Neuronal cell death is a common outcome of multiple pathophysiological processes and a key factor in neurological dysfunction after subarachnoid hemorrhage.Neuronal ferroptosis in particular plays an important role in...Neuronal cell death is a common outcome of multiple pathophysiological processes and a key factor in neurological dysfunction after subarachnoid hemorrhage.Neuronal ferroptosis in particular plays an important role in early brain injury.Bromodomain-containing protein 4,a member of the bromo and extraterminal domain family of proteins,participated in multiple cell death pathways,but the mechanisms by which it regulates ferroptosis remain unclear.The primary aim of this study was to investigate how bromodomain-containing protein 4 affects neuronal ferroptosis following subarachnoid hemorrhage in vivo and in vitro.Our findings revealed that endogenous bromodomain-containing protein 4 co-localized with neurons,and its expression was decreased 48 hours after subarachnoid hemorrhage of the cerebral cortex in vivo.In addition,ferroptosis-related pathways were activated in vivo and in vitro after subarachnoid hemorrhage.Targeted inhibition of bromodomain-containing protein 4 in neurons increased lipid peroxidation and intracellular ferrous iron accumulation via ferritinophagy and ultimately led to neuronal ferroptosis.Using cleavage under targets and tagmentation analysis,we found that bromodomain-containing protein 4 enrichment in the Raf-1 promoter region decreased following oxyhemoglobin stimulation in vitro.Furthermore,treating bromodomain-containing protein 4-knockdown HT-22 cell lines with GW5074,a Raf-1 inhibitor,exacerbated neuronal ferroptosis by suppressing the Raf-1/ERK1/2 signaling pathway.Moreover,targeted inhibition of neuronal bromodomain-containing protein 4 exacerbated early and long-term neurological function deficits after subarachnoid hemorrhage.Our findings suggest that bromodomain-containing protein 4 may have neuroprotective effects after subarachnoid hemorrhage,and that inhibiting ferroptosis could help treat subarachnoid hemorrhage.展开更多
Alzheimer’s disease is a multi-amyloidosis disease characterized by amyloid-βdeposits in brain blood vessels,microaneurysms,and senile plaques.How amyloid-βdeposition affects axon pathology has not been examined ex...Alzheimer’s disease is a multi-amyloidosis disease characterized by amyloid-βdeposits in brain blood vessels,microaneurysms,and senile plaques.How amyloid-βdeposition affects axon pathology has not been examined extensively.We used immunohistochemistry and immunofluorescence staining to analyze the forebrain tissue slices of Alzheimer’s disease patients.Widespread axonal amyloidosis with distinctive axonal enlargement was observed in patients with Alzheimer’s disease.On average,amyloid-β-positive axon diameters in Alzheimer’s disease brains were 1.72 times those of control brain axons.Furthermore,axonal amyloidosis was associated with microtubule-associated protein 2 reduction,tau phosphorylation,lysosome destabilization,and several blood-related markers,such as apolipoprotein E,alpha-hemoglobin,glycosylated hemoglobin type A1C,and hemin.Lysosome destabilization in Alzheimer’s disease was also clearly identified in the neuronal soma,where it was associated with the co-expression of amyloid-β,Cathepsin D,alpha-hemoglobin,actin alpha 2,and collagen type IV.This suggests that exogenous hemorrhagic protein intake influences neural lysosome stability.Additionally,the data showed that amyloid-β-containing lysosomes were 2.23 times larger than control lysosomes.Furthermore,under rare conditions,axonal breakages were observed,which likely resulted in Wallerian degeneration.In summary,axonal enlargement associated with amyloidosis,micro-bleeding,and lysosome destabilization is a major defect in patients with Alzheimer’s disease.This finding suggests that,in addition to the well-documented neural soma and synaptic damage,axonal damage is a key component of neuronal defects in Alzheimer’s disease.展开更多
Intracerebral hemorrhage is the most dangerous subtype of stroke,characterized by high mortality and morbidity rates,and frequently leads to significant secondary white matter injury.In recent decades,studies have rev...Intracerebral hemorrhage is the most dangerous subtype of stroke,characterized by high mortality and morbidity rates,and frequently leads to significant secondary white matter injury.In recent decades,studies have revealed that gut microbiota can communicate bidirectionally with the brain through the gut microbiota–brain axis.This axis indicates that gut microbiota is closely related to the development and prognosis of intracerebral hemorrhage and its associated secondary white matter injury.The NACHT,LRR,and pyrin domain-containing protein 3(NLRP3)inflammasome plays a crucial role in this context.This review summarizes the dysbiosis of gut microbiota following intracerebral hemorrhage and explores the mechanisms by which this imbalance may promote the activation of the NLRP3 inflammasome.These mechanisms include metabolic pathways(involving short-chain fatty acids,lipopolysaccharides,lactic acid,bile acids,trimethylamine-N-oxide,and tryptophan),neural pathways(such as the vagus nerve and sympathetic nerve),and immune pathways(involving microglia and T cells).We then discuss the relationship between the activated NLRP3 inflammasome and secondary white matter injury after intracerebral hemorrhage.The activation of the NLRP3 inflammasome can exacerbate secondary white matter injury by disrupting the blood–brain barrier,inducing neuroinflammation,and interfering with nerve regeneration.Finally,we outline potential treatment strategies for intracerebral hemorrhage and its secondary white matter injury.Our review highlights the critical role of the gut microbiota–brain axis and the NLRP3 inflammasome in white matter injury following intracerebral hemorrhage,paving the way for exploring potential therapeutic approaches.展开更多
Refined rhubarb tablets were used to treat 182 cases of acute hemorrhaging of the upperdigestive tract with a total effective rate of 96. 1 % and an average hemostatic time ot 2. 8 days. Prospec-tive and double blind ...Refined rhubarb tablets were used to treat 182 cases of acute hemorrhaging of the upperdigestive tract with a total effective rate of 96. 1 % and an average hemostatic time ot 2. 8 days. Prospec-tive and double blind comparative studies of the drug revealed that it had a rernarkably higher hemostaticeffect than compound western medicines (P<0. 01) and was superior to crude rhubarb, which usuallycaused nausea and vomiting and had unstable therapeutic effects- Acute and subacute toxicity determina-tions. genetic toxicologic tests, as well as determinations of various indexes ot blood vessels, pepsin.blood rheology, platelets, bleeding and blood coagulation factors were done, suggesting that refinedrhubarb tablets were nontoxic. safe and effective in local hemostasis and general hemodilution-likehemostasis.展开更多
AIM:To evaluate the efficacy and safety of decellularized conjunctival stroma(DCS)as a novel biomaterial by comparing its grafting outcomes with amniotic membrane(AM)when used for conjunctival reconstruction after pri...AIM:To evaluate the efficacy and safety of decellularized conjunctival stroma(DCS)as a novel biomaterial by comparing its grafting outcomes with amniotic membrane(AM)when used for conjunctival reconstruction after primary pterygium excision.METHODS:This randomized,parallel-controlled study with allocation concealment enrolled 40 patients with primary pterygium.Participants were randomly assigned to two groups using the sealed envelope method:the DCS group(n=20)and the AM group(n=18),receiving DCS and AM grafts respectively.Slit-lamp photography of the operative eyes was performed preoperatively and at 1,3,5,7,10,30,90,and 180d postoperatively.Best-corrected visual acuity(BCVA)and symptom scores were recorded simultaneously.In vivo confocal microscopy was conducted at 3 and 6mo postoperatively.RESULTS:All participants exhibited improved postoperative symptoms.The mean age was 60±9y(male/female ratio:6/14)in the DCS group and 56±12y(male/female ratio:7/11)in the AM group.The average epithelial healing time was 9.89±3.54d in the DCS group and 8.17±1.34d in the AM group(P=0.084).One recurrence case was observed in each group.Postoperative graft hemorrhage was significantly more severe in the DCS group than in the AM group only at 30d postoperatively(P=0.011).In vivo confocal microscopy revealed conjunctival epithelial cell growth in both groups at 90d postoperatively,while clear corneo-conjunctival cell boundaries were observed until 180d postoperatively.CONCLUSION:DCS used in primary pterygium surgery has a safety profile comparable to AM.It promotes rapid postoperative conjunctival healing,achieves a relatively low pterygium recurrence rate,and yields outcomes similar to AM.DCS provides a novel biomaterial option for conjunctival reconstruction after pterygium excision and the treatment of other conjunctival injuries.展开更多
