Evaluation of using a double helical, closed-cell stent-retriever(Skyflow) for thrombectomy procedures in acute arterial occlusion: A preclinical study and a clinical trial

Background and purpose:Stent retriever thrombectomy is the standard therapeutic approach for ischemic stroke with acute large-vessel occlusion.This study evaluated the safety and efficacy of a new thrombectomy device(Skyflow)in the treatment of acute ischemic stroke.Methods:After an arterial occlusion model was established,stent-retriever thrombectomy was performed.Digital subtraction angiography(DSA)and autopsy were carried out immediately after thrombectomy in six animals in the acute experimental group.Simulated stent-retriever thrombectomy was performed for three animals in the subacute experimental group,and follow-up angiography and vascular pathological examination were assessed 90 days after the operation.In the clinical trial,192 patients with intracranial anterior circulation large vessel occlusion,within 8 h of symptom onset,were included to undergo thrombectomy with either Skyflow or Solitaire FR stent retriever.Efficacy and safety endpoints were recorded(including successful reperfusion,favorable clinical outcomes,time from puncture to reperfusion,instrument operation success rates and National Institutes of Health Stroke Scale(NIHSS)scores at 7 days for efficacy endpoints,and symptomatic intracranial hemorrhage(sICH),subarachnoid hemorrhage(SAH)and all-cause mortality rates for safety endpoints).Results:All blood vessels achieved successful recanalization in the animal models.In the clinical trial,successful recanalization was attained in 88.4%of patients of the Skyflow group,which was comparable to that of the Solitaire FR group(82.5%)in the full analysis set of the clinical trial.There were no severe complications on DSA,an animal autopsy,or vessel pathological examination in animal experiments.Additionally,no statistically significant difference was observed between the Skyflow and Solitaire FR groups in the clinical trial regarding the safety endpoints.Conclusion:This study showed that the new Skyflow stent retriever is safe and effective for the treatment of acute large vessel occlusion,as demonstrated in our animal study and human trial.

Safety and efficacy of the Separ GateTM balloon-guiding catheter in neurointerventional surgery: Study protocol of a prospective multicenter single-arm clinical trial

Background: The balloon-guiding catheter(BGC) reportedly reduces the number of retrievals and occurrence of distal emboli, achieving superior revascularization results and improved clinical outcomes in acute stroke. This study will aim to examine the efficacy and safety of the new Separ GateTM BGC.Design: This prospective multicenter single-arm clinical trial will aim to include 128 patients who fulfill its inclusion and exclusion criteria. All patients will receive endovascular interventional therapy with BGC assistance.The primary endpoint will be the immediate surgical success rate, while the secondary endpoint will be product performance. The safety evaluation will include serious adverse events such as puncture site hematoma and bleeding, cerebral vasospasm, vessel dissection, vessel perforation, air embolism, thrombus(acute or subacute),vessel occlusion, distal embolization, infection, adverse reaction to antiplatelet and anticoagulant drugs, intracranial hemorrhage, stroke, death, and device defect.Discussion: The prospective multicenter trial will provide safety and efficacy information for the Separ GateTM BGC.Its findings will provide a clinical reference for endovascular adjuvant therapy of cerebrovascular disease.Trial registration: Chi CTR1800014459.

A novel cerebrovascular drug-coated balloon catheter for treating symptomatic intracranial atherosclerotic stenosis lesions:Study protocol for a prospective,multicenter,single-arm,target-value clinical trial

Background:Previous single-center studies have demonstrated that drug-coated balloons(DCBs)may reduce restenosis rates,which is an important factor affecting the prognosis for intracranial interventional therapy.However,currently available cardiac DCBs are not always suitable for the treatment of intracranial atherosclerotic stenosis(ICAS).This study aimed to evaluate the safety and efficacy of a novel DCB catheter designed for patients with severely symptomatic ICAS.Methods:This prospective,multicenter,single-arm,target-value clinical trial was conducted in 9 Chinese stroke centers to evaluate the safety and efficacy of a novel DCB catheter for treating symptomatic severe ICAS.Primary metrics and other indicators were collected and analyzed using SAS version 9.4(SAS Institute,Cary,NC,USA).Results:A total of 155 patients were enrolled in this study.The preliminary collection of follow-up data has been completed,while data quality control is ongoing.Conclusion:Results of this study demonstrated the patency rate,safety,and effectiveness of a novel on-label paclitaxel DCB designed for the treatment of ICAS.Ethics and dissemination:This study,involving human participants,was reviewed and approved by the Ethics Committee of Drugs(Devices)Clinical Experiment at Henan Provincial People’s Hospital(reference number:2020-145-03)and other research centers participating in the clinical trial.The results of this study will be presented at international conferences and sent to peer-reviewed journals for publication.Standard protocol items:The Recommendations for Interventional Trials checklist was used when drafting the study protocol.Trial registration number:Registered with the Chinese Clinical Trial Registry on June 11,2021(Chi CTR2100047223).

