Experimental hematology最新文献

FT-4202, a selective pyruvate kinase R activator for sickle cell disease. 治疗镰状细胞病的选择性丙酮酸激酶 R 激活剂 FT-4202。

IF 2.5 4区医学

Experimental hematology Pub Date : 2024-11-14 DOI: 10.1016/j.exphem.2024.104673

Anna Ericsson, David J Richard, Erik Wilker, Jr David R Lancia, Shawn Fessler, Paul Troccolo, Xiaozhang Zheng, Angela Toms, Christopher Dinsmore, Lili Yao, Frans A Kuypers, Sandra Larkin, Douglas Marcotte, Keertik Fulzele, Maria Ribadeneira, Sylvie M Guichard, Gary Marshall

{"title":"FT-4202, a selective pyruvate kinase R activator for sickle cell disease.","authors":"Anna Ericsson, David J Richard, Erik Wilker, Jr David R Lancia, Shawn Fessler, Paul Troccolo, Xiaozhang Zheng, Angela Toms, Christopher Dinsmore, Lili Yao, Frans A Kuypers, Sandra Larkin, Douglas Marcotte, Keertik Fulzele, Maria Ribadeneira, Sylvie M Guichard, Gary Marshall","doi":"10.1016/j.exphem.2024.104673","DOIUrl":"https://doi.org/10.1016/j.exphem.2024.104673","url":null,"abstract":"<p><p>Anemia in patients with sickle cell disease (SCD) increases 2,3-diphosphoglycerate (2,3-DPG), decreasing hemoglobin-oxygen (Hb-O<sub>2</sub>) affinity to improve oxygen offloading and promote hemoglobin polymerization (sickling) of red blood cells (RBCs). We report the discovery of FT-4202, an investigational, selective pyruvate kinase type-R (PKR) activator with a multimodal mechanism of action and potential to increase ATP and decrease 2,3-DPG, resulting in increased Hb-O<sub>2</sub> affinity, decreased Hb polymerization, and improved RBC health. FT-4202 was identified via structure-enabled lead optimization medicinal chemistry using X-ray crystallography, molecular modeling, and thermal shift assays. FT-4202, an allosteric PKR activator, stabilizes the tetrameric enzyme and increases PKR activity in human and mouse RBCs in vitro. Seven-day oral administration of FT-4202 in Berkeley SCD mice reduced 2,3-DPG, increased Hb-O<sub>2</sub> affinity, and reduced RBC sickling versus control. There were no adverse in vitro safety findings. FT-4202 offers a therapeutic opportunity to modify the course of SCD.</p>","PeriodicalId":12202,"journal":{"name":"Experimental hematology","volume":" ","pages":"104673"},"PeriodicalIF":2.5,"publicationDate":"2024-11-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142644307","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Structural diversity and function of the granulocyte colony-stimulating factor in medaka fish. 青鳉体内粒细胞集落刺激因子的结构多样性与功能

IF 2.5 4区医学

Experimental hematology Pub Date : 2024-11-13 DOI: 10.1016/j.exphem.2024.104672

Ayame Ogawa, Shungo Konno, Satoshi Ansai, Kiyoshi Naruse, Takashi Kato

{"title":"Structural diversity and function of the granulocyte colony-stimulating factor in medaka fish.","authors":"Ayame Ogawa, Shungo Konno, Satoshi Ansai, Kiyoshi Naruse, Takashi Kato","doi":"10.1016/j.exphem.2024.104672","DOIUrl":"https://doi.org/10.1016/j.exphem.2024.104672","url":null,"abstract":"<p><p>Diversity in the granulocyte repertoire, including neutrophils, basophils, and eosinophils, has been reported in vertebrate species. Medaka fish (Oryzias latipes) have only neutrophils; however, the storage pool of granulopoiesis tissues and the molecular mechanism of granulopoiesis in medaka fish have not been explored. Granulocyte colony-stimulating factor (G-CSF) is a cytokine responsible for neutrophil differentiation, survival, and proliferation. We performed in silico analysis to molecularly characterize the medaka G-CSF and G-CSF receptor (G-CSFR) genes. This study showed that medaka G-CSF differs considerably from human and mouse G-CSF in terms of the primary protein structure; however, the predicted tertiary structure was largely conserved. Analyses of lipopolysaccharide stimulation and G-CSF knockout and overexpression in medaka revealed that G-CSF mobilizes neutrophils into the peripheral blood. The analysis of G-CSF-deficient medaka revealed that G-CSF is involved in erythropoiesis. These findings represent an important first step toward understanding granulocyte hematopoiesis in non-mammalian species.</p>","PeriodicalId":12202,"journal":{"name":"Experimental hematology","volume":" ","pages":"104672"},"PeriodicalIF":2.5,"publicationDate":"2024-11-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142638408","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Platelet ultrastructural changes stored at room temperature versus cold storage observed by electron microscopy and structured illumination microscopy. 用电子显微镜和结构照明显微镜观察血小板在室温储存与低温储存下的超微结构变化。

