Ju Mei

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) inxa0vitro and in a monocrotaline (MCT)-induced model of PAH inxa0vivo. 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.

Over-expression of prolyl hydroxylase-1 blocks NF-κB-mediated cyclin D1 expression and proliferation in lung carcinoma cells

Prolyl hydroxylase-1 (PHD1), a member of the hypoxia inducible factor (HIF)-PHD family, plays an important role in regulating the stability of HIFs. The nuclear factor-κB (NF-κB) pathway consists of a family of transcription factors that play critical roles in inflammation, immunity, cell proliferation, differentiation, and survival. In this study, we demonstrate that PHD1 can inhibit NF-κB activity and its target genes in lung cancer cells based on both over-expression and RNA interference-mediated knockdown of PHD1 in human A549 lung cancer cells and HEK293xa0Txa0cells. Of medical importance, PHD1 could induce cell cycle arrest in lung cancer cells, resulting in the suppression of cell proliferation. Xenograft tumor growth assays indicate that PHD1 plays a critical role in suppressing lung cancer growth. These findings reveal a new role of PHD1 in lung cancer and provide new treatment perspectives for cancer therapy by characterizing PHD1 as a potential target.

Modified Nuss procedure in the treatment of recurrent pectus excavatum after open repair.

OBJECTIVESnThe purpose of this study was to evaluate the efficacy of the modified Nuss procedure with a subxiphoid incision in correcting recurrent pectus excavatum.nnnMETHODSnFrom August 2006 to July 2010, 28 patients with recurrent pectus excavatum underwent a secondary repair using the modified Nuss procedure with a subxiphoid incision and bilateral thoracoscopy. Data concerning symptoms, operative course, complications, pulmonary function and early outcome were recorded.nnnRESULTSnPrior repairs of the reoperation patients included 16 Ravitch, 9 modified Ravitch and 3 sterno-turnover procedures. The median Haller index was 4.52 for the redo patients. Presenting symptoms included decreased endurance, dyspnoea on exertion, chest pain, frequent respiratory infections and palpitations. The median duration of reoperation was slightly longer than that of the primary surgeries. Blood loss and postoperative hospitalization were similar between groups. Complications from pectus reoperations included pneumothorax, pleural effusion, postoperative pain and wound infection in the lateral incision. There were no perioperative deaths or cardiac perforations. Initial postoperative results varied from excellent to good. The patients were followed up for 24-74 months. No steel bar malposition or stabilizer displacement was found in any case.nnnCONCLUSIONSnThe modified Nuss procedure with subxiphoid incision and bilateral thoracoscopy can avoid cardiac injury to the greatest degree. It would be a minimally invasive and safe approach for patients with recurrent pectus excavatum after failed open repair.

Complete thoracoscopic ablation of the left atrium via the left chest for treatment of lone atrial fibrillation.

OBJECTIVEnWe developed a new thoracoscopic ablation procedure for lone atrial fibrillation (AF) based on new endoscopic technology and the adoption of new types of energy.nnnMETHODSnFifty-five patients with lone atrial fibrillation underwent this therapy. Patient age ranged from 30 to 81 years and there were 39 men and 16 women. Of these patients, 38 had paroxysmal atrial fibrillation, 14 had persistent atrial fibrillation, and 3 had longstanding atrial fibrillation. The procedure was performed on the beating heart through 3 ports in the left chest wall. Pulmonary vein isolation and ablation of the left atrium were achieved by bipolar radiofrequency ablation. Ganglionic plexus ablation was completed using the ablation pen. The left atrial appendage was excluded.nnnRESULTSnMean procedure duration was 106.6 ± 42.8 minutes. No conversion to sternotomy or pacemaker implantation occurred and no patients died. Their hospital stay was 5.3 ± 2.0 days with a mean follow-up of 12.6 ± 2.2 months. Forty-nine of 55 patients (89.1%) patients were in sinus rhythm. Six patients could not maintainxa0sinus rhythm. Thrombus in the left atrium and stenosis of the pulmonary vein were not found postoperatively.nnnCONCLUSIONSnThis less invasive procedure proved to be safe and presented optimistic outcomes, so it deserves to be promoted as a treatment for lone atrial fibrillation.

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 (CLAAxa0+xa0PVI group). AF was induced by rapid atrial pacing. After AF was induced, CLAA and PVI were performed for pigs in CLAAxa0+xa0PVI 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 6.27xa0±xa00.69xa0weeks of rapid atrial pacing. All pigs successfully underwent isolated PVI or CLAA with PVI on the beating heart in PVI group or CLAAxa0+xa0PVI group. Isolated PVI terminated AF in 3 of 20 pigs (15xa0%), and CLAA with PVI terminated AF in 5 of 8 pigs (62.5xa0%, Pxa0=xa00.022). Compared with AF group (10/10), the incidence of sustained AF by burst pacing was significantly decreased in PVI group (3/10, Pxa0=xa00.003) or CLAAxa0+xa0PVI group (0/10, Pxa0<xa00.001). There was no significant difference between PVI group and CLAAxa0+xa0PVI group (Pxa0=xa00.211). AF duration was significantly decreased in CLAAxa0+xa0PVI group (734.70xa0±xa0177.81xa0s, 95xa0% CI 607.51–861.89) compared with PVI group (1217.90xa0±xa0444.10xa0s, 95xa0% CI 900.21–1535.59, Pxa0=xa00.008). Also, AF duration was significantly decreased in PVI group (Pxa0=xa00.003) or CLAAxa0+xa0PVI group (Pxa0<xa00.001) in comparison with AF duration in AF group (average 1800xa0s). 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.

