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The effects of genotype on histopathological alterations in hypertrophic obstructive cardiomvopathy patients
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作者 Kunlun Yin Yi Ma +10 位作者 Hao Cui Yang Sun Tianjiao Li Weizhen Zhou Hang Yang Wenke Li Bianmei Han Xuewen Liu Hongyue Wang Shuiyun Wang Zhou Zhou 《中国循环杂志》 CSCD 北大核心 2018年第S01期126-126,共1页
Objective Genotype has been related to specific phenotype of hypertrophic cardiomyopathy (HCM) patients, but its relationship with histopathological alterations remains uncertain. The purpose of the study is to explor... Objective Genotype has been related to specific phenotype of hypertrophic cardiomyopathy (HCM) patients, but its relationship with histopathological alterations remains uncertain. The purpose of the study is to explore the relationship between the genotype and histopathological alterations under different genetic Backgrounds. 展开更多
关键词 HYPERTROPHIC cardiomyopathy(HCM) HISTOPATHOLOGICAL alterations different genetic BACKGROUNDS
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Efficacy Differences of First-line EGFR-TKIs Alone vs in Combination with Chemotherapy in Advanced Lung Adenocarcinoma Patients with Sensitive EGFR Mutation and Concomitant Non-EGFR Genetic Alterations 被引量:1
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作者 Guowei ZHANG Ruirui CHENG +7 位作者 Yuanyuan NIU Huijuan WANG Xiangtao YAN Mina ZHANG Xiaojuan ZHANG Jinpo YANG Chunhua WEI Zhiyong MA 《中国肺癌杂志》 CAS CSCD 北大核心 2022年第9期651-657,共7页
Background and objective:Epidermal growth factor receptor(EGFR)mutations are often associated with non-EGFR genetic alterations,which maybe a reason for the poor efficacy of EGFR tyrosine kinase inhibitors(TKIs).Here ... Background and objective:Epidermal growth factor receptor(EGFR)mutations are often associated with non-EGFR genetic alterations,which maybe a reason for the poor efficacy of EGFR tyrosine kinase inhibitors(TKIs).Here we conducted this study to explore whether EGFR-TKIs combined with chemotherapy would benefit advanced lung adenocarcinoma patients with both sensitive EGFR mutation and concomitant non-EGFR genetic alterations.Materials and methods:Cases of advanced lung adenocarcinoma with EGFR mutation combined with concomitant nonEGFR genetic alterations were retrospectively collected.And the patients were required to receive first-line EGFR-TKIs and chemotherapy combination or EGFR-TKIs monotherapy.Demographic,clinical and pathological data were collected,and the electronic imaging data were retrieved to evaluate the efficacy and time of disease progression.Survival data were obtained through face-to-face or telephone follow-up.The differences between the two groups in objective response rate(ORR),disease control rate(DCR),progression-free survival(PFS)and overall survival(OS)were investigated.Results:107 patients were included,including 63 cases in the combination group and 44 cases in the monotherapy group.The ORR were 78%and 50%(P=0.003),and DCR were 97%and 77%(P=0.002),respectively.At a median follow-up of 13.7 mon,a PFS event occurred in 38.1%and 81.8%of patients in the two groups,with median PFS of18.8 mon and 5.3 mon,respectively(P<0.000,1).Median OS was unreached in the combination group,and 27.8 mon in the monotherapy group(P=0.31).According to the Cox multivariate regression analysis,combination therapy was an independent prognostic factor of PFS.Conclusion:In patients with EGFR-mutant advanced lung adenocarcinoma with concomitant non-EGFR genetic alterations,combination of TKIs and chemotherapy was significantly superior to EGFR-TKIs monotherapy,which should be the preferred treatment option. 展开更多
关键词 Lung neoplasms EGFR mutation Concomitant genetic alteration Targeted therapy CHEMOTHERAPY
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Mechanobiology of airway smooth muscle cells and its regulations in pathogenesis of asthma
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作者 Linhong Deng 《医用生物力学》 EI CAS CSCD 北大核心 2013年第S1期104-106,共3页
Introduction Excessive narrowing of airways is the most important pathological feature of asthma,but its mechanism remains puzzling.One certain thing is that the contraction of airway smooth muscle(ASM)ultimately caus... Introduction Excessive narrowing of airways is the most important pathological feature of asthma,but its mechanism remains puzzling.One certain thing is that the contraction of airway smooth muscle(ASM)ultimately causes airway narrowing,thus both structural and functional alterations of airway smooth muscle(ASM)are thought as common final pathway responsible for the bronchial hyperresponsiveness(BHR),the hall mark of asthma.Many chemical and physical factors such as air pollutants,inflammatory agents,mechanical and geometrical properties of the microenvironment could influence structure and/or function of ASM cells.In addition,some re- 展开更多
