Journal of vascular anomalies最新文献

{"title":"Trametinib Inhibits Lymphatic Vessel Invasion of Bone in a Mouse Model of Gorham-Stout Disease","authors":"Anna L. McCarter, M. Dellinger","doi":"10.1097/jova.0000000000000070","DOIUrl":"https://doi.org/10.1097/jova.0000000000000070","url":null,"abstract":"Gorham-Stout disease (GSD) is a rare lymphatic anomaly that can be caused by somatic activating mutations in KRAS. This discovery has led investigators to suggest that MEK inhibitors could be a novel treatment for GSD. However, the effect of MEK inhibitors on bone disease in animal models of GSD has not been investigated. We recently reported that Osx-tTA;TetO-Vegfc mice exhibit a phenotype that resembles GSD. Osx-tTA;TetO-Vegfc mice overexpress vascular endothelial growth factor-C (VEGF-C) in bone, which stimulates the development of lymphatic vessels in bone and the gradual loss of cortical bone. The objective of this study was to characterize the effect of trametinib, an FDA-approved MEK1/2 inhibitor, on lymphangiogenesis and osteolysis in Osx-tTA;TetO-Vegfc mice. Immunoblotting was performed to assess the effect of trametinib on VEGF-C-induced phosphorylation of ERK1/2, AKT, and S6 in primary human lymphatic endothelial cells. Prevention and intervention experiments were performed to determine the effect of trametinib on lymphangiogenesis and osteolysis in Osx-tTA;TetO-Vegfc mice. We found that trametinib blocked VEGF-C-induced phosphorylation of ERK1/2 in primary human lymphatic endothelial cells. We also found that trametinib prevented VEGF-C-induced lymphatic invasion of bone and cortical bone loss in Osx-tTA;TetO-Vegfc mice. Additionally, trametinib slowed the progression of disease in Osx-tTA;TetO-Vegfc mice with established disease. However, it did not reverse disease in Osx-tTA;TetO-Vegfc mice. Our results show trametinib impacts bone disease in Osx-tTA;TetO-Vegfc mice. These findings further support the testing of MEK inhibitors in patients with GSD and other RAS pathway-driven complex lymphatic anomalies with bone involvement.","PeriodicalId":74008,"journal":{"name":"Journal of vascular anomalies","volume":"44 9","pages":""},"PeriodicalIF":0.0,"publicationDate":"2023-11-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139273498","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}

{"title":"Surgical Treatment of Vascular Anomalies in the Extremities: A Single Surgeon Experience","authors":"Ricardo Rodriguez Colon, Courtney Cripps, Francine Blei, Sheel Sharma","doi":"10.1097/jova.0000000000000072","DOIUrl":"https://doi.org/10.1097/jova.0000000000000072","url":null,"abstract":"The literature on surgical management of vascular anomalies has primarily focused on the head and neck area, while studies of anomalies on the extremities have typically included larger and more dramatic clinical presentations. In this article, we aim to present our experience with surgical management of smaller symptomatic anomalies of the extremities. We performed a retrospective review of a single surgeon’s experience at a large academic center on patients from January 2013 to March 2022. We collected data on patient demographics, past medical and surgical history, operative dictations, clinic notes, and postoperative follow-up. Included patients were required to have confirmed vascular anomalies based on final pathology reports. A total of 47 patients underwent a total of 50 procedures, with 2 patients experiencing recurrence requiring repeat operative management. Our cohort had average age (standard deviation) of 27.16 (18.67). Sixteen patients had prior history of vascular anomalies upon presentation to our institution. The majority of lesions were located in a digit of the hand, the arm, or the foot. On surgical excision, the average size (range) of the excised lesions was 3.54 cm (0.5–15.0 cm) by 2.22 cm (0.3–8.0 cm). Four required coverage with local flaps, 3 with full-thickness skin graft (FTSG) and 2 with microvascular free flap. The 2 most common pathologic diagnoses were arteriovenous malformation and hemangioma, each with 14 patients. Overall complication rate was 2%, with 1 patient experiencing wound dehiscence requiring FTSG. Follow-up ranged from 0.1 months to 46.9 months with an average of 3.86 months. In the appropriately selected patient, surgical excision of symptomatic vascular anomalies of the extremities can be successfully performed with a low complication rate. Most lesions can be appropriately treated with direct excision and direct closure, although some may require FTSG, local flap, or microvascular free flap.","PeriodicalId":74008,"journal":{"name":"Journal of vascular anomalies","volume":"59 2","pages":""},"PeriodicalIF":0.0,"publicationDate":"2023-11-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139272255","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}

