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Metastatic melanoma is the most deadly skin neoplasm in the United States. Outcomes for this lethal disease have improved dramatically due to the use of both targeted and immunostimulatory drugs. Immunogenic cell death (ICD) has emerged as another approach for initiating antitumor immunity. ICD is triggered by tumor cells that display damage-associated molecular patterns (DAMPs). These DAMP molecules recruit and activate dendritic cells (DCs) that present tumor-specific antigens to T cells which eliminate neoplastic cells. Interestingly, the expression of DAMP molecules occurs in an endoplasmic reticulum (ER) stress-dependent manner. We have previously shown that ER stress was required for the cytotoxic activity of the endocannabinoid metabolite, 15-deoxy, Δ12,14 prostamide J2 (15dPMJ2). As such, the current study investigates whether 15dPMJ2 induces DAMP signaling in melanoma. In B16F10 cells, 15dPMJ2 caused a significant increase in the cell surface expression of calreticulin (CRT), the release of ATP and the secretion of high-mobility group box 1 (HMGB1), three molecules that serve as surrogate markers of ICD. 15dPMJ2 also stimulated the cell surface expression of the DAMP molecules, heat shock protein 70 (Hsp70) and Hsp90. In addition, the display of CRT and ATP was increased by 15dPMJ2 to a greater extent in tumorigenic compared to non-tumorigenic melanocytes. Consistent with this finding, the activation of bone marrow-derived DCs was upregulated in co-cultures with 15dPMJ2-treated tumor compared to non-tumor melanocytes. Moreover, 15dPMJ2-mediated DAMP exposure and DC activation required the electrophilic cyclopentenone double bond within the structure of 15dPMJ2 and the ER stress pathway. These results demonstrate that 15dPMJ2 is a tumor-selective inducer of DAMP signaling in melanoma.  相似文献   
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Background and objectivesPatients with cancer experience many side effects due to its nature and usual treatments. Sleep disorders and anorexia are the most commonly reported symptoms in cancer patients undergoing chemotherapy. The present study aimed to investigate the effect of Benson's Relaxation Response (BRR) on sleep quality and anorexia in cancer patients undergoing chemotherapy.Methodology and participantsIn the present clinical trial, a total of 84 patients were enrolled and randomly divided into two groups of experimental and control. Benson's relaxation response was administered to the experimental group twice a day over 5 consecutive days. Data was collected using St. Mary's Hospital Sleep Questionnaire (SMHSQ) and anorexia questionnaire with Visual Analog Scale (VAS).ResultsThe results of our study showed a significant improvement in the sleep quality in the experimental group at 24 (p = 0.02) and 48 (p = 0.001) hours after the intervention compared to the control group. Benson's relaxation response (BRR) also had a significant effect on the anorexia in the experimental group at 24 (7.5 ± 1.6) and 48 (6.9 ± 2.1) hours after the intervention compared to the control group. No side effects were reported during the study and follow-up period.ConclusionBenson's relaxation response as a complementary method may improve sleep quality and anorexia in cancer patients undergoing chemotherapy. Further studies with greater sample size and longer follow-up period are needed to confirm the current findings.  相似文献   
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PURPOSE: The purpose of this study was to investigate the effects of chewing and clenching on salivary cortisol levels as an indicator of stress. MATERIALS AND METHODS: Seventeen healthy dentulous subjects were given arithmetic exercises to perform within a 20-minute time limit in order to elicit stress (stress loading). In the first experiment (chewing), after stress loading, the subjects were asked to chew a paraffin wax while reading printed material (books, magazines, etc.) in silence for 10 minutes. The same procedure was then carried out again for control purposes, but this time the subjects were not required to chew wax. In the second experiment (light clenching), after stress loading, the subjects were required to carry out 5 seconds of light clenching followed by 5 seconds of rest repeatedly over a 3-minute period. The whole 3-minute process was repeated a total of three times. The