IntroductionIncreasing evidence suggests that beta-blocker use might be associated with reduced mortality in prostate cancer patients. To provide a quantitative assessment of this association, we pooled data available to examine the association between beta-blocker use and mortality of prostate cancer.MethodsWe identified studies by a literature search of MEDLINE (from 1 January 1966) and EMBASE (from 1 January 1974), through 10 September 2014, and by searching the reference lists of pertinent articles. Two authors independently screened and reviewed the eligibility of each study. The primary outcomes were prostate cancer-specific mortality and all-cause mortality.ResultsA total of four studies including 16,825 patients were included in this meta-analysis. Analysis of all studies showed that beta-blocker use was associated with reduced prostate cancer-specific mortality (hazard ratio =0.85, 95% confidence interval =0.77–0.94), without any heterogeneity between studies (Q=3.59, I 2=16.5%, P=0.309). However, we observed no association with all-cause mortality (hazard ratio =0.97, 95% confidence interval =0.90–1.04). There was also no evidence of the presence of significant heterogeneity between the four studies (Q=2.48, I 2=0.0%, P=0.480).ConclusionThese findings indicate that beta-blocker use was associated with reduced cancer-specific mortality among prostate cancer patients taking beta-blockers.

This study evaluated the analgesia effect and the effect on adverse reaction of using dexmedetomidine (Dex) in post-cesarean section. Eighty women who had been performed caesarean delivery with combined spinal and epidural anesthesia were selected. The experimental group (group D) included 40 random patients and the control group (group C) included the other 40 women. Patients in group D were given ropivacaine hydrochloride and Dex while patients in group C were given ropivacaine hydrochloride and morphine. We assessed and recorded the patient status at 2, 6, 12, 24 and 48 h using Ramsay sedation scale and visual analogue scale (VAS) in resting state and coughing state and we also recorded their adverse reactions. Except for the first 2 h after surgery, group D gets a lower VAS score than group C all the time in either resting state or coughing state (p<0.05); at 12 h, group D had a lower Ramsay score than group C (p<0.05) and no significant difference during the rest of the time was found; group D had a significantly lower rate of nausea, emesis and pruritus than group C (p<0.05). In conclusion, the usage of Dex in analgesia for post-cesarean can increase the analgesia effect produced by local anesthetics, increase puerpera sedation scores and decrease adverse reactions.

Neuropathic pain is an unfavorable pathological pain, often persistent over time, thus leading to significant impairment of quality of life and public health burden. Notably, microRNAs have been implicated in the pathophysiological process of neuropathic pain. The potential mechanism by which miR‐34c‐5p functions in neuropathic pain remains unclear. This study aimed to test the hypothesis that miR‐34c‐5p can modulate neuropathic pain in rat models with chronic constriction injury (CCI) of sciatic nerve, via interaction with the SIRT1/STAT3 signaling pathway SIRT1 was validated as a target gene of miR‐34c‐5p and could be negatively regulated by miR‐34c‐5p. We induced miR‐34c‐5p overexpression/inhibition, SIRT1 knockdown, and STAT3 knockdown in the model rats to assess pain behavior patterns. Meanwhile, dorsal root ganglion (DRG) was transduced with overexpression or knockdown of miR‐34c‐5p or lipopolysaccharide to induce the production of inflammatory factors. It was observed that miR‐34c‐5p was up‐regulated, and SIRT1 was under‐expressed in the DRG neurons of dorsal spinal cords of the CCI rats. Furthermore, the ectopic expression of miR‐34c‐5p and knockdown of SIRT1 in CCI rats resulted in increased hyperalgesia and inflammation, corresponding to reduced paw withdrawal threshold and paw withdrawal latency, and elevated levels of IL‐6, IL‐1β, and TNF‐α. More importantly, miR‐34c‐5p inhibition reduced the hyperalgesia and inflammation by blocking the STAT3 signaling pathway through up‐regulation of SIRT1. Conjointly, our results indicated that the down‐regulation of miR‐34c‐5p could potentially provide sustained relief in neuropathic pain by promoting SIRT1 expression through STAT3 signaling pathway inactivation. image

This study was performed to characterize the effect of microRNA‐101 (miR‐101) on the pain hypersensitivity in CCI rat models with the involvement of mitogen‐activated protein kinase phosphatase 1 (MKP‐1) in spinal cord microglial cells. The mechanical withdrawal threshold (MWT) and thermal withdrawal latency (TWL) in the developed CCI models were determined to assess the hypersensitivity of rats to mechanical stimulation and thermal pain. To assess inflammation, the levels of interleukin (IL)‐1β, IL‐6 and tumour necrosis factor‐α (TNF‐α) in the spinal dorsal horns of CCI rats and lipopolysaccharide (LPS)‐activated microglial cells were examined. miR‐101 and MKP‐1 gain‐ and loss‐of‐function experiments were conducted in in vivo and in vitro settings to examine the roles of miR‐101 and MKP‐1 in CCI hypersensitivity and inflammation. The results showed that miR‐101 was highly expressed in the spinal dorsal horn and microglial cells of CCI rat models. Furthermore, overexpression of miR‐101 promoted the pain hypersensitivity in CCI rat models by reducing MWT and TWL. The overexpression of miR‐101 also promoted inflammation in LPS‐exposed microglial cells, as indicated by increased levels of IL‐1β, IL‐6 and TNF‐α. MiR‐101 was shown to target MKP‐1, inhibiting its expression. Moreover, miR‐101 promoted pain hypersensitivity in CCI rat models by inhibiting MKP‐1 expression and activating the mitogen‐activated protein kinase (MAPK) signalling pathway. Taken together, miR‐101 could potentially promote hypersensitivity and inflammatory response of microglial cells and aggravate neuropathic pain in CCI rat models by inhibiting MKP‐1 in the MAPK signalling pathway.

Metabolism-mediated drug adverse effects (e.g., drug-drug interaction, bioactivation, etc.) strongly limit the utilization of clinical drugs. The present study aims to predict the metabolic capability of cytochrome P450 (CYP) 3A4 toward pazopanib which is an excellent drug exhibiting therapeutic role toward various cancers especially for ovarian cancer. Pazopanib can be well docked into the activity cavity of CYP3A4, and the interaction structure in pazopanib was methyl group located besides nitrogen in the five-membered ring. The distance between the hydrogen atom in methyl group and active center is 3.64 Å. The interaction amino acid is Glu374. Furthermore, both pazopanib and ketoconazole were docked into the activity cavity of CYP3A4 to compare their binding potential. The distance between ketoconazole and activity center (2.10 Å) is closer than the distance between pazopanib and activity center of CYP3A4, indicating the easy influence of CYP3A4 inhibitor toward the metabolism of pazopanib. All these data were helpful for the clinical application of pazopanib, and R&D of other tinib drug candidates as new anti-tumor drugs.