Nerve guidance channels are limited by lack of topographical guidance: Treatment of sizeable nerve gaps remains problematic following peripheral nerve injury. Functional outcomes are good when neurorrhaphy, or direct end-to-end suture repair, is possible.The problem arises when there is signi fi cant segmental loss, which can occur following trauma as well as oncological procedures. In such scenarios, it is often not possible to appose severed nerve ends without causing signi fi cant tension. The current gold standard for management is to utilize autologous nerve grafts, commonly obtained from the sural nerve, to bridge these defects. This inevitably results in loss of cutaneous sensation over the lower limb, and the risk of donor site morbidities including infection and scarring.Suitable donor nerves remain finite in supply, and are often not ideally matched with recipient sites in terms of calibre and length.Nerve guidance channels have been designed to address these limitations, with proximal and distal nerve stumps telescoped and sutured to the ends of the arti fi cial conduit during operative repair.Design objectives of nerve guidance channels have evolved over time with the emergence of new materials (Gaudin et al., 2016). Silicone represents a fi rst-generation channel utilized to restore continuity and to prevent fi brous ingrowth from surrounding tissues. In being non-resorbable, silicone tubes frequently had to be removed as they caused extrinsic compression, offsetting their usefulness despite promising functional recovery. Thus, second-generation conduits shifted towards usage of biodegradable materials. These include commercially available products composed of collagen(Neuragen, Neuroflex, NeuroMatrix), polyglycolic acid (Neurotube), polylactide-caprolactone (Neurolac) and polyvinylalcohol-based hydrogel (SaluTunnel). It is essential that the next generation of guidance channels can facilitate repair across larger nerve gaps, with 2 cm representing a critical threshold beyond which the performance of arti fi cial conduits remains fair. The present generation of nerve guidance channels are lacking in microstructure to provide physical guidance of the regenerative process. Provision of nanotopography within the channel lumen serves to minimize aberrant sprouting, and potentially enhance regeneration along the intended axis.

Electrospinning is a means of generating aligned nano fi bers to mimic the nerve microstructure and thus guide axonal growth and cellular migration within nerve guidance channels. Here, we emphasise how determination of appropriate physical and biological properties of the nano fi ber scaffold can optimize neural regeneration, and in doing so, contribute towards design of a new generation of nerve guidance channels.

大尺寸化，例如55吋以上的彩电，400L以上的冰箱，8.1KG以上的洗衣机，19m3+超大风量油烟机，13L+燃气热水器，200加仑以上大通量净水器等产品越来越受市场欢迎。

企业价值链的全部构成部分为九类作业，其中每一类作业又可细致划分为更加具体的作业，对企业来说，企业价值链是其市场竞争优势的根本来源，而物流作为企业价值链当中的重要内容则可对企业竞争力产生巨大影响。

Optimizing physical properties of the nanofiber scaffold for neural regeneration: Electrospinning is a common and versatile technique for manufacturing uniaxial nano fi bers intended for use as a scaffold for neural repair. A number of biocompatible materials have been utilized alone and in combination to generate aligned nano fi bers, including poly-L-lactic acid (PLLA), polycaprolactone (PCL), poly(lactic-co-glycolic acid) (PLGA), poly{(lactic acid)-co-[(glycolic acid)-alt-(L-lysine)]} (PLGL), polycaprolactone(PCL), collagen, carbon, and chitosan. In the context of nerve guidance channel design it is important that nano fi bers support axonal attachment and maximize outgrowth parallel to the main fiber axis. Equally important are their effects on Schwann cell growth and migration. In response to peripheral nerve injury, Schwann cells proliferate, upregulate neurotrophic factors, phagocytose inhibitory myelin debris and form aligned columns known as Bands of Büngner to guide axonal regeneration, thus forming a critical cellular component of the endogenous repair response (Jessen and Mirsky, 2016).

