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
Border-associated macrophages are located at the interface between the brain and the periphery, including the perivascular spaces, choroid plexus, and meninges. Until recently, the functions of border-associated macro...Border-associated macrophages are located at the interface between the brain and the periphery, including the perivascular spaces, choroid plexus, and meninges. Until recently, the functions of border-associated macrophages have been poorly understood and largely overlooked. However, a recent study reported that border-associated macrophages participate in stroke-induced inflammation, although many details and the underlying mechanisms remain unclear. In this study, we performed a comprehensive single-cell analysis of mouse border-associated macrophages using sequencing data obtained from the Gene Expression Omnibus(GEO) database(GSE174574 and GSE225948). Differentially expressed genes were identified, and enrichment analysis was performed to identify the transcription profile of border-associated macrophages. CellChat analysis was conducted to determine the cell communication network of border-associated macrophages. Transcription factors were predicted using the ‘pySCENIC' tool. We found that, in response to hypoxia, borderassociated macrophages underwent dynamic transcriptional changes and participated in the regulation of inflammatory-related pathways. Notably, the tumor necrosis factor pathway was activated by border-associated macrophages following ischemic stroke. The pySCENIC analysis indicated that the activity of signal transducer and activator of transcription 3(Stat3) was obviously upregulated in stroke, suggesting that Stat3 inhibition may be a promising strategy for treating border-associated macrophages-induced neuroinflammation. Finally, we constructed an animal model to investigate the effects of border-associated macrophages depletion following a stroke. Treatment with liposomes containing clodronate significantly reduced infarct volume in the animals and improved neurological scores compared with untreated animals. Taken together, our results demonstrate comprehensive changes in border-associated macrophages following a stroke, providing a theoretical basis for targeting border-associated macrophages-induced neuroinflammation in stroke treatment.展开更多
BACKGROUND Ischemic stroke is one of the leading global causes of disability and death.Despite advances in modern medical technology that improve acute treatment and rehabilitation measures,post-stroke anxiety and dep...BACKGROUND Ischemic stroke is one of the leading global causes of disability and death.Despite advances in modern medical technology that improve acute treatment and rehabilitation measures,post-stroke anxiety and depression(PSD)do not receive sufficient attention.AIM To systematically evaluate risk factors and early identification markers for PSD for more precise screening and intervention strategies in clinical practice.METHODS This retrospective study analyzed clinical data from 112 patients with ischemic stroke admitted between January 2022 and December 2024.Based on assessments using the Hamilton Rating Scale for Anxiety(HAMA)and Hamilton Rating Scale for Depression(HAMD)at 2 weeks(±3 days)post-stroke,patients were classified into the PSD group(HAMA≥7 and/or HAMD≥7)and the non-PSD group(HAMA<7 and HAMD<7).Observation indicators included psychological assessment,demographic and clinical characteristics,stroke-related clinical indicators,neuroimaging assessments,and laboratory biomarkers.Multivariate logistic regression analysis was used to identify independent risk factors for PSD,and receiver operating characteristic curve analysis was used to evaluate the diagnostic value of potential biomarkers.RESULTS Of the 112 patients,46(41.1%)were diagnosed with PSD.Multivariate analysis identified five independent risk factors:Female gender[Odds ratio(OR)=2.32,95%confidence interval(CI):1.56-3.45],history of mental disorders prior to stroke(OR=3.17,95%CI:1.89-5.32),infarct location in the frontal lobe or limbic system(OR=2.86,95%CI:1.73-4.71),stroke severity with National Institutes of Health Stroke Scale≥8 at admission(OR=2.54,95%CI:1.62-3.99),and low social support(Social Support Rating Scale<35,OR=2.18,95%CI:1.42-3.36).Subgroup analysis showed that depression patients more commonly had left hemisphere lesions(68.4%vs 45.2%),while anxiety patients more frequently presented with right hemisphere lesions(59.5%vs 39.5%).The PSD group exhibited larger infarct volumes(8.7 cm^(3) vs 5.3 cm^(3)),more severe white matter hyperintensities,and more pronounced frontal lobe atrophy.Analysis of inflammatory markers showed significantly elevated levels of interleukin-6(7.8 pg/mL vs 4.5 pg/mL)and tumor necrosis factor-alpha(15.6 pg/mL vs 9.8 pg/mL)in the PSD group,while hypothalamicpituitary-adrenal axis function assessment revealed higher cortisol levels(386.5±92.3 nmol/L vs 328.7±75.6 nmol/L)and flattened diurnal rhythm in the PSD group.CONCLUSION PSD is a complex neuropsychiatric consequence of stroke involving disruption of the frontal-limbic circuitry,neuroinflammatory responses,and dysfunction of the hypothalamic-pituitary-adrenal axis.展开更多
Strokes include both ischemic stroke,which is mediated by a blockade or reduction in the blood supply to the brain,and hemorrhagic stroke,which comprises intracerebral hemorrhage and subarachnoid hemorrhage and is cha...Strokes include both ischemic stroke,which is mediated by a blockade or reduction in the blood supply to the brain,and hemorrhagic stroke,which comprises intracerebral hemorrhage and subarachnoid hemorrhage and is characterized by bleeding within the brain.Stroke is a lifethreatening cerebrovascular condition characterized by intricate pathophysiological mechanisms,including oxidative stress,inflammation,mitochondrial dysfunction,and neuronal injury.Critical transcription factors,such as nuclear factor erythroid 2-related factor 2 and nuclear factor kappa B,play central roles in the progression of stroke.Nuclear factor erythroid 2-related factor 2 is sensitive to changes in the cellular redox status and is crucial in protecting cells against oxidative damage,inflammatory responses,and cytotoxic agents.It plays a significant role in post-stroke neuroprotection and repair by influencing mitochondrial function,endoplasmic reticulum stress,and lysosomal activity and regulating metabolic pathways and cytokine expression.Conversely,nuclear factor-kappa B is closely associated with mitochondrial dysfunction,the generation of reactive oxygen species,oxidative stress exacerbation,and inflammation.Nuclear factor-kappa B contributes to neuronal injury,apoptosis,and immune responses following stroke by modulating cell adhesion molecules and inflammatory mediators.The interplay between these pathways,potentially involving crosstalk among various organelles,significantly influences stroke pathophysiology.Advancements in single-cell sequencing and spatial transcriptomics have greatly improved our understanding of stroke pathogenesis and offer new opportunities for the development of targeted,individualized,cell typespecific treatments.In this review,we discuss the mechanisms underlying the involvement of nuclear factor erythroid 2-related factor 2 and nuclear factor-kappa B in both ischemic and hemorrhagic stroke,with an emphasis on their roles in oxidative stress,inflammation,and neuroprotection.展开更多
Nerve trauma commonly results in chronic neuropathic pain. This is by triggering the release of proinflammatory mediators from local and invading cells that induce inflammation and nociceptive neuron hyperexcitability...Nerve trauma commonly results in chronic neuropathic pain. This is by triggering the release of proinflammatory mediators from local and invading cells that induce inflammation and nociceptive neuron hyperexcitability. Even without apparent inflammation, injury sites are associated with increased inflammatory markers. This review focuses on how it might be possible to reduce neuropathic pain by reducing inflammation. Physiologically, pain is resolved by a combination of the out-migration of pro-inflammatory cells from the injury site, the down-regulation of the genes underlying the inflammation, up-regulating genes for anti-inflammatory mediators, and reducing nociceptive neuron hyperexcitability. While various techniques reduce chronic neuropathic pain, the best are effective on < 50% of patients, no technique reliably or permanently eliminates neuropathic pain. This is because most techniques are predominantly aimed at reducing pain, not inflammation. In addition, while single factors reduce pain, increasing evidence indicates significant and longer-lasting pain relief requires multiple factors acting simultaneously. Therefore, it is not surprising that extensive data indicate that the application of platelet-rich plasma provides more significant and longer-lasting pain suppression than other techniques, although its analgesia is neither complete nor permanent. However, several case reports indicate that platelet-rich plasma can induce permanent neuropathic pain elimination when the platelet concentration is significantly increased and is applied to longer nerve lengths. This review examines the primary triggers of the development and maintenance of neuropathic pain and techniques that reduce chronic neuropathic pain. The application of plateletrich plasma holds great promise for providing complete and permanent chronic neuropathic pain elimination.展开更多
