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1.
Renal cell cancer (RCC) represents 2%-3% of all adulthood cancers and is the most common malignant neoplasm of the kidney (90%). In the mid-nineties of the last century, the standard of treatment for patients with metastatic RCC was cytokines. Sunititib and pazopanib were registered in 2007 and 2009, respectively, and have since been the standard first-line treatment for metastatic clear cell RCC (mccRCC). Renal cell cancer is a highly immunogenic tumor with tumor infiltrating cells, including CD8+ T lymphocytes, dendritic cells, natural killer cells (NK) and macrophages. This observation led to the design of new clinical trials in which patients were treated with immunotherapy. With the growing evidence that proangiogenic factors can have immunomodulatory effects on the host’s immune system, the idea of combining angiogenic drugs with immunotherapy has emerged, and new clinical trials have been designed. In the last few years, several therapeutic options have been approved [immunotherapy and immunotherapy/tyrosine kinase inhibitors (TKI)] for the first-line treatment of mccRCC. Nivolumab/ipilimumab is approved for the treatment of patients with intermediate and poor prognoses. Several checkpoint inhibitors (pembrolizumab, nivolumab, avelumab) in combination with TKI (axitinib, lenvatinib, cabozantinib) are approved for the treatment of patients regardless of their International mRCC Database Consortium prognostic group and PD-L1 expression. There is no specific and ideal biomarker that could help in selecting the ideal patient for the appropriate first-line treatment.  相似文献   
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《Saudi Pharmaceutical Journal》2022,30(10):1486-1496
IntroductionPreclinical studies have demonstrated the possible anticancer effects of statins, but the synergistic effect of concomitant statin use with standard chemotherapy protocols in patients with breast cancer has not yet been investigated.AimThe current study aimed to evaluate the efficacy of concomitant pitavastatin use with neoadjuvant chemotherapy protocols in patients with breast cancer.MethodsThis study was a randomized controlled clinical trial. A total of 70 adult female patients with pathologically-proven invasive breast cancer were randomized to receive or not receive pitavastatin (2 mg) oral tablets once daily concomitantly with standard neoadjuvant chemotherapy protocols for 6 months. The primary outcomes of this study were changes in tumor size and changes to the Ki67 index. In addition, secondary outcomes were changes in cyclin D1 and cleaved caspase-3 serum levels. This study was registered at ClinicalTrials.gov (Identifier: NCT04705909).ResultsPatients in the pitavastatin group showed significantly higher median (IQR) reductions in tumor size [?19.8 (?41.5, 9.5)] compared to those in the control group [?5.0 (?15.5, 0.0), p = 0.0009]. The change in Ki67 from baseline to the end of therapy was similar between the two groups (p = 0.12). By the end of therapy, the cyclin D1 levels in the pitavastatin group were significantly decreased [median (IQR) change of ? 