Objective:To anatomically and phenotypically characterize the insular cortex(IC)-nucleus tractus soli-tari(NTS)neural pathway.Methods:Adult male Sprague-Dawley rats were divided into three experimental cohorts for neu...Objective:To anatomically and phenotypically characterize the insular cortex(IC)-nucleus tractus soli-tari(NTS)neural pathway.Methods:Adult male Sprague-Dawley rats were divided into three experimental cohorts for neural circuit tracing.Anterograde labeling was achieved by injecting anterograde self-complementary adeno-associated viruses(scAAVs)into the IC.Retrograde tracing involved NTS injections of either retrograde scAAVs or FluoroGold(FG),combined with immunofluorescence histochemical staining to identify IC-originating projection neurons.For postsynaptic neurochemical phenotype characterization,IC was injected with AAV2/1-CaMKII-Cre,while a mixture of AAV2/9-Syn-DIO-mCherry and AAV2/9-VGAT1-EGFP was injected into the NTS.The rats were allowed to survive for one week following scAAVs or FG injection or four weeks after recombinase-dependent systems injection.Then the rats were sacrificed,and serial brain sections were prepared for immunofluorescence histochemical staining(brain section containing FG)and subsequent fluorescence/confocal microscopic analysis.Results:(1)Anterograde viral tracing re-vealed dense axonal terminals from the IC projecting to the medial subnucleus of the NTS,while retrograde tracing re-vealed that IC neurons projecting to the NTS were predominantly localized within the dysgranular layer;(2)IC-NTS projection neurons were exclusive glutamatergic(100%,n=3);(3)NTS neurons receiving IC inputs were mainly lo-calized in the medial subnucleus,and were predominantly GABAergic(79.8±3.2%,n=3).Conclusion:The pres-ent results indicate that a descending pathway from excitatory neurons of the IC terminates onto inhibitory neurons of the NTS,which might represent a potential neuromodulatory target for visceral pain disorders.展开更多
目的 在动物水平探讨铁死亡脂质过氧化损伤调控通路与帕金森病(Parkinson's disease, PD)的发病机制。方法 建立PD斑马鱼动物模型,取受精后48 h斑马鱼胚胎为对照组(n=100),200μmol/L的1-甲基-4-苯基-1,2,3,6-四氢吡啶(1-methyl-4-p...目的 在动物水平探讨铁死亡脂质过氧化损伤调控通路与帕金森病(Parkinson's disease, PD)的发病机制。方法 建立PD斑马鱼动物模型,取受精后48 h斑马鱼胚胎为对照组(n=100),200μmol/L的1-甲基-4-苯基-1,2,3,6-四氢吡啶(1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine, MPTP)为MPTP组(n=100),200μmol/L的MPTP+1.5μg/ml诺米芬辛为诺米芬辛组(n=100)。