Variant rs8400 enhances ALKBH5 expression through disrupting miR-186 binding and promotes neuroblastoma progression

Objective:AlkB homolog 5(ALKBH5)has been proven to be closely related to tumors.However,the role and molecular mechanism of ALKBH5 in neuroblastomas have rarely been reported.Methods:The potential functional single-nucleotide polymorphisms(SNPs)in ALKBH5 were identified by National Center for Biotechnology Information(NCBI)dbSNP screening and SNPinfo software.TaqMan probes were used for genotyping.A multiple logistic regression model was used to evaluate the effects of different SNP loci on the risk of neuroblastoma.The expression of ALKBH5 in neuroblastoma was evaluated by Western blotting and immunohistochemistry(IHC).Cell counting kit-8(CCK-8),plate colony formation and 5-ethynyl-2'-deoxyuridine(EdU)incorporation assays were used to evaluate cell proliferation.Wound healing and Transwell assays were used to compare cell migration and invasion.Thermodynamic modelling was performed to predict the ability of miRNAs to bind to ALKBH5 with the rs8400 G/A polymorphism.RNA sequencing,N6-methyladenosine(mA)sequencing,mA methylated RNA immunoprecipitation(MeRIP)and a luciferase assay were used to identify the targeting effect of ALKBH5 on SPP1.Results:ALKBH5 was highly expressed in neuroblastoma.Knocking down ALKBH5 inhibited the proliferation,migration and invasion of cancer cells.miR-186-3p negatively regulates the expression of ALKBH5,and this ability is affected by the rs8400 polymorphism.When the G nucleotide was mutated to A,the ability of miR-186-3p to bind to the 3'-UTR of ALKBH5 decreased,resulting in upregulation of ALKBH5.SPPI is the downstream target gene of the ALKBH5 oncogene.Knocking down SPP1 partially restored the inhibitory effect of ALKBH5 downregulation on neuroblastoma.Downregulation of ALKBH5 can improve the therapeutic efficacy of carboplatin and etoposide in neuroblastoma.Conclusions:We first found that the rs8400 G>A polymorphism in the m6A demethylase-encoding gene ALKBH5 increases neuroblastoma susceptibility and determines the related mechanisms.The aberrant regulation of ALKBH5 by miR-186-3p caused by this genetic variation in ALKBH5 promotes the occurrence and development of neuroblastoma through the ALKBH5-SPP1 axis.

Electroacupuncture effect on synaptic ultrastructure in focal cerebral ischemia marginal zone of the rat

BACKGROUND：Synapses undergo high levels of plasticity within the nervous system, and cerebral ischemia induces synaptic plasticity changes.OBJECTIVE：To demonstrate the effects of electroacupuncture on ultrastructural synaptic changes in the focal cerebral ischemia marginal zone in rats using quantitative analysis of stereological measurement.DESIGN, TIME AND SETTING：A randomized, controlled, animal experiment was performed at the Experimental Animal Center and Laboratory of Electron Microscopy, Guangzhou University of Traditional Chinese Medicine from January 2008 to January 2009.MATERIALS：The G-6805 electric acupuncture apparatus was provided by Shanghai Huayi Instrument Factory, China.METHODS：A total of 90 male, Wistar rats were randomly assigned to sham-surgery, model, and electroacupuncture groups, with 30 animals in each group. Each group was subdivided into 1 hour, as well as 1, 3, 7, and 21 days post-surgery groups, with six animals assigned to each time point. Heat coagulation-induced occlusion of the middle cerebral artery was performed to establish a model of focal cerebral ischemia. Electroacupuncture was applied immediately following surgery to the electroacupuncture group [4/20 Hz, 2.0-3.0 V, 1-3 mA, to Baihui （GV 20） and Dazhui （GV 14）] for 30 minutes. Treatment was performed once a day, and experimental animals were sacrificed, at 1 hour, as well as 1, 3, 7 and 21 days post-surgery.MAIN OUTCOME MEASURES：At different time points after intervention, changes in synaptic ultrastructure, such as postsynaptic density thickness, synaptic cleft width, and synaptic interface curvature, were observed in the focal cerebral ischemia marginal zone in rats through the use of transmission electronic microscopy.RESULTS：Broken synapses were observed following cerebral ischemia, and the number of synapses was significantly decreased. Compared to the model group, synaptic ultrastructure was significantly improved in the electroacupuncture group. Compared to the sham-surgery group, postsynaptic density thickness was significantly decreased, as were synaptic cleft width and synaptic interface curvature in the electroacupuncture and model groups. However, compared to the model group, postsynaptic density thickness was significantly increased in the electroacupuncture group at the same time point post-surgery （P 〈 0.05 or P 〈 0.01）. In addition, synaptic cleft width and synaptic interface curvature were significantly increased with the passage of time （P〈 0.05 or P〈 0.01）.CONCLUSION：Electroacupuncture significantly ameliorated structural synapse lesion during the early stage of cerebral ischemic injury, promoted repair of synaptic structure, improved structural parameters of synapses, and increased synaptic structural plasticity, which suggested that the therapeutic effect of electroacupuncture was related to synaptic reorganization.

