Skeletal Blood Flow in Bone Repair and Maintenance

Bone is a highly vascularized tissue, although this aspect of bone is often overlooked. In this article, the importance of blood flow in bone repair and regeneration will be reviewed. First, the skeletal vascular anato- my, with an emphasis on long bones, the distinct mechanisms for vascularizing bone tissue, and methods for remodeling existing vasculature are discussed. Next, techniques for quantifying bone blood flow are briefly summarized. Finally, the body of experimental work that demonstrates the role of bone blood flow in fracture healing, distraction osteogenesis, osteoporosis, disuse osteopenia, and bone grafting is examined. These results illustrate that adequate bone blood flow is an important clinical consideration, particularly during bone regeneration and in at-risk patient groups.

韧带和肌腱的生物力学和力学生物学研究（英文）

国际韧带和肌腱研讨会(The International Symposium on Ligaments and Tendons,ISI&T)于2000年在美国佛罗里达州奥兰多市首次召开。研讨会的宗旨是引起对韧带和肌腱研究的重视,并为生物工程师、生物学家、临床医师提供一个可以分享、评论、讨论韧带和肌腱最新研究成果的论坛。从2000年起,国际韧带和肌腱研讨会已经开展了15届;每届研讨会上涌现了大量令人振奋的关于当前韧带和肌腱研究热点和未来挑战的讨论。多年来,韧带和肌腱领域内的研究数量大幅增加,研究质量不断提升。为纪念《医用生物力学》杂志创刊30周年,本文总结过去30年里韧带和肌腱研究的主要进展,包括组织力学、力学生物学、损伤与治愈机制、组织修复和再生。

A comprehensive study of long-term skeletal changes after spinal cord injury in adult rats

Spinal cord injury（SCI）-induced bone loss represents the most severe osteoporosis with no effective treatment.Past animal studies have focused primarily on long bones at the acute stage using adolescent rodents. To mimic chronic SCI in human patients, we performed a comprehensive analysis of long-term structural and mechanical changes in axial and appendicular bones in adult rats after SCI. In this experiment, 4-month-old Fischer 344 male rats received a clinically relevant T13 contusion injury. Sixteen weeks later, sublesional femurs, tibiae,and L4 vertebrae, supralesional humeri, and blood were collected from these rats and additional non-surgery rats for micro-computed tomography（m CT）, micro-finite element, histology, and serum biochemical analyses.At trabecular sites, extreme losses of bone structure and mechanical competence were detected in the metaphysis of sublesional long bones after SCI, while the subchondral part of the same bones showed much milder damage. Marked reductions in bone mass and strength were also observed in sublesional L4 vertebrae but not in supralesional humeri. At cortical sites, SCI induced structural and strength damage in both sub- and supralesional long bones. These changes were accompanied by diminished osteoblast number and activity and increased osteoclast number and activity. Taken together, our study revealed site-specific effects of SCI on bone and demonstrated sustained inhibition of bone formation and elevation of bone resorption at the chronic stage of SCI.

The Use of the Matrix Method for the Study of Human Motion:Theory and Applications

Kinematics has been successfully used to describe body motion without reference to the kinetics (or forces causing the motion). In this article, both the theory and applications of the matrix method are provided to describe complex human motion. After the definition of a Cartesian coordinate frame is introduced, the description of transformations between multiple coordinate frames is given; the decomposition of a transformation matrix into anatomical joint motion parameters (e.g. Euler angles) is then explained. The advantages of the matrix method are illustrated by three examples related to biomechanical studies. The first describes a reaching and grasping task in which matrix transformations are applied to position the hand with respect to an object during grasping. The second example demonstrates the utility of the matrix method in revealing the coupling motion of the wrist between flexion-extension and radial-ulnar deviation. The last example highlights the indispensable use of the matrix method for the study of knee biomechanics, including the description of knee joint kinematics during functional activities and determination of in-situ ligament forces using robotic technology, which has advanced our understanding of the functions of the cruciate ligaments to knee joint kinematics. It is hoped that the theoretical development and biomechanical application examples will help the readers apply the matrix method to research problems related to human motion.

