Accumulating evidence has demonstrated that up-regulation of the angiotensin (Ang)-converting enzyme (ACE)/AngII/AngII type 1 receptor (AT1R) axis aggravates pulmonary fibrosis. The recently discovered ACE2/Ang-(1-7)/Mas axis, which counteracts the activity of the ACE/AngII/AT1R axis, has been shown to protect against pulmonary fibrosis. However, the mechanisms by which ACE2 and Ang-(1-7) attenuate pulmonary fibrosis remain unclear. We hypothesized that up-regulation of the ACE2/Ang-(1-7)/Mas axis protects against bleomycin (BLM)-induced pulmonary fibrosis by inhibiting the mitogen-activated protein kinase (MAPK)/NF-κB pathway. In vivo, Ang-(1-7) was continuously infused into Wistar rats that had received BLM or AngII. In vitro, human fetal lung-1 cells were pretreated with compounds that block the activities of AT1R, Mas (A-779), and MAPKs before exposure to AngII or Ang-(1-7). The human fetal lung-1 cells were infected with lentivirus-mediated ACE2 before exposure to AngII. In vivo, Ang-(1-7) prevented BLM-induced lung fibrosis and AngII-induced lung inflammation by inhibiting the MAPK phosphorylation and NF-κB signaling cascades. However, exogenous Ang-(1-7) alone clearly promoted lung inflammation. In vitro, Ang-(1-7) and lentivirus-mediated ACE2 inhibited the AngII-induced MAPK/NF-κB pathway, thereby attenuating inflammation and α-collagen I production, which could be reversed by the Mas inhibitor, A-779. Ang-(1-7) inhibited AngII-induced lung fibroblast apoptotic resistance via inhibition of the MAPK/NF-κB pathway and activation of the BCL-2-associated X protein/caspase-dependent mitochondrial apoptotic pathway. Ang-(1-7) alone markedly stimulated extracellular signal-regulated protein kinase 1/2 phosphorylation and the NF-κB cascade. Up-regulation of the ACE2/Ang-(1-7)/Mas axis protected against pulmonary fibrosis by inhibiting the MAPK/NF-κB pathway. However, close attention should be paid to the proinflammatory effects of Ang-(1-7).
medRxiv preprint 6 datasets. The predictive performance was further evaluated in test dataset on lung lobe-and patients-level. Main outcomesShort-term hospital stay (≤10 days) and long-term hospital stay (>10 days). ResultsThe CT radiomics models based on 6 second-order features were effective in discriminating short-and long-term hospital stay in patients with pneumonia associated with SARS-CoV-2 infection, with areas under the curves of 0.97 (95%CI 0.83-1.0) and 0.92 (95%CI 0.67-1.0) by LR and RF, respectively, in the test dataset. The LR model showed a sensitivity and specificity of 1.0 and 0.89, and the RF model showed similar performance with sensitivity and specificity of 0.75 and 1.0 in test dataset. ConclusionsThe machine learning-based CT radiomics models showed feasibility and accuracy for predicting hospital stay in patients with pneumonia associated with SARS-CoV-2 infection.All rights reserved. No reuse allowed without permission.author/funder, who has granted medRxiv a license to display the preprint in perpetuity. Results Patient characteristicsA total of 52 patients with laboratory-confirmed SARS-CoV-2 infection and initial CT images were enrolled from 5 designated hospitals in Ankang, Lishui, Zhenjiang, Lanzhou, and Linxia, China. As of February 20, 14 patients were still hospitalized, and 7 patients had non-findings in CT images. Therefore, 31 patients with 72 lesion segments were included in the final analysis. The training and inter-validation cohort comprised 26 patients (12 from Ankang, 8 from Lishui, 4 from Lanzhou, and 2 from Linxia) with 59 lesion segments, and test cohort comprised 5 patients from Zhenjiang with 13 lesion segments. The median age was 38.00 (interquartile range, 26.00-47.00) years and 17 (57%) were male. Comorbidities, symptoms and laboratory findings at admission were summarized in Table 1. Performance of CT radiomics modelThe CT radiomics model, based on 6 features (supplementary Table1), showed the highest AUC on the training and inter-validation dataset. The performance of modeling using LR and RF methods was shown in Figure 2. On lung lobe-level, models using LR method significantly distinguished short-and long-term hospital stay (In training and inter-validation datasets, cut-off value 0.31, AUC 0.94 (95%CI 0.92-0.97), sensitivity 1.0, specificity 0.87, NPV 1.0, and PPV 0.88; In test dataset, AUC 0.97 (95%CI 0.83-1.0), sensitivity 1.0, specificity 0.89, NPV 1.0, and PPV 0.8). Besides, models using RF method obtained satisfied results (In training and inter-validation datasets, cut-off value 0.68, AUC 1.0 (95%CI 1.0-1.0), All rights reserved. No reuse allowed without permission.author/funder, who has granted medRxiv a license to display the preprint in perpetuity.
