A highly tumor-targeted nanoparticle of podophyllotoxin penetrated tumor core and regressed multidrug resistant tumors

Podophyllotoxin (PPT) exhibited significant activity against P-glycoprotein mediated multidrug resistant (MDR) tumor cell lines; however, due to its poor solubility and high toxicity, PPT cannot be dosed systemically, preventing its clinical use for MDR cancer. We developed a nanoparticle dosage form of PPT by covalently conjugating PPT and polyethylene glycol (PEG) with acetylated carboxymethyl cellulose (CMC-Ac) using one-pot esterification chemistry. The polymer conjugates self-assembled into nanoparticles (NPs) of variable sizes (20–120 nm) depending on the PPT-to-PEG molar ratio (2–20). The conjugate with a low PPT/PEG molar ratio of 2 yielded NPs with a mean diameter of 20 nm and released PPT at ∼5%/day in serum, while conjugates with increased PPT/PEG ratios (5 and 20) produced bigger particles (30 nm and 120 nm respectively) that displayed slower drug release (∼2.5%/day and ∼1%/day respectively). The 20 nm particles exhibited 2- to 5-fold enhanced cell killing potency and 5- to 20-fold increased tumor delivery compared to the larger NPs. The biodistribution of the 20 nm PPT-NPs was highly selective to the tumor with 8-fold higher accumulation than all other examined tissues, while the larger PPT-NPs (30 and 120 nm) exhibited increased liver uptake. Within the tumor, >90% of the 20 nm PPT-NPs penetrated to the hypovascular core, while the larger particles were largely restricted in the hypervascular periphery. The 20 nm PPT-NPs displayed significantly improved efficacy against MDR tumors in mice compared to the larger PPT-NPs, native PPT and the standard taxane chemotherapies, with minimal toxicity.     

放疗在肝癌治疗中应用的研究进展

肝癌是临床上常见的恶性肿瘤，因早期症状不典型，至发现时往往已为中晚期，失去最佳手术治疗时机和机会。作为非手术治疗之一的放射治疗技术，其发展在近年来已有了较大的进步。放疗包括体外放疗和体内放疗，皆具有一定的治疗效果和相对可控的不良反应。本文就肝癌放射治疗的应用进展作一综述。     

PTPN6通过抑制SP1/p38 MAPK信号通路促进前列腺癌细胞的化疗敏感性

目的:研究PTPN6对前列腺癌细胞PC3的作用及其作用机制。方法:RT-PCR和Western blot实验检测前列腺癌组织和细胞以及癌旁组织和人前列腺上皮细胞中PTPN6的表达量；CCK-8和EDU染色实验检测PTPN6对前列腺癌细胞PC3增殖的影响；Western blot实验检测耐药相关蛋白P-gp和MRP-1的蛋白表达水平。结果:RT-PCR和Western blot结果显示，PTPN6在前列腺癌组织和细胞中的表达量显著低于癌旁组织和人前列腺上皮细胞中的表达量；过表达PTPN6显著抑制前列腺癌PC3细胞的增殖，并降低PC3细胞的耐药性；进一步的研究结果表明PTPN6可通过抑制SP1，并抑制p38 MAPK通路抑制PC3细胞的增殖和耐药。结论:PTPN6能够抑制前列腺癌细胞PC3的增殖和耐药，提高其化疗敏感性，作用机制是通过调控SP1/p38 MAPK信号通路来实现的，这一结果能够为临床上前列腺癌的诊断和治疗提供分子基础。     

Increased IL-10/IL-17 ratio is aggravated along with the prognosis of patients with chronic lymphocytic leukemia

ObjectiveThis study is to investigate the association between the Treg/Th17 cells and prognosis of chronic lymphocytic leukemia (CLL).MethodsTotally 50 CLL patients and 20 Health controls were included in this study. Regulatory T (Treg) cells and the cell subset secreting IL-17 (Th17) in peripheral blood were detected with flow cytometry. Serum levels of IL-10 and IL-17 were determined with ELISA, and expression of Foxp3 and RORγt was assessed with quantitative real-time PCR.ResultsTreg and Th17 cell proportions in peripheral blood in the CLL patients were significantly higher than control. Serum levels of IL-10 and IL-17, and expression of Foxp3 and RORγt, were significantly increased in the CLL patients. Ratios of Treg/Th17 and IL-10/IL-17 were significantly elevated in the CLL patients. Compared with those before treatment, Treg/Th17 and IL-10/IL-17 ratios were declined in the CLL patients in remission. Compared with the non-remission group, Treg cells were significantly decreased, while Th17 cells were significantly increased, resulting in decreased Treg/Th17 ratio, in the remission group. Moreover, the serum IL-10 level was significantly decreased, while the serum IL-17 level was significantly increased, resulting in declined IL-10/IL-17 ratio, in the remission group. Correlation analysis showed that, Treg and Th17 cell counts were significantly associated with CD38 and ZAP-70 expression in the CLL patients. Moreover, the IL-10/IL-17 ratio was also significantly associated with CLL prognostic factors.ConclusionAltered Treg/Th17 and IL-10/IL-17 ratios in CLL would be aggravated along with the disease progression, which might be used as indicators for the disease prognosis.     

