Neural selectivity,efficiency, and dose equivalence in deep brain stimulation through pulse width tuning and segmented electrodes

BackgroundAchieving deep brain stimulation (DBS) dose equivalence is challenging, especially with pulse width tuning and directional contacts. Further, the precise effects of pulse width tuning are unknown, and recent reports of the effects of pulse width tuning on neural selectivity are at odds with classic biophysical studies.MethodsWe created multicompartment neuron models for two axon diameters and used finite element modeling to determine extracellular influence from standard and segmented electrodes. We analyzed axon activation profiles and calculated volumes of tissue activated.ResultsWe find that long pulse widths focus the stimulation effect on small, nearby fibers, suppressing distant white matter tract activation (responsible for some DBS side effects) and improving battery utilization when equivalent activation is maintained for small axons. Directional leads enable similar benefits to a greater degree. Reexamining previous reports of short pulse stimulation reducing side effects, we explore a possible alternate explanation: non-dose equivalent stimulation may have resulted in reduced spread of neural activation. Finally, using internal capsule avoidance as an example in the context of subthalamic stimulation, we present a patient-specific model to show how long pulse widths could help increase the biophysical therapeutic window.DiscussionWe find agreement with classic studies and predict that long pulse widths may focus the stimulation effect on small, nearby fibers and improve power consumption. While future pre-clinical and clinical work is necessary regarding pulse width tuning, it is clear that future studies must ensure dose equivalence, noting that energy- and charge-equivalent amplitudes do not result in equivalent spread of neural activation when changing pulse width.     

近几年中药附子的文献研究

附子作为有毒中药常用于多种疾病的治疗,由于广泛的临床应用和潜在的毒性受到青睐,其中,附子化学成分和药理作用等研究取得了许多实验成果。本文通过检索中国知网、万方、维普等数据库,分析梳理大量文献,对附子结构及药理进行探讨分析,旨在扩大附子使用范围和提高使用频率,为附子实验研究和应用研究提供参考和借鉴。     

桃红四物汤化学成分、药理作用、临床应用的研究进展及质量标志物的预测分析

桃红四物汤,活血祛瘀之经典名方。该文对近年来桃红四物汤的化学成分、药理作用以及临床应用研究进展进行总结与分析。目前,桃红四物汤不同提取部位化学成分的研究较为系统,其药理作用研究主要集中在活血化瘀、调经镇痛、促进骨折愈合等方面,临床可应用于多系统、多脏腑疾病的治疗,例如妇科疾病、内科疾病、骨伤科疾病、皮肤科疾病等。在此基础上,依照质量标志物(Q-marker)有效、特有、传递与溯源、可测和处方配伍的"五原则"对桃红四物汤Q-marker进行预测分析,提示阿魏酸、芍药苷、苦杏仁苷、芍药内酯苷、梓醇、没食子酸、羟基红花黄色素A可作为该复方的Q-marker,后续可选择这些Q-marker为指标,根据药材、饮片、中间体、对应实物的量值传递进行桃红四物汤全程质量控制并创建其质量可溯源体系。     

