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In silico simulation of the effect of hypoxia on MCF-7 cell cycle kinetics under fractionated radiotherapy 分次放疗下缺氧对MCF-7细胞周期动力学影响的硅模拟
IF 1.8 4区 生物学 Q3 Physics and Astronomy Pub Date : 2021-09-17 DOI: 10.1007/s10867-021-09580-x
Adrian S. Remigio

The treatment outcome of a given fractionated radiotherapy scheme is affected by oxygen tension and cell cycle kinetics of the tumor population. Numerous experimental studies have supported the variability of radiosensitivity with cell cycle phase. Oxygen modulates the radiosensitivity through hypoxia-inducible factor (HIF) stabilization and oxygen fixation hypothesis (OFH) mechanism. In this study, an existing mathematical model describing cell cycle kinetics was modified to include the oxygen-dependent G1/S transition rate and radiation inactivation rate. The radiation inactivation rate used was derived from the linear-quadratic (LQ) model with dependence on oxygen enhancement ratio (OER), while the oxygen-dependent correction for the G1/S phase transition was obtained from numerically solving the ODE system of cyclin D-HIF dynamics at different oxygen tensions. The corresponding cell cycle phase fractions of aerated MCF-7 tumor population, and the resulting growth curve obtained from numerically solving the developed mathematical model were found to be comparable to experimental data. Two breast radiotherapy fractionation schemes were investigated using the mathematical model. Results show that hypoxia causes the tumor to be more predominated by the tumor subpopulation in the G1 phase and decrease the fractional contribution of the more radioresistant tumor cells in the S phase. However, the advantage provided by hypoxia in terms of cell cycle phase distribution is largely offset by the radioresistance developed through OFH. The delayed proliferation caused by severe hypoxia slightly improves the radiotherapy efficacy compared to that with mild hypoxia for a high overall treatment duration as demonstrated in the 40-Gy fractionation scheme.

一个给定的分割放疗方案的治疗结果受氧张力和肿瘤细胞周期动力学的影响。大量的实验研究支持细胞周期阶段的放射敏感性的可变性。氧通过缺氧诱导因子(HIF)稳定和氧固定假说(OFH)机制调节辐射敏感性。在这项研究中,我们修改了一个现有的描述细胞周期动力学的数学模型,加入了氧依赖的G1/S过渡率和辐射失活率。使用的辐射失活率由氧增强比(OER)的线性二次(LQ)模型导出,而G1/S相变的氧依赖校正是通过数值求解不同氧张力下cyclin D-HIF动力学的ODE系统得到的。通过对所建立的数学模型进行数值求解得到的充气MCF-7肿瘤群体相应的细胞周期相分数和生长曲线与实验数据相当。应用数学模型对两种乳腺放射治疗分割方案进行了研究。结果表明,缺氧导致肿瘤在G1期更多地以肿瘤亚群为主,而在S期更耐辐射的肿瘤细胞的分数贡献降低。然而,缺氧在细胞周期阶段分布方面的优势在很大程度上被OFH产生的辐射抗性所抵消。40-Gy分割方案显示,与轻度缺氧相比,重度缺氧导致的增殖延迟略微提高了放射治疗的疗效,总体治疗时间较长。
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引用次数: 1
Double-diffusion convective biomimetic flow of nanofluid in a complex divergent porous wavy medium under magnetic effects 磁作用下纳米流体在复杂多孔波介质中的双扩散仿生对流流动
IF 1.8 4区 生物学 Q3 Physics and Astronomy Pub Date : 2021-09-16 DOI: 10.1007/s10867-021-09583-8
Khurram Javid, Mohsan Hassan, Dharmendra Tripathi, Salahuddin Khan, Elena Bobescu, Muhammad Mubashir Bhatti

We explore the physical influence of magnetic field on double-diffusive convection in complex biomimetic (peristaltic) propulsion of nanofluid through a two-dimensional divergent channel. Additionally, porosity effects along with rheological properties of the fluid are also retained in the analysis. The mathematical model is developed by equations of continuity, momentum, energy, and mass concentration. First, scaling analysis is introduced to simplify the rheological equations in the wave frame of reference and then get the final form of equations after applying the low Reynolds number and lubrication approach. The obtained equations are solved analytically by using integration method. Physical interpretation of velocity, pressure gradient, pumping phenomena, trapping phenomena, heat, and mass transfer mechanisms are discussed in detail under magnetic and porous environment. The magnitude of velocity profile is reduced by increasing Grashof parameter. The bolus circulations disappeared from trapping phenomena for larger strength of magnetic and porosity medium. The magnitude of temperature profile and mass concentration are increasing by enhancing the Brownian motion parameter. This study can be productive in manufacturing non-uniform and divergent shapes of micro-lab-chip devices for thermal engineering, industrial, and medical technologies.

