完全磁悬浮心室辅助装置的体外模拟循环系统实验研究

目的研究我国自主研发的第3代完全磁悬浮心室辅助装置(CH-VAD)对于心衰患者的循环辅助效果。方法建立一套体外模拟循环系统(mock circulatory system,MCS)。该系统能够模拟人体健康休息状态以及心力衰竭状态,并与CH-VAD协同工作,测试CH-VAD在连续流状态下的辅助效果。另外,对CH-VAD的搏动流控制方法进行测试,该模式采用正弦波速度波形,使CH-VAD的运行与MCS心室周期同步。结果 CH-VAD在正常连续流状态下能够使心衰状态的血流动力学参数(动脉压、心排量)恢复到正常范围。初步的搏动流测试结果显示,当前的速度搏动幅值对血流动力学影响较小,搏动流状态下与连续流状态所对应的平均动脉压、动脉脉压、平均心排量与心排量波形等差异不大。结论 CH-VAD能够通过搏动控制器产生一定程度的速度搏动,提供足够的心室辅助,并可以进一步改良优化,提供符合生理条件的搏动血流。所研制的MCS能够提供心室辅助装置以及其他机械循环辅助装置一个有效、可控的体外测试平台,是机械循环辅助装置设计、优化和验证的重要工具。     

用于心室辅助装置血流动力学性能评价的体外模拟循环系统技术进展

体外模拟循环系统(mock circulatory systems,MCS)是一个模拟人体循环系统血流动力学状态的试验平台,被广泛用于心室辅助装置和人工瓣膜等心血管人工器官的体外性能评价和生机电系统中的血流动力学响应研究。通过调整模拟心脏的驱动元件和模拟血管系统的集中参数元件,MCS可以模拟人体健康、运动、心力衰竭等不同生理状态的血流动力学特性。自1960年代至今,MCS研发目标从满足最基本的心室辅助装置或机械瓣膜的系统性能评价要求,已发展到能够复现局部重要器官的血流动力学状态。总结MCS目前的设计原则、系统搭建以及研究进展和未来展望。     

纳米机器人给药装置

正近日,以色列巴伊兰大学开发一种纳米机器人给药装置,该装置只是在病患者需要时给药,可以缓解病情,降低药物的副作用。当精神分裂症患者突然发病,开始狂躁不安时,由脑电波能推动体内的纳米机器人释放镇定药物使病情得到缓解。这种方式给药,药物对病人的副作用降到最小。该纳米机器人利用DNA折纸技术制成,结构简     

聚羟基脂肪酸酯和聚酰胺-胺树状高分子构筑的经皮给药系统

背景:聚羟基脂肪酸化合物具有黏着性及与药物分子混合、分散的特性,可作为体外给药剂型的基质;树状高分子具有独特的物理、化学性质,能够作为药物的载体。目的:将聚羟基脂肪酸化合物与聚酰胺-胺树状高分子混合,构筑能够促进难溶型药物的透皮的经皮给药系统。方法:将恶臭假单胞菌KT2442在含有NH4Cl的培养基中30℃培养72 h,然后在培养体系中添加5 g/L辛烷酸培养24 h,用氯仿抽提聚羟基脂肪酸化合物。各取10 mg聚羟基脂肪酸化合物基质与含聚酰胺-胺与苯乙胺树状高分子的聚羟基脂肪酸化合物基质,分别与5 mg磺酰胺衍生物Tamsulosin混合,构建经皮给药系统;同时构建体外渗透研究装置,研究基质促进药物渗透的效果。X射线衍射分析Tamsulosin、聚羟基脂肪酸化合物基质、基质聚羟基脂肪酸化合物-Tamsulosin及含聚酰胺-胺树状高分子聚羟基脂肪酸化合物基质-Tamsulosin的内部原子空间分布状况。结果与结论:聚羟基脂肪酸化合物及聚羟基脂肪酸化合物与聚酰胺-胺树状高分子的混合物都能作为经皮给药的基质,促进难溶药物的透皮作用;并且在相同的条件下,聚羟基脂肪酸化合物与聚酰胺-胺树状高分子的混合物作为基质的经皮给药系统能够满足药物的临床血药浓度。聚羟基脂肪酸化合物与聚酰胺-胺树状高分子的混合物能够使模型药物很好地晶体化并呈现高度有序的方向性。     

