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Hepatic Encephalopathy: From the Pathogenesis to the New Treatments. 肝性脑病:从发病机制到新的治疗方法。
Pub Date : 2014-06-04 eCollection Date: 2014-01-01 DOI: 10.1155/2014/236268
Juan Cordoba

Hepatic encephalopathy is a frequent and serious complication of liver cirrhosis; the pathophysiology of this complication is not fully understood although great efforts have been made during the last years. There are few prospective studies on the epidemiology of this complication; however, it is known that it confers with high short-term mortality. Hepatic encephalopathy has been classified into different groups depending on the degree of hepatic dysfunction, the presence of portal-systemic shunts, and the number of episodes. Due to the large clinical spectra of overt EH and the complexity of cirrhotic patients, it is very difficult to perform quality clinical trials for assessing the efficacy of the treatments proposed. The physiopathology, clinical manifestation, and the treatment of HE is a challenge because of the multiple factors that converge and coexist in an episode of overt HE.

肝性脑病是肝硬化常见而严重的并发症;尽管在过去的几年里已经做出了很大的努力,但这种并发症的病理生理学尚不完全清楚。关于该并发症流行病学的前瞻性研究很少;然而,众所周知,它具有很高的短期死亡率。肝性脑病根据肝功能障碍的程度、门静脉-全身分流的存在和发作次数被分为不同的组。由于明显EH的临床频谱大,肝硬化患者的复杂性,很难进行高质量的临床试验来评估所提出的治疗方法的疗效。HE的生理病理、临床表现和治疗是一个挑战,因为在一个显性HE发作中,多种因素汇聚和共存。
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引用次数: 29
The Wide and Complex Field of NAFLD Biomarker Research: Trends. NAFLD生物标志物研究的广泛和复杂领域:趋势。
Pub Date : 2014-04-28 eCollection Date: 2014-01-01 DOI: 10.1155/2014/846923
Erika Wichro, Tanja Macheiner, Jasmin Schmid, Barbara Kavsek, Karine Sargsyan

Background. Nonalcoholic fatty liver disease is now acknowledged as a complex public health issue linked to sedentary lifestyle, obesity, and related disorders like type 2 diabetes and metabolic syndrome. Aims. We aimed to retrieve its trends out of the huge amount of published data. Therefore, we conducted an extensive literature search to identify possible biomarker and/or biomarker combinations by retrospectively assessing and evaluating common and novel biomarkers to predict progression and prognosis of obesity related liver diseases. Methodology. We analyzed finally 62 articles accounting for 157 cohorts and 45,288 subjects. Results. Despite the various approaches, most cohorts were considerably small and rarely comparable. Also, we found that the same standard parameters were measured rather than novel biomarkers. Diagnostics approaches appeared incomparable. Conclusions. Further collaborative investigations on harmonizing ways of data acquisition and identifying such biomarkers for clinical use are necessary to yield sufficient significant results of potential biomarkers.

背景。非酒精性脂肪肝现在被认为是一个复杂的公共卫生问题,与久坐不动的生活方式、肥胖以及2型糖尿病和代谢综合征等相关疾病有关。目标我们的目标是从大量已发表的数据中检索其趋势。因此,我们进行了广泛的文献检索,通过回顾性评估和评估常见和新型生物标志物来预测肥胖相关肝脏疾病的进展和预后,以确定可能的生物标志物和/或生物标志物组合。方法。我们最终分析了62篇文章,涉及157个队列和45288名受试者。结果。尽管采用了各种方法,但大多数队列都相当小,很少具有可比性。此外,我们发现测量的是相同的标准参数,而不是新的生物标志物。诊断方法似乎无可比拟。结论。为了获得足够的潜在生物标志物的重要结果,有必要进一步合作研究协调数据获取方式和识别临床使用的这些生物标志物。
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引用次数: 1
Application of Real-Time Tissue Elastography with a Low Frequency Convex Array Probe: A Noninvasive Approach to Differential Diagnosis of Liver Tumors. 实时组织弹性成像与低频凸阵列探针的应用:一种无创肝肿瘤鉴别诊断方法。
Pub Date : 2014-04-01 eCollection Date: 2014-01-01 DOI: 10.1155/2014/378243
Juan Wang, Hong Ai, Long Guo, Lifang Tan, Huilin Gong, Wei Wei, Litao Ruan

