BACKGROUND Malignant fibrous histiocytoma(MFH)is one of the most common soft tissue sarcomas among adults.It is characterized by large size,high grade,and biological aggressiveness.There are many reports of MFH after ...BACKGROUND Malignant fibrous histiocytoma(MFH)is one of the most common soft tissue sarcomas among adults.It is characterized by large size,high grade,and biological aggressiveness.There are many reports of MFH after local stimulation,such as bone fracture,implants,and chronic osteomyelitis.In this paper,we report a patient who developed MFH 6 years after amputation,suggesting that wound healing and mechanical force play a role in the local stimulation of this disease.CASE SUMMARY A 66-year-old man complained of persistent pain in his residual mid-thigh.He had undergone amputation surgery due to a traffic accident 6 years prior.Physical examination showed tenderness but no abnormalities in appearance.Xray radiographs and magnetic resonance imaging supported the diagnosis of a tumor,and a biopsy confirmed that the lesion was MFH.The patient received neoadjuvant chemotherapy and left hip disarticulation.During the 6-mo followup,there were no symptoms of recurrence.CONCLUSION Postsurgery MFH has been reported before,and many studies have attributed it to the biological effects of implants.Our case report shows that this disease can develop without an implant and thus highlights the importance of local stimulation.The wound-healing process and mechanical force can both promote this tumor,but whether they directly cause MFH needs further investigation.展开更多
Background:Limb loss has a drastic impact on a patient’s life.Severe trauma to the extremities is common in current military conflicts.Among other aspects,"life before limb"damage control surgery hinders im...Background:Limb loss has a drastic impact on a patient’s life.Severe trauma to the extremities is common in current military conflicts.Among other aspects,"life before limb"damage control surgery hinders immediate replantation within the short post-traumatic timeframe,which is limited in part by the ischemic time for successful replantation.Ex vivo limb perfusion is currently being researched in animal models and shows promising results for its application in human limb replantation and allotransplantation.Presentation of the hypothesis:The current lack of replantation possibilities in military operations with high rates of amputation can be addressed with the development of a portable ex vivo limb perfusion device,as there are several opportunities present with the introduction of this technique on the horizon.We hypothesize that ex vivo limb perfusion will enable overcoming the critical ischemic time,provide surgical opportunities such as preparation of the stump and limb,allow for spare-part surgery,enable rigorous antibiotic treatment of the limb,reduce ischemiareperfusion injuries,enable a tissue function assessment before replantation,and enable the development of large limb transplant programs.Testing the hypothesis:Data from in vivo studies in porcine models are limited by the relatively short perfusion time of 24 h.In the military setting,notably longer perfusion times need to be realized.Therefore,future animal studies must focus especially on long-term perfusion,since this represents the military setting,considering the time for stabilization of the patient until evacuation to a tertiary treatment center.Implications of the hypothesis:The development and clinical introduction of ex vivo limb perfusion in the military setting could lead to a drastic reduction in the number of limb amputations among service members.Ex vivo limb perfusion enables replantation surgery in Role 4 facilities and changes the clinical setting from a highly urgent,lifethreatening situation to a highly methodical,well-prepared starting point for optimal treatment of the wounded service member.With its introduction,the principle of"life before limb"will change to"life before limb before elective replantation/allotransplantation after ex vivo limb perfusion".展开更多
BACKGROUND To report the application of supermicroscopy combined with arterio-venolization without venous anastomosis for replantation of digits following traumatic amputation in young children.CASE SUMMARY In March 2...BACKGROUND To report the application of supermicroscopy combined with arterio-venolization without venous anastomosis for replantation of digits following traumatic amputation in young children.CASE SUMMARY In March 2016,we treated two children aged 2 years and 7 years with traumatic digit amputation,no venous anastomosis,and bilateral digital inherent arteries on the palmar side.Supermicroscopy combined with an arteriovenous technique was adopted to improve the replantation surgery.Postoperative management involved auxiliary treatments such as anticoagulation,composure,antiinflammatory drugs,and insulation.After treatment,the amputated fingers survived completely without major complications,with good recovery.CONCLUSION Supermicroscopy combined with arterio-venolization is a safe and effective approach to treat traumatic digit amputation in young children without venous anastomosis.展开更多
Background: In combat operations, patients with traumatic injuries require expeditious evacuation to improve survival. Studies have shown that long transport times are associated with increased morbidity and mortality...Background: In combat operations, patients with traumatic injuries require expeditious evacuation to improve survival. Studies have shown that long transport times are associated with increased morbidity and mortality. Limited data exist on the influence of transport time on patient outcomes with specific injury types. The objective of this study was to determine the impact of the duration of time from the initial request for medical evacuation to arrival at a medical treatment facility on morbidity and mortality in casualties with traumatic extremity amputation and noncompressible torso injury(NCTI).Methods: We completed a retrospective review of MEDEVAC patient care records for United States military personnel who sustained traumatic amputations and NCTI during Operation Enduring Freedom between January 2011 and March 2014. We grouped patients as traumatic amputation and NCTI(AMP+NCTI), traumatic amputation only(AMP),and neither AMP nor NCTI(Non-AMP/NCTI). Analysis was performed using chi-squared tests, Fisher's exact tests,Cochran-Armitage Trend tests, Shapiro-Wilks tests, Wilcoxon and Kruskal-Wallis techniques and Cox proportional hazards regression modeling.Results: We reviewed 1267 records, of which 669 had an injury severity score(ISS) of 10 or greater and were included in the analysis. In the study population, 15.5% sustained only amputation injuries(n=104, AMP only), 10.8% sustained amputation and NCTI(n=72, AMP+NCTI), and 73.7% did not sustain either an amputation or an NCTI(n=493,Non-AMP/NCTI). AMP+NCTI had the highest mortality(16.7%) with transport time greater than 60 min. While the AMP+NCTI group had decreasing survival with longer transport times, AMP and Non-AMP/NCTI did not exhibit the same trend.Conclusions: A decreased transport time from the point of injury to a medical treatment facility was associated with decreased mortality in patients who suffered a combination of amputation injury and NCTI. No significant association between transport time and outcomes was found in patients who did not sustain NCTI. Priority for rapid evacuation of combat casualties should be given to those with NCTI.展开更多