碘[131I]-美妥昔单抗注射液的人体药代动力学研究

研究碘[131I]-美妥昔单抗注射液的人体药代动力学特征,为临床给药方案及临床应用提供依据。将按纳入标准、排除标准和剔除标准选择的患原发性肝细胞肝癌受试者24例平均分为低、中、高剂量组,各组每位受试者经插管注入相应的注射液,分别在不同时刻采集静脉血及收集尿液,测定样品的放射性计数率(min-1);采用纸层析确定各血样血清中药物的比例,依此校正各血样中药物的放射性计数率;用DASver1.0(Drug And Statistics for Windows)药代动力学程序拟合、计算血液药代动力学参数;鉴定尿液中放射性物质的组成,计算各时间段尿液放射性占注入剂量的百分率(%ID),以分析注射液在尿液的清除动力学特点。研究表明:该注射液血液药代动力学符合动力学二室模型,其在人体内分解代谢产物主要以游离131I的形式通过肾脏排泄,注入后120h内排出尿液的放射性占注入剂量的47.70%~51.16%。因此,该注射液的药代动力学特征满足临床要求,推荐临床的给药剂量为每kg人体27.75MBq注射液。     

一种新型可降解缓释微系统的优化设计

多腔体的微型可降解高分子聚合物药物缓释系统是一种新型给药技术,其载体结构是利用MEMS工艺的制备特点,结合药物释放的要求和高分子聚合物生物降解特性进行设计的.为了达到该系统在体内长期释药的性能,对释药载体的结构进行参数优化十分必要.文中建立了具有多腔体的微型可降解高分子聚合物给药载体的释药模型以及载体的结构优化模型,仿真及优化结果表明该模型可以用来指导基于可降解材料的结构优化设计.     

脉冲电磁场辅助骨细胞培养装置的研制

目的 根据脉冲电磁场对骨细胞的作用机制,设计了能够产生均匀磁场、参数可调的脉冲电磁场发生装置和磁场作用板;叙述了实验装置的硬件构成、软件控制功能以及磁场作用板的设计,并通过试验测试,观察记录了在未加入磁性材料和加入磁性材料后磁场的分布情况.方法 设计了强度为4～6 mT、频率8 Hz的参数可调的脉冲电磁场发生装置和专用的适合细胞培养的磁场作用装置,并对产生的磁场进行了实验测定.结果 实验装置运行时,对各参数检测表明,实验装置满足设计的要求:在加入磁性材料后,磁场作用表面的磁场分布均匀.结论 实验装置满足设计要求,可为进一步进行骨细胞培养提供可靠的实验手段.     

简箭毒碱自动给药系统数学模型的建立

在外科麻醉中,希望肌松诱导期短,同时术后肌肉麻痹消失迅速。按此种要求,所给予的肌松药物剂量,应为取得合适效应下的最小量。自动反馈给药系统,根据病人对药物的反应,自动调整所给剂量,以期满足上述要求。在该系统中,反映剂量和效应之间动力学关系的数学模型,是设计反馈回路的基础。本文根据给药的过程中,病人大拇指内收肌对刺激尺神经和正中神经的四个一组脉冲的反应率(T_4率),建立相应的数学模型。 1、数学模型_1根据药效动力学研究,筒箭毒     