关键词 airway ASTHMA PATHOGENESIS BRONCHIAL REGULATIONS OVALBUMIN alterations contraction ultimately cytometry
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Opportunity and challenge of target-based therapy for leukemia:lessons from APL and CML
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作者 CHEN Guo-qiang(Department of Pathophysiology,Key Laboratory of Cell Differentiation and Apoptosis of Chinese Ministry of Education & Chemical Biology Division of Shanghai Universities E-Institutes,Shanghai Jiaotong University School of Medicine,Shanghai 200025,China) 《中国病理生理杂志》 CAS CSCD 北大核心 2010年第A10期1946-1947,共2页
In the past two decades,target-based therapies achieve the great success in adult leukemia.Two typical examples are the applications of all-trans retinoic acid(ATRA)/arsenic trioxide(ATO)and specific tyrosine kinase i... In the past two decades,target-based therapies achieve the great success in adult leukemia.Two typical examples are the applications of all-trans retinoic acid(ATRA)/arsenic trioxide(ATO)and specific tyrosine kinase inhibitor imatinib respectively in acute promyelocytic leukemia(APL)and chronic myeloid leukemia(CML).These successful clinical practices originated from our understanding on 展开更多
关键词 TRIOXIDE MYELOID ATRA arsenic originated challenge GRANULOCYTE alterations targeting LYMPHOID
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Muscovite 40Ar-39Ar age and its geological significance in Zhuxi W(Cu) deposit, northeastern Jiangxi 被引量:9
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作者 OUYANG Yong-peng WEI Jin +5 位作者 LU Yi ZHANG Wei YAO Zai-yu RAO Jian-feng CHEN Guo-hua PAN Xiao-fei 《Journal of Central South University》 SCIE EI CAS CSCD 2019年第12期3488-3501,共14页
The Zhuxi W(Cu)skarn deposit,the world’s largest tungsten deposit is newly discovered in Jingdezhen city,northeastern Jiangxi province,China.It mainly occurs near the contact zone between the Yanshanian granites and ... The Zhuxi W(Cu)skarn deposit,the world’s largest tungsten deposit is newly discovered in Jingdezhen city,northeastern Jiangxi province,China.It mainly occurs near the contact zone between the Yanshanian granites and the Late Paleozoic carbonate rocks.Three types of mineralization including skarn type,altered granite type and quartz vein veinlet type orebodies have been observed.In this study,the 40Ar 39Ar age of hydrothermal muscovite coexisting with copper mineralization in the altered granite type orebody formed near the unconformity interface is determined by step-heating technology using CO2 laser.The plateau age,isochron age,and inverse isochron age of muscovite are(147.39±0.94)Ma,(147.2±1.5)Ma,and(147.1±1.5)Ma,respectively.These ages are almost identical to the ages of ore-related granite and other mineralization types in the Zhuxi W(Cu)deposit,indicating that the Cu mineralizations occurred at the shallow depth and near the unconformity interface are contemporaneous during the Late Jurassic.This further suggested that the acompanied W and Cu mineralization in the Zhuxi W(Cu)deposit which may be controlled by the magma source is enriched in both W and Cu. 展开更多
关键词 MUSCOVITE 40Ar 39Ar age altered granite-type orebody Zhuxi W(Cu)deposit northeastern Jiangxi
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Ilvaite as a thermodynamic recorder of multistage retrograde alteration in large Galinge skarn Fe deposit, western China 被引量:2
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作者 YU Miao Jeffrey MDICK +5 位作者 MAO Jing-wen FENG Cheng-you LI Bin LU An-huai ZHU Yong-feng LAI Jian-qing 《Journal of Central South University》 SCIE EI CAS CSCD 2019年第12期3534-3550,共17页
