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High‑Resolution and Multidimensional Phenotypes Can Complement Genomics Data to Diagnose Diseases in the Neonatal Population

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Phenomics 2023年第2期3卷 204-215页

作者： tiantian xiao Xinran Dong Yulan Lu Wenhao Zhou Division of Neonatology Children’s Hospital of Fudan UniversityNational Children’s Medical Center399 Wanyuan RoadShanghai 201102China Center for Molecular Medicine Pediatric Research InstituteChildren’s Hospital of Fudan UniversityNational Children’s Medical CenterShanghai 201102China Department of Neonatology Chengdu Women’s and Children’s Central HospitalSchool of MedicineUniversity of Electronic Science and Technology of ChinaChengdu 610000China

Advances in genomic medicine have greatly improved our understanding of human diseases.However,phenome is not well understood.High-resolution and multidimensional phenotypes have shed light on the mechanisms underlying neonatal diseases in greater details and have the potential to optimize clinical strategies.In this review,we first highlight the value of analyzing traditional phenotypes using a data science approach in the neonatal population.We then discuss recent research on high-resolution,multidimensional,and structured phenotypes in neonatal critical diseases.Finally,we briefly introduce current technologies available for the analysis of multidimensional data and the value that can be provided by integrating these data into clinical practice.In summary,a time series of multidimensional phenome can improve our understanding of disease mechanisms and diagnostic decision-making,stratify patients,and provide clinicians with optimized strategies for therapeutic intervention;however,the available technologies for collecting multidimensional data and the best platform for connecting multiple modalities should be considered.

关键词： Multidimensional phenotype Neonatal phenome Personalized medicine Neonatal diseases

Chemotactic nanomotor for multimodal combined therapy of glioblastoma

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Science China Chemistry 2024年第4期67卷 1277-1288页

作者： Ting Li Lin Chen Yunxin Xue Xiangyu xiao Wenjun Dai Kaiyuan Tan tiantian Chen Yingfang Tao Chun Mao Jian Shen Mimi Wan National and Local Joint Engineering Research Center of Biomedical Functional Materials School of Chemistry and Materials ScienceNanjing Normal UniversityNanjing 210023China

Glioblastoma(GBM) is the most aggressive malignant brain tumor. Due to the infiltration and heterogeneity of GBM, the obstruction of the blood-brain barrier(BBB) and the unique immunosuppressive mechanism, it is hard to achieve significant effects of GBM treatment. Here, a kind of chemotactic nanomotor that loaded with glucose oxidase(GOx) and carboxylated cisplatin(Pt(IV)) prodrug on the L-arginine-derived polymer is proposed. The nanomotors are driven by catalysis of glucose decomposition and the positive chemotaxis towards the GBM microenvironment where inducible nitric oxide synthase and reactive oxygen species are highly expressed. This facilitates the BBB crossing and GBM targeting of the nanomotors. In addition, the released nitric oxide(NO) during propulsion as well as the loaded GOx and Pt(IV) can exert combined NO/starvation/chemotherapy. Meanwhile, it is able to induce and enhance the immune response through multiple pathways, thus better coping with the complexities of GBM treatment.

关键词： chemotaxis combined therapy glioblastoma nanomotors

Precision medicine via the integration of phenotype-genotype information in neonatal genome project

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Fundamental Research 2022年第6期2卷 873-884页

作者： Xinran Dong tiantian xiao Bin Chen Yulan Lu Wenhao Zhou Center for Molecular Medicine Children's Hospital of Fudan UniversityNational Children's Medical CenterShanghai 201102China Division of Neonatology Children's Hospital of Fudan UniversityNational Children's Medical CenterShanghai 201102China Department of Neonatology Chengdu Women's and Children's Central HospitalSchool of MedicineUniversity of Electronic Science and Technology of ChinaChengdu 610066China

The explosion of next-generation sequencing(NGS)has enabled the widespread use of genomic data in precision medicine.Currently,several neonatal genome projects have emerged to explore the advantages of NGS to diagnose or screen for rare genetic disorders.These projects have made remarkable achievements,but still the genome data could be further explored with the assistance of phenotype collection.In contrast,longitudinal birth cohorts are great examples to record and apply phenotypic information in clinical studies starting at the neonatal period,especially the trajectory analyses for health development or disease progression.It is obvious that efficient integration of genotype and phenotype benefits not only the clinical management of rare genetic disorders but also the risk assessment of complex diseases.Here,we first summarize the recent neonatal genome projects as well as some longitudinal birth cohorts.Then,we propose two simplified strategies by integrating genotypic and phenotypic information in precision medicine based on current studies.Finally,research collaborations,sociological issues,and future perspectives are discussed.How to maximize neonatal genomic information to benefit the pediatric population remains an area in need of more research and effort.

