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Serotonin 1A receptor inhibits the status epilepticus induced by lithium-pilocarpine in rats

Neuroscience Bulletin 2014年第3期30卷 401-408页

作者： Yi Yang Yi Guo yifang kuang Shan Wang Yan Jiang Yao Ding Shuang Wang Meiping Ding Department of Neurology Second Affiliated Hospital School of Medicine Zhejiang University

Status epilepticus （SE） is a life-threatening neurological emergency associated with a high mortality rate. The serotonin 1A （5-HTIA） receptor is a possible target for the treatment of SE, but its role in animal models and the precise area of brain involved remain controversial. The hippocampus is a candidate site due to its key role in the development of SE and the existence of a high density of 5-HT1A receptors. Therefore, we investigated the effects of subcutaneous and intrahippocampal activation of 5-HT1A receptors in lithium-pilocarpine-induced SE, and tested whether the hippocampus is a true effector site. We developed SE in male Sprague-Dawley rats by giving lithium chloride （LiCI; 3 meq/kg, i.p.） 22-24 h prior to pilocarpine （25 mg/kg, i.p.）, and found that 8-OH-DPAT, a 5-HT1A receptor agonist administered subcutaneously （s.c.） at 0.5 or 1.0 mg/kg 1 h before pilocarpine injection increased the latency to the first epileptiform spikes, the electrographic SE, and the behavioral generalized seizures （GS）, while reducing the total EEG seizure time （P 〈0.01）. The duration of GS was shortened only by 1.0 mg/kg 8-OH-DPAT s.c. （P 〈0.05）. All these effects were inhibited by combined administration of WAY-100635 （1.0 mg/kg, s.c.）（P 〈0.05）, an antagonist of the 5-HT1A receptor, but WAY-100635 alone and low doses of 8-OH- DPAT （0.01 and 0.1 mg/kg） did not alter seizure activity. Furthermore, intrahippocampal 8-OH-DPAT only shortened the GS duration （P 〈0.05）. These findings imply that the 5-HT1A receptor is a promising therapeutic target against the generation and propagation of SE, and hippocampal receptors are involved in reducing the seizure severity.

关键词： status epilepticus serotonin 1A receptor 8-OH-DPAT WAY-100635 lithium pilocarpine

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Desipramine reverses remote memory deficits by activating calmodulin- CaMKII pathway in a UTX knockout mouse model of Kabuki syndrome

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General Psychiatry 2024年第5期37卷 522-531页

作者： Lei Chen Yuting Li Minggang Liu Zhaohui Lan Xu Zhang Xiujuan Yang Qian Zhao Shuai Wang Longyong Xu Ying Zhou yifang kuang Tatsuo Suzuki Katsuhiko Tabuchi Eiki Takahashi Miou Zhou Charlie Degui Chen Tianle Xu Weidong Li Bio-X Institutes Key Laboratory for the Genetics of Development and Neuropsychiatric Disorders(Ministry of Education)Brain Health and Brain Technology Center at Global Institute of Future TechnologyInstitute of Psychology and Behavioral ScienceShanghai Jiao Tong UniversityShanghaiChina Department of Anatomy and Physiology Shanghai Jiao Tong University School of MedicineShanghaiChina institute of Mental Health and Drug Discovery Oujiang LaboratoryWenzhouZhejiangChina Shanghai Institutes for Biological Sciences Chinese Academy of SciencesShanghaiChina Shinshu University School of Medicine NaganoJapan western University of Health Sciences PomonaCaliforniaUSA WLA Laboratories World Laureates AssociationShanghaiChina

Background Kabukisyndrome(KS)is arare developmental disorder characterised by multiple congenital anomalies and intellectual ***(ubiquitously transcribed tetratricopeptide repeat,X chromosome),which encodes a histone demethylase,is one of the two major pathogenic risk genes for *** intellectual disability is a key phenotype of KS,the role of UTX in cognitive function remains ***,no targeted therapies are available for *** This study aimed to investigate how UTX regulates cognition,to explore the mechanisms underlying UTX dysfunction and to identify potential molecular targets for *** WegeneratedUTXconditional knockoutmice and found that UTX deletion downregulated calmodulin transcription by disrupting H3K27me3(trimethylated histone H3 at lysine 27)*** UTX-knockout mice showeddecreased phosphorylation of calcium/calmodulin-dependent protein kinase I,impaired long-term potentiation and deficit in remote contextual fear *** effects were reversed by an Food and Drug Administration-approved drug *** Our results reveal an epigenetic mechanism underlying the important role of UTX in synaptic plasticity and cognitive function,and suggest that desipramine could be a potential treatment for KS.

