Experimental hematology最新文献_第3页

Sex differences alter primitive progenitors in the C57BL/6 Tet2 knockout mouse model 性别差异改变C57BL/6 Tet2敲除小鼠模型中的原始祖细胞。

IF 2.5 4区医学

Experimental hematology Pub Date : 2025-05-01 DOI: 10.1016/j.exphem.2025.104747

Samantha M. Holmes , Christopher J. Wells , Christine Hall , Amy J.M. McNaughton , Michael J. Rauh , Sheela A. Abraham

{"title":"Sex differences alter primitive progenitors in the C57BL/6 Tet2 knockout mouse model","authors":"Samantha M. Holmes , Christopher J. Wells , Christine Hall , Amy J.M. McNaughton , Michael J. Rauh , Sheela A. Abraham","doi":"10.1016/j.exphem.2025.104747","DOIUrl":"10.1016/j.exphem.2025.104747","url":null,"abstract":"<div><div>The precancerous expansion of hematopoietic cells, termed clonal hematopoiesis (CH), has been correlated to disease development and all-cause mortality. Despite multiple observations that hematopoietic stem cell and progenitors (HSPCs) are significantly affected by both sex and age, there remain few studies quantifying male and female HSPC populations in wild-type and transgenic <em>Tet2</em> models over time. Here, we determine that male mice (with a hematopoietic deficiency of <em>Tet2</em> and control) have more Lin<sup>−</sup>Sca-1<sup>+</sup>c-kit<sup>+</sup> (LSK) cells, that include multipotent progenitor cells (MPPs; LSK CD48<sup>−</sup>CD150<sup>−</sup>) and long-term hematopoietic stem cells (LT-HSC; LSK CD48<sup>−</sup>CD150<sup>+</sup>) compared with females. LT-HSC, MPP, and progenitor populations were observed to possess equal male/female ratios in mice at 6 weeks of age; however, the LSK compartment was found most susceptible to sex-based effects in transgenic mice between 6 weeks and 4 months. In contrast, all differentiated progenitor populations analyzed in mice were observed to be unaffected by sex between 6 weeks to 4 months. This study provides a comprehensive analysis of bone-sourced HSPCs in <em>Tet2</em>-deficient mouse models and reveals important sex and age considerations that must be taken into account when using C57BL/6 mice for transgenic studies.</div></div>","PeriodicalId":12202,"journal":{"name":"Experimental hematology","volume":"145 ","pages":"Article 104747"},"PeriodicalIF":2.5,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143523041","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}

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IFC Editorial Board IFC编委会

IF 2.5 4区医学

Experimental hematology Pub Date : 2025-05-01 DOI: 10.1016/S0301-472X(25)00064-5

引用次数: 0

Large-scale mediator Mendelian randomization analysis identifies multiple immune cells mediating the causal link between gut microbes and chronic graft-versus-host disease risk 大规模中介孟德尔随机化分析确定了多种免疫细胞介导肠道微生物和慢性移植物抗宿主病风险之间的因果关系。

