Background: MiRNAs have been recently implicated in the pathogenesis underlying ischemia-reperfusion (IR) injury. We investigated the miRNAs expression profiles in the early stages after lung transplantation (LT) and studied the involvement of Toll-like receptor(TLR) signaling pathway in lung IR injury following LT. Methods: We established the left LT model in mice, The mice were injected with a miRNA-122 specific inhibitor, following which pathological changes in the lung tissue were studied using different lung injury indicators. In addition, we performed deep sequencing in transplanted lung tissues to indentify differentially expressed (DE) miRNAs and their target genes. Results: A total of 12DE miRNAs were selected and 2,476 target genes were identified; The gene ontology (GO) enrichment analysis predicted 6,063 terms and the Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis predicted 1,554 biological pathways. Compared with the control group, inhibiting the expression of miRNA-122 significantly reduced the lung injury and lung W / D ratio (p<0.05). In addition, the activity of myeloperoxidase (MPO) and expression of tumor necrosis factor (TNF)-α and TLR2/4 decreased (p<0.05); whereas the expression of interleukin-10(IL-10) expression levels increased (p<0,05). Furthermore, the inhibition of miRNA-122 suppressed the IR injury-induced activation of the TLR signaling pathway. Conclusions: Our findings showed the differential expression of several miRNAs in the early inflammatory response following LT. Of these, miRNA-122 promoted the IR injury following LT, whereas its inhibition prevented IR injury in a TLR-dependent manner.

Introduction: Although D-dimer was reported to be elevated in COVID-19 death, few studies about changes in serial D-Dimer Levels with different severity of illness. Early prophylactic anticoagulation contributes to improve patient outcomes in COVID-19, the perception of timing of anticoagulant treatment is mixed. Methods: Retrospective analysis of 38 severity COVID-19 patients, compared changes in serial D-Dimer Levels between low-flow oxygen therapy and higher concentration oxygen therapy. Patients were stratified into two groups distinguished by D-Dimer value in start of anticoagulation treatment, definition D-Dimer=3mg/L of a cut-off value. Compare the improvement within 7 and 14 days, the time to the first appearance of improvement with chest CT and the days of hospital stay between two groups. Results: A total of 38 severe patients who accept anticoagulant therapy were enrolled into the study from consecutive 59 confirmed cases. Regression analysis showed that compared to those D-Dimer≤3mg/L, patients with higher D-Dimer increase the risk (OR=15.697, P＜0.001) to develop to further severe illness. The difference of patient’s improvement within 14 days (P=0.043) was much more significant compared to 7 days (P=0.757) in two groups. The days at the time of CT imaging improvement were 12.1±3.6 days in the D-Dimer≤3, while 16.2±6.4 days in D-Dimer＞3 (p=0.028). The hospital stays in the two groups were 27 (25.5-30.5) days and 28 (27-36.5) days separately (p=0.086). Conclusions: D-dimer is available for the evaluation of illness condition and the timing of anticoagulant therapy in severe COVID-19, and its role should not be ignored and required further study.