内皮祖细胞在血管相关疾病治疗中的作用

背景：内皮祖细胞由于其高增殖潜能和多向分化性,近年来在治疗血管相关疾病方面的应用研究广泛开展。 目的：总结内皮祖细胞在治疗血管相关疾病应用方面的研究进展。 方法：应用计算机检索2004-01/2009-09 PubMed数据库相关文章,检索词为“endothelial progenitor cells,vascular-related disease”,并限定文章语言种类为English。同时计算机检索2004-01/2009-09清华同方数据库相关文章,检索词为“内皮祖细胞,血管相关疾病”,并限定文章语言种类为中文。由第一作者和第二作者对文献根据纳入及排除标准进行分类筛选,符合研究目的者对其内容、结果进行评价。最终纳入30篇文献。 结果与结论：内皮祖细胞是血管内皮细胞的前体细胞。目前已被证实内皮祖细胞不仅参与人胚胎血管发生,同时也参与出生后的血管新生。正常情况下内皮的损伤与周围成熟内皮细胞和内皮祖细胞对血管内皮的修复处于一种动态平衡状态;病理状态下,内皮祖细胞增殖并向外周血定向迁移、黏附功能减弱,导致血管内皮损伤不可修复甚至加重,从而成为许多血管相关疾病重要的致病因素之一。内皮祖细胞在治疗血管相关疾病方面有着很大的应用价值和前景,值得进一步深入研究与开发。     

泌尿系统组织工程支架材料的发展与应用

背景：应用组织工程方法进行膀胱、尿道、输尿管以及阴茎海绵体等各类泌尿器官重建的报道逐年增加,其中各类重建器官中支架材料的应用显得十分重要。 目的：结合近年来的相关文献,对组织工程支架材料在泌尿系统修复和重建中的应用进行总结。 方法：由第一作者应用计算机检索Pubmed 2003-01/2009-11 相关文章,检索词为“tissue engineering, biomaterials ,urethra,bladder,urology”,并限定语言种类为“English”;同时检索中国期刊数据库2003-01/2009-11 的相关文章,检索词为“组织工程,支架材料, 尿道,膀胱,尿路”,并限定文章语言种类为中文。选择文章内容与组织工程支架在泌尿系统中的应用相关,同一领域文献则选择近期发表或发表在权威杂志文章。 结果与结论：利用组织工程生物材料作为支架进行组织或器官修复与重建是目前泌尿系统组织工程研究的主要领域,各种天然、人工及复合材料相继用于动物实验或临床应用,尤其最近纳米技术的发展及应用为组织工程又开辟了一条新的途径,因此根据组织特性选取理化性质及超微结构相似的替代材料将是泌尿系统组织工程支架材料发展的方向。 关键词：泌尿系统;组织工程;生物材料;支架;种子细胞 doi:10.3969/j.issn.1673-8225.2010.29.043     

脐带血干细胞：组织工程人工心脏研究种子细胞的新来源*

背景：脐带血干细胞富含多种干/祖细胞,其各种干/祖细胞移植治疗和作为种子细胞在组织工程领域的研究成为当前的热点。 目的：综述脐带血干细胞中存在的多种干/祖细胞的生物学特性及在心脏疾病的实验应用和脐带血干细胞在心脏疾病的实验应用。 方法：应用计算机检索1999-01/2009-10中国数字图书馆、维普期刊数据库相关文章,检索词为“脐带血干细胞,造血干/祖细胞,间充质干细胞,内皮祖细胞,内皮细胞,心肌细胞,组织工程,种子细胞”,并限定文章语言种类为中文。同时计算机检索1999-01/2009-10 PubMed 数据库相关文章,检索词为“umbilical cord blood stem cells,hematopoietic progenitor cells/hematopoietic stem cells,mesenchymal stem cells,endothelial progenitor cells,endothelial cells,myocardial cells,tissue engineering,seeded cells”,并限定文章语言种类为English。同时手工检索《干细胞生物学》专著,共检索到文献95篇。根据纳入标准最终纳入文献30篇。 结果与结论：脐带血干细胞是一种成体多能干细胞,富含造血干/祖细胞、间充质干细胞、内皮祖细胞、非限制性体干细胞等。相对于骨髓干细胞和外周血干细胞,脐带血干细胞来源丰富,获得更为容易,更为原始,分化增殖能力更强,排斥反应小,在体外可以分化为血管内皮细胞、心肌细胞等多种细胞。基于脐带血干细胞独特的生物特性、资源优势及在冠心病和缺血性心肌病的治疗上取得了一定的成果,为构建组织工程人工心脏的种子细胞来源提供可能,在心脏再生和组织工程人工心脏方面的应用展示了广阔的前景。     

