Outcome of meniscal repairs in paediatric population:A tertiary centre experience

BACKGROUND Meniscal sparing surgery is a widely utilised treatment option for unstable meniscal tears with the aim of minimising the risk of progression towards osteoarthritis.However,there is limited data in the literature on meniscal repair outcomes in skeletally immature patients.AIM To evaluate the re-operation rate and functional outcomes of meniscal repairs in children and adolescents.METHODS We performed a retrospective review of all patients who underwent arthroscopic meniscal repair surgery between January 2007 and January 2018.All patients were under the age of 18 at the time of surgery.Procedures were all performed by a single surgeon.Information was gathered from our hospital Electronic Patient Records system.The primary outcome measure was re-operation rate(need for further surgery on the same meniscus).Secondary outcome measures were surgical complications and patient reported outcome measures that were International Knee Documentation Committee(IKDC),Tegner and Lysholm scores.RESULTS We identified 59 patients who underwent 66 All-inside meniscal repairs(32 medial meniscus and 34 Lateral meniscus).Meniscal repairs were performed utilizing FasT-Fix(Smith and Nephew)implants.There were 37 males and 22 females with an average age of 14 years(range 6-16).The average follow-up time was 53 months(range 26-140).Six patients had concomitant anterior cruciate ligament reconstruction surgery along with the meniscal repair.There were no requiring further meniscal repairs and 9 patients underwent partial meniscectomies.The mean postoperative IKDC score was 88(44-100),Tegner score was 7(2-10)and Lysholm score was 94(57-100).CONCLUSION Our results showed that arthroscopic repair of meniscal tears in the paediatric population is an effective treatment option that has a low failure rate and good postoperative clinical with the advantage of preserving meniscal tissues.

Analysis of a POMDP Model for an Optimal Maintenance Problem with Multiple Imperfect Repairs

I consider a system whose deterioration follows a discrete-time and discrete-state Markov chain with an absorbing state. When the system is put into practice, I may select operation (wait), imperfect repair, or replacement at each discrete-time point. The true state of the system is not known when it is operated. Instead, the system is monitored after operation and some incomplete information concerned with the deterioration is obtained for decision making. Since there are multiple imperfect repairs, I can select one option from them when the imperfect repair is preferable to operation and replacement. To express this situation, I propose a POMDP model and theoretically investigate the structure of an optimal maintenance policy minimizing a total expected discounted cost for an unbounded horizon. Then two stochastic orders are used for the analysis of our problem.

Granular Effect of Fly Ash Repairs Damage of Recycled Coarse Aggregate

Repairing effect of fly ash （FA） on damage of recycled coarse aggregate was evaluated by characteristics of pores and cracks in the vicinity of interracial transition zone （ITZ）. The interracial structure between the virgin aggregate and the attached old mortar was investigated and compared with ITZ of recycled aggregate concrete in the presence of FA or ultra-fine FA（UFA） by means of scanning electron microscope （SEM）. Diameter and plumpness frequency distribution of pores as well as width of the old ITZ, length of contacting points and cracks density were analyzed. The SEM results reveal that the diameter of pores is decreases significantly but pores plumpness increases. A decreased ITZ width and cracks density as well as an increased bonding zone length can also been observed, which indicates that FA or UFA repairs damage of recycled coarse aggregate due to its granular effect.

A novel tissue engineered nerve graft constructed with autologous vein and nerve microtissue repairs a longsegment sciatic nerve defect

Veins are easy to obtain,have low immunogenicity,and induce a relatively weak inflammatory response.Therefore,veins have the potential to be used as conduits for nerve regeneration.However,because of the presence of venous valves and the great elasticity of the venous wall,the vein is not conducive to nerve regeneration.In this study,a novel tissue engineered nerve graft was constructed by combining normal dissected nerve microtissue with an autologous vein graft for repairing 10-mm peripheral nerve defects in rats.Compared with rats given the vein graft alone,rats given the tissue engineered nerve graft had an improved sciatic static index,and a higher amplitude and shorter latency of compound muscle action potentials.Furthermore,rats implanted with the microtissue graft had a higher density and thickness of myelinated nerve fibers and reduced gastrocnemius muscle atrophy compared with rats implanted with the vein alone.However,the tissue engineered nerve graft had a lower ability to repair the defect than autogenous nerve transplantation.In summary,although the tissue engineered nerve graft constructed with autologous vein and nerve microtissue is not as effective as autologous nerve transplantation for repairing long-segment sciatic nerve defects,it may nonetheless have therapeutic potential for the clinical repair of long sciatic nerve defects.This study was approved by the Experimental Animal Ethics Committee of Chinese PLA General Hospital(approval No.2016-x9-07)on September 7,2016.