关键词： impaired reversed UTX

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胎儿营养不良与小于胎龄儿的区别及临床意义

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中华围产医学杂志 1998年第2期1卷 96-98页

作者：杨丽丽匡谊芳万芳萍武汉市第四医院儿科 430033

目的探讨胎儿营养不良(FM)与小于胎龄儿(SGA)之间的差异及临床意义。方法对548例单胎足月儿进行临床营养状态评估(CANS),从9个方面迅速地对新生儿进行体表视查评分,总分≤24为FM。结果 40例SGA中21例(占52.5%)为FM,另19例(47.5%)评分>24... 详细信息

目的探讨胎儿营养不良(FM)与小于胎龄儿(SGA)之间的差异及临床意义。方法对548例单胎足月儿进行临床营养状态评估(CANS),从9个方面迅速地对新生儿进行体表视查评分,总分≤24为FM。结果 40例SGA中21例(占52.5%)为FM,另19例(47.5%)评分>24;而508例适于胎龄儿中也有13例(占2.8%)为FM。结论 SGA与FM并非同义名称,CANS评分可迅速识别FM,对高危孕母应于孕中期作生化及超声波检测,以便及时发现FM,及时进行营养疗法干预,从而防止FM儿出生。

关键词：婴儿新生营养障碍小于胎龄营养状况

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Gene mutations and clinical phenotypes in Chinese children with Blau syndrome

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Science China(Life Sciences) 2017年第7期60卷 758-762页

作者： Caifeng Li Junmei Zhang Shipeng Li Tongxin Han Weiying kuang yifang Zhou Jianghong Deng Xiaohua Tan Department of Rheumatology and Immunology Beijing Children's Hospital Capital Medical University National Center for Children's Health Beijing 100045 China

The mutations of CARD15 gene and clinical features of Chinese patients with Blau syndrome were analyzed. We identified10 missense mutations, out of which five were new: R334 L, E383 D, R471 C, C495 R and D512 F. The rest of them, R334 W,R334Q, G481 D, M513 T and R587 C, have been reported previously. Among all the mutations, R334 W, R334 Q and C495 R had the highest frequency. Blau syndrome was found at early age after birth. It began with lepidic rash and symmetric polyarthritis and was phenotypically characterized by typical rash, arthritis, iridocyclitis and arteritis. Cardiac involvement was also found in Blau syndrome. In addition to nerve deafness, renal involvement, osteochondroma and central nervous system involvement were also found in our patients. Therefore, Chinese children with Blau syndrome have unique gene mutations and complicated clinical phenotypes. Pathologic examination and CARD15 mutation testing should be considered for diagnosis as early as possible for suspected patients.

关键词： Blau syndrome genetic mutation clinical phenotype

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Gene mutations and clinical phenotypes in 15 Chinese children with cryopyrin-associated periodic syndrome(CAPS)

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Science China(Life Sciences) 2017年第12期60卷 1436-1444页

作者： Caifeng Li Xiaohua Tan Junmei Zhang Shipeng Li Wenxiu Mo Tongxin Han Weiying kuang yifang Zhou Jianghong Deng Department of Rheumatology and Immunology Beijing Children's HospitalCapital Medical UniversityNational Center for Children"s HealthBeijing 100045China

The aim of our study is to explore the features of clinical manifestations and genetic mutations in Chinese CAPS patients. Fifteen confirmed patients with CAPS were enrolled. The onset time ranges from 2 days after birth to 6 years and 1 month. Recurrent urticaria rash(93.3%) with fever(100%) were two dominant characteristics of these patients that were presented as either acute or chronic process. Systemic involvements were found in all patients except for one with only rash and fever. The top three symptoms were fever(100%), rash(93.3%) and myalgia(76%). Other clinical manifestations include arthritis(11 cases), lung involvement(seven cases), optical dysfunction(seven cases), nerve deafness(six cases), nervous system involvement(five cases), hepatomegaly, splenomegaly and lymphadenectasis(five cases). Also, four patients had heart involvement and one patient suffered kidney involvement. The laboratory inflammation index such as leukocyte counts, platelet counts, erythrocyte sedimentation rate(ESR), C-reactive protein(CRP), serum amyloid A(SAA) and fibrinogen(FIB) increased significantly at initial stage, but decreased after therapy. As for gene mutation detection, Twelve out of 15 patients were confirmed with mutation in NLRP3, including 11 mutant site: c1789 A>G, c.1703 T>A, c.913 G>A, c.1710 G>C, c.1057 G >T, c.2335 C>T, c.932 T>C,c.296 G>C, c.663 C>T, t.1702 T>A, 299 G>A. Mutation sites c.1703 T>A, c.2335 C>T, c.296 G>C, c.663 C>T, and 299 G>A were newly identified. The association between gene mutation and clinical manifestation shows that D305 N was highly associated with severe organs involvements, and therefore, the time of therapy and regimen were critical for the prognosis of disease. As the largest cohort study of Chinese CAPS patients, we confirmed that all patients presented typical clinical manifestations, identified five new mutation sites on NLRP3 and analyzed the correlation between the genotypes and phenotypes. We also raise concerns for one case