研究了磁场对纳米流体在二维发散通道中复杂仿生(蠕动)推进过程中双扩散对流的物理影响。此外,在分析中还保留了孔隙度影响以及流体的流变性能。数学模型是由连续性、动量、能量和质量浓度方程发展起来的。首先,引入标度分析对波动参照系下的流变方程进行简化,然后采用低雷诺数和润滑方法得到最终的方程形式。利用积分法对得到的方程进行解析求解。详细讨论了磁性和多孔环境下的速度、压力梯度、泵送现象、俘获现象、传热和传质机理的物理解释。增大Grashof参数可以减小速度剖面的大小。当磁性和孔隙介质强度较大时,颗粒循环消失。随着布朗运动参数的增大,温度分布和质量浓度的变化幅度增大。该研究可用于热工程、工业和医疗技术的非均匀和不同形状的微实验室芯片设备的制造。
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引用次数: 10
Comparison of the histology and stiffness of ventricles in Anura of different habitats 不同生境无尾动物脑室组织学和硬度的比较
IF 1.8 4区 生物学 Q3 Physics and Astronomy Pub Date : 2021-09-13 DOI: 10.1007/s10867-021-09579-4
Megumi Ito, Yoshihiro Ujihara, Shukei Sugita, Masanori Nakamura

Vertebrate hearts have undergone marked morphological and structural changes to adapt to different environments and lifestyles as part of the evolutionary process. Amphibians were the first vertebrates to migrate to land. Transition from aquatic to terrestrial environments required the ability to circulate blood against the force of gravity. In this study, we investigated the passive mechanical properties and histology of the ventricles of three species of Anura (frogs and toads) from different habitats, Xenopus laevis (aquatic), Pelophylax nigromaculatus (semiaquatic), and Bufo japonicus formosus (terrestrial). Pressure-loading tests demonstrated stiffer ventricles of P. nigromaculatus and B. j. formosus compared X. laevis ventricles. Histological analysis revealed a remarkable difference in the structure of cardiac tissue: thickening of the compact myocardium layer of P. nigromaculatus and B. j. formosus and enrichment of the collagen fibers of B. j. formosus. The amount of collagen fibers differed among the species, as quantitatively confirmed by second-harmonic generation light microscopy. No significant difference was observed in cardiomyocytes isolated from each animal, and the sarcomere length was almost the same. The results indicate that the ventricles of Anura stiffen during adaptation to life on land.

作为进化过程的一部分,脊椎动物的心脏经历了显著的形态和结构变化,以适应不同的环境和生活方式。两栖动物是最早迁移到陆地上的脊椎动物。从水生环境过渡到陆地环境需要血液循环能力来对抗重力。本研究研究了三种不同生境的无尾动物(青蛙和蟾蜍)的脑室的被动力学特性和组织学,分别是水生爪蟾(Xenopus laevis)、半水生佩狐(Pelophylax nigromaculatus)和陆生蟾(Bufo japonicus formosus)。压力负荷试验表明,黑斑马鱼的心室较黑斑马鱼的心室更硬。组织学分析显示心肌组织结构有显著差异:黑斑鱼和台湾黑斑鱼致密心肌层增厚,台湾黑斑鱼胶原纤维丰富。胶原纤维的数量不同的物种,定量证实了二次谐波一代光学显微镜。各组分离的心肌细胞无明显差异,肌节长度几乎相同。结果表明,在适应陆地生活的过程中,无尾动物的脑室变硬。
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引用次数: 2
Fitness landscapes for coupled map lattices 耦合地图格的适应度景观
IF 1.8 4区 生物学 Q3 Physics and Astronomy Pub Date : 2021-09-08 DOI: 10.1007/s10867-021-09577-6
Noelle Driver, Michael Frame

