组织工程骨在口腔种植中的应用与思考

背景：种植部位骨量不足是临床上种植牙治疗经常遇到的不利因素。组织工程骨在解决种植部位骨量不足方面取得了一定进展。 目的：从种子细胞、支架材料、生长因子、以及口腔种植应用等方面,全面了解组织工程骨的构成及其在口腔种植中的应用。 方法：以“组织工程骨(tissue-engineered bone),口腔种植(oral implantology)”为检索词,应用计算机检索维普数据库,Pubmed数据库2000/2009有关文章,排除重复性研究。 结果与结论：共检索到258篇文献,排除无关重复性的文献,保留25篇文献进行综述。目前口腔种植应用的种子细胞来源主要有骨、软骨、骨外膜、骨外组织、胚胎骨等;生长因子的应用可诱导、加快、和增强牙槽骨的形成;支架材料主要为合成材料,不同支架材料构建的骨移植物植入体内后的修复效果差异很大。组织工程骨由于所需供体组织少,不易发生排斥反应,具有良好的应用前景;但存在临床应用的技术难度大,生长速度缓慢等问题。     

组织工程技术在下尿路修复重建中的应用

背景：下尿路损伤、炎症、肿瘤以及先天性畸形等原因常可造成下尿路组织的严重缺损。传统手术对于下尿路修复重建存在诸多弊端。组织工程利用脱细胞基质与复合种子细胞的生物支架构建组织器官，为下尿路的临床修复与重建开辟了新的治疗思路。 目的：就组织工程技术在男性下尿路修复重建中成熟技术做简单概述,并指出现阶段组织工程在临床应用之不足。 方法：以“tissue engineering，urethra engineering，bladder；urethra，testicle”为英文检索词；以“组织工程；尿道重建；膀胱；尿道；睾丸”为中文检索词。应用计算机检索1994-01/2009-06 PubMed数据库和CNKI数据库相关文章，检索到文献72篇，排除重复性研究，最终纳入29篇文献进行分析。 结果与结论：目前用膀胱替代材料重建膀胱的实验主要有两种模型，即脱细胞基质支架模型和复合种子细胞的生物支架模型。脱细胞基质支架材料主要有膀胱细胞外基质、尿道细胞外基质、小肠黏膜下基质等。复合种子细胞的生物支架则是将种子细胞接种与相应的支架上，经过相应的处理再回植入体内。这两种模型目前正处于实验与临床研究中。组织工程化尿道方面的应用技术与组织工程化膀胱类似。睾丸组织工程研究目前还处于萌芽阶段。目前组织工程“替代品”还无法与正常的组织器官相媲美，还有一定的缺陷。     

组织工程皮肤支架材料和种子细胞的研究进展*

目的：综述近年来国内外组织工程皮肤种子细胞和支架材料方面的研究进展，介绍了用静电纺丝法制备新型三维纳米纤维支架材料的研究进展及其在组织工程皮肤中的应用前景。 资料来源：检索人为第一作者，检索文献时限为1992/2009。检索数据库为CNKI数字图书馆全文数据库，Sciencedirect 数据库，I.S.I 数据库。中文检索关键词为“组织工程皮肤，创伤修复，种子细胞，支架，静电纺丝”。英文检索关键词为“tissue-engineering，skin，wound healing，seed cell，scaffold，electrospunning” 。 资料选择：近年来对皮肤组织工程的研究起着重大影响，以及开启和引领新的方向的重要研究成果。 结局评价指标：①与组织工程材料治疗皮肤损伤相关的文章。②与组织工程种子细胞和支架材料相关的文章。③与静电纺丝相关的文章。 结果：利用皮肤干细胞的增殖分化特性制备人工皮肤是目前重要的研究方向，较受关注的研究有表皮干细胞、骨髓间充质干细胞、毛囊干细胞和脂肪干细胞等。对于组织工程来说，如何制备出满足应用的细胞对支架的力学性能、物理结构及生物相容性等方面的要求无疑又是一个至关重要的难题。支架材料主要可分为微米级多孔支架材料与纳米纤维支架材料。静电纺丝法是近年来兴起的一种能快速、简便制备纳米纤维支架材料的方法，利用电纺技术制备的支架材料孔隙率高，孔道连通性好，有利于维持创面血运和氧气交换，可有效防止创面水分和蛋白质的流失。 结论：组织工程皮肤研究是再生医学的重要组成部分，种子细胞和支架材料基材是其最核心的问题。随着生命科学、纳米技术和计算机技术的不断发展和相互融合，对种子细胞之间相互影响、相互调节机制的研究，以及支架材料的构建和性能研究取得了很大进展。 关键词：组织工程皮肤；创伤修复；种子细胞；支架材料；静电纺丝 doi:10.3969/j.issn.1673-8225.2009.47.029     