10.0 (?20.2, ?2.9) from baseline], whereas the control group showed an increase in cyclin D1 levels [14.8 (4.1, 56.4)]. The median (IQR) caspase?3 was elevated in the pitavastatin group 1.6 (0.2, 2.2), and decreased in the control group (?0.2 (?1.1, 0.0), p = 0.0002).Subgroup analysis of the pitavastatin group revealed that patients with positive human epidermal growth receptor 2 (HER2) had higher median (IQR) reductions in Ki67 [?35.0 (?70.0, ?12.5)] than those with negative HER2 [2.5 (?15.0, 10.0), p = 0.04]. All patients who achieved a complete pathological response (n = 9) exhibited an HER2-neu positive receptor at baseline.ConclusionConcomitant use of pitavastatin with standard neoadjuvant chemotherapy protocols may improve neoadjuvant chemotherapy responses in patients with breast cancer.  相似文献   
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《Vaccine》2022,40(19):2679-2695
Vaccinations are essential for preventing infectious diseases in children with chronic diseases as they have increased risk of infection from frequent use of biologics. Response to immunizations in this group is not well known.ObjectiveA systematic review was performed to evaluate three primary outcomes: efficacy; immunogenicity; and safety of vaccines in children with chronic conditions treated with biologics.MethodsThe protocol for our systematic review and meta-analysis was registered and published with PROSPERO. We searched electronic bibliographic databases for studies published from 2009 to 2019, focusing on vaccinations in children with chronic conditions treated with biologics.ResultsWe retrieved 532 records. Thirty-one full-text articles were selected, and 14 were included in the meta-analysis. No significant publication bias was found. Efficacy: limited data are available regarding the efficacy of vaccination, as most studies have focused on immunogenicity as surrogate outcome for efficacy. Immunogenicity: patients receiving anti-TNF-alpha therapy had a statistically significant risk of poor seroconversion (p = 0.028) and seroprotection by the serotype B influenza vaccine [inflammatory bowel disease (IBD) p = 0.013; juvenile idiopathic arthritis (JIA) p = 0.004]. We found adequate responses with H1N1 and H3N2 serotypes. Few studies existed for pneumococcal, hepatitis A virus, hepatitis B virus, varicella-zoster virus, Measles Mumps Rubella virus, and multiple vaccine administration. Safety: vaccine administration was not associated with serious side effects, but JIA patients on anti-TNF alpha therapy had a statistically significant risk of presenting with myalgia or arthralgia postinfluenza vaccine (p = 0.014).ConclusionsMore evidence concerning efficacy, immunogenicity, and safety of vaccinations is needed to guide physicians in the vaccine decision process for this pediatric population.  相似文献   
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BackgroundIntraabdominal and retroperitoneal sarcomas (IaRS) are malignant connective tissue tumors. Surgical resection is often the only curative treatment. The primary objective was to report the mid-term outcomes following contemporary treatment protocols and identify prognostic factors.MethodsA retrospective review of consecutive patients (n = 107) with IaRS treated at single center from 2013 until 2018 was conducted. Histological diagnosis, tumor grade, perioperative complications, mortality, and long-time survival were registered and retrieved from patient records. Primary and recurrent tumors were analyzed separately.ResultsA total of 107 patients