青光眼药物跨角膜输运数学模型及特性分析

为研究青光眼药物跨角膜输运特性,首先,通过实验结果修正了基于菲克第二定律的药物输运数学模型,验证了数学模型的可行性。其次,通过对数学模型的求解,分析了眼表给药浓度恒定、眼药膏以及受泪液清除作用的眼药水3种给药方式对药物进入眼球前房输运通量以及累积量的影响。结果表明,提高扩散系数可以缩短药物累积从非稳态阶段进入伪稳态阶段的时间,提高药物累积量;给出了不同给药方式下药物累积规律和后两种给药方式下药物进入眼球前房药物输运通量达到峰值的时间及峰值量。此结果可为建立更加完善的青光眼药物输运数学模型及青光眼药物设计提供理论分析基础。     

一种用于偏瘫患者的减重多态康复训练评定系统的设计

设计一台减重式多态康复训练评定系统,通过具有倾斜功能的训练床来实现人体不同程度的减重,通过主控计算机控制驱动装置来实现患者在减重状态下进行下肢主动屈伸和被动屈伸的运动训练,并能对主动运动和被动运动状态下的足底压力、运动参数以及静态平衡参数进行测试和统计分析。对45名健康受试者进行测试,静态平衡各参数的组内相关系数(ICC)均大于0.7,说明该系统具有良好的可靠性。结果表明,该系统可为临床制定康复治疗方案提供科学数据,具有重要的临床应用价值。     

方波激励的生物电阻抗谱自动测试系统

目的为解决多频率方波自动测量生物电阻抗谱的问题,本文设计了一个方波激励的生物电阻抗谱自动测试系统。方法将任意波形函数发生器、仪表放大器和采集卡以及PC组成电阻抗谱自动测试系统,利用PC中的Labview程序分别控制函数发生器和采集卡自动完成激励的产生和数据采集,并将采集到的数据自动保存在PC中,最后利用Matlab程序对数据进行快速傅里叶变换得到阻抗谱。首先对阻抗网络模型进行阻抗谱的仿真,将仿真得到的阻抗谱和理论计算得到的阻抗谱对比;再分别使用此系统和阻抗分析仪对阻抗网络模型进行阻抗测量,将测试得到的阻抗谱进行曲线拟合得到元件值,根据元件值比较测试误差。最后,使用方波激励和稳态正弦激励对酵母细胞悬浮液进行阻抗测量,根据酵母细胞悬浮液的阻抗谱计算介电谱,将得到的介电谱和参考文献中的介电谱作比较,并比较两种激励的测量时间。结果仿真得到的阻抗谱和理论计算得到的阻抗谱一致,验证了方波激励的可行性。测试系统对阻抗网络模型的测试结果和阻抗分析仪的相比误差小于10%,验证了测试系统的正确性。使用方波激励和稳态正弦激励测试酵母细胞悬浮液的阻抗谱,转换成介电谱后,发现其变化规律和参考文献所得结果相符。在100Hz^2MHz的测试范围内,方波激励的测量时间为0.9s,稳态正弦激励的测试时间为1.7s,方波激励的测试速度快。结论本文设计的方波激励的生物电阻抗谱自动测试系统具有自动测试生物阻抗谱的能力,由于使用方波激励,可以兼顾速度和信噪比的要求,实现了计算机控制,可根据实际情况调整激励信号的参数,具有很强的灵活性和可扩展性。     

