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IGFBP7和CaN异常表达预测射血保留型心力衰竭合并心房颤动患者左心房纤维化程度和形变功能的研究

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中国心血管病研究 2024年第5期22卷 422-427页

作者：达迎晓狄宁宁周松崔振川黄玲芳邢台市中心医院心内二科河北省邢台市054000

目的探究胰岛素样生长因子结合蛋白7(IGFBP7)和钙调神经磷酸酶(CaN)异常表达对射血保留型心力衰竭(HFpEF)合并心房颤动(af)患者左心房纤维化程度和形变功能的预测价值。方法选取邢台市中心医院收治的HFpEF患者180例,根据是否合并af分为... 详细信息

目的探究胰岛素样生长因子结合蛋白7(IGFBP7)和钙调神经磷酸酶(CaN)异常表达对射血保留型心力衰竭(HFpEF)合并心房颤动(af)患者左心房纤维化程度和形变功能的预测价值。方法选取邢台市中心医院收治的HFpEF患者180例,根据是否合并af分为单纯HFpEF组(n=94)及合并组(n=86),同时选取同期健康体检人群为对照组(n=80)。比较三组受试者左心房纤维化程度和形变功能、IGFBP7及CaN水平,并采用多元logistic回归分析影响HFpEF合并af的危险因素,Spearman相关性分析血清IGFBP7和CaN水平与左心房纤维化程度和形变功能的相关性,受试者工作特征曲线(ROC曲线)分析IGFBP7和CaN水平对HFpEF合并af的预测价值。结果HFpEF患者左心房收缩期整体峰值纵向应变值(LAS-a)、左心室收缩期左心房整体峰值纵向应变值(LAS-s)、左心房整体总排空分数(LATEF)显著低于对照组[(35.02±4.03)比(38.86±3.89),(15.03±2.31)比(18.74±2.96),(41.87±9.46)比(51.98±9.87),Paf的危险因素(Paf的曲线下面积分别为0.903、0.999(Paf患者左心房纤维化程度和左心房形变功能有关,其可作为HFpEF合并af的预测指标。

关键词：射血保留型心力衰竭心房颤动胰岛素样生长因子结合蛋白7 钙调神经磷酸酶左心房

Detection of the FecX^R Mutation of BMP15 Gene in Sheep and Goats

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畜牧兽医学报 2010年第S1期41卷 17-20页

作者： di Ran FENG Tao CHU Ming-xing ZHANG Ying-jie FANG Li Key Laboratory of Farm Animal Genetic Resources and Utilization of Ministry of Agriculture Institute of Animal ScienceChinese Academy of Agricultural SciencesBeijing 100193China College of Animal Science and Technology Gansu Agricultural UniversityLanzhou 730070China

PCR-SSCP was used to detect mutations of bone morphogenetic protein 15(BMP15) gene in both high prolificacy(Small Tail Han sheep,Hu sheep,Jining Grey goat and Boer goat) and low prolificacy breeds(Dorset sheep,Texel sheep,Inner Mongolia Cashmere goat and Angora goat).Both the nucleotide sequences and the amino acid sequences were compared in amplification fragments of both Small Tail Han sheep and Jining Grey *** results indicated that none of the four sheep and the four goat breeds carried the same FecXR mutation of the BMP15 gene as do Rasa Aragonesa *** nucleotide sequence of Small Tail Han sheep was completely identical with that of the sheep BMP15 sequence(GenBank af236079,NM001114767).Three base substitutions(T529G,C530G and T576C) and two amino acid changes(V155G and S171P) were found in Jining Grey goat compared with Small Tail Han *** FecXR mutation of the BMP15 gene had no significant effect on high prolificacy of Small Tail Han sheep, Hu sheep,Jining Grey goat and Boer goat.

关键词： sheep goat prolificacy BMP15 gene FecX^R mutation PCR-SSCP

Bone Morphogenetic Protein 15 as a Candidate Gene for Prolificacy of Jining Grey Goat

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畜牧兽医学报 2009年第S1期40卷 1-7页

作者： FENG Tao ZHAO You-zhang CHU Ming-xing di Ran ZHANG Ying-jie FANG Li College of Animal Science and Technology Gansu Agricultural University Key Laboratory of Farm Animal Genetic Resources and Utilization of Ministry of Agriculture Institute of Animal ScienceChineseAcademy of Agricultural Sciences College of Animal Science and Technology Agricultural University of Hebei

