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BACKGROUND:Neuronal necroptosis induced by intracerebral hemorrhage is an important cause of secondary brain injury.Activating transcription factor 4(ATF4)is a member of the transcription activator family,which plays an important role in secondary brain injury after intracerebral hemorrhage.However,the mechanism of ATF4 in neuronal necroptosis after intracerebral hemorrhage remains unclear. OBJECTIVE:To explore the effect of ATF4 silencing(ATF4 small interfering RNA,ATF4 siRNA)on neuronal necroptosis after intracerebral hemorrhage. METHODS:The HT-22 mouse hippocampal neuron cell line and the BV-2 mouse microglial cell line were co-cultured,and hemin was used to mimic an in vitro model of intracerebral hemorrhage.A gradient concentration of hemin was used to treat cells and was set in the interval of 0-100 μmol/L,and the cell viability was evaluated by MTT assay after 24 hours of administration of hemin.The cells were divided into four groups:the blank control group without any intervention;the control group was treated with hemin(50 μmol/L),and the other two groups were treated with negative control small interfering RNA(NC siRNA)and ATF4 small interfering RNA(ATF4 siRNA)48 hours before administration of hemin.After the cells were treated with hemin(50 μmol/L)for 24 hours,PI/Hoechst staining was used to detect neuronal necroptosis.Western blot assay was used to detect the protein expression of ATF4,receptor-interacting protein 3(RIP3),and mixed lineage kinase domain-like protein(MLKL),and double immunofluorescent staining was located in neurons to observe the level of neuronal necroptosis and the regulatory effect of ATF4 on it. RESULTS AND CONCLUSION:(1)50 μmol/L of hemin could induce neuronal necroptosis to a greater extent.(2)The number of PI+/Hoechst+ cells in the control group and NC siRNA group was higher than that in the blank control group(P<0.000 1).The number of PI+/Hoechst+ cells in the ATF4 siRNA group was lower than that in the control group(P<0.000 1).(3)Compared with the control group,the ATF4 siRNA group not only inhibited the expression of ATF4 protein(P<0.001),but also inhibited the expression of RIP3 and MLKL protein(P<0.001).(4)Through double immunofluorescent staining,compared with the control group,the protein expression of RIP3 and MLKL was significantly reduced in the ATF4 siRNA group(P<0.000 1).(5)The results show that the silencing of the ATF4 gene can directly or indirectly inhibit the expression of genes related to neuronal necroptosis after intracerebral hemorrhage,and play a vital role in alleviating secondary brain injury.
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BACKGROUND:There are differentially expressed genes in acute intracerebral hemorrhage,which are related to the occurrence and development of intracerebral hemorrhage. OBJECTIVE:To screen differentially expressed genes and key genes in brain tissue of a rat model with acute intracerebral hemorrhage,to validate them through qPCR,and to analyze the relationships between key genes and the neurological function and brain tissue water content after intracerebral hemorrhage. METHODS:Seventy-eight Sprague-Dawley rats were randomly divided into two groups:in intracerebral hemorrhage group,a rat model of acute intracerebral hemorrhage was made using collagenase injection at the right caudate nucleus;and in sham-operated group,rats were injected with equal amount of saline at the same site.RNA was extracted from rat brain tissues of both groups using the TRIzol method and transcriptome sequencing technology was used to identify differentially expressed genes in brain tissues of acute intracerebral hemorrhage,which were then verified by qPCR and analyzed for the relationships between the genes and neurological function and brain tissue water content after intracerebral hemorrhage.And the key genes were analyzed by GO and KEGG functional enrichment analysis in combination with bioinformatics. RESULTS AND CONCLUSION:Ten key genes were identified,including CXCL8,SERPINE1,TFPI2,CXCR4,GDA,KCNQ5,ERICH3,SCN3B,CACNA1E,and CCL20.The contents of GDA,KCNQ5,ERICH3,SCN3B,and CACNA1E in the intracerebral hemorrhage group were lower than those in the sham-operated group(P＜0.05).The contents of CXCL8,SERPINE1,TFPI2,CXCR4 and CCL20 in the intracerebral hemorrhage group were higher than those in the sham-operated group(P＜0.05).The contents of GDA,KCNQ5,ERICH3,SCN3B,and CACNA1E were positively correlated with brain tissue water content and neurologic deficit score(P＜0.05),while the contents of CXCL8,SERPINE1,TFPI2,CXCR4 and CCL20 were negatively correlated with brain tissue water content and neurologic deficit score(P＜0.05).GO analysis indicated that differentially expressed genes were mainly enriched in two biological processes(leukocyte chemotaxis and chemokine-mediated signaling pathways),two cell components(cation channel complexes and ion channel complexes),and two molecular functions(gated channel activity and ion channel activity).KEGG analysis indicated that differentially expressed genes were concentrated in tumor necrosis factor signaling pathway,glutamatergic synapses and GABAergic synapses.To conclude,the differentially expressed genes in intracerebral hemorrhage include CXCL8,SERPINE1,TFPI2,CXCR4,GDA,KCNQ5,ERICH3,SCN3B,CACNA1E,and CCL20,and these genes are related to brain tissue water content and neurological function after intracerebral hemorrhage.These genes are mainly enriched in cell components,binding functions,cellular protrusions,and other related biological functions.
