Haematologica最新文献

{"title":"The Gordian knot: ruxolitinib or transplants for high-risk myelofibrosis.","authors":"Robert Peter Gale, Giovanni Barosi","doi":"10.3324/haematol.2024.285972","DOIUrl":"10.3324/haematol.2024.285972","url":null,"abstract":"","PeriodicalId":12964,"journal":{"name":"Haematologica","volume":" ","pages":"3469-3470"},"PeriodicalIF":8.2,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11532677/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141579544","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Asciminib stands out as the superior tyrosine kinase inhibitor to combine with anti-CD20 monoclonal antibodies for the treatment of CD20⁺ Philadelphia-positive B-cell precursor acute lymphoblastic leukemia in preclinical models.","authors":"Krzysztof Domka, Agnieszka Dąbkowska, Martyna Janowska, Zuzanna Urbańska, Agata Pastorczak, Magdalena Winiarska, Klaudyna Fidyt, Mieszko Lachota, Elżbieta Patkowska, Łukasz Sędek, Bartosz Perkowski, Jaromir Hunia, Justyna Jakubowska, Beata Krzymieniewska, Ewa Lech-Marańda, Wojciech Młynarski, Tomasz Szczepański, Małgorzata Firczuk","doi":"10.3324/haematol.2023.284853","DOIUrl":"10.3324/haematol.2023.284853","url":null,"abstract":"<p><p>Philadelphia chromosome-positive B-cell precursor acute lymphoblastic leukemia (Ph+ BCP-ALL) is a high-risk subtype of acute lymphoblastic leukemia characterized by the presence of the BCR::ABL1 fusion gene. Tyrosine kinase inhibitors (TKI) combined with chemotherapy are established as the first-line treatment. Additionally, rituximab, an anti-CD20 monoclonal antibody is administered to adult BCP-ALL patients with ≥20% CD20+ blasts. In this study, we observed a marked prevalence of CD20 expression in patients diagnosed with Ph+ BCP-ALL, indicating a potential widespread clinical application of rituximab in combination with TKI. Consequently, we examined the influence of TKI on the antitumor effectiveness of anti-CD20 monoclonal antibodies by evaluating levels of CD20 on the cell surface and conducting in vitro functional assays. All tested TKI were found to uniformly downregulate CD20 on leukemic cells, diminishing the efficacy of rituximab-mediated complement- dependent cytotoxicity. Interestingly, these TKI displayed varied effects on natural killer (NK) cell-mediated antibody- dependent cytotoxicity and macrophage phagocytic function. While asciminib demonstrated no inhibition of effector cell functions, dasatinib notably suppressed the anti-CD20-monoclonal antibody-mediated NK cell cytotoxicity and macrophage phagocytosis of BCP-ALL cells. Dasatinib and ponatinib also decreased NK cell degranulation in vitro. Importantly, oral administration of dasatinib, but not asciminib, compromised NK cell activity in patients' blood, as determined by an ex vivo degranulation assay. Our results indicate that asciminib might be preferred over other TKI for combination therapy with anti-CD20 monoclonal antibodies.</p>","PeriodicalId":12964,"journal":{"name":"Haematologica","volume":" ","pages":"3520-3532"},"PeriodicalIF":8.2,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11532687/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141261242","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Superior outcomes and high-risk features with carfilzomib, lenalidomide, and dexamethasone combination therapy for patients with relapsed and refractory multiple myeloma: results of the multicenter KMMWP2201 study.","authors":"Ji Hyun Lee, Jimin Choi, Chang-Ki Min, Sung-Soo Park, Jae-Cheol Jo, Yoo Jin Lee, Jin Seok Kim, Hyeon-Seok Eom, Jongheon Jung, Joon Ho Moon, Hee Jeong Cho, Myung-Won Lee, Sung-Soo Yoon, Ja Min Byun, Jae Hoon Lee, Je-Jung Lee, Sung-Hoon Jung, Ho-Jin Shin, Do Young Kim, Jun Ho Yi, Seung-Shin Lee, Young Rok Do, Dok Hyun Yoon, Hyungwoo Cho, Won Sik Lee, Ho Sup Lee, Jieun Uhm, Hyo Jung Kim, Hee Ryeong Jang, Sung-Hyun Kim, Kihyun Kim","doi":"10.3324/haematol.2024.285534","DOIUrl":"10.3324/haematol.2024.285534","url":null,"abstract":"<p><p>Carfilzomib, lenalidomide, and dexamethasone (KRd) combination therapy improves the survival of patients with relapsed and/or refractory multiple myeloma (RRMM). Nonetheless, evidence on the use of KRd in Asian populations remains scarce. Accordingly, this study aimed to investigate this regimen's efficacy in a large group of patients. This retrospective study included patients with RRMM who were treated with KRd at 21 centers between February 2018 and October 2020. Overall, 364 patients were included (median age, 63 years). The overall response rate was 90% in response-evaluable patients, including 69% who achieved a very good partial response or deeper responses. With a median follow-up duration of 34.8 months, the median progression-free survival (PFS) was 23.4 months and overall survival (OS) was 59.5 months. Among adverse