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孙莹璞：以科技摇篮托起健康新生命 006

孙莹璞：以科技摇篮托起健康新生命

Reproductive management through integration of pgd and MPS-based noninvasive prenatal screening/diagnosis for a family with GJB2-associated hearing impairment

医学科学报

作者：陈祎琪

名医简介孙莹璞：医学博士、教授、主任医师、博士生导师，郑州大学第一附属医院首席科学家，河南省试管婴儿技术和生殖医学学科创始人，中华医学会生殖医学分会前任主任委员，中国人体健康科技促进会生殖医学与生殖遗传专委会主任委... 详细信息

名医简介孙莹璞：医学博士、教授、主任医师、博士生导师，郑州大学第一附属医院首席科学家，河南省试管婴儿技术和生殖医学学科创始人，中华医学会生殖医学分会前任主任委员，中国人体健康科技促进会生殖医学与生殖遗传专委会主任委员。获国家科技进步奖二等奖1项，以通讯作

关键词：人类辅助生殖技术 pgd 我国大陆郑州大学第一附属医院生殖医学试管婴儿

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Science China(Life Sciences) 2015年第9期58卷 829-838页

作者： XIONG WenPing WANG DaYong GAO Yuan GAO Ya WANG HongYang GUAN Jing LAN Lan YAN JunHao ZONG Liang YUAN Yuan DONG Wei HUANG SeXin WU KeLiang WANG YaoShen WANG ZhiLi PENG HongMei LU YanPing XIE LinYi ZHAO Cui WANG Li ZHANG QiuJing GAO Yun LI Na YANG Ju YIN ZiFang HAN Bing WANG Wei CHEN Zi-Jiang WANG QiuJu Department of Otolaryngology-Head and Neck Surgery Chinese PLA Institute of Otolaryngology Chinese PLA General Hospital Center for Reproductive Medicine Shandong Provincial Hospital Affiliated to Shandong University National Research Center for Assisted Reproductive Technology and Reproductive Genetics BGI-Shenzhen Department of Ultrasonography Chinese PLA General Hospital Department of Obstetrics and Gynecology Chinese PLA General Hospital The Key laboratory for Reproductive Endocrinology of Ministry of Education

A couple with a proband child of GJB2(encoding the gap junction protein connexin 26)-associated hearing impairment and a previous pregnancy miscarriage sought for a reproductive solution to bear a healthy child. Our study aimed to develop a customized preconception-to-neonate care trajectory to fulfill this clinical demand by integrating preimplantation genetic diagnosis(pgd), noninvasive prenatal testing(NIPT), and noninvasive prenatal diagnosis(NIPD) into the strategy. Auditory and genetic diagnosis of the proband child was carried out to identify the disease causative mutations. The couple then received in-vitro-fertilization treatment, and eight embryos were obtained for day 5 biopsy. pgd was performed by short-tandem-repeat linkage analysis and Sanger sequencing of GJB2 gene. Transfer of a GJB2 c.235del C heterozygous embryo resulted in a singleton pregnancy. At the 13 th week of gestation, genomic DNA(g DNA) from the trio family and cell-free DNA(cf DNA) from maternal plasma were obtained for assessment of fetal chromosomal aneuploidy and GJB2 mutations. NIPT and NIPD showed the absence of chromosomal aneuploidy and GJB2-associated disease in the fetus, which was later confirmed by invasive procedures and postnatal genetic/auditory diagnosis. This strategy successfully prevented the transmission of hearing impairment in the newborn, thus providing a valuable experience in reproductive management of similar cases and potentially other monogenic disorders.