Electroacupuncture at the Renzhong (DU 26) and Neiguan (PC 6) acupoints repairs the DNA of nervous tissue supplied by the middle cerebral artery in rats

This study compares the changes of DNA repair in brain tissue dominated by the middle cerebral artery after electroacupuncture at the acupoints of Renzhong （DU 26）, Neiguan （PC 6）, Quchi （LI 11） and Zusanli （ST 36） in rats. In the apurinic/apyrimidinic endonuclease DNA basic group reparative excision experiments, the apurinic/apyrimidinic endonuclease activity of brain tissue increased slightly after electroacupuncture in rats. In the DNA polymerase β （Pol β）experiments, the Pol β ac-tivity of brain tissue increased after electroacupuncture, especially at DU 26 and PC 6. In the DNA ligase experiments, the expression of DNA ligase 1 in brain tissue increased significantly after electroacupuncture. These findings demonstrate increased activity of apurinic/apyrimidinic en-donuclease, Pol β and DNA ligase 1 after electroacupuncture at DU 26 and PC 6. Also, DNA repair in brain tissue supplied by the middle cerebral artery is promoted after electroacupuncture at DU 26 and PC 6, which are more effective than the LI 11 and ST 36 acupoints .

Design and Verification of Selected Technological Procedures for the Repairs of Land Vehicles Combat Damage

The paper deals with temporary repairs. Applying a different technology, using a reproduction part, or performing a repair by a serviceman without the competence is typical features of temporary repairs. Temporary repair makes possible for an object to fulfil its function for a limited time, until regular repairs can be made. The complexity perplex modern vehicles their reparability. It is necessary to look for the new procedures of the implementation so-called temporary repairs. The authors suggested procedure battle damage assessment and repair, which they expressed in the form of diagrams. There is also description of new technological procedures, which could be possibly applied in field of temporary repairs. These new procedures are applied on land (wheeled and tracked) vehicles parts and their sufficiency for Czech Army conditions is tested. The main purpose of the thesis is defining operating procedures of the most useful methods, including their verifications and proposal of tools needed for repairs. These tools should be included in equipment of vehicles operated in Czech Army. The thesis is primarily focused on repairs of mechanical parts and units and also of reparation of fuel, hydraulic and high pressure systems.

Allocating redundancy,maintenance and spare parts for minimizing system cost under decentralized repairs

Reliability-redundancy allocation,preventive maintenance,and spare parts logistics are crucial for achieving system reliability and availability goal.Existing methods often concentrate on specific scopes of the system’s lifetime.This paper proposes a joint redundancymaintenance-inventory allocation model that simultaneously optimizes redundant component,replacement time,spares stocking,and repair capacity.Under reliability and availability criteria,our objective is to minimize the system’s lifetime cost,including design,manufacturing,and operational phases.We develop a unified system availability model based on ten performance drivers,serving as the foundation for the establishment of the lifetimebased resource allocation model.Superimposed renewal theory is employed to estimate spare part demand from proactive and corrective replacements.A bisection algorithm,enhanced by neighborhood exploration,solves the complex mixed-integer,nonlinear optimization problem.The numerical experiments show that component redundancy is preferred and necessary if one of the following situations occurs:extremely high system availability is required,the fleet size is small,the system reliability is immature,the inventory holding is too costly,or the handson replacement time is prolonged.The joint allocation model also reveals that there exists no monotonic relation between spares stocking level and system availability.

