Traumatic peripheral nerve injuries are a major contributor to long-term disability,accounting for nearly half of all peripheral nervous system disorders.Although autologous nerve grafting remains the clinical gold st...Traumatic peripheral nerve injuries are a major contributor to long-term disability,accounting for nearly half of all peripheral nervous system disorders.Although autologous nerve grafting remains the clinical gold standard,it is limited by donor-site morbidity and often fails to achieve full functional recovery.Biodegradable collagen conduits have emerged as an appealing alternative,providing a scaffold for directed axonal growth without requiring graft harvest.We reported three cases of chronic nerve injuries(6-12 months post-trauma):two involving 2.0-3.5 cm ulnar nerve defects in the forearm and one with a 2.5 cm median nerve defect at the wrist.Under microscopic guidance,each defect was bridged with a tubular type I collagen conduit secured by epineurial sutures,followed by standardized physiotherapy and sensory reeducation.At 12-18 months of follow-up,all patients demonstrated near-complete sensory recovery—two-point discrimination and Semmes-Weinstein thresholds returned to≤6 mm—and motor function improved to Medical Research Council grades 4-5,restoring fine dexterity and grip strength.Patient-reported measures indicated marked reductions in neuropathic pain and paresthesia.No conduit-related adverse events or neuroma formation were observed.This case series highlights the potential of collagen-based conduits to promote robust axonal regeneration and functional restoration even in delayed presentations.By eliminating donor-site morbidity and simplifying the reconstructive procedure,conduit-assisted repair offers a less invasive,reproducible alternative to autologous grafts for both acute and chronic peripheral nerve injuries.展开更多
Peripheral nerve injuries(PNI)that result in nerve gaps represent a major clinical challenge,frequently leading to long-term disability and a diminished quality of life for affected individuals.Despite advances in sur...Peripheral nerve injuries(PNI)that result in nerve gaps represent a major clinical challenge,frequently leading to long-term disability and a diminished quality of life for affected individuals.Despite advances in surgical techniques,functional recovery remains limited,highlighting the need for innovative therapeutic strategies.Mesenchymal stem cells(MSCs)have emerged as a promising avenue for nerve repair due to their regenerative,immunomodulatory,and neuropro-tective properties.Thus,this review explored current approaches utilizing MSCs in the treatment of PNI,emphasizing their potential to enhance nerve rege-neration and functional recovery.Furthermore,tissue engineering and transdiffer-entiation of MSCs into Schwann-like cells offer a versatile strategy to optimize therapeutic effects,paving the way for personalized medicine.Nevertheless,challenges persist regarding the clinical application of MSCs in PNI,including transplant safety,delivery methods,optimal dosing,and ethical considerations.A deeper understanding of the mechanisms underlying MSC action in PNI may contribute to more effective treatment protocols in the management of peripheral nerve defects.展开更多
Peripheral nerve injury causes severe neuroinflammation and has become a global medical challenge.Previous research has demonstrated that porcine decellularized nerve matrix hydrogel exhibits excellent biological prop...Peripheral nerve injury causes severe neuroinflammation and has become a global medical challenge.Previous research has demonstrated that porcine decellularized nerve matrix hydrogel exhibits excellent biological properties and tissue specificity,highlighting its potential as a biomedical material for the repair of severe peripheral nerve injury;however,its role in modulating neuroinflammation post-peripheral nerve injury remains unknown.Here,we aimed to characterize the anti-inflammatory properties of porcine decellularized nerve matrix hydrogel and their underlying molecular mechanisms.Using peripheral nerve injury model rats treated with porcine decellularized nerve matrix hydrogel,we evaluated structural and functional recovery,macrophage phenotype alteration,specific cytokine expression,and changes in related signaling molecules in vivo.Similar parameters were evaluated in vitro using monocyte/macrophage cell lines stimulated with lipopolysaccharide and cultured on porcine decellularized nerve matrix hydrogel-coated plates in complete medium.These comprehensive analyses revealed that porcine decellularized nerve matrix hydrogel attenuated the activation of excessive inflammation at the early stage of peripheral nerve injury and increased the proportion of the M2 subtype in monocytes/macrophages.Additionally,porcine decellularized nerve matrix hydrogel negatively regulated the Toll-like receptor 4/myeloid differentiation factor 88/nuclear factor-κB axis both in vivo and in vitro.Our findings suggest that the efficacious anti-inflammatory properties of porcine decellularized nerve matrix hydrogel induce M2 macrophage polarization via suppression of the Toll-like receptor 4/myeloid differentiation factor 88/nuclear factor-κB pathway,providing new insights into the therapeutic mechanism of porcine decellularized nerve matrix hydrogel in peripheral nerve injury.展开更多
Traumatic axonal lesions of peripheral nerves disrupt neuronal connections with their targets,resulting in the loss of motor and sensory functions.Despite the peripheral nervous system’s capacity for axonal regrowth,...Traumatic axonal lesions of peripheral nerves disrupt neuronal connections with their targets,resulting in the loss of motor and sensory functions.Despite the peripheral nervous system’s capacity for axonal regrowth,this may lead to permanent impairements resulting in a loss of quality of life and a high socioeconomic burden.展开更多
Spinal cord injury is a severe neurological condition characterized by the permanent loss of nerve cell function and a failure in neural circuit reconstruction-key factors contributing to disability.Therefore,explorin...Spinal cord injury is a severe neurological condition characterized by the permanent loss of nerve cell function and a failure in neural circuit reconstruction-key factors contributing to disability.Therefore,exploring effective strategies to promote the repair and regeneration of nerve cells after spinal cord injury is crucial for optimizing patient prognosis.The purpose of this paper is to conduct an in-depth review of the pathological changes in nerve cells after spinal cord injury and to present the state of research on the role of exercise training in promoting the repair and regeneration of nerve cells after spinal cord injury.In terms of the intrinsic growth capacity of neurons,disruptions in the dynamic balance between growth cones and the cytoskeleton,the dysregulation of transcription factors,abnormal protein signaling transduction,and altered epigenetic modifications collectively hinder axonal regeneration.Additionally,the microenvironment of neurons undergoes a series of complex changes,initially manifesting as edema,which may be exacerbated by spinal cord ischemia-reperfusion injury,further increasing the extent of nerve cell damage.The abnormal proliferation of astrocytes leads to the formation of glial scars,creating a physical barrier to nerve regeneration.The inflammatory response triggered by the excessive activation of microglia negatively impacts the process of nerve repair.Non-invasive interventions involving exercise training have shown significant potential in promoting nerve repair as part of a comprehensive treatment strategy for spinal cord injury.Specifically,exercise training can reshape the growth cone and cytoskeletal structures of neurons,regulate transcription factor activity,modulate protein signaling pathways,and influence epigenetic modifications,thereby activating the intrinsic repair mechanisms of neurons.Moreover,exercise training can regulate the activation state of astrocytes,optimize the inflammatory response and metabolic processes,promote astrocyte polarization,enhance angiogenesis,reduce glial scar formation,and modulate the expression levels of nerve growth factors.It also effectively helps regulate microglial activation,promotes axonal regeneration,and improves phagocytic function,thereby optimizing the microenvironment for nerve repair.In terms of clinical translation,we summarize the preliminary results of new drug research and development efforts,the development of innovative devices,and the use of exercise training in promoting clinical advancements in nerve repair following spinal cord injury,while considering their limitations and future application prospects.In summary,this review systematically analyzes findings relating to the pathological changes occurring in nerve cells after spinal cord injury and emphasizes the critical role of exercise training in facilitating the repair and regeneration of nerve cells.This work is expected to provide new ideas and methods for the rehabilitation of patients with spinal cord injury.展开更多
