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1S100A8/A9 induces autophagy and apoptosis via ROS-mediated cross-talk between mitochondria and lysosomes that involves BNIP3显示文摘建筑群由 S100 钙绑定蛋白质家庭,的二个成员形成了 S100A8/A9,在不同起源的各种各样的房间施加导致 apoptosis 活动。这里,我们内在的分子的机制包含的现在的证据两个都规划了房间死亡我(PCD 我, apoptosis ) 并且象死亡一样的 PCD II (autophagy ) 。有 S100A8/A9 的房间的处理引起了 Beclin-1 表示以及 Atg12-Atg5 形成的增加。S100A8/A9-induced 房间死亡被特定的 PI3-kinase 班 III 禁止者部分禁止, 3-methyladenine (3 麻省) ,并且由液泡 H+-ATPase 禁止者, bafilomycin-A1 (Baf-A1 ) 。S100A8/A9 挑起了 BNIP3 的 translocation, BH3 仅仅 pro-apoptotic Bcl2 家庭成员,到线粒体。与这发现一致,螖 T M-BNIP3 overexpression 部分禁止了 S100A8/A9-induced 细胞死亡,减少的反应的氧种(ROS ) 产生,并且部分在 S100A8/A9-treated 细胞在 mitochondrial transmembrane 潜力免于减少。另外,任何一个螖 T M-BNIP3 overexpression 或 N-acetyl-L-cysteine 合作处理减少了在与 S100A8/A9 对待的房间的 lysosomal 激活。我们的数据显示 S100A8/A9-promoted 房间死亡通过线粒体的串音发生,经由 ROS 和这个过程的 lysosomes 包含 BNIP3。Saeid Ghavami Mehdi Eshragi Sudharsana R Ande Walter J Chazin Thomas Klonisch Andrew J Halayko Karol D Mcneill Mohammad Hashemi Claus Kerkhoff Marek Los 2010Cell Research2010,20,3:13
2Consequences of bullying victimization in childhood and adolescence:A systematic review and meta-analysis显示文摘AIM To identify health and psychosocial problems associated with bullying victimization and conduct a meta-analysis summarizing the causal evidence.METHODS A systematic review was conducted using Pub Med, EMBASE, ERIC and Psyc INFO electronic databases up to 28 February 2015. The study included published longitudinal and cross-sectional articles that examined health and psychosocial consequences of bullying victimization. All meta-analyses were based on qualityeffects models. Evidence for causality was assessed using Bradford Hill criteria and the grading system developed by the World Cancer Research Fund.RESULTS Out of 317 articles assessed for eligibility, 165 satisfied the predetermined inclusion criteria for meta-analysis.Statistically significant associations were observed between bullying victimization and a wide range of adverse health and psychosocial problems. The evidence was strongest for causal associations between bullying victimization and mental health problems such as depression, anxiety, poor general health and suicidal ideation and behaviours. Probable causal associations existed between bullying victimization and tobacco and illicit drug use. CONCLUSION Strong evidence exists for a causal relationship between bullying victimization, mental health problems and substance use. Evidence also exists for associations between bullying victimization and other adverse health and psychosocial problems, however, there is insufficient evidence to conclude causality. The strong evidence that bullying victimization is causative of mental illness highlights the need for schools to implement effective interventions to address bullying behaviours.Sophie E Moore Rosana E Norman Shuichi Suetani Hannah J Thomas Peter D Sly James G Scott 2017World Journal of Psychiatry2017,7,1:12