Our goal is to match some dynamical aspects of biological systems with that of networks of coupled logistic maps. With these networks we generate sequences of iterates, convert them to symbol sequences by coarse-graining, and count the number of times combinations of symbols occur. Comparison of this with the number of times these combinations occur in experimental data—a sequence of interbeat intervals for example—is a measure of the fitness of each network to describe the target data. The most fit networks provide a cartoon that suggests a decomposition of the experimental data into a component that may be produced by a simple dynamical subsystem, and a residual component, the result of detailed, particular characteristics of the system that generated the target data. In the space of all network parameters, each point corresponds to a particular network. We construct a fitness landscape when we assign a fitness to each point. Because the parameters are distributed continuously over their ranges, and because fitnesses are estimated numerically, any plot of the landscape involves a finite sample of parameter values. We’ll investigate how the local landscape geometry changes when the array of sample parameters is refined, and use the landscape geometry to explore complex relations between local fitness maxima.

我们的目标是将生物系统的一些动力学方面与耦合逻辑映射网络的动力学方面相匹配。使用这些网络,我们生成迭代序列,通过粗粒度将它们转换为符号序列,并计算符号组合出现的次数。将其与这些组合在实验数据中出现的次数进行比较(例如,间隔序列),可以衡量每个网络描述目标数据的适应度。最合适的网络提供了一幅图,表明将实验数据分解为一个可能由简单的动态子系统产生的组件和一个残差组件,残差组件是产生目标数据的系统的详细、特定特征的结果。在所有网络参数的空间中,每个点对应一个特定的网络。当我们为每个点分配一个适应度时,我们构建了一个适应度景观。由于参数在其范围内连续分布,并且由于适应度是数值估计的,因此任何景观图都涉及参数值的有限样本。我们将研究当样本参数数组被细化时,局部景观几何是如何变化的,并利用景观几何来探索局部适应度最大值之间的复杂关系。
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引用次数: 0
Spontaneous circulation of active microtubules confined by optical traps 受光阱限制的活性微管的自发循环
IF 1.8 4区 生物学 Q3 Physics and Astronomy Pub Date : 2021-09-08 DOI: 10.1007/s10867-021-09578-5
Stephen E Martin, Matthew E Brunner, Joshua M Deutsch

We propose an experiment to demonstrate spontaneous ordering and symmetry breaking of kinesin-driven microtubules confined to an optical trap. Calculations involving the feasibility of such an experiment are first performed which analyze the power needed to confine microtubules and address heating concerns. We then present the results of first-principles simulations of active microtubules confined in such a trap and analyze the types of motion observed by the microtubules as well as the velocity of the surrounding fluid, both near the trap and in the far-field. We find three distinct phases characterized by breaking of distinct symmetries and also analyze the power spectrum of the angular momenta of polymers to further quantify the differences between these phases. Under the correct conditions, microtubules were found to spontaneously align with one another and circle the trap in one direction.

我们提出了一个实验来证明自发有序和对称破缺的驱动微管局限于光阱。首先进行了涉及这种实验可行性的计算,分析了限制微管和解决加热问题所需的功率。然后,我们提出了在这种陷阱中被限制的活性微管的第一性原理模拟的结果,并分析了微管观察到的运动类型以及周围流体的速度,无论是在陷阱附近还是在远场。我们发现了三种不同的相,其特征是打破了不同的对称性,并分析了聚合物角动量的功率谱,以进一步量化这些相之间的差异。在正确的条件下,发现微管自发地彼此排列,并在一个方向上环绕陷阱。
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引用次数: 0
A continuum mechanics model for the Fåhræus-Lindqvist effect f<s:1> æus- lindqvist效应的连续介质力学模型
IF 1.8 4区 生物学 Q3 Physics and Astronomy Pub Date : 2021-07-03 DOI: 10.1007/s10867-021-09575-8
Angiolo Farina, Fabio Rosso, Antonio Fasano

