BackgroundAlthough N6-methyladenosine (m6A) RNA methylation is the most abundant reversible methylation of mRNA, which plays a critical role in regulating cancer processing, few studies have examined the role of m6A in nonsmall-cell lung cancer-derived cancer stem-like cells (CSCs).MethodsCSCs were enriched by culturing NSCLC cells in a serum-free medium, and stem factors, including CD24, CD44, ALDH1, Nanog, Oct4, and Sox2 were detected by Western blot. ALKBH5 expression was measured by employing a tissue array. Global m6A methylation was measured after ALKBH5 knockdown. Malignances of CSCs were detected by performing CCK-8 assay, invasion assay, cell cycle analysis, and tumor formation in vitro and in vivo.Resultsm6A demethylase ALKBH5 is highly expressed in CSCs derived from NSCLC. Knockdown of ALKBH5 increased global m6A level, and also increased E-cadherin, decreased stem hallmarkers, Nanog and Oct4, and inhibited stemness of CSCs. In lung carcinoma, ALKBH5 is found to be positively correlated with p53 by using Gene Expression Profiling Interactive Analysis (GEPIA) online tool. P53 transcriptionally regulates ALKBH5 and subsequently regulates the global m6A methylation level. Knockdown of p53 or inhibition of p53’s transcriptional activity by addition of its specific inhibitor PFT-α decreased expression of ALKBH5 and CSCs’ malignancies, including proliferation, invasion, and tumor formation ability, indicating that p53 may partially regulate CSC’s malignancies via ALKBH5. Furthermore, we also found p53 transcriptionally regulates PRRX1, which is consistent with our previous report.ConclusionCollectively, our findings indicate the pivotal role of ALKBH5 in CSCs derived from NSCLC and highlight the regulatory function of the p53/ALKBH5 axis in modulating CSC progression, which could be a promising therapeutic target for NSCLC.
Artificial intelligence (AI), the technique of extracting information from complex database using sophisticated computer algorithms, has incorporated itself in medical field. AI techniques have shown the potential to accelerate the progression of diagnosis and treatment of cardiovascular diseases (CVDs), including heart failure, atrial fibrillation, valvular heart disease, hypertrophic cardiomyopathy, congenital heart disease and so on. In clinical scenario, AI have been proved to apply well in CVD diagnosis, enhance effectiveness of auxiliary tools, disease stratification and typing, and outcome prediction. Deeply developed to capture subtle connections from massive amounts of healthcare data, recent AI algorithms are expected to handle even more complex tasks than traditional methods. The aim of this review is to introduce current applications of AI in CVDs, which may allow clinicians who have limited expertise of computer science to better understand the frontier of the subject and put AI algorithms into clinical practice.
Rationale: Postoperative chylothorax is a rare complication after pulmonary resection. Thoracic duct variations may play a key role in postoperative chylothorax occurrence and make treatment difficult. No studies in the literature have reported the successful treatment of chylothorax second to thoracic duct variation by lipiodol-based lymphangiography.Patient concerns: A 63-year-old male and a 28-year-old female with primary lung adenocarcinoma were treated by videoassisted thoracoscopic cancer resection, and suffered postoperative chylothorax. Conservative treatment was ineffective, including nil per os, persistent thoracic drainage, fatty food restriction, and somatostatin administration.Diagnosis: Postoperative chylothorax.Interventions: Patients received lipiodol-based lymphangiography under fluoroscopic guidance. Iatrogenic injuries were identified at thoracic duct variations, including an additional channel in case 1 and the lymphatic plexus instead of the thoracic duct in case 2.Outcomes: Thoracic duct variations were identified by lipiodol-based lymphangiography, and postoperative chylothorax was successfully treated by lipiodol embolizing effect.Lessons: Thoracic duct variations should be considered after the failure of conservative treatment for postoperative chylothorax secondary to pulmonary resection. Lipiodol-based lymphangiography is valuable for identifying the thoracic duct variations and embolizing chylous leakage.
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