目的探讨NOTCH3基因第5外显子C260S位点突变导致的伴有皮层下梗死和白质脑病的常染色体显性遗传性脑动脉病(cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy,CADASIL)家系的临床和影像学...目的探讨NOTCH3基因第5外显子C260S位点突变导致的伴有皮层下梗死和白质脑病的常染色体显性遗传性脑动脉病(cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy,CADASIL)家系的临床和影像学特征。方法选取2021年12月首都医科大学附属北京同仁医院来自同一家庭的CADASIL患者,对所有患者进行NOTCH3基因测序,回顾性分析患者的临床表现和头颅影像学特征。复习既往文献报道的导致同一位置氨基酸改变的其他突变类型的临床及影像学特征。结果4名家庭成员中,包括先证者(46岁,女)及其两个姐姐(分别为48岁和50岁)和女儿(18岁)。先证者及其父亲、两个姐姐都有偏头痛病史,其中大姐有记忆力减退;先证者患有脑梗死及伴有视觉先兆的偏头痛;先证者女儿体健;先证者父亲因脑梗死去世。4名家庭成员均存在C260S位点的NOTCH3基因突变。既往文献无此位点突变的报道,先证者头颅MRI示右侧脑桥亚急性梗死,颞叶、脑室周围及脑干异常高信号改变,其大姐脑桥可见腔隙性梗死灶。结论NOTCH3基因第5外显子c.778T>A(p.C260S)的罕见突变导致的CADASIL发病时间早,早期会出现认知障碍。合并偏头痛的脑干梗死患者,需警惕CADASIL的可能。展开更多
The applicability of sequence stratigraphic models to continental fluvial successions has long been topic for debate. To improve our understanding of how fluvial architectures record responses to changes in the ratio ...The applicability of sequence stratigraphic models to continental fluvial successions has long been topic for debate. To improve our understanding of how fluvial architectures record responses to changes in the ratio between accommodation rate and sediment-supply rate (A/S), two case studies are analyzed, including a densely drilled subsurface fluvial reservoir imaged with a seismic cube, and an outcropping fluvial succession. The subsurface dataset provides a larger, three-dimensional perspective, whereas the outcrop dataset enables observation at higher resolution. On the basis of both datasets, channel-body density, channel-body stacking patterns and their formative river types are interpreted at different scales, and how these may reflect responses to A/S change (the rate of accommodation creation relative to the rate of sediment supply) are discussed. The results indicate that (i) channel-body stacking patterns undergo four evolutionary stages along with the A/S increase, i.e., multi-story, mixed multi- and two-story, two-story, and isolated patterns;(ii) channel-body density decreases along with the channel-body stacking patterns varying from multi-story to isolated;(iii) formative rivers types are interpreted as evolving from braided planforms to braided-meandering planforms and then to meandering ones, with the increase of A/S.展开更多
目的:探究单纯疱疹病毒(HSV)感染后脑脊液(CSF)中S100B、Cys-C、MMP-9水平对自身免疫性脑炎(AE)的预测价值。方法:选取2016年1月至2021年3月河北中石油中心医院收治的200例HSV感染患者为研究对象,根据是否继发AE分为研究组(继发AE,35例...目的:探究单纯疱疹病毒(HSV)感染后脑脊液(CSF)中S100B、Cys-C、MMP-9水平对自身免疫性脑炎(AE)的预测价值。方法:选取2016年1月至2021年3月河北中石油中心医院收治的200例HSV感染患者为研究对象,根据是否继发AE分为研究组(继发AE,35例)和对照组(未继发AE,165例)。多因素Logistic回归分析HSV感染患者继发AE的独立影响因素。Spearman法分析脑脊液中Cys-C、MMP-9与S100B水平的相关性。受试者工作特征(ROC)曲线分析S100B、Cys-C、MMP-9对AE的预测价值。构建风险预测模型并进行评价。结果:多因素Logistic回归分析显示,MRI异常、脑脊液S100B、MMP-9升高、EEG异常是HSV感染患者继发AE的独立危险因素,脑脊液Cys-C是其保护因素(P<0.05)。Spearman分析显示,HSV感染患者Cys-C浓度与S100B水平呈负相关(r=-0.83,P<0.05),MMP-9浓度与S100B水平呈正相关(r=0.88,P<0.05)。构建的联合预测因子pre1诊断HSV患者继发AE的AUC明显大于S100B、Cys-C、MMP-9单独预测的AUC(0.876 vs 0.827、0.787、0.750)。构建的风险预测模型具有良好的区分度和一致性。结论:脑脊液中S100B、Cys-C、MMP-9水平均可对HSV感染患者诱发AE的可能性进行有效预测,且三项指标联合预测价值最大,其次是S100B蛋白、Cys-C、MMP-9。展开更多
