[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
Spinal cord injury results in paralysis, sensory disturbances, sphincter dysfunction, and multiple systemic secondary conditions, most arising from autonomic dysregulation. All this produces profound negative psychoso...Spinal cord injury results in paralysis, sensory disturbances, sphincter dysfunction, and multiple systemic secondary conditions, most arising from autonomic dysregulation. All this produces profound negative psychosocial implications for affected people, their families, and their communities;the financial costs can be challenging for their families and health institutions. Treatments aimed at restoring the spinal cord after spinal cord injury, which have been tested in animal models or clinical trials, generally seek to counteract one or more of the secondary mechanisms of injury to limit the extent of the initial damage. Most published works on structural/functional restoration in acute and chronic spinal cord injury stages use a single type of treatment: a drug or trophic factor, transplant of a cell type, and implantation of a biomaterial. Despite the significant benefits reported in animal models, when translating these successful therapeutic strategies to humans, the result in clinical trials has been considered of little relevance because the improvement, when present, is usually insufficient. Until now, most studies designed to promote neuroprotection or regeneration at different stages after spinal cord injury have used single treatments. Considering the occurrence of various secondary mechanisms of injury in the acute and sub-acute phases of spinal cord injury, it is reasonable to speculate that more than one therapeutic agent could be required to promote structural and functional restoration of the damaged spinal cord. Treatments that combine several therapeutic agents, targeting different mechanisms of injury, which, when used as a single therapy, have shown some benefits, allow us to assume that they will have synergistic beneficial effects. Thus, this narrative review article aims to summarize current trends in the use of strategies that combine therapeutic agents administered simultaneously or sequentially, seeking structural and functional restoration of the injured spinal cord.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
BACKGROUND Patients with multiple injuries endure not just physical trauma and suffering but are also at risk of psychological conditions such as posttraumatic stress disorder(PTSD),anxiety,and depression.The co-occur...BACKGROUND Patients with multiple injuries endure not just physical trauma and suffering but are also at risk of psychological conditions such as posttraumatic stress disorder(PTSD),anxiety,and depression.The co-occurrence of PTSD in these patients may cause prolonged physical and mental health complications,thereby further increasing their healthcare expenses.AIM To determine the association between the high-risk factors of PTSD and anxiety as well as depression among patients with multiple injuries.METHODS This study selected 110 patients with multiple injuries who were admitted to our hospital from November 2022 to November 2024.The number and percentage of patients developing PTSD were tallied.Univariate and multivariate analyses were conducted to investigate the high-risk factors of PTSD in these patients.Subse-quently,the associations between these factors and the anxiety and depression levels of patients were analyzed.RESULTS Of the 110 patients,33 suffered from PTSD,representing an incidence rate of 30.0%.The univariate analysis identified age,personality,Hamilton Anxiety Scale(HAMA),Hamilton Depression Scale(HAMD),economic status,negative life events,and smoking history to be significantly associated with PTSD in patients with multiple injuries.Further,the multivariate analysis revealed age,HAMA,HAMD,monthly income,and negative life events as prominent high-risk factors for PTSD in such patients.Regarding the relationships between these factors and HAMA and HAMD,age exhibited a significant positive correlation(r=0.398,P<0.001;r=0.387,P<0.001),monthly income showed a significant negative correlation(r=-0.437,P<0.001;r=-0.319,P<0.001),and negative life events demonstrated a significant positive correlation(r=0.505,P<0.001;r=0.365,P<0.001).CONCLUSION These results indicate age,HAMA,HAMD,monthly income,negative life events,etc.as high-risk factors for PTSD in patients with multiple injuries,among which age,monthly income,and negative life events are closely associated with anxiety and depression.展开更多
BACKGROUND The purpose of this systematic review was to evaluate the clinical and radiological outcomes at short-term follow-up following suture button fixation for the management of ligamentous Lisfranc injuries.AIM ...BACKGROUND The purpose of this systematic review was to evaluate the clinical and radiological outcomes at short-term follow-up following suture button fixation for the management of ligamentous Lisfranc injuries.AIM To assess the effectiveness of suture button fixation in managing ligamentous Lisfranc injuries through a systematic evaluation of short-term clinical and radiological outcomes.METHODS During March 2024,the PubMed,EMBASE,and Cochrane library databases were systematically reviewed to identify clinical studies examining outcomes following suture button fixation for the management of ligamentous Lisfranc injuries.Data regarding patient demographics,pathological characteristics,subjective clinical outcomes,radiological outcomes,complications,and failure rates were extracted and analyzed.RESULTS Eight studies were included.In total,94 patients(94 feet)underwent suture button fixation for the management of ligamentous Lisfranc injuries at a weighted mean follow-up of 27.2±10.2 months.The American Orthopaedic Foot and Ankle Society score improved from a weighted mean pre-operative score of 39.2±11.8 preoperatively to a post-operative score of 82.8±5.4.The weighted mean visual analogue scale score improved from a weighted mean pre-operative score of 7.7±0.6 preoperatively to a post-operative score of 2.0±0.4.In total,100%of patients returned to sport at a mean time of 16.8 weeks.The complication rate was 5%,the most common complication of which was residual midfoot stiffness(3.0%).No failures nor secondary surgical procedures were recorded.CONCLUSION This systematic review demonstrated that suture button fixation for ligamentous Lisfranc injuries produced improved clinical outcomes at short-term follow-up.In addition,there was an excellent return-to-sport rate(100%)at a weighted mean time of 16.8 weeks.This review highlights that suture button fixation is a potent surgical treatment strategy for ligamentous Lisfranc injuries;however,caution should be taken when evaluating this data in light of the lack of high quality,comparative studies,and short-term follow-up.展开更多
BACKGROUND Sub-acromial injections are a therapeutic option for rotator cuff injuries;however,evidence regarding the most effective drug in this context is unclear,which needs to be investigated.AIM To evaluate the ef...BACKGROUND Sub-acromial injections are a therapeutic option for rotator cuff injuries;however,evidence regarding the most effective drug in this context is unclear,which needs to be investigated.AIM To evaluate the effectiveness of various sub-acromial injections for rotator cuff injuries.METHODS We conducted a systematic review and pair-wise and network meta-analyses of randomized clinical trials(RCTs)comparing sub-acromial injections for rotator cuff injuries.The interventions evaluated were hyaluronic acid(HA),platelet-rich plasma(PRP),prolotherapy,and corticosteroids.The outcomes of interest were pain and functional improvement,which were evaluated with standardized scores.The Risk of Bias 2 tool and the Grading of Recommendations,Assessment,Development and Evaluation methodology were used to assess data quality.RESULTS Twenty RCTs,comprising 1479 participants,were included.In the short term,HA achieved the best outcomes[pain mean difference(MD)=-1.48,95%confidence interval(CI)-2.37 to-0.59;function MD=10.18,95%CI:4.96-15.41].In the medium term,HA,PRP,HA+PRP,and corticosteroids were not superior to placebo in improving pain.Based on function,HA+PRP was superior to placebo,corticosteroids,and PRP(MD=26.72;95%CI:8.02-45.41).In the long term,HA,PRP,and corticosteroids were not superior to placebo in reducing pain.However,based on function,HA+PRP,PRP,and HA were superior to placebo,and HA+PRP had the best result(MD=36.64;95%CI:31.66-33.62).CONCLUSION HA provides satisfactory short-term results,while HA with PRP demonstrates functional improvement in the medium and long terms.However,no intervention maintained the pain-relief effect on>3-month follow-up.展开更多
