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Prediction of treatment response to antipsychotic drugs for precision medicine approach to schizophrenia:randomized trials and multiomics analysis

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Military Medical Research 2024年第1期11卷 19-33页

作者： Liang-Kun Guo Yi Su Yu-Ya-Nan Zhang Hao Yu Zhe Lu Wen-Qiang Li Yong-Feng Yang Xiao Xiao Hao Yan Tian-Lan Lu jun Li Yun-Dan liao Zhe-Wei Kang Li-Fang Wang Yue Li Ming Li Bing Liu Hai-Liang Huang Lu-xian Lv Yin Yao Yun-Long Tan Gerome Breen Ian Everall Hong-Xing Wang Zhuo Huang Dai Zhang Wei-Hua Yue Institute of Mental Health Peking University Sixth HospitalBeijing 100191China National Clinical Research Center for Mental Disorders Peking University Sixth HospitalBeijing 100191China NHC Key Laboratory of Mental Health and Research Unit of Diagnosis and Treatment of Mood Cognitive Disorder(2018RU006) Chinese Academy of Medical SciencesBeijing 100191China Peking University Huilongguan Clinical Medical School Beijing Huilongguan HospitalBeijing 100096China Department of Psychiatry Jining Medical UniversityJining 272067ShandongChina Henan Key Lab of Biological Psychiatry the Second Affiliated Hospital of Xinxiang Medical UniversityXinxiang 435001HenanChina Key Laboratory of Animal Models and Human Disease Mechanisms of the Chinese Academy of Sciences and Yunnan Province Kunming Institute of ZoologyChinese Academy of SciencesKunming 650223China Institute of Psychiatry Psychology and NeuroscienceKing’s College LondonLondon WC2R 2LSUK State Key Laboratory of Cognitive Neuroscience and Learning Beijing Normal UniversityBeijing 100875China Analytic and Translational Genetics Unit Massachusetts General HospitalBostonMA 02114USA Stanley Center for Psychiatric Research the Broad Institute of MIT and HarvardCambridgeMA 02141USA Department of Medicine Harvard Medical SchoolBostonMA 02115USA Department of Biostatistics and Computational Biology School of Life SciencesFudan UniversityShanghai 200438China Department of Neurology Xuanwu HospitalCapital Medical UniversityBeijing 100053China State Key Laboratory of Natural and Biomimetic Drugs Key Laboratory for Neuroscience for Ministry of EducationSchool of Pharmaceutical SciencesPeking University Health Science CenterBeijing 100191China PKU-IDG/McGovern Institute for Brain Research Peking UniversityBeijing 100871China Chinese Institute for Brain Research Beijing 102206China

Background:Choosing the appropriate antipsychotic drug(APD)treatment for patients with schizophrenia(SCZ)can be challenging,as the treatment response to APD is highly variable and difficult to predict due to the lack of effective *** studies have indicated the association between treatment response and genetic and epigenetic factors,but no effective biomarkers have been ***,further research is imperative to enhance precision medicine in SCZ ***:Participants with SCZ were recruited from two randomized *** discovery cohort was recruited from the CAPOC trial(n=2307)involved 6 weeks of treatment and equally randomized the participants to the Olanzapine,Risperidone,Quetiapine,Aripiprazole,Ziprasidone,and Haloperidol/Perphenazine(subsequently equally assigned to one or the other)*** external validation cohort was recruited from the CAPEC trial(n=1379),which involved 8 weeks of treatment and equally randomized the participants to the Olanzapine,Risperidone,and Aripiprazole ***,healthy controls(n=275)from the local community were utilized as a genetic/epigenetic *** genetic and epigenetic(DNA methylation)risks of SCZ were assessed using the polygenic risk score(PRS)and polymethylation score,*** study also examined the genetic-epigenetic interactions with treatment response through differential methylation analysis,methylation quantitative trait loci,colocalization,and promoteranchored chromatin *** learning was used to develop a prediction model for treatment response,which was evaluated for accuracy and clinical benefit using the area under curve(AUC)for classification,R^(2) for regression,and decision curve ***:Six risk genes for SCZ(LINC01795,DDHD2,SBNO1,KCNG2,SEma7A,and RUFY1)involved in cortical morphology were identified as having a genetic-epigenetic interaction associated with treatment *** developed and externally validated predictio