关键词： CAPS genetic mutation clinical phenotTpe NLRP3

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Targeting lactate dehydrogenase A (LDHA) exerts antileukemic effects on T-cell acute lymphoblastic leukemia

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Cancer Communications 2020年第10期40卷 501-517页

作者： Haizhi Yu Yafei Yin yifang Yi Zhao Cheng Wenyong kuang Ruijuan Li Haiying Zhong Yajuan Cui Lingli Yuan Fanjie Gong Zhihua Wang Heng Li Hongling Peng Guangsen Zhang Department of Hematology the Second Xiangya HospitalCentral South UniversityChangshaHunan 410011P.R.China Institute of Hematology Central South UniversityChangshaHunan 410011P.R.China Department of Respiratory and Critical Medicine NHC Key Laboratory of Pulmonary Immune-related DiseasesPeople’s Hospital of Guizhou UniversityGuizhou Provincial People’s HospitalGuiyangGuizhou 550002P.R.China Department of Hematology Xiangtan Central HospitalXiangtanHunan 411100P.R.China Department of Hematology Hunan Provincial People’s Hospitalthe First Affiliated Hospital of Hunan Normal UniversityChangshaHunan 410005P.R.China Department of Hematology Hunan Children’s HospitalChangshaHunan 410005P.R.China Hunan Key Laboratory of Tumor Models and Individualized Medicine ChangshaHunan 410011P.R.China

Background:T-cell acute lymphoblastic leukemia(T-ALL)is an uncommon and aggressive subtype of acute lymphoblastic leukemia(ALL).In the serum of T-ALL patients,the activity of lactate dehydrogenase A(LDHA)is *** proposed that targeting LDHA may be a potential strategy to improve T-ALL *** current study was conducted to investigate the antileukemic effect of LDHA gene-targeting treatment on T-ALL and the underlying molecular ***:Primary T-ALL cell lines Jurkat and DU528 were treated with the LDH inhibitor ***,colony formation,apoptosis,and cell cycle assays were performed to investigate the effects of oxamate on T-ALL *** real-time PCR(qPCR)and Western blotting analyses were applied to determine the related signaling pathways.A mitochondrial reactive oxygen species(ROS)assay was performed to evaluate ROS production after T-ALL cells were treated with oxamate.A T-ALL transgenic zebrafish model with LDHA gene knockdown was established using CRISPR/Cas9 gene-editing technology,and then TUNEL,Western blotting,and T-ALL tumor progression analyses were conducted to investigate the effects of LDHA gene knockdown on T-ALL transgenic ***:Oxamate significantly inhibited proliferation and induced apoptosis of Jurkat and DU528 *** also arrested Jurkat and DU528 cells in G0/G1 phase and stimulated ROS production(all P<0.001).Blocking LDHA significantly decreased the gene and protein expression of c-Myc,as well as the levels of phosphorylated serine/threonine kinase(AKT)and glycogen synthase kinase 3 beta(GSK-3β)in the phosphatidylinositol 3′-kinase(PI3K)signaling *** gene knockdown delayed disease progression and down-regulated c-Myc mRNA and protein expression in T-ALL transgenic ***:Targeting LDHA exerted an antileukemic effect on T-ALL,representing a potential strategy for T-ALL treatment.

