Pub Date : 2022-04-01DOI: 10.1358/dot.2022.58.4.3381586
J. Sobel
Worldwide, effective management of vulvovaginal candidiasis (VVC) continues to serve as a major therapeutic goal with numerous unmet drug treatment challenges. After 3 decades of azole drug dominance, with few recent new antifungal agents and little progress in VVC management, the first-in-class oral triterpenoid glucan synthase inhibitor agent ibrexafungerp has emerged in the treatment of acute VVC. After reviewing existing treatment standards and unmet needs, the pharmacology, pharmacokinetics, antimicrobial activity and clinical efficacy of ibrexafungerp are reviewed in this article together with phase III clinical trial results and drug safety. The projected role and status of ibrexafungerp are reviewed together with perspectives of its future development and role in the treatment of VVC.
{"title":"Ibrexafungerp for the treatment of vulvovaginal candidiasis.","authors":"J. Sobel","doi":"10.1358/dot.2022.58.4.3381586","DOIUrl":"https://doi.org/10.1358/dot.2022.58.4.3381586","url":null,"abstract":"Worldwide, effective management of vulvovaginal candidiasis (VVC) continues to serve as a major therapeutic goal with numerous unmet drug treatment challenges. After 3 decades of azole drug dominance, with few recent new antifungal agents and little progress in VVC management, the first-in-class oral triterpenoid glucan synthase inhibitor agent ibrexafungerp has emerged in the treatment of acute VVC. After reviewing existing treatment standards and unmet needs, the pharmacology, pharmacokinetics, antimicrobial activity and clinical efficacy of ibrexafungerp are reviewed in this article together with phase III clinical trial results and drug safety. The projected role and status of ibrexafungerp are reviewed together with perspectives of its future development and role in the treatment of VVC.","PeriodicalId":85144,"journal":{"name":"Medicamentos de actualidad. Drugs of today","volume":"58 4 1","pages":"149-158"},"PeriodicalIF":0.0,"publicationDate":"2022-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"42580238","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2022-04-01DOI: 10.1358/dot.2022.58.4.3400573
Xinting Zheng, Jiamin Luo, Wei Liu, C. Ashby, Zhe S Chen, Lizhu Lin
Sotorasib, a direct inhibitor of the enzyme Kirsten rat sarcoma viral oncogene (KRAS) with the G12C mutation, was approved by the U.S. Food and Drug Administration (FDA), as a second-line treatment for locally advanced or metastatic non-small cell lung cancer (NSCLC) containing the KRAS G12C mutation, on the basis of results of a phase II clinical trial (Code- BreaK100). In this article, we review the mechanism of action of KRAS G12C inhibitors and the latest clinical trials with sotorasib to provide a comprehensive understanding of its efficacy and toxicity. We also review the mechanisms that produce resistance to the KRAS G12C inhibitors and the preclinical research related to combination treatments for KRAS G12C-mutated tumors. Currently, clinical data suggests that sotorasib monotherapy has significant efficacy in NSCLC patients with the KRAS G12C mutation and tolerable toxicity, and it could represent a novel targeted therapy. Additional research will be required to delineate the mechanisms of resistance to sotorasib and determine the efficacy and safety of combination therapy for the treatment of NSCLC containing the KRAS G12C mutation.