对受精后5 d斑马鱼进行行为学分析(检测运动能力、运动速率及运动距离);免疫荧光检测斑马鱼脑内α突触核蛋白和酪氨酸羟化酶表达,评估多巴胺能神经元(dopaminergic neurons, DA)活性;检测铁、谷胱甘肽(glutathione, GSH)及脂质过氧化水平,包括过氧化氢酶(catalase, CAT)、谷胱甘肽过氧化物酶4(glutathione peroxidase 4,GPX4)、脂质过氧化物(lipid peroxide, LPO)、丙二醛、活性氧,验证铁沉积可能通过铁死亡的脂质过氧化代谢调控机制引起DA损伤。结果 与对照组比较,MPTP组运动速率和运动距离明显降低,差异有统计学意义(P<0.01);与MPTP组比较,诺米芬辛组运动速率和运动距离明显升高,差异有统计学意义(P<0.01)。免疫荧光检测显示,与对照组比较,MPTP组DA损伤明显增加,诺米芬辛组DA损伤明显轻于MPTP组。各组CAT水平比较,差异无统计学意义(P>0.05)。与对照组比较,MPTP组铁、LPO和丙二醛水平明显升高,GSH、GPX4水平明显降低,差异有统计学意义(838.18±143.42 vs 478.53±112.58,P<0.05;1.71±0.11 vs 1.48±0.14,P<0.05;4.50±0.64 vs 4.23±0.13,P<0.05;38.93±1.72 vs 45.97±2.32,P<0.05;0.17±0.03 vs 0.39±0.04,P<0.05);与MPTP组比较,诺米芬辛组GSH、GPX4水平明显升高,铁、LPO水平明显降低,差异有统计学意义(40.79±1.02 vs 38.93±1.72,P<0.05;0.26±0.05 vs 0.17±0.03,P<0.05;326.75±110.95 vs 838.18±143.42,P<0.05;1.01±0.27 vs 1.71±0.11,P<0.05)。活性氧流式细胞检测结果显示,对照组、MPTP组及诺米芬辛组活性氧阳性细胞占比分别为直方图:31.6%、46.2%、31.3%,散点图:62.4%、73.0%、65.7%。结论 在MPTP诱导的斑马鱼基础上,PD斑马鱼存在铁死亡。从动物水平阐明铁沉积引起DA损伤与铁死亡脂质过氧化代谢机制有关。展开更多
做好法律文书的实体识别可极大地帮助推动“智慧司法”,但目前对法律文书的命名实体识别存在着公共数据集缺乏、低频生僻和长实体识别效果不好、句法信息捕捉不足等问题。因此,该文针对民事案件提出了实体定义方案,构建了民事案件法律...做好法律文书的实体识别可极大地帮助推动“智慧司法”,但目前对法律文书的命名实体识别存在着公共数据集缺乏、低频生僻和长实体识别效果不好、句法信息捕捉不足等问题。因此,该文针对民事案件提出了实体定义方案,构建了民事案件法律文书数据集,并且提出了GLYCE-ONLSTM-CRF(GOC)模型来识别法律文书的实体。该模型嵌入层基于BERT预训练模型并融合了汉字字形特征,再通过ONLSTM(Ordered Neuron Long Short Term Memory Networks)层学习句子的层级结构,最后通过条件随机场(CRF)算法输出结果。在构建的民事案件数据集上进行实验,测试集的F 1值提高了5.15%,证明了模型的优越性,为法律文书命名实体识别提供了新思路。展开更多
帕金森病(Parkinson’s disease,PD)是一种常见的神经退行性疾病,其主要病理特征为中脑黑质致密部(substantia nigra pars compacta,SNpc)多巴胺(dopamine,DA)能神经元的丢失和α-突触核蛋白(alpha-synuclein,α-syn)的病理性积累。神...帕金森病(Parkinson’s disease,PD)是一种常见的神经退行性疾病,其主要病理特征为中脑黑质致密部(substantia nigra pars compacta,SNpc)多巴胺(dopamine,DA)能神经元的丢失和α-突触核蛋白(alpha-synuclein,α-syn)的病理性积累。神经元自噬功能障碍在PD的发生和发展中起着关键作用。自噬是一种细胞自我降解和循环利用胞内组分的过程,通过清除异常蛋白或有缺陷的细胞器维持神经元的健康,并防止中枢神经系统内的细胞毒性损伤和神经元死亡。因而,促进神经元自噬被认为是一种潜在的PD治疗策略。运动疗法(如有氧运动、步态训练、平衡训练、抗阻训练和身心运动等)在PD全程管理中显示出积极的效益,其潜在机制可能是通过AMP活化的蛋白激酶(AMP-activated protein kinase,AMPK)抑制哺乳动物雷帕霉素靶蛋白(mammalian target of rapamycin,mTOR)活性,激活Unc-51样自噬激活激酶1启动自噬,同时通过PTEN诱导的假定激酶1(PTENinduced putative kinase 1,PINK1)/E3泛素蛋白连接酶Parkin(E3 ubiquitin-protein ligase Parkin,Parkin)信号通路清除受损线粒体,协同调控并增强神经元自噬功能,从而维持神经元内环境稳态,减少DA能神经元丢失,进而延缓PD相关行为功能障碍。本文从神经元自噬的角度,对AMPK/mTOR和PINK1/Parkin信号通路在PD神经退行性病变及PD运动防治中的作用与机制进行综述。展开更多
