced PAH and inversely correlated with the levels of peroxisome proliferator-activated receptor (PPAR)-γ, and miR-27b inhibition attenuated MCT-induced endothelial dysfunction and remodeling and prevented PAH associated right ventricular hypertrophy and systolic pressure in rats. PPARγ was confirmed as a direct target of miR-27b in HPAECs and shown to mediate the effect of miR-27b on the disruption of endothelial nitric oxide synthase (eNOS) coupling to Hsp90 and the suppression of NO production associated with the PAH phenotype. We showed that miR-27b plays a role endothelial function and NO release and elucidated a potential mechanism by which miR-27b regulates Hsp90-eNOS and NO signaling by modulating PPARγ expression, providing potential therapeutic targets for the treatment of PAH.

USP22 acts as an oncogene by regulating the stability of cyclooxygenase-2 in non-small cell lung cancer.

The histone ubiquitin hydrolase ubiquitin-specific protease 22 (USP22) is an epigenetic modifier and an oncogene that is upregulated in many types of cancer. In non-small cell lung cancer (NSCLC), aberrant expression of USP22 is a predictor of poor survival, as is high expression of cyclooxygenase-2 (COX-2). Despite its oncogenic role, few substrates of USP22 have been identified and its mechanism of action in cancer remains unclear. Here, we identified COX-2 as a direct substrate of USP22 and showed that its levels are modulated by USP22 mediated deubiquitination. Silencing of USP22 downregulated COX-2, decreased its half-life, and inhibited lung carcinoma cell proliferation by directly interacting with and modulating the stability and activity of COX-2 through the regulation of its ubiquitination status. The findings of the present study suggest a potential mechanism underlying the oncogenic role of USP22 mediated by the modulation of the stability and activity of COX-2.

miR-342-3p targets RAP2B to suppress proliferation and invasion of non-small cell lung cancer cells.

MicroRNAs (miRNAs) play critical roles in cancer development and progression. In this study, we examined the roles and molecular mechanisms of miR-342-3p in human non-small cell lung cancer (NSCLC). The results showed that miR-342-3p is downregulated in NSCLC cell lines and tissues, and its overexpression induces significant inhibition of NSCLC cell proliferation, invasion, and tumor growth in nude mice. In addition, miR-342-3p repressed RAP2B expression through interactions with its 3'-UTR region. Restoration of RAP2B expression reversed miR-342-3p-mediated inhibitory activity in NSCLC cells. Finally, analyses of miR-342-3p and RAP2B levels in NSCLCs revealed that miR-342-3p inversely correlated with RAP2B mRNA expression. Our collective findings provide preliminary evidence that miR-342-3p acts as a tumor suppressor in NSCLC through repression of RAP2B.

Efficacy and safety of novel epicardial circumferential left atrial ablation with pulmonary vein isolation in sustained atrial fibrillation.

The aim of this study was to examine the efficacy and safety of this novel epicardial circumferential left atrial ablation (CLAA) with pulmonary vein isolation (PVI) in sustained atrial fibrillation (AF). Thirty domestic pigs were divided equally into 3 groups: AF without ablation (AF group), AF with PVI (PVI group), and AF with CLAA and PVI (CLAA + PVI group). AF was induced by rapid atrial pacing. After AF was induced, CLAA and PVI were performed for pigs in CLAA + PVI group, and PVI was performed for pigs in PVI group. AF vulnerability, AF duration, and histology were performed in all groups. All pigs developed sustained AF after 6.27 ± 0.69 weeks of rapid atrial pacing. All pigs successfully underwent isolated PVI or CLAA with PVI on the beating heart in PVI group or CLAA + PVI group. Isolated PVI terminated AF in 3 of 20 pigs (15 %), and CLAA with PVI terminated AF in 5 of 8 pigs (62.5 %, P = 0.022). Compared with AF group (10/10), the incidence of sustained AF by burst pacing was significantly decreased in PVI group (3/10, P = 0.003) or CLAA + PVI group (0/10, P < 0.001). There was no significant difference between PVI group and CLAA + PVI group (P = 0.211). AF duration was significantly decreased in CLAA + PVI group (734.70 ± 177.81 s, 95 % CI 607.51-861.89) compared with PVI group (1217.90 ± 444.10 s, 95 % CI 900.21-1535.59, P = 0.008). Also, AF duration was significantly decreased in PVI group (P = 0.003) or CLAA + PVI group (P < 0.001) in comparison with AF duration in AF group (average 1800 s). Epicardial CLAA could ablate the left atrial roof and posterior wall together safely and reliably. Compared with PVI alone, CLAA with PVI may be able to improve the rate of acute termination of persistent AF. It may be useful in selecting the best ablation approaches for patients with persistent AF.

Effect of novel modified bipolar radiofrequency ablation for preoperative atrial fibrillation combined with off-pump coronary artery bypass grafting surgery.