Netrin-1 and its receptors play crucial roles in inducing axonal growth and neuronal migration during neuronal development.Their profound impacts then extend into adulthood to encompass the maintenance of neuronal sur...Netrin-1 and its receptors play crucial roles in inducing axonal growth and neuronal migration during neuronal development.Their profound impacts then extend into adulthood to encompass the maintenance of neuronal survival and synaptic function.Increasing amounts of evidence highlight several key points:(1)Diminished Netrin-1 levels exacerbate pathological progression in animal models of Alzheimer’s disease and Parkinson’s disease,and potentially,similar alterations occur in humans.(2)Genetic mutations of Netrin-1 receptors increase an individuals’susceptibility to neurodegenerative disorders.(3)Therapeutic approaches targeting Netrin-1 and its receptors offer the benefits of enhancing memory and motor function.(4)Netrin-1 and its receptors show genetic and epigenetic alterations in a variety of cancers.These findings provide compelling evidence that Netrin-1 and its receptors are crucial targets in neurodegenerative diseases.Through a comprehensive review of Netrin-1 signaling pathways,our objective is to uncover potential therapeutic avenues for neurodegenerative disorders.展开更多
文摘目的探讨NOTCH3基因第5外显子C260S位点突变导致的伴有皮层下梗死和白质脑病的常染色体显性遗传性脑动脉病(cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy,CADASIL)家系的临床和影像学特征。方法选取2021年12月首都医科大学附属北京同仁医院来自同一家庭的CADASIL患者,对所有患者进行NOTCH3基因测序,回顾性分析患者的临床表现和头颅影像学特征。复习既往文献报道的导致同一位置氨基酸改变的其他突变类型的临床及影像学特征。结果4名家庭成员中,包括先证者(46岁,女)及其两个姐姐(分别为48岁和50岁)和女儿(18岁)。先证者及其父亲、两个姐姐都有偏头痛病史,其中大姐有记忆力减退;先证者患有脑梗死及伴有视觉先兆的偏头痛;先证者女儿体健;先证者父亲因脑梗死去世。4名家庭成员均存在C260S位点的NOTCH3基因突变。既往文献无此位点突变的报道,先证者头颅MRI示右侧脑桥亚急性梗死,颞叶、脑室周围及脑干异常高信号改变,其大姐脑桥可见腔隙性梗死灶。结论NOTCH3基因第5外显子c.778T>A(p.C260S)的罕见突变导致的CADASIL发病时间早,早期会出现认知障碍。合并偏头痛的脑干梗死患者,需警惕CADASIL的可能。
基金This research was financially supported by the National Natural Science Foundation Project of China(No.42202109,42272186)the China Postdoctoral Science Foundation1(BX20220351,2022M713458)+2 种基金the Research Institute of Petroleum Exploration and Development,China(2021DJ1101)the Cooperation Project of the PetroChina Corporation(ZLZX2020-02)Anonymous reviewers are thanked for their constructive comments,which helped improve the paper.Additionally,associate professor Luca Colombera is thanked for his suggestions and language polishing work.