Dear Editor,Chronic pain is a significant concern after major lower limb amputations that often preclude prosthetic fitting,decrease ambulation,and impact the quality of life[1,2].In the last decade,targeted muscle re...Dear Editor,Chronic pain is a significant concern after major lower limb amputations that often preclude prosthetic fitting,decrease ambulation,and impact the quality of life[1,2].In the last decade,targeted muscle reinnervation(TMR)has been proposed as a surgical strategy for treating or preventing symptomatic neuromas and phantomlimb phenomena in major amputees[1].This technique involves the transfer of an amputated mixed-motor and sensory nerve to a nearby recipient motor nerve[1,2].Unlike most surgical strategies that aim to hide or protect the neuroma,TMR gives the amputated nerves“somewhere to go and something to do”[2].In a randomized clinical trial on neuroma and phantom pain,Dumanian et al.[1]demonstrated that TMR reduces amputationrelated chronic pain at 1-year post-intervention when compared with the excision and muscle-burying technique,which remains the current gold standard.Valerio et al.[2]also proposed applying TMR at the time of major limb amputation for preventing chronic pain and found that TMR patients experienced less residual limb pain(RLP)and phantom limb pain(PLP)when compared with untreated amputee controls.展开更多
Circumcision remains a frequently performed surgical procedure and could be associated with various complications, ranging from mild to catastrophic. Penile amputation is a rare and severe complication usually complex...Circumcision remains a frequently performed surgical procedure and could be associated with various complications, ranging from mild to catastrophic. Penile amputation is a rare and severe complication usually complex and challenging to manage. We describe three cases of penile amputation injuries following circumcision referred within a week at the urological service of the Yaoundé Central Hospital. The first case was a 5-year-old who had complete penile amputation during circumcision by a nurse assistant at a rural health center. The second was a 7-year-old boy who sustained total penile glans amputation while undergoing circumcision by a nurse under local anesthesia at a rural health facility. The third involved a 6-year-old who had total penile amputation with loss of the amputated stump during circumcision by a traditional practitioner at home. Non-microsurgical penile re-implantations were done with diverse outcomes. The preservation of the amputated stump, the ischemic time and the severity of injury are factors affecting surgical outcome. The aim of this study is to evaluate our management experience and outcome of penile amputation injuries in resource-limited settings. Microsurgical replantation remains the gold standard in the management of penile amputation injuries. However, in resource-limited settings macroscopic replantation could be used as an alternative remedy to salvage the amputated penis.展开更多
Objective: to explore the role of narrative breast-feeding in clinical nursing of traumatic amputees. Methods: from January 2019 to January 2019, 68 amputees were divided into control group and observation group with ...Objective: to explore the role of narrative breast-feeding in clinical nursing of traumatic amputees. Methods: from January 2019 to January 2019, 68 amputees were divided into control group and observation group with 34 cases in each group. The control group received routine orthopedic hospitalization, while the observation group received narrative hospitalization on the basis of routine hospitalization. Anxiety, depression and quality of life scale were used to compare the patients anxiety, depression and quality of life. The narrative results of lactation, anxiety, depression and quality of life in the observation group were better than those in the control group (p0.05). The narrative conclusion of breast feeding can improve the negative emotions of traumatic amputees, promote their self-management and improve their quality of life.展开更多
Traumatic brain injury, chronic traumatic encephalopathy, and Alzheimer's disease are three distinct neurological disorders that share common pathophysiological mechanisms involving neuroinflammation. One sequela ...Traumatic brain injury, chronic traumatic encephalopathy, and Alzheimer's disease are three distinct neurological disorders that share common pathophysiological mechanisms involving neuroinflammation. One sequela of neuroinflammation includes the pathologic hyperphosphorylation of tau protein, an endogenous microtubule-associated protein that protects the integrity of neuronal cytoskeletons. Tau hyperphosphorylation results in protein misfolding and subsequent accumulation of tau tangles forming neurotoxic aggregates. These misfolded proteins are characteristic of traumatic brain injury, chronic traumatic encephalopathy, and Alzheimer's disease and can lead to downstream neuroinflammatory processes, including assembly and activation of the inflammasome complex. Inflammasomes refer to a family of multimeric protein units that, upon activation, release a cascade of signaling molecules resulting in caspase-induced cell death and inflammation mediated by the release of interleukin-1β cytokine. One specific inflammasome, the NOD-like receptor protein 3, has been proposed to be a key regulator of tau phosphorylation where it has been shown that prolonged NOD-like receptor protein 3 activation acts as a causal factor in pathological tau accumulation and spreading. This review begins by describing the epidemiology and pathophysiology of traumatic brain injury, chronic traumatic encephalopathy, and Alzheimer's disease. Next, we highlight neuroinflammation as an overriding theme and discuss the role of the NOD-like receptor protein 3 inflammasome in the formation of tau deposits and how such tauopathic entities spread throughout the brain. We then propose a novel framework linking traumatic brain injury, chronic traumatic encephalopathy, and Alzheimer's disease as inflammasomedependent pathologies that exist along a temporal continuum. Finally, we discuss potential therapeutic targets that may intercept this pathway and ultimately minimize long-term neurological decline.展开更多
BACKGROUND Traumatic fractures are mainly caused by various exogenous traumatic events,which not only damage patients’physical health but also affect their psychological state and aggravate stress responses.AIM To an...BACKGROUND Traumatic fractures are mainly caused by various exogenous traumatic events,which not only damage patients’physical health but also affect their psychological state and aggravate stress responses.AIM To analyze the influencing factors of psychological resilience of patients with traumatic fractures and the effect of psychological resilience on posttraumatic growth(PTG).METHODS This study included 188 patients with traumatic fractures admitted to the First People’s Hospital of Shangqiu from November 2022 to November 2023.The participants were categorized based on the patient’s psychological resilience assessed by the Connor-Davidson Resilience Scale(CD-RISC)into the better resilience group(CD-RISC score≥60 points,n=80)and the poor resilience group(CD-RISC score<60 points,n=108).Patients’sleep quality was assessed with the Pittsburgh Sleep Quality Index(PSQI).The identification of the influencing factors of psychological resilience in patients with traumatic fractures was realized by binary Logistic regression(with factors such as sex,age,injury cause,trauma severity,fracture site,personality,and PSQI included for analysis).The determination of the PTG status of all participants used the Chinese version of the Posttraumatic Growth Inventory(C-PTGI).Furthermore,a