IF 2.5 4区医学

Experimental hematology Pub Date : 2025-04-30 DOI: 10.1016/j.exphem.2025.104794

Yiyin Chen , Xinghao Yu , Yiming Cai , Zhou Jin , Yang Xu

{"title":"Large-scale mediator Mendelian randomization analysis identifies multiple immune cells mediating the causal link between gut microbes and chronic graft-versus-host disease risk","authors":"Yiyin Chen , Xinghao Yu , Yiming Cai , Zhou Jin , Yang Xu","doi":"10.1016/j.exphem.2025.104794","DOIUrl":"10.1016/j.exphem.2025.104794","url":null,"abstract":"<div><div>Disorders of gut microbiota and immune cells have been observed to be involved in the occurrence of chronic graft-versus-host disease (cGVHD), but their causal connections have yet to be fully understood. This study utilized Mendelian randomization (MR), integrating genome-wide association study (GWAS) meta-analyses from the MiBioGen consortium (microbial taxa), the SardiNIA project (immune traits), and disease data from the Fred Hutchinson Cancer Research Center (FHCRC) cohort to investigate their relationships. The aim was to explore the causal effects of microbiota and immune traits on the incidence of cGVHD, using mediation analysis to identify which immune traits might mediate the effects of microbiota on this condition. The main analysis observed significant causal associations of 3 specific microbial taxa with cGVHD: <em>Lactococcus.id.1851</em> (odds ratio [OR] = 1.989, 95% confidence interval [CI] = 1.311–3.019, <em>p =</em> 0.001), <em>Ruminiclostridium9.id.11357</em> (OR = 3.273, 95% CI = 1.604–6.679, <em>p =</em> 0.001), and <em>Intestinimonas.id.2062</em> (OR = 0.400, 95% CI = 0.230–0.697, <em>p =</em> 0.001). Sensitivity analysis and multivariable MR analysis ruled out possible horizontal pleiotropy and bias. Additionally, 10 immune traits, predominantly covering regulatory T cells (Tregs) and B cells, were identified as influencing cGVHD risk. The two-step mediation MR analysis presented the effect of identified microbial taxa on Tregs and B cells and detailed the pathways through which <em>Intestinimonas</em> impacts cGVHD via CD27 on memory B cells (proportion mediated = 4.2%). Similarly, the role of interactions between <em>Ruminiclostridium9</em> and effector memory double-negative T cells in mediating cGVHD was quantified, accounting for 9.5% of the total effect.</div></div>","PeriodicalId":12202,"journal":{"name":"Experimental hematology","volume":"147 ","pages":"Article 104794"},"PeriodicalIF":2.5,"publicationDate":"2025-04-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143980232","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

Mtg16 NHR1 mutations cause defects in lymphopoiesis and the response to anemia Mtg16 NHR1突变导致淋巴系统缺陷和对贫血的反应。

IF 2.5 4区医学

Experimental hematology Pub Date : 2025-04-30 DOI: 10.1016/j.exphem.2025.104793

Monica Bomber , Pankaj Acharya , Anna E. Johnson , Shilpa Sampathi , David K. Flaherty , Brittany K. Matlock , Jacob D. Ellis , Luke N. Bartlett , Christopher S. Williams , Scott W. Hiebert , Kristy R. Stengel

{"title":"Mtg16 NHR1 mutations cause defects in lymphopoiesis and the response to anemia","authors":"Monica Bomber , Pankaj Acharya , Anna E. Johnson , Shilpa Sampathi , David K. Flaherty , Brittany K. Matlock , Jacob D. Ellis , Luke N. Bartlett , Christopher S. Williams , Scott W. Hiebert , Kristy R. Stengel","doi":"10.1016/j.exphem.2025.104793","DOIUrl":"10.1016/j.exphem.2025.104793","url":null,"abstract":"<div><div>The Eight-Twenty-One (ETO)/Myeloid Translocation Gene (MTG) family of transcriptional corepressors play a key role in adult stem cell function across multiple tissues and may be affected by mutation, deletion, or translocation in solid tumors and leukemia. Structural studies of the first conserved domain identified residues that make specific contacts with E proteins, such as HEB and E2A. We generated mice with a mutation in a critical phenylalanine (F210A) in Mtg16 to test the physiological significance of Mtg16 association with E proteins and compared these mice to mice containing a nearby cancer-associated mutation (P209T). We found that <em>Mtg16<sup>−/−</sup></em> and <em>Mtg16<sup>F210A/F210A</sup></em> mice showed impaired lymphopoiesis following competitive bone marrow transplant, suggesting that the repression of E protein-dependent transcription is critical for B- and T-cell development. Although <em>Mtg16<sup>−/−</sup>, Mtg16<sup>P209T/P209T</sup></em>, and <em>Mtg16<sup>F210A/F210A</sup></em> animals showed significant defects in burst forming potential (BFU-E) after phenylhydrazine treatment, only <em>Mtg16<sup>−/−</sup></em> mice showed overt signs of anemia. Thus, we propose that, although Mtg16 is a critical regulator of hematopoietic stem and progenitor cell (HSPC) function, response to hemolytic anemia, and lymphoid development, the interaction between Mtg16 and E proteins is particularly important for lymphopoiesis.</div></div>","PeriodicalId":12202,"journal":{"name":"Experimental hematology","volume":"147 ","pages":"Article 104793"},"PeriodicalIF":2.5,"publicationDate":"2025-04-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144005446","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

Distinct transcriptional changes in hematopoietic progenitor subsets on LPS-induced emergency granulopoiesis lps诱导的紧急粒细胞生成中造血祖细胞亚群的明显转录变化。