{"title":"Music Therapy for Pediatric Pain Management During Bedside Sclerotherapy","authors":"Sheryl Tulin-Silver, Gabriela Asch-Ortiz, D. Tsze","doi":"10.1097/jova.0000000000000074","DOIUrl":"https://doi.org/10.1097/jova.0000000000000074","url":null,"abstract":"The management of pain is one of the primary concerns when administering sclerotherapy in children with vascular malformations. However, there is currently no standard of care and limited data regarding the effective treatment of pain associated with sclerotherapy. In this case report, we describe the successful management of pain using music therapy in a child undergoing bedside sclerotherapy for a lymphatic malformation. This report is novel in that it demonstrates the effectiveness of music therapy as an individualized integrative approach for providing pain management to children undergoing bedside sclerotherapy.","PeriodicalId":74008,"journal":{"name":"Journal of vascular anomalies","volume":"65 2","pages":""},"PeriodicalIF":0.0,"publicationDate":"2023-11-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139278603","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}

{"title":"Parkes Weber Syndrome: Contribution of the Genotype to the Diagnosis","authors":"T. A. Andreoti, A. Tuleja, Y. Döring, Massimo Maiolo, André Schaller, Erik Vassella, C. Zweier, L. Boon, M. Vikkula, Jochen Rössler, S. Bernhard, Iris Baumgartner","doi":"10.1097/jova.0000000000000076","DOIUrl":"https://doi.org/10.1097/jova.0000000000000076","url":null,"abstract":"Parkes Weber syndrome (PWS) is a rare disorder that combines overgrowth, capillary malformations, and arteriovenous malformations (AVM)/arteriovenous fistulas, for which underlying activating mutations in the ras/mitogen-activated protein kinase/extracellular-signal-regulated kinase signaling pathway have been described. The clinical overlap with Klippel-Trenauny syndrome, associated with mutations in PIK3CA, is significant. This case series aimed to elaborate on the phenotypic description of PWS, to underline its clinical overlap with Klippel-Trenauny syndrome and nonsyndromic AVM, and to evaluate the contribution of genotypic characterization to the diagnosis. All patients diagnosed with PWS upon enrollment in the Bernese VAScular COngenital Malformations (VASCOM) cohort were included. The diagnostic criteria of PWS were retrospectively reviewed. A next-generation sequencing (NGS) gene panel (TSO500, Illumina) was used on tissue biopsy samples. Overall, 10/559 patients of the VAScular COngenital Malformations cohort were initially diagnosed with PWS. Three patients were reclassified as nonsyndromic AVM (Kristen Rat Sarcoma Viral oncogene homolog [KRAS], KRAS+tumor protein p53, and protein tyrosine phosphatase non-receptor type 11). Finally, 7 patients fulfilled all clinical diagnostic criteria of PWS. Genetic testing was available in 5 PWS patients. Only 1 patient had the classic RASA1 mutation; another patient had mutations in G protein subunit alpha q (GNAQ) and phosphatase and tensin homolog. In a third case, a PIK3CA mutation was detected. In 2 patients, no mutations were identified. Overgrowth syndromes with vascular malformations are rare and their clinical overlap hampers the classification of individual phenotypes under specific syndrome labels, sometimes even despite genetic testing. To provide optimal patient care, an accurate phenotypic description combined with the identification of molecular targets for precision medicine may be more meaningful than the syndrome classification itself.","PeriodicalId":74008,"journal":{"name":"Journal of vascular anomalies","volume":"232 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2023-11-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139278847","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}

