ABSTRACT
This study aims to characterize the cell atlas of the epididymis derived from a 46,XY disorders of sex development (DSD) patient with a novel heterozygous mutation of the nuclear receptor subfamily 5 group A member 1 (NR5A1) gene. Next-generation sequencing found a heterozygous c.124C>G mutation in NR5A1 that resulted in a p.Q42E missense mutation in the conserved DNA-binding domain of NR5A1. The patient demonstrated feminization of external genitalia and Tanner stage 1 breast development. The surgical procedure revealed a morphologically normal epididymis and vas deferens but a dysplastic testis. Microfluidic-based single-cell RNA sequencing (scRNA-seq) analysis found that the fibroblast cells were significantly increased (approximately 46.5%), whereas the number of main epididymal epithelial cells (approximately 9.2%), such as principal cells and basal cells, was dramatically decreased. Bioinformatics analysis of cell-cell communications and gene regulatory networks at the single-cell level inferred that epididymal epithelial cell loss and fibroblast occupation are associated with the epithelial-to-mesenchymal transition (EMT) process. The present study provides a cell atlas of the epididymis of a patient with 46,XY DSD and serves as an important resource for understanding the pathophysiology of DSD.
Subject(s)
Male , Humans , Epididymis , Disorder of Sex Development, 46,XY/genetics , Disorders of Sex Development , Mutation , Mutation, Missense , Steroidogenic Factor 1/geneticsABSTRACT
<p><b>OBJECTIVE</b>To evaluate the value of human fatty acid binding protein (h-FABP) in predicting myocardial ischemia and injury in the perioperative period of cardiac surgery, we observed the dynamic changes of h-FABP in perioperative period of patients underwent coronary artery bypass grafting and ventricular septal defects repairing surgery, and evaluated the relationship of h-FABP and ischemia modified albumin (IMA), CK-MB, cTnI.</p><p><b>METHODS</b>Patients underwent coronary artery bypass grafting (n=30) and ventricular septal defect repairing (n=30) surgery between February 2008 and December 2008 were included in this study. Venous blood sample was obtained at preoperative, aortic clamping, aortic unclamping of 10 min, 2 h, 6 h, 12 h, 24 h for the measurements of h-FABP, IMA, cTnI and CK-MB.</p><p><b>RESULTS</b>h-FABP and IMA changed in the same way at various examined time points, h-FABP changes also paralleled cTnI and CK-MB changes, h-FABP peaked early during myocardial ischemia and injury and returned to baseline level at 2 h post myocardial ischemia and injury. Linear correlation analysis showed that the peak value of h-FABP was positively correlated with IMA, CK-MB and cTnI in both CABG group (r = 0.948, 0.964 and 0.961, P < 0.05) and in the VSD group (r = 0.986, 0.978 and 0.957).</p><p><b>CONCLUSIONS</b>h-FABP is an early diagnostic parameter reflecting perioperative myocardial ischemia and injury in cardiac surgery. Quantitative h-FABP monitoring could predict the severity of myocardial ischemia and injury early during cardiac surgery.</p>