Damage of the blood vessels in retina due to diabetes is called diabetic retinopathy(DR).Hemorrhages is thefirst clinically visible symptoms of DR.This paper presents a new technique to extract and classify the hemorrh...Damage of the blood vessels in retina due to diabetes is called diabetic retinopathy(DR).Hemorrhages is thefirst clinically visible symptoms of DR.This paper presents a new technique to extract and classify the hemorrhages in fundus images.The normal objects such as blood vessels,fovea and optic disc inside retinal images are masked to distinguish them from hemorrhages.For masking blood vessels,thresholding that separates blood vessels and background intensity followed by a newfilter to extract the border of vessels based on orienta-tions of vessels are used.For masking optic disc,the image is divided into sub-images then the brightest window with maximum variance in intensity is selected.Then the candidate dark regions are extracted based on adaptive thresholding and top-hat morphological techniques.Features are extracted from each candidate region based on ophthalmologist selection such as color and size and pattern recognition techniques such as texture and wavelet features.Three different types of Support Vector Machine(SVM),Linear SVM,Quadratic SVM and Cubic SVM classifier are applied to classify the candidate dark regions as either hemor-rhages or healthy.The efficacy of the proposed method is demonstrated using the standard benchmark DIARETDB1 database and by comparing the results with methods in silico.The performance of the method is measured based on average sensitivity,specificity,F-score and accuracy.Experimental results show the Linear SVM classifier gives better results than Cubic SVM and Quadratic SVM with respect to sensitivity and accuracy and with respect to specificity Quadratic SVM gives better result as compared to other SVMs.展开更多
BACKGROUND Factor XIII(FXIII)deficiency is a rare yet profound coagulopathy.FXIII plays a pivotal role in hemostasis,and deficiencies in this factor can precipitate unchecked or spontaneous hemorrhaging.Immunological ...BACKGROUND Factor XIII(FXIII)deficiency is a rare yet profound coagulopathy.FXIII plays a pivotal role in hemostasis,and deficiencies in this factor can precipitate unchecked or spontaneous hemorrhaging.Immunological assays for detecting FXIII inhibitors are indispensable for diagnosing acquired FXIII deficiency;however,the availability of suitable testing facilities is limited,resulting in prolonged turnaround times for these assays.CASE SUMMARY In this case study,a 53-year-old male devoid of significant medical history presented with recurrent intracranial hemorrhages and a hematoma in the right hip.Subsequent genetic analysis revealed a homozygous mutation in the ACE gene,confirming the diagnosis of acquired FXIII deficiency.CONCLUSION This case underscores the significance of considering acquired deficiencies in clotting factors when evaluating patients with unexplained bleeding episodes.展开更多
Dear Editor,W e present three anatomical forms of premacular hemorrhage with niveau formation:hemorrhage in posterior precortical vitreous pocket(intrapocket hemorrhage),sub-internal limiting membrane(ILM)hemorrhage,a...Dear Editor,W e present three anatomical forms of premacular hemorrhage with niveau formation:hemorrhage in posterior precortical vitreous pocket(intrapocket hemorrhage),sub-internal limiting membrane(ILM)hemorrhage,and premacular retrocortical hemorrhage.Niveau formation is the formation of a horizonal boundary between fluid and blood cells when they accumulate in a closed space,because blood cells with higher specific gravity settle in a standing position.展开更多
Aims: Hemorrhages in the first trimester of pregnancy constitute a public health problem in developing countries with maternal mortality which is still very high. This is the most common reason for consultation in ear...Aims: Hemorrhages in the first trimester of pregnancy constitute a public health problem in developing countries with maternal mortality which is still very high. This is the most common reason for consultation in early pregnancy. The objectives of this study were to describe the sociodemographic characteristics of the patients, identify the etiologies, describe the management and evaluate the maternal prognosis in patients presenting with hemorrhage in the first trimester of pregnancy. Methods: This was a descriptive-type prospective study lasting 12 months from January 1 to December 31, 2020, carried out at the maternity ward of Ignace Deen National Hospital. Results: During the study period, we recorded 163 cases of hemorrhage in the first trimester of pregnancy out of 5478 deliveries, i.e. a frequency of 2.97%. The main incriminated etiologies were spontaneous abortion (46.62%), ectopic pregnancy (28.22%), hydatidiform mole (16.56%), threatened abortion (5.52%) and pregnancy stopped (3.06%). The socio-demographic profile of the patients was that of a woman in the age group of 26 - 30 years (33.12%), married (79.14%), with secondary level (35.58%), exercising a liberal profession (36.19%) and nulliparous (60.12%). More than half of the patients came directly from home (57.66%) with metrorrhagia (44.78%) and abdominal pain (33.12%) as reasons for consultation. The gestational age between 7-11SA was more represented (82.82%). Manual intrauterine aspiration (58.89%) and salpingectomy (28.22%) were the most practiced therapeutic procedures. We transfused 10.42% of patients and 20.85% received medical treatment. The maternal prognosis was good in 47.87%. The main complications recorded were anemia (38.65%) and the state of shock (10.42%). Conclusion: Hemorrhages in the first trimester of pregnancy represent an important cause of maternal morbidity in developing countries. The improvement of the maternal prognosis would pass by the early consultation in front of any case of pregnancy.展开更多