Objective:To assess the effectiveness of intravenous immunoglobulin(IVIg)therapy in patients diagnosed with Crimean-Congo hemorrhagic fever(CCHF)disease.Methods:A single-center retrospective cohort study was conducted...Objective:To assess the effectiveness of intravenous immunoglobulin(IVIg)therapy in patients diagnosed with Crimean-Congo hemorrhagic fever(CCHF)disease.Methods:A single-center retrospective cohort study was conducted on hospitalized patients with confirmed severe CCHF at a tertiary care hospital in Turkey between 2010 and 2022.Cases were categorized into two groups based on whether they received IVIg therapy,with the treatment plan determined by the primary healthcare provider.The clinical,epidemiological,and laboratory parameters of these patients were evaluated.Demographic,laboratory findings,platelet counts on the day of IVIg indication and the third day,bleeding status during follow-up beyond 24 hours after IVIg administration,and prognosis recorded in patient information forms were retrieved.Results:72 patients were included in the analysis,with IVIg administered to 42 cases(58.3%)and not given to 30 cases(41.7%).Among the patients,37(51.4%)were female.Fever(65.3%)was the most common clinical presentation.The overall mortality rate was 19.4%,and IVIg administration did not significantly impact overall survival outcomes(P=0.48).On Day 3 following IVIg administration or indication,the platelet count was higher in the IVIg-treated group compared to the non-treated group(P=0.02).Furthermore,during follow-up beyond 24 hours after IVIg administration,bleeding was observed in 19.0%of the IVIg-treated group,compared to 46.6% in the non-treated group(P=0.01).Conclusions:This study underscores the potential advantages of IVIg therapy in managing severe CCHF.Although IVIg administration did not significantly affect overall survival,it was associated with earlier improvement in platelet counts and a notable reduction in bleeding complications.These findings indicate that IVIg may serve as an adjunctive treatment in CCHF,particularly for addressing hemorrhagic manifestations.展开更多
Stroke can be categorized as ischemic and hemorrhagic on the basis of its origin.The pathophysiology following a stroke is complex,and is characterized by ongoing inflammation,neuronal injury,and the accumulation of r...Stroke can be categorized as ischemic and hemorrhagic on the basis of its origin.The pathophysiology following a stroke is complex,and is characterized by ongoing inflammation,neuronal injury,and the accumulation of reactive oxygen species in the brain,all of which reflect a dynamic process of change.This complexity hinders achievement of significant therapeutic outcomes with standard stroke treatment procedures,limiting post-stroke recovery.This review presents an innovative post-stroke therapeutic approach that utilizes nanomedicines to modify the cerebral microenvironment.It highlights the primary roles of chronic inflammation and nerve repair issues in causing prolonged impairment in stroke patients.Traditional therapies show limited effectiveness in achieving neuroprotection,immunoregulation,and neural regeneration during the subacute and chronic phases of stroke.Therefore,effective stroke management requires the use of specific therapeutic strategies tailored to the pathological characteristics of each phase.Various types of nanomedicines possess distinct physicochemical properties and can be selected on the basis of the specific therapeutic needs.Surface-modification technologies have significantly enhanced the ability of nanomedicines to penetrate the blood-brain barrier and improve their targeting capabilities in drug administration.However,the stability,biocompatibility,and long-term safety of nanomedicines require further optimization for clinical application.Nanomedicines represent a novel approach to stroke treatment through targeted delivery and multifaceted regulatory mechanisms.These medicines provide distinct advantages,particularly in addressing chronic inflammation and promoting nerve regeneration.As a result,nanomedicines are expected to significantly improve rehabilitation outcomes and quality of life for stroke patients in the future,emerging as a crucial modality for stroke treatment.展开更多
Objective:To explore the impact of systematic stepwise rehabilitation nursing intervention on the prognosis and disease uncertainty of patients with hypertensive intracerebral hemorrhage,and to provide feasible strate...Objective:To explore the impact of systematic stepwise rehabilitation nursing intervention on the prognosis and disease uncertainty of patients with hypertensive intracerebral hemorrhage,and to provide feasible strategies for clinical nursing.Methods:Eighty patients with hypertensive intracerebral hemorrhage admitted to our hospital from January 2023 to June 2025 were selected and randomly divided into an observation group(n=40,receiving systematic stepwise rehabilitation nursing)and a control group(n=40,receiving conventional nursing).The intervention effects were analyzed by comparing changes in the National Institutes of Health Stroke Scale(NIHSS)scores for neurological recovery,Short Form 36 Health Survey(SF-36)scores for quality of life,Exercise of Self-Care Agency Scale(ESCA)scores for self-management ability,compliance,and the Mishel Uncertainty in Illness Scale(MUIS)scores between the two groups.Results:All scores in the observation group were significantly better than those in the control group after the intervention(p<0.05).Specifically,the NIHSS scores decreased more significantly,the total SF-36 scores increased,the ESCA scores increased significantly,while the MUIS scores decreased significantly,and compliance improved markedly,indicating a reduction in disease uncertainty among patients.Conclusion:Systematic stepwise rehabilitation nursing intervention can significantly improve neurological recovery,quality of life,self-management ability,and compliance in patients with hypertensive intracerebral hemorrhage,while effectively reducing disease uncertainty.It is worthy of clinical promotion and application.展开更多
Severe trauma often involves complex injuries,leading to high disability and fatality rates.Effective treatment requires prompt and coordinated efforts across multiple disciplines to enhance success rates.Time-based c...Severe trauma often involves complex injuries,leading to high disability and fatality rates.Effective treatment requires prompt and coordinated efforts across multiple disciplines to enhance success rates.Time-based chain rescue is crucial in managing severe trauma.A patient with chest and abdominal injuries and hemorrhagic shock was transferred from an ambulance to our hospital.Our trauma team-initiated pre-hospital first aid,utilized an emergency green channel,and conducted rapid ultrasound,collaborating across disciplines.The patient eventually recovered and was discharged.展开更多
Regulatory T cells are crucial immunomodulatory cells that play essential roles in both ischemic stroke and intracerebral hemorrhage.These cells are vital in post-stroke inflammation since they suppress immune respons...Regulatory T cells are crucial immunomodulatory cells that play essential roles in both ischemic stroke and intracerebral hemorrhage.These cells are vital in post-stroke inflammation since they suppress immune responses and promote tissue repair.This review thoroughly examines the dynamic changes in the number and function of regulatory T cells and highlights their distinct roles at various stages of stroke progression.In the acute phase(within 5-7 days),regulatory T cells exert neuroprotective effects primarily by reducing inflammation.In the chronic phase(7 days post-onset),these cells support neuroregeneration and functional recovery.The review also explores the emerging role of regulatory T cells in the brain-gut axis,a key mediator of the systemic immune responses following stroke,and discusses its relevance in modulating post-stroke inflammation and repair.Various strategies aimed at enhancing regulatory T cell responses include adoptive transfer of regulatory T cells,administration of pharmacological agents,and induction of mucosal tolerance.All these approaches can potentially enhance the immunomodulatory and repair functions of regulatory T cells.Nevertheless,despite the promising preclinical results,the translation of regulatory T cell-based therapies into clinical practice is associated with challenges related to optimal timing,dosage,and long-term efficacy.Overall,targeting regulatory T cells is a novel and promising immunoregulatory approach for mitigating stroke-induced injury and promoting neural repair.展开更多
Lassa fever(LF)is an acute viral hemorrhagic illness caused by the Lassa virus(LASV),an enveloped,spherical virus belonging to the Arenaviridae family.LASV possess a single-stranded RNA genome of negative polarity and...Lassa fever(LF)is an acute viral hemorrhagic illness caused by the Lassa virus(LASV),an enveloped,spherical virus belonging to the Arenaviridae family.LASV possess a single-stranded RNA genome of negative polarity and exhibits high genetic diversity,corresponding to the geographical distribution of its seven principal distinct clades across West Africa[1].LASV was first isolated in 1969 from an American missionary nurse stationed in the rural town of Lassa,Borno State,Nigeria,following her return from a brief vacation in the United States[2].展开更多
