Minimal active domain of human salivary histatin 1 is efficacious in promoting acute skin wound healing

Dear Editor,The skin barrier can be impaired by acute skin wounds,which may lead to a series of complications.It is essential to accelerate wound healing and rapidly restore the structural integrity and functionality of skin.One of the promising bioactive agents is human salivary histatin 1(Hst1),a 38-amino acid histidine-rich peptide that functions to maintain the homeostasis of oral mucosa with a cellular mechanism of promoting the adhesion,spreading,migration of epithelial cells and thus re-epithelialization[1].In recent years,Hst1 has been shown to be effective against various skin-related cell types,such as fibroblasts,myo-fibroblasts,keratinocytes and endothelial cells.In our latest in-vivo study,Hst1 not only promotes angiogenesis,re-epithelialization and collagen production,but also suppresses inflammation,thereby significantly accelerating acute skin wound healing in mice[2].All these studies show that Hst1 is a potent bioactive agent for accelerating acute skin wound healing.

背压向心汽轮机出口变工况特性数值仿真

背压式向心汽轮机适用于工业蒸汽的余压回收,而该应用场景常因流量不稳定造成汽轮机的出口工况变动,使机组的运行效率受到影响。为了掌握变工况时汽轮机的工作特性,本文使用商用软件ANSYS对背压汽轮机中的向心涡轮进行数值计算,绘制出向心涡轮特性曲线;同时,针对性能较差的小流量工况,文章采用了部分进汽的方式优化涡轮性能,并借助全圆周定常计算论证了部分进汽优化方式在向心汽轮机上的可行性。结果表明,出口压力会对涡轮的通流特性产生较大影响,随着出口总压的减小,流量逐步增大并最终趋于临界值,涡轮整体性能较为理想;但若出口压力持续增大,则涡轮的通流能力变差,其气动效率将急剧下降。采用部分进汽方式调节涡轮性能时,若速比小于0.85,可采用较大部分进汽度及分散进汽方式适当提升输出功;而若速比大于0.85,通道流量始终处于较低水平,此时应通过降低部分进汽度并采用集中进汽的方式可改善流动状态,提升涡轮气动效率。

Regenerative medicine in China:main progress in different fields

Regenerative medicine(RM) is an emerging interdisciplinary field of research and China has developed the research quickly and impressed the world with numerous research findings in stem cells,tissue engineering,active molecules and gene therapy.Important directions are induced differentiation of induced pluripotent stem and embryo stem cells as well as somatic stem cell differentiation potential and their application in trauma,burns,diseases of aging and nerve regeneration.The products Activ Skin and bone repair scaffolds have been approved and are applied in the clinic,and similar products are being studied.About 10 engineered growth-factor drugs for repair and regeneration have been approved and are used in the clinic.Gene therapy,therapeutic cloning and xenotransplantation are some of the strategies being studied.However,China needs to develop standards,regulations and management practices suitable for the healthy development of RM.Aspects that should be strengthened include sound administrative systems,laws,and technical specifications and guidelines;conservation of stem cell resources;emphasis on training and retention of talented stem cell researchers;and reasonable allocation of resources,diversification of investment and breakthroughs in key areas.Finally,broad and deep international cooperation is necessary.

Basing on microRNA-mRNA analysis identifies microRNA in exosomes associated with wound repair of diabetic ulcers