3Intentional ingestions of foreign objects among prisoners: A review显示文摘The intentional ingestion of foreign objects(IIFO) is described more commonly in prison populations than in the general population, with an estimated annual incidence of 1 in 1900 inmates in our state correctional facilities. Incidents often involve ingestion of small metal objects(e.g., paperclips, razor blades) or other commonly available items like pens or eating utensils. Despite ingestion of relatively sharp objects, most episodes can be clinically managed with either observation or endoscopy. Surgery should be reserved for those with signs or symptoms of gastrointestinal perforation or obstruction. For those with a history of IIFO, efforts should focus on prevention of recurrenceas subsequent episodes are associated with higher morbidity, significant healthcare and security costs. The pattern of IIFO is often repetitive, with escalation both in frequency of ingestions and in number of items ingested. Little is known about successful prevention strategies, but efforts to monitor patients and provide psychiatric care are potential best-practice strategies. This article aims to provide state-of-the art review on the topic, followed by a set of basic recommendations.David C Evans Thomas R Wojda Christian D Jones Andrew J Otey Stanislaw P Stawicki 2015World Journal of Gastrointestinal Endoscopy2015,7,3:10
4Current and future applications of magnetic resonance imaging and spectroscopy of the brain in hepatic encepha-lopathy显示文摘肝的脑病(他) 普通 neuro 精神病学的畸形,它从肝细胞失败或 portosystemic 与肝疾病和结果复杂化病人的功课正在推延。表明他是广泛地可变的并且从温和无临床症状的骚乱包含一个系列到深昏迷。研究兴趣集中于传播导出勇气的毒素的角色,特别地氨,胀大的大脑的开发和在导致全球 CNS 消沉和混乱功能的服的 neurotransmitter 系统的变化。直到最近,服的功能的直接调查有在人是困难的。然而,当磁性的回声光谱学( 1H 太太)检测的质子在大脑生物化学变化时,新磁性的回声成像( MRI )技术在大脑体积( coregistered MRI )和损害大脑功能( fMRI )提供对变化的评价的一个非侵略的工具,包括服的 osmolytes 的直接测量,例如 myoinositol ,充斥管理对细胞的动态平衡内在的过程的使挫折和夫酸安,包括细胞内部的水的累积。这些细胞内部的 osmolytes 的集中与 hyperammonaemia 改变。有 neuropsychiatric 缺陷并且自从先生系列的严厉的检测太太的代谢物畸形相互关联向正常术后疗法回来,技术可能具有在客观耐心的监视并且在估计各种各样的治疗政体的有效性的使用。VP Bob Graver M Alex Dresner Daniel M Forton Serena Counsell David J Larkman Nayna Patel Howard C Thomas Simon D Taylor-Robinson 2006World Journal of Gastroenterology2006,12,19:8
5Early combined immunosuppression or conventional management in patients with newly diagnosed Crohn’s disease: an open randomised trial显示文摘Geert D’Haens Filip Baert Gert van Assche Philip Caenepeel Philippe Vergauwe Hans Tuynman Martine De Vos Sander van Deventer Larry Stitt Allan Donner Severine Vermeire Frank J Van De Mierop Jean-Charles R Coche Janneke van der Woude Thomas Ochsenkühn Ad A 2008The Lancet2008,,9613:5
6RANK-ligand and osteoprotegerin as biomarkers in the differentiation between periprosthetic joint infection and aseptic prosthesis loosening显示文摘AIM To assess serum levels of RANK-ligand(RANKL) and osteoprotegerin(OPG) as biomarkers for periprosthetic joint infection(PJI) and compare their accuracy with standard tests.METHODS One hundred and twenty patients presenting with a painful total knee or hip arthroplasty with indication for surgical revision were included in this prospective clinical trial. Based on standard diagnostics(joint aspirate, microbiological, and histological samples) and Musculoskeletal Infection Society consensus classification,patients were categorized into PJI, aseptic loosening,and control groups. Implant loosening was assessed radiographically and intraoperatively. Preoperative serum samples were collected and analyzed for RANKL, OPG, calcium, phosphate, alkaline phosphatase(AP), and the bone-specific subform of AP(b AP). Statistical analysis was carried out, testing for significant differences between the three groups and between stable and loose implants. RESULTS All three groups were identical in regards to age, gender, and