PGLA编织支架的制备与初步体内评价

目的:热拉伸会改变纤维的结构和性能,进而影响由纤维编织而成的支架的性能。本文考察了PGLA纤维的拉伸倍数对编织支架在SD大鼠皮下的体内降解行为的影响。方法:制备了基于生物可降解高分子材料聚乙交酯丙交酯(PGLA,GA/LA摩尔比=90/10)的完全生物可降解编织支架,通过测试支架在大鼠体内降解过程中的失重、表面形貌、热性能、径向压缩力等变化情况,考察了纤维的不同的拉伸倍数对支架体内降解过程的影响。结果:用拉伸倍数为5的PGLA纤维编织的支架在植入SD大鼠皮下后降解最慢,重量、吸水率、结晶度、化学成分和径向压缩力的变化最慢,植入体内10天后能够保持完整的支架形态。结论:纤维的拉伸倍数会影响由纤维编织成的支架的热性能和力学性能的变化,本研究结果表明这种新的手工编织的支架具有短暂支撑管腔狭窄的潜在应用,为支架的材料选择和制备方法提供了参考,为在体内起到短暂支撑作用的支架的深入研究提供了实验基础。     

尿道下裂术后两种不同尿液引流方式的临床护理和效果观察

目的探讨尿道下裂术后2种不同尿液引流方式的临床护理和效果。方法选取我院泌尿外科2014年8月~2016年8月收治的46例接受尿道下裂成形术治疗的患者为研究对象。根据术后尿液引流方式不同分为A、B两组,其中A组22例患者采用新尿道内留置支架管的方式引流,B组24例患者采用耻骨上膀胱造瘘管+新尿道内留置支架管的方式引流,两组患者均按照尿道下裂术后护理常规实施术后护理,并根据尿液的不同引流方式给予相关护理。结果两组患者均顺利完成手术治疗,术后采用耻骨上膀胱造瘘管+新尿道内留置支架管方式引流尿液的B组尿瘘及尿道狭窄发生率显著低于实施新尿道内留置支架管引流尿液的A组,两组比较差异有统计学意义(P0.05)。结论尿道下裂术后采用耻骨上膀胱造瘘管+新尿道内留置支架管方式引流尿液,能有效保持尿液及分泌物的充分引流,减少管道堵塞的发生,减少术后尿瘘和尿道狭窄的发生,提高了手术成功率,提高了患者满意度。     

全降解聚合物血管内支架植入后的力学微环境变化与MGF*

动脉粥样硬化作为一种主要的心血管疾病,威胁着全世界人类的健康. 全降解聚合物血管内支架是由生物可降解的高分子聚合物材料制作的用于治疗动脉粥样硬化病变变窄管腔的血管支架. 它克服了金属药物洗脱支架引起的慢性局部炎症反应、血管生理舒缩功能缺失和晚期支架内血栓形成以及未来可能在同一位置再次植入支架的缺陷. 但全降解聚合物支架由于各级降解产物的刺激引起炎症反应以及支架植入部位力学微环境的变化,从而引起支架内再狭窄和血栓形成,结合力生长因子(mechano growth factor, MGF)对力学刺激敏感的特性,MGF可能对心血管支架植入引起的局部力学变化作出响应. 因此本文对全降解聚合物支架植入后支架的降解特性与力学微环境变化引起的再狭窄、血栓形成等不良反应,以及MGF在其中的作用和研究进展进行了综述,以期为临床冠脉介入支架治疗提供参考.     

PLGA的不同组成对支架材料性能的影响研究

研究PLGA的不同组成对支架材料的力学性能、降解性能和生物学性能的影响。采用溶液浇注/颗粒沥取法制备出不同组成的PLGA多孔支架,对支架的力学性能和降解速率进行考察,同时将人真皮成纤维细胞接种于不同组成的PLGA支架材料上,培养不同时间后,检测细胞的粘附率和增殖率,以及细胞产生的总胶原含量,并通过扫描电镜观察支架上的细胞形态。结果显示,随PLA比例的增加,支架的力学强度增加,降解速率降低,但都不是线性变化。70:30比例的支架,拉伸强度最高,而70:30和80:20两种比例的支架,其降解速率没有显著性差异。PLGA不同组成的支架,均具有良好的细胞相容性,成纤维细胞粘附率和增殖率在三种比例的支架上没有显著性差异,细胞在支架表面生长良好,分泌大量的细胞外基质,细胞基本铺满整个支架。本文研究发现,PLGA的组成对支架力学性能、降解性能和生物学性能有细小但显著的影响,这将对组织构建选用PLGA支架材料提供有益的帮助。     

