HAX-1 interferes in assembly of NLRP3-ASC to block microglial pyroptosis in cerebral I/R injury.

Acute cerebral ischemia has a high rate of disability and death. Although timely recanalization therapy may rescue the ischemic brain tissue, cerebral ischemia-reperfusion injury has been shown to limit the therapeutic effects of vascular recanalization. Protein HAX-1 has been reported as a pro-survival protein that plays an important role in various disorders, particularly in association with the nervous system. However, the effects and mechanisms of HAX-1 in cerebral IR injury have yet to be elucidated. So, we aimed to investigate the effect of HAX-1 on microglial pyroptosis and explore its potential neuroprotective effects in ischemia-reperfusion injury. Our results show that the expression of HAX-1 decreased after cerebral IR injury, accompanied by an increase in pyroptosis pathway activation. In addition, HAX-1 could inhibit microglial pyroptosis both in vivo and in vitro and reduce the release of inflammatory mediators. The above neuroprotective effects might be partially mediated by inhibiting of interaction of NLRP3 and ASC through competitive binding, followed by the attenuation of NLRP3 inflammasome formation. In conclusion, Our findings support that HAX-1 exhibits a protective role in cerebral I/R injury, and further study on HAX-1 expression regulation will contribute to cerebral infarction therapy.

Pipeline embolization of complex, wide-necked middle cerebral artery bifurcation aneurysms: A single-center experience.

PURPOSE: To evaluate the performance of Pipeline Embolization Device (PED) in complex, wide-necked middle cerebral artery (MCA) bifurcation aneurysms. METHODS: We performed a retrospective review of patients treated with PED for complex, wide-necked MCA bifurcation aneurysms between August 2016 and March 2021. In addition to demographic data, we collected aneurysmal neck width, dome-to-neck ratio, complications, and clinical and angiographic follow-up. The embolization degree of aneurysms was evaluated by O'Kelly-Marotta (OKM) grading scale, and the prognosis was assessed with the modified Rankin Scale (mRS). RESULTS: From August 2016 to March 2021, a total of 46 patients with 49 MCA bifurcation aneurysms in our center were enrolled, of whom all received PEDs successfully. The O'Kelly-Marotta (OKM) grading showed that post-procedure 15 patients (32.6%) were grade C, another 8 patients (17.4%) were grade D. Aneurysms with small remnant or complete occlusion were 50%, symptomatic ischemic events occurred in 3 (6.5%), and bleeding events in 1 (2.2%). 41 patients underwent a 6-month angiography follow-up, in which 7 patients (17.1%) remained OKM grade C and 30 patients (73.2%) achieved OKM grade D. Complete occlusion and small remnant aneurysms were up to 90.3%. 40 (97.6%) patients' mRS scores were 0, and 1 (2.4%) patient was 2. No new bleeding and ischemic events occurred during the 6-month. CONCLUSIONS: The Pipeline Embolization Device provides a safe and effective treatment alternative for complex, wide-necked MCA aneurysms. A larger number with longer-term follow-up data is needed for further verification.

The relationship between the level of vitamin D and ruptured intracranial aneurysms.

The purpose of our research is to explore whether vitamin D levels were associated with the rupture of intracranial aneurysms. In this retrospective study, 105 patients diagnosed with ruptured intracranial aneurysms (RIAs) and 185 patients diagnosed with unruptured intracranial aneurysms (UIAs) at The First Affiliated Hospital of Zhengzhou University were recruited from September 2019 to September 2020. Patients' demographic and clinical information, including vitamin D levels, were recorded and compared. Univariate analysis showed that patients with UIAs had higher vitamin D levels than RIAs (p = 0.019). In addition, there were significant differences in aneurysm location (p < 0.001), aspirin use (p = 0.001), and comorbid diabetes mellitus (p = 0.037) between patients with UIAs and RIAs. Binary logistic regression analysis showed that the level of vitamin D was independently associated with RIAs [odds ratio (OR) 0.960; 95% confidence intervals (CI), 0.926-0.996, p = 0.028].

The clinical analysis and treatment strategy of endovascular treatment for cerebral venous sinus thrombosis combined with intracerebral hemorrhage.