涂层材料及技术在医学临床领域的应用

背景：涂层材料及技术已在人们的生产生活中广泛应用,在医学领域里也得到了蓬勃发展。 目的：综述涂层材料及技术在医学领域中的应用进展。 方法：应用计算机检索2000-01/2010-12万方数据库相关文章,检索词“涂层,医学,应用”,并限定文章语言种类为中文。同时计算机检索2000-01/2010-12 PubMed数据库相关文章,检索词“coating,medicine,application”,并限定文章语言种类为English。共检索到文献614篇,最终纳入符合标准的文献30篇。 结果与结论：涂层技术在生活的方方面面都有应用,在医学领域里的应用也日渐蓬勃,目前研制出了很多生物相容性好排斥反应小的涂层材料并应用于临床。文章分别从口腔、体外循环、骨科等领域对涂层支架进行介绍,发现开发新的涂层药物,寻找更加合理有效的药物组合,可能会使药物涂层支架的治疗作用产生质的飞跃。     

中医药在脑血管支架置入后防治并发症中的作用

目的：评价中医药在脑血管支架置入后并发症中的作用效果。 方法：应用计算机检索Science Direct 数据库、Ei数据库1960-01/2009-10期间的相关文章，检索词为“traditional Chinese medicine，stent placement，complication”，并限定文章语言种类为English。同时计算机检索中国期刊全文数据库、中国生物医学文献数据库等1994-01/2009-10期间的相关文章，检索词为“中医药，脑血管，支架置入，并发症”，并限定文章语言种类为中文。此外还手工查阅相关专著数部。纳入有关中医药防治脑血管支架置入后并发症的基础与临床实验。 结果：脑血管支架置入后的中医药干预方法以益气、活血、涤痰为基本治法,亦可佐以疏肝理气、安神利水、凉血止血之品。常用的中药复方有生脉散、补阳还五汤、血府逐瘀汤加减、四逆汤及抵挡汤加减等。现代药理学研究表明，大量益气活血化瘀涤痰的中药及复方，通过多组分、多靶点、多途径的整合调节作用，有效地干预脑血管支架置入后并发症的发生。 结论：对脑血管支架置入围手术期进行中医药干预，发挥中医药特色，对于提高手术成功率，防治、减少围手术期及远期并发症具有重要意义。     

表皮干细胞的研究进展

背景：随着分子生物学、细胞生物学及生物工程学的发展，表皮干细胞凭借其特有的生物学优势在基因治疗、细胞治疗中越来越受到重视。 目的：综述表皮干细胞的相关研究进展。 方法：第一作者应用计算机检索2000-01/2009-01 PubMed数据库(网址http://www.ncbi.nlm.nih.gov/PubMed)相关文章，检索词为“epidermal stem cell，marker，clinical application”，并限定文章语言种类为English。同时计算机检索2000-01/2009-01 CNKI数据库(网址http://www.cnki.net/index.htm)相关文章，检索词为“表皮干细胞，标记物，临床应用”，并限定文章语言种类为中文。共检索到文献815篇，最终纳入21篇。 结果与结论：了解表皮干细胞的来源、分布特征、鉴定方法、增殖与分化调控的机制、临床应用现状等方面的研究进展是进一步应用表皮干细胞治疗疾病的重要前提和理论基础。表皮干细胞具有无限增殖和多向分化的潜能，对维持表皮的自我更新、保持皮肤的正常结构以及对皮肤的创伤修复具有重要意义。表皮干细胞已引起越来越多研究者的关注。     

