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BackgroundCOVID-19 patients with comorbidities such as hypertension or heart failure (HF) are associated with poor clinical outcomes. Angiotensin-converting enzyme 2 (ACE2), the critical enzyme for SARS-CoV-2 infection, is broadly expressed in many organs including heart. However, the cellular distribution of ACE2 in the human heart, particularly the failing heart is unknown. MethodsWe analyzed single-cell RNA sequencing (scRNA-seq) data in both normal and failing hearts, and characterized the ACE2 gene expression profile in various cell subsets, especially in cardiomyocyte subsets, as well as its interaction with gene networks relating to various defense and immune responses at the single cell level. ResultsThe results demonstrated that ACE2 is present in cardiomyocytes (CMs), endothelial cells, fibroblasts and smooth muscle cells in the heart, while the number of ACE2-postive (ACE2+) CMs and ACE2 gene expression in these CMs are significantly increased in the failing hearts. Interestingly, both brain natriuretic peptides (BNP) and atrial natriuretic peptide (ANP) are significantly up-regulated in the ACE2+ CMs. Further analysis shows that ANP, BNP and ACE2 may form a negative feedback loop with a group of genes associated with the development of heart failure. To our surprise, we found that genes related to virus entry, virus replication and suppression of interferon-gamma (IFN-{gamma}) signaling are all up-regulated in CMs in failing hearts, and the increases were significantly higher in ACE2+ CMs as compared with ACE2 negative (ACE2-) CMs, suggesting that these ACE2+ CMs may be more vulnerable to virus infection. Since ACE2 expression is correlated with BNP expression, we further performed retrospective analysis of the plasma BNP levels and clinic outcome of 91 COVID-19 patients from a single-center. Patients with higher plasma BNP were associated with significantly higher mortality rate and expression levels of inflammatory and infective markers such as procalcitonin and C-reactive protein. ConclusionIn the failing heart, the upregulation of ACE2 and virus infection associated genes, as well as the increased expression of ANP and BNP could facilitate SARS-CoV-2 virus entry and replication in these vulnerable cardiomyocyte subsets. These findings may advance our understanding of the underlying molecular mechanisms of myocarditis associated with COVID-19.
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Objective:To observe the curative effect of titanium-clip combined with mucosal injection for peptic ulcer bleeding and the impact on inflammation and stress.Methods:126 patients were randomly divided into the control group and the observation group according to the method of random number table, 63 cases in each group. The control group received endoscopic mucosal injection of adrenaline, and the study group received titanium-clip additionally. The blood loss, amount of blood transfusion and hospital stay, the levels of inflammatory cytokines [C-reactive protein (CRP), interleukin (IL)-6 and IL-8] and stress indexes (blood sugar, adrenaline, cortisol and C-peptide) were compared between the two groups.Results:Compared with the control group, the blood loss, amount of blood transfusion and hospital stay in the observation group were significantly less ( P<0.05), and the contents of CRP, IL-6, IL-8, blood glucose, adrenaline, cortisol and C-peptide were significantly reduced at 12 hours after operation ( P<0.05). Conclusions:The joint application of titanium-clip and mucosal injection shows fewer impacts on inflammation and stress, and is safe for peptic ulcer bleeding.
