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Background@#and Purpose To examine the clinical and safety outcomes after endovascular treatment (EVT) for acute basilar artery occlusion (BAO) with different anesthetic modalities. @*Methods@#This was a retrospective analysis using data from the Endovascular Treatment for Acute Basilar Artery Occlusion (ATTENTION) registry. Patients were divided into two groups defined by anesthetic modality performed during EVT: general anesthesia (GA) or non-general anesthesia (non-GA). The association between anesthetic management and clinical outcomes was evaluated in a propensity score matched (PSM) cohort and an inverse probability of treatment weighting (IPTW) cohort to adjust for imbalances between the two groups. @*Results@#Our analytic sample included 1,672 patients from 48 centers. The anesthetic modality was GA in 769 (46.0%) and non-GA in 903 (54.0%) patients. In our primary analysis with the PSM-based cohort, non-GA was comparable to GA concerning the primary outcome (adjusted common odds ratio [acOR], 1.01; 95% confidence interval [CI], 0.82 to 1.25; P=0.91). Mortality at 90 days was 38.4% in the GA group and 35.8% in the non-GA group (adjusted risk ratio, 0.95; 95% CI, 0.83 to 1.08; P=0.44). In our secondary analysis with the IPTW-based cohort, the anesthetic modality was significantly associated with the distribution of modified Rankin Scale at 90 days (acOR: 1.45 [95% CI: 1.20 to 1.75]). @*Conclusion@#In this nationally-representative observational study, acute ischemic stroke patients due to BAO undergoing EVT without GA had similar clinical and safety outcomes compared with patients treated with GA. These findings provide the basis for large-scale randomized controlled trials to test whether anesthetic management provides meaningful clinical effects for patients undergoing EVT.
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Objective:To investigate the effects of artesunate ( ART ) on neuronal apoptosis, inflammatory response after stroke in rats and microglia polarization.Methods:(1)Animal experiment: twenty-seven male SD rats of SPF grade were divided into sham operation group, model group and ART treatment group according to the random number table method, with 9 rats in each group.Rats in the model group and ART treatment group were used to establish a stroke model by middle cerebral artery occlusion (MCAO). And rats in the ART treatment group were intraperitoneally injected with ART (25 mg/kg) once a day for three days before modeling, while the rats in sham operation group and the model group were injected with the same amount of solvent.And 24 h after the modeling, TTC staining was used to evaluate the volume of cerebral infarction, Western blot was used to detect the expression of Bcl2 in the infarct area, penumbra and hippocampus, TUNEL method was used to detect neuronal apoptosis, and tissue immunofluorescence was used to observe the expression of tumor necrosis factor-α(TNF-α) in the penumbra region of cerebral cortex.(2)Cell experiments: microglia BV2 were cultured and divided into control group, oxygen-glucose deprivation/reoxygenation group, oxygen-glucose deprivation/reoxygenation + 0.05 μmol/L ART group, oxygen-glucose deprivation/reoxygenation + 0.1 μmol/L ART group and oxygen-glucose deprivation/reoxygenation + 0.5 μmol/L ART group.The levels of inflammatory factors interleukin-6(IL-6), interleukin-1β(IL-1β) and TNF-α were detected by qRT-PCR, the expressions of M2 type microglia marker protein CD206 and ARG1 were detected by Western blot, the BV2 cell medium after treatment in each of the above groups was collected as conditioned medium to culture HT22 hippocampal neuron cells and cell activity was measured by CCK8 method.GraphPad Prism 7 software was used for data analysis.One-way ANOVA was used for comparison of differences among multiple groups, and LSD was used for further two-by-two comparisons.Results:(1)Animal experiment results: TTC staining results showed that the percentage of cerebral infarction volume in the ART treatment group was smaller than that in the model group ((23.09±8.51)%, (39.63±5.71)%, t=33.93, P<0.01). The results of TUNEL staining showed that the number of apoptotic cells in the model group and ART treatment group was higher than that in the sham operation group ((638.90±177.82)cells/mm 2, (72.75±13.21) cells/mm 2, (16.16±2.73) cells/mm 2, both