Annals of Hematology最新文献

{"title":"Trans-acting genetic modifiers of clinical severity in heterozygous β-Thalassemia trait","authors":"Joanna B. Loh,&nbsp;Jules M. Ross,&nbsp;Khaled M. Musallam,&nbsp;Kevin H. M. Kuo","doi":"10.1007/s00277-024-06007-0","DOIUrl":"10.1007/s00277-024-06007-0","url":null,"abstract":"<div><p>There is a group of beta (β)-thalassemia trait ‘carriers’ (with heterozygous mutations) who should be asymptomatic with minor abnormalities in their hematological parameters, but experience more severe disease manifestations than predicted based solely on their β-globin genotype. This review focuses on literature describing <i>trans</i>-acting genetic modifiers outside of the α- and β-globin gene clusters that could cause this phenomenon. These genetic modifiers are categorized into: mutations affecting the quantity of alpha-globin products, non-globin mutations affecting erythropoiesis, membranopathies, enzymopathies and erythrocyte-independent modifiers of complications relating to β-thalassemia. Although some genetic determinants seem to correlate more directly with β-thalassemia trait severity, such as mutations in <i>SUPT5H</i>, <i>PIEZO1</i> and hereditary elliptocytosis, the difficulties of linking the contribution of other modulating factors are elucidated in this review. Targeted next generation sequencing of hemolytic anemias can be helpful but also raises another quandary in interpreting variants of uncertain significance. The accrual of knowledge, along with the increased availability of genetic testing for genetic modifiers has considerable potential for clinical applications such as genetic counselling, decision-making for clinical interventions and prognostication, and perhaps generating new therapeutic targets.</p></div>","PeriodicalId":8068,"journal":{"name":"Annals of Hematology","volume":"103 11","pages":"4437 - 4447"},"PeriodicalIF":3.0,"publicationDate":"2024-09-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142307003","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A study of the relationship between circulating cytokines (interleukin-2 receptor and tumor necrosis factor receptor 2) and risk of B-cell non-hodgkin lymphoma.","authors":"Sara El-Sayed Abd El-Ghani, Heba Youssef Abido, Nehad Mohamed Tawfik, Gehan Shaheen, Hend Nabil Ellithy","doi":"10.1007/s00277-024-05996-2","DOIUrl":"https://doi.org/10.1007/s00277-024-05996-2","url":null,"abstract":"<p><p>Mature B-cell non-Hodgkin lymphoma (B-NHL) occurs due to uncontrolled B-lymphocyte clonal expansion. Cytokines can directly stimulate B-cell proliferation and prevent B-cell apoptosis. Dysregulation of cytokines may play an important role in the development of B-NHL by enhancing chromosomal translocation, which is the hallmark of B-NHL. Both interleukin 2 and tumor necrosis factor-α are proinflammatory cytokines and play important roles in the growth, differentiation, and apoptosis of B cells.We conducted a prospective case-control study applied to 50 patients with B-NHL at Kasr Al Aini Hospital, Cairo University, and 50 age- and sex-matched controls. Clinical, laboratory and imaging data were collected. In all patients and controls, sIL-2R and sTNF-R2 levels were measured by enzyme-linked immunosorbent assay (ELISA). The Spearman correlation test was used to evaluate the correlation between the studied cytokines and clinical, laboratory and imaging findings. Sensitivity analysis was conducted to detect the cutoff values of the studied cytokines.Serum levels of sIL-2R and sTNF-R2 were significantly higher in patients than in controls. Additionally, their levels were significantly higher in aggressive types and advanced stages of lymphoma. Also, the studied cytokines were significantly correlated with different clinical and laboratory parameters of lymphoma. The level of sIL-2R and sTNF-R2 were closely related to the type of lymphoma (P value ˂ 0.001 and 0.012, respectively), further it was also associated with the natural history of lymphoma (aggressive vs. indolent) (P value ˂0.001 and 0.04 respectively).We concluded that Pretreatment levels of sIL-2R and sTNF-R2 may play a role in the natural history and prognosis of lymphoma. They may be used as a prognostic factor for B-NHL patients and may also help with treatment decisions.