{"title":"Sotorasib: a treatment for non-small cell lung cancer with the KRAS G12C mutation.","authors":"Xinting Zheng, Jiamin Luo, Wei Liu, C. Ashby, Zhe S Chen, Lizhu Lin","doi":"10.1358/dot.2022.58.4.3400573","DOIUrl":"https://doi.org/10.1358/dot.2022.58.4.3400573","url":null,"abstract":"Sotorasib, a direct inhibitor of the enzyme Kirsten rat sarcoma viral oncogene (KRAS) with the G12C mutation, was approved by the U.S. Food and Drug Administration (FDA), as a second-line treatment for locally advanced or metastatic non-small cell lung cancer (NSCLC) containing the KRAS G12C mutation, on the basis of results of a phase II clinical trial (Code- BreaK100). In this article, we review the mechanism of action of KRAS G12C inhibitors and the latest clinical trials with sotorasib to provide a comprehensive understanding of its efficacy and toxicity. We also review the mechanisms that produce resistance to the KRAS G12C inhibitors and the preclinical research related to combination treatments for KRAS G12C-mutated tumors. Currently, clinical data suggests that sotorasib monotherapy has significant efficacy in NSCLC patients with the KRAS G12C mutation and tolerable toxicity, and it could represent a novel targeted therapy. Additional research will be required to delineate the mechanisms of resistance to sotorasib and determine the efficacy and safety of combination therapy for the treatment of NSCLC containing the KRAS G12C mutation.","PeriodicalId":85144,"journal":{"name":"Medicamentos de actualidad. Drugs of today","volume":"58 4 1","pages":"175-185"},"PeriodicalIF":0.0,"publicationDate":"2022-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"42750264","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2022-04-01DOI: 10.1358/dot.2022.58.4.3378056
A. Labib, A. Vander Does, Gil Yosipovitch
Atopic dermatitis (AD) is a common inflammatory skin disease that has emerging treatments targeting the underlying immunological mechanism. Interleukin-31 (IL-31) is associated with the pathobiological mechanism of AD, contributing to symptoms such as dermatitis and pruritus. Nemolizumab is an anti-IL-31 receptor α-chain (IL-31RA) monoclonal antibody agent that is efficacious in improving symptoms of AD in several phase II and phase III studies in recent years. Nemolizumab demonstrates great efficacy in reducing pruritus and to a lesser degree, dermatitis associated with AD. Additionally, one advantage of nemolizumab is its quick speed of action. Adverse effects are mild and transient in nature, including exacerbation of AD, nasopharyngitis, upper respiratory tract infections, elevated creatine kinase and peripheral edema. Severe adverse effects were not common and consisted of exacerbation of AD and asthma exacerbation. Therefore, nemolizumab has the potential to be an important treatment of choice for AD given its efficacy, mild side effect profile and rapid time of onset. In this review, we examine the preclinical and clinical studies of the novel drug nemolizumab for the treatment of AD with a focus on its mechanism of action, pharmacokinetics, safety, efficacy, indications and drug interactions.
{"title":"Nemolizumab for atopic dermatitis.","authors":"A. Labib, A. Vander Does, Gil Yosipovitch","doi":"10.1358/dot.2022.58.4.3378056","DOIUrl":"https://doi.org/10.1358/dot.2022.58.4.3378056","url":null,"abstract":"Atopic dermatitis (AD) is a common inflammatory skin disease that has emerging treatments targeting the underlying immunological mechanism. Interleukin-31 (IL-31) is associated with the pathobiological mechanism of AD, contributing to symptoms such as dermatitis and pruritus. Nemolizumab is an anti-IL-31 receptor α-chain (IL-31RA) monoclonal antibody agent that is efficacious in improving symptoms of AD in several phase II and phase III studies in recent years. Nemolizumab demonstrates great efficacy in reducing pruritus and to a lesser degree, dermatitis associated with AD. Additionally, one advantage of nemolizumab is its quick speed of action. Adverse effects are mild and transient in nature, including exacerbation of AD, nasopharyngitis, upper respiratory tract infections, elevated creatine kinase and peripheral edema. Severe adverse effects were not common and consisted of exacerbation of AD and asthma exacerbation. Therefore, nemolizumab has the potential to be an important treatment of choice for AD given its efficacy, mild side effect profile and rapid time of onset. In this review, we examine the preclinical and clinical studies of the novel drug nemolizumab for the treatment of AD with a focus on its mechanism of action, pharmacokinetics, safety, efficacy, indications and drug interactions.","PeriodicalId":85144,"journal":{"name":"Medicamentos de actualidad. Drugs of today","volume":"58 4 1","pages":"159-173"},"PeriodicalIF":0.0,"publicationDate":"2022-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"41724305","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2022-04-01DOI: 10.1358/dot.2022.58.4.3352752
F. Gondal, J. Bilal, C. Kent Kwoh
Tanezumab is a novel humanized IgG2 monoclonal antibody that works by selectively targeting, binding to and inhibiting nerve growth factor (NGF). NGF is upregulated in response to injury and inflammation, and preclinical data indicate it plays a role in pain signaling by inducing peripheral and central sensitization. Tanezumab potentially reduces sensitization and pain by blocking the interaction between NGF and the tropomyosin receptor kinase A (TrkA), and it has been studied extensively for the treatment of pain in patients with osteoarthritis (OA). In 2017, tanezumab was granted fast track designation in the U.S. for the treatment of chronic pain in patients with OA, as well as for the treatment of chronic low-back pain. This review discusses the mechanism of action, preclinical data and phase I, II and III studies of efficacy and safety of tanezumab in patients with OA.