Previous research has demonstrated the feasibility of repairing nerve defects through acellular allogeneic nerve grafting with bone marrow mesenchymal stem cells.However,adult tissue–derived mesenchymal stem cells en...Previous research has demonstrated the feasibility of repairing nerve defects through acellular allogeneic nerve grafting with bone marrow mesenchymal stem cells.However,adult tissue–derived mesenchymal stem cells encounter various obstacles,including limited tissue sources,invasive acquisition methods,cellular heterogeneity,purification challenges,cellular senescence,and diminished pluripotency and proliferation over successive passages.In this study,we used induced pluripotent stem cell-derived mesenchymal stem cells,known for their self-renewal capacity,multilineage differentiation potential,and immunomodulatory characteristics.We used induced pluripotent stem cell-derived mesenchymal stem cells in conjunction with acellular nerve allografts to address a 10 mm-long defect in a rat model of sciatic nerve injury.Our findings reveal that induced pluripotent stem cell-derived mesenchymal stem cells exhibit survival for up to 17 days in a rat model of peripheral nerve injury with acellular nerve allograft transplantation.Furthermore,the combination of acellular nerve allograft and induced pluripotent stem cell-derived mesenchymal stem cells significantly accelerates the regeneration of injured axons and improves behavioral function recovery in rats.Additionally,our in vivo and in vitro experiments indicate that induced pluripotent stem cell-derived mesenchymal stem cells play a pivotal role in promoting neovascularization.Collectively,our results suggest the potential of acellular nerve allografts with induced pluripotent stem cell-derived mesenchymal stem cells to augment nerve regeneration in rats,offering promising therapeutic strategies for clinical translation.展开更多
Our recent study demonstrated that knockout of microRNA-301a attenuates migration and phagocytosis in macrophages.Considering that macrophages and Schwann cells synergistically clear the debris of degraded axons and m...Our recent study demonstrated that knockout of microRNA-301a attenuates migration and phagocytosis in macrophages.Considering that macrophages and Schwann cells synergistically clear the debris of degraded axons and myelin during Wallerian degeneration,which is a prerequisite for nerve regeneration,we hypothesized that microRNA-301a regulates Wallerian degeneration and nerve regeneration via impacts on Schwann cell migration and phagocytosis.Herein,we found low expression of microRNA-301a in intact sciatic nerves,with no impact of the microRNA-301a knockout on nerve structure and function.By contrast,we found significant upregulation of microRNA-301a in injured sciatic nerves.We established a sciatic nerve crush model in microRNA-301a knockout mice,which exhibited attenua9ted morphological and functional regeneration following sciatic nerve crush injury.The microRNA-301a knockout also led to significantly inhibited Wallerian degeneration in an in vivo sciatic nerve-transection model and in an in vitro nerve explant block model.Schwann cells with the microRNA-301a knockout showed inhibition of phagocytosis and migration,which was reversible under transfection with microRNA-301a mimics.Rescue experiments involving transfection of microRNA-301a-knockout Schwann cells with microRNA-301a mimics or treatment with the C-X-C motif receptor 4 inhibitor WZ811 indicated the mechanistic involvement of the Yin Yang 1/C-X-C motif receptor 4 pathway in the role of microRNA-301a.Combined with our previous findings in macrophages,we conclude that microRNA-301a plays a key role in peripheral nerve injury and repair by regulating the migratory and phagocytic capabilities of Schwann cells and macrophages via the Yin Yang 1/C-X-C motif receptor 4 pathway.展开更多
Peripheral nerve injury is a complex condition presenting significant clinical treatment challenges due to the limited regenerative capacity of peripheral nerves.Nerve conduits have been seen as a promising strategy t...Peripheral nerve injury is a complex condition presenting significant clinical treatment challenges due to the limited regenerative capacity of peripheral nerves.Nerve conduits have been seen as a promising strategy to overcome the shortage of other treatment options(e.g.,nerve graft).However,nerve regeneration occurs within a complex environment,and elaborate modulation is needed to meet repair requirements.The aim of this study was to investigate and explore a multifunctional nerve conduit with reactive oxygen species clearing,immune modulation to reshape the regenerative environment,and topographic cues and electrical signals to guide nerve growth.We developed an electroactive nerve guidance conduit composed of polylactic-glycolic acid and carbon nanotubes with an oriented structure using electrospinning and modified it with mussel-inspired polydopamine combining neurotrophin-3.The resulting nerve scaffold exhibited favorable orientation,electrical conductivity,and mechanical properties.Continuous release of neurotrophin-3 from the nerve conduit supported nerve regeneration throughout the repair process.In vitro assessments confirmed the cytocompatibility,reactive oxygen species scavenging,and immune regulation capabilities of the nerve scaffolds.In a rat sciatic nerve defect model,the nerve scaffolds effectively prevented muscle atrophy and promoted nerve regeneration and functional recovery over a 12-week period.These findings suggest that polydopamine-modified,electroactive,oriented nerve guidance conduits with multiple bioactive functions hold great promise for the repair of peripheral nerve injuries.展开更多
Neural injuries can cause considerable functional impairments,and both central and peripheral nervous systems have limited regenerative capacity.The existing conventional pharmacological treatments in clinical practic...Neural injuries can cause considerable functional impairments,and both central and peripheral nervous systems have limited regenerative capacity.The existing conventional pharmacological treatments in clinical practice show poor targeting,rapid drug clearance from the circulatory system,and low therapeutic efficiency.Therefore,in this review,we have first described the mechanisms underlying nerve regeneration,characterized the biomaterials used for drug delivery to facilitate nerve regeneration,and highlighted the functionalization strategies used for such drug-delivery systems.These systems mainly use natural and synthetic polymers,inorganic materials,and hybrid systems with advanced drug-delivery abilities,including nanoparticles,hydrogels,and scaffoldbased systems.Then,we focused on comparing the types of drug-delivery systems for neural regeneration as well as the mechanisms and challenges associated with targeted delivery of drugs to facilitate neural regeneration.Finally,we have summarized the clinical application research and limitations of targeted delivery of these drugs.These biomaterials and drug-delivery systems can provide mechanical support,sustained release of bioactive molecules,and enhanced intercellular contact,ultimately reducing cell apoptosis and enhancing functional recovery.Nevertheless,immune reactions,degradation regulation,and clinical translations remain major unresolved challenges.Future studies should focus on optimizing biomaterial properties,refining delivery precision,and overcoming translational barriers to advance these technologies toward clinical applications.展开更多
Retinal ganglion cells,a crucial component of the central nervous system,are often affected by irreversible visual impairment due to various conditions,including trauma,tumors,ischemia,and glaucoma.Studies have shown ...Retinal ganglion cells,a crucial component of the central nervous system,are often affected by irreversible visual impairment due to various conditions,including trauma,tumors,ischemia,and glaucoma.Studies have shown that the optic nerve crush model and glaucoma model are commonly used to study retinal ganglion cell injury.While these models differ in their mechanisms,both ultimately result in retinal ganglion cell injury.With advancements in high-throughput technologies,techniques such as microarray analysis,RNA sequencing,and single-cell RNA sequencing have been widely applied to characterize the transcriptomic profiles of retinal ganglion cell injury,revealing underlying molecular mechanisms.This review focuses on optic nerve crush and glaucoma models,elucidating the mechanisms of optic nerve injury and neuron degeneration induced by glaucoma through single-cell transcriptomics,transcriptome analysis,and chip analysis.Research using the optic nerve crush model has shown that different retinal ganglion cell subtypes exhibit varying survival and regenerative capacities following injury.Single-cell RNA sequencing has identified multiple genes associated with retinal ganglion cell protection and regeneration,such as Gal,Ucn,and Anxa2.In glaucoma models,high-throughput sequencing has revealed transcriptomic changes in retinal ganglion cells under elevated intraocular pressure,identifying genes related to immune response,oxidative stress,and apoptosis.These genes are significantly upregulated early after optic nerve injury and may play key roles in neuroprotection and axon regeneration.Additionally,CRISPR-Cas9 screening and ATAC-seq analysis have identified key transcription factors that regulate retinal ganglion cell survival and axon regeneration,offering new potential targets for neurorepair strategies in glaucoma.In summary,single-cell transcriptomic technologies provide unprecedented insights into the molecular mechanisms underlying optic nerve injury,aiding in the identification of novel therapeutic targets.Future researchers should integrate advanced single-cell sequencing with multi-omics approaches to investigate cell-specific responses in retinal ganglion cell injury and regeneration.Furthermore,computational models and systems biology methods could help predict molecular pathways interactions,providing valuable guidance for clinical research on optic nerve regeneration and repair.展开更多