The clinical treatment of severe trauma withsternoclavicular joint injury is challenging,primarilydue to the irregular shape of the bones surrounding thesternoclavicular joint,as well as the posterior clavicle beingcl...The clinical treatment of severe trauma withsternoclavicular joint injury is challenging,primarilydue to the irregular shape of the bones surrounding thesternoclavicular joint,as well as the posterior clavicle beingclose to the aorta and mediastinal organs.^([1])These patientsnot only suffer direct injuries to the sternoclavicularjoint,but also frequently experience severe injuries toother body parts.The systemic physiological disordersand multi-organ dysfunction caused by severe traumaincrease the surgery di?culty and mortality risk.^([2])展开更多
AIM:To evaluate the prevalence of early post-traumatic stress disorder(PTSD)among young and middle-aged patients who have suffered open globe injuries,and to identify the psychosocial factors influencing PTSD in these...AIM:To evaluate the prevalence of early post-traumatic stress disorder(PTSD)among young and middle-aged patients who have suffered open globe injuries,and to identify the psychosocial factors influencing PTSD in these patients.METHODS:A total of 280 patients who underwent ocular trauma surgery between January 2023 and January 2024 were selected through convenience sampling.Data were collected using a custom-designed demographic questionnaire,the Connor-Davidson Resilience Scale(CDRISC),the Cognitive Emotion Regulation Questionnaire(C-ERRI),and the PTSD Checklist-Civilian Version(PCL-C).Univariate analysis and stepwise multiple linear regression analysis were performed to determine the factors affecting PTSD in these patients.RESULTS:The average PTSD score for the patients was 33.22±13.48.The scores for individual PTSD dimensions,ranked from highest to lowest,were recurrent traumatic experiences,heightened arousal,avoidance reactions,and social dysfunction.Positive PTSD symptoms were observed in 85 patients(30.36%).Univariate analysis indicated that gender,postoperative vision,marital status,psychological resilience,and rumination were significant factors affecting PTSD symptoms(χ^(2)/t=6.53,17.88,8.83,2.17,and 14.1,respectively;all P<0.05).Pearson correlation analysis showed a positive correlation between rumination and PTSD symptoms(r=0.73,P<0.01)and a negative correlation between psychological resilience and PTSD symptoms(r=-0.14,P<0.05).Stepwise multiple linear regression analysis identified postoperative vision(notably eye removal),rumination levels,and psychological resilience(optimism)as major factors influencing PTSD in these patients(R^(2)=0.57,P<0.001).CONCLUSION:Young and middle-aged patients with open globe injuries have a high incidence of PTSD.Significant risk factors for early PTSD include primary enucleation,high levels of rumination,and low psychological resilience(optimism).Conversely,patients with good postoperative vision recovery,low rumination levels,and high levels of optimism are less likely to develop PTSD.Healthcare providers should pay special attention to patients who undergo primary enucleation,strive to reduce their rumination levels,and enhance their psychological resilience,thereby promoting a positive and optimistic attitude towards their condition and reducing the incidence of PTSD.展开更多
BACKGROUND Pedicle screw fixation is frequently used to treat unstable thoracolumbar injuries;however,the rate of instrumentation failure remains considerable.The primary contributing factor leading to instrumentation...BACKGROUND Pedicle screw fixation is frequently used to treat unstable thoracolumbar injuries;however,the rate of instrumentation failure remains considerable.The primary contributing factor leading to instrumentation failure is poor bone quality.On the other hand,some evidence suggests that surgical tactics can influence long-term instrumentation stability.AIM To assess factors that influence the stability of spinal instrumentation in patients with thoracolumbar injuries.METHODS This study is a non-randomized single center ambispective evaluation of 204 consecutive patients(117 men;87 women)with unstable thoracolumbar injuries.All patients underwent either stand-alone or combined with anterior column reconstruction instrumentation.In cases with spinal cord and nerve root injuries,either posterior or anterior decompression were performed.Patients with pedicle screw loosening were identified via computed tomography imaging.Out of those,cases with clinically significant instrumentation failure were registered.RESULTS The rate of pedicle screw loosening detected by computed tomography was inversely correlated with bone radiodensity figures and an increased association with the number of instrumented levels,residual kyphotic deformity,laminectomy,and lumbosacral fixation.Intermediate screws and anterior reconstruction were associated with a clinically relevant decreased risk of pedicle screw loosening development.Either complete or partial posterior fusion within instrumented levels was capable of decreasing instrumentation failure risk,while extensive decompression with laminectomy and at least one-level total facetectomy were associated with an increased risk of instrumentation failure.Anterior decompression does not have a negative impact on instrumentation stability.CONCLUSION Intermediate screws,anterior reconstruction and posterior tension band preservation are associated with decreased rates of instrumentation instability development.Posterior fusion is beneficial in terms of instrumentation failure prevention.展开更多
Neural injuries can be induced by various neurological disorders and traumas,such as brain and spinal cord injuries,cerebrovascular diseases,and neurodegeneration.Due to the designable physicochemical properties,bioma...Neural injuries can be induced by various neurological disorders and traumas,such as brain and spinal cord injuries,cerebrovascular diseases,and neurodegeneration.Due to the designable physicochemical properties,biomaterials are applied for various purposes in neural repair,including promoting axonal regeneration,reducing glial scar formation,delivering drugs,and providing temporary mechanical support to the injured tissue.They need to match the extracellular matrix(ECM)environment,support threedimensional(3D)cell growth,repair the cellular microenvironment,mimic the tissue's biomechanical forces,and possess biodegradability and plasticity suitable for local intracavity applications.Meanwhile,functionalized biomaterials have been conducted to mimic the structural components of cellular ecological niches and the specific functions of the ECM.They can be engineered to carry a variety of bioactive components,such as stem cells and extracellular vesicles,which are used in neuroscience-related tissue engineering.Researchers also have developed biomaterial-based brain-like organs for high-throughput drug screening and pathological mechanistic studies.This review will discuss the interactions between biomaterials and cells,as well as the advances in neural injuries and engineered microtissues.展开更多
