Identification of Bone Metastatic and Prognostic Alternative Splicing Signatures in Prostate Adenocarcinoma.

As the most common nonepithelial malignancy, prostate adenocarcinoma (PRAD) is the fifth chief cause of cancer mortality in men. Distant metastasis often occurs in advanced PRAD and most patients are dying from it. However, the mechanism of PRAD progression and metastasis is still unclear. It's widely reported that more than 94% of genes are selectively splicing in humans and many isoforms are particularly related with cancer progression and metastasis. Spliceosome mutations occur in a mutually exclusive manner in breast cancer, and different components of spliceosomes are targets of somatic mutations in different types of breast cancer. Existing evidence strongly supports the key role of alternative splicing in breast cancer biology, and innovative tools are being developed to use splicing events for diagnostic and therapeutic purposes. In order to identify if the PRAD metastasis is associated with alternative splicing events (ASEs), the RNA sequencing data and ASEs data of 500 PRAD patients were retrieved from The Cancer Genome Atlas (TCGA) and TCGASpliceSeq databases. By Lasso regression, five genes were screened to construct the prediction model, with a good reliability by ROC curve. Additionally, results in both univariate and multivariate Cox regression analysis confirmed the well prognosis efficacy of the prediction model (both P < 0.001). Moreover, a potential splicing regulatory network was established and after multiple-database validation, we supposed that the signaling axis of HSPB1 up-regulating the PIP5K1C - 46,721 - AT (P < 0.001) might mediate the tumorigenesis, progression and metastasis of PRAD via the key members of Alzheimer's disease pathway (SRC, EGFR, MAPT, APP and PRKCA) (P < 0.001).

Comparison of sleep condition and sleep-related psychological activity after cognitive-behavior and pharmacological therapy for chronic insomnia.

BACKGROUND: Previous studies of insomnia focused mainly on the improvement of sleep condition and ignored the effects of sleep-related psychological activity and daytime function after pharmacological and behavioral treatments. We compared the clinical effects of both therapies on sleep condition, sleep-related psychological activity and daytime function in chronic insomnia. METHODS: Seventy-one patients with chronic insomnia were randomly divided into 4 groups and either received cognitive-behavior therapy (CBT, n = 19), pharmacological therapy (PCT, n = 17), CBT plus medication (Combined, n = 18) or placebo (n = 17). The treatments lasted for 8 weeks with follow-ups conducted at 3 and 8 months. On the day after treatment ended, all patients were assessed using a polysomnogram (PSG), a sleep diary and a psychological assessment. RESULTS: The three active treatments were more effective than placebo at the time the treatments were completed. Subjective sleep-onset latency, sleep efficacy and total sleep time were better in the PCT group than in the CBT group. At the 3-month follow-up, subjective and objective sleep-onset latency, sleep efficacy and total sleep time were better in the CBT group than in both the PCT and the Combined group. At the 8-month follow-up, the CBT group showed a steady comfortable sleep state, while the PCT and Combined groups were gradually returning to the pre-treatment condition. The Combined group showed a variable long-term effect. On the other hand, pre-sleep arousal at nighttime, dysfunctional beliefs about sleep as well as daytime functioning in the CBT group not only improved, but was better than in the other active treatment groups. CONCLUSION: Medication and Combined therapy produced a short-term effect on chronic insomnia while CBT had a long-term effect of improved sleep-related psychological activity and daytime functioning.