Cerebral venous sinus thrombosis (CVST) combined with intracerebral hemorrhage(ICH) is a special subgroup, and whether intrasinus thrombolysis (IST) or mechanical thrombectomy (MT) therapy should be carried out is controversial because of previous hemorrhage and possible delayed hemorrhage.The aim of this study was to analyze the safety and effectiveness of endovascular treatment of CVST with ICH and further discuss the treatment strategy. This is a retrospective study of 56 cases admitted from January 2010 to June 2019 diagnosed with CVST combined with ICH, and all were treated with endovascular treatment including IST with or without MT. We reviewed the clinical, radiological, and outcome data of all patients. The percentage of cases that showed complete and partial recanalization were 67.8% and 26.9% after endovascular treatment. ICH exacerbation occurred in 5 cases during thrombolysis. The percentage of cases with good outcome was 87.5% at discharge. 51 cases were followed up at sixth month. 49 cases had a mRS score of 0-2,and 2 cases had a mRS score of 3-4 at sixth month.Our data suggest that endovascular treatment may improve clinical and radiological outcome in most patients of CVST with ICH, but confirmation in prospective, controlled studies is warranted.

[Seasonal variation and driving factors of forest fire in Zhejiang Province, China, based on MODIS satellite hot spots]. / 基于MODISå«æ˜Ÿç«ç‚¹çš„æµ™æ±Ÿçœæž—ç«å­£èŠ‚å˜åŒ–åŠé©±åŠ¨å› å­.

Understanding the changes and driving factors of forest fire can provide scientific basis for prevention and management of forest fire. In this study, we analyzed the changes and driving factors of forest fire in Zhejiang Province during 2001-2016 based on trend analysis and Logistic regression model with the MODIS satellite fire point data combined with meteorological (daily ave-rage wind speed, daily average temperature, daily relative humidity, daily temperature difference, daily cumulative precipitation), human activities (distance from road, distance from railway, distance from resident, population, per capita GDP), topographic and vegetation factors (elevation, slope, vegetation coverage). The results showed that the number of forest fires in spring and summer had significantly increased, while the forest fires in the autumn and winter increased first and then decreased. Forest fire in autumn significantly declined. The four seasons' fire occurrence prediction models had good prediction accuracy, reaching 75.8% (spring), 79.1% (summer), 74.7% (autumn) and 79.6% (winter). The meteorological, human activity, topographic and vegetation factors significantly affected fire occurrence in spring and summer, while meteorological factors were the main fire drivers in autumn and winter in Zhejiang. The focus of forest fire management should be on human activities. Fire prevention campaign should be done in spring and summer when high-risk forest fires were scattered in the study area. In autumn and winter, observatory and monitoring equipment could be built to facilitate fire management and detect in the area of high fire risk that was concentrated in the southwest region.

[Forest fire management in the United States]. / 美国林火管理概况及分析.

With the intensification of climate change and human activities, megafires frequently occur, with serious impacts on ecosystems, atmospheric environment, and human health. The United States has accumulated a large amount of practical experience in forest fire management. A comprehensive review of the framework of forest fire management in the United States can provide an inspiring reference for forest fire prevention in China. Starting from the process of historical evolution of forest fire policy, we systematically introduced the four stages of policy evolution and the characteristics of each stage in the US. Moreover, a comprehensive analysis of forest fire management situation in the US from four aspects was conducted, including the management of combustible fuels, administrative responsibility, fire suppression and forest fire management research support. We summarized relevant literature and proposed improvement strategies for future combustibles management, policy politics and fire fighting in the United States. Through the comprehensive analysis of forest fire management in the United States, we put forward some inspiring opinions on forest fire management in China to promote the establishment of a sound forest fire management system with Chinese characteristics.

Intracranial Venous Pressures Manometry for Patients With Idiopathic Intracranial Hypertension: Under Awake Setting or General Anesthesia.