On the basis of the ovine bone morphogenetic protein 15(BMP15)gene,two pairs of primers(PI and P2)were designed to amplify exons 1 and 2 of the BMP15 gene in five randomly selected does of both Angora and Jining Grey *** sequences of BMP15 exon 1(P1 amplification)of Angora and Jining Grey goats were *** was a 3-nucleotide(CTT)insertion in positions 268 to 270 of goat BMP 15 exon1 compared with that of sheep(GenBank accession number af236078),which caused a leucine insertion in the 12th position of amino acid *** length of goat BMP 15 exon 2(P2 amplification)was identical with that of sheep(af236079),but there were seven nucleotide and four amino acid changes between goat and *** nucleotide in the 963rd position of BMP15 exon 2 was A for Angora goat and sheep,and G for Jining Grey *** on this A963G mutation,primer pair P3 was designed to detect single nucleotide polymorphism of BMP15 exon 2 in breeds of high prolificacy(Jining Grey),moderate prolificacy(Boer)and low prolificacy(Angora and Inner Mongolia Cashmere)by polymerase chain reactionsingle strand conformation polymorphism(PCR-SSCP).Three genotypes(AA,AG and GG)were detected in Jining Grey goats,two genotypes(AG and GG)in Boer,and only the AA genotype in Angora and Inner Mongolia Cashmere *** revealed one mutation(A963G)in genotype GG compared with genotype AA,and this mutation resulted in an amino acid change of serine→glycine(S300G).In Jining Grey goats,frequencies of AA,AG and GG genotypes were 0.008,0.059 and 0.933,*** distributions of the BMP 15 gene were significantly different(Pditional kids than did those with AG or AA genotypes,and does with the AG genotype had 0.86(Pdid those with the AA *** results tentatively indicate that t

关键词： goat prolificacy bone morphogenetic protein 15 gene PCR-SSCP

Recent advances in the translation of drug metabolism and pharmacokinetics science for drug discovery and development

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Acta Pharmaceutica Sinica B 2022年第6期12卷 2751-2777页

作者： Yurong Lai Xiaoyan Chu Li di Wei Gao Yingying Guo Xingrong Liu Chuang Lu Jialin Mao Hong Shen Huaping Tang Cindy Q.Xia Lei Zhang Xinxin ding Drug Metabolism Gilead Sciences Inc.Foster CityCA 94404USA Department of Pharmacokinetics Pharmacodynamics and Drug MetabolismMerck&Co.Inc.KenilworthNJ 07033USA Pharmacokinetics Dynamics and MetabolismPﬁzer Worldwide Research and DevelopmentGrotonCT 06340USA Eli Lilly and Company IndianapolisIN 46221USA Drug Metabolism and Pharmacokinetics BiogenCambridgeMA 02142USA Drug Metabolism and Pharmacokinetics Accent TherapeuticsInc.LexingtonMA 02421USA Department of Drug Metabolism and Pharmacokinetics GenentechA Member of the Roche GroupSouth San FranciscoCA 94080USA Drug Metabolism and Pharmacokinetics Department Bristol-Myers Squibb CompanyPrincetonNJ 08540USA Bioanalysis and Biomarkers Glaxo Smith KlineKing of the PrussiaPA 19406USA Department of Drug Metabolism and Pharmacokinetics Takeda Pharmaceuticals International Co.CambridgeMA 02139USA Ofﬁce of Research and Standards Ofﬁce of Generic DrugsCDERFDASilver SpringMD 20993USA Department of Pharmacology and Toxicology College of PharmacyUniversity of ArizonaTucsonAZ 85721USA Current afﬁliation:Translational Medicine EMD Serono Research&Development InstituteInc.BillericaMA 01821USA Current afﬁliation:Drug Metabolism Gilead Sciences Inc.Foster CityCA 94404USA

Drug metabolism and pharmacokinetics(DMPK) is an important branch of pharmaceutical *** nature of ADME(absorption,distribution,metabolism,excretion) and PK(pharmacokinetics) inquiries during drug discovery and development has evolved in recent years from being largely descriptive to seeking a more quantitative and mechanistic understanding of the fate of drug candidates in biological *** progress has been made in the past decade,not only in the characterization of physiochemical properties of drugs that influence their ADME,target organ exposure,and toxicity,but also in the identification of design principles that can minimize drug-drug interaction(Ddi) potentials and reduce the *** importance of membrane transporters in drug disposition,efficacy,and safety,as well as the interplay with metabolic processes,has been increasingly *** increases in investments on new modalities beyond traditional small and large molecule drugs,such as peptides,oligonucleotides,and antibody-drug conjugates,necessitated further innovations in bioanalytical and experimental tools for the characterization of their ADME *** this review,we highlight some of the most notable advances in the last decade,and provide future perspectives on potential major breakthroughs and innovations in the translation of DMPK science in various stages of drug discovery and development.

