Inhibition of autophagy enhances apoptosis induced by bortezomib in AML cells

Bortezomib is a novel proteasome inhibitor, which has been successfully used to treat mantle cell lymphoma and multiple myeloma. However, the direct effects of bortezomib on acute promyelocytic leukaemia (APL) have not been fully investigated. In the present study, the WST-8 assay, western blotting, flow cytometry, monodansylcadaverine staining and transmission electron microscopy were performed. It was demonstrated that bortezomib treatment induced a time- and dose-dependent decrease in the viability of NB4 cells. Bortezomib treatment induced cell apoptosis in NB4 cells, as assessed by Annexin V/propidium iodide analysis, and the detection of cleaved caspase-3, cleaved poly(ADP-ribose) polymerase, Bax and Bcl-2 expression. Furthermore, bortezomib treatment induced autophagy in NB4 cells, as indicated by autophagosome formation, p62 degradation, LC3-I to LC3-II conversion and formation of acidic autophagic vacuoles. Notably, autophagy induced by bortezomib was initiated prior to apoptosis. Inhibition of autophagy by knocking down Beclin-1 expression increased bortezomib-induced apoptosis in NB4 cells. Therefore, the present study revealed that the combination of bortezomib and autophagy inhibition may be a potential treatment strategy for APL.     

中医药治疗糖尿病周围神经病变的研究进展

糖尿病渐以年轻化的趋势呈现,糖尿病周围神经病变(DPN)是糖尿病最常见的慢性并发症之一,因其高致残率严重影响病患的生活品质。本文简单阐述糖尿病周围神经病变的病因,并就中医药的角度对该病的治疗概况进行综述,以期为临床诊治提供新见解和新研究策略。     

Mimengosides J and K: two new neuroprotective triterpenoids from the fruits of Buddleja lindleyana

Two new 11-methoxyl substituted triterpenoids, named as mimengosides J (1) and K (2), along with seven known compounds, were isolated from the fruits of Buddleja lindleyana. Their structures were elucidated on the basis of spectroscopic analysis. In addition, the new ones were evaluated for protective effects against damage of SH-SY5Y cells induced by 1-methyl-4-phenylpyridinium ion (MPP⁺) and the results indicated that those may be one of the candidate compositions of Buddleja lindleyana for the treatment of neurodegenerative disease.

     

百蕊草药材与标准汤剂量值传递规律研究及分析

目的 建立百蕊草Thesii Herba标准汤剂的UPLC特征图谱及其指标成分的含量测定方法;研究百蕊草药材与标准汤剂特征图谱的变化,并分析指标成分百蕊草素I在药材-标准汤剂的量值传递规律。方法 采用Waters Acquity UPLC BEH Shield RP18色谱柱（150 mm×2.1 mm,1.7μm）,流动相为乙腈-0.2%甲酸水溶液,梯度洗脱,体积流量0.4 mL/min,检测波长330、270 nm,柱温30℃,建立特征图谱与含量测定方法。以出膏率、含量及转移率、特征图谱共有峰传递数为主要评价指标,分析百蕊草标准汤剂的量值传递规律。结果 19批百蕊草药材、标准汤剂与各自的对照特征图谱相似度分别为0.986～1.000、0.989～1.000。百蕊草标准汤剂特征图谱标定6个共有峰,药材中的5个共有峰全部转移至标准汤剂并被指认,其中4个共有峰采用对照品比对确认,分别为5-O-阿魏酰奎宁酸（峰2）、4-O-阿魏酰奎宁酸（峰3）、百蕊草素I（峰5）、山柰酚-3-O-(2″-O-α-鼠李糖基-6″-O-丙二酰基)-β-葡萄糖苷（峰6）。19批标准汤剂的平均出膏率为27.45%...     

胃癌免疫细胞浸润相关预后基因的共表达网络分析鉴定

背景与目的：肿瘤免疫细胞浸润在胃癌（GC）的进展和预后中起到关键作用,然而,目前影响GC预后的免疫细胞浸润调控基因还不清楚。本研究联合共表达网络分析研究和反卷积分法鉴定了GC免疫相关预后基因。  方法：从TCGA数据库中下载GC的mRNA表达数据并使用CIBERSORT反卷积算法来确定每个样品中免疫细胞的比例,并构建共表达网络,结合Kaplan-Meier法确定免疫相关预后基因。 结果：在纳入分析的22种免疫细胞中,有11种免疫细胞在肿瘤组织中显著高于正常组织（均P<0.05）。对上述11种免疫细胞进行生存分析,发现静止记忆性CD4 T细胞和调节型T细胞的浸润情况与GC患者生存率呈明显相关（均P<0.05）。基于上结果论进行共表达网络分析,得绿松石模块中的基因与上述两种类型的细胞相关性最显著,并鉴定得到了3个与记忆性CD4 T细胞相关（CGB5、LINC00106、LINC00392）和1个与调节型T细胞相关（UPK1B）的预后基因（均P<0.05)。 结论：本研究鉴定的4个胃癌免疫细胞浸润相关预后基因可能在GC的进展和预后中起到重要作用,这些基因可能会通过影响肿瘤免疫过程而作为潜在的胃癌免疫治疗靶点。      

