Blood最新文献

{"title":"A phase 1 trial of fully human BCMA CAR-T therapy for relapsed/refractory multiple myeloma with 5-year follow-up.","authors":"Sherilyn A Tuazon, Andrew J Portuguese, Margot J Pont, Andrew J Cowan, Gabriel O Cole, Blythe D Sather, Xiaoling Song, Sushma Thomas, Brent L Wood, Michelle Blake, Melissa G Works, Mazyar Shadman, Emily C Liang, Qian V Wu, Jenna M Voutsinas, Ted A Gooley, Cameron J Turtle, Brian G Till, David G Coffey, David G Maloney, Stanley R Riddell, Damian J Green","doi":"10.1182/blood.2024027681","DOIUrl":"10.1182/blood.2024027681","url":null,"abstract":"<p><strong>Abstract: </strong>FCARH143, an autologous B-cell maturation antigen (BCMA)-targeted chimeric antigen receptor (CAR) T-cell (CAR-T) therapy, which incorporates a fully human BCMA-specific single chain variable fragment and 4-1BB costimulatory domain, was evaluated in a phase 1 trial for relapsed/refractory multiple myeloma (RRMM). Patients were stratified by bone marrow plasma cell involvement (10%-30% or >30%) and received lymphodepleting chemotherapy followed by escalating CAR-T doses (50 × 106 to 450 × 106). The primary end point was safety; secondary end points were overall response rate (ORR), duration of response, and progression-free survival (PFS). Among 28 enrolled patients, all underwent leukapheresis and successful CAR-T manufacturing, although 3 (11%) did not proceed to infusion. The 25 treated patients (median age, 64 years) had a median of 8 prior therapies, 80% were triple-class refractory, and 44% had extramedullary disease. Cytokine release syndrome occurred in 84% (8% grade 3-4 and no grade 5), and neurotoxicity in 24% (12% grade 3 and no grade 4-5). No treatment-related deaths occurred. At a median follow-up of 67.3 months, treated patients had an ORR of 100%, including a stringent complete response in 64%. Median PFS and overall survival (OS) were 15.5 and 32.1 months, respectively. In an intention-to-treat analysis (median follow-up, 69.6 months), the ORR was 89.3%, and OS was 30.2 months. FCARH143 demonstrated potent antimyeloma activity, with a 100% response rate and manageable toxicity, independent of disease burden or cytogenetic risk. Further evaluation in high-risk RRMM is warranted. This trial was registered at www.clinicaltrials.gov as #NCT03338972.</p>","PeriodicalId":9102,"journal":{"name":"Blood","volume":" ","pages":"535-545"},"PeriodicalIF":23.1,"publicationDate":"2025-07-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143810458","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":"Two clones, one niche: how CH shapes the MM microenvironment.","authors":"Adam S Sperling","doi":"10.1182/blood.2025029174","DOIUrl":"https://doi.org/10.1182/blood.2025029174","url":null,"abstract":"","PeriodicalId":9102,"journal":{"name":"Blood","volume":"1 1","pages":"524-525"},"PeriodicalIF":20.3,"publicationDate":"2025-07-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144756035","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":"Magrolimab plus azacitidine vs physician's choice for untreated TP53-mutated acute myeloid leukemia: the ENHANCE-2 study.","authors":"Joshua F Zeidner, David A Sallman, Christian Récher, Naval G Daver, Anskar Y H Leung, Devendra K Hiwase, Marion Subklewe, Thomas Pabst, Pau Montesinos, Richard A Larson, Lindsay Wilde, Anoop K Enjeti, Ichiro Kawashima, Cristina Papayannidis, Jenny O'Nions, Lisa Johnson, Mei Dong, Julie Huang, Taravat Bagheri, Gal Hacohen Kleiman, Calvin Lee, Paresh Vyas","doi":"10.1182/blood.2024027408","DOIUrl":"10.1182/blood.2024027408","url":null,"abstract":"<p><strong>Abstract: </strong>Patients with TP53-mutated acute myeloid leukemia (AML) have an extremely poor prognosis, necessitating new treatments. The global, randomized, phase 3 ENHANCE-2 trial evaluated the anti-CD47 monoclonal antibody magrolimab plus azacitidine (Magro/Aza) for previously untreated TP53-mutated AML. Patients determined ineligible for intensive