脂质体作为骨靶向药物载体的应用研究进展

目的：通过探究脂质体作为骨靶向药物载体的研究进展，以促进其作为特异性骨靶向给药系统进入临床应用。方法应用计算机检索PubMed、中国期刊全文数据库（ CNKI）的相关文献，选择文章内容与骨靶向脂质体相关者，同一领域文献则选择近期发表在权威杂志的文章。结果根据纳入标准选择22篇文献进行综述。结论脂质体作为药物载体，因其制备简单、无毒、无免疫原性、易携载和释放各种药物等特点而备受关注。脂质体经修饰后可通过被动靶向、主动靶向和双重靶向三种靶向方式携带药物沉积于骨中，从而使药物能选择性地作用于骨组织，这将解决一些治疗骨病的药物疗效低、不良反应大的问题。迄今为止研究最多的是主动骨靶向脂质体，即通过对脂质体表面进行化学修饰，使脂质体具有骨趋向性。目前，脂质体作为骨靶向递药系统的研究已取得较大进展，这些研究初步解决了药物骨靶向性的问题，但是脂质体要作为一个理想的骨靶向性药物载体进入临床应用尚有许多待解决的问题。     

胆道系统恶性肿瘤靶向治疗研究进展

正胆道系统恶性肿瘤发病率不高,总体预后差。手术、化疗、放疗等治疗手段效果均不佳。近年来,人们对胆道系统恶性肿瘤分子机制逐步深入了解,确立了一些新的关键性基因和信号通路改变,认识到不同来源胆道系统恶性肿瘤的发生发展分子机制存在明显不同,从而为其向药物个体化治疗确定了新方向。本文就相关内容进行综述。1胆道系统恶性肿瘤常见的基因和信号通路改变近年来,随着二代测序等分子检测技术的日趋完善,一     

肝内胆管癌分子靶向治疗的研究进展

肝内胆管癌（ICC）在原发性肝癌中发病率仅次于肝细胞性肝癌。近年来ICC的发病率明显增加,手术切除是根治ICC唯一的治疗方法。但由于其恶性程度高,早期缺少有效的筛查策略,大多数患者确诊时多处于中晚期而不能行根治性手术,因此患者总体生存率低、预后差。对于无法手术切除的晚期ICC患者5年生存率仅为5%～10%,辅助治疗对于提高晚期ICC患者生存率具有非常重要的意义。分子靶向治疗是当下治疗中晚期肿瘤的研究热点和最新方向,并已在临床上取得良好的治疗效果。现就分子靶向治疗在ICC治疗中的研究进展进行综述以供参考。     

进展期胃癌分子靶向治疗

胃癌是消化系统最常见的恶性肿瘤,在世界范围内,死亡率位居第二位.与日本等国家不同的是,我国90%以上的胃癌患者在就诊时处于进展期.外科手术和围手术期化疗是进展期胃癌治疗的主要手段.标准D2手术和新型化疗药物的出现在一定程度上改善了胃癌治疗效果,但仍然未能达到人们的期望.     

破骨细胞与骨吸收

骨吸收可发生于骨骼系统的各个部位．可见于全身性疾患与局部病变，骨骼肿瘤与骨囊肿，还可见于正常的生理性骨吸收，维持骨的生长、代谢平衡。骨吸收与破骨细胞相伴随，对破骨细胞的形态、结构、功能及来源的研究探讨，对各种骨疾病防治，具有重要的意义。     

肾细胞癌靶向治疗预后相关因素研究进展

肾细胞癌（RCC）是泌尿系统常见的恶性肿瘤之一。分子靶向治疗是通过干预肿瘤细胞信号传导通路,抑制肿瘤的生长。相比于传统的细胞冈子治疗手段．肾癌靶向治疗效果更好。但是目前对肾癌靶向治疗的预后仍缺乏有效判断手段,本文结合最新研究综述了RCC靶向治疗预后密切相关的影响冈素研究现状及进展。     

髂骨巨大骨软骨瘤1例报告

患者,男,８４岁。１５年前无明显诱因出现左髋部无痛硬性包块,未经诊治。随时间推延包块逐渐增大,于１９９７年５月３０日入院。检查全身情况无特殊。血沉、血磷、血钙、碱性磷酸酶、肝功能均在正常范围。胸片、Ｂ超无异常。左髂前上棘处可见７ｃｍ×５ｃｍ×２ｃｍ凸...     