Spearman correlation analysis was conducted to analyze the association between psychological resilience and PTG.RESULTS The psychological resilience of patients with traumatic fractures was related to age,sex,trauma severity,and personality.The better resilience group demonstrated statistically lower PSQI scores than the poor resilience group(P<0.05).The Logistic regression analysis revealed sex,age,trauma severity,personality,and sleep quality as influencing factors of CD-RISC scores in patients with traumatic fractures(all P<0.05).The score of each C-PTGI dimension and the total score(relating to others,new possibilities,personal strength,spiritual change,and appreciation of life)were higher in the better resilience group than in the poor resilience group(all P<0.05).Spearman correlation analysis indicated a positive association of the CD-RISC score in patients with traumatic fractures with the scores of all dimensions of C-PTGI and the total C-PTGI score(all P<0.05).CONCLUSION The factors influencing the psychological resilience of patients with traumatic fractures include age,sex,trauma severity,personality,and sleep quality,and psychological resilience is closely associated with PTG.展开更多
BACKGROUND Traumatic subdural effusion is a common complication of traumatic brain injury,especially after decompressive craniectomy(DC).For neurosurgeons,early diagnosis and timely treatment are particularly importan...BACKGROUND Traumatic subdural effusion is a common complication of traumatic brain injury,especially after decompressive craniectomy(DC).For neurosurgeons,early diagnosis and timely treatment are particularly important,which can help improve patient prognosis and enhance quality of life.CASE SUMMARY A 47 year old male underwent DC for traumatic brain herniation.After surgery,he developed stubborn subdural effusion(SDE)on the contralateral side and underwent multiple subdural drilling and drainage surgeries,but only temporarily improved the patient’s symptoms.After the final cranioplasty,the contralateral SDE completely disappeared.The patient did not experience any new contralateral neurological dysfunction,and the Glasgow prognostic score was 11 points(E4V1M6).CONCLUSION For neurosurgeons,accurate assessment of the condition is necessary when treating patients with stubborn SDE after DC surgery,and timely cranioplasty can be performed to avoid multiple surgeries.This is a safe and effective surgical method for treating traumatic subdural effusion.展开更多
Traumatic penumbra(TP)is a region with recoverable potential around the primary lesion of brain injury.Rapid and accurate imaging for identifying TP is essential for treating traumatic brain injury(TBI).In this study,...Traumatic penumbra(TP)is a region with recoverable potential around the primary lesion of brain injury.Rapid and accurate imaging for identifying TP is essential for treating traumatic brain injury(TBI).In this study,we first established traumatic brain injuries(TBIs)in rats using a modified Feeney method,followed by label-free imaging of brain tissue sections with multiphoton fluorescence microscopy.The results showed that the technique effectively imaged normal and traumatic brain tissues,and revealed pathological features such as extracellular matrix changes,vascular cell proliferation,and intracellular edema in the traumatic penumbra.Compared with normal brain tissue,the extracellular matrix in the TP was sparse,cells were disorganized,and hyperplastic vascular cells emitted higher two-photon excited fluorescence(TPEF)signals.Our research demonstrates the potential of multiphoton fluorescence technology in the rapid diagnosis and therapeutic evaluation of TBI.展开更多
Traumatic carotid-cavernous arteriovenous fistula(TCCAVF)is a rare but severe cerebrovascular disorder,often resulting from head trauma with temporal bone fractures.The pathogenesis involves vessel wall injury due to ...Traumatic carotid-cavernous arteriovenous fistula(TCCAVF)is a rare but severe cerebrovascular disorder,often resulting from head trauma with temporal bone fractures.The pathogenesis involves vessel wall injury due to traction,frequently associated with fractures near the middle meningeal artery.This case highlights the typical clinical presentation,diagnostic approaches,and therapeutic management of TCCAVF,emphasizing the challenges in treating this condition.Transcatheter embolization proved effective in occluding the fistula,underscoring its role as a key intervention for traumatic meningeal arteriovenous fistulas.展开更多
Obese individuals who subsequently sustain a traumatic brain injury(TBI)exhibit worsened outcomes including longer periods of rehabilitation(Eagle et al.,2023).In obese individuals,prolonged symptomology is associated...Obese individuals who subsequently sustain a traumatic brain injury(TBI)exhibit worsened outcomes including longer periods of rehabilitation(Eagle et al.,2023).In obese individuals,prolonged symptomology is associated with increased levels of circulato ry pro-inflammatory marke rs up to 1 year postTBI(Eagle et al.,2023).展开更多
Advanced microsystems in traumatic brain injury research:Traumatic brain injury(TBI)results from a mechanical insult to the brain,leading to neuronal and axonal damage and subsequently causing a secondary injury.Withi...Advanced microsystems in traumatic brain injury research:Traumatic brain injury(TBI)results from a mechanical insult to the brain,leading to neuronal and axonal damage and subsequently causing a secondary injury.Within minutes of TBI,a neuroinflammatory response is triggered,driven by intricate molecular and cellular inflammatory processes.展开更多
Traumatic brain injury is a prevalent disorder of the central nervous system.In addition to primary brain parenchymal damage,the enduring biological consequences of traumatic brain injury pose long-term risks for pati...Traumatic brain injury is a prevalent disorder of the central nervous system.In addition to primary brain parenchymal damage,the enduring biological consequences of traumatic brain injury pose long-term risks for patients with traumatic brain injury;however,the underlying pathogenesis remains unclear,and effective intervention methods are lacking.Intestinal dysfunction is a significant consequence of traumatic brain injury.Being the most densely innervated peripheral tissue in the body,the gut possesses multiple pathways for the establishment of a bidirectional“brain-gut axis”with the central nervous system.The gut harbors a vast microbial community,and alterations of the gut niche contribute to the progression of traumatic brain injury and its unfavorable prognosis through neuronal,hormonal,and immune pathways.A comprehensive understanding of microbiota-mediated peripheral neuroimmunomodulation mechanisms is needed to enhance treatment strategies for traumatic brain injury and its associated complications.We comprehensively reviewed alterations in the gut microecological environment following traumatic brain injury,with a specific focus on the complex biological processes of peripheral nerves,immunity,and microbes triggered by traumatic brain injury,encompassing autonomic dysfunction,neuroendocrine disturbances,peripheral immunosuppression,increased intestinal barrier permeability,compromised responses of sensory nerves to microorganisms,and potential effector nuclei in the central nervous system influenced by gut microbiota.Additionally,we reviewed the mechanisms underlying secondary biological injury and the dynamic pathological responses that occur following injury to enhance our current understanding of how peripheral pathways impact the outcome of patients with traumatic brain injury.This review aimed to propose a conceptual model for future risk assessment of central nervous system-related diseases while elucidating novel insights into the bidirectional effects of the“brain-gut-microbiota axis.”展开更多