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Objective To explore the effect of head CT blend signs on short-term outcomes in patients with spontaneous supraten-torial intracerebral hemorrhage(ICH)after craniotomy.Methods A total of 435 patients with spontaneous supratentorial ICH who un-derwent craniotomy in the Department of Neurosurgery,Jinyang Hospital Affiliated to Guizhou Medical University from January 2019 to December 2022 were enrolled retrospectively.The patients were divided into the blend sign group(n=105)and control group(n=330)based on the CT features at admission.The general clinical data,imaging data,surgical data,complications and prognosis were collected and compared between the two groups.The outcome was assessed by the mRS(modified Rankin scale)at discharge.Multivariate Logistic regression model was used to analyze the independent correlation between CT blend sign and poor outcomes.Results During the follow-up period,there was no significant differences in the proportion of patients with poor outcomes between the two groups.The poor outcomes after craniotomy was independently correlated with age,smoking history,diabetes history and Glasgow coma scale(GCS)at admission,but not with blend signs.Conclusion Head CT blend signs on admission is not associated with the poor outcomes in patients with sponta-neous supratentorial ICH after craniotomy.
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Objective:To explore role of miR-146a in regulating TLR4/NF-κB pathway on inflammatory injury and neuropro-tection in intracerebral hemorrhage model rats and its possible mechanism.Methods:A total of 40 rats were selected and randomly divided into sham,model,over-expressing miR-146a adenovirus and negative virus injection groups,with 10 rats in each group.Garcia score was used for neurological function;HE staining was used to observe changes of brain tissues.ELISA was used to detect inflammatory factors levels.TLR4,NF-κB protein and gene expressions in brain tissues were detected by Western blot and RT-PCR.Results:Compared with model group,neural function score of overexpressed miR-146a adenovirus injection group was increased(P<0.05).Model group had abnormal cell morphology,edema and inflammation.Cell morphology,edema and inflammation were alleviated in overexpressed miR-146a adenovirus injection group.Inflammatory factors levels in model group were higher than sham group(P<0.05).Inflammatory factors levels in overexpressed miR-146a adenovirus injection group were lower than model group(P<0.05).TLR4,NF-κB protein and mRNA expressions in model group were increased than sham group(P<0.05).TLR4,NF-κB protein and mRNA expressions in overexpressed miR-146a adenovirus injection group were decreased than model group(P<0.05).Conclusion:miR-146a can improve neural function and reduce inflammatory injury in rats with intracerebral hemorrhage,possibly by inhibiting activation of TLR4/NF-κB signaling pathway and reducing inflammatory factors levels of brain tissues.
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Spontaneous intracerebral hemorrhage (sICH), the most prevalent and lethal subtype of stroke, is characterized by spontaneous hemorrhage in the brain parenchyma. Presently, there are no effective methods for preventing and treating sICH. The existing sICH animal models can be broadly categorized into three classes: (1) induced intracerebral hemorrhage models, including autologous blood injection model, collagenase injection model, microballoon inflation model, and hyperglycemia-induced sICH hematoma expansion model; (2) spontaneous hypertensive intracerebral hemorrhage models mainly include stroke-prone spontaneously hypertensive rats (SHRsp) and stroke-prone renovascular hypertensive rats (RHRsp); (3) gene-modified models encompassing transgentic hypertensive intracerebral hemorrhage, transgentic cerebral amyloid angiopathy, arteriovenous malformation-related, cerebral cavernous malformation-related and collagen-related genetically modified animal models for sICH. These models contribute not only to unraveling the pathogenesis of sICH and exploring preventive or therapeutic interventions, but also serve as invaluable tools for conducting preclinical drug trials to advance novel treatments. This guide comprehensively reviews sICH pathogenesis, delineates the superiority and inferiority of different species of modeling animals, explains the modeling principles and techniques for various sICH animal models, elucidates the technical details of animal model production, summarizes the pathophysiological mechanism simulated by the models and their clinical relevance, outlines the neurobehavioral evaluation methodologies for sICH animal models, compares the advantages and disadvantages of various models, and suggests their applicable research areas. Additionally, it underscores critical considerations in the design of preclinical drug trials for sICH.