The decrease in apparent relative viscosity that occurs when blood is made to flow through a tube whose diameter is less than about 0.3 mm is a well-known and documented phenomenon in physiology, known as the Fåhræus-Lindqvist effect. However, since the historical work of Fåhræus and Lindqvist (Amer. J. Physiol. 96(3): pp. 562–568, 1931), the underlying physical mechanism has remained enigmatic. A widely accepted qualitative explanation was provided by Haynes (Amer. J. Physiol. 198, pp. 1193–1200, 1960) according to which blood flows in microvessels with a core-annulus structure, where the erythrocytes concentrate within a central core surrounded by a plasma layer. Although sustained by observations, this conjecture lacks a rigorous deduction from the basic principles of continuum dynamics. Moreover, relations aimed to reproduce the blood apparent relative viscosity, extensively used in micro-circulation, are all empirical and not derived from the analysis of the fluid mechanical phenomena involved. In this paper, we apply the recent results illustrated in Guadagni and Farina (Int. J. Nonlinear Mech. 126, p. 103587, 2020), with the purpose of showing that Haynes’ conjecture, slightly corrected to make it more realistic, can be proved and can be used to reach a sound explanation of the Fåhræus-Lindqvist effect based on continuum mechanics. We propose a theoretical model for the blood apparent relative viscosity which is validated by matching not only the original experimental data reported by Fåhræus and Lindqvist (Amer. J. Physiol. 96(3), pp. 562–568, 1931), but also those provided by several subsequent authors.

当血液流经直径小于0.3毫米的管道时,表观相对粘度会下降,这是生理学上众所周知的记录现象,称为f æus- lindqvist效应。然而,由于fastur æus和Lindqvist(美国)的历史工作。生理学报,96(3):pp. 562-568, 1931),潜在的物理机制仍然是谜。海恩斯(美国)提供了一个被广泛接受的定性解释。J. Physiol. 198, pp. 1193 - 1200,1960),血液在微血管中流动,具有核环结构,红细胞集中在被血浆层包围的中心核内。虽然这一猜想得到了观测结果的支持,但它缺乏从连续介质动力学基本原理的严格推导。此外,在微循环中广泛使用的旨在再现血液表观相对粘度的关系都是经验的,而不是从所涉及的流体力学现象的分析中得出的。在本文中,我们应用了Guadagni和Farina (Int)最近的研究结果。J.非线性力学,126,p. 103587, 2020),目的是证明Haynes的猜想可以被证明,并且可以用于基于连续介质力学对f æus- lindqvist效应进行合理的解释。我们提出了一个血液表观相对粘度的理论模型,该模型不仅通过匹配f h æus和Lindqvist (Amer)报告的原始实验数据进行了验证。J. Physiol. 96(3), pp. 562-568, 1931),以及后来几位作者提供的资料。
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引用次数: 10
Exciton transfer between LH1 antenna complex and photosynthetic reaction center dimer LH1天线复合物与光合反应中心二聚体之间的激子传递
IF 1.8 4区 生物学 Q3 Physics and Astronomy Pub Date : 2021-07-02 DOI: 10.1007/s10867-021-09576-7
Michal Pudlák, Richard Pinčák

The exciton transfer between light-harvesting complex 1(LH1) and photosynthetic reaction center dimer is investigated theoretically. We assume a ring shape structure of the LH1 complex with dimer in the ring centre. The kinetic equations which describe the energy transfer between the antenna complex and reaction center dimer were derived. It was shown that the dimer does not act as a photon trap. There is a weak localization of the exciton on the dimer and there is relatively rapid back exciton transfer from dimer to antenna complex which depends on the number of the pigment molecules in the antenna ring. The relation between the rates of the exciton transfer from the antenna complex to dimer and back transfer from dimer to antenna complex has been derived.

