Hydrasys-hyrys电泳系统在血清蛋白电泳中的应用评价

目的：探讨Hydrasys-hyrys电泳系统在血清蛋白电泳中的应用。方法：利用Hydrasys-hyrys(Sebia)全自动电泳系统进行血清蛋白琼脂糖凝胶电泳(AGE)，并与常规的醋酸纤维膜电泳(CAE)比较。结果：AGE法批内精密度(CV)为0．90％(白蛋白)至4．61％(β-球蛋白)之间。总精密度(CV)为3．42％(白蛋白)和7．65％(β-球蛋白)之间，较CAE法显示较好的精密度。AGE法还显示出独特的区带扫描特征。结论：Hydrasys-hyrys(Sebia)全自动电泳系统可显示独特的区带扫描特征，具有自动化程度高、高精密度、省时省力的优势。     

High-throughput single strand conformation polymorphism mutation detection by automated capillary array electrophoresis: validation of the method

Capillary array electrophoresis (CAE) is a novel technique, which allows for high throughput analysis of DNA fragments. When screening for mutations in whole populations or large patient groups it is necessary to have robust and well-characterized setups for high throughput analysis. For large-scale mutation screening, we have developed procedures for single strand conformation polymorphism (SSCP) assays using CAE (CAE-SSCP) whereby we may increase both the sensitivity and the throughput compared to conventional SSCP analysis. In this study we have validated CAE-SSCP by 1) comparing detection by slab-gel based SSCP with CAE-SSCP of mutations in the MYH7, MYL2, and MYL3 genes encoding sarcomere proteins from patients suffering from hypertrophic cardiomyopathy; and 2) by constructing a series of 185 mutants having substitution mutations, as well as insertion/deletion mutations, or some combinations of these, in different sequence contexts in four exons and different positions relative to the end of the amplicon (three from the KCNQ1 gene, encoding a cardiac potassium channel, and one from the TNNI3 gene encoding cardiac troponin I). The method identified 181 out of 185 mutations (98%), and the data suggest that the position of mutation in the fragment had no effect on the sensitivity. Analysis of the specificity of the method showed that only very few mutants could not be distinguished from each other and there were no false positives.     

CAD/CAE of Jaipur foot for standardized and contemporary manufacturing

Abstract

Objective: Despite immense popularity of Jaipur foot as low cost prosthetic, not much work has been reported on its design for manufacturing standardization. Without manufacturing standardization, it cannot be mass produced using contemporary manufacturing technologies. The objective of this work is to carry out its computer aided design (CAD) followed by computer aided engineering (CAE) based on the material properties obtained from the previous work [1 Rachel HT, Kristine MF, Benjamin BW, et al. Assessment of the compressive and tensile mechanical properties of materials used in the Jaipur foot prosthesis. Prosthet Orthot Int. 2018;42:511–517.[Crossref], [PubMed], [Web of Science ®] , [Google Scholar]] of the authors. This may lead to the possible use of modern manufacturing processes for the Jaipur foot design.

Design: After modelling using CAD tool including its organic surfaces, the designed foot was analysed using a CAE tool for balanced standing load conditions to determine maximum stresses and deformation in its various parts. The bending analysis was done to check the dorsiflexion movement so that the strained sections could be identified for more reliable and durable prosthetic foot. For the static load analysis, base of the foot was constrained and 300–500 N load was applied through the bolt whereas for bending, the part near the bolt was fixed and pressure was applied at junction of front foot and toes.

Results: The results show that the maximum stress and deformation occur at the bolt, while the skin undergoes maximum strain. CAE analysis also proves the robustness of the Jaipur foot design and a well manufactured Jaipur foot as per standardized design should be able to withstand the real life conditions without failure. The CAD model is also used for FDM based printing for a nonfunctional prototype of Jaipur foot.

• Implications for rehabilitation

• The results of this study will serve as an important guideline for further research regarding equivalent material replacement, material optimization and obtaining an optimized design after studying the foot for dynamic analysis.

