桡骨远端骨折锁定钢板刚度的拓扑优化研究

目的对桡骨远端骨折锁定钢板结构进行优化设计,以应对骨折内固定个性化刚度需求。方法运用三维建模和计算机辅助设计软件完成桡骨远端骨折模型和常规钢板的模型构建,基于初始有限元分析结果,以轴向刚度下调33.33%且保留扭转刚度的90.00%以上作为优化目标,对常规钢板进行拓扑优化和重设计;通过有限元分析计算,对比常规钢板和优化钢板在轴向压缩和扭转工况下的内固定刚度和产生的骨折区应变。结果所获得的优化钢板轴向刚度为636.5 N/mm,下调幅度为19.7%,基本接近既定的目标刚度,优化后的扭转刚度为634.12 Nmm/°,下调幅度为8.8%,并未超出既定的目标限值;而骨折区应变变化方面,轴向应变相比切向应变呈现出更为显著的增加趋势,与刚度调控效果基本一致。结论通过拓扑优化的方法从钢板结构层面进行重设计,可实现骨折愈合的个性化内固定刚度调控。     

Growing Neural Gas approach for obtaining homogeneous maps by restricting the insertion of new nodes

The Growing Neural Gas model is used widely in artificial neural networks. However, its application is limited in some contexts by the proliferation of nodes in dense areas of the input space. In this study, we introduce some modifications to address this problem by imposing three restrictions on the insertion of new nodes. Each restriction aims to maintain the homogeneous values of selected criteria. One criterion is related to the square error of classification and an alternative approach is proposed for avoiding additional computational costs. Three parameters are added that allow the regulation of the restriction criteria. The resulting algorithm allows models to be obtained that suit specific needs by specifying meaningful parameters.     

下颌角缺损修复钛板构型的拓扑优化研究

目的 为下颌骨缺损修复植入体的构型设计提供优化方法和基本构型。方法 使用基于密度法的拓扑优化算法,针对下颌角缺损的修复体钛板进行拓扑优化计算。结果 通过比较和分析体积分数F和惩罚因子p对优化构型的影响,最终选择F=0.65和p=3.5作为优化的参数组合。用此参数组合对下颌角缺损修复体进行优化计算,认为3孔构型是其基本优化构型。同时发现,对同一构型,磨牙咬合较前牙咬合对植入体应力分布影响更显著。结论 获得了一套适用于下颌骨修复植入体构型优化的参数和方法,得到了优化后的钛板基本构型,可为临床下颌缺损修复体的设计提供借鉴。     

Topologically defined composites of collagen types I and V as in vitro cell culture scaffolds

Cell fate is known to be triggered by cues from the extracellular matrix, including its chemical, biological and physical characteristics. Specifically, mechanical and topological properties are increasingly recognized as important signals. The aim of this work was to provide an easily accessible biomimetic in vitro platform of topologically defined collagen I matrices to dissect cell behaviour under various conditions in vitro. We reconstituted covalently bound layers of three-dimensional (3-D) networks of collagen type I and collagen type V with a defined network topology. A new erosion algorithm enabled us to analyse the mean pore diameter and fibril content, while the mean fibril diameter was examined by an autocorrelation method. Different concentrations and ratios of collagen I and V resulted in pore diameters from 2.4 to 4.5 μm and fibril diameters from 0.6 to 0.8 μm. A comparison of telopeptide intact collagen I to telopeptide deficient collagen I revealed obvious differences in network structure. The good correlation of the topological data to measurements of network stiffness as well as invasion of human dermal fibroblasts proves that the topological analysis provides meaningful measures of the functional characteristics of the reconstituted 3-D collagen matrices.     

椎体结构及其生长过程模拟

目前,关于骨自优化,或称自适应的定量描述,只有线性的骨再造速率方程,用它与有限元相结合去预测骨结构,仅限于在实测骨的外部几何形状基础上,预测其内部组织结构.至于骨的外部几何形状的模拟预测未见报道.本文的目的是利用骨自优化理论完成椎体的外部几何形状、内部组织结构及生长过程的模拟.采用了一种新的高阶非线性骨再造速率方程与有限元相结合,引入工程拓扑优化思想,从不确定的外形出发进行模拟;并且实测了人第三腰椎椎体冠状面的外部几何形状及内部组织结构.预测的结果在外部几何形状和内部组织结构上与实测相一致.外形上老年期比年轻期椎体具有更向内凹的腰鼓形,小梁骨主要沿主应力即垂直方向排列,只不过,老年期更疏松.是否可以说,采用这种自优化方程与有限元相结合,引入拓扑优化思想,不但能模拟预测骨的外部几何形状和内部组织结构,而且可以模拟其生长过程.尤其值得强调的是实现了外部几何形状的模拟,只有这样才能得以实现生长过程的模拟预测.     