factors affecting PFS, high-risk cytogenetics, extramedullary disease, and doubling of monoclonal protein within 2-3 months prior to start of KRd treatment significantly decreased PFS and OS in multivariate analyses. Patients who underwent post-KRd stem cell transplantation (i.e., delayed transplant) showed prolonged PFS and OS. Grade 3 or higher adverse events (AE) were observed in 56% of the patients, and non-fatal or fatal AE that resulted in discontinuation of KRd were reported in 7% and 2% of patients, respectively. Cardiovascular toxicity was comparable to that reported in the ASPIRE study. In summary, KRd was effective in a large, real-world cohort of patients with RRMM with long-term follow-up. These findings may further inform treatment choices in the treatment of patients with RRMM.</p>","PeriodicalId":12964,"journal":{"name":"Haematologica","volume":" ","pages":"3681-3692"},"PeriodicalIF":8.2,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11532698/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141261481","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Myeloid neoplasm with histiocytosis and spleen tyrosine kinase fusion responds to fostamatinib.","authors":"Zachary Risch, Benjamin H Kaffenberger, Catherine G Chung, Eric Samorodnitsky, Emily L Hoskins, Thuy Dao, Amy Smith, Sarah A Wall, Jonathan Brammer, Julie W Reeser, Michele R Wing, Julia F Hopkins, Lee A Albacker, Lynne V Abruzzo, Caprice D Eisele, Aharon G Freud, Sameek Roychowdhury, Katherine E Walsh","doi":"10.3324/haematol.2024.285146","DOIUrl":"10.3324/haematol.2024.285146","url":null,"abstract":"","PeriodicalId":12964,"journal":{"name":"Haematologica","volume":" ","pages":"3816-3820"},"PeriodicalIF":8.2,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11532718/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141175135","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Event-free survival at 36 months is a suitable endpoint for diffuse large B-cell lymphoma patients treated with immunochemotherapy: real-world evidence from the North Japan Hematology Study Group.","authors":"Koh Izumiyama, Tasuku Inao, Hideki Goto, Shinpei Harada, Hajime Senjo, Keito Suto, Junichi Hashiguchi, Reiki Ogasawara, Tomoyuki Saga, Tetsuyuki Igarashi, Kentaro Wakasa, Ikumi Kasahara, Yukari Takeda, Keisuke Yamaguchi, Akio Shigematsu, Mutsumi Takahata, Katsuya Fujimoto, Yoshihito Haseyama, Takahiro Nagashima, Hajime Sakai, Yasutaka Kakinoki, Mitsutoshi Kurosawa, Isao Yokota, Takanori Teshima","doi":"10.3324/haematol.2023.284841","DOIUrl":"10.3324/haematol.2023.284841","url":null,"abstract":"<p><p>Information regarding follow-up duration after treatment for newly diagnosed diffuse large B-cell lymphoma (DLBCL) is important. However, a clear endpoint has yet to be established. We enrolled a total of 2,182 patients newly diagnosed with DLBCL between 2008 and 2018. The median age of the patients was 71 years. All patients were treated with rituximab- and anthracycline-based chemotherapies. Each overall survival (OS) was compared with the age- and sex-matched Japanese general population (GP) data. At a median follow-up of 3.4 years, 985 patients experienced an event and 657 patients died. Patients who achieved an event-free survival (EFS) at 36 months (EFS36) had an OS equivalent to that of the matched GP (standard mortality ratio [SMR], 1.17; P=0.1324), whereas those who achieved an EFS24 did not have an OS comparable to that of the matched GP (SMR, 1.26; P=0.0095). Subgroup analysis revealed that relatively old patients (>60 years), male patients, those with limited-stage disease, those with a good performance status, and those with low levels of soluble interleukin 2 receptor already had a comparable life expectancy to the matched GP at an EFS24. In contrast, relatively young patients had a shorter life expectancy than matched GP, even with an EFS36. In conclusion, an EFS36 was shown to be a more suitable endpoint for newly diagnosed DLBCL patients than an EFS24. Of note, younger patients require a longer EFS period than older patients in order to obtain an equivalent life expectancy to the matched GP.