Objective: In the Healthy Child Action Enhancement Program (2021-2025), it is proposed to ensure the safety and health of newborns and to promote high-quality development of health. Our department established risk ass...Objective: In the Healthy Child Action Enhancement Program (2021-2025), it is proposed to ensure the safety and health of newborns and to promote high-quality development of health. Our department established risk assessment criteria for medical adhesives in neonates by applying the best evidence in the management program for the reduction of medical adhesive-associated skin injuries in neonates, in terms of the use and removal of adhesives. Methods: A systematic search and quality assessment of topics related to medical adhesive-related skin injury in neonates was conducted to summarize the best evidence and to conduct a quality review in the neonatal unit. Results: After 2 rounds of review, medical and nursing staff in the neonatal unit had a 98% compliance rate for the knowledge of neonatal medical adhesive-related skin injury and a satisfactory compliance rate for the other 9 indicators;after the application of the evidence, the incidence of neonatal medical adhesive-related skin injury was significantly lower than that before the application of the evidence, and the differences were statistically significant (P Conclusion: The application of the best evidence-based management program in neonatal medical adhesive-associated skin injury can reduce the incidence of neonatal medical adhesive-associated skin injury, reduce neonatal infections, and improve the integrity of the protective skin barrier in neonates.展开更多
Objective:This study aimed to investigate the longitudinal trajectories of cumulative fluid balance(CFB)in intensive care unit(ICU)patients and analyze the relationship between different trajectory groups and the occu...Objective:This study aimed to investigate the longitudinal trajectories of cumulative fluid balance(CFB)in intensive care unit(ICU)patients and analyze the relationship between different trajectory groups and the occurrence of pressure injuries(PIs).Methods:In this retrospective longitudinal study,we obtained health-related data from the Medical Information Mart for Intensive Care IV database,including sociodemographic,disease-related variables,and ICU treatment variables.The daily CFB adjusted for body weight was calculated,and the occurrence of PIs during the ICU stay was recorded.A group-based trajectory model was used to explore the different CFB trajectories.Binary logistic regression was used to analyze the relationship between the CFB trajectory group and PIs.Results:Among the 4,294 included participants,we identified four distinct trajectories of CFB in ICU patients:the rapid accumulation group(12.5%),the slow accumulation group(28.5%),the neutral balance group(41.7%),and the negative decrease group(17.3%).After adjusting for some sociodemographic,disease-related variables,and ICU treatment variables,the rapid accumulation group had an OR of 1.63(95%CI:1.30,2.04)for all stages of PIs and an OR of 1.36(95%CI:1.08,1.72)for stage II or higher PIs compared to the neutral balance group.Conclusions:Four unique trajectories of CFB were identified among patients in the ICU,including rapid accumulation,slow accumulation,neutral balance,and negative decrease.Rapid accumulation independently increased the risk of PIs during ICU stay.展开更多
In recent years,the issue of pressure injuries prevention and management of in patients with acute respiratory distress syndrome(ARDS)undergoing prone position ventilation.Based on recent domestic and international re...In recent years,the issue of pressure injuries prevention and management of in patients with acute respiratory distress syndrome(ARDS)undergoing prone position ventilation.Based on recent domestic and international research,it comprehensively summarizes the multidimensional risk factors for pressure injuries,including patient conditions,prone ventilation time,individual patient factors,nursing staff,environment,and patient psychological factors,among others.Nursing strategies center on standardized procedures combined with individualized interventions,utilizing graded risk assessment,dynamic skin monitoring,prophylactic dressings,high-performance support surfaces,positional optimization,minimal effective sedation management,standardized management of tubing and pressure points,as well as PDCA cycle-based quality control.These comprehensive measures can effectively reduce the incidence and healthcare burden of pressure injuries while ensuring the therapeutic benefits of oxygenation.展开更多
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
Traumatic brain injury can be categorized into primary and secondary injuries.Secondary injuries are the main cause of disability following traumatic brain injury,which involves a complex multicellular cascade.Microgl...Traumatic brain injury can be categorized into primary and secondary injuries.Secondary injuries are the main cause of disability following traumatic brain injury,which involves a complex multicellular cascade.Microglia play an important role in secondary injury and can be activated in response to traumatic brain injury.In this article,we review the origin and classification of microglia as well as the dynamic changes of microglia in traumatic brain injury.We also clarify the microglial polarization pathways and the therapeutic drugs targeting activated microglia.We found that regulating the signaling pathways involved in pro-inflammatory and anti-inflammatory microglia,such as the Toll-like receptor 4/nuclear factor-kappa B,mitogen-activated protein kinase,Janus kinase/signal transducer and activator of transcription,phosphoinositide 3-kinase/protein kinase B,Notch,and high mobility group box 1 pathways,can alleviate the inflammatory response triggered by microglia in traumatic brain injury,thereby exerting neuroprotective effects.We also reviewed the strategies developed on the basis of these pathways,such as drug and cell replacement therapies.Drugs that modulate inflammatory factors,such as rosuvastatin,have been shown to promote the polarization of antiinflammatory microglia and reduce the inflammatory response caused by traumatic brain injury.Mesenchymal stem cells possess anti-inflammatory properties,and clinical studies have confirmed their significant efficacy and safety in patients with traumatic brain injury.Additionally,advancements in mesenchymal stem cell-delivery methods—such as combinations of novel biomaterials,genetic engineering,and mesenchymal stem cell exosome therapy—have greatly enhanced the efficiency and therapeutic effects of mesenchymal stem cells in animal models.However,numerous challenges in the application of drug and mesenchymal stem cell treatment strategies remain to be addressed.In the future,new technologies,such as single-cell RNA sequencing and transcriptome analysis,can facilitate further experimental studies.Moreover,research involving non-human primates can help translate these treatment strategies to clinical practice.展开更多
After spinal cord injury,impairment of the sensorimotor circuit can lead to dysfunction in the motor,sensory,proprioceptive,and autonomic nervous systems.Functional recovery is often hindered by constraints on the tim...After spinal cord injury,impairment of the sensorimotor circuit can lead to dysfunction in the motor,sensory,proprioceptive,and autonomic nervous systems.Functional recovery is often hindered by constraints on the timing of interventions,combined with the limitations of current methods.To address these challenges,various techniques have been developed to aid in the repair and reconstruction of neural circuits at different stages of injury.Notably,neuromodulation has garnered considerable attention for its potential to enhance nerve regeneration,provide neuroprotection,restore neurons,and regulate the neural reorganization of circuits within the cerebral cortex and corticospinal tract.To improve the effectiveness of these interventions,the implementation of multitarget early interventional neuromodulation strategies,such as electrical and magnetic stimulation,is recommended to enhance functional recovery across different phases of nerve injury.This review concisely outlines the challenges encountered following spinal cord injury,synthesizes existing neurostimulation techniques while emphasizing neuroprotection,repair,and regeneration of impaired connections,and advocates for multi-targeted,task-oriented,and timely interventions.展开更多
