Blood advances最新文献

{"title":"Characterization and prediction of hematotoxicity in pediatric patients receiving tisagenlecuecel.","authors":"Swati Naik, Subodh Selukar, Aimee C Talleur, Samira Deshpande, Gabriela Llaurador Caraballo, Vanessa A Fabrizio, Rayne H Rouce, Xiaopei Lily Zeng, Anant Vatsayan, Jenna Rossoff, Holly L Pacenta, Samuel John, Christine L Phillips, Julie-An M Talano, Amy Moskop, Michael R Verneris, Gary Douglas Myers, Erin M Hall, Nicole A Karras, Challice L Bonifant, Muna Qayed, Emily Bakinowski, Amy Keating, Susanne H C Baumeister, Emily Tomilson, Michelle L Hermiston, Prakash Satwani, Christa Krupski, Vasant Chinnabhandar, Heather E Stefanski, Emily Egeler, Kevin J Curran, Theodore W Laetsch, Crystal L Mackall, Snehit Prabhu, Khanh Nguyen, Christina Baggott, Liora M Schultz, Kevin O McNerney","doi":"10.1182/bloodadvances.2025016824","DOIUrl":"https://doi.org/10.1182/bloodadvances.2025016824","url":null,"abstract":"<p><p>Hematotoxicity is the most frequent severe toxicity following chimeric antigen receptor (CAR) T therapy. However, limited data exist on risk factors and outcomes for hematotoxicity for children and young adults (CAYA) with B-acute lymphoblastic leukemia (B-ALL) treated with tisagenlecleucel. We conducted a multi-institutional study involving 326 CAYA, with 144 evaluable in an initial training cohort and 141 evaluable in a validation cohort, through the Pediatric Real World CAR Consortium to characterize the incidence and outcomes of prolonged severe neutropenia (PSN) and to develop a predictive risk score for PSN, tailored for use in this population. The incidence of PSN, defined as an absolute neutrophil count (ANC) of <500 cells/µL for ≥ 30 days, was 15.3% in the initial training cohort and 21% in the validation cohort. Development of PSN was associated with inferior overall survival (p<0.001), relapse-free survival (p=0.01), higher non-relapse mortality (p=0.003), and a greater risk of infections within 30 days (p=0.03). Multivariable penalized regression analysis identified key risk factors for PSN which included pre-infusion C-reactive protein and bone marrow disease burden, and post-infusion peak ferritin and occurrence of severe CRS, which were used to create the CytoRisk score. In the validation cohort, the CytoRisk score discriminated between patients with and without PSN (area under the curve: 0.90, specificity: 93%, sensitivity: 71%, positive predictive value: 74%, negative predictive value: 92%). The CytoRisk score may be used to a priori identify patients at highest risk of PSN and overall worse outcomes.</p>","PeriodicalId":9228,"journal":{"name":"Blood advances","volume":" ","pages":""},"PeriodicalIF":7.4,"publicationDate":"2025-07-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144681973","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":"YX0798 Is a Highly Potent, Selective, and Orally Effective CDK9 Inhibitor for Treating Aggressive Lymphoma.","authors":"Vivian Jiang, Yu Xue, Hong Kim, Qingsong Cai, Tianci Zhang, Lei Nie, Joseph McIntosh, Yang Liu, Haiying Chen, Jia Zhou, Michael L Wang","doi":"10.1182/bloodadvances.2025016511","DOIUrl":"https://doi.org/10.1182/bloodadvances.2025016511","url":null,"abstract":"<p><p>Non-genetic transcription evolution has been increasingly explored and recognized to drive tumor cell progression and therapeutic resistance. As the regulation hub of transcription machinery, cyclin-dependent kinase 9 (CDK9) is the gatekeeper of RNA polymerase II (Pol II) transcription, and CDK9 dysfunction results in transcriptomic reprogramming and tumor cell progression. We recently reported that the HSP90-MYC-CDK9 network drives therapeutic resistance in mantle cell lymphoma (MCL) through transcriptomic reprogramming. We also showed that targeting CDK9 by AZD4573 and enitociclib is a safe and effective treatment in preclinical MCL models, supporting CDK9 as a valid therapeutic target for MCL. However, current