Search

Xiao Xie, Fangbao Ding, Haibo Xiao Department of Cardiothoracic Surgery, Xinhua Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, 200092, People’s Republic of ChinaCorrespondence: Fangbao Ding; Haibo XiaoDepartment of Cardiothoracic Surgery, Xinhua Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, No. 1665 Kongjiang Road, Shanghai, 200092, People’s Republic of ChinaEmail dingfangbao@xinhuamed.com.cn; xiaohaibo@xinhuamed.com.cnBackground: Non-small cell lung cancer (NSCLC) is a subtype of lung cancer which seriously threatens the health of people. Circular RNAs (CircRNAs) are endogenous RNAs which have stable closed structure; they are known to be involved in tumorigenesis of NSCLC. Meanwhile, hsa_circ_0000729 was reported to be upregulated in NSCLC. Nevertheless, the function of hsa_circ_0000729 in NSCLC remains unclear.Methods: Western blot and RT-qPCR were performed to investigate protein and mRNA levels, respectively. CCK-8 assay was performed to test the cell viability and cell death was investigated by flow cytometry. NSCLC cell pyroptosis was observed by electron microscope. In addition, the migration and invasion of NSCLC cells were detected by wound healing and transwell assay. The relation among hsa_circ_0000729, miR-1281 and FOXO3 was explored by dual luciferase reporter assay and RNA pull-down.Results: Hsa_circ_0000729 was found to be upregulated in NSCLC cells, and hsa_circ_0000729 knockdown obviously suppressed the proliferation of NSCLC cells through inducing pyroptosis. In addition, silencing of hsa_circ_0000729 notably inhibited the invasion and migration of NSCLC cells. Meanwhile, hsa_circ_0000729 could bind with miR-1281, and FOXO3 was directly targeted by miR-1281. Moreover, the anti-tumor effect of hsa_circ_0000729 siRNAs on NSCLC was markedly reversed by miR-1281 antagomir. Furthermore, silencing of hsa_circ_0000729 inhibited the tumor growth of NSCLC in vivo.Conclusion: Knockdown of hsa_circ_0000729 inhibits the tumorigenesis of NSCLC through mediation of miR-1281/FOXO3 axis. Thus, hsa_circ_0000729 might be served as a crucial mediator in NSCLC.Keywords: hsa_circ_0000729, miR-1281, FOXO3, pyroptosis

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 inboth 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.

Lung cancer is the most common cause of cancer-related death worldwide. Long noncoding RNAs (lncRNAs) are longer than 200 nt transcripts and are not translated into proteins. Increasing evidence has shown that lncRNAs are associated with several biological processes in cancer. However, the roles of LINC00511 in lung cancer progression remain unknown. In the present study, we confirmed that LINC00511 knockdown significantly inhibited cell proliferation and migration in A549, SPCA1, and H460 cells. Western blot results showed that silencing LINC00511 inhibited epithelial-mesenchymal transition (EMT), which resulted in decreased expression levels of ZEB2, N-cadherin, and vimentin and increased expression levels of E-cadherin. Additionally, silencing LINC00511 significantly upregulated PTEN mRNA and protein expression, increased FOXO1, and inactivated AKT. Furthermore, we found that PTEN knockdown reversed the inhibition of cell migration and proliferation induced by LINC00511 siRNA, markedly reduced p-FOXO1 expression, and promoted p-AKT expression and EMT in A549 and H460 cells. Therefore, these findings revealed that LINC00511 functions as an oncogene through the PTEN-AKT-FOXO1 signaling pathway in lung cancer, providing a potential target of metastasis in lung cancer.

