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
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
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
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
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
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
Nature makes the most beautiful solution to involuted problems.Among them,the parallel tubular structures are capable of transporting fluid quickly in plant trunks and leaf stems,which demonstrate an ingenious evoluti...Nature makes the most beautiful solution to involuted problems.Among them,the parallel tubular structures are capable of transporting fluid quickly in plant trunks and leaf stems,which demonstrate an ingenious evolutionary design.This study develops a mini-thermoelectric semiconductor P-N module to create gradient and parallel channeled hydrogels.The modules decrease quickly the temperature of polymer solution from 20◦C to20◦C within 5 min.In addition to the exceptional liquid absorption rate,the foams exhibited shape memory mechanics.Our mini device universally makes the inspired structure in such as chitosan,gelatin,alginate and polyvinyl alcohol.Non-compressible hemorrhages are the primary cause of death in emergency.The rapid liquid absorption leads to fast activation of coagulation,which provides an efficient strategy for hemostasis management.We demonstrated this by using our semiconductor modules on collagen-kaolin parallel channel foams with their high porosity(96.43%)and rapid expansion rate(2934%).They absorb liquid with 37.25 times of the own weight,show 46.5-fold liquid absorption speed and 24-fold of blood compared with random porous foams.These superior properties lead to strong hemostatic performance in vitro and in vivo.展开更多
Background:Repeated intracranial hemorrhages caused by cardiac myxoma is very rare.It is essential for physicians to be aware of such uncommon clinical feature of myxoma.Case presentation:We report a-49-year-old femal...Background:Repeated intracranial hemorrhages caused by cardiac myxoma is very rare.It is essential for physicians to be aware of such uncommon clinical feature of myxoma.Case presentation:We report a-49-year-old female patient complained of repeated multiple intracranial hemorrhages,with no sign of cardiac dysfunction or cerebral infarction before admission.Cavernous angioma (CA) was misdiagnosded due to the clinical and magnetic resonance (MR) presentation.A sudden ischemic event after admission led to the finding of a left atrial myxoma.Conclusions:Repeated intracranial hemorrhages can be the early and primary clinical presentation of cardiac myxoma,probably caused by its metastasis,without obvious ischemic stroke or cardiac symptoms.展开更多
Background:Acute lymphoblastic leukemia is a rare hematological malignancy.Pure subdural hemorrhages in a patient with acute lymphoblastic leukemia patient are extremely rare.Case presentation:This case presented acut...Background:Acute lymphoblastic leukemia is a rare hematological malignancy.Pure subdural hemorrhages in a patient with acute lymphoblastic leukemia patient are extremely rare.Case presentation:This case presented acute spontaneous subdural hemorrhage without head trauma at first,and acute lymphoblastic leukemia was diagnosed later.The second time,the patient was admitted with multiple pure subdural hemorrhages in different locations and periods with a history of slight head trauma.Conclusions:Pure subdural hemorrhages can occur in a patient with acute lymphoblastic leukemia.More care would be needed for pure subdural hemorrhages without obvious head trauma,and patients with hematological malignancies should be protected from even mild head trauma.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
Cholesterol is an important component of plasma membranes and participates in many basic life functions,such as the maintenance of cell membrane stability,the synthesis of steroid hormones,and myelination.Cholesterol ...Cholesterol is an important component of plasma membranes and participates in many basic life functions,such as the maintenance of cell membrane stability,the synthesis of steroid hormones,and myelination.Cholesterol plays a key role in the establishment and maintenance of the central nervous system.The brain contains 20%of the whole body’s cholesterol,80%of which is located within myelin.A huge number of processes(e.g.,the sterol regulatory element-binding protein pathway and liver X receptor pathway)participate in the regulation of cholesterol metabolism in the brain via mechanisms that include cholesterol biosynthesis,intracellular transport,and efflux.Certain brain injuries or diseases involving