1Introduction A 25-year-old woman presented with a 3-month history of otalgia and aural fullness in the left ear,without associated otological or systemic symptoms.Her medical history was unremarkable,and she denied a...1Introduction A 25-year-old woman presented with a 3-month history of otalgia and aural fullness in the left ear,without associated otological or systemic symptoms.Her medical history was unremarkable,and she denied any history of hepatitis,hypertension,diabetes,cardiovascular disease,or other significant conditions.The patient was diagnosed with external auditory canal cholesteatoma and subsequently underwent canalplasty under general anesthesia.Routine anesthetic drugs,including 2%lidocaine,dexamethasone,propofol,sufentanil,rocuronium bromide,ondansetron,flurbiprofen axetil,neostigmine,and atropine,were used during surgery and anesthesia recovery.No significant events were noted,and the patient experienced only a blood loss of 10 mL.展开更多
Tactile feedback is critical for human interaction with external information.Similarly,tactile feedback can enrich the user's sensations when using prosthesis.To explore a potential scheme for tactile feedback,thi...Tactile feedback is critical for human interaction with external information.Similarly,tactile feedback can enrich the user's sensations when using prosthesis.To explore a potential scheme for tactile feedback,this study applied a non-inva-sive Transcutaneous Electrical Nerve Stimulation(TENS)to elicit tactile sensations in the hand,which involved median nerve,ulnar nerve,and radial nerve.Ten able-bodied subjects(8 males,2 females)were recruited to participate in the study.An array of 4×2 electrodes was positioned on the medial aspect of the brachii muscle's short head in the upper arm,which is in proximity to the median nerve,ulnar nerve,and radial nerve.Different electrode pairs were randomly selected to elicit distinct sensations at various positions on the hand,and the subjects reported the sensory areas.Then,the sensory areas and sensory thresholds were confirmed through psychophysical methods.According to the experimental results,tactile sensations were elicited at different locations on the subjects'hand through TENS of different electrode pairs.All subjects reported extensive and detailed sensory areas in the fingers,palm,and dorsum,corresponding to the sensory innervation areas of different nerves.The study effectively demonstrated the ability of TENS in evoking tactile feedback in the hand,paving the way for future optimization and development of prosthetic hands.展开更多
Dear Editor,Dorsal pontine lesions may cause a variety of complex neuro-ophthalmic deficits,including horizontal gaze palsy(HGP),internuclear ophthalmoplegia,one-and-ahalf syndrome,abducens nerve palsy,skew deviation,...Dear Editor,Dorsal pontine lesions may cause a variety of complex neuro-ophthalmic deficits,including horizontal gaze palsy(HGP),internuclear ophthalmoplegia,one-and-ahalf syndrome,abducens nerve palsy,skew deviation,or any combination of these.Here we present a rare case of an adult patient who developed multiple complicated clinical manifestations after surgical removal of a pontine cavernous hemangioma(PCH).Our case highlights a single pontine lesion may involve complicated neural pathways and result in complicated symptoms and signs,in which abducens nerve palsy or skew deviation is easily missed when combined with HGP.展开更多
This study compared the acute effects of electrical energy transfer(TECAR) and transcutaneous electrical stimulation(TENS) on pain and flexibility after a hamstring injury. Young athletes received either a 20 min TECA...This study compared the acute effects of electrical energy transfer(TECAR) and transcutaneous electrical stimulation(TENS) on pain and flexibility after a hamstring injury. Young athletes received either a 20 min TECAR(n = 24) or TENS(n = 26) session within 5 days following a hamstring injury, while the control(CON, n = 25)group was instructed to rest. Visual analogue scale(VAS), functional Assessment Scale for Acute Hamstring Injuries(FASH), straight leg raise test(SLR), and sit-and-reach scores(STR) were obtained prior to, immediately,24, and 48 h after therapy. Group differences were detected after therapy in VAS and FASH scores(p < 0.05).Compared to pre-therapy measurements, VAS scores showed a greater decrease in the TECAR group(-38.75% to-63.33%) than in the TENS group(-16.67% to-25.00%) and both were greater than in the CON group(-2.81%to-9.81%)(p < 0.05). The TECAR group improved FASH scores(28.57%–48.21%) more than the TENS group(15.89%–27.79%) and both groups more than the CON group(0%–8.33%)(p < 0.05). The increase in SLR and STR was greater in the TECAR group(6.26%–13.96%) than in the TENS(1.72%–9.53%) and CON groups(0%–3.03%). These results suggest that in the acute phase of hamstring injury, the use of TECAR and, to a lesser extent, TENS may relieve pain symptoms and bring some improvements in flexibility more than instructing patients to rest.展开更多
The visual system of teleost fish grows continuously,which is a useful model for studying regeneration of the central nervous system.Glial cells are key for this process,but their contribution is still not well define...The visual system of teleost fish grows continuously,which is a useful model for studying regeneration of the central nervous system.Glial cells are key for this process,but their contribution is still not well defined.We followed oligodendrocytes in the visual system of adult zebrafish during regeneration of the optic nerve at 6,24,and 72 hours post-lesion and at 7 and 14 days post-lesion via the sox10:tagRFP transgenic line and confocal microscopy.To understand the changes that these oligodendrocytes undergo during regeneration,we used Sox2 immunohistochemistry,a stem cell marker involved in oligodendrocyte differentiation.We also used the Click-iT™ Plus TUNEL assay to study cell death and a BrdU assay to determine cell proliferation.Before optic nerve crush,sox10:tagRFP oligodendrocytes are located in the retina,in the optic nerve head,and through all the entire optic nerve.Sox2-positive cells are present in the peripheral germinal zone,the mature retina,and the optic nerve.After optic nerve crush,sox10:tagRFP cells disappeared from the optic nerve crush zone,suggesting that they died,although they were not TUNEL positive.Concomitantly,the number of Sox2-positive cells increased around the crushed area,the optic nerve head,and the retina.Then,between 24 hours post-lesion and 14 days post-lesion,double sox10:tagRFP/Sox2-positive cells were detected in the retina,optic nerve head,and whole optic nerve,together with a proliferation response at 72 hours post-lesion.Our results confirm that a degenerating process may occur prior to regeneration.First,sox10:tagRFP oligodendrocytes that surround the degenerated axons stop wrapping them,change their“myelinating oligodendrocyte”morphology to a“nonmyelinating oligodendrocyte”morphology,and die.Then,residual oligodendrocyte progenitor cells in the optic nerve and retina proliferate and differentiate for the purpose of remyelination.As new axons arise from the surviving retinal ganglion cells,new sox10:tagRFP oligodendrocytes arise from residual oligodendrocyte progenitor cells to guide,nourish and myelinate them.Thus,oligodendrocytes play an active role in zebrafish axon regeneration and remyelination.展开更多