Role of transforming growth factor-βin peripheral nerve regeneration

Injuries caused by trauma and neurodegenerative diseases can damage the peripheral nervous system and cause functional deficits.Unlike in the central nervous system,damaged axons in peripheral nerves can be induced to regenerate in response to intrinsic cues after reprogramming or in a growth-promoting microenvironment created by Schwann cells.However,axon regeneration and repair do not automatically result in the restoration of function,which is the ultimate therapeutic goal but also a major clinical challenge.Transforming growth factor(TGF)is a multifunctional cytokine that regulates various biological processes including tissue repair,embryo development,and cell growth and differentiation.There is accumulating evidence that TGF-βfamily proteins participate in peripheral nerve repair through various factors and signaling pathways by regulating the growth and transformation of Schwann cells;recruiting specific immune cells;controlling the permeability of the blood-nerve barrier,thereby stimulating axon growth;and inhibiting remyelination of regenerated axons.TGF-βhas been applied to the treatment of peripheral nerve injury in animal models.In this context,we review the functions of TGF-βin peripheral nerve regeneration and potential clinical applications.

Molecular insights into clinical trials for immune checkpoint inhibitors in colorectal cancer:Unravelling challenges and future directions

Colorectal cancer(CRC)is a complex disease with diverse etiologies and clinical outcomes.Despite considerable progress in development of CRC therapeutics,challenges remain regarding the diagnosis and management of advanced stage metastatic CRC(mCRC).In particular,the five-year survival rate is very low since mCRC is currently rarely curable.Over the past decade,cancer treatment has significantly improved with the introduction of cancer immunotherapies,specifically immune checkpoint inhibitors.Therapies aimed at blocking immune checkpoints such as PD-1,PD-L1,and CTLA-4 target inhibitory pathways of the immune system,and thereby enhance anti-tumor immunity.These therapies thus have shown promising results in many clinical trials alone or in combination.The efficacy and safety of immunotherapy,either alone or in combination with CRC,have been investigated in several clinical trials.Clinical trials,including KEYNOTE-164 and CheckMate 142,have led to Food and Drug Administration approval of the PD-1 inhibitors pembrolizumab and nivolumab,respectively,for the treatment of patients with unresectable or metastatic microsatellite instability-high or deficient mismatch repair CRC.Unfortunately,these drugs benefit only a small percentage of patients,with the benefits of immunotherapy remaining elusive for the vast majority of CRC patients.To this end,primary and secondary resistance to immunotherapy remains a significant issue,and further research is necessary to optimize the use of immunotherapy in CRC and identify biomarkers to predict the response.This review provides a comprehensive overview of the clinical trials involving immune checkpoint inhibitors in CRC.The underlying rationale,challenges faced,and potential future steps to improve the prognosis and enhance the likelihood of successful trials in this field are discussed.

Neuronal conversion from glia to replenish the lost neurons

Neuronal injury,aging,and cerebrovascular and neurodegenerative diseases such as cerebral infarction,Alzheimer’s disease,Parkinson’s disease,frontotemporal dementia,amyotrophic lateral sclerosis,and Huntington’s disease are characte rized by significant neuronal loss.Unfo rtunately,the neurons of most mammals including humans do not possess the ability to self-regenerate.Replenishment of lost neurons becomes an appealing therapeutic strategy to reve rse the disease phenotype.Transplantation of pluripotent neural stem cells can supplement the missing neurons in the brain,but it carries the risk of causing gene mutation,tumorigenesis,severe inflammation,and obstructive hydrocephalus induced by brain edema.Conversion of neural or non-neural lineage cells into functional neurons is a promising strategy for the diseases involving neuron loss,which may overcome the above-mentioned disadvantages of neural stem cell therapy.Thus far,many strategies to transfo rm astrocytes,fibroblasts,microglia,Muller glia,NG2 cells,and other glial cells to mature and functional neurons,or for the conversion between neuronal subtypes have been developed thro ugh the regulation of transcription factors,polypyrimidine tra ct binding protein 1(PTBP1),and small chemical molecules or are based on a combination of several factors and the location in the central nervous system.However,some recent papers did not obtain expected results,and discrepancies exist.Therefore,in this review,we discuss the history of neuronal transdifferentiation,summarize the strategies for neuronal replenishment and conversion from glia,especially astrocytes,and point out that biosafety,new strategies,and the accurate origin of the truly co nverted neurons in vivo should be focused upon in future studies.It also arises the attention of replenishing the lost neurons from glia by gene therapies such as up-regulation of some transc ription factors or downregulation of PTBP1 or drug interfe rence therapies.