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@#Pediatric intracerebral hemorrhage is a rare condition among children. We discuss the case of a 7-year-old Filipino male with generalized tonic seizures and diagnosed to have both SARS-CoV-2 infection and hypertension secondary to renal arterial stenosis. The occurrence of intracerebral hemorrhage in children, though commonly caused by arteriovenous malformations, may be secondary to an acute hypertensive episode. In this case, the presence of COVID-19 in the patient may have been contributory to the development of spontaneous intracerebral hemorrhage due to its direct endothelial effects, as well as its dysregulatory action on the renin-angiotensin-aldosterone system.
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COVID-19 , Hypertension, Malignant , Renal Artery ObstructionABSTRACT
Objective To explore the effect of dexmedetomidine on the neurological function and mast cells activation in the mouse with intracerebral hemorrhage(ICH).Methods The mouse was intraperitoneal-ly injected with dexmedetomidine at 30 min before intracerebral hemorrhage.After the preparation of intrace-rebral hemorrhage model,the neurological function,brain water content,number of mast cells around hemato-ma and expression levels of tryptase,IL-1β,TNF-α were detected.Results Compared with the control group,the neurological function score in the intracerebral hemorrhage group was significantly elevated(P＜0.05),the brain water content was significantly increased(P＜0.05),the mast cells number was significantly in-creased(P＜0.05),and the tryptase,IL-1β and TNF-α expression levels were sinificantly increased(P＜0.05);while the neurological function score in the dexmedetomidine group was significantly decreased(P＜0.05),the brain water content was significantly decreased(P＜0.05),the number of mast cells was signifi-cantly reduced and the tryptase,IL-1β and TNF-α expression levels were significantly decreased(P＜0.05).Conclusion Dexmedetomidine could inhibit the activation of mast cells around hematoma and reduce the dam-age of neurological function after mouse intracerebral hemorrhage.
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Objective:To investigate the effects of gene silencing inducible cyclooxygenase-2 (COX-2) combined with hyperbaric oxygen (HBO) on neuronal cell edema, apoptosis, autophagy and neural functional recovery in rats with intracerebral hemorrhage.Methods:SPF-grade adult male SD rats ( n=96) were used to establish a cerebral hemorrhage model through stereotactic injection of thrombin VII into the caudate nucleus. They were randomized (random number) into 4 groups ( n=24/group): control group, hyperbaric oxygen (HBO) group, COX-2 RNAi group and combined group (COX-2 RNAi+HBO). The siRNA plasmid targeting silencing COX-2 gene expression was constructed. After group treatment, the four rats were randomly selected from each group for testing in each category. Postoperative day 1, 7, and 14 were assessed using the modified neurological severity score (mNSS) for evaluating neurofunctional deficits. On the 7th day, the water content of the brain tissue was measured using the dry/wet weight method. The blood-brain barrier permeability was assessed using the Evans method. Annexin V and TUNEL assays were employed to assess the apoptotic rate of neural cells. The mRNA expression level of COX-2 in brain tissue was determined using the RT-PCR method. The protein expression levels of Beclin-1, COX-2, aquaporin 4 (AQP-4), B cell lymphoma/lewkmia-2 (Bcl-2), caspase-3, hypoxia-inducible factor-1α (HIF-1α) and matrix metalloprotein-2/9 (MMP-2/9) were detected by Western blot (WB). SPSS software was used for data analysis. One-way ANOVA was used for inter group comparisons and LSD- t test was used for further pairwise comparison. Results:The SD rat intracerebral hemorrhage model and plasmid construction were successfully achieved. The mNSS scores were significantly decreased in COX-2 RNAi, HBO and combined groups compared with control group on the 7th day and 14th day (all P<0.01), especially in combined group ( P<0.01). The contents of Evans blue and the water content of brain tissue of all treatment groups were significantly lower than those in control group (all P<0.05), especially in combined group ( P<0.01). The apoptotic rate of neural cells decreased in all treatment groups compared with the control group (all P<0.05), and the combined group decreased the most ( P<0.01). The mRNA expression levels of COX-2 were significantly decreased in all treatment groups compared with the control group (all P<0.01), and combined group silenced COX-2 expression most obviously ( P<0.05). The results of WB showed that the protein expression levels of Beclin-1, COX-2, AQP-4, Caspase-3, HIF-1α, MMP-2/9 were significantly lower than control group (all P<0.05), while the expression of Bcl-2 was increased in all treatment groups (all P<0.01). Among them, the combined group exhibited the most pronounced trend ( P<0.01). Conclusions:Gene silencing of COX-2 in combination with hyperbaric oxygen therapy can effectively restore neurological function in rats with cerebral hemorrhage. The mechanism may be associated with reduced blood-brain barrier permeability, alleviated brain edema, and inhibition of neuronal apoptosis and autophagy.