The ilvaite-bearing skarn associations in the Galinge skarn deposit were studied to determine their physicochemical formation conditions.A thermodynamic model setting pressure of 50 MPa(Pf=Ps=50 MPa)was set up to trac... The ilvaite-bearing skarn associations in the Galinge skarn deposit were studied to determine their physicochemical formation conditions.A thermodynamic model setting pressure of 50 MPa(Pf=Ps=50 MPa)was set up to trace the skarn evolution.Petrographic evidence for replacement of garnet and magnetite by ilvaite in the early retrograde stage(Stage I)combined with thermodynamic modeling suggests that the alteration may have occurred at 400470°C under moderately high fO withΔlgfO(HM)ranges from 4 to 4.2.The model is based on a maximum 22 pressure of 50 MPa calculated from magmatic amphibole geobarometer.The continuous breakdown of ilvaite with quartz to form ferro-actinolite and magnetite occur in the late retrograde stage(Stage II).The reactions occurred at 400440°C under moderate fO(ΔlgfO(HM):4 to 4.4).In Stage III,the breakdown of ilvaite to form calcite,pyrite 22 and ferroactinolite depends on XCO which can be estimated to be in a range of 0.005 to 0.05,and the reaction would 2 occur at higher temperatures with increasing XCO.Under these conditions,the breakdown occurs at 270350°C and 2 low fO(ΔlgfO(HM):up to 5.2).The thermodynamic model for continuous evolution from Stage I to Stage III 22 completely records the conditions of the retrograde alteration,which is inconsistent with the thermobarometry imprints of fluid inclusions.Therefore,the petrography and phase relations of ilvaite are useful indicators of reaction conditions in various skarn deposit types. 展开更多
关键词 Galinge skarn deposit ILVAITE retrograde alteration thermodynamic properties
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Spectrum spatial structure characteristic analysis of remote sensing alteration information and interference factors 被引量:1
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作者 杨自安 彭省临 +3 位作者 朱谷昌 石菲菲 邹林 张远飞 《Journal of Central South University》 SCIE EI CAS 2009年第4期647-652,共6页
Based on the statistical characteristics of remote sensing data, the spatial geometric structure characteristics of spectral data and distribution of background, interference and alteration information in characterist... Based on the statistical characteristics of remote sensing data, the spatial geometric structure characteristics of spectral data and distribution of background, interference and alteration information in characteristic space were researched through the analysis of two-dimensional and three-dimensional scatter diagrams. The results indicate that the hyper-space of remote sensing multi-data aggregation belongs to low-dimensional geometric structure, i.e. hyperplane form, and anomalous point groups including alteration information usually dissociate out of hyperplane. Scatter diagrams of remote sensing data band are mainly presented as two distribution forms of single-ellipse and dual-ellipse. Clarifying the relations of three objects of background, disturbance and alteration information in remote sensing images provides an important technical thought and guidance for accurately detecting and extracting remote sensing alteration information. 展开更多
关键词 remote sensing data alteration information BACKGROUND interference factor spectrum spatial structure scatter diagram
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Method for electromagnetic detection satellites scheduling based on genetic algorithm with alterable penalty coefficient 被引量:1
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作者 Jun Li Hao Chen +2 位作者 Zhinong Zhong Ning Jing Jiangjiang Wu 《Journal of Systems Engineering and Electronics》 SCIE EI CSCD 2014年第5期822-832,共11页
The electromagnetic detection satellite (EDS) is a type of earth observation satellites (EOSs). The Information collected by EDSs plays an important role in some fields, such as industry, science and military. The... The electromagnetic detection satellite (EDS) is a type of earth observation satellites (EOSs). The Information collected by EDSs plays an important role in some fields, such as industry, science and military. The scheduling of EDSs is a complex combinatorial optimization problem. Current research mainly focuses on the scheduling of imaging satellites and SAR satellites, but little work has been done on the scheduling of EDSs for its specific characteristics. A multi-satellite scheduling model is established, in which the specific constrains of EDSs are considered, then a scheduling algorithm based on the genetic algorithm (GA) is proposed. To deal with the specific constrains of EDSs, a penalty function method is introduced. However, it is hard to determine the appropriate penalty coefficient in the penalty function. Therefore, an adaptive adjustment mechanism of the penalty coefficient is designed to solve the problem, as well as improve the scheduling results. Experimental results are used to demonstrate the correctness and practicability of the proposed scheduling algorithm. 展开更多
关键词 electromagnetic detection satellite (EDS) scheduling genetic algorithm (GA) constraint handling penalty function method alterable penalty coefficient.