关键词： Drug discovery and development New drug application Biologics license application Pharmacokinetics ADME New modalities Model-informed drug development Micro-physiological systems

Assessment of the morphology and mechanical function of the left atrial appendage by real-time three-dimensional transesophageal echocardiography

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Chinese Medical Journal 2012年第19期125卷 3416-3420页

作者： CHEN Ou-di WU Wei-chun JIANG Yong XIAO Ming-hu WANG Hao Department of Echocardiography State Key Laboratory of Cardiovascular Disease Fuwai Hospital National Center for Cardiovascular Diseases Chinese Academy of Medical Sciences and Peking Union Medical College Beijing 100037 China Cardiovascular Institute General Hospital and Academy of Medical Sciences of Guangdong Province Guangzhou Guangdong 510080 China

Background The left atrial appendage （LAA） is an important source of thrombus formation. We investigated the feasibility of the recently developed real-time three-dimensional transesophageal echocardiography （RT3D-TEE） method in assessment of the morphology and function of the LAA. Methods Ninety-six consecutive patients （58 males with a mean age of （43.4±12.5） years） who were referred for 2-dimensional （2D） transesophageal echocardiography （TEE） underwent additional RT3D-TEE. LAA morphology was visualized in multiple views. Orifice size, depth, volumes and ejection fraction （EF） of the LAA, were measured. Results All the patients underwent RT3D-TEE examination without complications. Ninety-two patients （95.8%） had adequate images for visualization and quantitative analysis of the LAA. The LAA exhibited great variability with respect to relative dimensions and morphology. LAA orifice area was （3.8±1.2） cm^2 with a diameter of （2.4±0.9） cm x （1.4±0.6） cm. The mean depth of the LAA was （2.9±0.7） cm. End-diastolic volume （EDV-LAA）, end-systolic volume （ESV-LAA） and EF of the LAA were （6.2±3.7） ml, （4.1±2.8） ml, and 0.35±0.16, respectively. EDV-LAA, ESV-LAA and the orifice area of the LAA in patients with atrial fibrillation （af） were larger than those without af, whereas the EF was smaller in the af patients. Conclusions Defining LAA morphology and quantitative analysis of the size and function of the LAA with superior quality and resolution of images using RT3D-TEE is feasible. This technique may be an ideal tool for guidance of the LAA occlusion procedure. Determination of LAA volumes and volume-derived EF by RT3D-TEE provides new insights into the analysis of LAA function.

关键词： real-time three-dimensional transesophageal echocardiography left atrial appendage function

Decoding the annulus fibrosus cell atlas by scRNA-seq to develop an inducible composite hydrogel:A novel strategy for disc reconstruction

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Bioactive Materials 2022年第8期7卷 350-363页

作者： Han Wang di Wang Beier Luo Dong Wang Haoruo Jia Pandi Peng Qiliang Shang Jianxin Mao Chu Gao Ye Peng Lu Gan Junjie Du Zhuojing Luo Liu Yang Department of Orthopedics Xijing HospitalFourth Military Medical UniversityXi’an710032China Department of Orthopedics Air Force Medical Center100142BeijingChina Department of Spinal Surgery Changhai HospitalNaval Medical UniversityShanghai200433China Medical Research Institute Northwestern Polytechnical UniversityXi’an710072China

Low back pain is one of the most serious public health problems worldwide and the major clinical manifestation of intervertebral disc degeneration(IVDD).The key pathological change during IVDD is dysfunction of the annulus fibrosus(af).However,due to the lack of an in-depth understanding of af biology,the methods to reconstruct the af are very *** this study,the mice af cell atlas were decoded by single-cell RNA sequencing to provide a guide for af *** results first identify a new population of af cells,fibrochondrocyte-like af cells,which synthesize both collagen Ⅰ and collagen Ⅱ and are potential functional cells for af *** to the dual features of the af extracellular matrix,a composite hydrogel based on the acylation of methacrylated silk fibroin with methacrylated hyaluronic acid was *** obtain the ability to stimulate differentiation,the composite hydrogels were combined with a fibrochondrocyte-inducing ***,reconstruction of the af defects,by the novel af stem cell-loaded composite hydrogel,could be observed,its amount of chondroid matrices recovered to 31.7% of af aera which is significantly higher than that in other control *** summary,this study decodes the af cell atlas,based on which a novel strategy for af reconstruction is proposed.