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Resumen OBJETIVO: Describir las características de la población afectada y los retrasos que contribuyeron a la mortalidad materna, secundaria a los trastornos hipertensivos del embarazo. MATERIALES Y MÉTODOS: Estudio descriptivo y retrospectivo efectuado con base en la vigilancia epidemiológica de casos centinela de muertes maternas tempranas de mujeres residentes en Antioquia, Colombia, durante el embarazo, el parto y los 42 días siguientes a éste ocurridas en el periodo 2012-2020. Se creó una base de datos en Microsoft Access 2007 (Microsoft, Redmond, WA, USA) y los datos se analizaron en Microsoft Excel y SPSS versión 22. RESULTADOS: Se registraron 266 muertes maternas, de las que 38 fueron secundarias a trastornos hipertensivos del embarazo. La eclampsia fue causa de 15 fallecimientos; 12 por síndrome HELLP, 9 por hemorragia intracerebral y 2 por desprendimiento prematuro de placenta y coagulación intravascular diseminada. En 13 de los 38 casos no hubo una pauta adecuada del sulfato de magnesio, 19 no recibieron tratamiento antihipertensivo, que estaba indicado y 17 no tuvieron un control antihipertensivo adecuado. CONCLUSIÓN: La atención prenatal es una oportunidad decisiva para la detección, prevención y estratificación del riesgo. Todos los centros de atención obstétrica deben estar preparados para gestionar urgencias asociadas con los trastornos hipertensivos del embarazo. Los desenlaces mejoran con la aplicación de protocolos de emergencia estandarizados, organizados y la participación de equipos multidisciplinarios que garanticen una atención de calidad y un efecto positivo en la morbilidad y mortalidad materna susceptible de prevención.
Abstract OBJECTIVE: To describe the characteristics of the affected population and the delays that contributed to maternal mortality secondary to hypertensive disorders of pregnancy. MATERIALS AND METHODS: Descriptive and retrospective study based on the epidemiologic surveillance of sentinel cases of early maternal deaths of women residing in Antioquia, Colombia, during pregnancy, delivery and the 42 days after delivery occurring in the period 2012-2020. A database was created in Microsoft Access 2007 (Microsoft, Redmond, WA, USA), and data were analyzed in Microsoft Excel and SPSS version 22. RESULTS: There were 266 maternal deaths, of which 38 were secondary to hypertensive disorders of pregnancy. Eclampsia was the cause of 15 deaths; 12 due to HELLP syndrome, 9 due to intracerebral hemorrhage, and 2 due to placental abruption and disseminated intravascular coagulation. In 13 of the 38 cases, there was no adequate magnesium sulfate regimen, 19 did not receive indicated antihypertensive treatment, and 17 did not have adequate antihypertensive control. CONCLUSION: Antenatal care is a critical opportunity for detection, prevention, and risk stratification. All obstetric care centers should be prepared to manage emergencies associated with hypertensive disorders of pregnancy. Outcomes improve with the use of standardized, organized emergency protocols and the participation of multidisciplinary teams that ensure quality care and a positive impact on preventable maternal morbidity and mortality.