therapy were randomized to receive Magro/Aza or venetoclax plus Aza (Ven/Aza); those eligible for intensive therapy were randomized to receive Magro/Aza or 7+3 induction chemotherapy. The primary end point was overall survival (OS) in the nonintensive arm. At interim analysis, nonintensive-arm OS hazard ratio (HR) between treatment groups was 1.191 (95% confidence interval [CI], 0.744-1.906), meeting the study's definition for futility and resulting in study termination. At final analysis, median OS was 4.4 vs 6.6 months (HR, 1.132; 95% CI, 0.783-1.637; P = .5070) in the nonintensive arm (n = 205) and 7.3 vs 11.1 months (HR, 1.434; 95% CI, 0.635-3.239; P = .3798) in the intensive arm (n = 52) between Magro/Aza and control groups, respectively. Incidences of grade ≥3 adverse events were similar across Magro/Aza and control groups (nonintensive, n = 194: 96.9% and 95.9%; intensive, n = 50: 92.6% and 95.7%), including grade ≥3 anemia (nonintensive: 27.1% and 23.5%; intensive: 25.9% and 21.7%). Grade ≥3 infections were observed in 50.0% and 53.1% of patients in the nonintensive arm and 44.4% and 65.2% of intensive-arm patients. ENHANCE-2 did not meet its primary end point of OS in TP53-mutated AML but provides important data informing future studies in this challenging population. This trial was registered at www.clinicaltrials.gov as #NCT04778397.</p>","PeriodicalId":9102,"journal":{"name":"Blood","volume":" ","pages":"590-600"},"PeriodicalIF":23.1,"publicationDate":"2025-07-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143514606","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":"Multiomics analysis reveals the genetic and epigenetic features of high-risk NK cell-type chronic active EBV infection.","authors":"Ryo Akazawa,Takashi Mikami,Masaki Yamada,Itaru Kato,Hirohito Kubota,Satoshi Saida,Yoshinori Uchihara,Yuriko Ishikawa,Tatsuya Kamitori,Keiji Tasaka,Kiyotaka Isobe,Tomoya Isobe,Kazushi Izawa,Katsutsugu Umeda,Hidefumi Hiramatsu,Keita Jinnouchi,Masahiro Hirata,Masakazu Fujimoto,Tomoo Daifu,Hiroo Ueno,Seishiro Nodomi,Machiko Sawada,Hisanori Fujino,Katsuyoshi Koh,Mitsuteru Hiwatari,Motohiro Kato,Hiroaki Goto,Ikumi Katano,Ryoji Ito,Mamoru Ito,Nobuyuki Kakiuchi,Masahiro Marshall Nakagawa,Yuichi Shiraishi,Yoshitaka Honda,Hiroyuki Yoshitomi,Hideki Ueno,Maho Sato,Satoru Miyano,Hironori Haga,Akihisa Sawada,Ken-Ichi Imadome,Seishi Ogawa,Junko Takita","doi":"10.1182/blood.2024026805","DOIUrl":"https://doi.org/10.1182/blood.2024026805","url":null,"abstract":"Chronic active Epstein-Barr virus (EBV) infection (CAEBV) is an orphan disease characterized by the proliferation and infiltration of EBV-infected T/natural killer (NK) cells into multiple organs. Although CAEBV is a heterogeneous disease with diverse clinical courses, its pathogenesis remains poorly understood. In this study, we explored the molecular mechanisms underlying CAEBV by performing a comprehensive multi-omics analysis, including genome, transcriptome, epigenome, and single-cell transcriptome and surface proteome analyses, of 65 CAEBV patients. Methylation analysis identified two distinct subtypes of NK cell-type CAEBV based on the CpG island methylator phenotype (CIMP). In CIMP-positive CAEBV, regions associated with enhancer of zeste homolog 2 binding sites and histone H3 lysine 27 trimethylation exhibited increased DNA hypermethylation, resulting in downregulation of tumor suppressor and anti-herpes virus genes. CIMP-positive CAEBV had a particularly poor prognosis and displayed a \"neoplastic\" phenotype with a DNA methylation pattern similar to that of extranodal NK/T-cell lymphoma, a higher tumor mutation burden, and frequent copy number alterations. In addition, both in vitro and in vivo functional assays demonstrated that 5-Azacytidine, a hypomethylating agent, was a potentially effective agent for high-risk CIMP-positive CAEBV. Finally, we established a method to effectively detect EBV-infected cells in single-cell