Shear-slip Mesh Update Method: implementation and applications

The Shear-slip Mesh Update Method (SSMUM) is being used in flow simulations involving large but regular displacements of one or more boundaries of the computational domain. We follow up the earlier discussion of the method with notes on practical implementation aspects. In order to establish a benchmark problem for this class of flow problems, we define and report results from a two-dimensional viscous flow around a rotating stirrer in a square chamber. The application potential of the method is demonstrated in the context of biomedical design problem, as we perform an analysis of blood flow in a centrifugal left ventricular assist device, or blood pump, which involves a rotating impeller in a non-axisymmetric housing.     

Quantification of the Blood Platelet Reactivity in the ADP-Induced Model of Non-Lethal Pulmonary Thromboembolism in Mice with the Use of Laser Doppler Flowmetry

IntroductionThe paper describes an alternative method for quantification of in vivo ADP-induced thromboembolism. The aim of the studies was to develop a method of quantification which would not require either extravasation or labelling of platelets. Our proposed approach is based on the monitoring of changes of blood flow with the use of laser Doppler flowmetry.ResultsThe injection of ADP resulted in a dose-dependent reduction of the blood flow in the mesentery. These responses were fully attributable to blood platelet aggregation, as shown by the lack of the effect in platelet-depleted mice, and significantly reduced responses in mice pretreated with cangrelor and eptifibatide. No platelet aggregate formation in mesenteric vessels was revealed by intravital microscopy, while ex vivo imaging showed accumulation of fluorescent labelled platelets in the lung.ConclusionsInjection of ADP to the venous system results in the formation of platelet aggregates predominantly in the lung. This results in reversible blood flow cessation in peripheral blood vessels. The measurement of this blood flow cessation in the mesentery allows indirect measurement of ADP-induced pulmonary thromboembolism. We suggest that this approach can be useful for in vivo screening for antiplatelet drug candidates.     

Novel methods for segment-specific blood flow simulation for the liver

Abstract

One challenge for hepatic flow simulation is to divide the hepatic vasculature into individual Couinaud segments, and to simulate flow at both segmental and organ levels. We propose to integrate a segment simulation algorithm with the flow solver in a Constructive Constraint Optimisation (CCO) algorithm to address this problem. In this way blood flow simulations can be conducted for large segment-specific vasculatures as relevant to surgical procedures. In this short communication we outline the methods and present some preliminary results.     

Using matrix summation method for three dimensional dose calculation in brachytherapy

AimThe purpose of this study is to calculate radiation dose around a brachytherapy source in a water phantom for different seed locations or rotation the sources by the matrix summation method.BackgroundMonte Carlo based codes like MCNP are widely used for performing radiation transport calculations and dose evaluation in brachytherapy. But for complicated situations, like using more than one source, moving or rotating the source, the routine Monte Carlo method for dose calculation needs a long time running.Materials and methodsThe MCNPX code has been used to calculate radiation dose around a ¹⁹²Ir brachytherapy source and saved in a 3D matrix. Then, we used this matrix to evaluate the absorbed dose in any point due to some sources or a source which shifted or rotated in some places by the matrix summation method.ResultsThree dimensional (3D) dose results and isodose curves were presented for ¹⁹²Ir source in a water cube phantom shifted for 10 steps and rotated for 45 and 90° based on the matrix summation method. Also, we applied this method for some arrays of sources.ConclusionThe matrix summation method can be used for 3D dose calculations for any brachytherapy source which has moved or rotated. This simple method is very fast compared to routine Monte Carlo based methods. In addition, it can be applied for dose optimization study.     

尾静脉注射骨髓间充质干细胞对1型糖尿病幼鼠的治疗作用实验研究

目的:比较尾静脉注射骨髓间充质干细胞(BMSCs)治疗1型糖尿病(type 1 diabetes,T1D)幼鼠的效果.方法:选用3周龄C57bl/c幼鼠作为受试动物,连续5d腹腔注射50 mg/kg的链脲佐菌素(STZ),建立T1D模型;采用酶消化法联合骨片法从2周龄C57bl/c幼鼠的胫骨和股骨中分离出BMSCs;碱...     