Modulations of mitochondrial dysfunction,which involve a series of dynamic processes such as mitochondrial biogenesis,mitochondrial fusion and fission,mitochondrial transport,mitochondrial autophagy,mitochondrial apop...Modulations of mitochondrial dysfunction,which involve a series of dynamic processes such as mitochondrial biogenesis,mitochondrial fusion and fission,mitochondrial transport,mitochondrial autophagy,mitochondrial apoptosis,and oxidative stress,play an important role in the onset and progression of stroke.With a better understanding of the critical role of mitochondrial dysfunction modulations in post-stroke neurological injury,these modulations have emerged as a potential target for stroke prevention and treatment.Additionally,since effective treatments for stroke are extremely limited and natural products currently offer some outstanding advantages,we focused on the findings and mechanisms of action related to the use of natural products for targeting mitochondrial dysfunction in the treatment of stroke.Natural products achieve neuroprotective through multi-target regulation of mitochondrial dysfunction encompassing the following processes:(1)Mitochondrial biogenesis:Cordyceps and hydroxysafflor yellow A activate the peroxisome proliferator-activated receptor gamma coactivator 1-alpha/nuclear respiratory factor pathway,promote mitochondrial DNA replication and respiratory chain protein synthesis,and thereby restore energy supply in the ischemic penumbra.(2)Mitochondrial dynamics balance:Ginsenoside Rb3 promotes Opa1-mediated neural stem cell migration and diffusion for recovery of damaged brain tissue.(3)Mitochondrial autophagy:Gypenoside XVII selectively eliminates damaged mitochondria via the phosphatase and tensin homolog-induced kinase 1/Parkin pathway and blocks reactive oxygen species and the NOD-like receptor protein 3 inflammasome cascade,thereby alleviating blood-brain barrier damage.(4)Anti-apoptotic mechanisms:Ginkgolide K inhibits Bax mitochondrial translocation and downregulates caspase-3/9 activity,reducing neuronal programmed death induced by ischemia-reperfusion.(5)Oxidative stress regulation:Scutellarin exerts antioxidant properties and improves neurological function by modulating the extracellular signal-regulated kinase 5-Kruppel-like factor 2-endothelial nitric oxide synthase signaling pathway.(6)Intercellular mitochondrial transport:Neuroprotective effects of Chrysophanol are associated with accelerated mitochondrial transfer from astrocytes to neurons.Existing studies have confirmed that natural products exhibit neuroprotective effects through multidimensional interventions targeting mitochondrial dysfunction in both ischemic and hemorrhagic stroke models.However,their clinical translation still faces challenges,such as the difficulty in standardization due to component complexity,insufficient cross-regional clinical data,and the lack of long-term safety evaluations.Future research should aim to integrate new technologies,such as single-cell sequencing and organoid models,to deeply explore the mitochondria-targeting mechanisms of natural products and validate their efficacy through multicenter clinical trials,providing theoretical support and translational pathways for the development of novel anti-stroke drugs.展开更多
AIM:To evaluate the clinical features,diagnosis,treatment,and outcome of peripheral exudative hemorrhagic chorioretinopathy(PEHCR),a variant of polypoidal choroidal vasculopathy(PCV),in a case series of Chinese patien...AIM:To evaluate the clinical features,diagnosis,treatment,and outcome of peripheral exudative hemorrhagic chorioretinopathy(PEHCR),a variant of polypoidal choroidal vasculopathy(PCV),in a case series of Chinese patients.METHODS:This study was retrospectively conducted from September 2018 to March 2025.Clinical examinations included color fundus photography,B-scan ultrasonography,fluorescein angiography(FA),indocyanine green angiography(ICGA),swept-source optical coherence tomography(SS-OCT),and optical coherence tomography angiography(OCTA),and two active or inactive subgroups and misdiagnosed cases were analyzed.RESULTS:Totally 19 patients(21 eyes)with a mean age of 54.3±9.4(range,36–68)y were included,with a majority of women(n=13,68.4%).The mean follow-up period was 13±1.4(range:1–57)mo.Decreased visual acuity was the most frequent initial manifestation(17 eyes,84.2%),and lesions were mainly distributed in the inferotemporal or temporal quadrant(14 eyes,66.7%),with choroidal polyps and branching neovascular networks revealed by OCTA and ICGA.Nine patients had been previously misdiagnosed with choroidal melanoma,and 6 of them had massive vitreous hemorrhage(VH).PEHCR manifested along a spectrum ranging from active or inactive subretinal hemorrhagic forms to chronic fibrotic or atrophic forms.One patient experienced natural regression.Ten eyes received a mean of 4.7±1.1(range:3–7)intravitreal anti-vascular endothelial growth factor(VEGF)injections,two eyes underwent vitrectomy,and six eyes were treated with vitrectomy combined with anti-VEGF therapy.Best-corrected visual acuity(logMAR)in treated eyes(18 eyes)improved to 0.31±0.25 from the baseline of 1.50±0.75(P<0.001).CONCLUSION:PEHCR is a variant of PCV.Chinese patients with PEHCR have a relatively younger age of onset.Anti-VEGF injections and/or vitrectomy are treatment options for lesion regression or dense VH to gain better visual outcomes.展开更多
Germinal matrix hemorrhage in preterm neonates often leads to white matter injury,contributing to long-term neurodevelopmental impairments.As resident brain immune cells,microglia play a complex role in injury respons...Germinal matrix hemorrhage in preterm neonates often leads to white matter injury,contributing to long-term neurodevelopmental impairments.As resident brain immune cells,microglia play a complex role in injury response,including inflammation and repair.Although colony-stimulating factor 1 receptor inhibitors such as PLX5622 enable the selective depletion of microglia,their therapeutic potential in neonatal germinal matrix hemorrhage remains underexplored.Here,we used a collagenase-induced germinal matrix hemorrhage model in postnatal day 5 mice,and intraperitoneally administered PLX562272 hours post-germinal matrix hemorrhage to achieve targeted,temporary microglial depletion during the peak injury response.We then assessed the effects of this delayed intervention on oligodendrocyte lineage cell maturation,white matter integrity,and neurobehavioral outcomes.Additionally,RNA sequencing data from a germinal matrix hemorrhage rat model were analyzed using weighted gene co-expression network analysis to identify the critical phases for interventions.RNA sequencing data revealed a critical period in which key synaptic functions declined while immune responses intensified post-germinal matrix hemorrhage,thus pinpointing the critical response phases for potential interventions.Delayed PLX5622 treatment effectively depleted activated microglia,protecting against white matter injury and enhancing oligodendrocyte lineage cell maturation and myelination in subcortical white matter regions.Moreover,magnetic resonance imaging analysis revealed reduced brain lesion volumes in treated mice.Behaviorally,PLX5622-treated mice exhibited significant improvements in motor coordination and reduced hyperactivity compared with vehicle-treated germinal matrix hemorrhage model mice.These findings suggest that,when timed to avoid interference with initial oligodendrocyte lineage cell proliferation,targeted microglial depletion with PLX5622 significantly mitigates white matter damage and improves neurobehavioral outcomes in neonatal germinal matrix hemorrhage.The present study highlights the therapeutic potential of selectively modulating microglial reactivity to support neurodevelopment in preterm infants with brain injury.展开更多
Subarachnoid hemorrhage(SAH) is a devastating condition that affects a total of 8 million people worldwide each year(Lauzier and Athiraman, 2024). Etiologies of SAH can be traumatic or nontraumatic, with the majority ...Subarachnoid hemorrhage(SAH) is a devastating condition that affects a total of 8 million people worldwide each year(Lauzier and Athiraman, 2024). Etiologies of SAH can be traumatic or nontraumatic, with the majority of non-traumatic SAH occurring due to intracranial aneurysm rupture(Rutledge et al., 2014).展开更多
AIM:To compare spontaneous brain regional activities between diabetic vitreous hemorrhage patients(DVHs)and healthy controls(HCs).METHODS:Thirty-two DVHs and 32 HCs were enrolled in this study.Baseline demographic and...AIM:To compare spontaneous brain regional activities between diabetic vitreous hemorrhage patients(DVHs)and healthy controls(HCs).METHODS:Thirty-two DVHs and 32 HCs were enrolled in this study.Baseline demographic and vision data were compared between groups using an independent sample t-test.Resting-state functional magnetic resonance imaging(rs-fMRI)was used in all participants.fMRI data was obtained and analyzed using MRIcro and SPM8 software.Fractional amplitude of low-frequency fluctuation(fALFF)technology was used to measure regional spontaneous brain activity,and sensitivity was tested using receiver operating characteristic curves(ROCs).The fALFF values were analyzed using REST software and two-sample t-tests were used to compare values between groups.Hospital anxiety and depression scale(HADS)score was assessed in DVHs and Pearson’s correlation was used to test relationships between mean fALFF value and both HADS score and duration of DVH.RESULTS:Except for the best-corrected visual acuity(BCVA)in both eyes,which showed a statistically significant difference(P<0.05),there were no statistically significant differences in the other indicators(P>0.05)between the HCs and DVHs group.Compared with controls,fALFF value was higher in DVH in cerebellum posterior lobe(CPL)and lower in right anterior cingulate cortex(ACC)and right medial orbitofrontal cortex(OFC).In DVH patients,mean fALFF value of CPL was positively correlated with HADS score and duration of diabetes.However,no such correlation was found,for right ACC or right medial OFC.DVH may lead to abnormal activities in certain brain regions related to visual control and mood.CONCLUSION:Visual impairment caused by DVH may lead to adjustment in regional visual brain activities and may be related to depression or reward system processing in some brain regions.展开更多