BACKGROUND Post-transplant tertiary hyperparathyroidism(PT-tHPT)is a well-recognized complication following kidney transplantation,characterized by persistent excessive secretion of parathyroid hormone(PTH)despite imp...BACKGROUND Post-transplant tertiary hyperparathyroidism(PT-tHPT)is a well-recognized complication following kidney transplantation,characterized by persistent excessive secretion of parathyroid hormone(PTH)despite improved renal function.It is potentially associated with an increased risk of cardiovascular events,renal osteodystrophy,pathologic fractures,graft loss,and mortality.AIM To evaluate the incidence,risk factors,and outcomes of PT-tHPT amongst kidney transplant recipients.METHODS A total of 887 transplant recipients who underwent transplantation between 2000 and 2020 were evaluated.Univariable and multivariable logistic regression was performed to determine the predictors of tertiary hyperparathyroidism.Graft and recipient outcomes were assessed using multivariable Cox regression.A separate multivariable Cox regression was performed to determine the effect of treatment strategies on outcomes.RESULTS PT-tHPT,defined as elevated PTH(>65 ng/L)and persistent hypercalcemia(>2.60 mmol/L),was diagnosed in 14%of recipients.Risk factors for PT-tHPT included older age[odds ratio(OR)=1.36,P<0.001],Asian ethnicity(OR=0.33,P=0.006),total ischemia time(OR=1.03,P=0.048 per hour),pre-transplant serum calcium(OR=1.38,P<0.001)per decile increase,pre-transplant PTH level(OR=1.31,P<0.001)per decile increase,longer dialysis duration(OR=1.12,P=0.002)per year,history of acute rejection(OR=2.37,P=0.012),and slope of estimated glomerular filtration rate change(OR=0.91,P=0.001).There were a 3.4-fold higher risk of death-censored graft loss and a 1.9-fold greater risk of recipient death with PT-tHPT.The three treatment strategies of conservative management,calcimimetic and parathyroidectomy did not significantly change the graft or patient outcome.CONCLUSION Pretransplant elevated calcium and PTH levels,older age and dialysis duration are associated with PT-tHPT.While PT-tHPT significantly affects graft and recipient survival,the treatment strategies did not affect survival.展开更多
BACKGROUND Aseptic loosening remains the leading cause of revision in primary total hip arthroplasty(pTHA).However,the literature demonstrates significant variability regarding the relative contributions of different ...BACKGROUND Aseptic loosening remains the leading cause of revision in primary total hip arthroplasty(pTHA).However,the literature demonstrates significant variability regarding the relative contributions of different factors.AIM To investigate the key determinants of aseptic loosening,we performed a systematic review and meta-analysis.METHODS A comprehensive search of PubMed,Web of Science,EMBASE,and the Cochrane Library was conducted,encompassing studies from database inception to January 1,2025.Meta-analyses were performed to evaluate factors associated with aseptic loosening following pTHA.Inclusion and exclusion criteria were systematically applied at each stage to ensure methodological transparency and reproducibility.Study quality was assessed using standardized categories.Pooled odds ratio(OR)with corresponding 95%confidence interval were calculated with random-or fixed-effects models to generate reliability estimates,and study heterogeneity was visualized using forest plots.Ten factors,categorized into patient-,surgeon-,and device-related domains,were reviewed and meta-analyzed.Funnel plot analysis demonstrated a relatively symmetrical distribution,suggesting minimal publication bias.RESULTS A meta-analysis of 20 studies(520789 participants)found a pooled prevalence of 1.96%.Significant risk factors for aseptic loosening after pTHA included elevated body mass index(OR=1.116,P<0.001),higher Charlson comorbidity index(OR=1.378,P<0.001),prosthesis-related factors(OR=1.497,P<0.001),and adverse lifestyles(OR=2.198,P=0.037).Protective factors were non-white race(OR=0.445,P<0.001)and favorable genetics(OR=0.723,P<0.001).Male sex increased risk(OR=1.232,P=0.016),while age and anatomy were not significant.Surgical expertise showed a slight protective effect(OR=1.048,P<0.001).A comprehensive understanding of the modifiable and non-modifiable factors contributing to aseptic loosening after pTHA requires consideration of patient-related factors,surgical expertise,and prosthesis characteristics.CONCLUSION The identification of these factors is critical for risk mitigation.High-risk patients should receive targeted counseling regarding individualized profiles.Further studies are warranted to establish clearer causal relationships and identify additional contributing factors.展开更多
BACKGROUND Lumbar interbody fusion(LIF)is the primary treatment for lumbar degenerative diseases.Elderly patients are prone to anxiety and depression after undergoing surgery,which affects their postoperative recovery...BACKGROUND Lumbar interbody fusion(LIF)is the primary treatment for lumbar degenerative diseases.Elderly patients are prone to anxiety and depression after undergoing surgery,which affects their postoperative recovery speed and quality of life.Effective prevention of anxiety and depression in elderly patients has become an urgent problem.AIM To investigate the trajectory of anxiety and depression levels in elderly patients after LIF,and the influencing factors.METHODS Random sampling was used to select 239 elderly patients who underwent LIF from January 2020 to December 2024 in Shenzhen Pingle Orthopedic Hospital.General information and surgery-related indices were recorded,and participants completed measures of psychological status,lumbar spine dysfunction,and quality of life.A latent class growth model was used to analyze the post-LIF trajectory of anxiety and depression levels,and unordered multi-categorical logistic regression was used to analyze the influencing factors.RESULTS Three trajectories of change in anxiety level were identified:Increasing anxiety(n=26,10.88%),decreasing anxiety(n=27,11.30%),and stable anxiety(n=186,77.82%).Likewise,three trajectories of change in depression level were identified:Increasing depression(n=30,12.55%),decreasing depression(n=26,10.88%),and stable depression(n=183,76.57%).Regression analysis showed that having no partner,female sex,elevated Oswestry dysfunction index(ODI)scores,and reduced 36-Item Short Form Health Survey scores all contributed to increased anxiety levels,whereas female sex,postoperative opioid use,and elevated ODI scores all contributed to increased depression levels.CONCLUSION During clinical observation,combining factors to predict anxiety and depression in post-LIF elderly patients enables timely intervention,quickens recovery,and enhances quality of life.展开更多
The growing prevalence of exercise-induced tibial stress fractures demands wearable sensors capable of monitoring dynamic musculoskeletal loads with medical-grade precision.While flexible pressure-sensing insoles show...The growing prevalence of exercise-induced tibial stress fractures demands wearable sensors capable of monitoring dynamic musculoskeletal loads with medical-grade precision.While flexible pressure-sensing insoles show clinical potential,their development has been hindered by the intrinsic trade-off between high sensitivity and full-range linearity(R^(2)>0.99 up to 1 MPa)in conventional designs.Inspired by the tactile sensing mechanism of human skin,where dermal stratification enables wide-range pressure adaptation and ion-channelregulated signaling maintains linear electrical responses,we developed a dual-mechanism flexible iontronic pressure sensor(FIPS).This innovative design synergistically combines two bioinspired components:interdigitated fabric microstructures enabling pressure-proportional contact area expansion(αP1/3)and iontronic film facilitating self-adaptive ion concentration modulation(αP^(2/3)),which together generate a linear capacitance-pressure response(CαP).The FIPS achieves breakthrough performance:242 kPa^(-1)sensitivity with 0.997linearity across 0-1 MPa,yielding a record linear sensing factor(LSF=242,000).The design is validated across various substrates and ionic materials,demonstrating its versatility.Finally,the FIPS-driven design enables a smart insole demonstrating 1.8%error in tibial load assessment during gait analysis,outperforming nonlinear counterparts(6.5%error)in early fracture-risk prediction.The biomimetic design framework establishes a universal approach for developing high-performance linear sensors,establishing generalized principles for medical-grade wearable devices.展开更多
