JVS-vascular science最新文献

{"title":"Glucose transporter 1 in vascular smooth muscle cells is dispensable for abdominal aortic aneurysm induced by angiotensin II","authors":"Keiichi Torimoto MD, PhD ,&nbsp;Hymavathi Reddy Vari PhD ,&nbsp;Yuki Nakayama MD, PhD ,&nbsp;Hirotoshi Utsunomiya PhD ,&nbsp;Masatoshi Takeda MD, PhD ,&nbsp;Tomoki Hashimoto MD, PhD ,&nbsp;Victor Rizzo PhD ,&nbsp;Satoru Eguchi MD, PhD","doi":"10.1016/j.jvssci.2024.100270","DOIUrl":"10.1016/j.jvssci.2024.100270","url":null,"abstract":"<div><div>Treatment with an inhibitor of glucose use via glucose transporters (GLUT) has been shown to attenuate experimental abdominal aortic aneurysm (AAA) development in mice. Vascular smooth muscle cell (VSMC) signaling seems to be essential for angiotensin II (Ang II)-induced AAA in mice. Accordingly, we have tested a hypothesis that VSMC silencing of the major GLUT, GLUT1, prevents AAA development and rupture in mice treated with Ang II plus β-aminopropionitrile. A mouse model of inducible VSMC GLUT1 deletion was created and aortic GLUT1 silencing was confirmed. Without Ang II plus β-aminopropionitrile treatment, no difference was observed regarding the external aortic diameter (control 1.06 ± 0.18 mm vs deletion 0.97 ± 0.26 mm) or systolic blood pressure (control 102 ± 9 mm Hg vs deletion 107 ± 11 mm Hg) between control or GLUT1-silenced mice. With treatment, control mice as well as VSMC GLUT1-silenced mice equally developed AAA (control 2.37 ± 0.75 mm vs deletion 2.41 ± 0.93 mm), whereas a tendency toward lower blood pressure was observed in GLUT1 silenced mice (control 150 ± 9 mm Hg vs deletion 135 ± 22 mm Hg). No significant difference was observed regarding the rate of rupture-dependent mortality. We concluded that VSMC GLUT1 is dispensable for AAA development induced by Ang II in mice.</div></div>","PeriodicalId":74035,"journal":{"name":"JVS-vascular science","volume":"6 ","pages":"Article 100270"},"PeriodicalIF":0.0,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11728061/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142985642","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":"Proteomic analysis of carotid artery plaques with and without vulnerable features on magnetic resonance angiography with vessel wall imaging: a pilot study","authors":"Benjamin J. Madden BSc ,&nbsp;Camilo Polania-Sandoval MD ,&nbsp;Ganesh P. Pujari MD ,&nbsp;Kiran K. Mangalaparthi PhD ,&nbsp;M. Cristine Charlesworth PhD, MS ,&nbsp;Mercedes Prudencio PhD ,&nbsp;Tania Gendron PhD ,&nbsp;Sukhwinder J.S. Sandhu MD ,&nbsp;Aziza Nassar MD, MPH ,&nbsp;Leonard Petrucelli PhD ,&nbsp;James F. Meschia MD ,&nbsp;Akhilesh Pandey MD, PhD ,&nbsp;Young Erben MD","doi":"10.1016/j.jvssci.2025.100281","DOIUrl":"10.1016/j.jvssci.2025.100281","url":null,"abstract":"<div><h3>Objective</h3><div>Extracranial carotid artery pathology accounts for 15% to 20% of ischemic strokes. Advancements in magnetic resonance angiography (MRA) with vessel wall imaging (VWI) have enabled the identification of vulnerable plaques, aiding in risk stratification for neurovascular events. This pilot study aimed to identify proteins in plaques with and without vulnerable features on MRA with VWI.</div></div><div><h3>Methods</h3><div>Consecutive patients undergoing carotid endarterectomy were included in the study cohort with preoperative MRA with VWI. A retrospective chart review was conducted to extract pertinent clinical data including cardiovascular risk factors and medications. Proteomic analysis involved Tandem Mass Tag (TMTpro) labeling of peptides, basic pH high-performance liquid chromatography fractionation, and NanoLC-tandem mass spectrometry.</div></div><div><h3>Results</h3><div>Proteomic analysis revealed 23 proteins significantly elevated in vulnerable plaques, including Proteinase 3 (PRTN3), Phospholipid Transfer Protein (PLTP), and S100 Calcium-Binding Protein A12 (S100A12), with increased abundance exceeding two-fold changes or above (<em>P</em> &lt; .001). Conversely, three proteins exhibited reduced abundance in vulnerable plaques including Dynamin-3 (DNM3), Transmembrane Protein 181 (TMEM181), and Adducin-3 (ADD3) (<em>P</em> &lt; .05).</div></div><div><h3>Conclusions</h3><div>This study contributes to the understanding of protein biomarkers associated with carotid plaque vulnerability, offering insights into disease progression and stroke prevention. Proteins secreted by vulnerable plaques may offer not only the potential for early disease recognition; but can also become a target for future pharmacologic therapy prior to a devastating neurologic event. Further validation studies and multi-center trials will be needed to confirm the value of these potential biomarkers.