自回归模型和基于数据处理分组法的非线性模型的比较研究

为信号建立非线性模型，既是非线性动力学（例如混沌理论）研究中关心的课题，也是信号处理及系统辨识的核心课题之一。由于实际生物系统总是有非线性的，因此建立非线性模型比线性模型更具普遍意义。数据处理的群集算法（ＧｒｏｕｐＭｅｔｈｏｄｏｆＤａｔａＨａｎｄｌｉｎｇ，ＧＭＤＨ）是根据给定数据建立非线性模型的有效方法。作者吸收人工神经网络中反传算法的思想，把ＧＭＤＨ算法进一步发展成自适应算法，使之可以随着数据的不断输入自动调整参数，以跟随数据统计特性的变化。作者还以心电数据为例进行了处理，结果证明其性能确实比线性的ＡＲ模型更优。     

驻极体促进药物透皮吸收的研究进展

近年来，经皮给药的促透方法和技术发展迅速，有关物理学、化学、药剂学的方法和技术的研究都很多。许多新方法和新技术的应用，使经皮给药系统逐渐成为一种成熟的给药方法。本文主要介绍驻极体透皮给药制剂的研究进展及其相关透皮机理。     

一种新的正交参数选优法及其在非线性回归分析中的应用

非线性回归分析是工程中经常采用的一种用来估计数学模型参数的方法，该方法能否顺利运用与参数初始值的选择有极大关系。本研究提出一种新的正交参数选优法——阻尼正交表法，它不仅可以保证非线性回归分析算法的顺利收敛，而且能够显著提高后者的收敛速度，进而极大改善非线性回归分析算法的应用性能。本研究的数值试验及心肌造影超声心动图定量分析应用实例表明，作为对传统正交参数选优法的一种改进，阻尼正交表法在科学与工程计算或信号与信息处理领域有着很好的应用前景。     

一种非线性呼吸力学模型及其参数估计

本文报道了一个非线性呼吸力学模型,该模型可以反映深呼吸过程中呼吸气体流率、跨肺压力及肺容积变化之间的动态关系。模型参数分别反映气道阻力状态及肺弹性特性。敏感度分析表明,该模型肺弹性参数估计值的准确度高于气道阻力。实验测定了10名被试者的呼吸气体流率、食道压力及肺容积。参数估计结果表明,动、静态肺弹性参数之间存在显著差异(P<0.01)。我们认为肺组织及肺泡表面活性物质的应力松驰机制是造成这种差异的主要原因。     

离体皮肤药物经皮渗透电穿孔技术的研究

经皮级药电穿孔技术是采用电穿孔脉冲作用在皮肤上,使产生可逆水性电孔道,以促进药物的经皮渗透速率的方法,由于以往研究所采用的均系高压脉冲,于实际应用上仍存在困难,本文根据根据脉冲冲量和经皮能量控制药物经皮渗透速率和分析安全性的基本原理,并据此原理设计了OX4-3经皮给药电穿孔仪,并应用此仪器进行了萘普生经皮渗透速率的实验研究。结果表明,电穿孔处理后的萘普生经皮渗透速率比被动渗透提高了近四倍,脉冲期皮肤阻抗约5kΩ。     

利用两种线性回归模型估计大连市1991-2008年流感相关超额死亡

目的 估计大连市1991-2008年流感相关超额死亡率,并比较两种模型估计结果.方法 收集大连市5个市辖区的死因监测数据、我国北方地区2003-2008年流感病原学监测数据,分别采用Serfling回归模型和负二项回归模型分年龄组估计流感相关超额死亡.结果 1991-2008年,大连市年均观察死亡率为605.2/105(538.1/105-658.6/105),其中呼吸及循环系统疾病死亡占47.2％.1991-1992至2002-2003年度,流感相关的呼吸及循环系统疾病年均超额死亡率为8.5/105 (4.2/105-12.8/105).2002-2003至2007-2008年度,Serfling回归模型估计流感相关的呼吸及循环系统疾病的年均超额死亡率为5.7/105 (2.3/105-9.0/105),负二项回归模型估计结果为5.6/105(1.7/105-27.7/105).结论 两种模型估计结果一致,表明模型的可靠性.大连市流感超额死亡平均水平较低,但≥65岁年龄组所占死亡比例仍维持在90％以上,老年人群仍然是流感防控和疫苗接种的优先人群.     