Corrigendum to " Curcumin alleviates the synaptic dysfunction in APPswe/PS1dE9 double transgenic mice"[J Trad Chin Med Sci 5 (2018) 168e176]

This is Dr.Pengwen Wang,from Dongzhimen Hospital,Beijing University of Chinese Medicine.Our group published the article"Curcumin can influence synaptic dysfunction in APPswe/PS1dE9 mice"in your Journal in 2018.We sincerely apologize for the controversies caused by our figures.In Fig.2A and 3A,there are embellishments of figures to make the cells more visible.There were no intentions in any way to alter the cell count.In Fig.3A,therewas a misuse of segments.We truly apologize for this negligence.With careful inspection,the result presented in the article was consistent with the original experiment.

Safety and efficacy of the SeparGateTM balloon-guiding catheter in neurointerventional surgery:A prospective,multicenter,single-arm clinical trial

Objective:To evaluate the safety and efficacy of the SeparGateballoon-guiding catheter(BGC)for blocking flow and delivering devices in neurointerventional surgery.Method:This prospective multicenter single-arm trial enrolled patients who received BGC adjuvant therapy to provide temporary blood flow arrest of the supra-aortic arch arteries and their branch vessels in interventional therapy.The primary endpoint was immediate procedural success rate in flow arrest,device delivery,and withdrawal.The efficacy endpoints were intraoperative product performance,including rigidity,smoothness,fracture resistance of the catheter wall,catheter push performance,compatibility and radiopaque display,integrity,adhesion thrombus after withdrawal and balloon rupture.The safety endpoints were adverse and serious adverse events associated with the test device and serious adverse events resulting in death or serious health deterioration.Result:A total of 129 patients were included;of them,128 were analyzed in the full analysis set(FAS)and per protocol set(PPS).Immediate procedural success was achieved in 97.7%of patients with FAS and PPS.The lower bound of the 95%confidence interval was 94.6%,higher than the preset efficacy margin of 94%.Device-related adverse events occurred in 2(1.6%)cases.One was mild adverse event of vasospasm,which resolved spontaneously.The other was serious adverse event of dissection aggravation,which was treated with stenting angioplasty.No device defects were observed.Conclusion:In neurointerventional surgery,the SeparGateBGC can be used to temporarily block the flow of the supra-aortic arch arteries and their branch vessels and guide the interventional device to the target vascular position.

Application of 3D T1-SPACE combined with 3D-TOF sequence for follow-up evaluation of stent-assisted coil embolization for intracranial aneurysm

Objectives:To assess 3D T1-SPACE combined with 3D-TOF sequence for follow-up evaluation of stent-assisted coil embolization for intracranial aneurysm.Materials and methods:Between Oct 2018 and May 2019,we enrolled 25 patients with intracranial aneurysm who underwent stent-assisted coil embolization.All patients were followed up for 6 to10 months after endovascular treatment(EVT)using 3D-TOF MRA,3D T1-SPACE and DSA to evaluate aneurysm occlusion and parent artery patency.Results:With regards to aneurysm occlusion,the specificity of 3D-TOF MRA was 86.9%(20/23)and the accuracy was 84%(21/25).There was no statistical significance(P=0.409)compared with the DSA.The parent artery by3D-TOF MRA showed that there were 14 patients with grade 3,8 patients with grade 2 and 3 patients with grade1.However,3D T1-SPACE showed that all 25 patients were grade 4,and were clearly displayed without metal artifacts.The comparison of the two MR techniques demonstrated that 3D T1-SPACE was superior to 3D-TOF MRA in the evaluation of parent artery(P<0.001).Conclusions:3D T1-SPACE sequence provides better image quality and higher accuracy for evaluating stented parent arteries compared to TOF-MRA.This study also shows that 3D-TOF MRA has a merit to evaluate aneurysm occlusion.The combination of these two modalities can be used as an optional follow-up evaluation after EVT of intracranial aneurysms.

Curcumin can influence synaptic dysfunction in APPswe/PS1dE9 mice

Objective:Synaptic loss in the hippocampus in Alzheimer's disease (AD) has been shown to be closely associated with the cognitive impairment.Synaptic dysfunction is a pathological feature that occurs prior to synaptic loss and mainly depends on structural changes and alterations of synaptic proteins.Evidence has suggested that curcumin,obtained from the traditional Chinese medicine—Turmeric (Curcuma longa L.),can ameliorate cognitive impairment,but few studies have focused on the mechanism by which curcumin affects synapses at early stages of AD.Therefore,we performed a study to investigate whether curcumin exerted its effect on synapses at the early stage in AD.Methods:We used 3-month-old APPswe/PS1dE9 mice and wild type (WT) littermates of the APPswe/PS1dE9 mice from the same colony as the normal controls.Seventy-five APPswe/ PS1dE9 mice were allocated to the Model group,Rosiglitazone group,and Curcumin groups randomly.The Wild and Model groups were orally administered an equal amount of 0.5% carboxymethyl cellulose (CMC).We observed the ultrastructure of synapses in the CA1 area of hippocampus and analyzed the expression levels of PSD95 and Shank1,two important synapseassociated proteins,in APPswe/PS1dE9 mice by immunohistochemical staining and western blot after gavage for three months.Results:Our findings showed that curcumin treatment not only improved the quantity and ultrastructure of synapses but also increased the expression of PSD95 and Shank1.Conclusion:The results indicate that curcumin improves synaptic dysfunction and the potential mechanism may involve improving the structure of synapses and regulating the synapse related proteins PSD95 and Shank1.

