Critical reviews in oncology/hematology最新文献

{"title":"Clinical benefit of immune checkpoint inhibitors in elderly cancer patients: Current evidence from immunosenescence pathophysiology to clinical trial results","authors":"Dimitrios C. Ziogas,&nbsp;Charalampos Theocharopoulos,&nbsp;Katerina Aravantinou,&nbsp;Aristeidis E. Boukouris,&nbsp;Dimitra Stefanou,&nbsp;Amalia Anastasopoulou,&nbsp;Panagiotis-Petros Lialios,&nbsp;George Lyrarakis,&nbsp;Helen Gogas","doi":"10.1016/j.critrevonc.2025.104635","DOIUrl":"10.1016/j.critrevonc.2025.104635","url":null,"abstract":"<div><div>The age-related decline in immunity appears to be associated not only with cancer development but also with differential responses to immune checkpoint inhibitors (ICIs). Despite their increasing utility across various malignancies and therapeutic settings, limited data -derived primarily from subgroup analyses of randomized controlled trials (RCTs), pooled meta-analyses, and retrospective studies- are available on the effects of aging on their efficacy and toxicity. Immunosenescence, characterized by the progressive decline of the function of the immune system, and inflammaging, a state of persistent low-grade sterile inflammation, may influence ICI outcomes. Additionally, the incidence, severity, and subtypes of immune-related adverse events (irAEs) may differ between older and younger individuals due to loss of immunotolerance. In the current review, starting from a a comprehensive discussion of the pathophysiology of immunosenescence, we proceed to critically review age-related retrospective and randomized evidence supporting FDA-approved ICIs. We highlight similarities or differences across age groups and the clinical benefit of ICIs in elderly versus younger cancer patients. The optimal integration of ICIs in geriatric oncology necessitates greater inclusion of this patient demographic in RCTs along with real-world data in order to acquire robust data which will guide evidence-based treatment decisions for this population.</div></div>","PeriodicalId":11358,"journal":{"name":"Critical reviews in oncology/hematology","volume":"208 ","pages":"Article 104635"},"PeriodicalIF":5.5,"publicationDate":"2025-01-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143076703","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Combining gut microbiota modulation and immunotherapy: A promising approach for treating microsatellite stable colorectal cancer","authors":"Yujie Chang ,&nbsp;Min Long ,&nbsp;Hanguo Shan ,&nbsp;Logen Liu ,&nbsp;Shangwei Zhong ,&nbsp;Jun-Li Luo","doi":"10.1016/j.critrevonc.2025.104629","DOIUrl":"10.1016/j.critrevonc.2025.104629","url":null,"abstract":"<div><div>Colorectal cancer (CRC) is one of the most prevalent and lethal cancers worldwide, ranking third in incidence and second in mortality. While immunotherapy has shown promise in patients with deficient mismatch repair (dMMR) or high microsatellite instability (MSI-H), its effectiveness in proficient mismatch repair (pMMR) or microsatellite stable (MSS) CRC remains limited. Recent advances highlight the gut microbiota as a potential modulator of anti-tumor immunity. The gut microbiome can significantly influence the efficacy of immune checkpoint inhibitors (ICIs), especially in pMMR/MSS CRC, by modulating immune responses and systemic inflammation. This review explores the role of the gut microbiota in pMMR/MSS CRC, the mechanisms by which it may enhance immunotherapy, and current strategies for microbiota modulation. We discuss the potential benefits of combining microbiota-targeting interventions with immunotherapy to improve treatment outcomes for pMMR/MSS CRC patients.</div></div>","PeriodicalId":11358,"journal":{"name":"Critical reviews in oncology/hematology","volume":"208 ","pages":"Article 104629"},"PeriodicalIF":5.5,"publicationDate":"2025-01-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143048903","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Rhythm is essential: Unraveling the relation between the circadian clock and cancer","authors":"Olajumoke Ogunlusi ,&nbsp;Abantika Ghosh ,&nbsp;Mrinmoy Sarkar ,&nbsp;Kayla Carter ,&nbsp;Harshini Davuluri ,&nbsp;Mahul Chakraborty ,&nbsp;Kristin Eckel-Mahan ,&nbsp;Alex Keene ,&nbsp;Jerome S. Menet ,&nbsp;Deborah Bell-Pedersen ,&nbsp;Tapasree Roy