纳米颗粒和外泌体靶向载药系统诊治动脉粥样硬化的机遇与挑战

动脉粥样硬化是一种慢性炎症性疾病,粥样斑块慢性聚集并沉积于大中型动脉内膜,导致严重的狭窄和血运障碍,引发组织器官缺血缺氧。纳米药物相对于传统药物在动脉粥样硬化治疗中因其具有独特的优势而广泛受到关注。本文重点综述几种纳米靶向颗粒（系统）和外泌体靶向载药系统在抗动脉粥样硬化研究中的应用,简述代表性纳米材料的合成过程,对其靶向性进行分析,并概述纳米药物的益处和内在挑战。尽管面临着一些需要解决和完善的挑战,但是纳米颗粒和外泌体靶向载药治疗的前景广阔,并有望将其推广应用于临床实践中。     

综合矫正训练方案联合中药熏蒸治疗上交叉综合征疗效观察

<正>上交叉综合征(upper crossed syndrome,UCS)是指因上半身长期处于不良姿势,造成相关肌群功能失衡,进而引起颈肩背部疼痛不适、胸闷、睡眠障碍等一系列不良症状的一种亚健康状态^[1]。UCS常见的体态是圆肩、驼背、头前倾^[2]。目前临床上主要通过纠正局部的肌肉失衡来治疗UCS,常用的方法有运动疗法、肌肉能量技术、针灸和推拿等^[3]。     

七年制生物物理技术教学探索

根据七年制医学生培养要求，在“生物物理技术”教学中，除介绍有关物理方法与技术的原理及在生物医学中的应用外，还尝试了小论文写作和渗透科研思路、方法培养的探索。     

Mutations in VMK1, a mitogen-activated protein kinase gene, affect microsclerotia formation and pathogenicity in Verticillium dahliae

Verticillium dahliae is an important soil-borne fungal pathogen that causes vascular wilt diseases in a large variety of important crop plants. Due to its persistence in the soil, control of Verticillium wilt relies heavily on soil fumigation. The global ban on methyl bromide, a highly effective soil fumigant, poses an urgent need to develop alternative control measures against Verticillium wilt; and these might be more forthcoming with a better understanding of the molecular and cellular mechanisms that underpin the pathogenicity of V. dahliae. In this study, we assessed the role in growth, development, and pathogenicity of VMK1, a gene encoding a mitogen-activated protein (MAP) kinase (hence, Verticillium MAP Kinase 1). Disruption of VMK1 via Agrobacterium tumefaciens-mediated transformation, in two V. dahliae isolates, one from lettuce and the other from tomato, resulted in severely reduced virulence in diverse host plants, suggesting that VMK1 is essential for pathogenicity and that the MAP kinase-mediated signaling pathway has a conserved role in fungal pathogenicity. The vmk1 mutants also exhibited reduced conidiation and microsclerotia formation, suggesting that the gene is important for multiple cellular processes. P.R. and R.G.B. equally contributed to the work     

Randomized Controlled Clinical Trial of Blood Glucose Awareness Training (BGAT III) in Switzerland and Germany

Although both diabetes and the efficacy of medical management are international issues, psycho-educational interventions might be culturally bound. Blood Glucose Awareness Training (BGAT) is a psycho-educational program for patients with type 1 diabetes mellitus. It is focused on improving recognition and management of extreme blood glucose levels, and is the best documented American psycho-educational program for this purpose. A randomized controlled clinical trial of BGAT's long-term benefits in a non-American setting has been lacking. One hundred and eleven adults with type 1 diabetes mellitus from Switzerland and Germany participated. After a 6 months baseline assessment, subjects were randomly assigned to receive either 2 months of BGAT (n = 56) or a physician-guided self-help control intervention (n = 55). BGAT improved recognition of low (p = 0.008), high (p = .03), and overall blood glucose (p = 0.001), and reduced frequency of severe hypoglycemia (p = 0.04), without compromising metabolic control. BGAT reduced both the external locus of control (p < 0.02) and fear of hypoglycemia (p < 0.02). BGAT was efficacious in reducing adverse clinical events and achieving clinically desirable goals in a European, as well as American setting.     