IF 2.5 4区医学

Experimental hematology Pub Date : 2025-04-30 DOI: 10.1016/j.exphem.2025.104792

Sladjana Kosanovic , Karolina Vanickova , Mirko Milosevic , Irina Ribeiro Bas , Mateusz Chilinski , Dariusz Plewczynski , Petr Danek , Jakub Rohlena , Katerina Rohlenova , Meritxell Alberich-Jorda

{"title":"Distinct transcriptional changes in hematopoietic progenitor subsets on LPS-induced emergency granulopoiesis","authors":"Sladjana Kosanovic , Karolina Vanickova , Mirko Milosevic , Irina Ribeiro Bas , Mateusz Chilinski , Dariusz Plewczynski , Petr Danek , Jakub Rohlena , Katerina Rohlenova , Meritxell Alberich-Jorda","doi":"10.1016/j.exphem.2025.104792","DOIUrl":"10.1016/j.exphem.2025.104792","url":null,"abstract":"<div><div>Emergency granulopoiesis is a critical process by which hematopoietic progenitors and stem cells facilitate enhanced granulocytic production during severe infections. However, the role of distinct multipotent progenitors (MPPs) at early stages of this process remains underexplored. Here, we investigated the contribution of MPPs to granulocytic production following lipopolysaccharide (LPS) administration in wild-type mice, simulating a bacterial infection. Transplantation assays demonstrated that LPS exposure reduces the engraftment capacity of lymphoid-biased MPP4 and enhances lymphoid production, rather than supporting myeloid lineage output. Further, single-cell RNA sequencing (scRNA-seq) of MPPs isolated from control and LPS-challenged mice revealed transcriptional reprogramming of nonlineage committed MPPs toward myeloid- and erythroid-biased progenitors. Notably, inflammatory progenitor populations emerged on activation of LPS-induced emergency granulopoiesis, displaying chromatin accessibility changes that align with a commitment to myeloid and erythroid fates. Pseudotime analysis elucidated cellular trajectories that suggest a developmental pathway where unbiased progenitors, present under nonstress conditions, transition toward myeloid and erythroid lineage outputs on LPS administration. In line with our functional MPP4 assessment, scRNA-seq suggested that lymphoid-biased progenitors do not transcriptionally rewire during early stages of emergency granulopoiesis. Collectively, our data highlight the critical role of specific MPP subsets in responding to LPS-induced inflammatory signals and underscore the dynamic adaptations that occur during granulocyte production in response to infection.</div></div>","PeriodicalId":12202,"journal":{"name":"Experimental hematology","volume":"147 ","pages":"Article 104792"},"PeriodicalIF":2.5,"publicationDate":"2025-04-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143963814","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

Hematopoietic stem cells in human fetal liver selectively express CD49f. 人胎儿肝脏造血干细胞选择性表达CD49f。

IF 2.5 4区医学

Experimental hematology Pub Date : 2025-04-29 DOI: 10.1016/j.exphem.2025.104788

Margarita E MacAldaz, Jeremy Shu, Glenn Edin, Margaret Hale, Connie J Eaves

{"title":"Hematopoietic stem cells in human fetal liver selectively express CD49f.","authors":"Margarita E MacAldaz, Jeremy Shu, Glenn Edin, Margaret Hale, Connie J Eaves","doi":"10.1016/j.exphem.2025.104788","DOIUrl":"10.1016/j.exphem.2025.104788","url":null,"abstract":"<p><p>Identification of phenotypes of human hematopoietic cells that display long-term mature cell outputs in vitro and repopulating capability in immunodeficient mice has been important to anticipating the therapeutic potential of fresh harvests of bone marrow or cord blood before or after their physical or genetic manipulation. However, characterizing their key properties and strategies for their isolation from multiple sources at increasing cell purities and elucidating the mechanisms that regulate their ability to sustain mature blood cell production continues to be of major interest. Previous studies have shown that fetal and adult human cells with long-term blood cell output potential are highly enriched in their respective glycosylphosphatidylinositol (GPI)-anchored surface protein GPI80+ and CD49f+ subsets of a developmentally preserved CD45+CD34+CD38-CD45RA-CD90+ population. The so-called \"GPI80\" hematopoietic cells found in first-trimester human fetal liver are of particular interest because of their very high regenerative capability compared with their adult or even neonatal (cord blood) \"CD49f\" counterparts. Here, it was hypothesized that high regenerative activity of the GPI80+ cells could be further enriched within a CD49f+ subset. We now demonstrated that coexpression of CD49f within the GPI80+ population identifies a subset with reduced short-term myeloid colony-forming activity in semisolid medium and greater progeny outputs in both 12-week growth factor-supplemented stromal cocultures and in transplanted immunodeficient mice. These findings demonstrated that CD49f is a pervasive marker of human hematopoietic stem cells (HSCs) throughout ontogeny and aging.</p>","PeriodicalId":12202,"journal":{"name":"Experimental hematology","volume":" ","pages":"104788"},"PeriodicalIF":2.5,"publicationDate":"2025-04-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143980895","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

