Khaled M. Musallam , Susanna Barella , Raffaella Origa , Giovanni Battista Ferrero , Roberto Lisi , Annamaria Pasanisi , Filomena Longo , Barbara Gianesin , Gian Luca Forni , Webthal® project
{"title":"Differential effects of iron chelators on iron burden and long-term morbidity and mortality outcomes in a large cohort of transfusion-dependent β-thalassemia patients who remained on the same monotherapy over 10 years","authors":"Khaled M. Musallam , Susanna Barella , Raffaella Origa , Giovanni Battista Ferrero , Roberto Lisi , Annamaria Pasanisi , Filomena Longo , Barbara Gianesin , Gian Luca Forni , Webthal® project","doi":"10.1016/j.bcmd.2024.102859","DOIUrl":"10.1016/j.bcmd.2024.102859","url":null,"abstract":"<div><p>We conducted a retrospective cohort study on 663 transfusion-dependent β-thalassemia patients receiving the same iron chelation monotherapy with deferoxamine, deferiprone, or deferasirox for up to 10 years (median age 31.8 years, 49.9 % females). Patients on all three iron chelators had a steady and significant decline in serum ferritin over the 10 years (median deferoxamine: −170.7 ng/mL, <em>P</em> = 0.049, deferiprone: −236.7 ng/mL, <em>P</em> = 0.001; deferasirox: −323.7 ng/mL, <em>P</em> < 0.001) yet had no significant change in liver iron concentration or cardiac T2*; while noting that patients generally had low hepatic and cardiac iron levels at study start. Median absolute, relative, and normalized changes were generally comparable between the three iron chelators. Patients receiving deferasirox had the highest morbidity and mortality-free survival probability among the three chelators, although the difference was only statistically significant when compared with deferoxamine (<em>P</em> = 0.037). On multivariate Cox regression analysis, there was no significant association between iron chelator type and the composite outcome of morbidity or mortality. In a real-world setting, there is comparable long-term iron chelation effectiveness between the three available iron chelators for patients with mild-to-moderate iron overload.</p></div>","PeriodicalId":8972,"journal":{"name":"Blood Cells Molecules and Diseases","volume":"107 ","pages":"Article 102859"},"PeriodicalIF":2.3,"publicationDate":"2024-05-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141183152","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}
A. Guarina , P. Farruggia , E. Mariani , P. Saracco , A. Barone , D. Onofrillo , S. Cesaro , R. Angarano , W. Barberi , S. Bonanomi , P. Corti , B. Crescenzi , G. Dell'Orso , A. De Matteo , G. Giagnuolo , A.P. Iori , S. Ladogana , A. Lucarelli , M. Lupia , B. Martire , C. Dufour
{"title":"Diagnosis and management of acquired aplastic anemia in childhood. Guidelines from the Marrow Failure Study Group of the Pediatric Haemato-Oncology Italian Association (AIEOP)","authors":"A. Guarina , P. Farruggia , E. Mariani , P. Saracco , A. Barone , D. Onofrillo , S. Cesaro , R. Angarano , W. Barberi , S. Bonanomi , P. Corti , B. Crescenzi , G. Dell'Orso , A. De Matteo , G. Giagnuolo , A.P. Iori , S. Ladogana , A. Lucarelli , M. Lupia , B. Martire , C. Dufour","doi":"10.1016/j.bcmd.2024.102860","DOIUrl":"10.1016/j.bcmd.2024.102860","url":null,"abstract":"<div><p>Acquired aplastic anemia (AA) is a rare heterogeneous disorder characterized by pancytopenia and hypoplastic bone marrow. The incidence is 2–3 per million population per year in the Western world, but 3 times higher in East Asia. Survival in severe aplastic anemia (SAA) has improved significantly due to advances in hematopoietic stem cell transplantation (HSCT), immunosuppressive therapy, biologic agents, and supportive care. In SAA, HSCT from a matched sibling donor (MSD) is the first-line treatment. If a MSD is not available, options include immunosuppressive therapy (IST), matched unrelated donor, or haploidentical HSCT. The purpose of this guideline is to provide health care professionals with clear guidance on the diagnosis and management of pediatric patients with AA. A preliminary evidence-based document prepared by a group of pediatric hematologists of the Bone Marrow Failure Study Group of the Italian Association of Pediatric Hemato-Oncology (AIEOP) was discussed, modified and approved during a series of consensus conferences that started online during COVID 19 and continued in the following years, according to procedures previously validated by the AIEOP Board of Directors.</p></div>","PeriodicalId":8972,"journal":{"name":"Blood Cells Molecules and Diseases","volume":"108 ","pages":"Article 102860"},"PeriodicalIF":2.3,"publicationDate":"2024-05-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141417573","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}