     

Driving GDNF expression: the green and the red traffic lights

Glial cell line-derived neurotrophic factor (GDNF) is widely recognized as a potent survival factor for dopaminergic neurons of the nigrostriatal pathway that degenerate in Parkinson's disease (PD). In animal models of PD, GDNF delivery to the striatum or the substantia nigra protects dopaminergic neurons against subsequent toxin-induced injury and rescues previously damaged neurons, promoting recovery of the motor function. Thus, GDNF was proposed as a potential therapy to PD aimed at slowing down, halting or reversing neurodegeneration, an issue addressed in previous reviews. However, the use of GDNF as a therapeutic agent for PD is hampered by the difficulty in delivering it to the brain. Another potential strategy is to stimulate the endogenous expression of GDNF, but in order to do that we need to understand how GDNF expression is regulated. The aim of this review is to do a comprehensive analysis of the state of the art on the control of endogenous GDNF expression in the nervous system, focusing mainly on the nigrostriatal pathway. We address the control of GDNF expression during development, in the adult brain and after injury, and how damaged neurons signal glial cells to up-regulate GDNF. Pharmacological agents or natural molecules that increase GDNF expression and show neuroprotective activity in animal models of PD are reviewed. We also provide an integrated overview of the signalling pathways linking receptors for these molecules to the induction of GDNF gene, which might also become targets for neuroprotective therapies in PD.     

三维成像与计算机辅助软件在单侧牙槽突裂的应用进展

牙槽突裂植骨术是牙槽突裂修复的金标准,随着唇腭裂患者及其家属对牙列美观度要求的提升,该手术在唇腭裂序列治疗中日益受重视,而精确并快速地测量术前牙槽突缺损体积、协助外科手术及评估术后移植骨组织吸收率,是目前牙槽突裂植骨术研究的热点及难点。三维CT是骨组织评估的可靠检查工具,已有实验对单侧牙槽突裂植骨术前后的三维图像进行研究分析。计算机辅助工程(CAE)技术逐渐用于协助三维图像的测量与评估。通过阐述近年来三维成像与计算机辅助软件在牙槽突裂的研究及应用,归纳总结牙槽突裂治疗中,三维成像与传统二维成像的优缺点及计算机辅助软件在单侧牙槽突裂中的应用。     

Subhepatotoxic exposure to arsenic enhances lipopolysaccharide-induced liver injury in mice

Exposure to arsenic via drinking water is a serious health concern in the US. Whereas studies have identified arsenic alone as an independent risk factor for liver disease, concentrations of arsenic required to damage this organ are generally higher than found in the US water supply. The purpose of the current study was to test the hypothesis that arsenic (at subhepatotoxic doses) may also sensitize the liver to a second hepatotoxin. To test this hypothesis, the effect of chronic exposure to arsenic on liver damage caused by acute lipopolysaccharide (LPS) was determined in mice. Male C57Bl/6J mice (4-6 weeks) were exposed to arsenic (49 ppm as sodium arsenite in drinking water). After 7 months of exposure, animals were injected with LPS (10 mg/kg i.p.) and sacrificed 24 h later. Arsenic alone caused no overt hepatotoxicity, as determined by plasma enzymes and histology. In contrast, arsenic exposure dramatically enhanced liver damage caused by LPS, increasing the number and size of necroinflammatory foci. This effect of arsenic was coupled with increases in indices of oxidative stress (4-HNE adducts, depletion of GSH and methionine pools). The number of apoptotic (TUNEL) hepatocytes was similar in the LPS and arsenic/LPS groups. In contrast, arsenic pre-exposure blunted the increase in proliferating (PCNA) hepatocytes caused by LPS; this change in the balance between cell death and proliferation was coupled with a robust loss of liver weight in the arsenic/LPS compared to the LPS alone group. The impairment of proliferation after LPS caused by arsenic was also coupled with alterations in the expression of key mediators of cell cycle progression (p27, p21, CDK6 and Cyclin D1). Taken together, these results suggest that arsenic, at doses that are not overtly hepatotoxic per se, significantly enhances LPS-induced liver injury. These results further suggest that arsenic levels in the drinking water may be a risk modifier for the development of chronic liver diseases.     