The diabetic ulcer is one of the serious complications of diabetes.In this study,we aimed to establish an exosomal microRNA(miRNA)-targetedmessenger RNA(mRNA)regulatory network for screening new biomarkers for diabetic ulcer treatment.For this purpose,exosomes were extracted from bone marrow stem cells(BMSCs)collected from diabetic ulcer patients and healthy adults.The miRNAs in exosomes was detected by high-throughput sequencing analysis.The Gene Ontology(GO)and Kyoto Encyclopedia of Genes and Genomes(KEGG)pathway enrichment analysis of the differential miRNAs were performed.The miRNA-mRNA regulatory network between candidate miRNAs and their target genes were constructed by Cytoscape software basing on mRNA expression profiles data of diabetic ulcer patients from Gene Expression Omnibus(GEO).GO and KEGG analyses of the core genes were performed.A total of 63 differential expressed miRNAs in BMSCs exosomes were identified between diabetic ulcer patients and healthy adults.The GO analysis of miRNAs showed that it was mainly related to signal transduction and intercellular transport,and KEGG analysis showed that it was related to the vascular endothelial growth factor(VEGF)signaling pathway.The core genes of the miRNA-mRNA network were thioredoxin interacting protein(TXNIP),cell division cycle 14A(CDC14A),cache domain containing 1(CACHD1),interferon-induced protein 44 like(IFI44L),late cornified envelope 1AL(CE1A),leucine-rich repeats and immunoglobulin-like domains 2(LRIG2),palmdelphin(PALMD)and serine and arginine-rich splicing factor 11(SRSF11).GO analysis of the core genes was related to platelet-derived growth factor receptor signaling pathway.The KEGG analysis of the core genes was related to the cell cycle and nucleotide-binding oligomerization domain(NOD)-like receptor signaling pathway.A potential miRNA-mRNA regulatory network provides a comprehensive understanding of the molecular mechanisms and promising new targets such as miR-130a-5p,SESN2,LRIG2,and CDC14A for the wound repair of diabetic ulcers.

Assessment of load-sharing thoracolumbar injury: A modified scoring system

BACKGROUND Many classification systems of thoracolumbar spinal fractures have been proposed to enhance treatment protocols,but none have achieved universal adoption.AIM To develop a new patient scoring system for cases with thoracolumbar injury classification and severity score(TLICS)=4,namely the load-sharing thoracolumbar injury score(LSTLIS).METHODS Based on thoracolumbar injury classification and severity score,this study proposes the use of the established load-sharing classification(LSC)to develop an improved classification system(LSTLIS).To prove the reliability and reproducibility of LSTLIS,a retrospective analysis for patients with thoracolumbar vertebral fractures has been conducted.RESULTS A total of 102 cases were enrolled in the study.The scoring trend of LSTLIS is roughly similar as the LSC scoring,however,the average deviation based on the former method is relatively smaller than that of the latter.Thus,the robustness of the LSTLIS scoring method is better than that of LSC.LSTLIS can further classify patients with TLICS=4,so as to assess more accurately this particular circumstance,and the majority of LSTLIS recommendations are consistent with actual clinical decisions.LSTLIS is a scoring system that combines LSC and TLICS to compensate for the lack of appropriate inclusion of anterior and middle column compression fractures with TLICS.Following preliminary clinical verification,LSTLIS has greater feasibility and reliability value,is more practical in comprehensively assessing certain clinical circumstances,and has better accuracy with clinically significant guidelines.

Recovery of sympathetic nerve function after lumbar sympathectomy is slower in the hind limbs than in the torso

Local sympathetic denervation by surgical sympathectomy is used in the treatment of lower limb ulcers and ischemia,but the restoration of cutaneous sympathetic nerve functions is less clear.This study aims to explore the recovery of cutaneous sympathetic functions after bilateral L2-4 sympathectomy.The skin temperature of the left feet,using a point monitoring thermometer,increased intraoperatively after sympathectomy.The cytoplasm of sympathetic neurons contained tyrosine hydroxylase and dopamineβ-hydroxylase,visualized by immunofluorescence,indicated the accuracy of sympathectomy.Iodine starch test results suggested that the sweating function of the hind feet plantar skin decreased 2 and 7 weeks after lumbar sympathectomy but had recovered by 3 months.Immunofluorescence and western blot assay results revealed that norepinephrine and dopamineβ-hydroxylase expression in the skin from the sacrococcygeal region and hind feet decreased in the sympathectomized group at 2 weeks.Transmission electron microscopy results showed that perinuclear space and axon demyelination in sympathetic cells in the L5 sympathetic trunks were found in the sympathectomized group 3 months after sympathectomy.Although sympathetic denervation occurred in the sacrococcygeal region and hind feet skin 2 weeks after lumbar sympathectomy,the skin functions recovered gradually over 7 weeks to 3 months.In conclusion,sympathetic functional recovery may account for the recurrence of hyperhidrosis after sympathectomy and the normalization of sympathetic nerve trunks after incomplete injury.The recovery of sympathetic nerve function was slower in the limbs than in the torso after bilateral L（2-4） sympathectomy.