</div></div>","PeriodicalId":74035,"journal":{"name":"JVS-vascular science","volume":"6 ","pages":"Article 100281"},"PeriodicalIF":0.0,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143403651","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":"Evaluation of sex-based differences in below-the-knee plaque histology in patients who underwent amputation for chronic limb-threatening ischemia","authors":"Fouzul Kansul ,&nbsp;Deborah Vela MD ,&nbsp;Judit Csore MD ,&nbsp;Bright Benfor MD ,&nbsp;Sasha Suarez MD ,&nbsp;Anahita Dua MD, MBA, MSC ,&nbsp;Trisha L. Roy MD, PhD","doi":"10.1016/j.jvssci.2024.100269","DOIUrl":"10.1016/j.jvssci.2024.100269","url":null,"abstract":"<div><h3>Objective</h3><div>With the growing incidence of peripheral arterial disease (PAD) and the historic under-representation of female patients in cardiovascular trials, a comprehensive evaluation of sex-based variances in PAD presentation and treatment outcomes is needed. This study aims to evaluate sex-based differences in the vessel wall characteristics of patients who underwent amputation owing to critical limb-threatening ischemia to optimize personalized treatment planning and aid in the selection of endovascular devices for PAD patients.</div></div><div><h3>Methods</h3><div>A total of 35 lower limbs were collected from 34 patients with end-stage PAD undergoing major amputation. We selected, harvested, and cross-sectioned at 3- to 4-mm intervals 163 diseased below-the-knee arterial segments resulting in 1260 arterial rings. Histological analyses were conducted on each individual ring and later summarized by arterial segment.</div></div><div><h3>Results</h3><div>Male and female patients were remarkably similar across multiple plaque characteristics, including degree of stenosis, calcification severity and localization, and atherosclerotic patterns. A significant sex-based difference was noted in the presence of luminal thrombus, which was more prevalent in females (38.7% vs 25.0%; <em>P</em> = .016). Histopathological differences were noted between popliteal and tibial lesions, with popliteal segments demonstrating increased chronic total occlusion presence and atherosclerosis, whereas severe calcification occurred more often in tibial segments. A sex-based evaluation of the popliteal segments showed increased calcification (60.71% vs 28.0%; <em>P</em> = .003) and atherosclerosis (96.4% vs 73.0%; <em>P</em> = .028) in males compared with females.</div></div><div><h3>Conclusions</h3><div>Differences in the degree of calcification, incidence of atherosclerosis, and presence of luminal thrombus may pose important clinical implications for antiplatelet and anticoagulation regimen choice and guide treatment options. Further studies are warranted to evaluate the impact of these differences on outcomes of endovascular procedures.</div></div>","PeriodicalId":74035,"journal":{"name":"JVS-vascular science","volume":"6 ","pages":"Article 100269"},"PeriodicalIF":0.0,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11787704/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143082227","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":"Comparative analysis between abdominal aortic aneurysm and popliteal artery aneurysm","authors":"Marcos Vinícius Melo de Oliveira MD, PhD ,&nbsp;Alexandre Malta Brandão MD, PhD ,&nbsp;Gina Camillo Rocha Silvestre BS ,&nbsp;Alexandre Queiroz Silva BS ,&nbsp;Michele Alberto Marques BS ,&nbsp;Marcia Martins Reis PhD ,&nbsp;Maria de Lourdes Higuchi MD, PhD ,&nbsp;Erasmo Simão da Silva MD, PhD","doi":"10.1016/j.jvssci.2024.100279","DOIUrl":"10.1016/j.jvssci.2024.100279","url":null,"abstract":"<div><h3>Objective</h3><div>Infrarenal abdominal aortic aneurysm (AAA) and popliteal artery aneurysm (PAA) are localized arterial dilatations with distinct clinical outcomes. This study aimed to comprehensively compare these two types of aneurysms' biomechanical, histological, and immunohistochemical characteristics.</div></div><div><h3>Methods</h3><div>This study included 180 patients with AAA and 18 with PAA. Medical history and imaging data were collected. Biomechanical testing assessed arterial wall mechanical strength and elasticity, and histological and immunohistochemical analyses examined tissue composition and inflammatory markers.</div></div><div><h3>Results</h3><div>PAA wall fragments demonstrate higher failure strain energy (13.36 N/m² vs 9.95 N/m²; <em>P</em> = .023), a measure of mechanical strength. Regarding immunohistochemical markers, AAA exhibited more B lymphocyte cells in the adventitia (CD20 1475.50 vs 320; <em>P</em> = .003) compared with PAA. Additionally, AAA demonstrated more adipogenic differentiation in the adventitia (PPARgamma 4854.50 vs 778; <em>P</em> = .009), whereas PAA showed more adipogenic differentiation in the intima (KLF5 283.50 vs 77.50; <em>P</em> = .039).