IF 2.5 4区医学

Experimental hematology Pub Date : 2024-11-07 DOI: 10.1016/j.exphem.2024.104671

Yang Sun, Shunli Gu, Yan Ma, Aowei Song, Lili Xing, Jiameng Niu, Ru Yang, Xiaoyu Hu, Wenhua Wang, Ting Ma, Fenfang Tian, Liqin Wang, Xinxin Xie, Xiaofeng Huang, Wen Yin, Jiangcun Yang

{"title":"Platelet ultrastructural changes stored at room temperature versus cold storage observed by electron microscopy and structured illumination microscopy.","authors":"Yang Sun, Shunli Gu, Yan Ma, Aowei Song, Lili Xing, Jiameng Niu, Ru Yang, Xiaoyu Hu, Wenhua Wang, Ting Ma, Fenfang Tian, Liqin Wang, Xinxin Xie, Xiaofeng Huang, Wen Yin, Jiangcun Yang","doi":"10.1016/j.exphem.2024.104671","DOIUrl":"https://doi.org/10.1016/j.exphem.2024.104671","url":null,"abstract":"<p><p>Our study seeks to provide a theoretical foundation for the clinical use of Cold-stored platelets (CSPs) by interpreting ultrastructural images and quantitatively analyzing structural changes. CSPs, room temperature-stored platelets (RTPs), and delayed cold stored platelets(Delayed-CSPs) were continuously observed using scanning electron microscopy and transmission electron microscopy at 8 time points. Super-resolution fluorescence microscopy was employed to observe changes in platelet microtubules and mitochondrial structure and function, while platelet counts, metabolism, and relevant functional indicators were measured concurrently. Quantitative statistical analysis of platelet size, morphology, canalicular systems, and five organelles was performed under electron microscopy. CSPs stored for 1 day, platelet shape changed from circular or elliptical to spherical, with size decreasing from 2.8 × 2.2µm to 2.0 × 2.0µm. CSPs occurred wrinkling and reorganization of platelet microtubule proteins, with organelles aggregating towards the central region. CSPs stored for 14 days and Delayed-CSPs for 10 days exhibited numerous structurally intact and active cells. The structure-intact active cells in both group were 92% . RTPs stored for 5 and 7 days showed minimal changes in size, a normal microtubule skeleton, and were primarily in a resting state. However, RTPs stored for 10 and 14 days displayed swelling, irregular disintegration of the microtubule skeleton, and the presence of membranous structures and vacuolated cells,the structure-intact active cells was only 45% and 7%, respectively. Our findings confirmed that the maximum storage time of platelets was 5-7 days for RTPs, within 10 days for Delayed-CSPs, and 14 days for CSPs.</p>","PeriodicalId":12202,"journal":{"name":"Experimental hematology","volume":" ","pages":"104671"},"PeriodicalIF":2.5,"publicationDate":"2024-11-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142617211","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Efficacy and safety of avatrombopag in combination with standard immunosuppressive therapy for severe aplastic anemia 阿伐曲波帕与标准免疫抑制疗法联合治疗重型再生障碍性贫血的有效性和安全性

IF 2.5 4区医学

Experimental hematology Pub Date : 2024-11-05 DOI: 10.1016/j.exphem.2024.104670

Jianping Li , Weiru Liang , Huihui Fan , Kang Zhou , Yuan Li , Wenrui Yang , Liping Jing , Li Zhang , Lei Ye , Youzhen Xiong , Guangxin Peng , Yang Yang , Weiping Yuan , Jun Shi , Fengkui Zhang , Xin Zhao