Mesenchymal stem cell-derived extracellular vesicles in skin wound healing:roles,opportunities and challenges

Skin wounds are characterized by injury to the skin due to trauma,tearing,cuts,or contusions.As such injuries are common to all human groups,they may at times represent a serious socioeconomic burden.Currently,increasing numbers of studies have focused on the role of mesenchymal stem cell(MSC)-derived extracellular vesicles(EVs)in skin wound repair.As a cell-free therapy,MSC-derived EVs have shown significant application potential in the field of wound repair as a more stable and safer option than conventional cell therapy.Treatment based on MSC-derived EVs can significantly promote the repair of damaged substructures,including the regeneration of vessels,nerves,and hair follicles.In addition,MSC-derived EVs can inhibit scar formation by affecting angiogenesis-related and antifibrotic pathways in promoting macrophage polarization,wound angiogenesis,cell proliferation,and cell migration,and by inhibiting excessive extracellular matrix production.Additionally,these structures can serve as a scaffold for components used in wound repair,and they can be developed into bioengineered EVs to support trauma repair.Through the formulation of standardized culture,isolation,purification,and drug delivery strategies,exploration of the detailed mechanism of EVs will allow them to be used as clinical treatments for wound repair.In conclusion,MSCderived EV-based therapies have important application prospects in wound repair.Here we provide a comprehensive overview of their current status,application potential,and associated drawbacks.

High quality repair of osteochondral defects in rats using the extracellular matrix of antler stem cells

BACKGROUND Cartilage defects are some of the most common causes of arthritis.Cartilage lesions caused by inflammation,trauma or degenerative disease normally result in osteochondral defects.Previous studies have shown that decellularized extracellular matrix(ECM)derived from autologous,allogenic,or xenogeneic mesenchymal stromal cells(MSCs)can effectively restore osteochondral integrity.AIM To determine whether the decellularized ECM of antler reserve mesenchymal cells(RMCs),a xenogeneic material from antler stem cells,is superior to the currently available treatments for osteochondral defects.METHODS We isolated the RMCs from a 60-d-old sika deer antler and cultured them in vitro to 70%confluence;50 mg/mL L-ascorbic acid was then added to the medium to stimulate ECM deposition.Decellularized sheets of adipocyte-derived MSCs(aMSCs)and antlerogenic periosteal cells(another type of antler stem cells)were used as the controls.Three weeks after ascorbic acid stimulation,the ECM sheets were harvested and applied to the osteochondral defects in rat knee joints.RESULTS The defects were successfully repaired by applying the ECM-sheets.The highest quality of repair was achieved in the RMC-ECM group both in vitro(including cell attachment and proliferation),and in vivo(including the simultaneous regeneration of well-vascularized subchondral bone and avascular articular hyaline cartilage integrated with surrounding native tissues).Notably,the antler-stem-cell-derived ECM(xenogeneic)performed better than the aMSC-ECM(allogenic),while the ECM of the active antler stem cells was superior to that of the quiescent antler stem cells.CONCLUSION Decellularized xenogeneic ECM derived from the antler stem cell,particularly the active form(RMC-ECM),can achieve high quality repair/reconstruction of osteochondral defects,suggesting that selection of decellularized ECM for such repair should be focused more on bioactivity rather than kinship.

Star power: harnessing the reactive astrocyte response to promote remyelination in multiple sclerosis

Astrocytes are indispensable for central nervous system development and homeostasis.In response to injury and disease,astrocytes are integral to the immunological-and the,albeit limited,repair response.In this review,we will examine some of the functions reactive astrocytes play in the context of multiple sclerosis and related animal models.We will consider the heterogeneity or plasticity of astrocytes and the mechanisms by which they promote or mitigate demyelination.Finally,we will discuss a set of biomedical strategies that can stimulate astrocytes in their promyelinating response.