AIM:To compare the anatomical and functional outcomes of combined phacoemulsification with intravitreal dexamethasone implant(DEX-I)versus anti-vascular endothelial growth factor(VEGF)injections in patients with diabe...AIM:To compare the anatomical and functional outcomes of combined phacoemulsification with intravitreal dexamethasone implant(DEX-I)versus anti-vascular endothelial growth factor(VEGF)injections in patients with diabetic macular edema(DME)and visually significant cataract.METHODS:This nonrandomized,retrospective analysis included 54 eyes undergoing phacoemulsification with DEX-I(DEX-I group)and 47 eyes receiving anti-VEGF injections(anti-VEGF group).Best-corrected visual acuity(BCVA)and central macular thickness(CMT)were measured preoperatively and postoperatively at 1 and 3mo.RESULTS:The two groups had comparable baseline characteristics,with similar age(DEX-I:66.83±7.27y;anti-VEGF:66.81±6.79y)and gender distribution(51.9%vs 59.6%males).Both groups showed significant BCVA improvement at 1 and 3mo,with no significant intergroup differences.CMT reduction was significantly greater in the DEX-I group at 3mo(25.03%vs 14.07%;P=0.049),particularly in recalcitrant eyes(25.09%vs 11.10%;P=0.007).Postoperative intraocular pressure(IOP)>21 mm Hg was observed in 14.8%of DEX-I eyes and 4.25%of anti-VEGF eyes(P=0.08),normalizing by 3mo.DEX-I required no reinjection,while 29.79%of anti-VEGF eyes needed a fourth dose at 3mo.Complications were minimal,with one posterior capsular injury in the DEX-I group.CONCLUSION:Combined phacoemulsification with intravitreal DEX-I offers superior CMT reduction and comparable visual acuity improvement to anti-VEGF injections in DME,with fewer required treatments.It is an effective strategy for managing cataract with DME,offering benefits,especially for recalcitrant cases.Both therapies have favourable safety profiles,but further long-term studies are needed for clinical guidance.展开更多
For diverse neurodegenerative disorders,microglial cells are activated.Furthermore,dysfunctional and hyperactivated microglia initiate mitochondrial autophagy,oxidative stress,and pathological protein accumulation,end...For diverse neurodegenerative disorders,microglial cells are activated.Furthermore,dysfunctional and hyperactivated microglia initiate mitochondrial autophagy,oxidative stress,and pathological protein accumulation,ending with neuroinflammation that exacerbates damage to dopaminergic neurons and contributes significantly to the pathology of neurodegenerative disorder.Microglial overactivation is closely associated with the secretion of pro-inflammatory cytokines,the phagocytosis of injured neurons,and the modulation of neurotoxic environments.This review summarizes the role of microglia neurodegenerative diseases,such as Alzheimer's disease,Parkinson's disease,multiple sclerosis,multiple system atrophy,amyotrophic lateral sclerosis,frontotemporal dementia,progressive supranuclear palsy,cortical degeneration,Lewy body dementia,and Huntington's disease.It also discusses novel forms of cell death such as ferroptosis,cuproptosis,disulfidptosis,and parthanatos(poly(adenosine diphosphate ribose)polymerase 1-dependent cell death),as well as the impact of regulatory factors related to microglial inflammation on microglial activation and neuroinflammation.The aim is to identify potential targets for microglial cell therapy in neurodegenerative diseases.展开更多
BACKGROUND Esophageal cancer is highly malignant and frequently metastasizes to bones.Concomitant depression worsens prognosis;however,its incidence and determinants in this specific population remain poorly defined.A...BACKGROUND Esophageal cancer is highly malignant and frequently metastasizes to bones.Concomitant depression worsens prognosis;however,its incidence and determinants in this specific population remain poorly defined.AIM To determine the incidence of depression and its independent risk factors in patients with esophageal cancer and bone metastasis.METHODS A total of 100 consecutive eligible patients admitted between March 2022 and March 2025 were recruited.Depression was assessed with the Beck Depression Inventory-II;scores>4 defined the depression group(n=42)and scores≤4 the non-depression group(n=58).Demographic,clinical,and laboratory variables were compared between the groups.Multivariate logistic regression was used to identify independent risk factors.RESULTS Depression prevalence was 42.0%(42/100).Univariate analysis demonstrated significant differences in monthly per-capita household income,education level,social support,sleep disorders,and serum high-sensitivity C-reactive protein(all P<0.05);no differences were observed in sex,age,tumor characteristics,or other laboratory indices(all P>0.05).Multivariable analysis revealed the following independent risk factors for depression:Low income[odds ratio(OR)=2.66,95%confidence interval(CI):1.17-6.03],low education(OR=2.46,95%CI:1.08-5.61),low social support(OR=5.10,95%CI:1.81-14.39),sleep disorders(OR=2.79,95%CI:1.23-6.35),and elevated high-sensitivity C-reactive protein(OR=1.31 per unit increase,95%CI:1.18-1.46).CONCLUSION Depression is common among patients with esophageal cancer and bone metastasis.Low socioeconomic status,limited education,insufficient social support,sleep disturbances,and systemic inflammation were independent predictors.Interventions that address these modifiable factors may reduce depression risk in this population.展开更多
BACKGROUND Ulcerative colitis(UC)is a chronic and treatment-resistant disorder requiring potent therapeutics that are effective and safe.Cedrol(CE)is a bioactive natural product present in many traditional Chinese med...BACKGROUND Ulcerative colitis(UC)is a chronic and treatment-resistant disorder requiring potent therapeutics that are effective and safe.Cedrol(CE)is a bioactive natural product present in many traditional Chinese medicines.It is known for its suppression of inflammation and mitigation of oxidative stress.Its therapeutic efficacy and mechanistic underpinnings in UC remain uncharacterized.AIM To investigate the therapeutic potential and mechanisms of CE in UC.METHODS The anti-inflammatory activity and intestinal barrier-repairing effects of CE were assessed in a dextran sulfate sodium-induced murine colitis model.Network pharmacology was employed to predict potential targets and pathways.Then molecular docking and dynamics simulations were utilized to confirm a stable interaction between CE and the toll-like receptor 4(TLR4)/myeloid differentiation factor 2(MD2)complex.The anti-inflammatory mechanisms were further verified using in vitro assays.Additionally,the gut microbiota composition was analyzed via 16S rRNA gene sequencing.RESULTS CE significantly alleviated colitis symptoms,mitigated histopathological damage,and suppressed inflammation.Moreover,CE restored intestinal barrier integrity by enhancing mucus secretion and upregulating tight junction proteins(zonula occludens 1,occludin,claudin-1).Mechanistically,CE stably bound to MD2,inhibiting lipopolysaccharide-induced TLR4 signaling in RAW264.7 cells.This led to suppression of the downstream mitogen-activated protein kinase and nuclear factor kappa B signaling pathways,downregulating the expression of tumor necrosis factor-alpha,interleukin-1β,and interleukin-6.Gut microbiota analysis revealed that CE reversed dextran sulfate sodium-induced dysbiosis with significant enrichment of butyrogenic Christensenella minuta.CONCLUSION CE acted on MD2 to suppress proinflammatory cascades,promoting mucosal barrier reconstitution and microbiota remodeling and supporting its therapeutic use in UC.展开更多
