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The aim of this study was to identify a urine extracellular vesicle circular RNA (circRNA) classifier that could detect high-grade prostate cancer (PCa) of Grade Group (GG) 2 or greater. For this purpose, we used RNA sequencing to identify candidate circRNAs from urinary extracellular vesicles from 11 patients with high-grade PCa and 11 case-matched patients with benign prostatic hyperplasia. Using ddPCR in a training cohort (n = 263), we built a urine extracellular vesicle circRNA classifier (Ccirc, containing circPDLIM5, circSCAF8, circPLXDC2, circSCAMP1, and circCCNT2), which was evaluated in two independent cohorts (n = 497, n = 505). Ccirc showed higher accuracy than two standard of care risk calculators (RCs) (PCPT-RC 2.0 and ERSPC-RC) in both the training cohort and the validation cohorts. In all three cohorts, this novel urine extracellular vesicle circRNA classifier plus RCs was statistically more predictive than RCs alone for predicting ≥ GG2 PCa. This assay, which does not require precollection digital rectal examination nor special handling, is repeatable, noninvasive, and can be easily implemented as part of the basic clinical workflow.

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Oesophageal perforation is a rare complication occurring during or after cervical spine surgery, and the risk factors are not well understood. This study presents a case of a 25-year-old man with oesophageal perforation after anterior cervical spine surgery. It is suggested that four factors (anatomical structure, mechanism of trauma, implant dislodgment, and the operation) could induce postoperative oesophageal perforation after cervical spine surgery performed using the anterior surgical approach. A comprehensive understanding and early management of this complication are necessary for successful therapy.

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Metastasis is the main cause of death from muscle-invasive urothelial carcinoma of the bladder (UCB), and the metastatic potential of tumors is often unpredictable. The role of Dachshund homolog 2 gene (DACH2) in tumorigenesis remains unexplored. We aimed to investigate whether DACH2 can be used as a biomarker to predict metastasis and prognosis of muscle-invasive UCB in a sequential training and validation fashion. For the training set (n = 40), compared with UCB patients without lymph node (LN) metastasis, both DACH2 protein and mRNA expression were greatly increased in case-matched patients with LN metastasis. For the independent validation set (n = 243), patients with primary UCB that did not express DACH2 had a longer metastasis-free survival (MFS) and overall survival (OS) than did those with tumors expressing DACH2 (5-year MFS: 88% [95% CI 80-96] versus 19% [95% CI 7-31], p < 0.001; 5-year OS: 93% [95% CI 87-99] versus 37% [95% CI 23-51], p < 0.001). Multivariable analysis of DACH2 status showed hazard ratios of 7.34 (95% CI 3.15-11.87, p < 0.001) for MFS and 3.96 (95% CI 2.04-7.16, p < 0.001) for OS which were much higher than hazard ratios associated with other independent risk factors. Collectively, DACH2 is an independent prognostic marker that can be used at initial diagnosis of UCB to identify patients who have a high potential to develop metastasis.

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The roles of spinal N-methyl-d-aspartic acid receptor 2B (NR2B) subunit in central sensitization of chronic visceral pain were investigated. A rat model with irritable bowel syndrome (IBS) was established by colorectal distention (CRD) on post-natal days 8-14. Responses of the external oblique muscle of the abdomen to CRD were measured to evaluate the sensitivity of visceral pain in rats. The sensitivity of visceral pain significantly increased in IBS-like rats. Expressions of spinal NR2B subunit and phosphorylated NR2B subunit significantly increased by 50-55% in IBS-like rats when compared with those in control rats. Ro 25-6981, a selective antagonist of NR2B subunit, has a dose-dependent anti-allodynic and anti-hyperalgesic effect without causing motor dysfunction in IBS-like rats. Furthermore, the activation mechanism of the spinal NR2B subunit in chronic visceral pain was also investigated. Spinal administration of genistein, a specific inhibitor of tyrosine kinases, also decreased the visceral pain hypersensitivity of IBS-like rats in a dose-dependent manner. In addition, the expression of phosphorylated NR2B subunit was decreased after spinal administration of Ro 25-6981 or genistein in IBS-like rats. In conclusion, tyrosine kinase activation-induced phosphorylation of NR2B subunit may play a crucial role in central sensitization of chronic visceral pain.

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OBJECTIVE: To investigate the expressions of CD4+ CD25(high) regulatory T cells, TGF-beta 1 and COX-2 in the peripheral blood of prostate cancer (PCa) patients, and analyze the role of CD4+ CD25(high) regulatory T cells in the pathogenesis of PCa and their relationship with TGF-beta 1 and COX-2. METHODS: We used flow cytometry to calculate the percentage of CD4+ CD25(high) regulatory T cells in the CD4+ T cells in the peripheral blood mononuclear cells (PBMC) from 30 PCa patients (11 localized and 19 non-localized cases) and 20 healthy volunteer controls, determined the expressions of TGF-beta 1 and COX-2 in the serum by ELISA, and analyzed their correlation with the CD4+ CD25(high) regulatory T cells in the PCa patients as well as the differences between the localized and non- localized cases. RESULTS: CD4+ CD25(high) regulatory T cells accounted for (18.32 +/- 7.49) % in the CD4+ T cells in PBMCs from the PCa patients, significantly higher than (7.77 +/- 1.86) % from the controls (P < 0.05), but with no statistically significant difference between pre- and post-treatment in the PCa patients (P > 0.05). The expressions of TGF-beta 1 and COX-2 in the peripheral blood were (215.97 +/- 55.16) ng/ml and (6.88 +/- 5.14) ng/ml in the PCa patients, in comparison with (149.75 +/- 47.11) ng/ml (P < 0.05) and (6.88 +/- 5.14) ng/ml (P > 0.05) in the controls. Multiple linear regression analysis showed no significant correlation between the expression of CD4+ CD25(high) regulatory T cells in PBMCs and those of TGF-beta 1 and COX-2 in the peripheral blood of the PCa patients. There were no significant differences between the localized and non-localized PCa groups in the expressions of CD4+ CD25(high) regulatory T cells, TGF-beta 1 and COX-2 (P > 0.05). CONCLUSION: CD4+ CD25(high) regulatory T cells in in PBMCs are involved in the pathogenesis of PCa. The proliferation of CD4+ CD25(high) regulatory T cells is not significantly correlated to the expressions of TGF-beta 1 and COX-2 in the peripheral blood, but maybe to the tumor itself and the local tumor microenvironment.

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