[Objectives]To investigate the clinical effects of implementing structured phased rehabilitation training,in addition to conventional rehabilitation,on shoulder joint function and pain alleviation in patients with rot...[Objectives]To investigate the clinical effects of implementing structured phased rehabilitation training,in addition to conventional rehabilitation,on shoulder joint function and pain alleviation in patients with rotator cuff injuries managed conservatively.[Methods]Eighty patients diagnosed with rotator cuff injury were selected and randomly assigned to either the control group or the experimental group,each comprising 40 individuals.The control group received conventional rehabilitation treatment,whereas the experimental group underwent phased rehabilitation training in addition to the conventional treatment for 6 weeks.Assessments were conducted prior to treatment,6 weeks following treatment,and 8 weeks after the completion of treatment(follow-up period).The visual analogue scale(VAS)was employed to evaluate pain intensity,the Constant-Murley score was utilized to assess shoulder joint function,and the shoulder joint range of motion was measured.[Results]Prior to treatment,no statistically significant differences were observed between the two patient groups across all measured indicators(P>0.05).Following 6 weeks of treatment and throughout the follow-up period,both groups exhibited significant reductions in VAS scores compared to baseline measurements,alongside improvements in Constant-Murley scores and shoulder joint range of motion(P<0.05).Furthermore,the magnitude of improvement in the experimental group was significantly greater than that in the control group(P<0.05).[Conclusions]Phased rehabilitation training can enhance shoulder joint function and alleviate pain in patients with rotator cuff injuries beyond the effects of conventional rehabilitation treatment,demonstrating notable clinical application value.展开更多
Acute central nervous system injuries,including ischemic stro ke,intracerebral hemorrhage,subarachnoid hemorrhage,traumatic brain injury,and spinal co rd injury,are a major global health challenge.Identifying optimal ...Acute central nervous system injuries,including ischemic stro ke,intracerebral hemorrhage,subarachnoid hemorrhage,traumatic brain injury,and spinal co rd injury,are a major global health challenge.Identifying optimal therapies and improving the long-term neurological functions of patients with acute central nervous system injuries are urgent priorities.Mitochondria are susceptible to damage after acute central nervous system injury,and this leads to the release of toxic levels of reactive oxygen species,which induce cell death.Mitophagy,a selective form of autophagy,is crucial in eliminating redundant or damaged mitochondria during these events.Recent evidence has highlighted the significant role of mitophagy in acute central nervous system injuries.In this review,we provide a comprehensive overview of the process,classification,and related mechanisms of mitophagy.We also highlight the recent developments in research into the role of mitophagy in various acute central nervous system injuries and drug therapies that regulate mitophagy.In the final section of this review,we emphasize the potential for treating these disorders by focusing on mitophagy and suggest future research paths in this area.展开更多
The gut microbiota:The human body is colonized by a diverse and complex microbial community–including bacteria,viruses,archaea,and unicellular eukaryotes–that plays a central role in human wellbeing.Indeed,microbiot...The gut microbiota:The human body is colonized by a diverse and complex microbial community–including bacteria,viruses,archaea,and unicellular eukaryotes–that plays a central role in human wellbeing.Indeed,microbiota is crucial for several functions,including host metabolism,physiology,maintenance of the intestinal epithelial integrity,nutrition,and immune function,earning it the designation of a“vital organ”(Guinane and Cotter,2013).展开更多
OBJECTIVE： To investigate the factors associated with sensory and motor recovery after the repair of upper limb peripheral nerve injuries. DATA SOURCES： The online PubMed database was searched for English articles d...OBJECTIVE： To investigate the factors associated with sensory and motor recovery after the repair of upper limb peripheral nerve injuries. DATA SOURCES： The online PubMed database was searched for English articles describing outcomes after the repair of median, ulnar, radial, and digital nerve injuries in humans with a publication date between 1 January 1990 and 16 February 2011. STUDY SELECTION： The following types of article were selected： （1） clinical trials describ- ing the repair of median, ulnar, radial, and digital nerve injuries published in English; and （2） studies that reported sufficient patient information, including age, mechanism of injury, nerve injured, injury location, defect length, repair time, repair method, and repair materials. SPSS 13.0 software was used to perform univariate and multivariate logistic regression analyses and to in- vestigate the patient and intervention factors associated with outcomes. MAIN OUTCOME MEASURES： Sensory function was assessed using the Mackinnon-Dellon scale and motor function was assessed using the manual muscle test. Satisfactory motor recovery was defined as grade M4 or M5, and satisfactory sensory recovery was defined as grade S3＋ or S4. RESULTS： Seventy-one articles were included in this study. Univariate and multivariate logistic regression analyses showed that repair time, repair materials, and nerve injured were inde- pendent predictors of outcome after the repair of nerve injuries （P 〈 0.05）, and that the nerve injured was the main factor affecting the rate of good to excellent recovery. CONCLUSION： Predictors of outcome after the repair of peripheral nerve injuries include age, gender, repair time, repair materials, nerve injured, defect length, and duration of follow-up.展开更多
Peripheral nerve injuries（PNI） are caused by a range of etiologies and result in a broad spectrum of disability. While nerve autografts are the current gold standard for the reconstruction of extensive nerve damage,...Peripheral nerve injuries（PNI） are caused by a range of etiologies and result in a broad spectrum of disability. While nerve autografts are the current gold standard for the reconstruction of extensive nerve damage, the limited supply of autologous nerve and complications associated with harvesting nerve from a second surgical site has driven groups from multiple disciplines, including biomedical engineering, neurosurgery, plastic surgery, and orthopedic surgery, to develop a suitable or superior alternative to autografting. Over the last couple of decades, various types of scaffolds, such as acellular nerve grafts（ANGs）, nerve guidance conduits, and non-nervous tissues, have been filled with Schwann cells, stem cells, and/or neurotrophic factors to develop tissue engineered nerve grafts（TENGs）. Although these have shown promising effects on peripheral nerve regeneration in experimental models, the autograft has remained the gold standard for large nerve gaps. This review provides a discussion of recent advances in the development of TENGs and their efficacy in experimental models. Specifically, TENGs have been enhanced via incorporation of genetically engineered cells, methods to improve stem cell survival and differentiation, optimized delivery of neurotrophic factors via drug delivery systems（DDS）, co-administration of platelet-rich plasma（PRP）, and pretreatment with chondroitinase ABC（Ch-ABC）. Other notable advancements include conduits that have been bioengineered to mimic native nerve structure via cell-derived extracellular matrix（ECM） deposition, and the development of transplantable living nervous tissue constructs from rat and human dorsal root ganglia（DRG） neurons. Grafts composed of non-nervous tissues, such as vein, artery, and muscle, will be briefly discussed.展开更多
文摘Traumatic peripheral nerve injuries are a major contributor to long-term disability,accounting for nearly half of all peripheral nervous system disorders.Although autologous nerve grafting remains the clinical gold standard,it is limited by donor-site morbidity and often fails to achieve full functional recovery.Biodegradable collagen conduits have emerged as an appealing alternative,providing a scaffold for directed axonal growth without requiring graft harvest.We reported three cases of chronic nerve injuries(6-12 months post-trauma):two involving 2.0-3.5 cm ulnar nerve defects in the forearm and one with a 2.5 cm median nerve defect at the wrist.Under microscopic guidance,each defect was bridged with a tubular type I collagen conduit secured by epineurial sutures,followed by standardized physiotherapy and sensory reeducation.At 12-18 months of follow-up,all patients demonstrated near-complete sensory recovery—two-point discrimination and Semmes-Weinstein thresholds returned to≤6 mm—and motor function improved to Medical Research Council grades 4-5,restoring fine dexterity and grip strength.Patient-reported measures indicated marked reductions in neuropathic pain and paresthesia.No conduit-related adverse events or neuroma formation were observed.This case series highlights the potential of collagen-based conduits to promote robust axonal regeneration and functional restoration even in delayed presentations.By eliminating donor-site morbidity and simplifying the reconstructive procedure,conduit-assisted repair offers a less invasive,reproducible alternative to autologous grafts for both acute and chronic peripheral nerve injuries.