Sarkar","doi":"10.1016/j.critrevonc.2025.104632","DOIUrl":"10.1016/j.critrevonc.2025.104632","url":null,"abstract":"<div><div>Physiological processes such as the sleep-wake cycle, metabolism, hormone secretion, neurotransmitter release, sensory capabilities, and a variety of behaviors, including sleep, are controlled by a circadian rhythm adapted to 24-hour day-night periodicity. Disruption of circadian rhythm may lead to the risks of numerous diseases, including cancers. Several epidemiological and clinical data reveal a connection between the disruption of circadian rhythms and cancer. On the contrary, oncogenic processes may suppress the homeostatic balance imposed by the circadian clock. The integration of circadian biology into cancer research offers new options for making cancer treatment more effective, and the pharmacological modulation of core clock genes is a new approach in cancer therapy. This review highlights the role of the circadian clock in tumorigenesis, how clock disruption alters the tumor microenvironment, and discusses how pharmacological modulation of circadian clock genes can lead to new therapeutic options.</div></div>","PeriodicalId":11358,"journal":{"name":"Critical reviews in oncology/hematology","volume":"208 ","pages":"Article 104632"},"PeriodicalIF":5.5,"publicationDate":"2025-01-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143048908","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Optimization of immunotherapy-based combinations for metastatic renal cell carcinoma: A network meta-analysis","authors":"Sohyeon Park,&nbsp;Kalynn Park,&nbsp;Chaeyoon Kim,&nbsp;Sandy Jeong Rhie","doi":"10.1016/j.critrevonc.2025.104630","DOIUrl":"10.1016/j.critrevonc.2025.104630","url":null,"abstract":"<div><h3>Background</h3><div>Despite numerous meta-analyses comparing the efficacy and safety of immunotherapy-based combination therapies, the optimal therapeutic combinations remain unclear. This study aims to evaluate the optimal application of all immunotherapy-based combination therapy for advanced/metastatic renal cell carcinoma, focusing on efficacy and safety.</div></div><div><h3>Methods</h3><div>We systemically searched the Web of Science, Cochrane Library, and PubMed for studies regarding the first-line immunotherapy-based combination therapy in patients with advanced or metastatic renal cell carcinoma until April 15, 2024. We used network meta-analysis using a random effect model to facilitate direct and indirect treatment comparisons across outcomes.</div></div><div><h3>Results</h3><div>Seven clinical studies, including 5542 patients with metastatic renal cell carcinoma, were included in the network meta-analysis analysis. Regarding progression-free survival and overall survival, combined Toripalimab + Axitinib significantly outperformed other immunotherapy-based combination therapies. This regimen significantly improved progression-free survival in the intermediate/poor risk group when stratified by prognosis prediction risks compared to sunitinib alone. For the objective response rate, Avelumab + Axitinib was the most preferred strategy in the favorable-risk group, while Nivolumab + Cabozantinib was favored in the intermediate/poor-risk group compared to other immunotherapy-based combinations. The combinations of Nivolumab + Ipilimumab and Atezolizumab + Bevacizumab had favorable safety profiles.</div></div><div><h3>Conclusions</h3><div>Immunotherapy-based combination therapies significantly improved progression-free survival, overall survival and objective response rate in patients with metastatic renal cell carcinoma compared to sunitinib monotherapy. However, careful monitoring and personalized treatment strategies are required to balance efficacy and safety in patients with underlying conditions. Future research should focus on optimizing treatment protocols and elucidating the mechanisms of adverse events.