joint distribution. No statistically significant differences in the serum concentration of RANKL(P = 0.16) and OPG(P = 0.45) were found between aseptic loosening and PJI, with a trend towards lower RANKL concentrations and higher OPG concentrations in the PJI group. The RANKL/OPG ratio was significant for the comparison between PJI and non-PJI(P = 0.005). A ratio > 60 ruled out PJI in all cases(specificity: 100%, 95%CI: 89, 11% to 100.0%) but only 30% of non-PJI patients crossed this threshold. The positive predictive value remained poor at any cut-off. In the differentiation between stable and loose implants, none of the parameters measured(calcium, phosphate, AP, and b AP) showed a significant difference, and only AP and b AP measurements showed a tendency towards higher values in the loosened group(with P = 0.09 for AP and P = 0.19 for b AP). CONCLUSION Lower RANKL and higher OPG concentrations could be detected in PJI, without statistical significance.Max J Friedrich Matthias D Wimmer Jan Schmolders Andreas C Strauss Milena M Ploeger Hendrik Kohlhof Dieter C Wirtz Sascha Gravius Thomas M Randau 2017World Journal of Orthopedics2017,8,4:4
7Silvicultural alternatives to conventional even-aged forest man-agement-what limits global adoption?显示文摘Background: The development of forestry as a scientific and management discipline over the last two centuries has mainly emphasized intensive management operations focused on increased commodity production, mostly wood. This 'conventional' forest management approach has typically favored production of even-aged, single-species stands. While alternative management regimes have generally received less attention, this has been changing over the last three decades, especially in countries with developed economies. Reasons for this change include a combination of new information and concerns about the ecological consequences of intensive forestry practices and a willingness on the part of many forest owners and society to embrace a wider set of management objectives. Alternative silvicultural approaches are characterized by a set of fundamental principles, including avoidance of clearcutting, an emphasis on structural diversity and small-scale variability, deployment of mixed species with natural regeneration,and avoidance of intensive site-preparation methods.Methods: Our compilation of the authors' experiences and perspectives from various parts of the world aims to initiate a larger discussion concerning the constraints to and the potential of adopting alternative silvicultural practices.Results: The results suggest that a wider adoption of alternative silvicultural practices is currently hindered by a suite of ecological, economic, logistical, informational, cultural, and historical constraints. Individual contexts display their own unique combinations and relative significance of these constraints, and accordingly, targeted efforts, such as regulations and incentives, may help to overcome specific challenges.Conclusions: In a broader context, we propose that less emphases on strict applications of principles and on stand structures might provide additional flexibility and facilitate the adoption of alternative silvicultural regimes in a broader set of circumstances. At the same time, the acceptance of alternative silvicultural systems as the 'preferred or default mode of management' wil necessitate and benefit from the continued development of the scientific basis and valuation of a variety of ecosystem goods and services. This publication is aimed to further the discussion in this context.Klaus J Puettmann Scott McG Wilson Susan C Baker Pablo J Donoso Lars Dr?ssler Girma Amente Brian D Harvey Thomas Knoke Yuanchang Lu Susanna Nocentini Francis E Putz Toshiya Yoshida Jürgen Bauhus 2015Forest Ecosystems2015,2,2:4
