他汀类调脂药物作用的多效性研究

动脉粥样硬化是一个复杂性全身性炎症性过程.病变部位形成粥样斑块,斑块破裂引发血栓形成是导致急性冠脉综合征发生的主要原因.心室重构是慢性心力衰竭的前奏.他汀类药物在动脉粥样硬化的治疗中发挥着越来越重要的作用,除了降脂作用,更具有多效性,包括提高一氧化氮生物利用度、抗炎、抗氧化、稳定动脉粥样硬化、改善心功能等.现就当前他汀类调脂药物作用多效性的主要研究进展作一综述.     

Localized Chemical Remodeling for Live Cell Imaging of Protein-Specific Glycoform

Live cell imaging of protein-specific glycoforms is important for the elucidation of glycosylation mechanisms and identification of disease states. The currently used metabolic oligosaccharide engineering (MOE) technology permits routinely global chemical remodeling (GCM) for carbohydrate site of interest, but can exert unnecessary whole-cell scale perturbation and generate unpredictable metabolic efficiency issue. A localized chemical remodeling (LCM) strategy for efficient and reliable access to protein-specific glycoform information is reported. The proof-of-concept protocol developed for MUC1-specific terminal galactose/N-acetylgalactosamine (Gal/GalNAc) combines affinity binding, off-on switchable catalytic activity, and proximity catalysis to create a reactive handle for bioorthogonal labeling and imaging. Noteworthy assay features associated with LCM as compared with MOE include minimum target cell perturbation, short reaction timeframe, effectiveness as a molecular ruler, and quantitative analysis capability.     

生物力学进展和趋向(续)

三、运动关节力学运动关节(diarthrodial joint)的功能在于使动物能灵巧地运动肢体。译成力学术语就是:传递载荷,吸收冲击、振动,承受相当高的应力,且运动时摩擦系数很小。L.L.Malcom曾精细地测量过牛肱关节的摩擦系数,在正应力1—20kg/cm~2的范围内,动摩擦系数为0.0025—0.0040,而最好的工程材料的摩擦系数为0.01—0.05,整整差一个量级。      

Boundary elements and β-spline surface modeling for medical applications

The aim of this paper is to present and discuss an approach based on the integration of the boundary element method (BEM) with β-spline geometric modeling of the different surfaces involved in the external bone remodeling phenomena. The purpose of combining these two techniques is to avoid the jagged edges shapes and thus, to increase the convergence speed of the bone remodeling function. In this study, the external bone remodeling model proposed by Fridez et al. [P. Fridez, L. Rakotomanana, A. Terrier, P.F. Leyvraz, Three dimensional model of bone external adaptation, Comput. Methods Biomech. Biomed. Eng. 2 (1998) 189–196] is used. This model shows the change of the external bone surface remodeling at a boundary point, as a function of the stimulus variable Ψ. This variable is related to the stress tensor and the normal vector to that point. The β-spline surfaces were used because they are simple and reliable to smooth the contour by using the less possible number of geometric constraints. Some numerical examples are presented and discussed in order to show the versatility of the proposed approach.     

老年冠心病合并退行性心瓣膜病对左室重构的影响

本文探讨合并退行性心瓣膜病对老年冠心病患者心脏结构与功能的影响.作者测定了80例老年冠心病合并退行性心瓣膜病者和80例老年冠心病患者的心脏超声指标结果,方差分析两组上述指标的差异,卡方检验比较两组心衰和左室重构的发生率.结果表明,两组在心脏结构和功能及心律失常等方面存在统计学差异,合并退行性瓣膜病组的左室重量指数较大,心功能较差,心衰发生率高.从而得到退行性心瓣膜病变能促进老年冠心病患者心脏重构的发生,促进心衰的发生的结论.     

