BACKGROUNDThe mechanism of cerebral vasospasm following subarachnoid haemorrhage (SAH) is not understood. Here, we hypothesized that apoptosis of endothelial cells induced by p53 and its target gene em dash p53 upregulated modulator of apoptosis (PUMA) played an important role in development of cerebral vasospasm. We also observed the effects of a p53 inhibitor, pifithrin-alpha (PFT-alpha), on reducing the expression of p53 and PUMA, consequently decreasing the apoptosis of endothelial cells and alleviating cerebral vasospasm.

METHODSMale Sprague-Dawley rats weighing 300-350 g were randomly divided into five groups: a control group (sham surgery), a SAH group, a SAH+dimethyl sulfoxide (DMSO) group, a SAH + PFT-alpha (0.2 mg/kg) group and a SAH + PFT-alpha (2.0 mg/kg) group. PFT-alpha was injected intraperitoneally immediately after SAH. Rats were sacrificed 24 hours after SAH. Western blot and immunohistochemical staining were used to detect the levels of p53, PUMA and caspase-3 protein. In addition, mortality and neurological scores were assessed for each group. Statistical significance was assured by analysis of variance performed in one way ANOVA followed by the Tukey test. The neurological and mortality scores were analyzed by Dunn's method and Fisher exact test, respectively.

RESULTSAfter SAH, Western blot and immunohistochemical staining showed the levels of p53, PUMA and caspase-3 in the endothelial cells and the numbers of TdT mediated dUTP nick end labelling (TUNEL) positive endothelial cells were all significantly increased in the basilar arteries (P<0.05), but significantly reduced by PFT-alpha (P<0.05). These changes were accompanied by increasing diameters and declining wall thickness of basilar arteries (P<0.05), as well as reduced mortality and neurological deficits of the rats (P<0.05).

CONCLUSIONSPFT-alpha could protect cerebral vessels from development of vasospasm and improve neurological outcome as well as reduce the mortality via suppressing apoptosis induced by p53 in the endothelial cells of cerebral vessels.

Animals ; Apoptosis ; drug effects ; Benzothiazoles ; pharmacology ; therapeutic use ; Blotting, Western ; Disease Models, Animal ; Endothelial Cells ; drug effects ; pathology ; Male ; Rats ; Rats, Sprague-Dawley ; Subarachnoid Hemorrhage ; complications ; drug therapy ; pathology ; physiopathology ; Toluene ; analogs & derivatives ; pharmacology ; therapeutic use ; Tumor Suppressor Protein p53 ; physiology ; Vasospasm, Intracranial ; prevention & control

OBJECTIVE: To explore the risk factors, clinical characteristics, precaution and treatment of hyper perfusion syndrome (HPS) after carotid artery stenting (CAS). METHODS: From September 2014 to March 2018, the clinical data of 226 patients with severe carotid stenosis (70%-99%) treated with carotid artery stenting (CAS)at Department of Interventional Radiology and Vascular Surgery, Peking University Third Hospital, were analyzed retrospectively．Five of them developed HPS after CAS．The relationship between the clinical baseline data, imaging characteristics, perioperative management and HPS were assessed. RESULTS: In this group, 5 patients of them (2.21%, 5/226) developed HPS after CAS, and 2 patients of them (0.88%, 2/226) were hyper perfusion induced intracranial hemorrhage (HICH). The 5 patients consisted of 4 men and 1 woman whose age ranged from 58 to 74 years. The symptoms of HPS occurred within 4 hours to 3 days after CAS. Among the 5 cases, the clinical manifestations were that 2 cases with headache, 1 case with delirium,1 case with hemiparesis of left limbs, and 1 case with coma(died ultimately).The main manifestations of case 1 and case 2 were headache in the frontal parietal temporal region of the operative side, accompanied by nausea and vomiting. The symptoms were relieved after blood pressure lowering treatment and mannitol dehydration. The main manifestations of case 3 were excitement and delirium. The symptoms were relieved by a small dose of sedatives, also with blood pressure lowering treatment and mannitol dehydration. The initial symptoms of case 4 were excitement and delirium, accompanied by mild headache of the operative side, and hemiplegia of the contralateral limb occurred within a short time. The main manifestation of case 5 was severe headache and went into deep coma within a short time. This patient died of massive cerebral hemorrhage ultimately. CONCLUSION HPS is an uncommon but serious complication after CAS. Improving our understanding and heightening vigilance of HPS is necessary. The earlier diagnosis, the earlier treatment.
Aged ; Carotid Arteries ; Carotid Artery, Common ; Carotid Stenosis/surgery* ; Female ; Humans ; Male ; Middle Aged ; Retrospective Studies ; Stents