超声电导透皮给药与静脉给药后脑脊液及组织药物浓度相似

超声电导透皮给药是近年来国内外新兴的技术,临床广泛应用于内、外、妇、儿诸科疾病的治疗,它症状控制快,避免了全身用药的缺点,在较少的毒副作用下获得满意的疗效。我科应用超声电导靶向治疗仪和特制贴片进行了动物实验研究,旨在为超导给药的临床应用提供客观依据。1材料与方法1·1试药:水杨酸(北京化工厂,AR);头孢哌酮钠(白云山制药厂,批号0408051);头孢哌酮对照品,含量92·9%(中国药品生物制品鉴定所,420-9402);其他试剂均为分析纯。1·2仪器:Agilent1100型色谱仪。1·3动物与分组:家兔64只,平均体重(2·5±0·43)kg,随机分成2组,每组3…     

实体肿瘤药物输运与给药方式的集中参数模型及实验研究

目的研究不同给药方式对实体肿瘤抗癌药物疗效的影响,并通过动物实验验证。方法分别建立体内药代动力学和肿瘤内药物输运的集中参数模型,模拟单次快速注射和等时间间隔三次快速注射时肿瘤间质组织药物浓度Ct随时间的变化。实验小鼠分为两组,分别进行抗癌药羟基喜树碱(HCPT)单次快速注射和等时间间隔3次快速注射,观察其肿瘤内药物平均浓度。对数值模拟结果和动物实验结果进行比较。结果数值模拟结果显示,对于相同总量药物,等量等间隔的三次给药,肿瘤间质组织药物浓度Ct高于单次给药。动物实验的实测结果相同。结论3次给药的效果显著优于单次给药。集中参数模型基本能够定量反映不同给药方式的效果。     

2006年度中国基础研究十大新闻简介——发现一种可有效通过皮肤传送大分子药物的透皮短肽

通过皮肤给药对于像糖尿病这样需要多次重复给药的疾病具有独特的优点，其关键是如何使大分子药物能够有效透过皮肤进入循环系统。中国科技大学生命科学学院和合肥微尺度物质科学国家实验室（筹）温龙平研究组，将体内噬菌体展示技术应用于透皮研究，找到了一个由11个氨基酸组成的能高效帮助蛋白质类药物透皮的短肽（ACSSSPSKHCG）。     

应用Serfling回归模型估计北京市流行性感冒相关超额流感样病例数

目的 构建Serfling回归模型,估计北京市2007-2011年流行性感冒(简称流感)相关的超额流感样病例数.方法 使用“北京市医疗机构传染病监测预警系统”中二级以上医院流感样病例周数据,拟合Seffling回归模型,估计超额流感样病例数.结果 2007/2008、2008/2009、2009/2010和2010/2011年度各有6、3、19和8个流行周,包括有2007/2008年度第524周、2008/2009年度第51-1周、2009/2010年度第37-38周和第42-6周、2010/2011年度第48-3周.2007/2008、2008/2009、2009/2010和2010/2011年度流行周的超额流感样病例数分别为41905(95％ CI:21541～62265)、17936(95％ CI:7747～28124)、226150(95％ CI:162531 ～289768)和40083(95％ CI:13013～67154)人,占同期全部流感样病例数的44.75％ (95％ CI:23.00 ～ 66.49％)、37.93％ (95％ CI:16.38～58.47％)、50.01％ (95％ CI:35.94 ～64.08％)和27.89％ (95％ CI:8.05 ～46.73％).结论 应用本模型估算,北京市每年在流感季节性流行期间和大流行期间,流感病毒均可造成数万至数十万的超额流感样病例和超额门诊就诊量.     