Ischemic stroke is a significant global health crisis,frequently resulting in disability or death,with limited therapeutic interventions available.Although various intrinsic reparative processes are initiated within t...Ischemic stroke is a significant global health crisis,frequently resulting in disability or death,with limited therapeutic interventions available.Although various intrinsic reparative processes are initiated within the ischemic brain,these mechanisms are often insufficient to restore neuronal functionality.This has led to intensive investigation into the use of exogenous stem cells as a potential therapeutic option.This comprehensive review outlines the ontogeny and mechanisms of activation of endogenous neural stem cells within the adult brain following ischemic events,with focus on the impact of stem cell-based therapies on neural stem cells.Exogenous stem cells have been shown to enhance the proliferation of endogenous neural stem cells via direct cell-tocell contact and through the secretion of growth factors and exosomes.Additionally,implanted stem cells may recruit host stem cells from their niches to the infarct area by establishing so-called“biobridges.”Furthermore,xenogeneic and allogeneic stem cells can modify the microenvironment of the infarcted brain tissue through immunomodulatory and angiogenic effects,thereby supporting endogenous neuroregeneration.Given the convergence of regulatory pathways between exogenous and endogenous stem cells and the necessity for a supportive microenvironment,we discuss three strategies to simultaneously enhance the therapeutic efficacy of both cell types.These approaches include:(1)co-administration of various growth factors and pharmacological agents alongside stem cell transplantation to reduce stem cell apoptosis;(2)synergistic administration of stem cells and their exosomes to amplify paracrine effects;and(3)integration of stem cells within hydrogels,which provide a protective scaffold for the implanted cells while facilitating the regeneration of neural tissue and the reconstitution of neural circuits.This comprehensive review highlights the interactions and shared regulatory mechanisms between endogenous neural stem cells and exogenously implanted stem cells and may offer new insights for improving the efficacy of stem cell-based therapies in the treatment of ischemic stroke.展开更多
Overt and harmful diabetes mellitus(DM)has detrimental effects on individuals and,by extension,the community.Among the microvascular DM complications is diabetic retinopathy(DR).DR may cause irreversible vision deteri...Overt and harmful diabetes mellitus(DM)has detrimental effects on individuals and,by extension,the community.Among the microvascular DM complications is diabetic retinopathy(DR).DR may cause irreversible vision deterioration in cases of poor blood glucose regulation.Changes in vascular permeability are key trigger points for diabetic macular edema(DME),a condition characterized by the accumulation of fluid in the macula.The development of vascular endothelial growth factor(VEGF)pathway inhibitors has provided a pathogenesis-based treatment approach for DME.Optical coherence tomography(OCT)provides highresolution imaging of the anatomy,including the aging of DME and its structural damage,in distinct morphologic subtypes of macular edema,thereby supporting the assessment of macular edema treatment.The availability of repeated OCT monitoring provides clinical reassurance through the treatment.OCT angiography(OCTA)provides retinal blood flow maps with high spatial resolution.The ability promotes an understanding of disease pathogenesis and facilitates the implementation of new therapeutic methods.This review compares the potential of OCT and OCTA in the diagnosis and treatment of DME,as well as their respective therapeutic applications.展开更多
BACKGROUND Early renal artery thrombosis after kidney transplantation is rare but often leads to graft loss.Prompt diagnosis and intervention are essential,particularly in patients with inherited thrombophilias such a...BACKGROUND Early renal artery thrombosis after kidney transplantation is rare but often leads to graft loss.Prompt diagnosis and intervention are essential,particularly in patients with inherited thrombophilias such as factor V Leiden(FVL)mutation.CASE SUMMARY A kidney transplant recipient with FVL mutation developed an acute transplant renal artery thrombosis.The immediate post-operative Doppler ultrasonography revealed thrombosis of the main and inferior polar renal arteries.Emergent thrombectomy and separate arterial re-anastomoses were performed after cold perfusion with heparinized saline and vasodilator solution.Reperfusion was successful with immediate urine output and gradual improvement in renal function.The patient was discharged on direct oral anticoagulation therapy.CONCLUSION Early detection and surgical intervention can preserve graft function in posttransplant renal artery thrombosis even in patients at high risk.展开更多
Intrathecal administration of human umbilical cord mesenchymal stem cells may be a promising approach for the treatment of stroke,but its safety,effectiveness,and mechanism remain to be elucidated.In this study,good m...Intrathecal administration of human umbilical cord mesenchymal stem cells may be a promising approach for the treatment of stroke,but its safety,effectiveness,and mechanism remain to be elucidated.In this study,good manufacturing practice-grade human umbilical cord mesenchymal stem cells(5×105 and 1×106 cells)and saline were administered by cerebellomedullary cistern injection 72 hours after stroke induced by middle cerebral artery occlusion in rats.The results showed(1)no significant difference in mortality or general conditions among the three groups.There was no abnormal differentiation or tumor formation in various organs of rats in any group.(2)Compared with saline-treated animals,those treated with human umbilical cord mesenchymal stem cells showed significant functional recovery and reduced infarct volume,with no significant differences between different human umbilical cord mesenchymal stem cell doses.(3)Human umbilical cord mesenchymal stem cells were found in the ischemic brain after 14 and 28 days of follow-up,and the number of positive cells significantly decreased over time.(4)Neuronal nuclei expression in the human umbilical cord mesenchymal stem cell group was greater than that in the saline group,while glial fibrillary acidic protein and ionized calcium binding adaptor molecule 1 expression levels decreased.(5)Human umbilical cord mesenchymal stem cell treatment increased the number of CD31+microvessels and doublecortin-positive cells after ischemic stroke.Human umbilical cord mesenchymal stem cells also upregulated the expression of CD31+/Ki67+.(6)At 14 days after intrathecal administration,brain-derived neurotrophic factor expression in the peri-infarct area and the concentrations of brain-derived neurotrophic factor in the cerebrospinal fluid in both human umbilical cord mesenchymal stem cell groups were significantly greater than those in the saline group and persisted until the 28th day.Taken together,these results indicate that the intrathecal administration of human umbilical cord mesenchymal stem cells via cerebellomedullary cistern injection is safe and effective for the treatment of ischemic stroke in rats.The mechanisms may include alleviating the local inflammatory response in the peri-infarct region,promoting neurogenesis and angiogenesis,and enhancing the production of neurotrophic factors.展开更多
The neuroinflammatory response mediated by microglial activation plays an important role in the secondary nerve injury of traumatic brain injury.The post-transcriptional modification of N^(6)-methyladenosine is ubiqui...The neuroinflammatory response mediated by microglial activation plays an important role in the secondary nerve injury of traumatic brain injury.The post-transcriptional modification of N^(6)-methyladenosine is ubiquitous in the immune response of the central nervous system.The fat mass and obesity-related protein catalyzes the demethylation of N^(6)-methyladenosine modifications on mRNA and is widely expressed in various tissues,participating in the regulation of multiple diseases’biological processes.However,the role of fat mass and obesity in microglial activation and the subsequent neuroinflammatory response after traumatic brain injury is unclear.In this study,we found that the expression of fat mass and obesity was significantly down-regulated in both lipopolysaccharide-treated BV2 cells and a traumatic brain injury mouse model.After fat mass and obesity interference,BV2 cells exhibited a pro-inflammatory phenotype as shown by the increased proportion of CD11b^(+)/CD86^(+)cells and the secretion of pro-inflammatory cytokines.Fat mass and obesity-mediated N^(6)-methyladenosine demethylation accelerated the degradation of ADAM17 mRNA,while silencing of fat mass and obesity enhanced the stability of ADAM17 mRNA.Therefore,down-regulation of fat mass and obesity expression leads to the abnormally high expression of ADAM17 in microglia.These results indicate that the activation of microglia and neuroinflammatory response regulated by fat mass and obesity-related N^(6)-methyladenosine modification plays an important role in the pro-inflammatory process of secondary injury following traumatic brain injury.展开更多
