黏附于血管壁表面的白细胞在稳定剪切流动下发生变形的生物力学模型

白细胞与血管表面的黏附是重要的生物医学工程问题，引起了学者们的广泛研究。我们用复合液滴来模拟黏附于血管表面的白细胞，根据二维计算流体动力方法研究了流体切应力作用下白细胞黏附引起的压力分布。同时，通过引入“变形指数”的概念，研究稳定剪切流动下白细胞变形的生物力学特性，数值结果表明：（1）随着初始接触角，毛细血管数，外界流场雷诺数的增大，细胞的变形也增大，而细胞浆比细胞核更易于变形，表明细胞核更能耐受切流动；（2）当切应力增大到一定值时，细胞不能进一步变形，变形指数达到峰值；（3）压力分布曲线表明，在细胞的下游形成一个高压区，提供促使细胞受力达到平衡的升力，从而阻止了细胞的进一步变形，我们关于细胞核变形的结果有助于理解白细胞如何将外界流体作用力（如切应力）等力学信号向核内转导的生物力学机理。     

螺旋型种植牙受力角度对骨界面应力分布影响的三维有限元分析

为了探讨受力角度对螺旋型种植牙周骨界面应力分布规律的影响，本实验采用三维有限元方法，在相同载荷不同受力角度时，对单个螺旋型种植牙骨界面的应力分布特点进行了比较分析。结果表明：种植牙受力角度的增加，主要对种植牙颈周密质骨影响明显，受力角度越大，应力就越大。颈部应力与种植牙受力角度成正比。颈部位移运动随种植牙受力角度的增加而增加。侧向载荷时，以水平向危害最大。     

螺旋型种植牙受力角度对骨界面应力分布影响的三维有限元分析

为了探讨受力角度对螺旋型种植牙周骨界面应力分布规律的影响，本实验采用三维有限元方法，在相同载荷不同受力角度时，对单个螺旋型种植牙骨界面的应力分布特点进行了比较分析。结果表明：种植牙受力角度的增加，主要对种植牙颈周密质骨影响明显，受力角度越大，应力就越大。颈部应力与种植牙受力角度成正比。颈部位移运动随种植牙受力角度的增加而增加。侧向载荷时，以水平向危害最大。     

椎动脉狭窄临床病例介入治疗前后椎基底动脉血流状况分析

目的:基于血液和弹性血管壁相互作用的流固耦合方法,探究1例椎动脉颅内段狭窄的临床病例支架植入前后椎基底动脉的血流动力学特性。方法:应用医学建模软件对二维CT数据进行三维重建,得到支架植入前后的椎基底动脉血管模型,采用流固耦合方法对支架植入前后的椎基底动脉血流特性进行数值模拟,分析椎基底动脉的血流动力学特性。结果:支架植入前后椎基底动脉的血液流场、血液压力、血管壁面切应力以及管壁形变量有显著的变化。在支架植入后,基底动脉中间部位两侧受力变得均匀,椎基底动脉内血流速度明显增大,支架植入处压力增大,支架上游压力和支架处切应力减小。结论:在介入治疗后,椎基底动脉内的血流环境及受力情况得到明显改善,当椎动脉发生狭窄后应及时干预治疗,避免累及基底动脉和后循环系统。     

下肢截肢水平对主动脉血流动力学影响的数值研究EI北大核心CSCD

已有研究发现,下肢截肢患者心血管疾病发病率显著高于正常人,但少有学者从血流动力学角度研究下肢截肢与心血管疾病之间的关系。本文采用数值仿真,通过改变外周阻抗和电容模拟不同截肢水平,研究截肢对主动脉血流动力学环境的影响。结果发现,截肢后主动脉血压升高,肾下腹主动脉时均壁面切应力降低,且左右侧壁振荡剪切指数呈不对称分布;截肢侧髂动脉时均壁面切应力降低且振荡剪切指数增大;同时随截肢水平提高,上述变化更加显著,增加了截肢者患动脉粥样硬化与腹主动脉瘤的风险。本文初步揭示了下肢截肢对心血管疾病的影响规律,为截肢后康复训练设计与心血管疾病治疗方案优化提供理论指导。     