药物肝清除一室扩散模型的参数估计

对药物肝清除一室扩散模型，给出了一组利用最小二乘法估计动力学参数的计算公式，并对流出肝脏的药物浓度关于时间变化的曲线形状进行了讨论。     

计算中国男性人体环节惯性参数的数学模型及其三元回归方程的研究

目的：确定计算中国男性青年人体惯性参数的数学模型。方法：采用CT－图像分析仪测算法,对50例中国男性样本（18－23岁）进行了全身CT横断层扫描,影像分析和测算,结果：设计了由15个环节组成的中国男性青年人体数学模型,并据此建立了以身高,体重,坐高／身高为自变量的直接计算中国男性青年人体惯性参数的三元回归方程,结论：为直接计算中国男性青年人体整体及各环节的质量,质心提供了可靠的手段。     

放射状角膜切开术预测系统中数学模型的建立

本文运用逐步回归方法建立放射状角膜切开术预测系统的非线性数学模型,分析各因素对手术效果的影响。该模型基于１０个参数,分别为：年龄、球镜、角膜屈光１（垂直方面屈光）、角膜屈光２（水平方向屈光）角膜周边厚度、角膜直径１（垂直方向直径）、角膜直径２（水平方向直径）、弹性眼差、视区、切口刀数,所要预测的值为角膜屈光改变值。应用医院提供的眼科病人手术两年后复查的数据,提取参数齐全的数据,剔除可疑数据,得到５２３组可用数据。用Ｃ语言编程对数据进行计算,分析各因素、各因素平方项及各因素间交互作用对角膜屈光改变值的影响,分别在显著性水平为0.25、0.1、0.05、0.01下进行显著性检验,得到两种不同结果,两个模型预测值与实际手术值的误差小于２Ｄ的百分比分别为９２.6５％和９１.４３％。     

计算中国女性青年人体惯性参数的数学模型及其回归方程

采用ＣＴ－图像分析仪测算法，对５０例女性样本（１８￣２３）进行扫描、分析和测算。获得了人体惯性数据及样本的体态参数，并设计了一个由１５个环节组成的中国女性青年人体数学模型，建立了以体重、射高、坐高与身高比为自变量的直接计算人体惯性参数的三元回归方程。     

急性心肌梗塞后心肌酶代谢动力学二房室模型的理论研究

急性心肌梗塞后心肌酶的动态变化是估计梗塞面积的方法之一，本文在口服给药的二房室药物动力学数学模型的基础上设计了新的数学模型用以拟合急性心肌梗塞后心肌酶的时间－活性曲线，可望能够准确计算心肌酶释放总量，较好地估计梗塞面积。     

THE USE OF A COMPUTER MODEL TO SIMULATE EPITHELIAL PATHOLOGIES

The complexity of the interactions of the many rules governing cell behaviour and the changes that lead to the pathological features seen in disease is such that linking cause and effect can be very difficult. However, the use of computers to model normal biological and pathological processes provides a powerful technique for studying the effects of the interactions of a variety of biological rules. Such an approach is strengthened by using a graphical display that simulates the organization of cells in a tissue. Skin, and specifically the epidermis, is characterized by a regular morphology and the ability to regenerate itself throughout adult life and there are considerable biological data available on the normal and pathological processes that affect this organ. A model of normal skin has been developed which shows a structure similar to normal epidermis and is capable of healing itself if damaged. This paper describes the effects on the overall structure of introducing mutations to individual rules in the model. Changes that alter cell proliferation or differentiation are introduced and the effects that these produce are compared with epidermal pathologies. Even a simple model is capable of producing insights into the types of events that may occur in a variety of dermatopathological conditions.     

