BloodPub Date : 2024-11-19DOI: 10.1182/blood.2024024861
Peihua Lu, Xian Zhang, Junfang Yang, Jingjing Li, Liyuan Qiu, Meiwei Gong, Hui Wang, Jiaqi Chen, Hongxing Liu, Min Xiong, Ying Liu, Lin Wang
{"title":"Nanobody-based Naturally Selected CD7-Targeted CAR-T Therapy for Acute Myeloid Leukemia.","authors":"Peihua Lu, Xian Zhang, Junfang Yang, Jingjing Li, Liyuan Qiu, Meiwei Gong, Hui Wang, Jiaqi Chen, Hongxing Liu, Min Xiong, Ying Liu, Lin Wang","doi":"10.1182/blood.2024024861","DOIUrl":"https://doi.org/10.1182/blood.2024024861","url":null,"abstract":"<p><p>Approximately 30% of acute myeloid leukemia (AML) patients express CD7 on their myeloblasts. We have previously demonstrated that scFv-based \"naturally selected\" CD7 CAR-T (NS7CAR-T) therapy shows significant efficacy with a favorable safety profile in T-cell lymphoid malignancies. Here we derived dual nanobody-based dVHH NS7CAR-T cells that have superior CD7 binding specificity, affinity to their scFv-based counterparts and improved proliferative capability. In this phase I clinical trial, we evaluated the efficacy and safety of dVHH NS7CAR-T cells in patients with CD7-positive refractory/relapsed (r/r) AML. A cohort of ten patients received dVHH NS7CAR-T cells across two dosage levels of 5×105/kg and 1×106/kg. Before enrollment, patients had undergone a median of 8 (range: 3-17) prior lines of therapy. Seven patients had prior transplants. Following NS7CAR-T cell infusion, 7/10 (70%) patients achieved complete remission (CR). The median observation time was 178 days (28-776 days). Among the seven patients who achieved CR, 3 who relapsed from prior transplants underwent a second allogeneic hematopoietic stem cell transplant (allo-HSCT). One patient remained leukemia-free on day 401, and the other two died on day 241 and day 776 from non-relapse-related causes. Three CR patients without consolidative allo-HSCT relapsed within 90 days. All the nonresponders and relapsed patients had CD7 loss. The treatment was well-tolerated, with 80% experiencing mild cytokine release syndrome and none had neurotoxicity. This trial underscores the potential promising treatment of dVHH NS7CAR-T in providing clinical benefits with a manageable safety profile to CD7-positive AML patients, warranting further investigation. NCT04938115.</p>","PeriodicalId":9102,"journal":{"name":"Blood","volume":" ","pages":""},"PeriodicalIF":21.0,"publicationDate":"2024-11-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142674721","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}
BloodPub Date : 2024-11-19DOI: 10.1182/blood.2024025910
Monica S Nair, Sara K Silbert, Kai Rejeski, Karilynn A Wilson, Adam Joseph Lamble, Yannis K Valtis, Bonnie Yates, Alexa Morales Arana, Roni Shouval, Kevin J Curran, Rebecca A Gardner, Haneen Shalabi, Colleen Annesley, Jae H Park, Marion Subklewe, Nirali N Shah
{"title":"Development of ALL-Hematotox (ALL-HT): Predicting post CAR T-cell hematotoxicity in B-cell acute lymphoblastic leukemia.","authors":"Monica S Nair, Sara K Silbert, Kai Rejeski, Karilynn A Wilson, Adam Joseph Lamble, Yannis K Valtis, Bonnie Yates, Alexa Morales Arana, Roni Shouval, Kevin J Curran, Rebecca A Gardner, Haneen Shalabi, Colleen Annesley, Jae H Park, Marion Subklewe, Nirali N Shah","doi":"10.1182/blood.2024025910","DOIUrl":"https://doi.org/10.1182/blood.2024025910","url":null,"abstract":"<p><p>Immune effector cell-associated hematotoxicity (ICAHT) is a major B-cell targeted chimeric antigen receptor (CAR) T-cell related toxicity. While ICAHT incidence and severity is documented in large B-cell lymphoma (LBCL), mantle cell lymphoma (MCL), and multiple myeloma (MM), ICAHT has not been described in B-cell acute lymphoblastic leukemia (B-ALL). Similarly, the CAR-HEMATOTOX (CAR-HT) model, designed