To evaluate diagnostic performance of real-time tissue elastography (RTE) with a low frequency convex array probe for distinguishing benign from malignant hepatic tumors through trans-abdominal examination, elasticity images of 210 liver tumors were obtained by EUB-7500 (Hitachi Medical Systems and 3.5 MHz probe) and eventually 121 liver tumors were analyzed in the study. Elasticity images were classified into four types, from type a to d. Regarding type a or b as benign tumors and type c or d as malignant ones, sensitivity, specificity, and accuracy were calculated and the consistency between the findings of RTE and the pathohistological diagnosis was evaluated. The sensitivity, specificity, and accuracy were separately 97.2%, 88.0%, and 93.4% (P < 0.001). Moreover, there was a good consistency between the findings of RTE and the pathological diagnosis (kappa value 0.86). Among elasticity images of all the malignant tumors, the hepatocellular carcinomas (HCCs) mainly appeared in type c, and liver metastatic cancers in type d. Thus, RTE utilized as a novel noninvasive imaging examination method enables us to distinguish benign from malignant liver tumors. Moreover, it provides certain information for the differential diagnosis between HCCs and liver metastatic cancers.

为了评估低频凸阵探头实时组织弹性成像(RTE)对经腹肝肿瘤良恶性鉴别的诊断效果,我们使用EUB-7500(日立医疗系统公司,3.5 MHz探头)获取了210个肝脏肿瘤的弹性图像,最终分析了121个肝脏肿瘤。将弹性图像分为a - d四种类型,将a型或b型为良性肿瘤,c型或d型为恶性肿瘤,计算其敏感性、特异性和准确性,并评价RTE的表现与病理组织学诊断的一致性。灵敏度为97.2%,特异性为88.0%,准确度为93.4% (P < 0.001)。RTE表现与病理诊断具有较好的一致性(kappa值0.86)。在所有恶性肿瘤的弹性图像中,肝细胞癌(hcc)主要出现在c型,肝转移癌主要出现在d型。因此,RTE作为一种新的无创影像学检查方法,使我们能够区分肝肿瘤的良恶性。此外,它为hcc和肝转移癌的鉴别诊断提供了一定的信息。
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引用次数: 5
The Evolution of Transjugular Intrahepatic Portosystemic Shunt: Tips. 经颈静脉肝内门静脉系统分流的演变:提示。
Pub Date : 2014-03-18 eCollection Date: 2014-01-01 DOI: 10.1155/2014/762096
Fabrizio Fanelli

Since Richter's description in the literature in 1989 of the first procedure on human patients, transjugular intrahepatic portosystemic shunt (TIPS) has been worldwide considered as a noninvasive technique to manage portal hypertension complications. TIPS succeeds in lowering the hepatic sinusoidal pressure and in increasing the circulatory flow, thus reducing sodium retention, ascites recurrence, and variceal bleeding. Required several revisions of the shunt TIPS can be performed in case of different conditions such as hepatorenal syndrome, hepatichydrothorax, portal vein thrombosis, and Budd-Chiari syndrome. Most of the previous studies on TIPS procedure were based on the use of bare stents and most patients chose TIPS 2-3 years after traditional treatment, thus making TIPS appear to be not superior to endoscopy in survival rates. Bare stents were associated with higher incidence of shunt failure and consequently patients required several revisions during the follow-up. With the introduction of a dedicated e-PTFE covered stent-graft, these problems were completely solved, No more reinterventions are required with a tremendous improvement of patient's quality of life. One of the main drawbacks of the use of e-PTFE covered stent-graft is higher incidence of hepatic encephalopathy. In those cases refractory to the conventional medical therapy, a shunt reduction must be performed.