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

PurposeTo 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.MethodsThe subjects were 47 consecutive adult patients who underwent ASD closure with limited right atrial ablation (RA, nxa0=xa019) or biatrial ablation (BA, nxa0=xa028) 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.ResultsAF 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 100xa0% of the BA group patients and 78.9xa0% of the RA group patients (Pxa0=xa00.045). By 2xa0years postoperatively, cumulative maintenance of normal sinus rhythm off antiarrhythmic drugs was confirmed in 87.7xa0±xa06.7xa0% of the BA group patients and 47.4xa0±xa011.5xa0% of the RA group patients (Pxa0=xa00.003).ConclusionBiatrial 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.

Application of endovascular occlusion of both caval veins in minimally invasive isolated redo tricuspid surgery through right thoracotomy.

OBJECTIVEnTo summarise the experiences of applying vena cava endovascular occlusion technique in minimally invasive isolated redo tricuspid surgery.nnnMETHODSnForty-six consecutive patients received minimally invasive redo tricuspid surgery through right thoracotomy at our institute. All the patients had isolated significant tricuspid regurgitation after previous cardiac surgeries. Preoperative chest computed tomography showed high risk of conventional median sternotomy and vena cava exposure. A right anterolateral thoracotomy incision was made from the fourth intercostal space. The arterial cannula was placed in femoral artery, and balloon cannulas were used for bicaval cannulation. The venous cannulation was guided by transoesophageal echocardiography. Tricuspid valve operation was performed with heart beating after both venous cannulas were endovascularly occluded by inflating the balloons.nnnRESULTSnThere were no complications related to this cannulation technique. Two patients needed position adjustment or re-inflation of the balloon to obtain complete occlusion. The average time of cardiopulmonary bypass establishment was 55 ± 15 min and pump time was 58 ± 23 min. The length of stay was 8 ± 7 days. There was no early death in hospital.nnnCONCLUSIONnEndovascular occlusion of both vena cava in isolated redo tricuspid surgery was safe, effective and reliable. This approach significantly simplified the complexity of the surgery.

Phosphorylation of eIF2α suppresses cisplatin-induced A549 cell apoptosis via p38 inhibition.

Cisplatin-based chemotherapy is considered a golden standard for treatment of advanced non-small cell lung cancer (NSCLC). However, drug resistance is one of the major problems in NSCLC chemotherapy. The mechanisms and related biological pathways that contribute to chemoresistance are relatively poorly understood. Here, we demonstrated that the phosphorylation of eukaryotic translation initiation factor 2α (eIF2α) suppresses cisplatin-induced A549 cell apoptosis. Cisplatin induced eIF2α phosphorylation through protein kinase RNA. Importantly, phospho-eIF2α inhibited cisplatin-induced A549 cells apoptosis, at least in part, by suppressing the p38 pathway. Moreover, analysis of tissue microarrays information demonstrated that phospho-eIF2α predicted a poor prognosis in patients with NSCLC. Taken together, these results provide a potential mechanism that is used for explaining how eIF2α promotes cisplatin resistance in A549 cells. Therefore, the regulation of eIF2α may improve treatment outcomes of cisplatin-based chemotherapy for patients with NSCLC.

Minimally invasive nuss technique allows for repair of recurrent pectus excavatum following the ravitch procedure: Report of 12 cases

This work aimed to determine the efficacy of recurrent pectus excavatum repair using a minimally invasive Nuss procedure. We performed a secondary repair in 12 patients with recurrent pectus excavatum by using the minimally invasive Nuss procedure. Prior repairs had been performed using the Ravitch procedure in all cases. The values obtained in preoperative pulmonary function tests were less than 80% of the normal values. The median duration of surgery was slightly longer than that of the primary surgeries. The procedural complications included hemothorax (16.7%) and pleural effusion (25.0%). None of the patients developed a pneumothorax, pericarditis, pneumonia, wound infection, or immune rejection. There were no deaths or cardiac perforations. Exercise tolerance increased in 7 of the 12 cases. We achieved excellent results from surgical correction using the Nuss procedure in these 12 patients who showed recurrent pectus excavatum after failed repair surgery using the Ravitch procedure.

Cardiopulmonary bypass increases pulmonary microvascular permeability through the Src kinase pathway: Involvement of caveolin-1 and vascular endothelial cadherin

Changes in pulmonary microvascular permeability following cardiopulmonary bypass (CPB) and the underlying mechanisms have not yet been established. Therefore, the aim of the present study was to elucidate the alterations in pulmonary microvascular permeability following CPB and the underlying mechanism. The pulmonary microvascular permeability was measured using Evans Blue dye (EBD) exclusion, and the neutrophil infiltration and proinflammatory cytokine secretion was investigated. In addition, the activation of Src kinase and the phosphorylation of caveolin-1 and vascular endothelial cadherin (VE-cadherin) was examined. The results revealed that CPB increased pulmonary microvascular leakage, neutrophil count and proinflammatory cytokines in the bronchoalveolar lavage fluid, and activated Src kinase. The administration of PP2, an inhibitor of Src kinase, decreased the activation of Src kinase and attenuated the increase in pulmonary microvascular permeability observed following CPB. Two important proteins associated with vascular permeability, caveolin-1 and VE-cadherin, were significantly activated at 24 h in the lung tissues following CPB, which correlated with the alterations in pulmonary microvascular permeability and Src kinase. PP2 administration inhibited their activation, suggesting that they are downstream factors of Src kinase activation. The data indicated that the Src kinase pathway increased pulmonary microvascular permeability following CPB, and the activation of caveolin-1 and VE-cadherin may be involved. Inhibition of this pathway may provide a potential therapy for acute lung injury following cardiac surgery.