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In surgery of patients with hypertensive intracerebral hemorrhage, precise positioning and minimally invasive operation provide a strong guarantee for overall curative effect. As an emerging visualization software, 3D-Slicer can optimize surgical approach, achieve precise intraoperative positioning, and accurately measure hematoma volume to guide treatment plan implementation. This article reviews the application of 3D-Slicer in surgery of patients with hypertensive intracerebral hemorrhage.
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In 2022, the American Heart Association/American Stroke Association (AHA/ASA) issued Guidelines for Diagnosis and Treatment of Spontaneous Cerebral Hemorrhage (2022). This evidence-based guidelines provide treatment recommendations of cerebral hemorrhage. In particular, the guidelines emphasize the concepts of cerebral small-vessel disease, treatment of anticoagulant-related cerebral hemorrhage, and early rehabilitation at home. The authors interprets this guideline based on relevant research progress.
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Objective:To verify the clinical efficacy and safety of Qufeng Tongxuan method in treating low- and moderate-volume intracerebral hemorrhage at acute stage.Methods:A prospective, multicenter, randomized, double-blind, placebo-controlled study was performed; patients with low- and moderate-volume intracerebral hemorrhage at the basal ganglia and/or thalamus accepted treatment in 16 hospitals from September 2019 to April 2022 were enrolled. These patients were divided into experimental and control groups with a block randomized method by SAS software. Patients in control group were given conventional western medicine treatment; those in experimental group accepted Qufeng Tongxuan method (sequential therapy of Shexiang Huayu Xingnao granules and Zhilong Huoxue Tongyu granules) besides conventional western medicine treatment. NIHSS was used to assess neurological function before treatment and on 7 th, 14 th, 30 th, and 90 th d of treatment. Prognoses of these patients were assessed by modified Rankin scale (mRS) before treatment and on 180 th d of treatment. Brain CT was performed before treatment and on 7 th and 14 th d of treatment to calculate the hematoma volume. Before treatment and on 14 th d of treatment, changes of coagulation function, liver and kidney functions of the 2 groups were compared. Adverse reactions during treatment in the 2 groups were recorded. Results:No significant differences in NIHSS scores were noted between the 2 groups before treatment, on 7 th, 14 th, and 30 th d of treatment ( P>0.05); NIHSS scores in experimental group on 90 th d of treatment were signficantly lower than those in control group ( P<0.05); NIHSS scores in experimental group decreased gradually before treatment and on 7 th, 14 th, 30 th and 90 th d of treatment, with statistical significances ( P<0.05). No significant differences in mRS scores were noted between the 2 groups before treatment ( P>0.05); mRS scores in experimental group on 180 th d of treatment were signfciantly lower than those in control group ( P<0.05). No significant difference in hematoma volume was noted between the 2 groups before treatment and on 7 th and 14 th d of treatment ( P>0.05); both groups had gradually decreased hematoma volumes before treatment and on 7 th and 14 th d of treatment, respectively, with significant differences ( P<0.05); the volume difference of hematoma between 14 th d of treatment and before treatment in experimental group (6.42[4.10, 11.73]) was significantly higher than that in control group (4.00[1.25, 10.58], P<0.05). No significant differences in liver and kidney function indexes or coagulation function indexes were noted between the 2 groups before treatment and on 14 th d of treatment ( P>0.05). Adverse reaction incidence was 9.52% ( n=12) in experimental group and 10.34% ( n=12) in control group, without statistical difference ( P>0.05). Conclusion:Under premise of conventional western medicine treatment, Qufeng Tongxuan method can promote hematoma absorption and improve neurological deficit symptoms in low- and moderate-volume intracerebral hemorrhage at acute stage, without obvious adverse reactions.