Accumulating studies suggest that circular RNAs (circRNAs) function as key regulators in human cancers. We found that hsa_circ_0001869 participated in non-small cell lung cancer (NSCLC) progression. However, its expression and function during NSCLC remain unknown. The data advised that hsa_circ_0001869 expression was increased in NSCLC cell lines and tissues. High hsa_circ_0001869 expression had negatively correlation with the NSCLC patients prognosis. Bioinformatics and luciferase report analyses confirmed that miR-638 and FOSL2 were hsa_circ_0001869 downstream target. hsa_circ_0001869 downregulation decreased tumor proliferation, invasion and migration by promoting miR-638 expression and decreasing FOSL2 expression. As a result of overexpression of FOSL2 or silencing of miR-638, the recovery of proliferation, migration, and invasion after hsa_circ_0001869 silencing. Overexpression of FOSL2 also led to recovery of migration, invasion and proliferation after upregulation of miR-638. In vivo studies confirmed that overexpression of FOSL2 or silencing of miR-638 led to the recovery of tumor growth ability regarding A549 cells after hsa_circ_0001869 knockdown. Present investigation discovered that hsa_circ_0001869 enhanced NSCLC progression via sponging miR-638 and promoting FOSL2 expression. hsa_circ_0001869 downregulation suppressed tumor growth and invasion ability.

Deubiquitinases (DUBs) and noncoding RNAs have been the subjects of recent extensive studies regarding their roles in lung cancer, but the mechanisms involved are largely unknown. In our study, we used The Cancer Genome Atlas data set and bioinformatics analyses and identified USP21, a DUB, as a potential contributor to oncogenesis in non-small-cell lung cancer (NSCLC). We further demonstrated that USP21 was highly expressed in NSCLCs. We then conducted a series of in vitro and in vivo assays to explore the effect of USP21 on NSCLC progression and the underlying mechanism involved. USP21 promoted NSCLC cell proliferation, migration, and invasion and in vivo tumor growth by stabilizing a well-known oncogene, Yin Yang-1 (YY1), via mediating its deubiquitination. Furthermore, YY1 transcriptionally regulates the expression of SNHG16. Moreover, StarBase bioinformatics analyses predicted that miR-4500 targets SNHG16 and USP21. A series of in vitro experiments indicated that SNHG16 increased the expression of USP21 through miR-4500. In summary, the USP21/YY1/SNHG16 axis plays a role in promoting the progression of NSCLC. Therefore, the USP21/YY1/SNHG16/miR-4500 axis may be a potential therapeutic target in NSCLC treatment., Lung cancer: Targeting a vicious circle Therapies targeting a molecular feedback loop involved in tumor growth may prove valuable for treating non-small-cell lung cancer. Fangbao Ding, Jianbing Huang, and co-workers at Shanghai Jiao Tong University in Shanghai, China, have shown how an enzyme called USP21 promotes cancer cell proliferation and tumor growth in non-small-cell lung cancer. The team took cancerous and non-cancerous lung tissue samples from 42 patients, and analyzed the expression and behavior of USP21. The enzyme was highly expressed in cancerous tissues, where it stabilized a known gene with the potential to cause cancer called YY1. This gene also regulated the expression of a particular RNA molecule, which in turn worked to increase levels of USP21. This cyclical process encouraged the proliferation, migration and invasion of non-small-cell lung cancer cells, and may provide a future therapeutic target.

Background Intracardiac septal defect is repaired using median sternotomy in most centers; however, there are several reports using minimally invasive surgery in both children and adults. This study summarized our strategy of minimally invasive therapy using various lateral mini-thoracotomies in patients with congenital septal defect. Methods In this study, 472 patients who underwent minimally invasive repair of intracardiac septal defects (atrial septal defect, (ASD), ventricular septal defect, (VSD), and atrioventricular septal defect, (AVSD)) from January 2012 to June 2020 were retrospectively reviewed. Those who underwent device closure were excluded. The minimally invasive strategy included three groups: the right sub-axillary vertical incision (RSAVI) group (N = 335, including192 ASDs, 135 VSDs and 8 AVSDs); the right anterolateral thoracotomy (RALT) group (N = 132, including 77 ASDs, 51 VSDs and 4 AVSDs); and the left anterolateral thoracotomy (LALT) group (N = 5, all subpulmonary VSDs). Results Concomitant surgeries included nine cases of right ventricular outflow tract obstruction relief, nine cases of mitral repairs and 37 cases of tricuspid repairs. There was one transition from thoracotomy to sternotomy. Three patients required second pump run for residual lesions (two residual VSD shunts and one mitral regurgitation). The age and body weight of the RSAVI group were significantly lower than those of the RALT and LALT groups (all P Conclusions Intracardiac septal defects can be safely and effectively repaired by minimally invasive surgery with good cosmetic results. RSAVI is suitable in infants and children, while RALT is more commonly used in adolescents and adults. LALT is an alternative incision to repair subpulmonary VSD.

