Immunotherapy Is Changing First-Line Treatment of Metastatic Renal-Cell Carcinoma

The incidence of renal-cell carcinoma has been increasing each year, with nearly one third of new cases diagnosed at advanced or metastatic stage. The advent of targeted therapies for metastatic renal-cell carcinoma (mRCC) has underscored the need to subtype tumors according to tumor-immune expression profiles that may more reliably predict treatment outcomes. Over the past 2 decades, several vascular endothelial growth factor (VEGF) and tyrosine kinase inhibitors have been the mainstay for first- and second-line treatment of mRCC. Very recently, immunotherapy checkpoint inhibitors have significantly changed the treatment landscape for patients with mRCC, particularly for first-line treatment of intermediate to poor risk mRCC patients. Now, combination immunotherapy as well as combinations of immunotherapy with targeted agents can significantly alter disease outcomes. The field of immuno-oncology for mRCC has unveiled a deeper understanding of the immunoreactivity inherent to these tumors, and as a result combination therapy is evolving as a first-line modality. This review provides a timeline of advances and controversies in first-line treatment of mRCC, describes recent advances in understanding the immunoreactivity of these tumors, and addresses the future of combination anti-VEGF and immunotherapeutic platforms.     

How do parents' child-feeding behaviours influence child weight? Implications for childhood obesity policy

BACKGROUND: Parents have some responsibility for children's dietary habits and they are often the focus of public health interventions designed to improve children's diets and thereby reduce the prevalence of childhood obesity. The current UK interventions promote awareness of healthy food choices, but offer little guidance for parents on child-feeding behaviours. METHODS: A review of recent literature regarding child-feeding behaviours and child weight. RESULTS: Parents report using a wide range of child-feeding behaviours, including monitoring, pressure to eat and restriction. Restriction of children's eating has most frequently and consistently been associated with child weight gain. Furthermore, there is substantial evidence for a causal relationship between parental restriction and childhood overweight. CONCLUSIONS: Parents may inadvertently promote excess weight gain in childhood by using inappropriate child-feeding behaviours. We recommend the development of interventions to increase awareness of the possible consequences of inappropriate child-feeding behaviours. Parents who are concerned about their child's weight will also require guidance and support in order to adopt more appropriate child-feeding behaviours.     

基于复杂网络分析针灸治疗乳腺增生症的腧穴配伍规律及核心腧穴刺灸法应用特点

目的:利用复杂网络技术分析针灸治疗乳腺增生症的腧穴配伍规律及核心腧穴刺灸法应用特点,为临床针灸治疗乳腺增生症提供选穴依据和治疗思路.方法:检索中国知网(CNKI)、万方数据知识服务平台、维普资讯中文期刊服务平台、Pubmed、Embase、Cochrane Library、Web of Science、Ovid数据库中...     

复方陈皮组合物的降脂减肥作用研究

目的:研究复方陈皮组合物(CPZHW)对营养肥胖型大鼠的降脂减肥作用。方法:喂饲高脂饲料以复制营养性肥胖模型大鼠。实验分为空白对照(等容生理盐水)、模型(等容生理盐水)、阿托伐他汀(10mg·kg-1)和CPZHW高、中、低剂量(600、300、150mg·kg-1)组,灌胃给药,每天1次,连续45d。检测血清中甘油三酯(TG)、总胆固醇(TC)、高密度脂蛋白胆固醇(HDL-C)、低密度脂蛋白胆固醇(LDL-C)的含量和糖耐量,计算体重、摄食量、食物利用率、Lee’s指数、脂/体比、附睾、肾周脂肪垫重和脂肪细胞数。结果:与模型组比较,CPZHW高、中、低剂量组体重、脂/体比、附睾、肾周脂肪垫重显著减少(P<0.01或P<0.05),大鼠血清TG含量显著降低(P<0.01或P<0.05),HDL-C含量显著升高(P<0.01);CPZHW高、中剂量组大鼠脂肪细胞数显著增加(P<0.01或P<0.05),CPZHW中剂量组大鼠Lee’s指数显著降低(P<0.01)。各组糖耐量无显著性差异(P>0.05)。结论:CPZHW对营养肥胖型大鼠有降脂减肥的作用。     

复方维A酸软膏的制备及临床研究

目的研制具有抗角质化、抗菌、抗过敏的复方维A酸软膏。方法针对病因筛选合理的处方,确定配制方法,建立鉴别方法及采用薄层扫描法测其含量,进行药理试验。结果制剂质量稳定、安全、可控,临床验证450例,总有效率为95.3%。结论复方维A酸软膏是治疗皮肤病(炎症角质化)有效药物,值得推广、应用于临床。     