The aging process is an inexorable fact throughout our lives and is considered a major factor in develo ping neurological dysfunctions associated with cognitive,emotional,and motor impairments.Aging-associated neurode...The aging process is an inexorable fact throughout our lives and is considered a major factor in develo ping neurological dysfunctions associated with cognitive,emotional,and motor impairments.Aging-associated neurodegenerative diseases are characterized by the progressive loss of neuronal structure and function.展开更多
We read with great interest the study by Zhang et al on Yiyi Fuzi Baijiang powder(YFB),which exemplifies the power of modern methods to validate traditional Chinese medicine(TCM).The key insight is that YFB doesn’t m...We read with great interest the study by Zhang et al on Yiyi Fuzi Baijiang powder(YFB),which exemplifies the power of modern methods to validate traditional Chinese medicine(TCM).The key insight is that YFB doesn’t merely alter“good”or“bad”bacteria but restores the gut microbiota’s holistic equilibrium.This is powerfully shown by its paradoxical reduction of anaerobic probiotics like Bifidobacterium,rectifying the diseased,hypoxic environment,causing their aberrant overgrowth.This challenges the conventional probiotic paradigm and underscores a core TCM principle:Herbal formulas treat disease by restoring the body’s overall functional balance.Future research should focus on the interplay between herbal components,intestinal oxygen,and microbial metabolites to further unravel this sophisticated dialogue.展开更多
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 Qingdao Key Medical and Health Discipline ProjectThe Intramural Research Program of the Affiliated Hospital of Qingdao University,No. 4910Qingdao West Coast New Area Science and Technology Project,No. 2020-55 (all to SW)。
文摘Border-associated macrophages are located at the interface between the brain and the periphery, including the perivascular spaces, choroid plexus, and meninges. Until recently, the functions of border-associated macrophages have been poorly understood and largely overlooked. However, a recent study reported that border-associated macrophages participate in stroke-induced inflammation, although many details and the underlying mechanisms remain unclear. In this study, we performed a comprehensive single-cell analysis of mouse border-associated macrophages using sequencing data obtained from the Gene Expression Omnibus(GEO) database(GSE174574 and GSE225948). Differentially expressed genes were identified, and enrichment analysis was performed to identify the transcription profile of border-associated macrophages. CellChat analysis was conducted to determine the cell communication network of border-associated macrophages. Transcription factors were predicted using the ‘pySCENIC' tool. We found that, in response to hypoxia, borderassociated macrophages underwent dynamic transcriptional changes and participated in the regulation of inflammatory-related pathways. Notably, the tumor necrosis factor pathway was activated by border-associated macrophages following ischemic stroke. The pySCENIC analysis indicated that the activity of signal transducer and activator of transcription 3(Stat3) was obviously upregulated in stroke, suggesting that Stat3 inhibition may be a promising strategy for treating border-associated macrophages-induced neuroinflammation. Finally, we constructed an animal model to investigate the effects of border-associated macrophages depletion following a stroke. Treatment with liposomes containing clodronate significantly reduced infarct volume in the animals and improved neurological scores compared with untreated animals. Taken together, our results demonstrate comprehensive changes in border-associated macrophages following a stroke, providing a theoretical basis for targeting border-associated macrophages-induced neuroinflammation in stroke treatment.
文摘BACKGROUND Ischemic stroke is one of the leading global causes of disability and death.Despite advances in modern medical technology that improve acute treatment and rehabilitation measures,post-stroke anxiety and depression(PSD)do not receive sufficient attention.AIM To systematically evaluate risk factors and early identification markers for PSD for more precise screening and intervention strategies in clinical practice.METHODS This retrospective study analyzed clinical data from 112 patients with ischemic stroke admitted between January 2022 and December 2024.Based on assessments using the Hamilton Rating Scale for Anxiety(HAMA)and Hamilton Rating Scale for Depression(HAMD)at 2 weeks(±3 days)post-stroke,patients were classified into the PSD group(HAMA≥7 and/or HAMD≥7)and the non-PSD group(HAMA<7 and HAMD<7).Observation indicators included psychological assessment,demographic and clinical characteristics,stroke-related clinical indicators,neuroimaging assessments,and laboratory biomarkers.Multivariate logistic regression analysis was used to identify independent risk factors for PSD,and receiver operating characteristic curve analysis was used to evaluate the diagnostic value of potential biomarkers.RESULTS Of the 112 patients,46(41.1%)were diagnosed with PSD.Multivariate analysis identified five independent risk factors:Female gender[Odds ratio(OR)=2.32,95%confidence interval(CI):1.56-3.45],history of mental disorders prior to stroke(OR=3.17,95%CI:1.89-5.32),infarct location in the frontal lobe or limbic system(OR=2.86,95%CI:1.73-4.71),stroke severity with National Institutes of Health Stroke Scale≥8 at admission(OR=2.54,95%CI:1.62-3.99),and low social support(Social Support Rating Scale<35,OR=2.18,95%CI:1.42-3.36).Subgroup analysis showed that depression patients more commonly had left hemisphere lesions(68.4%vs 45.2%),while anxiety patients more frequently presented with right hemisphere lesions(59.5%vs 39.5%).The PSD group exhibited larger infarct volumes(8.7 cm^(3) vs 5.3 cm^(3)),more severe white matter hyperintensities,and more pronounced frontal lobe atrophy.Analysis of inflammatory markers showed significantly elevated levels of interleukin-6(7.8 pg/mL vs 4.5 pg/mL)and tumor necrosis factor-alpha(15.6 pg/mL vs 9.8 pg/mL)in the PSD group,while hypothalamicpituitary-adrenal axis function assessment revealed higher cortisol levels(386.5±92.3 nmol/L vs 328.7±75.6 nmol/L)and flattened diurnal rhythm in the PSD group.CONCLUSION PSD is a complex neuropsychiatric consequence of stroke involving disruption of the frontal-limbic circuitry,neuroinflammatory responses,and dysfunction of the hypothalamic-pituitary-adrenal axis.
基金supported by grants from the Zhejiang Provincial TCM Science and Technology Plan Project,No.2023ZL156(to YH)Ningbo Top Medical and Health Research Program,No.2022020304(to XG)+1 种基金the Natural Science Foundation of Ningbo,No.2023J019(to YH)Key Laboratory of Precision Medicine for Atherosclerotic Diseases of Zhejiang Province,No.2022E10026(to YH)。
文摘Strokes include both ischemic stroke,which is mediated by a blockade or reduction in the blood supply to the brain,and hemorrhagic stroke,which comprises intracerebral hemorrhage and subarachnoid hemorrhage and is characterized by bleeding within the brain.Stroke is a lifethreatening cerebrovascular condition characterized by intricate pathophysiological mechanisms,including oxidative stress,inflammation,mitochondrial dysfunction,and neuronal injury.Critical transcription factors,such as nuclear factor erythroid 2-related factor 2 and nuclear factor kappa B,play central roles in the progression of stroke.Nuclear factor erythroid 2-related factor 2 is sensitive to changes in the cellular redox status and is crucial in protecting cells against oxidative damage,inflammatory responses,and cytotoxic agents.It plays a significant role in post-stroke neuroprotection and repair by influencing mitochondrial function,endoplasmic reticulum stress,and lysosomal activity and regulating metabolic pathways and cytokine expression.Conversely,nuclear factor-kappa B is closely associated with mitochondrial dysfunction,the generation of reactive oxygen species,oxidative stress exacerbation,and inflammation.Nuclear factor-kappa B contributes to neuronal injury,apoptosis,and immune responses following stroke by modulating cell adhesion molecules and inflammatory mediators.The interplay between these pathways,potentially involving crosstalk among various organelles,significantly influences stroke pathophysiology.Advancements in single-cell sequencing and spatial transcriptomics have greatly improved our understanding of stroke pathogenesis and offer new opportunities for the development of targeted,individualized,cell typespecific treatments.In this review,we discuss the mechanisms underlying the involvement of nuclear factor erythroid 2-related factor 2 and nuclear factor-kappa B in both ischemic and hemorrhagic stroke,with an emphasis on their roles in oxidative stress,inflammation,and neuroprotection.