从理论上研究了光收集配合物1(LH1)与光合反应中心二聚体之间的激子转移。我们假设LH1配合物为环状结构,二聚体位于环中心。推导了天线配合物与反应中心二聚体之间能量传递的动力学方程。结果表明,二聚体不具有光子阱的作用。激子在二聚体上存在弱的局部化,而激子从二聚体向天线复合物的反向转移相对较快,这取决于天线环中色素分子的数量。推导了激子从天线配合物向二聚体的转移速率和从二聚体向天线配合物的反向转移速率之间的关系。
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引用次数: 1
Kinetic aspects of virus targeting by nanoparticles in vivo 纳米颗粒在体内靶向病毒的动力学方面
IF 1.8 4区 生物学 Q3 Physics and Astronomy Pub Date : 2021-06-02 DOI: 10.1007/s10867-021-09570-z
Vladimir P. Zhdanov

One of the suggested ways of the use of nanoparticles in virology implies their association with and subsequent deactivation of virions. The conditions determining the efficiency of this approach in vivo are now not clear. Herein, I propose the first kinetic model describing the corresponding processes and clarifying these conditions. My analysis indicates that nanoparticles can decrease concentration of infected cells by a factor of one order of magnitude, but this decrease itself (without feedback of the immune system) is insufficient for full eradication of infection. It can, however, induce delay in the progress of infection, and this delay can help to form sufficient feedback of the immune system.

在病毒学中使用纳米颗粒的建议方法之一意味着它们与病毒粒子的关联并随后使其失活。决定这种方法在体内效率的条件现在还不清楚。在此,我提出了第一个动力学模型,描述了相应的过程并澄清了这些条件。我的分析表明,纳米颗粒可以将感染细胞的浓度降低一个数量级,但这种降低本身(没有免疫系统的反馈)不足以完全根除感染。然而,它可以诱导感染进程的延迟,这种延迟可以帮助形成免疫系统的充分反馈。
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引用次数: 3
Interaction of chloramphenicol with titin I27 probed using single-molecule force spectroscopy 用单分子力谱法研究氯霉素与titin I27的相互作用
IF 1.8 4区 生物学 Q3 Physics and Astronomy Pub Date : 2021-06-01 DOI: 10.1007/s10867-021-09573-w
Jyoti Yadav, Yashwant Kumar, Gayathri S. Singaraju, Shivprasad Patil

Titin is a giant elastic protein which is responsible for passive muscle stiffness when muscle sarcomeres are stretched. Chloramphenicol, besides being a broad-spectrum antibiotic, also acts as a muscle relaxant. Therefore, it is important to study the interaction between titin I27 and chloramphenicol. We investigated the interaction of chloramphenicol with octamer of titin I27 using single-molecule force spectroscopy and fluorescence spectroscopy. The fluorescence data indicated that binding of chloramphenicol with I27 results in fluorescence quenching. Furthermore, it is observed that chloramphenicol binds to I27 at a particular concentration ((sim ) 40 μM). Single-molecule force spectroscopy shows that, in the presence of 40 μM chloramphenicol concentration, the I27 monomers become mechanically stable, resulting in an increment of the unfolding force. The stability was further confirmed by chemical denaturation experiments on monomers of I27, which corroborate the evidence for enhanced mechanical stability at 40 μM drug concentration. The free energy of stabilization for I27 (wild type) was found to be 1.95 ± 0.93 kcal/mole and I27 with 40 μM drug was 3.25 ± 0.63 kcal/mole. The results show a direct effect of the broad-spectrum antibiotic chloramphenicol on the passive elasticity of muscle protein titin. The I27 is stabilized both mechanically and chemically by chloramphenicol.

肌凝蛋白是一种巨大的弹性蛋白,当肌肉肌节被拉伸时,它负责被动肌肉僵硬。氯霉素除了是一种广谱抗生素外,还具有肌肉松弛剂的作用。因此,研究titin I27与氯霉素的相互作用具有重要意义。利用单分子力光谱和荧光光谱研究了氯霉素与titin I27八聚体的相互作用。荧光数据表明氯霉素与I27结合导致荧光猝灭。此外,我们观察到氯霉素在特定浓度((sim ) 40 μM)下与I27结合。单分子力谱分析结果表明,在40 μM氯霉素浓度下,I27单体力学稳定,展开力增大。通过I27单体的化学变性实验进一步证实了其稳定性,证实了在40 μM药物浓度下其机械稳定性得到增强。野生型I27的稳定自由能为1.95±0.93 kcal/mol, 40 μM药物I27的稳定自由能为3.25±0.63 kcal/mol。结果表明,广谱抗生素氯霉素对肌蛋白titin的被动弹性有直接影响。氯霉素在机械上和化学上都稳定了I27。
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引用次数: 0
Local hemodynamic analysis after coronary stent implantation based on Euler-Lagrange method 基于欧拉-拉格朗日方法的冠状动脉支架植入术后局部血流动力学分析
IF 1.8 4区 生物学 Q3 Physics and Astronomy Pub Date : 2021-05-27 DOI: 10.1007/s10867-021-09571-y
Yuchen Wang, Jingmei Zhan, Weiguo Bian, Xiaoli Tang, Min Zeng