关键词： Schizophrenia Antipsychotic drug Treatment response Prediction model Genetics Epigenetics

Investigation of Absorption of Nanocrystalline Silicon

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Chinese Physics Letters 1999年第11期16卷 833-835页

作者： ma Zhi-xun liao xian-bo KONG Guang-lin CHU jun-hao State Key Laboratory for Surface Physics Institute of SemiconductorsCenter for Condensed Matter PhysicsChinese Academy of SciencesBeijing 100083 National Laboratory for Infrared Physics Shanghai Institute of Technical PhysicsChinese Academy of SciencesShanghai 200083

Nanocrystalline silicon embedded SiO2 matrix is formed by annealing the SiOx films fabricated by plasma enhanced chemical vapor deposition technique. In conjunction with the micro-Raman spectra, the absorption spectra of the films have been investigated. The blue-shift of absorption edge with decreasing size of silicon crystallites is due to quantum confinement effect. It is found that nanocrystalline silicon is of an indirect band structure, and that the absorption presents an exponential dependence of absorption coefficient on photon energy in the range of 2.0-3.0eV, and a sub-band appears in the range of 1.0-1.5eV. We believe that the exponential absorption is due to the indirect band-to-band transition of electrons in silicon nanocrystallites, while the sub-band absorption is ascribed to transitions between the amorphous silicon states existing in the films.

关键词： technique. absorption exponential

Spinal CCL2 Promotes Pain Sensitization by Rapid Enhancement of NMDA-Induced Currents Through the ERK-GluN2B Pathway in Mouse Lamina Ⅱ Neurons

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Neuroscience Bulletin 2020年第11期36卷 1344-1354页

作者： Hui Zhang Sui-Bin ma Yong-Jing Gao jun-Ling Xing Hang xian Zhen-Zhen Li Shu-Ning Shen Sheng-Xi Wu Ceng Luo rou-Gang Xie Department of Neurobiology Fourth Military Medical UniversityXi'an 710032China Department of Health Statistics Fourth Military Medical UniversityXi'an 710032China Pain Research Laboratory Institute of Nautical MedicineJiangsu Key laboratory of NeuroregenerationNantong UniversityNantong 226001China Department of Radiation Biology Faculty of Preventive MedicineFourth Military Medical UniversityXi'an 710032China Department of Orthopedics Xijing HospitalFourth Military Medical UniversityXi'an 710032China Department of Stomatology No.984 Hospital of the People's Liberation ArmyBeijing 100094China

Previous studies have shown that CCL2(C-C motif chemokine ligand 2)induces chronic pain,but the exact mechanisms are still ***,we established models to explore the potential *** experiments revealed that an antagonist of extracellular signal-regulated kinase(ERK)inhibited not only CCL2-induced inflammatory pain,but also pain responses induced by complete Freund’s *** posed the question of the intracellular signaling cascade *** experiments showed that CCL2 up-regulated the expression of phosphorylated ERK(pERK)and N-methyl D-aspartate receptor[NMDAR]subtype 2B(GluN2B);meanwhile,antagonists of CCR2 and ERK effectively reversed these ***-cell patchclamp recordings revealed that CCL2 enhanced the NMDAR-induced currents via activating the pERK pathway,which was blocked by antagonists of GluN2B and *** summary,we demonstrate that CCL2 directly interacts with CCR2 to enhance NMDAR-induced currents,eventually leading to inflammatory pain mainly through the CCL2-CCR2-pERK-GluN2B pathway.