黄芪和三七的主要有效成分配伍对脑缺血/再灌注小鼠NF-κB信号通路及炎性因子表达的影响

目的从炎症反应探讨黄芪和三七主要有效成分配伍抗脑缺血/再灌注损伤的机制。方法将C57BL/6小鼠随机分为假手术组、模型组、黄芪甲苷(ASTⅣ)组、人参皂苷Rg1(Rg1)组、人参皂苷Rb1(Rb1)组、三七皂苷R1(R1)组、4种有效成分配伍组、ASTⅣ+Rg1组、ASTⅣ+Rb1组、ASTⅣ+R1组及阳性对照药依达拉奉组。预先给药3 d,末次给药1 h后,结扎双侧颈总动脉,造成脑缺血20 min,再灌注24h。RT-PCR法测定TNF-α、IL-1β、ICAM-1 mRNA表达,Western blot法测定脑组织p-IκBα蛋白及胞质、胞核NF-κB蛋白表达,计算NF-κB核转位率。结果 1脑缺血/再灌注后,脑组织TNF-α、IL-1β、ICAM-1 mRNA表达增加。ASTⅣ可降低TNF-αmRNA表达,Rg1可降低ICAM-1 mRNA的表达,R1能同时下调TNF-α、ICAM-1 mRNA的表达。ASTⅣ与Rg1、Rb1、R1配伍对TNF-α、IL-1β、ICAM-1 mRNA的表达均有不同程度的抑制作用,且以4种有效成分配伍组和ASTⅣ+R1组对炎性细胞因子表达的抑制效应更加明显。2脑缺血/再灌注后,脑组织p-IκBα蛋白表达明显增加,胞质NF-κB蛋白表达明显减少,而胞核NF-κB蛋白表达增加,NF-κB核转位率升高。ASTⅣ、Rg1、R1及各有效成分配伍均能抑制IκB磷酸化,减少NF-κB核转位的发生,且配伍组的效应大于各有效成分单用,4种有效成分配伍组的效应大于ASTⅣ+Rb1和ASTⅣ+Rg1组。结论黄芪和三七的主要有效成分配伍能通过抑制缺血/再灌注后脑组织NF-κB信号通路的激活,减少炎性细胞因子的生成,从而减轻脑缺血后脑组织的继发性炎症反应,发挥对脑组织的保护作用。     

戊己丸活性代表成分在大鼠肝脏中分布的研究

采用L9(34)正交设计将戊己丸中黄连,吴茱萸,白芍提取物组成9组配伍方,以及相应剂量的单味药方,共计18个方。建立并采用UPLC-MS/MS方法测定并比较不同配伍方代表成分小檗碱、巴马汀、吴茱萸碱、吴茱萸次碱、芍药苷在大鼠口服给药2 h后在肝脏中的浓度比较戊己丸不同配伍方中有效成分在大鼠肝脏中的浓度。结果显示戊己丸配伍方中有效成分在肝中的浓度与相同剂量的单味药组方存在明显差异,相同剂量配伍方之间也存在差异。黄连与低、高剂量吴茱萸中吴茱萸碱浓度成正相关,吴茱萸与低剂量黄连中小檗碱的浓度成负相关,与中剂量黄连中小檗碱的浓度成正相关,与中剂量白芍中芍药苷浓度成正相关。白芍与中剂量黄连中巴马汀浓度成负相关、与中剂量吴茱萸中吴茱萸碱、吴茱萸次碱浓度成负相关。提示了黄连、吴茱萸、白芍之间相互作用导致了各活性成分在肝中分布的差异,分析显示各代表成分2 h在肝中浓度最大的配伍比为12∶6∶6。     

Co-administration of curcumin with other phytochemicals improves anticancer activity by regulating multiple molecular targets

Natural plant phytochemicals are effective against different types of diseases, including cancer. Curcumin, a powerful herbal polyphenol, exerts inhibitory effects on cancer cell proliferation, angiogenesis, invasion, and metastasis through interaction with different molecular targets. However, the clinical use of curcumin is limited due to poor solubility in water and metabolism in the liver and intestine. The synergistic effects of curcumin with some phytochemicals such as resveratrol, quercetin, epigallocatechin-3-gallate, and piperine can improve its clinical efficacy in cancer treatment. The present review specifically focuses on anticancer mechanisms related to the co-administration of curcumin with other phytochemicals, including resveratrol, quercetin, epigallocatechin-3-gallate, and piperine. According to the molecular evidence, the phytochemical combinations exert synergistic effects on suppressing cell proliferation, reducing cellular invasion, and inducing apoptosis and cell cycle arrest. This review also emphasizes the significance of the co-delivery vehicles-based nanoparticles of such bioactive phytochemicals that could improve their bioavailability and reduce their systemic dose. Further high-quality studies are needed to firmly establish the clinical efficacy of the phytochemical combinations.