颈动脉支架置入术改善认知功能

目的:观察颈动脉狭窄患者支架置入术时其认知功能的影响及简易精神评估量表(MMSE)与蒙特利尔认知评估北京版(MoCA)有无相关性。方法:收集124例颈动脉支架置入患者,在支架置入前及置入后1、3、6月分别应用简易精神评估量表(MMSE)、蒙特利尔认知评估北京版(MoCA)、P300检测患者认知功能的变化,同时对患者卒中有无复发进行登记,所有患者意识清楚,能配合完成上述检查。结果:所有患者安全、成功的置入颈动脉支架,无相关并发症出现;支架置入前颈动脉的狭窄率为(84±8.6)%,支架置入以后颈动脉狭窄率为(4.8±3.8)%,狭窄率较术前明显狭窄:支架置入前患者的MMSE、MoCA及P300潜伏期分别为21±3.1、14±3.6 ms,在治疗后随访的1、3及6个月,MMSE、MoCA明显提高而P300明显缩短;MMSE与MocA呈正相关;在随访期内患者无有症状的卒中复发。结论:颈动脉狭窄是导致认知功能障碍的原因之一,颈动脉支架置入可以改善患者认知功能障碍。     

药物涂层球囊概述及其在外周动脉疾病治疗中的应用进展

经皮经腔血管成形术(PTA)已广泛用于外周动脉疾病(PAD)的治疗。然而,该技术存在血管壁弹性回缩和内膜增生等不足。PTA术后植入金属裸支架(BMS)虽然可以减少血管壁弹性回缩,但由此引起的支架内再狭窄(ISR)又成为治疗中的一个突出问题。药物洗脱支架(DES)被用来解决狭窄问题,但晚期支架内血栓形成(LST)、内皮化延迟和必须长期抗血小板治疗等问题也随之而来。在这样的背景下,药物涂层球囊(DCB)获得了快速发展。DCB作为非支架方案,可将所携载的活性药物转移至病变段血管壁,对ISR或原发病变均有较好的治疗效果。本文简要介绍了DCB的发展历史,并通过实验室研究、动物实验和临床试验,从机制上阐述涂层技术、涂层药物、赋形剂等对DCB功效和安全性的影响以及DCB在PAD治疗中的应用进展。     

B超诊断尿道狭窄一例

B超诊断尿道疾患报道少见,最近笔者应用B超对一例尿道狭窄的病人进行了检查,现报道如下: 患者男性,37岁。尿道外伤后排尿不畅而来我院。五月前因尿道骑跨伤行膀胱造瘘及会师术,之后,尿线变细排尿费力。进而加重,尿线呈点滴状伴尿液不能控制从尿道溢出。体检:会阴部、球部尿道处有一疤痕,里结节状,质硬。5号尿道探子进入15cm时,感凹凸不平,不能进入。临床诊断:尿道狭窄。 B超检查:病人取截面位,将探头置于会阴部,采用加压探测法,作纵、横扫查。声     

生物可降解材料构建组织工程软骨的研究进展

关节软骨修复困难,目前临床上治疗关节软骨损伤难以达到满意的效果。组织工程学的兴起为其提供了新的选择。本文介绍了组织工程软骨的发展历史,重点叙述了各种天然支架材料、人工合成材料、复合材料及纳米材料在软骨组织工程中的应用及其优势。目前应用的天然材料存在力学强度差及免疫源性的不足;人工合成材料降解速率快,降解产物具有细胞毒性,有待进一步完善。表面修饰等技术的应用在一定程度上克服了某些材料的不足;复合材料综合了数种材料的优点,是今后材料技术发展的方向;纳米技术的出现使新合成的材料成为纳米量级,具有了普通材料无可比拟的优势,这为组织工程材料的发展提供了新的思路。本文还对组织工程支架材料存在的问题、下一步的发展方向和前瞻性研究做了介绍。     

四环素类抗生素降解途径及其主要降解产物研究进展

四环素类抗生素在生产和贮存过程中会发生一系列非生物降解反应,其中某些代谢及降解产物,与母体相比,虽然其活性降低,但毒性却大大增强.此类抗生素随着畜禽废弃物等途径进入到环境中,随环境条件的不同将发生一种或多种降解反应,其降解方式除了非生物降解外,还包括生物降解.本文综述了四环素类抗生素在不同生态环境中的降解途径以及降解产物,并对今后的研究方向进行了探计,旨在为其生态风险评价提供有价值的参考.     