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Spectrum of fluid/rock alteration in the IOCG system of eastern Gawler Craton
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作者 Cheng-lin YANG David Giles +1 位作者 Adrian Fabris Caroline Forbes 《矿物学报》 CAS CSCD 北大核心 2015年第S1期1069-,共1页
In this paper we present petrology and geochemistry from a range of metasomatically altered rocks within the Eastern Gawler Craton mineralised province of South Australia.The rocks represent four protolith types;grani... In this paper we present petrology and geochemistry from a range of metasomatically altered rocks within the Eastern Gawler Craton mineralised province of South Australia.The rocks represent four protolith types;granite,basalt,non-carbonate metasediment and calc-silicate metasediment.Alteration paragenesis varies in intensity and between the protolith types.I.The alteration paragenesis of granites has the first pervasive chlorite and the second filled hematite with two generations of chalcopyrite.After the 展开更多
关键词 ALTERATION carbonate Australia geochemistry ROCK granite BASALT ALTERED filled PERVASIVE
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Bisphosphonate rescue post-traumatic osteoarthritis by promoting the calcium signaling in chondrocytes
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作者 Yilu Zhou Wen Li +2 位作者 Liyun Wang Christopher Price X.Lucas Lu 《医用生物力学》 EI CAS CSCD 北大核心 2013年第S1期56-60,共5页
Introduction Post-traumatic osteoarthritis(PTOA)is a long-term adverse consequence of joint trauma,e.g.,meniscus or ligament tears,which are among the most common injuries for young adults with excessive physical acti... Introduction Post-traumatic osteoarthritis(PTOA)is a long-term adverse consequence of joint trauma,e.g.,meniscus or ligament tears,which are among the most common injuries for young adults with excessive physical activities,such as athletes and military employees.Currently,few preventive treatments exist for PTOA,with typical outcomes being gradual cartilage degeneration and eventual loss of joint function.Apoptosis and altered etabolism of chondrocytes,the sole cell type in cartilage,may be responsible for the development of PTOA in a subset of patients without traumatic cartilage destruction but with persistent altered joint loading post-trauma,which is the focus of this study. 展开更多
关键词 TRAUMATIC cartilage LIGAMENT altered degeneration Apoptosis military destruction CONSEQUENCE MEDIAL
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Cyclic mechanical stretch regulates MMPs and TIMPs expression in corneal fibroblasts
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作者 Chengxing Liu Pengfei Feng +2 位作者 Xiaona Li Xiaojun Wang Weiyi Chen 《医用生物力学》 EI CAS CSCD 北大核心 2013年第S1期7-8,共2页
Laser in situ keratomileusis(LASIK)is a relatively new ophthalmic procedure in refractive surgery.It involves the use of a microkeratome to create a thin corneal flap followed by excimer laser ablation of the corneal ... Laser in situ keratomileusis(LASIK)is a relatively new ophthalmic procedure in refractive surgery.It involves the use of a microkeratome to create a thin corneal flap followed by excimer laser ablation of the corneal stroma and repositioning of the flap.However,complications are bound to occur when a surgical procedure is performed with increasing frequency.In some cases,serious complications such as keratectasia occurred.Risk factors for corneal keratectasia include a thin cornea at baseline,thick corneal flap,excessive ablation,irregular corneal thickness,diverse ablation rates,preexisting keratoconus or form fruste keratoconus,and high intraocular pressure(IOP)~[1].It is evident from incisional refractive surgery that the cornea is not mechanically inert.The mechanical environment of the central corneal tissue is also altered un- 展开更多
关键词 CORNEAL KERATOMILEUSIS ablation INTRAOCULAR STRETCH altered refractive diverse TIMPS mechanically
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Simulation of rock mass balance of two typical altered rocks in Wulong gold deposit of Liaoning, China
