A pilot study of a cardiovascular virtual endoscopy system based on multi-detector computed tomography in diagnosing tetralogy of Fallot in pediatric patients.

The present study aimed to investigate the capabilities of the cardiovascular virtual endoscopy (VE) system in diagnosing tetralogy of Fallot (TOF) and performing measurements. A total of 37 patients underwent two-dimensional echocardiography (2-DE) and multi-detector computed tomography (MDCT) examinations. The obtained MDCT images were applied to a cardiovascular VE system. Diagnostic time by VE was first studied and compared with MDCT. Subsequently, with surgical findings as the ground truth, the capabilities of VE, 2-DE and MDCT in diagnosing TOF and its complications were investigated. Additionally, measurements on aorta overriding ratio and diameters for the left pulmonary artery, right pulmonary artery and right ventricular outflow tract by 2-DE and VE were analyzed. Diagnostic time by VE was significantly shorter than MDCT (188±42 vs. 303±42 sec, respectively; P<0.0001). VE, MDCT and 2-DE demonstrated comparable diagnostic rates of TOF (35/37 vs. 34/37 vs. 32/37, respectively; P>0.05). Similar findings were demonstrated in diagnosing complications of the muscular ventricular septal defects, patent ductus arteriosus, vagus subclavian artery, right arch, double superior vena cava and pulmonary artery. Furthermore, in diagnosing the atrial septal defect, 2-DE outperformed MDCT and VE (accuracy, 100 vs. 81 vs. 73%, respectively; all P<0.05). In performing relevant measurements, VE outperformed MDCT and 2-DE, particularly in accessing aorta overriding ratios with no intra-operator difference (P=0.3770) and high consistency (r=0.916). In conclusion, cardiovascular VE was demonstrated to have acceptable accuracy in diagnosing TOF, and possess advantages in shortening the diagnostic time and in performing measurements.

Application of cardiovascular virtual endoscopy: a pilot study on roaming path planning for diagnosis of congenital heart diseases in children.

To investigate roaming paths planning for diagnosis of congenital heart diseases (CHD) using a cardiovascular virtual endoscopy (VE) system. Forty children were enrolled. VE system was applied to support in establishing a diagnosis. Performance in diagnosing CHDs by CT, VE using automatically planned roaming paths (VE-auto, objects were treated as left heart system and right heart system), VE using manually planned paths (VE-manual), and VE using automatically planned path for left heart system and manually planned path for right heart system (VE-combined) were studied and compared. Comparable accuracy of 93%, 93%, 95% and 95% was found by CT, VE-auto, VE-manual and VE-combined. However, in diagnosing tetralogy of Fallot, significantly higher performance was found by VEs, compared with CT. For VE-auto, poor performance with an accuracy of 85% and sensitivity of 22% was revealed in diagnosing muscular ventricular septal defect, compared with VE-manual and VE-combined. Compared with VE-manual, VE-combined illustrated comparable diagnostic accuracy on all CHDs; however, significantly smaller diagnostic time was utilized (P < 0.05).Cardiovascular VE system demonstrated considerable clinical value in the diagnosis of CHDs. Left and right heart system should not be modeled as two cavity objects simultaneously. When one of two systems is treated as one object, the other system should be treated as three separate objects when using VE to diagnose CHDs.

Comparison of the Outcomes of Modified Artificial Chordae Technique for Mitral Regurgitation through Right Minithoracotomy or Median Sternotomy.

BACKGROUND: Right minithoracotomy (RM) has been proven to be a safe and effective approach for mitral valve surgery, but the differences of artificial chordae technique between RM and median sternotomy (MS) were seldom reported. Here, we compared the outcomes of modified artificial chordae technique for mitral regurgitation (MR) through RM or MS approaches. METHODS: One hundred and eighteen consecutive adult patients who received mitral valve repair with artificial chordae and annuloplasty for MR through RM (n = 58) or MS (n = 60) from January 2006 to January 2015 were analyzed. RESULTS: All of the selected patients underwent mitral valve repair successfully without any complication during the surgery. There was no significant difference between RM group and MS group in cardiopulmonary bypass time, aortic cross-clamp time, and early postoperative complications. However, compared with the MS group, the RM group had shorter hospital stay and faster surgical recovery. At a mean follow-up of 44.8 ± 25.0 months, the freedom from more than moderate MR was 93.9% ± 3.5% in RM group and 94.8% ± 2.9% in MS group at 3 years postoperatively. Log-rank test showed that there was no significant difference in the freedom from recurrent significant MR between the two groups (χ2 = 0.247, P = 0.619). Multivariate analysis revealed that the presence of mild MR at discharge was the independent risk factor for the recurrent significant MR. CONCLUSION: Right minithoracotomy can achieve the similar therapeutic effects with MS for the patients who received modified artificial chordae technique for treating MR.