Third trimester bleeding is a common concern in obstetrics. The main objective of this work was to study the management of hemorrhages in the third trimester of pregnancy in the maternity ward of the Sominé Dolo ...Third trimester bleeding is a common concern in obstetrics. The main objective of this work was to study the management of hemorrhages in the third trimester of pregnancy in the maternity ward of the Sominé Dolo hospital in Mopti. Our prospective descriptive cross-sectional survey type study conducted at the maternity ward of Sominé Dolo hospital in Mopti over a period from January 1, 2017 to December 31, 2017 included 94 cases collected. During this period we had performed 1485 deliveries including 94 cases of pregnancies complicated by 3rd trimester hemorrhage, a frequency of 6.33%. The main cause of hemorrhage in the third trimester was represented by placenta preavia 42.6% followed by retroplacental hematoma 28.7%, uterine rupture 26.6% and association Placenta preavia and retroplacental hematoma 2.1%. The type of intervention depended on the cause of the hemorrhage and the maternal and fetal condition. More than half of the cases of uterine rupture 52% had benefited from a hysterorrhaphy during a laparotomy (n = 13/25) against 48% from hysterectomy (n = 12/25). Caesarean section was performed in 87.5% (n = 35/40) against 12.5% vaginal delivery (n = 5/40) in case of placenta preavia. In the end, in 74% of cases (n = 20/27) of retroplacental hematoma, first-line cesarean section was performed. The maternal prognosis was represented by a mortality rate of 12% (n = 11/94) and morbidity dominated by hypovolemic shock 48.9% (n = 22/94), infections 28.8% (n = 13/94) and coagulopathy 11.1% (n = 5/94). The fetal prognosis was very poor. More than half (55%) of the newborns had succumbed against 45% of the newly born. In 55.3% of cases neonatal mortality occurred antenatally. Neonatal morbidity was represented by prematurity, i.e. 20.2% (n = 19/94) and low birth weight, i.e. 22.3% (n = 21/94).展开更多
Background: The treatment of cerebellar hemorrhage (CH) may be different surgery or conservative according to the hematoma volume, compression of vital structures or hydrocephalus existence. In the present study, the ...Background: The treatment of cerebellar hemorrhage (CH) may be different surgery or conservative according to the hematoma volume, compression of vital structures or hydrocephalus existence. In the present study, the authors investigated the risk factors, the indications and the situation of external ventricular drainage (EVD) on the treatment line. Methods: 63 pure cerebellar hemorrhage patients were enrolled in the study. 36 cases underwent surgery;the other 27 were received conservative treatment. 15 and 13 cases received EVD in both groups. Hospital stay and mortality rates were investigated. Results: 4 cases in the conservative group underwent surgery secondary to treatment failure. Both of the groups had equal rates of morbidity and mortality. On the other hand, the group that received surgical intervention had shorter median hospital stay. The EVD does not seem to be life-saving at first but it gives time for preparing for surgery. Conclusions: We found that CH was strongly associated with early hydrocephalus and mortality. The early diagnosis and surgical evacuation of the mass are mandatory and life-saving if hematoma is larger than 10 ml. The EVD may not being a life-saving instrument but majorly it may be a time earning device if acute hydrocephalus present.展开更多
Neuronal cell death is a common outcome of multiple pathophysiological processes and a key factor in neurological dysfunction after subarachnoid hemorrhage.Neuronal ferroptosis in particular plays an important role in...Neuronal cell death is a common outcome of multiple pathophysiological processes and a key factor in neurological dysfunction after subarachnoid hemorrhage.Neuronal ferroptosis in particular plays an important role in early brain injury.Bromodomain-containing protein 4,a member of the bromo and extraterminal domain family of proteins,participated in multiple cell death pathways,but the mechanisms by which it regulates ferroptosis remain unclear.The primary aim of this study was to investigate how bromodomain-containing protein 4 affects neuronal ferroptosis following subarachnoid hemorrhage in vivo and in vitro.Our findings revealed that endogenous bromodomain-containing protein 4 co-localized with neurons,and its expression was decreased 48 hours after subarachnoid hemorrhage of the cerebral cortex in vivo.In addition,ferroptosis-related pathways were activated in vivo and in vitro after subarachnoid hemorrhage.Targeted inhibition of bromodomain-containing protein 4 in neurons increased lipid peroxidation and intracellular ferrous iron accumulation via ferritinophagy and ultimately led to neuronal ferroptosis.Using cleavage under targets and tagmentation analysis,we found that bromodomain-containing protein 4 enrichment in the Raf-1 promoter region decreased following oxyhemoglobin stimulation in vitro.Furthermore,treating bromodomain-containing protein 4-knockdown HT-22 cell lines with GW5074,a Raf-1 inhibitor,exacerbated neuronal ferroptosis by suppressing the Raf-1/ERK1/2 signaling pathway.Moreover,targeted inhibition of neuronal bromodomain-containing protein 4 exacerbated early and long-term neurological function deficits after subarachnoid hemorrhage.Our findings suggest that bromodomain-containing protein 4 may have neuroprotective effects after subarachnoid hemorrhage,and that inhibiting ferroptosis could help treat subarachnoid hemorrhage.展开更多