</p>","PeriodicalId":8068,"journal":{"name":"Annals of Hematology","volume":" ","pages":""},"PeriodicalIF":3.0,"publicationDate":"2024-09-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142307002","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Response to daratumumab-retreatment in patients with multiple myeloma.","authors":"Laura Souren, Gabriele Ihorst, Christine Greil, Monika Engelhardt, Ralph Wäsch","doi":"10.1007/s00277-024-05991-7","DOIUrl":"https://doi.org/10.1007/s00277-024-05991-7","url":null,"abstract":"<p><p>Daratumumab is an effective therapy in multiple myeloma (MM). We assessed whether daratumumab retreatment may re-induce significant responses and which patients do benefit the most. We hypothesized, that there is effective synergism between daratumumab and alternating antimyeloma drug combinations during retreatment and that retreatment is safe and effective. Here, we analyzed 293 consecutive MM patients receiving daratumumab at our institution from 2016 until 2023 retrospectively, and compared responses, side effects and survival of the first daratumumab treatment line and its retreatment. We identified 22/293 (8%) patients with daratumumab retreatment. These patients showed an advanced age and ISS/R-ISS stages, and ≥ 3 lines of prior antimyeloma therapy in 91%. Of note, the median durations of the first and subsequent daratumumab treatment were similarly long. We confirmed a therapy break between daratumumab lines as advantageous. Daratumumab retreatment was effective, with responses declining only gradually from its first use to subsequent first and second retreatment with 64%, 46% and 43%, respectively. Interestingly, comparable progression free survival rates were observed with 11.5, 12 months and not reached, respectively. Consistently, adverse events per daratumumab line did not increase. Our findings suggest that well-selected daratumumab-exposed MM patients may show rewarding responses to daratumumab retreatment, the more with alternating antimyeloma combinations, initial good response and CD38-antibody-treatment pauses, thereby proving CD38-antibody-retreatment as feasible, effective and non-toxic. Confirmatory studies are required to further validate our results.</p>","PeriodicalId":8068,"journal":{"name":"Annals of Hematology","volume":" ","pages":""},"PeriodicalIF":3.0,"publicationDate":"2024-09-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142279618","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Broadening perspectives: redefining the role of obesity in ITP.","authors":"Chenglong Liang, Chen Zhou, Jingye Pan","doi":"10.1007/s00277-024-06018-x","DOIUrl":"https://doi.org/10.1007/s00277-024-06018-x","url":null,"abstract":"","PeriodicalId":8068,"journal":{"name":"Annals of Hematology","volume":" ","pages":""},"PeriodicalIF":3.0,"publicationDate":"2024-09-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142279691","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Distinct pathway activities are associated with prognosis and response to bortezomib-containing treatment in MCL1-M based molecular subtypes of multiple myeloma.","authors":"Yuan Yang, Sitao Jiang, Hang Du, Jingling Tang, Pengli Xiao, Yin Wu, Jiuyi Li, Jing Feng, Yanfei Wei, Ayaz Ali Samo, Xuzhang Lu, Xiaolong Fan","doi":"10.1007/s00277-024-06009-y","DOIUrl":"https://doi.org/10.1007/s00277-024-06009-y","url":null,"abstract":"<p><p>Multiple myeloma (MM) is the second most prevalent hematological malignancy and remains incurable with remarkable heterogeneity in prognosis and treatment response across the patients. Clinical diagnosis and the existing molecular classification systems are inadequate for predicting treatment responses. Based on the convergence between plasma cell development and MM pathogenesis, we identified a gene co-expression module centered on the plasma cell survival regulator MCL1 (MCL1 module, MCL1-M) in the transcriptomes of pre-treated MM, which enabled stratification of MM patients into MCL1-M high and MCL1-M low molecular