辐射诱导对犬胆管平滑肌细胞凋亡中BCL-2活性的影响

目的:探讨γ射线对BCL-2基因在犬胆管壁增殖平滑肌细胞凋亡中的活性影响。方法:实验犬24只(15～18kg),随机分为普通支架组和~(125)I支架组各12只。用切断吻合法,造成胆总管损伤。术后30天胆道狭窄形成后,分组将普通支架及125I支架从胆总管末端开口处释放到胆总管内。置入支架后60d分别行病理形态学检测,用免疫组织化学方法进行凋亡细胞,BCL-2蛋白基因检测,并用计算机图像检测系统检侧两组胆管腔面积。结果:~(125)I支架组犬胆管组织中BCL-2基因表达较普通支架组减弱,且BCL-2基因低表达组犬胆管出现明显增殖平滑肌细胞凋亡,而且犬肝外胆管无明显狭窄;而普通支架BCL-2基因高表达,且犬胆管未出现增殖平滑肌细胞明显凋亡,而且犬肝外胆管有明显狭窄。结论:~(125)I放射性支架通过抑制BCL-2基因,促进犬胆管增殖平滑肌细胞凋亡,可以抑制犬肝外胆管狭窄。     

Optimization of Cardiovascular Stent against Restenosis: Factorial Design-Based Statistical Analysis of Polymer Coating Conditions

The objective of this study was to optimize the physicodynamic conditions of polymeric system as a coating substrate for drug eluting stents against restenosis. As Nitric Oxide (NO) has multifunctional activities, such as regulating blood flow and pressure, and influencing thrombus formation, a continuous and spatiotemporal delivery of NO loaded in the polymer based nanoparticles could be a viable option to reduce and prevent restenosis. To identify the most suitable carrier for S-Nitrosoglutathione (GSNO), a NO prodrug, stents were coated with various polymers, such as poly (lactic-co-glycolic acid) (PLGA), polyethylene glycol (PEG) and polycaprolactone (PCL), using solvent evaporation technique. Full factorial design was used to evaluate the effects of the formulation variables in polymer-based stent coatings on the GSNO release rate and weight loss rate. The least square regression model was used for data analysis in the optimization process. The polymer-coated stents were further assessed with Differential scanning calorimetry (DSC), Fourier transform infrared spectroscopy analysis (FTIR), Scanning electron microscopy (SEM) images and platelet adhesion studies. Stents coated with PCL matrix displayed more sustained and controlled drug release profiles than those coated with PLGA and PEG. Stents coated with PCL matrix showed the least platelet adhesion rate. Subsequently, stents coated with PCL matrix were subjected to the further optimization processes for improvement of surface morphology and enhancement of the drug release duration. The results of this study demonstrated that PCL matrix containing GSNO is a promising system for stent surface coating against restenosis.     

General patterns and asymptotic dose in the design of coated stents

Stents are used in interventional cardiology to keep a diseased vessel open. New stents are coated with a medicinal agent to prevent early reclosure due to the proliferation of smooth muscle cells. It is recognised that it is the dose of the agent that effectively controls the growth. This paper focusses on the asymptotic behaviour of the dose for general families of coated stents under a fixed ratio between the coated region of the stent and the targeted region of the vessel and set therapeutic bounds on the dose. It generalises the results of Delfour, Garon and Longo for stents made of a sequence of thin equally spaced rings to stents with an arbitrary pattern. It gives the equation of the asymptotic dose for a normal tiling of the target region using the theory of tilings, patterns and motifs on a cylinder.     

Comparison of coronary artery dynamics pre- and post-stenting

Stents have dramatically improved the treatment of coronary artery disease. Since the implantation of stents changes the geometry and dynamics of the coronary artery, it is reasonable to hypothesize that some of these changes may have an important effect on the development of atherosclerosis by modulating the mechanical environment. In this paper, we presented a method to compare the geometric dynamics of the coronary artery before and after stenting using biplane angiography. Two cases are reviewed and a number of parameters are proposed to describe the longitudinal change of the vessel before and after stenting. This analysis technique has the potential to identify some aspects of stent design and procedure that might improve the success rate with this therapeutic approach.     