文摘The applicability of sequence stratigraphic models to continental fluvial successions has long been topic for debate. To improve our understanding of how fluvial architectures record responses to changes in the ratio between accommodation rate and sediment-supply rate (A/S), two case studies are analyzed, including a densely drilled subsurface fluvial reservoir imaged with a seismic cube, and an outcropping fluvial succession. The subsurface dataset provides a larger, three-dimensional perspective, whereas the outcrop dataset enables observation at higher resolution. On the basis of both datasets, channel-body density, channel-body stacking patterns and their formative river types are interpreted at different scales, and how these may reflect responses to A/S change (the rate of accommodation creation relative to the rate of sediment supply) are discussed. The results indicate that (i) channel-body stacking patterns undergo four evolutionary stages along with the A/S increase, i.e., multi-story, mixed multi- and two-story, two-story, and isolated patterns;(ii) channel-body density decreases along with the channel-body stacking patterns varying from multi-story to isolated;(iii) formative rivers types are interpreted as evolving from braided planforms to braided-meandering planforms and then to meandering ones, with the increase of A/S.
文摘目的:探究单纯疱疹病毒(HSV)感染后脑脊液(CSF)中S100B、Cys-C、MMP-9水平对自身免疫性脑炎(AE)的预测价值。方法:选取2016年1月至2021年3月河北中石油中心医院收治的200例HSV感染患者为研究对象,根据是否继发AE分为研究组(继发AE,35例)和对照组(未继发AE,165例)。多因素Logistic回归分析HSV感染患者继发AE的独立影响因素。Spearman法分析脑脊液中Cys-C、MMP-9与S100B水平的相关性。受试者工作特征(ROC)曲线分析S100B、Cys-C、MMP-9对AE的预测价值。构建风险预测模型并进行评价。结果:多因素Logistic回归分析显示,MRI异常、脑脊液S100B、MMP-9升高、EEG异常是HSV感染患者继发AE的独立危险因素,脑脊液Cys-C是其保护因素(P<0.05)。Spearman分析显示,HSV感染患者Cys-C浓度与S100B水平呈负相关(r=-0.83,P<0.05),MMP-9浓度与S100B水平呈正相关(r=0.88,P<0.05)。构建的联合预测因子pre1诊断HSV患者继发AE的AUC明显大于S100B、Cys-C、MMP-9单独预测的AUC(0.876 vs 0.827、0.787、0.750)。构建的风险预测模型具有良好的区分度和一致性。结论:脑脊液中S100B、Cys-C、MMP-9水平均可对HSV感染患者诱发AE的可能性进行有效预测,且三项指标联合预测价值最大,其次是S100B蛋白、Cys-C、MMP-9。
基金supported by the National Natural Science Foundation of China(Youth Science Fund Project),No.81901292(to GC)the National Key Research and Development Program of China,No.2021YFC2502100(to GC)the National Natural Science Foundation of China,No.82071183(to ZZ).
文摘Netrin-1 and its receptors play crucial roles in inducing axonal growth and neuronal migration during neuronal development.Their profound impacts then extend into adulthood to encompass the maintenance of neuronal survival and synaptic function.Increasing amounts of evidence highlight several key points:(1)Diminished Netrin-1 levels exacerbate pathological progression in animal models of Alzheimer’s disease and Parkinson’s disease,and potentially,similar alterations occur in humans.(2)Genetic mutations of Netrin-1 receptors increase an individuals’susceptibility to neurodegenerative disorders.(3)Therapeutic approaches targeting Netrin-1 and its receptors offer the benefits of enhancing memory and motor function.(4)Netrin-1 and its receptors show genetic and epigenetic alterations in a variety of cancers.These findings provide compelling evidence that Netrin-1 and its receptors are crucial targets in neurodegenerative diseases.Through a comprehensive review of Netrin-1 signaling pathways,our objective is to uncover potential therapeutic avenues for neurodegenerative disorders.