Bone/cartilage targeted hydrogel: Strategies and applications

The skeletal system is responsible for weight-bearing,organ protection,and movement.Bone diseases caused by trauma,infection,and aging can seriously affect a patient’s quality of life.Bone targeted biomaterials are suitable for the treatment of bone diseases.Biomaterials with bone-targeted properties can improve drug utilization and reduce side effects.A large number of bone-targeted micro-nano materials have been developed.However,only a few studies addressed bone-targeted hydrogel.The large size of hydrogel makes it difficult to achieve systematic targeting.However,local targeted hydrogel still has significant prospects.Molecules in bone/cartilage extracellular matrix and bone cells provide binding sites for bone-targeted hydrogel.Drug delivery systems featuring microgels with targeting properties is a key construction strategy for bone-targeted hydrogel.Besides,injectable hydrogel drug depot carrying bone-targeted drugs is another strategy.In this review,we summarize the bone-targeted hydrogel through application environment,construction strategies and disease applications.We hope this article will provide a reference for the development of bone-targeted hydrogels.We also hope this article could increase awareness of bone-targeted materials.

Bone/cartilage organoid on-chip:Construction strategy and application

The necessity of disease models for bone/cartilage related disorders is well-recognized,but the barrier between ex-vivo cell culture,animal models and the real human body has been pending for decades.The organoid-on-a-chip technique showed opportunity to revolutionize basic research and drug screening for diseases like osteoporosis and arthritis.The bone/cartilage organoid on-chip(BCoC)system is a novel platform of multi-tissue which faithfully emulate the essential elements,biologic functions and pathophysiological response under real circumstances.In this review,we propose the concept of BCoC platform,summarize the basic modules and current efforts to orchestrate them on a single microfluidic system.Current disease models,unsolved problems and future challenging are also discussed,the aim should be a deeper understanding of diseases,and ultimate realization of generic ex-vivo tools for further therapeutic strategies of pathological conditions.

重复性机械拉伸肌腱成纤维细胞与前列腺素E2和白三烯B4水平异常升高的关系

目的 探讨机械拉伸肌腱成纤维细胞导致的前列腺素E2 (PGE2 )和白三烯B4(LTB4)水平升高与肌腱腱病的关系。 方法 应用改进的细胞培养、拉伸系统,把人肌腱成纤维细胞种植于有微型沟槽的可变形硅胶盘中,分别在不同的拉伸应变(4%、8%、12% )下进行单轴、重复性机械拉伸。非拉伸组设为对照。检测PGE2和LTB4水平以及相关酶[环氧化酶(COX)、5脂加氧酶(5-LO) ]的变化。 结果 拉伸肌腱成纤维细胞可产生高水平的PGE2和LTB4,其产生量与拉伸应变有关。阻断COX可减少PGE2的产生,但产生更多的LTB4,反之亦然。 结论 重复拉伸肌腱成纤维细胞产生高水平的PGE2和LTB4,并且其二者存在平衡关系。临床上应慎用非甾体类抗炎药治疗肌腱腱病。

Therapeutic potential of TNFa inhibitors in chronic inflammatory disorders:Past and future

In the past 20 years,patients with rheumatoid arthritis(RA),Crohn’s disease(CD),and other immune diseases have witnessed the impact of a great treatment advance with the availability of biological TNFa inhibitors.With 5 approved anti-TNFa biologics on the market and soon available biosimilars,patients have more treatment options and have benefited from understanding the biology of TNFa.Nevertheless,many unmet needs remain for people living with TNFa-related diseases,namely some side effects and tolerance of current anti-TNFa biologics and resistance to therapies.Furthermore,common diseases such as osteoarthritis and back/neck pain may respond to anti-TNFa therapies at early onset of symptoms.Development of new TNFa inhibitors focusing on TNFR1 specific inhibitors,preferably small molecules that can be delivered orally,is much needed.