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
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
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
Stroke is a major cause of death and disability worldwide,and its pathogenesis is complex,involving multiple pathological processes,such as thrombosis,ischemia-repe rfusion injury,inflammato ry response,and blood-brai...Stroke is a major cause of death and disability worldwide,and its pathogenesis is complex,involving multiple pathological processes,such as thrombosis,ischemia-repe rfusion injury,inflammato ry response,and blood-brain barrier disruption.In recent years,neutrophil extracellular traps have been found to be involved in the body's anti-infection defense and to play an important role in stroke.Studies have shown that neutrophil extracellular traps promote thrombus expansion and neuroinflammation in ischemic stroke,and they may be involved in disease progression and recove ry in hemorrhagic stroke by modulating local inflammation and influencing hematoma clearance.This review systematically summarizes the evolution and mechanism of action of neutrophil extracellular traps in stroke pathology.Reactive oxygen species drive the formation of neutrophil extra cellular traps 6-24 hours after cerebral infarction.At 24-48 hours,they exacerbate vascular injury and thrombosis,at 48-72 hours,they aggravate neurological injury,and after 72 hours,neutrophil extra cellular tra ps are involved in the disruption of the blood-brain barrier and the maintenance of the inflammatory response.During stroke development,neutrophil extracellular traps are involved in multiple pathological mechanisms after cerebral infa rction.They induce vascular endothelial damage,exacerbating vascular leakage and edema,injuring neuro ns,inducing apoptosis,promoting thrombosis,participating in reperfusion injury,and damaging the blood-brain barrier.In hemorrhagic stroke,neutrophil extracellular traps are closely associated with hematoma clearance,early brain injury,and delayed cerebral ischemia,and can be used as a biomarker to assess disease progression and efficacy.In the acute phase of stroke,neutrophil extracellular traps mainly promote injury,and in the chronic phase,they mainly promote repair.Neutrophil extracellular traps,as an important biomarker of stro ke,are closely correlated with stroke severity.Additionally,neutrophil extra cellular traps play an important role in atheroscle rosis and intracranial venous thrombosis.Current research has confirmed that deoxyribonuclease is a key drug for degrading neutrophil extracellular traps and has shown significant therapeutic potential.Peptidyl arginine deiminase 4 inhibitors and high mobility group box 1 antagonists effectively inhibit the formation of neutrophil extra cellular traps through their own unique mechanisms.M ulti-targeted inte rvention strategies for neutrophil extracellular traps have shown broad clinical application prospects.Neutrophil extracellular traps exhibit syne rgistic effects with anticoagulants and thrombolytic drugs,and interventions targeting neutrophil extracellular traps can influence the efficacy of anticoagulation and thrombolytic therapy.These findings provide a theoretical basis for developing new anticoagulation and thrombolysis strategies for stroke and im p roving clinical outcomes for patients.展开更多
Epizootic Hemorrhagic Disease(EHD),a vector-borne disease affecting both wild and domestic ruminants,is transmitted by biting midges of the genus Culicoides.Since 2008,it has been classified as a notifiable disease by...Epizootic Hemorrhagic Disease(EHD),a vector-borne disease affecting both wild and domestic ruminants,is transmitted by biting midges of the genus Culicoides.Since 2008,it has been classified as a notifiable disease by the World Organization for Animal Health(WOAH).The causative agent,Epizootic Hemorrhagic Disease Virus(EHDV),belongs to the genus Orbivirus within the family Reoviridae and possesses a viral genome comprising ten double-stranded RNA(dsRNA)segments(JiménezCabello et al.2023).To date,ten distinct serotypes of EHDV,designated as EHDV-1,2,and 4 through 11,have been identified globally(Anthony et al.2009;Maan et al.2017;Shirafuji et al.2017;Yang et al.2020).展开更多
Microglia,lipids,and their interaction are found to play important roles in post-stroke immunity.Microglia are sensitive to detect environment change in injured brain.Activated microglia undergo phenotypical remodelin...Microglia,lipids,and their interaction are found to play important roles in post-stroke immunity.Microglia are sensitive to detect environment change in injured brain.Activated microglia undergo phenotypical remodeling and trigger complex signal casca d es to regulate immune responses after stroke.Lipids including peripheral lipid metabolism and lipid droplet biogenesis are involved in the control of microglia functions,such as activation,phagocytosis,proliferation,and pro-inflammation.In this review,we explore new scope of microglia and lipids in immune regulation of stro ke.Implication of peripheral lipid metabolism after stroke is mentioned and advances in microglia-lipid inte raction are discussed We give a special focus on how diet and gut microbiome influence neuroinflammation system via gut-brain axis,and how these processes associate with the risk and outcome of stroke.Moreove r,we reviewed the therapeutic targets related to lipid metabolism and microglial modulation after stro ke.These can provide a prospective strategy for more efficient and safer treatment for ischemic and hemorrhagic stroke.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