自Richter于1989年在文献中描述首例人类患者的手术以来,经颈静脉肝内门静脉系统分流术(TIPS)已被全世界认为是一种治疗门静脉高压并发症的无创技术。TIPS成功地降低了肝窦压力,增加了循环流量,从而减少了钠潴留、腹水复发和静脉曲张出血。在不同的情况下,如肝肾综合征、肝性胸水、门静脉血栓形成和Budd-Chiari综合征,需要对分流TIPS进行多次修改。以往关于TIPS手术的研究大多是基于裸支架的使用,大多数患者在传统治疗后2-3年选择了TIPS,因此TIPS在生存率上似乎并不优于内镜。裸支架与更高的分流失败发生率相关,因此患者在随访期间需要多次修改。随着专用的e-PTFE覆盖支架移植的引入,这些问题完全解决了,不再需要再干预,极大地提高了患者的生活质量。使用e-PTFE覆盖支架移植物的主要缺点之一是肝性脑病的发生率较高。对于那些常规药物治疗无效的病例,必须进行分流复位。
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引用次数: 16
Liver Transplantation for Hepatocellular Carcinoma beyond Milan Criteria: Multidisciplinary Approach to Improve Outcome. 超越米兰标准的肝细胞癌肝移植:多学科方法提高疗效。
Pub Date : 2014-03-04 eCollection Date: 2014-01-01 DOI: 10.1155/2014/706945
A Kornberg

The implementation of the Milan criteria (MC) in 1996 has dramatically improved prognosis after liver transplantation (LT) in patients with hepatocellular carcinoma (HCC). Liver transplantation has, thereby, become the standard therapy for patients with "early-stage" HCC on liver cirrhosis. The MC were consequently adopted by United Network of Organ Sharing (UNOS) and Eurotransplant for prioritization of patients with HCC. Recent advancements in the knowledge about tumor biology, radiographic imaging techniques, locoregional interventional treatments, and immunosuppressive medications have raised a critical discussion, if the MC might be too restrictive and unjustified keeping away many patients from potentially curative LT. Numerous transplant groups have, therefore, increasingly focussed on a stepwise expansion of selection criteria, mainly based on tumor macromorphology, such as size and number of HCC nodules. Against the background of a dramatic shortage of donor organs, however, simple expansion of tumor macromorphology may not be appropriate to create a safe extended criteria system. In contrast, rather the implementation of reliable prognostic parameters of tumor biology into selection process prior to LT is mandatory. Furthermore, a multidisciplinary approach of pre-, peri-, and posttransplant modulating of the tumor and/or the patient has to be established for improving prognosis in this special subset of patients.

1996 年米兰标准(MC)的实施大大改善了肝细胞癌(HCC)患者肝移植(LT)后的预后。因此,肝移植已成为肝硬化 "早期 "HCC 患者的标准疗法。因此,器官共享联合网络(UNOS)和欧洲器官移植协会(Eurotransplant)采用 MC 作为 HCC 患者的优先治疗方案。近年来,随着对肿瘤生物学、放射成像技术、局部介入治疗和免疫抑制药物等方面知识的不断进步,人们开始批判性地讨论MC是否过于严格和不合理,导致许多患者无法接受可能治愈的LT治疗。因此,许多移植团体越来越重视逐步扩大选择标准,主要以肿瘤大体形态为依据,如 HCC 结节的大小和数量。然而,在供体器官急剧短缺的背景下,简单地扩展肿瘤大体形态学可能并不适合建立一个安全的扩展标准系统。与此相反,在 LT 前的选择过程中,必须采用可靠的肿瘤生物学预后参数。此外,为了改善这一特殊亚群患者的预后,还必须建立一种对肿瘤和/或患者进行移植前、移植期和移植后调节的多学科方法。
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引用次数: 0
Tumor Hemodynamics and Hepatocarcinogenesis: Radio-Pathological Correlations and Outcomes of Carcinogenic Hepatocyte Nodules. 肿瘤血流动力学和肝癌发生:致癌肝细胞结节的放射病理相关性和预后。
Pub Date : 2014-03-03 eCollection Date: 2014-01-01 DOI: 10.1155/2014/607628
Kazuhiko Ueda, Osamu Matsui, Azusa Kitao, Satoshi Kobayashi, Jun Nakayama, Shinich Miyagawa, Masumi Kadoya