Repetitive traumatic brain injury impacts adult neurogenesis in the hippocampal dentate gyrus,leading to long-term cognitive impairment.However,the mechanism underlying this neurogenesis impairment remains unknown.In ...Repetitive traumatic brain injury impacts adult neurogenesis in the hippocampal dentate gyrus,leading to long-term cognitive impairment.However,the mechanism underlying this neurogenesis impairment remains unknown.In this study,we established a male mouse model of repetitive traumatic brain injury and performed long-term evaluation of neurogenesis of the hippocampal dentate gyrus after repetitive traumatic brain injury.Our results showed that repetitive traumatic brain injury inhibited neural stem cell proliferation and development,delayed neuronal maturation,and reduced the complexity of neuronal dendrites and spines.Mice with repetitive traumatic brain injuryalso showed deficits in spatial memory retrieval.Moreover,following repetitive traumatic brain injury,neuroinflammation was enhanced in the neurogenesis microenvironment where C1q levels were increased,C1q binding protein levels were decreased,and canonical Wnt/β-catenin signaling was downregulated.An inhibitor of C1 reversed the long-term impairment of neurogenesis induced by repetitive traumatic brain injury and improved neurological function.These findings suggest that repetitive traumatic brain injury–induced C1-related inflammation impairs long-term neurogenesis in the dentate gyrus and contributes to spatial memory retrieval dysfunction.展开更多
Traumatic brain injury involves complex pathophysiological mechanisms,among which oxidative stress significantly contributes to the occurrence of secondary injury.In this study,we evaluated hypidone hydrochloride(YL-0...Traumatic brain injury involves complex pathophysiological mechanisms,among which oxidative stress significantly contributes to the occurrence of secondary injury.In this study,we evaluated hypidone hydrochloride(YL-0919),a self-developed antidepressant with selective sigma-1 receptor agonist properties,and its associated mechanisms and targets in traumatic brain injury.Behavioral experiments to assess functional deficits were followed by assessment of neuronal damage through histological analyses and examination of blood-brain barrier permeability and brain edema.Next,we investigated the antioxidative effects of YL-0919 by assessing the levels of traditional markers of oxidative stress in vivo in mice and in vitro in HT22 cells.Finally,the targeted action of YL-0919 was verified by employing a sigma-1 receptor antagonist(BD-1047).Our findings demonstrated that YL-0919 markedly improved deficits in motor function and spatial cognition on day 3 post traumatic brain injury,while also decreasing neuronal mortality and reversing blood-brain barrier disruption and brain edema.Furthermore,YL-0919 effectively combated oxidative stress both in vivo and in vitro.The protective effects of YL-0919 were partially inhibited by BD-1047.These results indicated that YL-0919 relieved impairments in motor and spatial cognition by restraining oxidative stress,a neuroprotective effect that was partially reversed by the sigma-1 receptor antagonist BD-1047.YL-0919 may have potential as a new treatment for traumatic brain injury.展开更多
Although microglial polarization and neuroinflammation are crucial cellular responses after traumatic brain injury,the fundamental regulatory and functional mechanisms remain insufficiently understood.As potent anti-i...Although microglial polarization and neuroinflammation are crucial cellular responses after traumatic brain injury,the fundamental regulatory and functional mechanisms remain insufficiently understood.As potent anti-inflammato ry agents,the use of glucoco rticoids in traumatic brain injury is still controversial,and their regulatory effects on microglial polarization are not yet known.In the present study,we sought to determine whether exacerbation of traumatic brain injury caused by high-dose dexamethasone is related to its regulatory effects on microglial polarization and its mechanisms of action.In vitro cultured BV2 cells and primary microglia and a controlled cortical impact mouse model were used to investigate the effects of dexamethasone on microglial polarization.Lipopolysaccharide,dexamethasone,RU486(a glucocorticoid receptor antagonist),and ruxolitinib(a Janus kinase 1 antagonist)were administered.RNA-sequencing data obtained from a C57BL/6 mouse model of traumatic brain injury were used to identify potential targets of dexamethasone.The Morris water maze,quantitative reverse transcription-polymerase chain reaction,western blotting,immunofluorescence and confocal microscopy analysis,and TUNEL,Nissl,and Golgi staining were performed to investigate our hypothesis.High-throughput sequencing results showed that arginase 1,a marker of M2 microglia,was significantly downregulated in the dexamethasone group compared with the traumatic brain injury group at3 days post-traumatic brain injury.Thus dexamethasone inhibited M1 and M2 microglia,with a more pronounced inhibitory effect on M2microglia in vitro and in vivo.Glucocorticoid receptor plays an indispensable role in microglial polarization after dexamethasone treatment following traumatic brain injury.Additionally,glucocorticoid receptor activation increased the number of apoptotic cells and neuronal death,and also decreased the density of dendritic spines.A possible downstream receptor signaling mechanism is the GR/JAK1/STAT3 pathway.Overactivation of glucocorticoid receptor by high-dose dexamethasone reduced the expression of M2 microglia,which plays an antiinflammatory role.In contrast,inhibiting the activation of glucocorticoid receptor reduced the number of apoptotic glia and neurons and decreased the loss of dendritic spines after traumatic brain injury.Dexamethasone may exe rt its neurotoxic effects by inhibiting M2 microglia through the GR/JAK1/STAT3 signaling pathway.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
Introduction: Foot amputation in a diabetic patient is a real public health problem due to its functional and psychological repercussions. The objective was to study the factors associated with amputation in patients ...Introduction: Foot amputation in a diabetic patient is a real public health problem due to its functional and psychological repercussions. The objective was to study the factors associated with amputation in patients monitored for a diabetic foot in the internal medicine hospitalization of the Abass Ndao University Hospital Center (CHU) in Dakar. Methods: This was a retrospective, descriptive and analytical study conducted from the records of hospitalized patients over a 24-month period. The analysis included a descriptive phase, followed by a bivariate phase completed by logistic modeling following a descending procedure. Results: Of 1499 hospitalized patients, 224 cases had diabetic foot (14.9%). Among the cases of diabetic foot, 198 patients met the inclusion criteria. Their mean age was 61.7 ± 11.3 years, the sex ratio (M/F) was 1.2. Other associated cardiovascular risk factors were high blood pressure (54.0% 107 cases), and smoking (10.9% 21 cases). A history of lower limb amputation was found in 21.2% (42 cases). It was type 2 diabetes in 184 cases (92.9%) and the mean blood sugar was 2.7 ± 1.3 g/l. Chronic complications included neuropathy in 112 cases (78.3%), arteriopathy in 172 cases (86.9%), and chronic kidney disease in 167 cases (84.4%). The mean consultation time was 47.6 days. The main lesions were gangrene (64.6%), ulcer (24.7%), phlegmon (5.6%), and necrotizing fasciitis (5.1%). According to the University of Texas classification, patients presented with a stage D lesion (86.4%), grade 3 (51.0%). The hospital prevalence of amputation was 57.6% (114 cases), including major amputation in 55.1% (109 cases). The mortality rate was 36.4% (72 cases). Risk factors for amputation were peripheral arterial disease (ORa = 4.96 [1.33 - 18.43] p = 0.017), foot gangrene (Ora = 3.16 [1.24 - 8.04] p = 0.016) and Texas classification grade 3 (ORa = 17.49 [1.67 - 190] p = 0.019). Conclusion: The prevalence of foot and amputations remains a health problem. Reducing amputations will necessarily require strengthening prevention through education and early monitoring of diabetic patients.展开更多