Ferroptosis plays a key role in nerve injury in intracerebral hemorrhage and is associated with the upregulation of murine double minute 2.Investigating the mechanism underlying murine double minute 2-related ferropto...Ferroptosis plays a key role in nerve injury in intracerebral hemorrhage and is associated with the upregulation of murine double minute 2.Investigating the mechanism underlying murine double minute 2-related ferroptosis could help identify new therapies for intracerebral hemorrhage.An in vitro intracerebral hemorrhage model was established by treating BV2 microglial cells with oxygen-glucose deprivation combined with hemin.The role of murine double minute 2 in regulating ferroptosis was investigated via transduction with RNA interference and lentivirus overexpression.Furthermore,intracerebral hemorrhage mouse models were constructed with and without an murine double minute 2 inhibitor(brigimadlin),and behavioral assays were performed to assess the learning ability and cognitive function.Murine double minute 2 dysregulation was associated with oxygen-glucose deprivation combined with hemin-induced BV2 microglial cell ferroptosis and M1/M2 polarization.The results suggested that murine double minute 2 induced glutathione peroxidase 4 ubiquitination and degradation to regulate ferroptosis and inflammatory responses in BV2 microglial cells.Mechanistically,Wilms tumor 1-associated protein induced murine double minute 2 N6-methyladenosine(m6A)modification and regulated ferroptosis and inflammatory responses.In vivo analysis showed that brigimadlin improved neurological deficits and spatial memory in mice with intracerebral hemorrhage.In summary,the results indicate that Wilms tumor 1-associated protein regulates murine double minute 2 m6A modification,and murine double minute 2 induces glutathione peroxidase 4 ubiquitination and degradation.This regulation promotes ferroptosis and inflammatory responses in oxygen-glucose deprivation combined with hemin-induced BV2 microglial cells,suggesting that the murine double minute 2-glutathione peroxidase 4-ferroptosis regulatory axis exerts neurotoxic effects.These findings identify glutathione peroxidase 4 as a potential gene therapy target for intracerebral hemorrhage-related brain injury.展开更多
Hemorrhagic shock(HS)is a leading cause of death worldwide,particularly within the first 24 h post-injury.Current treatments are limited,especially in low-resource settings.Therapeutic hypothermia(TH)offers potential ...Hemorrhagic shock(HS)is a leading cause of death worldwide,particularly within the first 24 h post-injury.Current treatments are limited,especially in low-resource settings.Therapeutic hypothermia(TH)offers potential benefits by reducing metabolic demands and protecting organs,but its application in HS is challenged by cooling difficulties and side effects.This study introduces a novel nasal gel formulation of N6-cyclohexyladenosine(CHA),an adenosine A1 receptor agonist,designed to enhance brain delivery while minimizing peripheral side effects.In a mouse model of HS,administration of CHA nasal gel significantly improved survival rates,reduced metabolic rates,and protected major organs without worsening coagulopathy.Metabolomics analysis revealed a shift towards fatty acid oxidation and increased antioxidant capacity.These findings demonstrate that CHA nasal gel effectively induces TH,offering a safe and innovative treatment strategy for HS,particularly in resource-limited environments.展开更多
Fatty liver hemorrhagic syndrome(FLHS)in laying hens is a metabolic disorder characterized by excessive hepatic lipid accumulation,inflammation,and hemorrhage,bearing pathological similarities to human non-alcoholic f...Fatty liver hemorrhagic syndrome(FLHS)in laying hens is a metabolic disorder characterized by excessive hepatic lipid accumulation,inflammation,and hemorrhage,bearing pathological similarities to human non-alcoholic fatty liver disease.With the rise of intensive poultry farming,the incidence of FLHS has markedly increased,resulting in significant economic losses in the poultry industry.The gut microbiota plays a crucial role in host digestion,metabolism,and immune regulation,particularly in liver diseases.Gut microbiota and its metabolites influence liver health via the gut-liver axis.This review aims to explore metabolite-mediated interactions between the laying hens and the gut microbiota,elucidating their role in the pathogenesis of FLHS.Host-derived metabolites,such as lipids,bile acids,amino acids,and carbohydrates,regulate the structure and function of the gut microbiota through the gut-liver axis,playing a role in FLHS progression.Concurrently,microbial metabolites,including short-chain fatty acids,bile acids,and amino acid derivatives,influence hepatic lipid metabolism,inflammation,and oxidative stress,driving the development of FLHS.Key microbes,such as Bacteroides,Lactobacillus,and Akkermansia muciniphila,are considered potential therapeutic targets due to their involvement in metabolite production.By integrating multi-omics data and mechanistic studies,this review highlights the central role of host–gut microbiota communication in FLHS and provides a theoretical basis and research direction for the development of microbiota-based intervention strategies.展开更多
基金supported by the ministry of education and the deanship of scientific research-Najran University-Kingdom of Saudi Arabia for their financial and technical support under code number NU/-/SERC/10/640.