Recombinant tissue plasminogen activator is commonly used for hematoma evacuation in minimally invasive surgery following intracerebral hemorrhage.However,during minimally invasive surgery,recombinant tissue plasminog...Recombinant tissue plasminogen activator is commonly used for hematoma evacuation in minimally invasive surgery following intracerebral hemorrhage.However,during minimally invasive surgery,recombinant tissue plasminogen activator may come into contact with brain tissue.Therefore,a thorough assessment of its safety is required.In this study,we established a mouse model of intracerebral hemorrhage induced by type VII collagenase.We observed that the administration of recombinant tissue plasminogen activator without hematoma aspiration significantly improved the neurological function of mice with intracerebral hemorrhage,reduced pathological damage,and lowered the levels of apoptosis and autophagy in the tissue surrounding the hematoma.In an in vitro model of intracerebral hemorrhage using primary cortical neurons induced by hemin,the administration of recombinant tissue plasminogen activator suppressed neuronal apoptosis,autophagy,and endoplasmic reticulum stress.Transcriptome sequencing analysis revealed that recombinant tissue plasminogen activator upregulated the phosphoinositide 3-kinase/RAC-alpha serine/threonine-protein kinase/mammalian target of rapamycin pathway in neurons.Moreover,the phosphoinositide 3-kinase inhibitor LY294002 abrogated the neuroprotective effects of recombinant tissue plasminogen activator in inhibiting excessive apoptosis,autophagy,and endoplasmic reticulum stress.Furthermore,to specify the domain of recombinant tissue plasminogen activator responsible for its neuroprotective effects,various inhibitors were used to target distinct domains.It has been revealed that the epidermal growth factor receptor inhibitor AG-1478 reversed the effect of recombinant tissue plasminogen activator on the phosphoinositide 3-kinase/RAC-alpha serine/threonineprotein kinase/mammalian target of rapamycin pathway.These findings suggest that recombinant tissue plasminogen activator exerts a direct neuroprotective effect on neurons following intracerebral hemorrhage,possibly through activation of the phosphoinositide 3-kinase/RAC-alpha serine/threonine-protein kinase/mammalian target of rapamycin pathway.展开更多
Phosphodiesterase 4 is a key enzyme involved in the regulation of cell signal transduction,but its role in subarachnoid hemorrhage remains unclear.Neuronal pyroptosis has been reported to be involved in early brain in...Phosphodiesterase 4 is a key enzyme involved in the regulation of cell signal transduction,but its role in subarachnoid hemorrhage remains unclear.Neuronal pyroptosis has been reported to be involved in early brain injury after subarachnoid hemorrhage.This study aimed to investigate whether phosphodiesterase 4 contributes to early brain injury after subarachnoid hemorrhage by mediating neuronal pyroptosis and its related mechanisms.Endovascular perforation of male C57BL/6J mice was performed to model subarachnoid hemorrhage in vivo,and oxyhemoglobin was added to the culture medium of primary neurons to model subarachnoid hemorrhage in vitro.A phosphodiesterase 4-specific inhibitor,etazolate,was intraperitoneally injected 30 minutes after subarachnoid hemorrhage induction.Small interfering RNA(siRNA)was administered intracerebroventricularly 72 hours before subarachnoid hemorrhage to achieve genetic knockdown of phosphodiesterase 4.To investigate the mechanism,a nucleotide-binding oligomerization domain-like receptor pyrin domain containing 3(NLRP3)-specific agonist,nigericin,was intracerebroventricularly injected 60 minutes before subarachnoid hemorrhage.Neuronal phosphodiesterase 4 expression increased after subarachnoid hemorrhage and reached the highest point at 24 hours.Etazolate treatment reduced neurological deficits and brain edema in mice,alleviated neuronal pyroptosis and inflammatory response,and improved neuronal injury.Treatment with phosphodiesterase 4 siRNA had the same neuroprotective effects as etazolate.Mechanistically,phosphodiesterase 4 triggered the nuclear factor kappa-B pathway,and simultaneously caused lysosomal and mitochondrial dysfunction after subarachnoid hemorrhage,which promoted NLRP3 inflammasome activation and induced neuronal pyroptosis.Blocking of phosphodiesterase 4 inhibited the nuclear factor kappa-B pathway,and improved lysosome and mitochondrial function.Activation of NLRP3 reversed the neuroprotective effects of etazolate without affecting phosphodiesterase 4 expression.Together,the results indicate that phosphodiesterase 4 regulates NLRP3-mediated neuronal pyroptosis in early brain injury after subarachnoid hemorrhage.Phosphodiesterase 4 may be a potential therapeutic molecular target for subarachnoid hemorrhage.展开更多
Hemorrhage control requires hemostatic materials that are both efective and biocompatible.Among these,diatom biosilica(DBs)could signifcantly improve hemorrhage control,but it induces hemolysis(the hemolysis rate>5...Hemorrhage control requires hemostatic materials that are both efective and biocompatible.Among these,diatom biosilica(DBs)could signifcantly improve hemorrhage control,but it induces hemolysis(the hemolysis rate>5%).Thus,the purpose of this study was to explore the infuence of Ca^(2+)biomineralization on DBs for developing fast hemostatic materials with a low hemolysis rate.Here,CaCl_(2)was added to the diatom medium under high light(cool white,fuorescent lamps,67.5µmol m^(−2) s^(−1)),producing Ca-DBs-3 with a particle size of 40-50μm and a Ca^(2+)content of Ca-DBs-3 obtained from the higher concentration CaCl_(2)group(6.7 mmol L^(−1))of 0.16%.The liquid absorption capacity of Ca-DBs-3 was 30.43±0.57 times its dry weight;the in vitro clotting time was comparable to QuikClot®zeolite;the hemostatic time and blood loss using the rat tail amputation model were 36.40±2.52 s and 0.39±0.12 g,which were 40.72%and 19.50%of QuikClot®zeolite,respectively.Ca-DBs-3 showed no apparent toxicity to L929 cells(cell viability>80%)and was non-hemolysis(the hemolysis rate<2%).This study prepared Ca-DBs-3 with a rapid hemostatic efect and good biocompatibility,providing a path to develop diatom biosilica hemostatic materials.展开更多
Stroke is classified as ischemic or hemorrhagic,and there are few effective treatments for either type.Immunologic mechanisms play a critical role in secondary brain injury following a stroke,which manifests as cytoki...Stroke is classified as ischemic or hemorrhagic,and there are few effective treatments for either type.Immunologic mechanisms play a critical role in secondary brain injury following a stroke,which manifests as cytokine release,blood–brain barrier disruption,neuronal cell death,and ultimately behavioral impairment.Suppressing the inflammatory response has been shown to mitigate this cascade of events in experimental stroke models.However,in clinical trials of anti-inflammatory agents,longterm immunosuppression has not demonstrated significant clinical benefits for patients.This may be attributable to the dichotomous roles of inflammation in both tissue injury and repair,as well as the complex pathophysiologic inflammatory processes in stroke.Inhibiting acute harmful inflammatory responses or inducing a phenotypic shift from a pro-inflammatory to an anti-inflammatory state at specific time points after a stroke are alternative and promising therapeutic strategies.Identifying agents that can modulate inflammation requires a detailed understanding of the inflammatory processes of stroke.Furthermore,epigenetic reprogramming plays a crucial role in modulating post-stroke inflammation and can potentially be exploited for stroke management.In this review,we summarize current findings on the epigenetic regulation of the inflammatory response in stroke,focusing on key signaling pathways including nuclear factor-kappa B,Janus kinase/signal transducer and activator of transcription,and mitogen-activated protein kinase as well as inflammasome activation.We also discuss promising molecular targets for stroke treatment.The evidence to date indicates that therapeutic targeting of the epigenetic regulation of inflammation can shift the balance from inflammation-induced tissue injury to repair following stroke,leading to improved post-stroke outcomes.展开更多
基金supported by the National Natural Science Foundation of China,Nos.82371310(to YJ),82271306(to JP)the Sichuan Science and Technology Support Program,Nos.2023YFH0069(to JP),2023NSFSC0028(to YJ),2023NSFSC1559(to YJ),2022YFS0615(to JP),2022NSFSC1421(to JP)+1 种基金Scientific Research Project of Sichuan Provincial Health Commission,No.23LCYJ040(to YJ)Youth Foundation of Southwestern Medical University and Southwest Medical University Project,Nos.2020ZRQNA038(to JP),2021ZKZD013(to JP),2021LZXNYD-P01(to YJ),2023QN014(to JP).