{"title":"Efficacy and safety of avatrombopag in combination with standard immunosuppressive therapy for severe aplastic anemia","authors":"Jianping Li , Weiru Liang , Huihui Fan , Kang Zhou , Yuan Li , Wenrui Yang , Liping Jing , Li Zhang , Lei Ye , Youzhen Xiong , Guangxin Peng , Yang Yang , Weiping Yuan , Jun Shi , Fengkui Zhang , Xin Zhao","doi":"10.1016/j.exphem.2024.104670","DOIUrl":"10.1016/j.exphem.2024.104670","url":null,"abstract":"<div><div>Severe aplastic anemia (SAA) is a life-threatening bone marrow failure disease. The addition of eltrombopag to immunosuppressive therapy (IST) improves the response rate, but its hepatotoxicity is concerning. Avatrombopag (AVA), a small-molecule thrombopoietin-receptor agonist without hepatotoxicity, has unknown efficacy in SAA treatment. This retrospective study assessed the efficacy and safety of AVA added to IST 42 SAA patients compared to a historical cohort of 84 patients receiving IST alone, using propensity score matching. The median age was 31.5 (6.0–67.0 years) years old in group A and 26 (16.0–45.0 years) years old in group B. At 3 months, group A showed higher complete response (CR) and overall response (OR) rates than group B (CR: 19.0% vs. 4.8%, <em>p</em> = 0.024; OR: 54.8% vs. 39.3%, <em>p</em> = 0.145). Higher CR and OR rates were also found at 6 months in group A than in group B (CR: 31.0% vs. 14.3%, <em>p</em> = 0.145; OR 71.4% vs. 51.2%, <em>p</em> = 0.048). In multivariate analysis of group A, a shorter interval from disease onset to antithymocyte globulin (ATG) treatment (≤6 months) (<em>p</em> = 0.005) predicted better responses rate at 6 months. Event-free survival was also improved in group A (60.7% vs. 49.6%). AVA was well-tolerated, with no hepatic injury observed during treatment, even in those with pre-existing hepatic impairment. The addition of AVA to IST improves both the response rate and response quality in patients with SAA while ensuring safety.</div></div>","PeriodicalId":12202,"journal":{"name":"Experimental hematology","volume":"140 ","pages":"Article 104670"},"PeriodicalIF":2.5,"publicationDate":"2024-11-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142589453","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Inducible pluripotent stem cell models to study bone marrow failure and MDS predisposition syndromes. 研究骨髓衰竭和 MDS 易感综合征的可诱导多能干细胞模型。

IF 2.5 4区医学

Experimental hematology Pub Date : 2024-11-02 DOI: 10.1016/j.exphem.2024.104669

Sushree S Sahoo, Majd Khiami, Marcin W Wlodarski

{"title":"Inducible pluripotent stem cell models to study bone marrow failure and MDS predisposition syndromes.","authors":"Sushree S Sahoo, Majd Khiami, Marcin W Wlodarski","doi":"10.1016/j.exphem.2024.104669","DOIUrl":"10.1016/j.exphem.2024.104669","url":null,"abstract":"<p><p>Induced pluripotent stem cells (iPSCs) have emerged as powerful tools for in vitro modeling of bone marrow failure (BMF) syndromes and hereditary conditions predisposing to myelodysplastic syndrome (MDS) and acute myeloid leukemia (AML). This review synthesizes recent advances in iPSC-based disease modeling for various inherited BMF/MDS disorders, including Fanconi anemia, dyskeratosis congenita, Diamond Blackfan anemia syndrome, Shwachman-Diamond syndrome, and severe congenital neutropenia as well as GATA2, RUNX1, ETV6, ANKRD26, SAMD9, SAMD9L, and ADH5/ALDH2 syndromes. Although the majority of these iPSC lines are derived from patient cells, some are generated by introducing patient-specific mutations into healthy iPSC backgrounds, offering complementary approaches to disease modeling. The review highlights the ability of iPSCs to recapitulate key disease phenotypes, such as impaired hematopoietic differentiation, telomere dysfunction, and defects in DNA repair or ribosome biogenesis. We discuss how these models have enhanced our understanding of disease pathomechanisms, hematopoietic defects, and potential therapeutic approaches. Challenges in generating and maintaining disease-specific iPSCs are examined, particularly for disorders involving DNA repair. We emphasize the necessity of creating isogenic controls to elucidate genotype-phenotype relationships. Furthermore, we address limitations of current iPSC models, including genetic variability among iPSC clones derived from the same patient, and difficulties in achieving robust engraftment of iPSC-derived hematopoietic progenitor cells in mouse transplantation models. The review also explores future directions, including the potential of iPSC models for drug discovery and personalized medicine approaches. This review underscores the significance of iPSC technology in advancing our understanding of inherited hematopoietic disorders and its potential to inform novel therapeutic strategies.</p>","PeriodicalId":12202,"journal":{"name":"Experimental hematology","volume":" ","pages":"104669"},"PeriodicalIF":2.5,"publicationDate":"2024-11-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142568286","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