关键词： Neonatal genome project Rare genetic disorders Precision medicine Genotype and phenotype integration Longitudinal birth cohort

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中西方文化差异对虚拟人道德责任判断的影响

心理学报 2024年第2期56卷 161-178,I0001-I0009页

作者：闫霄莫田甜周欣悦浙江大学管理学院杭州310058

近年来,社交网络上涌现出大量具有真人特征的虚拟人物,他们以第一人称视角叙事以获得影响力,然而其背后的道德伦理问题也逐渐浮现。当社交媒体虚拟人犯错时,不同文化背景的人们对其道德判断会有何不同?本文基于心智感知理论,通过5个主... 详细信息

近年来,社交网络上涌现出大量具有真人特征的虚拟人物,他们以第一人称视角叙事以获得影响力,然而其背后的道德伦理问题也逐渐浮现。当社交媒体虚拟人犯错时,不同文化背景的人们对其道德判断会有何不同?本文基于心智感知理论,通过5个主要实验探索中西方文化差异对虚拟人道德责任判断的影响和机制。研究表明,在被告知虚拟人的不道德行为后,比起西方文化,中国文化影响下的人们认为虚拟人需要承担更大的道德责任;但这种文化差异没有出现在对真人的道德责任判断上(实验1a~1c)。并且不论虚拟人是由真实人类还是人工智能驱动,这种文化差异都会存在(实验1c)。这种文化差异通过感知心智能力来中介(实验2)。具体而言,比起西方文化,中国文化影响下的人们认为虚拟人的心智能力(特别是感知力)更高,因此需要承担更大的道德责任。此外,对虚拟人更大的道德责任判断会导致中国文化(相比西方文化)影响下的人们更倾向于对虚拟人施加道德惩罚(实验3)。本文通过实证研究将道德责任判断和心智感知的对象拓展到虚拟人上,并揭示了中西方文化差异及其后续影响。

关键词：虚拟人道德责任文化差异心智能力

High-risk phenotypes of genetic disease in a Neonatal Intensive Care Unit population

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Chinese Medical Journal 2022年第5期135卷 625-627页

作者： tiantian xiao Qi Ni Huiyao Chen Huijun Wang Lin Yang Bingbing Wu Yun Cao Guoqiang Cheng Laishuan Wang Liyuan Hu Hongfang Mei Yulan Lu Mengchun Gong Xinran Dong Wenhao Zhou Department of Neonatology Key Laboratory of Neonatal DiseasesMinistry of HealthChildren’s Hospital of Fudan UniversityNational Children’s Medical CenterShanghai 201102China Center for Molecular Medicine Children’s Hospital of Fudan UniversityNational Children’s Medical CenterShanghai 201102China Institute of Health Management Southern Medical UniversityGuangzhouGuangdong 510515China

To the Editor: Genetic diseases contribute to 35% of deaths during the first year of life and are a significant cause of intensive care.[1] A previous study based on the China Neonatal Genomes Project investigated the genetic causes of early infant deaths and found that >25% of deceased neonates with genetic diagnoses can be cured if diagnosed in time.[2] Therefore, it is crucial to target and diagnose neonates with genetic diseases as early as possible. According to our experience, the typical phenotypes, such as special facial features or multiple congenital anomalies (MCAs), indicate a high risk of genetic disease and lead physicians to perform genetic testing in neonates as early as possible. However, in practice, infants without typical phenotypes typically undergo a long and costly diagnostic process before genetic diagnoses are confirmed. Moreover, a recent survey by the American College of Medical Genetics and Genomics (ACMG) and other national professional organizations indicated that there are insufficient numbers of qualified geneticists to fulfil genetic service needs.[3] The ACMG published the general clinical features for genetic testing indications. For example, patients with phenotypes or family history data that strongly implicate a genetic cause may undergo genetic testing.[1] However, the study indicated that many genetic conditions arise de novo or are inherited with no family history.[1] A previous study attempted to apply the non-phenotype-driven panel approach in neonates admitted to the neonate intensive care unit (NICU).[4] However, at present, the diagnostic yield is only 3.45% (1/29).[4] In addition, the economic and ethical issues associated with genomic screening remain challenging. Therefore, the available indications for genetic testing may improve the management of genetic diseases.