文摘Neuronal cell death is a common outcome of multiple pathophysiological processes and a key factor in neurological dysfunction after subarachnoid hemorrhage.Neuronal ferroptosis in particular plays an important role in early brain injury.Bromodomain-containing protein 4,a member of the bromo and extraterminal domain family of proteins,participated in multiple cell death pathways,but the mechanisms by which it regulates ferroptosis remain unclear.The primary aim of this study was to investigate how bromodomain-containing protein 4 affects neuronal ferroptosis following subarachnoid hemorrhage in vivo and in vitro.Our findings revealed that endogenous bromodomain-containing protein 4 co-localized with neurons,and its expression was decreased 48 hours after subarachnoid hemorrhage of the cerebral cortex in vivo.In addition,ferroptosis-related pathways were activated in vivo and in vitro after subarachnoid hemorrhage.Targeted inhibition of bromodomain-containing protein 4 in neurons increased lipid peroxidation and intracellular ferrous iron accumulation via ferritinophagy and ultimately led to neuronal ferroptosis.Using cleavage under targets and tagmentation analysis,we found that bromodomain-containing protein 4 enrichment in the Raf-1 promoter region decreased following oxyhemoglobin stimulation in vitro.Furthermore,treating bromodomain-containing protein 4-knockdown HT-22 cell lines with GW5074,a Raf-1 inhibitor,exacerbated neuronal ferroptosis by suppressing the Raf-1/ERK1/2 signaling pathway.Moreover,targeted inhibition of neuronal bromodomain-containing protein 4 exacerbated early and long-term neurological function deficits after subarachnoid hemorrhage.Our findings suggest that bromodomain-containing protein 4 may have neuroprotective effects after subarachnoid hemorrhage,and that inhibiting ferroptosis could help treat subarachnoid hemorrhage.
基金supported by the National Natural Science Foundation of China,No.81472235(to HF)the Shanghai Jiao Tong University Medical and Engineering Project,Nos.YG2021QN53(to HF),YG2017MS71(to HF)+1 种基金the International Cooperation Project of the National Natural Science Foundation of China,No.82020108017(to DC)the Innovation Group Project of the National Natural Science Foundation of China,No.81921002(to DC).
文摘Alzheimer’s disease is a multi-amyloidosis disease characterized by amyloid-βdeposits in brain blood vessels,microaneurysms,and senile plaques.How amyloid-βdeposition affects axon pathology has not been examined extensively.We used immunohistochemistry and immunofluorescence staining to analyze the forebrain tissue slices of Alzheimer’s disease patients.Widespread axonal amyloidosis with distinctive axonal enlargement was observed in patients with Alzheimer’s disease.On average,amyloid-β-positive axon diameters in Alzheimer’s disease brains were 1.72 times those of control brain axons.Furthermore,axonal amyloidosis was associated with microtubule-associated protein 2 reduction,tau phosphorylation,lysosome destabilization,and several blood-related markers,such as apolipoprotein E,alpha-hemoglobin,glycosylated hemoglobin type A1C,and hemin.Lysosome destabilization in Alzheimer’s disease was also clearly identified in the neuronal soma,where it was associated with the co-expression of amyloid-β,Cathepsin D,alpha-hemoglobin,actin alpha 2,and collagen type IV.This suggests that exogenous hemorrhagic protein intake influences neural lysosome stability.Additionally,the data showed that amyloid-β-containing lysosomes were 2.23 times larger than control lysosomes.Furthermore,under rare conditions,axonal breakages were observed,which likely resulted in Wallerian degeneration.In summary,axonal enlargement associated with amyloidosis,micro-bleeding,and lysosome destabilization is a major defect in patients with Alzheimer’s disease.This finding suggests that,in addition to the well-documented neural soma and synaptic damage,axonal damage is a key component of neuronal defects in Alzheimer’s disease.
基金supported by the Guangdong Basic and Applied Basic Research Foundation,No.2023A1515030045(to HS)Presidential Foundation of Zhujiang Hospital of Southern Medical University,No.yzjj2022ms4(to HS)。
文摘Intracerebral hemorrhage is the most dangerous subtype of stroke,characterized by high mortality and morbidity rates,and frequently leads to significant secondary white matter injury.In recent decades,studies have revealed that gut microbiota can communicate bidirectionally with the brain through the gut microbiota–brain axis.This axis indicates that gut microbiota is closely related to the development and prognosis of intracerebral hemorrhage and its associated secondary white matter injury.The NACHT,LRR,and pyrin domain-containing protein 3(NLRP3)inflammasome plays a crucial role in this context.This review summarizes the dysbiosis of gut microbiota following intracerebral hemorrhage and explores the mechanisms by which this imbalance may promote the activation of the NLRP3 inflammasome.These mechanisms include metabolic pathways(involving short-chain fatty acids,lipopolysaccharides,lactic acid,bile acids,trimethylamine-N-oxide,and tryptophan),neural pathways(such as the vagus nerve and sympathetic nerve),and immune pathways(involving microglia and T cells).We then discuss the relationship between the activated NLRP3 inflammasome and secondary white matter injury after intracerebral hemorrhage.The activation of the NLRP3 inflammasome can exacerbate secondary white matter injury by disrupting the blood–brain barrier,inducing neuroinflammation,and interfering with nerve regeneration.Finally,we outline potential treatment strategies for intracerebral hemorrhage and its secondary white matter injury.Our review highlights the critical role of the gut microbiota–brain axis and the NLRP3 inflammasome in white matter injury following intracerebral hemorrhage,paving the way for exploring potential therapeutic approaches.
文摘Refined rhubarb tablets were used to treat 182 cases of acute hemorrhaging of the upperdigestive tract with a total effective rate of 96. 1 % and an average hemostatic time ot 2. 8 days. Prospec-tive and double blind comparative studies of the drug revealed that it had a rernarkably higher hemostaticeffect than compound western medicines (P<0. 01) and was superior to crude rhubarb, which usuallycaused nausea and vomiting and had unstable therapeutic effects- Acute and subacute toxicity determina-tions. genetic toxicologic tests, as well as determinations of various indexes ot blood vessels, pepsin.blood rheology, platelets, bleeding and blood coagulation factors were done, suggesting that refinedrhubarb tablets were nontoxic. safe and effective in local hemostasis and general hemodilution-likehemostasis.
基金Supported by grants from the National Natural Science Foundation of China(No.82171018,No.82371022)Beijing Hospitals Authority’s Ascent Plan(No.DFL20240202)+2 种基金The Youth Beijing Scholars Program(No.022)High Level Public Health Technical Talents Construction Project from Beijing(Jie Y)Beijing Municipal Public Welfare Development and Reform Pilot Project for Medical Research Institutes(No.2023YFC2410401).
文摘AIM:To evaluate the efficacy and safety of decellularized conjunctival stroma(DCS)as a novel biomaterial by comparing its grafting outcomes with amniotic membrane(AM)when used for conjunctival reconstruction after primary pterygium excision.METHODS:This randomized,parallel-controlled study with allocation concealment enrolled 40 patients with primary pterygium.Participants were randomly assigned to two groups using the sealed envelope method:the DCS group(n=20)and the AM group(n=18),receiving DCS and AM grafts respectively.Slit-lamp photography of the operative eyes was performed preoperatively and at 1,3,5,7,10,30,90,and 180d postoperatively.Best-corrected visual acuity(BCVA)and symptom scores were recorded simultaneously.In vivo confocal microscopy was conducted at 3 and 6mo postoperatively.RESULTS:All participants exhibited improved postoperative symptoms.The mean age was 60±9y(male/female ratio:6/14)in the DCS group and 56±12y(male/female ratio:7/11)in the AM group.The average epithelial healing time was 9.89±3.54d in the DCS group and 8.17±1.34d in the AM group(P=0.084).One recurrence case was observed in each group.Postoperative graft hemorrhage was significantly more severe in the DCS group than in the AM group only at 30d postoperatively(P=0.011).In vivo confocal microscopy revealed conjunctival epithelial cell growth in both groups at 90d postoperatively,while clear corneo-conjunctival cell boundaries were observed until 180d postoperatively.CONCLUSION:DCS used in primary pterygium surgery has a safety profile comparable to AM.It promotes rapid postoperative conjunctival healing,achieves a relatively low pterygium recurrence rate,and yields outcomes similar to AM.DCS provides a novel biomaterial option for conjunctival reconstruction after pterygium excision and the treatment of other conjunctival injuries.