关键词：产前诊断听力障碍三人家庭繁殖管理 pgd 整合生殖 B2相

Adjunctive Peony-Glycyrrhiza decoction for antipsychotic-induced hyperprolactinaemia:a meta-analysis of randomised controlled trials

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General Psychiatry 2018年第4期31卷 3-9页

作者： Wei Zheng Dong-Bin Cai Hai-Yan Li Yu-Jie Wu Chee H Ng Gabor S Ungvari Shan-Shan Xie Zhan-Ming Shi Xiao-Min Zhu Yu-Ping Ning Yu-Tao Xiang Department of Psychiatry The Affliated Brain Hospital of Guangzhou Medical University(Guangzhou Huiai Hospital)GuangzhouChina Department of Neurology Shenzhen Traditional Chinese Medicine HospitalShenzhenChina Department of Psychiatry University of MelbourneMelbourneAustralia The University of Notre Dame Australia FremantleAustralia Division of Psychiatry Medical SchoolUniversity of Western AustraliaPerthAustralia Department of Psychiatry Mental Health Center of Hebei ProvinceBaodingChina Department of Psychiatry Chongqing Jiangbei Mental Health HospitalChongqingChina Department of Psychiatry Suzhou Psychiatric HospitalThe Affliated Guangji Hospital of Soochow UniversitySuzhouChina Unit of Psychiatry Faculty of Health SciencesUniversity of MacaoMacaoChina

Background Hyperprolactinaemia is a common adverse effect of antipsychotics(APs). The results of PeonyGlycyrrhiza decoction(pgd) as a potentially useful adjunctive treatment for hyperprolactinaemia are inconsistent.Aim This meta-analysis of randomised controlled trials(RCTs) examined the efficacy and safety of adjunctive pgd therapy for AP-induced hyperprolactinaemia.Methods English(PubMed, Embase, Cochrane Library,PsycINFO) and Chinese(Chinese National Knowledge Infrastructure, Wanfang Data) databases were systematically searched up to 10 June 2018. The inclusion criteria were based on PIC0 S一/^rticipants: adult patients with schizophrenia; Aitervention: pgd plus APs; Cbmparison: APs plus placebo or AP monotherapy;(Xjtcomes: efficacy and safety; Study design: RCTs. The weighted mean difference(WMD) and risk ratio(RR) along with their 95% CIs were calculated using Review Manager(RevMan) V.5.3 software.Results Five RCTs(n=450) were included and analysed.Two RCTs(n=140) were double-blind and four RCTs(n=409) reported ‘random' assignment with specific description. The pgd group showed a significantly lower serum prolactin level at endpoint than the control group(n=380, WMD:-32.69 ng/mL(95% Cl-41.66 to 23.72),/X0.00001, ^=97%). Similarly, the superiority of pgd over the control groups was also found in the improvement of hyperprolactinaemia-related symptoms. No difference was found in the improvement of psychiatric symptoms assessed by the Positive and Negative Syndrome Scale(n=403,WMD:-0.62(95% Cl-2.38 to 1.15), p=0.49, ^=0%). There were similar rates of all-cause discontinuation(n=330, RR0.93(95% Ci 0.63 to 1.37),/t=0.71, ^=0%) and adverse drug reactions between the two groups. According to the Grading of Recommendations Assessment, Development and Evaluation approach, the level of evidence of primary and secondary outcomes ranged from ‘very low'(14.3%),‘low'(42.8%),‘moderate'(14.3%),to ‘high,(28.6%>.Conclusions Current evidence supports the adjunctive use of pgd to suppress elevated prolactin and improve prolactin

关键词： pgd Adjunctive Peony-Glycyrrhiza decoction for antipsychotic-induced hyperprolactinaemia a meta-analysis of randomised controlled trials

Nonlinear polarization effects and mitigation in polarization-division-multiplexed coherent transmission systems

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Chinese Optics Letters 2010年第9期8卷 844-851页

作者：谢崇进 Bell Laboratories Alcatel-Lucent 791 Holmdel-Keyport Road Holmdel NJ 07733 USA

Using numerical simulations, the nonlinear transmission performance of polarization-division-multiplexed quadrature-phase-shift-keying （PDM-QPSK） coherent systems is studied. It is found that inter-channel cross-polarization modulation （XPolM） induced nonlinear polarization scattering can significantly degrade the transmission performance of PDM-QPSK coherent systems and change the perspective of dispersion management in optical coherent transmission systems. Some techniques to mitigate nonlinear polarization scattering in dispersion-managed PDM coherent transmission systems are discussed, including the use of time-interleaved return-to-zero （RZ） PDM formats, the use of periodic-group-delay pgd dispersion compensators, and the judicious addition of some polarization-mode-dispersion （PMD） in the transmission link. It is shown that if nonlinear polarization scattering can be well mitigated, a polarization multiplexed optical coherent transmission system with dispersion management could perform better than that without it.

