Simultaneous thoracoscopic surgery in patients with atrial fibrillation and early-stage lung cancer.

OBJECTIVES: Atrial fibrillation (AF) and early-stage lung cancer can both be treated under thoracoscopy. This study aims to evaluate the feasibility and safety of simultaneous thoracoscopic surgery for atrial fibrillation and early-stage lung cancer. METHODS: This was a single-center, retrospective study of 865 patients with paroxysmal or non-paroxysmal AF who underwent surgical ablation between October 2014 and December 2021. Patients were divided into two groups according to whether they have undergone simultaneous thoracoscopic early-stage lung cancer surgery and resulting in 24 pairs of patients. RESULTS: In total, 48 patients (24 matched pairs) were analyzed. The age was 63.71 ± 8.43 years. Procedure time and postoperative mechanical ventilation time were significantly lower in the group AF than group AFLC (Atrial fibrillation and lung cancer) (140.38 ± 27.53 vs. 230.79 ± 59.06 min, P<0.001; 5 vs 6.5 h, P = 0.002). There was no significant difference between the groups in terms of operative bleeding volume (90.00 ± 29.78 vs 85.83 ± 53.56 ml, P = 0.741), total postoperative drainage volume (1020.83 ± 516.5 vs 1406.25 ± 840.33 ml, P = 0.067), ICU (intensive care unit) length of stay (LOS) (43.5 vs 44 h, P = 0.33), hospitalization LOS (9.29 ± 1.92 vs 8.58 ± 1.98 days, P = 0.214) and incidence of freedom from AF or complications. CONCLUSIONS: Simultaneous thoracoscopic surgical AF ablation and early-stage lung cancer is safe and feasible. It can be used as an alternative method for coexisting atrial fibrillation and lung cancer with acceptable operative risks.

Surgical treatment of atrial fibrillation in mitral valve surgery: a narrative review.

Background and Objective: Atrial fibrillation (AF) is one of the most common arrhythmias in clinical practice, which leads to cardiac decompensation, cardiovascular and cerebrovascular infarction, and other thromboembolic diseases. AF is one of the most common comorbidities of valvular heart disease, especially in mitral valve disease. At the time of their mitral valve surgery, 20-42% of patients have AF. It is beneficial to maintain postoperative sinus rhythm and minimize complications when AF surgery is performed concurrently with mitral valve surgery. This review describes the surgical management of AF in mitral valve surgery, including AF surgical route, surgical ablation technology and surgical approaches. The aim of this review is to enable more patients with AF to receive more appropriate and individualised treatment. Methods: A narrative review was conducted on the literature on PubMed, Embase including all relevant studies published until November 2023. Key Content and Findings: This review focuses on the surgical management of AF during mitral valve surgery, including AF surgical route, surgical ablation technology and surgical approaches. Conclusions: Mitral valve surgery combined with AF surgery facilitates the maintenance of postoperative sinus rhythm in patients, reduces the risk of postoperative stroke, and improves survival. Advances in ablation technology have reduced the difficulty of the procedure, making it possible for more patients to undergo surgical ablation. In the future, it will be possible to tailor specific lesion sets and ablation modalities for individual patients. This would make surgical treatment of AF more effective and applicable to a larger population of patients with AF and mitral valve disease.

Raman spectroscopy for esophageal tumor diagnosis and delineation using machine learning and the portable Raman spectrometer.

Esophageal cancer is one of the leading causes of cancer-related deaths worldwide. The identification of residual tumor tissues in the surgical margin of esophageal cancer is essential for the treatment and prognosis of cancer patients. But the current diagnostic methods, either pathological frozen section or paraffin section examination, are laborious, time-consuming, and inconvenient. Raman spectroscopy is a label-free and non-invasive analytical technique that provides molecular information with high specificity. Here, we report the use of a portable Raman system and machine learning algorithms to achieve accurate diagnosis of esophageal tumor tissue in surgically resected specimens. We tested five machine learning-based classification methods, including k-Nearest Neighbors, Adaptive Boosting, Random Forest, Principal Component Analysis-Linear Discriminant Analysis, and Support Vector Machine (SVM). Among them, SVM shows the highest accuracy (88.61 %) in classifying the esophageal tumor and normal tissues. The portable Raman system demonstrates robust measurements with an acceptable focal plane shift of up to 3 mm, which enables large-area Raman mapping on resected tissues. Based on this, we finally achieve successful Raman visualization of tumor boundaries on surgical margin specimens, and the Raman measurement time is less than 5 min. This work provides a robust, convenient, accurate, and cost-effective tool for the diagnosis of esophageal cancer tumors, advancing toward Raman-based clinical intraoperative applications.