二维静态及稳态冲刷24h后内皮细胞表面切应力分布的数值模拟

本文对静态及经过平均切应力τavg=12dyn/cm2 的流体稳态冲刷 2 4h后 ,内皮细胞 (EC)表面的切应力分布进行了有限差分方法的数值模拟。结果表明 :单个EC表面切应力分布是不均匀的 ,静态EC表面切应力的最大值为平均切应力的 1.8倍 ,最小值趋于零 ;经 2 4h稳态冲刷后 ,EC表面切应力的最大值为平均切应力的 1.3倍 ,最小值为 0 .8倍 ,应力分布明显均匀化。单个EC的R(高 /长 )值对切应力及切应力梯度分布有很重要的影响 ,切应力值随R的增加几乎呈线性增长     

基于三维医学影像的脑动脉瘤内血液流动的数值模拟

目的 利用数值模拟研究具有病人特异性的脑动脉瘤内的血液流动,为脑动脉瘤的破裂风险的评价和动脉瘤介入栓塞后复发风险的评价提供帮助。方法 从两例脑动脉瘤病人的3D-RA数据中重建动脉瘤几何模型,血液流变学模型选择假塑性非牛顿流体模型,利用商用CFD软件Fluent对两例动脉瘤内的血液流动进行数值模拟。结果 数值模拟给出了动脉瘤内的流线图、重要截面上的速度分布图、壁面上的切应力分布和压力分布图。并且绘制了在收缩期时刻动脉瘤颈部和瘤顶部各20个点上的壁面切应力和压力的变化情况。结论 血流动力学因素如流速、压力、壁面切应力、流动对壁面的冲击状况等因素与动脉瘤的生长和破裂密切相关,而由于脑动脉瘤形态各异、载瘤动脉与动脉瘤体的几何关系复杂,所以具有病人特异性的数值模拟对于研究动脉瘤破裂和复发风险具有重要价值。动脉瘤颈部的壁面切应力和壁面切应力的波动的变化规律并不相同,需要进一步研究壁面切应力的波动与脑动脉瘤生长与破裂之间的定量关系。     

心室辅助下切应力对红细胞形态的影响

目的心室辅助是晚期心衰最有效的治疗方法之一。但是,心室辅助装置产生的高流体切应力会对红细胞造成损伤。目前,大多数研究仅利用心室辅助装置造成的溶血值评价其对血液的损伤程度,却忽略了对还未破裂的红细胞受到损伤的关注。本文重点探究流体切应力所造成的红细胞形态的变化。方法首先,利用数值计算软件FLUENT,采用拉格朗日离散模型计算出心室辅助装置在一个心动周期内作用于红细胞的流体切应力曲线;然后,根据数值计算得出的切应力范围,对不同切应力下和不同暴露时间下的血液样本进行实验,并设立无受力对照组减小实验误差;最后,以实验后血样的游离血红蛋白含量作为判断血样溶血情况参数,并以血涂片中非常态红细胞的数量占总体的百分比作为衡量红细胞受损伤但未破裂状态的参数。结果非常态红细胞数目和切应力的相关系数是0.725,P=0.027(0.05)。实验结果显示,血泵产生切应力会导致非常态红细胞出现,并且暴露时间一定,非常态红细胞数目随着切应力增大而增大。结论在心室辅助下,血泵流场除了会产生溶血这一极端现象,同时也会导致非常态红细胞数量的增多,降低血液质量,影响人体血液功能。     

囊式充液抗荷服过载响应特性仿真研究

目的高性能战机飞行时会产生很高的过载加速度,导致人体血液聚集在下肢和足部,不能回流到上肢和大脑,造成飞行员黑视、呼吸障碍以及丧失意识等。目前通常采用充气式抗荷服对抗过载造成的生理障碍,但使用充气式抗荷服操作复杂且反应延迟,会使飞行员产生疲劳。为解决充气抗荷服的这些问题,一种具有快速冲压效果的新型充液抗荷服已被提出。为研究充液抗荷服的过载响应特性,本文以囊式充液抗荷服为例,建立了人体下肢有限元模型,对不同充液水平、不同过载下的肌肉和服装进行了数值仿真研究。方法首先通过ABAQUS有限元软件进行建模,再将不同静水压模拟不同过载并通过改变充液管管腔厚度模拟不同充液水平,最后计算囊式充液抗荷服在不同过载、不同充液水平作用下的体表压力、肌肉变形等生理和物理参数变化情况。结果 (1)肌肉体表压力随过载增加而增大;(2)肌肉体表压力随充液量增加而减小;(3)服装最大应力和最大变形量随过载增加和充液水平增加而增大。结论应当寻找合适的充液水平,保证体表压力和服装应力在不同过载下均处于较合适的水平,从而保证囊式充液抗荷服的设计更为有效、安全。     