组织工程化肌腱在肌腱修复过程中的作用

摘要 目的：综述肌腱组织工程在肌腱修复过程中的应用进展。 方法：应用计算机检索1993-01/2009-10 PubMed数据库及维普数据库有关肌腱组织工程研究进展、肌腱支架材料生物力学分析、生物材料在肌腱组织工程中应用及组织工程技术在修复肌腱缺损临床应用方面的相关文献,英文检索词为“tendon transplantation,tissue engineering,biologicalmaterial,cell stent”,中文检索词为“肌腱移植,组织工程,生物材料,细胞支架”。检索文献量总计132篇。 结果：目前组织工程化肌腱的研究已经取得了显著的成果,但要真正应用于临床,大批量生产,仍存在一些问题。诸如最适的种子细胞来源、理想的支架材料、最佳的培养条件以及植入体内的检测方法等,在组织工程真正成为一种治疗肌腱缺损和功能重建的选择之前,这些问题都是有待进一步研究和解决的。 结论：要真正实现体外预制有生命的种植体完全替代人体组织、器官功能,尚面临着许多挑战。 关键词：肌腱组织工程;生物材料;细胞支架;修复;综述文献 doi:10.3969/j.issn.1673-8225.2011.03.042     

不同种类组织工程化细胞移植修复关节软骨的损伤

背景：单纯药物治疗不能有效促进关节软骨缺损的愈合;自体软骨来源有限,软骨移植手术也相应受到限制。 目的：分析关节软骨损伤类型及局部微环境的改变,总结近年来国内外组织工程种子细胞移植研究相关进展以及细胞移植修复关节软骨损伤治疗进展。 方法：以Tissue engineering,cell transplantation,articular cartilage defects为检索词,检索Pubmed数据库(1993-01/2008-12);以组织工程,细胞移植,关节软骨损伤为检索词,检索CNKI数据库(2000-01/2008-12)。文献检索语种限制为英文和中文。纳入与关节软骨损伤以及分类密切相关性研究,组织工程种子细胞移植技术相关性应用研究。排除重复性研究。以种子细胞的存活和迁移,以及移植后关节功能的恢复和不良反应为评价指标。 结果与结论：计算机初检得到201篇文献,根据纳入排除标准,对组织工程细胞移植修复关节软骨损伤的研究进行分析。临床上,创伤性或骨关节炎造成的关节软骨损伤较为常见,关节软骨自身修复能力差,一旦损伤将很难修复。组织工程细胞移植技术的出现为成功治愈关节软骨损伤带来了新的希望。在动物模型和临床研究中,细胞移植治疗关节软骨损伤已经取得良好的修复效果,但这一技术仍有改进的余地。目前的研究集中在如何从技术上改善组织工程3要素,即细胞,生物支架材料和生物活性因子。自体软骨再生仍然是关节软骨缺损修复的理论支柱,但进一步的研究需要优化其再生效果以及维持更加稳定的软骨细胞表型等等。组织工程细胞移植修复关节软骨损伤疗效较好,随着目前组织工程研究的深入,细胞移植修复技术有望成为临床上治疗关节软骨损伤的新方法。     

组织工程支架材料在脊髓损伤修复中的应用*

背景：脊髓损伤最初往往会导致细胞和组织的不断丢失,组织工程支架可以模拟细胞外基质的生理状态,从而有利于细胞的黏附、迁移、扩增和分化。 目的：总结近年来组织工程支架材料联合细胞和/或细胞因子修复脊髓损伤的新进展。 方法：应用计算机检索PubMed、Ovid Medline及CBM数据库中2000-10/2010-10 与组织工程支架材料修复脊髓损伤相关的文章。 结果与结论：组织工程材料治疗脊髓损伤需要3 因素：种子细胞、组织工程支架、细胞因子。组织工程支架对于损伤脊髓断端起到桥接作用,而种植于材料的种子细胞和/或细胞因子可以促进神经轴突的生长和迁移。可用于组织工程支架的材料可分为天然材料和人工合成材料,包括胶原、壳聚糖、琼脂糖/藻酸盐、聚乳酸、纤连蛋白、聚羟基乙酸/聚乳酸、聚β羟丁酸等,动物实验已经取得一些成果,显示组织工程支架材料联合细胞移植修复效果更好,但临床上目前尚无开展组织工程支架材料修复脊髓损伤的研究。     

