OBJECTIVE Glioblastoma multiforme(GBM) is the most malignant primary tumor of the central nervous system and is associated with a very poor prognosis.No further improvements in outcomes have been reported since radiot...OBJECTIVE Glioblastoma multiforme(GBM) is the most malignant primary tumor of the central nervous system and is associated with a very poor prognosis.No further improvements in outcomes have been reported since radiotherapy-temozolomide therapy was introduced.Therefore,de.veloping new agents to treat GBM is important.This study aimed to evaluate the anti-tumor effect of evodiamine(Evo) on GBM cells,and to determine the underlying mechanisms involved.METHODS U251,LN229,HEB and PC12 cells were treated with various concentrations of evodiamine for 24 and48 hours,cell viability was measured by MTT assay.The U251 and LN229 cells were treated with evo.diamine(0-10 μmol·L^(-1)) for 24 h,and then stained with Hoechst 33258.An Annexin V-FITC Apoptosis Detection Kit was used to detect apoptosis in the cells.Reactive oxygen species(ROS) production was detected using dichlorofluorescein diacetate(DCFH-DA) staining.The changes in mitochondrial mem.brane potential(MMP) were assessed by JC-1 after cells were treated with evodiamine.The expres.sion levels of p-PI3K,PI3K,p-Akt,Akt,Bax,Bcl-2,p-p38,p38,p-JNK,JNK,p-ERK,ERK,Cytochrome c,Caspase-3,cleaved Caspase-3,PRAP,and cleaved PARP were measured by Western blot analy.ses.RESULTS According to MTT assay results,Evo significantly inhibited the cell proliferation in a time-and dose-dependent manner.Fluorescence microscopy and flow cytometry analyses revealed that Evo induced cell apoptosis in a concentration-dependent manner.Moreover,Evo induced reactive oxygen species(ROS) production and mitochondrial membrane potential(MMP) disruption.Finally,Evo induced apoptosis in cancer cells by suppressing PI3K/AKT signaling and inducing MAPK phos.phorylation(p38 and JNK,but not ERK) to regulate apoptotic proteins(Bax,Bcl-2,Cytochrome c,Cas.pase-3,and PARP).CONCLUSION In summary,Evo inhibits cell proliferation by inducing cellular apoptosis via suppressing PI3K/AKT and activating MAPK in GBM;these results indicate that Evo may be regarded as a new approach for GBM treatment.展开更多
Prompt diagnosis and therapy of aneurysms are critical for patients with nontraumatic subarachnoid hemorrhage （SAH）.The aim of our study was to assess the clinical usefulness of multislice computed tomography angiog...Prompt diagnosis and therapy of aneurysms are critical for patients with nontraumatic subarachnoid hemorrhage （SAH）.The aim of our study was to assess the clinical usefulness of multislice computed tomography angiography （CTA） in the surgical and endovascular treatment of intracranial aneurysms.A total of 195 cases with 206 intracranial aneurysms underwent CTA.Fifty （24%） aneurysms underwent surgical clipping while 156 （76%） aneurysms underwent endovascular coiling.In the five missed aneurysms at digital substraction angiography and the nine aneurysms with mass intracerebral hematomas,surgical treatment was successfully performed based on 16-slice CTA alone,and the other 36 aneurysms were clipped on the main basis of the CTA.The intraoperative findings correlated well with the CTA findings and all aneurysms were clipped successfully.Sixteen-slice CTA image information has been shown to determine the choice of aneurysm therapy and assist the surgical and endovascular treatment of intracranial aneurysms.展开更多
Objective:Cancer/testis antigen FMR1NB is aberrantly expressed in various types of cancer,but not in normal tissues except for testis.This study aimed to investigate the expression and functional role of FMR1NB in gli...Objective:Cancer/testis antigen FMR1NB is aberrantly expressed in various types of cancer,but not in normal tissues except for testis.This study aimed to investigate the expression and functional role of FMR1NB in glioma.Methods:The expression of FMR1NB mRNA and protein was determined using RT-PCR and immunohistochemistry,respectively,in glioma specimens from 83 patients at follow-up.The effects of siRNA-mediated FMR1NB silencing on malignant biological behaviors were evaluated in glioma cell lines Al 72 and U251.Results:FMR1NB mRNA and protein expression was detected in 58.8%(77/131)and 46.34%(57/123)of glioma tissues,respectively.FMR1NB protein was positively correlated with World Health Organization grade and found to be an independent prognostic marker for poor outcome.Knockdown of FMR1NB induced apoptosis and suppressed proliferation,adhesion,migration,and invasion by modulating the expression of cyclin A,CDK2,caspase-3,E-cadherin,and N-cadherin in A172 and U251 cells.Conclusion:Our findings suggest that FMR1NB contributes to the tumorigenesis of glioma cells and may represent a potential prognostic biomarker and an attractive therapeutic target in glioma.展开更多