Spinal cord injury represents a severe form of central nervous system trauma for which effective treatments remain limited.Microglia is the resident immune cells of the central nervous system,play a critical role in s...Spinal cord injury represents a severe form of central nervous system trauma for which effective treatments remain limited.Microglia is the resident immune cells of the central nervous system,play a critical role in spinal cord injury.Previous studies have shown that microglia can promote neuronal survival by phagocytosing dead cells and debris and by releasing neuroprotective and anti-inflammatory factors.However,excessive activation of microglia can lead to persistent inflammation and contribute to the formation of glial scars,which hinder axonal regeneration.Despite this,the precise role and mechanisms of microglia during the acute phase of spinal cord injury remain controversial and poorly understood.To elucidate the role of microglia in spinal cord injury,we employed the colony-stimulating factor 1 receptor inhibitor PLX5622 to deplete microglia.We observed that sustained depletion of microglia resulted in an expansion of the lesion area,downregulation of brain-derived neurotrophic factor,and impaired functional recovery after spinal cord injury.Next,we generated a transgenic mouse line with conditional overexpression of brain-derived neurotrophic factor specifically in microglia.We found that brain-derived neurotrophic factor overexpression in microglia increased angiogenesis and blood flow following spinal cord injury and facilitated the recovery of hindlimb motor function.Additionally,brain-derived neurotrophic factor overexpression in microglia reduced inflammation and neuronal apoptosis during the acute phase of spinal cord injury.Furthermore,through using specific transgenic mouse lines,TMEM119,and the colony-stimulating factor 1 receptor inhibitor PLX73086,we demonstrated that the neuroprotective effects were predominantly due to brain-derived neurotrophic factor overexpression in microglia rather than macrophages.In conclusion,our findings suggest the critical role of microglia in the formation of protective glial scars.Depleting microglia is detrimental to recovery of spinal cord injury,whereas targeting brain-derived neurotrophic factor overexpression in microglia represents a promising and novel therapeutic strategy to enhance motor function recovery in patients with spinal cord injury.展开更多
Neuronal cell death is a common outcome of multiple pathophysiological processes and a key factor in neurological dysfunction after subarachnoid hemorrhage.Neuronal ferroptosis in particular plays an important role in...Neuronal cell death is a common outcome of multiple pathophysiological processes and a key factor in neurological dysfunction after subarachnoid hemorrhage.Neuronal ferroptosis in particular plays an important role in early brain injury.Bromodomain-containing protein 4,a member of the bromo and extraterminal domain family of proteins,participated in multiple cell death pathways,but the mechanisms by which it regulates ferroptosis remain unclear.The primary aim of this study was to investigate how bromodomain-containing protein 4 affects neuronal ferroptosis following subarachnoid hemorrhage in vivo and in vitro.Our findings revealed that endogenous bromodomain-containing protein 4 co-localized with neurons,and its expression was decreased 48 hours after subarachnoid hemorrhage of the cerebral cortex in vivo.In addition,ferroptosis-related pathways were activated in vivo and in vitro after subarachnoid hemorrhage.Targeted inhibition of bromodomain-containing protein 4 in neurons increased lipid peroxidation and intracellular ferrous iron accumulation via ferritinophagy and ultimately led to neuronal ferroptosis.Using cleavage under targets and tagmentation analysis,we found that bromodomain-containing protein 4 enrichment in the Raf-1 promoter region decreased following oxyhemoglobin stimulation in vitro.Furthermore,treating bromodomain-containing protein 4-knockdown HT-22 cell lines with GW5074,a Raf-1 inhibitor,exacerbated neuronal ferroptosis by suppressing the Raf-1/ERK1/2 signaling pathway.Moreover,targeted inhibition of neuronal bromodomain-containing protein 4 exacerbated early and long-term neurological function deficits after subarachnoid hemorrhage.Our findings suggest that bromodomain-containing protein 4 may have neuroprotective effects after subarachnoid hemorrhage,and that inhibiting ferroptosis could help treat subarachnoid hemorrhage.展开更多
Intracerebral hemorrhage is the most dangerous subtype of stroke,characterized by high mortality and morbidity rates,and frequently leads to significant secondary white matter injury.In recent decades,studies have rev...Intracerebral hemorrhage is the most dangerous subtype of stroke,characterized by high mortality and morbidity rates,and frequently leads to significant secondary white matter injury.In recent decades,studies have revealed that gut microbiota can communicate bidirectionally with the brain through the gut microbiota–brain axis.This axis indicates that gut microbiota is closely related to the development and prognosis of intracerebral hemorrhage and its associated secondary white matter injury.The NACHT,LRR,and pyrin domain-containing protein 3(NLRP3)inflammasome plays a crucial role in this context.This review summarizes the dysbiosis of gut microbiota following intracerebral hemorrhage and explores the mechanisms by which this imbalance may promote the activation of the NLRP3 inflammasome.These mechanisms include metabolic pathways(involving short-chain fatty acids,lipopolysaccharides,lactic acid,bile acids,trimethylamine-N-oxide,and tryptophan),neural pathways(such as the vagus nerve and sympathetic nerve),and immune pathways(involving microglia and T cells).We then discuss the relationship between the activated NLRP3 inflammasome and secondary white matter injury after intracerebral hemorrhage.The activation of the NLRP3 inflammasome can exacerbate secondary white matter injury by disrupting the blood–brain barrier,inducing neuroinflammation,and interfering with nerve regeneration.Finally,we outline potential treatment strategies for intracerebral hemorrhage and its secondary white matter injury.Our review highlights the critical role of the gut microbiota–brain axis and the NLRP3 inflammasome in white matter injury following intracerebral hemorrhage,paving the way for exploring potential therapeutic approaches.展开更多
Ischemia–reperfusion injury is a common pathophysiological mechanism in retinal degeneration.PANoptosis is a newly defined integral form of regulated cell death that combines the key features of pyroptosis,apoptosis,...Ischemia–reperfusion injury is a common pathophysiological mechanism in retinal degeneration.PANoptosis is a newly defined integral form of regulated cell death that combines the key features of pyroptosis,apoptosis,and necroptosis.Oligomerization of mitochondrial voltage-dependent anion channel 1 is an important pathological event in regulating cell death in retinal ischemia–reperfusion injury.However,its role in PANoptosis remains largely unknown.In this study,we demonstrated that voltage-dependent anion channel 1 oligomerization-mediated mitochondrial dysfunction was associated with PANoptosis in retinal ischemia–reperfusion injury.Inhibition of voltage-dependent anion channel 1 oligomerization suppressed mitochondrial dysfunction and PANoptosis in retinal cells subjected to ischemia–reperfusion injury.Mechanistically,mitochondria-derived reactive oxygen species played a central role in the voltagedependent anion channel 1-mediated regulation of PANoptosis by promoting PANoptosome assembly.Moreover,inhibiting voltage-dependent anion channel 1 oligomerization protected against PANoptosis in the retinas of rats subjected to ischemia–reperfusion injury.Overall,our findings reveal the critical role of voltage-dependent anion channel 1 oligomerization in regulating PANoptosis in retinal ischemia–reperfusion injury,highlighting voltage-dependent anion channel 1 as a promising therapeutic target.展开更多
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.