to predict severe prolonged neutropenia (>14 days of ANC <500/µl), has been validated in LBCL, MCL, and MM, but not in B-ALL. As B-ALL bone marrow (BM) infiltration can impact cytopenias, we sought to describe ICAHT and assess CAR-HT for predicting hematotoxicity in B-ALL. In a cohort of 156 children and young adults with relapsed/refractory B-ALL, the median duration of severe neutropenia (ANC <500/µl) was 13 days (95% CI 10-16), with 83 (53%) experiencing grade >3 ICAHT. Applying CAR-HT, nearly 90% were classified as high-risk, demonstrating limited discriminative power and prompting further development. Using the association identified between BM disease burden and post-infusion neutropenia (r=0.64, p<0.0001), we developed the ALL-Hematotox (ALL-HT) score which substitutes BM disease burden for ferritin in CAR-HT. The ALL-HT score associated with severe prolonged neutropenia (area under the curve=0.84, p<0.0001), and appropriately discriminated high-risk patients (47%) who had more cumulative days of neutropenia (26 vs 4 days, p<0.0001), fewer rates of complete response (88% vs 98%, p=0.03), and shorter median overall survival (9.8 vs 24 months, logrank p=0.0002). ALL-HT was also validated in two independent cohorts. The ALL-HT score refines a widely accepted predictive model of post-infusion hematotoxicity, applicable in B-ALL.</p>","PeriodicalId":9102,"journal":{"name":"Blood","volume":" ","pages":""},"PeriodicalIF":21.0,"publicationDate":"2024-11-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142674796","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}
BloodPub Date : 2024-11-19DOI: 10.1182/blood.2024025277
Jihong Ma, Zhaohui Wang, Danielle Mintzlaff, Huiping Zhang, Rashmi Ramakrishna, Eduardo Davila, Matthew T Witkowski, M Scott Lucia, Marc S Schwartz, Elizabeth A Pomfret, David W Mathes, Zhirui Wang
{"title":"Bivalent CD47 Immunotoxin for Targeted Therapy of T-Cell Acute Lymphoblastic Leukemia.","authors":"Jihong Ma, Zhaohui Wang, Danielle Mintzlaff, Huiping Zhang, Rashmi Ramakrishna, Eduardo Davila, Matthew T Witkowski, M Scott Lucia, Marc S Schwartz, Elizabeth A Pomfret, David W Mathes, Zhirui Wang","doi":"10.1182/blood.2024025277","DOIUrl":"https://doi.org/10.1182/blood.2024025277","url":null,"abstract":"<p><p>CD47 is overexpressed on the surface of many types of cancer cells, including T-cell acute lymphoblastic leukemia (T-ALL) cells. In this study, we have developed a diphtheria toxin-based bivalent anti-human CD47 immunotoxin (bi-CD47-IT) for the targeted therapy of CD47+ cancers using a unique diphtheria toxin-resistant yeast Pichia pastoris expression system. Bi-CD47-IT demonstrated compelling in vivo efficacy in multiple T-ALL cell line-derived xenograft (CDX) and patient-derived xenograft (PDX) mouse models. Bi-CD47-IT significantly prolonged the median survival of the tumor-bearing mice and highly effectively depleted the T-ALL blast cells in the peripheral blood, spleen, liver, bone marrow, brain, and spinal cord in the T-ALL CDX and PDX mouse models. Bi-CD47-IT cured 60% of tumor-bearing mice in a T-ALL Molt-4 CDX mouse model. Because CD47 is also expressed on normal tissues, including red blood cells and lymphocytes, specificity is a concern. We thus analyzed the in vitro binding avidity and hemagglutination of bi-CD47-IT in human red blood cells, finding no binding or hemagglutination. We further performed a toxicity study of bi-CD47-IT in humanized mice, which showed that bi-CD47-IT transiently depleted the human lymphocytes for ~4 weeks after the 10-day treatment. No clinical adverse events were observed. As a result, bi-CD47-IT appears to possess the \"optimal\" binding avidity, with effective binding to human CD47+ T-ALL tumor cells, no binding to human red blood cells and weak binding to human lymphocytes. We believe that bi-CD47-IT is a promising and safe therapeutic drug candidate for the targeted therapy of CD47+ cancers.</p>","PeriodicalId":9102,"journal":{"name":"Blood","volume":" ","pages":""},"PeriodicalIF":21.0,"publicationDate":"2024-11-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142674708","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}