CDK9 inhibitors (CDK9i) under therapeutic development have room for improvement due to limited target selectivity and oral bioavailability. To this end, YX0798 was discovered to be a novel CDK9i through structural optimization. YX0798 demonstrated remarkable target selectivity and high affinity in binding to CDK9. Furthermore, YX0798 showed good oral bioavailability. YX0798, when administrated orally (5 mg/kg, daily), led to an efficacious anti-tumor activity in vivo and showed the potency in overcoming therapeutic resistance. Mechanistically, YX0798 downregulated the short-lived oncoprotein c-MYC and pro-survival protein MCL-1 as a common mechanism of CDK9 inhibition. Moreover, YX0798 disrupted the cell cycle and resulted in transcriptomic reprogramming, eventually leading to cell death. Furthermore, YX0798 has the potential to be used in combination therapy with clinical agents to improve treatment efficacy. Together, these data demonstrate that YX0798 has oral bioavailability, exquisite selectivity, and anti-tumor potency that results from driving transcription reprogramming towards tumor cell killing.</p>","PeriodicalId":9228,"journal":{"name":"Blood advances","volume":" ","pages":""},"PeriodicalIF":7.4,"publicationDate":"2025-07-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144681976","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":"IVIG prophylaxis should be initiated following bispecific antibody therapy in multiple myeloma regardless of IgG levels.","authors":"Rahul Banerjee, Meera Mohan, Kai Rejeski, Benjamin R Puliafito, Diana D Cirstea, Gurbakhash Kaur, Shonali Midha, Georgia J McCaughan, Nikhil M Kumar, Nikita Mehra, Bhausaheb Bagal, Noopur S Raje","doi":"10.1182/bloodadvances.2025016490","DOIUrl":"https://doi.org/10.1182/bloodadvances.2025016490","url":null,"abstract":"<p><p>Bispecific antibodies (bsAbs) such as teclistamab, elranatamab, linvoseltamab, and talquetamab have impressive efficacy in multiple myeloma (MM) but come with substantial infectious risks that do not dissipate over time. Immunoglobulin replacement therapy (IgRT), which includes intravenous immunoglobulin (IVIG) and subcutaneous immunoglobulin (SCIG), may lower these risks. In this Viewpoint, we contrast primary IgRT prophylaxis (initiation regardless of IgG levels) with preemptive IgRT treatment (initiation only once IgG levels fall below a certain threshold) in this setting. We make evidence-based arguments for primary prophylaxis as a safer and simpler approach compared to preemptive IgG-guided IgRT. We also discuss strategies to improve the cost-effectiveness of IVIG and SCIG across the world. Given the overwhelmingly favorable benefit-risk profile of IgRT coupled with the limitations inherent to IgG measurements in MM, withholding IgRT access based on arbitrary IgG thresholds is neither scientifically sound nor clinically appropriate for patients with MM receiving bsAb therapy.</p>","PeriodicalId":9228,"journal":{"name":"Blood advances","volume":" ","pages":""},"PeriodicalIF":7.4,"publicationDate":"2025-07-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144681974","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":"Survival after anti-CD19 CAR T-cell therapy for B-cell non-Hodgkin lymphoma and CLL with 10 years of follow-up.","authors":"Tatyana Gavrilova, Lori McIntyre, Stephanie L Goff, James C Yang, Danielle A Natrakul, Steven A Rosenberg, James N Kochenderfer, Jennifer N Brudno","doi":"10.1182/bloodadvances.2025016504","DOIUrl":"https://doi.org/10.1182/bloodadvances.2025016504","url":null,"abstract":"","PeriodicalId":9228,"journal":{"name":"Blood advances","volume":" ","pages":""},"PeriodicalIF":7.4,"publicationDate":"2025-07-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144681975","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":"A Simple and Efficient Method for the Robust Expansion of Human ILC2s to Prevent Acute GvHD.","authors":"Danny W Bruce, Sonia J Laurie, Yan