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.

Continuous vagal nerve stimulation affects atrial neural remodeling and reduces atrial fibrillation inducibility in rabbits.

BACKGROUND: The effects of continuous vagal nerve stimulation (VNS) on atrial neural remodeling during atrial fibrillation (AF) remain unclear. OBJECTIVE: To test the hypothesis that VNS affects atrial neural remodeling and reduces AF inducibility. METHODS: Twenty rabbits were randomly divided into two groups: rapid atrial pacing (RAP) group and RAP with VNS group. AF inducibility studies and atrial histologic analyses were performed after 4 weeks. RESULTS: Five rabbits of RAP group (5/10) in the RAP group developed sustained AF. None of rabbits in RAP with VNS group had developed AF. The incidence of sustained AF in VNS group was significant lower than that in rapid pacing group (P<.01). Treatment with VNS resulted in a significant reduction in atrial neural remodeling and AF duration (P<.01). CONCLUSIONS: Atrial neural remodeling plays an important role in the initiation and maintenance of AF. Modulating autonomic nerve function with VNS can contribute to AF control.

miR-106a promotes growth and metastasis of non-small cell lung cancer by targeting PTEN.

MicroRNAs are a class of small non-coding RNAs that play essential roles in cancer development and progression. Recent studies suggested that abnormal expression of miRNAs occurs frequently in non-small cell lung cancer (NSCLC) tissues compared to adjacent normal tissues. In this study, we investigated the expression and the biological roles of miR-106a in non-small cell lung cancer. Our results showed that miR-106a was up-regulated in NSCLC tissues and cell lines. Inhibition of miR-106a in NSCLC cells substantially inhibited cell proliferation, migration, and invasion. Phosphatase and tensin homolog (PTEN) was identified as a direct target of miR-106a, and over-expression of miR-106a suppressed PTEN by direct binding to its 3'-untranslated region (3'-UTR). Furthermore, the presence of miR-106a was inversely correlated with PTEN in NSCLC tissues. Overall, this study suggested that miR-106a inhibited the growth and metastasis of NSCLC cells by decreasing PTEN expression. These data provide novel insights with potential therapeutic applications for the treatment of NSCLC.

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.

LncRNA HMlincRNA717 is down-regulated in non-small cell lung cancer and associated with poor prognosis.

INTRODUCTION: Long non coding RNAs (lncRNAs) have emerged recently as major players in tumor biology and may be used for cancer diagnosis, prognosis, and potential therapeutic targets. The lncRNA HMlincRNA717, a newly identified lncRNA, was demonstrated to be down-regulated in gastric cancer. However, little is known about its role in non small cell lung cancer (NSCLC). METHODS: Expression of lncRNA HMlincRNA717 in tumor and their matched non-tumor tissues was determined by quantitative real-time PCR (qRT-PCR) in NSCLC patients. Then, we analyzed the potential relationship between lncRNA HMlincRNA717 expression levels in tumor tissues and clinicopathological features of NSCLC, and clinical outcome. RESULTS: lncRNA HMlincRNA717 expression level was significantly decreased in NSCLC tissues in comparison to adjacent non-tumor tissues. It was also proved that HMlincRNA717 expression was to be associated with NSCLC histological grade, and lymph node metastasis. In addition, survival analysis proved that down-regulated HMlincRNA717 expression was associated with poor overall survival of NSCLC patients. Multivariate survival analysis also proved that HMlincRNA717 was an independent prognostic factor for NSCLC patients. CONCLUSIONS: The present study showed the down-regulation of HMlincRNA717 and its association with tumor progression in human NSCLC. It also provided that HMlincRNA717 expression was an independent prognostic factor for patients with NSCLC, which might be a potential prognostic biomarker and therapeutic target for NSCLC.

