Tau Accumulation via Reduced Autophagy Mediates GGGGCC Repeat Expansion-Induced Neurodegeneration in Drosophila Model of ALS

Expansions of trinucleotide or hexanucleotide repeats lead to several neurodegenerative disorders, including Huntington disease [caused by expanded CAG repeats (CAGr) in the HTT gene], and amyotrophic lateral sclerosis [ALS, possibly caused by expanded GGGGCC repeats (G4C2r) in the C9ORF72 gene], of which the molecular mechanisms remain unclear. Here, we demonstrated that lowering the Drosophila homologue of tau protein (dtau) significantly rescued in vivo neurodegeneration, motor performance impairments, and the shortened life-span in Drosophila expressing expanded CAGr or expanded G4C2r. Expression of human tau (htau4R) restored the disease-related phenotypes that had been mitigated by the loss of dtau, suggesting an evolutionarily-conserved role of tau in neurodegeneration. We further revealed that G4C2r expression increased tau accumulation by inhibiting autophagosome–lysosome fusion, possibly due to lowering the level of BAG3, a regulator of autophagy and tau. Taken together, our results reveal a novel mechanism by which expanded G4C2r causes neurodegeneration via an evolutionarily-conserved mechanism. Our findings provide novel autophagy-related mechanistic insights into C9ORF72-ALS and possible entry points to disease treatment.Electronic supplementary materialThe online version of this article (10.1007/s12264-020-00518-2) contains supplementary material, which is available to authorized users.     

肿瘤患者代谢综合征及其组分异常的患病现况研究

2017年12月至2018年12月,在天津医科大学总医院健康管理中心定期健康体检的3 509名研究对象中,曾罹患肿瘤、罹患慢病和健康对照三组分别有399、1 555、1 555名。年龄为(55.87±11.98)岁,男性占31.38%。慢病组MS患病率(42.44%)高于曾罹患肿瘤组(34.59%)和健康对照组(18.65%)( P<0.001)。与健康对照组相比,曾罹患肿瘤组和慢病组MS患病风险 OR(95% CI)值分别为2.13(1.61~2.83)和2.85(2.23~3.66);曾罹患乳腺癌和甲状腺癌MS患病风险 OR(95% CI)值分别为3.56(2.04~6.21)和2.77(1.46~5.25)。     

基于证候要素的中风辨证论治

中风病是临床的常见病、多发病。本病病因较多,病情变化迅速,证型繁杂,不同的文献中证候分类差异较大。证候分类的繁杂给临床工作者治疗中风病带来极大不便。本文对以证候要素(内风、内火、痰湿、瘀血、气虚、阴虚)为切入点论治中风病的理论进行探讨,并举例论证其临床疗效。     

三级公立医院行政总值班管理现状分析与研究*

探索一套符合现代化医院的行政总值班管理体系，确保医院管理工作安全、稳定运行。分析国内外医院总值班现状和问题，运用系统性、科学性、规范性等综合干预措施，进一步提高值班人员责任意识、分析问题和解决问题能力等综合管理能力，使总值班管理从粗放式向精细化转变，实现目标标准化、过程规范化、结果同质化的服务格局。