{"title":"Tanezumab for the treatment of osteoarthritis pain.","authors":"F. Gondal, J. Bilal, C. Kent Kwoh","doi":"10.1358/dot.2022.58.4.3352752","DOIUrl":"https://doi.org/10.1358/dot.2022.58.4.3352752","url":null,"abstract":"Tanezumab is a novel humanized IgG2 monoclonal antibody that works by selectively targeting, binding to and inhibiting nerve growth factor (NGF). NGF is upregulated in response to injury and inflammation, and preclinical data indicate it plays a role in pain signaling by inducing peripheral and central sensitization. Tanezumab potentially reduces sensitization and pain by blocking the interaction between NGF and the tropomyosin receptor kinase A (TrkA), and it has been studied extensively for the treatment of pain in patients with osteoarthritis (OA). In 2017, tanezumab was granted fast track designation in the U.S. for the treatment of chronic pain in patients with OA, as well as for the treatment of chronic low-back pain. This review discusses the mechanism of action, preclinical data and phase I, II and III studies of efficacy and safety of tanezumab in patients with OA.","PeriodicalId":85144,"journal":{"name":"Medicamentos de actualidad. Drugs of today","volume":"58 4 1","pages":"187-200"},"PeriodicalIF":0.0,"publicationDate":"2022-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"46635312","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2022-03-01DOI: 10.1358/dot.2022.58.3.3381585
K. Nishie, Seiichi Sato, M. Hanaoka
Cancer anorexia-cachexia syndrome is a multifactorial condition characterized by significant weight loss due to muscle loss. It is associated with functional impairment, changes in body composition and nutritional disorders. Ghrelin receptors are involved in the release of growth hormone (GH) in the pituitary gland and increase appetite via the hypothalamus. The secretion of GH from the pituitary gland stimulates the liver to secrete insulin-like growth factor 1 (IGF-1), which promotes muscle protein synthesis. Anamorelin is a ghrelin receptor agonist used to treat cancer cachexia. It promotes GH secretion via ghrelin receptor activation and increases appetite, resulting in increased muscle mass and weight. Clinical trials of anamorelin have demonstrated a significant increase in lean body mass index, improved cachexia and no significant increase in serious adverse events. The present review describes the processes leading to the approval of anamorelin in Japan, focusing on pharmacology, metabolism, efficacy, safety and clinical trials.
{"title":"Anamorelin for cancer cachexia.","authors":"K. Nishie, Seiichi Sato, M. Hanaoka","doi":"10.1358/dot.2022.58.3.3381585","DOIUrl":"https://doi.org/10.1358/dot.2022.58.3.3381585","url":null,"abstract":"Cancer anorexia-cachexia syndrome is a multifactorial condition characterized by significant weight loss due to muscle loss. It is associated with functional impairment, changes in body composition and nutritional disorders. Ghrelin receptors are involved in the release of growth hormone (GH) in the pituitary gland and increase appetite via the hypothalamus. The secretion of GH from the pituitary gland stimulates the liver to secrete insulin-like growth factor 1 (IGF-1), which promotes muscle protein synthesis. Anamorelin is a ghrelin receptor agonist used to treat cancer cachexia. It promotes GH secretion via ghrelin receptor activation and increases appetite, resulting in increased muscle mass and weight. Clinical trials of anamorelin have demonstrated a significant increase in lean body mass index, improved cachexia and no significant increase in serious adverse events. The present review describes the processes leading to the approval of anamorelin in Japan, focusing on pharmacology, metabolism, efficacy, safety and clinical trials.","PeriodicalId":85144,"journal":{"name":"Medicamentos de actualidad. Drugs of today","volume":"58 3 1","pages":"97-104"},"PeriodicalIF":0.0,"publicationDate":"2022-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"43021500","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2022-03-01DOI: 10.1358/dot.2022.58.3.3367994
Vijay K. Singh, T. Seed
Detonation of an improvised nuclear weapon, or a radiological dispersal device by terrorists, or an unintended radiological/nuclear accident in populated areas would result in a mass casualty scenario with radiation exposures of different severities. Such incidences are perceived as national security threats of major consequences. Acute radiation syndrome (ARS) is triggered by an exposure to a high dose of penetrating ionizing radiation during a short time window. In humans, moderate exposure to 2 to 4 Gy of ionizing radiation results in clinically manageable hematopoietic ARS (H-ARS), characterized by severe depletion of vital blood cells and bone marrow progenitors. Since 2015, the United States Food and Drug Administration (U.S. FDA) has approved four radiation medical countermeasures for H-ARS following the Animal Rule; namely, Neupogen, Neulasta, Leukine and Nplate (romiplostim). Here, we briefly present the treatment modalities for H-ARS. We have discussed the latest FDA-approved agent, romiplostim, as a treatment modality for H-ARS. The nature of this agent and the preclinical and clinical work that preceded its FDA approval as a radiation medical countermeasure are discussed, as are the development and use of related thrombopoietic agents for the treatment of radiation-exposed victims.