IFC Editorial Board 国际金融公司编辑委员会

IF 2.5 4区医学

Experimental hematology Pub Date : 2024-10-24 DOI: 10.1016/S0301-472X(24)00522-8

引用次数: 0

Ever-evolving insights into the cellular and molecular drivers of lymphoid cell development 对淋巴细胞发育的细胞和分子驱动因素的认识不断发展。

IF 2.5 4区医学

Experimental hematology Pub Date : 2024-10-23 DOI: 10.1016/j.exphem.2024.104667

Vu L. Tran , Myriam L.R. Haltalli , Jingjing Li , Dawn S. Lin , Masayuki Yamashita , Shalin H. Naik , Ellen V. Rothenberg

引用次数: 0

Splicing the Difference: Harnessing the Complexity of the Transcriptome in Hematopoiesis 剪接差异：利用造血过程中转录组的复杂性。

IF 2.5 4区医学

Experimental hematology Pub Date : 2024-10-10 DOI: 10.1016/j.exphem.2024.104655

Hannah M. Maul-Newby, Stephanie Halene

{"title":"Splicing the Difference: Harnessing the Complexity of the Transcriptome in Hematopoiesis","authors":"Hannah M. Maul-Newby, Stephanie Halene","doi":"10.1016/j.exphem.2024.104655","DOIUrl":"10.1016/j.exphem.2024.104655","url":null,"abstract":"<div><div>Alternative splicing has long been recognized as a powerful tool to expand the diversity of the transcriptome and the proteome. The study of hematopoiesis, from hematopoietic stem cell maintenance and differentiation into committed progenitors to maturation into functional blood cells, has led the field of stem cell research and cellular differentiation for decades. The importance of aberrant splicing due to mutations in <em>cis</em> has been exemplified in thalassemias, resulting from aberrant expression of β-globin. The simultaneous development of increasingly sophisticated technologies, in particular the combination of multicolor flow cytometric cell sorting with bulk and single-cell sequencing, has provided sophisticated insights into the complex regulation of the blood system. The recognition that mutations in key splicing factors drive myeloid malignancies, in particular myelodysplastic syndromes, has galvanized research into alternative splicing in hematopoiesis and its diseases.</div><div>In this review, we will update the audience on the exciting novel technologies, highlight alternative splicing events and their regulators with essential functions in hematopoiesis, and provide a high-level overview how splicing factor mutations contribute to hematologic malignancies.</div></div>","PeriodicalId":12202,"journal":{"name":"Experimental hematology","volume":"140 ","pages":"Article 104655"},"PeriodicalIF":2.5,"publicationDate":"2024-10-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142406302","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Cellular uptake of CPX-351 by scavenger receptor class B type 1-mediated nonendocytic pathway. 细胞通过清道夫受体 B 类 1 型介导的非内皮细胞途径摄取 CPX-351。