Tumor hemodynamics of carcinogenic hepatocytes nodules, that is, low grade dysplastic nodules, high grade dysplastic nodules, early hepatocellular carcinomas (HCCs), and progressed HCCs, change during multistep dedifferentiation of the nodules. Morphometric analyses of inflow vessels of these nodules indicate that the portal veins of carcinogenic hepatocyte nodules monotonically decrease whereas the arteries bitonically change, first decrease and then increase. Findings on imaging techniques depicting these changes in tumor blood inflows, especially intra-arterial contrast-enhanced computed tomography, closely related not only to the histological differentiation of the nodules but also to the outcomes of the nodules. Histological analyses of connections between the vessels within the tumors and those in the surrounding livers and findings on imaging techniques indicate that drainage vessels of HCC change from hepatic veins to hepatic sinusoids and then to portal veins during multistep hepatocarcinogenesis. Understanding of tumor hemodynamics through radio-pathological correlations will be helpful in drawing up therapeutic strategies for carcinogenic hepatocyte nodules arising in cirrhosis.

癌性肝细胞结节,即低级别发育不良结节、高级别发育不良结节、早期肝细胞癌(hcc)和进展型hcc,其血流动力学在结节的多步去分化过程中发生变化。癌性肝细胞结节的门静脉呈单调减少,而动脉呈双曲线变化,先减少后增加。影像学技术的发现描述了肿瘤血流的这些变化,尤其是动脉内增强ct,不仅与结节的组织学分化密切相关,而且与结节的预后密切相关。肿瘤内血管与肝周围血管连接的组织学分析和影像学检查结果表明,肝癌的引流血管在多步肝癌发生过程中由肝静脉到肝窦再到门静脉。通过影像学病理相关性了解肿瘤血流动力学将有助于制定肝硬化致癌性肝细胞结节的治疗策略。
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引用次数: 9
Cholangiocarcinoma: Biology, Clinical Management, and Pharmacological Perspectives. 胆管癌:生物学、临床管理和药理学观点。
Pub Date : 2014-02-16 eCollection Date: 2014-01-01 DOI: 10.1155/2014/828074
Rocio I R Macias

Cholangiocarcinoma (CCA), or tumor of the biliary tree, is a rare and heterogeneous group of malignancies associated with a very poor prognosis. Depending on their localization along the biliary tree, CCAs are classified as intrahepatic, perihilar, and distal, and these subtypes are now considered different entities that differ in tumor biology, the staging system, management, and prognosis. When diagnosed, an evaluation by a multidisciplinary team is essential; the team must decide on the best therapeutic option. Surgical resection of tumors with negative margins is the best option for all subtypes of CCA, although this is only achieved in less than 50% of cases. Five-year survival rates have increased in the recent past owing to improvements in imaging techniques, which permits resectability to be predicted more accurately, and in surgery. Chemotherapy and radiotherapy are relatively ineffective in treating nonoperable tumors and the resistance of CCA to these therapies is a major problem. Although the combination of gemcitabine plus platinum derivatives is the pharmacological treatment most widely used, to date there is no standard chemotherapy, and new combinations with targeted drugs are currently being tested in ongoing clinical trials. This review summarizes the biology, clinical management, and pharmacological perspectives of these complex tumors.

胆管癌(CCA),或胆道树肿瘤,是一种罕见且异质性的恶性肿瘤,预后非常差。根据其沿胆道树的定位,cca被分为肝内、肝门周围和远端,这些亚型现在被认为是不同的实体,在肿瘤生物学、分期系统、管理和预后方面存在差异。诊断时,由多学科小组进行评估是必不可少的;团队必须决定最好的治疗方案。手术切除阴性切缘的肿瘤是所有CCA亚型的最佳选择,尽管只有不到50%的病例能做到这一点。近年来,由于影像技术的改进,可以更准确地预测可切除性和手术,五年生存率有所提高。化疗和放疗在治疗不可手术的肿瘤中相对无效,CCA对这些治疗的耐药性是一个主要问题。虽然吉西他滨加铂衍生物的联合治疗是最广泛使用的药物治疗,但迄今为止还没有标准的化疗,目前正在进行的临床试验中正在测试与靶向药物的新组合。本文综述了这些复杂肿瘤的生物学、临床管理和药理学观点。
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引用次数: 27
Improved Serum Alpha-Fetoprotein Levels after Iron Reduction Therapy in HCV Patients. HCV患者铁还原治疗后血清甲胎蛋白水平的改善。
Pub Date : 2014-02-04 eCollection Date: 2014-01-01 DOI: 10.1155/2014/875140
Hidenao Noritake, Yoshimasa Kobayashi, Yukimasa Ooba, Kensuke Kitsugi, Shin Shimoyama, Satoru Yamazaki, Takeshi Chida, Shinya Watanabe, Kazuhito Kawata, Takafumi Suda