P<0.05), and the number of apoptotic cells in the ART treatment group was lower than that in the model group ( P<0.05). Western blot results showed that the levels of Bcl2 protein in penumbra and infarct area of the model group were both lower than those in sham group(both P<0.05). The levels of Bcl2 protein in penumbra, the hippocampus and infarcted area of the ART treatment group were significantly lower than those of the model group(all P<0.05). The results of tissue immunofluorescence showed that the fluorescence intensities of TNF-α in the model group and ART treatment group were higher than those in the sham group (all P<0.05), while the fluorescence intensity of TNF-α in the ART treatment group was lower than that in the model group ( P<0.05). (2)Cell experiment: qRT-PCR results showed that compared with the control group, the mRNA levels of IL-6, IL-1β and TNF-α (all P<0.05) in oxygen-glucose deprivation/reoxygenation group were significantly higher than those of the control group.And the mRNA levels of IL-1β, IL-6 and TNF-α in oxygen-glucose deprivation/reoxygenation + 0.05 μmol/L ART group, oxygen-glucose deprivation/reoxygenation + 0.1 μmol/L ART group and oxygen-glucose deprivation/reoxygenation + 0.5 μmol/L ART group were significantly lower than those of the oxygen-glucose deprivation/reoxygenation group (all P<0.05). Western blot results showed that compared with the control group, the expression of CD206 ((0.85±0.04), (1.07±0.07), P<0.05) was significantly down-regulated in the oxygen-glucose deprivation/reoxygenation group.The CD206 and ARG in oxygen-glucose deprivation/reoxygenation + 0.1 μmol/L ART group((1.22±0.06), (1.35±0.08)) and oxygen-glucose deprivation/reoxygenation + 0.5 μmol/L ART group((1.24±0.14), (1.14±0.07)) were significantly higer than those of oxygen-glucose deprivation/reoxygenation group((0.85±0.04), (0.85±0.05))(all P<0.05). The results of CCK8 showed that compared with the control group, the cell viability in the oxygen-glucose deprivation/reoxygenation group was significantly decreased( P<0.05). The cell viability of the oxygen-glucose deprivation/reoxygenation + 0.05 μmol/L ART group, the oxygen-glucose deprivation/reoxygenation + 0.1 μmol/L ART group, the oxygen-glucose deprivation/reoxygenation + 0.5 μmol/L ART group were all higher than those of oxygen-glucose deprivation/reoxygenation group(all P<0.05). Conclusion:ART reduces neuronal apoptosis after stroke, decreases the neuroinflammatory response after stroke, and promotes oxygen-glucose deprivation/reoxygenation-activated microglia BV2 polarization to the M2 type.
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【Objective】 In this study， reactive oxygen species （ROS） scavenger N-acetyl-L-cysteine （NAC） was used to explore the inhibitory effect and mechanism of artesunate （ART） on pancreatic carcinoma （PC） cells. 【Methods】 Different concentrations of ART interfered with 3 PC cell lines CFPAC-1， Capan-2 and BxPC3. Cell viability was measured by CCK8； cell migration ability was measured by Transwell method， and the expressions of migration-related proteins E-cadherin， N-cadherin and Vimentin were measured by Western blotting. ROS probe DCFH-DA was used to measure intracellular ROS； LC3 cell immunofluorescence （IF） was used to detect the formation of intracellular autophagosomes. After adding NAC or autophagy inhibitor 3-MA， the cell viability was tested again by CCK8， and the expressions of p-AMPK/ AMPK， p-mTOR/mTOR， p62 and LC3Ⅱ/Ⅰ were detected by Western blotting. 【Results】 ART inhibited the growth of CFPAC-1 and Capan-2 in a time- and dose-dependent manner. After treatment of CFPAC-1 and Capan-2 cells with 200 μmol/L of ART for 48 h， the expression of E-cadherin was upregulated， while N-cadherin and Vimentin were downregulated， and the cell migration ability was significantly reduced. ART significantly upregulated intracellular ROS level and promoted the formation of autophagosomes. NAC could reduce the inhibitory effect of ART on CFPAC-1 and Capan-2 cells， upregulate p-AMPK/AMPK， P62 and LC3Ⅱ/Ⅰ， downregulate the expression of p-mTOR/mTOR， and intensify autophagy. 3-MA could not reverse the inhibitory effect of ART on PC cells. 【Conclusion】 ART is dependent on ROS， but not on autophagy， in exerting an anti-pancreatic carcinoma effect. NAC attenuates the inhibitory effect of ART on PC cells by activating protective autophagy through AMPK/mTOR signaling pathway.