subtypes with subtype-specific prognosis and response to bortezomib-containing treatment. Here, we aimed to examine the mechanism underlying the disparate prognosis and treatment responses between the two molecular subtypes. Our findings reveal that MCL1-M high MM displays significant activation of pathways associated with cell proliferation, while MCL1-M low MM exhibits activation of immune-related signaling pathways. The relative enrichment of immune cells within the bone marrow microenvironment of MCL1-M low MM, particularly plasmacytoid dendritic cells, likely contributes to the activation of immune-related signaling pathways in this subset of myeloma cells. Using phase III trial data, we show that responses to bortezomib-containing treatment are associated with the extent of unfolded protein response (UPR) signaling activity. Further, bortezomib-mediated killing of MM cells could be enhanced or inhibited by in vitro manipulation of UPR activities in representative cell lines. In conclusion, MCL1-M based molecular subtypes of MM are characterized by distinct signaling activities from both malignant cells and bone marrow microenvironment, which may drive distinct prognosis and treatment responses.</p>","PeriodicalId":8068,"journal":{"name":"Annals of Hematology","volume":" ","pages":""},"PeriodicalIF":3.0,"publicationDate":"2024-09-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142279696","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"CAR-T cells for the treatment of pediatric chronic myeloid leukemia in repeatedly relapsed lymphoid blast phase","authors":"Laura-Jane Kramp,&nbsp;Christiane Heydrich-Karsten,&nbsp;Stephanie Sembill,&nbsp;Axel Karow,&nbsp;Thomas Lion,&nbsp;Guranda Chitadze,&nbsp;Meinolf Suttorp,&nbsp;Gunnar Cario,&nbsp;Markus Metzler","doi":"10.1007/s00277-024-06011-4","DOIUrl":"10.1007/s00277-024-06011-4","url":null,"abstract":"<div><p>Chronic myeloid leukemia presenting de novo in the blast phase (CML-BP) is a rare diagnosis among pediatric malignancies. We report on a 16-year-old male who presented with CML-BP lymphoid at diagnosis. He was treated with shortened acute lymphoblastic leukemia induction plus the tyrosine kinase inhibitor (TKI) imatinib followed by dasatinib. After achieving molecular remission (MR), hematopoietic stem cell transplantation (HSCT) was performed early after diagnosis. Despite prophylactic dasatinib, he relapsed 3 months later with the kinase domain mutation T315I. Multiple therapeutic approaches including ponatinib, blinatumomab, a 2nd HSCT from a different donor, donor lymphocyte infusions, and high-dose asciminib all resulted in subsequent relapse. Another molecular response was achieved by combining ponatinib plus asciminib with chemotherapy. In this situation, CD19-directed CAR-T cells (Kymriah^®) were administered for compassionate use and tolerated without adverse events. Compared to all prior therapies, CAR T-cells maintained remission. After 12 months of follow-up, complete B-cell aplasia and low numbers of CAR-T cells are detectable in the peripheral blood, potentially mediating long-term disease control.</p></div>","PeriodicalId":8068,"journal":{"name":"Annals of Hematology","volume":"103 11","pages":"4811 - 4815"},"PeriodicalIF":3.0,"publicationDate":"2024-09-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://link.springer.com/content/pdf/10.1007/s00277-024-06011-4.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142279692","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Optimizing individualized therapy decision-making in multiple myeloma (MM): integration and impact of the Revised Myeloma Comorbidity Index in the MM-tumor board.","authors":"Esther Dreyling, Gabriele Ihorst, Heike Reinhardt, Jan Räder, Maximilian Holler, Georg Herget, Christine Greil, Ralph Wäsch, Monika Engelhardt","doi":"10.1007/s00277-024-06010-5","DOIUrl":"https://doi.org/10.1007/s00277-024-06010-5","url":null,"abstract":"<p><p>Multiple Myeloma (MM) is a hematological disease predominantly affecting elderly patients. The complexity of current treatment necessitates individualized approaches. Therein, functional assessment (FA) tools, such as