Department of Orthopaedics and Traumatology, The University of Hong Kong, Hong Kong Special Administrative Region, China(Shea GKH)

不可否认，高校退休教师这一特殊群体有自身的特点。如文化水平相对较高、相信科学、易接受新兴事物等等。但对这一特殊群体实施健康管理有哪些优势，也是我们必须要深入思考的。认清优势有助于健康管理的有效实施。结合高校退休教师群体的现状和健康管理的特点，发现有以下几个优势。

Utilizing nano fi ber scaffolds to maintain and direct transplanted cell populations: Another limitation of nerve guidance channels as compared to nerve grafts originates from the lack of supporting cells. Seeding of immunocompatible cell types into the channel lumen is a means of providing trophic and functional support, with Schwann cells being a leading cell candidate. Exogenous cells must be available for transplantation within a defined window period,as prolonged denervation leads to irreversible functional de fi cits.Towards this end, our group has been able to rapidly generate functional Schwann cells from human bone marrow stromal cells,allowing for a robust autologous cell source that spares the need to sacri fi ce a peripheral nerve for cell harvest (Cai et al., 2017). It is essential that nanofibers support the attachment, proliferation and migration of seeded cells, and that the chosen biomaterial and breakdown products have minimal cytotoxicity. A further consideration when seeding stem/progenitor cells is in the effect that nanofiber properties have on cellular differentiation. Nanofiber alignment, diameter, and surface properties all have bearing on neural precursor differentiation towards the Schwann cell lineage(Xue et al., 2017). In this context, the nano fi ber scaffold must be considered a key aspect of the microenvronment that influences differentiation and maintenance of phenotype. Nanofiber scaffolds pre-seeded with stem/progenitor cells may even be cultured in vitro prior to transplantation to direct differentiation. In order to approach the performance of nerve grafts, augmentation by transplantation of exogenous cell types contained within the intraluminal scaffold will become a necessity (Figure 1). Towards this end, expeditous generation of autologous bone marrow-derived Schwann cells together with optimized genipin-treated uniaxial nano fi bers to bridge the injured peripheral nerve illustrates combined biological and mechanical approaches towards addressing the present de fi ciencies of commercially available conduits.

orcid: 0000-0003-3480-371X (Graham Ka-Hon Shea)

Figure 1 Nerve guidance channels utilizing optimized nanofiber scaffolds in conjunction with exogenous Schwann cells.

Advances in electrospinning techniques have allowed for adjustability in the shape of extruded nanofibers, imparting secondary surface characteristics. The presence of longitudinal grooves along nanofibers increased total surface area, which had the biological impact of enhancing cell adhesion and proliferation (Huang et al.,2015). Upon incorporation into nerve guidance channels, grooved nano fi bers enhanced peripheral nerve regeneration in comparison to channels containing control nano fi bers with a smooth surface.

3.全面落实管党治党责任。狠抓党建工作责任制逐级全面落实，建立任务、责任、问题、整改“四张清单”，抓细抓实党建工作。坚持书记抓、抓书记，稳步推行党支部书记抓党建述职评议考核，认真落实下级党组织向上级党组织报告年度党建工作。发挥党建工作领导小组及其办公室作用。完善党建工作联系点制度，加强对基层党支部党建工作的指导。

Surface modification and biological functionalization of the nanofiber scaffold: Cell attachment upon the native nanofiber surface is often limited by hydrophobicity. Surface modification by means of plasma treatment allows for addition of hydrophilic chemical groups in order to facilitate cell adhesion. Coating of appropriate extracellular matrix components upon the nano fi ber surface is another strategy to promote growth cone development and neurite pathfinding. Laminin in particular allows for robust cell attachment and interactions via integrins. Neurites demonstrate a clear preference for guided growth along the axis of laminin-coated nano fi bers, resultant in a concentration-dependent increase in axonal displacement and reduction in perpendicular outgrowth (Xie et al., 2014). Schwann cells similarly favour laminin-coated substrata and demonstrate increased proliferation. Immunogenicity and early biodegradability of laminin are potential barriers to in vivo application and incorporation of shortened motifs such as RGD and IKVAV to enhance attachment and neurite outgrowth respectively(Sun et al., 2016) have been utilized as an alternative.

Conclusion: These advances highlight the interdependency between physical and cellular processes when considering biomaterials for nerve guidance channel design. Conceptually, the nano fi ber scaffold must be considered a biologically active component that has the capacity to expedite the regenerative process. In considering appropriate biomaterials, it is imperative that results are validated in animal models that allow for histological and functional assessment of regeneration, while ensuring biocompatibility and biodegradability.

＊Correspondence to: Graham Ka-Hon Shea, MBBS, Ph.D.,gkshea@hku.hk.