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Objective To observe the effect of monosialoteterahexosyl ganglioside (GM1) combined with Shuxuening injection on nerve function in patients with acute cerebral infarction (ACI) and its mechanism.Methods A total of 94 patients with ACI admitted to the Department of Neurology in Xiangyang First Peoples' Hospital Affiliated to Hubei Medical College from January 2013 to June 2016 were enrolled,and they were divided into two groups by random number table,each group 47 cases.The patients in two groups were all given conventional western medicine treatment;The patients in one group (single group) were treated by intravenous (Ⅳ) drip of GM1,100 mg once a day;and the patients in another group (combined group),by above GM1 Ⅳ drip combined with Shuxuening intramuscular injection,once 2 mL,twice a day;the therapeutic course in two groups was 14 days.Before and after treatment,the changes of China stroke clinical neurological impairment score (CSS score),glasgow coma score (GCS),nerve factor,oxidative stress index and hemodynamics index of two groups were observed.Results Compared with those before treatment,after treatment the CSS score,the levels of neuron specific enolase (NSE),and malondialdehyde (MDA) were significantly lower,while the GCS score,the levels of nerve growth factor (NGF),neurotrophic factor (NTF),maximum blood flow velocity (Vmax),minimum blood flow velocity (Vmin),mean blood flow velocity (Vmean),mean blood flow quantity (Qmean),glutathione peroxidase (GSH-Px),catalase (CAT) and superoxide dismutase (SOD) were all significantly higher in the combined group (all P ＜ 0.05).After treatment,the CSS score,levels of NSE and MDA in the combined group were significantly lower than those of the single group [CSS:11.20 ± 1.78 vs.16.24 ± 1.95,NSE (μg/L):13.17± 1.00 vs.17.68 ± 1.84,MDA (μmol/L):4.14±0.49 vs.5.61 ±0.50,all P ＜ 0.05],GCS score,NGF,NTF,GSH-Px,CAT,SOD,Vmax,Vmin,Vmean and Qmean of the combined group were all significantly higher than those of the single group [GCS:13.68± 1.85 vs.12.01±1.76,NGF (ng/L):88.10±8.83 vs.68.13±7.16,NTF (pg/L):5.13±0.38 vs.3.71±0.30,GSH-Px (U/L):128.13±8.07 vs.103.90±6.58,CAT (U/L):25.74±2.15 vs.19.43± 1.84,SOD (μU/L):94.36±8.00 vs.77.29±7.34,Vmax (cm/min):48.23±3.36 vs.43.17±2.88,Vmin (cm/'min):8.11±0.76 vs.6.85 ± 0.64,Vmean (cm/min):18.69 ± 1.37 vs.15.60 ± 1.24,Qmean (mL/min):9.10 ± 0.74 vs.7.79 ± 0.66,all P ＜ 0.05].Conclusions GM1 combined with Shuxuening injection can improve nerve function in patients with ACI by improving brain blood flow,secreting neurotrophic related factors and inhibiting oxidative stress reaction,thus it has important clinical significance for repairing the damaged nerve function.
