Butyrate attenuates the stemness of lung cancer cells through lysosome Fe2+- and SLC7A11-mediated ferroptosis.

Cancer stem cells (CSCs) are considered key contributors to tumor progression, and ferroptosis has been identified as a potential target for CSCs. We have previously shown that butyrate enhances the ferroptosis induced by erastin in lung cancer cell, this study aimed to investigate the impact of butyrate on the progression of lung CSCs. To investigate these effects, we constructed a series of in vitro experiments, including 3D non-adherent sphere-formation, cytometry analysis, assessment of CSC marker expression, cell migration assay, and in vivo tumorigenesis analyses. Additionally, the influence of butyrate on chemotherapeutic sensitivity were determined through both in vitro and in vivo experiments. Mechanistically, immunofluorescence analysis was employed to examine the localization of biotin-conjugated butyrate. We identified that butyrate predominantly localized in the lysosome and concurrently recruited Fe2+ in lysosome. Moreover, butyrate reduced the stability of SLC7A11 protein stability in lung cancer cells through ubiquitination and proteasome degradation. Importantly, the effects of butyrate on lung CSCs were found to be dependent on lysosome Fe2+- and SLC7A11-mediated ferroptosis. In summary, our results demonstrate that butyrate could induce the ferroptosis in lung CSCs by recruiting Fe2+ in lysosome and promoting the ubiquitination-lysosome degradation of SLC7A11 protein.

SUMOylation of TEAD1 Modulates the Mechanism of Pathological Cardiac Hypertrophy.

Pathological cardiac hypertrophy is the leading cause of heart failure and has an extremely complicated pathogenesis. TEA domain transcription factor 1 (TEAD1) is recognized as an important transcription factor that plays a key regulatory role in cardiovascular disease. This study aimed to explore the role of TEAD1 in cardiac hypertrophy and to clarify the regulatory role of small ubiquitin-like modifier (SUMO)-mediated modifications. First, the expression level of TEAD1 in patients with heart failure, mice, and cardiomyocytes is investigated. It is discovered that TEAD1 is modified by SUMO1 during cardiac hypertrophy and that the process of deSUMOylation is regulated by SUMO-specific protease 1 (SENP1). Lysine 173 is an essential site for TEAD1 SUMOylation, which affects the protein stability, nuclear localization, and DNA-binding ability of TEAD1 and enhances the interaction between TEAD1 and its transcriptional co-activator yes-associated protein 1 in the Hippo pathway. Finally, adeno-associated virus serotype 9 is used to construct TEAD1 wild-type and KR mutant mice and demonstrated that the deSUMOylation of TEAD1 markedly exacerbated cardiomyocyte enlargement in vitro and in a mouse model of cardiac hypertrophy. The results provide novel evidence that the SUMOylation of TEAD1 is a promising therapeutic strategy for hypertrophy-related heart failure.

Butyrate enhances erastin-induced ferroptosis of lung cancer cells via modulating the ATF3/SLC7A11 pathway.

Ferroptosis is a novel form of programmed cell death triggered by iron-dependent lipid peroxidation and has been associated with various diseases, including cancer. Erastin, an inhibitor of system Xc-, which plays a critical role in regulating ferroptosis, has been identified as an inducer of ferroptosis in cancer cells. In this study, we investigated the impact of butyrate, a short-chain fatty acid produced by gut microbiota, on erastin-induced ferroptosis in lung cancer cells. Our results demonstrated that butyrate significantly enhanced erastin-induced ferroptosis in lung cancer cells, as evidenced by increased lipid peroxidation and reduced expression of glutathione peroxidase 4 (GPX4). Mechanistically, we found that butyrate modulated the pathway involving activating transcription factor 3 (ATF3) and solute carrier family 7 member 11 (SLC7A11), leading to enhanced erastin-induced ferroptosis. Furthermore, partial reversal of the effect of butyrate on ferroptosis was observed upon knockdown of ATF3 or SLC7A11. Collectively, our findings indicate that butyrate enhances erastin-induced ferroptosis in lung cancer cells by modulating the ATF3/SLC7A11 pathway, suggesting its potential as a therapeutic agent for cancer treatment.

Enhancing percutaneous coronary intervention with heuristic path planning and deep-learning-based vascular segmentation.