文摘Spinal cord injury results in paralysis, sensory disturbances, sphincter dysfunction, and multiple systemic secondary conditions, most arising from autonomic dysregulation. All this produces profound negative psychosocial implications for affected people, their families, and their communities;the financial costs can be challenging for their families and health institutions. Treatments aimed at restoring the spinal cord after spinal cord injury, which have been tested in animal models or clinical trials, generally seek to counteract one or more of the secondary mechanisms of injury to limit the extent of the initial damage. Most published works on structural/functional restoration in acute and chronic spinal cord injury stages use a single type of treatment: a drug or trophic factor, transplant of a cell type, and implantation of a biomaterial. Despite the significant benefits reported in animal models, when translating these successful therapeutic strategies to humans, the result in clinical trials has been considered of little relevance because the improvement, when present, is usually insufficient. Until now, most studies designed to promote neuroprotection or regeneration at different stages after spinal cord injury have used single treatments. Considering the occurrence of various secondary mechanisms of injury in the acute and sub-acute phases of spinal cord injury, it is reasonable to speculate that more than one therapeutic agent could be required to promote structural and functional restoration of the damaged spinal cord. Treatments that combine several therapeutic agents, targeting different mechanisms of injury, which, when used as a single therapy, have shown some benefits, allow us to assume that they will have synergistic beneficial effects. Thus, this narrative review article aims to summarize current trends in the use of strategies that combine therapeutic agents administered simultaneously or sequentially, seeking structural and functional restoration of the injured spinal cord.
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 Nanjing Municipal Special Fund for Health Science and Technology Development Support Project,No.GBX21333.
文摘BACKGROUND Patients with multiple injuries endure not just physical trauma and suffering but are also at risk of psychological conditions such as posttraumatic stress disorder(PTSD),anxiety,and depression.The co-occurrence of PTSD in these patients may cause prolonged physical and mental health complications,thereby further increasing their healthcare expenses.AIM To determine the association between the high-risk factors of PTSD and anxiety as well as depression among patients with multiple injuries.METHODS This study selected 110 patients with multiple injuries who were admitted to our hospital from November 2022 to November 2024.The number and percentage of patients developing PTSD were tallied.Univariate and multivariate analyses were conducted to investigate the high-risk factors of PTSD in these patients.Subse-quently,the associations between these factors and the anxiety and depression levels of patients were analyzed.RESULTS Of the 110 patients,33 suffered from PTSD,representing an incidence rate of 30.0%.The univariate analysis identified age,personality,Hamilton Anxiety Scale(HAMA),Hamilton Depression Scale(HAMD),economic status,negative life events,and smoking history to be significantly associated with PTSD in patients with multiple injuries.Further,the multivariate analysis revealed age,HAMA,HAMD,monthly income,and negative life events as prominent high-risk factors for PTSD in such patients.Regarding the relationships between these factors and HAMA and HAMD,age exhibited a significant positive correlation(r=0.398,P<0.001;r=0.387,P<0.001),monthly income showed a significant negative correlation(r=-0.437,P<0.001;r=-0.319,P<0.001),and negative life events demonstrated a significant positive correlation(r=0.505,P<0.001;r=0.365,P<0.001).CONCLUSION These results indicate age,HAMA,HAMD,monthly income,negative life events,etc.as high-risk factors for PTSD in patients with multiple injuries,among which age,monthly income,and negative life events are closely associated with anxiety and depression.
文摘BACKGROUND The purpose of this systematic review was to evaluate the clinical and radiological outcomes at short-term follow-up following suture button fixation for the management of ligamentous Lisfranc injuries.AIM To assess the effectiveness of suture button fixation in managing ligamentous Lisfranc injuries through a systematic evaluation of short-term clinical and radiological outcomes.METHODS During March 2024,the PubMed,EMBASE,and Cochrane library databases were systematically reviewed to identify clinical studies examining outcomes following suture button fixation for the management of ligamentous Lisfranc injuries.Data regarding patient demographics,pathological characteristics,subjective clinical outcomes,radiological outcomes,complications,and failure rates were extracted and analyzed.RESULTS Eight studies were included.In total,94 patients(94 feet)underwent suture button fixation for the management of ligamentous Lisfranc injuries at a weighted mean follow-up of 27.2±10.2 months.The American Orthopaedic Foot and Ankle Society score improved from a weighted mean pre-operative score of 39.2±11.8 preoperatively to a post-operative score of 82.8±5.4.The weighted mean visual analogue scale score improved from a weighted mean pre-operative score of 7.7±0.6 preoperatively to a post-operative score of 2.0±0.4.In total,100%of patients returned to sport at a mean time of 16.8 weeks.The complication rate was 5%,the most common complication of which was residual midfoot stiffness(3.0%).No failures nor secondary surgical procedures were recorded.CONCLUSION This systematic review demonstrated that suture button fixation for ligamentous Lisfranc injuries produced improved clinical outcomes at short-term follow-up.In addition,there was an excellent return-to-sport rate(100%)at a weighted mean time of 16.8 weeks.This review highlights that suture button fixation is a potent surgical treatment strategy for ligamentous Lisfranc injuries;however,caution should be taken when evaluating this data in light of the lack of high quality,comparative studies,and short-term follow-up.
文摘BACKGROUND Sub-acromial injections are a therapeutic option for rotator cuff injuries;however,evidence regarding the most effective drug in this context is unclear,which needs to be investigated.AIM To evaluate the effectiveness of various sub-acromial injections for rotator cuff injuries.METHODS We conducted a systematic review and pair-wise and network meta-analyses of randomized clinical trials(RCTs)comparing sub-acromial injections for rotator cuff injuries.The interventions evaluated were hyaluronic acid(HA),platelet-rich plasma(PRP),prolotherapy,and corticosteroids.The outcomes of interest were pain and functional improvement,which were evaluated with standardized scores.The Risk of Bias 2 tool and the Grading of Recommendations,Assessment,Development and Evaluation methodology were used to assess data quality.RESULTS Twenty RCTs,comprising 1479 participants,were included.In the short term,HA achieved the best outcomes[pain mean difference(MD)=-1.48,95%confidence interval(CI)-2.37 to-0.59;function MD=10.18,95%CI:4.96-15.41].In the medium term,HA,PRP,HA+PRP,and corticosteroids were not superior to placebo in improving pain.Based on function,HA+PRP was superior to placebo,corticosteroids,and PRP(MD=26.72;95%CI:8.02-45.41).In the long term,HA,PRP,and corticosteroids were not superior to placebo in reducing pain.However,based on function,HA+PRP,PRP,and HA were superior to placebo,and HA+PRP had the best result(MD=36.64;95%CI:31.66-33.62).CONCLUSION HA provides satisfactory short-term results,while HA with PRP demonstrates functional improvement in the medium and long terms.However,no intervention maintained the pain-relief effect on>3-month follow-up.