关键词： Single cell RNA-Seq Annulus fibrosus-derived stem cells Lineage tracing Composite hydrogel Annulus fibrosus reconstruction

Effectiveness and safety of antithrombotic strategies in elderly patients with acute myocardial infarction

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World Journal of Cardiology 2020年第11期12卷 513-525页

作者： Elisa Rondano Marzia Bertolazzi Alessandro Galluzzo Ludovica Maltese Paolo Caccianotti Sergio Macciò Stefano Mazza Maria Virginia di Ruocco Serena Favretto Eraldo Occhetta Francesco Rametta Cardiology Department St.Andrea HospitalVercelli 13100Italy

BACKGROUND Elderly patients represent a rapidly growing part of the population more susceptible to acute coronary syndromes and their ***,literature evidence is lacking in this clinical *** To describe the clinical features,in-hospital management and outcomes of“elderly”patients with myocardial infarction treated with antiplatelet and/or anticoagulation *** This study was a retrospective analysis of all consecutive patients older than 80 years admitted to the division of Cardiology of *** Hospital of Vercelli from January 2018 to December 2018 due to ST-elevation myocardial infarction(STEMI)or non-ST elevation myocardial infarction(NSTEMI).Clinical and laboratory data were collected for each patient,as well as the prevalence of previous or in-hospital atrial fibrillation(af).In-hospital management,consisting of an invasive or conservative strategy,and the anti-thrombotic therapy used are *** evaluated at 1 year follow-up included an efficacy ischemic endpoint and a safety bleeding *** Of the 105 patients enrolled(mean age 83.9±3.6 years,52.3%males),68(64.8%)were admitted due to NSTEMI and 37(35.2%)due to *** the STEMI patients,34(91.9%)underwent coronary angiography and all of them were treated with percutaneous coronary intervention(PCI);among the NSTEMI patients,42(61.8%)were assigned to an invasive strategy and 16(38.1%)of them underwent a *** significant difference between the groups was found concerning the prevalence of previous or in-hospital de-novo af.10.5%of the whole population received triple antithrombotic therapy and 9.5%single antiplatelet therapy plus oral anticoagulation(OAC),with no significant difference between the subgroups,although a higher number of STEMI patients received dual antiplatelet therapy without OAC as compared with NSTEMI patients.A low rate of in-hospital death(5.7%)and 1-year cardiovascular death(3.3%)was ***(7.8%)patients experienced

关键词： Antiplatelet therapy Anticoagulant therapy Elderly patients Safety Acute myocardial infarction

基于LSTM特征提取的有限新息率畸变信号重构

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电子学报 2022年第1期50卷 217-225页

作者：刘狄钱慧王中风福州大学物理与信息工程学院福建福州350108 南京大学电子科学与工程学院江苏南京210023

有限新息率(Finite Rate of Innovation,FRI)采样利用已知的信号波形结构实现信号的亚奈奎斯特率采样,在宽带信息系统应用中具有广泛的前景.但是,在实际的信息系统中,信号波形结构常常因噪声、远距离传输等非理想因素而发生畸变,从而导... 详细信息

有限新息率(Finite Rate of Innovation,FRI)采样利用已知的信号波形结构实现信号的亚奈奎斯特率采样,在宽带信息系统应用中具有广泛的前景.但是,在实际的信息系统中,信号波形结构常常因噪声、远距离传输等非理想因素而发生畸变,从而导致FRI重构失败.本文依据波形再生的原理,提出了一种基于长短时记忆(Long and Short-Term Memory,LSTM)自动编码器的FRI重构方法.该方法利用LSTM自动编码器取代FRI采样系统中的采样核函数,通过离线训练获取畸变信号的未知波形结构,从而将波形序列投影为狄拉克特征序列,实现了波形畸变信号的FRI采样及重构.结果表明,本文的方法可以借助经典的零化滤波器有效地重构由于多径效应而发生畸变的FRI波形信号.

关键词：亚奈奎斯特率采样有限新息率波形再生长短时记忆自动编码器零化滤波器

从人口学的视角看中国“三农”问题——试论中国农村人口数量变化与社会经济发展的交互影响

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人口学刊 2005年第6期27卷 8-12页

作者：王涤顾宝昌杭州师范学院人口所浙江杭州310012 中国计划生育协会北京100029

中国农村人口数量的减少,是中国工业化、城市化的必然结果之一,有利于缓解农村人口过多的压力,有利于“三农”问题的解决,是我国经济发展、社会进步在人口领域的反映,农村人口数量与结构的变化与农村社会经济发展具有一定的互动性。

关键词：人口学农村人口 “三农”问题人口普查