</div></div>","PeriodicalId":11358,"journal":{"name":"Critical reviews in oncology/hematology","volume":"208 ","pages":"Article 104630"},"PeriodicalIF":5.5,"publicationDate":"2025-01-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143048907","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Cellular senescence in tumor immune escape: Mechanisms, implications, and therapeutic potential","authors":"Li You ,&nbsp;Qinghua Wu","doi":"10.1016/j.critrevonc.2025.104628","DOIUrl":"10.1016/j.critrevonc.2025.104628","url":null,"abstract":"<div><div>Cellular senescence, a hallmark of aging, has emerged as a captivating area of research in tumor immunology with profound implications for cancer prevention and treatment. In the tumor microenvironment, senescent cells exhibit a dual role, simultaneously hindering tumor development through collaboration with immune cells and evading immune cell attacks by upregulating immunoinhibitory proteins. However, the intricate immune escape mechanism of cellular senescence in the tumor microenvironment remains a subject of intense investigation. Chronic inflammation is exacerbated by cellular senescence through the upregulation of pro-inflammatory factors such as interleukin-1β, thereby augmenting the risk of tumorigenesis. Additionally, the interplay between autophagy and cellular senescence adds another layer of complexity. Autophagy, known to slow down the aging process by reducing p53/p21 levels, may be downregulated by cellular senescence. To harness the therapeutic potential of cellular senescence, targeting its immunological aspects has gained significant attention. Strategies such as immune checkpoint inhibitors and T-cell senescence inhibition are being explored in the context of cellular senescence immunotherapy. In this comprehensive review, we provide a compelling overview of the regulation of cellular senescence and delve into the influencing factors, including chronic inflammation, autophagy, and circadian rhythms, associated with senescence in the tumor microenvironment. We specifically focus on unraveling the enigmatic dual role of cellular senescence in tumor immune escape. By deciphering the intricate nature of cellular senescence in the tumor microenvironment, this review aims to advance our understanding and pave the way for leveraging senescence as a promising target for tumor immunotherapy applications.</div></div>","PeriodicalId":11358,"journal":{"name":"Critical reviews in oncology/hematology","volume":"208 ","pages":"Article 104628"},"PeriodicalIF":5.5,"publicationDate":"2025-01-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143048890","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Future directions in the evaluation and management of newly diagnosed metastatic cancer","authors":"Eric J. Lehrer ,&nbsp;Chachrit Khunsriraksakul ,&nbsp;Sara Garrett ,&nbsp;Daniel M. Trifiletti ,&nbsp;Jason P. Sheehan ,&nbsp;Matthias Guckenberger ,&nbsp;Alexander V. Louie ,&nbsp;Shankar Siva ,&nbsp;Piet Ost ,&nbsp;Karyn A. Goodman ,&nbsp;Laura A. Dawson ,&nbsp;Leila T. Tchelebi ,&nbsp;Jonathan T. Yang ,&nbsp;Timothy N. Showalter ,&nbsp;Henry S. Park ,&nbsp;Daniel E. Spratt ,&nbsp;Amar U. Kishan ,&nbsp;Gaorav P. Gupta ,&nbsp;Chirag Shah ,&nbsp;Stefano Fanti ,&nbsp;Nicholas G. Zaorsky","doi":"10.1016/j.critrevonc.2025.104631","DOIUrl":"10.1016/j.critrevonc.2025.104631","url":null,"abstract":"<div><div>There is much debate regarding optimal selection in patients with metastatic cancer who should undergo local treatment (surgery or radiation treatment) to the primary tumor and/or metastases. Additionally, the optimal treatment of newly diagnosed metastatic cancer is largely unclear. Current prognostication systems to best inform these clinical scenarios are limited, as all metastatic patients are grouped together as having Stage IV disease without further incorporation of patient and disease-specific covariates that significantly impact patient outcomes. Therefore, improving current prognostic scoring systems and incorporation of these covariates is essential to best individualize treatment for patients with metastatic cancer. In this narrative review article, we provide a detailed review of prognostication systems that can be used for both the site of metastasis and primary site to best tailor treatment in these patients. Additionally, we discuss the incorporation and ongoing developments in radiographic, genomic, and biostatistical techniques that can be used as prognostication tools.