CHD1 deletion stabilizes HIF1α to promote angiogenesis and glycolysis in prostate cancer / 亚洲男科学杂志(英文版)

Chromodomain-helicase-DNA-binding protein 1 (CHD1) deletion is among the most common mutations in prostate cancer (PCa), but its role remains unclear. In this study, RNA sequencing was conducted in PCa cells after clustered regularly interspaced palindromic repeat (CRISPR)/CRISPR-associated protein 9 (Cas9)-based CHD1 knockout. Gene set enrichment analysis (GSEA) indicated upregulation of hypoxia-related pathways. A subsequent study confirmed that CHD1 deletion significantly upregulated hypoxia-inducible factor 1α (HIF1α) expression. Mechanistic investigation revealed that CHD1 deletion upregulated HIF1α by transcriptionally downregulating prolyl hydroxylase domain protein 2 (PHD2), a prolyl hydroxylase catalyzing the hydroxylation of HIF1α and thus promoting its degradation by the E3 ligase von Hippel-Lindau tumor suppressor (VHL). Functional analysis showed that CHD1 deletion promoted angiogenesis and glycolysis, possibly through HIF1α target genes. Taken together, these findings indicate that CHD1 deletion enhances HIF1α expression through PHD2 downregulation and therefore promotes angiogenesis and metabolic reprogramming in PCa.

Clinical efficacy of anterior cervical plate fixation for type II and type II A Hangman’s fracture / 医学研究生学报

Objective　There are still disputes about the clinical treatment of type II and type II A Hangman’s fracture. The article aimed to explore the clinical efficacy of anterior cervical plate fixation for type II and type II A Hangman’s fracture.　Methods　Seventeen patients with type II and type II A Hangman’s fracture combined with intervertebral disc injury were analyzed in our department from January 2013 to August 2017, including 12 males and 5 females, aged from 27 to 76 years old, with an average age of 54.9 years. The operative time and intraoperative blood loss and postoperative drainage were recorded. The effectiveness was evaluated using visual analogue scale (VAS) for occipitocervical pain, and the Neck Disability Index (NDI) score for cervical vertebra function. Radiological indices (C2/3 local kyphotic angle, C2 translation) and bone graft fusion were evaluated by X-ray.　Results　All the patients were followed up successfully. No cerebrospinal fluid leakage occurred during the operation. There were no broken nails, broken slab, and loose internal fixation. All the patients were almost free from occipitocervical pain and neurological function of all patients improved partially. The VAS and NDI scores were significantly improved at 3 months after operation and one year when compared with preoperative scores (P<0.05). The C2/3 local kyphotic angle was corrected significantly with the mean preoperative 12.24±2.17 degrees, initial postoperative -2.12±3.20 degrees and the latest follow-up -1.88±2.67 degrees respectively (P<0.05). The C2 translation was also corrected significantly with the mean preoperative 3.47±1.46 mm, initial postoperative 1.02±0.63 mm, and the latest follow-up 1.21±0.56 mm respectively (P<0.05). All the patients had good bone graft fusion.　Conclusion　For type II and type II A Hangman’s fracture, the method of anterior cervical plate fixation can effectively restore cervical curvature and reconstruct cervical stability, which is featured by the advantage of less trauma, fewer complications and faster recovery.