Thrombolysis and anticoagulation were the main treatment methods for acute pulmonary embolism. However, the use of thrombolysis drugs may lead to bleeding complications. We compared intermittent low-dose urokinase (UK) and alteplase (recombinant tissue plasminogen activator [rt-PA]) in normotensive patients with intermediate-high-risk pulmonary embolism. The UK group was treated with intravenous UK 10 000 U/kg once a day for 7 days. The rt-PA group was given alteplase 50 mg by intravenous injection within 2 hours of admission. After thrombolytic therapy, 48 patients were included in this trial. Compared with before treatment, right and left ventricular diastolic diameter ratio, systolic pulmonary artery pressure, and cardiac troponin I of the 2 groups all significantly decreased 8 and 14 days after treatment, which indicated that right heart function improved. Total efficacy rates for the UK group 8 and 14 days after treatment (79.2%, 87.5%) and the rt-PA group (75.0%, 91.67%) were not significantly different. Adverse bleeding reactions were higher in the rt-PA group (20.8%) than in the UK group (8.3%). This pilot study indicates that intermittent low-dose UK thrombolysis is equally effective as rt-PA. However, future large-scale studies must also determine whether small doses of UK thrombolysis reduce the risk of bleeding.
Salamanders possess a pair of lungs for active air breathing, but the lung respiration is fully operational only during the late stage of development, particularly after metamorphosis. Larval salamanders mainly exchange air through the gills and skin, thus sparing the developing lungs. Salamanders can repair their lungs after injury, but a comparative analysis of regenerative responses between the lungs of young and adult animals is lacking. In this study, lung resections were performed in both larval and adult newts (Pleurodeles waltl). The cellular dynamics, tissue morphology and organ function during lung regeneration were examined and the Yap mutants were produced with CRISPR tools. We found that salamander switches the regenerative strategies from morphological replication through the blastema formation to compensatory growth via resident epithelial cells proliferation upon pulmonary resection injury as it transitions beyond metamorphosis. The larval animals achieve lung regeneration by forming a transient blastema‐like structure and regrowing full‐sized developing lungs, albeit unventilated. The adults repair injured lungs via massive proliferating epithelial cells and by expanding the existing alveolar epithelium without neo‐alveolarization. Yap signalling promotes epithelial cell proliferation and prevents epithelial‐to‐mesenchymal transition to restore functional respiration. The salamanders have evolved distinct regenerative strategies for lung repair during different phases of life. Our results demonstrate a novel strategy for functional lung recovery by inducing epithelial cell proliferation to strengthen the remaining alveoli without rebuilding new alveoli.
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