文摘Nerve trauma commonly results in chronic neuropathic pain. This is by triggering the release of proinflammatory mediators from local and invading cells that induce inflammation and nociceptive neuron hyperexcitability. Even without apparent inflammation, injury sites are associated with increased inflammatory markers. This review focuses on how it might be possible to reduce neuropathic pain by reducing inflammation. Physiologically, pain is resolved by a combination of the out-migration of pro-inflammatory cells from the injury site, the down-regulation of the genes underlying the inflammation, up-regulating genes for anti-inflammatory mediators, and reducing nociceptive neuron hyperexcitability. While various techniques reduce chronic neuropathic pain, the best are effective on < 50% of patients, no technique reliably or permanently eliminates neuropathic pain. This is because most techniques are predominantly aimed at reducing pain, not inflammation. In addition, while single factors reduce pain, increasing evidence indicates significant and longer-lasting pain relief requires multiple factors acting simultaneously. Therefore, it is not surprising that extensive data indicate that the application of platelet-rich plasma provides more significant and longer-lasting pain suppression than other techniques, although its analgesia is neither complete nor permanent. However, several case reports indicate that platelet-rich plasma can induce permanent neuropathic pain elimination when the platelet concentration is significantly increased and is applied to longer nerve lengths. This review examines the primary triggers of the development and maintenance of neuropathic pain and techniques that reduce chronic neuropathic pain. The application of plateletrich plasma holds great promise for providing complete and permanent chronic neuropathic pain elimination.
文摘BACKGROUND Post-transplant tertiary hyperparathyroidism(PT-tHPT)is a well-recognized complication following kidney transplantation,characterized by persistent excessive secretion of parathyroid hormone(PTH)despite improved renal function.It is potentially associated with an increased risk of cardiovascular events,renal osteodystrophy,pathologic fractures,graft loss,and mortality.AIM To evaluate the incidence,risk factors,and outcomes of PT-tHPT amongst kidney transplant recipients.METHODS A total of 887 transplant recipients who underwent transplantation between 2000 and 2020 were evaluated.Univariable and multivariable logistic regression was performed to determine the predictors of tertiary hyperparathyroidism.Graft and recipient outcomes were assessed using multivariable Cox regression.A separate multivariable Cox regression was performed to determine the effect of treatment strategies on outcomes.RESULTS PT-tHPT,defined as elevated PTH(>65 ng/L)and persistent hypercalcemia(>2.60 mmol/L),was diagnosed in 14%of recipients.Risk factors for PT-tHPT included older age[odds ratio(OR)=1.36,P<0.001],Asian ethnicity(OR=0.33,P=0.006),total ischemia time(OR=1.03,P=0.048 per hour),pre-transplant serum calcium(OR=1.38,P<0.001)per decile increase,pre-transplant PTH level(OR=1.31,P<0.001)per decile increase,longer dialysis duration(OR=1.12,P=0.002)per year,history of acute rejection(OR=2.37,P=0.012),and slope of estimated glomerular filtration rate change(OR=0.91,P=0.001).There were a 3.4-fold higher risk of death-censored graft loss and a 1.9-fold greater risk of recipient death with PT-tHPT.The three treatment strategies of conservative management,calcimimetic and parathyroidectomy did not significantly change the graft or patient outcome.CONCLUSION Pretransplant elevated calcium and PTH levels,older age and dialysis duration are associated with PT-tHPT.While PT-tHPT significantly affects graft and recipient survival,the treatment strategies did not affect survival.
基金Supported by the National Natural Science Foundation of China,No.82402789Beijing Jishuitan Hospital Youcai Plan,No.KYYC202402+2 种基金Beijing Jishuitan Research Funding,No.HL202402and Beijing Natural Science Foundation,No.L232062No.L222063.
文摘BACKGROUND Aseptic loosening remains the leading cause of revision in primary total hip arthroplasty(pTHA).However,the literature demonstrates significant variability regarding the relative contributions of different factors.AIM To investigate the key determinants of aseptic loosening,we performed a systematic review and meta-analysis.METHODS A comprehensive search of PubMed,Web of Science,EMBASE,and the Cochrane Library was conducted,encompassing studies from database inception to January 1,2025.Meta-analyses were performed to evaluate factors associated with aseptic loosening following pTHA.Inclusion and exclusion criteria were systematically applied at each stage to ensure methodological transparency and reproducibility.Study quality was assessed using standardized categories.Pooled odds ratio(OR)with corresponding 95%confidence interval were calculated with random-or fixed-effects models to generate reliability estimates,and study heterogeneity was visualized using forest plots.Ten factors,categorized into patient-,surgeon-,and device-related domains,were reviewed and meta-analyzed.Funnel plot analysis demonstrated a relatively symmetrical distribution,suggesting minimal publication bias.RESULTS A meta-analysis of 20 studies(520789 participants)found a pooled prevalence of 1.96%.Significant risk factors for aseptic loosening after pTHA included elevated body mass index(OR=1.116,P<0.001),higher Charlson comorbidity index(OR=1.378,P<0.001),prosthesis-related factors(OR=1.497,P<0.001),and adverse lifestyles(OR=2.198,P=0.037).Protective factors were non-white race(OR=0.445,P<0.001)and favorable genetics(OR=0.723,P<0.001).Male sex increased risk(OR=1.232,P=0.016),while age and anatomy were not significant.Surgical expertise showed a slight protective effect(OR=1.048,P<0.001).A comprehensive understanding of the modifiable and non-modifiable factors contributing to aseptic loosening after pTHA requires consideration of patient-related factors,surgical expertise,and prosthesis characteristics.CONCLUSION The identification of these factors is critical for risk mitigation.High-risk patients should receive targeted counseling regarding individualized profiles.Further studies are warranted to establish clearer causal relationships and identify additional contributing factors.
基金Supported by the Scientific Research Projects of the Health System in Pingshan District,No.2023122.
文摘BACKGROUND Lumbar interbody fusion(LIF)is the primary treatment for lumbar degenerative diseases.Elderly patients are prone to anxiety and depression after undergoing surgery,which affects their postoperative recovery speed and quality of life.Effective prevention of anxiety and depression in elderly patients has become an urgent problem.AIM To investigate the trajectory of anxiety and depression levels in elderly patients after LIF,and the influencing factors.METHODS Random sampling was used to select 239 elderly patients who underwent LIF from January 2020 to December 2024 in Shenzhen Pingle Orthopedic Hospital.General information and surgery-related indices were recorded,and participants completed measures of psychological status,lumbar spine dysfunction,and quality of life.A latent class growth model was used to analyze the post-LIF trajectory of anxiety and depression levels,and unordered multi-categorical logistic regression was used to analyze the influencing factors.RESULTS Three trajectories of change in anxiety level were identified:Increasing anxiety(n=26,10.88%),decreasing anxiety(n=27,11.30%),and stable anxiety(n=186,77.82%).Likewise,three trajectories of change in depression level were identified:Increasing depression(n=30,12.55%),decreasing depression(n=26,10.88%),and stable depression(n=183,76.57%).Regression analysis showed that having no partner,female sex,elevated Oswestry dysfunction index(ODI)scores,and reduced 36-Item Short Form Health Survey scores all contributed to increased anxiety levels,whereas female sex,postoperative opioid use,and elevated ODI scores all contributed to increased depression levels.CONCLUSION During clinical observation,combining factors to predict anxiety and depression in post-LIF elderly patients enables timely intervention,quickens recovery,and enhances quality of life.
基金supported by the National Natural Science Foundation of China(NSFC 52175281,52475315)Youth Innovation Promotion Association of CAS(2021382)。
文摘The growing prevalence of exercise-induced tibial stress fractures demands wearable sensors capable of monitoring dynamic musculoskeletal loads with medical-grade precision.While flexible pressure-sensing insoles show clinical potential,their development has been hindered by the intrinsic trade-off between high sensitivity and full-range linearity(R^(2)>0.99 up to 1 MPa)in conventional designs.Inspired by the tactile sensing mechanism of human skin,where dermal stratification enables wide-range pressure adaptation and ion-channelregulated signaling maintains linear electrical responses,we developed a dual-mechanism flexible iontronic pressure sensor(FIPS).This innovative design synergistically combines two bioinspired components:interdigitated fabric microstructures enabling pressure-proportional contact area expansion(αP1/3)and iontronic film facilitating self-adaptive ion concentration modulation(αP^(2/3)),which together generate a linear capacitance-pressure response(CαP).The FIPS achieves breakthrough performance:242 kPa^(-1)sensitivity with 0.997linearity across 0-1 MPa,yielding a record linear sensing factor(LSF=242,000).The design is validated across various substrates and ionic materials,demonstrating its versatility.Finally,the FIPS-driven design enables a smart insole demonstrating 1.8%error in tibial load assessment during gait analysis,outperforming nonlinear counterparts(6.5%error)in early fracture-risk prediction.The biomimetic design framework establishes a universal approach for developing high-performance linear sensors,establishing generalized principles for medical-grade wearable devices.