Some considerations on biomaterials and bone

Osteoinduction is a property not traditionally attributed to Calcium Phosphate ceramics. Histologic, SEM and X-ray microanalyses of a biopsy of pulmonary alveolar microlithiasis allow to discredit this opinion. Bone, even lamellar type, was ectopically formed on microliths undergoing osteoclastic erosion. The SEM and X-ray microanalyses of coral granules implanted in humans indicate an osteoconductive property for both Calcium and Phosphorus. Analysis of in vitro allows to propose an enhancement of the osteocapability of coral. Lamellar bone formation in the near absence of loads undermines the opinion which sees a correlation between lamellar bone and mechanical loads. Analysis of the bone surrounding an uncemented titanium hip prosthesis highlights that both remodeled and newly formed bone have lamellae oriented parallel to prosthesis surfaces, i.e. orthogonal to loads, as opposed to that of lamellar bone of osteons which are oriented parallel to loads. Analysis of longitudinal sections of cortical bone under polarized light points out that lamellae are displaced parallel to the cement line surface both in the conic end of osteons and in Volkman's canals with thick wall, i.e. undergoing sloped load directions. In conclusion, there may be a relationship between lamellae formation and gravity.     

Preparation of Well‐Defined Antibody–Drug Conjugates through Glycan Remodeling and Strain‐Promoted Azide–Alkyne Cycloadditions

Antibody–drug conjugates hold considerable promise as anticancer agents, however, producing them remains a challenge and there is a need for mild, broadly applicable, site‐specific conjugation methods that yield homogenous products. It was envisaged that enzymatic remodeling of the oligosaccharides of an antibody would enable the introduction of reactive groups that can be exploited for the site‐specific attachment of cytotoxic drugs. This is based on the observation that glycosyltransferases often tolerate chemical modifications in their sugar nucleotide substrates, thus allowing the installation of reactive functionalities. An azide was incorporated because this functional group is virtually absent in biological systems and can be reacted by strain‐promoted alkyne–azide cycloaddition. This method, which does not require genetic engineering, was used to produce an anti‐CD22 antibody modified with doxorubicin to selectively target and kill lymphoma cells.     

Advance from biomechanics to mechanobiology

本文介绍了现代生物力学的发展历程和冯元帧先生的贡献、力学生物学的概念与发展以及我国生物力学的发展历程和力学生物学的研究新进展;思考了从生物力学到力学生物学的进展与现状;展望了我国生物力学学科发展的愿景.     

Distribution of late gadolinium enhancement in end-stage hypertrophic cardiomyopathy and dilated cardiomyopathy: Differential diagnosis and prediction of cardiac outcome

Background

The prognostic implications of late gadolinium enhancement (LGE) have been evaluated in ischemic and non-ischemic cardiomyopathies. The present study analyzed LGE distribution in patients with end-stage hypertrophic cardiomyopathy (ES-HCM) and with dilated cardiomyopathy (DCM), and tried to identify high risk patients in DCM.

Methods

Eleven patients with ES-HCM and 72 with DCM underwent cine- and LGE-cardiac magnetic resonance and ultrasound cardiography. The patient outcome was analyzed retrospectively for 5 years of follow-up.

Results

LGE distributed mainly in the inter-ventricular septum, but spread more diffusely into other left ventricular segments in patients with ES-HCM and in a certain part of patients with DCM. Thus, patients with DCM can be divided into three groups according to LGE distribution; no LGE (n = 24), localized LGE (localized at septum, n = 36), and extensive LGE (spread into other segments, n = 12). Reverse remodeling occurred after treatment in patients with no LGE and with localized LGE, but did not in patients with extensive LGE and with ES-HCM. The event-free survival rate for composite outcome (cardiac death, hospitalization for decompensated heart failure or ventricular arrhythmias) was lowest in patients with extensive LGE (92%, 74% and 42% in no LGE, localized LGE, and extensive LGE, p = 0.02 vs. no LGE), and was comparable to that in patients with ES-HCM (42%).

Conclusions

In DCM, patients with extensive LGE showed no functional recovery and the lowest event-free survival rate that were comparable to patients with ES-HCM. The analysis of LGE distribution may be valuable to predict reverse remodeling and to identify high-risk patients.     

兔矢状缝扩张过程中环腺苷酸含量的变化

目的：了解兔矢状缝扩张过程中环腺苷酸含量的变化规律。方法：选用兔顶骨矢状状缝,用放射免疫法测定骨髓受不同大小,不同时间扩张力后,骨改建相关因子环腺苷酸（ｃＡＭＰ）的含量变化规律。结果：（１）骨缝受扩张力后,内源性ｃＡＭＰ在受力后１ｄ时低于对照水平,以后又上升至高于对照组水平;（２）大力组ｃＡＭＰ含量下降程度比小力组大。结论：较大的力引起的组织损伤大,骨改建延迟。在临床上快速扩大骨缝需更长的保持时间