analysis, suggesting that EBV-infected NK cells have tissue-resident properties and that innate and adaptive immunity to EBV is compromised in patients with CAEBV. The present findings provide insight into the complex molecular features of CAEBV and suggest potential molecular therapies.","PeriodicalId":9102,"journal":{"name":"Blood","volume":"55 1","pages":""},"PeriodicalIF":20.3,"publicationDate":"2025-07-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144747881","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":"Final analysis of the RESONATE-2 study: up to 10 years of follow-up of first-line ibrutinib treatment for CLL/SLL.","authors":"Jan A Burger,Paul M Barr,Tadeusz Robak,Carolyn Owen,Alessandra Tedeschi,Anita Sarma,Piers Em Patten,Sebastian Grosicki,Helen McCarthy,Fritz Offner,Edith Szafer Glusman,Cathy Zhou,Anita Szoke,Lynne Neumayr,James P Dean,Paolo Ghia,Thomas Kipps","doi":"10.1182/blood.2024028205","DOIUrl":"https://doi.org/10.1182/blood.2024028205","url":null,"abstract":"With up to 10 years of follow-up, we report results from the final analysis of RESONATE-2 (NCT01722487/NCT01724346), a phase 3 study of first-line ibrutinib versus chlorambucil for the treatment of chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL). Patients aged ≥65 years with previously untreated CLL/SLL without del(17p) were randomly assigned to receive either single-agent ibrutinib (420 mg/day; n = 136) or chlorambucil (0.5-0.8 mg/kg ≤12 cycles; n = 133) until disease progression/unacceptable toxicity. With a median follow-up of 9.6 in the ibrutinib arm, median PFS was 8.9 years (95% CI, 7.0-NE) versus 1.3 years (95% CI, 0.9-1.6) for the chlorambucil arm. Among patients with unmutated IGHV, del(11q), mutated TP53, or complex karyotype median PFS was 8.4 years (95% CI, 6.8-NE) with ibrutinib and 0.7 years (95% CI, 0.4-1.2) with chlorambucil. Median overall survival (OS) with ibrutinib was not reached. Most common adverse events (AEs) of any grade included diarrhea (52%), fatigue (41%), cough (39%), nausea (32%), arthralgia (31%), peripheral edema (31%), and hypertension (30%). During the entire study period, 34/136 patients (25%) had an ibrutinib dose reduction due to AEs; these AEs improved in 30/34 patients (88%). At study completion, 27% of patients remained on first-line ibrutinib treatment. With the longest follow-up to date from a phase 3 study of any targeted CLL/SLL therapy, this landmark RESONATE-2 study defines median PFS and demonstrates continued OS benefit of first-line ibrutinib treatment for patients with CLL/SLL, including those with high-risk genomic features. Sustained efficacy and tolerability of ibrutinib reemphasize the favorable benefit-risk profile.","PeriodicalId":9102,"journal":{"name":"Blood","volume":"143 1","pages":""},"PeriodicalIF":20.3,"publicationDate":"2025-07-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144747880","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":"Disease risk but not remission status determines transplant outcomes in AML: long-term outcomes of the ASAP trial.","authors":"Matthias Stelljes,Jan Moritz Middeke,Gesine Bug,Eva Maria Wagner-Drouet,Lutz P Mueller,Christoph Schmid,Stefan W Krause,Wolfgang Andreas Bethge,Edgar Jost,Uwe Platzbecker,Stefan Klein,Judith Niederland,Martin Kaufmann,Kerstin Schäfer-Eckart,Henning Baldauf,Friedrich Stölzel,Sarah Trost,Christoph Röllig,Malte von Bonin,Katharina Egger-Heidrich,Desiree Kunadt,Björn Steffen,Beate Hauptrock,Christoph Schliemann,Katja Sockel,Fabian Lang,Oliver Kriege,Judith Schaffrath,Christian Reicherts,Wolfgang E Berdel,Hubert Serve,Gerhard Ehninger,Alexander H Schmidt,Jan-Henrik Mikesch,Martin Bornhäuser,Johannes Schetelig","doi":"10.1182/blood.2025028730","DOIUrl":"https://doi.org/10.1182/blood.2025028730","url":null,"abstract":"Attempting to induce a complete remission (CR) prior to allogeneic hematopoietic cell transplantation (alloHCT) is current practice in patients with AML. A benefit of