Brain impedance variation of directional leads implanted in subthalamic nuclei of Parkinsonian patients

ObjectiveConventional deep brain stimulation (DBS) systems with ring-shaped leads generate spherical electrical fields. In contrast, novel directional leads use segmented electrodes. Aim of this study was to quantify the impedance variations over time in subjects with the directional Cartesia-Boston® system.MethodsImpedance records, programming settings, and clinical data of 11 consecutive Parkinsonian patients implanted with DBS directional leads in two Italian centers (Udine and Vicenza) were retrospectively evaluated. Data were collected before starting stimulation (in the operating room and at days 5 and 40) and after switching stimulation on at the successive follow-up visits (1, 6 and 12 months).ResultsDirectional leads have significantly higher impedance than ring leads. Stimulated contacts had always lower impedance compared to non-stimulated contacts. Before DBS-on, all contacts had higher impedance in the operating room, with an initial decrease five days post-surgery and a subsequent increase at day 40, more evident for directional contacts. The impedance of directional leads increased post-implantation at 1 and 6 months with a plateau at 12 months.ConclusionsThere was a significant difference between the directional and ring leads at baseline (before activation of DBS) and during follow-up (chronic DBS).SignificanceOur study reveals new information about the impedance of segmented electrodes that is useful for patient management during the initial test period, as well as during long-term DBS follow-up.     

结肠癌T-cadherin表达水平分析与5-Aza-CdR对其表达和结肠癌细胞增殖、侵袭及凋亡的影响

背景与目的：结肠癌是临床常见恶性肿瘤，探讨抑癌蛋白T-cadherin在结肠癌中的表达情况及其与患者临床病理学特征的关系，并分析5-Aza-CdR对T-cadherin表达和结肠癌细胞增殖、侵袭及凋亡的影响。方法：收集福建医科大学附属第二医院2015—2016年40例手术切除的结肠癌组织及癌旁组织新鲜样本，并经过病理学检查验证，分别提取总RNA和总蛋白质。采用实时荧光定量聚合酶链反应（real-time fluorescence quantitative polymerase chain reaction，RTFQ-PCR）分析T-cadherin mRNA的表达，采用蛋白质印迹法（Western blot）分析T-cadherin蛋白水平，并分析T-cadherin的mRNA表达变化与患者临床病理学特征的关系。进一步以人结肠癌细胞系HT-29为研究对象，采用甲基化抑制剂5-Aza-CdR处理HT-29细胞，分别采用RTFQ-PCR和Western blot分析T-cadherin表达变化，采用细胞计数试剂盒（cell counting kit-8，CCK-8）分析细胞增殖，采用Transwell实验验证细胞侵袭能力，采用流式细胞术分析细胞凋亡。结果：T-cadherin在结肠癌组织的蛋白水平和mRNA表达均明显低于癌旁组织，其mRNA表达与淋巴结转移（F=5.316，P=0.009 3）和分化程度（F=5.807，P=0.006 4）明显相关，而与其他病理变量（包括性别、年龄、肿瘤大小和肿瘤浸润深度）无明显相关。药物5-Aza-CdR可以显著上调HT-29细胞中T-cadherin的表达水平，抑制HT-29细胞增殖、侵袭并促进细胞凋亡。结论：T-cadherin表达可能与结肠癌恶性程度密切相关，药物5-Aza-CdR处理可上调结肠癌细胞T-cadherin的表达，并抑制结肠癌细胞的增殖、迁移，促进结肠癌细胞凋亡，提示T-cadherin可能是结肠癌患者使用甲基化抑制剂5-Aza-CdR治疗的靶点。     

Gd-EOB-DTPA增强MRI评估功能性肝体积与肝功能Child-Pugh分级的相关性

目的：对比解剖性肝脏体积（ALV）和功能性肝脏体积（FLV）与肝功能Child-Pugh分级的相关性。方法：选择温州医科大学附属第二医院育英儿童医院2014年1月至2019年4月同时行增强CT和Gd-EOB-DTPA增强MRI扫描的肝硬化患者25例。对所有患者进行肝功能Child-Pugh评分，检测所有入组患者每个肝段的Gd-EOB-DTPA增强MRI平扫期和肝胆特异期的信号对比增强率（CER），以CT扫描的数据为基础利用MI-3DVS计算每个肝段的ALV和全肝的FLV。分析ALV和FLV与肝功能Child-Pugh分级的相关性。结果：肝功能Child-Pugh分级与ALV呈负相关（r=-0.792，P＜0.001），曲线拟合的决定系数（R2）=0.63；肝功能Child-Pugh分级与FLV亦呈负相关（r=-0.911，P＜0.001），曲线拟合的R2=0.80。FLV与肝功能Child-Pugh分级有更显著的负相关性。结论：结合Gd-EOB-DTPA增强MRI平扫期和肝胆特异期的信号CER和ALV计算所得的FLV较ALV能更好地反映肝脏的功能状态。     

