Blood最新文献

{"title":"Platelet activation and signaling in thrombus formation.","authors":"Frauke Swieringa, Johan W M Heemskerk, Alice Assinger","doi":"10.1182/blood.2024025320","DOIUrl":"https://doi.org/10.1182/blood.2024025320","url":null,"abstract":"<p><p>In thrombosis and hemostasis, the formation of a platelet-fibrin thrombus or clot is a highly controlled process that varies, depending on the pathological context. Major signaling pathways in platelets are well established. However, studies with genetically modified mice have identified the contribution of hundreds of additional platelet-expressed proteins in arterial thrombus formation and bleeding. Using phenotype information of 540 mouse genes, involved in arterial thrombosis and hemostasis, we review current insights into established and novel platelet signaling mechanisms. We discuss pathways involved in platelet adhesion, shape change, integrin activation, intracellular vesicle trafficking and protein processing, granule secretion, aggregate formation and procoagulant activity. Specific attention is paid to the signaling routes used by ITAM-linked, ITIM-linked and G protein-coupled receptors, as well as downstream events feeding into GTPase regulation and protein kinase activation. We further summarize known alterations in platelet responses under conditions of venous, inflammatory and infection-dependent thrombosis, taking into account interactions of platelets with the endothelium, leukocytes and red blood cells. Understanding the genes and proteins involved in platelet signaling in the context of hemostasis, thrombosis and inflammation may lead to improved therapies to prevent and treat thrombotic disorders.</p>","PeriodicalId":9102,"journal":{"name":"Blood","volume":" ","pages":""},"PeriodicalIF":21.0,"publicationDate":"2025-01-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143051028","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Protection of β2GPI-Deficient Mice from Thrombosis Reflects a Defect in PAR3-facilitated Platelet Activation.","authors":"Paresh P Kulkarni, Ravi Kumar Alluri, Matthew J Godwin, Gabriel L Forbes, Alona A Merkulova, Sylviane Lambert, Aatira Vijay, Maierdan Palihati, Suman Kundu, Young Jun Shim, Kevin N Kalonji, Alvin H Schmaier, Michael Holinstat, Scott J Cameron, Keith R McCrae","doi":"10.1182/blood.2024024469","DOIUrl":"10.1182/blood.2024024469","url":null,"abstract":"<p><p>Antibodies to β2-glycoprotein I (β2GPI) cause thrombosis in antiphospholipid syndrome, however the role of β2GPI in coagulation in vivo is not understood. To address this issue, we developed β2GPI-deficient mice (Apoh-/-) by deleting exon 2 and 3 of Apoh using CRISPR/Cas9 and compared the development of thrombosis in wild-type (WT) and Apoh-/- mice using rose bengal and FeCl3-induced carotid thrombosis, laser-induced cremaster arteriolar injury, and inferior vena cava (IVC) stasis models. We also compared tail bleeding times and activation of platelets from WT and Apoh-/- mice in the absence and presence of β2GPI. Apoh-/- mice demonstrated prolonged time to occlusion of the carotid after exposure to rose bengal or FeCl3, and reduced platelet and fibrin accumulation in cremasteric arterioles after laser injury. Significantly smaller thrombi formed in the IVC of Apoh-/- mice 48 hours after IVC occlusion. The activated partial thromboplastin time and prothrombin time, as well as aPTT reagent and tissue factor-induced thrombin generation times of Apoh-/- and WT plasma revealed no differences. However, we observed significant prolongation of tail bleeding in Apoh-/- mice, and reduced P-selectin expression and fibrinogen binding to activated α2bβ3 on platelets from these mice after stimulation with thrombin; these changes were reversed by β2GPI. A PAR3 antibody blocked thrombin-induced activation of WT platelets and the ability of β2GPI to restore activation of Apoh-/- platelets by thrombin. These studies demonstrate that β2GPI may promote platelet activation by enhancing the ability of PAR3 to present thrombin to PAR4.