The role of aquaporin 1 activated by cGMP in myocardial edema caused by cardiopulmonary bypass in sheep.

BACKGROUND/AIMS: Most cardiac procedures involve the use of cardiopulmonary bypass (CPB), which pumps oxygenated blood to the body while the heart and lungs are isolated. CPB can cause profound alterations V in the homeostasis of physiological fluids, which often results in myocardial edema. In our study, we used sheep CPB model of in vivo and in vitro to assess the relationship between cGMP and AQP1 during CPB. METHODS: ODQ, a specific inhibitor of soluble guanylate cyclase (sGC), was used to treat the CPB animals or cardiomyocytes. Left ventricular function of each group was determined by pressure-volume system. Water content of myocardial tissue was assessed by dry-wet weight, and cardiomyocytes water permeability was also calculated. The concentration of cGMP was determined by Radioimmunoassay (RIA). mRNA and protein expression of AQP1 were detected by real-time PCR and western blot, respectively. RESULTS: The relative expression level of AQP1 mRNA and protein at each time point (0, 6, 12, 24 or 48 h) after CPB was significantly increased (1.18-fold at 12 h, 1.77-fold at 24 h and 2.18-fold at 48h) compared with each sham group, the protein expression of AQP1 also showed a rising trend after CPB. The degree of myocardial edema (75.1% at 12 h, 79.3% at 24 h and 81.0% at 48h) increased following the CPB surgery. The mRNA expression level of AQP1 was significantly decreased by 39.7% (p<0.01) upon treatment with ODQ compared with the CPB-only group, and inhibition of cGMP pathway also can significantly decrease the degree of myocardial edema (84.7% in control group, while 75.2% in ODQ group) and improve cardiac function in sheep after CPB. Results of in vitro experiments showed the same changing trends as in vivo. CONCLUSION: cGMP pathway controls water channels and then affects water intake during CPB through an AQP1-mediated pathway.

The involvement of AQP1 in heart oedema induced by global myocardial ischemia.

Aquaporin-1 (AQP1) is a member of aquaporin family that was previously proven to be involved in myocardial dysfunction; however, the role of AQP1 in myocardial stunning is less clear. To determine the change of AQP1 expression level in the heart and its effect on oedema after global myocardial ischemia, 40 adult goats underwent cardiopulmonary bypass (CPB) with an aortic cross-clamp time of 2 h and total bypass time of 6, 12, 24, 48 and 72 h followed by subsequent reperfusion. AQP1 function of eight goats was inhibited by HgCl(2) during the 24 h on CPB. All groups were compared with eight sham bypass control goats. Myocardial water content was measured, and the APQ1 mRNA and protein levels were detected by RT-PCR and immunoblotting, respectively. The results showed that the degree of myocardial oedema increased significantly at 6, 12, 24 and 48 h of reperfusion after CPB as compared with the control and recovered at 72 h of subsequent reperfusion. Expression levels of AQP1 mRNA and protein began to increase at 12 h and peaked at 24 h of CPB following reperfusion. Furthermore, myocardial oedema was reduced in the HgCl(2) group compared with the time-matched CPB and control groups. These data suggested that AQP1 expression increases in CPB and AQP1 plays an important role in myocardial oedema during CPB.

Bone marrow mesenchymal stem cells can differentiate into type II alveolar epithelial cells in vitro.

In this study, we demonstrate that BMSCs (bone marrow mesenchymal stem cells) can be successfully differentiated into type II alveolar epithelial cells in vitro under mimic pulmonary microenvironment. BMSCs were co-cultured with MRC-5 cells in modified SAGM (small airway growth medium). The BMSC-derived type II alveolar epithelial cells morphologically resemble human lung epithelial cells. They began to appear after 10 days in co-culture and became morphologically dominant after day 15. Correspondingly, SPC (surfactant protein C), a specific functional marker of human type II alveolar epithelial cells, was detected in differentiated cells by RT-PCR (reverse transcription-PCR) analysis after day 15. Immunostaining analysis revealed the present of scattered SPC-positive cells with a differentiation efficiency of 2.43-4.21%. Our study further showed that the SPC gene expression level in differentiated cells was related to the ratio of BMSCs to MRC-5 cells and the components of modified SAGM.