IF 2.5 4区医学

Experimental hematology Pub Date : 2024-10-02 DOI: 10.1016/j.exphem.2024.104651

Hiroaki Araie, Naoko Hosono, Takahiro Yamauchi

{"title":"Cellular uptake of CPX-351 by scavenger receptor class B type 1-mediated nonendocytic pathway.","authors":"Hiroaki Araie, Naoko Hosono, Takahiro Yamauchi","doi":"10.1016/j.exphem.2024.104651","DOIUrl":"10.1016/j.exphem.2024.104651","url":null,"abstract":"<p><p>The proper uptake of drugs in liposome formulations into target cells markedly impacts therapeutic efficacy. The protein corona (PC), formed by the adsorption of serum proteins onto the liposome surface, binds to specific surface receptors of target cells, influencing the uptake pathway. We investigated the uptake pathway into leukemia cells based on PC analysis of CPX-351, a liposome containing cytarabine and daunorubicin in a fixed 5:1 synergistic molar ratio. The PC of CPX-351 mixed with fetal bovine serum was analyzed by nanoflow liquid chromatography-tandem mass spectrometry. CPX-351 uptake in HL-60, K562, and THP-1 leukemia cell lines was measured by flow cytometry using daunorubicin fluorescence. The major components of CPX-351 PC include apolipoproteins A-I and A-II, which bind to scavenger receptor class B type 1 (SR-BI), a nonendocytic pathway that takes up only liposome contents. SR-BI was expressed in each cell, and its expression correlated with CPX-351 uptake. The uptake was significantly decreased by the inhibition of clathrin-mediated endocytosis and macropinocytosis. Additionally, blocks lipid transport-1 (BLT-1), a selective inhibitor of SR-BI, decreased the uptake; however, high-dose BLT-1 addition significantly increased the uptake, which was more strongly inhibited by macropinocytosis suppression compared with clathrin-mediated endocytosis. BLT-1 enhances the binding of SR-BI to liposomes in a dose-dependent manner. These findings indicate that the enhancement of binding between SR-BI and CPX-351 activates different pathways, such as macropinocytosis, distinct from CPX-351 alone. SR-BI may be a biomarker for CPX-351 therapy, and the combination of CPX-351 with high-dose BLT-1 may augment therapeutic efficacy.</p>","PeriodicalId":12202,"journal":{"name":"Experimental hematology","volume":" ","pages":"104651"},"PeriodicalIF":2.5,"publicationDate":"2024-10-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142371404","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

BST2 facilitates activation of hematopoietic stem cells through ERK signaling BST2 通过 ERK 信号促进造血干细胞的活化

IF 2.5 4区医学

Experimental hematology Pub Date : 2024-10-02 DOI: 10.1016/j.exphem.2024.104653

Marcus A. Florez , Apoorva Thatavarty , Duy T. Le , Holly A. Hill , Youngjae Jeong , Brian M. Ho , Pawel Kus , Trisha K. Wathan , Bailee N. Kain , Shixia Huang , Dongsu Park , Katherine Y. King

{"title":"BST2 facilitates activation of hematopoietic stem cells through ERK signaling","authors":"Marcus A. Florez , Apoorva Thatavarty , Duy T. Le , Holly A. Hill , Youngjae Jeong , Brian M. Ho , Pawel Kus , Trisha K. Wathan , Bailee N. Kain , Shixia Huang , Dongsu Park , Katherine Y. King","doi":"10.1016/j.exphem.2024.104653","DOIUrl":"10.1016/j.exphem.2024.104653","url":null,"abstract":"<div><div>The proinflammatory cytokine interferon gamma (IFNγ) is upregulated in a variety of infections and contributes to bone marrow failure through hematopoietic stem cell (HSC) activation and subsequent exhaustion. The cell-surface protein, bone marrow stromal antigen 2 (BST2), is a key mediator of this process, because it is induced upon IFN stimulation and required for IFN-dependent HSC activation. To identify the mechanism by which BST2 promotes IFN-dependent HSC activation, we evaluated its role in niche localization, immune cell function, lipid raft formation, and intracellular signaling. Our studies indicated that knockout (KO) of BST2 in a murine model does not disrupt immune cell responses to IFN-inducing mycobacterial infection. Furthermore, intravital imaging studies indicate that BST2 KO does not disrupt localization of HSCs relative to endothelial or osteoblastic niches in the bone marrow. However, using imaging-based flow cytometry, we found that IFNγ treatment shifts the lipid raft polarity of wild-type (WT) but not <em>Bst2<sup>−/−</sup></em> hematopoietic stem and progenitor cells (HSPCs). Furthermore, RNAseq analysis, reverse-phase protein array and western blot analysis of HSPCs indicate that BST2 promotes ERK1/2 phosphorylation during IFNγ-mediated stress. Overall, we find that BST2 facilitates HSC division by promoting cell polarization and ERK activation, thus elucidating a key mechanism of IFN-dependent HSPC activation. These findings inform future approaches in the treatment of cancer and bone marrow failure.</div></div>","PeriodicalId":12202,"journal":{"name":"Experimental hematology","volume":"140 ","pages":"Article 104653"},"PeriodicalIF":2.5,"publicationDate":"2024-10-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142371403","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0