华细辛和北细辛HPLC特征图谱识别与抗炎靶点及抗炎成分分析

建立华细辛和北细辛HPLC特征图谱并结合聚类分析研究2种来源细辛的识别方法;应用网络药理学方法预测细辛潜在抗炎靶点并寻找潜在抗炎成分。对89批细辛药材(12批华细辛和77批北细辛)的数据进行分析确定了11个特征峰,用对照品、紫外光谱和LC-MS指认了11个特征成分。特征峰面积聚类分析显示华细辛和北细辛被分为2类,且利用特征峰面积比值可实现两者区分,当特征峰9(细辛素)/参照峰S(卡枯醇)峰面积比值大于5时为华细辛,小于2时为北细辛。对119种细辛成分进行网络药理学分析的结果表明细辛抗炎作用可能与COX-2,COX-1,iNOS,MAPK14,LAT4H,NR3C1,PPARG和TNF等8个靶点相关,其中COX-2最为关键,与5种特征成分细辛脂素、芝麻脂素、细辛素、甲基丁香酚和黄樟醚均存在相互作用。此外,细辛脂素、芝麻脂素与iNOS,MAPK14也存在相互作用关系,黄樟醚和细辛素可作用于iNOS,COX-1,LAT4H,甲基丁香酚可作用于COX-1,LAT4H。细辛脂素与芝麻脂素均可作用在COX-2,iNOS和MAPK143个靶点上,提示它们是细辛发挥抗炎作用的活性成分;COX-2分子对接结果和COX-2活性实验结果验证了细辛脂素、芝麻脂素可抑制COX-2活性,为细辛抗炎作用活性成分。基于HPLC特征图谱的华细辛和北细辛识别方法简便易行;预测到的细辛抗炎靶点和抗炎成分为完善细辛质量评价体系奠定了基础。     

我院药物代谢酶和药物作用靶点基因检测与精准药学服务实践与总结

目的回顾我院药物代谢酶和药物作用靶点相关基因检测与精准药学服务实践过程,总结经验,与同行分享。方法从准备工作、相关检测项目的确定,学术推广、项目优化和开展情况等方面详细阐述我院基因检测开展过程与精准药学服务情况。结果根据临床需求,我院已开展了以心脑血管药和抗精神病药为主的27种药物,26项检测,2018年全年位1587名患者提供个体化用药建议,受到临床医生和患者欢迎。结论基于代谢酶和药物作用靶点相关基因检测的个体化用药建议是临床药师参与精准治疗的重要途径,有助于医生和药师之间的沟通,有利于提高药学服务水平。     

Evaluation of <i>MGMT</i> Gene Methylation in Neuroendocrine Neoplasms

Unresectable neuroendocrine neoplasms (NENs) often poorly respond to standard therapeutic approaches. Alkylating agents, in particular temozolomide, commonly used to treat high-grade brain tumors including glioblastomas, have recently been tested in advanced or metastatic NENs, where they showed promising response rates. In glioblastomas, prediction of response to temozolomide is based on the assessment of the methylation status of the MGMT gene, as its product, O6 -methylguanine-DNA methyltransferase, may counteract the damaging effects of the alkylating agent. However, in NENs, such a biomarker has not been validated yet. Thus, we have investigated MGMT methylation in 42 NENs of different grades and from various sites of origin by two different approaches: in contrast to methylation-specific PCR (MSP), which is commonly used in glioblastoma management, amplicon bisulfite sequencing (ABS) is based on high-resolution, next-generation sequencing and interrogates several additional CpG sites compared to those covered by MSP. Overall, we found MGMT methylation in 74% (31/42) of the NENs investigated. A higher methylation degree was observed in welldifferentiated tumors and in tumors originating in the gastrointestinal tract. Comparing MSP and ABS results, we demonstrate that the region analyzed by the MSP test is sufficiently informative of the MGMT methylation status in NENs, suggesting that this predictive parameter could routinely be interrogated also in NENs.