8ACC/AHA guidelines for the management of patients with unstable angina and non–st-segment elevation myocardial infarction显示文摘Eugene Braunwald Elliott M Antman John W Beasley Robert M Califf Melvin D Cheitlin Judith S Hochman Robert H Jones Dean Kereiakes Joel Kupersmith Thomas N Levin Carl J Pepine John W Schaeffer Earl E Smith David E Steward Pierre Theroux Raymond J Gibbons J 2000Journal of the American College of Cardiology2000,,3:4
9Epigenetics of gastroenteropancreatic neuroendocrine tumors:A clinicopathologic perspective显示文摘Gastroenteropancreatic neuroendocrine tumors(GEP-NETs) are a heterogeneous group of rare tumors whose site-specific tumor incidence and clinical behavior vary widely. Genetic alterations associated with familial inherited syndromes have been well defined; however, the genetic profile of sporadic tumors is less clear as their tumorigenesis does not appear to be controlled by classic oncogenes such as P53, RB, or KRAS. Even within GEP-NETs, there are no common oncogenic drivers; for example, DAXX/ATRX mutations are strongly implicated in the tumorigenesis of pancreatic but not small bowel NETs. Accordingly, the dysregulation of epigenetic mechanisms has been hypothesized as a potential regulator of GEPNET tumorigenesis and has become a major focus of recent studies. Despite the heterogeneity of tumor cohorts evaluated in these studies, it is obvious that there are methylation patterns, chromatin remodeling alterations, and microR NA and long non-coding RNA(lncR NA) differential expression profiles that are distinctive of GEPNETs, some of which are correlated with significant differences in clinical outcomes. Several translational studies have provided convincing data identifying potential prognostic biomarkers, and some of these have demonstrated preliminary success as serum biomarkers that can be used clinically. Nevertheless, there are many opportunities to further define the mechanisms by which these epigenetic modifications influence tumorigenesis, and this will provide better insight into their prognostic and therapeutic utility. Furthermore, these findings form the foundation for future studies evaluating the clinical efficacy of epigenetic modifications as prognostic biomarkers, as well as potential therapeutic targets.Brendan M Finnerty Katherine D Gray Maureen D Moore Rasa Zarnegar Thomas J FaheyⅢ 2017World Journal of Gastrointestinal Oncology2017,9,9:4
10Nat Genet:单基因突变导致过敏性皮炎的发生显示文摘最近,研究者们鉴定出了一类导致神经性皮炎发生的关键基因突变:CARDll。来自美国NIH过敏与传染病研究所的研究者们通过对四个没有血缘关系的患病家庭进行分析,发现了这一导致疾病产生的基因、Chi A Ma, Yuan Zhang, Michael A Weinreich, Jonathan J Lyons, Celeste G Nelson, Thomas DiMaggio, Kelly D Stone, Joshua D Milner Jeffrey R Stinson, Elisa Ruffo, Batsukh Dorjbal, Swadhinya Arjunaraja, Kelsey Voss, Andrew L Snow Jordan K Abbott, Pia J Hauk, Paul R Reynolds, Erwin W Gelfand Elisa Ruffo Salomé Glauzy, Natsuko Yamakawa, Eric Meffre Jennifer Stoddard, Julie Niemela, Sergio D Rosenzweig Yu Zhang, Helen F Matthews Joshua J McElwee Nina Jones Alejandro Palma, Matías Oleastro, Emma Prieto, Andrea R Bernasconi, Geronimo Dubra, Silvia Danielian, Jonathan Zaiat, Marcelo A Marti Brian Kim Megan A Cooper Neil Romberg 2017现代生物医学进展2017,17,27:3