Development and aging of resident endothelial stem cells in pre-existing blood vessels. 血管内皮干细胞的发育和衰老。

IF 2.5 4区医学

Experimental hematology Pub Date : 2025-04-29 DOI: 10.1016/j.exphem.2025.104795

Fitriana N Rahmawati, Nobuyuki Takakura

引用次数: 0

C-COUNT: a convolutional neural network-based tool for automated scoring of erythroid colonies. C-COUNT：一种基于卷积神经网络的红系克隆自动评分工具。

IF 2.5 4区医学

Experimental hematology Pub Date : 2025-04-24 DOI: 10.1016/j.exphem.2025.104786

Rui Li, Ashley Winward, Logan R Lalonde, Daniel Hidalgo, John P Sardella, Yung Hwang, Aishwarya Swaminathan, Sean Thackeray, Kai Hu, Lihua Julie Zhu, Merav Socolovsky

{"title":"C-COUNT: a convolutional neural network-based tool for automated scoring of erythroid colonies.","authors":"Rui Li, Ashley Winward, Logan R Lalonde, Daniel Hidalgo, John P Sardella, Yung Hwang, Aishwarya Swaminathan, Sean Thackeray, Kai Hu, Lihua Julie Zhu, Merav Socolovsky","doi":"10.1016/j.exphem.2025.104786","DOIUrl":"10.1016/j.exphem.2025.104786","url":null,"abstract":"<p><p>Despite advances in flow cytometry and single-cell transcriptomics, colony-formation assays (CFAs) remain an essential component in the evaluation of erythroid and hematopoietic progenitors. These assays provide functional information on progenitor differentiation and proliferative potential, making them a mainstay of hematology research and clinical diagnosis. However, the utility of CFAs is limited by the time-consuming and error-prone manual counting of colonies, which is also prone to bias and inconsistency. Here we present \"C-COUNT,\" a convolutional neural network-based tool that scores the standard colony-forming-unit-erythroid (CFU-e) assay by reliably identifying CFU-e colonies from images collected by automated microscopy and outputs both their number and size. We tested the performance of C-COUNT against three experienced scientists and find that it is equivalent or better in reliably identifying CFU-e colonies on plates that also contain myeloid colonies and other cell aggregates. We further evaluated its performance in the response of CFU-e progenitors to increasing erythropoietin concentrations and to a spectrum of genotoxic agents. We provide the C-COUNT code, a Docker image, a trained model, and training data set to facilitate its download, usage, and model refinement in other laboratories. The C-COUNT tool transforms the traditional CFU-e CFA into a rigorous and efficient assay with potential applications in high-throughput screens for novel erythropoietic factors and therapeutic agents.</p>","PeriodicalId":12202,"journal":{"name":"Experimental hematology","volume":" ","pages":"104786"},"PeriodicalIF":2.5,"publicationDate":"2025-04-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143980222","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

Engineered cytokine-expressing MSCs support ex vivo culture of human HSPCs and AML cells 表达工程化细胞因子的MSCs支持人造血干细胞和AML细胞的体外培养。

IF 2.5 4区医学

Experimental hematology Pub Date : 2025-04-22 DOI: 10.1016/j.exphem.2025.104790

Johannes Foßelteder , Thomas Brauchart , Angelika Schlacher , Tommaso Sconocchia , Erdem Özkaya , Lisa Auinger , Peter Schlenke , Heinz Sill , Armin Zebisch , Andreas Reinisch