Background and Purpose: Venous sinus stenting (VSS) is a well-acknowledged treatment strategy for patients with a high venous sinus pressure gradient across the site of outflow obstruction. It is not clear whether intracranial venous pressure manometry should be performed awake or under general anesthesia (GA). The aim of this study is to compare the accuracy of venous manometry performed under GA or awake setting, and to evaluate stenting candidates to be determined under awake setting or under GA. Methods: The manometry results of 32 patients with idiopathic intracranial hypertension (IIH) were recorded under awake setting and general anesthesia before stenting. Mean venous pressures (MVPs) and trans-stenosis pressure gradients were obtained and compared between awake setting and general anesthesia status. Results: MVPs and trans-stenosis pressure gradients of 32 patients under GA and awake pressure setting were recorded. MVPs in the superior sagittal sinus, torcula, and transverse sinus were lower in the GA group, without statistical significant difference (P > 0.05). MVPs were significantly higher in the sigmoid sinus and jugular bulb under GA group (p < 0.05). Mean trans-stenosis pressure gradient was significantly lower in the group under GA (p < 0.05). Conclusions: Intracranial venous pressure seems to be affected by different levels of consciousness. Our study reveals that intracranial venous pressure is lower under general anesthesia than in the awake setting, which may have a potential impact on patient selection for venous sinus stenting.

Corrigendum: HAX-1 Protects Glioblastoma Cells From Apoptosis Through the Akt1 Pathway.

[This corrects the article DOI: 10.3389/fncel.2017.00420.].

A rabbit model of cerebral venous sinus thrombosis established by ferric chloride and thrombin injection.

OBJECTIVE: Cerebral venous sinus thrombosis (CVST) is a life-threatening disease with high misdiagnosis and mortality rates due to its complex etiology and unknown pathophysiology. The present study aimed to establish an animal model suitable for assessing the pathophysiology of CVST and develop treatment methods. METHODS: 40% ferric chloride (FeCl3) was administered for 5min followed by thrombin injection to induce superior sagittal sinus thrombosis (SSST). Digital subtraction angiography (DSA) was performed to ensure thrombosis and evaluate the recanalization rate 7days post-CVST. Neurological evaluation, Evans blue injection, 2,3,5-Triphenyltetrazolium chloride (TTC), and hematoxylin-eosin (H&E) staining were used to assess thrombosis and the accompanying brain parenchyma. RESULTS: SSST was detected in all model rabbits, with a thrombus recanalization rate of 10%. Brain infarction, hemorrhage, cell edema, and disruption of the blood-brain barrier (BBB) were also observed. CONCLUSION: The method of inducing cerebral venous sinus thrombosis by applying 40% FeCl3 and injecting thrombin is feasible and efficient. This experimental model mimics the pathogenesis and pathophysiology of actual CVST.

Hematopoietic Substrate-1-Associated Protein X-1 Regulates the Proliferation and Apoptosis of Endothelial Progenitor Cells Through Akt Pathway Modulation.

Endothelial precursor cells (EPCs) are involved in vasculogenesis of various physiological and pathological processes. The proliferation and survival mechanism of EPCs needs to be explored further for the purpose of developing an effective glioma treatment. Hematopoietic substrate-1-associated protein X-1 (HAX-1) has been reported as an anti-apoptotic protein that plays an important role in several malignant tumors. However, the effect and mechanism of HAX-1 on EPCs remains unknown. This study aims to investigate the effect of HAX-1 on the proliferation and apoptosis of EPCs and explore its mechanism. According to our results, HAX-1 was overexpressed in EPCs. The results of clone formation and 5-ethynyl-2'-deoxyuridine proliferation assay showed that HAX-1 promoted multiplication of EPCs. Flow cytometry showed HAX-1 knockout cell cycle arrest mainly in G0/G1 phase. Apoptosis analysis showed that HAX-1 could protect EPCs from apoptosis in oxidative stress. Western blot assay indicated that HAX-1 could inhibit the activation of caspase cascade and reduce the expression of p21, Bcl-2-associated X protein, and p53. HAX-1 also enhanced the degradation rate and ubiquitination of p53 through the promotion of phosphorylation of proteins MDM-2 and Akt1. Co-immunoprecipitation and immunofluorescent colocalization assays were performed to test the influence of HAX-1 on the interaction between Akt1 and heat shock protein 90 (Hsp90), which is crucial for the activity of Akt1. In conclusion, this novel study suggests that HAX-1 could facilitate the Akt1 pathway through Hsp90, which led to a decline in the levels of p53, and finally promoted the proliferation and inhibited the apoptosis of EPCs. Stem Cells 2018;36:406-419.