We described a novel modified bipolar radiofrequency (RF) ablation for preoperative atrial fibrillation (AF) combined with off-pump coronary artery bypass grafting (OPCABG) for patients with AF and coronary artery disease (CAD). The aim of this study was to assess the effect of this novel procedure and to determine whether it can eliminate AF for CAD patients. From January 2007 to June 2013, 45 patients (26 male patients) with AF (9 paroxysmal, 17 persistent, and 19 long-standing persistent) and CAD underwent the novel modified bipolar RF ablation combined with OPCABG in our department. After median sternotomy, the modified bipolar RF ablation and OPCABG were performed on beating heart without cardiopulmonary bypass. Pulmonary vein isolation and left atrium ablation were achieved using a bipolar RF champ. Mitral annular lesion and ganglionic plexus were ablated with a bipolar RF pen. The left atrial appendage was excluded using a surgical stapler. 24 h holter monitoring and echocardiography were performed at discharge and 3, 6, 12 months postoperatively as well as every year thereafter. The modified bipolar RF ablation and OPCABG were performed successfully in all patients. Mean AF ablation time was 33.6 ± 4.2 min, and mean OPCABG time was 87.6 ± 13.3 min. Mean postoperative hospital stay was 12.6 ± 5.5 days. The maintenance of sinus rhythm was 95.6 % (43/45) at discharge. There was no early death and permanent pacemaker implantation in perioperation. At a mean follow-up of 29.8 ± 10.2 months, 38 of 45 (84.4 %) patients were in sinus rhythm. Follow-up TTE at 6 months postoperatively showed that left atrial diameter was significantly reduced and left ventricular ejection fraction was significantly increased. The novel modified bipolar RF ablation procedure was safe, feasible and effective. It may be useful in selecting the best ablation approaches for patients with AF and CAD.

Biatrial ablation versus limited right atrial ablation for atrial fibrillation associated with atrial septal defect in adults.

PURPOSE: To compare the efficacy and safety of limited right atrial ablation versus biatrial ablation for atrial fibrillation (AF) associated with atrial septal defect (ASD) in adults. METHODS: The subjects were 47 consecutive adult patients who underwent ASD closure with limited right atrial ablation (RA, n = 19) or biatrial ablation (BA, n = 28) for AF, between January, 2007 and December, 2012. Eighteen patients had persistent AF and 29 had long-standing persistent AF. Bipolar RF ablation was performed for all patients. RESULTS: AF ablation and ASD closure were performed successfully in all patients. The BA group had longer cardiopulmonary bypass time, aortic cross-clamp time, and hospital stay than the RA group, but the incidence of major postoperative complications was not significantly different between the groups. On discharge, normal sinus rhythm was maintained in 100% of the BA group patients and 78.9% of the RA group patients (P = 0.045). By 2 years postoperatively, cumulative maintenance of normal sinus rhythm off antiarrhythmic drugs was confirmed in 87.7 ± 6.7% of the BA group patients and 47.4 ± 11.5% of the RA group patients (P = 0.003). CONCLUSION: Biatrial ablation restored and maintained sinus rhythm more effectively than limited right atrial ablation, without increasing the risk of postoperative complications for AF associated with ASD in adults.

MiR-196a2 rs11614913 T>C Polymorphism is Associated with an Increased Risk of Tetralogy of Fallot in a Chinese Population.

BACKGROUND: MicroRNAs (miRNAs) are a family of endogenous, small, noncoding single-stranded RNAs that act as post-transcriptional gene regulatory elements. MiRNA polymorphisms may be associated with susceptibility to congenital heart disease (CHD). The aim of this study was to evaluate the impact of miRNA single nucleotide polymorphisms (SNPs) on CHD susceptibility. METHODS: We genotyped two functional SNPs, miR-196a2 rs11614913 and miR-146a rs2910164, in a case-control cohort of 173 Chinese patients with tetralogy of Fallot (TOF) and 207 non-CHD controls. RESULTS: When the miR-196a2 rs11614913 TT homozygote genotype was used as the reference group, the TC genotype was not associated with an increased risk of TOF. The CC genotype was associated with a borderline significantly increased risk for TOF. In the recessive model, when the miR-196a2 rs11614913 TT/TC genotypes were used as the reference group, the CC homozygote genotype was associated with a significantly increased risk of TOF (OR = 1.96, 95% CI = 1.18-3.25, p = 0.01). The miR-146a rs2910164 C>G polymorphism was not associated with developing TOF. CONCLUSIONS: Our findings suggested that the miR-196a2 rs11614913 T>C polymorphism may play a role in the development of TOF. Future larger studies that include populations of other ethnicities are required to confirm these findings. KEY WORDS: Congenital heart disease; MiRNA; Molecular epidemiology; Polymorphisms; Tetralogy of Fallot.

The early and mid-term results of mitral valve repair for mitral regurgitation in children.

PURPOSE: To review the surgical techniques and mid-term results of mitral valve repair in children with moderate or severe mitral regurgitation (MR). METHODS: One hundred and seven children with moderate or severe MR, aged 19.6 ± 8.5 months, were enrolled in this study. The surgical techniques used for mitral valve repair varied according to the mitral valve morphology, and included annuloplasty, annuloplasty ring, cleft closure, reconstruction of the posterior leaflet, etc. The concomitant cardiac anomalies were treated simultaneously. The results of repair were evaluated by transesophageal echocardiography performed during the operation and by serial transthoracic echocardiography performed during the follow-up. RESULTS: One hundred and six cases had no more than mild regurgitation intraoperatively, whereas only one case had moderate regurgitation. This patient underwent redo repair immediately, and the subsequent regurgitation was trivial. The in-hospital mortality rate was 0.9 % (1/107). The average follow-up was 46.5 ± 8.2 months. One patient died of heart failure 10 months postoperatively. The freedom from moderate or severe regurgitation after mitral valve repair was 92.3 ± 3.3 %. CONCLUSION: Pediatric patients with moderate or severe MR require early surgical treatment. The early and mid-term results of mitral valve repair in pediatric patients were satisfactory.