往复式电磁铁驱动搏动式血泵的可行性研究

目的为了得到更适合血液循环的动力装置,提出一种用于体外膜肺氧合(extracorporeal membrane oxygenation,ECMO)系统由电磁铁驱动的搏动式血泵,并研究其可行性。方法首先利用电磁原理设计出电磁驱动机构,主要部件包括对称的两个电磁铁和压簧,两个电磁铁交替通电下使得动铁芯往复运动;利用容积控制原理,泵腔在动铁芯的驱动下收缩舒张;然后根据上述原理设计出血泵模型,包括电磁驱动部件和泵腔;最后建立包括血泵、电路控制部分、示波器、加速度传感器、输入输出管路和储液池的试验台,对血泵模型进行驱动力和流量输出测试。结果血泵模型在通电电压7～12 V时动铁芯的初始驱动力为2. 97～8. 00 N。血泵模型产生的初始驱动力与工作电压呈正相关非线性关系,当通入电压12 V时血泵模型初始驱动力满足要求。当前压与后压为0、频率80次/min、工作电压7～12 V时的流量输出为0. 97～3. 81 L/min。当前压与后压为0,工作电压12 V、频率60～90次/min时的流量输出为3. 1～3. 8 L/min。当工作电压12 V、频率80次/min、前压0～40 cm H2O和后压50～110 cm H2O时的流量输出为0. 55～3. 59 L/min。血泵流量与工作电压和频率呈正相关,与后压呈负相关,与前压无显著性相关。结论往复式电磁铁驱动搏动式血泵基本满足ECMO临床要求,具有广泛的应用前景,对体外循环血泵的发展具有重要意义,但仍需进一步研究和改进。     

帕金森病冻结步态的实时监测系统

目的由于帕金森病冻结步态的突发性,临床上对其进行评估存在一定困难,为此本文研究了一种用于实时监测冻结步态的系统。方法该系统由可穿戴设备和配套的APP两部分构成,其中设备通过惯性传感器和超声波传感器采集患者腿部运动的加速度和抬脚高度数据,并传输至APP软件中,通过软件中的冻结步态识别模型进行分析。系统为构建冻结步态识别模型,首先通过实验采集12位患者的运动数据,然后经过信号预处理、特征提取和机器学习算法训练出模型,最后通过对数据集采用十折交叉验证来评估模型的准确度和精确度。结果系统对冻结步态的识别准确率可达98.6%,精确率达97.2%。结论该系统能够实时监测帕金森病患者日常生活中的冻结步态发作情况,为医生的诊疗提供定量、可靠的参考依据。     

血清TK-1、SE-CAD表达及联合HE4、CEA、CYFRA21-1检测在非小细胞肺癌诊断中的意义

目的探讨可溶性E-钙黏蛋白(soluble E-cadherin,SE-CAD)、胸苷激酶-1(thymidine kinase 1,TK-1)在非小细胞肺癌(NSCLC)患者血清中的水平,并分析其与附睾蛋白4(HE4)、癌胚抗原(CEA)、细胞角蛋白19片段(CYFRA21-1)联合检测在NSCLC诊断中的临床应用价值。方法收集本院2016年1月至2018年1月期间初诊NSCLC患者86例、小细胞肺癌患者45例、同期良性疾病患者42例、同期初诊其他恶性肿瘤(除肺癌外)患者30例、健康受试者的血清标本40例,应用液态芯片技术对受试者血清标本进行CEA、CYFRA21-1水平检测,ELISA方法检测SE-CAD、TK-1、HE4。结果①非小细胞肺癌患者血清中SE-CAD水平明显高于良性对照组、正常对照组( P <0.05),差异具有统计学意义,但与小细胞肺癌组及其他恶性肿瘤组比较差异无统计学意义( P >0.05);②非小细胞肺癌组患者血清 TK1 与CYFRA21-1水平明显高于良性对照组、小细胞肺癌组、其他恶性肿瘤组和健康对照组,差异均有统计学意义(均 P <0.05)。③单项检测时,CYFRA21-1对非小细胞肺癌的诊断灵敏度最高,为87.2%,TK-1的诊断特异性最高。5种肿瘤标志物联合检测,灵敏度高达93.2%,特异性有所降低为85.7%。结论 SE-CAD、TK1 与CYFRA21-1均可作为鉴别良恶性肿瘤的检验指标,联合HE4、CEA、CYFRA21-1等指标对非小细胞肺癌诊断的灵敏度远高于单项检测。     

Identification of WU polyomavirus from pediatric patients with acute respiratory infections in Beijing, China