基金Supported by the Doctoral Scholarship granted by the Sao Paulo Research Foundation(FAPESP),2024/19980-0.
文摘Peripheral nerve injuries(PNI)that result in nerve gaps represent a major clinical challenge,frequently leading to long-term disability and a diminished quality of life for affected individuals.Despite advances in surgical techniques,functional recovery remains limited,highlighting the need for innovative therapeutic strategies.Mesenchymal stem cells(MSCs)have emerged as a promising avenue for nerve repair due to their regenerative,immunomodulatory,and neuropro-tective properties.Thus,this review explored current approaches utilizing MSCs in the treatment of PNI,emphasizing their potential to enhance nerve rege-neration and functional recovery.Furthermore,tissue engineering and transdiffer-entiation of MSCs into Schwann-like cells offer a versatile strategy to optimize therapeutic effects,paving the way for personalized medicine.Nevertheless,challenges persist regarding the clinical application of MSCs in PNI,including transplant safety,delivery methods,optimal dosing,and ethical considerations.A deeper understanding of the mechanisms underlying MSC action in PNI may contribute to more effective treatment protocols in the management of peripheral nerve defects.
基金supported by the Shenzhen Hong Kong Joint Funding Project,No.SGDX20230116093645007(to LY)the Shenzhen Science and Technology Innovation Committee International Cooperation Project,No.GJHZ20200731095608025(to LY)+7 种基金Shenzhen Development and Reform Commission’s Intelligent Diagnosis,Treatment and Prevention of Adolescent Spinal Health Public Service Platform,No.S2002Q84500835(to LY)Shenzhen Medical Research Fund,No.B2303005(to LY)Team-based Medical Science Research Program,No.2024YZZ02(to LY)Zhejiang Provincial Natural Science Foundation of China,No.LWQ20H170001(to RL)Basic Research Project of Shenzhen Science and Technology from Shenzhen Science and Technology Innovation Commission,No.JCYJ20210324103010029(to BY)Shenzhen Second People’s Hospital Clinical Research Fund of Guangdong Province High-level Hospital Construction Project,Nos.2023yjlcyj029(to BY),2023yjlcyj021(to LL)Guangdong Basic and Applied Basic Research Foundation,No.2022A1515110679(to LL)China Postdoctoral Science Foundation,No.2022M722203(to GL).
文摘Peripheral nerve injury causes severe neuroinflammation and has become a global medical challenge.Previous research has demonstrated that porcine decellularized nerve matrix hydrogel exhibits excellent biological properties and tissue specificity,highlighting its potential as a biomedical material for the repair of severe peripheral nerve injury;however,its role in modulating neuroinflammation post-peripheral nerve injury remains unknown.Here,we aimed to characterize the anti-inflammatory properties of porcine decellularized nerve matrix hydrogel and their underlying molecular mechanisms.Using peripheral nerve injury model rats treated with porcine decellularized nerve matrix hydrogel,we evaluated structural and functional recovery,macrophage phenotype alteration,specific cytokine expression,and changes in related signaling molecules in vivo.Similar parameters were evaluated in vitro using monocyte/macrophage cell lines stimulated with lipopolysaccharide and cultured on porcine decellularized nerve matrix hydrogel-coated plates in complete medium.These comprehensive analyses revealed that porcine decellularized nerve matrix hydrogel attenuated the activation of excessive inflammation at the early stage of peripheral nerve injury and increased the proportion of the M2 subtype in monocytes/macrophages.Additionally,porcine decellularized nerve matrix hydrogel negatively regulated the Toll-like receptor 4/myeloid differentiation factor 88/nuclear factor-κB axis both in vivo and in vitro.Our findings suggest that the efficacious anti-inflammatory properties of porcine decellularized nerve matrix hydrogel induce M2 macrophage polarization via suppression of the Toll-like receptor 4/myeloid differentiation factor 88/nuclear factor-κB pathway,providing new insights into the therapeutic mechanism of porcine decellularized nerve matrix hydrogel in peripheral nerve injury.
文摘Traumatic axonal lesions of peripheral nerves disrupt neuronal connections with their targets,resulting in the loss of motor and sensory functions.Despite the peripheral nervous system’s capacity for axonal regrowth,this may lead to permanent impairements resulting in a loss of quality of life and a high socioeconomic burden.
基金supported by the National Natural Science Foundation of China,No.81641048Research Project of Yan’an University,No.2023JBZR-011(both to LZ).
文摘Spinal cord injury is a severe neurological condition characterized by the permanent loss of nerve cell function and a failure in neural circuit reconstruction-key factors contributing to disability.Therefore,exploring effective strategies to promote the repair and regeneration of nerve cells after spinal cord injury is crucial for optimizing patient prognosis.The purpose of this paper is to conduct an in-depth review of the pathological changes in nerve cells after spinal cord injury and to present the state of research on the role of exercise training in promoting the repair and regeneration of nerve cells after spinal cord injury.In terms of the intrinsic growth capacity of neurons,disruptions in the dynamic balance between growth cones and the cytoskeleton,the dysregulation of transcription factors,abnormal protein signaling transduction,and altered epigenetic modifications collectively hinder axonal regeneration.Additionally,the microenvironment of neurons undergoes a series of complex changes,initially manifesting as edema,which may be exacerbated by spinal cord ischemia-reperfusion injury,further increasing the extent of nerve cell damage.The abnormal proliferation of astrocytes leads to the formation of glial scars,creating a physical barrier to nerve regeneration.The inflammatory response triggered by the excessive activation of microglia negatively impacts the process of nerve repair.Non-invasive interventions involving exercise training have shown significant potential in promoting nerve repair as part of a comprehensive treatment strategy for spinal cord injury.Specifically,exercise training can reshape the growth cone and cytoskeletal structures of neurons,regulate transcription factor activity,modulate protein signaling pathways,and influence epigenetic modifications,thereby activating the intrinsic repair mechanisms of neurons.Moreover,exercise training can regulate the activation state of astrocytes,optimize the inflammatory response and metabolic processes,promote astrocyte polarization,enhance angiogenesis,reduce glial scar formation,and modulate the expression levels of nerve growth factors.It also effectively helps regulate microglial activation,promotes axonal regeneration,and improves phagocytic function,thereby optimizing the microenvironment for nerve repair.In terms of clinical translation,we summarize the preliminary results of new drug research and development efforts,the development of innovative devices,and the use of exercise training in promoting clinical advancements in nerve repair following spinal cord injury,while considering their limitations and future application prospects.In summary,this review systematically analyzes findings relating to the pathological changes occurring in nerve cells after spinal cord injury and emphasizes the critical role of exercise training in facilitating the repair and regeneration of nerve cells.This work is expected to provide new ideas and methods for the rehabilitation of patients with spinal cord injury.