Kinetic investigations including quasi-classical trajectory and canonical unified statistical theory method calculations are carried out on a potential energy surface for the hydrogen-abstraction reaction from methane...Kinetic investigations including quasi-classical trajectory and canonical unified statistical theory method calculations are carried out on a potential energy surface for the hydrogen-abstraction reaction from methane by atom O(^3P).The surface is constructed using a modified Shepard interpolation method.The ab initio calculations are performed at the CCSD(T)level.Taking account of the contribution of inner core electrons to electronic correlation interaction in ab initio electronic structure calculations,modified optimized aug-cc-pCVQZ basis sets are applied to the all-electrons calculations.On this potential energy surface,the triplet oxygen atom attacks methane in a near-collinear H-CH3 direction to form a saddle point with barrier height of 13.55 kcal/mol,which plays a key role in the kinetics of the title reaction.For the temperature range of 298-2500 K,our calculated thermal rate constants for the O(^3P)+CH4→OH+CH3 reaction show good agreement with relevant experimental data.This work provides detailed mechanism of this gas-phase reaction and a theoretical guidance for methane combustion.展开更多
The dynamics of the ground-state reaction of CH4＋ O（~3P） → CH3（ν = 0） ＋ OH（ ν= 0） have attracted a great deal of attention both theoretically and experimentally. This rapid communication represents extensiv...The dynamics of the ground-state reaction of CH4＋ O（~3P） → CH3（ν = 0） ＋ OH（ ν= 0） have attracted a great deal of attention both theoretically and experimentally. This rapid communication represents extensive quasi-classical trajectory calculations of the vibrational distributions on a unique full-dimensional ab initio potential energy surface for the title reaction, at the collision energy of relevance to previous crossed molecular beam experiments. The surface is constructed using the all electrons coupled-cluster singles and doubles approach plus quasi-perturbative triple excitations with optimized basis sets. A modified Shepard interpolation method is also employed for the construction. Good agreement between our calculations and the available experimental results has been achieved, opening the door for accurate dynamics on this surface.展开更多
Background and purpose:5 recent trials have shown the benefit of endovascular treatment for acute ischaemic stroke(AIS)due to large vessel occlusion of the anterior circulation.This study aims to evaluate the safety a...Background and purpose:5 recent trials have shown the benefit of endovascular treatment for acute ischaemic stroke(AIS)due to large vessel occlusion of the anterior circulation.This study aims to evaluate the safety and efficacy of Solitaire thrombectomy in patients with moderate-to-severe stroke in the Chinese population,which has a high prevalence of intracranial atherosclerosis.Methods and analysis:This multicentre prospective control study will involve 17 stroke centres in China,and plans to recruit 150 patients in the intervention group,and 150 patients in the medical group,in which patients meet enrolment criteria but refuse intervention.Patients with AIS due to large vessel occlusion indicated for treatment with Solitaire stent retriever within 12 hours of symptom onset,and who meet the inclusion and exclusion criteria,will be enrolled in this study.The primary efficacy endpoint is functional independence as defined by a modified Rankin Scale(mRS)score≤2 at 90 days or by functional improvement as defined by mRS,using shift analysis.The procedural efficacy endpoint is arterial recanalisation of the occluded target vessel measured by a modified Thrombolysis in Cerebral Infarction(mTICI)score equal or superior to 2b right following the use of the study device.The primary safety endpoint is symptomatic intracranial haemorrhage(sICH)within 24±3 hours postprocedure.Ethics and dissemination:The protocol was approved by the Ethics Committee at the coordinating centre and by the local Institutional Review Board of each participating centre.Trial registration number:NCT02350283.展开更多