Concurrent vs Staged Hybrid Ablation for Long-Standing Persistent Atrial Fibrillation: A Propensity-Matched Cohort Study.

BACKGROUND: Long-term success rates of catheter ablation (CA) for long-standing persistent atrial fibrillation (LSPAF) are less than satisfactory. Further improvement of ablation methods is crucial for enhancing the treatment of LSPAF. OBJECTIVES: This study sought to compare the outcomes of concurrent vs staged minimally invasive surgical-catheter hybrid ablation for LSPAF. METHODS: From December 2015 to December 2021, 104 matched patients (concurrent and staged, 1:1) were included in study. In the concurrent group, both left unilateral thoracoscopic epicardial ablation (EA) and CA were performed simultaneously in one procedure. In the staged group, EA was performed at the first hospitalization. If the patients experienced atrial fibrillation (AF) recurrence, CA was performed between 3 months and 1 year after EA. RESULTS: In the concurrent group, 4 patients were restored to sinus rhythm after EA, and 41 were patients restored to sinus rhythm during CA; 86.5% (45 of 52) achieved intraprocedural AF termination during concurrent hybrid ablation. In the staged group, all 52 patients underwent staged CA because of the recurrence of AF or atrial tachycardia (AT). Forty-seven (90.4%) patients achieved intraprocedural AF or AT termination during CA. Freedom from AF or AT off antiarrhythmic drugs at 2 years after hybrid ablation was 79.9% ± 5.7% in the concurrent group and 86.0% ± 4.9% in the staged group (P = 0.390). Failure of intraprocedural AF termination (HR: 14.378) was an independent risk factor for AF recurrence after hybrid ablation. CONCLUSIONS: Both concurrent and staged hybrid ablation could be safely and effectively applied to treat LSPAF. Improving the intraprocedural AF termination rate predicted better outcomes.

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

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

Depleting DDX1 sensitizes non-small cell lung cancer cells to chemotherapy by attenuating cancer stem cell traits.

AIMS: DEAD-box helicase 1 (DDX1) has oncogenic properties in several human cancers. However, the clinical significance and biological role of DDX1 in non-small cell lung cancer (NSCLC) remain elusive. Here, we examined the chemotherapeutic relevance of DDX1 in NSCLC. MAIN METHODS: We used the UALCAN database, Western blot analysis, and immunohistochemical and RT-qPCR assays to assess DDX1 expression in NSCLC cell lines (H1650 and A549) and patient tissues. The role of DDX1 in the chemosensitivity of NSCLC cells and the underlying mechanisms were determined using colony formation, CCK-8, flow cytometry, wound healing, Transwell, tumor sphere formation, and immunostaining assays, together with a xenograft tumor model in nude mice. KEY FINDINGS: Our study revealed that DDX1 was overexpressed in NSCLC cell lines and tissues. We further found that depleting DDX1 increased the sensitivity of NSCLC cells to the chemotherapy drug cisplatin, increased cell apoptosis, and inhibited cell migration and invasion. Co-immunoprecipitation assays revealed that DDX1 bound to ADAR1, and increased ADAR1 protein expression. Furthermore, we found that ADAR1 mediated cancer-promoting effects, independent of deaminase activity, by binding to RAC3 mRNA. Our findings not only show that DDX1 mediates chemosensitivity to cisplatin via the ADAR1/RAC3 axis but also highlight the importance of ADARs as essential RNA-binding proteins for cell homeostasis, as well as cancer progression. SIGNIFICANCE: Our results suggest that DDX1 plays an important role in the development and progression of human NSCLC and that DDX1 may serve as a therapeutic target in NSCLC patients.

Losartan attenuates upstream vasculopathy in a modified piglet model of pulmonary vein stenosis: contribution of the Hippo pathway.

Background: 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. Methods: 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 mechanism in vitro. Results: The 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 (P<0.01). Losartan treatment improved the pathological changes in piglets and decreased YAP expression in the neointima (P<0.01). In vitro, losartan suppressed angiotensin II-induced cell proliferation by inhibiting dephosphorylation and nuclear translocation of YAP in human umbilical vein endothelial cells (P<0.05). Conclusions: 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 abnormal expression of circ-ARAP2 promotes ESCC progression through regulating miR-761/FOXM1 axis-mediated stemness and the endothelial-mesenchymal transition.

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

Individualized strategy of minimally invasive cardiac surgery in congenital cardiac septal defects.