BloodPub Date : 2024-11-19DOI: 10.1182/blood.2024026388
Warren Fiskus, Christopher P Mill, Prithviraj Bose, Lucia Masarova, Naveen Pemmaraju, Andrew Dunbar, Christine Birdwell, John A Davis, Kaberi Das, Hanxi Hou, Taghi Manshouri, Antrix Jain, Anna Malovannaya, Kevin Philip, Noor Alhamadani, Alicia Matthews, Katie Lin, Lauren Flores, Sanam Loghavi, Courtney D DiNardo, Xiaoping Su, Raajit K Rampal, Kapil N Bhalla
{"title":"Preclinical efficacy of CDK7 inhibitor-based combinations against myeloproliferative neoplasms transformed to AML.","authors":"Warren Fiskus, Christopher P Mill, Prithviraj Bose, Lucia Masarova, Naveen Pemmaraju, Andrew Dunbar, Christine Birdwell, John A Davis, Kaberi Das, Hanxi Hou, Taghi Manshouri, Antrix Jain, Anna Malovannaya, Kevin Philip, Noor Alhamadani, Alicia Matthews, Katie Lin, Lauren Flores, Sanam Loghavi, Courtney D DiNardo, Xiaoping Su, Raajit K Rampal, Kapil N Bhalla","doi":"10.1182/blood.2024026388","DOIUrl":"https://doi.org/10.1182/blood.2024026388","url":null,"abstract":"<p><p>Rising blast-percentage or secondary (s) AML transformation (sAML) in MPNs leads to JAK inhibitor (JAKi) therapy-resistance and poor survival. Here, we demonstrate that the CDK7 inhibitor (CDK7i) SY-5609 treatment depletes phenotypically-characterized post-MPN-sAML stem/progenitor cells. In the cultured post-MPN sAML SET2 and HEL as well as patient-derived (PD) post-MPN-sAML cells, SY-5609 treatment inhibited growth and induced lethality, while sparing normal cells. RNA-Seq analysis following SY-5609 treatment demonstrated reduced mRNA expressions of MYC, MYB, CDK4/6, PIM1, and CCND1, but increased mRNA levels of CDKN1A and BCL2L1. Mass spectrometry of SY-5609-treated MPN-sAML cells also demonstrated reduced c-Myc, c-Myb, PIM1, and CDK4/6 but increased p21, caspase 9 and BAD protein levels. CRISPR-mediated CDK7 depletion also reduced viability of HEL cells. CyTOF analysis of SY-5609-treated PD, post-MPN-sAML stem/progenitor cells showed reduced c-Myc, CDK6 and PU.1, but increased protein levels of CD11b, p21 and cleaved Caspase 3. Co-treatment with SY-5609 and ruxolitinib was synergistically lethal in HEL, SET2 and PD post-MPN-sAML cells. A CRISPR screen in SET2 and HEL cells revealed BRD4, CBP and p300 as co-dependencies with SY-5609 treatment. Accordingly, co-treatment with SY-5609 and the BETi OTX015 or pelabresib or with the CBP/p300 inhibitor GNE-049 was synergistically lethal in MPN-sAML cells (including those exhibiting TP53 loss). Finally, in the HEL-Luc/GFP xenograft model, compared to each agent alone, co-treatment with SY-5609 and OTX015 reduced post-MPN-sAML burden and improved survival without inducing host toxicity. These findings demonstrate promising preclinical activity of the CDK7i-based combinations with BETi or HATi against advanced-MPNs, including post-MPN-sAML.</p>","PeriodicalId":9102,"journal":{"name":"Blood","volume":" ","pages":""},"PeriodicalIF":21.0,"publicationDate":"2024-11-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142674726","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}
BloodPub Date : 2024-11-14DOI: 10.1182/blood.2024026571
Rick Kapur, John W Semple
{"title":"Let's YAP about ITP.","authors":"Rick Kapur, John W Semple","doi":"10.1182/blood.2024026571","DOIUrl":"https://doi.org/10.1182/blood.2024026571","url":null,"abstract":"","PeriodicalId":9102,"journal":{"name":"Blood","volume":"144 20","pages":"2072-2073"},"PeriodicalIF":21.0,"publicationDate":"2024-11-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142614362","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}