关键词： QPSK NRZ Nonlinear polarization effects and mitigation in polarization-division-multiplexed coherent transmission systems PDM WDM pgd

A pgd Pregnancy Achieved by Embryo Copy Number Variation Sequencing with Confirmation by Non-Invasive Prenatal Diagnosis

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Journal of Genetics and Genomics 2014年第8期41卷 453-456页

作者： Hui Wang Li Wang Minyue Ma Zhuo Song Jianguang Zhang Genming Xu Junmei Fan Na Li David S.Cram Yuanqing Yao Department of Obstetrics and Gynecology Chinese PLA General Hospital Department of Obstetrics and Gynecology Beijing Shi Jing Shan Hospital Berry Genomics Co.Ltd.

Aneuploidy rates in embryos produced by assisted reproduc- tive technologies commonly exceed 50%, particularly in couples where the woman is of advanced maternal age or has experienced repeated implantation failure （Harper et al., 2012）. Pre-implantation genetic diagnosis （pgd） conducted at many fertility clinics worldwide is now a frontline treatment for infertile couples with a poor prognosis for pregnancy as well as couples where one partner is a carrier of a balanced translocation （Munne, 2012）.

关键词： pgd CNVs IVF

Identifying normal embryos from reciprocal translocation carriers by whole chromosome haplotyping

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Journal of Genetics and Genomics 2018年第9期45卷 505-508页

作者： Zhiqiang Yan Yuqian Wang Yanli Nie Xu Zhi Xiaohui Zhu Meng Qin Shuo Guan Yixin Ren Ying Kuo Di Chang Wei Chen Peng Yuan Liying Yan Jie Qiao Center for Reproductive Medicine Department of Obstetrics andGynecology Peking University Third Hospital Beijing 100191 China Key Laboratory of Assisted Reproduction Ministry of Education Beijing 100191 China Peking-Tsinghua Center for Life Sciences Peking University Belting 100871 China Academy for Advanced Interdisciplinary Studies Peking University Beijing 100871 China Beijing Key Laboratory of Reproductive Endocrinology and Assisted Reproduction Beijing 100191 China Beijing Advanced Innovation Center for Genomics (ICG) Peking University Beijing 100871 China

Reciprocal translocation is a chromosomal structural abnormal- ity that arises when two non-homologous chromosomes rearrange and attach with each other, an incidence that occurs in about 1/500 to 1/625 newborns （Mackie and Scriven, 2002）. This event typically does not lead to any significant loss of genetic material, thus recip- rocal translocation carriers do not exhibit any severe abnormal phenotypes （Scriven et al., 1998; Zhang et al., 2016）.

关键词： Identifying normal embryos from reciprocal translocation carriers by whole chromosome haplotyping CNV pgd cycle IVF

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基于迁移模型的人脸识别攻击技术研究与实现

基于迁移模型的人脸识别攻击技术研究与实现

作者：程永锦西南大学

学位级别：硕士

随着人工智能的不断发展,人脸识别技术已成为公安、金融、零售等领域的重要应用,以卷积神经网络为代表的深度学习算法作为主流的人脸识别方法应用得最为广泛。然而,很多研究证明卷积神经网络存在一个致命缺陷——对抗攻击。对抗攻击通... 详细信息