文摘AIM:To compare the anatomical and functional outcomes of combined phacoemulsification with intravitreal dexamethasone implant(DEX-I)versus anti-vascular endothelial growth factor(VEGF)injections in patients with diabetic macular edema(DME)and visually significant cataract.METHODS:This nonrandomized,retrospective analysis included 54 eyes undergoing phacoemulsification with DEX-I(DEX-I group)and 47 eyes receiving anti-VEGF injections(anti-VEGF group).Best-corrected visual acuity(BCVA)and central macular thickness(CMT)were measured preoperatively and postoperatively at 1 and 3mo.RESULTS:The two groups had comparable baseline characteristics,with similar age(DEX-I:66.83±7.27y;anti-VEGF:66.81±6.79y)and gender distribution(51.9%vs 59.6%males).Both groups showed significant BCVA improvement at 1 and 3mo,with no significant intergroup differences.CMT reduction was significantly greater in the DEX-I group at 3mo(25.03%vs 14.07%;P=0.049),particularly in recalcitrant eyes(25.09%vs 11.10%;P=0.007).Postoperative intraocular pressure(IOP)>21 mm Hg was observed in 14.8%of DEX-I eyes and 4.25%of anti-VEGF eyes(P=0.08),normalizing by 3mo.DEX-I required no reinjection,while 29.79%of anti-VEGF eyes needed a fourth dose at 3mo.Complications were minimal,with one posterior capsular injury in the DEX-I group.CONCLUSION:Combined phacoemulsification with intravitreal DEX-I offers superior CMT reduction and comparable visual acuity improvement to anti-VEGF injections in DME,with fewer required treatments.It is an effective strategy for managing cataract with DME,offering benefits,especially for recalcitrant cases.Both therapies have favourable safety profiles,but further long-term studies are needed for clinical guidance.
基金funded by the Science and Technology Research of Henan Province,No.242103810041(to JY)。
文摘For diverse neurodegenerative disorders,microglial cells are activated.Furthermore,dysfunctional and hyperactivated microglia initiate mitochondrial autophagy,oxidative stress,and pathological protein accumulation,ending with neuroinflammation that exacerbates damage to dopaminergic neurons and contributes significantly to the pathology of neurodegenerative disorder.Microglial overactivation is closely associated with the secretion of pro-inflammatory cytokines,the phagocytosis of injured neurons,and the modulation of neurotoxic environments.This review summarizes the role of microglia neurodegenerative diseases,such as Alzheimer's disease,Parkinson's disease,multiple sclerosis,multiple system atrophy,amyotrophic lateral sclerosis,frontotemporal dementia,progressive supranuclear palsy,cortical degeneration,Lewy body dementia,and Huntington's disease.It also discusses novel forms of cell death such as ferroptosis,cuproptosis,disulfidptosis,and parthanatos(poly(adenosine diphosphate ribose)polymerase 1-dependent cell death),as well as the impact of regulatory factors related to microglial inflammation on microglial activation and neuroinflammation.The aim is to identify potential targets for microglial cell therapy in neurodegenerative diseases.
文摘BACKGROUND Esophageal cancer is highly malignant and frequently metastasizes to bones.Concomitant depression worsens prognosis;however,its incidence and determinants in this specific population remain poorly defined.AIM To determine the incidence of depression and its independent risk factors in patients with esophageal cancer and bone metastasis.METHODS A total of 100 consecutive eligible patients admitted between March 2022 and March 2025 were recruited.Depression was assessed with the Beck Depression Inventory-II;scores>4 defined the depression group(n=42)and scores≤4 the non-depression group(n=58).Demographic,clinical,and laboratory variables were compared between the groups.Multivariate logistic regression was used to identify independent risk factors.RESULTS Depression prevalence was 42.0%(42/100).Univariate analysis demonstrated significant differences in monthly per-capita household income,education level,social support,sleep disorders,and serum high-sensitivity C-reactive protein(all P<0.05);no differences were observed in sex,age,tumor characteristics,or other laboratory indices(all P>0.05).Multivariable analysis revealed the following independent risk factors for depression:Low income[odds ratio(OR)=2.66,95%confidence interval(CI):1.17-6.03],low education(OR=2.46,95%CI:1.08-5.61),low social support(OR=5.10,95%CI:1.81-14.39),sleep disorders(OR=2.79,95%CI:1.23-6.35),and elevated high-sensitivity C-reactive protein(OR=1.31 per unit increase,95%CI:1.18-1.46).CONCLUSION Depression is common among patients with esophageal cancer and bone metastasis.Low socioeconomic status,limited education,insufficient social support,sleep disturbances,and systemic inflammation were independent predictors.Interventions that address these modifiable factors may reduce depression risk in this population.
基金Supported by the Provincial Key Cultivation Laboratory for Digestive Disease Research,No.2021SYS13Shanxi Province’s“Si Ge Yi Pi”Science and Technology Driven Medical Innovation Project,No.2021MX03Shanxi Provincial Basic Research Program,No.202403021222423.
文摘BACKGROUND Ulcerative colitis(UC)is a chronic and treatment-resistant disorder requiring potent therapeutics that are effective and safe.Cedrol(CE)is a bioactive natural product present in many traditional Chinese medicines.It is known for its suppression of inflammation and mitigation of oxidative stress.Its therapeutic efficacy and mechanistic underpinnings in UC remain uncharacterized.AIM To investigate the therapeutic potential and mechanisms of CE in UC.METHODS The anti-inflammatory activity and intestinal barrier-repairing effects of CE were assessed in a dextran sulfate sodium-induced murine colitis model.Network pharmacology was employed to predict potential targets and pathways.Then molecular docking and dynamics simulations were utilized to confirm a stable interaction between CE and the toll-like receptor 4(TLR4)/myeloid differentiation factor 2(MD2)complex.The anti-inflammatory mechanisms were further verified using in vitro assays.Additionally,the gut microbiota composition was analyzed via 16S rRNA gene sequencing.RESULTS CE significantly alleviated colitis symptoms,mitigated histopathological damage,and suppressed inflammation.Moreover,CE restored intestinal barrier integrity by enhancing mucus secretion and upregulating tight junction proteins(zonula occludens 1,occludin,claudin-1).Mechanistically,CE stably bound to MD2,inhibiting lipopolysaccharide-induced TLR4 signaling in RAW264.7 cells.This led to suppression of the downstream mitogen-activated protein kinase and nuclear factor kappa B signaling pathways,downregulating the expression of tumor necrosis factor-alpha,interleukin-1β,and interleukin-6.Gut microbiota analysis revealed that CE reversed dextran sulfate sodium-induced dysbiosis with significant enrichment of butyrogenic Christensenella minuta.CONCLUSION CE acted on MD2 to suppress proinflammatory cascades,promoting mucosal barrier reconstitution and microbiota remodeling and supporting its therapeutic use in UC.