Effects and mechanism of platelet-rich plasma on military drill injury: A review

Military drill injury is a significant part of military medical research.The increase of training intensity and changes in training methods lead to differences in injury types.The ideal therapeutic modality should allow rapid healing at a reasonable cost and minimize impact on patients’life.Platelet-rich plasma(PRP),a platelet concentrate,is rich in a variety of growth factors and widely used clinically as a minimally invasive treatment.It plays an important role in injury repair and rehabilitation.In this article,we review the therapeutic role of PRP in military drill injury and its possible underlying mechanisms,with a focus on plantar fasciitis,stress fractures and other common injuries,in order to provide basic support for military reserve.

Luminescence-activated Pt(Ⅳ)prodrug for in situ triggerable cancer therapy

Anticancer platinum prodrugs that can be controllably activated are highly desired for personalized precision medicine and patient compliance in cancer therapy.However,the clinical application of platinum(Ⅳ)prodrugs(Pt(Ⅳ))is restricted by tissue penetration of external irradiation.Here,we report a novel Pt(Ⅳ)activation strategy based on endogenous luminescence of tumor microenvironment responsiveness,which completely circumvents the limitation of external irradiation.The designed Pt(Ⅳ)–Lu,a mixture of trans,trans,trans-[Pt(N_(3))_(2)(OH)_(2)(py)_(2)]and luminol(Lu),has controllable activation property:it remains inert in reductant environment and normal tissues,but under tumor microenvironment,Lu will be oxidized to produce blue luminescence,which rapidly reduce Pt(Ⅳ)to Pt(Ⅱ)without the need of any external activator.Pt(Ⅳ)–Lu shows excellent responsive antitumor ability both in vitro and in vivo.Compared to cisplatin,the median lethal dose in BALB/c mice increased by an order of magnitude.Our results suggest that Pt(Ⅳ)–Lu exhibits highly controllable activation property,superior antitumor activity,and good biosafety,which may provide a novel strategy for the design of platinum prodrugs.

Platelet-rich plasma accelerates skin wound healing by promoting re-epithelialization

Background:Autologous platelet-rich plasma(PRP)has been suggested to be effective for wound healing.However,evidence for its use in patients with acute and chronic wounds remains insufficient.The aims of this study were to comprehensively examine the effectiveness,synergy and possible mechanism of PRP-mediated improvement of acute skin wound repair.Methods:Full-thickness wounds were made on the back of C57/BL6 mice.PRP or saline solution as a control was administered to the wound area.Wound healing rate,local inflammation,angiogenesis,re-epithelialization and collagen deposition were measured at days 3,5,7 and 14 after skin injury.The biological character of epidermal stem cells(ESCs),which reflect the potential for re-epithelialization,was further evaluated in vitro and in vivo.Results:PRP strongly improved skin wound healing,which was associated with regulation of local inflammation,enhancement of angiogenesis and re-epithelialization.PRP treatment significantly reduced the production of inflammatory cytokines interleukin-17A and interleukin-1β.An increase in the local vessel intensity and enhancement of re-epithelialization were also observed in animals with PRP administration and were associated with enhanced secretion of growth factors such as vascular endothelial growth factor and insulin-like growth factor-1.Moreover,PRP treatment ameliorated the survival and activated the migration and proliferation of primary cultured ESCs,and these effects were accompanied by the differentiation of ESCs into adult cells following the changes of CD49f and keratin 10 and keratin 14.Conclusion:PRP improved skin wound healing by modulating inflammation and increasing angiogenesis and re-epithelialization.However,the underlying regulatory mechanism needs to be investigated in the future.Our data provide a preliminary theoretical foundation for the clinical administration of PRP in wound healing and skin regeneration.

Highly Regioselective Sequential 1,1-Dihydrosilylation of Terminal Aliphatic Alkynes with Primary Silanes

Summary of main observation and conclusion A regioselective double 1,1-hydrosilylation of terminal aliphatic alkynes with primary silanes catalyzed by one cobalt catalyst has been developed. gem-Bis(dihydrosilyl)alkanes containing four silicon-hydrogen bonds are efficiently constructed in an atom-economical man ner. Tolerated substrates include simplest alkyne-ethyne, a complicated drug derivative and various functi on alized terminal aliphatic alkynes. Asymmetric approach using two catalysts is achieved with excelle nt enan tioselectivities to access corresp on ding chiral products. The tra nsformations of Si—H bonds into Si—C, Si—O, and Si —F bonds and the synthesis of enantioriched a-hydroxysilane show synthetic utility.