随着人工智能的不断发展,人脸识别技术已成为公安、金融、零售等领域的重要应用,以卷积神经网络为代表的深度学习算法作为主流的人脸识别方法应用得最为广泛。然而,很多研究证明卷积神经网络存在一个致命缺陷——对抗攻击。对抗攻击通过在原始样本上添加不明显的非随机扰动来生成对抗样本,对抗样本可以欺骗模型并使模型输出错误的识别结果。这一攻击方法可能会对人脸识别系统的安全性和隐私保护造成威胁。在真实场景下,大多面对的是不可知被攻击人脸识别模型内部结构及参数的黑盒攻击,由于对抗样本具有迁移性,可以迁移到不同的模型上进行攻击,从而间接地完成黑盒攻击任务。因此,本文研究了基于迁移模型的人脸识别攻击技术,该研究不仅对大数据时代人脸图像隐私保护具有重要的意义,还可以为如何防御人脸识别任务中的恶意攻击以及提高人脸识别模型的鲁棒性提供一些重要的启发。针对黑盒环境下的攻击,本文提出了基于自适应攻击步长的pgd迁移攻击算法(AM-pgd)和基于多尺度特征融合的AdvGAN对抗样本生成方法(MultiAdvGAN)。首先选取和优化了满足本研究需求的人脸图像数据库,训练了Cos Face、Arc Face和Mobile Face Net三个人脸识别模型作为攻击对象;其次,使用基于自适应攻击步长的pgd迁移攻击算法对这些模型进行了迁移攻击,并对攻击结果进行对比和分析,研究攻击算法的有效性和泛化性;接着,使用基于多尺度特征融合的AdvGAN对抗样本生成方法继续进行迁移攻击,记录和分析实验结果,研究生成对抗样本的仿真性和攻击效果;最后,设计并开发了一个人脸图像的对抗样本生成系统,将以上两种攻击方法生成的对抗样本保存并进行可视化输出。具体研究工作包括:(1)选取CASIA-Web Face和LFW人脸图像数据库,对这些数据进行优化处理。并且训练了Cos Face、Arc Face和Mobile Face Net三个人脸识别模型,训练实验结果表明经过相对大规模数据训练之后的人脸识别模型均取得较好的识别效果。(2)提出基于自适应攻击步长的pgd迁移攻击方法,该算法在反向传播计算梯度时动态调整攻击步长,引入梯度的一阶和二阶矩估计,从而有效地克服了梯度更新过程中的震荡和不稳定性,并增加校正偏执,以此来帮助模型更快更好地收敛到全局最优解。由于现实环境中攻击目标通常是黑盒模型,攻击者很难获得关键参数和网络结构等信息。因此,本文借鉴黑盒迁移攻击的算法思想,并利用本文提出的AM-pgd攻击方法攻击替代模型生成对抗样本,再使用这些对抗样本来攻击迁移模型,从而完成黑盒攻击的任务。分别将Cos Face、Arcface和Mobile Face Net模型中的一个设置为替代模型,另外两个为迁移模型,进行三组迁移攻击实验,实验结果表明本文提出算法在迁移攻击实验中攻击效果有所提升。(3)提出基于多尺度特征融合的AdvGAN对抗样本生成方法,该算法在生成对抗网络的生成器之前加入特征提取器,将提取到的多尺度特征进行特征融合,使用生成器和判别器进行双网络的训练,并通过多轮迭代得到仿真性更强且迁移性提高的对抗样本。在本研究中将Mobile Face Net模型作为替代模型,将攻击替代模型得到的对抗样本依次转移到Cos Face和Arcface模型上,并进行迁移攻击实验,结果显示,与传统的AdvGAN算法相比,该算法生成的对抗样本具有更强的隐蔽性,同时也得到了更强的迁移攻击效果。(4)设计并开发一个人脸图像的对抗样本生成系统,该系统实现人脸图像的上传、人脸图像的识别、攻击算法的选择、扰动系数的修改以及对抗样本的输出等功能。

关键词：迁移攻击人脸识别 pgd 多尺度特征融合

基于ALBERT的多标签文本分类问题的研究

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基于ALBERT的多标签文本分类问题的研究

作者：李悦华中科技大学

学位级别：硕士

文本分类是自然语言处理中一项基本任务,主要分为单标签分类和多标签分类两个应用场景,单标签文本分类的算法已趋于完善,实际中一段文本也往往涵盖多个主题,对应多个标签,因此多标签文本分类的研究重要且必要。目前主流的多标签文本分... 详细信息