神经组织工程支架或异种神经移植在面神经缺损中的应用

背景：了解面神经损伤的修复方法,以及各种组织支架的特性与优势,对于修复方法与材料的合理选择是十分必要的。 目的：总结神经组织工程支架或异种神经移植在面神经缺损中的应用进展。 方法：应用计算机检索PubMed数据库及CNKI数据库,在标题和摘要中以“组织工程支架,神经移植,面神经,修复”或“tissue engineering scaffolds,nerve transplantation,facial,repair”为检索词进行检索。根据纳入标准选择21篇文献进行综述。 结果与结论：面神经缺损后立即直接缝合神经的断端是最好的修复方法。自体神经移植受神经移植体来源之限,常造成供区失神经支配;以及产生束外有髓和无髓轴突无规则生长会导致神经纤维错向再生,造成严重的联带运动的不足。异体或异种神经移植法虽然取得了一定的效果,但仍处于动物实验的研究阶段,尚难以应用于临床。     

运动性半月板损伤及组织工程半月板的应用

背景：半月板损伤是常见的膝关节运动损伤之一,常伴有关节软骨的损伤,其原因是膝关节内环境的紊乱。 目的：评价组织工程半月板在半月板构建中的生物支架材料的性能,以寻求合理的半月板替代物。 方法：以“组织工程;半月板修复;生物材料支架;运动性半月板损伤”为中文关键词,以“tissue engineering, the meniscus repair,biological material scaffold; athletic meniscal injury”为英文关键词,应用计算机检索维普数据库(1994-01/2009-12)和Pubmed数据库(1994-01/2009-12),纳入30篇运动性半月板损伤和组织工程半月板相关的文献。对半月板组织的特征、半月板组织工程种子细胞的来源、组织工程半月板支架材料生物相容性和可降解性以及细胞因子在组织工程半月板构建过程中的作用进行综合评价。 结果与结论：与传统半月板修复相比,组织工程化半月板具有无抗原性,来源不受限制,可按预先设计塑型,具有生命力等许多优点。但是组织工程化半月板仍有许多问题有待研究和解决,如何模拟体内环境,在体外成功构建半月板组织,如何提高支架材料的应用性,研制具有与正常人体半月板组织相接近的力学性能的支架材料是一个半月板修复的关键性问题。     

软骨修复材料种类的比较

摘要 背景：软骨修复材料要求具有特定的生化、物理性质,如极强的生物相容性、合适的生物降解性、可控的孔径大小、足够的孔隙率等。 目的：对比分析各种软骨修复材料的特点。 方法：应用计算机检索万方数据库、CNKI数据库2001/2010与软骨修复材料相关的文章,检索关键词为“软骨,修复,支架材料,组织工程,生物材料”。 结果与结论：软骨组织工程支架材料分为天然支架材料、复合支架材料、可注射支架材料、仿生支架材料等。但是各种材料具有各自的优势与不足,目前多采用复合支架材料或利用仿生原理制备仿生支架材料或是可注射型支架材料,以充分发挥材料的优势,克服不足,使其生物力学特性更加接近天然骨组织。尽管骨组织工程研究已经取得了相当快速的进展和成果,但仍有许多问题需要解决：支架的免疫原性即降解转归及对机体的影响;支架是否可与软骨下骨有效结合;支架材料的降解速度是否可与组织形成相匹配;支架的生物力学性能是否与软骨组织相同或接近等。 关键词：软骨;修复;支架材料;组织工程;生物材料 doi:10.3969/j.issn.1673-8225.2011.08.040     

半月板运动损伤修复中组织工程材料的应用

目的：以半月板运动损伤修复中组织工程材料为出发点，介绍了半月板的结构与功能、半月板种子细胞来源、细胞因子的作用及半月板损伤组织工程修复材料的应用。 方法：以“半月板，组织工程，运动损伤，支架”为中文检索词；以“Meniscus，tissue engineering, Sports Injuries，Bracket” 为英文检索词，应用计算机检索中文期刊全文数据库1998-01/2009-12期间的相关文章。纳入与组织工程半月板生物支架材料研究相关文献，排除重复分析，重点对21篇文献进行归纳分析。 结果：半月板生物支架材料按其来源可分为：天然生物材料、人工合成高分子材料和复合材料。在半月板组织工程中支架材料起着非常重要的作用，选择合适的载体是一个首先要解决的问题。在生物材料研制与开发过程中，应特别注重细胞与生物材料相互作用的研究；避免生物材料研究与种子细胞研究脱节；复合材料的制备不仅包括同一类生物材料的复合，还包括不同类别生物材料之间的交叉复合；对材料进行生物或化学修饰的复合材料、纳米材料、仿生材料及智能材料等的研制与开发将是未来生物材料研究的重要内容。 结论：通过对支架材料进行表面修饰、采用新型构建技术以及利用天然和合成材料的各自优势联合应用，进行多材料复合，以研制出具有生物相容性好、力学适应能力强的复合材料、仿生材料、智能材料将是近年来半月板生物支架材料的主要研究方向。 关键词：半月板；组织工程学；运动损伤；修复；生物材料 doi:10.3969/j.issn.1673-8225.2010.12.037     