文摘The clinical treatment of severe trauma withsternoclavicular joint injury is challenging,primarilydue to the irregular shape of the bones surrounding thesternoclavicular joint,as well as the posterior clavicle beingclose to the aorta and mediastinal organs.^([1])These patientsnot only suffer direct injuries to the sternoclavicularjoint,but also frequently experience severe injuries toother body parts.The systemic physiological disordersand multi-organ dysfunction caused by severe traumaincrease the surgery di?culty and mortality risk.^([2])
文摘AIM:To evaluate the prevalence of early post-traumatic stress disorder(PTSD)among young and middle-aged patients who have suffered open globe injuries,and to identify the psychosocial factors influencing PTSD in these patients.METHODS:A total of 280 patients who underwent ocular trauma surgery between January 2023 and January 2024 were selected through convenience sampling.Data were collected using a custom-designed demographic questionnaire,the Connor-Davidson Resilience Scale(CDRISC),the Cognitive Emotion Regulation Questionnaire(C-ERRI),and the PTSD Checklist-Civilian Version(PCL-C).Univariate analysis and stepwise multiple linear regression analysis were performed to determine the factors affecting PTSD in these patients.RESULTS:The average PTSD score for the patients was 33.22±13.48.The scores for individual PTSD dimensions,ranked from highest to lowest,were recurrent traumatic experiences,heightened arousal,avoidance reactions,and social dysfunction.Positive PTSD symptoms were observed in 85 patients(30.36%).Univariate analysis indicated that gender,postoperative vision,marital status,psychological resilience,and rumination were significant factors affecting PTSD symptoms(χ^(2)/t=6.53,17.88,8.83,2.17,and 14.1,respectively;all P<0.05).Pearson correlation analysis showed a positive correlation between rumination and PTSD symptoms(r=0.73,P<0.01)and a negative correlation between psychological resilience and PTSD symptoms(r=-0.14,P<0.05).Stepwise multiple linear regression analysis identified postoperative vision(notably eye removal),rumination levels,and psychological resilience(optimism)as major factors influencing PTSD in these patients(R^(2)=0.57,P<0.001).CONCLUSION:Young and middle-aged patients with open globe injuries have a high incidence of PTSD.Significant risk factors for early PTSD include primary enucleation,high levels of rumination,and low psychological resilience(optimism).Conversely,patients with good postoperative vision recovery,low rumination levels,and high levels of optimism are less likely to develop PTSD.Healthcare providers should pay special attention to patients who undergo primary enucleation,strive to reduce their rumination levels,and enhance their psychological resilience,thereby promoting a positive and optimistic attitude towards their condition and reducing the incidence of PTSD.
基金Supported by AI For Spinal Surgery Planning and Results Assessment Project under the“Priority 2030”Academic Leadership Initiative,No.6.18-01/240724-15.
文摘BACKGROUND Pedicle screw fixation is frequently used to treat unstable thoracolumbar injuries;however,the rate of instrumentation failure remains considerable.The primary contributing factor leading to instrumentation failure is poor bone quality.On the other hand,some evidence suggests that surgical tactics can influence long-term instrumentation stability.AIM To assess factors that influence the stability of spinal instrumentation in patients with thoracolumbar injuries.METHODS This study is a non-randomized single center ambispective evaluation of 204 consecutive patients(117 men;87 women)with unstable thoracolumbar injuries.All patients underwent either stand-alone or combined with anterior column reconstruction instrumentation.In cases with spinal cord and nerve root injuries,either posterior or anterior decompression were performed.Patients with pedicle screw loosening were identified via computed tomography imaging.Out of those,cases with clinically significant instrumentation failure were registered.RESULTS The rate of pedicle screw loosening detected by computed tomography was inversely correlated with bone radiodensity figures and an increased association with the number of instrumented levels,residual kyphotic deformity,laminectomy,and lumbosacral fixation.Intermediate screws and anterior reconstruction were associated with a clinically relevant decreased risk of pedicle screw loosening development.Either complete or partial posterior fusion within instrumented levels was capable of decreasing instrumentation failure risk,while extensive decompression with laminectomy and at least one-level total facetectomy were associated with an increased risk of instrumentation failure.Anterior decompression does not have a negative impact on instrumentation stability.CONCLUSION Intermediate screws,anterior reconstruction and posterior tension band preservation are associated with decreased rates of instrumentation instability development.Posterior fusion is beneficial in terms of instrumentation failure prevention.
基金supported by the National Natural Science Foundation of China(No.82273487)the Young Medical Scientists Training Program(No.21QNPY051)the Shanghai Integration Achievement Program(No.2022-RH17)。
文摘Neural injuries can be induced by various neurological disorders and traumas,such as brain and spinal cord injuries,cerebrovascular diseases,and neurodegeneration.Due to the designable physicochemical properties,biomaterials are applied for various purposes in neural repair,including promoting axonal regeneration,reducing glial scar formation,delivering drugs,and providing temporary mechanical support to the injured tissue.They need to match the extracellular matrix(ECM)environment,support threedimensional(3D)cell growth,repair the cellular microenvironment,mimic the tissue's biomechanical forces,and possess biodegradability and plasticity suitable for local intracavity applications.Meanwhile,functionalized biomaterials have been conducted to mimic the structural components of cellular ecological niches and the specific functions of the ECM.They can be engineered to carry a variety of bioactive components,such as stem cells and extracellular vesicles,which are used in neuroscience-related tissue engineering.Researchers also have developed biomaterial-based brain-like organs for high-throughput drug screening and pathological mechanistic studies.This review will discuss the interactions between biomaterials and cells,as well as the advances in neural injuries and engineered microtissues.
文摘Objective: In the Healthy Child Action Enhancement Program (2021-2025), it is proposed to ensure the safety and health of newborns and to promote high-quality development of health. Our department established risk assessment criteria for medical adhesives in neonates by applying the best evidence in the management program for the reduction of medical adhesive-associated skin injuries in neonates, in terms of the use and removal of adhesives. Methods: A systematic search and quality assessment of topics related to medical adhesive-related skin injury in neonates was conducted to summarize the best evidence and to conduct a quality review in the neonatal unit. Results: After 2 rounds of review, medical and nursing staff in the neonatal unit had a 98% compliance rate for the knowledge of neonatal medical adhesive-related skin injury and a satisfactory compliance rate for the other 9 indicators;after the application of the evidence, the incidence of neonatal medical adhesive-related skin injury was significantly lower than that before the application of the evidence, and the differences were statistically significant (P Conclusion: The application of the best evidence-based management program in neonatal medical adhesive-associated skin injury can reduce the incidence of neonatal medical adhesive-associated skin injury, reduce neonatal infections, and improve the integrity of the protective skin barrier in neonates.