Background and Aims. To examine the changes in serum alpha-fetoprotein (AFP) levels after iron reduction by therapeutic phlebotomy in chronic hepatitis C patients. Methods. This retrospective study included 26 chronic hepatitis C patients. The patients were developed iron depletion by repeated therapeutic phlebotomies. Results. Iron reduction therapy significantly reduced the median level of serum AFP from 13 to 7 ng/mL, ALT from 96 to 50 IU/L, gamma-glutamyl transpeptidase (GGT) from 55 to 28 IU/L, and ferritin from 191 to 10 ng/mL (P < 0.001 for each). The rate of decline in the AFP level correlated positively only with that in GGT (r = 0.695, P = 0.001), although a spurious correlation was observed between the rates of decline for AFP and ALT. The AFP level normalized (<10 ng/mL) posttreatment in eight (50%) of 16 patients who had elevated pretreatment AFP levels. Normalized post-treatment ALT and GGT levels were seen in 12% (3 of 26) and 39% (7 of 18) of the patients, respectively. Multivariate analysis identified a post-treatment GGT level of <30 IU/L as an independent factor associated with post-treatment AFP normalization (odds ratio, 21; 95% confidence interval, 1.5-293; P = 0.024). Conclusions. Iron reduction by therapeutic phlebotomy can reduce serum AFP and GGT levels in chronic hepatitis C patients.

背景和目的。目的探讨慢性丙型肝炎患者治疗性放血减铁后血清甲胎蛋白(AFP)水平的变化。方法。本回顾性研究包括26例慢性丙型肝炎患者。患者因反复治疗性放血而出现缺铁。结果。铁还原治疗显著降低血清AFP中位水平,从13至7 ng/mL, ALT从96至50 IU/L, γ -谷氨酰转肽酶(GGT)从55至28 IU/L,铁蛋白从191至10 ng/mL (P < 0.001)。甲胎蛋白水平的下降率仅与GGT的下降率呈正相关(r = 0.695, P = 0.001),尽管在甲胎蛋白和ALT的下降率之间观察到虚假相关。
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引用次数: 4
Chylous Ascites: Evaluation and Management. 乳糜腹水:评估和管理。
Pub Date : 2014-02-03 eCollection Date: 2014-01-01 DOI: 10.1155/2014/240473
Said A Al-Busafi, Peter Ghali, Marc Deschênes, Philip Wong

Chylous ascites refers to the accumulation of lipid-rich lymph in the peritoneal cavity due to disruption of the lymphatic system secondary to traumatic injury or obstruction. Worldwide, abdominal malignancy, cirrhosis, and tuberculosis are the commonest causes of CA in adults, the latter being most prevalent in developing countries, whereas congenital abnormalities of the lymphatic system and trauma are commonest in children. The presence of a milky, creamy appearing ascitic fluid with triglyceride content above 200 mg/dL is diagnostic, and, in the majority of cases, unless there is a strong suspicion of malignancy, further investigations are not required in patients with cirrhosis. If an underlying cause is identified, targeted therapy is possible, but most cases will be treated conservatively, with dietary support including high-protein and low-fat diets supplemented with medium-chain triglycerides, therapeutic paracentesis, total parenteral nutrition, and somatostatins. Rarely, resistant cases have been treated by transjugular intrahepatic portosystemic shunt, surgical exploration, or peritoneovenous shunt.