11Meeting report:a hard look at the state of enamel research显示文摘The Encouraging Novel Amelogenesis Models and Ex vivo cell Lines(ENAMEL) Development workshop was held on 23 June 2017 at the Bethesda headquarters of the National Institute of Dental and Craniofacial Research(NIDCR). Discussion topics included model organisms, stem cells/cell lines, and tissues/3 D cell culture/organoids. Scientists from a number of disciplines,representing institutions from across the United States, gathered to discuss advances in our understanding of enamel, as well as future directions for the field.ophir d klein olivier duverger wendy shaw rodrigo s lacruz derk joester janet moradian-oldak megan k pugach j timothy wright sarah e millar ashok b kulkarni john d bartlett thomas gh diekwisch pamela den besten james p simmer 2017International Journal of Oral Science2017,9,4:3
12Bevacizumab plus oxaliplatin-based chemotherapy as adjuvant treatment for colon cancer (AVANT): a phase 3 randomised controlled trial显示文摘Aimery de Gramont Eric Van Cutsem Hans-Joachim Schmoll Josep Tabernero Stephen Clarke Malcolm J Moore David Cunningham Thomas H Cartwright J Randolph Hecht Fernando Rivera Seock-Ah Im Gy?rgy Bodoky Ramon Salazar Frédérique Maindrault-Goebel Einat Shacham- 2012Lancet Oncology2012,,12:3
13Acid‐suppressive therapy is associated with spontaneous bacterial peritonitis in cirrhotic patients: A meta‐analysis显示文摘Abhishek Deshpande Vinay Pasupuleti Priyaleela Thota Chaitanya Pant Sulaiman Mapara Sohaib Hassan David D K Rolston Thomas J Sferra Adrian V Hernandez 2013J Gastroenterol Hepatol2013,,2:3
14Macrophage secretory products induce an inflammatory phenotype in hepatocytes显示文摘AIM:To investigate the influence of macrophages on hepatocyte phenotype and function.METHODS:Macrophages were differentiated from THP-1 monocytes via phorbol myristate acetate stimulation and the effects of monocyte or macrophageconditioned medium on HepG2 mRNA and protein expression determined.The in vivo relevance of these findings was confirmed using liver biopsies from 147 patients with hepatitis C virus(HCV)infection.RESULTS:Conditioned media from macrophages,but not monocytes,induced a transient morphological change in hepatocytes associated with upregulation of vimentin(7.8±2.5-fold,P=0.045)and transforming growth factor(TGF)-β1(2.6±0.2-fold,P<0.001)and downregulation of epithelial cadherin(1.7±0.02-fold,P=0.017)mRNA expression.Microarray analysis revealed significant upregulation of lipocalin-2(17-fold,P <0.001)and pathways associated with inflammation,and substantial downregulation of pathways related to hepatocyte function.In patients with chronic HCV,realtime polymerase chain reaction and immunohistochemistry confirmed an increase in lipocalin-2 mRNA(F0 1.0 ±0.3,F1 2.2±0.2,F2 3.0±9.3,F3/4 4.0±0.8,P= 0.003)and protein expression(F1 1.0±0.5,F2 1.3± 0.4,F3/4 3.6±0.4,P=0.014)with increasing liver injury.High performance liquid chromatography-tandem mass spectrometry analysis identified elevated levels of matrix metalloproteinase(MMP)-9 in macrophageconditioned medium,and a chemical inhibitor of MMP-9 attenuated the change in morphology and mRNA expression of TGF-β1(2.9±0.2 