crosstalk among the processes above can affect normal cholesterol metabolism to induce detrimental consequences.Therefore,we hypothesized that cholesterol-related molecules and pathways can serve as therapeutic targets for central nervous system diseases.Intracerebral hemorrhage is the most severe hemorrhagic stroke subtype,with high mortality and morbidity.Historical cholesterol levels are associated with the risk of intracerebral hemorrhage.Moreover,secondary pathological changes after intracerebral hemorrhage are associated with cholesterol metabolism dysregulation,such as neuroinflammation,demyelination,and multiple types of programmed cell death.Intracellular cholesterol accumulation in the brain has been found after intracerebral hemorrhage.In this paper,we review normal cholesterol metabolism in the central nervous system,the mechanisms known to participate in the disturbance of cholesterol metabolism after intracerebral hemorrhage,and the links between cholesterol metabolism and cell death.We also review several possible and constructive therapeutic targets identified based on cholesterol metabolism to provide cholesterol-based perspectives and a reference for those interested in the treatment of intracerebral hemorrhage.展开更多
Subarachnoid hemorrhage leads to a series of pathological changes,including vascular spasm,cellular apoptosis,blood–brain barrier damage,cerebral edema,and white matter injury.Microglia,which are the key immune cells...Subarachnoid hemorrhage leads to a series of pathological changes,including vascular spasm,cellular apoptosis,blood–brain barrier damage,cerebral edema,and white matter injury.Microglia,which are the key immune cells in the central nervous system,maintain homeostasis in the neural environment,support neurons,mediate apoptosis,participate in immune regulation,and have neuroprotective effects.Increasing evidence has shown that microglia play a pivotal role in the pathogenesis of subarachnoid hemorrhage and affect the process of injury and the prognosis of subarachnoid hemorrhage.Moreover,microglia play certain neuroprotective roles in the recovery phase of subarachnoid hemorrhage.Several approaches aimed at modulating microglia function are believed to attenuate subarachnoid hemorrhage injury.This provides new targets and ideas for the treatment of subarachnoid hemorrhage.However,an in-depth and comprehensive summary of the role of microglia after subarachnoid hemorrhage is still lacking.This review describes the activation of microglia after subarachnoid hemorrhage and their roles in the pathological processes of vasospasm,neuroinflammation,neuronal apoptosis,blood–brain barrier disruption,cerebral edema,and cerebral white matter lesions.It also discusses the neuroprotective roles of microglia during recovery from subarachnoid hemorrhage and therapeutic advances aimed at modulating microglial function after subarachnoid hemorrhage.Currently,microglia in subarachnoid hemorrhage are targeted with TLR inhibitors,nuclear factor-κB and STAT3 pathway inhibitors,glycine/tyrosine kinases,NLRP3 signaling pathway inhibitors,Gasdermin D inhibitors,vincristine receptorαreceptor agonists,ferroptosis inhibitors,genetic modification techniques,stem cell therapies,and traditional Chinese medicine.However,most of these are still being evaluated at the laboratory stage.More clinical studies and data on subarachnoid hemorrhage are required to improve the treatment of subarachnoid hemorrhage.展开更多
Some studies have confirmed the neuroprotective effect of remote ischemic conditioning against stroke. Although numerous animal researches have shown that the neuroprotective effect of remote ischemic conditioning may...Some studies have confirmed the neuroprotective effect of remote ischemic conditioning against stroke. Although numerous animal researches have shown that the neuroprotective effect of remote ischemic conditioning may be related to neuroinflammation, cellular immunity, apoptosis, and autophagy, the exact underlying molecular mechanisms are unclear. This review summarizes the current status of different types of remote ischemic conditioning methods in animal and clinical studies and analyzes their commonalities and differences in neuroprotective mechanisms and signaling pathways. Remote ischemic conditioning has emerged as a potential therapeutic approach for improving stroke-induced brain injury owing to its simplicity, non-invasiveness, safety, and patient tolerability. Different forms of remote ischemic conditioning exhibit distinct intervention patterns, timing, and application range. Mechanistically, remote ischemic conditioning can exert neuroprotective effects by activating the Notch1/phosphatidylinositol 3-kinase/Akt signaling pathway, improving cerebral perfusion, suppressing neuroinflammation, inhibiting cell apoptosis, activating autophagy, and promoting neural regeneration. While remote ischemic conditioning has shown potential in improving stroke outcomes, its full clinical translation has not yet been achieved.展开更多