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 < 0.01). No postoperative death was observed. Postoperative complications included one case of chest exploration for bleeding, one case of reoperation due to patch dehiscence during the same admission, one case of transient neural dysfunction, three cases of diaphragmatic paresis and 13 cases of atelectasis. The median stay in the intensive care unit was two days, while the median postoperative hospitalization duration was six days. The echocardiography results before discharge indicated no significant residual lesions. No reoperation, no new onset of chest deformities and no sclerosis were observed during the follow-up. 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.

Identification of NLE1/CDK1 axis as key regulator in the development and progression of non-small cell lung cancer.

Non-small cell lung cancer (NSCLC) is the most common pathological type of lung cancer, which is a severer threaten to human health because of its extremely high morbidity and mortality. In this study, the role of Notchless homolog 1 (NLE1) in the development of NSCLC was investigated and the underlying mechanism was explored. The outcomes showed that NLE1 expression is significantly higher in tumor tissues than normal tissues, and is correlated with the pathological stage. The regulation of NSCLC development by NLE1 was also visualized by the in vitro and in vivo loss-of-function studies, which indicated the inhibition of cell growth and migration, as well as enhancement of cell apoptosis on condition of NLE1 knockdown. As for the mechanism, it was demonstrated that NLE1 may execute its tumor-regulating function through activating E2F1-mediated transcription of CDK1, and PI3K/Akt signaling pathway was also supposed as a downstream of NLE1 in the regulation of NSCLC. Both CDK1 overexpression and treatment of Akt pathway activator could reverse the NLE1 knockdown induced NSCLC inhibition to some extent. In conclusion, this study identified NLE1 as a novel tumor promotor in the development and progression of NSCLC, which may be a potential therapeutic target in the treatment of NSCLC.

Knockdown of hsa_circ_0000729 Inhibits the Tumorigenesis of Non-Small Cell Lung Cancer Through Mediation of miR-1281/FOXO3 Axis.

BACKGROUND: 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.

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.

Down Regulation of SIRT2 Reduced ASS Induced NSCLC Apoptosis Through the Release of Autophagy Components via Exosomes.

Metastasis of cancer is the main cause of death in many types of cancer. Acute shear stress (ASS) is an important part of tumor micro-environment, it plays a crucial role in tumor invasion and spread. However, less is known about the role of ASS in tumorigenesis and metastasis of NSCLC. In this study, NSCLC cells were exposed to ASS (10 dyn/cm2) to explore the effect of ASS in regulation of autophagy and exosome mediated cell survival. Finally, the influence of SIRT2 on NSCLC cell metastasis was verified in vivo. Our data demonstrates that ASS promotes exosome and autophagy components releasing in a time dependent manner, inhibition of exosome release exacerbates ASS induced NSCLC cell apoptosis. Furthermore, we identified that this function was regulated by sirtuin 2 (SIRT2). And, RNA immunoprecipitation (RIP) assay suggested SIRT2 directly bound to the 3'UTR of transcription factor EB (TFEB) and facilitated its mRNA stability. TFEB is a key transcription factor involved in the regulation of many lysosome related genes and plays a critical role in the fusion of autophagosome and lysosome. Altogether, this data revealed that SIRT2 is a mechanical sensitive protein, and it regulates ASS induced cell apoptosis by modulating the release of exosomes and autophagy components, which provides a promising strategy for the treatment of NSCLCs.

Hsa_circ_0001869 promotes NSCLC progression via sponging miR-638 and enhancing FOSL2 expression.

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.

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).

Knockdown of Linc00511 inhibits TGF-ß-induced cell migration and invasion by suppressing epithelial-mesenchymal transition and down-regulating MMPs expression.

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-ß1-induced EMT in lung cancer. Our results showed that knockdown of linc00511 significantly inhibited TGF-ß1-induced migration and invasion and down-regulated the mRNA and protein levels of MMP2, MMP9 and MMP12 in TGF-ß1 treated SPCA1 and H1975 cells. Also, western blotting results showed that inhibition of linc00511 remarkably suppressed TGF-ß1-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-ß1-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-ß1-induced migration and invasion via inhibiting EMT and MMPs in lung cancer cells.

The USP21/YY1/SNHG16 axis contributes to tumor proliferation, migration, and invasion of non-small-cell lung cancer.

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.

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

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

Minimally invasive and conventional surgical treatment of primary benign cardiac tumors.

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 < 0.01) and transfusion rate (5.9% vs 33.3%, P = 0.033) than those who had sternotomy. There was no peri-operative death, and all the patients were alive and free of recurrence at the latest follow-up. CONCLUSIONS: Surgical resection of primary benign cardiac tumors is safe, effective and durable. The right anterolateral minithoracotomy provides the same postoperative recovery as standard median sternotomy, but less transfusion. It can be considered as a promising alternative approach.