文摘Damage of the blood vessels in retina due to diabetes is called diabetic retinopathy(DR).Hemorrhages is thefirst clinically visible symptoms of DR.This paper presents a new technique to extract and classify the hemorrhages in fundus images.The normal objects such as blood vessels,fovea and optic disc inside retinal images are masked to distinguish them from hemorrhages.For masking blood vessels,thresholding that separates blood vessels and background intensity followed by a newfilter to extract the border of vessels based on orienta-tions of vessels are used.For masking optic disc,the image is divided into sub-images then the brightest window with maximum variance in intensity is selected.Then the candidate dark regions are extracted based on adaptive thresholding and top-hat morphological techniques.Features are extracted from each candidate region based on ophthalmologist selection such as color and size and pattern recognition techniques such as texture and wavelet features.Three different types of Support Vector Machine(SVM),Linear SVM,Quadratic SVM and Cubic SVM classifier are applied to classify the candidate dark regions as either hemor-rhages or healthy.The efficacy of the proposed method is demonstrated using the standard benchmark DIARETDB1 database and by comparing the results with methods in silico.The performance of the method is measured based on average sensitivity,specificity,F-score and accuracy.Experimental results show the Linear SVM classifier gives better results than Cubic SVM and Quadratic SVM with respect to sensitivity and accuracy and with respect to specificity Quadratic SVM gives better result as compared to other SVMs.
基金Supported by the Medical and Health Science Foundation of Zhejiang,No.2023KY186Hangzhou Science and Technology Development Plan Guide Project,No.20220919Y023the Hangzhou Medical Key Discipline Construction Program,No.2021.
文摘BACKGROUND Factor XIII(FXIII)deficiency is a rare yet profound coagulopathy.FXIII plays a pivotal role in hemostasis,and deficiencies in this factor can precipitate unchecked or spontaneous hemorrhaging.Immunological assays for detecting FXIII inhibitors are indispensable for diagnosing acquired FXIII deficiency;however,the availability of suitable testing facilities is limited,resulting in prolonged turnaround times for these assays.CASE SUMMARY In this case study,a 53-year-old male devoid of significant medical history presented with recurrent intracranial hemorrhages and a hematoma in the right hip.Subsequent genetic analysis revealed a homozygous mutation in the ACE gene,confirming the diagnosis of acquired FXIII deficiency.CONCLUSION This case underscores the significance of considering acquired deficiencies in clotting factors when evaluating patients with unexplained bleeding episodes.
文摘Dear Editor,W e present three anatomical forms of premacular hemorrhage with niveau formation:hemorrhage in posterior precortical vitreous pocket(intrapocket hemorrhage),sub-internal limiting membrane(ILM)hemorrhage,and premacular retrocortical hemorrhage.Niveau formation is the formation of a horizonal boundary between fluid and blood cells when they accumulate in a closed space,because blood cells with higher specific gravity settle in a standing position.
文摘Aims: Hemorrhages in the first trimester of pregnancy constitute a public health problem in developing countries with maternal mortality which is still very high. This is the most common reason for consultation in early pregnancy. The objectives of this study were to describe the sociodemographic characteristics of the patients, identify the etiologies, describe the management and evaluate the maternal prognosis in patients presenting with hemorrhage in the first trimester of pregnancy. Methods: This was a descriptive-type prospective study lasting 12 months from January 1 to December 31, 2020, carried out at the maternity ward of Ignace Deen National Hospital. Results: During the study period, we recorded 163 cases of hemorrhage in the first trimester of pregnancy out of 5478 deliveries, i.e. a frequency of 2.97%. The main incriminated etiologies were spontaneous abortion (46.62%), ectopic pregnancy (28.22%), hydatidiform mole (16.56%), threatened abortion (5.52%) and pregnancy stopped (3.06%). The socio-demographic profile of the patients was that of a woman in the age group of 26 - 30 years (33.12%), married (79.14%), with secondary level (35.58%), exercising a liberal profession (36.19%) and nulliparous (60.12%). More than half of the patients came directly from home (57.66%) with metrorrhagia (44.78%) and abdominal pain (33.12%) as reasons for consultation. The gestational age between 7-11SA was more represented (82.82%). Manual intrauterine aspiration (58.89%) and salpingectomy (28.22%) were the most practiced therapeutic procedures. We transfused 10.42% of patients and 20.85% received medical treatment. The maternal prognosis was good in 47.87%. The main complications recorded were anemia (38.65%) and the state of shock (10.42%). Conclusion: Hemorrhages in the first trimester of pregnancy represent an important cause of maternal morbidity in developing countries. The improvement of the maternal prognosis would pass by the early consultation in front of any case of pregnancy.
