目的总结肝动脉化疗栓塞(transarterial chemoembolization,TACE)术后栓塞综合征(post-embolization syndrome,PES)相关性疼痛结构化管理的最佳证据,为临床提供参考。方法根据循证护理的方法,通过计算机检索Up To Date、医脉通、中国知...目的总结肝动脉化疗栓塞(transarterial chemoembolization,TACE)术后栓塞综合征(post-embolization syndrome,PES)相关性疼痛结构化管理的最佳证据,为临床提供参考。方法根据循证护理的方法,通过计算机检索Up To Date、医脉通、中国知网等国内外相关数据库及网站等中有关TACE术后疼痛相关文献,包括指南、专家共识、系统评价、荟萃分析等,检索时限为建库至2024年5月30日。结果总计纳入文献21篇,其中2篇计算机决策、6篇指南、7篇专家共识、5篇系统评价和1篇临床循证实践;证据总结包括了疼痛预测、精细化TACE、非药物镇痛、超前镇痛、三阶梯镇痛、中药镇痛和疼痛危象管理7个维度,共计20条证据。结论本研究总结的TACE术后患者PES关联性疼痛管理的最佳证据,为临床医护人员对TACE术后疼痛规范管理提供依据。展开更多
目的从木立芦荟(Aloe arborescens)中寻找新的BACE(β-分泌酶)抑制活性成分。方法用硅胶正相色谱及反相色谱技术进行活性成分的分离纯化,根据理化性质、光谱资料进行结构鉴定。结果从木立芦荟95%乙醇提取物的乙酸乙酯部分和正丁醇部分,...目的从木立芦荟(Aloe arborescens)中寻找新的BACE(β-分泌酶)抑制活性成分。方法用硅胶正相色谱及反相色谱技术进行活性成分的分离纯化,根据理化性质、光谱资料进行结构鉴定。结果从木立芦荟95%乙醇提取物的乙酸乙酯部分和正丁醇部分,分离得到了8个化合物:异丁酰基芦荟宁A(1),芦荟宁A(2),芦荟大黄素(3),(E)-2-acetonyl-8-(2′-O-feru loxyl)-β-D-glucopyranosyl-7-m ethoxy-5-m ethyl-chromone(4),7-O-m ethyl aloeresin A(5),芦荟苷A(6),elgon ica-d im er A(7)和elgon ica-d im er B(8)。结论化合物1为新化合物,化合物4为首次从该植物中分离得到。活性测试结果表明,化合物2,4,5,6对BACE有一定的抑制活性。展开更多
目的探讨Aβ3-10重复片段质粒免疫接种3月龄APPswe/PSEN1双转基因(AD)鼠脑内BACE1的影响。方法应用Aβ3-10重复片段质粒免疫3月龄APPswe/PSEN1双转基因鼠,同等剂量的PBS免疫对照组及C57BL/6J组小鼠,各组小鼠均在免疫后2、4、6次后通过RT...目的探讨Aβ3-10重复片段质粒免疫接种3月龄APPswe/PSEN1双转基因(AD)鼠脑内BACE1的影响。方法应用Aβ3-10重复片段质粒免疫3月龄APPswe/PSEN1双转基因鼠,同等剂量的PBS免疫对照组及C57BL/6J组小鼠,各组小鼠均在免疫后2、4、6次后通过RT-PCR法检测BACE1 m RNA水平,Western blotting法检测BACE1/GFAP/NF-κB蛋白水平,免疫组化法观察Aβ1-42脑内分布情况。水迷宫检测其行为学改变。结果在免疫2次后BACE1 m RNA表达水平C57BL/6J组<Aβ3-10组<对照组(F=4.649,P=0.021);免疫4次Aβ3-10组<C57BL/6J组<对照组(F=115.683,P=0.001);免疫6次C57BL/6J组<Aβ3-10组<对照组(F=86.600,P<0.001)。BACE1的蛋白表达水平在免疫2、4、6次后C57BL/6J组<Aβ3-10组<对照组(F=432.843,P<0.001;F=57.673,P<0.001;F=26.550,P=0.001),NF-κB的蛋白表达水平在免疫2次后C57BL/6J组<Aβ3-10组<对照组(F=109.127,P<0.001);免疫4,6次后Aβ3-10组<C57BL/6J组<对照组(F=30.301,P<0.001;F=129.967,P<0.001)。GFAP的蛋白表达水平在免疫2、4、6次后C57BL/6J组<Aβ3-10组<对照组(F=27.782,P=0.001;F=26.132,P=0.001;F=26.450,P=0.001);Aβ1-42在脑内的分布C57BL/6J组<Aβ3-10组<对照组(皮质:F=5.395,P=0.021;F=47.135,P=0.000;F=25.306,P=0.000,海马:F=11.023,P=0.002;F=14.936,P=0.001;F=50.132,P=0.000)。总潜伏期C57BL/6J组<Aβ3-10组<对照组(F=8.938,P=0.016;F=5.745,P=0.04;F=7.073,P=0.017)。结论 Aβ3-10重复片段质粒可以影响脑内BACE1的表达,影响Aβ产生,改善空间记忆能力。展开更多
