Phase I trial of human umbilical cord-derived mesenchymal stem cells for treatment of severe bronchopulmonary dysplasia

Severe bronchopulmonary dysplasia(BPD)is a chronic lung disorder that primarily affects premature babies with extremely low birth weight and involves in multiple organ system;no effective pharmacotherapy for this disease exists,and mortality remains high.Based on the evidence from previous preclinical studies and phase I clinical trials,this study aims to test the safety of intravenous application of a single dose of human umbilical cord-derived mesenchymal stem cells(hUC-MSCs)in patients with severe BPD.The Mesenchymal Stem cells for Bronchopulmonary Dysplasia Treatment(MSBDT)trial is a single center,open-label,dose-escalation phase I clinical trial.Severe BPD patients were enrolled in Children Hospital of Chongqing Medical University,Chongqing,China.The first six patients were treated with low-dose hUC-MSCs(1×10^(6) cells/kg)and the next seven patients were treated with high-dose hUC-MSCs(5×10^(6) cells/kg).This study is registered with ClinicalTrials.gov,number NCT03558334.No prespecified infusion-associated adverse events,immediate complication,respiratory or cardiovascular compromise were observed during infusion and 24 h after infusion.No significant changes in safety laboratory values were observed.One death event occurred in the low-dose group on study day 10,and one death event occurred in the high-dose group on study day 24,while,after review in detail,the two cases are not believed to be infusion-associated events.In conclusion,intravenous application of a single dose of hUC-MSCs was tolerated in thirteen patients with severe BPD.

Development of a molecular feature-based survival prediction model of ovarian cancer using the deep neural network

Ovarian cancer(OC)is one of the most lethal gynecologic cancer worldwide,and survival prediction is meaningful for personalized treatment.^(1)The survival outcome of cancer patients mainly depended on the malignancy of the primary tumor which is tightly linked with the expression profile of the molecular features.^(2)Therefore,in this study,we developed a molecular feature-based survival prediction model of OC using a deep neural network(DNN).

Deletion of SMARCA4 impairs alveolar epithelial type II cells proliferation and aggravates pulmonary fibrosis in mice

Alveolar epithelial cells(AECs)injury and failed reconstitution of the AECs barrier are both integral to alveolar flooding and subsequent pulmonary fibrosis(PF).Nevertheless,the exact mechanisms regulating the regeneration of AECs post-injury still remain unclear.SMARCA4 is a part of the large ATP-dependent chromatin remodelling complex SWI/SNF,which is essential for kidney and heart fibrosis.We investigates SMARCA4 function in lung fibrosis by establishing PF mice model with bleomycin firstly and found that the expression of SMARCA4 was mainly enhanced in alveolar type II(ATII)cells.Moreover,we established an alveolar epithelium-specific SMARCA4-deleted SP-C-rtTA/(tetO)7-Cre/SMARCA4f/f mice(SOSM4D/D)model,as well as a new SMARCA4-deleted alveolar type II(ATII)-like mle-12 cell line.We found that the bleomycin-induced PF was more aggressive in SOSM4D/D mice.Also,the proliferation of ATII cells was decreased with the loss of SMARCA4 in vivo and in vitro.In addition,we observed increased proliferation of ATII cells accompanied by abnormally high expression of SMARCA4 in human PF lung sections.These data uncovered the indispensable role of SMARCA4 in the proliferation of ATII cells,which might affect the progression of PF.