基于“性状-质量标志物-生物效应”的饮片质量整体识别研究思路

中药饮片作为中医临床用药的原料，其质量控制与中医药事业的健康发展息息相关。《中国药典》2020年版对中药饮片的质量标准进一步修订完善，但仍缺乏符合中药饮片整体性与专属性特点的质量评价方法和标准。基于上述问题，通过综述性状电子检测、色谱-质谱联用、多效应生物评价等技术在中药饮片质量识别方面的研究进展，探索中药饮片“性状-质量标志物-生物效应”的关联性，为构建符合中药饮片整体性及专属性的质量识别关键技术，实现中药饮片质量识别模式的现代化转变提供参考。     

基于胸部CT分析基线骨骼肌含量对ICU患者预后的影响

目的 探讨危重患者入ICU时基线骨骼肌含量与病情危重程度及预后的相关性。方法 纳入在ICU治疗时间≥48 h的危重患者79例,测量其入ICU时胸部CT第七胸椎（T7）水平横断面胸肌面积（PMA）,分析PMA与90 d病死率、90 d内生存率、28 d内非ICU生存日数、28 d内无机械通气生存日数、ICU病死率、院内病死率等指标的相关性。结果 在校正性别、危重症营养风险评分、 Charlson共病指数、血红蛋白等因素后,基线PMA较大患者90 d病死率更低,90 d内生存率更高,28 d内非ICU生存日数更多,院内病死率也更低,与基线PMA较小患者比较差异均具有统计学意义（P均< 0.05）。结论 危重患者入ICU时的基线骨骼肌含量可用于预测病情严重程度、需要体外生命支持和ICU治疗的时间和临床预后。     

针刺督脉组穴治疗血管性认知障碍临床观察

目的 观察针刺督脉组穴治疗血管性认知障碍（vascular cognitive impairment，VCI）的临床疗效。方法 将51例VCI患者随机分为针刺组（25例）和药物组（26）例，针刺组采用针刺督脉穴位神庭、百会、风府、大椎进行治疗，药物组采用口服多奈哌齐进行治疗。观察并比较治疗前后患者血清血红蛋白（hemoglobin, Hgb）水平及中医证候量表、MMSE量表、Hachinski量表、额叶功能评定量表（frontal assessment battery, FAB）评分。结果 两组治疗前Hgb水平比较，差异无统计学意义(P＞0.05）。两组治疗后Hgb水平均较治疗前显著升高（P＜0.05），且针刺组升高值显著大于药物组（P＜0.05）。两组治疗前中医证候评分比较，差异无统计学意义（P＞0.05）。两组治疗后中医证候评分均较治疗前显著降低（P＜0.05），且针刺组降低值显著大于药物组（P＜0.05）。两组治疗前MMSE、Hachinski、FAB评分比较，差异均无统计学意义（P＞0.05）。与治疗前比较，两组治疗后MMSE、FAB评分均显著增加(P＜0.05)，且针刺组增加值显著大于药物组（P＜0.05）。与治疗前比较，两组治疗后Hachinski评分显著降低（P＜0.05），且针刺组降低值显著大于药物组（P＜0.05）。两组疗效分布比较，差异具有统计学意义（P＜0.05），针刺组疗效优于药物组。结论 针刺督脉组穴可改善VCI患者认知能力，且疗效优于多奈哌齐。     

Comparative examination of adsorption of serum proteins on HSA- and PLGA-based nanoparticles using SDS–PAGE and LC–MS

The behavior of nanosized drug carrier systems under cell culture conditions and therefore also the destiny in the body are highly influenced by the protein corona, which is formed upon entering a biological environment. Some of the adsorbed proteins, named opsonins, lead to a shortened plasma circulation half-life of the nanoparticles. Others are attributed to promote the transport of nanoparticles into other compartments of the body, just to mention two examples. Hence, detailed knowledge concerning the composition of the protein corona is of great importance. The aim of this work was to investigate the influence of the nanoparticle starting material and the surface modification on the composition of the adsorbed serum proteins in a cell culture environment. Therefore, positively charged nanoparticles based on the biodegradable polymer poly(dl-lactide-co-glycolide) (PLGA) stabilized with didodecyldimethylammonium bromide (DMAB) and negatively charged nanoparticles based on human serum albumin (HSA) were prepared and modified with hydrophilic polymers. By incubating the nanoparticles with fetal bovine serum (FBS) the adsorption of serum proteins on the colloidal system was investigated. Using sodium dodecyl sulfate polyacrylamide gel electrophoresis (SDS–PAGE) a semi-quantitative analysis of the protein corona was performed and after enzymatic in-solution-digestion the adsorbed proteins were identified using high resolution LC–MS. Our study accentuates the influence of the core material, surface charge, and surface modification on the amount and nature of the adsorbed proteins. The combination of SDS–PAGE and LC–MS turns out to be a simple and reliable method to investigate the protein corona of nanoparticles.     

某省主要城市医疗机构药品使用缺陷分析

目的探索提高医疗机构药品使用质量的办法。方法采取回顾性分析方法,通过对2016年9月~2017年9月某省食品药品监督管理局药化流通监管处每月公示药品流通监督检查信息中医疗机构检查信息的汇总,找出医疗机构药品使用中的高频次缺陷项目,归类分析并提出解决对策。结果缺陷主要集中在养护与维护,收货验收,贮存,调剂,采购5个方面,占总缺陷项目的 91.5%。结论应采取措施加大对医疗机构药品使用质量的监管力度和省内不发达地区药品安全教育,提高其药事管理水平,保障最广大人民群众的用药安全。