表皮干细胞的生物学特性及应用*★

背景：尽早去除创面坏死组织、重建皮肤结构和功能，是大面积深度烧伤治疗的关键和最终目标。表皮干细胞作为皮肤组织特异性干细胞，拥有无可置疑的潜能。 目的：总结表皮干细胞的生物学特性及应用现状。 方法：应用计算机检索2000-01/2010-10 PubMed数据库相关文章，检索词“epidermal stem cells，basic study”，并限定文章语言种类为English。同时计算机检索2005-01/2010-10万方数据库相关文章，检索词为“表皮干细胞”，并限定文章语言种类为中文。共检索到文献271篇，最终纳入符合标准的文献38篇。 结果与结论：表皮干细胞是具有多向分化潜能、自我更新能力和高度增殖能力的细胞，具有慢周期性和对基底膜的黏附能力，其增殖分化受到壁龛及Wnt信号通路、MAPK、c-Myc、Notch信号传导通路、细胞因子等的调控。目前尚无公认的特异性标志物，可用于创面修复、基因治疗、组织工程领域。随着表皮干细胞研究的深入，将为皮肤基础研究、创面功能修复和皮肤遗传病的治疗提供新途径。     

不同类型支架材料治疗颅内动脉狭窄：并发症防治及应用进展

目的：探讨不同类型支架材料治疗颅内动脉狭窄治疗效果及并发症防治情况。 方法：应用计算机应用计算机检索Science Direct 数据库、Ei数据库1998-01/2009-10期间的相关文章,检索词为“intracranial arteriostenosis,stent placement”,并限定文章语言种类为English。同时计算机检索中国期刊全文数据库、中国生物医学文献数据库等1998-01/2009-10期间的相关文章,检索词为“颅内动脉狭窄,支架置入”,并限定文章语言种类为中文。此外还手工查阅相关专著数部。纳入不同支架置入治疗颅内动脉狭窄的研究,包括基础与临床实验。 结果：从目前世界范围内的多中心研究结果看,颈动脉狭窄的支架置入治疗较颈动脉内膜剥脱有明显的优势。近年来,随着球囊和支架柔顺性的改进及支架技术的发展,各种新型材料及脑保护伞的应用,支架治疗颅内动脉狭窄已逐渐成为一种安全有效的方法,血管内支架已成为治疗颅内动脉狭窄相对安全有效的新途径。但支架置入治疗后会发生不同并发症如再狭窄、缺血性脑卒中、脑出血高灌注综合征、脑血管痉挛等。 结论：颅内动脉支架置入治疗安全性和有效性还缺乏多中心前瞻性研究的支持。支架置入治疗术后较高的再狭窄率尚无很有效办法,有待支架材料的进一步发展。     

椎间盘源性腰痛的病理生理学机制及组织工程学技术

背景：椎间盘源性腰痛的发病机制存在争议，认识其病理生理学机制，可为临床诊断和治疗提供重要的理论基础。 目的：综述国内外关于椎间盘源性腰痛的病理生理学机制及组织工程学技术在其应用中的研究概况。 方法：应用计算机检索PubMed 1980-01/2009-08 期间的相关文章，检索词为“椎间盘源性腰痛，下腰痛，Discogenic low back pain，low back pain，tissue engineering”，并限定文章语言种类为English。同时计算机检索中国期刊全文数据库2000-01/2009-08期间的相关文章，检索词为“椎间盘源性腰痛”，并限定文章语言种类为中文。此外还手工查阅相关专著数部。纳入椎间盘退变的病理生理机制、椎间盘突出致疼痛的病理生理学机制研究。 结果与结论：慢性下腰痛部分是椎间盘本身内部结构病变导致的。自然退变和机械压力改变导致髓核和纤维环的破裂，神经纤维通过破裂的纤维环长入到椎间盘的内部，椎间盘内的髓核等组织破裂后能够刺激周围产生炎症因子，这些炎症因子刺激神经产生疼痛；腰部机械压力的改变，炎症因子进一步刺激神经导致疼痛加重。治疗盘源性下腰痛，传统手术治疗如椎间盘切除、腰椎融合、椎间盘内射频消融等会牺牲正常脊柱的高度和脊柱节段的活动，促进椎间盘的再生和椎间盘置换有可能解决这个问题，故组织工程方面治疗盘源性腰痛成为新的热门。     