Control of nanofiber diameter is a means towards optimizing axonal outgrowth and Schwann cell migration (Wang et al., 2010).Rat dorsal root ganglia cultured upon PLLA fi bers demonstrated maximal axonal outgrowth upon fibers of intermediate diameter(760 nm) whilst Schwann cell migration was highest upon large fibers (1325 nm). The lowest displacement in both axonal outgrowth and Schwann cell migration was observed upon fibers of small diameter (293 nm), where neurites also exhibited an increased tendency to grow perpendicular to the main fi ber axis. It is known that reduction of nanofiber diameter limits cell adhesion due to an inability for focal adhesion cues to be recognized (Huang et al.,2015). Furthermore, fiber dimensions had differential effects on neurite outgrowth and Schwann cell migration, leading to pioneer neurites extending beyond the Schwann cell front as guided by the nanofibers. Separately, it has been shown that undesired neurite outgrowth perpendicular to the main fi ber axis is increased when fi bers of the same diameter are deposited at a higher density (Xie et al., 2014). The strength of adherence between neurites and the nanofiber surface in comparison to the underlying substrata are crucial determinants in the directionality of axonal sprouting, and can be adjusted by coating with extracellular matrix components such as laminin (Xie et al., 2014). These physical parameters need to be purposely determined in the generation of nano fi ber scaffolds towards achieving intended regenerative effects.

Li Ka Shing Faculty of Medicine, The University of Hong Kong,Hong Kong Special Administrative Region, China (Mok F)

Graham Ka-Hon Shea＊, Francis Mok

Crosslinkers can be utilized to modify the biological interface between nano fi bers and neural cell types. We recently demonstrated that treatment with genipin, a biocompatible cross-linker extracted from the fruit of Gardenia jasminoides, enhanced the intra-fiber mechanical and regenerative properties of electrospun chitosan nanofibers (Lau et al., 2017). Whilst not affecting fiber diameter,an increase in genipin treatment concentration resulted in proportional elevation in nano fi ber stiffness. Genipin treatment preserved nano fi ber integrity which otherwise lead to swelling and degradation resulting in loss of surface topography. Dorsal root ganglion(DRG) neurites were able to adhere to genipin-treated nano fi bers without additional coating of potentially immunogenic peptides.Strikingly, axonal outgrowth from neurons of dorsal root ganglia cultured upon genipin-treated fibers doubled the length of those in untreated controls. This was consistent with the prior finding that axonal regrowth from injured nerves in the peripheral nervous system, but not central nervous system, was affected by stiffness of the underlying substrate (Koch et al., 2012). Crosslinking therefore provides for tunable control of the properties of nano fi bers towards application in nerve guidance channel design.

Ligands with desired biological properties can be incorporated into the nanofiber scaffold to enhance neural regeneration. Here, the scaffold functions as delivery system for immobilization and controlled release of relevant cues to allow for localized enhancement of the regenerative response. An example of this is in the grafting of neurotrophins such as GDNF to the scaffold by means of microencapsulation. In combination with topography provided via aligned PCL nanofibers, GDNF-grafted nanofibers had an enhanced ca-pacity to promote neurite outgrowth (Mohtaram et al., 2015). In targeting the crucial Schwann cell response to injury (Jessen and Mirsky, 2016), neuregulin-1 has been conjugated to PCL fibers(Tonazzini et al., 2017) and these functionalized fibers showed improved capacity to provide for Schwann cell colonization of the directional scaffold.

Accepted: 2018-04-28

doi: 10.4103/1673-5374.235023

这时，一个朋友告诉他让他们寻找“代孕妈妈”，这重新燃起了陈清和方达生夫妇的希望。他们去医院咨询，医生告诉他们，雇佣“代孕母亲”就是将雇主的受精卵移植到“代孕妈妈”的子宫内孕育，生出来的孩子仍然属于雇主。

Copyright license agreement: The Copyright License Agreement has been signed by all authors before publication.

Plagiarism check: Checked twice by iThenticate.

Peer review: Externally peer reviewed.

首先，由检察日报在2016年11月23日报道的标题为“动物园猛兽伤人：如何避免悲剧重演”一文关于北京八达岭野生动物园老虎致害案中，动物园采取的保护措施有：

Open access statement: This is an open access journal, and articles are distributed under the terms of the Creative Commons Attribution-NonCommercial-ShareAlike 4.0 License, which allows others to remix, tweak, and build upon the work non-commercially, as long as appropriate credit is given and the new creations are licensed under the identical terms.

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