Cerebral edema caused by blood-brain barrier injury after intracerebral hemorrhage is an important factor leading to poor prognosis.Human-induced pluripotent stem cell-derived neural stem cell exosomes(hiPSC-NSC-Exos)...Cerebral edema caused by blood-brain barrier injury after intracerebral hemorrhage is an important factor leading to poor prognosis.Human-induced pluripotent stem cell-derived neural stem cell exosomes(hiPSC-NSC-Exos)have shown potential for brain injury repair in central nervous system diseases.In this study,we explored the impact of hiPSC-NSC-Exos on blood-brain barrier preservation and the underlying mechanism.Our results indicated that intranasal delivery of hiPSC-NSC-Exos mitigated neurological deficits,enhanced blood-brain barrier integrity,and reduced leukocyte infiltration in a mouse model of intracerebral hemorrhage.Additionally,hiPSC-NSC-Exos decreased immune cell infiltration,activated astrocytes,and decreased the secretion of inflammatory cytokines like monocyte chemoattractant protein-1,macrophage inflammatory protein-1α,and tumor necrosis factor-αpost-intracerebral hemorrhage,thereby improving the inflammatory microenvironment.RNA sequencing indicated that hiPSC-NSC-Exo activated the PI3K/AKT signaling pathway in astrocytes and decreased monocyte chemoattractant protein-1 secretion,thereby improving blood-brain barrier integrity.Treatment with the PI3K/AKT inhibitor LY294002 or the monocyte chemoattractant protein-1 neutralizing agent C1142 abolished these effects.In summary,our findings suggest that hiPSC-NSC-Exos maintains blood-brain barrier integrity,in part by downregulating monocyte chemoattractant protein-1 secretion through activation of the PI3K/AKT signaling pathway in astrocytes.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,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.
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 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,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the supports from the National Key R&D Program of China(2022YFC3006200)the National Natural Science Foundation of China(82302841)the Jiangsu Provincial Department of Science and Technology(BE2018626).
文摘Nature makes the most beautiful solution to involuted problems.Among them,the parallel tubular structures are capable of transporting fluid quickly in plant trunks and leaf stems,which demonstrate an ingenious evolutionary design.This study develops a mini-thermoelectric semiconductor P-N module to create gradient and parallel channeled hydrogels.The modules decrease quickly the temperature of polymer solution from 20◦C to20◦C within 5 min.In addition to the exceptional liquid absorption rate,the foams exhibited shape memory mechanics.Our mini device universally makes the inspired structure in such as chitosan,gelatin,alginate and polyvinyl alcohol.Non-compressible hemorrhages are the primary cause of death in emergency.The rapid liquid absorption leads to fast activation of coagulation,which provides an efficient strategy for hemostasis management.We demonstrated this by using our semiconductor modules on collagen-kaolin parallel channel foams with their high porosity(96.43%)and rapid expansion rate(2934%).They absorb liquid with 37.25 times of the own weight,show 46.5-fold liquid absorption speed and 24-fold of blood compared with random porous foams.These superior properties lead to strong hemostatic performance in vitro and in vivo.
基金The authors sincerely thank Dr.zakaria shahab for editorial assistance,and this study was sponsored by the National Natural Science Foundation of China (Nos.81400962，81571102
文摘Background:Repeated intracranial hemorrhages caused by cardiac myxoma is very rare.It is essential for physicians to be aware of such uncommon clinical feature of myxoma.Case presentation:We report a-49-year-old female patient complained of repeated multiple intracranial hemorrhages,with no sign of cardiac dysfunction or cerebral infarction before admission.Cavernous angioma (CA) was misdiagnosded due to the clinical and magnetic resonance (MR) presentation.A sudden ischemic event after admission led to the finding of a left atrial myxoma.Conclusions:Repeated intracranial hemorrhages can be the early and primary clinical presentation of cardiac myxoma,probably caused by its metastasis,without obvious ischemic stroke or cardiac symptoms.