</p>","PeriodicalId":12964,"journal":{"name":"Haematologica","volume":" ","pages":"3631-3640"},"PeriodicalIF":8.2,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11532691/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141310631","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Anti-CD19 chimeric antigen receptor T-cell therapy has less efficacy in Richter transformation than in <I>de novo</I> large B-cell lymphoma and transformed low-grade B-cell lymphoma.","authors":"Ohad Benjamini, Shalev Fried, Roni Shouval, Jessica R Flynn, Ofrat Beyar-Katz, Lori A Leslie, Tsilla Zucherman, Ronit Yerushalmi, Noga Shem-Tov, Maria Lia Palomba, Ivetta Danylesko, Inbal Sdayoor, Hila Malka, Orit Itzhaki, Hyung Suh, Sean M Devlin, Ronit Marcus, Parastoo B Dahi, Elad Jacoby, Gunjan L Shah, Craig S Sauter, Andrew Ip, Miguel-Angel Perales, Arnon Nagler, Avichai Shimoni, Michael Scordo, Abraham Avigdor","doi":"10.3324/haematol.2023.284664","DOIUrl":"10.3324/haematol.2023.284664","url":null,"abstract":"<p><p>The activity of anti-CD19 chimerci antigen receptor (CAR) T-cell therapy in chronic lymphocytic leukemia (CLL) with Richter's transformation (RT) to aggressive large B-cell lymphoma (LBCL) is largely unknown. In a multicenter retrospective study, we report the safety and efficacy of CAR T-cell therapy in patients with RT (N=30) compared to patients with aggressive B-cell lymphoma (N=283) and patients with transformed indolent non-Hodgkin lymphoma (iNHL) (N=141) between April 2016 and January 2023. Two-thirds of patients received prior therapy for CLL before RT and 89% of them received B-cell receptor and B-cell lymphoma 2 inhibitors. Toxicities of CAR T-cell therapy in RT were similar to other lymphomas, with no fatalities related to cytokine release syndrome or immune effector-cell associated neurotoxicity synderome. The 100-day overall response rate and complete response rates in patients with RT were 57% and 47%, respectively. With a median follow-up of 19 months, the median overall survival (OS) was 9.9 months in patients with RT compared to 18 months in de novo LBCL and not reached in patients with transformed iNHL. The OS at 12 months was 45% in patients with RT compared with 62% and 75% in patients with de novo LBCL and transformed iNHL, respectively. In a multivariate analysis, worse OS was associated with RT histology, elevated lactate dehydrogenase, and more prior lines of therapy. CAR T-cell therapy can salvage a proportion of patients with CLL and RT exposed to prior targeted agents; however, efficacy in RT is inferior compared to de novo LBCL and transformed iNHL.</p>","PeriodicalId":12964,"journal":{"name":"Haematologica","volume":" ","pages":"3566-3577"},"PeriodicalIF":8.2,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11532690/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141426731","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A novel role of AURKA kinase in erythroblast enucleation.","authors":"Yuanlin Xu, Peijun Jia, Yating Li, Huan Zhang, Jingxin Zhang, Wanxin Li, Yazhe Zhen, Yan Li, Jiaming Cao, Tingting Zheng, Yihan Wang, Yanyan Liu, Xiuli An, Shijie Zhang","doi":"10.3324/haematol.2023.284873","DOIUrl":"10.3324/haematol.2023.284873","url":null,"abstract":"<p><p>Generation of mammalian red blood cells requires the expulsion of polarized nuclei late in terminal erythroid differentiation. However, the mechanisms by which spherical erythroblasts determine the direction of nuclear polarization and maintain asymmetry during nuclear expulsion are poorly understood. Given the analogy of erythroblast enucleation to asymmetric cell division and the key role of Aurora kinases in mitosis, we sought to investigate the function of Aurora kinases in erythroblast enucleation. We found that AURKA (Aurora kinase A) is abundantly expressed in orthochromatic erythroblasts. Intriguingly, high-resolution confocal microscopy analyses revealed that AURKA co-localized with the centrosome on the side of the nucleus opposite its membrane contact point during polarization and subsequently translocated to the anterior end of the protrusive nucleus upon nuclear exit. Mechanistically, AURKA regulated centrosome maturation and localization via interaction with γ-tubulin to provide polarization orientation for the nucleus. Furthermore, we identified ECT2 (epithelial cell transforming 2), a guanine nucleotide exchange factor, as a new interacting protein and ubiquitination substrate of AURKA. After forming the nuclear protrusion, AURKA translocated to the anterior end of the protrusive nucleus to directly degrade ECT2, which is partly dependent on kinase activity of AURKA. Moreover, knockdown of ECT2 rescued impaired enucleation caused by AURKA inhibition. Our findings have uncovered a previously unrecognized role of Aurora kinases in the establishment of nuclear polarization and eventual nuclear extrusion and provide new mechanistic insights into erythroblast enucleation.