Xing, Heather E Stefanski, Keli L Hippen, Alec Wilkinson, Mark G Woodcock, James Coghill, Karen Peterson McKinnon, Bruce R Blazar, Jonathan Serody","doi":"10.1182/bloodadvances.2024013609","DOIUrl":"https://doi.org/10.1182/bloodadvances.2024013609","url":null,"abstract":"<p><p>Reconstitution of stem cells and enhancement of the barrier function of the gastrointestinal (GI) tract is critical to the resolution of intestinal acute graft-versus-host disease (aGvHD). Previously, our group has shown in murine models that type II innate lymphoid cells (ILC2) cells generate proteins in the GI tract that enhanced GI tract barrier function and diminished the expansion and function of pro-inflammatory donor cells when given to allogeneic stem cell transplant recipients. Therefore, the infusion of donor ILC2 cells could treat or prevent GI tract acute GvHD, but for this approach to be clinically applicable, robust expansion of a homogenous population of human ILC2 cells is needed. Here, we describe a method for the rapid expansion of a uniform population of human ILC2 cells which decrease GvHD in (NOD scid gamma mouse) NSG mice. The addition of IL-4 to the culture was critical to prevent the expansion of pro-inflammatory ILC1-like cells. Our approach should allow for the evaluation of human ILC2 cells to treat therapy-resistant GI tract acute GvHD.</p>","PeriodicalId":9228,"journal":{"name":"Blood advances","volume":" ","pages":""},"PeriodicalIF":7.4,"publicationDate":"2025-07-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144681971","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":"Advances and updates in pediatric anaplastic large cell lymphoma.","authors":"Lianna J Marks, Eric J Lowe, Kala Y Kamdar","doi":"10.1182/bloodadvances.2025015935","DOIUrl":"https://doi.org/10.1182/bloodadvances.2025015935","url":null,"abstract":"<p><p>Anaplastic large cell lymphoma (ALCL) is a rare form of mature T-cell non-Hodgkin lymphoma. In pediatric patients, the majority of cases are Anaplastic Lymphoma Kinase (ALK)-positive. Despite intensive multi-agent chemotherapy regimens, treatment failure rates remain at 25-30%. Recent advancements in targeted therapies, notably ALK inhibitors and the anti-CD30 antibody-drug conjugate brentuximab vedotin, have demonstrated substantial activity in relapsed and refractory settings. Molecular detection of minimal disseminated disease (MDD) and minimal residual disease (MRD) offer improved prognostic stratification. For patients with relapsed or refractory disease, targeted therapies have increased treatment options, but more work needs to be done to define optimal treatment regimens, duration, and need for hematopoietic stem cell transplantation in this group. Immune therapies such as checkpoint inhibitors or Chimeric Antigen Receptor T-cell therapy provide additional therapeutic options. Incorporating targeted therapies and MDD/MRD assessments into clinical trials could significantly improve outcomes for pediatric and adolescent patients with ALCL.</p>","PeriodicalId":9228,"journal":{"name":"Blood advances","volume":" ","pages":""},"PeriodicalIF":7.4,"publicationDate":"2025-07-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144681972","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":"Can baseline Cytomegalovirus IgG titers predict Cytomegalovirus reactivation after ide-cel therapy?","authors":"Taku Kikuchi, Ukyo Kondo, Shotaro Sugita, Miyu Watanabe, Chiaki Matsumoto, Moe Yogo, Kodai Kunisada, Haruka Sawada, Kota Sato, Tomomi Takei, Mizuki Ogura, Yu Abe, Kenshi Suzuki, Osamu Hosoya, Tadao Ishida, Nobuhiro Tsukada","doi":"10.1182/bloodadvances.2025017174","DOIUrl":"https://doi.org/10.1182/bloodadvances.2025017174","url":null,"abstract":"","PeriodicalId":9228,"journal":{"name":"Blood advances","volume":" ","pages":""},"PeriodicalIF":7.4,"publicationDate":"2025-07-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144658484","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":"High-grade