文摘Objective:To assess the effectiveness of intravenous immunoglobulin(IVIg)therapy in patients diagnosed with Crimean-Congo hemorrhagic fever(CCHF)disease.Methods:A single-center retrospective cohort study was conducted on hospitalized patients with confirmed severe CCHF at a tertiary care hospital in Turkey between 2010 and 2022.Cases were categorized into two groups based on whether they received IVIg therapy,with the treatment plan determined by the primary healthcare provider.The clinical,epidemiological,and laboratory parameters of these patients were evaluated.Demographic,laboratory findings,platelet counts on the day of IVIg indication and the third day,bleeding status during follow-up beyond 24 hours after IVIg administration,and prognosis recorded in patient information forms were retrieved.Results:72 patients were included in the analysis,with IVIg administered to 42 cases(58.3%)and not given to 30 cases(41.7%).Among the patients,37(51.4%)were female.Fever(65.3%)was the most common clinical presentation.The overall mortality rate was 19.4%,and IVIg administration did not significantly impact overall survival outcomes(P=0.48).On Day 3 following IVIg administration or indication,the platelet count was higher in the IVIg-treated group compared to the non-treated group(P=0.02).Furthermore,during follow-up beyond 24 hours after IVIg administration,bleeding was observed in 19.0%of the IVIg-treated group,compared to 46.6% in the non-treated group(P=0.01).Conclusions:This study underscores the potential advantages of IVIg therapy in managing severe CCHF.Although IVIg administration did not significantly affect overall survival,it was associated with earlier improvement in platelet counts and a notable reduction in bleeding complications.These findings indicate that IVIg may serve as an adjunctive treatment in CCHF,particularly for addressing hemorrhagic manifestations.
基金supported by the National Natural Science Foundation of China,Nos.82272616(to ZL),82271325(to WS)the Natural Science Foundation of Beijing,No.7252076(to YR).
文摘Stroke can be categorized as ischemic and hemorrhagic on the basis of its origin.The pathophysiology following a stroke is complex,and is characterized by ongoing inflammation,neuronal injury,and the accumulation of reactive oxygen species in the brain,all of which reflect a dynamic process of change.This complexity hinders achievement of significant therapeutic outcomes with standard stroke treatment procedures,limiting post-stroke recovery.This review presents an innovative post-stroke therapeutic approach that utilizes nanomedicines to modify the cerebral microenvironment.It highlights the primary roles of chronic inflammation and nerve repair issues in causing prolonged impairment in stroke patients.Traditional therapies show limited effectiveness in achieving neuroprotection,immunoregulation,and neural regeneration during the subacute and chronic phases of stroke.Therefore,effective stroke management requires the use of specific therapeutic strategies tailored to the pathological characteristics of each phase.Various types of nanomedicines possess distinct physicochemical properties and can be selected on the basis of the specific therapeutic needs.Surface-modification technologies have significantly enhanced the ability of nanomedicines to penetrate the blood-brain barrier and improve their targeting capabilities in drug administration.However,the stability,biocompatibility,and long-term safety of nanomedicines require further optimization for clinical application.Nanomedicines represent a novel approach to stroke treatment through targeted delivery and multifaceted regulatory mechanisms.These medicines provide distinct advantages,particularly in addressing chronic inflammation and promoting nerve regeneration.As a result,nanomedicines are expected to significantly improve rehabilitation outcomes and quality of life for stroke patients in the future,emerging as a crucial modality for stroke treatment.
文摘Objective:To explore the impact of systematic stepwise rehabilitation nursing intervention on the prognosis and disease uncertainty of patients with hypertensive intracerebral hemorrhage,and to provide feasible strategies for clinical nursing.Methods:Eighty patients with hypertensive intracerebral hemorrhage admitted to our hospital from January 2023 to June 2025 were selected and randomly divided into an observation group(n=40,receiving systematic stepwise rehabilitation nursing)and a control group(n=40,receiving conventional nursing).The intervention effects were analyzed by comparing changes in the National Institutes of Health Stroke Scale(NIHSS)scores for neurological recovery,Short Form 36 Health Survey(SF-36)scores for quality of life,Exercise of Self-Care Agency Scale(ESCA)scores for self-management ability,compliance,and the Mishel Uncertainty in Illness Scale(MUIS)scores between the two groups.Results:All scores in the observation group were significantly better than those in the control group after the intervention(p<0.05).Specifically,the NIHSS scores decreased more significantly,the total SF-36 scores increased,the ESCA scores increased significantly,while the MUIS scores decreased significantly,and compliance improved markedly,indicating a reduction in disease uncertainty among patients.Conclusion:Systematic stepwise rehabilitation nursing intervention can significantly improve neurological recovery,quality of life,self-management ability,and compliance in patients with hypertensive intracerebral hemorrhage,while effectively reducing disease uncertainty.It is worthy of clinical promotion and application.
基金Jiangsu Provincial Hospital Association Hospital Management Innovation Research Fund(Project Ni.:JSYGY-3-2025-267)。
文摘Severe trauma often involves complex injuries,leading to high disability and fatality rates.Effective treatment requires prompt and coordinated efforts across multiple disciplines to enhance success rates.Time-based chain rescue is crucial in managing severe trauma.A patient with chest and abdominal injuries and hemorrhagic shock was transferred from an ambulance to our hospital.Our trauma team-initiated pre-hospital first aid,utilized an emergency green channel,and conducted rapid ultrasound,collaborating across disciplines.The patient eventually recovered and was discharged.
基金supported by National Key R&D Program:Key Special Project on Research for the Prevention and Treatment of Common Diseases-2022 Annual Project,Nos.2022YFC2504900,2022YFC2504902(both to ZL).
文摘Regulatory T cells are crucial immunomodulatory cells that play essential roles in both ischemic stroke and intracerebral hemorrhage.These cells are vital in post-stroke inflammation since they suppress immune responses and promote tissue repair.This review thoroughly examines the dynamic changes in the number and function of regulatory T cells and highlights their distinct roles at various stages of stroke progression.In the acute phase(within 5-7 days),regulatory T cells exert neuroprotective effects primarily by reducing inflammation.In the chronic phase(7 days post-onset),these cells support neuroregeneration and functional recovery.The review also explores the emerging role of regulatory T cells in the brain-gut axis,a key mediator of the systemic immune responses following stroke,and discusses its relevance in modulating post-stroke inflammation and repair.Various strategies aimed at enhancing regulatory T cell responses include adoptive transfer of regulatory T cells,administration of pharmacological agents,and induction of mucosal tolerance.All these approaches can potentially enhance the immunomodulatory and repair functions of regulatory T cells.Nevertheless,despite the promising preclinical results,the translation of regulatory T cell-based therapies into clinical practice is associated with challenges related to optimal timing,dosage,and long-term efficacy.Overall,targeting regulatory T cells is a novel and promising immunoregulatory approach for mitigating stroke-induced injury and promoting neural repair.
文摘Lassa fever(LF)is an acute viral hemorrhagic illness caused by the Lassa virus(LASV),an enveloped,spherical virus belonging to the Arenaviridae family.LASV possess a single-stranded RNA genome of negative polarity and exhibits high genetic diversity,corresponding to the geographical distribution of its seven principal distinct clades across West Africa[1].LASV was first isolated in 1969 from an American missionary nurse stationed in the rural town of Lassa,Borno State,Nigeria,following her return from a brief vacation in the United States[2].
基金supported by the National Natural Science Foundation of China,No.82204663(to TZ)the Natural Science Foundation of Shandong Province,No.ZR2022QH058(to TZ).