</p>","PeriodicalId":9102,"journal":{"name":"Blood","volume":" ","pages":""},"PeriodicalIF":21.0,"publicationDate":"2025-01-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143051034","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Babesiosis and Sickle Red blood Cells: Loss of Deformability, Heightened Osmotic fragility, and Hypervesiculation.","authors":"Divya Beri, Marilis A Rodriguez, Manpreet Singh, Daniel McLaughlin, Yunfeng Liu, Hui Zhong, Avital Mendelson, Xiuli An, Deepa G Manwani, Karina Yazdanbakhsh, Cheryl A Lobo","doi":"10.1182/blood.2024027602","DOIUrl":"https://doi.org/10.1182/blood.2024027602","url":null,"abstract":"<p><p>Babesiosis in sickle cell disease (SCD) is marked by severe anemia but the underlying red blood cell (RBC) rheological parameters remain largely undefined. Here, we describe altered RBC deformability from both primary (host RBC sickle hemoglobin mediated) and secondary changes (Babesia parasite infection mediated) to the RBC membrane using wild type AA, sickle trait AS and sickle SS RBCs. Our ektacytometry (LORRCA) analysis demonstrates that the changes in the host RBC bio-mechanical properties, pre- and post- Babesia infection, reside on a spectrum of severity, with wild type infected AA cells, despite showing a significant reduction of deformability under both shear and osmolarity gradients, exhibiting only a mild phenotype; compared to infected AS RBCs which show median changes in deformability and infected SS RBCs which exhibit the most dramatic impact of infection on cellular rheology, including an increase in Point of Sickling values. Further, using Image stream cytometric technology to quantify changes in cellular shape and area along with a tunable resistive pulse sensor to measure release of extra-cellular vesicles (EV) from these host RBCs, before and after infection, we offer a potential mechanistic basis for this extreme SS RBC rheologic profile, which include enhanced sickling rates and osmotic fragility, loss of RBC surface area and hypervesiculation in infected SS host RBCs. These results underly the importance of understanding the impact of intra-erythrocytic parasitic infections of SCD RBCs, especially on their cellular membranes and studying the mechanisms that lead to hyper hemolysis and extreme anemia in the SCD patient population.</p>","PeriodicalId":9102,"journal":{"name":"Blood","volume":" ","pages":""},"PeriodicalIF":21.0,"publicationDate":"2025-01-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143051772","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Frontline treatment of follicular lymphoma: What will it take to change current practice?","authors":"Emmanuel Bachy, Kim Linton","doi":"10.1182/blood.2024026019","DOIUrl":"https://doi.org/10.1182/blood.2024026019","url":null,"abstract":"<p><p>Follicular lymphoma is the most common subtype of indolent lymphoma. Despite multiple trials over the past decade showing improved progression-free survival with new first-line therapeutic strategies -such as anti-CD20 maintenance therapy and new glycoengineered anti-CD20 antibodies- no standardized approach has been widely adopted in routine clinical practice. Several factors may explain this, including the increased incidence of infectious adverse events associated with these therapies, particularly during the COVID-19 pandemic, and the lack of overall survival benefit despite long-term follow-up. A general consensus has emerged acknowledging the high prognostic variability of follicular lymphoma, which complicates the adoption of a one-size-fits-all first-line treatment strategy. A plethora of prognostic scores (FLIPI, FLIPI2, PRIMA-PI, m7-FLIPI, FLEX, 23-gene score, etc) has been proposed but none can reliably identify the ~20% of patients that will die within 10 years of first-line immunochemotherpay and for whom a critical medical need remains despite recent therapeutic improvements. Consequently, current prognostic models mainly serve as tools to cross-compare and stratify clinical trials. In this review, we highlight current and future strategies aimed at reshaping frontline treatment paradigms to improve outcomes, including tailored approaches based on risk- or response-adapted designs, development of new predictive -rather than prognostic- tools, approaches to reduce adverse events to enhance health-related quality of life, and the potential use of T-cell-engaging therapies to improve survival in the highest risk patients.