BloodPub Date : 2024-11-14DOI: 10.1182/blood.2024024248
Alexander E Perl
{"title":"Approaching a therapeutic inflection point for FLT3-mutated AML.","authors":"Alexander E Perl","doi":"10.1182/blood.2024024248","DOIUrl":"https://doi.org/10.1182/blood.2024024248","url":null,"abstract":"<p><p>Combining FLT3 inhibitors with intensive chemotherapy and transplant has substantially improved AML outcomes, prompting a recent re-evaluation of FLT3-ITD's historically negative prognostic effect. Treatment approaches may soon undergo major changes as emerging data suggest maximal intensity does not benefit all patients and MRD potentially can guide several treatment choices. Finally, recent data also suggest FLT3 inhibitors could transform outcomes in patients unsuitable for intensive therapy. If confirmed, this has important implications for fit patients and could revolutionize the treatment paradigm.</p>","PeriodicalId":9102,"journal":{"name":"Blood","volume":" ","pages":""},"PeriodicalIF":21.0,"publicationDate":"2024-11-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142614324","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}
BloodPub Date : 2024-11-14DOI: 10.1182/blood.2024025699
Gloria Iacoboni, Franck Morschhauser
{"title":"Building the Future Management of Follicular Lymphoma with T-Cell-Redirecting Strategies.","authors":"Gloria Iacoboni, Franck Morschhauser","doi":"10.1182/blood.2024025699","DOIUrl":"https://doi.org/10.1182/blood.2024025699","url":null,"abstract":"<p><p>Follicular lymphoma (FL) usually requires multiple lines of therapy and disease control remains largely insufficient with conventional chemoimmunotherapy. Several T-cell redirecting strategies recently approved in the relapsed/refractory setting have the potential to improve outcomes and change the treatment algorithm in FL. This review focuses on the role of chimeric antigen receptor T-cells and bispecific antibodies in FL, paying special attention to sequencing approaches and future directions.</p>","PeriodicalId":9102,"journal":{"name":"Blood","volume":" ","pages":""},"PeriodicalIF":21.0,"publicationDate":"2024-11-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142614242","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":"Ruxolitinib for pediatric patients with treatment-naïve and steroid-refractory acute graft-versus-host disease: the REACH4 study.","authors":"Franco Locatelli, Hyoung Jin Kang, Bénédicte Bruno, Virginie Gandemer, Fanny Rialland, Maura Faraci, Yoshiyuki Takahashi, Katsuyoshi Koh, Henrique Bittencourt, Grace Cleary, Christine Rosko, Xuechan Li, Annie St Pierre, Anirudh Prahallad, Cristina Diaz-de-Heredia","doi":"10.1182/blood.2023022565","DOIUrl":"10.1182/blood.2023022565","url":null,"abstract":"<p><strong>Abstract: </strong>In REACH4, a phase 1/2, open-label, single-arm, multicenter study, the pharmacokinetics (PK), efficacy, and safety of ruxolitinib were evaluated in treatment-naïve and steroid-refractory pediatric patients with grade 2 to 4 acute graft-versus-host disease (aGVHD; n = 45). Ruxolitinib dosing was based on age and targeted the exposure in adults receiving 10 mg twice daily; group 1 (aged ≥12 to <18 years) received 10 mg twice daily and preliminary starting doses for groups 2 (aged ≥6 to <12 years) and 3 (aged ≥2 to <6 years) were 5 mg twice daily and 4 mg/m2 twice daily, respectively. The phase 1 primary objective was to assess ruxolitinib PK parameters and define an age-appropriate recommended phase 2 dose (RP2D) for patients aged <12 years. The phase 2 primary objective was to measure the activity of ruxolitinib