{"title":"An update on romiplostim for treatment of acute radiation syndrome.","authors":"Vijay K. Singh, T. Seed","doi":"10.1358/dot.2022.58.3.3367994","DOIUrl":"https://doi.org/10.1358/dot.2022.58.3.3367994","url":null,"abstract":"Detonation of an improvised nuclear weapon, or a radiological dispersal device by terrorists, or an unintended radiological/nuclear accident in populated areas would result in a mass casualty scenario with radiation exposures of different severities. Such incidences are perceived as national security threats of major consequences. Acute radiation syndrome (ARS) is triggered by an exposure to a high dose of penetrating ionizing radiation during a short time window. In humans, moderate exposure to 2 to 4 Gy of ionizing radiation results in clinically manageable hematopoietic ARS (H-ARS), characterized by severe depletion of vital blood cells and bone marrow progenitors. Since 2015, the United States Food and Drug Administration (U.S. FDA) has approved four radiation medical countermeasures for H-ARS following the Animal Rule; namely, Neupogen, Neulasta, Leukine and Nplate (romiplostim). Here, we briefly present the treatment modalities for H-ARS. We have discussed the latest FDA-approved agent, romiplostim, as a treatment modality for H-ARS. The nature of this agent and the preclinical and clinical work that preceded its FDA approval as a radiation medical countermeasure are discussed, as are the development and use of related thrombopoietic agents for the treatment of radiation-exposed victims.","PeriodicalId":85144,"journal":{"name":"Medicamentos de actualidad. Drugs of today","volume":"58 3 1","pages":"133-145"},"PeriodicalIF":0.0,"publicationDate":"2022-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"44059786","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2022-03-01DOI: 10.1358/dot.2022.58.3.3381592
W. Tu, Ya-juan Xiao, Yadong Wang, R. Luo, Zhe S Chen
The introduction of new classes of drugs for the treatment of multiple myeloma (MM) in the past 2 decades, such as proteasome inhibitors, immunomodulators and anti-CD38 monoclonal antibodies, coupled with autologous stem cell transplantation, has approximately doubled the 5-year survival rate of MM patients. However, the patients eventually relapse and/or become resistant to the drugs and treatment. The recent emergence of anti-B-cell maturation antigen (BCMA) therapies, especially chimeric antigen receptor T-cell (CAR-T) immunotherapy targeting BCMA, holds great prospect in MM treatment. In this article, we review in detail the advances of idecabtagene vicleucel (ide-cel, bb-2121), the first CAR-T therapy targeting BCMA for treating relapse or refractory MM approved by the U.S. Food and Drug Administration (FDA) in 2021, including the preclinical study and phase I and II clinical trials. Also, it is predicted in this review that despite its amazing clinical efficacy and relatively lower toxicity, a lot of challenges and unsolved problems for ide-cel therapy remain in the way ahead.