文摘Modulations of mitochondrial dysfunction,which involve a series of dynamic processes such as mitochondrial biogenesis,mitochondrial fusion and fission,mitochondrial transport,mitochondrial autophagy,mitochondrial apoptosis,and oxidative stress,play an important role in the onset and progression of stroke.With a better understanding of the critical role of mitochondrial dysfunction modulations in post-stroke neurological injury,these modulations have emerged as a potential target for stroke prevention and treatment.Additionally,since effective treatments for stroke are extremely limited and natural products currently offer some outstanding advantages,we focused on the findings and mechanisms of action related to the use of natural products for targeting mitochondrial dysfunction in the treatment of stroke.Natural products achieve neuroprotective through multi-target regulation of mitochondrial dysfunction encompassing the following processes:(1)Mitochondrial biogenesis:Cordyceps and hydroxysafflor yellow A activate the peroxisome proliferator-activated receptor gamma coactivator 1-alpha/nuclear respiratory factor pathway,promote mitochondrial DNA replication and respiratory chain protein synthesis,and thereby restore energy supply in the ischemic penumbra.(2)Mitochondrial dynamics balance:Ginsenoside Rb3 promotes Opa1-mediated neural stem cell migration and diffusion for recovery of damaged brain tissue.(3)Mitochondrial autophagy:Gypenoside XVII selectively eliminates damaged mitochondria via the phosphatase and tensin homolog-induced kinase 1/Parkin pathway and blocks reactive oxygen species and the NOD-like receptor protein 3 inflammasome cascade,thereby alleviating blood-brain barrier damage.(4)Anti-apoptotic mechanisms:Ginkgolide K inhibits Bax mitochondrial translocation and downregulates caspase-3/9 activity,reducing neuronal programmed death induced by ischemia-reperfusion.(5)Oxidative stress regulation:Scutellarin exerts antioxidant properties and improves neurological function by modulating the extracellular signal-regulated kinase 5-Kruppel-like factor 2-endothelial nitric oxide synthase signaling pathway.(6)Intercellular mitochondrial transport:Neuroprotective effects of Chrysophanol are associated with accelerated mitochondrial transfer from astrocytes to neurons.Existing studies have confirmed that natural products exhibit neuroprotective effects through multidimensional interventions targeting mitochondrial dysfunction in both ischemic and hemorrhagic stroke models.However,their clinical translation still faces challenges,such as the difficulty in standardization due to component complexity,insufficient cross-regional clinical data,and the lack of long-term safety evaluations.Future research should aim to integrate new technologies,such as single-cell sequencing and organoid models,to deeply explore the mitochondria-targeting mechanisms of natural products and validate their efficacy through multicenter clinical trials,providing theoretical support and translational pathways for the development of novel anti-stroke drugs.
基金Supported by the National Natural Science Foundation of China(No.82220108017,No.82141128)The Capital Health Research and Development of Special(No.2024-1-2052)+1 种基金Science&Technology Project of Beijing Municipal Science&Technology Commission(No.Z201100005520045)Sanming Project of Medicine in Shenzhen(No.SZSM202311018)。
文摘AIM:To evaluate the clinical features,diagnosis,treatment,and outcome of peripheral exudative hemorrhagic chorioretinopathy(PEHCR),a variant of polypoidal choroidal vasculopathy(PCV),in a case series of Chinese patients.METHODS:This study was retrospectively conducted from September 2018 to March 2025.Clinical examinations included color fundus photography,B-scan ultrasonography,fluorescein angiography(FA),indocyanine green angiography(ICGA),swept-source optical coherence tomography(SS-OCT),and optical coherence tomography angiography(OCTA),and two active or inactive subgroups and misdiagnosed cases were analyzed.RESULTS:Totally 19 patients(21 eyes)with a mean age of 54.3±9.4(range,36–68)y were included,with a majority of women(n=13,68.4%).The mean follow-up period was 13±1.4(range:1–57)mo.Decreased visual acuity was the most frequent initial manifestation(17 eyes,84.2%),and lesions were mainly distributed in the inferotemporal or temporal quadrant(14 eyes,66.7%),with choroidal polyps and branching neovascular networks revealed by OCTA and ICGA.Nine patients had been previously misdiagnosed with choroidal melanoma,and 6 of them had massive vitreous hemorrhage(VH).PEHCR manifested along a spectrum ranging from active or inactive subretinal hemorrhagic forms to chronic fibrotic or atrophic forms.One patient experienced natural regression.Ten eyes received a mean of 4.7±1.1(range:3–7)intravitreal anti-vascular endothelial growth factor(VEGF)injections,two eyes underwent vitrectomy,and six eyes were treated with vitrectomy combined with anti-VEGF therapy.Best-corrected visual acuity(logMAR)in treated eyes(18 eyes)improved to 0.31±0.25 from the baseline of 1.50±0.75(P<0.001).CONCLUSION:PEHCR is a variant of PCV.Chinese patients with PEHCR have a relatively younger age of onset.Anti-VEGF injections and/or vitrectomy are treatment options for lesion regression or dense VH to gain better visual outcomes.
基金supported by the National Key Research and Development Program of China,No.2022YFC2704801(to CZhu)the National Natural Science Foundation of China,Nos.U21A20347(to CZhu),82203969(to YX),82371472(to XZ)+3 种基金Health Commission of Henan Province,Nos.SBGJ202303039(to XZ),SBGJ202301009(to CZhu),YQRC2024018(to XZ),YQRC2024019(to YX)Henan Science and Technology Department,Nos.242102311054(to XZ),241111521300(to CZhu),GZS2023003(to XW)Swedish Research Council,Nos.2022-01019(to CZhu),2021-01950(to XW)Swedish Governmental Grants to Scientists Working in Healthcare,Nos.ALFGBG-1005209(to CZhu),ALFBG-1005257(to XW),ALFGBG-965197(to CZhu).
文摘Germinal matrix hemorrhage in preterm neonates often leads to white matter injury,contributing to long-term neurodevelopmental impairments.As resident brain immune cells,microglia play a complex role in injury response,including inflammation and repair.Although colony-stimulating factor 1 receptor inhibitors such as PLX5622 enable the selective depletion of microglia,their therapeutic potential in neonatal germinal matrix hemorrhage remains underexplored.Here,we used a collagenase-induced germinal matrix hemorrhage model in postnatal day 5 mice,and intraperitoneally administered PLX562272 hours post-germinal matrix hemorrhage to achieve targeted,temporary microglial depletion during the peak injury response.We then assessed the effects of this delayed intervention on oligodendrocyte lineage cell maturation,white matter integrity,and neurobehavioral outcomes.Additionally,RNA sequencing data from a germinal matrix hemorrhage rat model were analyzed using weighted gene co-expression network analysis to identify the critical phases for interventions.RNA sequencing data revealed a critical period in which key synaptic functions declined while immune responses intensified post-germinal matrix hemorrhage,thus pinpointing the critical response phases for potential interventions.Delayed PLX5622 treatment effectively depleted activated microglia,protecting against white matter injury and enhancing oligodendrocyte lineage cell maturation and myelination in subcortical white matter regions.Moreover,magnetic resonance imaging analysis revealed reduced brain lesion volumes in treated mice.Behaviorally,PLX5622-treated mice exhibited significant improvements in motor coordination and reduced hyperactivity compared with vehicle-treated germinal matrix hemorrhage model mice.These findings suggest that,when timed to avoid interference with initial oligodendrocyte lineage cell proliferation,targeted microglial depletion with PLX5622 significantly mitigates white matter damage and improves neurobehavioral outcomes in neonatal germinal matrix hemorrhage.The present study highlights the therapeutic potential of selectively modulating microglial reactivity to support neurodevelopment in preterm infants with brain injury.
文摘Subarachnoid hemorrhage(SAH) is a devastating condition that affects a total of 8 million people worldwide each year(Lauzier and Athiraman, 2024). Etiologies of SAH can be traumatic or nontraumatic, with the majority of non-traumatic SAH occurring due to intracranial aneurysm rupture(Rutledge et al., 2014).
基金Supported by National Natural Science Foundation of China(No.82160195,No.82460203)Zhejiang Traditional Chinese Medicine Science and Technology Plan Project(No.2025ZR172).
文摘AIM:To compare spontaneous brain regional activities between diabetic vitreous hemorrhage patients(DVHs)and healthy controls(HCs).METHODS:Thirty-two DVHs and 32 HCs were enrolled in this study.Baseline demographic and vision data were compared between groups using an independent sample t-test.Resting-state functional magnetic resonance imaging(rs-fMRI)was used in all participants.fMRI data was obtained and analyzed using MRIcro and SPM8 software.Fractional amplitude of low-frequency fluctuation(fALFF)technology was used to measure regional spontaneous brain activity,and sensitivity was tested using receiver operating characteristic curves(ROCs).The fALFF values were analyzed using REST software and two-sample t-tests were used to compare values between groups.Hospital anxiety and depression scale(HADS)score was assessed in DVHs and Pearson’s correlation was used to test relationships between mean fALFF value and both HADS score and duration of DVH.RESULTS:Except for the best-corrected visual acuity(BCVA)in both eyes,which showed a statistically significant difference(P<0.05),there were no statistically significant differences in the other indicators(P>0.05)between the HCs and DVHs group.Compared with controls,fALFF value was higher in DVH in cerebellum posterior lobe(CPL)and lower in right anterior cingulate cortex(ACC)and right medial orbitofrontal cortex(OFC).In DVH patients,mean fALFF value of CPL was positively correlated with HADS score and duration of diabetes.However,no such correlation was found,for right ACC or right medial OFC.DVH may lead to abnormal activities in certain brain regions related to visual control and mood.CONCLUSION:Visual impairment caused by DVH may lead to adjustment in regional visual brain activities and may be related to depression or reward system processing in some brain regions.