Self-reinforced Calcium Phosphate Cement Inspired by Sea Cucumber Dermis

A composite bone cement based onα-TCP with self-reinforcing characteristics is prepared by compounding cellulose whiskers and polyvinyl alcohol in different proportions.In this system,we are inspired by the sea cucumber,which can alter the stiffness of their inner dermis reversibly.Through the formation of hydrogen bonds between the hydroxyl groups on the cellulose whiskers and PVA,the bone cement matrix can be strengthened during the curing process of cement.In the process of bone cement blending,there is more water,the hydrogen bond connection is destroyed,so the slurry has better fluidity at this time.As the hydration of the bone cement progresses,the reduction of the water phase leads to the formation of a permeable network structure of hydrogen bond connections between the whiskers.The dual-phase action of PVA and whiskers greatly increases the mechanical strength of the bone cement system(5.5 to 23.8 MPa),while the presence of polyvinyl alcohol improves the toughness of the bone cement system.This work was supposed to explore whether the chemoresponsive materials can be adapted to biomedical materials,for example,bone repair.

Neural membrane repair at the core of regeneration

Loss of plasma membrane integrity can compromise cell functioning and viability.To countera ct this eminent threat,euka ryotic cells have developed efficient repair mechanisms,which seem to have co-evolved with the emergence of vital membrane processes(Cooper and McNeil,2015).This relationship between basic cellular functioning and membrane repair highlights the fundamental significance of preserving membrane integrity for cellular life.

Experimental Study on Engineering Behavior of Solidified Soil for Scour Repair and Protection

A new scour countermeasure using solidified slurry for offshore foundation has been proposed recently.Fluidized solidified slurry is pumped to seabed area around foundation for scour protection or pumped into the developed scour holes for scour repair as the fluidized material solidifies gradually.In the pumping operation and solidification,the engineering behaviors of solidified slurry require to be considered synthetically for the reliable application in scour repair and protection of ocean engineering such as the pumpability related flow value,flow diffusion behavior related rheological property,anti-scour performance related retention rate in solidification and bearing capacity related strength property after solidification.In this study,a series of laboratory tests are conducted to investigate the effects of mix proportion(initial water content and binder content)on the flow value,rheological properties,density,retention rate of solidified slurry and unconfined compressive strength(UCS).The results reveal that the flow value increases with the water content and decreases with the binder amount.All the solidified slurry exhibits Bingham plastic behavior when the shear rate is larger than 5 s^(-1).The Bingham model has been employed to fit the rheology test results,and empirical formulas for obtaining the density,yield stress and viscosity are established,providing scientific support for the numerical assessment of flow and diffusion of solidified slurry.Retention rate of solidified slurry decreases with the water flow velocity and flow value,which means the pumpability of solidified slurry is contrary to anti-scour performance.The unconfined compressive strength after solidification reduces as the water content increases and binder content decreases.A design and application procedure of solidified soil for scour repair and protection is also proposed for engineering reference.

Stiffness-tunable biomaterials provide a good extracellular matrix environment for axon growth and regeneration

Neuronal growth, extension, branching, and formation of neural networks are markedly influenced by the extracellular matrix—a complex network composed of proteins and carbohydrates secreted by cells. In addition to providing physical support for cells, the extracellular matrix also conveys critical mechanical stiffness cues. During the development of the nervous system, extracellular matrix stiffness plays a central role in guiding neuronal growth, particularly in the context of axonal extension, which is crucial for the formation of neural networks. In neural tissue engineering, manipulation of biomaterial stiffness is a promising strategy to provide a permissive environment for the repair and regeneration of injured nervous tissue. Recent research has fine-tuned synthetic biomaterials to fabricate scaffolds that closely replicate the stiffness profiles observed in the nervous system. In this review, we highlight the molecular mechanisms by which extracellular matrix stiffness regulates axonal growth and regeneration. We highlight the progress made in the development of stiffness-tunable biomaterials to emulate in vivo extracellular matrix environments, with an emphasis on their application in neural repair and regeneration, along with a discussion of the current limitations and future prospects. The exploration and optimization of the stiffness-tunable biomaterials has the potential to markedly advance the development of neural tissue engineering.