{"title":"Baseline Quality of Life in Low-Flow Head and Neck Vascular Malformations in Children","authors":"Sean S. Evans, Steven L. Goudy, Ching Siong Tey, R. Swerdlin, C. M. Hawkins","doi":"10.1097/jova.0000000000000075","DOIUrl":"https://doi.org/10.1097/jova.0000000000000075","url":null,"abstract":"To determine baseline quality of life characteristics in patients with low-flow head and neck vascular malformations. Retrospective review of prospectively collected data. Tertiary Pediatric Hospital. Patients with low-flow head and neck vascular malformations (age 0–18 years) evaluated through our vascular anomalies clinic from 2016 to 2019 were reviewed. Patients with completed PedsQL surveys using parent-proxy reports for children 2–7 years old and both patient and parent-proxy data for patients ≥8 years old were included. In total 94 consecutive patients were included, with a mean age of 9.2 ± 4.7 years. Diagnoses included lymphatic malformations (n = 50), venous malformations (n = 41), and combined venolymphatic malformations (n = 3). Total parental quality of life scores were lower than their children’s (84.23 vs 87.45; P = .037), with lower emotional scores as age at presentation increased (d = −0.60; P < .01). Lower parental scores were also noted across multiple domains for submandibular/sublingual, oropharyngeal, hypopharyngeal, and orbital involvement. (g = −0.68 to −1.10; P < .05). Increasing subsite number involvement affected parents and children similarly (−0.30 vs −0.35; P ≤ .02). Higher physical function scores were noted in venous versus lymphatic malformations (d =−1.07; P = .01). The child-reported school function scores were lower in African-American versus Caucasian children (P = .04). Prior treatment was associated with lower parental scores (d = 0.59; P = .04). The parent and patient’s quality of life is reduced across multiple domains for low-flow head and neck vascular malformations based on age, lesion location and type, disease burden, race, and prior treatment.","PeriodicalId":74008,"journal":{"name":"Journal of vascular anomalies","volume":"20 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2023-11-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139282749","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}