文摘BACKGROUND Malignant fibrous histiocytoma(MFH)is one of the most common soft tissue sarcomas among adults.It is characterized by large size,high grade,and biological aggressiveness.There are many reports of MFH after local stimulation,such as bone fracture,implants,and chronic osteomyelitis.In this paper,we report a patient who developed MFH 6 years after amputation,suggesting that wound healing and mechanical force play a role in the local stimulation of this disease.CASE SUMMARY A 66-year-old man complained of persistent pain in his residual mid-thigh.He had undergone amputation surgery due to a traffic accident 6 years prior.Physical examination showed tenderness but no abnormalities in appearance.Xray radiographs and magnetic resonance imaging supported the diagnosis of a tumor,and a biopsy confirmed that the lesion was MFH.The patient received neoadjuvant chemotherapy and left hip disarticulation.During the 6-mo followup,there were no symptoms of recurrence.CONCLUSION Postsurgery MFH has been reported before,and many studies have attributed it to the biological effects of implants.Our case report shows that this disease can develop without an implant and thus highlights the importance of local stimulation.The wound-healing process and mechanical force can both promote this tumor,but whether they directly cause MFH needs further investigation.
文摘Background:Limb loss has a drastic impact on a patient’s life.Severe trauma to the extremities is common in current military conflicts.Among other aspects,"life before limb"damage control surgery hinders immediate replantation within the short post-traumatic timeframe,which is limited in part by the ischemic time for successful replantation.Ex vivo limb perfusion is currently being researched in animal models and shows promising results for its application in human limb replantation and allotransplantation.Presentation of the hypothesis:The current lack of replantation possibilities in military operations with high rates of amputation can be addressed with the development of a portable ex vivo limb perfusion device,as there are several opportunities present with the introduction of this technique on the horizon.We hypothesize that ex vivo limb perfusion will enable overcoming the critical ischemic time,provide surgical opportunities such as preparation of the stump and limb,allow for spare-part surgery,enable rigorous antibiotic treatment of the limb,reduce ischemiareperfusion injuries,enable a tissue function assessment before replantation,and enable the development of large limb transplant programs.Testing the hypothesis:Data from in vivo studies in porcine models are limited by the relatively short perfusion time of 24 h.In the military setting,notably longer perfusion times need to be realized.Therefore,future animal studies must focus especially on long-term perfusion,since this represents the military setting,considering the time for stabilization of the patient until evacuation to a tertiary treatment center.Implications of the hypothesis:The development and clinical introduction of ex vivo limb perfusion in the military setting could lead to a drastic reduction in the number of limb amputations among service members.Ex vivo limb perfusion enables replantation surgery in Role 4 facilities and changes the clinical setting from a highly urgent,lifethreatening situation to a highly methodical,well-prepared starting point for optimal treatment of the wounded service member.With its introduction,the principle of"life before limb"will change to"life before limb before elective replantation/allotransplantation after ex vivo limb perfusion".
文摘BACKGROUND To report the application of supermicroscopy combined with arterio-venolization without venous anastomosis for replantation of digits following traumatic amputation in young children.CASE SUMMARY In March 2016,we treated two children aged 2 years and 7 years with traumatic digit amputation,no venous anastomosis,and bilateral digital inherent arteries on the palmar side.Supermicroscopy combined with an arteriovenous technique was adopted to improve the replantation surgery.Postoperative management involved auxiliary treatments such as anticoagulation,composure,antiinflammatory drugs,and insulation.After treatment,the amputated fingers survived completely without major complications,with good recovery.CONCLUSION Supermicroscopy combined with arterio-venolization is a safe and effective approach to treat traumatic digit amputation in young children without venous anastomosis.
基金Department of Defense Joint Program Committee(JPC-6)
文摘Background: In combat operations, patients with traumatic injuries require expeditious evacuation to improve survival. Studies have shown that long transport times are associated with increased morbidity and mortality. Limited data exist on the influence of transport time on patient outcomes with specific injury types. The objective of this study was to determine the impact of the duration of time from the initial request for medical evacuation to arrival at a medical treatment facility on morbidity and mortality in casualties with traumatic extremity amputation and noncompressible torso injury(NCTI).Methods: We completed a retrospective review of MEDEVAC patient care records for United States military personnel who sustained traumatic amputations and NCTI during Operation Enduring Freedom between January 2011 and March 2014. We grouped patients as traumatic amputation and NCTI(AMP+NCTI), traumatic amputation only(AMP),and neither AMP nor NCTI(Non-AMP/NCTI). Analysis was performed using chi-squared tests, Fisher's exact tests,Cochran-Armitage Trend tests, Shapiro-Wilks tests, Wilcoxon and Kruskal-Wallis techniques and Cox proportional hazards regression modeling.Results: We reviewed 1267 records, of which 669 had an injury severity score(ISS) of 10 or greater and were included in the analysis. In the study population, 15.5% sustained only amputation injuries(n=104, AMP only), 10.8% sustained amputation and NCTI(n=72, AMP+NCTI), and 73.7% did not sustain either an amputation or an NCTI(n=493,Non-AMP/NCTI). AMP+NCTI had the highest mortality(16.7%) with transport time greater than 60 min. While the AMP+NCTI group had decreasing survival with longer transport times, AMP and Non-AMP/NCTI did not exhibit the same trend.Conclusions: A decreased transport time from the point of injury to a medical treatment facility was associated with decreased mortality in patients who suffered a combination of amputation injury and NCTI. No significant association between transport time and outcomes was found in patients who did not sustain NCTI. Priority for rapid evacuation of combat casualties should be given to those with NCTI.
