Atopic dermatitis is a chronic, relapsing form of inflammatory skin disorder that is affected by genetic and environmental factors. We performed a genome-wide association study of atopic dermatitis in a Chinese Han population using 1,012 affected individuals (cases) and 1,362 controls followed by a replication study in an additional 3,624 cases and 12,197 controls of Chinese Han ethnicity, as well as 1,806 cases and 3,256 controls from Germany. We identified previously undescribed susceptibility loci at 5q22.1 (TMEM232 and SLC25A46, rs7701890, P(combined) = 3.15 × 10(-9), odds ratio (OR) = 1.24) and 20q13.33 (TNFRSF6B and ZGPAT, rs6010620, P(combined) = 3.0 × 10(-8), OR = 1.17) and replicated another previously reported locus at 1q21.3 (FLG, rs3126085, P(combined) = 5.90 × 10(-12), OR = 0.82) in the Chinese sample. The 20q13.33 locus also showed evidence for association in the German sample (rs6010620, P = 2.87 × 10(-5), OR = 1.25). Our study identifies new genetic susceptibility factors and suggests previously unidentified biological pathways in atopic dermatitis.

Certain chromosome rearrangements display a significant delay in chromosome replication timing (DRT) that is associated with a subsequent delay in mitotic chromosome condensation (DMC). DRT/DMC chromosomes are common in tumor cells in vitro and in vivo and occur frequently in cells exposed to ionizing radiation. A hallmark for these chromosomes is the delayed phosphorylation of serine 10 of histone H3 during mitosis. The chromosome passenger complex, consisting of multiple proteins including Aurora B kinase and INCENP is thought to be responsible for H3 phosphorylation, chromosome condensation and the subsequent segregation of chromosomes. In this report, we show that chromosomes with DRT/DMC contain phosphorylated Chk1, consistent with activation of the S-M phase checkpoint. Furthermore, we show that INCENP is recruited to the DRT/DMC chromosomes during all phases of mitosis. In contrast, Aurora B kinase is absent on DRT/DMC chromosomes when these chromosomes lack serine 10 phosphorylation of H3. We also show that mitotic arrest deficient 2 (Mad2), a member of the spindle assembly checkpoint, is present on DRT/DMC chromosomes at a time when the normally condensed chromosomes show no Mad2 staining, indicating that DRT/DMC activates the spindle assembly checkpoint. Finally, cells with DRT/ DMC chromosomes have centrosome amplification, abnormal spindle assembly, endoreduplication and significant chromosome instability.

y These authors contributed equally to this work.

No abstract

Background: Laparoscopic transcystic common bile duct exploration (LTCBDE) is the minimally traumatic surgical method for the treatment of choledocholithiasis secondary to cholecystolithiasis with dilated common bile duct (CBD). However, no report exists concerning LTCBDE in patients with nondilated CBD. The purpose of this study was thus to explore the safety, efficacy, and feasibility of LTCBDE in patients with choledocholithiasis secondary to cholecystolithiasis with nondilatation of the CBD.Methods: We retrospectively analyzed 47 patients with choledocholithiasis secondary to cholecystolithiasis who were treated with LTCBDE at the Second Affiliated Hospital of Nanchang University from January 2017 to August 2021 (all the patients had undergone endoscopic retrograde cholangio-pancreatography treatment, but this failed due to various reasons). Clinical data on disease characteristics, methods for cystic duct incision and CBD stone extraction, and surgical outcomes were collected and reviewed. Each patient was followed up for more than 3 months.Results: There were 47 patients in this study, including 21 females and 26 males, with their ages ranging from 15 to 82 years (51±15 years). All patients were treated with surgery, and the CBD stones were removed successfully. Among these patients, 45 underwent LTCBDE for the removal of stones in the CBD, with failure occurring in 2 patients who then accepted laparoscopic common bile duct stone removal (LCBDE) + T tube drainage. The diameter of the cystic duct was 0.30-0.73 cm (0.60±0.07 cm), the diameter of the CBD was 0.60-0.80 cm (0.73±0.05 cm), the operation time was 75-220 minutes (159±33 minutes), and the postoperative hospital stay was 2-13 days (6±2 days). None of the patients experience any serious postoperative complications, and all were discharged safely. During the follow-up, no postoperative biliary stenosis, bile leakage, or other complications occurred.Conclusions: LTCBDE is feasible to treat patients with choledocholithiasis secondary to cholecystolithiasis with nondilatation of the CBD. This choice of treatment plan reduces the length of hospital stay and the occurrence of postoperative complications. However, it is recommended that this be attempted on the basis of the experience of LTCBDE with dilated CBD.