The Prognostic Role of Peritumoral Edema in Patients with Newly Diagnosed Glioblastoma: A Retrospective Analysis

ObjectivePrevious studies on glioblastomas (GBMs) have not reached a consensus on peritumoral edema (PTE)’s influence on survival. This study evaluated the PTE index’s prognostic role in newly diagnosed GBMs using a well-designed method.MethodsSelected patients were reviewed after a rigorous screening process. Their general information was obtained from electronic medical records. The imaging metrics (MTD, TTM, TTE) representing tumor diameter, laterality, and PTE extent were obtained by manual measurement in Syngo FastView software. The PTE index was a ratio of TTE to MTD. Multiple variables were evaluated using analysis of variance and Cox regression model.ResultsOf 143 patients, 62 were included in this study. MGMT promoter methylation and tumor laterality were both independent prognostic factors (p = 0.020, 0.042; HR = 0.272, 2.630). The lateral tumors’ index was higher than that of the medial tumors (57.7% vs. 42.6%, p = 0.027). Low-index tumors were located in relatively medial positions compared with high-index tumors (TTM, 4.9 vs. 12.8, p = 0.032). This finding indicated that the PTE index tended to increase with tumor laterality. Moreover, the patients with low-index tumors had a significant survival disadvantage in the univariate analysis but not in the multivariate analysis (p = 0.023, 0.220). However, further analysis found that the combination of tumor laterality and PTE statistically stratified the survival outcome. The patients with lateral high-index tumors survived significantly longer (p = 0.022, HR = 1.927).ConclusionsIn contrast with the previous studies, this study recommends combining PTE and tumor laterality for survival stratification in newly diagnosed GBMs.     

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.     

抑郁症大鼠模型海马区及前额叶组织BDNF因子、Trkb蛋白表达的实验研究

目的:观察抑郁症大鼠模型脑组织不同部位神经营养因子水平的变化及抗抑郁药物使用后改变。方法:将成年SD大鼠30只分为正常对照组、模型对照组、药物干预组,每组10只,雌雄对半;正常组正常养殖,模型组采用慢性不可预知应激结合孤养方式制备抑郁模型大鼠4周。药物干预组采用模型组造模过程4周后给予药物(氟西汀)给入,自实验开始之后每周观察大鼠体重、糖水消耗、旷场实验指标的变化,最后采用荧光定量PCR法观察大鼠脑部BDNF因子及Trkb的表达。结果:与正常对照组大鼠相比,模型组大鼠体重增加缓慢、糖水消耗减少、旷场试验各项指标较正常组间差异具有统计学意义;荧光定量PCR结果显示:模型组较对照组各脑区BDNF及Trkb受体表达减少,药物干预组脑区BDNF及Trkb受体表达显著高于模型对照组。结论:脑部BDNF因子及Trkb的表达在抑郁症发生与治疗中有所改变。     

高压氧治疗对局灶性脑梗死大鼠的神经保护作用

目的 观察单次9 h高压氧（hyp erbaric oxygen，HBO）治疗对局灶性脑梗死大鼠凋亡诱导因子 （apoptosis-inducing factor，AIF）、线粒体膜电位（mitochondrial membrane potential，MMPo）的影响，探讨 HBO治疗的神经保护作用。 方法 108只SD大鼠制作永久性大脑中动脉闭塞模型，随机分为对照组和HBO组，每组各54只。造 模成功3 h后，HBO组实行HBO干预，压力0.2 MPa持续9 h，对照组呼吸常压空气。采用Garcia评分评估 大鼠神经功能，比较两组造模后13 h、24 h和72 h神经功能改善情况，并在各时间点检测大鼠缺血半 暗带脑组织凋亡细胞数、线粒体和细胞核AIF表达及MMPo水平。 结果 ①神经功能评分：HBO组13 h（P <0.001）、24 h（P =0.04）神经功能评分改善比对照组更明显。 ②凋亡细胞数：HBO组13 h、24 h凋亡细胞数较对照组更少（均P <0.001）。③AIF在线粒体和细胞核的 表达：13 h、24 h、72 h各时间点HBO组AI F在线粒体的表达均较对照组多（均P <0.001）；各时间点HBO 组AIF在细胞核的表达均较对照组少（均P <0.001）。④MMPo：各时间点HBO组MMPo均高于对照组（均 P <0.001）。 结论 HBO治疗可改善大鼠神经功能，稳定MMPo，抑制AIF由线粒体向细胞核转移可能是其神经保 护作用的机制之一。     

缺血性脑血管病患者脑微出血相关因素及其对抗血小板单药治疗的影响分析

目的 研究缺血性脑血管病患者脑微出血（CMB）危险因素及其对抗血小板单药治疗的影响。方法 选取2018年1月至2018年6月该院神经内科接受抗血小板单药治疗的急性缺血性脑血管病患者300例为样本，入院后采集基本资料并完善相关检查，根据梯度回波T2^*加权成像（GRE-T2^*WI）检查结果将患者分为CMB组（176例）和非CMB组（124例），均给予抗血小板聚集治疗，比较两组临床资料及治疗1年内再发梗死、脑出血和病死率，分析影响CMB发病的危险因素以及CMB对抗血小板单药治疗的影响。结果 高龄、高血压、肥胖、脑卒中病史、ACI和脑白质疏松为CMB发生的危险因素（P<0.05）。CMB组和非CMB组抗血小板单药治疗期间脑出血率分别为14.20%和6.45%，差异有统计学意义（P<0.05）。轻度组、中度组和重度组脑出血率分别为9.18%、10.64%和35.48%，差异有统计学意义（P<0.05）。不同部位CMB患者抗血小板单药治疗期间再发脑梗死、脑出血及病死率比较，差异无统计学意义（P>0.05）。结论 高龄、高血压、肥胖、脑卒中病史、ACI及脑白质疏松为缺血性脑血管疾病合并CMB的危险因素。CMB可导致抗血小板单药治疗期间脑出血风险增加，重度CMB者更甚。     