Amyloid-β （Aβ） peptide, the primary constituent of senile plaques in Alzheimer＇s disease （AD）, is generated by β-secretase- and y-secretase-mediated sequential proteolysis of the amyloid precursor protein （AP...Amyloid-β （Aβ） peptide, the primary constituent of senile plaques in Alzheimer＇s disease （AD）, is generated by β-secretase- and y-secretase-mediated sequential proteolysis of the amyloid precursor protein （APP）. The aspartic protease, β -site APP cleavage enzyme （BACE）, has been identified as the main β-secretase in brain but the regulation of its activity is largely unclear. Here, we demonstrate that both BACE activity and subsequent Aβ production are enhanced after stimulation of receptor tyrosine kinases （RTKs）, such as the receptors for epidermal growth factor （EGF） and nerve growth factor （NGF）, in cultured cells as well as in mouse hippocampus. Furthermore, stimulation of RTKs also induces BACE internalization into endosomes and Golgi apparatus. This enhancement of BACE activity and A β production upon RTK activation could be specifically inhibited by Src family kinase inhibitors and by depletion of endogenous c-Src with RNAi, and could be mimicked by over-expressed c-Src. Moreover, blockage of BACE internalization by a dominant negative form of Rab5 also abolished the enhancement of BACE activity and Aβ production, indicating the requirement of BACE internalization for the enhanced activity. Taken together, our study presents evidence that BACE activity and Aβ production are under the regulation of RTKs and this is achieved via RTK-stimulated BACE internalization, and suggests that an aberration of such regulation might contribute to pathogenic Aβ production.展开更多
文摘目的总结肝动脉化疗栓塞(transarterial chemoembolization,TACE)术后栓塞综合征(post-embolization syndrome,PES)相关性疼痛结构化管理的最佳证据,为临床提供参考。方法根据循证护理的方法,通过计算机检索Up To Date、医脉通、中国知网等国内外相关数据库及网站等中有关TACE术后疼痛相关文献,包括指南、专家共识、系统评价、荟萃分析等,检索时限为建库至2024年5月30日。结果总计纳入文献21篇,其中2篇计算机决策、6篇指南、7篇专家共识、5篇系统评价和1篇临床循证实践;证据总结包括了疼痛预测、精细化TACE、非药物镇痛、超前镇痛、三阶梯镇痛、中药镇痛和疼痛危象管理7个维度,共计20条证据。结论本研究总结的TACE术后患者PES关联性疼痛管理的最佳证据,为临床医护人员对TACE术后疼痛规范管理提供依据。
文摘目的从木立芦荟(Aloe arborescens)中寻找新的BACE(β-分泌酶)抑制活性成分。方法用硅胶正相色谱及反相色谱技术进行活性成分的分离纯化,根据理化性质、光谱资料进行结构鉴定。结果从木立芦荟95%乙醇提取物的乙酸乙酯部分和正丁醇部分,分离得到了8个化合物:异丁酰基芦荟宁A(1),芦荟宁A(2),芦荟大黄素(3),(E)-2-acetonyl-8-(2′-O-feru loxyl)-β-D-glucopyranosyl-7-m ethoxy-5-m ethyl-chromone(4),7-O-m ethyl aloeresin A(5),芦荟苷A(6),elgon ica-d im er A(7)和elgon ica-d im er B(8)。结论化合物1为新化合物,化合物4为首次从该植物中分离得到。活性测试结果表明,化合物2,4,5,6对BACE有一定的抑制活性。