血管狭窄下游流场边壁压力分布的模型实验和数值模拟

针对低切应力不能完全解释狭窄下游流场内病变和病变严重程度分布的规律，本研究在已经建立的狭窄体外流体力学特性实验研究模型上，对流体力学的另一重要因素——压力进行检测，结合数值模拟的方法对其分布及分布变化规律进行深入研究。结果显示：模型实验检测和数值模拟计算结果一致性良好；狭窄下游流场出现显著的压力下降。低压力的分布区域与心血管狭窄病变的分布区域及其严重程度之间有高度的相似。研究提示：数值模拟计算可应用于微观流场的流体力学特性研究；狭窄下游流场低压力的分布和变化可能是低切应力之外导致局部血管边壁损伤的又一重要流体力学因素。     

The mechanism of outer membrane penetration by the eubacterial flagellum and implications for spirochete evolution

The rod component of the bacterial flagellum polymerizes from the inner membrane across the periplasmic space and stops at a length of 25 nm at the outer membrane. Bushing structures, the P- and L-rings, polymerize around the distal rod and form a pore in the outer membrane. The flagellar hook structure is then added to the distal rod growing outside the cell. Hook polymerization stops after the rod-hook structure reaches approximately 80 nm in length. This study describes mutants in the distal rod protein FlgG that fail to terminate rod growth. The mutant FlgG subunits continue to polymerize close to the length of the normal rod-hook structure of 80 nm. These filamentous rod structures have multiple P-rings and fail to form the L-ring pore at the outer membrane. The flagella grow within the periplasm similar to spirochete flagella. This provides a simple method to evolve intracellular flagella as in spirochetes. The mechanism that couples rod growth termination to the ring assembly and outer membrane penetration exemplifies the importance of stopping points in the construction of a complex macromolecular machine that facilitate efficient coupling to the next step in the assembly pathway.     

胃肠吻合钉织构表面对细胞外液流速与剪切力的影响

目的 研究胃肠微环境中的吻合钉表面微织构的几何参数变化对细胞外液流速与壁面处剪切力的影响规律,为吻合钉织构化表面对细胞黏附的促进作用提供理论依据。 方法 将吻合钉表面微织构结构引入到平板流动腔底面,应用 ANSYS Fluent 建立平板流动腔的二维模型并进行网格划分,研究不同高度、边长、间距参数的织构化底面的平板流动腔中细胞外液流速与壁面处剪切力数值,并对数据进行处理分析。 结果 吻合钉表面微织构的引入增强了平板流动腔内细胞外液的流速,且合适的微织构几何参数的引入可以增大微织构微脊处的壁面处剪切力。 微凹坑内的细胞外液流速较低且会形成漩涡,微织构高度、间距的增加以及边长的减小可以增强微凹坑内漩涡的强度。 结论 通过控制微织构的参数可以改变细胞外液流速与壁面处剪切力,进而促进细胞的黏附。     

Mechanotransduction of flow-induced shear stress by endothelial glycocalyx fibers is torque determined

To test the hypothesis that the mechanotransduction of flow-induced shear stress on endothelial cells (ECs) might be triggered by the total torque transmitted from the glycocalyx fibers to the ECs rather than by the total shear force acting directly on the membrane of ECs, we formulated the arterial wall as a five-layer model and numerically investigated the effect of two types of damages to the endothelial glycocalyx layer (EGL) on the flow in the EGL and on the drag force and bending moment acting on the glycocalyx fibers. One type of damage was to alter the thickness of the EGL, and the other was to damage its integrity. The results revealed that almost all amount of the shear stress acting on ECs was transmitted to the cells by the EGL and that the flow-induced shear stress acting directly on the cell membrane was negligibly small. In addition, the total force transmitted from the glycocalyx fibers to the cell membrane in the forms of drag force was hardly affected by the damages to the EGL. However, such damages could significantly influence the total torque at the roots of the EGL fibers. In conclusion, the mechanotransduction of shear stress by the EGL might be torque determined rather than force determined.     