</p>","PeriodicalId":9102,"journal":{"name":"Blood","volume":" ","pages":""},"PeriodicalIF":21.0,"publicationDate":"2025-01-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143051776","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"IAP dependency of T-cell prolymphocytic leukemia identified by high-throughput drug screening.","authors":"Marcel F Pohly, Kerstin Putzker, Sebastian Scheinost, Lena Ben Taarit, Tatjana Walther, Sandra Kummer, Tobias Wertheimer, Minqi Lin, Thi Huong Lan Do, Kristina Handler, Jan Michler, Jarno Kivioja, Karsten Bach, Samanta Kisele, James Kim, Sascha Dietrich, Beat Bornhauser, Wendy Wei-Lynn Wong, Burkhard Becher, Andreas Moor, Joe David Lewis, Xenia Maria Ficht, Junyan Lu, Wolfgang Huber, Thorsten Zenz","doi":"10.1182/blood.2024027171","DOIUrl":"https://doi.org/10.1182/blood.2024027171","url":null,"abstract":"<p><p>T-cell prolymphocytic leukemia (T-PLL) is an aggressive lymphoid malignancy with limited treatment options. To discover new treatment targets for T-PLL, we performed high-throughput drug sensitivity screening on 30 primary patient samples ex-vivo. After screening over 2'800 unique compounds, we found T-PLL to be more resistant to most drug classes, including chemotherapeutics, compared to other blood cancers. Furthermore, we discovered previously not reported vulnerabilities of T-PLL. T-PLL cells exhibited a particular sensitivity to drugs targeting autophagy (thapsigargin, bafilomycin A1), nuclear export (selinexor), and inhibitor of apoptosis proteins (IAPs) (birinapant), sensitivities that were also shared by other T-cell malignancies. Through bulk and single-cell RNA-Sequencing we found these compounds to activate the toll-like-receptor (TLR) (bafilomycin A1), p53 (selinexor), and TNF-ɑ/NFκB signaling pathways (birinapant) in T-PLL cells. Focussing on birinapant for its potential in drug repurposing, we uncovered that IAP inhibitor-induced cell death was primarily necroptotic and dependent on TNF-ɑ. Through spectral flow cytometry we confirmed the absence of cleaved caspase-3 in IAP inhibitor treated T-PLL cells and show that IAP inhibition reduces the proliferation of T-PLL cells stimulated ex-vivo, while showing only a limited effect on non-malignant T-cells. In summary, our study maps the drug sensitivity of T-PLL across a broad range of targets and identifies new therapeutic approaches for T-PLL by targeting IAPs, XPO1 and autophagy, highlighting potential candidates for drug repurposing and novel treatment strategies.</p>","PeriodicalId":9102,"journal":{"name":"Blood","volume":" ","pages":""},"PeriodicalIF":21.0,"publicationDate":"2025-01-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143051779","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Integrative genomic analysis of DLBCL identifies immune environments associated with bispecific antibody response.","authors":"Sravya Tumuluru, James K Godfrey, Alan Cooper, Jovian Yu, Xiufen Chen, Brendan MacNabb, Girish Venkataraman, Yuanyuan Zha, Benedikt Pelzer, Joo Y Song, Gerben Duns, Brian Sworder, Sandeep S Raj, Christopher R Bolen, Elicia Penuel, Ekaterina Postovalova, Nikita Kotlov, Aleksander Bagaev, Nathan H Fowler, Roni Shouval, Sonali M Smith, Ash A Alizadeh, Christian Steidl, Justin P Kline","doi":"10.1182/blood.2024025355","DOIUrl":"https://doi.org/10.1182/blood.2024025355","url":null,"abstract":"<p><p>Most diffuse large B-cell lymphoma (DLBCL) patients treated with immunotherapies such as bispecific antibodies (BsAb) or chimeric antigen receptor (CAR) T cells fail to achieve durable treatment responses, underscoring the need for a deeper understanding of mechanisms that regulate the immune environment and response to treatment. Here, an integrative, multi-omic approach was applied to multiple large independent datasets in order to characterize DLBCL immune environments, and to define their association with tumor cell-intrinsic genomic alterations and outcomes to CD19-directed CAR T-cell and CD20 x CD3 BsAb therapies. This approach