Percutaneous coronary intervention (PCI) is a minimally invasive technique for treating vascular diseases. PCI requires precise and real-time visualization and guidance to ensure surgical safety and efficiency. Existing mainstream guiding methods rely on hemodynamic parameters. However, these methods are less intuitive than images and pose some challenges to the decision-making of cardiologists. This paper proposes a novel PCI guiding assistance system by combining a novel vascular segmentation network and a heuristic intervention path planning algorithm, providing cardiologists with clear and visualized information. A dataset of 1077 DSA images from 288 patients is also collected in clinical practice. A Likert Scale is also designed to evaluate system performance in user experiments. Results of user experiments demonstrate that the system can generate satisfactory and reasonable paths for PCI. Our proposed method outperformed the state-of-the-art baselines based on three metrics (Jaccard: 0.4091, F1: 0.5626, Accuracy: 0.9583). The proposed system can effectively assist cardiologists in PCI by providing a clear segmentation of vascular structures and optimal real-time intervention paths, thus demonstrating great potential for robotic PCI autonomy.

Minimally Invasive Surgery for Hypertrophic Obstructive Cardiomyopathy With Mitral Regurgitation.

BACKGROUND: 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. METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.

MicroRNA-92a -mediated endothelial to mesenchymal transition controls vein graft neointimal lesion formation.

PURPOSE: Long-term failure of vein grafts due to neointimal hyperplasia remains an important problem in coronary artery bypass graft surgery. Endothelial to mesenchymal transition (EndMT) contributes to vein graft vascular remodeling. However, there is little study on microRNA-mediated EndMT contributions to neointimal formation in vein graft. We hypothesized that microRNA-92a (miR-92a) might play an important role in determining EndMT contributions to neointimal formation. METHODS: miR-92a and EndMT-related proteins detected by qRT-PCR and Western blot in vitro and in vivo. Adeno-associated virus 6 (AAV6) delivery gene therapy was used to inhibit neointimal formation in vivo. The intimal hyperplasia of vein grafts was measured by HE staining, the expression of EndMT-related protein in vein grafts was measured by immunofluorescence. Immunohistochemistry and luciferase assay were used to detect potential targets of miR-92a. RESULTS: The expression of miR-92a was found to be upregulated in neointimal hyperplasic lesions after vein grafting. Using cultured human umbilical vein endothelial cells (HUVECs), we show that TGF-ß1 treatment of HUVECs significantly increased miR-92a expression and induced EndMT, characterized by suppression of endothelial-specific markers (CD31 and VE-cadherin) and an increase in mesenchymal-specific markers (a-SMA and vimentin), while inhibition of miR-92a expression blunted EndMT in cultured HUVECs. Furthermore, AAV6 mediated miR-92a suppression gene therapy effectively resulted in decreased EndMT and less neointimal formation in vein grafts in vivo. We further identified that integrin alpha 5 (ITGA5) is a potential target gene involved in the development of neointima formation in these vein grafts. CONCLUSION: This data suggests that neointimal formation does not solely rely on vascular smooth muscle cell phenotypic switching but is also related to EndMT, and miR-92a-mediated EndMT is an important mechanism underlying neointimal formation in vein grafts.

Reverse "L" surgical approach for the management of giant tumors of the cervicothoracic junction.

BACKGROUND: An isolated cervical or thoracic surgical approach provides insufficient exposure for achieving complete resection of tumors of the cervicothoracic junction. This study examines reverse "L" thoracotomy as a surgical approach to these tumors. Additionally, the feasibility, safety, and effectiveness of reverse "L" surgical incision for tumor resection was also analyzed. METHODS: Patients with cervicothoracic tumors were identified from an internal database. Subjects were selected on the basis of undergoing reverse "L" thoracotomy from August 2014 to August 2018. The tumor characteristics, surgical technique, completeness of resection, morbidity, and patient outcome were reviewed. RESULTS: All patients successfully underwent resection through reverse "L" surgical approach. No patients needed to undergo full sternotomy. There were 6 neurogenic tumors, 4 thyroid adenocarcinomas, 4 bronchogenic tumors, and 7 other cases in the study. The median operative time was 191.0 min (range, 113.0-348.0 min) and postoperative in-hospital stay ranged from 3 to 7 days. Horner syndrome was observed in 1 case. Hoarseness and lymphatic leakage were evident in 3 and 1 case(s), respectively. Hemidiaphragm paralysis was observed in 1 case. Three cases were unsuccessful in achieving R0 resection. The duration of follow-up ranged from 6 to 42 months. Eleven of 13 patients who underwent resection had no evidence of tumor recurrence. Two patients with metastatic disease died of distant progression within 15 months. CONCLUSIONS: Applying reverse "L" surgical approach is safe, feasible, and effective for the resection of giant tumors of the cervicothoracic junction.