文摘Objective:To anatomically and phenotypically characterize the insular cortex(IC)-nucleus tractus soli-tari(NTS)neural pathway.Methods:Adult male Sprague-Dawley rats were divided into three experimental cohorts for neural circuit tracing.Anterograde labeling was achieved by injecting anterograde self-complementary adeno-associated viruses(scAAVs)into the IC.Retrograde tracing involved NTS injections of either retrograde scAAVs or FluoroGold(FG),combined with immunofluorescence histochemical staining to identify IC-originating projection neurons.For postsynaptic neurochemical phenotype characterization,IC was injected with AAV2/1-CaMKII-Cre,while a mixture of AAV2/9-Syn-DIO-mCherry and AAV2/9-VGAT1-EGFP was injected into the NTS.The rats were allowed to survive for one week following scAAVs or FG injection or four weeks after recombinase-dependent systems injection.Then the rats were sacrificed,and serial brain sections were prepared for immunofluorescence histochemical staining(brain section containing FG)and subsequent fluorescence/confocal microscopic analysis.Results:(1)Anterograde viral tracing re-vealed dense axonal terminals from the IC projecting to the medial subnucleus of the NTS,while retrograde tracing re-vealed that IC neurons projecting to the NTS were predominantly localized within the dysgranular layer;(2)IC-NTS projection neurons were exclusive glutamatergic(100%,n=3);(3)NTS neurons receiving IC inputs were mainly lo-calized in the medial subnucleus,and were predominantly GABAergic(79.8±3.2%,n=3).Conclusion:The pres-ent results indicate that a descending pathway from excitatory neurons of the IC terminates onto inhibitory neurons of the NTS,which might represent a potential neuromodulatory target for visceral pain disorders.
文摘目的 在动物水平探讨铁死亡脂质过氧化损伤调控通路与帕金森病(Parkinson's disease, PD)的发病机制。方法 建立PD斑马鱼动物模型,取受精后48 h斑马鱼胚胎为对照组(n=100),200μmol/L的1-甲基-4-苯基-1,2,3,6-四氢吡啶(1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine, MPTP)为MPTP组(n=100),200μmol/L的MPTP+1.5μg/ml诺米芬辛为诺米芬辛组(n=100)。对受精后5 d斑马鱼进行行为学分析(检测运动能力、运动速率及运动距离);免疫荧光检测斑马鱼脑内α突触核蛋白和酪氨酸羟化酶表达,评估多巴胺能神经元(dopaminergic neurons, DA)活性;检测铁、谷胱甘肽(glutathione, GSH)及脂质过氧化水平,包括过氧化氢酶(catalase, CAT)、谷胱甘肽过氧化物酶4(glutathione peroxidase 4,GPX4)、脂质过氧化物(lipid peroxide, LPO)、丙二醛、活性氧,验证铁沉积可能通过铁死亡的脂质过氧化代谢调控机制引起DA损伤。结果 与对照组比较,MPTP组运动速率和运动距离明显降低,差异有统计学意义(P<0.01);与MPTP组比较,诺米芬辛组运动速率和运动距离明显升高,差异有统计学意义(P<0.01)。免疫荧光检测显示,与对照组比较,MPTP组DA损伤明显增加,诺米芬辛组DA损伤明显轻于MPTP组。各组CAT水平比较,差异无统计学意义(P>0.05)。