A Novel System to Study the Impact of Epithelial Barriers on Cellular Metabolism

Medications introduced into the systematic circulation must be transported across biological barriers such as skin, gastrointestinal, or bronchial epithelia, which can alter their kinetic and metabolic profiles. It is, therefore, important to understand diffusion kinetics across barrier membranes when choosing a dosing regime that will elicit the greatest cellular response. An in vitro system that combines membrane transport studies with a downstream cell culture chamber has been developed. The system has been tested with skin and a small intestine model (Caco-2 cell monolayers) as barriers, the peroxovanadium compound [VO(O₂)₂ 1, 10 phenanthroline] bpV(phen), as the test chemical, Hep-G2 (liver) as the test cells, and glucose consumption as the test assay. Peroxovanadium has insulin mimetic properties and has been previously demonstrated to effectively lower blood glucose levels in diabetic rats when administered transdermally. A dose of 10 mM bpV(phen) placed on the skin epidermis with a continuous iontophoretic current of 0.5 mA/cm² for 4.5 h led to a net 22% increase in glucose consumption by Hep-G2 cells. The same dose of bpV(phen) passively diffusing across a Caco-2 cell monolayer led to an increase in glucose consumption by Hep-G2 cells of 23%. This system is highly versatile and can be used to study many other processes, involving a variety of biological membranes, cell types, chemicals and assays, making it a valuable research tool. © 2000 Biomedical Engineering Society. PAC00: 8716Uv, 8715Vv     

Determination of the release of PEG and HPMC from nelfilcon A daily disposable contact lenses using a novel in vitro eye model

Abstract

The traditional method to measure release of components from CLs is a vial containing a static volume of PBS (phosphate buffered saline). However, this model does not simulate physiologically relevant tear volume and natural tear flow, air exposure, and mechanical rubbing. These factors can significantly impact release kinetics. We have developed an in vitro eye model (OcuFlow) that simulates these parameters. The aim of the study was to measure the release of PEG (polyethylene glycol), and HPMC (hydroxypropyl methylcellulose) from a daily disposable hydrogel contact lens material (nelfilcon A; Dailies AquaComfort PLUS; DACP;) over 24?hrs using the OcuFlow platform. The elution of PEG and HPMC from DACP lenses was analyzed using LCMS (liquid chromatography mass spectrometry). The release of all wetting agents from the lenses followed a burst release pattern, which occurred within the first 1.5?hrs (P?<?0.05). The release of PEG was greater than that of HPMC (P?<?0.05). The amount of PEG and HPMC released at any given time was less than 1% of the amount in the blister pack solution. Our results suggest that HPMC and PEG are rapidly released from the CL.     

A novel animal model to evaluate the ability of a drug delivery system to promote the passage through the BBB

The purpose of this investigation was to explore the potentiality of a novel animal model to be used for the in vivo evaluation of the ability of a drug delivery system to promote the passage through the blood–brain barrier (BBB) and/or to improve the brain localization of a bioactive compound. A Tween 80^®-coated poly-l-lactid acid nanoparticles was used as a model of colloidal drug delivery system, able to trespass the BBB. Tacrine, administered in LiCl pre-treated rats, induces electrocorticographic seizures and delayed hippocampal damage. The toxic effects of tacrine-loaded poly-l-lactid acid nanoparticles (5 mg/kg), a saline solution of tacrine (5 mg/kg) and an empty colloidal nanoparticle suspension were compared following i.p. administration in LiCl-pre-treated Wistar rats. All the animals treated with tacrine-loaded nanoparticles showed an earlier outcome of CNS adverse symptoms, i.e. epileptic onset, with respect to those animals treated with the free compound (10 min vs. 22 min respectively). In addition, tacrine-loaded nanoparticles administration induced damage of neuronal cells in CA1 field of the hippocampus in all treated animals, while the saline solution of tacrine only in 60% of animals. Empty nanoparticles provided similar results to control (saline-treated) group of animals. In conclusion, the evaluation of time-to-onset of symptoms and the severity of neurodegenerative processes induced by the tacrine–lithium model of epilepsy in the rat, could be used to evaluate preliminarily the capability of a drug delivery system to trespass (or not) the BBB in vivo.