The Mei mini-maze procedure.

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).

Subcutaneous nerve stimulation reduces sympathetic nerve activity in ambulatory dogs with myocardial infarction.

BACKGROUND: Subcutaneous nerve stimulation (ScNS) remodels the stellate ganglion and reduces stellate ganglion nerve activity (SGNA) in dogs. Acute myocardial infarction (MI) increases SGNA through nerve sprouting. OBJECTIVE: The purpose of this study was to test the hypothesis that ScNS remodels the stellate ganglion and reduces SGNA in ambulatory dogs with acute MI. METHODS: In the experimental group, a radio transmitter was implanted during the first sterile surgery to record nerve activity and an electrocardiogram, followed by a second sterile surgery to create MI. Dogs then underwent ScNS for 2 months. The average SGNA (aSGNA) was compared with that in a historical control group (n = 9), with acute MI monitored for 2 months without ScNS. RESULTS: In the experimental group, the baseline aSGNA and heart rate were 4.08±0.35 µV and 98±12 beats/min, respectively. They increased within 1 week after MI to 6.91±1.91 µV (P=.007) and 107±10 beats/min (P=.028), respectively. ScNS reduced aSGNA to 3.46±0.44 µV (P<.039) and 2.14±0.50 µV (P<.001) at 4 and 8 weeks, respectively, after MI. In comparison, aSGNA at 4 and 8 weeks in dogs with MI but no ScNS was 8.26±6.31 µV (P=.005) and 10.82±7.86 µV (P=0002), respectively. Immunostaining showed confluent areas of remodeling in bilateral stellate ganglia and a high percentage of tyrosine hydroxylase-negative ganglion cells. Terminal deoxynucleotidyl transferase dUTP nick end labeling was positive in 26.61%±11.54% of ganglion cells in the left stellate ganglion and 15.94%±3.62% of ganglion cells in the right stellate ganglion. CONCLUSION: ScNS remodels the stellate ganglion, reduces SGNA, and suppresses cardiac nerve sprouting after acute MI.

Left Atrial Appendage Fibrosis and 3-Year Clinical Outcomes in Atrial Fibrillation After Endoscopic Ablation: A Histologic Analysis.

BACKGROUND: Interest has been increasing in the study of atrial fibrosis, an important mechanism in atrial matrix remodeling. However, histopathologic evaluation of atrial fibrosis in non-valvular atrial fibrillation (NVAF) has been limited. This study aimed to analyze the histologic relationship between atrial fibrosis and development or recurrence of NVAF after endoscopic ablation. METHODS: Patients (n = 136) with NVAF undergoing endoscopic ablation and 10 patients in sinus rhythm were enrolled in this study. Left atrial appendage was harvested from all patients. Collagen volume fraction (CVF) and fibrosis biomarkers were evaluated. Linear regression analysis was performed to determine the correlation between clinical variables and atrial fibrosis. The association between atrial fibrosis and NVAF recurrence was evaluated with the Cox proportional hazards model. RESULTS: A significant difference was found in the degree of atrial fibrosis between patients with NVAF and sinus rhythm (CVF: median 15 [interquartile range (IQR), 13-17] vs median 6.5 [IQR, 5-10.25]; P < .001, respectively). Factors independently associated with CVF in multivariate linear regression analysis included longer duration of NVAF and larger left atrial diameter. Among 136 patients with ablation, 19 (13.9%) had recurrent NVAF. In multivariate Cox regression analysis, CVF (hazard ratio [HR] 1.093; 95% confidence interval [CI], 1.007-1.186; P = .033) and left atrial diameter (HR for 3-mm change 1.240; 95% CI, 1.004-1.531; P = .046) were independent risk factors for NVAF recurrence. CONCLUSIONS: Atrial fibrosis in NVAF is not only associated with left atrial diameter and duration of atrial fibrillation but also with recurrence after ablation. Atrial fibrosis may be a future therapeutic target for reduction of recurrence after endoscopic ablation.