the Revised Comorbidity Index (R-MCI) at our University- and Comprehensive Cancer Center Freiburg, play a crucial role. This study aimed to determine (a) the implementation of the R-MCI in our MM-tumor board (MM-TB), (b) its impact on treatment guidance at baseline and (c) potential changes during follow-up. This exploratory study investigated R-MCI coverage and distribution in a cohort of patients with multiple TB presentations. Among them, a follow-up patient cohort undergoing subsequent MM-therapy was analyzed to determine treatment adjustments and changes in patients' condition measured by R-MCI alterations. During our 3-year assessment period, 565 patients were presented in our MM-TB, totaling 1256 TB-presentations. In the multiple TB presentation cohort, the median number of TB presentations was 3 (range: 2-12). R-MCI scores within the MM-TB were available in 94%, whereas in 6%, the R-MCI had not been integrated. Among these, potential failure to identify the need for treatment modifications was determined. In the follow-up cohort, patient characteristics were typical for referral/university centers. Dose reductions were performed in 55% and were more prevalent among patients with ≥ 4 vs. lesser TB presentations. Most patients (55%) showed a fitness stabilization or improvement via follow-up R-MCI. R-MCI integration in MM-TB exceeded > 90%, indicating its successful integration for treatment support. Our results underscore its value in guiding therapy decisions, providing a comprehensive assessment beyond age considerations.</p>","PeriodicalId":8068,"journal":{"name":"Annals of Hematology","volume":" ","pages":""},"PeriodicalIF":3.0,"publicationDate":"2024-09-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142279617","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Distinct mutation features and its clinical significance in myelodysplastic syndromes with normal karyotype","authors":"Nanfang Huang,&nbsp;Chunkang Chang,&nbsp;Lingyun Wu,&nbsp;Qi He,&nbsp;Zheng Zhang,&nbsp;Xiao Li,&nbsp;Feng Xu","doi":"10.1007/s00277-024-06005-2","DOIUrl":"10.1007/s00277-024-06005-2","url":null,"abstract":"<div><p>Myelodysplastic syndromes (MDS) is a highly heterogeneous myeloid neoplastic disease, which needs personalized evaluation and therapy. To analyze the features and significance of gene mutations for MDS patients with normal karyotype (NK) at diagnosis, targeted sequencing was conducted on 616 MDS patients with NK, alongside 457 MDS cases with abnormal karyotype (AK). The results showed that the incidence of somatic mutation reached 70.3% and 83.8% in the NK and AK group, respectively. Initial mutation including ASXL1, DNMT3A and TET2 were common in NK group, which is the same as AK group. Some karyotype-associated gene mutations, such as TP53 and U2AF1, were relatively rare in NK group. Moreover, 34 out of 91 samples who progressed to acute myeloid leukemia (AML) underwent repeat sequencing during follow-up. 25 cases were checked out with newly emerged mutations. The AML-associated genetic alterations mainly involved with active signaling and transcription factors. In patients with NK, serial targeted sequencing was employed for minimal residual disease (MRD) monitoring, indicating the efficacy and relapse of the patients. In summary, MDS with NK showed distinct mutation features from those with AK. High-frequency gene mutations together with the mutational evolution suggested the diagnostic and monitoring significance of next generation sequencing for NK-MDS.</p></div>","PeriodicalId":8068,"journal":{"name":"Annals of Hematology","volume":"103 11","pages":"4485 - 4495"},"PeriodicalIF":3.0,"publicationDate":"2024-09-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142279695","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Only FLT3-ITD co-mutation did not have a deleterious effect on acute myeloid leukemia patients with NPM1 mutation, but concomitant with DNMT3A co-mutation or a < 3log reduction of MRD2 predicted poor survival","authors":"Wenbing Duan,&nbsp;Jinsong Jia,&nbsp;Jing Wang,&nbsp;Xiaohong Liu,&nbsp;Wenjing Yu,&nbsp;Xiaolu Zhu,&nbsp;Ting Zhao,&nbsp;Qian Jiang,&nbsp;Guorui