High-Frequency Irreversible Electroporation Using 5,000-V Waveforms to Create Reproducible 2- and 4-cm Ablation Zones—A Laboratory Investigation Using Mechanically Perfused Liver

PurposeTo investigate if high-frequency irreversible electroporation (H-FIRE) treatments can be delivered at higher voltages and with greater energy delivery rates than currently implemented in clinical irreversible electroporation protocols.Materials and MethodsTreatments using 3,000 V and 5,000 V were administered to mechanically perfused ex vivo porcine liver via a single applicator and grounding pad (A+GP) as well as a 4-applicator array (4AA). Integrated energized times (IET) 0.01–0.08 seconds and energy delivery rates 25–300 μs/s were investigated. Organs were preserved at 4°C for 10–15 hours before sectioning and gross analysis using a metabolic stain to identify the size and shape of ablation zones.ResultsA+GP ablations measured between 1.6 cm and 2.2 cm, which did not increase when IET was increased from 0.02 seconds to 0.08 seconds (P > .055; range, 1.9–2.1 cm). Changes in tissue color and texture consistent with thermal damage were observed for treatments with energy delivery rates 50–300 μs/s, but not for treatments delivered at 25 μs/s. Use of the 4AA with a 3-cm applicator spacing resulted in ablations measuring 4.4–4.9 cm with energy delivery times of 7–80 minutes.ConclusionsH-FIRE treatments can rapidly and reproducibly create 2-cm ablations using an A+GP configuration. Treatments without thermal injury were produced at the expense of extended treatment times. More rapid treatments resulted in ablations with varying degrees of thermal injury within the H-FIRE ablation zone. Production of 4-cm ablations is possible using a 4AA.     

Endovascular deep brain stimulation: Investigating the relationship between vascular structures and deep brain stimulation targets

BackgroundEndovascular delivery of current using ‘stentrodes’ – electrode bearing stents – constitutes a potential alternative to conventional deep brain stimulation (DBS). The precise neuroanatomical relationships between DBS targets and the vascular system, however, are poorly characterized to date.ObjectiveTo establish the relationships between cerebrovascular system and DBS targets and investigate the feasibility of endovascular stimulation as an alternative to DBS.MethodsNeuroanatomical targets as employed during deep brain stimulation (anterior limb of the internal capsule, dentatorubrothalamic tract, fornix, globus pallidus pars interna, medial forebrain bundle, nucleus accumbens, pedunculopontine nucleus, subcallosal cingulate cortex, subthalamic nucleus, and ventral intermediate nucleus) were superimposed onto probabilistic vascular atlases obtained from 42 healthy individuals. Euclidian distances between targets and associated vessels were measured. To determine the electrical currents necessary to encapsulate the predefined neurosurgical targets and identify potentially side-effect inducing substrates, a preliminary volume of tissue activated (VTA) analysis was performed.ResultsSix out of ten DBS targets were deemed suitable for endovascular stimulation: medial forebrain bundle (vascular site: P1 segment of posterior cerebral artery), nucleus accumbens (vascular site: A1 segment of anterior cerebral artery), dentatorubrothalamic tract (vascular site: s2 segment of superior cerebellar artery), fornix (vascular site: internal cerebral vein), pedunculopontine nucleus (vascular site: lateral mesencephalic vein), and subcallosal cingulate cortex (vascular site: A2 segment of anterior cerebral artery). While VTAs effectively encapsulated mfb and NA at current thresholds of 3.5 V and 4.5 V respectively, incremental amplitude increases were required to effectively cover fornix, PPN and SCC target (mean voltage: 8.2 ± 4.8 V, range: 3.0–17.0 V). The side-effect profile associated with endovascular stimulation seems to be comparable to conventional lead implantation. Tailoring of targets towards vascular sites, however, may allow to reduce adverse effects, while maintaining the efficacy of neural entrainment within the target tissue.ConclusionsWhile several challenges remain at present, endovascular stimulation of select DBS targets seems feasible offering novel and exciting opportunities in the neuromodulation armamentarium.     

检测子宫内膜异位症患者血清中差异表达蛋白的研究

目的：检测子宫内膜异位症（内异症）患者血清中差异表达的蛋白。方法：采用表面增强激光解吸／离子化飞行时间质谱（SELDI—TOF—MS）技术，选用WCX2蛋白质芯片对50例内异症及48例对照组血清标本进行检测以筛选内异症血清中差异表达的蛋白。结果：在Mr 0～50000范围内，检测出106个蛋白峰。内异症患者血清中差异表达的蛋白峰有4个。将发现的差异蛋白峰在Swiss蛋白数据库中搜索，发现Mr 9280蛋白峰与玻璃粘连蛋白Vitronectin相符。Vitronectin属于整合素家族，在内异症的粘附、侵袭、血管形成过程中起重要作用。其他的蛋白峰没有发现与之相匹配的蛋白，提示可能为新的蛋白质。结论：内异症患者血清中存在差异表达的蛋白，其对内异症的早期诊断具有一定的临床意义。SELDI蛋白芯片技术是一种快速、简单易行、样本用量少、高通量、重复性好的分析方法，具有广阔的临床应用前景。     