</div></div>","PeriodicalId":11358,"journal":{"name":"Critical reviews in oncology/hematology","volume":"208 ","pages":"Article 104631"},"PeriodicalIF":5.5,"publicationDate":"2025-01-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143048904","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Small cell lung cancer unveiled: Exploring the untapped resource of circulating tumor cells-derived organoids","authors":"Jesús A. Pérez-Cabello ,&nbsp;Ana Artero-Castro ,&nbsp;Sonia Molina-Pinelo","doi":"10.1016/j.critrevonc.2025.104622","DOIUrl":"10.1016/j.critrevonc.2025.104622","url":null,"abstract":"<div><div>Small cell lung cancer (SCLC) remains a challenge in oncology due to its aggressive behavior and dismal prognosis. Despite advances in treatments, novel strategies are urgently needed. Enter liquid biopsy—a game-changer in SCLC management. This revolutionary non-invasive approach allows for the analysis of circulating tumor cells (CTCs), offering insights into tumor behavior and treatment responses. Our review focuses on a groundbreaking frontier: harnessing CTCs to create three-dimensional (3D) organoid models. These models, derived from CTCs that break away from the primary tumor or metastatic locations, hold immense potential for revolutionizing cancer research, especially in SCLC. We explore the essential conditions for successfully establishing CTC-derived organoids—a transformative approach with profound implications for personalized medicine. Our evaluation spans diverse isolation techniques, shedding light on their advantages and limitations. Furthermore, we uncover the critical factors governing the cultivation of 3D organoids from CTCs, meticulously mimicking the tumor microenvironment. This review comprehensively elucidates the molecular characterization of these organoids, showcasing their potential in identifying treatment targets and predicting responses. In essence, our review amalgamates cutting-edge methodologies for isolating CTCs, establishing transformative CTC-derived organoids, and characterizing their molecular landscape. This represents a promising frontier for advancing personalized medicine in the complex realm of SCLC management and holds significant implications for translational research.</div></div>","PeriodicalId":11358,"journal":{"name":"Critical reviews in oncology/hematology","volume":"207 ","pages":"Article 104622"},"PeriodicalIF":5.5,"publicationDate":"2025-01-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143017903","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"« Augmented radiotherapy » in the management of high-risk prostate cancer (PCa): A systematic review","authors":"Jennifer Le Guévelou ,&nbsp;Vedang Murthy ,&nbsp;Thomas Zilli ,&nbsp;Luca Nicosia ,&nbsp;Alberto Bossi ,&nbsp;Leonard P. Bokhorst ,&nbsp;Eric Barret ,&nbsp;Idir Ouzaid ,&nbsp;Paul L. Nguyen ,&nbsp;Federica Ferrario ,&nbsp;Cyrus Chargari ,&nbsp;Stefano Arcangeli ,&nbsp;Nicolas Magne ,&nbsp;Paul Sargos","doi":"10.1016/j.critrevonc.2025.104623","DOIUrl":"10.1016/j.critrevonc.2025.104623","url":null,"abstract":"<div><h3>Background</h3><div>In patients with high-risk (HR) prostate cancer (PCa) treated with radiotherapy and androgen deprivation therapy (ADT), intensification with androgen receptor pathway inhibitor (ARPI) improves overall survival (OS), at the cost of significant side-effects. We hypothesized that “augmented RT” schedules (defined as either dose-escalation on the prostate gland over 78 Gy and/or addition of whole pelvic radiotherapy (WPRT)), combined with long-term ADT can reach excellent prostate cancer specific survival (PCSS) in this population with little detrimental impact on quality of life.</div></div><div><h3>Methods</h3><div>We searched Pubmed database until February 8, 2024. Studies reporting both oncological and toxicity outcomes after “augmented RT” were deemed eligible. Studies without ADT or with ARPI intensification were deemed ineligible.</div></div><div><h3>Results</h3><div>Dose-escalation within the prostate gland at doses over 78 Gy halved the risk of biochemical recurrence at 5 years, with however no impact on PCSS. The addition of WPRT provides a 5-year disease-free survival (DFS) reaching 89.5 % at 5 years, with no significant increase in late grade≥ 2 genito-urinary (GU) or gastrointestinal (GI) toxicity. Combined approaches result in 9-year PCSS ranging between 96.1 % and 100 %. Most approaches demonstrated excellent safety profiles.</div></div><div><h3>Conclusions</h3><div>“Augmented RT” reached excellent oncological outcomes, with minimal additional toxicity. The development of biomarkers might lead to further treatment personalization, in the rapidly evolving landscape of systemic therapies.