{"title":"Pathophysiology of Slow-Flow Vascular Malformations: Current Understanding and Unanswered Questions.","authors":"Averill Clapp,&nbsp;Carrie J Shawber,&nbsp;June K Wu","doi":"10.1097/JOVA.0000000000000069","DOIUrl":"https://doi.org/10.1097/JOVA.0000000000000069","url":null,"abstract":"<p><strong>Background: </strong>Slow-flow vascular malformations include venous, lymphatic, and lymphaticovenous malformations. Recent studies have linked genetic variants hyperactivating either the PI3K/AKT/mTOR and/or RAS/RAF/MAPK signaling pathways with slow-flow vascular malformation development, leading to the use of pharmacotherapies such as sirolimus and alpelisib. It is important that clinicians understand basic and translational research advances in slow-flow vascular malformations.</p><p><strong>Methods: </strong>A literature review of basic science publications in slow-flow vascular malformations was performed on Pubmed, using search terms \"venous malformation,\" \"lymphatic malformation,\" \"lymphaticovenous malformation,\" \"genetic variant,\" \"genetic mutation,\" \"endothelial cells,\" and \"animal model.\" Relevant publications were reviewed and summarized.</p><p><strong>Results: </strong>The study of patient tissues and the use of primary pathogenic endothelial cells from vascular malformations shed light on their pathological behaviors, such as endothelial cell hyperproliferation and disruptions in vessel architecture. The use of xenograft and transgenic animal models confirmed the pathogenicity of genetic variants and allowed for preclinical testing of potential therapies. These discoveries underscore the importance of basic and translational research in understanding the pathophysiology of vascular malformations, which will allow for the development of improved biologically targeted treatments.</p><p><strong>Conclusion: </strong>Despite basic and translation advances, a cure for slow-flow vascular malformations remains elusive. Many questions remain unanswered, including how genotype variants result in phenotypes, and genotype-phenotype heterogeneity. Continued research into venous and lymphatic malformation pathobiology is critical in understanding the mechanisms by which genetic variants contribute to vascular malformation phenotypic features.</p>","PeriodicalId":74008,"journal":{"name":"Journal of vascular anomalies","volume":"4 3","pages":"e069"},"PeriodicalIF":0.0,"publicationDate":"2023-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/9d/56/jv9-4-e069.PMC10473035.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10158198","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Estimate of the Prevalence of Vascular Malformations","authors":"A. Penington, R. Phillips, Nerida Sleebs, J. Halliday","doi":"10.1097/jova.0000000000000068","DOIUrl":"https://doi.org/10.1097/jova.0000000000000068","url":null,"abstract":"\u0000 \u0000 To estimate the prevalence of vascular malformations using retrospective data collected from 1999 to 2020 in a specialty vascular anomalies service.\u0000 \u0000 \u0000 \u0000 The vascular anomalies service associated with the Royal Children’s Hospital provides a reference service to both adults and children, covering the entire state of Victoria, Australia, which has a population of 6.7 million and around 70,000 births per year. A database of patients was interrogated to identify those treated by the service over the study period with a diagnosis of vascular malformation, excluding capillary malformations. A total of 1501 patients were identified, including 1233 with slow-flow malformations and 147 with arteriovenous malformations. Prevalence was calculated as the number of cases born per year who attended the service plus those estimated as yet to attend for assessment, divided by the average number of live births each year. This was calculated for a selected period comprising the years when the numbers were expected to be most stable.\u0000 \u0000 \u0000 \u0000 The prevalence of slow-flow malformations is estimated to be 1 case per thousand livebirths. Approximate estimates of cases per 100,000 births for individual lesions are: venous malformation 45, lymphatic malformation 35, intramuscular slow-flow malformation 10, complex malformations (Klippel-Trenaunay and CLOVES) 4, glomuvenous malformation 5, and verrucous venous malformation 2. The prevalence of extracranial arteriovenous malformation is estimated to be around one case per 10,000 population.\u0000 \u0000 \u0000 \u0000 An updated estimate, more accurate than those previously published, of the prevalence of vascular malformations has been obtained.\u0000","PeriodicalId":74008,"journal":{"name":"Journal of vascular anomalies","volume":"1 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2023-07-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"88034805","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}

{"title":"Genotype–Phenotype and Genotype–Outcome Analysis of Capillary Malformation–Arteriovenous Malformation","authors":"Yi Sun, Li-xin Su, YunJie Zhang, Zhenfeng Wang, Shijie Chen, H. Gu, Xiaojie Yue, Xiong Zhao, Xi-tao Yang, Deming Wang, X. Fan, R. Cai","doi":"10.1097/jova.0000000000000052","DOIUrl":"https://doi.org/10.1097/jova.0000000000000052","url":null,"abstract":"\u0000 \u0000 Capillary malformation-arteriovenous malformation syndrome (CM-AVM) is a rare autosomal-dominant complex vascular disorder that can be associated with fast-flow vascular malformations (FFVMs). The purpose of this study is to explore the genotype–phenotype and genotype–outcome associations based on a large parallel sequencing of CM-AVM patients to improve the understanding of the development and risk factors for FFVM.\u0000 \u0000 \u0000 \u0000 A total of 117 patients with CM-AVMs were enrolled in this multicenter cohort study. All patients underwent detailed clinical phenotyping, including age, sex, capillary malformation (CM) size, with or without FFVM, and outcome (Schobinger stage). Next-generation sequencing was performed with peripheral blood and tissue samples. Genotype–phenotype, genotype–outcome, and phenotype–outcome analyses were performed.\u0000 \u0000 \u0000 \u0000 Germline or mosaic RASA1 variants were the most common cause of CM-AVM, found in 61.5%, with EPHB4 variants in 32.5%. A total of 76.9% of patients had a dominant CM lesion larger than 5 cm. No obvious correlations between genotypes and phenotypes, including sex, age, location, and size of CMs, were found in this cohort. Comparing the patients with FFVMs with those without FFVMs, we found significant differences in age and the size of dominant CM lesions but not in genotype, sex, or location.\u0000 \u0000 \u0000 \u0000 CM-AVMs can be categorized as complex vascular malformations caused by different gene alterations in the RAS/RAF/MEK pathway. No obvious correlations between genotypes and phenotypes were identified. Critically, the occurrence and progression of FFVM is strongly determined by phenotypes, including age and the size of the dominant CM, rather than genotypes.\u0000","PeriodicalId":74008,"journal":{"name":"Journal of vascular anomalies","volume":"27 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2023-07-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"89149256","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}