{"title":"Idecabtagene vicleucel for relapsed/refractory multiple myeloma: a review of recent advances.","authors":"W. Tu, Ya-juan Xiao, Yadong Wang, R. Luo, Zhe S Chen","doi":"10.1358/dot.2022.58.3.3381592","DOIUrl":"https://doi.org/10.1358/dot.2022.58.3.3381592","url":null,"abstract":"The introduction of new classes of drugs for the treatment of multiple myeloma (MM) in the past 2 decades, such as proteasome inhibitors, immunomodulators and anti-CD38 monoclonal antibodies, coupled with autologous stem cell transplantation, has approximately doubled the 5-year survival rate of MM patients. However, the patients eventually relapse and/or become resistant to the drugs and treatment. The recent emergence of anti-B-cell maturation antigen (BCMA) therapies, especially chimeric antigen receptor T-cell (CAR-T) immunotherapy targeting BCMA, holds great prospect in MM treatment. In this article, we review in detail the advances of idecabtagene vicleucel (ide-cel, bb-2121), the first CAR-T therapy targeting BCMA for treating relapse or refractory MM approved by the U.S. Food and Drug Administration (FDA) in 2021, including the preclinical study and phase I and II clinical trials. Also, it is predicted in this review that despite its amazing clinical efficacy and relatively lower toxicity, a lot of challenges and unsolved problems for ide-cel therapy remain in the way ahead.","PeriodicalId":85144,"journal":{"name":"Medicamentos de actualidad. Drugs of today","volume":"58 3 1","pages":"117-132"},"PeriodicalIF":0.0,"publicationDate":"2022-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"47056847","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2022-03-01DOI: 10.1358/dot.2022.58.3.3381593
Nathan W. Watson, H. Al‐Samkari
Hemophilia A and B are X-linked hereditary bleeding disorders due to factor VIII (FVIII) or factor IX (FIX) deficiency, respectively. Major advancements have been made in the care of patients with hemophilia, yet the development of inhibitors to infused FVIII or FIX continues to be a formidable challenge. The current first-line therapy for acute bleeding episodes in patients diagnosed with inhibitors are bypassing agents including activated prothrombin complex concentrates (aPCCs) and recombinant factor VIIa (rFVIIa). Eptacog beta (SevenFact; LFB Biotechnologies, Hema Biologics) is a new rFVIIa product produced via expression in the milk of transgenic rabbits. This emerging platform has demonstrated numerous cost advantages to traditional cell culture systems including a better ability to scale up production and better protein yields. Eptacog beta is currently approved by the U.S. Food and Drug Administration (FDA) for the on-demand control of bleeding episodes in patients with hemophilia aged 12 to 75 with inhibitors. A potential future expansion of its current label could occur given the recent completion of two major phase III clinical trials evaluating its efficacy in children as well as its use for perioperative management. In this paper, we describe the preclinical and clinical literature documenting the development of eptacog beta and discuss its current and future application for the management of patients with hemophilia and inhibitors.
{"title":"Eptacog beta, a novel recombinant factor VIIa, for the treatment of hemophilia.","authors":"Nathan W. Watson, H. Al‐Samkari","doi":"10.1358/dot.2022.58.3.3381593","DOIUrl":"https://doi.org/10.1358/dot.2022.58.3.3381593","url":null,"abstract":"Hemophilia A and B are X-linked hereditary bleeding disorders due to factor VIII (FVIII) or factor IX (FIX) deficiency, respectively. Major advancements have been made in the care of patients with hemophilia, yet the development of inhibitors to infused FVIII or FIX continues to be a formidable challenge. The current first-line therapy for acute bleeding episodes in patients diagnosed with inhibitors are bypassing agents including activated prothrombin complex concentrates (aPCCs) and recombinant factor VIIa (rFVIIa). Eptacog beta (SevenFact; LFB Biotechnologies, Hema Biologics) is a new rFVIIa product produced via expression in the milk of transgenic rabbits. This emerging platform has demonstrated numerous cost advantages to traditional cell culture systems including a better ability to scale up production and better protein yields. Eptacog beta is currently approved by the U.S. Food and Drug Administration (FDA) for the on-demand control of bleeding episodes in patients with hemophilia aged 12 to 75 with inhibitors. A potential future expansion of its current label could occur given the recent completion of two major phase III clinical trials evaluating its efficacy in children as well as its use for perioperative management. In this paper, we describe the preclinical and clinical literature documenting the development of eptacog beta and discuss its current and future application for the management of patients with hemophilia and inhibitors.","PeriodicalId":85144,"journal":{"name":"Medicamentos de actualidad. Drugs of today","volume":"58 3 1","pages":"105-116"},"PeriodicalIF":0.0,"publicationDate":"2022-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"48246556","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}