流式细胞仪分选人外周血T淋巴细胞的方法建立与评价

目的:利用流式细胞仪同时分离外人周血单个核细胞中T淋巴细胞并检测其分离纯度及存活率。方法:本文采用流式细胞仪同时分选人外周血CD4~+、CD8~+T淋巴细胞为例,推而广之,采用人外周血淋巴细胞分离液梯度离心法制备外周血单个核细胞,采用流式细胞仪同时分选CD4~+、CD8~+T淋巴细胞,分离细胞再通过流式细胞仪回测其分离纯度并通过台盼蓝染色检测分离细胞的存活率。结果:采用此方法能有效人外周血细胞CD4~+、CD8~+T淋巴细胞,分选前CD4~+淋巴细胞纯度为(50.5±11.5)%、CD8~+T淋巴细胞纯度为纯度为(15.4±7.1)%;分选后CD4~+T淋巴细胞纯度为(94.3±1.3)%、CD8~+T淋巴细胞纯度为(93.6±1.6)%;分选后CD4~+T淋巴细胞存活率为(95.3±1.8)%,CD8~+T淋巴细胞存活率为(94.8±1.5)%,细胞的形态完整。结论:采用人外周血淋巴细胞分离液梯度离心法制备外周血单个核细胞后利用流式细胞仪分选的方法能够高效、快速的分离人外周血CD4~+、CD8~+T淋巴细胞,且存活率高,为进一步研究其功能提供了保证。采用不同的荧光抗体标记其他淋巴细胞亚群,也能高效、快速的分离出细胞。     

体外循环血栓非侵入在线电阻抗成像方法

目的 在体外循环系统中,血栓的在线检测和可视化具有重要意义。本文提出了基于电阻抗成像（EIT）的体外循环血栓非侵入在线检测方法。方法 首先通过联合仿真研究了传感器尺寸对成像效果的影响。其次,根据仿真结果设计了直径为20 mm的16铜质电极EIT传感器,搭建了循环流动实验平台,并设计了静态和循环流动实验。使用尺寸为3～6 mm的猪血块代替血栓,将血块置于新鲜猪血样本中,采用Tikhonov正则化算法进行成像。将3 mm和5 mm的血块分别置于循环系统中,重建血块在传感器截面的大小和位置图像,并与高速相机拍摄结果进行对比。结果 仿真结果显示当目标物与传感器面积比（AR）不小于0.01时,传感器直径为20 mm和30 mm对应的图像相关系数（IC）均大于0.06,成像效果较好。静态成像结果显示,相对尺寸覆盖率误差（RCR）小于等于0.1。循环流动实验显示,血块经过传感器时,检测到归一化后的相对电导率变化值分别为80和200,结果显示该方法能够检测到循环系统中的血块。结论 该方法具有实时性和非侵入的优点,有望应用于体外血栓的检测。     

激光多普勒血流仪在断指再植术后血运监测应用的效果研究

目的:为了提高临床断指再植手术效果,分析断指再植术后彩色多普勒血流成像仪的临床应用效果价值。方法:从2016年9月至2017年9月在我院接受断指再植术治疗的60例患者中,采用随机数表法随机将其分为实验组和对照组各30例。实验组:采用激光多普勒血流成像仪监测再植肢体血运;对照组:采用传统方法监测再植肢体血运。探讨断指再植术后彩色多普勒血流成像仪的临床应用价值。结果:研究结果显示,和对照组相比观察组患者断指再植术后血管栓塞率、血管危象发生率明显降低,而断指成活率以及成活再植指术后功能恢复情况则明显增加(P0.05)。结论:将彩色多普勒血流监测应用于断指再植术后,能够无创、实时、灵敏的反应再植指术后的血运情况,有助于及时发现各种不良事件的,提高再植成功率,效果显著,值得推广。     

趋流行为下斑马鱼幼鱼的全脑成像

目的 趋流,意即在水中调整身体方向并逆流而上的能力,是一种在大多数鱼类与两栖类动物中存在的保守行为。虽然关于趋流的研究已有一段很长的历史,并且近年来斑马鱼幼鱼趋流行为的理论机制也被提出,但是分布式的神经环路是如何整合多感知信息、做出决策、并实现行为控制仍然是个未知数。对自由运动的斑马鱼进行全脑神经活动成像为理解这一困难的问题提供了特殊的机会。方法 本文开发了一种微流控装置精确控制环境水流并激发斑马鱼的趋流行为。将该微流控芯片与扩增视野光场显微镜以及追踪系统整合,从而记录自由行为下斑马鱼全脑的神经活动。结果 在整合的微流控装置中稳定观察到了斑马鱼在水流中保持自身位置不变、逆流而上等刻板的趋流行为现象。与此同时,实现了对斑马鱼幼鱼趋流行为过程中的全脑钙活动记录。本文初步发现了几个脑区的神经活动与趋流行为相关。结论 本研究第一次展示了在斑马鱼幼鱼趋流行为的同时记录全脑神经活动的技术。接下来对神经活动和行为数据的分析与建模将有助于更好地理解一种重要自然行为背后的感觉运动转换机制。     