双气囊小肠镜在小肠CT造影结果阴性患者中的诊断价值

目的探讨双气囊小肠镜(DBE)及小肠CT造影(CTE)在小肠疾病中的诊断价值,分析CTE结果阴性的患者出现DBE结果阳性的预测因素。方法纳入2018年5月至2022年5月因怀疑小肠疾病就诊安徽医科大学第一附属医院行CTE及DBE检查的患者1013例,收集相关资料并比较两种检查方法检出率、诊断率及对小肠疾病诊断价值的差别。结果以DBE结果为参考标准,CTE的灵敏度为89.6%,特异度为49.1%,阳性预测值为93.6%,阴性预测值为36.1%。DBE的总检出率及总诊断率均高于CTE。多因素分析显示,年龄<60岁、贫血、低白蛋白血症是CTE结果阴性的患者出现DBE结果阳性的预测因素。CTE结果阴性而DBE结果阳性的患者中,镜下表现以小肠炎症、糜烂和溃疡性病变最常见,其次为小肠血管性病变。结论在CTE结果阴性的患者中,年龄<60岁、贫血和低白蛋白血症的患者出现DBE结果阳性的可能性更大。在怀疑小肠黏膜病变、小肠出血时,若CTE结果阴性,应进一步行DBE检查以明确诊断。

Genome sequencing and phylogenetic analysis of Banna virus(genus Seadornavirus,family Reoviridae)isolated from Culicoides

In an investigation of blood-sucking insects and arboviruses, a virus(YN12243) was isolated from Culicoides samples collected in the Sino-Burmese border region of Yunnan Province, China. The virus caused cytopathic effect(CPE) in C6/36 cells and passaged stably. Polyacrylamide gel analysis showed that the genome of YN12243 was composed of 12 segments of double-stranded RNA(dsRNA), with a distribution pattern of 6-6. The nucleotide and amino acid sequences of the coding region(1.12 segments) were17,803 bp and 5,925 amino acids in length, respectively. The phylogenetic analysis of VP1 protein(RdRp) revealed that YN12243 belonged to genus Seadornavirus of family Reoviridae, and further analysis indicated that YN12243 belongs to the Banna virus(BAV) genotype A2. Additionally, YN12243 was located in the same evolutionary cluster as BAV strains isolated from different mosquito species, suggesting that the BAV isolated from Culicoides does not have species barriers. These results indicate that Culicoides can also be a vector for BAV. In view of the hematophagous habits of Culicoides on cattle, horses, deer, and other large animals, as well as the possibility of spreading and causing a variety of animal arboviral diseases, it is important to improve infection detection and monitor the BAV in large livestock.