文摘Third trimester bleeding is a common concern in obstetrics. The main objective of this work was to study the management of hemorrhages in the third trimester of pregnancy in the maternity ward of the Sominé Dolo hospital in Mopti. Our prospective descriptive cross-sectional survey type study conducted at the maternity ward of Sominé Dolo hospital in Mopti over a period from January 1, 2017 to December 31, 2017 included 94 cases collected. During this period we had performed 1485 deliveries including 94 cases of pregnancies complicated by 3rd trimester hemorrhage, a frequency of 6.33%. The main cause of hemorrhage in the third trimester was represented by placenta preavia 42.6% followed by retroplacental hematoma 28.7%, uterine rupture 26.6% and association Placenta preavia and retroplacental hematoma 2.1%. The type of intervention depended on the cause of the hemorrhage and the maternal and fetal condition. More than half of the cases of uterine rupture 52% had benefited from a hysterorrhaphy during a laparotomy (n = 13/25) against 48% from hysterectomy (n = 12/25). Caesarean section was performed in 87.5% (n = 35/40) against 12.5% vaginal delivery (n = 5/40) in case of placenta preavia. In the end, in 74% of cases (n = 20/27) of retroplacental hematoma, first-line cesarean section was performed. The maternal prognosis was represented by a mortality rate of 12% (n = 11/94) and morbidity dominated by hypovolemic shock 48.9% (n = 22/94), infections 28.8% (n = 13/94) and coagulopathy 11.1% (n = 5/94). The fetal prognosis was very poor. More than half (55%) of the newborns had succumbed against 45% of the newly born. In 55.3% of cases neonatal mortality occurred antenatally. Neonatal morbidity was represented by prematurity, i.e. 20.2% (n = 19/94) and low birth weight, i.e. 22.3% (n = 21/94).
文摘Background: The treatment of cerebellar hemorrhage (CH) may be different surgery or conservative according to the hematoma volume, compression of vital structures or hydrocephalus existence. In the present study, the authors investigated the risk factors, the indications and the situation of external ventricular drainage (EVD) on the treatment line. Methods: 63 pure cerebellar hemorrhage patients were enrolled in the study. 36 cases underwent surgery;the other 27 were received conservative treatment. 15 and 13 cases received EVD in both groups. Hospital stay and mortality rates were investigated. Results: 4 cases in the conservative group underwent surgery secondary to treatment failure. Both of the groups had equal rates of morbidity and mortality. On the other hand, the group that received surgical intervention had shorter median hospital stay. The EVD does not seem to be life-saving at first but it gives time for preparing for surgery. Conclusions: We found that CH was strongly associated with early hydrocephalus and mortality. The early diagnosis and surgical evacuation of the mass are mandatory and life-saving if hematoma is larger than 10 ml. The EVD may not being a life-saving instrument but majorly it may be a time earning device if acute hydrocephalus present.
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 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.
基金supported by the Guangdong Basic and Applied Basic Research Foundation,No.2023A1515030045(to HS)Presidential Foundation of Zhujiang Hospital of Southern Medical University,No.yzjj2022ms4(to HS)。
文摘Intracerebral hemorrhage is the most dangerous subtype of stroke,characterized by high mortality and morbidity rates,and frequently leads to significant secondary white matter injury.In recent decades,studies have revealed that gut microbiota can communicate bidirectionally with the brain through the gut microbiota–brain axis.This axis indicates that gut microbiota is closely related to the development and prognosis of intracerebral hemorrhage and its associated secondary white matter injury.The NACHT,LRR,and pyrin domain-containing protein 3(NLRP3)inflammasome plays a crucial role in this context.This review summarizes the dysbiosis of gut microbiota following intracerebral hemorrhage and explores the mechanisms by which this imbalance may promote the activation of the NLRP3 inflammasome.These mechanisms include metabolic pathways(involving short-chain fatty acids,lipopolysaccharides,lactic acid,bile acids,trimethylamine-N-oxide,and tryptophan),neural pathways(such as the vagus nerve and sympathetic nerve),and immune pathways(involving microglia and T cells).We then discuss the relationship between the activated NLRP3 inflammasome and secondary white matter injury after intracerebral hemorrhage.The activation of the NLRP3 inflammasome can exacerbate secondary white matter injury by disrupting the blood–brain barrier,inducing neuroinflammation,and interfering with nerve regeneration.Finally,we outline potential treatment strategies for intracerebral hemorrhage and its secondary white matter injury.Our review highlights the critical role of the gut microbiota–brain axis and the NLRP3 inflammasome in white matter injury following intracerebral hemorrhage,paving the way for exploring potential therapeutic approaches.