Management of Coronary Artery Aneurysms

Aneurysmal dilation of coronary arteries is observed in up to 5% of patients undergoing coronary angiography. Due to their poorly elucidated underlying mechanisms, their variable presentations, and the lack of largescale outcome data on their various treatment modalities, coronary artery aneurysms and coronary ectasia pose a challenge to the managing clinician. This paper aims to provide a succinct review of aneurysmal coronary disease, with a special emphasis on the challenges associated with its interventional treatment.     

CEA-McAbs的制备及其与肿瘤组织的反应性

本文用常规杂交瘤技术,制备了FB_(12)、DA_1,FD_3、FD_4、D_3、TE_7及TC_(10)七株CEA-McAbs。并将它们对各种来源的肿瘤组织进行ABC酶标染色,结果肠癌组织的CEA含量比肠外肿瘤的高,在组织中染色范围更广。间接免疫荧光技术证实结肠癌建株细胞HR8348及HCI与CEA-McAbs反应性良好,提示这组CEA-McAbs是特异针对CEA抗原的,因而有一定临床价值。还运用免疫组化方法研究这七株CEA-McAbs与CEA抗原表位的作用特征,并将McAbs分为与不同表位作用的三个组。     

Voltage-gated calcium channels in the etiopathogenesis and treatment of absence epilepsy

Voltage-gated calcium channels are key elements in regulating neuronal excitability and are thus of central importance in the pathogenesis of various forms of epilepsies. Among these, absence epilepsies represent about 10% of epileptic seizures in humans. They are electroencephalographically characterized by bilateral synchronous spike-wave discharge activity associated with loss or severe impairment of consciousness. Extensive studies during the last decades revealed that pathophysiologically increased oscillatory activity, i.e., hyperoscillation within the reticulothalamocortical circuitry, is the electrophysiological correlate of absence epilepsy, with extrathalamocortical structures, e.g., brainstem and cerebellum, projecting to the thalamocortical circuitry, thereby modulating its activity. Voltage-gated calcium channels are one of the central players regulating the transition from tonic to rebound burst-firing modes in both thalamic relay and reticular thalamic nucleus neurons, the burst-firing mode being the substrate of the thalamocortical oscillation. Thus, pharmacological interference with these channels enables effective control of spike-wave discharge activity in patients suffering from absence seizures. In this review, we summarize the medical history of absence epilepsies, their classification and terminology, the diagnostic armamentarium available today and the etiopathogenesis of absences. Finally, various antiepileptic drugs that have been proven to or are supposed to exert anti-absence effects are discussed with respect to their pharmacodynamics and pharmacokinetics.     

自适应装配包含螺纹种植体的下颌骨骨块三维有限元模型的建立

目的:借助Pro/E参数化建模软件建立可随种植体宏观结构参数自适应改变的种植体、皮质骨、松质骨、冠修复体的三维实体模型.方法:应用Pro/E与Ansys Workbench软件的无缝双向参数传递功能,将实体模型导入Ahnsys Workbench软件中划分单元,建立可随种植体宏观结构参数自适应改变的种植体骨块三维有限元模型,力学拥载后进行模型准确性的检测.结果:建立了包含不同种类螺纹种植体的颌骨骨块三维有限元模型.结论:应用Pro/E的自适应装配功能和Ansys Workbench与Pro/E软件的参数双向传递功能,建立了可自适应改变的种植体骨块三维有限元模型.与以往建模方法相比,该方法提高了建模的效率,增加了横型的扩展性,也为后期真正意义上的种植体优化设计分析提供了技术平台.