Trajectory control in targeted force impulses

Summary This study was undertaken in order to determine the time course of the process by which information derived from a visual target is used to accurately set the amplitude of a simple motor response. We refer to this process as response specification. Separate auditory and visual cues were given to the subjects in order to independently control the moment of response initiation and the time available for processing amplitude information from the target. Six subjects initiated impulses of isometric force in synchrony with the last of predictable series of regular tones. Response amplitudes were to match one of three visual target steps occurring at random times between 0 and 400 ms before the response-synchronizing tone. Using these separate auditory and visual cues, we were able to systematically vary the time interval between target presentation and response onset, termed here Stimulus-Response or S-R interval. Target steps were presented in blocks of either predictable (simple condition) or unpredictable (choice condition) amplitudes. The peak forces and the peaks of their time derivatives were analyzed to determine how subjects achieved accuracy under the different conditions and at different S-R intervals. The trajectories of responses produced in the simple condition were independent of the S-R interval. In contrast, when targets were presented in unpredictable order, the distribution of the peak forces of the subjects' responses depended on the S-R interval. At short S-R intervals (<125 ms), subjects made responses whose peak forces were distributed around the center of the range of target steps. These responses formed a unimodal, but broad distribution which was independent of actual target amplitude. With increasing S-R interval (>125 ms), the distributions of peak forces gradually shifted toward the correct target amplitudes, with the means reaching the appropriate amplitudes at S-R intervals of 250–400 ms. At S-R intervals comparable to a reaction time, the range of peak forces was constricted to a similar extent as previously observed in a reaction time task (Hening et al. 1988). We found that the gradual improvement of accuracy was not achieved through changes in trajectory control: at all S-R intervals, subjects utilized a pulse-height control policy (Gordon and Ghez 1987a). Different peak forces were achieved by varying the rate of rise of force, while force rise time was held relatively invariant. We did find, however, that within the constraints imposed by rise time regulation, compensatory adjustments to the force trajectories (Gordon and Ghez 1987b) were greatest during the period of specification. We conclude that (1) subjects can initiate their responses independent of the degree of specification achieved and that the normal process of specification of amplitude begins earlier and continues longer than the latency of responses in a reaction time task; (2) before target presentation, subjects prepare a default response whose amplitude is biased by prior experience with the targets presented in the task. We hypothesize that the central mechanisms that specify response amplitude do so by a progressive adjustment of the default parameters.     

Evaluation of telephone transmission for computer electrocardiographic interpretation in Japan

The reliability of the Japanese public telephone facilities to transmit electrocardiograms (e.c.g.) for computer interpretation was assessed. The International Business Machine's (IBM) e.c.g. computer program by Bonner was used. No appreciable distortion of e.c.g. was observed following repeated transmission from hospitals separated by 1000 km. Thirty-four normal and 66 abnormal e.c.g.s. were transmitted twice. Identical results were observed in 97% of normals and 92% of abnormals. Following these fundamental experiments, 1236 patients' e.c.g.s. were transmitted for computer intepretation. The study showed that 98·6% (1219 cases) were technically satisfactory and 1·4% (17 cases) were not. The 17 unsatisfactory cases were classified into ten unreceivable data formats, six inconsistent measurements and one unacceptable noise level. The authors concluded that the Japanese public telephone facilities were acceptable for the transmission of e.c.g.s. for computer interpretation.     

Chromatin interactions in differentiating keratinocytes reveal novel atopic dermatitis– and psoriasis-associated genes

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Program for generation of three-dimensional finite element mesh from magnetic resonance imaging scans of human limbs

A PC-AT based program for conversion of magnetic resonance imaging (MRI) scans into coordinate input for finite element mesh generation is presented. The program is written in Borland C + +3.1 and is compatible with every general-use personal computer, permitting the use of MS-DOS 3.0 or higher with a Microsoft mouse. The program is menu driven and does not demand specialised knowledge from the user. The system and memory requirements are minimal -- 640 kB RAM -- and it runs as a stand-alone program. A second program allows the construction of a three-dimensional representation of the limb sub-structure and generation of the FE mesh from the converted cross-sectional scans. The capabilities of the program are demonstrated using cross-sectional scans of the upper arm; the fat, muscle and bone contours were obtained to a very high level of precision (0.4 mm).     

Allele-specific PCR and Next-generation sequencing based genetic screening for Congenital Adrenal Hyperplasia in India

Genetic screening of Congenital Adrenal Hyperplasia (CAH) is known to be challenging due to the complexities in CYP21A2 genotyping and has not been the first-tier diagnostic tool in routine clinical practice. Also, with the advent of massive parallel sequencing technology, there is a need for investigating its utility in screening extended panel of genes implicated in CAH. In this study, we have established and utilized an Allele-Specific Polymerase Chain Reaction (ASPCR) based approach for screening eight common mutations in CYP21A2 gene followed by targeted Next Generation Sequencing (NGS) of CYP21A2, CYP11B1, CYP17A1, POR, and CYP19A1 genes in 72 clinically diagnosed CAH subjects from India. Through these investigations, 88.7% of the subjects with 21 hydroxylase deficiency were positive for eight CYP21A2 mutations with ASPCR. The targeted NGS assay was sensitive to pick up all the mutations identified by ASPCR. Utilizing NGS in subjects negative for ASPCR, five study subjects were homozygous positive for other CYP21A2 variants: one with a novel c.1274G>T, three with c.1451G>C and one with c.143A>G variant. One subject was compound heterozygous for c.955C>T and c.1042G>A variants identified using ASPCR and NGS. One subject suspected for a Simple Virilizing (SV) 21 hydroxylase deficiency was positive for a CYP19A1:c.1142A>T variant. CYP11B1 variants (c.1201-1G>A, c.1200+1del, c.412C>T, c.1024C>T, c.1012dup, c.623G>A) were identified in all six subjects suspected for 11 beta-hydroxylase deficiency. The overall mutation positivity was 97.2%. Our results suggest that ASPCR followed by targeted NGS is a cost-effective and comprehensive strategy for screening common CYP21A2 mutations and the CAH panel of genes in a clinical setting.