Stroke is the second leading cause of death and the third leading contributor to the loss of disability-adjusted life-years.The fatality rate of all stroke patients ranges from 15%to 50%at 1 month to 5 years after str...Stroke is the second leading cause of death and the third leading contributor to the loss of disability-adjusted life-years.The fatality rate of all stroke patients ranges from 15%to 50%at 1 month to 5 years after stroke.Ischemic stroke is the most common type of stroke and accounts for 87%of all stroke cases.展开更多
Background The Catfish stent retriever is a newly developed mechanical thrombectomy device for rapid recanalisation in emergent large vessel occlusion(ELVO)stroke.The current trial aimed to assess whether the Catfish ...Background The Catfish stent retriever is a newly developed mechanical thrombectomy device for rapid recanalisation in emergent large vessel occlusion(ELVO)stroke.The current trial aimed to assess whether the Catfish stent retriever is non-inferior to the Solitaire stent retriever in terms of outcomes in ELVO stroke.Methods This was a randomised,prospective,parallel-group,multicentre,open-label,non-inferiority study conducted at 18 sites in China.The primary outcome was the proportion of cases with successful recanalisation(modified thrombolysis in cerebral infarction score of 2b or 3)following the procedure.Secondary efficacy outcomes included the National Institutes of Health Stroke Scale scores at 24 hours and 7 days or discharge if earlier,time from artery puncture to successful recanalisation and good clinical outcome(modified Rankin scale score≤2)at 90 days.Safety outcomes included symptomatic intracranial haemorrhage,all cause-death and severe adverse events at 90 days.Results Between 3 March 2019 and 5 June 2021,118 and 120 patients were randomly allocated to the Catfish and Solitaire groups,respectively.The primary endpoint after all endovascular procedures was non-inferior in the Catfish group(88.5%,100/113)than in the Solitaire group(87.7%,100/114),with a rate difference(RD)of 0.78%(95%CI-7.64 to-9.20;p=0.001).Sensitivity analysis only considering the per-protocol set also yielded similar results,with an RD of 0.83%(95%CI-7.03 to-8.70;p<0.001).Additionally,the proportions of cases with good clinical outcomes(47.8%vs 50.0%,p=0.739)and all-cause death rates(17.7%vs 18.8%,p=0.700)were similar in both groups at 90 days.Conclusions The Catfish stent retriever is an effective and safe device for endovascular recanalisation in ELVO stroke..展开更多
基金supported by Jiangsu Provincial Special Programme of Medical Science(BL2014035) Changzhou Science and Technology Support Program(CE20155060+2 种基金CE20165048) Changzhou High-Level Medical Talents Training Project(2016CZBJ006) Changzhou Municipal Commissions o
文摘OBJECTIVE Glioblastoma multiforme(GBM) is the most malignant primary tumor of the central nervous system and is associated with a very poor prognosis.No further improvements in outcomes have been reported since radiotherapy-temozolomide therapy was introduced.Therefore,de.veloping new agents to treat GBM is important.This study aimed to evaluate the anti-tumor effect of evodiamine(Evo) on GBM cells,and to determine the underlying mechanisms involved.METHODS U251,LN229,HEB and PC12 cells were treated with various concentrations of evodiamine for 24 and48 hours,cell viability was measured by MTT assay.The U251 and LN229 cells were treated with evo.diamine(0-10 μmol·L^(-1)) for 24 h,and then stained with Hoechst 33258.An Annexin V-FITC Apoptosis Detection Kit was used to detect apoptosis in the cells.Reactive oxygen species(ROS) production was detected using dichlorofluorescein diacetate(DCFH-DA) staining.The changes in mitochondrial mem.brane potential(MMP) were assessed by JC-1 after cells were treated with evodiamine.The expres.sion levels of p-PI3K,PI3K,p-Akt,Akt,Bax,Bcl-2,p-p38,p38,p-JNK,JNK,p-ERK,ERK,Cytochrome c,Caspase-3,cleaved Caspase-3,PRAP,and cleaved PARP were measured by Western blot analy.ses.RESULTS According to MTT assay results,Evo significantly inhibited the cell proliferation in a time-and dose-dependent manner.Fluorescence microscopy and flow cytometry analyses revealed that Evo induced cell apoptosis in a concentration-dependent manner.Moreover,Evo induced reactive oxygen species(ROS) production and mitochondrial membrane potential(MMP) disruption.Finally,Evo induced apoptosis in cancer cells by suppressing PI3K/AKT signaling and inducing MAPK phos.phorylation(p38 and JNK,but not ERK) to regulate apoptotic proteins(Bax,Bcl-2,Cytochrome c,Cas.pase-3,and PARP).CONCLUSION In summary,Evo inhibits cell proliferation by inducing cellular apoptosis via suppressing PI3K/AKT and activating MAPK in GBM;these results indicate that Evo may be regarded as a new approach for GBM treatment.