基金Natural Science Foundation of Shandong Province,No.ZR2022MH124Taian Science and Technology Development Fund,Nos.2023NS155,2023NS164。
文摘Stroke is a major cause of death and disability worldwide,and its pathogenesis is complex,involving multiple pathological processes,such as thrombosis,ischemia-repe rfusion injury,inflammato ry response,and blood-brain barrier disruption.In recent years,neutrophil extracellular traps have been found to be involved in the body's anti-infection defense and to play an important role in stroke.Studies have shown that neutrophil extracellular traps promote thrombus expansion and neuroinflammation in ischemic stroke,and they may be involved in disease progression and recove ry in hemorrhagic stroke by modulating local inflammation and influencing hematoma clearance.This review systematically summarizes the evolution and mechanism of action of neutrophil extracellular traps in stroke pathology.Reactive oxygen species drive the formation of neutrophil extra cellular traps 6-24 hours after cerebral infarction.At 24-48 hours,they exacerbate vascular injury and thrombosis,at 48-72 hours,they aggravate neurological injury,and after 72 hours,neutrophil extra cellular tra ps are involved in the disruption of the blood-brain barrier and the maintenance of the inflammatory response.During stroke development,neutrophil extracellular traps are involved in multiple pathological mechanisms after cerebral infa rction.They induce vascular endothelial damage,exacerbating vascular leakage and edema,injuring neuro ns,inducing apoptosis,promoting thrombosis,participating in reperfusion injury,and damaging the blood-brain barrier.In hemorrhagic stroke,neutrophil extracellular traps are closely associated with hematoma clearance,early brain injury,and delayed cerebral ischemia,and can be used as a biomarker to assess disease progression and efficacy.In the acute phase of stroke,neutrophil extracellular traps mainly promote injury,and in the chronic phase,they mainly promote repair.Neutrophil extracellular traps,as an important biomarker of stro ke,are closely correlated with stroke severity.Additionally,neutrophil extra cellular traps play an important role in atheroscle rosis and intracranial venous thrombosis.Current research has confirmed that deoxyribonuclease is a key drug for degrading neutrophil extracellular traps and has shown significant therapeutic potential.Peptidyl arginine deiminase 4 inhibitors and high mobility group box 1 antagonists effectively inhibit the formation of neutrophil extra cellular traps through their own unique mechanisms.M ulti-targeted inte rvention strategies for neutrophil extracellular traps have shown broad clinical application prospects.Neutrophil extracellular traps exhibit syne rgistic effects with anticoagulants and thrombolytic drugs,and interventions targeting neutrophil extracellular traps can influence the efficacy of anticoagulation and thrombolytic therapy.These findings provide a theoretical basis for developing new anticoagulation and thrombolysis strategies for stroke and im p roving clinical outcomes for patients.
基金supported by the National Key Research and Development Program of China(2022YFF0710500 and 2023YFF0724603)the Key Research&Development Program of Heilongjiang Province,China(Innovation Base)(JD2023SJ10)the Central Public-interest Scientific Institution Basal Research,China(1610302023003)。
文摘Epizootic Hemorrhagic Disease(EHD),a vector-borne disease affecting both wild and domestic ruminants,is transmitted by biting midges of the genus Culicoides.Since 2008,it has been classified as a notifiable disease by the World Organization for Animal Health(WOAH).The causative agent,Epizootic Hemorrhagic Disease Virus(EHDV),belongs to the genus Orbivirus within the family Reoviridae and possesses a viral genome comprising ten double-stranded RNA(dsRNA)segments(JiménezCabello et al.2023).To date,ten distinct serotypes of EHDV,designated as EHDV-1,2,and 4 through 11,have been identified globally(Anthony et al.2009;Maan et al.2017;Shirafuji et al.2017;Yang et al.2020).
基金Shanghai Municipal Health Commission,No.20224Z0008(to PY)the National Natural Science Foundation of China,No.82101412(to MZ)+1 种基金the Science Foundation of Naval Medical Center of PLA,No.23M2702(to MZ)National Key Research and Development Program of China,No.2023YFC2506506(QL)。
文摘Microglia,lipids,and their interaction are found to play important roles in post-stroke immunity.Microglia are sensitive to detect environment change in injured brain.Activated microglia undergo phenotypical remodeling and trigger complex signal casca d es to regulate immune responses after stroke.Lipids including peripheral lipid metabolism and lipid droplet biogenesis are involved in the control of microglia functions,such as activation,phagocytosis,proliferation,and pro-inflammation.In this review,we explore new scope of microglia and lipids in immune regulation of stro ke.Implication of peripheral lipid metabolism after stroke is mentioned and advances in microglia-lipid inte raction are discussed We give a special focus on how diet and gut microbiome influence neuroinflammation system via gut-brain axis,and how these processes associate with the risk and outcome of stroke.Moreove r,we reviewed the therapeutic targets related to lipid metabolism and microglial modulation after stro ke.These can provide a prospective strategy for more efficient and safer treatment for ischemic and hemorrhagic stroke.