骨祖细胞的特征及其相关影响因素***★

学术背景：寻找能重建再造骨缺损的种子细胞，获得稳定可靠的细胞来源是组织工程化骨构建的重要先决条件。组织工程化骨已成为最有希望进入临床应用的组织工程成果之一。目前骨组织工程的研究集中于成骨细胞范畴，而对可以增殖、分化为成骨细胞并最终成骨的骨祖细胞的研究相对较少。 目的：本文就骨祖细胞的特征及其相关影响因素进行综述，以便了解骨祖细胞在骨组织工程学领域的应用前景和研究价值。 检索策略：由本文作者应用计算机检索PubMed1996-01/2007-06期间的相关文章，检索词为“osteoprogenitor cells，bone tissue engineering，bone formation”，同时检索维普数据库2000-01/2007-06期间的相关文章，检索词为“骨祖细胞，骨组织工程，骨形成”。对资料进行初审，并查看每篇文献后的引文。纳入标准：文章所述内容与骨祖细胞特性及其相关影响因素有关。排除标准：内容陈旧或重复文献。 文献评价：共收集到66篇关于骨祖细胞特征及其相关影响因素的文献， 纳入30篇。1 篇为综述，其余29篇为临床或基础研究。 资料综合：①骨祖细胞的特征：骨祖细胞具有阶段性的分化特征，第一代是增殖能力最强的骨祖细胞；随着年龄的增长，骨祖细胞的增殖能力逐渐减弱，但数目无明显减少。②传统观念认为骨形成过程主要是由内分泌系统及局部因子等调控。然而，越来越多的证据表明，骨组织内的一些神经细胞因子、富含脯氨酸的酪氨酸激酶2、骨形态发生蛋白2、内皮细胞等均可加强骨祖细胞的成骨能力。 结论：骨祖细胞具有阶段性分化和增龄性变化的生物学特性，其增殖分化受多种因素影响，但具体机制尚不明确。     

Diagnostic Difficulties and Treatment Implications

Summary: Differentiation between types of epileptic seizures has been aided in recent years by the introduction of intensive neurodiagnostic techniques and the development of increasingly detailed classification systems. Paradoxically, these developments have not simplified the task of matching the appropriate antiepileptic drug to a particular seizure type. It is reasonable to assume that anticonvulsant drugs will have different effects on different types of seizures, but faulty, circular reasoning can enter the picture if one also assumes that responses of seizures to different drugs signify different seizure types. There are several examples of differential diagnoses that can fall prey to this problem, including the diagnosis between partial seizures with secondary generalization and generalized tonic-clonic seizures, and the diagnosis between complex partial seizures and absence seizures with automatisms, among others. Considerations of etiology in future classification systems can further complicate the problem: should one then choose an anticonvulsant drug on the basis of individual seizure type or on the basis of the type of epilepsy? Ramifications of this issue extend even to the drug approval process. Official sanction is not given for use of a drug for a seizure type not included in the original efficacy studies, even if later scientific evidence shows that seizure type to be related to a type that is included. New trials must be undertaken. These problems arise from how we choose to classify seizures.     