骨形态计量学在骨质疏松研究领域的研究进展

骨质疏松症，是以骨量减少及骨组织显微结构退变为特征的一种全身性骨骼疾病，伴有骨脆性增加，易于发生骨折。骨质疏松症可分为原发性、继发性和特发性3大类。其中，原发性骨质疏松症约占骨质疏松症的90％，它又可分为两型：其一，为绝经后骨质疏松症，其二，为老年性骨质疏松症。目前，随着人口老龄化日趋明显，骨质疏松症的发病率已位居全球常见病的第7位，     

Clinical usefulness of bone markers in prostate cancer with bone metastasis

Bone metastases occur in approximately 70% of patients with advanced prostate cancer. Skeletal‐related events have been correlated with reduced survival and quality of life of patients with prostate cancer. Biochemical markers of bone metabolism (e.g. bone formation, bone resorption, osteoclastogenesis) might meet an unmet need for useful, non‐invasive and sensitive surrogate information for following patients' skeletal health. Recently, zoledronic acid and denosumab have been proven to have the potential for preventing skeletal‐related events among prostate cancer patients with bone metastasis. An improved understanding of the mechanisms underlying bone metastasis has also led to the recognition of multiple molecular targets and advances in therapy. However, estimating the efficacy of these agents is difficult. A clinical trial for castration‐resistant prostate cancer is currently underway based on the definition of The Prostate Cancer Clinical Trials Working Group, and bone turnover markers are being used as conventional end‐points for the clinical trial. Bone turnover markers are useful surrogate markers reflecting the effect of new therapeutic drugs and prognosis, as well as assessment of bone metastases. In particular, N‐terminal cross‐linked telopeptide of type 1 collagen and bone‐specific alkaline phosphatase are widely used bone metabolism markers, and offer reliable surrogate markers to detect bone metastatic spread and to predict prognosis for prostate cancer patients with bone metastases.     

In vivo bioluminescence imaging of magnetically targeted bone marrow‐derived mesenchymal stem cells in skeletal muscle injury model

The purpose of this study is to clarify the kinetics of transplanted mesenchymal stem cells (MSCs) in rat skeletal muscle injury model and the contribution of the magnetic cell delivery system to muscle injury repair. A magnetic field generator was used to apply an external magnetic force to the injury site of the tibia anterior muscle, and 1 × 10⁶ MSCs labeled with ferucarbotran–protamine complexes, which were isolated from luciferase transgenic rats, were injected into the injury site. MSCs were injected with and without an external magnetic force (MSC M+ and MSC M? groups, respectively), and phosphate‐buffered saline was injected into injury sites as a control. In vivo bioluminescence imaging was performed immediately after the transplantation and, at 12, 24, and 72 h, and 1 and 4 weeks post‐transplantation. Also, muscle regeneration and function were histologically and electromechanically evaluated. In vivo bioluminescence imaging showed that the photon of the MSC M+ group was significantly higher than that of the MSC M? group throughout the observation period. In addition, muscle regeneration and function in the MSC M+ group was histologically and functionally better than that of the MSC M? group. The results of our study indicated that magnetic cell delivery system may be of use in directing the transplanted MSCs to the injury site to promote skeletal muscle regeneration. © 2012 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 31: 754–759, 2013     

生物钟基因BMAL1调控颌骨及全身骨发育的研究进展

脑和肌肉ARNT样蛋白1（brain and muscle arnt?like 1,BMAL1）基因作为昼夜生物钟的核心组成部分,在多种信号通路的介导下参与并调控体内各项生理活动。BMAL1基因的失活可以抑制软骨细胞和成骨细胞并促进破骨细胞的分化,阻碍软骨内成骨、膜内成骨及骨代谢,造成颌骨发育畸形、骨关节炎及骨质疏松等骨骼疾病。因此,笔者就BMAL1基因调控骨骼发育的研究进展作一综述,探讨其在颌骨及全身骨发育中可能发挥的作用及分子机制,以期为寻求新的防治方法提供思路。     

Plastic surgical delivery systems for targeted gene therapy

The expansion of gene therapy applications from inherited disorders to acquired conditions has been mirrored by an exponential rise in both experimental work and clinical trials. This review highlights current plastic surgical delivery systems and clinical applications for targeted gene therapy. We revisit some of the vectors used both experimentally and in clinical gene therapy trials, with an emphasis on developments in plastic surgical delivery systems resulting in improved targeting of therapeutic genes. In addition, we discuss a novel technique for the delivery of gene therapy using the ex vivo transduction of free flaps, developed in our laboratory. This delivery system achieves targeted high-level transgene expression with minimal demonstrable systemic toxicity. Advances in delivery systems are essential for translating basic research into clinical therapeutics.     