Multi-digit coordination during lifting a horizontally oriented object: synergies control with referent configurations

We explored digit coordination during the acceleration phase of a quick lifting movement of a hand-held horizontal object. We tested three hypotheses related to: (1) the scaling of mechanical variables produced by the hand with changes in the external load, torque, and moment of inertia; (2) changes in the safety margin for the thumb with both the loading conditions and acceleration; and (3) changes in the indices of synergies. The subjects held a horizontal handle with a prismatic grasp (the thumb acted on top of the handle) and performed series of “very quick” lifting movements to a visual target. Multi-digit synergies were quantified as co-variation indices among elemental variables (forces and moments produced by individual digits). The resultant force scaled with the external load but not torque, while the grip force scaled with the external torque but not load. The safety margin dropped with an increase in acceleration; it also showed changes with the external torque and moment of inertia. Total moment of force was primarily produced by the tangential forces (over 80 %) across all movement phases and loading conditions. The index and little fingers produced close to zero moment with their normal forces, while the middle and ring fingers produced consistent moments due to the reproducible shifts of their centers of pressure. Synergy indices at the upper level of the assumed hierarchy (the task is shared between the thumb and virtual finger—an imagined digit with the action equal to that of the four fingers combined) did not drop with acceleration for the three force vector components and one of the moment vector components. They did drop with acceleration at the lower level (virtual finger action is shared among the four fingers). There was a trade-off between synergy indices computed at the two levels for the three force vector components, but not for the moment of force components. We confirmed specialization of different fingers with respect to different task components in quick manipulation tasks. The findings have implications for hypotheses on the control of voluntary movements involving redundant sets of effectors. Within the referent configuration hypothesis, components of a referent configuration may be adjusted to task mechanical characteristics using simple scaling rules. The neural organization of multi-digit synergies in a hierarchal system is able to selectively protect synergies related to stabilization of some performance variables from detrimental effects of the rate of change of those variables. A large number of apparently redundant elemental variables are not the source of additional computational problems but may be beneficial, allowing the central nervous system to facilitate synergies at both levels of the hierarchy.     

不同槽沟方向舌侧托槽转矩控制性能三维有限元分析

目的分析不同槽沟方向的舌侧托槽转矩控制性能以及不同弓丝尺寸、材质对其转矩的影响规律。方法建立上颌前牙垂直槽沟及水平槽沟舌侧托槽、3种材质(不锈钢弓丝、β钛丝、镍钛丝)、2种尺寸(0.43 mm×0.56 mm、0.41 mm×0.56 mm)弓丝的有限元模型,对左上颌中切牙施以±20°的转矩加载,分析对比其力学性能。结果随着弓丝弹性模量的增大,不同槽沟方向的舌侧托槽转矩力矩逐渐增大;槽沟方向对舌侧托槽的转矩性能有影响,但小于弓丝尺寸及材质变化带来的影响。相同转矩角度下,垂直槽沟舌侧托槽产生约为水平槽沟舌侧托槽1~2倍的转矩力。弓丝尺寸对两种托槽转矩控制的影响小于弓丝材质,两者协同变化影响最大。结论槽沟方向、弓丝尺寸、材质改变均能影响舌侧托槽转矩控制性能。临床应用中,可以根据所需转矩力大小,对舌侧托槽槽沟方向及弓丝尺寸、材质组合进行选择。     

More than a marine propeller – the flagellum of the probiotic Escherichia coli strain Nissle 1917 is the major adhesin mediating binding to human mucus

The flagellum of the probiotic Escherichia coli strain Nissle 1917 (EcN) is not just responsible for motility, but also for EcN's ability to induce the production of human β-defensin 2. Here, we report a third function of this EcN organell. In this study we investigated the role of the EcN flagellum in adhesion to different host tissues by ex vivo and in vitro studies. Ex vivo studies with cryosections of human gut biopsies revealed that the flagellum of EcN is most likely important for efficient adhesion to the human intestinal tract. These results and in vitro studies with different epithelial cells indicated that the presence of mucus is important for efficient mediation of adhesion by the flagellum of EcN. We observed direct interaction between isolated flagella from EcN wild type and porcine mucin 2 as well as human mucus. However, we could not observe any interaction of the flagella with murine mucus. For the first time, we identified the mucus component gluconate as one receptor for the binding of flagella from EcN and were able to exclude the flagellin domain D3 as a responsible interaction partner. We propose that the flagellum of EcN is its major adhesin in vivo, which enables this probiotic strain to compete efficiently for binding sites on host tissue with several bacterial pathogens.     

New infectious spirochete isolated from short-tailed shrews and white-footed mice.

A spirochete with two periplasmic flagella was isolated from the blood or tissues of spleens and kidneys from short-tailed shrews (Blarina brevicauda) and white-footed mice (Peromyscus leucopus) in Connecticut and Minnesota. After inoculation, the shrew-mouse spirochete infected Swiss mice and Syrian hamsters. This spirochete is morphologically and serologically distinct from the species of Treponema, Borrelia, Leptospira, and Spirochaeta examined.     

