基于网络药理学和分子对接技术研究黄芪-赤芍治疗COPD的作用机制＊

目的 基于网络药理学和分子对接技术探究黄芪-赤芍配伍对治疗慢性阻塞性肺疾病（chronic obstructive pulmonary disease，COPD）的作用机制。方法 利用TCMSP，Pharmmaper数据库，筛选黄芪-赤芍治疗COPD的活性成分和潜在靶点；结合Genecards数据库挖掘的COPD相关靶点，对黄芪-赤芍药对与COPD靶点进行PPI网络构建，交互处理得到黄芪-赤芍药对治疗COPD的关键靶点，并进行GO分析和KEGG通路富集分析；并采用分子对接技术将主要活性成分与TNF-α（肿瘤坏死因子），IL-6（白细胞介素6）等进行分子对接；最后利用A549炎症细胞与人脐静脉内皮细胞缺氧损伤模型进行体外细胞实验对结果加以验证。结果 黄芪-赤芍药对中44个有效成分作用于COPD，核心成分为：槲皮素、山奈酚、丁子香萜、芍药苷、（2R，3R）-4-methoxyl-distylin、二氢异黄酮；黄芪-赤芍药对通过IL6、PTGS2、TNF等113个靶蛋白，调控Ras、PI3KAkt、IL-17等多条信号通路治疗COPD，且分子对接结果显示槲皮素、山奈酚、丁子香萜、芍药苷与IL-6、PTGS2、TNF大分子蛋白有良好的结合性，体外细胞试验证实，槲皮素与山奈酚均能减少IL-8，MMP-9炎症因子的分泌，具有不同程度的抗炎效果；芍药苷有明显的扩血管、抗血栓之效。结论 黄芪-赤芍药对治疗COPD具有多成分、多靶点、多通路、整体调节的作用特点。初步揭示了黄芪-赤芍药对通过抑制炎症反应、调节上皮细胞生长增强保护屏障等预测出黄芪-赤芍药对治疗COPD的潜在作用机制，以期为其活性成分的药效物质基础提供理论研究和思路。     

健脾益肾方对非小细胞肺癌细胞体外增殖凋亡作用的实验研究

目的:探讨健脾益肾方对非小细胞肺癌(NSCLC)细胞体外增殖凋亡的作用。方法:人NSCLC细胞系A549分为四组:空白对照组(仅加入细胞培养液)、阴性对照组(加入细胞,不进行中药处理)、实验组(加细胞加中药处理)。荧光定量PCR和Western blot分别检测Survivin、Bcl-2和Caspase-3的mRNA和蛋白表达。MTT检测细胞增殖;流式细胞术检测细胞凋亡。结果:与空白对照组相比,阴性对照组细胞在24、48、72 h的吸光度值明显升高,细胞凋亡率下降,Survivin和Bcl-2 mRNA和蛋白相对表达量上调,Caspase-3 mRNA和蛋白相对表达量下调,组间比较差异有统计学意义(P<0.05);而健脾益肾方处理的实验组24、48、72 h的吸光度值均显著降低,细胞凋亡率显著上升,Survivin和Bcl-2 mRNA和蛋白相对表达量下调,Caspase-3 mRNA和蛋白相对表达量上调,与空白对照组相比差异有统计学意义(P<0.05)。结论:健脾益肾方可通过下调Survivin和Bcl-2、上调Caspase-3表达诱导NSCLC细胞凋亡,并抑制肿瘤细胞的增殖,进而抑制NSCLC的发展。     

Outcomes after neoadjuvant or adjuvant chemotherapy for cT2-4N0-1 non–small cell lung cancer: A propensity-matched analysis

Objective

Comparative survival between neoadjuvant chemotherapy and adjuvant chemotherapy for patients with cT2-4N0-1M0 non–small cell lung cancer has not been extensively studied.

养精种玉汤辅助体外受精-胚胎移植对排卵障碍性不孕患者的影响

目的：探究养精种玉汤辅助体外受精-胚胎移植（IVF-ET）对排卵障碍性不孕患者的影响。方法：选取2016年12月至2017年3月邯郸市中心医院收治的排卵障碍性不孕患者82例作为研究对象，按照随机数字表法随机分为对照组与观察组，每组41例。对照组给予促性腺激素释放激素激动剂（Gn）+控制性促排卵+IVF-ET治疗，观察组在此基础上联合养精种玉汤治疗，至HCG日停止服用。治疗后统计2组Gn使用情况、取卵数及妊娠率；检测并比较HCG日2组子宫内膜容受性指标；比较2组妊娠结局及治疗期间相关不良反应发生情况。结果：观察组Gn使用天数及使用剂量均低于对照组，而妊娠率高于对照组（P<0.05或P<0.01）；观察组子宫内膜类型为A型患者比例高于对照组，而子宫内膜类型为C型患者比例低于对照组（P<0.05或P<0.01）；观察组子宫内膜厚度大于对照组，而子宫内膜动脉血流参数PI及RI均低于对照组（P<0.01）；2组不良反应发生率差异无统计学意义（P>0.05），且治疗期间2组血清肝功能指标及血尿常规检测均未发现异常。结论：养精种玉汤辅助IVF-ET可有效增强排卵障碍性不孕患者子宫内膜容受性，提高患者妊娠率并改善其妊娠结局，具有良好的安全性。     