与对照组比较,MPTP组铁、LPO和丙二醛水平明显升高,GSH、GPX4水平明显降低,差异有统计学意义(838.18±143.42 vs 478.53±112.58,P<0.05;1.71±0.11 vs 1.48±0.14,P<0.05;4.50±0.64 vs 4.23±0.13,P<0.05;38.93±1.72 vs 45.97±2.32,P<0.05;0.17±0.03 vs 0.39±0.04,P<0.05);与MPTP组比较,诺米芬辛组GSH、GPX4水平明显升高,铁、LPO水平明显降低,差异有统计学意义(40.79±1.02 vs 38.93±1.72,P<0.05;0.26±0.05 vs 0.17±0.03,P<0.05;326.75±110.95 vs 838.18±143.42,P<0.05;1.01±0.27 vs 1.71±0.11,P<0.05)。活性氧流式细胞检测结果显示,对照组、MPTP组及诺米芬辛组活性氧阳性细胞占比分别为直方图:31.6%、46.2%、31.3%,散点图:62.4%、73.0%、65.7%。结论 在MPTP诱导的斑马鱼基础上,PD斑马鱼存在铁死亡。从动物水平阐明铁沉积引起DA损伤与铁死亡脂质过氧化代谢机制有关。
文摘做好法律文书的实体识别可极大地帮助推动“智慧司法”,但目前对法律文书的命名实体识别存在着公共数据集缺乏、低频生僻和长实体识别效果不好、句法信息捕捉不足等问题。因此,该文针对民事案件提出了实体定义方案,构建了民事案件法律文书数据集,并且提出了GLYCE-ONLSTM-CRF(GOC)模型来识别法律文书的实体。该模型嵌入层基于BERT预训练模型并融合了汉字字形特征,再通过ONLSTM(Ordered Neuron Long Short Term Memory Networks)层学习句子的层级结构,最后通过条件随机场(CRF)算法输出结果。在构建的民事案件数据集上进行实验,测试集的F 1值提高了5.15%,证明了模型的优越性,为法律文书命名实体识别提供了新思路。
文摘帕金森病(Parkinson’s disease,PD)是一种常见的神经退行性疾病,其主要病理特征为中脑黑质致密部(substantia nigra pars compacta,SNpc)多巴胺(dopamine,DA)能神经元的丢失和α-突触核蛋白(alpha-synuclein,α-syn)的病理性积累。神经元自噬功能障碍在PD的发生和发展中起着关键作用。自噬是一种细胞自我降解和循环利用胞内组分的过程,通过清除异常蛋白或有缺陷的细胞器维持神经元的健康,并防止中枢神经系统内的细胞毒性损伤和神经元死亡。因而,促进神经元自噬被认为是一种潜在的PD治疗策略。运动疗法(如有氧运动、步态训练、平衡训练、抗阻训练和身心运动等)在PD全程管理中显示出积极的效益,其潜在机制可能是通过AMP活化的蛋白激酶(AMP-activated protein kinase,AMPK)抑制哺乳动物雷帕霉素靶蛋白(mammalian target of rapamycin,mTOR)活性,激活Unc-51样自噬激活激酶1启动自噬,同时通过PTEN诱导的假定激酶1(PTENinduced putative kinase 1,PINK1)/E3泛素蛋白连接酶Parkin(E3 ubiquitin-protein ligase Parkin,Parkin)信号通路清除受损线粒体,协同调控并增强神经元自噬功能,从而维持神经元内环境稳态,减少DA能神经元丢失,进而延缓PD相关行为功能障碍。本文从神经元自噬的角度,对AMPK/mTOR和PINK1/Parkin信号通路在PD神经退行性病变及PD运动防治中的作用与机制进行综述。
文摘目的探讨急性脑梗死(acute cerebral infarction,ACI)患者脑电图、血清胰岛素生长因子1(insulin-like growth factor 1,IGF-1)、神经元特异性烯醇化酶(neuron-specific enolase,NSE)与病灶体积及美国国立卫生研究院卒中量表(National Institute of Health stroke scale,NIHSS)评分的关系。方法选择2021年8月至2022年12月在南京市溧水区人民医院神经内科首次确诊的ACI患者218例,根据病灶体积分为大体积组63例、中体积组103例和小体积组52例。检测患者脑电图(δ+θ)与(α+β)功率比[(δ+θ)/(α+β)ratio,DTABR]、大脑对称指数(brainspine interface,BSI)、血清IGF-1和NSE水平,观察上述指标与MRI检查脑梗死病灶体积、NIHSS评分、阿替普酶溶栓后2周、4周时NIHSS评分的相关性。结果中体积组和大体积组IGF-1水平明显低于小体积组,NSE、DTABR、BSI明显高于小体积组(P<0.05);大体积组IGF-1水平明显低于中体积组,NSE、DTABR、BSI明显高于中体积组(P<0.05)。DTABR、BSI、血清NSE与病灶体积(r=0.563,P=0.000;r=0.318,P=0.038;r=0.673,P=0.000)和治疗前NIHSS评分(r=0.499,P=0.000;r=0.362,P=0.013;r=0.750,P=0.001)呈显著正相关。血清IGF-1水平与病灶体积(r=-0.572,P=0.000)和治疗前NIHSS评分(r=-0.438,P=0.001)呈显著负相关。DTABR、BSI、血清NSE、病灶体积均与溶栓后2、4周NIHSS评分呈正相关,IGF-1与溶栓后2、4周NIHSS评分呈负相关(P<0.05,P<0.01)。结论ACI患者脑电图、IGF-1和NSE与病灶体积和溶栓后NIHSS评分显著相关。