</div></div>","PeriodicalId":11358,"journal":{"name":"Critical reviews in oncology/hematology","volume":"207 ","pages":"Article 104623"},"PeriodicalIF":5.5,"publicationDate":"2025-01-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143018357","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Real-world evidence in extensive disease small cell lung cancer: The missing piece of the puzzle","authors":"Paola Damiano ,&nbsp;Alessio Stefani ,&nbsp;Alice Avancini ,&nbsp;Lorenzo Belluomini ,&nbsp;Emilio Bria ,&nbsp;Sara Pilotto","doi":"10.1016/j.critrevonc.2025.104618","DOIUrl":"10.1016/j.critrevonc.2025.104618","url":null,"abstract":"<div><div>Small cell lung cancer (SCLC) is a highly aggressive disease, often diagnosed at an advanced stage and with limited treatment options. In recent years, immunotherapy has been approved in combination with chemotherapy in the first line setting of extensive stage disease (ES-SCLC). However, only 10–15 % of patients with ES-SCLC treated with chemoimmunotherapy (CT-IO) experience a long-term benefit. In addition, patients are often clinically frail due to advanced age, comorbidities, and disease-related symptoms, making SCLC a challenging condition. Real-world evidence (RWE) becomes particularly valuable in this scenario, not only to confirm the results of pivotal trials, but also to evaluate the outcomes of CT-IO in populations that are generally excluded from clinical trials. RWE could also define the role of integrative treatments such as thoracic consolidation radiotherapy and prophylactic cranial irradiation, which are used in selected patients in the clinical practice but were scarcely applied in pivotal trials. In this review, we focused on RWE in ES-SCLC, with the aim of improving clinical decision making. Notably, real-world data have largely confirmed the efficacy and safety of CT-IO observed in pivotal clinical trials, with a possible benefit even in more fragile patients. However, these studies also highlight that a significant proportion of the ES-SCLC population remains untreated due to poor clinical conditions.</div></div>","PeriodicalId":11358,"journal":{"name":"Critical reviews in oncology/hematology","volume":"207 ","pages":"Article 104618"},"PeriodicalIF":5.5,"publicationDate":"2025-01-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143017730","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Fibrinogen: A new player and target on the formation of pre-metastatic niche in tumor metastasis","authors":"Yuxin Zhang ,&nbsp;Zelin Li ,&nbsp;Jiamao Zhang ,&nbsp;Tatenda Mafa ,&nbsp;Jingyu Zhang ,&nbsp;Hui Zhu ,&nbsp;Lifang Chen ,&nbsp;Zhen Zong ,&nbsp;Lingling Yang","doi":"10.1016/j.critrevonc.2025.104625","DOIUrl":"10.1016/j.critrevonc.2025.104625","url":null,"abstract":"<div><div>Tumor metastasis involves a series of complex and coordinated processes, which is the main cause of patient death and still a significant challenge in cancer treatment. Pre-metastatic niches (PMN), a specialized microenvironment that develops in distant organs prior to the arrival of metastatic cancer cells, plays a crucial role in driving tumor metastasis. The development of PMN depends on a complex series of cellular and molecular components including tumor-derived factors, bone marrow-derived cells, resident immune cells, and extracellular matrix. Fibrinogen, a key factor in the typical blood clotting process, is related to tumor metastasis and prognosis, according to a growing body of evidence in recent years. Fibrinogen has emerged as an important factor in mediating the formation of tumor microenvironment. Nevertheless, a clear and detailed mechanism by which fibrinogen promotes tumor metastasis remains unknown. In this review, we first explore the roles of fibrinogen in the development of PMN from four perspectives: immunosuppression, inflammation, angiogenesis, and extracellular matrix remodeling. We highlight the significance of fibrinogen in shaping PMN and discuss its potential therapeutic values, opening new avenues for targeting fibrinogen to prevent or treat metastasis.</div></div>","PeriodicalId":11358,"journal":{"name":"Critical reviews in oncology/hematology","volume":"207 ","pages":"Article 104625"},"PeriodicalIF":5.5,"publicationDate":"2025-01-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143017628","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}