A novel polyomavirus (WU virus) has been identified in pediatric patients with acute respiratory tract infections (ARI), but its role as a respiratory pathogen has not yet been demonstrated. To investigate if WU virus is related to acute respiratory infections in infants and children in Beijing, specimens collected from 674 pediatric patients with ARI from April 2007 to May 2008 and from 202 children without ARI were used for this investigation. Common respiratory viruses were tested by virus isolation and/or antigen detection by indirect immunofluorescent assay followed by RT-PCR or PCR for other viruses associated with respiratory infections in specimens collected from patients with ARI before WU virus DNA was detected. WU virus DNA was detected by initial screening and secondary confirmation PCR for all specimens. The region encoding the VP2 gene of the virus was amplified from 17 WU-virus-positive clinical specimens, and sequence analysis was performed. Thirty-eight of 674 (5.6%) specimens from patients with ARI and 3 of 202 (1.5%) specimens from children without ARI yielded PCR products with the predicted molecular weight, using either screening or confirmation primer sets, indicating that these specimens were WU virus positive. However, more than 60% of the 38 WU-virus-positive specimens from patients with ARI were also positive for one or more respiratory viruses. The nucleotide and deduced amino acid sequences of the region encoding the VP2 gene from 17 Beijing WU viruses shared high homology (>98.5%) with sequences from GenBank and among themselves. The data indicated that WU virus in Beijing occurred 3.7 times more frequently in pediatric patients with ARI than in those without ARI (p < 0.05).     

WU and KI polyomavirus infections in Filipino children with lower respiratory tract disease

BackgroundWU and KI are human polyomaviruses initially detected in the respiratory tract, whose clinical significance remains uncertain.ObjectivesTo determine the epidemiology, viral load and clinical characteristics of WU and KI polyomaviruses.Study designWe tested respiratory specimens collected during a randomized, placebo-controlled pneumococcal conjugate vaccine trial and related epidemiological study in the Philippines. We analyzed 1077 nasal washes from patients aged 6 weeks to 5 years who developed lower respiratory tract illness using quantitative real-time PCR for WU and KI. We collected data regarding presenting symptoms, signs, radiographic findings, laboratory data and coinfection.ResultsThe prevalence and co-infection rates for WU were 5.3% and 74% respectively and 4.2% and 84% respectively for KI. Higher KI viral loads were observed in patients with severe or very severe pneumonia, those presenting with chest indrawing, hypoxia without wheeze, convulsions, and with KI monoinfection compared with co-infection. There was no significant association between viral load and clinical presentation for WU.ConclusionsThese findings suggest a potential pathogenic role for KI, and that there is an association between KI viral load and illness severity.     

骨折患者血清25-羟基维生素D和甲状旁腺素水平与骨密度的相关性

目的探究骨折患者血清25-羟基维生素D(250HD)和甲状旁腺素(PTH)水平与骨密度的相关性。方法选择2015年12月至2017年12月于我院骨科住院治疗的110例骨折患者作为研究对象,所有患者均行骨密度检查,根据骨密度T值将患者分为正常组、骨质减少组、骨质疏松组。测定骨质疏松四项标志物即血清250HD、PTH、血清1型胶原氨基端前肽(PINP)、β胶原降解产物(β-CTX)水平。结果正常组各部位骨密度值显著高于骨量减少组、骨质疏松组(P<0.05);骨量减少组各部位骨密度值显著高于骨质疏松组,差异具有统计学意义(P <0.05);骨量正常患者血清250HD显著高于骨量减少、骨质疏松组(P <0. 05);血清PINP、PTH水平均显著低于骨量减少、骨质疏松组(P <0. 05);相关性分析示骨质疏松患者血清250HD与腰椎1-4、全髓关节及股骨颈骨密度值呈正相关关系(P<0. 05)。结论骨质疏松患者血清中250HD明显下降,与患者骨密度呈正相关,PTH水平虽在骨质疏松患者中明显上升,但其与骨密度无相关性。     