文摘Dear Editor,Chronic pain is a significant concern after major lower limb amputations that often preclude prosthetic fitting,decrease ambulation,and impact the quality of life[1,2].In the last decade,targeted muscle reinnervation(TMR)has been proposed as a surgical strategy for treating or preventing symptomatic neuromas and phantomlimb phenomena in major amputees[1].This technique involves the transfer of an amputated mixed-motor and sensory nerve to a nearby recipient motor nerve[1,2].Unlike most surgical strategies that aim to hide or protect the neuroma,TMR gives the amputated nerves“somewhere to go and something to do”[2].In a randomized clinical trial on neuroma and phantom pain,Dumanian et al.[1]demonstrated that TMR reduces amputationrelated chronic pain at 1-year post-intervention when compared with the excision and muscle-burying technique,which remains the current gold standard.Valerio et al.[2]also proposed applying TMR at the time of major limb amputation for preventing chronic pain and found that TMR patients experienced less residual limb pain(RLP)and phantom limb pain(PLP)when compared with untreated amputee controls.
文摘Circumcision remains a frequently performed surgical procedure and could be associated with various complications, ranging from mild to catastrophic. Penile amputation is a rare and severe complication usually complex and challenging to manage. We describe three cases of penile amputation injuries following circumcision referred within a week at the urological service of the Yaoundé Central Hospital. The first case was a 5-year-old who had complete penile amputation during circumcision by a nurse assistant at a rural health center. The second was a 7-year-old boy who sustained total penile glans amputation while undergoing circumcision by a nurse under local anesthesia at a rural health facility. The third involved a 6-year-old who had total penile amputation with loss of the amputated stump during circumcision by a traditional practitioner at home. Non-microsurgical penile re-implantations were done with diverse outcomes. The preservation of the amputated stump, the ischemic time and the severity of injury are factors affecting surgical outcome. The aim of this study is to evaluate our management experience and outcome of penile amputation injuries in resource-limited settings. Microsurgical replantation remains the gold standard in the management of penile amputation injuries. However, in resource-limited settings macroscopic replantation could be used as an alternative remedy to salvage the amputated penis.
文摘Objective: to explore the role of narrative breast-feeding in clinical nursing of traumatic amputees. Methods: from January 2019 to January 2019, 68 amputees were divided into control group and observation group with 34 cases in each group. The control group received routine orthopedic hospitalization, while the observation group received narrative hospitalization on the basis of routine hospitalization. Anxiety, depression and quality of life scale were used to compare the patients anxiety, depression and quality of life. The narrative results of lactation, anxiety, depression and quality of life in the observation group were better than those in the control group (p0.05). The narrative conclusion of breast feeding can improve the negative emotions of traumatic amputees, promote their self-management and improve their quality of life.
文摘Traumatic brain injury, chronic traumatic encephalopathy, and Alzheimer's disease are three distinct neurological disorders that share common pathophysiological mechanisms involving neuroinflammation. One sequela of neuroinflammation includes the pathologic hyperphosphorylation of tau protein, an endogenous microtubule-associated protein that protects the integrity of neuronal cytoskeletons. Tau hyperphosphorylation results in protein misfolding and subsequent accumulation of tau tangles forming neurotoxic aggregates. These misfolded proteins are characteristic of traumatic brain injury, chronic traumatic encephalopathy, and Alzheimer's disease and can lead to downstream neuroinflammatory processes, including assembly and activation of the inflammasome complex. Inflammasomes refer to a family of multimeric protein units that, upon activation, release a cascade of signaling molecules resulting in caspase-induced cell death and inflammation mediated by the release of interleukin-1β cytokine. One specific inflammasome, the NOD-like receptor protein 3, has been proposed to be a key regulator of tau phosphorylation where it has been shown that prolonged NOD-like receptor protein 3 activation acts as a causal factor in pathological tau accumulation and spreading. This review begins by describing the epidemiology and pathophysiology of traumatic brain injury, chronic traumatic encephalopathy, and Alzheimer's disease. Next, we highlight neuroinflammation as an overriding theme and discuss the role of the NOD-like receptor protein 3 inflammasome in the formation of tau deposits and how such tauopathic entities spread throughout the brain. We then propose a novel framework linking traumatic brain injury, chronic traumatic encephalopathy, and Alzheimer's disease as inflammasomedependent pathologies that exist along a temporal continuum. Finally, we discuss potential therapeutic targets that may intercept this pathway and ultimately minimize long-term neurological decline.
文摘BACKGROUND Traumatic fractures are mainly caused by various exogenous traumatic events,which not only damage patients’physical health but also affect their psychological state and aggravate stress responses.AIM To analyze the influencing factors of psychological resilience of patients with traumatic fractures and the effect of psychological resilience on posttraumatic growth(PTG).METHODS This study included 188 patients with traumatic fractures admitted to the First People’s Hospital of Shangqiu from November 2022 to November 2023.The participants were categorized based on the patient’s psychological resilience assessed by the Connor-Davidson Resilience Scale(CD-RISC)into the better resilience group(CD-RISC score≥60 points,n=80)and the poor resilience group(CD-RISC score<60 points,n=108).Patients’sleep quality was assessed with the Pittsburgh Sleep Quality Index(PSQI).The identification of the influencing factors of psychological resilience in patients with traumatic fractures was realized by binary Logistic regression(with factors such as sex,age,injury cause,trauma severity,fracture site,personality,and PSQI included for analysis).The determination of the PTG status of all participants used the Chinese version of the Posttraumatic Growth Inventory(C-PTGI).Furthermore,a Spearman correlation analysis was conducted to analyze the association between psychological resilience and PTG.RESULTS The psychological resilience of patients with traumatic fractures was related to age,sex,trauma severity,and personality.The better resilience group demonstrated statistically lower PSQI scores than the poor resilience group(P<0.05).The Logistic regression analysis revealed sex,age,trauma severity,personality,and sleep quality as influencing factors of CD-RISC scores in patients with traumatic fractures(all P<0.05).The score of each C-PTGI dimension and the total score(relating to others,new possibilities,personal strength,spiritual change,and appreciation of life)were higher in the better resilience group than in the poor resilience group(all P<0.05).Spearman correlation analysis indicated a positive association of the CD-RISC score in patients with traumatic fractures with the scores of all dimensions of C-PTGI and the total C-PTGI score(all P<0.05).CONCLUSION The factors influencing the psychological resilience of patients with traumatic fractures include age,sex,trauma severity,personality,and sleep quality,and psychological resilience is closely associated with PTG.