OBJECTIVE: To assess the safety and efficacy of Neuroform EZ stent used in treatment of symptomatic complex severe intracranial atherosclerotic stenosis (ICAS). METHODS: Clinical data of 18 patients with symptomatic complex severe ICAS undergoing Neuroform EZ stent angioplasty from January 2016 to December 2017 were retrospectively analyzed. All the lesions of the patients in this group were considered as complex ICAS, i.e. with severe tortuous access, long (>10 mm) or occlusive or bifurcation lesions, with concurrent aneurysms near the stenotic lesion. The primary outcome was defined as any stroke (including ischemic or hemorrhagic) or deaths from any cause after stenting procedure within 30 days. The secondary outcome was defined as successful revascularization and occurrence of >50% in-stent restenosis during the follow-up period. RESULTS: All the 18 patients achieved technical success (100%) and mean stenosis rate was reduced from 85%±7% to 18%±6%. Of the 18 patients included, the 30-day stroke or death was 5.6% (1/18), which presented as basal ganglia region infarction in a patient with tandem lesions on the left vertebral artery. There was no hemorrhagic and death complications that occurred in the patients of this group. One concurrent aneurysm was embolized with micro coil (stent assisted) by stages after 1 month. In this group 12 patients were followed up with digital subtraction angiography (DSA) after hospital discharge. The follow-up period ranged from 8 months to 26 months [mean: (16±8) months]．During the follow-up period 2 patients in the 12 patients (2/12, 16.7%) developed in-stent restenosis (ISR) confirmed by DSA, and one of them was symptomatic restenosis and restored unobstructed blood flow after balloon angioplasty. CONCLUSION Neuroform EZ stent for the treatment of highly screened symptomatic complex severe ICAS is safe and effective. It has its advantages over traditional stent.
Cerebral Angiography ; Constriction, Pathologic ; Follow-Up Studies ; Humans ; Retrospective Studies ; Stents ; Treatment Outcome

Objective: To identify and analyze 3D architecture of the mutational sites of susceptible genes in a pedigree with familial hypercholesterolemia-like phenotype (FHLP). Methods: This is a case series study. A pedigree with suspected familial hypercholesterolemia was surveyed. The proband admitted in Beijing Anzhen Hospital in April 2019. Whole-exome sequencing was performed to determine the mutational sites of susceptible genes in the proband. Polymerase chain reaction (PCR) sequencing was used to verify the pathogenic variant on proband's relatives. The structural and functional changes of the proteins were analyzed and predicted by Discovery Studio 4.0 and PyMol 2.0. Results: The patients in the pedigree showed abnormal lipid profiles, especially elevated levels of total cholesterol(TC). The genetic screening detected the c.1330C>T SNP in the exon 8 of lipase C (LIPC) gene, this mutation leads to an amino acid substitution from arginine to cysteine at position 444 (Arg444Cys), in the proband and proband's father and brother. In this family, members with this mutation exhibited elevated TC, whereas lipid profile was normal from the proband's mother without this mutation. This finding indicated that LIPC: c.1330C>T mutation might be the mutational sites of susceptible genes. The analysis showed that Arg444Cys predominantly affected the ligand-binding property of the protein, but had a limited impact on catalytic function. Conclusion: LIPC: c.1330C>T is a new mutational site of susceptible genes in this FHLP pedigree.
Humans ; Male ; Hyperlipoproteinemia Type II/genetics* ; Lipase/genetics* ; Lipids ; Mutation ; Pedigree ; Phenotype ; Proteins

Adolescent ; Adult ; China ; epidemiology ; ethnology ; Female ; HIV Infections ; epidemiology ; ethnology ; transmission ; Humans ; Male ; Middle Aged ; Models, Theoretical ; Sexual Partners ; Social Networking ; Unsafe Sex ; ethnology ; Young Adult

Introduction: During the early phase of Coronavirus disease (COVID-19), there were various uncertainties, which had a detrimental impact on the prevalence of burnout among critical care personnel worldwide. This study aims to investigate the prevalence of burnout and its associated factors in critical care personnel involved in the COVID-19 pandemic. Methods: This is a single-center, cross-sectional study with 81 critical care personnel for a survey using Copenhagen Burnout Inventory. Binary logistic regression analysis was conducted to identify factors associated with personal burnout. Results: More than half of the respondents were female (60.5%) over the age of 30 (61.7%), and 54.3% were medical doctors. A large number (72.8%) of the respondents experienced personal burnout, with twothirds of them experiencing work-related (65.4%) and client-related burnout (59.3%). Personal burnout was found to be associated with those who had children [OR: 11.31 (1.90, 67.37), p = 0.008], stayed with family, relatives, or friends [OR: 9.40 (1.27, 69.46), p = 0.028], were medical doctors [OR: 26.52 (2.79, 252.22), p = 0.004], worked more than 45 hours per week [OR: 8.68 (1.45, 58.09), p = 0.018], and previously never had COVID-19 viral test [OR: 6.93 (1.17, 40.89), p = 0.033]. Conclusion: Overall, more than half of the critical care personnel experienced burnout. There were possible associations between personal burnout with social characteristics such as having children and living with family, relatives, or friends, and occupational characteristics such as being a medical doctor, long working hours, and previously never had COVID-19 viral test.