B-cell lymphoma, not otherwise specified: an LLMPP study.","authors":"Brett J Collinge, Laura K Hilton, Jasper Chun Hei Wong, Waleed Alduaij, Susana Ben-Neriah, Graham W Slack, Pedro Farinha, Merrill Boyle, Barbara Meissner, James R Cook, German Ott, Andreas Rosenwald, Elías Campo, Catalina Amador, Timothy C Greiner, Philipp W Raess, Joo Y Song, Giorgio Ga Inghirami, Sarah L Ondrejka, Elaine S Jaffe, Dennis D Weisenburger, Wing C Chan, Harald Holte, Klaus Beiske, Kai Fu, Jan Delabie, Stefania Pittaluga, Javeed Iqbal, George Wright, Kerry J Savage, Andrew J Mungall, Louis M Staudt, Christian Steidl, Andrew L Feldman, Ryan D Morin, Lisa M Rimsza, David W Scott","doi":"10.1182/bloodadvances.2025016651","DOIUrl":"10.1182/bloodadvances.2025016651","url":null,"abstract":"<p><p>Molecular characterization of high-grade B-cell lymphoma, not otherwise specified (HGBCL-NOS), is hindered by its rarity, evolving definition, and poor diagnostic reproducibility. To address this challenge, we analyzed 92 HGBCL-NOS tumors collected across Lymphoma/Leukemia Molecular Profiling Project sites. Leveraging comparison cohorts of diffuse large B-cell lymphoma (DLBCL-NOS) and Burkitt lymphoma (BL), and molecular frameworks described in these entities, our analysis revealed a heterogenous molecular landscape, reminiscent of DLBCL-NOS but with an enrichment of BL features. By cell-of-origin, 59% were germinal center B-cell-like (GCB), and 25% were activated B-cell-like (ABC). LymphGen, a genetic classifier for DLBCL-NOS, assigned a genetic subtype to 34% of HGBCL-NOS. Although classification rate was lower than in DLBCL-NOS (66%), assigned subtypes spanned the spectrum of LymphGen classes, including 31% of ABCs classified as MCD. Features differentiating HGBCL-NOS from DLBCL-NOS included MYC-rearrangement (47% vs. 6%), dark zone signature (DZsig) expression (45% vs. 7%), and more frequent mutation of ID3, MYC, CCND3, and TP53 - all common to BL. A genetic classifier that differentiates DLBCL-NOS from BL classified 53% of DZsig+ tumors as BL-like, with those classified as DLBCL-like frequently BCL2-rearranged. Among DZsig- GCB tumors, 95% were DLBCL-like. Centralized pathology review reclassified almost half of tumors as DLBCL-NOS but did not identify a more homogenous HGBCL-NOS population, with no difference in features between confirmed and reclassified tumors. In conclusion, molecular testing enables a subset of HGBCL-NOS to be assigned to established categories. Based on rarity and diagnostic challenges, broader inclusion of HGBCL-NOS should be considered in biomarker-driven DLBCL trials.</p>","PeriodicalId":9228,"journal":{"name":"Blood advances","volume":" ","pages":""},"PeriodicalIF":7.4,"publicationDate":"2025-07-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144658486","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":"Interferon gamma rebalances immunopathological signatures in Chronic Granulomatous Disease through metabolic rewiring.","authors":"Mariolina Bruno, Charlotte Kröger, Anaísa V Ferreira, Bowen Zhang, Rutger J Röring, Ruiqi Liu, Caspar I van der Made, Norman van Rhijn, Lazslo Groh, Viola Klück, Nico A F Janssen, Wenchao Li, Diletta Rosati, Ahmed Alaswad, Helin Tercan, Jorge Saiz, Carolina Gonzalez-Riano, Martina van Uelft, Orsi Gaal, Sophie Müller, Humberto J Ferreira, Stefanie Warnat-Herresthal, Matthias Becker, Lisa Holsten, Michael Kraut, Jonas Schulte-Schrepping, Lorenzo Bonaguro, Kristian Händler, Cristina Cunha, Manfred Schmolz, Joachim L Schultze, Leo Joosten, Coral Barbas, Mihai G Netea, Yang Li, Anna C Aschenbrenner, Agostinho Carvalho, Frank L van de Veerdonk","doi":"10.1182/bloodadvances.2025016213","DOIUrl":"https://doi.org/10.1182/bloodadvances.2025016213","url":null,"abstract":"<p><p>Chronic granulomatous disease (CGD) is a primary immunodeficiency characterized by recurrent life-threatening infections and hyperinflammatory complications. It