文摘Background:Acute lymphoblastic leukemia is a rare hematological malignancy.Pure subdural hemorrhages in a patient with acute lymphoblastic leukemia patient are extremely rare.Case presentation:This case presented acute spontaneous subdural hemorrhage without head trauma at first,and acute lymphoblastic leukemia was diagnosed later.The second time,the patient was admitted with multiple pure subdural hemorrhages in different locations and periods with a history of slight head trauma.Conclusions:Pure subdural hemorrhages can occur in a patient with acute lymphoblastic leukemia.More care would be needed for pure subdural hemorrhages without obvious head trauma,and patients with hematological malignancies should be protected from even mild head trauma.
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.
基金supported by the National Natural Science Foundation of China,No.82072110Suzhou Municipal Science and Technology Bureau,No.SKJY2021046+1 种基金Shanghai Key Lab of Forensic Medicine&Key Lab of Forensic Science,Ministry of Justice,China(Academy of Forensic Science),No.KF202201a Project Funded by the Priority Academic Program Development of Jiangsu Higher Education Institutions(PAPD)(all to TW).
文摘Cholesterol is an important component of plasma membranes and participates in many basic life functions,such as the maintenance of cell membrane stability,the synthesis of steroid hormones,and myelination.Cholesterol plays a key role in the establishment and maintenance of the central nervous system.The brain contains 20%of the whole body’s cholesterol,80%of which is located within myelin.A huge number of processes(e.g.,the sterol regulatory element-binding protein pathway and liver X receptor pathway)participate in the regulation of cholesterol metabolism in the brain via mechanisms that include cholesterol biosynthesis,intracellular transport,and efflux.Certain brain injuries or diseases involving crosstalk among the processes above can affect normal cholesterol metabolism to induce detrimental consequences.Therefore,we hypothesized that cholesterol-related molecules and pathways can serve as therapeutic targets for central nervous system diseases.Intracerebral hemorrhage is the most severe hemorrhagic stroke subtype,with high mortality and morbidity.Historical cholesterol levels are associated with the risk of intracerebral hemorrhage.Moreover,secondary pathological changes after intracerebral hemorrhage are associated with cholesterol metabolism dysregulation,such as neuroinflammation,demyelination,and multiple types of programmed cell death.Intracellular cholesterol accumulation in the brain has been found after intracerebral hemorrhage.In this paper,we review normal cholesterol metabolism in the central nervous system,the mechanisms known to participate in the disturbance of cholesterol metabolism after intracerebral hemorrhage,and the links between cholesterol metabolism and cell death.We also review several possible and constructive therapeutic targets identified based on cholesterol metabolism to provide cholesterol-based perspectives and a reference for those interested in the treatment of intracerebral hemorrhage.
基金supported by the Natural Science Foundation of Shandong Province,No.ZR2022MH124the Youth Science Foundation of Shandong First Medical University,No.202201–105(both to YX)。
文摘Subarachnoid hemorrhage leads to a series of pathological changes,including vascular spasm,cellular apoptosis,blood–brain barrier damage,cerebral edema,and white matter injury.Microglia,which are the key immune cells in the central nervous system,maintain homeostasis in the neural environment,support neurons,mediate apoptosis,participate in immune regulation,and have neuroprotective effects.Increasing evidence has shown that microglia play a pivotal role in the pathogenesis of subarachnoid hemorrhage and affect the process of injury and the prognosis of subarachnoid hemorrhage.Moreover,microglia play certain neuroprotective roles in the recovery phase of subarachnoid hemorrhage.Several approaches aimed at modulating microglia function are believed to attenuate subarachnoid hemorrhage injury.This provides new targets and ideas for the treatment of subarachnoid hemorrhage.However,an in-depth and comprehensive summary of the role of microglia after subarachnoid hemorrhage is still lacking.This review describes the activation of microglia after subarachnoid hemorrhage and their roles in the pathological processes of vasospasm,neuroinflammation,neuronal apoptosis,blood–brain barrier disruption,cerebral edema,and cerebral white matter lesions.It also discusses the neuroprotective roles of microglia during recovery from subarachnoid hemorrhage and therapeutic advances aimed at modulating microglial function after subarachnoid hemorrhage.Currently,microglia in subarachnoid hemorrhage are targeted with TLR inhibitors,nuclear factor-κB and STAT3 pathway inhibitors,glycine/tyrosine kinases,NLRP3 signaling pathway inhibitors,Gasdermin D inhibitors,vincristine receptorαreceptor agonists,ferroptosis inhibitors,genetic modification techniques,stem cell therapies,and traditional Chinese medicine.However,most of these are still being evaluated at the laboratory stage.More clinical studies and data on subarachnoid hemorrhage are required to improve the treatment of subarachnoid hemorrhage.