基金supported by the National Natural Science Foundation of China,Nos.92148206,82071330(both to ZT)a grant from the Major Program of Hubei Province,No.2023BAA005(to ZT)+1 种基金a grant from the Key Research and Discovery Program of Hubei Province,No.2021BCA109(to ZT)the Research Foundation of Tongji Hospital,No.2022B37(to PZ)。
文摘Recombinant tissue plasminogen activator is commonly used for hematoma evacuation in minimally invasive surgery following intracerebral hemorrhage.However,during minimally invasive surgery,recombinant tissue plasminogen activator may come into contact with brain tissue.Therefore,a thorough assessment of its safety is required.In this study,we established a mouse model of intracerebral hemorrhage induced by type VII collagenase.We observed that the administration of recombinant tissue plasminogen activator without hematoma aspiration significantly improved the neurological function of mice with intracerebral hemorrhage,reduced pathological damage,and lowered the levels of apoptosis and autophagy in the tissue surrounding the hematoma.In an in vitro model of intracerebral hemorrhage using primary cortical neurons induced by hemin,the administration of recombinant tissue plasminogen activator suppressed neuronal apoptosis,autophagy,and endoplasmic reticulum stress.Transcriptome sequencing analysis revealed that recombinant tissue plasminogen activator upregulated the phosphoinositide 3-kinase/RAC-alpha serine/threonine-protein kinase/mammalian target of rapamycin pathway in neurons.Moreover,the phosphoinositide 3-kinase inhibitor LY294002 abrogated the neuroprotective effects of recombinant tissue plasminogen activator in inhibiting excessive apoptosis,autophagy,and endoplasmic reticulum stress.Furthermore,to specify the domain of recombinant tissue plasminogen activator responsible for its neuroprotective effects,various inhibitors were used to target distinct domains.It has been revealed that the epidermal growth factor receptor inhibitor AG-1478 reversed the effect of recombinant tissue plasminogen activator on the phosphoinositide 3-kinase/RAC-alpha serine/threonineprotein kinase/mammalian target of rapamycin pathway.These findings suggest that recombinant tissue plasminogen activator exerts a direct neuroprotective effect on neurons following intracerebral hemorrhage,possibly through activation of the phosphoinositide 3-kinase/RAC-alpha serine/threonine-protein kinase/mammalian target of rapamycin pathway.
基金supported by the National Natural Science Foundation of China,No.81870927(to ZH)the Natural Science Foundation Project ofChongqing Science and Technology Commission,No.CSTB2023NSCQ-MSX0112(to ZH).
文摘Phosphodiesterase 4 is a key enzyme involved in the regulation of cell signal transduction,but its role in subarachnoid hemorrhage remains unclear.Neuronal pyroptosis has been reported to be involved in early brain injury after subarachnoid hemorrhage.This study aimed to investigate whether phosphodiesterase 4 contributes to early brain injury after subarachnoid hemorrhage by mediating neuronal pyroptosis and its related mechanisms.Endovascular perforation of male C57BL/6J mice was performed to model subarachnoid hemorrhage in vivo,and oxyhemoglobin was added to the culture medium of primary neurons to model subarachnoid hemorrhage in vitro.A phosphodiesterase 4-specific inhibitor,etazolate,was intraperitoneally injected 30 minutes after subarachnoid hemorrhage induction.Small interfering RNA(siRNA)was administered intracerebroventricularly 72 hours before subarachnoid hemorrhage to achieve genetic knockdown of phosphodiesterase 4.To investigate the mechanism,a nucleotide-binding oligomerization domain-like receptor pyrin domain containing 3(NLRP3)-specific agonist,nigericin,was intracerebroventricularly injected 60 minutes before subarachnoid hemorrhage.Neuronal phosphodiesterase 4 expression increased after subarachnoid hemorrhage and reached the highest point at 24 hours.Etazolate treatment reduced neurological deficits and brain edema in mice,alleviated neuronal pyroptosis and inflammatory response,and improved neuronal injury.Treatment with phosphodiesterase 4 siRNA had the same neuroprotective effects as etazolate.Mechanistically,phosphodiesterase 4 triggered the nuclear factor kappa-B pathway,and simultaneously caused lysosomal and mitochondrial dysfunction after subarachnoid hemorrhage,which promoted NLRP3 inflammasome activation and induced neuronal pyroptosis.Blocking of phosphodiesterase 4 inhibited the nuclear factor kappa-B pathway,and improved lysosome and mitochondrial function.Activation of NLRP3 reversed the neuroprotective effects of etazolate without affecting phosphodiesterase 4 expression.Together,the results indicate that phosphodiesterase 4 regulates NLRP3-mediated neuronal pyroptosis in early brain injury after subarachnoid hemorrhage.Phosphodiesterase 4 may be a potential therapeutic molecular target for subarachnoid hemorrhage.
基金The work was supported by National Natural Science Foundation of China(U22A20588,82172095)Shandong Provincial Natural Science Foundation(ZR2019QD005)Qingdao Science and Technology Demonstration and Guidance Project(20-3-4-50-nsh).
文摘Hemorrhage control requires hemostatic materials that are both efective and biocompatible.Among these,diatom biosilica(DBs)could signifcantly improve hemorrhage control,but it induces hemolysis(the hemolysis rate>5%).Thus,the purpose of this study was to explore the infuence of Ca^(2+)biomineralization on DBs for developing fast hemostatic materials with a low hemolysis rate.Here,CaCl_(2)was added to the diatom medium under high light(cool white,fuorescent lamps,67.5µmol m^(−2) s^(−1)),producing Ca-DBs-3 with a particle size of 40-50μm and a Ca^(2+)content of Ca-DBs-3 obtained from the higher concentration CaCl_(2)group(6.7 mmol L^(−1))of 0.16%.The liquid absorption capacity of Ca-DBs-3 was 30.43±0.57 times its dry weight;the in vitro clotting time was comparable to QuikClot®zeolite;the hemostatic time and blood loss using the rat tail amputation model were 36.40±2.52 s and 0.39±0.12 g,which were 40.72%and 19.50%of QuikClot®zeolite,respectively.Ca-DBs-3 showed no apparent toxicity to L929 cells(cell viability>80%)and was non-hemolysis(the hemolysis rate<2%).This study prepared Ca-DBs-3 with a rapid hemostatic efect and good biocompatibility,providing a path to develop diatom biosilica hemostatic materials.
基金supported by the National Natural Science Foundation of China,Nos.32070735(to QL),82371321(to QL),82171270(to ZL)Public Service Platform for Artificial Intelligence Screening and Auxiliary Diagnosis for the Medical and Health Industry,Ministry of Industry and Information Technology of the People's Republic of China,No.2020-0103-3-1(to ZL)+2 种基金the Natural Science Foundation of Beijing,No.Z200016(to ZL)Beijing Talents Project,No.2018000021223ZK03(to ZL)Beijing Municipal Committee of Science and Technology,No.Z201100005620010(to ZL)。
文摘Stroke is classified as ischemic or hemorrhagic,and there are few effective treatments for either type.Immunologic mechanisms play a critical role in secondary brain injury following a stroke,which manifests as cytokine release,blood–brain barrier disruption,neuronal cell death,and ultimately behavioral impairment.Suppressing the inflammatory response has been shown to mitigate this cascade of events in experimental stroke models.However,in clinical trials of anti-inflammatory agents,longterm immunosuppression has not demonstrated significant clinical benefits for patients.This may be attributable to the dichotomous roles of inflammation in both tissue injury and repair,as well as the complex pathophysiologic inflammatory processes in stroke.Inhibiting acute harmful inflammatory responses or inducing a phenotypic shift from a pro-inflammatory to an anti-inflammatory state at specific time points after a stroke are alternative and promising therapeutic strategies.Identifying agents that can modulate inflammation requires a detailed understanding of the inflammatory processes of stroke.Furthermore,epigenetic reprogramming plays a crucial role in modulating post-stroke inflammation and can potentially be exploited for stroke management.In this review,we summarize current findings on the epigenetic regulation of the inflammatory response in stroke,focusing on key signaling pathways including nuclear factor-kappa B,Janus kinase/signal transducer and activator of transcription,and mitogen-activated protein kinase as well as inflammasome activation.We also discuss promising molecular targets for stroke treatment.The evidence to date indicates that therapeutic targeting of the epigenetic regulation of inflammation can shift the balance from inflammation-induced tissue injury to repair following stroke,leading to improved post-stroke outcomes.