{"title":"Aberrant baseline cytokine profile in patients with newly diagnosed acquired aplastic anaemia correlates with disease severity and the treatment response","authors":"Rahul Vatsayan , Ankur Jain , Aditya Jandial , Parveen Bose , Man Updesh Singh Sachdeva , Neelam Varma , Arihant Jain , Gaurav Prakash , Alka Khadwal , Pankaj Malhotra","doi":"10.1016/j.bcmd.2024.102857","DOIUrl":"10.1016/j.bcmd.2024.102857","url":null,"abstract":"<div><h3>Background</h3><p>Immune dysregulation is crucial in the pathogenesis of acquired aplastic anaemia (aAA). There is paucity of data regarding correlation of baseline cytokine profile with treatment response in aAA.</p></div><div><h3>Objective</h3><p>Present prospective case-control study aimed to correlate the baseline cytokines in patients with aAA with the treatment response.</p></div><div><h3>Methods</h3><p>Fifty-one patients with newly-diagnosed aAA > 13 years of either sex were enrolled over 1.5 years. Twenty age-and sex-matched healthy controls (HC) were also included. The cytokine profile (IL-2, 4, 6, 8, 10, 17, IFN-γ and TNF-α) in the peripheral blood plasma of aAA patients was performed at the baseline using cytometric bead analysis. The cytokine levels were compared with HC and correlated with response to immunosuppressive therapy (IST) at 3-months.</p></div><div><h3>Results</h3><p>The median age of cases was 29 years (range,13–74). The cases had higher mean levels of IL2 (<em>p</em> = 0.326), IL4 (<em>p</em> = 0.038), IL6 (<em>p</em> = 0.000), IL10 (<em>p</em> = 0.002), TNF-α (<em>p</em> = 0.302), IFN-γ (<em>p</em> = 0.569) and IL-17 (<em>p</em> = 0.284) than the HC. The baseline levels of all the cytokines were higher (statistically non-significant) among responders (<em>n</em> = 13) than the non-responders (<em>n</em> = 14) to IST.</p></div><div><h3>Conclusions</h3><p>Baseline cytokine profile in patients with aAA might predict response to the IST. Larger studies are needed to validate our results.</p></div>","PeriodicalId":8972,"journal":{"name":"Blood Cells Molecules and Diseases","volume":"107 ","pages":"Article 102857"},"PeriodicalIF":2.3,"publicationDate":"2024-05-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141030757","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}
{"title":"Daucosterol regulates JAK2-STAT3 signaling pathway to promote megakaryocyte differentiation","authors":"Zhongkang Zhang, Guangbin Shang, Zhen Lu, Jia Hu, Huizhen Liu, Ting Lu, Xiaonan Lu","doi":"10.1016/j.bcmd.2024.102858","DOIUrl":"10.1016/j.bcmd.2024.102858","url":null,"abstract":"<div><p>Immune thrombocytopenia (ITP) is an autoimmune disease caused by the loss of immune tolerance to platelet autoantigens, resulting in reduced platelet production and increased platelet destruction. Impaired megakaryocyte differentiation and maturation is a key factor in the pathogenesis and treatment of ITP. <em>Sarcandra glabra</em>, a plant of the Chloranthaceae family, is commonly used in clinical practice to treat ITP, and daucosterol (Dau) is one of its active ingredients. However, whether Dau can treat ITP and the key mechanism of its effect are still unclear. In this study, we found that Dau could effectively promote the differentiation and maturation of megakaryocytes and the formation of polyploidy in the megakaryocyte differentiation disorder model constructed by co-culturing Dami and HS-5 cells. In vivo experiments showed that Dau could not only increase the number of polyploidized megakaryocytes in the ITP rat model, but also promote the recovery of platelet count. In addition, through network pharmacology analysis, we speculated that the JAK2-STAT3 signaling pathway might be involved in the process of Dau promoting megakaryocyte differentiation. Western blot results showed that Dau inhibited the expression of P-JAK2 and P-STAT3. In summary, these results provide a basis for further studying the pharmacological mechanism of Dau in treating ITP.