ABSTRACT
Coronavirus disease 2019 (COVID-19) is a global pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) that seriously endangers human health. There is an urgent need to build physiological relevant human models for deep understanding the complex organ-level disease processes and facilitating effective therapeutics for COVID-19. Here, we first report the use of microengineered alveolus chip to create a human disease model of lung injury and immune responses induced by native SARS-CoV-2 at organ-level. This biomimetic system is able to reconstitute the key features of human alveolar-capillary barrier by co-culture of alveolar epithelial and microvascular endothelial cells under microfluidic flow. The epithelial cells on chip showed higher susceptibility to SARS-CoV-2 infection than endothelial cells identified by viral spike protein expression. Transcriptional analysis showed distinct responses of two cell types to SARS-CoV-2 infection, including activated type I interferon (IFN-I) signaling pathway in epithelium and activated JAK-STAT signaling pathway in endothelium. Notably, in the presence of circulating immune cells, a series of alveolar pathological changes were observed, including the detachment of endothelial cells, recruitment of immune cells, and increased production of inflammatory cytokines (IL-6, IL-8, IL-1{beta} and TNF-). These new findings revealed a crucial role of immune cells in mediating lung injury and exacerbated inflammation. Treatment with antiviral compound remdesivir could suppress viral copy and alleviate the disruption of alveolar barrier integrity induced by viral infection. This bioengineered human organ chip system can closely mirror human-relevant lung pathogenesis and immune responses to SARS-CoV-2 infection, not possible by other in vitro models, which provides a promising and alternative platform for COVID-19 research and preclinical trials.
ABSTRACT
Objective To investigate the diagnostic value of intraductal ultrasonography (IDUS) and bile tumor marker in differential diagnosis of suspected biliary stricture.Methods A total of 57 patients with biliary stricture (8 benign strictures,49 cases of malignant strictures),who underwent IDUS and tests of serum and bile tumor markers (CA19-9 and CEA),were analyzed.The sensitivity,specificity,positive predictive value,negative predictive value and accuracy were compared among the outcomes of B-ultrasonography,CT,MRCP,IDUS,as well as IDUS combined with bile tumor markers.Results The specificity of the IDUS and the combined group were 63.6％ (7/11) and 77.8％ (7/9) respectively (P ＞ 0.05).The positive predictive value of the IDUS and the combined group were 91.8％ (45/49) and 95.9％ (47/49) respectively (P ＞0.05).The diagnostic accuracy of the IDUS and the combined group were 91.2％ (52/57) and 94.7％ (54/57) respectively (P ＞0.05).Data of the two groups were significantly higher than conventional imaging like B-ultrasound,CT and MRCP.The accuracy of IDUS combined with bile CEA for the diagnosis of distal bile duct cancer was 97.9％ (46/47),significantly higher than that of IDUS.Conclusion IDUS combined with biliary tumor markers is of high value for distinguishing the bile benign from malignant stricture.IDUS combined with biliary CEA test can improve the diagnostic accuracy of distal malignant biliary stricture diseases.