The influence of yttrium and manganese additions on the degradation and biocompatibility of magnesium-zinc-based alloys:In vitro and in vivo studies

The repair and regeneration of bone defects are highly challenging orthopedic problems.Recently,Mg-based implants have gained popularity due to their unique biodegradation and elastic modulus similar to that of human bone.The aim of our study is to develop a magnesium alloy with a controllable degradation that can closely match bone tissue to help injuries heal in vivo and avoid cytotoxicity caused by a sudden increase in ion concentration.In this study,we prepared and modified Mg-3Zn,Mg-3Zn-1Y,and Mg-2Zn-1Mn by hot extrusion,and used Mg-2.5Y-2.5Nd was as a control.We then investigated the effect of additions of Y and Mn on alloys'properties.Our results show that Mn and Y can improve not only compression strength but also corrosion resistance.The alloy Mg-2Zn-1Mn demonstrated good cytocompatibility in vitro,and for this reason we selected it for implantation in vivo.The degraded Mg-2Zn-1Mn implanted a bone defect area did not cause obvious rejection and inflammatory reaction,and the degradation products left no signs of damage to the heart,liver,kidney,or brain.Furthermore,we find that Mg-2Zn-1Mn can promote an osteoinductive response in vivo and the formation of bone regeneration.

The DNA damage repair complex MoMMS21-MoSMC5 is required for infection-related development and pathogenicity of Magnaporthe oryzae

The conserved DNA damage repair complex,MMS21-SMC5/6(Methyl methane sulfonate 21-Structural maintenance of chromosomes 5/6),has been extensively studied in yeast,animals,and plants.However,its role in phytopathogenic fungi,particularly in the highly destructive rice blast fungus Magnaporthe oryzae,remains unknown.In this study,we functionally characterized the homologues of this complex,MoMMS21 and MoSMC5,in M.oryzae.We first demonstrated the importance of DNA damage repair in M.oryzae by showing that the DNA damage inducer phleomycin inhibited vegetative growth,infection-related development and pathogenicity in this fungus.Additionally,we discovered that MoMMS21 and MoSMC5 interacted in the nuclei,suggesting that they also function as a complex in M.oryzae.Gene deletion experiments revealed that both MoMMS21 and MoSMC5 are required for infection-related development and pathogenicity in M.oryzae,while only MoMMS21 deletion affected growth and sensitivity to phleomycin,indicating its specific involvement in DNA damage repair.Overall,our results provide insights into the roles of MoMMS21 and MoSMC5 in M.oryzae,highlighting their functions beyond DNA damage repair.

Nucleotide excision repair gene polymorphisms and hepatoblastoma susceptibility in Eastern Chinese children:A five-center case-control study

Objective:Nucleotide excision repair(NER)plays a vital role in maintaining genome stability,and the effect of NER gene polymorphisms on hepatoblastoma susceptibility is still under investigation.This study aimed to evaluate the relationship between NER gene polymorphisms and the risk of hepatoblastoma in Eastern Chinese Han children.Methods:In this five-center case-control study,we enrolled 966 subjects from East China(193 hepatoblastoma patients and 773 healthy controls).The TaqMan method was used to genotype 19 single nucleotide polymorphisms(SNPs)in NER pathway genes,including ERCC1,XPA,XPC,XPD,XPF,and XPG.Then,multivariate logistic regression analysis was performed,and odds ratios(ORs)and 95%confidence intervals(95%CIs)were utilized to assess the strength of associations.Results:Three SNPs were related to hepatoblastoma risk.XPC rs2229090 and XPD rs3810366 significantly contributed to hepatoblastoma risk according to the dominant model(adjusted OR=1.49,95%CI=1.07−2.08,P=0.019;adjusted OR=1.66,95%CI=1.12−2.45,P=0.012,respectively).However,XPD rs238406 conferred a significantly decreased risk of hepatoblastoma under the dominant model(adjusted OR=0.68,95%CI=0.49−0.95;P=0.024).Stratified analysis demonstrated that these significant associations were more prominent in certain subgroups.Moreover,there was evidence of functional implications of these significant SNPs suggested by online expression quantitative trait loci(eQTLs)and splicing quantitative trait loci(sQTLs)analysis.Conclusions:In summary,NER pathway gene polymorphisms(XPC rs2229090,XPD rs3810366,and XPD rs238406)are significantly associated with hepatoblastoma risk,and further research is required to verify these findings.