were identified. Median follow-up time was 3.5 years. Thirty-day mortality was 3.4% and 90-day mortality was 5.6% for all tumors. The major complication rate was 18%. The 5-year estimated survival for primary and recurrent tumors was 55.4% and 48.4%, respectively. Multifocal disease was evident in 32% of the patient cohort, and 58% of patients in the recurrent group. Multivariate analysis for survival revealed a hazard ratio (HR) of 3.1 (95% CI 1.68–8.41) for multifocality, HR 2.9 (95% CI 1.28–6.98) for Clavien-Dindo grade, HR 2.3 (95% CI 1.21–4.31) for tumor grades 2 or 3, and HR 1.002 (95% CI 1.001–1.004) for surgical margins.ConclusionsOur study found overall acceptable morbidity and mortality, and identified prognostic markers for overall survival. Recurrent tumors were not associated with worse survival. Multifocality is associated with a worse overall survival. The prognostic factors identified were; tumor grade, multifocality, intralesional margins and postoperative complications.  相似文献   
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目的:研究Piezo1机械敏感性离子通道对骨细胞的调控作用。方法:应用课题组研发的流体剪切力(FSS)加载装置,使用免疫荧光探究FSS对Piezo1通道在MLO-Y4中影响的最佳强度;对Piezo1使用FSS、激动剂Yoda1或阻滞剂GsMTx4进行干预。使用Western Blot探究Cleaved Caspase-3、Bcl-2、Bax凋亡相关蛋白的表达量;使用Hoechst-33258以及流式细胞凋亡检测MLO-Y4骨细胞的凋亡比例。结果:免疫荧光染色结果表明FSS对MLO-Y4骨细胞中Piezo1的表达呈现先增加后降低的单峰趋势,其中以9 dyne/cm2加载30 min为最佳刺激条件。使用Yoda1抑制MLO-Y4细胞凋亡(P<0.05),使用GsMTx4促进MLO-Y4细胞凋亡(P<0.05)。Piezo1介导的FSS抑制MLO-Y4细胞凋亡(P<0.05)。结论:Piezo1机械敏感性离子通道介导的FSS在9 dyne/cm2条件下抑制MLO-Y4骨细胞凋亡,且FSS在该条件下可以有效逆转Piezo1阻滞剂GsMTx4在4 μmol/L作用0.5 h下促进MLO-Y4细胞凋亡作用。  相似文献   
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背景 在老龄化背景下,缺血性中风发病呈年轻化、患病率呈逐年上升的趋势,而失眠是该病常见的并发症之一。 目的 探究经筋解结联合涌泉贴敷治疗缺血性中风后失眠的效果及其对血清白介素6(IL-6)、肿瘤坏死因子α(TNF-α)的影响。 方法 选取2020年5月至2021年5月在广东药科大学附属第一医院门诊就诊或住院的缺血性中风后失眠患者80例,采用完全随机分组方法将其分为中医治疗组、西药治疗组,各40例。中医治疗组采用经筋解结联合涌泉贴敷治疗,西药治疗组采用艾司唑仑治疗,均治疗2个疗程(10次为1个疗程)。比较两组治疗前、治疗1个疗程、治疗2个疗程匹兹堡睡眠质量指数(PSQI)总分及各维度(睡眠质量、入睡时间、睡眠时间、睡眠效率、睡眠障碍、催眠药物和日间功能障碍)评分、阿森斯失眠量表(AIS)评分、血清IL-6与TNF-α水平,治疗后临床疗效。 结果 研究过程中中医治疗组脱落1例、西药治疗组脱落2例,最终中医治疗组39例、西药治疗组38例纳入研究。组别与时间对PSQI总分及各维度评分、AIS评分存在交互作用,组别及时间对PSQI总分及各维度评分、AIS评分主效应显著(P<0.05)。治疗1、2个疗程,两组患者PSQI总分及各维度评分、AIS评分均低于治疗前(P<0.05);治疗2个疗程,两组患者PSQI总分及各维度评分、AIS评分均低于治疗1个疗程(P<0.05)。治疗1、2个疗程中医治疗组患者PSQI总分及各维度评分、AIS评分均低于西药治疗组(P<0.05)。组别与时间对血清IL-6、TNF-α水平存在交互作用,组别及时间对血清IL-6、TNF-α水平主效应显著(P<0.05)。治疗1、2个疗程,两组患者血清IL-6、TNF-α水平均低于治疗前(P<0.05);治疗2个疗程,两组患者血清IL-6、TNF-α水平均低于组内治疗1个疗程(P<0.05)。中医治疗组患者治疗1、2个疗程血清IL-6、TNF-α水平低于西药治疗组P<0.05)。中医治疗组患者治疗后临床疗效优于西药治疗组(Z=2.234,P<0.05)。 结论 经筋解结联合涌泉贴敷可明显改善缺血性中风后失眠患者的睡眠质量,降低血清IL-6、TNF-α水平,提高临床疗效。  相似文献   
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目的探讨血浆硫氧还蛋白还原酶(TR)在肺癌化疗疗效监测中的价值。方法将482例肺癌患者依据化疗疗效分为治疗未获益组(211例)和治疗获益组(271例),检测所有患者TR、癌胚抗原(CEA)、鳞状上皮细胞癌抗原(SCC-Ag)、细胞角蛋白19片段(CYFRA 21-1)、神经元特异性烯醇化酶(NSE)及胃泌素释放肽前体(ProGRP)水平。采用受试者工作特征(ROC)曲线评估各项指标单项及联合检测判断化疗疗效的价值。结果治疗未获益组TR、CEA及NSE水平均高于治疗获益组(P<0.05),2个组之间SCC-Ag、CYFRA21-1及ProGRP水平差异均无统计学意义(P>0.05)。治疗未获益组TR阳性率为56.40%,显著高于治疗获益组(13.16%)(P<0.05)。ROC曲线分析结果显示,TR、CEA、CYFRA 21-1、SCCAg、NSE及ProGRP单项检测判断肺癌化疗疗效的曲线下面积(AUC)分别为0.759、0.667、0.579、0.530、0.619、0.544。将各项指标进行组合,TR+CEA、TR+CEA+CYFRA21-1、TR+CEA+CYFRA21-1+NSE及TR+CEA+CYFRA 21-1+NSE+ProGRP联合检测判断肺癌化疗疗效的AUC分别为0.757、0.749、0.752和0.788。TR与CEA、NSE、SCC-Ag、CYFRA 21-1及ProGRP均无相关性(r值分别为0.05、0.02、-0.15、0.05、0.10,P>0.05)。结论TR或可作为更有效的肺癌疗效监测的生物标志物。  相似文献   
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