as assessed by overall response rate (ORR) at day 28; the key secondary objective was to assess the durable ORR at day 56. Ruxolitinib exposure was comparable across age groups; starting doses were confirmed as the RP2D. The median duration of ruxolitinib exposure was 3.8 months (range, 0.3-11.2). ORR in all patients was 84.4% (90% confidence interval [CI], 72.8-92.5) at day 28, with a durable ORR at day 56 of 66.7% (90% CI, 53.4-78.2); high response rates were observed across age groups and in both treatment-naïve and steroid-refractory subgroups. Adverse events were consistent with those expected in patients with aGVHD (anemia, decreased neutrophil and leukocyte count) treated with ruxolitinib. In pediatric patients with aGVHD, ruxolitinib showed clinically meaningful efficacy with no new safety signals. This trial was registered at www.clinicaltrials.gov as #NCT03491215.</p>","PeriodicalId":9102,"journal":{"name":"Blood","volume":" ","pages":"2095-2106"},"PeriodicalIF":21.0,"publicationDate":"2024-11-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141751066","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}
BloodPub Date : 2024-11-14DOI: 10.1182/blood.2023023601
Shuhong Hu, Yifei Liu, Xiang Zhang, Xiaoqi Wang, Yanting Li, Mengqian Chu, Jie Yin, Yanglan Fang, Changgeng Ruan, Li Zhu, Depei Wu, Yang Xu
{"title":"YAP1 regulates thrombopoiesis by binding to MYH9 in immune thrombocytopenia.","authors":"Shuhong Hu, Yifei Liu, Xiang Zhang, Xiaoqi Wang, Yanting Li, Mengqian Chu, Jie Yin, Yanglan Fang, Changgeng Ruan, Li Zhu, Depei Wu, Yang Xu","doi":"10.1182/blood.2023023601","DOIUrl":"10.1182/blood.2023023601","url":null,"abstract":"<p><strong>Abstract: </strong>Immune thrombocytopenia (ITP) is a complicated bleeding disease characterized by a sharp platelet reduction. As a dominating element involved in ITP, megakaryocytes (MKs) are responsible for thrombopoiesis. However, the mechanism underlying the dysregulation of thrombopoiesis that occurs in ITP remains unidentified. In this study, we examined the role of Yes-associated protein 1 (YAP1) in thrombopoiesis during ITP. We observed reduced YAP1 expression with cytoskeletal actin misalignment in MKs from patients with ITP. Using an experimental ITP mouse model, we showed that reduced YAP1 expression induced aberrant MK distribution, reduced the percentage of late MKs among the total MKs, and caused submaximal platelet recovery. Mechanistically, YAP1 upregulation by binding of GATA-binding protein 1 to its promoter promoted MK maturation. Phosphorylated YAP1 promoted cytoskeletal activation by binding its WW2 domain to myosin heavy chain 9, thereby facilitating thrombopoiesis. Targeting YAP1 with its activator XMU-MP-1 was sufficient to rescue cytoskeletal defects and thrombopoiesis dysregulation in YAP1+/- mice with ITP and patients. Taken together, these results demonstrate the crucial role of YAP1 in thrombopoiesis, providing potential for the development of diagnostic markers and therapeutic options for ITP.</p>","PeriodicalId":9102,"journal":{"name":"Blood","volume":" ","pages":"2136-2148"},"PeriodicalIF":21.0,"publicationDate":"2024-11-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142071999","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}
BloodPub Date : 2024-11-14DOI: 10.1182/blood.2024026120
Tomomi Toubai
{"title":"Ruxolitinib REACHes FOR children with GVHD.","authors":"Tomomi Toubai","doi":"10.1182/blood.2024026120","DOIUrl":"https://doi.org/10.1182/blood.2024026120","url":null,"abstract":"","PeriodicalId":9102,"journal":{"name":"Blood","volume":"144 20","pages":"2069-2070"},"PeriodicalIF":21.0,"publicationDate":"2024-11-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142614470","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}