Diffuse pulmonary vein stenosis (PVS) is an intractable congenital heart disease for which the underlying mechanism remains unclear. In this study, we investigated the effect of losartan and the role of the Hippo pathway in PVS.A total of 19 neonatal piglets were divided into 3 groups: a sham group (n=7), a banded group (n=6) with the left upper pulmonary vein and common trunk of both lower pulmonary veins banded, and a losartan group (n=6) with losartan treatment (1 mg/kg/d) after the banding operation. After 8 weeks, the piglets underwent hemodynamic measurement and harvesting. The upstream pulmonary veins were collected for histological staining and molecular biological analysis. Losartan and/or angiotensin II (stepwise concentrations from 0.1 to 100 µmol/L) were added to a human umbilical vein endothelial cell culture to investigate the potential mechanismThe modified model demonstrated the main characteristics of patients with PVS, including pulmonary hypertension and intimal hyperplasia in the upstream veins. Upregulation of yes-associated protein (YAP) and angiotensin II type 1 receptor was observed in the neointima (P0.01). Losartan treatment improved the pathological changes in piglets and decreased YAP expression in the neointima (P0.01). In vitro, losartan suppressed angiotensin II-induced cell proliferation by inhibiting dephosphorylation and nuclear translocation of YAP in human umbilical vein endothelial cells (P0.05).Losartan treatment ameliorates intimal hyperplasia and inhibits YAP activation. The activation of the Hippo-YAP pathway is involved in the vasculopathy of progressive PVS. These findings may contribute to the development of new approaches for treating PVS.

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

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 β-catenin inhibitor XAV-939 (10 µM) treatment, and the expression of MMP9, VEGF, and β-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 β-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 β-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 β-catenin in NCI-H1975 cells. CONCLUSIONS Our findings indicate that ARHGAP24 silencing promotes lung cancer cell migration and invasion through activating β-catenin signaling.

Xie X, Ding F, Xiao H. Cancer Manag Res. 2021;13:8445–8455. The Editor and Publisher of Cancer Management and Research wish to retract the published article. Concerns were raised following notification that another journal had also received the same manuscript from the authors while the article was still under consideration at Cancer Management and Research. On review of the original western blot data, that was provided with the initial submission, it was found elements of the western blot images had been duplicated with those from unrelated articles submitted by authors affiliated at different institutions. The authors did not respond to our queries and the Editor requested for the article to be retracted. Our decision-making was informed by our policy on publishing ethics and integrity and the COPE guidelines on retraction. The retracted article will remain online to maintain the scholarly record, but it will be digitally watermarked on each page as “Retracted”. This retraction relates to this paper

Atrial fibrillation is a common clinical arrhythmia with high morbidity and a risk of stroke. The Cox-maze IV procedure that uses radiofrequency energy for ablation is established as an effective way to eliminate atrial fibrillation. Compared to the Cox-maze IV procedure, the video-assisted Wolf mini-maze procedure is associated with reduced surgical trauma, but still requires bilateral thoracotomies, and the ablation line connecting the right and left pulmonary vein isolations cannot be created with a bipolar ablation clamp. We have developed a novel video-assisted mini-maze technique that uses a unilateral (left chest) thoracoscopic approach (the Mei mini-maze procedure).