基金supported partly by the National Natural Science Foundation of China,No.82071332the Chongqing Natural Science Foundation Joint Fund for Innovation and Development,No.CSTB2023NSCQ-LZX0041 (both to ZG)。
文摘Some studies have confirmed the neuroprotective effect of remote ischemic conditioning against stroke. Although numerous animal researches have shown that the neuroprotective effect of remote ischemic conditioning may be related to neuroinflammation, cellular immunity, apoptosis, and autophagy, the exact underlying molecular mechanisms are unclear. This review summarizes the current status of different types of remote ischemic conditioning methods in animal and clinical studies and analyzes their commonalities and differences in neuroprotective mechanisms and signaling pathways. Remote ischemic conditioning has emerged as a potential therapeutic approach for improving stroke-induced brain injury owing to its simplicity, non-invasiveness, safety, and patient tolerability. Different forms of remote ischemic conditioning exhibit distinct intervention patterns, timing, and application range. Mechanistically, remote ischemic conditioning can exert neuroprotective effects by activating the Notch1/phosphatidylinositol 3-kinase/Akt signaling pathway, improving cerebral perfusion, suppressing neuroinflammation, inhibiting cell apoptosis, activating autophagy, and promoting neural regeneration. While remote ischemic conditioning has shown potential in improving stroke outcomes, its full clinical translation has not yet been achieved.
基金supported by the National Natural Science Foundation of China,No.8227050826(to PL)Tianjin Science and Technology Bureau Foundation,No.20201194(to PL)Tianjin Graduate Research and Innovation Project,No.2022BKY174(to CW).
文摘Cerebral edema caused by blood-brain barrier injury after intracerebral hemorrhage is an important factor leading to poor prognosis.Human-induced pluripotent stem cell-derived neural stem cell exosomes(hiPSC-NSC-Exos)have shown potential for brain injury repair in central nervous system diseases.In this study,we explored the impact of hiPSC-NSC-Exos on blood-brain barrier preservation and the underlying mechanism.Our results indicated that intranasal delivery of hiPSC-NSC-Exos mitigated neurological deficits,enhanced blood-brain barrier integrity,and reduced leukocyte infiltration in a mouse model of intracerebral hemorrhage.Additionally,hiPSC-NSC-Exos decreased immune cell infiltration,activated astrocytes,and decreased the secretion of inflammatory cytokines like monocyte chemoattractant protein-1,macrophage inflammatory protein-1α,and tumor necrosis factor-αpost-intracerebral hemorrhage,thereby improving the inflammatory microenvironment.RNA sequencing indicated that hiPSC-NSC-Exo activated the PI3K/AKT signaling pathway in astrocytes and decreased monocyte chemoattractant protein-1 secretion,thereby improving blood-brain barrier integrity.Treatment with the PI3K/AKT inhibitor LY294002 or the monocyte chemoattractant protein-1 neutralizing agent C1142 abolished these effects.In summary,our findings suggest that hiPSC-NSC-Exos maintains blood-brain barrier integrity,in part by downregulating monocyte chemoattractant protein-1 secretion through activation of the PI3K/AKT signaling pathway in astrocytes.