基于网络药理学方法探究补肾活血汤治疗激素性股骨头坏死的作用机制

目的:探讨补肾活血汤治疗激素性股骨头坏死(steroid-induced osteonecrosis of the femoral head,SONFH)的作用机制。方法:通过中医药整合药理学网络计算研究平台(integrative pharmacology-based network computational research platform of Traditional Chinese Medicine,TCMIP)v2.0预测、筛选补肾活血汤组方中14味中药的作用靶标,通过GeneCards、CTD和OMIM数据库查询SONFH的疾病靶点。根据获取的药物靶标和疾病靶点,进一步利用TCMIP v2.0中医药关联网络分析模块构建"药物靶标-疾病靶点"相互作用网络,根据网络拓扑特征值筛选补肾活血汤治疗SONFH的核心作用靶点。利用GO和KEGG数据库,采用富集算法挖掘上述方剂核心作用靶点的生物学功能和通路信息。结果:共获得891个补肾活血汤药物靶标和365个SONFH疾病靶点。经"药物靶标-疾病靶点"相互作用网络分析,最终筛选出31个补肾活血汤治疗SONFH核心靶点,GO功能分析富集出生物过程532条、分子功能29条,KEGG信号通路富集分析出相关通路共12条,主要涉及炎症免疫调节(chemokine signaling pathway,Toll-like receptor signaling pathway,NOD-like receptor signaling pathway,leukocyte transendothelial migration,Complement and coagulation cascades,cytokine-cytokine receptor interaction)、血管新生及血液循环调节(VEGF signaling pathway)、神经系统调节(neuroactive ligand-receptor interaction)和细胞功能调节(apoptosis,regulation of actin cytoskeleton)等方面。结论:结合SONFH的病理机制,排除缺乏特异性的信号通路,我们推测补肾活血汤可能通过调节TLR4/NF-κB和VEGF信号通路发挥补肾壮骨、活血化瘀的功效,这可能是其治疗SONFH的作用机制之一。     

针刺干预对肌萎缩侧索硬化症模型小鼠脑及脊髓中IBA-1和TNF-α表达的影响

目的:探讨电针治疗肌萎缩侧索硬化症(ALS)的机制。方法:将SOD1^G93A转基因小鼠随机分为正常组、模型组、针刺组及利鲁唑治疗组,每组各8-10只。小鼠日龄30 d后,针刺组选取双侧天枢穴(ST25)及足三里穴(ST36)予以电针治疗。利鲁唑治疗组按照30 mg/(kg·d)的剂量予以90 d日龄小鼠灌胃治疗,1次/d。模型组及对照组常规饲养,不予干预。于小鼠电针治疗前及治疗后分别对4组进行体质量记录及行为学观察。采用免疫组化法检测各组小鼠脑干及脊髓中IBA-1和TNF-α表达变化。结果:正常组小鼠精神状态及运动功能良好,针刺组及利鲁唑组小鼠较模型组精神状态及运动功能明显改善; 转棒实验结果显示针刺组及利鲁唑组小鼠潜伏期较模型组延长; 免疫组化检测结果表明在模型组脑干IBA-1阳性细胞表达高于正常组(P<0.05); 而利鲁唑组IBA-1阳性细胞表达虽有降低,但组间无统计学差异(P>0.05)。该结果与IBA-1阳性细胞在脊髓L_4-5节段表达趋于一致(P<0.05)。针刺治疗后脊髓中促炎因子TNF-α表达明显减少(P<0.05),但利鲁唑组较模型组无统计学差异(P>0.05)。结论:电针治疗及利鲁唑灌胃治疗均可以改善小鼠运动功能及生存质量,但早期针刺干预明显减少脑干及脊髓中小胶质细胞的活化,抑制促炎因子TNF-α释放,表明电针治疗ALS有效,其机制可能与针刺抑制神经炎症产生有关。     

黄连解毒汤对重度颅脑损伤合并肺部感染患者血气指标和炎症因子影响分析

目的:观察黄连解毒汤对重度颅脑损伤合并肺部感染患者血气指标和炎症因子的影响,探讨其治疗效果。方法:随机抽签方式将77例重度颅脑损伤合并肺部感染患者分为两组。对照组35例接受常规治疗,研究组42例在常规治疗基础上,联合黄连解毒汤直肠灌注及全身擦浴治疗。评估两组临床效果,记录两组呼吸机使用时间、ICU入住时间及治疗费用,测定两组治疗前后血气指标和炎症因子。结果:两组临床治疗效果间差异无统计学意义(P>0.05)。与对照组比,研究组呼吸机使用时间和ICU入住时间明显缩短,ICU治疗费用显著减少(P<0.01)。治疗后两组SaO、PaO₂水平明显上升,PaCO₂及血清PCT、IL-1β、HMGB-1、CRP水平明显下降(P<0.05)。组间比较,研究组SaO、PaO₂水平高于对照组,PaCO₂及血清PCT、IL-1β、HMGB-1、CRP水平低于对照组(P<0.05)。结论:黄连解毒汤直肠灌注联合全身擦浴可明显控制重度颅脑损伤合并肺部感染患者感染病症,改善血气指标,调节炎症反应,缩短呼吸机使用时间和ICU入住时间,减少患者的治疗费用。