文摘BACKGROUND Traumatic subdural effusion is a common complication of traumatic brain injury,especially after decompressive craniectomy(DC).For neurosurgeons,early diagnosis and timely treatment are particularly important,which can help improve patient prognosis and enhance quality of life.CASE SUMMARY A 47 year old male underwent DC for traumatic brain herniation.After surgery,he developed stubborn subdural effusion(SDE)on the contralateral side and underwent multiple subdural drilling and drainage surgeries,but only temporarily improved the patient’s symptoms.After the final cranioplasty,the contralateral SDE completely disappeared.The patient did not experience any new contralateral neurological dysfunction,and the Glasgow prognostic score was 11 points(E4V1M6).CONCLUSION For neurosurgeons,accurate assessment of the condition is necessary when treating patients with stubborn SDE after DC surgery,and timely cranioplasty can be performed to avoid multiple surgeries.This is a safe and effective surgical method for treating traumatic subdural effusion.
基金funded by the Science and Technology Research Program of Chongqing Municipal Education Commission(KJZD-K202301105,KJQN202201107)the Scienti¯c and Technological Transformative Program of Chongqing Banan District(KY202208161124020).
文摘Traumatic penumbra(TP)is a region with recoverable potential around the primary lesion of brain injury.Rapid and accurate imaging for identifying TP is essential for treating traumatic brain injury(TBI).In this study,we first established traumatic brain injuries(TBIs)in rats using a modified Feeney method,followed by label-free imaging of brain tissue sections with multiphoton fluorescence microscopy.The results showed that the technique effectively imaged normal and traumatic brain tissues,and revealed pathological features such as extracellular matrix changes,vascular cell proliferation,and intracellular edema in the traumatic penumbra.Compared with normal brain tissue,the extracellular matrix in the TP was sparse,cells were disorganized,and hyperplastic vascular cells emitted higher two-photon excited fluorescence(TPEF)signals.Our research demonstrates the potential of multiphoton fluorescence technology in the rapid diagnosis and therapeutic evaluation of TBI.
文摘Traumatic carotid-cavernous arteriovenous fistula(TCCAVF)is a rare but severe cerebrovascular disorder,often resulting from head trauma with temporal bone fractures.The pathogenesis involves vessel wall injury due to traction,frequently associated with fractures near the middle meningeal artery.This case highlights the typical clinical presentation,diagnostic approaches,and therapeutic management of TCCAVF,emphasizing the challenges in treating this condition.Transcatheter embolization proved effective in occluding the fistula,underscoring its role as a key intervention for traumatic meningeal arteriovenous fistulas.
文摘Obese individuals who subsequently sustain a traumatic brain injury(TBI)exhibit worsened outcomes including longer periods of rehabilitation(Eagle et al.,2023).In obese individuals,prolonged symptomology is associated with increased levels of circulato ry pro-inflammatory marke rs up to 1 year postTBI(Eagle et al.,2023).
基金FEDER Prostem Research Project,No.1510614(Wallonia DG06)the F.R.S.-FNRS Epiforce Project,No.T.0092.21+4 种基金the F.R.S.-FNRS Cell Squeezer Project,No.J.0061.23the F.R.S.-FNRS Optopattern Project,No.U.NO26.22the Interreg MAT(T)ISSE Project,which is financially supported by Interreg France-Wallonie-Vlaanderen(Fonds Européen de Développement Régional,FEDER-ERDF)Programme Wallon d’Investissement Région Wallone pour les instruments d’imagerie(INSTIMAG UMONS#1910169)support from the European Research Council(ERC)under the European Union’s Horizon 2020 research and innovation programme(AdG grant agreement no.834317,Fueling Transport,PI Frédéric Saudou)。
文摘Advanced microsystems in traumatic brain injury research:Traumatic brain injury(TBI)results from a mechanical insult to the brain,leading to neuronal and axonal damage and subsequently causing a secondary injury.Within minutes of TBI,a neuroinflammatory response is triggered,driven by intricate molecular and cellular inflammatory processes.
基金supported by the National Natural Science Foundation of China,No.82174112(to PZ)Science and Technology Project of Haihe Laboratory of Modern Chinese Medicine,No.22HHZYSS00015(to PZ)State-Sponsored Postdoctoral Researcher Program,No.GZC20231925(to LN)。
文摘Traumatic brain injury is a prevalent disorder of the central nervous system.In addition to primary brain parenchymal damage,the enduring biological consequences of traumatic brain injury pose long-term risks for patients with traumatic brain injury;however,the underlying pathogenesis remains unclear,and effective intervention methods are lacking.Intestinal dysfunction is a significant consequence of traumatic brain injury.Being the most densely innervated peripheral tissue in the body,the gut possesses multiple pathways for the establishment of a bidirectional“brain-gut axis”with the central nervous system.The gut harbors a vast microbial community,and alterations of the gut niche contribute to the progression of traumatic brain injury and its unfavorable prognosis through neuronal,hormonal,and immune pathways.A comprehensive understanding of microbiota-mediated peripheral neuroimmunomodulation mechanisms is needed to enhance treatment strategies for traumatic brain injury and its associated complications.We comprehensively reviewed alterations in the gut microecological environment following traumatic brain injury,with a specific focus on the complex biological processes of peripheral nerves,immunity,and microbes triggered by traumatic brain injury,encompassing autonomic dysfunction,neuroendocrine disturbances,peripheral immunosuppression,increased intestinal barrier permeability,compromised responses of sensory nerves to microorganisms,and potential effector nuclei in the central nervous system influenced by gut microbiota.Additionally,we reviewed the mechanisms underlying secondary biological injury and the dynamic pathological responses that occur following injury to enhance our current understanding of how peripheral pathways impact the outcome of patients with traumatic brain injury.This review aimed to propose a conceptual model for future risk assessment of central nervous system-related diseases while elucidating novel insights into the bidirectional effects of the“brain-gut-microbiota axis.”
基金supported by the Fundamental Research Program of Shanxi Province of China,No.20210302124277the Science Foundation of Shanxi Bethune Hospital,No.2021YJ13(both to JW)。
文摘Repetitive traumatic brain injury impacts adult neurogenesis in the hippocampal dentate gyrus,leading to long-term cognitive impairment.However,the mechanism underlying this neurogenesis impairment remains unknown.In this study,we established a male mouse model of repetitive traumatic brain injury and performed long-term evaluation of neurogenesis of the hippocampal dentate gyrus after repetitive traumatic brain injury.Our results showed that repetitive traumatic brain injury inhibited neural stem cell proliferation and development,delayed neuronal maturation,and reduced the complexity of neuronal dendrites and spines.Mice with repetitive traumatic brain injuryalso showed deficits in spatial memory retrieval.Moreover,following repetitive traumatic brain injury,neuroinflammation was enhanced in the neurogenesis microenvironment where C1q levels were increased,C1q binding protein levels were decreased,and canonical Wnt/β-catenin signaling was downregulated.An inhibitor of C1 reversed the long-term impairment of neurogenesis induced by repetitive traumatic brain injury and improved neurological function.These findings suggest that repetitive traumatic brain injury–induced C1-related inflammation impairs long-term neurogenesis in the dentate gyrus and contributes to spatial memory retrieval dysfunction.