Rationale: Chest computed tomography (CT) has been used for the coronavirus disease 2019 (COVID-19) monitoring. However, the imaging risk factors for poor clinical outcomes remain unclear. In this study, we aimed to assess the imaging characteristics and risk factors associated with adverse composite endpoints in patients with COVID-19 pneumonia. Methods: This retrospective cohort study enrolled patients with laboratory-confirmed COVID-19 from 24 designated hospitals in Jiangsu province, China, between 10 January and 18 February 2020. Clinical and initial CT findings at admission were extracted from medical records. Patients aged < 18 years or without available clinical or CT records were excluded. The composite endpoints were admission to ICU, acute respiratory failure occurrence, or shock during hospitalization. The volume, density, and location of lesions, including ground-glass opacity (GGO) and consolidation, were quantitatively analyzed in each patient. Multivariable logistic regression models were used to identify the risk factors among age and CT parameters associated with the composite endpoints. Results: In this study, 625 laboratory-confirmed COVID-19 patients were enrolled; among them, 179 patients without an initial CT at admission and 25 patients aged < 18 years old were excluded and 421 patients were included in analysis. The median age was 48.0 years and the male proportion was 53% (224/421). During the follow-up period, 64 (15%) patients had a composite endpoint. There was an association of older age (odds ratio [OR], 1.04; 95% confidence interval [CI]: 1.01-1.06; P = 0.003), larger consolidation lesions in the upper lung (Right: OR, 1.13; 95%CI: 1.03-1.25, P =0.01; Left: OR,1.15; 95%CI: 1.01-1.32; P = 0.04) with increased odds of adverse endpoints. Conclusion:There was an association of older age and larger consolidation in upper lungs on admission with higher odds of poor outcomes in patients with COVID-19.
Background: The coronavirus disease 2019 (COVID-19) has become a global challenge since the December 2019. The hospital stay is one of the prognostic indicators, and its predicting model based on CT radiomics features is important for assessing the patients' clinical outcome. The study aimed to develop and test machine learning-based CT radiomics models for predicting hospital stay in patients with COVID-19 pneumonia.Methods: This retrospective, multicenter study enrolled patients with laboratory-confirmed SARS-CoV-2 infection and their initial CT images from 5 designated hospitals in Ankang,
Aims: Angiotensin II (AngII), a vasoconstrictive peptide of the renin–angiotensin system (RAS), promotes hepatic fibrogenesis and induces microRNA-21(mir-21) expression. Angiotensin-(1–7) [Ang-(1–7)] is a peptide of the RAS, which attenuates liver fibrosis. Recently, it was reported that the NOD-like receptor family, pyrin domain containing 3 (NLRP3) inflammasome participated in liver fibrosis. However, it remains unclear how mir-21 mediates AngII-induced NLRP3 inflammasome activation. We investigate the role of AngII-induced mir-21 in the regulation of NLRP3 inflammasome/IL-1β axis in liver fibrosis.Results: In vivo, circulating mir-21 was upregulated in patients with liver fibrosis and was positively correlated with liver fibrosis and oxidation. Treatment with Ang-(1–7) inhibited mir-21, NLRP3 inflammasome, and liver fibrosis after bile duct ligation (BDL) or AngII infusion. Inhibition of mir-21 suppressed the Smad7/Smad2/3/NOX4, Spry1/ERK/NF-κB pathway, NLRP3 inflammasome, and liver fibrosis induced by AngII infusion. In vitro, AngII upregulated mir-21 expression via targeting Smad7 and Spry1 in primary hepatic stellate cells (HSCs). In contrast, Ang-(1–7) suppressed mir-21 expression and oxidation induced by AngII. Overexpression of mir-21 promoted oxidation, and collagen production enhanced the effect of AngII on NLRP3 inflammasome activation via the Spry1/ERK/NF-κB, Smad7/Smad2/3/NOX4 pathways. However, downregulation of mir-21 exerted the opposite effects.Innovation and Conclusions: Mir-21 mediates AngII-activated NLRP3 inflammasome and resultant HSC activation via targeting Spry1 and Smad7. Ang-(1–7) protected against BDL or AngII infusion-induced hepatic fibrosis and inhibited mir-21 expression. Antioxid. Redox Signal. 27, 1–20.
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