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Objective:To evaluate the clinical efficacy and safety of neuro-endoscopic evacuation and microsurgery via keyhole approach in early spontaneous supertentorial intracerebral hemorrhage (ICH). Methods:A prospective multi-center randomized controlled trial was performed; 114 patients with spontaneous supertentorial ICH (time from onset to surgery<6 h) admitted to Departments of Neurosurgery, Shunde Hospital of Southern Medical University, Jiangmen Central Hospital, Affiliated Hospital of School of Medicine of Yanbian University from January 2019 to December 2021 and met the surgical indications were selected. They were divided into endoscopic group (evacuation of intracerebral hematoma under neuroendoscope, n=71) and microscopic group (microsurgery of intracerebral hematoma via keyhole approach, n=43) according to different surgical methods. After 1:1 propensity score matching of the general data, surgical time, hematoma clearance rate, early postoperative re-bleeding rate, Glasgow coma scale (GCS) scores 7 d after surgery, activity of daily living (ADL) scores 6 months after surgery, mortality, and surgery-related complications of 66 patients (33 from each group after matching) were compared. Results:The difference of surgical time between endoscopic group and microscopic group was statistically significant (125[102, 157] mins vs. 175[125, 260] mins, P<0.05). However, hematoma clearance rate (93.00%[80.88%, 96.52%] vs. 93.31%[88.15%, 96.03%]), early postoperative re-bleeding rate (15.2% vs. 9.1%), GCS scores 7 d after surgery (13[10, 15] vs. 12[8, 14]), ADL scores 6 months after surgery (65[45, 85] vs. 55[0, 85]), mortality rate (18.2% vs. 21.2%) and incidences of postoperative intracranial infection and acquired pulmonary infection were not statistically significant between the two groups ( P>0.05). Conclusion:Comparing with microsurgery via keyhole approach, neuro-endoscopy could shorten the surgical time, but not improve the prognosis or safety in early spontaneous supertentorial ICH patients.
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Objective:To develop a short-term prognostic model of spontaneous cerebral hemorrhage based on eXtreme Gradient Boosting (XGBoost) machine learning, and to compare its predictive performance with a Logistic regression model.Methods:Patients with sICH admitted to Department of Neurology, Second People's Hospital of Hefei from January 2018 to March 2022 were chosen; their general demographic characteristics, medical history, laboratory indices and cranial imaging data were retrospectively collected. The prognoses of patients 90 d after discharge were evaluated according to modified Rankin Scale (mRS) scores (good prognosis: mRS scores<3; poor prognosis: mRS scores≥3). XGboost and multiple Logistic regression models were used to screen out the factors for prognoses of patients 90 d after discharge, and area under receiver operating characteristic (ROC) curves, sensitivity, specificity and prediction accuracy of the 2 models were analyzed and compared.Results:A total of 413 patients with sICH were included; 180 patients(43.6 %) had poor prognosis and 233 (56.4%) had good prognosis 90 d after discharge. Multivariate Logistic regression results showed that age≥65 years, hemorrhage into the ventricle, hematoma volume of 20-40 mL, hematoma volume>40 mL and National Institutes of Health Stroke Scale (NIHSS) scores were independent influencing factors for short-term prognoses of sICH ( P<0.05). The variables in the XGBoost model were ranked in order of importance: NIHSS scores, systolic blood pressure at admission, Glasgow coma scale (GCS) scores, age≥65 years, hemorrhage into the ventricle, hematoma volume of 20-40 mL, and hematoma volume>40 mL. AUC of XGBoost model in predicting the prognosis was 0.895 (95% CI: 0.820-0.947), enjoying sensitivity of 68.89%, specificity of 94.83%, and prediction accuracy of 83.5%. AUC of Logistic regression model in predicting the prognosis was 0.894 (95% CI: 0.818-0.946), enjoying sensitivity of 93.33%, specificity of 70.69%, and prediction accuracy of 80.58%. Conclusion:The short-term prognostic model based on XGboost for sICH patients has high predictive efficacy, whose predictive accuracy is better than traditional Logistic regression.
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Ubiquitin-specific protease 11 (USP11) is a family member of deubiquitylases (DUBs). It mediates substrates de-ubiquitination to inhibit their ubiquitin-proteasome degradation and participates in cell cycle process, DNA damage repair, cell death, autophagy, signal transduction, immune inflammatory response, cerebral cortex development, and other physiological processes. Studies show that USP11 also plays an important role in central nervous system diseases. This article starts with the structure and functions of USP11 to systematically review the mechanism of USP11 in central nervous system diseases and provide new ideas for USP11 as a therapeutic target.