</p></div>","PeriodicalId":8972,"journal":{"name":"Blood Cells Molecules and Diseases","volume":"107 ","pages":"Article 102858"},"PeriodicalIF":2.3,"publicationDate":"2024-05-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141032116","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}
{"title":"Decreasing circ_0014614 promotes the differentiation of bone marrow flineage cells into megakaryocytes in essential thrombocythemia via activiation of miR-138-5p/caspase3 axis","authors":"Guopan Yu, Xiaofan Chen, Weixiang Lu, Yanlin Li, Yanxiao Chen, Changxin Yin, Zhongxin Zheng, Xiaoshan Huang, Dan Xu","doi":"10.1016/j.bcmd.2024.102855","DOIUrl":"https://doi.org/10.1016/j.bcmd.2024.102855","url":null,"abstract":"<div><h3>Background</h3><p>Circular RNAs (circRNA) are pivotal in hematological diseases. Previous study showed that circ_0014614 (circDAP3) was significantly underexpressed in bone marrow–derived exosomes from essential thrombocythemia (ET) patients, affecting the differentiation of bone marrow lineage cells into megakaryocytes.</p></div><div><h3>Methods</h3><p>Fluorescence in situ hybridization (FISH) was used to display circ_0014614's primary cytoplasmic location in K562 cells. Cytoscape software was used to predict the circRNA-miRNA-mRNA networks, and their expression at the cellular level was detected by Quantitative reverse transcription-polymerase chain reaction (qRT-PCR). qRT-PCR was utilized to detect the expression levels of circ_0014614,miR-138-5p and caspase3 mRNA. Western blot was used to determine the protein levels of GATA-1, RUNX-1, NF-E2, CD41 and caspase3. The proliferation of K562 cells was assessed using the Cell Counting Kit-8 (CCK-8) Assay. Furthermore, the interplay between miR-138-5p and circ_0014614 or caspase3 was elucidated through a Dual-luciferase reporter assay.</p></div><div><h3>Results</h3><p>FISH assay indicated circ_0014614's primary cytoplasmic location in K562 cells. In ET bone marrow and K562 cells, circ_0014614 and caspase3 were down-regulated, whereas miR-138-5p saw a significant surge. Overexpressing circ_0014614 curtailed K562 cells' proliferation and differentiation. Further, circ_0014614 targeted miR-138-5p, with heightened miR-138-5p levels counteracting circ_0014614's inhibition. MiR-138-5p further targeted caspase3, and caspase3 silencing neutralized suppressed miR-138-5p's effects on K562 cell differentiation.</p></div><div><h3>Conclusion</h3><p>Circ_0014614 was down-regulated in ET bone marrow and bone marrow lineage cells, and upregulating circ_0014614 can inhibit bone marrow lineage cells' proliferation and differentiation into megakaryocytes. Mechanistically, circ_0014614 functioned as ceRNA via sponging miR-138-5p and alleviated the inhibitory effect of miR-138-5p on its target caspase3, which potentially deters tumor activity in ET.</p></div>","PeriodicalId":8972,"journal":{"name":"Blood Cells Molecules and Diseases","volume":"107 ","pages":"Article 102855"},"PeriodicalIF":2.3,"publicationDate":"2024-04-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140823572","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}
Matthew Hudkins , Heather Hamilton , Samantha J. Underwood , Diana E. Kazmierczak , Elizabeth N. Dewey , Steven C. Kazmierczak , William B. Messer , Akram Khan , Martin A. Schreiber , David H. Farrell