基于“骨肉不相亲”理论探讨骨骼肌源性外泌体在老年性骨质疏松中的作用

中医学"骨肉不相亲"理论高度概括了老年性骨质疏松(senile osteoporosis,SOP)骨骼和骨骼肌的内在失衡状态,外泌体作为一种细胞囊泡可携带多种生物活性分子在"骨-肌交联"中发挥关键的调控作用。本文基于"骨肉不相亲"理论探讨骨骼肌源性外泌体在SOP中的作用,对挖掘中医药防治SOP的新靶点及丰富"骨肉不相亲"理论的现代科学内涵具有重要意义。中医学调理脾肾、强肌健骨是治疗SOP"骨肉不相亲"的关键,为防治SOP提供了新的思路。     

局部应用抗生素缓释系统治疗创伤后及内固定相关骨感染临床疗效观察

[目的]探讨局部应用抗生素缓释系统治疗创伤后及内固定术后骨感染的临床疗效。[方法]自2009年5月~2013年9月采用抗生素缓释系统局部应用治疗创伤后骨感染32例,男14例,女18例,平均年龄46岁(15~61岁)。骨折内固定术后骨感染20例,胫骨开放骨折继发感染4例,外伤性骨髓炎8例。解剖部位:股骨4例,胫骨16例,肱骨2例,跟骨8例,跖骨2例。左16例,右16例。手术方法:首先彻底清创病灶,然后将自行制备负载抗生素PMMA骨水泥链珠或硫酸钙人工骨置入感染灶,常规放置引流,术后48~72 h内拔除。以感染清除率、骨愈合率、愈合时间和再手术率作为疗效评价指标。[结果]平均随访28个月(12~47个月)。25例骨感染Ⅰ期痊愈,Ⅰ期感染清除率(25/32)78.1%,剩余7例中5例再手术后愈合,再手术率21.9%,Ⅱ期感染清除率(30/32)93.7%。30例骨折/骨腔愈合,2例骨折骨腔未完全愈合,愈合率93.7%。骨折平均愈合时间4.2个月(3~6个月),骨腔平均愈合时间5.2个月(2~8个月)。硫酸钙人工骨吸收平均8周(4周~7个月)。[结论]清创后局部应用载抗生素缓释系统治疗创伤后及骨折内固定术后骨感染治愈率和骨折/骨腔愈合率高,而负载抗生素的硫酸钙人工骨具有抗感染和骨修复作用等,是用于治疗上述骨感染的理想方法。     

氟骨症性胸椎管狭窄症后路减压手术中骨刀和非骨刀减压方式的对比研究

目的比较氟骨症性胸椎管狭窄症后路减压手术中,应用骨刀和非骨刀两种减压方式。方法回顾性分析进行胸椎后路及部分上腰椎后路减压手术的出血量、手术时间及效果。220例氟骨症性胸椎管狭窄症患者分为两组：A组为应用骨刀减压组(126例)。B组为非骨刀减压组。比较术中出血量、手术历时、术后改善率,平均随访2年3个月。结果骨刀减压组术中出血量、手术历时、显著低于非骨刀减压组,而术后改善率与非骨刀减压组则无显著性差别。结论对于氟骨症性胸椎管狭窄症行后路减压手术,在获得相同疗效下应用骨刀减压比非骨刀减压更能减少术中出血量,缩短手术时间。     

脊柱骨纤维结构不良1例

1 病例资料 患者,女,64岁。2006年6月23日就诊。5年前无明显诱因出现双下肢无力,自觉腿软,抬腿无力。     

基于“骨肉不相亲”理论骨与骨骼肌关系的探讨

骨质疏松症和肌肉减少症是老龄化社会常见的增龄性肌骨疾病。现代研究提示,骨与骨骼肌作为共同的功能单位参与了增龄性肌骨疾病的病理过程,从生物力学机制、能量代谢、内分泌、细胞、基因和信号通路等多方面存在相互关联。因此,对骨与骨骼肌关系的研究将有助于预防和治疗此类疾病。中医对骨与骨骼肌关系多从"脾肾"关系来认识,其中,"骨肉不相亲"理论是这种认识的高度概括。现代研究从多维度验证了"骨肉不相亲"理论的合理性。基于"骨肉不相亲"理论和骨与骨骼肌关系的现代研究成果,笔者从生物力学机制、内分泌、能量代谢、基因和信号通路等方面讨论骨与骨骼肌的关系,为骨质疏松症和肌肉减少症等增龄性肌骨疾病的精准防治提供新的思路和有效药物。