effectively segregated DLBCLs into four immune quadrants (IQ) defined by cell-of-origin and immune-related gene set expression scores. These quadrants consisted of activated B cell-like (ABC) hot, ABC cold, germinal center B cell-like (GCB) hot, GCB cold DLBCLs. Recurrent genomic alterations were enriched in each IQ, suggesting that lymphoma cell-intrinsic alterations contribute significantly to orchestrating unique DLBCL immune environments. For instance, SOCS1 loss-of-function mutations were significantly enriched among GCB hot DLBCLs, identifying a putative subset of inflamed DLBCLs that may be inherently susceptible to immunotherapy. In relapsed/refractory DLBCL patients, DLBCL-IQ assignment correlated significantly with clinical benefit with a CD20 x CD3 BsAb (n = 74), but not with CD19-directed CAR T cells (Stanford, n = 51; MSKCC, n = 69). Thus, DLBCL-IQ provides a new framework to conceptualize the DLBCL immune landscape and suggests the endogenous immune environment has a more significant impact on outcomes to BsAb compared to CAR T cell treatment.</p>","PeriodicalId":9102,"journal":{"name":"Blood","volume":" ","pages":""},"PeriodicalIF":21.0,"publicationDate":"2025-01-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143051782","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"DDAVP response and its determinants in bleeding disorders: a systematic review and meta-analysis.","authors":"Sebastiaan N J Laan, Jessica Del Castillo, Suzanne C Cannegieter, Karin Fijnvandraat, Marieke J H A Kruip, Saskia le Cessie, Ruben Bierings, Jeroen C J Eikenboom, Iris van Moort","doi":"10.1182/blood.2024026804","DOIUrl":"https://doi.org/10.1182/blood.2024026804","url":null,"abstract":"<p><p>Desmopressin (DDAVP) can be used to prevent or stop bleeding. However, large inter-individual variability is observed in DDAVP response and determinants are largely unknown. In this systematic review and meta-analysis we aim to identify the response to DDAVP, and the factors that determine DDAVP response in patients. We included studies with patients with any bleeding disorder receiving DDAVP. First and second screening round and risk of bias assessment were performed by independent reviewers. The main outcome was proportion of patients with complete (factor level > 50 U/dL), or partial (30-50 U/dL) response to DDAVP. Determinants of response including disease type, age, sex, Von Willebrand factor (VWF) and factor VIII (FVIII) mutations, and baseline factor levels were investigated. In total, 591 articles were found and 103 were included. Of these, 71 articles (1772 patients) were suitable for the study's definition of response. Meta-analysis showed a pooled response proportion of 0·71 [0·64;0·78] and a significant difference in response between disease subtypes. For hemophilia A, baseline FVIII:C was a borderline significant determinant of response. In von Willebrand disease (VWD) type 1 patients, VWF:Ag, VWF:Act and FVIII:C were significant determinants. A large variation in response was observed for specific mutations in VWF and F8. Response to DDAVP varied between disease subtypes, and was largely determined by the baseline levels of FVIII:C for hemophilia A and VWF:Ag for VWD. Our findings highlight the significant differences in response and emphasize the need for a standardized response definition and further research into response mechanisms.</p>","PeriodicalId":9102,"journal":{"name":"Blood","volume":" ","pages":""},"PeriodicalIF":21.0,"publicationDate":"2025-01-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143031969","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The Fit Older Adult with Acute Myeloid Leukemia: Clinical Challenges to Providing Evidence-Based Frontline Treatment.","authors":"Sameem M Abedin, Geoffrey L Uy, Laura C Michaelis","doi":"10.1182/blood.2024026004","DOIUrl":"https://doi.org/10.1182/blood.2024026004","url":null,"abstract":"<p><p>Recent advances in acute myeloid leukemia (AML) come from studies investigating younger (age<60 years) adults or older (age≥75 years) or less fit adults. Uncertainty exists for the management of otherwise healthy adults with AML in their 60s and 70s, which also represents a significant proportion of AML cases. We discuss current considerations in older, fit adults with AML including determination of fitness, what factors beyond fitness should be assessed, and finally what challenges and innovations lie ahead to improve outcomes for these patients.