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作者 WEI Jun-hao LIU Cong-qang +1 位作者 LI Zhi-de ZHAO Yong-xin 《Journal of Central South University》 SCIE EI CAS 2001年第3期197-202,共6页
Wulong gold deposit hosted in granite and fine-grained d io rite dikes, is a typical gold deposit of quartz vein type. Granite and fine-gra ined diorite dikes in the ore deposit were altered by metallogenic fluid. Bas... Wulong gold deposit hosted in granite and fine-grained d io rite dikes, is a typical gold deposit of quartz vein type. Granite and fine-gra ined diorite dikes in the ore deposit were altered by metallogenic fluid. Based on the altered zoning, the samples of petrochemistry were collected and major an d trace elements were analyzed systematically. Calculation of rock mass balance shows that the major elements (SiO 2, K 2O, P 2O 5, Fe 2O 3) in the two ty pical altered rocks are clearly added into the altered system, and that trace el ements (V, Y, Zr, Ni, Co, Sr) assume an increasing and decreasing tendencies in the altered granite and altered diorite dike, respectively. The fluid/rock ratio s are 30.17-181.00 and 115.44-692.67 respectively for altered granite and alte red diorite dike, they have profoundly effects on metallogenesis. 展开更多
关键词 ALTERED ROCK ROCK mass BALANCE WULONG gold deposit
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Programmable extracellular matrix mimics for regenerative medicine
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作者 Yong Wang 《医用生物力学》 EI CAS CSCD 北大核心 2013年第S1期72-74,共3页
The extracellular matrix(ECM)plays an important role of determining the functionalities of cells and tissues.Thus,biomaterials that can recapitulate the biological and mechanical functionalities of the ECM are promisi... The extracellular matrix(ECM)plays an important role of determining the functionalities of cells and tissues.Thus,biomaterials that can recapitulate the biological and mechanical functionalities of the ECM are promising in the treatment of numerous complicated human diseases.Great efforts have been made to develop a variety of smart ECM mimics that can alter their functionalities dynamically in response to physical stimulation(e.g.,temperature variation).However,it remains challenging to develop a biomimetic ECM that can undergo functional changes regulated at the biomolecular level in the way natural ECMs are regulated. 展开更多
关键词 REGENERATIVE hydrogel challenging dynamically stimulation NUMEROUS ALTER determining biomaterial MIMIC
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Diagenetic Alteration Modes of the Deep Formation of Paleogene of Chezhen Depression,Bohai Bay Basin
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作者 Jing Yuan,Yuxin Guo,Xin Chen College of Geoscience and Information,China University of Petroleum,Qingdao 266555,China. 《地学前缘》 EI CAS CSCD 北大核心 2009年第S1期132-132,共1页
The deep buried clastic formation of Paleogene is an important hydrocarbon reservoir in the Chezhen depression.There are two types of diagenetic alteration modes in it.The first mode is weak compaction, strong cementa... The deep buried clastic formation of Paleogene is an important hydrocarbon reservoir in the Chezhen depression.There are two types of diagenetic alteration modes in it.The first mode is weak compaction, strong cementation,fracturing and weak dissolution in the sandstone and conglomerate on the steep slope of the depression.The reservoirs are cemented mainly by carbonate minerals strongly。 展开更多
关键词 DIAGENESIS DIAGENETIC ALTERATION mode porosity evolution DEEP formation PALEOGENE Chezhen DEPRESSION Bohai Bay basin
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Retroviral-mediated IL-2 and IFN-γ gene transfer in human bladder tumor cells
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作者 X. Wang, D.X. Feng, J. Xin, B.F. Shen, C.H. Li Department of Molecular Immunology, Beijing Institute of Basic Medical Sciences, Beijing, 100850 《中国实验血液学杂志》 CAS CSCD 1997年第3期305-305,共1页