remission induction prior to alloHCT, however, has never been proven in a prospective trial. Potent conditioning regimens exist which allow for successful alloHCT in patients with active AML. Therefore, the ASAP trial was conducted to test remission induction by salvage chemotherapy prior to alloHCT against immediate transplantation after intensified conditioning. In total 281 patients with AML with poor response after first induction or untreated first relapse were randomized 1:1 to remission induction (RIST) with high-dose cytarabine plus mitoxantrone versus immediate alloHCT with sequential conditioning after non-intensive disease control measures (DisC) preferentially watchful waiting only. Overall survival (OS) at 5 years from randomization analyzed according to ITT was 46.1% for DisC versus 47.5% for RIST (p=0.82). In multivariable Cox regression analysis, genetic AML risk according to ELN (p<0.0001), age (p=0.001) and comorbidities (p=0.046) predicted survival, but not treatment arm (HR 1.08 for DisC versus RIST, p=0.67). In conclusion, long-term follow-up of the ASAP trial showed no survival advantage for standard salvage chemotherapy prior to alloHCT as opposed to immediate alloHCT. The trial results question the general concept of remission induction with intensive standard salvage therapy prior to alloHCT for all patients, since immediate alloHCT may reduce time in hospital and health care expenses. Well tolerable novel bridging therapies and post-transplant maintenance with targeted drugs are urgently warranted, especially for adverse-risk AML, to improve outcome after alloHCT. NCT02461537.","PeriodicalId":9102,"journal":{"name":"Blood","volume":"25 1","pages":""},"PeriodicalIF":20.3,"publicationDate":"2025-07-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144747885","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":"New prognostic systems for multiple myeloma in the context of contemporary therapies.","authors":"Andrew Spencer","doi":"10.1182/blood.2024023841","DOIUrl":"https://doi.org/10.1182/blood.2024023841","url":null,"abstract":"Recent clinical trials in both transplant eligible and ineligible newly diagnosed multiple myeloma utilising three and four drug combinations have demonstrated unprecedented levels of response. However, two recently published studies redefining high-risk in newly diagnosed multiple myeloma in the context of these newer and more effective treatments demonstrate that a significant minority of patients likely derive little benefit from these newer approaches. These new prognostic systems thus provide an evidence-based framework for the development of much needed risk-stratified clinical trials.","PeriodicalId":9102,"journal":{"name":"Blood","volume":"8 1","pages":""},"PeriodicalIF":20.3,"publicationDate":"2025-07-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144747821","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":"XPO1 Drives Resistance to Eprenetapopt and Azacitidine and Can Be Targeted in TP53-Mutated Myeloid Malignancies.","authors":"Traci L Kruer,Ariel Quintana-Gonzalez,Hannah L Newman,Meghan C Ferrall-Fairbanks,Ling Zhang,Amy F McLemore,Surendra Neupane,Qin Yang,Nana Adjoa Ben-Crentsil,Maria E Balasis,Christopher T Letson,Rami S Komrokji,Sana Chaudhry,Tulasigeri M Totiger,Joshua A Traina,Maria E Figueroa,Christopher B Ryder,Thomas Cluzeau,Justin Taylor,David A Sallman,Eric Padron","doi":"10.1182/blood.2025028803","DOIUrl":"https://doi.org/10.1182/blood.2025028803","url":null,"abstract":"TP53 mutated myelodysplastic syndrome (MDS) and acute myeloid leukemia (AML) are among the most aggressive and chemotherapy refractory myeloid neoplasms with a median overall survival of less than 6 months. An enormous unmet need exists to develop novel therapeutic strategies and understand resistance mechanisms to suboptimal existing therapies for this disease. In two parallel phase 2 clinical trials that combined eprenetapopt with azacitidine