control data for this second experiment consisted of measurements taken during the rest periods. Saliva specimens were collected in both experiments both before stress loading and after each procedure during 1-minute intervals to measure cortisol levels. RESULTS: In the chewing experiment, salivary cortisol levels were significantly reduced by chewing, compared with those in the controls (p < 0.05). This reduction in salivary cortisol was observed during chewing over a 10-minute period following stress loading. In the clenching experiment, salivary cortisol levels also showed a significant reduction during clenching, compared with those in the controls (p < 0.05). CONCLUSIONS: These results suggest that chewing and clenching promote relaxation in subjects under stress.  相似文献   
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两种阴道缩窄术矫正阴道松弛症的疗效分析   总被引:3,自引:0,他引:3  
目的探讨改良阴道后壁修补术和阴道后壁环肌紧缩术的手术要点和效果,评价两种手术的优点及适应证。方法将42例不同程度阴道松弛的患者分为两组,其中24例行改良阴道后壁修补术,18例行阴道后壁环肌紧缩术,分析观察两组患者手术时间、术中出血量、术后伤口愈合情况,1年后评价两组患者的性生活满意度及阴道的松紧度。结果两种手术方法的手术时间、术中出血量及术后伤口愈合情况无明显差异,但1年后的远期效果包括性生活满意度和阴道的松紧度有明显差异。结论矫正阴道松弛症的目的不仅要达到解剖的恢复,更重要的是恢复功能。要根据患者的实际情况选择最佳的手术方法(A组优于B组)。  相似文献   
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目的:分析肛管松解加病理组织切除治疗陈旧性肛裂的疗效。方法:对l70例陈旧性肛裂病人采用裂口内直视下切断外括约肌皮下部和齿状线下内括约肌部分并修剪裂口、切除局部病理组织。结果:有效率为100%,治愈168例(98.8%),好转2例(1.2%)。结论:肛管松解加病理组织切除治疗陈旧性肛裂是一种安全可靠的治疗方法。  相似文献   
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AIM: To investigate the participation of adenosine receptors in the adenosine 5'-triphosphate (ATP)-induced relaxation in the corpus cavernosum penis (CCP) of rabbits. METHODS: The ATP-induced relaxation was assessed on the noradrenaline precontracted CCP of rabbits in the presence and absence of 8-(3-chlorostyryl)caffeine (CSC); an adenosine A(2A) receptor antagonist; alloxazine and MRS1754; adenosine A(2B) receptor antagonists; and ARL67156, an inhibitor of ecto-nucleoside triphosphate diphosphohydrolases. RESULTS: Adenosine and ATP relaxed the noradrenaline precontracted CCP of rabbits in a concentration-dependent manner. The adenosine- and ATP-induced relaxations were suppressed by alloxazine and MRS1754, but not by 8-(3-chlorostyryl)caffeine. ARL67156 potentiated the ATP-induced relaxation but not the adenosine-induced one. MRS1754 suppressed the ATP-induced relaxation potentiated by ARL67156. CONCLUSIONS: The above results suggest that, in the CCP of rabbits, the adenosine receptor mediating adenosine-induced relaxation is of the A(2B) receptor and the ATP directly causes relaxation through the A(2B) receptor on the CCP.  相似文献   
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Guidelines for design of clinical trials evaluating behavioral headache treatments were developed to facilitate production of quality research evaluating behavioral therapies for management of primary headache disorders. These guidelines were produced by a Workgroup of headache researchers under auspices of the American Headache Society. The guidelines are complementary to and modeled after guidelines for pharmacological trials published by the International Headache Society, but they address methodologic considerations unique to behavioral and other nonpharmacological treatments. Explicit guidelines for evaluating behavioral headache therapies are needed as the optimal methodology for behavioral (and other nonpharmacologic) trials necessarily differs from the preferred methodology for drug trials. In addition, trials comparing and integrating drug and behavioral therapies present methodological challenges not addressed by guidelines for pharmacologic research. These guidelines address patient selection, trial design for behavioral treatments and for comparisons across multiple treatment modalities (eg, behavioral vs pharmacologic), evaluation of results, and research ethics. Although developed specifically for behavioral therapies, the guidelines may apply to the design of clinical trials evaluating many forms of nonpharmacologic therapies for headache.  相似文献   
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目的探讨心房充血分数(AFF)在评价高血压患者左室舒张功能方面的临床应用价值。方法应用声学定量技术(AQ)对40名高血压患者及40名正常人的AAF值,快充血率峰值(PRFR)进行测定,并兼测了二尖瓣口E峰峰值速度与A峰峰值速度比(EV/AV)。结果高血压患者的AFF值明显高于正常人(P<0·001);而PRFR、EV/AV值明显低于正常人(P<0·001~P<0·05)。且所有受试者的AFF值与EV/AV值、PRFR值分别呈负相关(r=-0·51;r=-0·61)。结论AFF能够客观的反映高血压患者的左室舒张功能变化,对鉴别左室舒张功能异常有一定的诊断意义。  相似文献   
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