关键词： admitted apply fir

CYP2C9^(*)3 Increases the Ibuprofen Response of Hemodynamically Significant Patent Ductus Arteriosus in the Infants with Gestational Age of More Than 30 Weeks

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Phenomics 2022年第1期2卷 72-77页

作者： Xiang Chen Yuxi Chen tiantian xiao Xinran Dong Yulan Lu Yanyan Qian Huijun Wang Wenhao Zhou Departments of Neonatology National Children’s Medical CenterChildren’s Hospital of Fudan UniversityShanghai 201102China Shanghai Key Laboratory of Birth Defects The Translational Medicine Center of Children Development and Disease of Fudan UniversityChildren’s Hospital of Fudan UniversityShanghai 201102China

Hemodynamically significant patent ductus arteriosus(hsPDA)is a severe condition in newborns.Ibuprofen is an effective treatment to reduce the severe complications and the need for surgical treatment.Several single-nucleotide polymorphisms(SNPs)were related to the ibuprofen metabolism,treatment effects,and the onset of side effects.The effects of SNPs on hsPDA response after ibuprofen treatment are unknown.Therefore,in this study,we recruited hsPDA patients with standard ibuprofen treatment.Those patients had participated in China Neonatal Genomes Project(CNGP,ClinicalTrials.gov Identifier:NCT03931707)with next-generation sequencing data.We reanalyzed the sequencing data and compared the allele frequencies of known ibuprofen-related SNPs between ibuprofen Responder and Non-responder groups.In total,185 hsPDA patients were recruited with gestational age(GA)ranging from 24 to 40 weeks.No significant differences were detected in the basic information,period of ibuprofen treatment,rate of conservative treatment,complications,and side effects between ibuprofen Responder group and Non-responder group.Totally,17 hsPDA carried CYP2C9^(*)3 and one with CYP2C9^(*)2 were detected.In the GA group of more than 30 GA weeks(GA>30 wks group),we found higher allele frequency of CYP2C9^(*)3 in Responder group than in Non-responder group(16%vs.0,p=0.0391).In the GA group of less than 30 GA weeks(GA≤30 wks group),the sum allele frequency of CYP2C9^(*)3 and CYP2C9^(*)2 had no stastical difference between two groups(Responder group vs.Non-responder group,13%vs.11%,p=0.768).Therefore,we came to conclude that genetic tests of CYP2C9^(*)3 site may benefit the prediction of ibuprofen treatment outcome for hsPDA patients with gestational age of more than 30 weeks.

关键词： CYP2C9 Ibuprofen Patent ductus arteriosus Pharmacogenetics

基于K-means-LSTM模型的证券股价预测

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科技和产业 2024年第3期24卷 210-215页

作者：肖田田安徽建筑大学数理学院合肥230601

鉴于股票数据具有非平稳、非线性等特征,传统的统计模型无法精准预测股票价格的未来趋势。针对这个问题,构建一种混合深度学习方法来提高股票预测性能。首先,通过将距离算法修改为DTW(动态时间归整),令K-means聚类算法拓展为更适用于时... 详细信息

鉴于股票数据具有非平稳、非线性等特征,传统的统计模型无法精准预测股票价格的未来趋势。针对这个问题,构建一种混合深度学习方法来提高股票预测性能。首先,通过将距离算法修改为DTW(动态时间归整),令K-means聚类算法拓展为更适用于时间序列数据的K-means-DTW,聚类出价格趋势相似的证券;然后,通过聚类数据来训练LSTM(长短时记忆网络)模型,以实现对单支股票价格的预测。实验结果表明,混合模型K-means-LSTM表现出更好的预测性能,其预测精度和稳定性均优于单一LSTM模型。