{"title":"Engineered cytokine-expressing MSCs support ex vivo culture of human HSPCs and AML cells","authors":"Johannes Foßelteder , Thomas Brauchart , Angelika Schlacher , Tommaso Sconocchia , Erdem Özkaya , Lisa Auinger , Peter Schlenke , Heinz Sill , Armin Zebisch , Andreas Reinisch","doi":"10.1016/j.exphem.2025.104790","DOIUrl":"10.1016/j.exphem.2025.104790","url":null,"abstract":"<div><div>CD34<sup>+</sup> human hematopoietic stem and progenitor cells and primary patient-derived leukemia cells are important tools for basic and translational research. Their limited availability demands additional expansion ex vivo in many cases. The use of either cytokine cocktails or cocultures with mesenchymal stromal cells (MSCs) has advanced cell expansion but combinations of both have not been addressed extensively so far. Here, we presented a novel approach to generating human cytokine-expressing MSCs (ceMSCs) using genetic engineering. Coculture with ceMSCs and their culture supernatant led to an efficient expansion and maintenance of functional CD34<sup>+</sup>CD45RA<sup>-</sup>CD90<sup>+</sup>CD201<sup>+</sup>CD49c<sup>+</sup> hematopoietic stem cells ex vivo. Similarly, ceMSCs and their culture supernatant support the growth of cytokine-dependent leukemic cell lines in vitro and improve the survival, maintenance, and expansion of patient-derived acute myeloid leukemia cells, a cell population very challenging to be cultured ex vivo<em>.</em> ceMSCs even surpass the support provided by wild-type MSCs or external cytokines alone. Therefore, ceMSCs offer a cost-effective, straightforward alternative to traditional cytokine supplementation, enhancing the feasibility of ex vivo studies on healthy and leukemic stem and progenitor cells, including therapeutic drug testing and mechanistic investigations.</div></div>","PeriodicalId":12202,"journal":{"name":"Experimental hematology","volume":"147 ","pages":"Article 104790"},"PeriodicalIF":2.5,"publicationDate":"2025-04-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144001276","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

Unbiased analysis of NUP98-KDM5A-induced murine leukemia reveals phenotypic heterogeneity recapitulating human disease subtypes 对nup98 - kdm5a诱导的小鼠白血病的无偏分析揭示了再现人类疾病亚型的表型异质性。

IF 2.5 4区医学

Experimental hematology Pub Date : 2025-04-20 DOI: 10.1016/j.exphem.2025.104791

Marilaine Fournier , Marion Dubuissez , Mathieu Neault , Jean-Sébastien Delisle , Frédérick A. Mallette , Heather J. Melichar

{"title":"Unbiased analysis of NUP98-KDM5A-induced murine leukemia reveals phenotypic heterogeneity recapitulating human disease subtypes","authors":"Marilaine Fournier , Marion Dubuissez , Mathieu Neault , Jean-Sébastien Delisle , Frédérick A. Mallette , Heather J. Melichar","doi":"10.1016/j.exphem.2025.104791","DOIUrl":"10.1016/j.exphem.2025.104791","url":null,"abstract":"<div><div>NUP98-KDM5A (NK5) is an oncogenic fusion protein implicated in the development of several types of acute myeloid leukemia (AML) in humans, including rare pediatric acute megakaryoblastic leukemia (AMKL). NK5 expression in murine hematopoietic progenitor cells can induce AML in mice. However, the limited number of animals and phenotypic markers used in previous studies preclude the full characterization of the AML subtypes that develop. We used NK5-transduced hematopoietic progenitor cells from murine fetal liver to generate a large cohort of mice. We then assessed the expression of a panel of myeloid markers to characterize the lineage of leukemic blasts using flow cytometry. Finally, we used bioinformatic tools to perform an unbiased analysis of mouse-to-mouse heterogeneity in leukemic cellular phenotypes. We identified phenotypically distinct subgroups among the NK5 leukemias that were predominantly segregated based on the expression of the AMKL-associated marker CD41. Our findings indicate that NK5 expression in fetal liver cells causes different types of leukemia similar in proportion to that observed in pediatric patients. The heterogeneity and mixed phenotypes observed might explain the difficulty in accurately diagnosing leukemia in some patients carrying the NK5 fusion. In addition, this approach may enable the identification of the molecular or cellular basis of the diverse NK5-driven AML types.</div></div>","PeriodicalId":12202,"journal":{"name":"Experimental hematology","volume":"147 ","pages":"Article 104791"},"PeriodicalIF":2.5,"publicationDate":"2025-04-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144001277","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