Coronary stents are deployed to treat the coronary artery disease (CAD) by reopening stenotic regions in arteries to restore blood flow, but the risk of the in-stent restenosis (ISR) is high after stent implantation. One of the reasons is that stent implantation induces changes in local hemodynamic environment, so it is of vital importance to study the blood flow in stented arteries. Based on regarding the red blood cell (RBC) as a rigid solid particle and regarding the blood (including RBCs and plasma) as particle suspensions, a non-Newtonian particle suspensions model is proposed to simulate the realistic blood flow in this work. It considers the blood’s flow pattern and non-Newtonian characteristic, the blood cell-cell interactions, and the additional effects owing to the bi-concave shape and rotation of the RBC. Then, it is compared with other four common hemodynamic models (Newtonian single-phase flow model, Newtonian Eulerian two-phase flow model, non-Newtonian single-phase flow model, non-Newtonian Eulerian two-phase flow model), and the comparison results indicate that the models with the non-Newtonian characteristic are more suitable to describe the realistic blood flow. Afterwards, based on the non-Newtonian particle suspensions model, the local hemodynamic environment in stented arteries is investigated. The result shows that the stent strut protrusion into the flow stream would be likely to produce the flow stagnation zone. And the stent implantation can make the pressure gradient distribution uneven. Besides, the wall shear stress (WSS) of the region adjacent to every stent strut is lower than 0.5 Pa, and along the flow direction, the low-WSS zone near the strut behind is larger than that near the front strut. What’s more, in the regions near the struts in the proximal of the stent, the RBC particle stagnation zone is easy to be formed, and the erosion and deposition of RBCs are prone to occur. These hemodynamic analyses illustrate that the risk of ISR is high in the regions adjacent to the struts in the proximal and the distal ends of the stent when compared with struts in other positions of the stent. So the research can provide a suggestion on the stent design, which indicates that the strut structure in these positions of a stent should be optimized further.

冠状动脉支架是通过重新打开动脉狭窄区域以恢复血流来治疗冠状动脉疾病(CAD)的,但支架植入术后支架内再狭窄(ISR)的风险很高。其中一个原因是支架植入会引起局部血流动力学环境的改变,因此对支架内动脉血流的研究具有重要意义。在将红细胞(RBC)视为刚性固体颗粒,将血液(包括红细胞和血浆)视为颗粒悬浮液的基础上,提出了一个非牛顿粒子悬浮液模型来模拟真实的血流。它考虑了血液的流动模式和非牛顿特性,血细胞之间的相互作用,以及由于双凹形状和RBC的旋转而产生的额外影响。然后,将其与其他四种常用的血流动力学模型(牛顿单相流模型、牛顿欧拉两相流模型、非牛顿单相流模型、非牛顿欧拉两相流模型)进行比较,结果表明,具有非牛顿特性的模型更适合描述真实的血流。然后,基于非牛顿粒子悬浮液模型,研究了支架内局部血流动力学环境。结果表明,支架柱向流动中突出会产生流动停滞区。支架植入会使压力梯度分布不均匀。各支板相邻区域的壁面剪应力(WSS)均小于0.5 Pa,且沿流动方向,后支板附近的低剪应力区大于前支板附近的低剪应力区。此外,在支架近端支杆附近的区域,容易形成红细胞颗粒停滞区,容易发生红细胞的侵蚀和沉积。这些血流动力学分析表明,与支架其他位置的支撑物相比,支架近端和远端支撑物附近区域发生ISR的风险较高。因此,该研究可以为支架的设计提供建议,表明支架在这些位置的支撑结构需要进一步优化。
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引用次数: 5
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Journal of Biological Physics
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