Clinical guideline on topical growth factors for skin wounds

An increased number of patients with skin wounds have been witnessed in the past decades.Among the various kinds of treatments for skin wounds,topical exogenous growth factors are indispensable and have been used in many countries.However,whether they have reliable effects remains controversial,and their application for skin wound treatment needs to be further standardized and optimized in terms of socio-economic considerations.Thus,the Chinese Burn Association developed this guideline indicating efficacy,application details,adverse reactions and precautions of five clinically common topical growth factors using the Grading of Recommendations Assessment Development and Evaluation method to promote the rational application of topical exogenous growth factors in skin wounds and to benefit more patients.

Acellular nerve grafts supplemented with induced pluripotent stem cell-derived exosomes promote peripheral nerve reconstruction and motor function recovery

Peripheral nerve injury is a great challenge in clinical work due to the restricted repair gap and weak regrowth ability.Herein,we selected induced pluripotent stem cells(iPSCs)derived exosomes to supplement acellular nerve grafts(ANGs)with the aim of restoring long-distance peripheral nerve defects.Human fibroblasts were reprogrammed into iPSCs through non-integrating transduction of Oct3/4,Sox2,Klf4,and c-Myc.The obtained iPSCs had highly active alkaline phosphatase expression and expressed Oct4,SSEA4,Nanog,Sox2,which also differentiated into all three germ layers in vivo and differentiated into mature peripheral neurons and Schwann cells(SCs)in vitro.After isolation and biological characteristics of iPSCs-derived exosomes,we found that numerous PKH26-labeled exosomes were internalized inside SCs through endocytotic pathway and exhibited a proliferative effect on SCs that were involved in the process of axonal regeneration and remyelination.After that,we prepared ANGs via optimized chemical extracted process to bridge 15 mm long-distance peripheral nerve gaps in rats.Owing to the promotion of iPSCs-derived exosomes,satisfactory regenerative outcomes were achieved including gait behavior analysis,electrophysiological assessment,and morphological analysis of regenerated nerves.Especially,motor function was restored with comparable to those achieved with nerve autografts and there were no significant differences in the fiber diameter and area of reinnervated muscle fibers.Taken together,our combined use of iPSCs-derived exosomes with ANGs demonstrates good promise to restore long-distance peripheral nerve defects,and thus represents a cell-free strategy for future clinical applications.

Iatrogenic wounds:a common but often overlooked problem

Iatrogenic wounds are a common but often overlooked concept.They can lead to increases in hospital stays,therapy costs,repeat surgeries,and implant removal.If not handled properly,these wounds have a very poor prognosis and will cause serious physical and psychological harm to patients,which may result in medicolegal disputes.In recent years,the incidence of iatrogenic wounds has increased because of(1)an increase in the population of older people owing to increased life expectancy,(2)the continued expansion of surgical indications,(3)an increase in difficult surgeries,and(4)the constant emergence and application of new implantable biomaterials and other therapies.Thus,there is a pressing clinical need to improve the therapy of iatrogenic wounds.However,the difficulty in treating these wounds is considerable due to the emergence of drug-resistant bacteria,the high number of patients with metabolic diseases,and complex complications in patients.In particular,iatrogenic wounds caused by surgical site infections due to implantable biomaterials could lead to material leakage and conflicts regarding whether to retain or remove the implants.This review provides a definition of iatrogenic wounds,describes their characteristics,classifies them,and provides information about the importance of analyzing iatrogenic wounds.We hope that this review will provide useful information for the diagnosis and treatment of iatrogenic wounds and help to reduce their incidence in the future.