Endovascular transvenous treatment for superficial intracranial arteriovenous malformations

Objective:The objective of this study was to evaluate the feasibility and outcomes of transvenous endovascular embolization(TVE) for superficial intracranial arteriovenous malformations(AVMs).Methods:After collecting clinical and imaging data,a prospective series of 11 patients presenting with superficial AVMs were treated by endovascular embolization using a transvenous approach between November 2016 and October 2018.Results:Ten patients(90.9%) had ruptured AVMs before TVE.The mean nidus size was 3.27 ± 1.47 cm,and the median Spetzler-Martin grade was II.The rate of immediate angiographic occlusion of the AVMs was 90.9%(10/11).One patient was treated with transarterial embolization since TVE was not achieved due to an unsuccessful positioning of the microcatheter.Two patients(cases 8 and 11) suffered a intracranial hemorrhage and a cerebral infarction with encephaledema,respectively,but no procedure-related mortalities were observed.Eight patients(72.7%) were independent with a modified Rankin Score(mRS) 2 at discharge and the m RSs of all patients,which were collected 30 days postintervention,were not more than 2.The mean follow-up period was 17 months.There were no nidus recurrences during the follow-up period.Conclusions:The curative transvenous embolization of superficial AVMs seems feasible and effective while carefully monitoring for embolization-related complications.

围术期NLR变化可预测急性前循环大血管闭塞性卒中取栓患者的临床预后

目的探讨入院时中性粒细胞/淋巴细胞比值(neutrophils to lymphocyte ratio,NLR)、血管内机械取栓术后3~7 d NLR和围术期NLR变化与接受取栓治疗的前循环大血管闭塞性急性缺血性卒中患者临床预后关系。方法回顾性分析2018年1月至2021年6月在郑州大学人民医院接受血管内机械取栓治疗的前循环大血管闭塞性急性缺血性卒中患者的基线数据、临床表现和手术相关指标,将入院时NLR定义为NLR1,术后3~7 d NLR定义为NLR2,NLR2-NLR1定义为围术期NLR变化。根据术后90 d改良Rankin量表(modified Rankin scale,mRS)评分将患者分为临床预后良好组和临床预后不良组,将单因素分析P<0.05的因素纳入Logistics多因素回归分析中,探讨NLR1、NLR2及围术期NLR变化与临床预后的关系。结果本研究共纳入332例患者,其中268例(80.7%)患者实现成功再灌注,术后90 d随访时有147例(44.3%)患者临床预后良好。单因素分析显示,NLR2较低和围术期NLR变化较低与临床预后、成功再灌注、症状性颅内出血和术后90 d随访时死亡率有统计学意义(P<0.05);进一步多变量Logistic分析表明,年龄(OR:1.063,95%CI:1.034~1.092,P<0.001)、侧支循环(OR:0.454,95%CI:0.249~0.829,P=0.010)、首次通过再灌注(OR:0.318,95%CI:0.172~0.589,P<0.001)、围术期NLR变化(OR:2.474,95%CI:1.964~3.117,P<0.001)是临床预后的独立预测因素。受试者工作特征曲线分析发现,围术期NLR变化截断值为3.42时,预测临床预后敏感性和特异性分别为81.1%、74.1%。结论取栓术后3~7 d NLR和围术期NLR变化与成功再灌注、症状性颅内出血和死亡率相关,围术期NLR变化是临床预后的独立预测因子。

Colorectal cancer and adjacent normal mucosa differ in apoptotic and inflammatory protein expression

Colorectal cancer usually refers to the occurrence of the appendix,rectum or colon and other parts of the ma-lignant tumor in the large intestine mucosa and glands,is also one of the most common malignant tumors in human.In recent years,studies have shown that chronic inflammation is the"initiator"of cancer.Inflammation plays a causal role in the early formation of tumors by regulating the initiation and promotion of tumor genesis and development through a series of inflammatory cytokines.Inflammation plays a causal role in the early for-mation of tumors by regulating the initiation and promotion of tumor genesis and development through a series of inflammatory cytokines.The latter part of this review describes the role of several important inflammatory factors:tumor necrosis factor-α(TNF-α),interleukin-6(IL-6),and transforming growth factor-β(TGF-β)in col-orectal cancer.In normal mucosa,inflammatory factors play an important role in the immune response of the body.However,when a large number of inflammatory factors accumulate,they will cause pathological damage to the body,trigger inflammation and even deteriorate into cancer.Serum levels of most inflammatory factors were low in healthy controls,but were elevated in colorectal cancer patients.Here,we review the relationship be-tween apoptosis,inflammation and cancer,and analyze the difference in the expression of inflammatory proteins in colorectal cancer and its adjacent mucosa.