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

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

Myocardial ischemia/reperfusion (I/R) injury is a major pathological process in coronary heart disease and cardiac surgery, and is associated with aberrant microRNA (miR) expression. Previous studies have demonstrated that inhibition of miR-15a expression may ameliorate I/R‑induced myocardial injury. In the present study, the potential role and underlying mechanism of miR‑15a in hypoxia/reoxygenation‑induced apoptosis of cardiomyocytes was investigated. Myocardial I/R was simulated in cultured H9c2 cells by 24 h hypoxia followed by 24 h reoxygenation. Using recombinant lentivirus vectors, the inhibition of miR‑15a was indicated to significantly reduce cardiomyocyte apoptosis and release of lactate dehydrogenase and malondialdehyde. Conversely, upregulated miR‑15a expression was pro‑apoptotic. Mothers against decapentaplegic homolog 7 (SMAD7) was identified by bioinformatics analysis as a potential target of miR‑15a. Luciferase reporter assays and western blotting for endogenous SMAD7 protein indicated that miR‑15a inhibited SMAD7 expression via its 3'‑untranslated region. Nuclear levels of nuclear factor‑κB (NF‑κB) p65 were increased by miR‑15a expression and decreased by miR‑15a inhibition, which is consistent with the possibility that the inhibition of SMAD7 by miR-15a results in NF‑κB activation. These findings suggested that the therapeutic effects of miR‑15a inhibition on I/R injury may potentially be explained by its ability to release SMAD‑7‑dependent NF‑κB inhibition. This may provide evidence for miR‑15a as a potential therapeutic target for the treatment of cardiac I/R injury.

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.

To summarize the safety and effect of minimally invasive surgery for hypertrophic obstructive cardiomyopathy (HOCM) with significant mitral regurgitation through a single transaortic approach via right minithoracotomy.From 2008 to 2017, 51 HOCM patients with significant mitral regurgitation underwent minimally invasive surgery via right minithoracotomy. Preoperative peak left ventricular outflow tract pressure gradient (LVOTPG) was 96.53 ± 28.72 mm Hg. Preoperative average interventricular septum thickness was 24.31 ± 3.52 mm. All patients had significant mitral regurgitation with systolic anterior motion phenomenon. An oblique incision was made on the anterior wall of ascending aorta or aortic root. Modified Morrow procedure and edge-to-edge mitral valvuloplasty were performed through the single transaortic approach via right minithoracotomy.All patients successfully underwent the minimally invasive surgery through the single transaortic approach via right minithoracotomy. At discharge, postoperative peak LVOTPG (18.16 ± 6.41 mm Hg) and interventricular septum thickness (14.33 ± 1.99 mm) were significantly decreased compared with preoperative values (P.05). All patients had no or trivial mitral regurgitation. The average peak mitral valve pressure gradient was 3.39 ± 1.82 mm Hg. Systolic anterior motion phenomenon disappeared in all patients. During follow-up, peak LVOTPG was 19.27 ± 6.10 mm Hg; average interventricular septum thickness was 14.67 ± 1.87 mm. All patients had no or trivial mitral regurgitation. Average peak mitral valve pressure gradient was 3.04 ± 1.52 mm Hg. No systolic anterior motion phenomenon occurred.Minimally invasive surgery of modified Morrow procedure and edge-to-edge mitral valvuloplasty through a single transaortic approach via right minithoracotomy could be safely and effectively applied for patients with HOCM and significant mitral regurgitation, which could also effectively eliminate systolic anterior motion phenomenon and without mitral valve stenosis.

Background Primary cardiac tumors are rare and the majorities are benign. Conventional surgical treatment uses median sternotomy, while minimally invasive surgery from right anterolateral minithoracotomy has become an alternative method in recent years. In this study, we summarized the surgical outcomes of both approaches. Methods From January 2008 to August 2018, 50 patients with primary benign cardiac tumors underwent either conventional or minimally invasive surgery in our department. The baseline data were collected. The peri-operative data and follow up results were compared between the two groups. Results There were19 men and 31 women enrolled in this study with a mean age of 55.0 ± 17.5 years. The most common site of the tumor was left atrium (n = 40, 80%), followed by right atrium (n = 8, 16.0%), right ventricle (n = 1, 2.0%) and left ventricle (n = 1, 2.0%). All patients underwent surgery uneventfully, including 33 cases (66.0%) of median sternotomy and 17 cases (34.0%) of right anterolateral minithoracotomy. No significant differences were found between the two groups in terms of cardiopulmonary bypass time, aortic cross-clamp time, postoperative intubation time, intensive care unit days and length of the hospital stay. Patients with right anterolateral minithoracotomy had less post-operative chest drainage (536 ± 159 vs 773 ± 255 ml, P

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 ( χ 2 = 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.