基金supported by grant of Changzhou science and technology projects of social development (No. CS2007203)
文摘Prompt diagnosis and therapy of aneurysms are critical for patients with nontraumatic subarachnoid hemorrhage （SAH）.The aim of our study was to assess the clinical usefulness of multislice computed tomography angiography （CTA） in the surgical and endovascular treatment of intracranial aneurysms.A total of 195 cases with 206 intracranial aneurysms underwent CTA.Fifty （24%） aneurysms underwent surgical clipping while 156 （76%） aneurysms underwent endovascular coiling.In the five missed aneurysms at digital substraction angiography and the nine aneurysms with mass intracerebral hematomas,surgical treatment was successfully performed based on 16-slice CTA alone,and the other 36 aneurysms were clipped on the main basis of the CTA.The intraoperative findings correlated well with the CTA findings and all aneurysms were clipped successfully.Sixteen-slice CTA image information has been shown to determine the choice of aneurysm therapy and assist the surgical and endovascular treatment of intracranial aneurysms.
基金supported by grants from the National Natural Science Foundation of China(No.81960453,No.81860445)Natural Science Foundation of Guangxi Province(No.2022GXNSFAA035639,No.2018GXNSFAA281050,No.2018GXNSFAA050151)+1 种基金Key Laboratory of Early Prevention and Treatment for Regional High Frequency Tumor(Guangxi Medical University)and Ministry of Education(No.GK2018-09,No.GKE 2019-08,No.GKEZZ202006)Guangxi First-class Discipline Construction Projectin Basic Medical Sciences(No.GXMUBMSTC-T07,No.GXMUBMSTCF-G04).
文摘Objective:Cancer/testis antigen FMR1NB is aberrantly expressed in various types of cancer,but not in normal tissues except for testis.This study aimed to investigate the expression and functional role of FMR1NB in glioma.Methods:The expression of FMR1NB mRNA and protein was determined using RT-PCR and immunohistochemistry,respectively,in glioma specimens from 83 patients at follow-up.The effects of siRNA-mediated FMR1NB silencing on malignant biological behaviors were evaluated in glioma cell lines Al 72 and U251.Results:FMR1NB mRNA and protein expression was detected in 58.8%(77/131)and 46.34%(57/123)of glioma tissues,respectively.FMR1NB protein was positively correlated with World Health Organization grade and found to be an independent prognostic marker for poor outcome.Knockdown of FMR1NB induced apoptosis and suppressed proliferation,adhesion,migration,and invasion by modulating the expression of cyclin A,CDK2,caspase-3,E-cadherin,and N-cadherin in A172 and U251 cells.Conclusion:Our findings suggest that FMR1NB contributes to the tumorigenesis of glioma cells and may represent a potential prognostic biomarker and an attractive therapeutic target in glioma.
基金Project supported by the National Natural Science Foundation of China(Grant No.51574016)and completed while the author was in residence at UNSW,Australia supported by the International Cooperation Training Program for Innovative Talents of USTB.
文摘Kinetic investigations including quasi-classical trajectory and canonical unified statistical theory method calculations are carried out on a potential energy surface for the hydrogen-abstraction reaction from methane by atom O(^3P).The surface is constructed using a modified Shepard interpolation method.The ab initio calculations are performed at the CCSD(T)level.Taking account of the contribution of inner core electrons to electronic correlation interaction in ab initio electronic structure calculations,modified optimized aug-cc-pCVQZ basis sets are applied to the all-electrons calculations.On this potential energy surface,the triplet oxygen atom attacks methane in a near-collinear H-CH3 direction to form a saddle point with barrier height of 13.55 kcal/mol,which plays a key role in the kinetics of the title reaction.For the temperature range of 298-2500 K,our calculated thermal rate constants for the O(^3P)+CH4→OH+CH3 reaction show good agreement with relevant experimental data.This work provides detailed mechanism of this gas-phase reaction and a theoretical guidance for methane combustion.