A novel two-stage complete repair method for pulmonary atresia with ventricular septal defect and major aortopulmonary collateral arteries.

BACKGROUND: Pulmonary atresia with ventricular septal defect (PA-VSD) and major aortopulmonary collateral arteries (MAPCAs) remains a challenging complex congenital heart disease nowadays. In the present study, we aimed to develop a two-stage surgical method and to evaluate outcomes of this method in managing PA-VSD and MAPCAs. METHODS: Between December 2003 and December 2008, 7 female and 4 male patients between the age of 5 and 10 years who were suffering from PA-VSD and MAPCAs were selected and recruited. The native pulmonary artery trunks were absent in all patients; the lungs were solely supplied by major aortopulmonary collaterals, and the numbers of supplied lung segments ranged from 15 to 20 (17.9 +/- 1.6). There were a total of 43 MAPCAs in all the patients (3 - 5 (3.9 +/- 0.7) MAPCAs per patient). The accumulated Nakata index was (222.9 +/- 29.9) mm(2)/m(2) (ranged from 182 to 272). All the patients underwent two sequential operations. Stage one included left major aortopulmonary collateral unifocalization and modified Blalock-Taussig shunt from left posterior lateral thoracotomy; stage two comprised right unifocalization, ligation of the shunt, followed by ventricular septal defect closure and right ventricular outflow tract reconstruction assisted with cardiopulmonary bypass from midline sternotomy. RESULTS: All the patients survived the initial surgery, but one of them died of low cardiac output syndrome on the third day after the second operation. Postoperative complications included pneumonia in one case and capillary leak syndrome in another. Postoperative oxygen saturation maintained about 95% - 100%, which was significantly higher than pre-operation (P < 0.01). During the follow-up period of 3 - 51 (25.4 +/- 15.2) months, there were no late death and no need for re-intervention. All the patients enjoyed their lives with good conditions. CONCLUSIONS: This two-stage complete repair strategy was well-tolerated and effective with good outcome, thus offering an alternative surgical approach in the treatment of PA-VSD and MAPCAs.

[Clinical studies in the effect of operative strategies on the hemodynamics in off-pump coronary artery bypass grafting].

OBJECTIVE: To study the influence of anastomoses sequence on the hemodynamics in off-pump coronary artery bypass grafting (CABG), and to investigate the strategy to stabilize the hemodynamics. METHODS: From March 2005 to March 2007, 67 patients with serious triple-vessel coronary artery lesions (male 45, female 22) with a age range from 44 to 81-years-old were enrolled for off-pump CABG. All the patients underwent left internal mammary artery-left anterior descending branch (LIMA-LAD) anastomose firstly, followed by the foreword anastomose of the other two vessels. According to the anastomose sequence of posterior descending branch (PDA) and obtuse marginal branch (OM), the patients were divided into three groups. Group I (n = 22) did the sequence of PDA-OM-aortic root (Ao). Group II (n = 14) did the sequence of Ao-PDA-OM. Group III (n = 31) did the sequence of Ao-OM-PDA. The hemodynamics markers, including heart rate (HR), central venous pressure (CVP), mean artery pressure (MAP), cardiac index (CI), left ventricular-stroke work index (LVSWI) and right ventricular stroke work index (RVSWI), were analyzed before LIMA-LAD anastomose to serve as baseline. And these markers were re-measured at LIMA-LAD anastomose, immediately after LIMA-LAD anastomose, at PDA anastomose and at OM anastomose. RESULTS: All the patients survived after off-pump CABG. Compared with the baseline, there were no significant hemodynamic changes when doing LIMA-LAD anastomose. When the anastomose finished, the hemodynamic indices improved significantly. When performing OM anastomose, HR and CVP increased significantly, and MAP, CI, LVSWI and RVSWI decreased remarkably in group I and group III, while there were no significant changes of MAP, CI and RVSWI in group II . When performing PDA anastomose, HR and CVP increased significantly, and MAP, CI, LVSWI and RVSWI decreased remarkably in group I and group II, while there were no significant hemodynamic changes in group III except HR. CONCLUSION: Proximal anastomose first when performing off-pump CABG, followed by distal anastomoses of target vessels is beneficial to those who have hard exposure and difficult anastomose of OM and PDA.