芪月降脂片制剂处方的优化

[目的 ]优化芪月降脂片的制剂处方 .[方法 ]采用正交设计和多指标综合评分法对已筛选出的药剂辅料进行处方优化 .[结果 ]最佳制剂处方为糖粉 50 g ,辅料X 50g ,微晶纤维素 75g .[结论 ]该处方合理 ,成型性好     

电位滴定法测定胰激肽释放酶活力测试条件探讨

本文用ＦＩＰ推荐的方法，以具有国际单位的参照品为标样，滴定液为０．０１ｍｏｌ／ＬＮａＯＨ标准溶液，考查了以ＢＡＥＥ为底物的电位滴定法测定胰激肽释放酶活力的实验条件，通过正交试验得出直观和方差分析的结果，依据酶活力单位高、ＳＤ和ＲＳＤ％较小的原则，求出酶活力测定的最适条件是：酶反应温度为２５℃；缓冲液为０．００１５ｍｏｌ／ＬＮａ２Ｂ４Ｏ７－０．２５ｍｏｌ／ＬＮａＣＬ－２×１０（－４）ｍｏｌ／ＬＥＤＴＡ，ｐＨ为８．００；反应液中酶浓度为０．４８ＩＵ／ｍｌ；底物浓度为５×１０（－３）ｍｏｌ／Ｌ；胰蛋白酶抑制剂浓度为１２５μｇ／ｍｌ。胰激肽释放酶活力测定的实验数据的相对标准偏差小于５％。     

硫酸铁铵催化合成乙酰乙酸乙酯乙二醇缩酮

采用正交试验优选出最佳条件为：当乙酰乙酸乙酯为0.2moL时，硫酸铁铵0.7g，环乙烷10mL。乙酰乙酸乙酯和惭二醇摩尔比为1：1.5，反应时间为5h。所得产率为59.2%。     

悬浮阵列技术在研究与临床中的应用

悬浮阵列技术是一种以荧光编码微球为核心,集流式细胞、激光分析、高速数字信号处理等多种技术于一体的多指标并行分析技术平台,可一次同时准确定量检测100种不同的生物分子;具有高通量、高灵敏度,并行检测等特点;常用于免疫分析、核酸研究、酶学分析、受体、配体识别分析等研究.     

A simplified statistical method for local INR using linear regression

A simplified method of International Normalized Ratio (INR) derivation using linear regression of certified INR plotted against local prothrombin time (PT) results has been compared with INR from conventional orthogonal regression. Linear regression assumes error only with the local PT results whereas orthogonal regression assumes error with both reference and local results. The reliability of local INR derivation using lyophilized plasmas has been assessed in a collaborative study. INR from conventional fresh plasma International Sensitivity Index (ISI) calibrations have been compared with INR from calibrations with two types of lyophilized plasma, artificially depleted and coumarin.
Although calibration slopes differed with the two types of analysis and the different lyophilized plasmas, both gave reasonable approximations to fresh plasma ISI calibrations. With orthogonal regression the overall percentage INR deviation was 5.25% with the artificially depleted plasmas and 6.85% for the results with lyophilized coumarins. With the linear regression, deviation was 8.40% for the artificially depleted plasmas and 5.05% for coumarin-treated patients' lyophilized plasmas. The simpler regression method appears to be worthy of further study as the present report has demonstrated that if the calibrant plasmas are accurately certified with the thromboplastin International Reference Plasma (IRP) results approximate to the conventionally determined INR using the manual PT technique. Coagulometers require further assessment.     

修正正交分段线性函数及其在线性与时变线性系统中应用

把分段线性函数和斜波脉冲函数进行统一处理，定义成新的函数，使得新的函数既保持了原先两种函数的基本特性，又获得微分和积分递推算法。应用中具有方便，快速计算的优点。     

Analysis of differentially expressed genes in fetal skin of scarless and scar-forming periods of gestational rats

Objective: To study the differences of gene expression between earlier gestational skin and later gestational skin of rats with the aids of single primer amplification (SPA) and high-density oligonucleotide DNA array to understand the molecular mechanism of scarless healing. Methods: Total RNAs were isolated from fetal rat skin of the scarless (E15) and scar-forming (E18) periods of gestation (term =21.5 days). The RNAs from earlier gestational skin (EGS) and later gestational skin (LGS) were both reversely transcribed to cDNAs, then labeled with the incorporation of fluorescent dCTP for preparing the hybridization probes by SPA method. The mixed probes were then hybridized to the oligonucleotide DNA arrays which contained 5 705 probes representing 5 705 rat genes. After highly stringent washing, these DNA arrays were scanned for fluorescent signals to display the differentially expressed genes between the 2 groups of skin. Results: Among 5 705 rat genes, there were 53 genes (0.93%) with differentially expressed levels between EGS and LGS groups, 27 genes, including fibroblast growth factor 2 ( FGF2 ) and follistatin were up-regulated (0.47%) and 26 genes were down-regulated (0.46%) in fetal skin during scarless period versus scar-forming period. Higher expressions of FGF2 and follistatin in EGS than those in LGS were also revealed by RT-PCR method. Conclusions: High-density oligonucleotide DNA array provided a powerful tool for investigating differential gene expression in earlier and later gestational fetal skins. This technology validates that the mechanism of fetal scarless healing is very complicate and the change of many gene expressions is associated with fetal scarless healing.