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Objective To investigate the imaging features of the nigrosomes-1 region in the substantia nigra at 3.0 T with enhanced gradient echo T2 star weighted angiography(ESWAN), and to explore its clinical value in the evaluation of Parkinson disease (PD). Methods Fifty-four patients diagnosed with PD (PD group), and 51 non-PD volunteers (N-PD group) were scanned with 3.0 T ESWAN, who had selected randomly. The widths of the typical high signal correspondence with the nigrosomes-1 region (a), the width at the middle of the substantia nigra (b) and the width of the banded high signal of which the oval structure were not displayed (c) were measured and collected. The result of reclassification performed by 2 physicians were compared with clinical gold standard. Specificity and sensitivity were calculated; Eleven outpatients with clinically suspected PD but undiagnosed (UD group) were continusouly selected. They received the same scanning and were performed with imaging diagnosis according to the conclusions of previous studies, then compared the imaging diagnosis with the final clinical diagnosis. Results In non PD group, hyperintensity of nigrosomes-1 were shown in 49 cases (96.1%) in bilateral or unilateral of the SN, the hyperintensity were shaped as“drop”, wedge or oval and the average size (a/b) was (0.31 ± 0.07)mm approximately; PD group, all 54 cases (100.0%) of the oval rear the“drop”were completely disappeared. The sensitivity of the loss of the hyperintensity of nigrosomes-1 for the diagnosis of PD was about 100.0%(54/54)and the specificity of it was about 96.08%(49/51). In UD group, 7 cases with the“drop”completely missed and 1 case with smaller“c”were clinically proven to PD, 2 cases with the typical hyperintensity and 2 case with larger“c”were proven to Parkinson plus syndrome. Conclusions The nigrosomes-1 typical hyperintensity in PD patients' substantia nigra on the 3.0 T ESWAN are disappeared. There may be an effective method for PD and Parkinson's plus syndrome identification that by analyzing of the presence or absence of the typical hyperintensity and its size in the patients with symptoms of PD.
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Objective To explore the relationship between the levels of Cu, Fe, Mn, Zn in serum and Parkinson disease (PD). Methods A total of 40 patients with PD (PD group) and 40 control subjects (control group)were enrolled in this study. Serum levels of Mn were measured by graphite atomic absorption, and Cu ,Fe, Zn were measured by inductively coupled plasma(ICP)mass spectrometry. Resudts There were significantly increase in the levels of Mn and Fe in PD group than those in control group [(0.269±0.326) μ mol/L vs (0.125±0.054) μmol/L, P< 0.05, (1.512±0.949) μmol/L vs (0.676±0.111) μmol/L, P< 0.01)]. There were no significant difference in the levels of Cu and Zn between two groups (P> 0.05). Condusion Micreelements may play important roles in pathogenesis and development of PD, especially Fe and Mn.
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Objective To observe the effects of treating acute ischemic stroke in rats with interventional administration of nitric oxide precurcer L-Arginine or nitric oxide donor nitroglycerin.Methods The right middle cerebral arteries of rats were occluded by insertion of a suture to duplicate ischemia-reperfusion models.Forty-two male SD rats were randomly divided into four groups: MCAO group(n=12);sham operation group(n=6);NG group(n=12) and L-ARG group(n=12),intracarotid arteries administrated respectively by NS、NS、NG and ARG.Each of the four groups were subdivided into 2 groups according to the reperfusion time(3 h and 24 h),measurement of Longa scores,NO2-/NO3-in serum,HE staining and immunohistochemical(SABC)method were utilized to assess the changes of ischemic brain tissues in different groups.Results OX-42 positive cells of cortex and CA3 area of hippocampal: OX-42 positive cells were found,their features identified at 3 h after reperfusion.24 h the response of microglias was obvious,the number of the cells increased(P