Analysis of the expression of HAX-1 gene in human glioma.

Glioma, as the most common aggressive malignant tumor in the central nervous system, is still an insurmountable issue in neural diseases. The proliferation and survival mechanism of glioma cells need to be explored further for the development of glioma treatment. Hematopoietic cell-specific protein 1 associated protein X-1 (HAX-1) is well known for its anti-apoptotic effect. It was reported to play an important role in several malignant tumors. However, the effect of HAX-1 in glioma still remains unknown. This study aimed to investigate the expression of HAX-1 in glioma and the correlation between HAX-1 and the clinicopathological characteristics and prognosis of glioma. Quantitative reverse transcription polymerase chain reaction and Western blot analysis showed that HAX-1 was overexpressed in glioma cell lines compared with normal human astrocytes. This trend was confirmed by comparing the expression of HAX-1 in glioma tissues and nontumorous tissues. The study also analyzed the correlation between the expression of HAX-1 and clinicopathological characteristics of glioma and found the expression of HAX-1 to be highly related to the differentiation and World Health Organization stage of glioma tissues. The survival analysis revealed that HAX-1 was an independent prognostic factor. In conclusion, this novel study suggested that the overexpression of HAX-1 might contribute to the malignant progression of glioma.

Homing of Cultured Endothelial Progenitor Cells and Their Effect on Traumatic Brain Injury in Rat Model.

Transplanted endothelial progenitor cells (EPCs) may play an important role in reestablishing the endothelial integrity of the vessels after brain injury, and contribute to neurogenesis. We, therefore, tested the homing of ex vivo cultured peripheral blood-derived EPCs and their effect on injured brain tissue after intravenous administration. To track the homing of implanted EPCs in injured brain tissues, EPCs were labeled with DAPI and BrdU in vitro before transplantation. EPCs were transplanted into the host animal through peripheral administration through the femoral vein, and homing of EPCs was evaluated. The integration of intravenously injected EPCs into the injured brain tissue was demonstrated. Immunohistochemical staining showed that microvessel density in the perifocal region of EPCs-transplanted rats was significantly increased, and the numbers of BrdU+ cells in the DG of subventricular zone were increased in EPCs-transplanted rats as compared to the control group. Transplanted EPCs may play an important role in reestablishing the endothelial integrity in the vessels after brain injury and further contribute to neurogenesis. EPCs enhanced recovery following brain injury in a rat model of TBI.

HAX-1 Protects Glioblastoma Cells from Apoptosis through the Akt1 Pathway.

Glioblastoma is the most common malignant tumor in central nervous system (CNS), and it is still insurmountable and has a poor prognosis. The proliferation and survival mechanism of glioma cells needs to be explored further for the development of glioma treatment. Hematopoietic-substrate-1 associated protein X-1 (HAX-1) has been reported as an anti-apoptosis protein that plays an important role in several malignant tumors. However, the effect and mechanism of HAX-1 in glioblastomas remains unknown. This study aimed to investigate the effect of HAX-1 in glioblastoma cells and explore the mechanism. The results of clone formation and Edu proliferation assay showed slower multiplication in HAX-1 knock-out cells. Flow cytometry showed cell cycle arrest mainly in G0/G1 phase. Apoptosis due to oxidative stress was increased after HAX-1 was knocked out. Western-blot assay exhibited that the levels of p21, Bax, and p53 proteins were significantly raised, and that the activation of the caspase cascade was enhanced in the absence of HAX-1. The degradation rate and ubiquitination of p53 declined because of the decrease in phosphorylation of proteins MDM2 and Akt1. Co-immunoprecipitation (Co-IP) and immunefluorescent co-localization assays were performed to test the influence of HAX-1 on the interaction between Akt1 and Hsp90, which is crucial for the activity of Akt1. In conclusion, this novel study suggested that HAX-1 could affect the Akt1 pathway through Hsp90. The knock-out of HAX-1 leads to the inactivity of the Ak1t/MDM2 axis, which leads to increased levels of p53, and finally generates cell cycle arrest and results in the apoptosis of glioblastoma cells.

