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.     

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.     

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。     

乌鲁木齐市家蝇抗药性现状及发展趋势分析

目的 分析乌鲁木齐市家蝇对化学杀虫剂的抗药性现状及发展趋势，探讨防制对策。方法 常规微量点滴法。结果 对溴氰菊酯的抗性系数在24．00-253．67；对敌敌畏的抗性系数在11.44-53.24;对二氯苯醚菊酯抗性系数在9.29-36.10，对氯氰菊酯的抗性系数在2.32-9.62。结论：8年来家蝇对4种杀虫剂的抗药性在不断上升，仍保持较高水平，但迅速上升的趋势开始减缓。     

移植肾组织TGF-β1和MMP-2表达及IV型胶原沉积与慢性移植肾肾病的关系

目的 探讨移植肾组织中转化生长因子β1(TGF-β1)和基质金属蛋白酶2(MMP-2)的表达及IV型胶原沉积与慢性移植肾肾病(CAN)的关系.方法 对18例CAN患者进行了移植肾切除术.光镜下观察切除的肾组织标本并根据其纤维化的程度进行分期,用免疫组织化学技术和图像分析法检测移植肾组织中TGF-β1和MMP-2表达量及IV型胶原沉积情况,并分析患者血肌酐(Cr)和尿素氮(BUN)的水平与移植肾纤维化程度的关系.结果 随着患者移植肾纤维化程度的加重,血清肌酐、尿素氮及肾组织中TGF-β1、IV型胶原基因表达量均增加,MMP-2表达量于移植肾纤维化早期明显升高,并随移植肾纤维化程度加重而逐渐降低.结论 移植肾组织中TGF-β1表达量增高及IV型胶原沉积可以促进CAN的进程,而MMP-2则可抑制其进展.     

添喂纯植物提取物"益绿素"添加剂对奶牛生产性能的影响

选择体重、年龄、胎次、产乳量基本一致的荷斯坦泌乳奶牛10头,随机分为两组,分别为对照组(空白)和试验组;试验组每头奶牛每天一次补充10g添加剂。结果显示,添喂益绿素添加剂的试验组与对照组相比日产标准乳提高7.16%(P<0.01),奶料比提高7.31%(P<0.01),经济效益提高17.0%。表明添喂益绿素添加剂能有效提高奶牛产奶量,经济效益明显。     

胃前壁癌肿在双对比造影中的影像特征(附35例分析)

目的：通过分析胃前壁癌肿在双对比造影（DC）中的X线征象，提高对其影像特征的认识。方法：复查分析经术前、手术和病理证实，均做了DC的胃前壁癌肿35例。结果：悬滴、白雾状影、重叠白线及线征4个征象的出现率分别达78％、94％、66％、88％。当癌肿累及大小弯侧时，还可出现腔壁多边征。如能确定上述征象中的1、2个对诊断有重要意义。结论：胃前壁癌肿在DC中有其特征性的影像表现，注意观察并充分认识上述征象及其周围组织结构的变化，并紧密结合临床综合分析，有助于提高术前诊断的准确性。     

异位错构瘤性胸腺瘤1例及文献复习

目的探讨异位错构瘤性胸腺瘤(EHT)的临床及病理特征。方法复习1例EHT患者的临床病史、肿瘤组织的病理形态和免疫表型及相关文献。结果患者男性,56岁,以左胸锁关节下方皮下肿块为主要表现。肿瘤包膜完整,切面以灰白色实性为主。镜下表现复杂,以束状及平行排列的梭形细胞为主,混合有上皮成分及成熟的脂肪细胞等。瘤细胞均不具异型性,也缺乏坏死。免疫组化显示梭形细胞CK阳性,灶状细胞MSA阳性,S-100蛋白、desm in、vim entin和CD34均呈阴性。结论EHT有独特的发病部位和形态学表现,对梭形细胞上皮本质的认识是正确诊断的关键。     

新疆地区维吾尔族乳腺癌BRCA1基因突变分析

目的研究新疆地区维吾尔族乳腺癌患者BRCA1基因突变情况及突变位置。方法选取70例维吾尔族乳腺癌根治标本,对照组为32例维汉族乳腺良性病变（纤维腺病及纤维腺瘤）及乳腺癌旁非癌组织;应用PCR-单链构象多态性和DNA序列测定的方法检测BRCA1基因突变。结果（1）70例维吾尔族乳腺癌中发现9例BRCA1突变的12个新位点。（2）70例维吾尔族乳腺癌BRCA1的突变率为12.86%（9/70）,22例维吾尔族早发性乳腺癌（≤35岁）BRCA1突变率为31.82%（7/22）。维吾尔族早发性乳腺癌BRCA1突变率（7/22）高于维吾尔族晚发性乳腺癌（2/48）,差异有统计学意义（χ^2=10.295,P〈0.01）。（3）70例维吾尔族乳腺癌中发现9例BRCA1基因核苷酸多态性位点,其中8例多态性位点均为3232A〉G。（4）2例双侧乳腺癌中均检测出BRCA1基因的突变。结论BRCA1突变可能与新疆维吾尔族乳腺癌尤其是维吾尔族早发性乳腺癌及双侧乳腺癌的发生密切相关。