Tumor cells may escape immune surveillance mainlyby (1) down regulation of major histocompatibilitycomplex (MHC) molecules or alteration of antigen-processing pathways; (2) low-level of cytokines in thevicinity of the... Tumor cells may escape immune surveillance mainlyby (1) down regulation of major histocompatibilitycomplex (MHC) molecules or alteration of antigen-processing pathways; (2) low-level of cytokines in thevicinity of the tumor, which can’t activate immunosystemeffectively. Recent studies have shown that geneticallyengineered tumor cells expressing cytokines such as IL-2IFN-γ can induce greater CTL activity and activate NK,LAK and TIL. Besides IFN-γ can enhance the 展开更多
关键词 BLADDER alteration surveillance expressing ACTIVATE cytokines ESCAPE SECRET analysed eater
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Genetic immunotherapy ot hepatocellular carcinoma ( HCC) with adenovirus or retrovirus vectors carrying interleukin 12 ( IL-12 ) or costimulatory molecule B7-1
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作者 Cheng Qian, Yonglian Sun, Xiaoming Xie, Roberto Bilbao, Jesus PrietoDepartment of Internal Medicine, University Clinic and School of Medicine, University of Navarra, Pamplona,Spain 《中国实验血液学杂志》 CAS CSCD 1997年第3期313-314,共2页
The progressive growth of tumors in the presence ofan intact immune system suggests that immunemechanisms may have failed to defend the host fromtumor cells. One therapeutic approach to cnhanceeffective immune respons... The progressive growth of tumors in the presence ofan intact immune system suggests that immunemechanisms may have failed to defend the host fromtumor cells. One therapeutic approach to cnhanceeffective immune responses is to introduce the immuno-regulatory genes that alter the local immunologicalmicroenvironment and increase immunogenecity of 展开更多
关键词 IMMUNOTHERAPY interleukin ADENOVIRUS progressive carrying alter expressing antitumor FAILED INTACT
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The rearrangement and amplification of C-erbB-1 gene in the development of MDS and their clinical significance in diagnoses and prognoses
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作者 Jianping Hao, Baozhang Feng, Jianling Lei, Zonghong Shao, Chongli Yang Institute of Hematology, Chinese Academy of Medical Sciences, Tianjin 300020 《中国实验血液学杂志》 CAS CSCD 1997年第3期331-331,共1页
In order to explore whether the rearrangement and amplification of C-erbB-l gene were associatedwith the development of MDS and their clinicalsignificance in diagnoses and prognoses. digitoxin-labelled oligonucleotide... In order to explore whether the rearrangement and amplification of C-erbB-l gene were associatedwith the development of MDS and their clinicalsignificance in diagnoses and prognoses. digitoxin-labelled oligonucleotide probes were used to detect 展开更多
关键词 AMPLIFICATION REARRANGEMENT probes ALTER SUSPECTED
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Gene therapy for liver tumours
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作者 Nagy A.Habib FRCS ChM 《中国实验血液学杂志》 CAS CSCD 1997年第3期285-286,共2页
Liver tumours are among the most commonmalignancies worldwide. The international incidenceof the disease is about l million cases per year (male:femalc, 4: 1 ). These include primary and secondarytumours. Cancer is kn... Liver tumours are among the most commonmalignancies worldwide. The international incidenceof the disease is about l million cases per year (male:femalc, 4: 1 ). These include primary and secondarytumours. Cancer is known to be a genetic disease thatinvolves the alteration of activity of the products of atleast 2 genes, due to mutation (s) and/or otherfactors, e. g., the presence of viral oncoproteins. Thegenes most affected are the tumour suppressor 展开更多
关键词 alteration TUMOUR SUPPRESSOR mutation TRANSFECTION PLASMID METASTASES MORBIDITY spontaneously naked
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Characterization of Hydrothermal Alteration Mineralogy and Pathfinder Elements in the Exploration for gold in North Mara mines,Tanzania
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作者 Emmanuel Kazimoto Justinian R.Ikingura Scott Halley 《地学前缘》 EI CAS CSCD 北大核心 2009年第S1期165-165,共1页
