Enhanced antitumour activity of doxorubicin and simvastatin combination loaded nanoemulsion treatment against a Swiss albino mouse model of Ehrlich ascites carcinoma

Doxorubicin (DOX) is the most commonly used anticancer drug; however, it has limited use because prolonged administration may result in severe cardiotoxicity. Simvastatin (SIM), generally prescribed for hypercholesterolaemia, has also shown salubrious results in the monotherapy or combinational drug therapy of different cancers in various models. Nanoparticle drug delivery systems are a novel way of improving therapeutics and also improving the absorption and specificity of drugs towards tumour cells. In this study, we exploited this technology to increase drug specificity and minimize imminent adverse effects. In this study, the antitumour activity of the combination formulas of DOX and SIM, either loaded in water (DOX‐SIM‐Solution) or nanoemulsions (NEs) (DOX‐SIM‐NE), was evaluated in a Swiss albino mouse model of Ehrlich ascites carcinoma. The anticancer effect was assessed by quantifying the change in body weight, mean survival time, and percent increase in lifespan (%ILS), determining haematological and serum biochemical parameters (liver function test, kidney function test and lipid profile parameters) as well as studying the histopathological alterations in liver tissues. We observed a clear increase in %ILS of the DOX‐SIM‐Solution group (265.30) that was double the %ILS of the DOX‐SIM‐NE group (134.70). However, DOX‐SIM‐NE had a non‐toxic effect on the haematological parameters, whereas DOX‐SIM‐Solution increased the levels of haemoglobin and lymphocytes. Furthermore, the encapsulation of SIM and DOX into NEs improved the levels of all serum biochemical parameters compared to the DOX‐SIM‐Solution. A reduction in the side effects of DOX‐SIM‐NE on the liver was also established using light microscopy, which revealed that the morphologies of the hepatocytes of the mice were less affected by administration of the DOX‐SIM‐NE treatment than with the DOX‐SIM‐Solution treatment. The study showed that incorporating SIM into the DOX‐loaded‐NE formulation remarkably improved its efficiency and simultaneously reduced its adverse effects.     

陆芷青教授治疗肝炎后肝硬化经验探析

陆芷青教授治疗肝炎后肝硬化辨证病机明确,治法独特,疗效显著。认为本病多因湿热疫毒伤及脏腑气血而成,早期气滞血瘀,瘀阻肝络,而成肝积;晚期正虚邪留,虚实错杂,血水不利,形成臌胀。陆芷青认为早期应着眼于化瘀消癥兼顾肝脾,晚期逐水祛邪兼以扶正,并辅以验案加以佐证。     

雷火灸联合搐鼻疗法治疗脾肾阳虚型乙肝肝硬化腹水的疗效观察

[目的]观察雷火灸联合搐鼻疗法治疗脾肾阳虚型乙肝肝硬化腹水的临床疗效。[方法]将中医辨证为脾肾阳虚型乙肝肝硬化腹水患者随机分为对照1组、对照2组及观察组,每组42例,3组均接受西医常规治疗,对照1组采用雷火灸治水四穴;对照2组采用中草药搐鼻疗法;观察组采用雷火灸治水四穴联合搐鼻疗法。疗程为4周,治疗后对各项指标进行观察。[结果]观察组分别与2个对照组临床总有效率比较差异有统计学意义(P<0.05)。治疗后,3组患者的中医症状评分、丙氨酸转氨酶、总胆红素、体重、腹围、脾厚、门静脉内径显著降低,且观察组显著低于对照1组、对照2组,均差异有统计学意义(P<0.05);治疗后白蛋白、凝血酶原活动度、平均24 h尿量显著升高,且观察组显著高于对照1组、对照2组,均差异有统计学意义(P<0.05)。[结论]雷火灸治水四穴联合搐鼻疗法可以明显改善乙肝肝硬化腹水患者的肝功能、凝血功能及临床症状,降低门静脉压力、提高血浆胶体渗透压,临床疗效显著。     

miR-145调控肝癌腹水模型Th9细胞升高的机制研究

目的:探讨miR-145调控肝癌腹水模型Th9细胞升高的作用机制。方法:构建小鼠H22肝癌腹水模型。造模两周后处死小鼠并分离出脾脏组织，流式细胞术分析肝癌腹水组（MA组）与正常对照组（Control 组）小鼠脾脏Th9细胞表达水平。ELISA法检测脾脏IL-9表达水平。RT-PCR法检测脾脏miR-145表达水平。Western Blot法检测脾脏中PI3K/Akt/mTOR/P70S6K/HIF-1α相关蛋白表达水平。分选小鼠脾脏CD4+T细胞，随机分为miR-145 mimics组和NC组，分别应用miR-145-5P mimics、阴性对照寡核苷酸（negative control，NC）进行转染，RT-PCR检测各组miR-145、HIF-1α mRNA及IL-9 mRNA表达水平。结果:与Control 组相比，MA组Th9细胞及其细胞因子IL-9表达均升高（P<0.05），miR-145表达降低（P<0.05），p-PI3K、p-Akt、mTOR、p-mTOR、p-P70S6K、HIF-1α蛋白均升高（P<0.05）。与NC组相比，miR-145 mimics组miR-145显著升高，HIF-1α mRNA及IL-9 mRNA表达下降。结论:肝癌腹水中Th9细胞升高可能与miR-145下降导致的PI3K/Akt/mTOR/P70S6K/HIF-1α通路激活有关。     

恩度联合多西他赛序贯腹腔灌注治疗胃癌伴恶性腹水的临床观察

目的:回顾性分析恩度联合多西他赛序贯腹腔灌注治疗胃癌伴恶性腹水的疗效及不良反应。方法:收集72例胃癌伴腹水患者，曾接受过二线及以上方案化疗，观察组35例，采用恩度45 mg联合多西他赛35 mg/m2 d1，d5序贯腹腔灌注1周期；对照组37例，采用多西他赛35 mg/m2 d1，d5腹腔灌注1周期，统计患者腹水控制有效率、KPS改善率、腹水控制时间及不良反应。结果:治疗组中腹水控制有效率71.43%；对照组中腹水控制有效率48.65%，P=0.049，两组具有统计学差异；治疗组中KPS改善率77.14%，对照组中KPS改善率54.05%，P=0.04，两组具有统计学差异；观察组中腹水控制时间8~90天，中位控制时间44天，对照组中腹水控制时间5~66天，中位控制时间28天，两组控制时间比较，P=0.048，具有统计学差异；III级以上不良反应发生率低，无治疗相关性死亡，两组不良反应比较，P>0.05，无统计学差异。结论:恩度联合多西他赛序贯腹腔灌注治疗体力状况（performance status,PS）评分较差的胃癌伴恶性腹水患者，腹水控制较好，能明显提高患者生活质量，未见明显不良反应。