Treatment Considerations in Anticonvulsant Monotherapy

Summary: The long-standing practice of polypharmacy in treating epilepsy is giving way to use of monotherapy. Monotherapy can improve seizure control as well as reduce the risk of serious idiosyncratic reactions, dose-related side effects, and complex drug interactions. Monotherapy also offers improved compliance and cost-effectiveness. The basis of monotherapy is accurate diagnosis and assessment of the patient's seizure type(s), followed by selection of a single appropriate anticonvulsant drug. Many patients currently treated with multiple anticonvulsants can be successfully converted to monotherapy with a carefully monitored program in which troublesome and redundant drugs are gradually withdrawn from the therapeutic regimen.     

Dextromethorphan: Cellular Effects Reducing Neuronal Hyperactivity

Summary: Dextromethorphan is a dextrorotary morphinan without affinity for opioid receptors, commonly used as an antitussive medication. During the past 5 years, interest in the compound and its demethylated derivative, dextrorphan, has been revived because additional neuroprotective and an-tiepileptic properties were found in in vitro studies, animal experiments, and a few clinical cases. Both morphinans are able to inhibit N -methyl-D-aspartate (NMDA) receptor channels and voltage-operated calcium and sodium channels with different potencies. The inhibition of the NMDA receptor is believed to be the predominant mechanism of action responsible for the anticonvulsant and neuroprotective properties of the compounds.     

Pediatric Epilepsy Surgery

Summary: The use of implantable arrays of epidural electrodes has made it possible to carry out extraoperative electrocorticography (ECoG) and functional localization in the awake child. This has permitted cortical excisions that are determined by criteria similar to those obtained during surgical procedures performed under local anesthesia in adults. In addition, the method also permits simultaneous ECoG and video monitoring during the child's symptomatic seizures, providing additional important localizing information that is impractical to obtain in operations under local anesthesia. We report our experience with 75 children, ages 5 months to 15 years, whom we have managed with epidural electrode arrays. The method of extraoperative ECoG is described and illustrative cases are presented to demonstrate its feasibility and utility in children. In addition, we call attention to gliomas as a common cause of chronic focal seizures in children. Of 49 children undergoing resection and followed for from 1 to 14 years (mean of 5.8 years), 32 (65%) are either seizure free or have had a significant reduction in seizure frequency that has unambiguously improved their quality of life. The results are analyzed further by relating the surgical outcome to each of the pathologic entities that caused the seizures. This analysis reveals the variety of neurological conditions that commonly cause intractable focal seizure disorder in children and distinguishes those pathologic entities in which the seizure disorder is apt to respond to surgical intervention from those that will not.     

Un nouveau cadre conceptuel de travail pour une psychiatrie revisitée ? Introduction à deux articles de E. Kandel

In two articles which appeared in the American Journal of Psychiatry and that were subsequently translated for Évolution Psychiatrique, E. Kandel examines the bases for a reinterpreted psychiatry that is prepared to confront the major challenge of the 3rd millenium: that of insight into the mind and brain. This requires a major reorganization of the discipline, which involves a reinvestment of the scientific approach and a critical  assessment of the data provided by psychoanalytical psychiatry and cognitive neurosciences. Seven concepts have therefore been proposed for interactive re-examination: consciousness, the unconscious, memory, emotion, development, desire, impulse. The dynamic relations existing between genetics and the environment allow one to see how evolutions are possible from actions at different levels, both psychotherapeutic and pharmacological. Imaging and other techniques provide additional objective information to the process of human interaction which remains the basis of psychiatry. A common framework for psychiatry and the neurosciences, a reconsideration and renewal of the psychoanalytical approach are both possible and necessary.     