Recent advances in preclinical in vitro approaches towards quantitative prediction of hepatic clearance and drug-drug interactions involving organic anion transporting polypeptide (OATP) 1B transporters

Hepatic uptake mediated by organic anion transporting polypeptide (OATP) 1B1 and 1B3 can serve as a major elimination pathway for various anionic drugs and as a site of drug-drug interactions (DDIs). This article provides an overview of the in vitro approaches used to predict human hepatic clearance (CL_h) and the risk of DDIs involving OATP1Bs. On the basis of the so-called extended clearance concept, in vitro–in vivo extrapolation methods using human hepatocytes as in vitro systems have been used to predict the CL_h involving OATP1B-mediated hepatic uptake. CL_h can be quantitatively predicted using human donor lots possessing adequate OATP1B activities. The contribution of OATP1Bs to hepatic uptake can be estimated by the relative activity factor, the relative expression factor, or selective inhibitor approaches, which offer generally consistent outcomes. In OATP1B1 inhibition assays, substantial substrate dependency was observed. The time-dependent inhibition of OATP1B1 was also noted and may be a mechanism underlying the in vitro–in vivo differences in the inhibition constant of cyclosporine A. Although it is still challenging to quantitatively predict CL_h and DDIs involving OATP1Bs from only preclinical data, understanding the utility and limitation of the current in vitro methods will pave the way for better prediction.     

Same-Day Yttrium-90 Radioembolization: Feasibility with Resin Microspheres

Purpose

To evaluate the feasibility of a same-day yttrium-90 (⁹⁰Y) radioembolization protocol with resin microspheres (including pretreatment angiography, lung shunt fraction [LSF] determination, and radioembolization) for the treatment of hepatocellular carcinoma (HCC) and liver metastases.

用组织芯片技术检测Sema4C基因在小鼠不同组织的表达水平

目的：观察在小鼠不同组织中的表达水平。方法：用地高辛进行标记并制备Sema4C特异性RNA探针对小鼠组织芯片进行原位杂交。结果：Sema4C在成年小鼠的大脑皮层,小脑蒲肯野纤维层,视网膜视神经节细胞层和肾小管上皮细胞层中均有较高表达．而在肌肉,心脏．肺,脾脏．肝脏等组织中表达量比较低或未检测到表达。结论：Sema4C基因主要表达在神经系统和肾脏,这将有助于进一步认识Sema4C功能。     

心理干预对行体外受精病人的影响

体外受精(IVF)治疗对不育夫妇既是一种生理负担又是一种心理负担,在IVF各个时期均表现出心理应激,其中胚胎移植后至妊娠试验前和IVF失败后应激最强,出现负性心理反应,以焦虑、抑郁多见。研究表明,通过心理干预能有效缓解患者的负性心理,并可能提高妊娠率和降低治疗中断率。     

间期细胞原位PCR检测B细胞系恶性淋巴瘤

目的：应用原位PCR技术检测B细胞系恶性淋巴瘤。方法：采用免疫球蛋白重链（IgH)基因第三互补决定区（CDR－Ⅲ）的引物，dig-11-dUTP标记物，应用直接原位PCR技术检测Ⅲ-Ⅳ级恶性淋巴瘤的间期淋巴细胞，结果：在初诊的15例恶性淋巴瘤患中，12例检测到IgH基因重排；4例临床表现呈现淋巴瘤性白血病患，治疗后骨髓完全缓解，2例间期细胞原位PCR仍显示有IgH基因重排，6个月复发，结论：间期细胞原位PCR技术能敏感、准确地检测Ⅲ级以上的恶性淋巴瘤，并帮助预测复发，为一有效的基因诊断方法。     

Detailed mapping of CGRP mRNA expression in the rat central nervous system: Comparison with previous immunocytochemical findings

The localization of CGRP mRNA in neurons of the rat brain and spinal cord was assessed by in situ hybridization histochemistry (ISH) using a radiolabeled synthetic 57-mer oiigodeoxynucleotide probe complementary to the rat prepro CGRP mRNA. Results were compared with previously published findings of CGRP-immunoreactive (CGRP-IR) cell bodies revealed by an indirect immunofluorescence technique. The highest numbers of CGRP mRNA expressing neurons as well as the greatest intensity of staining were found in the lateral hypothalamic area, the parabrachial nuclei, and among the cranial motor nuclei, especially in the nuclei of the 7th and 12th nerve and the ambiguus nucleus, which is generally in good agreement with findings assessed by immunocytochemistry (ICH). However, some mismatches between the localizaton of the peptide by ICH and the localization of the CGRP mRNA were also observed. Thus, ISH was not able to confirm CGRP-IR in cells of the amygdaloid complex and parts of the medial hypothalamus, the central gray, and the inferior colliculus, but ISH revealed considerably more CGRP mRNA expressing cells in the lateral hypothalamic area, arcuate nucleus, posterior and peripeduncular thalamic nuclei, and all cranial motor nuclei than CGRP-IR containing cells found by ICH. Moreover, ISH also revealed CGRP mRNA synthesis in the nucleus of the lateral olfactory tract and in the perihypoglossal nuclei that were devoid of CGRP-IR. The reasons for the observed mismatches still remain to be elucidated; however, intracerebroventricular colchicine pretreatment used to increase immunocytochemical signals also might have induced or suppressed gene expression in certain brain regions in an unpredictable matter. On the other hand, detection of only the mRNA in a certain region does not necessarily mean that also the active peptide is synthesized there.