is caused by mutations in the NADPH oxidase complex and the consequent loss of reactive oxygen species (ROS) production. Recombinant human interferon gamma (rIFN-γ) prophylaxis reduces the risk of severe infections, but the mechanisms behind its efficacy in CGD are still an open question, as it does not restore NADPH oxidase-dependent ROS production. Here, we show that innate immune cells of CGD patients are transcriptionally and functionally reprogrammed to a hyperactive inflammatory status, displaying an impaired in vitro induction of trained immunity. CGD monocytes have reduced intracellular amino acids concentrations and profound functional metabolic defects, both at the level of glycolysis and mitochondrial respiration. Ex vivo and in vivo treatment with IFN-γ restored these metabolic defects and reduced excessive IL-1β and IL-6 production in response to fungal stimuli in CGD monocytes. These data suggest that prophylactic rIFN-γ modulates the metabolic status of innate immune cells in CGD. These data shed light on the effects of NADPH-oxidase-derived ROS deficiency to the metabolic programs of immune cells and pose the basis for targeting this immunometabolic axis, potentially beyond CGD, with IFN-γ immunotherapy.</p>","PeriodicalId":9228,"journal":{"name":"Blood advances","volume":" ","pages":""},"PeriodicalIF":7.4,"publicationDate":"2025-07-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144658489","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":"Dual targeting of G9a and DNMTs induces anti-tumour effects in multiple myeloma.","authors":"Patrick William Nylund, Berta Garrido-Zabala, Stefania Iliana Tziola, Tabassom Mohajershojai, Hanna Berglund, Catharina Muylaert, Lien Ann Van Hemelrijck, Alba Atienza Párraga, Louella Vasquez, Jim Jacob, Eric Bergquist, José-Ignacio Martín-Subero, Fredrik Öberg, Torbjörn Karlsson, Marika Nestor, Elke De Bruyne, Antonia Kalushkova, Helena Jernberg-Wiklund","doi":"10.1182/bloodadvances.2023010571","DOIUrl":"https://doi.org/10.1182/bloodadvances.2023010571","url":null,"abstract":"<p><p>Multiple myeloma (MM) is a haematological disease of the plasma cell that remains clinically challenging despite the development of novel therapies. Epigenetic alterations have been demonstrated to contribute to MM pathogenesis, yet comprehensive studies into the links between different epigenetic regulatory systems in myeloma progression and drug resistance though clinically relevant, are largely lacking. G9a and the DNMTs are epigenetic modifiers that exhibit increased activity in MM, correlating with poor prognosis. To investigate the partnership between G9a and DNMTs, we used a combinatorial treatment approach involving small molecule inhibitors. In-depth molecular analysis of the H3K9me2 distribution, the DNA methylome and the transcriptome of MM revealed a silencing mechanism involving G9a and DNMTs, that represses key tumour suppressor genes. Moreover, dual inhibition of G9a and DNMTs reduced cell viability in primary MM cells and induced apoptosis in MM cell lines. This was accompanied by increased expression of apoptosis-related genes and decreased protein levels of the MM-associated oncoproteins IRF4, XBP1, and MYC. To assess the translational relevance of our in vitro findings, we evaluated the combination therapy in an in vivo preclinical xenograft MM model. Specifically, we demonstrate that the G9a inhibitor A366 synergize with the DNMTs inhibitor Decitabine to promote a robust tumour regression in vivo. Together, these data provide new insights into the cooperative role of G9a and the DNMTs in regulating gene silencing in MM and support dual epigenetic inhibition as a promising therapeutic strategy.</p>","PeriodicalId":9228,"journal":{"name":"Blood advances","volume":" ","pages":""},"PeriodicalIF":7.4,"publicationDate":"2025-07-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144658485","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}