冠状动脉内重叠支架置入术的临床研究进展

重叠支架置入术是临床上用来治疗冠状动脉弥漫性长病变的常用方法,以往曾采取重叠裸金属支架置入术,但其临床预后不佳,目前较为常用的重叠药物洗脱支架置入术被认为相对安全、有效,但仍存在许多潜在问题。本文介绍了适合使用重叠支架置入术进行治疗的冠状动脉病变的特点,回顾了重叠裸金属支架的临床应用情况,阐述了近年来药物洗脱支架的发展以及重叠药物洗脱支架置入术的优势,比较了四种负载不同药物的药物洗脱支架同种重叠置入后的临床疗效,观察了异种药物洗脱支架混合重叠置入后的临床特点和支架重叠段对临床预后的影响,分析了重叠支架置入术与几种其它治疗冠状动脉弥漫性长病变方法的应用区别,并对新一代药物支架的重叠应用进行了展望。     

Release of plasmid DNA from intravascular stents coated with ultrathin multilayered polyelectrolyte films

Materials that permit control over the release of DNA from the surfaces of topologically complex implantable devices, such as intravascular stents, could contribute to the development of new approaches to the localized delivery of DNA. We report the fabrication of ultrathin, multilayered polyelectrolyte films that permit both the immobilization and controlled release of plasmid DNA from the surfaces of stainless steel intravascular stents. Our approach makes use of an aqueous-based, layer-by-layer method for the assembly of nanostructured thin films consisting of alternating layers of plasmid DNA and a hydrolytically degradable polyamine. Characterization of coated stents using scanning electron microscopy (SEM) demonstrated that stents were coated uniformly with an ultrathin film ca. 120 nm thick that adhered conformally to the surfaces of stent struts. These ultrathin films did not crack, peel, or delaminate substantially from the surface after exposure to a range of mechanical challenges representative of those encountered during stent deployment (e.g., balloon expansion). Stents coated with eight bilayers of degradable polyamine and a plasmid encoding enhanced green fluorescent protein (EGFP) sustained the release of DNA into solution for up to four days when incubated in phosphate buffered saline at 37 degrees C, and coated stents were capable of mediating the expression of EGFP in a mammalian cell line without the aid of additional transfection agents. The approach reported here could, with further development, contribute to the development of localized gene-based approaches to the treatment of cardiovascular diseases or related conditions.     

国产雷帕霉素药物洗脱支架在冠心病介入治疗中疗效评价

目的:观察国产雷帕霉素药物洗脱支架在冠心病介入治疗中有效性及安全性。方法:2010年1月至2010年12月我院心血管内科收治并行国产雷帕霉素药物洗脱支架(Firebird支架)置入术患者124例,收治并行进口雷帕霉素药物洗脱支架(Cypher^TM支架)置入术患者167例,于不同支架置入患者中各随机选68例,命名为国产组与进口组。术后1年、5年分别随访两组,观察两组患者支架置入后在不同时间段不良心血管事件发生情况及冠脉造影复查结果。结果:两组患者不良事件比较,国产组术后1年随访结果与术后5年随访结果比较,差异无统计学意义(P0.05);进口组术后1年随访结果与术后5年随访结果比较,差异无统计学意义(P0.05);国产组术后5年随访结果与进口组术后5年随访结果比较,差异无统计学意义(P0.05)。两组患者冠脉造影复查结果比较,差异无统计学意义(P0.05)。结论:国产雷帕霉素药物洗脱支架在冠脉介入治疗中具有安全性和有效性,与进口雷帕霉素药物洗脱支架比较无明显差异,值得临床推广应用。     

Rapid in vitro biocompatibility assay of endovascular stents by flow cytometry using platelet activation and platelet-leukocyte aggregation