关键词： C-C motif chemokine ligand 2 Monocyte chemoattractant protein 1 Neuron-glial interaction Extracellular signal-regulated kinase

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软件安全漏洞检测技术

计算机学报 2015年第4期38卷 717-732页

作者：李舟军张俊贤廖湘科马金鑫北京航空航天大学计算机学院北京100191 国防科学技术大学计算机学院长沙410073

软件安全漏洞检测技术是提高软件质量和安全性、减少软件安全漏洞的重要方法和基本手段,受到学术界和工业界的广泛关注和高度重视.其主要途径包括软件测试、程序分析、模型检验与符号执行等.近年来,综合利用多种研究方法和技术手段来检... 详细信息

软件安全漏洞检测技术是提高软件质量和安全性、减少软件安全漏洞的重要方法和基本手段,受到学术界和工业界的广泛关注和高度重视.其主要途径包括软件测试、程序分析、模型检验与符号执行等.近年来,综合利用多种研究方法和技术手段来检测软件安全漏洞已成为软件安全领域的研究热点.文中首先回顾了程序分析与软件安全漏洞检测的基本概念、核心问题和传统手段.然后重点介绍该领域的最新进展,主要包括轻量级动态符号执行、自动化白盒模糊测试以及其实现技术和相应的工具.最后,指出了其所面临的挑战和发展趋势.

关键词：安全漏洞静态分析动态分析符号执行白盒测试

琼脂扩散盒及琼脂平皿法培养粒系祖细胞性质异同的初步探讨

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生理学报 1983年第3期 345-350页

作者：谢仁敷麻柔廖军鲜彭登慧中医研究院西苑医院中医研究院西苑医院中医研究院西苑医院现在中日友好医院

将异丙肾上腺素直接加入培养体系或先与骨髓细胞孵育1小时后再作培养,能显著促进CFU-D 增殖。此效应能被心得安阻断。异丙却不能使 CFU-C 产率增加,证明 CFU-D 在具有β-受体似多能造血干细胞而 CFU-C 无β-受体。CFU-D 与 CFU-C 的 Ara... 详细信息

将异丙肾上腺素直接加入培养体系或先与骨髓细胞孵育1小时后再作培养,能显著促进CFU-D 增殖。此效应能被心得安阻断。异丙却不能使 CFU-C 产率增加,证明 CFU-D 在具有β-受体似多能造血干细胞而 CFU-C 无β-受体。CFU-D 与 CFU-C 的 Ara-C 自杀率和增殖动态基本相同,表明 CFU-D 和 CFU-C 是性能相似但又处于不同分化阶段的粒系祖细胞。

关键词： CFU-D CFU-C β-肾上腺素能受体

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CREST综合征2例

临床皮肤科杂志 2009年第1期38卷 26-28页

作者：马帅军栾琪齐显龙胡雪慧廖文俊高天文第四军医大学西京医院全军皮肤病研究所陕西西安710032

目的:探讨 CREST 综合征的临床特点及诊治方法。方法:报告2例 CREST 综合征患者,2例均为女性,年龄分别为45岁和58岁,将其临床表现、实验室检查及组织病理改变的资料,结合相关文献作回顾性分析。结果:2例患者中,1例表现为双上肢皮肤变硬2... 详细信息

目的:探讨 CREST 综合征的临床特点及诊治方法。方法:报告2例 CREST 综合征患者,2例均为女性,年龄分别为45岁和58岁,将其临床表现、实验室检查及组织病理改变的资料,结合相关文献作回顾性分析。结果:2例患者中,1例表现为双上肢皮肤变硬20余年,伴鼻根部两侧、左肩部、左臀部皮下结节及吞咽困难1年;另1例表现为面部、双手、下肢皮肤变硬,伴吞咽困难20年,部分手指萎缩、坏死伴右手背、左小趾背皮下结节5年。结合各项实验室检查结果和病史确诊为 CREST 综合征。结论:CREST 综合征临床较为少见,对于硬皮病患者,除做组织病理、自身抗体检查外,建议仔细进行体格检查、食管钡餐造影、胸部 X 线片及肺功能检查,以明确诊断,同时坚持长期治疗。