基金supported by the National Natural Science Foundation of China(Grant Nos.51574016 and 51604018)
文摘The dynamics of the ground-state reaction of CH4＋ O（~3P） → CH3（ν = 0） ＋ OH（ ν= 0） have attracted a great deal of attention both theoretically and experimentally. This rapid communication represents extensive quasi-classical trajectory calculations of the vibrational distributions on a unique full-dimensional ab initio potential energy surface for the title reaction, at the collision energy of relevance to previous crossed molecular beam experiments. The surface is constructed using the all electrons coupled-cluster singles and doubles approach plus quasi-perturbative triple excitations with optimized basis sets. A modified Shepard interpolation method is also employed for the construction. Good agreement between our calculations and the available experimental results has been achieved, opening the door for accurate dynamics on this surface.
基金This study is sponsored and conducted by the Cerebrovascular Disease Center of Tiantan Hospital,which is also responsible for data analysis.This study is funded by the National Science and Technology Major Project of China(2011BAI08B02,2015BAI12B04 and 2015BAI12B02).
文摘Background and purpose:5 recent trials have shown the benefit of endovascular treatment for acute ischaemic stroke(AIS)due to large vessel occlusion of the anterior circulation.This study aims to evaluate the safety and efficacy of Solitaire thrombectomy in patients with moderate-to-severe stroke in the Chinese population,which has a high prevalence of intracranial atherosclerosis.Methods and analysis:This multicentre prospective control study will involve 17 stroke centres in China,and plans to recruit 150 patients in the intervention group,and 150 patients in the medical group,in which patients meet enrolment criteria but refuse intervention.Patients with AIS due to large vessel occlusion indicated for treatment with Solitaire stent retriever within 12 hours of symptom onset,and who meet the inclusion and exclusion criteria,will be enrolled in this study.The primary efficacy endpoint is functional independence as defined by a modified Rankin Scale(mRS)score≤2 at 90 days or by functional improvement as defined by mRS,using shift analysis.The procedural efficacy endpoint is arterial recanalisation of the occluded target vessel measured by a modified Thrombolysis in Cerebral Infarction(mTICI)score equal or superior to 2b right following the use of the study device.The primary safety endpoint is symptomatic intracranial haemorrhage(sICH)within 24±3 hours postprocedure.Ethics and dissemination:The protocol was approved by the Ethics Committee at the coordinating centre and by the local Institutional Review Board of each participating centre.Trial registration number:NCT02350283.
基金supported by grants from the National Natural Science Foundation of China(No.81870906)Natural Science Foundation of Jiangsu Province(No.BK20181156)Changzhou Science and Technology Support Program(No.CE20205025)。
文摘Stroke is the second leading cause of death and the third leading contributor to the loss of disability-adjusted life-years.The fatality rate of all stroke patients ranges from 15%to 50%at 1 month to 5 years after stroke.Ischemic stroke is the most common type of stroke and accounts for 87%of all stroke cases.
文摘Background The Catfish stent retriever is a newly developed mechanical thrombectomy device for rapid recanalisation in emergent large vessel occlusion(ELVO)stroke.The current trial aimed to assess whether the Catfish stent retriever is non-inferior to the Solitaire stent retriever in terms of outcomes in ELVO stroke.Methods This was a randomised,prospective,parallel-group,multicentre,open-label,non-inferiority study conducted at 18 sites in China.The primary outcome was the proportion of cases with successful recanalisation(modified thrombolysis in cerebral infarction score of 2b or 3)following the procedure.Secondary efficacy outcomes included the National Institutes of Health Stroke Scale scores at 24 hours and 7 days or discharge if earlier,time from artery puncture to successful recanalisation and good clinical outcome(modified Rankin scale score≤2)at 90 days.Safety outcomes included symptomatic intracranial haemorrhage,all cause-death and severe adverse events at 90 days.Results Between 3 March 2019 and 5 June 2021,118 and 120 patients were randomly allocated to the Catfish and Solitaire groups,respectively.The primary endpoint after all endovascular procedures was non-inferior in the Catfish group(88.5%,100/113)than in the Solitaire group(87.7%,100/114),with a rate difference(RD)of 0.78%(95%CI-7.64 to-9.20;p=0.001).Sensitivity analysis only considering the per-protocol set also yielded similar results,with an RD of 0.83%(95%CI-7.03 to-8.70;p<0.001).Additionally,the proportions of cases with good clinical outcomes(47.8%vs 50.0%,p=0.739)and all-cause death rates(17.7%vs 18.8%,p=0.700)were similar in both groups at 90 days.Conclusions The Catfish stent retriever is an effective and safe device for endovascular recanalisation in ELVO stroke..