{"title":"Extreme γ′ fibrinogen levels in COVID-19 patients","authors":"Matthew Hudkins , Heather Hamilton , Samantha J. Underwood , Diana E. Kazmierczak , Elizabeth N. Dewey , Steven C. Kazmierczak , William B. Messer , Akram Khan , Martin A. Schreiber , David H. Farrell","doi":"10.1016/j.bcmd.2024.102856","DOIUrl":"10.1016/j.bcmd.2024.102856","url":null,"abstract":"<div><p>COVID-19 disease progression can be accompanied by a “cytokine storm” that leads to secondary sequelae such as acute respiratory distress syndrome. Several inflammatory cytokines have been associated with COVID-19 disease progression, but have high daily intra-individual variability. In contrast, we have shown that the inflammatory biomarker γ' fibrinogen (GPF) has a 6-fold lower coefficient of variability compared to other inflammatory markers such as hs-CRP. The aims of the study were to measure GPF in serial blood samples from COVID-19 patients at a tertiary care medical center in order to investigate its association with clinical measures of disease progression. COVID-19 patients were retrospectively enrolled between 3/16/2020 and 8/1/2020. GPF was measured using a commercial ELISA. We found that COVID-19 patients can develop extraordinarily high levels of GPF. Our results showed that ten out of the eighteen patients with COVID-19 had the highest levels of GPF ever recorded. The previous highest GPF level of 80.3 mg/dL was found in a study of 10,601 participants in the ARIC study. GPF levels were significantly associated with the need for ECMO and mortality. These findings have potential implications regarding prophylactic anticoagulation of COVID-19 patients.</p></div>","PeriodicalId":8972,"journal":{"name":"Blood Cells Molecules and Diseases","volume":"107 ","pages":"Article 102856"},"PeriodicalIF":2.3,"publicationDate":"2024-04-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S1079979624000342/pdfft?md5=e08897c9e445c8fe9f4eb50cb0df99cd&pid=1-s2.0-S1079979624000342-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141064544","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}
Constance P. Michel , Laurent A. Messonnier , Benoit Giannesini , Christophe Vilmen , Joevin Sourdon , Yann Le Fur , David Bendahan
{"title":"Endurance training and hydroxyurea have synergistic effects on muscle function and energetics in sickle cell disease mice","authors":"Constance P. Michel , Laurent A. Messonnier , Benoit Giannesini , Christophe Vilmen , Joevin Sourdon , Yann Le Fur , David Bendahan","doi":"10.1016/j.bcmd.2024.102853","DOIUrl":"https://doi.org/10.1016/j.bcmd.2024.102853","url":null,"abstract":"<div><p>Sickle cell disease (SCD) is an hemoglobinopathy resulting in the production of an abnormal Hb (HbS) which can polymerize in deoxygenated conditions, leading to the sickling of red blood cells (RBC). These alterations can decrease the oxygen-carrying capacity leading to impaired function and energetics of skeletal muscle. Any strategy which could reverse the corresponding defects could be of interest. In SCD, endurance training is known to improve multiples muscle properties which restores patient's exercise capacity but present reduced effects in anemic patients. Hydroxyurea (HU) can increase fetal hemoglobin production which can reduce anemia in patients. The present study was conducted to determine whether HU can improve the effects of endurance training to improve muscle function and energetics. Twenty SCD Townes mice have been trained for 8 weeks with (<em>n</em> = 11) or without (<em>n</em> = 9) HU. SCD mice muscle function and energetics were analyzed during a standardized rest-exercise-recovery protocol, using Phosphorus-31 Magnetic resonance spectroscopy (<sup>31</sup>P-MRS) and transcutaneous stimulation. The combination of training and HU specifically decreased fatigue index and PCr consumption while muscle oxidative capacity was improved. These results illustrate the potential synergistic effects of endurance training and HU on muscle function and energetics in sickle cell disease.</p></div>","PeriodicalId":8972,"journal":{"name":"Blood Cells Molecules and Diseases","volume":"107 ","pages":"Article 102853"},"PeriodicalIF":2.3,"publicationDate":"2024-03-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140347666","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}
Karolina Maciak , Aneta Jurkiewicz , Wojciech Strojny , Anna Adamowicz-Salach , Magdalena Romiszewska , Teresa Jackowska , Kinga Kwiecinska , Jaroslaw Poznanski , Monika Gora , Beata Burzynska