Maintenance of rat head direction cell firing during locomotion in the vertical plane

Previous studies have identified a subset of neurons in the rat anterodorsal thalamus (ADN) that encode head direction (HD) in absolute space and may be involved in navigation. These HD cells discharge selectively when the rat points its head in a specific direction (the preferred firing direction) in the horizontal plane. HD cells are typically recorded during free movement about a single horizontal surface. The current experiment examined how HD cell firing was influenced by 1) locomotion in the vertical plane and 2) locomotion on two different horizontal surfaces separated in height. Rats were trained in a cylindrical enclosure containing a single polarizing cue card attached to the cylinder wall, covering approximately 100 degrees of arc. The enclosure contained two horizontal surfaces: the cylinder floor and an annulus around the cylinder top 76 cm above the floor. A 90 degrees vertical mesh ladder that could be affixed at any angular position on the cylinder wall allowed the rats to locomote back and forth between the two horizontal surfaces. Rats were trained to retrieve food pellets on the cylinder floor as well as climb the mesh ladder to retrieve food pellets on the annulus. HD cell activity was monitored as the rat traversed the horizontal and vertical surfaces of the apparatus. When the angular position of the mesh corresponded to the cell's preferred firing direction, the HD cells maintained their peak discharge rate as the rat climbed up the mesh, but did not fire when the rat climbed down the mesh. In contrast, when the mesh was positioned 180 degrees opposite the preferred firing direction, HD cells did not fire when the rat climbed up the mesh, but exhibited maximal firing when the rat climbed down the mesh. When the mesh was placed 90 or 270 degrees from the preferred firing direction, HD cells exhibited background firing rates during climbing up or down the mesh. While preferred firing directions were maintained between the two horizontal surfaces, peak firing rate increased significantly (approximately 30%) on the annulus as compared with the cylinder floor. These data demonstrate that HD cells continue to discharge in the vertical plane if the vertical locomotion began with the rat's orientation corresponding to the preferred firing direction. One model consistent with these data are that HD cells define the horizontal reference frame as the animal's plane of locomotion. Further, we propose that HD cell firing, as viewed within a three-dimensional coordinate system, can be characterized as the surface of a hemitorus.     

Prehension synergies: trial-to-trial variability and principle of superposition during static prehension in three dimensions

We performed three-dimensional analysis of the conjoint changes of digit forces during prehension (prehension synergies) and tested applicability of the principle of superposition to three-dimensional tasks. Subjects performed 25 trials at statically holding a handle instrumented with six-component force/moment sensors under seven external torque conditions; -0.70, -0.47, -0.23, 0.00, 0.23, 0.47, and 0.70 Nm about a horizontal axis in the plane passing through the centers of all five digit force sensors (the grasp plane). The total weight of the system was always 10.24 N. The trial-to-trial variability of the forces produced by the thumb and the virtual finger (an imagined finger producing the same mechanical effects as all 4 finger forces and moments combined) increased in all three dimensions with the external torque magnitude. The sets of force and moment variables associated with the moment production about the vertical axis in the grasp plane and the axis orthogonal to the grasp plane consisted of two noncorrelated subsets each; one subset of variables was related to the control of grasping forces (grasp control) and the other sassociated with the control of the orientation of the hand-held object (torque control). The variables associated with the moment production about the horizontal axis in the grasp plane did not include the grip force (the normal thumb and virtual finger forces) and showed more complex noncorrelated subsets. We conclude that the principle of superposition is valid for the prehension in three dimensions. The observed high correlations among forces and moments associated with the control of object orientation could be explained by chain effects, the sequences of cause-effect relations necessitated by mechanical constraints.     

Isolation of the Outer Sheath of Leptospira and Its Immunogenic Properties in Hamsters

Spherical forms of Leptospira interrogans serotype canicola Hond Utrecht IV were induced with 1 m NaCl. Electron micrographs of these salt-altered cells (SAC) revealed that the outer envelope or sheath had pulled away from the protoplasmic cylinder. Treatment of SAC with 0.02% sodium lauryl sulfate solubilized the sheath and released the protoplasmic cylinder. Further processing of the solubilized sheath yielded a pellet which displayed a membrane structure in electron micrographs. The released protoplasmic cylinder showed loss of intracellular organization and the outer envelope present in normal cells. Immunization of hamsters with whole formalized cells, SAC, or sheath in doses as low as 10 μg/animal protected them from death upon challenge with virulent canicola 27.