Detection and discrimination of WU/KI polyomaviruses by real-time PCR with melting curve analysis

WU and KI polyomaviruses are novel viruses of the Polyomaviridae family, which have been identified recently in respiratory secretions from patients with acute respiratory tract infection. Their potential role in respiratory disease is still unclear and requires additional investigation. To facilitate further studies and diagnosis, a real-time PCR with melting curve analysis was optimized and evaluated to detect WU and KI polyomaviruses. Primers specific for the VP1 gene were designed from regions conserved among WU and KI polyomaviruses which provided amplification products of 198 and 231bp corresponding to WU and KI, respectively and thus yielded a difference in melting temperature (T(m)) between WU and KI polyomaviruses. The assay proved highly specific for WU and KI polyomaviruses as no cross amplification was detected with other respiratory viruses or human genomic DNA. The assay was also highly sensitive with a detection limit as low as 10copies/muL for both WU and KI polyomaviruses. The performance of the real-time PCR assay was evaluated in terms of amplification efficiency (92%). Finally, the assay was validated using DNA extracted from clinical respiratory specimens for WU and KI polyomaviruses and the results were confirmed by direct nucleotide sequencing. The results obtained by melting curve analysis were in perfect agreement with nucleotide sequencing. In conclusion, this method is advantageous because it is rapid, specific, sensitive, reproducible, accurate, cost-effective and thus, would be feasible and attractive for large-scale analysis aimed at investigating the clinical role of WU and KI polyomaviruses.     

Prevalence and molecular characterization of WU/KI polyomaviruses isolated from pediatric patients with respiratory disease in Thailand

WU and KI polyomaviruses represent novel viruses discovered in respiratory secretions from human patients with acute respiratory tract infection. However, the association between WU/KI polyomaviruses and human disease has remained unclear. In this study, the prevalence of these two novel viruses and occurrence of co-infection with other respiratory viruses were determined in Thai pediatric patients with respiratory disease. Previously described PCR assays were applied to detect WU/KI polyomaviruses as well as other respiratory viruses in 302 nasopharyngeal suction specimens collected from February 2006 through February 2007. The results revealed the anneal prevalence of WU and KI polyomaviruses in the Thai population was 6.29% and 1.99%, respectively. The frequency of co-detection of WU and KI polyomaviruses with other respiratory viral pathogens was 42.11% and 33.33%, respectively. Moreover, each of the two complete genome sequences of WU (CU_295 and CU_302) and KI (CU_255 and CU_258) polyomaviruses were genetically and phylogenetically characterized. Sequence analysis showed that they contained features common to those found in previous studies. However, there were several nucleotide variations within the non-coding regulatory regions and various non-synonymous mutations within the coding regions which may influence virulence and pathogenesis of these viruses. Nevertheless, it is still possible that these viruses are not the causative agents of clinical respiratory disease. Therefore, judging the association of WU/KI polyomavirus infections with a particular disease will be challenging and require more comprehensive case control investigations.     

WU polyomavirus in children with acute lower respiratory tract infections, China.

BACKGROUND: WU polyomavirus (WUPyV), a new member of the genus of Polyomavirus in the family Polyomaviridae, has been found and associated with respiratory tract infections recently. However, its clinical role and pathogenicity has not been known. OBJECTIVES: To confirm that WU polyomavirus has been found in Chinese children. STUDY DESIGN: WU polyomavirus was detected and identified using PCR methods. A total of 278 specimens of nasopharyngeal aspirate were collected, and then PCR products were sequenced directly. RESULTS: One of 278 nasopharyngeal aspirates was positive for WUPyV in one child, and the positive rate was 0.4%. The results showed that the sequences of genome, LTAg and VP2 gene was identical to the reference sequences of WU polyomavirus prototype strains. CONCLUSIONS: We confirmed that WU polyomavirus had been found and identified in the respiratory secretions in China.