关键词：股票价格预测 K-means DTW(动态时间归整) K-means-LSTM(K均值-长短时记忆网络)混合模型

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基于无波长偏移光学相位共轭的信号损伤补偿

光学学报 2024年第7期44卷 44-50页

作者：巩小雪肖汶玲张琦涵张天天尹星郭磊重庆邮电大学通信与信息工程学院重庆400065 东北大学计算机科学与工程学院辽宁沈阳110819

为了解决强度调制-直接检测正交频分复用(IM-DD OFDM)光通信系统中由光纤色散和非线性效应导致的传输性能下降的问题,提出利用正交偏振泵浦非简并四波混频(NFWM)产生的无波长偏移光学相位共轭(OPC)波对系统中的信号损伤进行光域补偿。... 详细信息

为了解决强度调制-直接检测正交频分复用(IM-DD OFDM)光通信系统中由光纤色散和非线性效应导致的传输性能下降的问题,提出利用正交偏振泵浦非简并四波混频(NFWM)产生的无波长偏移光学相位共轭(OPC)波对系统中的信号损伤进行光域补偿。首先在理论上推导了利用正交偏振泵浦NFWM生成OPC波的原理,基于上述原理,设计了无波长偏移OPC实现方式,在正交偏振态上得到与原信号波长完全一致的OPC波。然后对影响生成OPC波功率的因素进行了具体分析。最后依据优化参数设置,进行仿真验证,结果表明所提系统能够以114.375 Gbit/s的传输速率在长度为240 km的标准单模光纤链路中传输。

关键词：光通信强度调制-直接检测正交频分复用色散补偿非线性抑制光学相位共轭

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二甲醚和甲醇双直喷喷雾燃烧特性的光学研究

西安交通大学学报 2024年第6期58卷 153-161页

作者：南天天肖红亮张海涛黄吕萌陈占明陈昊何海斌吴杰长安大学陕西省交通新能源开发、应用与汽车节能重点实验室西安710018 宁波中策动力机电集团有限公司浙江宁波315020

为明晰高压喷射条件下二甲醚和甲醇双直喷的喷雾形态和火焰发展特性,通过高温高压定容燃烧弹,利用高速相机基于纹影法,对比研究了甲醇和二甲醚双直喷的喷雾燃烧特性。实验中,喷射压力设置为60、80、100 MPa,环境背压设置为0.2、4 MPa,... 详细信息

为明晰高压喷射条件下二甲醚和甲醇双直喷的喷雾形态和火焰发展特性,通过高温高压定容燃烧弹,利用高速相机基于纹影法,对比研究了甲醇和二甲醚双直喷的喷雾燃烧特性。实验中,喷射压力设置为60、80、100 MPa,环境背压设置为0.2、4 MPa,环境温度分别为500、800 K。背压为0.2 MPa时,二甲醚的气相和液相贯穿距以及喷雾投影面积小于甲醇;背压为4 MPa时情况相反。但是,二甲醚液相喷雾贯穿距和喷雾面积所占的比例在同工况下均小于甲醇,即两种背压条件下二甲醚的雾化效果均比甲醇的好。随着喷射压力的增加,双直喷喷雾的火焰浮起长度增加,喷射压力为100 MPa时的火焰浮起长度较60 MPa时增加约26.42%,着火延迟期变长,KL因子的总和减少了44.05%;随着二甲醚喷射延时的增加,两种喷雾碰撞后形成的双直喷喷雾发展变快,喷雾面积先变小后变大,燃烧火焰的着火延迟期变长。相比于同步喷射,二甲醚延迟1 ms喷射时火焰浮起长度增加8.34%,KL因子的总和下降26.12%。研究表明,增加喷射压力和二甲醚喷射延时对于优化二甲醚、甲醇双燃料发动机的喷雾与燃烧特性具有重要的促进作用。

关键词：二甲醚甲醇闪急沸腾喷雾特性燃烧特性