</div></div><div><h3>Conclusions</h3><div>PAA wall fragments demonstrate greater mechanical strength compared with AAA wall fragments. In contrast, AAA walls contain a greater number of B lymphocytes within the adventitia compared with PAA walls. Adipogenic differentiation is more pronounced in the adventitia of AAA than in PAA, whereas in PAA, it is more prominent in the intima compared with AAA.</div></div><div><h3>Clinical Relevance</h3><div>The clinical significance of this study lies in its potential to enhance our understanding of the distinct pathophysiological mechanisms underlying abdominal aortic aneurysms, which is often associated with rupture, and popliteal artery aneurysms, which are more prone to thrombosis and distal embolization. By comprehensively comparing the biomechanical, histological, and immunohistochemical aspects of these two aneurysm types, the study aims to illuminate the factors contributing to their differing clinical presentations and outcomes.</div></div>","PeriodicalId":74035,"journal":{"name":"JVS-vascular science","volume":"6 ","pages":"Article 100279"},"PeriodicalIF":0.0,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143139172","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":"Moving away from metal: Step toward the future with bioresorbable vascular scaffolds and novel antiproliferative agents","authors":"Blair E. Warren MD, MSCS ,&nbsp;Kong-Teng Tan MD ,&nbsp;Dheeraj K. Rajan MD ,&nbsp;Miranda Witheford MD, PhD ,&nbsp;Sean Crawford MD, MSc ,&nbsp;Arash Jaberi MD, MEd ,&nbsp;Sebastian Mafeld MBBS","doi":"10.1016/j.jvssci.2024.100277","DOIUrl":"10.1016/j.jvssci.2024.100277","url":null,"abstract":"<div><h3>Background</h3><div>Peripheral arterial disease (PAD) is a common source of morbidity and mortality globally and is expected to raise increase in prevalence. Many endovascular techniques exist to manage PAD; however, there remains room for improvement, especially as it relates to below-the-knee vessels. Recent evidence and devices are leading to a resurgence of interest in bioresorbable vascular scaffolds and the -limus family of antiproliferative drugs in the PAD treatment space.</div></div><div><h3>Methods</h3><div>This nonsystematic review examines emerging technology for treatment of PAD with a specific focus on below-the-knee vessels and bioresorbable vascular scaffolds. Additional emerging and early technology such as novel delivery platforms are also briefly discussed with directions of future research highlighted.</div></div><div><h3>Results</h3><div>Bioresorbable vascular scaffold biomechanics and history are highlighted. Foundational knowledge of antiproliferative agents and evolving agents in peripheral vascular disease are also described.</div></div><div><h3>Conclusions</h3><div>Bioresorbable vascular scaffolds are an additional endovascular tool for the treatment of peripheral vascular disease. The integration with an antiproliferative agent may result in improved patency and performance; however, there is a paucity of data in the literature at present.</div></div>","PeriodicalId":74035,"journal":{"name":"JVS-vascular science","volume":"6 ","pages":"Article 100277"},"PeriodicalIF":0.0,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143139171","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":"Atherosclerotic plaque instability in symptomatic non-significant carotid stenoses","authors":"Paul Cyréus MSc ,&nbsp;Katarina Wadén MD ,&nbsp;Sofie Hellberg MSc ,&nbsp;Otto Bergman PhD ,&nbsp;Mariette Lengquist MSc ,&nbsp;Eva Karlöf MD, PhD ,&nbsp;Andrew Buckler PhD ,&nbsp;Ljubica Matic PhD ,&nbsp;Joy Roy MD, PhD ,&nbsp;David Marlevi PhD ,&nbsp;Melody Chemaly PhD ,&nbsp;Ulf Hedin MD, PhD","doi":"10.1016/j.jvssci.2025.100280","DOIUrl":"10.1016/j.jvssci.2025.100280","url":null,"abstract":"&lt;div&gt;&lt;h3&gt;Objective&lt;/h3&gt;&lt;div&gt;Carotid endarterectomy for symptomatic carotid stenosis is recommended for patients with &gt;70% stenosis, but not in those with &lt;50%. Because non-significant, low-degree stenoses may still cause strokes, refined risk stratification is necessary, which could be improved by assessing biological features of plaque instability. To challenge risk-stratification based on luminal narrowing, we compared biological features of carotid plaques from symptomatic patients with low-degree (&lt;50%) vs high-degree (&gt;70%) stenosis and explored potential mechanisms behind plaque instability in low-degree stenoses.