拓扑优化技术在骨科植入物创新设计的应用进展

得益于近年来增材制造技术（又称3D打印技术）的迅速发展,有别于传统规格化骨科植入物,制造内外部结构复杂的新型植入物成为可能。有限元分析方法一直以来都是骨科植入物创新设计极具价值的研究手段之一,并具有高效率、低成本、可靠性高等特点,而在此基础上进一步延伸的拓扑优化技术因其在非参数结构优化中的广泛应用,现已从结构工程领域逐渐被拓展到定制化骨科植入物的设计中,初步显示出其巨大的应用价值。本文综述了拓扑优化技术在骨科植入物领域的应用和发展过程,特别对其在脊柱、关节和创伤骨科器械设计中的应用现状进行了详细的论述。最后,总结现有技术的局限性,展望了拓扑优化在定制化骨科植入物研究领域的发展趋势。     

Tyrosine hydroxylase expression within Balb/C and C57Black/6 mouse locus coeruleus. I. Topological organization and phenotypic plasticity of the enzyme-containing cell population

Tyrosine hydroxylase phenotype expression was investigated in the catecholaminergic population of the locus coeruleus neurons of two pure inbred mouse strains, Balb/C and C57Black/6. Therefore, we have characterized the precise organization of tyrosine hydroxylase-expressing perikarya population, in control animals and following RU24722 treatment, which is known to induce tyrosine hydroxylase expression. Serial coronal sections were selected along the caudo-rostral extent of the structure and were processed for tyrosine hydroxylase immunocytochemistry. Three days after the treatment, an increase in the number of cells which expressed tyrosine hydroxylase was observed all along the locus coeruleus in the Balb/C strain only. This increase equalized the catecholaminergic neuron populations of the two strains. In the caudal subdivision of the structure, these newly detected perikarya were intermingled with the perikarya which expressed tyrosine hydroxylase in control conditions. In the rostral half, the additional immnunoreactive perikarya enlarged the mean coerulean space, defined as the area delimited by the tyrosine hydroxylase-containing perikarya. These results demonstrate a plasticity of the tyrosine hydroxylase phenotype expression, topologically organized and specific to the Balb/C strain.     

Characterizing and optimizing human anticancer drug targets based on topological properties in the context of biological pathways

One of the challenging problems in drug discovery is to identify the novel targets for drugs. Most of the traditional methods for drug targets optimization focused on identifying the particular families of “druggable targets”, but ignored their topological properties based on the biological pathways. In this study, we characterized the topological properties of human anticancer drug targets (ADTs) in the context of biological pathways. We found that the ADTs tended to present the following seven topological properties: influence the number of the pathways related to cancer, be localized at the start or end of the pathways, interact with cancer related genes, exhibit higher connectivity, vulnerability, betweenness, and closeness than other genes. We first ranked ADTs based on their topological property values respectively, then fused them into one global-rank using the joint cumulative distribution of an N-dimensional order statistic to optimize human ADTs. We applied the optimization method to 13 anticancer drugs, respectively. Results demonstrated that over 70% of known ADTs were ranked in the top 20%. Furthermore, the performance for mercaptopurine was significant: 6 known targets (ADSL, GMPR2, GMPR, HPRT1, AMPD3, AMPD2) were ranked in the top 15 and other four out of the top 15 (MAT2A, CDKN1A, AREG, JUN) have the potentialities to become new targets for cancer therapy.     

Studies on the topology of the renal type II NaPi-cotransporter

 The rat type II sodium/phosphate cotransporter (NaPi-2) is a 85- to 90-kDa glycosylated protein located at the proximal tubular brush border membrane. Hydropathy predictions suggest eight transmembrane domains (sTM) with a large glycosylated loop between sTM 3 and sTM 4. We have studied the membrane topology of NaPi-2 expressed in oocytes. A 33-amino-acid fragment containing the FLAG epitope was inserted into seven loops connecting the sTMs and into the NH₂- and COOH-ends of the protein. FLAG-antibody binding suggested that the loops connecting sTM 1 and sTM 2 as well as sTM 3 and sTM 4 are located extracellularly. Based on the lack of FLAG-antibody binding we suggest intracellular locations for the NH₂- and COOH-termini and the region connecting sTM 4 and sTM 5. Immunoprecipitation studies of in vitro translated protein also suggest that the NH₂-terminus is sited extracellularly. In immunohistochemical studies with NaPi-2-transfected MDCK cells, an interaction with NH₂- and COOH- terminal antipeptide antibodies could only be obtained after membrane permeabilization. The presented data are an experimental documentation of the intracellular location of the NH₂- and COOH-termini, and of the extracellular location of extracellular loops 1 and 2. Received: 30 November 1998 / Received after revision: 19 January 1999 / Accepted: 20 January 1999     

蝶骨卵圆孔的形态学特征及临床意义

目的 探讨蝶骨卵圆孔的局部解剖特点,为相关手术提供形态学参数。方法 15例（30侧）成人颅骨干性标本,进行蝶骨卵圆孔区的形态学观察和测量。2例（4侧）成人颅骨湿标本,观察卵圆孔区组织结构对应关系。结果 卵圆孔呈标准卵圆形25侧（83.33%）,圆形3侧（10.00%）,裂隙状2侧（6.67%）。左侧卵圆孔前后长度（3.64±0.96）mm,内外宽度（6.72±0.41）mm;右侧卵圆孔前后长度（3.38 ±0.74）mm,内外宽度（7.26±0.38）mm。结论 蝶骨卵圆孔的形态变化不一,术前充分了解卵圆孔解剖学特征,有利于各种穿刺术中的准确定位,提高手术成功率。