Minimally Invasive Surgery for Coronary-Pulmonary Artery Fistula Via Parasternal Minithoracotomy.

Epicardial surgical repair has been proven to be effective for patients with coronary- pulmonary artery fistula (CPAF). However, most of the surgery has been performed through a median sternotomy under cardiopulmonary bypass. In this report, we describe a novel technique of performing minimally invasive surgery for CPAF patients without extracorporeal circulation via a parasternal minithoracotomy. This technique has proved to be safe and effective and may be worthy of use for patients with CPAF.

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.

Concomitant thoracoscopic surgery for solitary pulmonary nodule and atrial fibrillation.

OBJECTIVES: The incidence of both solitary pulmonary nodules (SPN) and non-valvular atrial fibrillation (NVAF) has increased over the past decade. We performed concomitant video-assisted thoracoscopic surgery with modified epicardial radiofrequency ablation procedure for NVAF and SPN resection. METHODS: Sixteen patients (7 men, mean age 62.6 ± 11.2 years) with SPN and NVAF underwent this procedure. Of these patients, 10 had paroxysmal atrial fibrillation and 6 persistent atrial fibrillation. A modified epicardial radiofrequency ablation combined with pulmonary vein isolation, circumferential left atrial ablation, ganglionic plexus ablation and left atrial appendage resection was performed for all patients. Left pulmonary surgery was carried out subsequently. RESULTS: The mean procedure duration was 203.1 ± 15.6 (range 177-224) min. All patients successfully underwent this procedure with no conversion to sternotomy or pacemaker implantation. Of the 16 included patients, 13 received lobectomy and 3 received wedge resection. No severe complications occurred postoperatively. The mean length of hospital stay was 9.1 ± 1.4 (range 7-11) days with a mean follow-up period of 18.7 ± 6.7 (range 8-32) months. One patient had AF recurrence 6 months postoperatively. No pulmonary vein stenosis was detected at the 3rd postoperative month. There were no deaths or thromboembolic events during follow-up. CONCLUSIONS: This concomitant therapy proved to be safe and yielded good clinical outcomes. Therefore, it deserves to be considered as a treatment for patients with SPN and NVAF.

Endothelin-1 is associated with dilatation of the left atrium and can be an independent predictor of atrial fibrillation after mitral valve surgery.

OBJECTIVES: This study analysed the association between endothelin-1 (ET-1) and left atrial dimension (LAD) and evaluated whether ET-1 can be a predictor of postoperative atrial fibrillation (POAF) after mitral valve surgery. METHODS: This is a prospective study that enrolled 80 patients who underwent isolated mitral valve surgery. Plasma concentrations of ET-1 from peripheral venous blood were tested. POAF was detected using a telemetry strip or 12-lead electrocardiogram until the time of discharge. RESULTS: Patients undergoing mitral valve surgery with preoperative sinus rhythm (n = 80; average age 63.9 ± 7.9 years) were recruited to this study. POAF was documented in 31 (38.8%) patients. Preoperative plasma ET-1 levels were higher in patients with POAF compared to those without POAF (2.23 ± 0.67 vs 1.68 ± 0.59 pg/ml; P < 0.001). The plasma concentrations of ET-1 were positively correlated with LAD (Pearson's r = 0.421; P < 0.001). Multivariate logistic regression analysis revealed that LAD (odds ratio 1.170, 95% confidence interval 1.039-1.317; P = 0.009) and preoperative plasma ET-1 levels (upper versus lower 50th percentile: odds ratio 3.713, 95% confidence interval 1.085-12.701; P = 0.037) were predictors of POAF after mitral valve surgery. CONCLUSIONS: Plasma levels of ET-1 were positively correlated with LAD in patients with mitral valve disease. An elevated preoperative plasma ET-1 level can be used as a predictor of POAF after mitral valve surgery.

Hemodynamic parameters predict the risk of atrial fibrillation after cardiac surgery in adults.