Cognitive Dysfunction Associated with Antiepileptic Drug Therapy

Summary: Epilepsy is frequently associated with cognitive dysfunction. However, the reasons for this correlation are unclear. Possible influential factors include patient age; duration, frequency, etiology, and type of seizures; hereditary factors; psychosocial issues; and antiepileptic drug (AED) therapy. Whereas many of these factors are beyond the physician's control, AED therapy is one element that can be addressed in treatment decisions by recognizing the potential cognitive effects of particular AEDs. For example, phenobarbital impairs memory and concentration; phenytoin affects attention, problem solving ability, and performance of visuomotor tasks. In contrast, carbamazepine may affect concentration, while valproate would appear to have minimal effects on cognition. Moreover, cognitive effects of AEDs are amplified with coadministration of multiple anticonvulsants (polytherapy). A review of studies on the cognitive effects of monotherapy with AEDs, as opposed to those of polytherapy, provides evidence that drug-related cognitive dysfunction can be reversed if patients are switched to a simpler therapeutic regimen. Future research should be directed toward developing reliable measures for assessing and monitoring cognition, and understanding the particular cognitive side effects of each AED. Physicians also need to revise their opinions about which side effects are "tolerable" for epileptic patients.     

Hepatic Considerations in the Use of Antiepileptic Drugs

Summary: Virtually all of the major antiepileptic drugs (AEDs) can cause hepatotoxicity, although fatal hepatic reactions are rare. The mechanisms, incidences, and risk profiles for such reactions differ from drug to drug. With carbamazepine and phenytoin, hepatotoxicity may be due to drug hypersensitivity. Although the profiles of patients at risk have not been well-defined for these two antiepileptic drugs, it would appear from reports in the literature that older adolescents and adults are at higher risk than children of developing serious or fatal hepatotoxicity. Once hepatotoxicity develops, mortality rates are 10–38% with phenytoin and 25% for carbamazepine. The risk profile for valproate fatal hepatotoxicity has been more clearly defined. Those at primary risk of fatal hepatic dysfunction are children under the age of 2 years who are receiving multiple anticonvulsants and also have significant medical problems in addition to severe epilepsy. The risk is considerably lower for patients over the age of 2 years on valproate monotherapy. In contrast to the risk profile with other AEDs, adults receiving valproate as monotherapy have the lowest risk of hepatotoxicity. Fatal hepatic dysfunction coincident with valproate may be the result of aberrant drug metabolism. Concomitant use of AEDs that induce microsomal P450 enzymes (e.g., phenytoin and phenobarbital) may enhance the production of a toxic metabolite, and hence the greater risk of hepatotoxicity with polypharmacy.     

Vascular Malformations and Epilepsy: Clinical Considerations and Basic Mechanisms

Summary: Vascular malformations (VMs) are associated with epilepsy. The natural history of the various VMs, clinical presentation, and tendency to provoke epilepsy determine treatment strategies. Investigations have probed the mechanisms of epileptogenesis associated with these lesions. Electrophysiologic changes are associated with epileptogenic cortex adjacent to VMs. Putative pathophysiologic mechanisms of epileptogenesis include neuronal cell loss, glial proliferation and abnormal glial physiology, altered neurotransmitter levels, free radical formation, and aberrant second messenger physiology.     

Carbamazepine Efficacy in Adults With Partial and Generalized Tonic-Clonic Seizures

Summary: Carbamazepine and phenytoin are drugs of choice in initial monotherapy for adult partial and secondarily generalized tonic-clonic seizures. These designations reflect the results of the Veterans Administration Epilepsy Cooperative Study Group of 1985. An earlier comparative study of carbamazepine and phenytoin by Ramsay and associates found both drugs equally effective in controlling new-onset seizures. Among the advantages of carbamazepine is that it causes relatively few cognitive and dysmorphic side effects. Its disadvantages are its unavailability in parenteral formulation and its metabolic autoinduction. The latter must be compensated for by planned dosage increases to maintain therapeutic plasma steady-state levels during the first 2 or 3 months of treatment. Carbamazepine is judged a drug of choice in the treatment of these secondarily generalized tonic-clonic seizures, and the drug of choice in children, adolescents, and women susceptible to the dysmorphic side effects associated with other anticonvulsant agents.     

