Summary Metastatic prostate cancer is characterized by recurrent genomic copy number alterations that are presumed to contribute to resistance to hormone therapy. We identified CHD1 loss as a cause of antiandrogen resistance in an in vivo small hairpin RNA (shRNA) screen of 730 genes deleted in prostate cancer. ATAC-seq and RNA-seq analyses showed that CHD1 loss resulted in global changes in open and closed chromatin with associated transcriptomic changes. Integrative analysis of this data, together with CRISPR-based functional screening, identified four transcription factors (NR3C1, POU3F2, NR2F1, and TBX2) that contribute to antiandrogen resistance, with associated activation of non-luminal lineage programs. Thus, CHD1 loss results in chromatin dysregulation, thereby establishing a state of transcriptional plasticity that enables the emergence of antiandrogen resistance through heterogeneous mechanisms.

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Purpose To compare the preliminary postoperative outcomes of percutaneous endoscopic transforaminal lumbar interbody fusion (Endo-TLIF) and minimally invasive transforaminal lumbar interbody fusion (MIS-TLIF) in the treatment of lumbar spondylolisthesis. Methods Sixty-two patients with single-segment lumbar spondylolisthesis received Endo-TLIF and MIS-TLIF were enrolled in present study. Perioperative parameters, including operation time, estimated blood loss (EBL), interoperative fluoroscopy time, ambulation time and operative complications were recorded, respectively. The results of clinical metrics such as the Visual Analog Scale (VAS) for back and leg pain, the Oswestry Disability Index (ODI) and the Japanese Orthopaedic Association (JOA) score were obtained, respectively. Postoperative fusion rates were assessed by clinical fusion and CT at 12-month after surgery. Results No significant differences were found in the demographic data between the two groups. Compared with MIS-TLIF group, Endo-TLIF group had similar operative time, less intraoperative blood loss and shorter ambulation time but longer duration of X-ray radiation. The postoperative VAS scores of back pain, ODI and JOA score were significantly improved comparing with the preoperative scores in two groups, but the Endo-TLIF group showed more significant improvement in the early follow-up (P < 0.05, respectively). There were no significant differences in terms of the interbody fusion rate between the two groups. Meanwhile, no serious postoperative complications were observed in the study. Conclusion Compared with MIS-TLIF, Endo-TLIF technique showed relatively faster recovery and better outcomes in terms of early curative effect, especially in 6 months after operation. However, intraoperative repeated fluoroscopy could result in highly cumulative radiation and longer operation time.

Recently, mutations in TBK1 (TANK-binding kinase 1) have been reported to be a cause of amyotrophic lateral sclerosis/frontotemporal dementia (ALS/FTD) spectrum, but the relationship between them remains unclear owing to the small sample size and low mutation rate. Therefore, we performed a two-stage meta-analysis to investigate the frequency of TBK1 mutations in ALS/FTD patients and the association between the mutations and risk of ALS/FTD spectrum. In the first stage, 12 studies involving 4173 ALS/FTD patients were included. The frequencies of loss of function (LoF) and missense mutations were 1.0% (95% CI 0.6-1.7%) and 1.8% (95% CI 0.9-3.4%) in ALS/FTD patients respectively. Subgroup analysis suggested a higher prevalence of TBK1 mutations in European patients than that in Asian patients. In the second stage, 7 studies involving 3146 cases and 4856 controls were enrolled. Results showed that TBK1 LoF mutations were associated with a significant increased risk for ALS/FTD spectrum (OR 11.78; 95% CI 4.21-33.00; p < 0.0001), while TBK1 missense mutations were associated with a moderately increased susceptibility for ALS/FTD spectrum (OR 1.62; 95% CI 1.19-2.19; p = 0.002). In conclusion, TBK1 LoF and missense mutations are not frequently found in ALS/FTD patients, and both of them are associated with an increased risk for ALS/FTD spectrum.

Low back pain, a common medical condition, could result in severe disability and inflict huge economical and public health burden. Its pathogenesis is attributed to multiple etiological factors, including intervertebral disc degeneration (IDD). Emerging evidence suggests that circular RNAs (circRNAs), a major type of regulatory non-coding RNA, play critical roles in cellular processes that are pertinent to IDD development, including nucleus pulposus cell proliferation and apoptosis as well as extracellular matrix deposition. Increasing number of translational studies also indicated that circRNAs could serve as novel biomarkers for the diagnosis of IDD and/or predicting its clinical outcomes. Our review aims to discuss the recent progress in the functions and mechanisms of newly discovered IDD-related circRNAs.