Infusions of Large Synthetic HDL Containing Trimeric apoA-I Stabilize Atherosclerotic Plaques in Hypercholesterolemic Rabbits

BackgroundAmong strategies to reduce the remaining risk of cardiovascular disease, interest has focused on using infusions of synthetic high-density lipoprotein (sHDL).MethodsNew Zealand rabbits underwent a perivascular injury at both carotids and were randomly allocated into 2 protocols: (1) a single-dose study, where rabbits were treated with a single infusion of sHDL containing a trimeric form of human apoA-I (TN-sHDL, 200 mg/kg) or with Placebo; (2) a multiple-dose study, where 4 groups of rabbits were treated 5 times with Placebo or TN-sHDL at different doses (8, 40, 100 mg/kg). Plaque changes were analysed in vivo by intravascular ultrasound. Blood was drawn from rabbits for biochemical analyses and cholesterol efflux capacity evaluation.ResultsIn both protocols, atheroma volume in the Placebo groups increased between the first and the second intravascular ultrasound evaluation. A stabilization or a slight regression was instead observed vs baseline in the TN-sHDL-treated groups (P < 0.005 vs Placebo after infusion). TN-sHDL treatment caused a sharp rise of plasma-free cholesterol levels and a significant increase of total cholesterol efflux capacity. Histologic analysis of carotid plaques showed a reduced macrophage accumulation in TN-sHDL-treated rabbits compared with Placebo (P < 0.05).ConclusionsOur results demonstrate that acute and subacute treatments with TN-sHDL are effective in stabilizing atherosclerotic plaques in a rabbit model. This effect appears to be related to a reduced intraplaque accumulation of inflammatory cells. Besides recent failures in proving its efficacy, sHDL treatment remains a fascinating therapeutic option for the reduction of cardiovascular risk.     

植入物乳房重建一步法和二步法临床对比研究

目的:探讨即刻乳房假体重建（一步法）和应用扩张器的假体重建（二步法）两种不同手术方式在术后并发症、美容效果和成本效益的差异。方法:回顾性分析我院乳腺外科2015年5月至2018年5月收治的285例乳腺癌植入物重建患者，依据手术方式不同分为一步法组（145例）和二步法组（140例），比较两组患者临床资料的差异。结果:一步法组术后出血发生率（6.8%）高于二步法组（1.4%），差异有统计学意义（P=0.021）。一步法组术后伤口皮瓣坏死率（6.2%）高于二步法组（1.4%），差异有统计学意义（P=0.036）。二步法组乳房满意度评分（81.5±7.1）分高于1步法组（78.6±6.2）分，差异有统计学意义（P=0.035）。二步法组住院总花费（80 334.8±6 149.8）元高于一步法组（60 966.5±5 544.9）元，差异有统计学意义（P=0.049）。二步法组住院天数（34.3±3.2）天多于一步法组（17.5±3.9）天，差异有统计学意义（P=0.014）。结论:在植入物乳房重建两种手术方式中，二步法相较于一步法，其并发症少，美容效果好，但在成本效益上并不优于一步法。     

盐生肉苁蓉栽培品中苯乙醇苷类的指纹图谱研究

  目的 为规范化种植盐生肉苁蓉药材的质量研究提供基础研究资料。 方法 选择 RP-HPLC 建立盐生肉苁蓉补肾助阳功能特征成分的指纹图谱，并进行栽培品与野生品、不同生长期、不同药用部位指纹图谱的比较研究，采用计算机辅助相似度评价软件分析了相似度。 结果 种植基地药材的指纹图谱具有较高的相似度，其化学组成相似，相对比例也基本稳定。不同生长期和不同部位药材的指纹图谱也具有较好的一致性，但特征峰的含量存在明显差异。 结论 利用 RP-HPLC 指纹图谱可以较为全面地反映盐生肉苁蓉补肾助阳功能整体特征成分的内在质量，方法重现性好。