关节置换术后手术部位感染细菌的抗生素敏感性研究

背景：目前，对于治疗疑似全髋或全膝关节置换术后假体周围感染的抗生素使用原则还没有共识。本研究旨在建立这样一个用药原则。方法：对146例患者进行回顾性研究。在这些患者进行全髋或全膝关节置换术后的翻修术时，共194个标本得到了细菌培养阳性结果。患者的一般信息、并存疾病情况、细菌种类、抗生素敏感性资料以及翻修术后细菌培养出现阳性结果所需要的天数均被记录。结果：共110髋、84膝得到的标本培养结果为阳性。其中70％为慢性感染，17％为急性术后局部感染，13％为急性血源性感染。翻修术后出现阳性培养结果的平均时间为3天。革兰氏阳性菌感染占绝大多数。在这些细菌中，88％对庆大霉素敏感，96％对万古霉素敏感，61％对头孢唑林敏感。多数的耐药菌来自于先前有过抗生素治疗失败史的患者。术后急性感染的菌株比慢性感染或血源性感染的菌株更易发生耐药。血源性感染患者分离得到的菌株对庆大霉素和头孢唑林都有高度的敏感性。结论：对疑似假体周围感染的经验性抗生素用药应该在对感染进行分类和确定革兰氏染色结果的指导下进行。我们认为，在得到培养结果之前，急性血源性感染应该一开始就使用头孢唑林和庆大霉素的联合治疗。所有术后慢性或急性革兰氏阳性菌感染或不能明确革兰氏染色结果的细菌感染都应该用万古霉素。革兰氏阴性菌感染应该用第三代或第四代头孢霉素。革兰氏阳性菌和阴性菌的混合感染应该联合使用万古霉素和第三代或第四代头孢霉素。另外，我们认为如果在术后第4天还没有得到细菌培养或是其他确诊的阳性结果就应该结束经验性抗生素治疗。可信水平：诊断性研究，Ⅳ级。进一步可信度参见作者介绍。

The effects of transcranial direct current stimulation on gait in patients with Parkinson’s disease:a systematic review

Background:Gait problems are an important symptom in Parkinson’s disease(PD),a progressive neurodegenerative disease.Transcranial direct current stimulation(tDCS)is a neuromodulatory intervention that can modulate cortical excitability of the gait-related regions.Despite an increasing number of gait-related tDCS studies in PD,the efficacy of this technique for improving gait has not been systematically investigated yet.Here,we aimed to systematically explore the effects of tDCS on gait in PD,based on available experimental studies.Methods:Using the PRISMA(Preferred Reporting Items for Systematic Reviews and Meta-Analyses)approach,PubMed,Web of Science,Scopus,and PEDro databases were searched for randomized clinical trials assessing the effect of tDCS on gait in patients with PD.Results:Eighteen studies were included in this systematic review.Overall,tDCS targeting the motor cortex and supplementary motor area bilaterally seems to be promising for gait rehabilitation in PD.Studies of tDCS targeting the dorosolateral prefrontal cortex or cerebellum showed more heterogeneous results.More studies are needed to systematically compare the efficacy of different tDCS protocols,including protocols applying tDCS alone and/or in combination with conventional gait rehabilitation treatment in PD.Conclusions:tDCS is a promising intervention approach to improving gait in PD.Anodal tDCS over the motor areas has shown a positive effect on gait,but stimulation of other areas is less promising.However,the heterogeneities of methods and results have made it difficult to draw firm conclusions.Therefore,systematic explorations of tDCS protocols are required to optimize the efficacy.

Mechanisms for increased systemic fracture risk after index fracture

The single best predictor of future fracture risk is a prior fracture at any skeletal site.However,the mechanisms underlying this relationship remain incompletely understood.Here we review three potential mechanisms underlying increased risk.An index fracture may reflect preexisting deficits in bone quality or impairments in physical function.Second,fracture may cause biomechanical changes that increase future fracture risk.Third,fracture induces a period of systemic bone loss that is never fully recovered.Further investigation into these mechanisms can inform treatments that prevent future fractures for individuals with a prior history of fracture.