The effects of continuous vagal nerve stimulation (VNS) on atrial neural remodeling during atrial fibrillation (AF) remain unclear.To test the hypothesis that VNS affects atrial neural remodeling and reduces AF inducibility.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.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).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.

Epithelial mesenchymal transition (EMT) is a critical step in cancer metastasis. Some evidences have been provided to verify up-regulation of linc00511 in multiple cancers and oncogenic roles during cancer malignant process. But, the roles of linc00511 on the metastasis of lung cancer are still largely unclear. Our study aims to reveal the functional effects of linc00511 on TGF-β1-induced EMT in lung cancer. Our results showed that knockdown of linc00511 significantly inhibited TGF-β1-induced migration and invasion and down-regulated the mRNA and protein levels of MMP2, MMP9 and MMP12 in TGF-β1 treated SPCA1 and H1975 cells. Also, western blotting results showed that inhibition of linc00511 remarkably suppressed TGF-β1-induced N-cadherin, Vimentin and snail and increased E-cadherin expression in SPCA1 and H1975 cells. Noteworthy, we further found that inhibition of linc00511 could down-regulate TGF-β1-induced ZEB2 mRNA and protein levels by sponging miR-183-5p in SPCA1 and H1975 cells. Taken together, our findings suggested knockdown linc00511 suppressed TGF-β1-induced migration and invasion via inhibiting EMT and MMPs in lung cancer cells.

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.

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.

Isolated aortic valve diseases can lead to atrial fibrillation (AF) by causing left atrium pressure overload and enlargement. At present, most patients with preoperative AF and isolated aortic valve disease have undergone a Cox-maze IV procedure through a left atriotomy under cardiopulmonary bypass with aortic cross-clamping. Here, we describe a novel modified epicardial radiofrequency ablation procedure performed on a beating heart without aortic cross-clamping or opening the left atrium. This technique has proved to be safe and feasible, with good clinical outcomes. It may be useful in selecting the best ablation approaches for patients with AF and aortic valve disease.

We describe the case of a 10-year-old boy with coarctation of the aorta complicated by innominate artery stenosis and agenesis of left common carotid artery and left subclavian artery. The patient was treated with an interposition graft between the ascending and descending aorta. The right subclavian was revascularized with another graft from the interposition graft to the distal right subclavian. This is a rare case of the combination of coarctation of the aorta and other vascular malformations.

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.

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

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 HEK293 T cells. 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.

Abnormal folate metabolism and common variants of folate-metabolizing enzymes have been described as possible risk factors for congenital heart disease (CHD). Two important folate-metabolizing enzymes involved in the folate/homocysteine metabolic pathway are 5,10-methylenetetrahydrofolate reductase (MTHFR) and methylenetetrahydrofolate dehydrogenase 1 (MTHFD1). MTHFR and MTHFD1 polymorphisms may be associated with CHD susceptibility. To evaluate the impact of MTHFR and MTHFD1 single-nucleotide polymorphisms (SNPs) on CHD susceptibility, we genotyped functional MTHFR SNPs rs1801133 C>T, rs1801131 A>C and rs2274976 G>A, and MTHFD SNPs rs2236225 C>T, rs1950902 G>A and rs1076991 A>G in a hospital-based case-control study of 173 tetralogy of Fallot (TOF) cases and 207 non-CHD controls. When MTHFR rs1801133 CC homozygote genotype was used as the reference group, the TT genotype was associated with a significantly increased risk for TOF [TT vs. CC: odds ratio (OR)=1.67; 95% confidence interval (CI): 1.01–2.75; P=0.046]. In the recessive model, when MTHFR rs1801133 CC/CT genotype was used as the reference group, the TT homozygote genotype was associated with a significantly increased risk for TOF (OR=1.81, 95% CI: 1.15–2.84; P=0.010). In conclusion, our findings suggest that MTHFR rs1801133 C>T polymorphism may play a role in susceptibility for TOF. Large-scale studies with a more rigorous study design including diverse ethnic populations are required to confirm these findings.