&lt;/div&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Methods&lt;/h3&gt;&lt;div&gt;Endarterectomy specimens were taken from symptomatic patients with high-degree (n = 204) and low-degree (n = 34) stenosis, all part of the Biobank of Karolinska Endarterectomies. Patient demographics, image-derived plaque morphology, and gene expression analyses of extracted lesions were used for comparisons. Plaque biology was assessed by transcriptomics using dimensionality reduction, differential gene expression, and gene-set enrichment analyses. Immunohistochemistry was used to study proteins corresponding to upregulated genes.&lt;/div&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Results&lt;/h3&gt;&lt;div&gt;The demographics of the two groups were statistically similar. Calcification, lipid-rich necrotic core, intraplaque hemorrhage, plaque burden, and fibrous cap thickness were similar in both groups, whereas the sum of lipid-rich necrotic core and intraplaque hemorrhage was higher (&lt;em&gt;P&lt;/em&gt; = .033) in the high-degree stenosis group. Dimensionality reduction analysis indicated poor clustering separation of plaque gene expression in low-compared with high-degree stenosis lesions, whereas differential gene expression showed upregulation of hypoxia-inducible factor 3A (log&lt;sub&gt;2&lt;/sub&gt; fold change, 0.7212; &lt;em&gt;P&lt;/em&gt; = .0003), and gene-set enrichment analyses identified pathways related to tissue hypoxia and angiogenesis in low-degree stenoses. Hypoxia-inducible factor 3-alpha protein was associated with smooth muscle cells in neo-vascularized plaque regions.&lt;/div&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Conclusions&lt;/h3&gt;&lt;div&gt;Plaques from symptomatic patients with non-significant low-degree carotid stenoses showed morphologic and biological features of atherosclerotic plaque instability that were comparable to plaques from patients with high-degree stenoses, emphasizing the need for improved stroke risk stratification for intervention in all patients with symptomatic carotid stenosis irrespective of luminal narrowing. An increased expression of hypoxia-inducible factor 3A in low-degree stenotic lesions suggested mechanisms of plaque instability associated with tissue hypoxia and plaque angiogenesis, but the exact role of hypoxia-inducible factor 3A in this process remains to be determined.&lt;/div&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Clinical relevance&lt;/h3&gt;&lt;div&gt;Carotid plaques from symptomatic patients with &lt;50% stenosis show morphologic and biological features of plaque ","PeriodicalId":74035,"journal":{"name":"JVS-vascular science","volume":"6 ","pages":"Article 100280"},"PeriodicalIF":0.0,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143403650","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":"Toll-Like Receptor 4, a potential therapeutic target of lower limb ischemic myopathy that raises further questions","authors":"Ali H. Hakim, Ulf Hedin","doi":"10.1016/j.jvssci.2024.100195","DOIUrl":"https://doi.org/10.1016/j.jvssci.2024.100195","url":null,"abstract":"","PeriodicalId":74035,"journal":{"name":"JVS-vascular science","volume":"60 6","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139824700","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":"A central arteriovenous fistula reduces systemic hypertension in a mouse model","authors":"Anand H. Brahmandam, Rafael Alves, Hao Liu, Luis Gonzalez, Y. Aoyagi, Yuichi Ohashi, John T. Langford, Carly Thaxton, R. Taniguchi, Weichang Zhang, Hualong Bai, B. Yatsula, Alan Dardik","doi":"10.1016/j.jvssci.2024.100191","DOIUrl":"https://doi.org/10.1016/j.jvssci.2024.100191","url":null,"abstract":"","PeriodicalId":74035,"journal":{"name":"JVS-vascular science","volume":"22 4","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139892707","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":"Predicting Future Occlusion or Stenosis of Lower Extremity Bypass Grafts Using Artificial Intelligence to Simultaneously Analyze All Flow Velocities Collected in Current and Previous Ultrasound Exams","authors":"Xiao Luo, Fattah Muhammad Tahabi, Dave M. Rollins, A. Sawchuk","doi":"10.1016/j.jvssci.2024.100192","DOIUrl":"https://doi.org/10.1016/j.jvssci.2024.100192","url":null,"abstract":"","PeriodicalId":74035,"journal":{"name":"JVS-vascular science","volume":"72 4","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139874367","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":"Role of Toll-like Receptor 4 in Skeletal Muscle Damage in Chronic Limb Threatening Ischaemia","authors":"Navi Ali, Patel Hemanshu, Shiwen Xu, Baker Daryll, Abraham David, Tsui Janice","doi":"10.1016/j.jvssci.2024.100194","DOIUrl":"https://doi.org/10.1016/j.jvssci.2024.100194","url":null,"abstract":"","PeriodicalId":74035,"journal":{"name":"JVS-vascular science","volume":"121 ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139829132","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}