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Objective To compare five public deep venous thrombosis(DVT)risk assessment models(RAM)in patients with acute cerebral hemorrhage,and to select one suitable assessment tool,with which medical staff are able to carry out effective individualized prevention accordingly in time.Methods In this retrospective study,256 in-patients with acute cerebral hemorrhage in the Neurology Department of the First Affliated Hospital of Wenzhou Medical University from January to December 2020 were randomly enrolled.The researchers applied five models and record the scores,including Padua RAM,Caprini RAM,Wells DVT RAM,Autar RAM and acute stroke DVT-RAM.The data were summarized and analyzed with SPSS 25.0 and R4.1.The predictive values of above RAMs are compared separately by TOPSIS(technique for order preference by similarity solution)to find out a suitable tool.Results Predictive value(Ci)ranking of five DVT-RAMs,Autar RAM,Padua RAM,Caprini RAM,acute stroke DVT-RAM and Wells DVT RAM,by TOPSIS were 0.681,0.636,0.385,0.363,0.315.Conclusion According to comprehensive comparison by TOPSIS,Autar RAM was the suitable assessment model to assess the DVT risk of patients with acute cerebral hemorrhage.It is suggested that medical staff apply the Autar risk assessment model to predict the risk of DVT in patients with acute cerebral hemorrhage.
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Objective To explore the effect of hematoma aspiration device combined with low posterior osteotomy and small bone window craniotomy on neurological function and prognosis in patients with hypertensive intracerebral hemorrhage(HICH).Methods The clinical data of 132 patients with HICH in the Department of Neurosurgery,Gansu Provincial people's Hospital from February 2020 to February 2022 were collected and divided into small bone window group(n=52)and aspiration group(n=80).The levels of serum neuron specific enolase(NSE)and interleukin-6(IL-6)were detected by enzyme linked immunosorbent assay(ELISA).The intraoperative condition(duration of operation and intraoperative blood loss),intracranial pressure,complete clearance rate of intracranial hematoma and the incidence of postoperative complications were compared.The prognosis of the patients was evaluated by activity of daily living scale(ADL).Results There was no significant difference in the levels of serum NSE and IL-6 between the two groups before operation(P>0.05).The levels of NSE and IL-6 in serum after operation were significantly lower than those before operation,and the intracranial pressure was improved after treatment,the difference has statistic significance(P<0.05).The postoperative serum NSE and IL-6 levels,operation duration,postoperative intracranial pressure and the total incidence of complications in aspiration group were lower than those in small bone window group(P<0.05),but there was no significant difference in intraoperative blood loss and the total incidence of long-term complications between the two groups(P>0.05).During the 6-month follow-up after surgery,the good prognosis rate of aspiration group was higher than that of small bone window group,and the difference was statistically significant(P<0.05);There was no statistically significant difference in the complete clearance rate of intracranial hematoma between the two groups of patients(P>0.05).Conclusion Low posterior osteotomy combined with hematoma aspiration can effectively treat HICH,promote the recovery of neurological function in patients.
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OBJECTIVE To investigate the improvement effect and mechanism of calycosin （CA） on acute inflammatory injury secondary to intracerebral hemorrhage. METHODS Male C57BL/6 mice were injected with type Ⅶ collagenase into the basal ganglia to establish an intracerebral hemorrhage model， which were divided into sham-operation group（phosphate buffered saline instead of collagenase）， model group， and different CA dose groups（15，30，60，120 mg/kg）. Based on the modified neurological severity score （mNSS） to screen the intervention doses， the volume of intracerebral hemorrhage， brain water content， the expressions of ionized calcium-binding adaptor molecule 1 （Iba1） in brain tissue， Toll-like receptor 4 （TLR4） and its downstream inflammatory factors [tumor necrosis factor-α （TNF-α）， inducible nitric-oxide synthase （iNOS）， interleukin-1β （IL- 1β）] in brain tissue， and the apoptosis of cells in brain tissue were detected. Primary microglia were cultured in vitro， and the expressions of TLR4 and its downstream inflammatory factors were detected. Primary neurons and primary microglia were co- cultured in vitro， and the apoptosis of neurons was detected. RESULTS The doses of 30 mg/kg and 60 mg/kg were selected as intervention doses of CA for subsequent experiments. Compared with the sham-operation group， the mice in the model group had cerebral hemorrhage， the volume of cerebral hemorrhage and brain water content were significantly increased （P＜0.05）； the positive expression rate of Iba1 protein in brain tissue was significantly increased， and the relative expression levels of TLR4， TNF-α， IL-1β and iNOS protein in brain tissue were up-regulated significantly. The apoptosis rate also increased significantly （P＜0.05）. Compared with model group， the above indexes of the mice in the 30 and 60 mg/kg CA groups were significantly improved （P＜0.05）. CA significantlyreduced the relative expression levels of TLR4 and its downstream inflammatory factors in microglia， and reduced the apoptosis of neurons in the co-culture system of primary neurons and primary microglia （P＜0.05）. CONCLUSIONS CA can exert a protective effect on the brain， which may be related to relieving the secondary acute inflammatory injury after intracerebral hemorrhage by inhibiting TLR4-mediated inflammatory response.