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the National Natural Science Foundation of China,Nos.82311530117(to RJ),82260260(to FC).
文摘Ferroptosis plays a key role in nerve injury in intracerebral hemorrhage and is associated with the upregulation of murine double minute 2.Investigating the mechanism underlying murine double minute 2-related ferroptosis could help identify new therapies for intracerebral hemorrhage.An in vitro intracerebral hemorrhage model was established by treating BV2 microglial cells with oxygen-glucose deprivation combined with hemin.The role of murine double minute 2 in regulating ferroptosis was investigated via transduction with RNA interference and lentivirus overexpression.Furthermore,intracerebral hemorrhage mouse models were constructed with and without an murine double minute 2 inhibitor(brigimadlin),and behavioral assays were performed to assess the learning ability and cognitive function.Murine double minute 2 dysregulation was associated with oxygen-glucose deprivation combined with hemin-induced BV2 microglial cell ferroptosis and M1/M2 polarization.The results suggested that murine double minute 2 induced glutathione peroxidase 4 ubiquitination and degradation to regulate ferroptosis and inflammatory responses in BV2 microglial cells.Mechanistically,Wilms tumor 1-associated protein induced murine double minute 2 N6-methyladenosine(m6A)modification and regulated ferroptosis and inflammatory responses.In vivo analysis showed that brigimadlin improved neurological deficits and spatial memory in mice with intracerebral hemorrhage.In summary,the results indicate that Wilms tumor 1-associated protein regulates murine double minute 2 m6A modification,and murine double minute 2 induces glutathione peroxidase 4 ubiquitination and degradation.This regulation promotes ferroptosis and inflammatory responses in oxygen-glucose deprivation combined with hemin-induced BV2 microglial cells,suggesting that the murine double minute 2-glutathione peroxidase 4-ferroptosis regulatory axis exerts neurotoxic effects.These findings identify glutathione peroxidase 4 as a potential gene therapy target for intracerebral hemorrhage-related brain injury.
基金supported by grants from the National Natural Science Foundation of China(No.81981340417 to LiSu)Natural Science Foundation of Jiangsu Province Outstanding Youth Fund(No.BK20240134 to Yuanqing Gao).
文摘Hemorrhagic shock(HS)is a leading cause of death worldwide,particularly within the first 24 h post-injury.Current treatments are limited,especially in low-resource settings.Therapeutic hypothermia(TH)offers potential benefits by reducing metabolic demands and protecting organs,but its application in HS is challenged by cooling difficulties and side effects.This study introduces a novel nasal gel formulation of N6-cyclohexyladenosine(CHA),an adenosine A1 receptor agonist,designed to enhance brain delivery while minimizing peripheral side effects.In a mouse model of HS,administration of CHA nasal gel significantly improved survival rates,reduced metabolic rates,and protected major organs without worsening coagulopathy.Metabolomics analysis revealed a shift towards fatty acid oxidation and increased antioxidant capacity.These findings demonstrate that CHA nasal gel effectively induces TH,offering a safe and innovative treatment strategy for HS,particularly in resource-limited environments.
基金supported by the Science Research Project of Hebei Education Department(BJK2024077)Key Research and Development Projects of Hebei Province(22326619D)the National Natural Science Foundation of China(No.32473073 and No.32503085)。
文摘Fatty liver hemorrhagic syndrome(FLHS)in laying hens is a metabolic disorder characterized by excessive hepatic lipid accumulation,inflammation,and hemorrhage,bearing pathological similarities to human non-alcoholic fatty liver disease.With the rise of intensive poultry farming,the incidence of FLHS has markedly increased,resulting in significant economic losses in the poultry industry.The gut microbiota plays a crucial role in host digestion,metabolism,and immune regulation,particularly in liver diseases.Gut microbiota and its metabolites influence liver health via the gut-liver axis.This review aims to explore metabolite-mediated interactions between the laying hens and the gut microbiota,elucidating their role in the pathogenesis of FLHS.Host-derived metabolites,such as lipids,bile acids,amino acids,and carbohydrates,regulate the structure and function of the gut microbiota through the gut-liver axis,playing a role in FLHS progression.Concurrently,microbial metabolites,including short-chain fatty acids,bile acids,and amino acid derivatives,influence hepatic lipid metabolism,inflammation,and oxidative stress,driving the development of FLHS.Key microbes,such as Bacteroides,Lactobacillus,and Akkermansia muciniphila,are considered potential therapeutic targets due to their involvement in metabolite production.By integrating multi-omics data and mechanistic studies,this review highlights the central role of host–gut microbiota communication in FLHS and provides a theoretical basis and research direction for the development of microbiota-based intervention strategies.