Ruan,&nbsp;Xiaosu Zhao,&nbsp;Hongxia Shi,&nbsp;Yingjun Chang,&nbsp;Yu Wang,&nbsp;Lanping Xu,&nbsp;Xiaohui Zhang,&nbsp;Xiaojun Huang,&nbsp;Hao Jiang","doi":"10.1007/s00277-024-06001-6","DOIUrl":"10.1007/s00277-024-06001-6","url":null,"abstract":"<div><p>Co-occurring mutations are frequently observed in acute myeloid leukemia (AML) with <i>NPM1</i> mutation, and <i>NPM1</i> measurable residual disease (MRD) is an effective prognostic biomarker. This retrospective study investigated the impact of gene co-mutations and <i>NPM1</i> MRD on outcomes in these patients. Among 234 patients, 11.5% carried the rare type <i>NPM1</i> mutation (<i>NPM1</i>^<i>RT</i>). The median age was 49 years (IQR 36–58), with a median follow-up of 30.4 months (IQR 12.1–55.7). Nine genes were mutated in &gt; 10%, with <i>DNMT3A</i> (53.8%) and <i>FLT3-ITD</i> (44.4%) being most prevalent. Univariable analysis in 137 patients showed <i>FLT3-ITD, DNMT3A</i> co-mutations, and MRD2 &lt; 3 log reduction predicted poorer survival. <i>FLT3-ITD</i> and <i>DNMT3A</i> co-mutations correlated with the lowest event-free (EFS) and overall survival (OS) (3-year EFS 30.0%; 3-year OS 34.4%; both <i>p</i> &lt; 0.001). <i>FLT3-ITD</i> alone did not worsen survival compared to patients without <i>FLT3-ITD</i>. Multivariable analysis identified <i>DNMT3A</i> co-mutation [EFS, HR = 1.9, <i>p</i> = 0.021; OS, HR = 2.2, <i>p</i> = 0.023] and MRD2 ≥ 3 log reduction (EFS, HR = 0.2; OS, HR = 0.1, both <i>p</i> &lt; 0.001) as independent survival predictors. Patients with <i>FLT3-ITD</i> and <i>DNMT3A</i> co-mutations or a MRD2 &lt; 3 log reduction were identified as high risk, but allogeneic hematopoietic stem cell transplantation (allo-HSCT) improved survival significantly compared to chemotherapy only (3-year EFS, 57.9% <i>vs</i>. 30.0%, <i>p</i> = 0.012; 3-year OS, 72.9% <i>vs</i>. 34.4%, <i>p</i> = 0.001). In AML patients with <i>NPM1</i> mutation, the detrimental impact of <i>FLT3-ITD</i> mutation was exacerbated by <i>DNMT3A</i> co-mutation. Poor-risk younger patients identified by <i>FLT3-ITD</i> and <i>DNMT3A</i> co-mutations or MRD2 &lt; 3 log reduction benefit from allo-HSCT.</p></div>","PeriodicalId":8068,"journal":{"name":"Annals of Hematology","volume":"103 11","pages":"4525 - 4535"},"PeriodicalIF":3.0,"publicationDate":"2024-09-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142257961","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Relapsed mantle cell lymphoma manifesting with soft tissue tumors of the extremities: University of Miami experience and review of the literature","authors":"Iris Margalit Trutzer,&nbsp;Izidore S. Lossos","doi":"10.1007/s00277-024-05997-1","DOIUrl":"10.1007/s00277-024-05997-1","url":null,"abstract":"<div><p>Mantle cell lymphoma (MCL) is frequently diagnosed at advanced stages and is characterized by multiple extranodal sites of disease, most notably the bone marrow, peripheral blood, and gastrointestinal tract. Historically the prognosis of mantle cell lymphoma has been poor with median survival of four to five years. With new treatment regimens, however, patients have been able to achieve prolonged remissions and require special attention while being evaluated for relapse. This report describes four patients treated for stage IV mantle cell lymphoma at the University of Miami who developed soft tissue relapse presenting as non-tender large masses of the extremities, including one patient who presented without associated nodal involvement. Average time to soft tissue relapse was 99 months (range: 28–240) following initial diagnosis. Providers who care for patients with mantle cell lymphoma should be aware of soft tissue lesions as a presentation of mantle cell lymphoma that merits evaluation for disease relapse.</p></div>","PeriodicalId":8068,"journal":{"name":"Annals of Hematology","volume":"103 11","pages":"4581 - 4588"},"PeriodicalIF":3.0,"publicationDate":"2024-09-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://link.springer.com/content/pdf/10.1007/s00277-024-05997-1.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142257959","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}