文摘Objective:This study aimed to investigate the longitudinal trajectories of cumulative fluid balance(CFB)in intensive care unit(ICU)patients and analyze the relationship between different trajectory groups and the occurrence of pressure injuries(PIs).Methods:In this retrospective longitudinal study,we obtained health-related data from the Medical Information Mart for Intensive Care IV database,including sociodemographic,disease-related variables,and ICU treatment variables.The daily CFB adjusted for body weight was calculated,and the occurrence of PIs during the ICU stay was recorded.A group-based trajectory model was used to explore the different CFB trajectories.Binary logistic regression was used to analyze the relationship between the CFB trajectory group and PIs.Results:Among the 4,294 included participants,we identified four distinct trajectories of CFB in ICU patients:the rapid accumulation group(12.5%),the slow accumulation group(28.5%),the neutral balance group(41.7%),and the negative decrease group(17.3%).After adjusting for some sociodemographic,disease-related variables,and ICU treatment variables,the rapid accumulation group had an OR of 1.63(95%CI:1.30,2.04)for all stages of PIs and an OR of 1.36(95%CI:1.08,1.72)for stage II or higher PIs compared to the neutral balance group.Conclusions:Four unique trajectories of CFB were identified among patients in the ICU,including rapid accumulation,slow accumulation,neutral balance,and negative decrease.Rapid accumulation independently increased the risk of PIs during ICU stay.
文摘In recent years,the issue of pressure injuries prevention and management of in patients with acute respiratory distress syndrome(ARDS)undergoing prone position ventilation.Based on recent domestic and international research,it comprehensively summarizes the multidimensional risk factors for pressure injuries,including patient conditions,prone ventilation time,individual patient factors,nursing staff,environment,and patient psychological factors,among others.Nursing strategies center on standardized procedures combined with individualized interventions,utilizing graded risk assessment,dynamic skin monitoring,prophylactic dressings,high-performance support surfaces,positional optimization,minimal effective sedation management,standardized management of tubing and pressure points,as well as PDCA cycle-based quality control.These comprehensive measures can effectively reduce the incidence and healthcare burden of pressure injuries while ensuring the therapeutic benefits of oxygenation.
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 Natural Science Foundation of Yunnan Province,No.202401AS070086(to ZW)the National Key Research and Development Program of China,No.2018YFA0801403(to ZW)+1 种基金Yunnan Science and Technology Talent and Platform Plan,No.202105AC160041(to ZW)the Natural Science Foundation of China,No.31960120(to ZW)。
文摘Traumatic brain injury can be categorized into primary and secondary injuries.Secondary injuries are the main cause of disability following traumatic brain injury,which involves a complex multicellular cascade.Microglia play an important role in secondary injury and can be activated in response to traumatic brain injury.In this article,we review the origin and classification of microglia as well as the dynamic changes of microglia in traumatic brain injury.We also clarify the microglial polarization pathways and the therapeutic drugs targeting activated microglia.We found that regulating the signaling pathways involved in pro-inflammatory and anti-inflammatory microglia,such as the Toll-like receptor 4/nuclear factor-kappa B,mitogen-activated protein kinase,Janus kinase/signal transducer and activator of transcription,phosphoinositide 3-kinase/protein kinase B,Notch,and high mobility group box 1 pathways,can alleviate the inflammatory response triggered by microglia in traumatic brain injury,thereby exerting neuroprotective effects.We also reviewed the strategies developed on the basis of these pathways,such as drug and cell replacement therapies.Drugs that modulate inflammatory factors,such as rosuvastatin,have been shown to promote the polarization of antiinflammatory microglia and reduce the inflammatory response caused by traumatic brain injury.Mesenchymal stem cells possess anti-inflammatory properties,and clinical studies have confirmed their significant efficacy and safety in patients with traumatic brain injury.Additionally,advancements in mesenchymal stem cell-delivery methods—such as combinations of novel biomaterials,genetic engineering,and mesenchymal stem cell exosome therapy—have greatly enhanced the efficiency and therapeutic effects of mesenchymal stem cells in animal models.However,numerous challenges in the application of drug and mesenchymal stem cell treatment strategies remain to be addressed.In the future,new technologies,such as single-cell RNA sequencing and transcriptome analysis,can facilitate further experimental studies.Moreover,research involving non-human primates can help translate these treatment strategies to clinical practice.
基金supported by the National Key Research and Development Program of China,No.2023YFC3603705(to DX)the National Natural Science Foundation of China,No.82302866(to YZ).
文摘After spinal cord injury,impairment of the sensorimotor circuit can lead to dysfunction in the motor,sensory,proprioceptive,and autonomic nervous systems.Functional recovery is often hindered by constraints on the timing of interventions,combined with the limitations of current methods.To address these challenges,various techniques have been developed to aid in the repair and reconstruction of neural circuits at different stages of injury.Notably,neuromodulation has garnered considerable attention for its potential to enhance nerve regeneration,provide neuroprotection,restore neurons,and regulate the neural reorganization of circuits within the cerebral cortex and corticospinal tract.To improve the effectiveness of these interventions,the implementation of multitarget early interventional neuromodulation strategies,such as electrical and magnetic stimulation,is recommended to enhance functional recovery across different phases of nerve injury.This review concisely outlines the challenges encountered following spinal cord injury,synthesizes existing neurostimulation techniques while emphasizing neuroprotection,repair,and regeneration of impaired connections,and advocates for multi-targeted,task-oriented,and timely interventions.
基金supported by the National Natural Science Foundation of China,Nos.82072165 and 82272256(both to XM)the Key Project of Xiangyang Central Hospital,No.2023YZ03(to RM)。
文摘Spinal cord injury represents a severe form of central nervous system trauma for which effective treatments remain limited.Microglia is the resident immune cells of the central nervous system,play a critical role in spinal cord injury.Previous studies have shown that microglia can promote neuronal survival by phagocytosing dead cells and debris and by releasing neuroprotective and anti-inflammatory factors.However,excessive activation of microglia can lead to persistent inflammation and contribute to the formation of glial scars,which hinder axonal regeneration.Despite this,the precise role and mechanisms of microglia during the acute phase of spinal cord injury remain controversial and poorly understood.To elucidate the role of microglia in spinal cord injury,we employed the colony-stimulating factor 1 receptor inhibitor PLX5622 to deplete microglia.We observed that sustained depletion of microglia resulted in an expansion of the lesion area,downregulation of brain-derived neurotrophic factor,and impaired functional recovery after spinal cord injury.Next,we generated a transgenic mouse line with conditional overexpression of brain-derived neurotrophic factor specifically in microglia.We found that brain-derived neurotrophic factor overexpression in microglia increased angiogenesis and blood flow following spinal cord injury and facilitated the recovery of hindlimb motor function.Additionally,brain-derived neurotrophic factor overexpression in microglia reduced inflammation and neuronal apoptosis during the acute phase of spinal cord injury.Furthermore,through using specific transgenic mouse lines,TMEM119,and the colony-stimulating factor 1 receptor inhibitor PLX73086,we demonstrated that the neuroprotective effects were predominantly due to brain-derived neurotrophic factor overexpression in microglia rather than macrophages.In conclusion,our findings suggest the critical role of microglia in the formation of protective glial scars.Depleting microglia is detrimental to recovery of spinal cord injury,whereas targeting brain-derived neurotrophic factor overexpression in microglia represents a promising and novel therapeutic strategy to enhance motor function recovery in patients with spinal cord injury.