关键词： CREST综合征硬皮病

碱性Zn-NiOOH/MnO_2一次电池的性能研究

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电源技术 2005年第11期29卷 762-764页

作者：符显珠李俊林敬东廖代伟厦门大学物理化学研究所

研制了以NiOOH与MnO2混合作正极活性物质、锌为负极的新一代实用碱性一次电池,弥补了目前广泛使用的碱锰电池大负荷放电性能不佳的缺陷。这种碱性Zn-NiOOH/MnO2电池1000ma大负荷放电至1.2V高压段的容量比碱锰电池提高了3.6倍,71!高温储... 详细信息

研制了以NiOOH与MnO2混合作正极活性物质、锌为负极的新一代实用碱性一次电池,弥补了目前广泛使用的碱锰电池大负荷放电性能不佳的缺陷。这种碱性Zn-NiOOH/MnO2电池1000ma大负荷放电至1.2V高压段的容量比碱锰电池提高了3.6倍,71!高温储存7d后,再放电至1.2V时容量保持率可达到73.8%,在室内储存1a后1000ma放电至1.2V的容量保持率还可达到85.6%。对这一新型电池在不同负荷下的放电容量和储存性能也进行了研究。

关键词： NiOOH 碱性一次电池碱锰电池大负荷放电

美国西南肿瘤组／东部肿瘤协作组染色体核型分组法与急性髓系白血病预后关系的研究

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白血病．淋巴瘤 2010年第1期19卷 20-22页

作者：马亮钟明华廖军鲜沈军龙红陈艳荣马一盖中日友好医院血液科北京100029 中日友好医院检验科北京100029

目的探讨急性髓系白血病（AML）患者染色体核型异常发生率、分布以及美国西南肿瘤组与东部肿瘤协作组（SWOG／ECOG）染色体核型分组法在预后评价中的意义。方法常规培养83例AML患者的骨髓细胞，吉姆萨显带分析染色体核型。根据SWOG／ECO... 详细信息

目的探讨急性髓系白血病（AML）患者染色体核型异常发生率、分布以及美国西南肿瘤组与东部肿瘤协作组（SWOG／ECOG）染色体核型分组法在预后评价中的意义。方法常规培养83例AML患者的骨髓细胞，吉姆萨显带分析染色体核型。根据SWOG／ECOG核型分类方法对核型进行分组，采用Kaplan—Meier方法观察不同危险组的生存情况。结果83例AML患者中56例细胞核型检出异常（67．47％）。AML伴t（15；17）易位与伴t（8；21）易位在异常核型患者中所占比例为53．57％（30／56），其余核型分布较分散。随访的74例患者中，42例死亡。预后良好、中等、不良3组生存期比较差异具有统计学意义（P〈0．001）。预后良好组完全缓解率高于预后中等及不良组（P〈0．05），预后中等组与不良组差异无统计学意义（P〉0．05）。结论细胞遗传学改变是影响白血病预后的主要因素之一，SWOG／ECOG核型分组能比较客观地反映AML的预后。

关键词：白血病粒细胞急性染色体细胞遗传学预后

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BP神经网络在湿法炼锌浸出工艺中的应用

矿冶工程 2006年第6期26卷 62-64页

作者：吉庆锋李先柏杨小中廖舟许彬马荣骏金瑞新材料科技股份有限公司湖南长沙410012 长沙矿冶研究院湖南长沙410012

针对湿法炼锌浸出工艺中影响生产的因素,利用BP神经网络技术和自适应变步长学习函数构造了一种新的神经网络模型,提高了训练速度,增强了网络的稳定性。结果表明,该模型能比较准确的预测浸出率和终酸浓度。

关键词：湿法炼锌浸出 BP神经网络自适应变步长