基金supported by the National Natural Science Foundation of China,Nos.82204360(to HM)and 82270411(to GW)National Science and Technology Innovation 2030 Major Program,No.2021ZD0200900(to YL)。
文摘Traumatic brain injury involves complex pathophysiological mechanisms,among which oxidative stress significantly contributes to the occurrence of secondary injury.In this study,we evaluated hypidone hydrochloride(YL-0919),a self-developed antidepressant with selective sigma-1 receptor agonist properties,and its associated mechanisms and targets in traumatic brain injury.Behavioral experiments to assess functional deficits were followed by assessment of neuronal damage through histological analyses and examination of blood-brain barrier permeability and brain edema.Next,we investigated the antioxidative effects of YL-0919 by assessing the levels of traditional markers of oxidative stress in vivo in mice and in vitro in HT22 cells.Finally,the targeted action of YL-0919 was verified by employing a sigma-1 receptor antagonist(BD-1047).Our findings demonstrated that YL-0919 markedly improved deficits in motor function and spatial cognition on day 3 post traumatic brain injury,while also decreasing neuronal mortality and reversing blood-brain barrier disruption and brain edema.Furthermore,YL-0919 effectively combated oxidative stress both in vivo and in vitro.The protective effects of YL-0919 were partially inhibited by BD-1047.These results indicated that YL-0919 relieved impairments in motor and spatial cognition by restraining oxidative stress,a neuroprotective effect that was partially reversed by the sigma-1 receptor antagonist BD-1047.YL-0919 may have potential as a new treatment for traumatic brain injury.
基金supported by research grants from the Ningbo Science and Technology Plan Project,No.2022Z143hezuo(to BL)the National Natural Science Foundation of China,No.82201520(to XD)。
文摘Although microglial polarization and neuroinflammation are crucial cellular responses after traumatic brain injury,the fundamental regulatory and functional mechanisms remain insufficiently understood.As potent anti-inflammato ry agents,the use of glucoco rticoids in traumatic brain injury is still controversial,and their regulatory effects on microglial polarization are not yet known.In the present study,we sought to determine whether exacerbation of traumatic brain injury caused by high-dose dexamethasone is related to its regulatory effects on microglial polarization and its mechanisms of action.In vitro cultured BV2 cells and primary microglia and a controlled cortical impact mouse model were used to investigate the effects of dexamethasone on microglial polarization.Lipopolysaccharide,dexamethasone,RU486(a glucocorticoid receptor antagonist),and ruxolitinib(a Janus kinase 1 antagonist)were administered.RNA-sequencing data obtained from a C57BL/6 mouse model of traumatic brain injury were used to identify potential targets of dexamethasone.The Morris water maze,quantitative reverse transcription-polymerase chain reaction,western blotting,immunofluorescence and confocal microscopy analysis,and TUNEL,Nissl,and Golgi staining were performed to investigate our hypothesis.High-throughput sequencing results showed that arginase 1,a marker of M2 microglia,was significantly downregulated in the dexamethasone group compared with the traumatic brain injury group at3 days post-traumatic brain injury.Thus dexamethasone inhibited M1 and M2 microglia,with a more pronounced inhibitory effect on M2microglia in vitro and in vivo.Glucocorticoid receptor plays an indispensable role in microglial polarization after dexamethasone treatment following traumatic brain injury.Additionally,glucocorticoid receptor activation increased the number of apoptotic cells and neuronal death,and also decreased the density of dendritic spines.A possible downstream receptor signaling mechanism is the GR/JAK1/STAT3 pathway.Overactivation of glucocorticoid receptor by high-dose dexamethasone reduced the expression of M2 microglia,which plays an antiinflammatory role.In contrast,inhibiting the activation of glucocorticoid receptor reduced the number of apoptotic glia and neurons and decreased the loss of dendritic spines after traumatic brain injury.Dexamethasone may exe rt its neurotoxic effects by inhibiting M2 microglia through the GR/JAK1/STAT3 signaling pathway.
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.
文摘Introduction: Foot amputation in a diabetic patient is a real public health problem due to its functional and psychological repercussions. The objective was to study the factors associated with amputation in patients monitored for a diabetic foot in the internal medicine hospitalization of the Abass Ndao University Hospital Center (CHU) in Dakar. Methods: This was a retrospective, descriptive and analytical study conducted from the records of hospitalized patients over a 24-month period. The analysis included a descriptive phase, followed by a bivariate phase completed by logistic modeling following a descending procedure. Results: Of 1499 hospitalized patients, 224 cases had diabetic foot (14.9%). Among the cases of diabetic foot, 198 patients met the inclusion criteria. Their mean age was 61.7 ± 11.3 years, the sex ratio (M/F) was 1.2. Other associated cardiovascular risk factors were high blood pressure (54.0% 107 cases), and smoking (10.9% 21 cases). A history of lower limb amputation was found in 21.2% (42 cases). It was type 2 diabetes in 184 cases (92.9%) and the mean blood sugar was 2.7 ± 1.3 g/l. Chronic complications included neuropathy in 112 cases (78.3%), arteriopathy in 172 cases (86.9%), and chronic kidney disease in 167 cases (84.4%). The mean consultation time was 47.6 days. The main lesions were gangrene (64.6%), ulcer (24.7%), phlegmon (5.6%), and necrotizing fasciitis (5.1%). According to the University of Texas classification, patients presented with a stage D lesion (86.4%), grade 3 (51.0%). The hospital prevalence of amputation was 57.6% (114 cases), including major amputation in 55.1% (109 cases). The mortality rate was 36.4% (72 cases). Risk factors for amputation were peripheral arterial disease (ORa = 4.96 [1.33 - 18.43] p = 0.017), foot gangrene (Ora = 3.16 [1.24 - 8.04] p = 0.016) and Texas classification grade 3 (ORa = 17.49 [1.67 - 190] p = 0.019). Conclusion: The prevalence of foot and amputations remains a health problem. Reducing amputations will necessarily require strengthening prevention through education and early monitoring of diabetic patients.