文本分类是自然语言处理中一项基本任务,主要分为单标签分类和多标签分类两个应用场景,单标签文本分类的算法已趋于完善,实际中一段文本也往往涵盖多个主题,对应多个标签,因此多标签文本分类的研究重要且必要。目前主流的多标签文本分类方法是先通过机器学习或者是深度学习的方法提取文本的语义特征,再通过分类器进行分类处理,对于标签信息挖掘十分有限,而多标签分类数据集也往往具有长尾效应,各个标签的类别比例十分不均衡,分类效果欠佳,BERT预训练模型在自然语言处理中效果理想,但BERT模型大量的参数使得算法的复杂度高,计算量大,针对上述问题,本文的研究就此展开。本文构建了文本表示与分类一体化的ML-ALBERT-pgd-BiLSTM-ATT多标签文本分类模型,实现了对于文本与标签关联关系的利用,并且通过对抗训练改善数据质量,提升了模型的分类准确性和泛化率,同时参数量仅为BERT模型的五分之一,大大降低了算法复杂度、提升了效率。其使用ALBERT模型提取文本词向量,将标签与文本拼接后一同传入ALBERT进行训练,将标签与文本映射到同一语义空间后利用ALBERT固有的Self-Attention机制获得融合标签信息的文本词向量表示,将获得的词向量输入双向长短时记忆网络BiLSTM提取文本的上下文语义信息,结合Attention机制对于BiLSTM隐层特征向量进行信息筛选,自适应地提取对于分类有帮助的关键信息,对BiLSTM隐层特征向量进行加权获得最终的篇级文本向量,最后连接全连接层进行分类。对于标签数据不均衡的问题,在训练过程中基于pgd算法进行对抗训练,通过迭代对于Embedding层添加动态噪声对文本进行数据增强,来提升模型的分类准确性。在电商评论、知乎问答和新闻主题识别三个数据集上应用本文提出的模型较现有模型中效果最佳的ALBERT-BiLSTM-ATT模型,Precision、Recall、F1-Score、Micro-AUC和Macro-AUC指标值都有所提升,最后进行的消融实验进一步验证了本文模型的有效性。

关键词：多标签文本分类数据增强注意力机制 pgd ALBERT

引物延伸预扩增法应用于β-地中海贫血患者胚胎植入前遗传学诊断——附一例报告

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中华妇产科杂志 2003年第3期38卷 143-146页

作者：焦泽旭庄广伦周灿权舒益民李洁梁晓燕张敏芳邓明芬中山大学附属第一医院妇产科生殖医学研究中心广州510080

目的　探讨对 β 地中海贫血进行胚胎植入前遗传学诊断 (pgd)的方法。方法　两对夫妇双方均分别为密码子 41 42 ( TCTT)及插入序列 (IVS) Ⅱ 65 4(C→T)突变杂合子 ,在本中心进行超排卵和体外受精胚胎移植治疗 ,胚胎活检后应用全基... 详细信息

目的　探讨对 β 地中海贫血进行胚胎植入前遗传学诊断 (pgd)的方法。方法　两对夫妇双方均分别为密码子 41 42 ( TCTT)及插入序列 (IVS) Ⅱ 65 4(C→T)突变杂合子 ,在本中心进行超排卵和体外受精胚胎移植治疗 ,胚胎活检后应用全基因组扩增技术及反向点杂交进行胚胎pgd ,根据诊断结果选择健康的胚胎移植入子宫。结果　 2例患者共获卵 3 5个 ,受精率为 87% ,共活检胚胎16个 ,获卵裂球 2 5个 ,单卵裂球总扩增效率为 84% ,等位基因脱扣率为 15 %。 2例患者共移植 5个胚胎 ,1例获得妊娠 ,已分娩健康双胎。结论　应用引物延伸预扩增技术可对 β 地中海贫血进行pgd 。

关键词： β-地中海贫血患者 pgd 遗传学诊断全基因组扩增胚胎植入治疗密码子卵裂球引物