Regenerative medicine in China:demands, capacity,and regulation

Regenerative medicine(RM)is an emerging interdisciplinary field of research.Its clinical application focuses on the repair,replacement,and regeneration of cells,tissues,and organs by approaches including cell reprogramming,stem cell transplantation,tissue engineering,activating factors,and clone treatment.RM has become a hot point of research in China and other countries.China's main and local governments have attached great importance to RM and given strong support in relevant policies and funding.About 3.5 billion RMB has been invested in this field.Since 1999,China has established about 30 RM centers and cooperates with many advanced countries in RM research and benefits from their cooperation.However,China needs to develop standards,regulations,and management practices suitable for the healthy development of RM.In this review,we focus on its great demand,capacity,and relative regulations.

Co-administration of platelet-rich plasma and small intestinal submucosa is more beneficial than their individual use in promoting acute skin wound healing

Background:Acute skin wounds may compromise the skin barrier,posing a risk of infection.Small intestinal submucosa(SIS)is widely used to treat acute and chronic wounds.However,the efficacy of SIS to accelerate wound healing still needs to be improved to meet clinical demands.To tackle this problem,platelet-rich plasma(PRP)is used due to its potency to promote proliferation,migration and adhesion of target cells.In this study,we applied PRP and SIS to skin wounds to explore their effects on wound healing by evaluating re-epithelialization,collagen production,angiogenesis and the inflammatory response.Methods:A1×1-cm full-thickness skin defectwas established in mice.Sixty mice were divided into four treatment groups:PRP+SIS,PRP,SIS and control.On days 3,5,7,10 and 14 post-surgery,tissue specimens were harvested.Haematoxylin and eosin,Masson’s trichrome,immunohistochemical and immunofluorescence double staining were used to visualize epidermal thickness,collagen and vascular regeneration and inflammation.Results:Wound contraction in the PRP and PRP+SIS groups was significantly greater,compared with the other groups,on days 3 and 5 post-surgery.A histological analysis showed higher collagen expression in the PRP and PRP+SIS groups on day 7,whichwas associated with a thicker epidermal layer on day 14.In addition,immunohistochemical staining showed that CD31-positive blood vessels and vascular endothelial growth factor expression in the PRP+SIS and PRP groups were significantly higher,compared with the control group.Furthermore,immunofluorescence double staining showed that the number of M1 and M2 macrophages in the PRP+SIS and PRP groups was higher,compared with the control and SIS groups alone,on day 3.However,on day 7,the number of M1 macrophages dramatically decreased in the PRP+SIS and PRP groups.The ratio of M2 to M1 macrophages in the PRP+SIS and PRP groups was 3.97 and 2.93 times that of the control group and 4.56 and 3.37 times that of the SIS group,respectively.Conclusion:Co-administration of SIS and PRP has a better effect on promoting angiogenesis,reepithelialization and collagen regeneration in managing acute wound healing than either agent alone.

Safety and efficacy of a low frame rate protocol for percutaneous coronary intervention for chronic total occlusions

Chronic total occlusion(CTO)is the complete obstruction of a coronary artery for>3 months,combined with thrombolysis in myocardial infarction(TIMI)flow grade 0.Percutaneous coronary intervention(PCI)is widely used to treat CTO but is less used than coronary artery bypass graft surgery(CABG).[1]However,PCI for CTO may increase the exposure of patients and operating physicians to radiation compared with non-CTO PCIs,[2]and higher radiation exposure is linked to long-term adverse outcomes.[3]PCI operators are exposed to significantly less radiation than patients during each procedure;however,repeated exposure during a lifetime may cause health problems.Therefore,reducing the exposure of PCI cardiologists to radiation without compromising the surgical success rate and clinical outcomes of patients is crucial.A low frame rate(LFR)protocol and/or selective fluoroscopy image storage decreases the exposure of PCI operators and patients to radiation during PCIs.The objective of this study is to evaluate the safety and efficacy of an LFR protocol for managing CTO patients.

Dynamic microenvironment and multiple damaged tissue regeneration in a de novo and synchronized manner

Regenerative medicine has rapidly developed over the past decade and created new opportunities to repair or replace tissue or organ function lost because of congenital defects,age,diseases,or serious damage(Cheng et al.,2016a;Cheng et al.,2016b).Regenerative medicine strategies include the transplantation of bioactive factors,stem cells,or biomaterials,even the induced regeneration in a de novo,depending on the application(Fu,2014a;Huang and Fu,