基于蛋白质组学分析色胺酮抑制小鼠乳腺癌的作用机制

目的:采用非标记定量(Label-free)蛋白质组学技术研究色胺酮抗小鼠体内乳腺癌的作用机制。方法:采用超高效液相色谱-质谱联用技术检测色胺酮抗小鼠乳腺癌的表达蛋白,选择Ionoptics nano UPLC C18色谱柱(0.075 mm×250 mm,1.6μm),流动相0.1%甲酸水溶液-0.1%甲酸乙腈溶液梯度洗脱,正离子模式,扫描范围m/z 100～1 700,使用MaxQuant 1.6.5.0进行数据库检索。采用Label-free高分辨质谱的蛋白质组学技术筛选4T1乳腺癌小鼠模型组与色胺酮(100 mg·kg~(-1))口服给药组之间的差异表达蛋白,进行色胺酮抗乳腺癌的蛋白质组学研究。结果:共鉴定出3 997个蛋白质,其中有2 911个蛋白可定量。模型组与色胺酮组共750个差异表达蛋白,其中286个蛋白上调,464个蛋白下调。基因本体分析表明,这些差异表达蛋白主要参与增殖、细胞迁移、凋亡、免疫、血管生成和炎症调节等生物学过程。京都基因与基因组百科全书通路分析进一步表明,这些蛋白主要集中于T细胞受体,B细胞受体,Toll样受体,核转录因子-κB(NF-κB),Ras蛋白,白细胞介素-17,肿瘤坏死因子,磷脂酰肌醇3-激酶/蛋白激酶B(PI3K-Akt)和丝裂原活化蛋白激酶(MAPK)等信号通路。结论:与色胺酮抗4T1乳腺癌作用密切相关的差异表达蛋白包括上调蛋白白细胞分化抗原14(CD14),前列腺素G/H合酶2(PTGS2),泛素蛋白连接酶E3和下调蛋白CD44,70 kDa热休克蛋白1A(HSPA1A),巨噬细胞移动抑制因子(MIF),NF-κB,核糖体蛋白S6激酶α-4(RPS6KA4)和高迁移率族蛋白B1(HMGB1),提示色胺酮主要通过调节肿瘤炎症微环境来达到抑制小鼠乳腺癌的作用。     

法半夏罗汉果川贝枇杷膏与强力枇杷露药理作用的比较研究

法半夏罗汉果川贝枇把膏与强力批他露均有镇咳祛痰作用，罗汉果川贝枇把膏尚能平喘抗炎。     

Specific statistical considerations relevantto the design and analysis of gingivitis trials demonstrating

Simulation studies were conducted to address specific statistical issues which arise in the design and analysis of gingivitis studies whose principal aim is the demonstration of superiority or equivalence of one product to another. The effects of measurement scale, using differences or ratios of group means, particular statistical test produces and specific rules demonstrating superiority or equivalence were investigated. An alternative concept to equivalence—denoted “least as good”—was also defined and evaluated. For a wide class of possible distributions of gingivitis scores, characterized by specific gamma distributions, the student-t test applied to means of subject GI gingivitis scores proved to be the most powerful of the test produces considered, having statistical properties quite similar to the randomization or permutation test procedure. Transformations of subject GI mean gingivitis scores did not produce an advantage in demonstrating either superiority or equivalence, and in some cases made it more difficult. Little difference was observed in test results when using the difference in group means as compared with using the ratio of group means for demonstrating either equivalence or superiority. The clinically significant rule produced the lowest false-positive rates for products slightly better than the active control, and similar false-positive and -negative rates as the statistically significant rule for products clearly superior to the active control. Demonstration of product equivalence will require more subjects per group than demonstrating product superiority, the size of this difference being a function of the definition of superiority that is accepted. Showing that the 90% confidence interval for 100*R is completely contained within the [90%, 110%] interval is the preferred method of demonstrating equivalence today, although much more research needs to be done to improve methods for demonstrating product equivalence. The “least as good” alternative to “equivalence” makes it easier to demonstrate “equivalence” for products slightly better than the active control product, but both experience great difficulty in demonstrating equivalence for lest products not quite as good as the active control.     

阿奇霉素治疗呼吸道感染的药理特性与临床分析

阿奇霉素是近年来开发的大环内酯类抗生素,本品是通过阻碍细菌转肽过程,抑制蛋白质合成达到抑菌作用。我院呼吸内科自2006年2月～8月收治35例肺部疾患患者,将阿奇霉素用于呼吸道感染取得满意疗效。本文将概述阿奇霉素的药理特性及报道治疗呼吸道感染的临床资料。     

香茶菜属植物的化学成分与药理作用研究进展

我们主要综述了国内近年来有关香茶菜属植物在化学成分、药理作用、临床应用方面的研究进 展,并且讨论了这一领域的研究方向。