基金supported by the National Key Research and Development Program of China,No.2018YFA0108602the CAMS Initiative for Innovative Medicine,No.2021-1-I2M-019National High-Level Hospital Clinical Research Funding,No.2022-PUMCH-C-042(all to XB)。
文摘Ischemic stroke is a significant global health crisis,frequently resulting in disability or death,with limited therapeutic interventions available.Although various intrinsic reparative processes are initiated within the ischemic brain,these mechanisms are often insufficient to restore neuronal functionality.This has led to intensive investigation into the use of exogenous stem cells as a potential therapeutic option.This comprehensive review outlines the ontogeny and mechanisms of activation of endogenous neural stem cells within the adult brain following ischemic events,with focus on the impact of stem cell-based therapies on neural stem cells.Exogenous stem cells have been shown to enhance the proliferation of endogenous neural stem cells via direct cell-tocell contact and through the secretion of growth factors and exosomes.Additionally,implanted stem cells may recruit host stem cells from their niches to the infarct area by establishing so-called“biobridges.”Furthermore,xenogeneic and allogeneic stem cells can modify the microenvironment of the infarcted brain tissue through immunomodulatory and angiogenic effects,thereby supporting endogenous neuroregeneration.Given the convergence of regulatory pathways between exogenous and endogenous stem cells and the necessity for a supportive microenvironment,we discuss three strategies to simultaneously enhance the therapeutic efficacy of both cell types.These approaches include:(1)co-administration of various growth factors and pharmacological agents alongside stem cell transplantation to reduce stem cell apoptosis;(2)synergistic administration of stem cells and their exosomes to amplify paracrine effects;and(3)integration of stem cells within hydrogels,which provide a protective scaffold for the implanted cells while facilitating the regeneration of neural tissue and the reconstitution of neural circuits.This comprehensive review highlights the interactions and shared regulatory mechanisms between endogenous neural stem cells and exogenously implanted stem cells and may offer new insights for improving the efficacy of stem cell-based therapies in the treatment of ischemic stroke.
文摘Overt and harmful diabetes mellitus(DM)has detrimental effects on individuals and,by extension,the community.Among the microvascular DM complications is diabetic retinopathy(DR).DR may cause irreversible vision deterioration in cases of poor blood glucose regulation.Changes in vascular permeability are key trigger points for diabetic macular edema(DME),a condition characterized by the accumulation of fluid in the macula.The development of vascular endothelial growth factor(VEGF)pathway inhibitors has provided a pathogenesis-based treatment approach for DME.Optical coherence tomography(OCT)provides highresolution imaging of the anatomy,including the aging of DME and its structural damage,in distinct morphologic subtypes of macular edema,thereby supporting the assessment of macular edema treatment.The availability of repeated OCT monitoring provides clinical reassurance through the treatment.OCT angiography(OCTA)provides retinal blood flow maps with high spatial resolution.The ability promotes an understanding of disease pathogenesis and facilitates the implementation of new therapeutic methods.This review compares the potential of OCT and OCTA in the diagnosis and treatment of DME,as well as their respective therapeutic applications.
文摘BACKGROUND Early renal artery thrombosis after kidney transplantation is rare but often leads to graft loss.Prompt diagnosis and intervention are essential,particularly in patients with inherited thrombophilias such as factor V Leiden(FVL)mutation.CASE SUMMARY A kidney transplant recipient with FVL mutation developed an acute transplant renal artery thrombosis.The immediate post-operative Doppler ultrasonography revealed thrombosis of the main and inferior polar renal arteries.Emergent thrombectomy and separate arterial re-anastomoses were performed after cold perfusion with heparinized saline and vasodilator solution.Reperfusion was successful with immediate urine output and gradual improvement in renal function.The patient was discharged on direct oral anticoagulation therapy.CONCLUSION Early detection and surgical intervention can preserve graft function in posttransplant renal artery thrombosis even in patients at high risk.
基金supported by the Medicine-Engineering Interdisciplinary Project of Sun Yat-sen Memorial Hospital,China,No.YXYGRH202203(to YW)Key-Area Research and Development Program of Guangdong Province,China,No.2023B1111050003(to HC)Guangzhou Science and Technology Talent Project of China,No.201909020006(to HC).
文摘Intrathecal administration of human umbilical cord mesenchymal stem cells may be a promising approach for the treatment of stroke,but its safety,effectiveness,and mechanism remain to be elucidated.In this study,good manufacturing practice-grade human umbilical cord mesenchymal stem cells(5×105 and 1×106 cells)and saline were administered by cerebellomedullary cistern injection 72 hours after stroke induced by middle cerebral artery occlusion in rats.The results showed(1)no significant difference in mortality or general conditions among the three groups.There was no abnormal differentiation or tumor formation in various organs of rats in any group.(2)Compared with saline-treated animals,those treated with human umbilical cord mesenchymal stem cells showed significant functional recovery and reduced infarct volume,with no significant differences between different human umbilical cord mesenchymal stem cell doses.(3)Human umbilical cord mesenchymal stem cells were found in the ischemic brain after 14 and 28 days of follow-up,and the number of positive cells significantly decreased over time.(4)Neuronal nuclei expression in the human umbilical cord mesenchymal stem cell group was greater than that in the saline group,while glial fibrillary acidic protein and ionized calcium binding adaptor molecule 1 expression levels decreased.(5)Human umbilical cord mesenchymal stem cell treatment increased the number of CD31+microvessels and doublecortin-positive cells after ischemic stroke.Human umbilical cord mesenchymal stem cells also upregulated the expression of CD31+/Ki67+.(6)At 14 days after intrathecal administration,brain-derived neurotrophic factor expression in the peri-infarct area and the concentrations of brain-derived neurotrophic factor in the cerebrospinal fluid in both human umbilical cord mesenchymal stem cell groups were significantly greater than those in the saline group and persisted until the 28th day.Taken together,these results indicate that the intrathecal administration of human umbilical cord mesenchymal stem cells via cerebellomedullary cistern injection is safe and effective for the treatment of ischemic stroke in rats.The mechanisms may include alleviating the local inflammatory response in the peri-infarct region,promoting neurogenesis and angiogenesis,and enhancing the production of neurotrophic factors.
基金supported by grants from the Major Projects of Health Science Research Foundation for Middle-Aged and Young Scientist of Fujian Province,China,No.2022ZQNZD01010010the National Natural Science Foundation of China,No.82371390Fujian Province Scientific Foundation,No.2023J01725(all to XC).
文摘The neuroinflammatory response mediated by microglial activation plays an important role in the secondary nerve injury of traumatic brain injury.The post-transcriptional modification of N^(6)-methyladenosine is ubiquitous in the immune response of the central nervous system.The fat mass and obesity-related protein catalyzes the demethylation of N^(6)-methyladenosine modifications on mRNA and is widely expressed in various tissues,participating in the regulation of multiple diseases’biological processes.However,the role of fat mass and obesity in microglial activation and the subsequent neuroinflammatory response after traumatic brain injury is unclear.In this study,we found that the expression of fat mass and obesity was significantly down-regulated in both lipopolysaccharide-treated BV2 cells and a traumatic brain injury mouse model.After fat mass and obesity interference,BV2 cells exhibited a pro-inflammatory phenotype as shown by the increased proportion of CD11b^(+)/CD86^(+)cells and the secretion of pro-inflammatory cytokines.Fat mass and obesity-mediated N^(6)-methyladenosine demethylation accelerated the degradation of ADAM17 mRNA,while silencing of fat mass and obesity enhanced the stability of ADAM17 mRNA.Therefore,down-regulation of fat mass and obesity expression leads to the abnormally high expression of ADAM17 in microglia.These results indicate that the activation of microglia and neuroinflammatory response regulated by fat mass and obesity-related N^(6)-methyladenosine modification plays an important role in the pro-inflammatory process of secondary injury following traumatic brain injury.
文摘The aging process is an inexorable fact throughout our lives and is considered a major factor in develo ping neurological dysfunctions associated with cognitive,emotional,and motor impairments.Aging-associated neurodegenerative diseases are characterized by the progressive loss of neuronal structure and function.
文摘We read with great interest the study by Zhang et al on Yiyi Fuzi Baijiang powder(YFB),which exemplifies the power of modern methods to validate traditional Chinese medicine(TCM).The key insight is that YFB doesn’t merely alter“good”or“bad”bacteria but restores the gut microbiota’s holistic equilibrium.This is powerfully shown by its paradoxical reduction of anaerobic probiotics like Bifidobacterium,rectifying the diseased,hypoxic environment,causing their aberrant overgrowth.This challenges the conventional probiotic paradigm and underscores a core TCM principle:Herbal formulas treat disease by restoring the body’s overall functional balance.Future research should focus on the interplay between herbal components,intestinal oxygen,and microbial metabolites to further unravel this sophisticated dialogue.