{"title":"PKLR mutations in pyruvate kinase deficient Polish patients: Functional characteristics of c.101-1G > A and c.1058delAAG variants","authors":"Karolina Maciak , Aneta Jurkiewicz , Wojciech Strojny , Anna Adamowicz-Salach , Magdalena Romiszewska , Teresa Jackowska , Kinga Kwiecinska , Jaroslaw Poznanski , Monika Gora , Beata Burzynska","doi":"10.1016/j.bcmd.2024.102841","DOIUrl":"https://doi.org/10.1016/j.bcmd.2024.102841","url":null,"abstract":"<div><p>Pyruvate kinase (PK) deficiency is a rare autosomal recessive disorder characterized by chronic hemolytic anemia of variable severity. Nine Polish patients with severe hemolytic anemia but normal PK activity were found to carry mutations in the <em>PKLR</em> gene encoding PK, five already known ones and one novel (c.178C > T). We characterized two of the known variants by molecular modeling (c.1058delAAG) and minigene splicing analysis (c.101-1G > A). The former gives a partially destabilized PK tetramer, likely of suboptimal activity, and the c.101-1G > A variant gives alternatively spliced mRNA carrying a premature stop codon, encoding a severely truncated PK and likely undergoing nonsense-mediated decay.</p></div>","PeriodicalId":8972,"journal":{"name":"Blood Cells Molecules and Diseases","volume":"107 ","pages":"Article 102841"},"PeriodicalIF":2.3,"publicationDate":"2024-03-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140347774","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}
{"title":"Platelet activation and blood extracellular vesicles: The influence of venepuncture and short blood storage","authors":"Ivica Marić , Klemen Žiberna , Ana Kolenc , Elvira Maličev","doi":"10.1016/j.bcmd.2024.102842","DOIUrl":"https://doi.org/10.1016/j.bcmd.2024.102842","url":null,"abstract":"<div><p>Extracellular vesicles (EVs) as membrane-bound particles released by various cells are potential tools for diagnosis and treatment. Blood cells, particularly platelets, are the source of circulating EVs.</p></div><div><h3>Material</h3><p>EVs were enriched with gradient ultracentrifugation and measured by nanoparticle tracking assay. A flow cytometric multiplex assay was used for cellular source determination. Activation of platelets was measured as a percentage of CD62p+/CD61+ platelets and correlated with the concentration and size of released EVs.</p></div><div><h3>Results</h3><p>In general there was no statistically significant correlation between EVs` concentration and degree of platelet activation. EVs from different cellular sources were detected. Comparing different needle thicknesses, there was a decrease in the EVs concentration for the 16G needle versus the 21G needle, but no difference was observed for EVs` size and phenotype or platelets activation. During blood storage, platelet activation increased, but there was no effect on the EVs` concentration, size, or phenotype.</p></div><div><h3>Conclusions</h3><p>Preanalytical factors like needle thickness and storage time can affect the MVs' properties. Activation of platelets during blood collection or blood storage occurs; however, it is difficult to determine its effect on the physiological properties of EVs since the mechanisms of EVs` biogenesis and especially clearness are not precisely known.</p></div>","PeriodicalId":8972,"journal":{"name":"Blood Cells Molecules and Diseases","volume":"106 ","pages":"Article 102842"},"PeriodicalIF":2.3,"publicationDate":"2024-03-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S1079979624000202/pdfft?md5=9311cf50b5aae847a6f9869128d371da&pid=1-s2.0-S1079979624000202-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140139049","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}
{"title":"Response to commentary on “Unmasking the morphological alteration of erythrocytes among women suffering from PCOS”","authors":"Sutithi Dey, Rajen Haldar","doi":"10.1016/j.bcmd.2024.102839","DOIUrl":"10.1016/j.bcmd.2024.102839","url":null,"abstract":"","PeriodicalId":8972,"journal":{"name":"Blood Cells Molecules and Diseases","volume":"106 ","pages":"Article 102839"},"PeriodicalIF":2.3,"publicationDate":"2024-02-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140054478","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}