Endovascular treatment with or without intravenous alteplase for acute ischaemic stroke due to basilar artery occlusion

Background and purpose It remains controversial if endovascular treatment(EVT)can improve the outcome of patients with acute basilar artery occlusion(BAO).This study aims to compare the functional outcomes between EVT with and without intravenous thrombolysis(IVT)first in patients who had acute ischaemic stroke(AIS)due to BAO.Methods Patients who had AIS with BAO who underwent EVT within 24 hours of onset were enrolled in this multicentre cohort study,and the efficacy and safety were compared between IVT+EVT and direct EVT.The primary outcome was 90-day functional independence.All outcomes were assessed with adjusted OR(aOR)from the multivariable logistic regression.In addition,a meta-analysis was performed on all recently published pivotal studies on functional independence after EVT in patients with BAO.Results Of 310 enrolled patients with BAO,241(78%)were treated with direct EVT and 69(22%)with IVT+EVT.Direct EVT was associated with a worse functional outcome(aOR,0.46(95%CI 0.24 to 0.85),p=0.01).IVT+EVT was associated with a lower percentage of patients who needed≥3 passes of stent retriever(10.14%vs 20.75%).The meta-analysis regression revealed a potential positive correlation between bridging with IVT first and functional independence(r=0.14(95%CI 0.05 to 0.24),p<0.01).Conclusions This study showed that compared with direct EVT,EVT with IVT first was associated with better functional outcomes in patients with BAO treated within 24 hours of onset.The meta-analysis demonstrated similar favourable efficacy of IVT first followed by EVT in patients with BAO.

Tranexamic acid for acute intracerebral haemorrhage growth based on imaging assessment (TRAIGE): a multicentre, randomised, placebo- controlled trial

Background Studies show tranexamic acid can reduce the risk of death and early neurological deterioration after intracranial haemorrhage.We aimed to assess whether tranexamic acid reduces haematoma expansion and improves outcome in intracerebral haemorrhage patients susceptible to haemorrhage expansion.Methods We did a prospective,double-blind,randomised,placebo-controlled trial at 10 stroke centres in China.Acute supratentorial intracerebral haemorrhage patients were eligible if they had indication of haemorrhage expansion on admission imaging(eg,spot sign,black hole sign or blend sign),and were treatable within 8 hours of symptom onset.Patients were randomly assigned(1:1)to receive either tranexamic acid or a matching placebo.The primary outcome was intracerebral haematoma growth(>33% relative or>6 mL absolute)at 24 hours.Clinical outcomes were assessed at 90 days.Results Of the 171 included patients,124(72.5%)were male,and the mean age was 55.9±11.6 years.89 patients received tranexamic acid and 82 received placebo.The primary outcome did not differ significantly between the groups:36(40.4%)patients in the tranexamic acid group and 34(41.5%)patients in the placebo group had intracranial haemorrhage growth(OR 0.96,95% CI 0.52 to 1.77,p=0.89).The proportion of death was lower in the tranexamic acid treatment group than placebo group(8.1%vs 10.0%),but there were no significant differences in secondary outcomes including absolute intracranial haemorrhage growth,death and dependency.Conclusions Among patients susceptible to haemorrhage expansion treated within 8 hours of stroke onset,tranexamic acid did not significantly prevent intracerebral haemorrhage growth.Larger studies are needed to assess safety and efficacy of tranexamic acid in intracerebral haemorrhage patients.