The effects of exposure to night shift work on liver function: A cross-sectional study with emphasis of alkaline phosphatase enzyme

ABSTRACT

Background: Previous studies have demonstrated that shift work can be significantly associated with adverse effects on liver function. However, the association between shift work and alkaline phosphatase (ALP) enzyme as a well-known biomarker of liver disease has been undefined. Methods: This cross-sectional study was conducted on a total number of 6,475 eligible oil refinery workers. According to shift work schedules, the participants divided to the following groups: 12-hr rotating night (n = 2,630) and 12-hr fixed day (n = 3845). The Spearman’s correlation and logistic regression were applied to assess the association between shift work and ALP. Results: We found significantly higher levels of ALP in 12-hr rotating night compared to 12-hr fixed-day shift work groups (196.2 ± 52.1 versus 191.5 ± 53.4). According to quartile (Q) logistic regression adjusted by significant variables between study group (age, body mass index, fasting blood sugar, and total cholesterol), the odds ratio and 95% confidence interval of high (Q2–<Q3 versus <Q1) and severe (≥Q3 versus <Q1) levels of ALP in 12-hr rotating night group in comparison to 12-hr fixed-day group were estimated as 1.26 (1.08–1.45) and 1.26 (1.09–1.45), respectively. Conclusions: This study indicated that 12-hr rotating night shift work may be associated with higher levels of ALP. More studies are needed to confirm our findings.     

SD大鼠骨髓间充质干细胞分离培养及鉴定的实验研究

摘要 目的：探讨应用全骨髓贴壁法体外分离培养SD大鼠骨髓间充质干细胞（BMSCs)的可行性,研究其生物学特性,为骨组织工程提供种子细胞。方法：取SPF级5周龄健康SD大鼠2只,脱颈处死,分离双下肢股骨、胫骨,全骨髓贴壁法分离培养、纯化BMSCs;通过倒置显微镜观察原代、传代细胞生长情况、绘制生长、贴壁率曲线,研究其生物学特性;流式细胞仪检测表面标志物、诱导成成骨等方法进行鉴定。结果：应用全骨髓贴壁法可在体外分离出活性好、纯度高的BMSCs。倒置显微镜下可见原代细胞呈梭形、多角形,传代细胞形态均一呈纤维样;P3代BMSCs经流式细胞鉴定：CD44、CD90高表达,CD31、CD45低表达;定向诱导向成骨细胞分化,可见明显矿化结节。结论：证实应用全骨髓贴壁培养法体外可成功分离BMSCs,所分离培养、纯化的细胞生物学稳定,纯度高、活性好,具有多向分化潜能,能为骨组织工程、骨质疏松症和骨折不愈合疾病的研究提供种子细胞。     

基于磁驱动技术的空肠营养管的设计

目的:为解决目前床旁鼻肠管快速置入成功率低这一临床难题,该文提出一种基于磁驱动技术的空肠营养管的设计。方法:分析了现有空肠营养管置管过程中的动力因素,结合磁驱动技术原理,提出了通过体外旋转磁场带动体内感应磁体螺旋式前进的设计方案,以期缩短空肠营养管的飘管时间。结果:该设计包括磁性空肠营养管和体外磁力驱动装置两部分。其中磁性空肠营养管由管体和感应磁头两部分构成,感应磁头包括磁体内核和硅胶外壳。磁力驱动装置由多极磁体和手持式微型电机组成。操作时通过体外磁力驱动装置发出大旋转磁场带动空肠营养管的感应磁头做轴向旋转运动,可加速空肠营养管在肠道内的移动,达到缩短飘管时间的目的。结论:该设计基于磁驱动技术原理,设计巧妙,符合磁力学原理,操作简单,具有临床应用潜力。     