in TP53 mutated MDS/AML, we observed complete remission rates of 40-50% and molecular remission rates of 38%. However, unless allogeneic stem cell transplantation was performed, relapse inevitably occurred. To understand the mechanisms of secondary resistance responsible for this, we genotyped sequential clinical trial samples, conducted a genome-wide CRISPR screen in TP53 mutated leukemia cells, and identified XPO1 as a therapeutically tractable mediator of resistance. We demonstrate that XPO1 is overexpressed in patient samples after eprenetapopt and azacitidine treatment, elucidate the mechanism by which this occurs, and determine that it is necessary and sufficient for resistance to combination therapy. Finally, we validate in a variety of model systems including a novel patient derived xenograft model of TP53 mutant MDS, that eprenetapopt in combination with XPO1 inhibitors can overcome this resistance, providing preclinical rationale that this novel combination strategy is a viable therapeutic approach in TP53 mutant MDS/AML patients.","PeriodicalId":9102,"journal":{"name":"Blood","volume":"718 1","pages":""},"PeriodicalIF":20.3,"publicationDate":"2025-07-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144747889","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":"Time to complete remission is an independent determinant of survival after intensive chemotherapy in AML.","authors":"Rithin Nedumannil,Michael Ashby,James P Rowland,Jacques A J Malherbe,Jared Fairbank,Kelli Gray,Sun Loo,Matthew Wright,John Reynolds,Devendra K Hiwase,Paula Marlton,Shaun A Fleming,Ashish Bajel,Andrew H Wei","doi":"10.1182/blood.2025028594","DOIUrl":"https://doi.org/10.1182/blood.2025028594","url":null,"abstract":"The purpose of this study was to explore and determine the optimal landmark for defining complete remission after intensive induction therapy that best correlates with long-term survival outcome among patients with newly diagnosed acute myeloid leukemia (AML).","PeriodicalId":9102,"journal":{"name":"Blood","volume":"1 1","pages":""},"PeriodicalIF":20.3,"publicationDate":"2025-07-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144737223","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 clinical guide to TP53 mutations in myeloid neoplasms.","authors":"Samuel Urrutia,Terrence N Wong,Daniel C Link","doi":"10.1182/blood.2025029691","DOIUrl":"https://doi.org/10.1182/blood.2025029691","url":null,"abstract":"TP53 mutations are found in 10-15% of myeloid neoplasms and are one of its most important prognostic factors. Emerging data show that TP53 mutational allele status is a key determinant of clinical outcomes, with multi-hit TP53 mutant myeloid neoplasms having a very poor prognosis. Significant differences exist among the methods used in clinical and research settings to assess TP53 mutational status, leading to variability in reported patient characteristics, response to therapy, and survival. Indeed, differences in the criteria used to define TP53 mutational states among professional societies and in landmark research studies have led to confusion, suboptimal clinical testing, and variability in therapy recommendations. We review the methods used to assess for TP53 mutational allele status and provide recommendations, based on clinically available testing, for the accurate evaluation of TP53 gene mutations in myeloid neoplasms. Hotspot mutations represent ~35% of all TP53 missense mutations in myeloid neoplasms. There is evidence that these hotspot mutations may have dominant-negative or gain-of function properties. Here, we review this evidence and discuss the potential impact of TP53 mutation identity on patient outcomes and clinical management.","PeriodicalId":9102,"journal":{"name":"Blood","volume":"9 1","pages":""},"PeriodicalIF":20.3,"publicationDate":"2025-07-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144737258","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}