Haemostatic therapy in spontaneous intracerebral haemorrhage patients with high-risk of haematoma expansion by CT marker: a systematic review and meta- analysis of randomised trials

Background and purpose Current randomised controlled trials(RCTs)showed an uncertain benefit of haemostatic therapy on preventing haematoma expansion and improving the outcome in patients with intracerebral haemorrhage(ICH).This meta-analysis aims to systematically evaluate the effect of haemostatic agents on the prevention of haemorrhage growth in patients with high-risk spontaneous ICH predicted by CT signs in RCTs.Methods A comprehensive search of PubMed,EMBASE and Cochrane library from 1 January 2005 to 30 June 2021 was conducted.RCTs that compared haemostatic agents with placebo for the treatment of spontaneous patients with ICH with high-risk haemorrhage growth were included.The primary endpoint was haematoma expansion at 24 hours.Other major endpoints of interest included 90-day functional outcome and mortality.Results The meta-analysis included four RCTs that randomised 2666 patients with ICH with high-risk haemorrhage growth.Haemostatic therapy reduced the rate of haematoma expansion at a marginally statistically significant level when compared with placebo(OR 0.84;95% CI 0.70 to 1.00;p=0.051).Subgroup analysis for patients with black hole sign on CT revealed a significant reduction of haematoma expansion with haemostatic therapy(OR 0.61;95% CI 0.39 to 0.94;p=0.03).However,both the primary analysis and subgroup analyses showed that haemostatic therapy could not reduce the rate of poor functional outcome(modified Rankin Scale>3)or death.Conclusions Haemostatic therapy showed a marginally significant benefit in reducing early haematoma expansion in patients with high-risk spontaneous ICH predicted by markers on CT scan.However,no significant improvement in functional outcome or reduction of mortality was observed.

In- hospital complications affect short- term and long- term mortality in ICH: a prospective cohort study

Background Medical complications strongly affected the mortality of patients with stroke.However,only limited research has studied the effect of in-hospital medical complications on the mortality of patients with spontaneous intracerebral haemorrhage(ICH)globally.Using the China National Stroke Registry,the effect was prospectively and systematically investigated in patients with spontaneous ICH during their hospitalisation,at 3,6 and 12 months after disease onset.Methods This study collected data on patients over 18 years old with spontaneous ICH from 132 Chinese clinical centres across 32 provinces and four municipalities(Hong Kong included),from September 2007 to August 2008.Data on patient complications,death and other information were acquired through paper-based registry forms.Using multivariable logistic regression,the association of medical complications with stroke outcomes was evaluated.Results Of 3255 patients with spontaneous ICH,878(26.97%)had in-hospital medical complications.In-hospital medical complications were independent risk factors for death during the hospitalisation(adjusted OR 4.41,95% CI 3.18 to 6.12),at 3 months(adjusted OR 2.18,95% CI 1.70 to 2.80),6 months(adjusted OR 1.84,95% CI 1.45 to 2.34)and 12 months(adjusted OR 1.59,95% CI 1.26 to 2.01)after spontaneous ICH.Conclusion The results revealed that the short-term and long-term mortality of patients with spontaneous ICH in China was significantly associated with their in-hospital medical complications.

用于纤维基可穿戴传感器和电致发光器件的多功能石墨烯/聚电解质水性分散液

导电分散液是构建用于可穿戴传感器、能源和柔性显示器件中导电纤维/织物的关键组成部分.尽管石墨烯具有稳定的化学性质和高电导性,但制备与纤维/织物材料兼容的石墨烯分散液仍然具有挑战性.本研究通过引入聚苯乙烯磺酸钠(PSS)分散剂,成功制备了环境友好且稳定的石墨烯水性分散液.PSS通过非共价作用改性石墨烯,使其表面带负电荷,由此产生的静电排斥促进了石墨烯的稳定分散.此外,PSS还有助于石墨烯与基底之间形成牢固的粘附.我们制备了基于石墨烯改性的纤维和纤维膜的柔性机械传感器,包括可拉伸应变传感器和压力传感器;其中,应变传感器具有100%的高拉伸性和144.6的灵敏度,也能够感知0.1%的小应变.此外,制备的柔性生理电极能够长时间记录肌电信号和心电信号.作为概念验证,制备的同轴电致发光纤维能够为潜艇模型提供照明,以完成水下复杂任务.这项工作将进一步推动先进纳米材料在可穿戴领域的应用.