BACKGROUND: Postoperative atrial fibrillation (POAF) is a common complication following cardiac surgery and is associated with poorer prognosis. This study attempted to evaluate whether hemodynamic parameters determined by a right heart catheter predict the occurrence of POAF. HYPOTHESIS: We hypothesized that atrial fibrillation after cardiac surgery can be predicted by hemodynamic parameters determined by a right heart catheter. METHODS: Between October 2015 and January 2017, 126 patients with preoperative sinus rhythm undergoing coronary artery bypass grafting and/or aortic valve replacement were enrolled in this study. Complete echocardiographic examination was performed preoperatively, and hemodynamic parameters were recorded via a right heart catheter before anesthesia induction. Postoperative telemetry strips and electrocardiogram were used to detect atrial fibrillation until discharge. Multivariate logistic regression was used to identify risk factors of POAF. RESULTS: The overall incidence of POAF was 40/126 (31.7%). Multivariate logistic regression analysis determined that left atrial dimension (LAD) (adjusted odds ratio [OR]: 1.118, 95% confidence interval [CI]: 1.020-1.227, P = 0.018), pulmonary capillary wedge pressure (PCWP) (adjusted OR: 1.225, 95% CI: 1.082-1.387, P = 0.001), and pulmonary artery systolic pressure (PASP) (adjusted OR: 1.076, 95% CI: 1.019-1.137, P = 0.008) were significant predictors of POAF. CONCLUSIONS: The present study suggested that LAD, PCWP, and PASP were robust predictors of POAF. These parameters may indicate a patient's susceptibility toward developing POAF and help to identify patients who need preventive treatment.

Surgical Management of Giant Left Sinus of Valsalva Aneurysm Causing Left Anterior Descending Coronary Artery Occlusion.

Sinus of Valsalva aneurysm (SVA) is a rare cardiac anomaly, which mostly occurs in the right or noncoronary sinus of Valsalva. Left sinus of Valsava is infrequent. Unruptured SVAs are usually asymptomatic, and the diagnosis of unruptured SVA is usually accidental. A giant unruptured SVA may compress the coronary artery and cause myocardial infarction. Here, we report a rare case of a 50-year-old patient with unruptured giant left SVA causing occlusion of the left anterior descending coronary artery, which was successfully managed with our apparently unique surgical procedure.

Effects of renal sympathetic denervation on the stellate ganglion and brain stem in dogs.

BACKGROUND: Renal sympathetic denervation (RD) is a promising method of neuromodulation for the management of cardiac arrhythmia. OBJECTIVE: We tested the hypothesis that RD is antiarrhythmic in ambulatory dogs because it reduces the stellate ganglion nerve activity (SGNA) by remodeling the stellate ganglion (SG) and brain stem. METHODS: We implanted a radiotransmitter to record SGNA and electrocardiogram in 9 ambulatory dogs for 2 weeks, followed by a second surgery for RD and 2 months SGNA recording. Cell death was probed by terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) assay. RESULTS: Integrated SGNA at baseline and 1 and 2 months after RD were 14.0 ± 4.0, 9.3 ± 2.8, and 9.6 ± 2.0 µV, respectively (P = .042). The SG from RD but not normal control dogs (n = 5) showed confluent damage. An average of 41% ± 10% and 40% ± 16% of ganglion cells in the left and right SG, respectively, were TUNEL positive in RD dogs compared with 0% in controls dogs (P = .005 for both). The left and right SG from RD dogs had more tyrosine hydroxylase-negative ganglion cells than did the left SG of control dogs (P = .028 and P = .047, respectively). Extensive TUNEL-positive neurons and glial cells were also noted in the medulla, associated with strongly positive glial fibrillary acidic protein staining. The distribution was heterogeneous, with more cell death in the medial than lateral aspects of the medulla. CONCLUSION: Bilateral RD caused significant central and peripheral sympathetic nerve remodeling and reduced SGNA in ambulatory dogs. These findings may in part explain the antiarrhythmic effects of RD.

miR-503 inhibits platelet-derived growth factor-induced human aortic vascular smooth muscle cell proliferation and migration through targeting the insulin receptor.

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.

Concomitant Maze IV Ablation Procedure Performed Entirely by Bipolar Clamp Through Right Lateral Minithoracotomy.

Atrial fibrillation ablation with bipolar clamp has proved to be effective for patients with valvular atrial fibrillation. However, left pulmonary vein ablation with bipolar clamp through right minithoracotomy was considered difficult or impossible. In this report, we described a novel technique of performing concomitant Maze IV ablation procedure entirely by bipolar clamp through right minithoracotomy. Left pulmonary vein ablation with bipolar clamp was performed through an established channel and a natural space. This technique has proved to be safe and feasible and to have good clinical outcomes that may deserve further use for patients with atrial fibrillation and mitral valve disease.

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.