基金supported by the National Natural Science Foundation of China,No.32171356(to YW)Self-Support Research Projects of Shihezi University,No.ZZZC2021105(to WJ)+1 种基金Capital Medical University Natural Science Cultivation Fund,No.PYZ23044(to FQM)Beijing Municipal Natural Science Foundation,No.7244410(to JHD)。
文摘Previous research has demonstrated the feasibility of repairing nerve defects through acellular allogeneic nerve grafting with bone marrow mesenchymal stem cells.However,adult tissue–derived mesenchymal stem cells encounter various obstacles,including limited tissue sources,invasive acquisition methods,cellular heterogeneity,purification challenges,cellular senescence,and diminished pluripotency and proliferation over successive passages.In this study,we used induced pluripotent stem cell-derived mesenchymal stem cells,known for their self-renewal capacity,multilineage differentiation potential,and immunomodulatory characteristics.We used induced pluripotent stem cell-derived mesenchymal stem cells in conjunction with acellular nerve allografts to address a 10 mm-long defect in a rat model of sciatic nerve injury.Our findings reveal that induced pluripotent stem cell-derived mesenchymal stem cells exhibit survival for up to 17 days in a rat model of peripheral nerve injury with acellular nerve allograft transplantation.Furthermore,the combination of acellular nerve allograft and induced pluripotent stem cell-derived mesenchymal stem cells significantly accelerates the regeneration of injured axons and improves behavioral function recovery in rats.Additionally,our in vivo and in vitro experiments indicate that induced pluripotent stem cell-derived mesenchymal stem cells play a pivotal role in promoting neovascularization.Collectively,our results suggest the potential of acellular nerve allografts with induced pluripotent stem cell-derived mesenchymal stem cells to augment nerve regeneration in rats,offering promising therapeutic strategies for clinical translation.
基金supported by the National Natural Science Foundation of China,No.82071386(to JG).
文摘Our recent study demonstrated that knockout of microRNA-301a attenuates migration and phagocytosis in macrophages.Considering that macrophages and Schwann cells synergistically clear the debris of degraded axons and myelin during Wallerian degeneration,which is a prerequisite for nerve regeneration,we hypothesized that microRNA-301a regulates Wallerian degeneration and nerve regeneration via impacts on Schwann cell migration and phagocytosis.Herein,we found low expression of microRNA-301a in intact sciatic nerves,with no impact of the microRNA-301a knockout on nerve structure and function.By contrast,we found significant upregulation of microRNA-301a in injured sciatic nerves.We established a sciatic nerve crush model in microRNA-301a knockout mice,which exhibited attenua9ted morphological and functional regeneration following sciatic nerve crush injury.The microRNA-301a knockout also led to significantly inhibited Wallerian degeneration in an in vivo sciatic nerve-transection model and in an in vitro nerve explant block model.Schwann cells with the microRNA-301a knockout showed inhibition of phagocytosis and migration,which was reversible under transfection with microRNA-301a mimics.Rescue experiments involving transfection of microRNA-301a-knockout Schwann cells with microRNA-301a mimics or treatment with the C-X-C motif receptor 4 inhibitor WZ811 indicated the mechanistic involvement of the Yin Yang 1/C-X-C motif receptor 4 pathway in the role of microRNA-301a.Combined with our previous findings in macrophages,we conclude that microRNA-301a plays a key role in peripheral nerve injury and repair by regulating the migratory and phagocytic capabilities of Schwann cells and macrophages via the Yin Yang 1/C-X-C motif receptor 4 pathway.
基金supported by the National Key R&D Program of China,No.2022YFC3006200(to YW)the Natural Science Foundation of Beijing,No.7232190(to YW)+1 种基金Zhejiang Province Medical and Health Technology Plan Project,Nos.2022020506(to XW),2024KY1612(to JX),2024KY1615(to MY)Ningbo Clinical Research Center for Orthopedics and Sports Rehabilitation,No.2024L004(to XW).
文摘Peripheral nerve injury is a complex condition presenting significant clinical treatment challenges due to the limited regenerative capacity of peripheral nerves.Nerve conduits have been seen as a promising strategy to overcome the shortage of other treatment options(e.g.,nerve graft).However,nerve regeneration occurs within a complex environment,and elaborate modulation is needed to meet repair requirements.The aim of this study was to investigate and explore a multifunctional nerve conduit with reactive oxygen species clearing,immune modulation to reshape the regenerative environment,and topographic cues and electrical signals to guide nerve growth.We developed an electroactive nerve guidance conduit composed of polylactic-glycolic acid and carbon nanotubes with an oriented structure using electrospinning and modified it with mussel-inspired polydopamine combining neurotrophin-3.The resulting nerve scaffold exhibited favorable orientation,electrical conductivity,and mechanical properties.Continuous release of neurotrophin-3 from the nerve conduit supported nerve regeneration throughout the repair process.In vitro assessments confirmed the cytocompatibility,reactive oxygen species scavenging,and immune regulation capabilities of the nerve scaffolds.In a rat sciatic nerve defect model,the nerve scaffolds effectively prevented muscle atrophy and promoted nerve regeneration and functional recovery over a 12-week period.These findings suggest that polydopamine-modified,electroactive,oriented nerve guidance conduits with multiple bioactive functions hold great promise for the repair of peripheral nerve injuries.
基金the support from Base for Interdisciplinary Innovative Talent Training,Shanghai Jiao Tong UniversityYouth Science and Technology Innovation Studio of Shanghai Jiao Tong University School of Medicine。
文摘Neural injuries can cause considerable functional impairments,and both central and peripheral nervous systems have limited regenerative capacity.The existing conventional pharmacological treatments in clinical practice show poor targeting,rapid drug clearance from the circulatory system,and low therapeutic efficiency.Therefore,in this review,we have first described the mechanisms underlying nerve regeneration,characterized the biomaterials used for drug delivery to facilitate nerve regeneration,and highlighted the functionalization strategies used for such drug-delivery systems.These systems mainly use natural and synthetic polymers,inorganic materials,and hybrid systems with advanced drug-delivery abilities,including nanoparticles,hydrogels,and scaffoldbased systems.Then,we focused on comparing the types of drug-delivery systems for neural regeneration as well as the mechanisms and challenges associated with targeted delivery of drugs to facilitate neural regeneration.Finally,we have summarized the clinical application research and limitations of targeted delivery of these drugs.These biomaterials and drug-delivery systems can provide mechanical support,sustained release of bioactive molecules,and enhanced intercellular contact,ultimately reducing cell apoptosis and enhancing functional recovery.Nevertheless,immune reactions,degradation regulation,and clinical translations remain major unresolved challenges.Future studies should focus on optimizing biomaterial properties,refining delivery precision,and overcoming translational barriers to advance these technologies toward clinical applications.
基金supported by the National Natural Science Foundation of China,Nos.82471123,82171053the Jilin Province Special Project for Talent in Medical and Health Sciences,No.2024WSXK-E01the Natural Science Foundation of Jilin Province,YDZJ202501ZYTS318(all to GL).