Opioids and the developing organism: A comprehensive bibliography, 1984–1988

A comprehensive bibliography of the literature concerned with opioids and the developing organism for 1984-1988 is presented. Utilized with companion papers (Neurosci. Biobehav. Rev. 6:439-479; 1982; 8:387-403; 1984), these articles cover the clinical and laboratory references beginning in 1875. For the years 1984, 1985, 1986, 1987, and 1988, a total of 877 citations were recorded. A series of indexes accompanies the citations in order to make the literature more accessible. These indexes are divided into clinical and laboratory topics, and subdivided into such topics as the type of opioid explored and the general area of biological interest (e.g., physiology).     

La biologie et le futur de la psychanalyse : un nouveau cadre conceptuel de travail pour une psychiatrie revisitée

The American Journal of Psychiatry has received a number of letters in response to my earlier “Framework” article (1). Some of these are reprinted elsewhere in this issue, and I have answered them briefly there. However, one issue raised by some letters deserves a more detailed answer, and that relates to whether biology is at all relevant to psychoanalysis. To my mind, this issue is so central to the future of psychoanalysis that it cannot be addressed with a brief comment. I therefore have written this article in an attempt to outline the importance of biology for the future of psychoanalysis.     

Classification of methods in transcranial Electrical Stimulation (tES) and evolving strategy from historical approaches to contemporary innovations

Transcranial Electrical Stimulation (tES) encompasses all methods of non-invasive current application to the brain used in research and clinical practice. We present the first comprehensive and technical review, explaining the evolution of tES in both terminology and dosage over the past 100 years of research to present day. Current transcranial Pulsed Current Stimulation (tPCS) approaches such as Cranial Electrotherapy Stimulation (CES) descended from Electrosleep (ES) through Cranial Electro-stimulation Therapy (CET), Transcerebral Electrotherapy (TCET), and NeuroElectric Therapy (NET) while others like Transcutaneous Cranial Electrical Stimulation (TCES) descended from Electroanesthesia (EA) through Limoge, and Interferential Stimulation. Prior to a contemporary resurgence in interest, variations of transcranial Direct Current Stimulation were explored intermittently, including Polarizing current, Galvanic Vestibular Stimulation (GVS), and Transcranial Micropolarization. The development of these approaches alongside Electroconvulsive Therapy (ECT) and pharmacological developments are considered. Both the roots and unique features of contemporary approaches such as transcranial Alternating Current Stimulation (tACS) and transcranial Random Noise Stimulation (tRNS) are discussed. Trends and incremental developments in electrode montage and waveform spanning decades are presented leading to the present day. Commercial devices, seminal conferences, and regulatory decisions are noted. We conclude with six rules on how increasing medical and technological sophistication may now be leveraged for broader success and adoption of tES.     

Facteurs de risque environnementaux à la schizophrénie

Schizophrenia is currently a major concern, its prevalence being estimated at around 1% and its social consequences being severe. The elucidation of the pathophysiology of the disease is difficult due to the great variability of clinical expressions, the instability of the clinical symptoms during the evolution and the absence of reliable biological markers. The existence of a familial aggregation in schizophrenia is well known, the risk of presenting the disease for first-degree relatives of patients being 5 to 10 times higher than the risk observed in the general population. The genetic component was further confirmed by twin and adoption studies. Although the concordance for the disease is higher (40 to 70%) among monozygotic twins as compared with dizygotic twins (15%) it does not reach 100%, which implies that environmental factors modulate the effects of the genotype. However, the role of these factors and especially their interaction with genetic factors remain unclear but the implications of some specific environmental factors are well documented by recent research data. The current literature on sex differences in schizophrenia is consistent. Several studies have suggested that male and female patients may differ in age at the onset and expression of clinical symptoms. Complications during pregnancy or birth-giving may increase the risk of developing schizophrenia later in life. The major complications are oxygen deprivation during pregnancy, bleeding, maternal malnutrition or infection (exposure to influenza, for example). A low birth weight is associated with an increased risk of schizophrenia. Psychoses are more common among people living in an urban environment and among those born during winter months. Schizophrenia is probably more prevalent in people who are living promiscuously, are subject to toxic abuse, poor nutrition and stress but here more precise data are needed. Moreover, immigrants have a higher risk of developing psychotic disorders. In addition, head traumas are associated with an increased risk of schizophrenia. Though they are contentious, some studies suggest that substance abuse (cannabis use in European countries) is related to the development of schizophrenia, especially in people with genetic vulnerability. Moreover, substance misuse may worsen the symptoms. If the environment is sufficiently stressful, people with a high genetic vulnerability will develop some degree of mental illness, including schizophrenia. Conversely, a less stressful or a protective environment may decrease the risk of its onset in persons with a predisposition to schizophrenia.