ABSTRACT
COVID-19 is an infectious disease caused by SARS-CoV-2, which enters host cells via the cell surface proteins ACE2 and TMPRSS2. Using a variety of normal and malignant models and tissues from the aerodigestive and respiratory tracts, we investigated the expression and regulation of ACE2 and TMPRSS2. We find that ACE2 expression is restricted to a select population of highly epithelial cells. Notably, infection with SARS-CoV-2 in cancer cell lines, bronchial organoids, and patient nasal epithelium, induces metabolic and transcriptional changes consistent with epithelial to mesenchymal transition (EMT), including upregulation of ZEB1 and AXL, resulting in an increased EMT score. Additionally, a transcriptional loss of genes associated with tight junction function occurs with SARS-CoV-2 infection. The SARS-CoV-2 receptor, ACE2, is repressed by EMT via TGFbeta, ZEB1 overexpression and onset of EGFR TKI inhibitor resistance. This suggests a novel model of SARS-CoV-2 pathogenesis in which infected cells shift toward an increasingly mesenchymal state, associated with a loss of tight junction components with acute respiratory distress syndrome-protective effects. AXL-inhibition and ZEB1-reduction, as with bemcentinib, offers a potential strategy to reverse this effect. These observations highlight the utility of aerodigestive and, especially, lung cancer model systems in exploring the pathogenesis of SARS-CoV-2 and other respiratory viruses, and offer important insights into the potential mechanisms underlying the morbidity and mortality of COVID-19 in healthy patients and cancer patients alike.
ABSTRACT
Objective To compare clinical effect of unipolar versus bipolar radiofrequency ablation in treating atrial fibrillation (AF) in elderly patients and discuss the correlated risk factors.Methods From October 2008 to December 2013,a total of 50 elderly patients with organic heart disease and AF underwent radiofrequency ablation surgery.All patients were divided into 2 groups of unipolar (group A,n=20) and bipolar (group B,n=30 patients) radiofrequency ablations.The variations of electrocardiogram (ECG) and ultrasonic cardiogram (UCG) in patients were collected and the complications and the NYHA class of the patients were recorded at 3,6 and 12 months after surgery.The total 43 elderly patients were divided into sinus group and non-sinus group according to their ECG at 12 months after surgery.Results The recovery rates of sinus rhythm at 3,6 and 12 months after surgery were 73.7％(14/19),66.7％(12/18) and 61.1％ (11/18)respectively in group A and 82.8％(24/29),85.2％(23/27)and 88.0％(22/25) respectively in group B.Two groups of the recovery rate of sinus rhythm had a statistically significant difference between the two groups (P＜0.05) at 12 months after surgery.The complication rate in group A was higher than in group B [55.0％ (11 cases) vs.26.7％ (8 cases),P＜0.05].Preoperative history of AF and left atrial diameter were the influencing factors for the sinus rhythm recovery rates (P＜0.05).Conclusions Bipolar radiofrequency ablation for AF is safe and has less complications and high success rate of restoring sinus rhythm.The patients with long preoperative history of AF and left atrium distension have a low success rate of restoring sinus rhythm with a high recurrence rate.