文摘目的探讨Aβ3-10重复片段质粒免疫接种3月龄APPswe/PSEN1双转基因(AD)鼠脑内BACE1的影响。方法应用Aβ3-10重复片段质粒免疫3月龄APPswe/PSEN1双转基因鼠,同等剂量的PBS免疫对照组及C57BL/6J组小鼠,各组小鼠均在免疫后2、4、6次后通过RT-PCR法检测BACE1 m RNA水平,Western blotting法检测BACE1/GFAP/NF-κB蛋白水平,免疫组化法观察Aβ1-42脑内分布情况。水迷宫检测其行为学改变。结果在免疫2次后BACE1 m RNA表达水平C57BL/6J组<Aβ3-10组<对照组(F=4.649,P=0.021);免疫4次Aβ3-10组<C57BL/6J组<对照组(F=115.683,P=0.001);免疫6次C57BL/6J组<Aβ3-10组<对照组(F=86.600,P<0.001)。BACE1的蛋白表达水平在免疫2、4、6次后C57BL/6J组<Aβ3-10组<对照组(F=432.843,P<0.001;F=57.673,P<0.001;F=26.550,P=0.001),NF-κB的蛋白表达水平在免疫2次后C57BL/6J组<Aβ3-10组<对照组(F=109.127,P<0.001);免疫4,6次后Aβ3-10组<C57BL/6J组<对照组(F=30.301,P<0.001;F=129.967,P<0.001)。GFAP的蛋白表达水平在免疫2、4、6次后C57BL/6J组<Aβ3-10组<对照组(F=27.782,P=0.001;F=26.132,P=0.001;F=26.450,P=0.001);Aβ1-42在脑内的分布C57BL/6J组<Aβ3-10组<对照组(皮质:F=5.395,P=0.021;F=47.135,P=0.000;F=25.306,P=0.000,海马:F=11.023,P=0.002;F=14.936,P=0.001;F=50.132,P=0.000)。总潜伏期C57BL/6J组<Aβ3-10组<对照组(F=8.938,P=0.016;F=5.745,P=0.04;F=7.073,P=0.017)。结论 Aβ3-10重复片段质粒可以影响脑内BACE1的表达,影响Aβ产生,改善空间记忆能力。
基金grants from the Ministry of Science and Technology （2003CB515405, 2005CB522406） the National Natural Science Foundation of China （30021003, 30400230, 30625014）+2 种基金 the Chinese Academy of Sciences （KSCX1- SW, KSCX2-SW） the Ministry of Education, Shanghai Municipal Commission for Science and Technology （06ZR14098） China Post Doctoral Science Foundation, and Shanghai Postdoctoral Science Foundation.
文摘Amyloid-β （Aβ） peptide, the primary constituent of senile plaques in Alzheimer＇s disease （AD）, is generated by β-secretase- and y-secretase-mediated sequential proteolysis of the amyloid precursor protein （APP）. The aspartic protease, β -site APP cleavage enzyme （BACE）, has been identified as the main β-secretase in brain but the regulation of its activity is largely unclear. Here, we demonstrate that both BACE activity and subsequent Aβ production are enhanced after stimulation of receptor tyrosine kinases （RTKs）, such as the receptors for epidermal growth factor （EGF） and nerve growth factor （NGF）, in cultured cells as well as in mouse hippocampus. Furthermore, stimulation of RTKs also induces BACE internalization into endosomes and Golgi apparatus. This enhancement of BACE activity and A β production upon RTK activation could be specifically inhibited by Src family kinase inhibitors and by depletion of endogenous c-Src with RNAi, and could be mimicked by over-expressed c-Src. Moreover, blockage of BACE internalization by a dominant negative form of Rab5 also abolished the enhancement of BACE activity and Aβ production, indicating the requirement of BACE internalization for the enhanced activity. Taken together, our study presents evidence that BACE activity and Aβ production are under the regulation of RTKs and this is achieved via RTK-stimulated BACE internalization, and suggests that an aberration of such regulation might contribute to pathogenic Aβ production.