Waffle-cone technique using solitaire AB stent for endovascular treatment of complex and wide-necked bifurcation cerebral aneurysms.

INTRODUCTION: To explore the safety and opportunity of the "waffle-cone" technique for the treatment of intracranial aneurysm. METHODS: From November 2009 and May 2012, consecutive data were collected from 136 patients with aneurysms treated by the stent-assisted coiling procedure. Six of these patients were treated using the "waffle-cone" technique. RESULTS: All the 6 patients were complex, wide-neck, bifurcation cerebral aneurysms. And the angles between the parent artery and distal vessels are acute. Two ruptured aneurysms located at the terminus of basilar artery, three ruptured aneurysms located at the anterior communicating artery, and one ruptured aneurysm located at trifurcation MCA. All the 6 patients were treated using the "waffle-cone" technique, 4 patients had Raymond classification Class I and 2 patients had Class II after the procedure. No complications occurred perioperative. There were no lesion-related strokes or deaths during the 6-month follow-up period. CONCLUSIONS: The "waffle-cone" technique is a safe, simple and alternative for the complex, wide-necked bifurcation aneurysms with acute angles between the parent artery and distal vessels. Long-term following-up results are needed to evaluate the efficacy of this technique.

Endovascular treatment of chronic, recurrent headache secondary to chronic cerebral venous sinus thrombosis.

Headache is a clinical diagnosis linked to a number of medical and surgical disorders. A common etiology has not yet been established. It would seem that these cases can be related to some degree of cerebral venous outflow obstruction. We report 2 cases of chronic superior sagittal sinus thrombosis causing isolated intracranial hypertension. The patients were treated with intrasinus thrombolytic therapy.

Reconstructive endovascular treatment of vertical stenosis associated with adjacent aneurysm at the same arterial anatomic segment.

One case had a symptomatic vertebral artery stenosis coupled with a coincidental unruptured cerebral aneurysm at the same arterial anatomic segment. And another case had an asymptomatic vertebral artery stenosis coupled with a ruptured cerebral aneurysm at the same arterial anatomic segment. They underwent intracranial stenting. Both lesions were treated successfully and neither complications nor strokes occurred after the procedures. Covered stent placement in an intracranial stenosis with an adjacent ruptured or unruptured aneurysm may be a feasible method.

Emergent angioplasty and stent placement recanalization without thrombolysis in acute middle cerebral artery occlusions.

A significant proportion of patients with infarcts from large-vessel lesions have shown a poor response to systemic thrombolysis. Stents have been used to recanalize occluded or severely stenosed intracranial arteries in patients with acute stroke. This study evaluated the feasibility, efficacy, and safety of intracranial artery recanalization for acute middle cerebral artery (MCA) occlusion using emergent angioplasty and stent placement without thrombolysis. All patients from a retrospectively collected database who met the inclusion criteria and were treated with an intracranial stent for acute MCA occlusion were included. Treatment comprised angioplasty and stenting without interventional thrombolytic therapy. Recanalization was assessed by angiography immediately after stent placement based on the Thrombolysis in Myocardial Infarction (TIMI) score. Complications related to the procedure and outcomes were assessed. Neurologic status was evaluated before and after treatment. Eleven patients were treated with emergent angioplasty and stent placement. Partial or complete recanalization (TIMI 2 and 3) was achieved in 11 patients (100%) assessed by digital subtraction angiography immediately after MCA stenting. One patient died due to reocclusion of MCA 2 days after the procedure. Among the survivors, 7 patients (70%) had a good outcome (modified Rankin Scale score, 0-2) and 3 patients (30%) had a moderate outcome (modified Rankin Scale score, 3). Follow-up computed tomography angiography or magnetic resonance angiography revealed mild restenosis in 2 of the 10 patients. This preliminary experience demonstrates the technical feasibility and high rate of recanalization with emergent angioplasty and stenting without thrombolysis in patients with acute MCA occlusion.

Local thrombolysis for patients of severe cerebral venous sinus thrombosis during puerperium.