乳糜腹水是指由于创伤性损伤或梗阻引起的淋巴系统破坏而导致的富脂淋巴在腹膜腔内的积聚。在世界范围内,腹部恶性肿瘤、肝硬化和肺结核是成人CA最常见的病因,后者在发展中国家最为普遍,而先天性淋巴系统异常和创伤在儿童中最为常见。乳白色、奶油状的腹水,甘油三酯含量超过200 mg/dL是诊断性的,在大多数情况下,除非有强烈的恶性怀疑,否则肝硬化患者不需要进一步检查。如果确定了潜在的原因,靶向治疗是可能的,但大多数病例将保守治疗,饮食支持包括高蛋白和低脂饮食,补充中链甘油三酯,治疗性穿刺,全肠外营养和生长抑素。很少有耐药病例采用经颈静脉肝内门静脉分流术、手术探查或腹膜静脉分流术治疗。
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引用次数: 121
Protective Effects of Guava Pulp on Cholestatic Liver Injury. 番石榴果肉对胆汁淤积性肝损伤的保护作用。
Pub Date : 2013-11-17 eCollection Date: 2013-01-01 DOI: 10.1155/2013/601071
Jian Peng, Chunyan Yue, Kai Qiu, Jie Chen, Maria-Angeles Aller, Kwang Suk Ko, Heping Yang

Background. Cholestatic liver injury is a leading cause of chronic liver diseases involved with oxidative stress changes and inflammation; thus, antioxidant and anti-inflammation compound-rich guava may play a pivotal role in protecting against the cholestatic liver damages. Our aims for this study are to determine whether guava pulp (GP) has protective effects on cholestatic liver injury-induced mouse model and on interleukin-6 (IL-6) mediated proliferation of QBC939 cholangiocarcinoma cell line. Methods. Mice were induced to cholestatic liver damage by left and median bile duct ligation (LMBDL) surgery and then treated with GP. Plasma and liver samples were collected for biochemical and pathological assays. 5-Bromo-2'-deoxyuridine (BrdU) assay and Western blots were used to detect proliferation and gene expression in QBC939 cells, respectively. Results. Compared with LMBDL only group, in GP-treated mice, the levels of alanine aminotransferase (ALT) and bilirubin decreased, biliary epithelial cell proliferation and liver fibrogenesis were suppressed, Src/MEK/ERK1/2/c-Myc pathway and expressions of transforming growth factor β1(TGF-β1), tissue inhibitor of metalloproteinases TIMP), and procollagen 1α1(COL1α1) were downregulated significantly. Moreover, the GP extract reduced IL-6-enhanced QBC939 cell proliferation, p-ERK, and c-Myc expression as well. Conclusions. GP may provide a new perspective for the treatment of cholestatic liver injury.

背景。胆汁淤积性肝损伤是与氧化应激变化和炎症有关的慢性肝病的主要原因;因此,富含抗氧化和抗炎症化合物的番石榴可能在防止胆汁淤积性肝损伤中起关键作用。我们的目的是研究番石榴浆(GP)是否对胆汁淤积性肝损伤小鼠模型和白细胞介素-6 (IL-6)介导的QBC939胆管癌细胞增殖具有保护作用。方法。采用左、中胆管结扎术(LMBDL)诱导小鼠胆汁淤积性肝损伤,并给予GP治疗。采集血浆和肝脏标本进行生化和病理分析。采用5-溴-2'-脱氧尿苷(BrdU)法和Western blot检测QBC939细胞的增殖和基因表达。结果。与LMBDL组比较,gp处理小鼠的谷丙转氨酶(ALT)、胆红素水平降低,胆道上皮细胞增殖和肝纤维化受到抑制,Src/MEK/ erk1 /c-Myc通路及转化生长因子β1(TGF-β1)、金属蛋白酶组织抑制剂TIMP、前胶原1α1(COL1α1)表达明显下调。此外,GP提取物还降低了il -6增强的QBC939细胞增殖、p-ERK和c-Myc表达。结论。GP可能为胆汁淤积性肝损伤的治疗提供新的视角。
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引用次数: 3
期刊
ISRN hepatology
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