{"title":"ISSVA World Congress 2022: The Latest in Vascular Anomalies","authors":"","doi":"10.1097/jova.0000000000000066","DOIUrl":"https://doi.org/10.1097/jova.0000000000000066","url":null,"abstract":"","PeriodicalId":74008,"journal":{"name":"Journal of vascular anomalies","volume":"26 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2023-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"74304711","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}

{"title":"The VASCERN-VASCA Working Group Diagnostic and Management Pathways for Venous Malformations.","authors":"Anne Dompmartin,&nbsp;Eulalia Baselga,&nbsp;Laurence M Boon,&nbsp;Andrea Diociaiuti,&nbsp;Veronika Dvorakova,&nbsp;May El Hachem,&nbsp;Paolo Gasparella,&nbsp;Emir Haxhija,&nbsp;Nader Ghaffarpour,&nbsp;Kristiina Kyrklund,&nbsp;Alan D Irvine,&nbsp;Friedrich G Kapp,&nbsp;Jochen Rößler,&nbsp;Päivi Salminen,&nbsp;Caroline van den Bosch,&nbsp;Carine van der Vleuten,&nbsp;Leo Schultze Kool,&nbsp;Miikka Vikkula","doi":"10.1097/JOVA.0000000000000064","DOIUrl":"https://doi.org/10.1097/JOVA.0000000000000064","url":null,"abstract":"<p><p>To elaborate expert consensus patient pathways to guide patients and physicians toward efficient diagnostics and management of patients with venous malformations.</p><p><strong>Methods: </strong>VASCERN-VASCA (https://vascern.eu/) is a European network of multidisciplinary centers for Vascular Anomalies. The Nominal Group Technique was used to establish the pathways. Two facilitators were identified: one to propose initial discussion points and draw the pathways, and another to chair the discussion. A dermatologist (AD) was chosen as first facilitator due to her specific clinical and research experience. The draft was subsequently discussed within VASCERN-VASCA monthly virtual meetings and annual face-to-face meetings.</p><p><strong>Results: </strong>The Pathway starts from the clinical suspicion of a venous type malformation (VM) and lists the clinical characteristics to look for to support this suspicion. Strategies for subsequent imaging and histopathology are suggested. These aim to inform on the diagnosis and to separate the patients into 4 subtypes: (1) sporadic single VMs or (2) multifocal, (3) familial, multifocal, and (4) combined and/or syndromic VMs. The management of each type is detailed in subsequent pages of the pathway, which are color coded to identify sections on (1) clinical evaluations, (2) investigations, (3) treatments, and (4) associated genes. Actions relevant to all types are marked in separate boxes, including when imaging is recommended. When definite diagnoses have been reached, the pathway also points toward disease-specific additional investigations and recommendations for follow up. Options for management are discussed for each subtype, including conservative and invasive treatments, as well as novel molecular therapies.</p><p><strong>Conclusion: </strong>The collaborative efforts of VASCERN-VASCA, a network of the 9 Expert Centers, has led to a consensus Diagnostic and Management Pathways for VMs to assist clinicians and patients. It also emphasizes the role of multidisciplinary expert centers in the management of VM patients. This pathway will become available on the VASCERN website (http://vascern.eu/).</p>","PeriodicalId":74008,"journal":{"name":"Journal of vascular anomalies","volume":"4 2","pages":"e064"},"PeriodicalIF":0.0,"publicationDate":"2023-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10275493/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10035947","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}