文摘Retinal ganglion cells,a crucial component of the central nervous system,are often affected by irreversible visual impairment due to various conditions,including trauma,tumors,ischemia,and glaucoma.Studies have shown that the optic nerve crush model and glaucoma model are commonly used to study retinal ganglion cell injury.While these models differ in their mechanisms,both ultimately result in retinal ganglion cell injury.With advancements in high-throughput technologies,techniques such as microarray analysis,RNA sequencing,and single-cell RNA sequencing have been widely applied to characterize the transcriptomic profiles of retinal ganglion cell injury,revealing underlying molecular mechanisms.This review focuses on optic nerve crush and glaucoma models,elucidating the mechanisms of optic nerve injury and neuron degeneration induced by glaucoma through single-cell transcriptomics,transcriptome analysis,and chip analysis.Research using the optic nerve crush model has shown that different retinal ganglion cell subtypes exhibit varying survival and regenerative capacities following injury.Single-cell RNA sequencing has identified multiple genes associated with retinal ganglion cell protection and regeneration,such as Gal,Ucn,and Anxa2.In glaucoma models,high-throughput sequencing has revealed transcriptomic changes in retinal ganglion cells under elevated intraocular pressure,identifying genes related to immune response,oxidative stress,and apoptosis.These genes are significantly upregulated early after optic nerve injury and may play key roles in neuroprotection and axon regeneration.Additionally,CRISPR-Cas9 screening and ATAC-seq analysis have identified key transcription factors that regulate retinal ganglion cell survival and axon regeneration,offering new potential targets for neurorepair strategies in glaucoma.In summary,single-cell transcriptomic technologies provide unprecedented insights into the molecular mechanisms underlying optic nerve injury,aiding in the identification of novel therapeutic targets.Future researchers should integrate advanced single-cell sequencing with multi-omics approaches to investigate cell-specific responses in retinal ganglion cell injury and regeneration.Furthermore,computational models and systems biology methods could help predict molecular pathways interactions,providing valuable guidance for clinical research on optic nerve regeneration and repair.
基金supported by grants from Young Scientists Fund of the National Natural Science Foundation of China(grant number.82301295).
文摘1Introduction A 25-year-old woman presented with a 3-month history of otalgia and aural fullness in the left ear,without associated otological or systemic symptoms.Her medical history was unremarkable,and she denied any history of hepatitis,hypertension,diabetes,cardiovascular disease,or other significant conditions.The patient was diagnosed with external auditory canal cholesteatoma and subsequently underwent canalplasty under general anesthesia.Routine anesthetic drugs,including 2%lidocaine,dexamethasone,propofol,sufentanil,rocuronium bromide,ondansetron,flurbiprofen axetil,neostigmine,and atropine,were used during surgery and anesthesia recovery.No significant events were noted,and the patient experienced only a blood loss of 10 mL.
基金National Natural Science Foundation of China(Grant No.52525504)Emerging Frontiers Cultivation Program of Tianjin University Interdisciplinary Center.
文摘Tactile feedback is critical for human interaction with external information.Similarly,tactile feedback can enrich the user's sensations when using prosthesis.To explore a potential scheme for tactile feedback,this study applied a non-inva-sive Transcutaneous Electrical Nerve Stimulation(TENS)to elicit tactile sensations in the hand,which involved median nerve,ulnar nerve,and radial nerve.Ten able-bodied subjects(8 males,2 females)were recruited to participate in the study.An array of 4×2 electrodes was positioned on the medial aspect of the brachii muscle's short head in the upper arm,which is in proximity to the median nerve,ulnar nerve,and radial nerve.Different electrode pairs were randomly selected to elicit distinct sensations at various positions on the hand,and the subjects reported the sensory areas.Then,the sensory areas and sensory thresholds were confirmed through psychophysical methods.According to the experimental results,tactile sensations were elicited at different locations on the subjects'hand through TENS of different electrode pairs.All subjects reported extensive and detailed sensory areas in the fingers,palm,and dorsum,corresponding to the sensory innervation areas of different nerves.The study effectively demonstrated the ability of TENS in evoking tactile feedback in the hand,paving the way for future optimization and development of prosthetic hands.
文摘Dear Editor,Dorsal pontine lesions may cause a variety of complex neuro-ophthalmic deficits,including horizontal gaze palsy(HGP),internuclear ophthalmoplegia,one-and-ahalf syndrome,abducens nerve palsy,skew deviation,or any combination of these.Here we present a rare case of an adult patient who developed multiple complicated clinical manifestations after surgical removal of a pontine cavernous hemangioma(PCH).Our case highlights a single pontine lesion may involve complicated neural pathways and result in complicated symptoms and signs,in which abducens nerve palsy or skew deviation is easily missed when combined with HGP.
文摘This study compared the acute effects of electrical energy transfer(TECAR) and transcutaneous electrical stimulation(TENS) on pain and flexibility after a hamstring injury. Young athletes received either a 20 min TECAR(n = 24) or TENS(n = 26) session within 5 days following a hamstring injury, while the control(CON, n = 25)group was instructed to rest. Visual analogue scale(VAS), functional Assessment Scale for Acute Hamstring Injuries(FASH), straight leg raise test(SLR), and sit-and-reach scores(STR) were obtained prior to, immediately,24, and 48 h after therapy. Group differences were detected after therapy in VAS and FASH scores(p < 0.05).Compared to pre-therapy measurements, VAS scores showed a greater decrease in the TECAR group(-38.75% to-63.33%) than in the TENS group(-16.67% to-25.00%) and both were greater than in the CON group(-2.81%to-9.81%)(p < 0.05). The TECAR group improved FASH scores(28.57%–48.21%) more than the TENS group(15.89%–27.79%) and both groups more than the CON group(0%–8.33%)(p < 0.05). The increase in SLR and STR was greater in the TECAR group(6.26%–13.96%) than in the TENS(1.72%–9.53%) and CON groups(0%–3.03%). These results suggest that in the acute phase of hamstring injury, the use of TECAR and, to a lesser extent, TENS may relieve pain symptoms and bring some improvements in flexibility more than instructing patients to rest.
基金supported by the Lanzadera TCUE and C2 program(Universidad de Salamanca)(to ASL)the Spanish National Research Council(CSIC)funded by the Junta de Castilla y León and co-financed by the European Regional Development Fund(ERDF“Europe drives our growth”):Internationalization Project“CL-EI-2021-08-IBFG Unit of Excellence”,Grant(PID2022-138478OA-100)funded by MICIU/AEI/10.13039/501100011033 and,by FEDER,UE(to MGM)+3 种基金Junta de Castilla y León(SA225P23)Gerencia Regional de Salud(2701/A1/2023)(to AV)the Plan Especial Grado Medicina(USAL)(to CPM)a Ramón y Cajal researcher:Grant RYC2021-033684-I funded by MICIU/AEI/10.13039/501100011033 and,by European Union NextGenerationEU/PRTR.
文摘The visual system of teleost fish grows continuously,which is a useful model for studying regeneration of the central nervous system.Glial cells are key for this process,but their contribution is still not well defined.We followed oligodendrocytes in the visual system of adult zebrafish during regeneration of the optic nerve at 6,24,and 72 hours post-lesion and at 7 and 14 days post-lesion via the sox10:tagRFP transgenic line and confocal microscopy.To understand the changes that these oligodendrocytes undergo during regeneration,we used Sox2 immunohistochemistry,a stem cell marker involved in oligodendrocyte differentiation.We also used the Click-iT™ Plus TUNEL assay to study cell death and a BrdU assay to determine cell proliferation.Before optic nerve crush,sox10:tagRFP oligodendrocytes are located in the retina,in the optic nerve head,and through all the entire optic nerve.Sox2-positive cells are present in the peripheral germinal zone,the mature retina,and the optic nerve.After optic nerve crush,sox10:tagRFP cells disappeared from the optic nerve crush zone,suggesting that they died,although they were not TUNEL positive.Concomitantly,the number of Sox2-positive cells increased around the crushed area,the optic nerve head,and the retina.Then,between 24 hours post-lesion and 14 days post-lesion,double sox10:tagRFP/Sox2-positive cells were detected in the retina,optic nerve head,and whole optic nerve,together with a proliferation response at 72 hours post-lesion.Our results confirm that a degenerating process may occur prior to regeneration.First,sox10:tagRFP oligodendrocytes that surround the degenerated axons stop wrapping them,change their“myelinating oligodendrocyte”morphology to a“nonmyelinating oligodendrocyte”morphology,and die.Then,residual oligodendrocyte progenitor cells in the optic nerve and retina proliferate and differentiate for the purpose of remyelination.As new axons arise from the surviving retinal ganglion cells,new sox10:tagRFP oligodendrocytes arise from residual oligodendrocyte progenitor cells to guide,nourish and myelinate them.Thus,oligodendrocytes play an active role in zebrafish axon regeneration and remyelination.