</p>","PeriodicalId":9102,"journal":{"name":"Blood","volume":" ","pages":""},"PeriodicalIF":21.0,"publicationDate":"2025-01-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143031930","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"One hundred thirty-four germ line PU.1 variants and the agammaglobulinemic patients carrying them.","authors":"Ainsley V C Knox, Lauren Y Cominsky, Di Sun, Emylette Cruz Cabrera, Brian E Nolan, Edann Ofray, Elisa Benetti, Camilla Visconti, Federica Barzaghi, Sergio D Rosenzweig, Monica Ghei Lawrence, Kathleen E Sullivan, Samuel Yoon, Suzanna Rachimi, Nurcicek Padem, Erin Conboy, Maja Stojanovic, Gordana Petrovic, Srdjan Pasic, Joseph A Church, Ronald M Ferdman, Fabio Candotti, Tiphaine Arlabosse, Katerina Theodoropoulou, Cullen M Dutmer, László Maródi, Gabriella Szücs, Arnon Broides, Amit Nahum, Jacov Levy, Kaisa Maria Kettunen, Ravindra Daddali, Mikko R J Seppänen, Markku Vänttinen, Timi Martelius, Juha Grönholm, Matilde Peri, Chiara Azzari, Silvia Ricci, Samar Ojaimi, Emily Sj Edwards, Menno C van Zelm, Jinqiao Sun, Hassan Abolhassani, Qiang Pan-Hammarström, Hakon Hakonarson, Daniel Mayr, Kaan Boztug, Bertrand Boisson, Jean-Laurent Casanova, Carole Le Coz, Gregory M K Poon, Neil Romberg","doi":"10.1182/blood.2024026683","DOIUrl":"https://doi.org/10.1182/blood.2024026683","url":null,"abstract":"<p><p>Leukopoiesis is lethally arrested in mice lacking the master transcriptional regulator PU.1. Depending on the animal model, subtotal PU.1 loss either induces acute myeloid leukemia or arrests early B cell and dendritic cell development. Although humans with absolute PU.1 deficiency have not been reported, a small cadre of congenital agammaglobulinemia patients with sporadic, inborn PU.1 haploinsufficiency were recently described. To better estimate the penetrance, clinical complications, immunophenotypic features, and malignancy risks of PU.1-mutated agammaglobulinemia (PU.MA), a collection of 134 novel or rare PU.1 variants from publicly available databases, institutional cohorts, previously published reports, and unsolved agammaglobulinemia cases were functionally analyzed. In total, 25 loss of function (LOF) variants were identified in 33 heterozygous carriers from 21 kindreds across 13 nations. Of subjects harboring LOF PU.1 variants, 22 were agammaglobulinemic, 5 displayed antibody deficiencies, and 6 were unaffected, indicating an estimated disease penetrance of 81.8% with variable expressivity. In a cluster of patients, disease onset was delayed, sometimes into adulthood. All LOF variants conveyed effects via haploinsufficiency, either by destabilizing PU.1, impeding nuclear localization, or directly interfering with transcription. PU.MA patient immunophenotypes consistently demonstrated B-cell, conventional dendritic-cell, and plasmacytoid dendritic-cell deficiencies. Associated infectious and non-infectious symptoms hewed closely to X-linked agammaglobulinemia and not monogenic dendritic cell deficiencies. No carriers of LOF PU.1 variants experienced hematologic malignancies. Collectively, in vitro and clinical data indicate heterozygous LOF PU.1 variants undermine humoral immunity but do not convey strong leukemic risks.</p>","PeriodicalId":9102,"journal":{"name":"Blood","volume":" ","pages":""},"PeriodicalIF":21.0,"publicationDate":"2025-01-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143031927","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Another cryo-EM success: structure of FXIII.","authors":"Enrico Di Cera","doi":"10.1182/blood.2024027405","DOIUrl":"https://doi.org/10.1182/blood.2024027405","url":null,"abstract":"","PeriodicalId":9102,"journal":{"name":"Blood","volume":"145 4","pages":"356-357"},"PeriodicalIF":21.0,"publicationDate":"2025-01-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143022108","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}