Treatment with human umbilical cord-derived mesenchymal stem cells for COVID-19 patients with lung damage: a randomised, double-blind, placebo controlled phase 2 trial

BACKGROUNDTreatment of severe Corona Virus Disease 2019 (COVID-19) is challenging. We performed a phase 2 trial to assess the efficacy and safety of human umbilical cord-mesenchymal stem cells (UC-MSCs) to treat severe COVID-19 patients with lung damage, based on our phase 1 data. METHODSIn this randomized, double-blind, and placebo-controlled trial, we recruited 101 severe COVID-19 patients with lung damage. They were randomly assigned to receive either UC-MSCs (4 x 107 cells per infusion) or placebo on day 0, 3, and 6. The primary endpoint was an altered proportion of whole lung lesion volumes from baseline to day 28. Other imaging outcomes, 6-minute walk test, maximum vital capacity, diffusing capacity, and adverse events were recorded and analysed. RESULTS100 COVID-19 patients were finally recruited to receive either UC-MSCs (n = 65) or placebo (n = 35). UC-MSCs administration exerted numerical improvement in whole lung lesion volume from baseline to day 28 compared with the placebo (the median difference was -13.31%, 95%CI -29.14%, 2.13%, P=0.080). UC-MSCs significantly reduced the proportions of solid component lesion volume compared with the placebo (median difference: -15.45%; 95% CI -30.82%, -0.39%; P=0.043). The 6-minute walk test showed an increased distance in patients treated with UC-MSCs (difference: 27.00 m; 95% CI 0.00, 57.00; P=0.057). The incidence of adverse events was similar in the two groups. CONCLUSIONSUC-MSCs treatment is a safe and potentially effective therapeutic approach for COVID-19 patients with lung damage. (Funded by The National Key R&D Program of China and others. ClinicalTrials.gov number, NCT04288102.)

Clinical phenotype and gene analysis of 86 cases of 5 alpha reductase deficiency / 中华儿科杂志

Objective@#Molecular genetics and clinical phenotypic characteristics of 5 alpha reductase deficiency were analyzed.@*Methods@#The genetic results and clinical features classied as Prader grade of external genitalia of 86 children with SRD5A2 mutation seen from 2007 to 2017 at Department of Endocrinology of Beijing Children′s Hospital were analyzed, and the mutation differences in different were compared regions according to the literatures.@*Results@#Among the 86 children, 15 had were homozygous mutations, accounting for 17%, and 71 cases of compound heterozygous mutations accounted for 83%. Totally 172 alleles mutations in this series. The mutation was mainly located on exon 1 and exon 4, in which the mutation frequency of exon 1 was 23.8% (41/172), and the frequency of exon 4 mutation was 55.8% (96/172). A total of 19 mutation types of the SRD5A2 gene in this group were detected, of which 5 were new mutations (p.A228F, p.E57D, p.V124D, p.A117D, p.E197K); 65 patients had p.R227Q mutation, accounting for 76%, while 31 had p.Q6* mutation, accounting for 36%. Other rare types such as p.R246W, p.R103* and so on were also seen in the present study, there was no significant difference between north China and south China (P>0.05). The clinical phenotypes of p.R227Q variation varied, mainly in Prader 3-4, accounting for 82%, while (Prader 0-1) were less, accounting only 2%. The variation of p.Q6* was mainly manifested in Prader 3, accounting for 50%. p.R246Q mainly presented Prader 3. The variation of p.G203S appeared to have Prader 2 and Prader 4-5, accounting for 20% and 73% respectively. There was no significant difference in clinical phenotype corresponding to each protein type (P>0.05) .@*Conclusion@#Among the 86 children have identified 19 SRD5A2 mutation types, p.R227Q is a hotspot mutation in Chinese. Variations at different types may have different clinical phenotypes, while the same variations may have different clinical features. There was no significance different in the variation types between the north and the south.

Recent progress of NR5A1 gene mutation / 国际儿科学杂志

NR5A1 gene mutation is one of the common cause of 46 XY dysplasia (46,XY disorder of sex development,46,XY DSD),which is an autosomal dominant disease.It has wide phenotypes:46,XY gonadal dysplasia is the most common one,site-specific mutations can lead to adrenal dysfunction and may affect the height.In recent years,more and more studies have shown that the mutation of NR5A1 gene can lead to 46,XX ovotesticular DSD and 46,XX testicular DSD.The disease is also characterized by hypergonadotropic hypogonadism,so LH and FSH are high,especially the FSH,leading to a decrease in LH/FSH.The treatment of NR5A1 gene mutation is mainly symptomatic.Gender identification needs to take many factors into consideration.Before puberty,children can use GnRHa to inhibit gonad development and avoid premature ovarian failure.In this review,recent progress of NR5A1 is summarized.