关键词： CRISPR/Cas9 gene-editing LDHA oxamate T-cell lymphoblastic leukemia transgenic zebrafish model

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神经胶质成熟因子β的研究进展

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中华病理学杂志 2021年第8期50卷 964-968页

作者：匡晓燕平轶芳陆军军医大学(第三军医大学)西南医院病理学研究所西南癌症中心重庆400038

神经胶质成熟因子(glia maturation factor,GMF)β主要表达于神经胶质细胞和某些神经元亚群,调控胶质细胞分化并促进神经元的生长和再生,因此,最初被认为是一种优势表达于脑的神经生长/分化因子。近年发现,该蛋白也表达于神经系统外的组... 详细信息

神经胶质成熟因子(glia maturation factor,GMF)β主要表达于神经胶质细胞和某些神经元亚群,调控胶质细胞分化并促进神经元的生长和再生,因此,最初被认为是一种优势表达于脑的神经生长/分化因子。近年发现,该蛋白也表达于神经系统外的组织,参与调节细胞骨架重组、免疫和氧化应激反应,与某些炎性疾病和肿瘤相关。目前认为GMF-β是一种适应性调节蛋白,其最终功能效应受组织微环境的影响。该文就GMF-β的研究进展进行综述。

关键词：炎性疾病神经胶质分化因子氧化应激反应功能效应神经元肿瘤相关适应性调节

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秦山核电站运行前周围环境放射性调查和居民所...

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中华放射医学与防护杂志 1992年第4期12卷 253-257页

作者：陈国佩陆尊榕浙江省卫生防疫站，杭州 310009 海盐县卫生防疫站

本文调查了1983～1988年秦山核电站周围5km、20km、80km范围内天然辐射外照射水平，20km范围内的土壤、食品和水中总 β、 90Sr、 137Cs活度。估算了当地居民所受的外照射剂量和因食入 90Sr、 137Cs造成的内剂量。... 详细信息

本文调查了1983～1988年秦山核电站周围5km、20km、80km范围内天然辐射外照射水平，20km范围内的土壤、食品和水中总 β、 90Sr、 137Cs活度。估算了当地居民所受的外照射剂量和因食入 90Sr、 137Cs造成的内剂量。结果表明：5km、20km和80km的天然辐射外照射剂量相近，其人均年有效剂量当量1.0mSv，由食品所致居民 90Sr和 137Cs的年有效剂量当量分别为0.62μSv·a -1和0.19μSv·a -1。其结果与浙江省全省环境调查结果基本一致。

关键词：剂量当量放射性环境

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一种柱状矢量偏振光的检测与评价方法

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光学学报 2014年第6期34卷 113-117页

作者：修鹏江芸珊王轶凡匡翠方李帅刘旭浙江大学光电系、现代光学仪器国家重点实验室浙江杭州310027

针对非均匀复杂偏振光束难以用一种偏振状态描述的现象,提出了一种点对点的偏振光检测方法,该方法能够同时检测光束横向切面内所有点的偏振态,为非均匀偏振光描述提供足够的信息,解决了柱状矢量偏振光光束的质量检测问题。运用这种方法... 详细信息

针对非均匀复杂偏振光束难以用一种偏振状态描述的现象,提出了一种点对点的偏振光检测方法,该方法能够同时检测光束横向切面内所有点的偏振态,为非均匀偏振光描述提供足够的信息,解决了柱状矢量偏振光光束的质量检测问题。运用这种方法,对已知偏振光束进行验证检验取得了良好的效果,证明了该方法可以作为一种可靠、稳定的方法用对柱状矢量偏振光检测与评价。另外,一些描述柱状矢量偏振光均匀性的参数被重新定义,为柱状偏振光的质量描述提供了量化指标。

关键词：物理光学光电检测柱状矢量偏振光检测径向偏振切向偏振

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基于GPS数据的震前电离层异常分析

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测绘通报 2015年第4期 1-4页

作者：马一方匡翠林周晓慧武汉大学卫星导航定位技术研究中心湖北武汉430079 中南大学地球科学与信息物理学院湖南长沙410083 武汉大学测绘学院湖北武汉430079

首先利用日本及周边区域IGS站提供的GPS观测数据,计算得到了测站上空垂直总电子含量VTEC的时间序列。采用滑动平均法与非滑动平均法两种统计学方法针对日本境内某震例进行了震前VTEC值异常分析,数值结果表明地震震前出现了电离层异常现... 详细信息

首先利用日本及周边区域IGS站提供的GPS观测数据,计算得到了测站上空垂直总电子含量VTEC的时间序列。采用滑动平均法与非滑动平均法两种统计学方法针对日本境内某震例进行了震前VTEC值异常分析,数值结果表明地震震前出现了电离层异常现象。此外,为了探讨异常情况与地震的相关性,进一步分析了电离层异常的全球空间分布。最后,通过对比两种异常检验方法的分析结果可知,两种方法分析结果的总体趋势一致,验证了本文结果的可靠性。

关键词：地震垂直方向总电子含量(VTEC) 电离层异常滑动平均法非滑动平均法

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