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Objective To explore the correlation between polarization status of microglia/macrophages(MG/MP)in brain tissue and edema around hematoma in patients with acute cerebral hemorrhage.Methods A total of 52 patients with acute intracerebral hemorrhage admitted to Anyang People's Hospital from December 2020 to November 2022 were selected as the research subjects.All patients underwent craniotomy to remove hematoma,and the normal brain tissue in the cortical area that was not invaded by the hematoma and the fragmented brain tissue around the hematoma(brain tissue around the hematoma)on the surgical pathway were obtained.The expression levels of inflammatory factors such as interleukin(IL)-1β,IL-6,tumor necrosis factor-α(TNF-α),IL-10 and transforming growth factor-β(TGF-β)protein in brain tissue were detected by Western blot.The expression levels of IL-1 β,IL-6,TNF-α,IL-10 and TGF-β mRNA in brain tissue were detected by fluorescence quantitative polymerase chain reaction.The levels of M1-type and M2-type MG/MP in brain tissue was detected by immunofluorescence confocal technique.CT images data of patients before operation were collected and the relative-erihema-tomal edema(r-PHE)was calculated.The patients were divided into high r-PHE group(2.0≤ r-PHE＜2.5)and low r-PHE group(1.5＜r-PHE＜2.0)according to r-PHE.The relative expression of IL-1 β,IL-6,TNF-α,IL-10 and TGF-β mRNA in brain tissue around the hematoma of patients between the high r-PHE group and the low r-PHE group was compared.Results The relative expressions of IL-1 β,IL-6,TNF-α protein and mRNA in brain tissue around the hematoma were significantly higher than those in the normal brain tissues(P＜0.05),but there was no significant difference in the relative expressions of IL-10 and TGF-β protein and mRNA between the brain tissue around the hematoma and the normal brain tissue(P＞0.05).The levels of M1 type and M2 type MG/MP in the brain tissue around the hematoma were significantly higher than those in normal brain tissue(P＜0.05).The relative expressions of IL-1β,IL-6 and TNF-α mRNA in the brain tissue around the hematoma of patients in the high r-PHE group were significantly higher than those in the low r-PHE group(P＜0.05),and there was no significant difference in the relative expressions of TGF-β and IL-10 mRNA in the brain tissue around the hematoma of patients between the two groups(P＞0.05).Conclusion The levels of pro-inflammatory factors and M1-type MG/MP are increased in the brain tissue around the hematoma in patients with acute cerebral hemorrhage,and the degree of polarization of M1-type MG/MP is consistent with the degree of edema around hematoma after cerebral hemorrhage.
ABSTRACT
The role of glial scar after intracerebral hemorrhage(ICH)remains unclear.This study aimed to inves-tigate whether microglia-astrocyte interaction affects glial scar formation and explore the specific function of glial scar.We used a pharmacologic approach to induce microglial depletion during different ICH stages and examine how ablating microglia affects astrocytic scar formation.Spatial transcriptomics(ST)analysis was performed to explore the potential ligand-receptor pair in the modulation of microglia-astrocyte interaction and to verify the functional changes of astrocytic scars at different periods.During the early stage,sustained microglial depletion induced disorganized astrocytic scar,enhanced neutrophil infiltration,and impaired tissue repair.ST analysis indicated that microglia-derived insulin like growth factor 1(IGF1)modulated astrocytic scar formation via mechanistic target of rapamycin(mTOR)signaling activation.Moreover,repopulating microglia(RM)more strongly activated mTOR signaling,facilitating a more protective scar formation.The combination of IGF1 and osteopontin(OPN)was necessary and sufficient for RM function,rather than IGF1 or OPN alone.At the chronic stage of ICH,the overall net effect of astrocytic scar changed from protective to destructive and delayed microglial depletion could partly reverse this.The vital insight gleaned from our data is that sustained microglial depletion may not be a reasonable treatment strategy for early-stage ICH.Inversely,early-stage IGF1/OPN treatment combined with late-stage PLX3397 treatment is a promising therapeutic strategy.This prompts us to consider the complex temporal dynamics and overall net effect of microglia and astrocytes,and develop elaborate treatment strategies at precise time points after ICH.