A combination of mineralogical and multielement analyses was used to characterize the hydrothermal alteration,pathfinder elements and their distribution within the gold deposits in North Mara mines,the Archean Musoma-... A combination of mineralogical and multielement analyses was used to characterize the hydrothermal alteration,pathfinder elements and their distribution within the gold deposits in North Mara mines,the Archean Musoma-Mara greenstone belt,Tanzania. The aim was to evaluate the suitability of alteration mineral assemblages and composition as an effective exploration marker for fingerprinting 展开更多
关键词 GOLD EXPLORATION ARCHEAN Musoma Mara GREENSTONE belt NORTH Mara mines short wavelength infrared spectrometry hydrothermal alteration
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Combined OVX and Concurrent Mechanical Disuse Induced Osteocytes Morphological Alteration, and Mitigation by Mechanobiology and Sclerostin Antibody
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作者 Tony Zhang Yixian Qin 《医用生物力学》 EI CAS CSCD 北大核心 2019年第A01期29-29,共1页
Osteoporosis and osteopenia are major health issues that mainly affect elderly people,women after menopause and immobilized patients.Our previous studies have proved that sclerostin antibody(Scl-Ab)can dramatically en... Osteoporosis and osteopenia are major health issues that mainly affect elderly people,women after menopause and immobilized patients.Our previous studies have proved that sclerostin antibody(Scl-Ab)can dramatically enhance bone formation and reduce bone resorption in a severe osteoporosis rat model with the combination of ovariectomy(OVX)and hindlimb immobilization(HLS).However,the mechanism in the cellular level is unclear.The objective of this study is to assess the effect of Scl-Ab on osteocytic morphology change in a combined OVX and HLS rat model via quantification of long-and short-axis and the ratio and osteocyte volume in midshaft cortical bone.Four-month-old virgin female SD rats were divided into 7 groups(n=11 per group):Sham+Veh,Sham+HLS+Veh,Sham+HLS+Scl-Ab,OVX+Veh,OVX+Scl-Ab,OVX+HLS+Veh,OVX+HLS+Scl-Ab.HLS was performed 2 weeks after sham or OVX surgery;and treatment was initiated at the time of HLS.Scl-Ab(25 mg/kg)or vehicle was subcutaneously injected twice per week for 5 weeks.Femurs were harvested at the end of study and embedded in PMMA and polished for SEM imaging.Cortical bone mid shaft osteocyte number per bone area was quantified under 1K magnification;the ratios between long axis and short axis of osteocytes were quantified under 2K magnification;osteocyte dendrite number and surface area were quantified under 5K magnification.Osteocyte dendrites width was quantified using 10K magnification.All the quantification was done by ImageJ.We have reported that multiple morphological and structural changes in osteocytes,including a decreased osteocyte density and reduced osteocyte dendrite number in HLS,OVX or the combination group and Scl-Ab’s ability to abolish these unfavorable alterations.We continued our SEM analysis on osteocytes and discovered that the oval shape of osteocyte under HLS,OVX or HLS+OVX has been distorted toward a spindle-like shape,with relatively longer long axis and shorter short axis,assuming osteocyte has a perfect spheroid shape.The ratio between long-and short-axis showed an increased trend in OVX and HLS condition,but Scl-Ab inhibited these increases(P<0.001,P<0.01,respectively).The volume decreased in HLS,OVX group,but Scl-Ab maintained osteocytes’volume in HLS condition(P<0.001).It indicates that cortical bone responds to HLS and/or OVX and Scl-Ab treatment via multiple cellular mechanisms,including density of osteocyte,dendrite number and osteocyte shape.The change of osteocyte shape may imply an altered cytoskeleton system within osteocyte and a subsequent disruption of mechanosensing ability for osteocyte,which lead to bone loss macroscopically.These data suggest Scl-Ab’s therapeutic potential could be related with its ability to maintain osteocyte’s morphologic and structural changes induced by OVX,HLS or both. 展开更多
关键词 OVX HLS Mitigation by MECHANOBIOLOGY SCLEROSTIN Antibody SCLEROSTIN Combined OVX and Concurrent Mechanical DISUSE Induced OSTEOCYTES Morphological ALTERATION
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