Objective We developed a new thoracoscopic ablation procedure for lone atrial fibrillation (AF) based on new endoscopic technology and the adoption of new types of energy. Methods Fifty-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. Results Mean 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 maintain sinus rhythm. Thrombus in the left atrium and stenosis of the pulmonary vein were not found postoperatively. Conclusions This less invasive procedure proved to be safe and presented optimistic outcomes, so it deserves to be promoted as a treatment for lone atrial fibrillation.

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.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.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% (p0.01) 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.cGMP pathway controls water channels and then affects water intake during CPB through an AQP1-mediated pathway.

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.

To assess the effects of three methods of inducing myogenic cells differentiation, umbilical blood mesenchymal stem cells (UCMSCs) from nearly full-term pregnancy mongrel dogs were purified and cultured. Fourth-passage UCMSCs were used to detect surface antigens, including CD11a, CD11b, CD29, CD34 and CD71. The cells were induced by 5-azacytidine (5-aza), myocardial lysates and myocardial induced fluid. Positive expression of Nkx2.5, α-actin, desmin, β-MHC and troponin-I (TN I) were detected after 3 weeks. The immunohistochemical results were CD11a (-), CD11b (-), CD34 (-), CD29 (+) and CD71 (+). Nkx2.5 was detected in 5-aza group, myocardial lysates group and myocardial induced fluid group. Semi-quantitative analysis showed Nkx2.5 expression significantly higher in myocardial lysates group than in the 5-aza group or myocardial-induced fluid group (P 0.05). MSCs did not express myocardial structural proteins before differentiation, but α-actin, desmin, β-MHC and troponin-I were present after differentiation. The positive expression of four proteins differed with the differentiation conditions. The UCMSCs can be differentiated into myogenic cells by three methods, but the degrees of differentiation are inconsistent. Our results show that the effects of 5-aza and myocardial lysates are better than that of myocardial induced fluid.

OBJECTIVES: The purpose of this study was to evaluate the efficacy of the modified Nuss procedure with a subxiphoid incision in correcting recurrent pectus excavatum. METHODS: From 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. RESULTS: Prior 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. CONCLUSIONS: The 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.

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.

Myocardial stunning, which is closely related to myocardial edema, is a severe complication that may occur following cardiac surgery. In this study, we examined the expression of aquaporin 1 (AQP1) and Connexin 43 (Cx43) following cardiopulmonary bypass (CPB) surgery in goats. We assessed myocardial muscle tissue water content according to changes in dry-wet weight. Our results showed that AQP1 expression and myocardial muscle tissue water content increased significantly 6 h after CPB surgery, reaching peak levels 48 h after surgery; additionally, the protein expression of Cx43 was inversely correlated with AQP1 expression. Overexpression of AQP1 during CPB surgery enhanced the degree of myocardial edema, whereas the addition of water channel protein inhibitor Hg2+ in cold crystalloid cardioplegia and knockdown of AQP1 during surgery weakened the degree of myocardial edema. These findings revealed that the severity of myocardial edema after CPB surgery is correlated with AQP1 protein expression levels, suggesting the important role played by AQP1 protein in the regulation of Cx43 in the pathological progression of myocardial edema.

Abnormal proliferation and migration of vascular smooth muscle cells (VSMC) is a common feature of disease progression in atherosclerosis. Here, we investigated the potential role of miR-503 in platelet-derived growth factor (PDGF)-induced proliferation and migration of human aortic smooth muscle cells and the underlying mechanisms of action. miR-503 expression was significantly downregulated in a dose- and time-dependent manner following PDGF treatment. Introduction of miR-503 mimics into cultured SMCs significantly attenuated cell proliferation and migration induced by PDGF. Bioinformatics analyses revealed that the insulin receptor (INSR) is a target candidate of miR-503. miR-503 suppressed luciferase activity driven by a vector containing the 3'-untranslated region of INSR in a sequence-specific manner. Downregulation of INSR appeared critical for miR-503-mediated inhibitory effects on PDGF-induced cell proliferation and migration in human aortic SMCs. Based on the collective data, we suggest a novel role of miR-503 as a regulator of VSMC proliferation and migration through modulating INSR.