OBJECTIVE: To explore and evaluate the efficacy of intrasinus thrombolysis (IST) in patients with cerebral venous sinus thrombosis (CVST) during postpartum period. METHODS: 11 patients during postpartum period with CVST who received IST during July 2007-November 2011 were included. Urokinase was infused into the sinuses via a microcatheter. Magnetic resonance venography (MRV) was performed to assess the recanalization of venous sinuses. RESULTS: Before discharge, the intracranial pressure in 11 patients was under 200 mmH(2)O. MRV confirmed that venous sinus of 9 patients were smooth. The cortex venous and deep venous recovered to normal. Venous sinus of 2 patients recanalized partly, and cortex venous and deep venous had compensation. 9 patients had good outcome and 2 patients had only mild deficits. CONCLUSION: Intrasinus thrombolysis is safe and effective in patients with severe cerebral venous sinus thrombosis during postpartum period.

HydroSoft coil versus HydroCoil for endovascular aneurysm occlusion study: a single center experience.

BACKGROUND AND PURPOSE: The HydroCoil Embolic System (HES) was developed to reduce recurrences of aneurysms relative to platinum coils. But the HydroCoil Embolic System was characterized with many limitations. The manufacturer had recognized the challenge and recently a new design of hydrogel-coated coil-HydroSoft has become available in the market as the new generation HydroCoil. We reported our initial experience using HydroSoft coil versus HydroCoil in our center. METHODS: 75 aneurysms embolized primarily using HydroSoft Coils from July 2008 to May 2009 were compared with 66 volume- and shape-matched aneurysms treated with HydroCoils from March 2006 to August 2008. Outcome measures included length and number of coils used, contrast volume, and length of hospital stay. During embolization, a stable framework was first established with bare coils, and hydrogel-coated coils were used subsequently to increase the packing density. Follow-up angiographic results 6 months after treatment were evaluated among some of the patients. RESULTS: Successful coil embolization was achieved in all patients. There were no differences in average total coil length used per aneurysm. There were no differences in length of hospital stay and packing density. HydroSoft coils were more suitable using as the finishing or final coil. HydroSoft coil decreased the procedure-related retreated rates, and aneurysm packing was finished with soft, flexible HydroSoft coil and decreased the neck remnant rates. Follow-up angiography in HydroSoft-treated patients at 6 months revealed aneurysm stability without significant residual neck. CONCLUSIONS: HydroSoft coil allowed us to deploy coated coils with good packing density. A slight expansion of these coils at the neck can be expected to reduce neck remnant and potentially inhibit recurrence.

Wingspan stent for symptomatic M1 stenosis of middle cerebral artery.

OBJECTIVE: Stent placement for intracranial atherosclerotic stenosis has become an alternative treatment technique; however, stent placement for middle cerebral artery (MCA) stenosis remains a technical and clinical challenge. Our purpose was to assess the safety and feasibility of Wingspan stent for patients with symptomatic M1 stenosis, and its initial effect on prevention of ischemic events. METHODS: Fifty-three cases with recurrent symptomatic MCA stenosis resistant to medical therapy treated by self-expanding stent were reviewed retrospectively (average 58±18.5 years old, 19 women). All patients underwent angioplasty and stenting with the Gateway balloon-Wingspan stent system, and advised follow-up with DSA or TCD at 6th month. RESULTS: Patients had an average stenosis ratio of 76.5±15.4% prior to the treatment. Of the 53 patients, the technical success rate was 98.1% as a whole (52/53). The mean degree of stenosis reduced from (76.5±15.4)% to (18.2±11.3)%. Complications associated with the procedure include subarachnoid hemorrhage (1.89%) and occlusion (3.78%) occurred. During a follow-up of 6 months, there was no recurrence of transient ischemic attack or stroke in 52 cases with successful stenting. Cerebral hemodynamics of MCA using transcranial Doppler monitoring were at normal level (<120 cm/s) in 41 follow-up patients. The follow up angiography at 6 month post-procedure was conducted in 32 patients and showed good patency in stented vessels. CONCLUSIONS: Wingspan stent for symptomatic stenosis of middle cerebral artery is a safe and feasible procedure. It improves clinical outcome in the intermediate follow up, but its long-term effect remains to be further evaluated.