文摘[Objectives]To investigate the clinical effects of implementing structured phased rehabilitation training,in addition to conventional rehabilitation,on shoulder joint function and pain alleviation in patients with rotator cuff injuries managed conservatively.[Methods]Eighty patients diagnosed with rotator cuff injury were selected and randomly assigned to either the control group or the experimental group,each comprising 40 individuals.The control group received conventional rehabilitation treatment,whereas the experimental group underwent phased rehabilitation training in addition to the conventional treatment for 6 weeks.Assessments were conducted prior to treatment,6 weeks following treatment,and 8 weeks after the completion of treatment(follow-up period).The visual analogue scale(VAS)was employed to evaluate pain intensity,the Constant-Murley score was utilized to assess shoulder joint function,and the shoulder joint range of motion was measured.[Results]Prior to treatment,no statistically significant differences were observed between the two patient groups across all measured indicators(P>0.05).Following 6 weeks of treatment and throughout the follow-up period,both groups exhibited significant reductions in VAS scores compared to baseline measurements,alongside improvements in Constant-Murley scores and shoulder joint range of motion(P<0.05).Furthermore,the magnitude of improvement in the experimental group was significantly greater than that in the control group(P<0.05).[Conclusions]Phased rehabilitation training can enhance shoulder joint function and alleviate pain in patients with rotator cuff injuries beyond the effects of conventional rehabilitation treatment,demonstrating notable clinical application value.
基金supported by the National Natural Science Foundation of China,Nos.81920108017(to YX),82130036(to YX),82371326(to XC),82171310(to XC)the STI2030-Major Projects,No.2022ZD0211800(to YX)Jiangsu Province Key Medical Discipline,No.ZDXK202216(to YX)。
文摘Acute central nervous system injuries,including ischemic stro ke,intracerebral hemorrhage,subarachnoid hemorrhage,traumatic brain injury,and spinal co rd injury,are a major global health challenge.Identifying optimal therapies and improving the long-term neurological functions of patients with acute central nervous system injuries are urgent priorities.Mitochondria are susceptible to damage after acute central nervous system injury,and this leads to the release of toxic levels of reactive oxygen species,which induce cell death.Mitophagy,a selective form of autophagy,is crucial in eliminating redundant or damaged mitochondria during these events.Recent evidence has highlighted the significant role of mitophagy in acute central nervous system injuries.In this review,we provide a comprehensive overview of the process,classification,and related mechanisms of mitophagy.We also highlight the recent developments in research into the role of mitophagy in various acute central nervous system injuries and drug therapies that regulate mitophagy.In the final section of this review,we emphasize the potential for treating these disorders by focusing on mitophagy and suggest future research paths in this area.
基金supported by the European Union-Next Generation EU,Mission 4 Component 1,Project Title:“Gut and Neuro Muscular system:investigating the impact of microbiota on nerve regeneration and muscle reinnervation after peripheral nerve injury”,CUP D53D23007770006,MUR:20227YB93W,to GR。
文摘The gut microbiota:The human body is colonized by a diverse and complex microbial community–including bacteria,viruses,archaea,and unicellular eukaryotes–that plays a central role in human wellbeing.Indeed,microbiota is crucial for several functions,including host metabolism,physiology,maintenance of the intestinal epithelial integrity,nutrition,and immune function,earning it the designation of a“vital organ”(Guinane and Cotter,2013).
基金supported by the National High-Technology Research and Development Program of China(863 Program),No.2012A A020507985 Program of Sun Yat-sen University,No.90035-3283312+1 种基金Specialized Research Fund for the Doctoral Program of Higher Education,No.20120171120075Doctoral Start-up Project of the Natural Science Foundation of Guangdong Province,No.S201204006336
文摘OBJECTIVE： To investigate the factors associated with sensory and motor recovery after the repair of upper limb peripheral nerve injuries. DATA SOURCES： The online PubMed database was searched for English articles describing outcomes after the repair of median, ulnar, radial, and digital nerve injuries in humans with a publication date between 1 January 1990 and 16 February 2011. STUDY SELECTION： The following types of article were selected： （1） clinical trials describ- ing the repair of median, ulnar, radial, and digital nerve injuries published in English; and （2） studies that reported sufficient patient information, including age, mechanism of injury, nerve injured, injury location, defect length, repair time, repair method, and repair materials. SPSS 13.0 software was used to perform univariate and multivariate logistic regression analyses and to in- vestigate the patient and intervention factors associated with outcomes. MAIN OUTCOME MEASURES： Sensory function was assessed using the Mackinnon-Dellon scale and motor function was assessed using the manual muscle test. Satisfactory motor recovery was defined as grade M4 or M5, and satisfactory sensory recovery was defined as grade S3＋ or S4. RESULTS： Seventy-one articles were included in this study. Univariate and multivariate logistic regression analyses showed that repair time, repair materials, and nerve injured were inde- pendent predictors of outcome after the repair of nerve injuries （P 〈 0.05）, and that the nerve injured was the main factor affecting the rate of good to excellent recovery. CONCLUSION： Predictors of outcome after the repair of peripheral nerve injuries include age, gender, repair time, repair materials, nerve injured, defect length, and duration of follow-up.
基金supported,in part,by a research grant from Baylor Scott&White Health Central Texas Foundation and NIH grant R01-NS067435(JHH)
文摘Peripheral nerve injuries（PNI） are caused by a range of etiologies and result in a broad spectrum of disability. While nerve autografts are the current gold standard for the reconstruction of extensive nerve damage, the limited supply of autologous nerve and complications associated with harvesting nerve from a second surgical site has driven groups from multiple disciplines, including biomedical engineering, neurosurgery, plastic surgery, and orthopedic surgery, to develop a suitable or superior alternative to autografting. Over the last couple of decades, various types of scaffolds, such as acellular nerve grafts（ANGs）, nerve guidance conduits, and non-nervous tissues, have been filled with Schwann cells, stem cells, and/or neurotrophic factors to develop tissue engineered nerve grafts（TENGs）. Although these have shown promising effects on peripheral nerve regeneration in experimental models, the autograft has remained the gold standard for large nerve gaps. This review provides a discussion of recent advances in the development of TENGs and their efficacy in experimental models. Specifically, TENGs have been enhanced via incorporation of genetically engineered cells, methods to improve stem cell survival and differentiation, optimized delivery of neurotrophic factors via drug delivery systems（DDS）, co-administration of platelet-rich plasma（PRP）, and pretreatment with chondroitinase ABC（Ch-ABC）. Other notable advancements include conduits that have been bioengineered to mimic native nerve structure via cell-derived extracellular matrix（ECM） deposition, and the development of transplantable living nervous tissue constructs from rat and human dorsal root ganglia（DRG） neurons. Grafts composed of non-nervous tissues, such as vein, artery, and muscle, will be briefly discussed.