基金supported by the National Natural Science Foundation of China,Nos.82371310(to YJ),82271306(to JP)the Sichuan Science and Technology Support Program,Nos.2023YFH0069(to JP),2023NSFSC0028(to YJ),2023NSFSC1559(to YJ),2022YFS0615(to JP),2022NSFSC1421(to JP)+1 种基金Scientific Research Project of Sichuan Provincial Health Commission,No.23LCYJ040(to YJ)Youth Foundation of Southwestern Medical University and Southwest Medical University Project,Nos.2020ZRQNA038(to JP),2021ZKZD013(to JP),2021LZXNYD-P01(to YJ),2023QN014(to JP).
文摘Neuronal cell death is a common outcome of multiple pathophysiological processes and a key factor in neurological dysfunction after subarachnoid hemorrhage.Neuronal ferroptosis in particular plays an important role in early brain injury.Bromodomain-containing protein 4,a member of the bromo and extraterminal domain family of proteins,participated in multiple cell death pathways,but the mechanisms by which it regulates ferroptosis remain unclear.The primary aim of this study was to investigate how bromodomain-containing protein 4 affects neuronal ferroptosis following subarachnoid hemorrhage in vivo and in vitro.Our findings revealed that endogenous bromodomain-containing protein 4 co-localized with neurons,and its expression was decreased 48 hours after subarachnoid hemorrhage of the cerebral cortex in vivo.In addition,ferroptosis-related pathways were activated in vivo and in vitro after subarachnoid hemorrhage.Targeted inhibition of bromodomain-containing protein 4 in neurons increased lipid peroxidation and intracellular ferrous iron accumulation via ferritinophagy and ultimately led to neuronal ferroptosis.Using cleavage under targets and tagmentation analysis,we found that bromodomain-containing protein 4 enrichment in the Raf-1 promoter region decreased following oxyhemoglobin stimulation in vitro.Furthermore,treating bromodomain-containing protein 4-knockdown HT-22 cell lines with GW5074,a Raf-1 inhibitor,exacerbated neuronal ferroptosis by suppressing the Raf-1/ERK1/2 signaling pathway.Moreover,targeted inhibition of neuronal bromodomain-containing protein 4 exacerbated early and long-term neurological function deficits after subarachnoid hemorrhage.Our findings suggest that bromodomain-containing protein 4 may have neuroprotective effects after subarachnoid hemorrhage,and that inhibiting ferroptosis could help treat subarachnoid hemorrhage.
基金supported by the Guangdong Basic and Applied Basic Research Foundation,No.2023A1515030045(to HS)Presidential Foundation of Zhujiang Hospital of Southern Medical University,No.yzjj2022ms4(to HS)。
文摘Intracerebral hemorrhage is the most dangerous subtype of stroke,characterized by high mortality and morbidity rates,and frequently leads to significant secondary white matter injury.In recent decades,studies have revealed that gut microbiota can communicate bidirectionally with the brain through the gut microbiota–brain axis.This axis indicates that gut microbiota is closely related to the development and prognosis of intracerebral hemorrhage and its associated secondary white matter injury.The NACHT,LRR,and pyrin domain-containing protein 3(NLRP3)inflammasome plays a crucial role in this context.This review summarizes the dysbiosis of gut microbiota following intracerebral hemorrhage and explores the mechanisms by which this imbalance may promote the activation of the NLRP3 inflammasome.These mechanisms include metabolic pathways(involving short-chain fatty acids,lipopolysaccharides,lactic acid,bile acids,trimethylamine-N-oxide,and tryptophan),neural pathways(such as the vagus nerve and sympathetic nerve),and immune pathways(involving microglia and T cells).We then discuss the relationship between the activated NLRP3 inflammasome and secondary white matter injury after intracerebral hemorrhage.The activation of the NLRP3 inflammasome can exacerbate secondary white matter injury by disrupting the blood–brain barrier,inducing neuroinflammation,and interfering with nerve regeneration.Finally,we outline potential treatment strategies for intracerebral hemorrhage and its secondary white matter injury.Our review highlights the critical role of the gut microbiota–brain axis and the NLRP3 inflammasome in white matter injury following intracerebral hemorrhage,paving the way for exploring potential therapeutic approaches.
基金supported by the National Natural Science Foundation of China,Nos.82172196(to KX),82372507(to KX)the Natural Science Foundation of Hunan Province,China,No.2023JJ40804(to QZ)the Key Laboratory of Emergency and Trauma(Hainan Medical University)of the Ministry of Education,China,No.KLET-202210(to QZ)。
文摘Ischemia–reperfusion injury is a common pathophysiological mechanism in retinal degeneration.PANoptosis is a newly defined integral form of regulated cell death that combines the key features of pyroptosis,apoptosis,and necroptosis.Oligomerization of mitochondrial voltage-dependent anion channel 1 is an important pathological event in regulating cell death in retinal ischemia–reperfusion injury.However,its role in PANoptosis remains largely unknown.In this study,we demonstrated that voltage-dependent anion channel 1 oligomerization-mediated mitochondrial dysfunction was associated with PANoptosis in retinal ischemia–reperfusion injury.Inhibition of voltage-dependent anion channel 1 oligomerization suppressed mitochondrial dysfunction and PANoptosis in retinal cells subjected to ischemia–reperfusion injury.Mechanistically,mitochondria-derived reactive oxygen species played a central role in the voltagedependent anion channel 1-mediated regulation of PANoptosis by promoting PANoptosome assembly.Moreover,inhibiting voltage-dependent anion channel 1 oligomerization protected against PANoptosis in the retinas of rats subjected to ischemia–reperfusion injury.Overall,our findings reveal the critical role of voltage-dependent anion channel 1 oligomerization in regulating PANoptosis in retinal ischemia–reperfusion injury,highlighting voltage-dependent anion channel 1 as a promising therapeutic target.