低浓度万古霉素复合PMMA骨水泥的细胞毒性研究

目的:研究低浓度万古霉素(1%)复合聚甲基丙烯酸甲酯PMMA骨水泥对SD仔鼠原代成骨细胞的增殖以及凋亡的影响。方法:采用分离SD仔鼠颅骨与胰酶消化法获取SD仔鼠原代成骨细胞,通过细胞爬片碱性磷酸酶染色对原代成骨细胞进行鉴定;利用CCK-8法检测低浓度万古霉素复合PMMA及纯PMMA骨水泥浸提液对SD大鼠原代成骨细胞的增殖影响、流式细胞仪检测万古霉素复合PMMA及纯PMMA骨水泥浸提液对对SD大鼠原代成骨细胞的凋亡影响。结果:SD大鼠原代成骨细胞在低浓度万古霉素复合PMMA骨水泥浸提液中第1、2、3天的增殖更明显(P0.05),在纯PMMA骨水泥浸提液中第1、5天凋亡显著增加(P0.05)。结论:低浓度万古霉素复合PMMA骨水泥相比PMMA骨水泥具有较低的细胞毒性,在临床应用于骨缺损伴局部骨感染的治疗方面具有一定的优势。     

A One-dimensional Finite Element Method for Simulation-based Medical Planning for Cardiovascular Disease

We have previously described a new approach to planning treatments for cardiovascular disease, Simulation-Based Medical Planning, whereby a physician utilizes computational tools to construct and evaluate a combined anatomic/physiologic model to predict the outcome of alternative treatment plans for an individual patient. Current systems for Simulation-Based Medical Planning utilize finite element methods to solve the time-dependent, three-dimensional equations governing blood flow and provide detailed data on blood flow distribution, pressure gradients and locations of flow recirculation, low wall shear stress and high particle residence. However, these methods are computationally expensive and often require hours of time on parallel computers. This level of computation is necessary for obtaining detailed information about blood flow, but likely is unnecessary for obtaining information about mean flow rates and pressure losses. We describe, herein, a space-time finite element method for solving the one-dimensional equations of blood flow. This method is applied to compute flow rate and pressure in a single segment model, a bifurcation, an idealized model of the abdominal aorta, in three alternate treatment plans for a case of aorto-iliac occlusive disease and in a vascular bypass graft. All of these solutions were obtained in less than 5 min of computation time on a personal computer.     

同型半胱氨酸水平与女性绝经期骨质疏松相关性研究

目的:通过分析女性绝经期不同骨密度人群的血浆同型半胱氨酸(HCY)指标,探讨同型半胱氨酸在女性绝经期骨质疏松发生过程中的作用及其潜在的临床价值。方法:收集2014年3月至2016年3月我院体检中心进行体检的女性绝经期妇女(60岁)血样标本共计625例,根据体检的骨密度报告对其进行分组,骨质疏松组215例,骨量减少组309例,骨量正常组101例,测量每组的同型半胱氨酸水平。结果:骨密度程度与同型半胱氨酸水平存在负相关关系(rs=-0.763,P=0.046),三组之间的同型半胱氨酸水平也存在显著差异(F=4.807,P0.016),其中骨质疏松组指标最高,骨量正常组指标最低。结论:同型半胱氨酸是重要的骨代谢指标,在衡量绝经期妇女骨质疏松进展中具有重要的意义。     

Pulsatile Flow Inside Moderately Elastic Arteries,Its Modelling and Effects of Elasticity

Pulsatile flow inside a moderately elastic circular conduit with a smooth expansion is studied as a model to understand the influence of wall elasticity in artery flow. The solution of the simultaneous fluid-wall evolution is evaluated by a perturbative method, where the zeroth order solution is represented by the flow in a rigid vessel; the first order correction gives the wall motion and induced flow modification without the need to solve the difficult coupled problem. Such an approach essentially assumes a locally infinite celerity, therefore it represent a good approximation for the fluid-wall interaction in sites of limited extent (branches, stenosis, aneurism, etc.), which include typical situations associated with vascular diseases. The problem is solved numerically in the axisymmetric approximation; the influence of wall elasticity on the flow and on the unsteady wall shear stress is studied in correspondence of parameters taken from realistic artery flow. Attention is posed to the role of phase difference between the incoming pressure and flow pulses.     