Etiologic and Preventive Aspects of Epilepsy in the Child–Bridging the Gap Between Laboratory and Clinic

Summary: Four broad categories of basic phenomena are pertinent to developing ways to prevent epilepsy. These include mechanisms of epileptogenesis, ictal initiation and temporary entrainment by the seizure discharge of normally functioning brain, seizure propagation, and control mechanisms that function both to restrain the cascade of epileptic events culminating in a seizure and to arrest the epileptic event and restore the interictal state. In newborns and children, hypoxia-ischemia is a major factor leading to epileptogenesis, and several schemes are proposed to classify, quantify, and prevent hypoxic-ischemic encephalopathy. Control mechanisms must be better understood in order to develop prophylactic recommendations for epilepsy, and an experimental model of "kindling antagonism" may increase our understanding of these. Programs of prevention of seizures in children will evolve only if basic researchers and clinicians work productively together to develop an adequate understanding of factors important in epileptogenesis and antiepileptogenic control mechanisms.     

Epilepsy and anomalies of neuronal migration: MRI and clinical aspects

Neuronal migration disorders are the result of disturbed brain development. In such disorders, neurons are abnormally located. In diagnosing these conditions, magnetic resonance imaging is superior to any other imaging technique. This enables us to improve our knowledge of the clinical correlates of neuronal migration. With reference to migrational disorder, a retrospective study of all 303 patients with epileptic seizures referred for magnetic resonance imaging during a 3-year period was performed, 13 patients (aged 12-41, mean age 27) were identified. They represent 4.3% of the entire study group. Of the patients with known epilepsy, 6.7% and of the mentally retarded, 13.7% had migrational disorders. Four patients had schizencephaly as the dominant finding, one was classified as hemimegalencephaly, 2 had isolated heterotopias, and 6 had localized pachy- and/or poly-microgyria. The clinical pictures are complex. Ectopias of grey matter are recognised foci of epilepsy, but from an epileptological and a clinical viewpoint little attention has been given to these disorders. The present study shows that malmigration is not rare in epilepsy patients, especially not in the mentally retarded.     

Carbamazepine Efficacy and Utilization in Children

Summary: Carbamazepine is effective for preventing partial and generalized tonic-clonic seizures in children. Although absence epilepsies are more common in children than adults, an estimated 80% of children with epilepsy have seizure types or epilepsies that are potentially responsive to carbamazepine. The differential diagnosis of ictal staring is an especially important issue in children because absence and atypical absence seizures are more prevalent in children than adults. Age-related pharmacokinetic differences and drug interactions are major considerations in children. On average, children have higher clearance rates of carbamazepine, shorter half-lives, and higher ratios of carbamazepine-10, 11-epoxide to carbamazepine than adults. In addition, children with severe epilepsy are more likely to require multiple-drug therapy, which can lead to complex drug interactions. When carbamazepine is administered along with valproate, drug protein binding interactions can cause intermittent side effects.     

Predisposing and Causative Factors in Childhood Epilepsy

Summary: We review information from large studies of defined populations, examining the role of known factors and especially of prenatal and perinatal factors in contributing to nonfebrile seizure disorders of early childhood. We depend especially, but not exclusively, on the recently completed analyses from the Collaborative Perinatal Project of the National Institute of Neurological and Communicative Disorders and Stroke, the NCPP. About 4% of children in the NCPP who had at least one non-febrile nonsymptomatic seizure by the age of 7 years had a previous seizure during acute neurologic illness, such as meningitis or during the acute illness after trauma. Many such seizures should potentially be preventable. Of children with seizures, 10% had had a neonatal seizure and 13% had had a febrile seizure. Among the hundreds of prenatal and perinatal factors explored as predictors of childhood seizure disorders, the principal predictors identified were congenital malformations of the fetus, cerebral and noncerebral; family history of certain neurologic disorders; and neonatal seizures. In agreement with the British National Child Development Study, labor and delivery factors in the NCPP appeared to contribute very little to childhood seizure disorders. Maldevelopment, rather than damage at birth to an initially intact nervous system, appeared to be the more common mechanism. Most seizure disorders of early childhood remained unexplained by the large set of prenatal and perinatal characteristics examined.     

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.