</p>","PeriodicalId":12964,"journal":{"name":"Haematologica","volume":" ","pages":"3721-3734"},"PeriodicalIF":8.2,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11532702/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141497895","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Reference interval of free light chains ratio in patients with end-stage renal disease on chronic hemodialysis.","authors":"Camila Peña, Ricardo Valjalo, Ramón Pérez, Marco Álvarez, Pablo Bustamante, Esteban Forray, Viviana Balboa, Alexis Bondi","doi":"10.3324/haematol.2024.285093","DOIUrl":"10.3324/haematol.2024.285093","url":null,"abstract":"","PeriodicalId":12964,"journal":{"name":"Haematologica","volume":" ","pages":"3751-3754"},"PeriodicalIF":8.2,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11532703/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141633295","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Revumenib for patients with acute leukemia: a new tool for differentiation therapy.","authors":"Meira Yisraeli Salman, Eytan M Stein","doi":"10.3324/haematol.2022.282621","DOIUrl":"10.3324/haematol.2022.282621","url":null,"abstract":"<p><p>Treatment of acute leukemia is gradually moving away from a \"one-size-fits-all\" approach, as scientific and clinical advances expand the arsenal of available targeted therapies. One of the recent additions is the group of menin inhibitors; oral, selective, small molecules that disrupt the interaction between the chromatin adapter menin, and an epigenetic regulator, the lysine methyltransferase 2A (KMT2A) complex. Two susceptible leukemia subtypes have been identified: (i) acute myeloid leukemia with a mutation in nucleophosmin 1 (NPM1), and (ii) any acute leukemia, myeloid or lymphoid, with a translocation resulting in the rearrangement of KMT2A. These leukemias share a distinct genetic expression, maintained by the KMT2A-menin interaction. Together they account for approximately 40% of patients with acute myeloid leukemia and 10% of patients with acute lymphoblastic leukemia. This spotlight review follows the journey of revumenib, as a representative of menin inhibitors, from bench to bedside. It focuses on the pathophysiology of leukemias sensitive to menin inhibition, delineation of how this understanding led to targeted drug development, and data from clinical trials. The important discovery of resistance mechanisms is also explored, as well as future directions in the use of menin inhibitors for treating leukemia.</p>","PeriodicalId":12964,"journal":{"name":"Haematologica","volume":" ","pages":"3488-3495"},"PeriodicalIF":8.2,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11532683/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141859563","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"LILRB4 represents a promising target for immunotherapy by dual targeting tumor cells and myeloid-derived suppressive cells in multiple myeloma.","authors":"Lixin Gong, Hao Sun, Lanting Liu, Xiyue Sun, Teng Fang, Zhen Yu, Weiwei Sui, Jingyu Xu, Tingyu Wang, Fangshuo Feng, Lei Lei, Wei Rui, Yuxuan Liu, Xueqiang Zhao, Gang An, Xin Lin, Lugui Qiu, Mu Hao","doi":"10.3324/haematol.2024.285099","DOIUrl":"10.3324/haematol.2024.285099","url":null,"abstract":"<p><p>Multiple myeloma (MM) remains an incurable hematologic malignancy. Despite tremendous advances in the treatment of this disease, about 10% of patients still have very poor outcomes with a median overall survival of less than 24 months. Our study aimed to underscore the critical mechanisms pertaining to rapid disease progression and provide novel therapeutic choices for these ultrahigh-risk patients. We utilized single-cell transcriptomic sequencing to dissect the characteristic bone marrow niche of patients who survived less than 2 years (EM24). Notably, enrichment of a LILRB4high pre-mature plasma-cell cluster was observed in EM24 patients compared to patients with durable remission. This cluster exhibited aggressive proliferation and a drug-resistance phenotype. High levels of LILRB4 promoted MM clonogenicity and progression. Clinically, high expression of LILRB4 was correlated with poor prognosis in both newly diagnosed MM patients and relapsed/ refractory MM patients. ATAC-sequencing analysis identified that pronounced chromosomal accessibility caused the elevation of LILRB4 on MM cells. CRISPR-Cas9 deletion of LILRB4 alleviated the growth of MM cells, inhibited the immunosuppressive function of myeloid-derived suppressive cells (MDSC), and further rescued T-cell dysfunction in the MM microenvironment. Greater infiltration of MDSC was observed in EM24 patients. We therefore generated an innovative T-cell receptor-based chimeric antigen receptor T cell, LILRB4-STAR-T. Cytotoxicity experiments demonstrated that LILRB4-STAR-T cells efficaciously eliminated tumor cells and impeded MDSC function. In conclusion, our study elucidates that LILRB4 is an ideal biomarker and promising immunotherapy target for high-risk MM. LILRB4-STAR-T-cell immunotherapy is promising against both tumor cells and the immunosuppressive tumor microenvironment in MM.</p>","PeriodicalId":12964,"journal":{"name":"Haematologica","volume":" ","pages":"3650-3669"},"PeriodicalIF":8.2,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11532705/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141175183","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}