A new bisphosphonate-containing <Superscript>99m</Superscript>Tc(I) tricarbonyl complex potentially useful as bone-seeking agent: synthesis and biological evaluation

Aiming to develop new bone-seeking radiotracers based on the organometallic core fac-[^99mTc(CO)₃]⁺ with improved radiochemical and biological properties, we have prepared new conjugates with phosphonate pendant groups. The conjugates comprise a chelating unit for metal coordination, which corresponds to a pyrazolyl-containing backbone (pz) with a N,N,N donor-atom set, and a pendant diethyl phosphonate (pz-MPOEt), phosphonic acid (pz-MPOH) or a bisphosphonic acid (pz-BPOH) group for bone targeting. Reactions of the conjugates with the precursor [^99mTc(H₂O)₃(CO)₃]⁺ yielded (mote than 95%) the single and well-defined radioactive species [^99mTc(CO)₃(κ³-pz-MPOEt)]⁺ (1a), [^99mTc(CO)₃(κ³-pz-MPOH]⁺ (2a) and [^99mTc(CO)₃(κ³-pz-BPOH)]⁺ (3a), which were characterized by reversed-phase high-performance liquid chromatography . The corresponding Re surrogates (1–3), characterized by the usual analytical techniques, including X-ray diffraction analysis in the case of 1, allowed for macroscopic identification of the radioactive conjugates. These radioactive complexes revealed high stability both in vitro (phosphate-buffered saline solution and human plasma) and in vivo, without any measurable decomposition. Biodistribution studies of the complexes in mice indicated a fast rate of blood clearance and high rate of total radioactivity excretion, occurring primarily through the renal–urinary pathway in the case of complex 3a. Despite presenting moderate bone uptake (3.04 ± 0.47% injected dose per gram of organ, 4 h after injection), the high stability presented by 3a and its adequate in vivo pharmacokinetics encourages the search for new ligands with the same chelating unit and different bisphosphonic acid pendant arms.     

基于主成分分析的双对比光学投影断层成像

目的 本文提出了一种基于主成分分析（PCA）的双对比光学投影断层成像（DC-OPT）方法,以获得活体中血流网络和骨骼的三维可视化。方法 使用主成分分析方法来提取吸收图像和血流图像,原始图像序列的第一主成分用于获取吸收图像;通过计算每个像素的调制深度来获得流动图像。不同投影位置的流动和吸收对比图像被用于三维血流网络和骨骼的同步重建。结果 采用PCA和OPT相结合的方法,通过将动态血流信号和静态背景信号分离,实现了对微生物样本的血流网络和骨骼的三维成像。结论 本文研究的新颖之处在于通过同一光学系统获得了快速、同步、双对比的血流网络和骨骼三维图像。实验结果可用于活体生物的生理发育研究。     

Quantification of cotinine in dried blood spots as a biomarker of exposure to tobacco smoke

Objective: We present an ultra-sensitive, minimally-invasive method for quantifying cotinine in dried blood spot (DBS) samples as a biomarker of exposure to tobacco smoke that can be collected using a simple heel or finger prick to obtain blood samples.

Methods: Cotinine levels were measured in matched plasma and reconstituted DBS samples from smokers and nonsmokers to evaluate assay parameters. In addition, we applied this new method to finger-prick DBS samples that were collected from infants, children and young adults ages 1–21 to estimate exposure to tobacco smoke. Partitioning of cotinine across red blood cells and haematocrit effects were investigated.

Results: Cotinine levels measured in matched plasma and reconstituted DBS samples from smokers and nonsmokers were found to be highly correlated (R²=0.94), with 100% sensitivity and 94% specificity to differentiate reported smokers from nonsmokers. With this method, the LOQ is <0.25?ng/mL using a single 3.2?mm punch of a DBS, and haematocrit effects are negligible.

Conclusions: This sensitive, high-throughput and minimally-invasive method for quantifying cotinine in DBS samples provides a simple and cost effective means for estimating exposure to tobacco smoke in population based studies, and has particular advantages in studies involving infants and children.     

A novel algorithm for alignment of multiple PPI networks based on simulated annealing

Background

To infer gene regulatory networks (GRNs) from gene-expression data is still a fundamental and challenging problem in systems biology. Several existing algorithms formulate GRNs inference as a regression problem and obtain the network with an ensemble strategy. Recent studies on data driven dynamic network construction provide us a new perspective to solve the regression problem.

Results

In this study, we propose a data driven dynamic network construction method to infer gene regulatory network (D3GRN), which transforms the regulatory relationship of each target gene into functional decomposition problem and solves each sub problem by using the Algorithm for Revealing Network Interactions (ARNI). To remedy the limitation of ARNI in constructing networks solely from the unit level, a bootstrapping and area based scoring method is taken to infer the final network. On DREAM4 and DREAM5 benchmark datasets, D3GRN performs competitively with the state-of-the-art algorithms in terms of AUPR.

Conclusions

We have proposed a novel data driven dynamic network construction method by combining ARNI with bootstrapping and area based scoring strategy. The proposed method performs well on the benchmark datasets, contributing as a competitive method to infer gene regulatory networks in a new perspective.