Clinical studies suggest that stent design and surface texture are responsible for differences in biocompatibility of metallic endovascular stents. A simple in vitro experimental setup was established to test stent-induced degree of platelet and leukocyte activation and platelet-leukocyte aggregation by flow cytometry. Heparin-coated tantalum stents and gold-coated and uncoated stainless steel stents were tested. Stents were implanted into silicone tubes and exposed to blood from healthy volunteers. Platelet and leukocyte activation and percentage of leukocyte-platelet aggregates were determined in a whole-blood assay by subsequent staining for activation-associated antigens (CD41a, CD42b, CD62p, and fibrinogen binding) and leukocyte antigens (CD14 and CD45) and flow cytometric analysis. Blood taken directly after venous puncture or exposed to the silicone tube alone was used as negative controls. Positive control was in vitro stimulation with thrombin receptor activating peptide (TRAP-6). Low degree of platelet activation and significant increase in monocyte- and neutrophil-platelet aggregation were observed in blood exposed to stents (P < 0.05). In addition, leukocyte activation was induced as measured by increased CD45 and CD14 expression. Heparin coated stents continuously induced less platelet activation and leukocyte-platelet aggregation than uncoated stainless steel stents of the same length and shorter stents of the same structure. Stent surface coating and texture plays a role in platelet and leukocyte activation and leukocyte-platelet aggregation. Using this simple in vitro assay and whole blood and flow cytometry, it seems possible to differentiate stents by their potency to activate platelets and/or leukocytes. This assay could be applied for improving the biocompatibility of coronary stents.     

On high-cycle fatigue of 316L stents

This paper deals with fatigue life prediction of 316L stainless steel cardiac stents. Stents are biomedical devices used to reopen narrowed vessels. Fatigue life is dominated by the cyclic loading due to the systolic and diastolic pressure and the design against premature mechanical failure is of extreme importance. Here, a life assessment approach based on the Dang Van high cycle fatigue criterion and on finite element analysis is applied to explore the fatigue reliability of 316L stents subjected to multiaxial fatigue loading. A finite element analysis of the stent vessel subjected to cyclic pressure is performed to carry out fluctuating stresses and strain at some critical elements of the stent where cracks or complete fracture may occur. The obtained results show that the loading path of the analysed stent subjected to a pulsatile load pressure is located in the safe region concerning infinite lifetime.     

Prevention of in-stent restenosis: towards an in situ treatment?

The use of intracoronary stents represent a major breakthrough in the armamentarium of interventional cardiology. Stents reduce significantly the incidence of recurrent stenosis (in-stent restenosis) via an improved post-procedure luminal diameter and an abrogation of the constrictive remodeling of the arterial wall. However, stent-related arterial injury results in intense proliferative and inflammatory responses and severe intimal hyperplasia, which, in 20% to 40% of the patients, may end up with clinically significant in-stent restenosis. Efficient prevention of in-stent restenosis has yet to be found. Systemic treatments have failed because they don't take into account the specific physiopathology and, most importantly, the focal nature of in-stent intimal hyperplasia. Hence, local prevention appears to be a straightforward approach to the unsolved issue of in-stent restenosis. In situ beta- or gamma-irradiation (brachytherapy) has received much attention as a curative treatment of in-stent restenosis but is not indicated for prevention. In contrast, drug-releasing stents have been tested in experimental models and have already provided very promising results in randomized clinical trials. Most of clinical studies have been performed with the antiproliferative agents sirolimus and paclitaxel, but other agents are under scrutiny. In addition, important research is carried out, in which the efficacy of antiproliferative genes is investigated. Clearly, drug-releasing stents are on the verge of profoundly modifying our practice of interventional cardiology. However, several questions remain unanswered as regard to the long term efficacy/toxicity and the cost-effectiveness of this new approach.     

铜在心血管系统中的有益作用

随着经济水平和生活水平的逐步提高,我国心血管疾病的患者数量也在逐年上升。因此,加深对心血管疾病的认知和预防乃是当务之急。在人体所需的众多微量金属元素中,铜对维护心血管的健康起到了重要的作用。铜的缺乏可能会导致一系列心血管疾病的发生,如冠心病、高血压、心律失常等。究其原因,是由于铜能影响血管的形成以及血管的正常生理功能,同时也参与了众多相关生长因子的调控。所以,人体要保证足量的铜摄入,避免铜元素的缺乏。向生物材料中主动添加铜元素,可以通过释放铜离子起到促进内皮细胞增殖和迁移的作用,进而加速伤口的愈合。目前,治疗高发的冠心病的重要手段是采用冠脉支架植入手术,但是其依旧面临着支架内再狭窄和血栓这两种风险。含铜的金属支架材料通过释放对血管有益的铜离子,有望加快支架植入后的内皮化过程,进而降低支架内再狭窄和血栓的发生率。所以,将来积极开发应用于心血管领域的含铜医用材料是一种缓解和治疗心血管疾病的有效途径。