vs 1.04±0.1,P<0.001) in macrophage-conditioned media treated HepG2 cells.In patients with chronic HCV infection,hepatic mRNA expression of CD163(F0 1.0±0.2,F1/2 2.8±0.3,F3/4 5.3±1.0,P=0.001)and MMP-9(F0 1.0±0.4,F1/2 2.8±0.3,F3/4 4.1±0.8,P=0.011)was significantly associated with increasing stage of fibrosis.CONCLUSION:Secreted macrophage products alter the phenotype and function of hepatocytes,with increased expression of inflammatory mediators,suggesting that hepatocytes actively participate in liver injury.Michelle Melino Victoria L Gadd Gene V Walker Richard Skoien Helen D Barrie Dinesh Jothimani Leigh Horsfall Alun Jones Matthew J Sweet Gethin P Thomas Andrew D Clouston Julie R Jonsson Elizabeth E Powell 2012World Journal of Gastroenterology2012,18,15:3
15一种房颤风险评分系统的建立(Framingham心脏研究):基于社区的队列研究显示文摘背景房颤导致了发病率和病死率的显著上升。本研究旨在建立一种预测个体罹患房颤绝对风险的风险评分系统,并提供研究人员评价新危险因素的流程。方法作者评估了Framingham心脏研究中于1968年6月至1987年9月间进行了8044次检测的4764例参与者(55%为女性,年龄45~95岁)。此后,参与者被随访至房颤首发,随访期最长达10年。多变量Coxi回归确认出1(1年内罹患房颤的临床危险因素。次级分析纳入了常规超声心动图检测指标(5152例4参与者,7156次检测)对房颤风险进行再分层评估,并评价超声检测指标能否提高风险预测能力。结果4764例参与者中的457例4(10%)罹患房颤。年龄、性别、体重指数、收缩压、降压治疗、PR间期、有临床意义的心脏杂音及心力衰竭与房颤相关,并被纳入了风险评分模型(除体重指数P=0.08外,其余均为P〈0.05),模型的C统计量为0.78(95%CI0.76~0.80)。10年房颤风险随年龄变化:年龄〈65岁的人群中53例(1%)风险高于15%,而〉65岁的人群中为783例(27%)。为提高预测能力而纳入超声检测指标仅使模型C统计量略微增高,由0.78(95%C10.75~0.80)增至0.79(95%CI0.77~0.82:P=0.005)。超声心动图检测指标并不能改善风险再分层评估(P=0.18)。结论基于社区医疗中易得的临床因素建立的风险评分系统,有助于确认社区个体罹患房颤的风险,评估技术或标志物能否改善风险预测,以及针对高危个体采取预防措施。Renate B Schnabel Lisa M Sullivan Daniel Levy Michael J Pencina Joseph M Massaro Ralph B D'Agostino Sr Christopher Newton-Cheh Jennifer F Yamamoto Jared W Magnani Thomas M Tadros William B Kannel Thomas J Wang Patrick T Ellinor Philip A Wolf Ramachanclran S Vasan Emelia J Benjamin 黄刚(译) 2009世界临床医学2009,,9:2
16Role of microbubble ultrasound contrast agents in the non-invasive assessment of chronic hepatitis C-related liver disease显示文摘长期地感染丙肝病毒的病人经常得长期的肝疾病,对肝损伤的严厉的评价在认为病毒的根除是治疗以前被要求。这篇文章检验从标准答案肝活体检视当前可得到的各种各样的评价方法到血清学的标记和成像。超声是在临床的实践的最广泛地使用的成像形式之一并且已经是为肝疾病的一个首要的诊断工具。Microbubble 超声对比代理人允许更高的分辨率要获得的图象和对要执行的微脉管的变化的功能的评价。在确定的这些代理人的角色肝的损害的状态作为与丙肝在病人决定肝疾病的阶段和等级的一个可行方法被讨论。尽管当前限制了到专家中心,提高对比的超声将不可避免地在临床的背景增加的微水泡的可获得性。Scott Grier Adrian KP Lim Nayna Patel Jeremy FL Cobbold Howard C Thomas Isobel J Cox Simon D Taylor-Robinson 2006World Journal of Gastroenterology2006,12,22:2
17Treatment of relapsing autoimmune pancreatitis with immunomodulators and rituximab: the Mayo Clinic experience显示文摘Phil A Hart Mark D Topazian Thomas E Witzig Jonathan E Clain Ferga C Gleeson Robin R Klebig Michael J Levy Randall K Pearson Bret T Petersen Thomas C Smyrk Aravind Sugumar Naoki Takahashi Santhi S Vege Suresh T Chari 2013Gut2013,,11:2
18Senescent human hepatocytes express a unique secretory phenotype and promote macrophage migration显示文摘AIM:To develop a model of stress-induced senescence to study the hepatocyte senescence associated secretory phenotype(SASP).METHODS:Hydrogen peroxide treatment was used to induce senescence in the human Hep G2 hepatocyte cell line.Senescence was confirmed by cytochemical staining for a panel of markers including Ki67,p21,heterochromatin protein 1β,and senescence-associated-β-galactosidase activity.Senescent hepatocytes were characterised by gene expression arrays and quantitative polymerase chain reaction(q PCR),and conditioned media was used in proteomic analyses,a human chemokine protein array,and cell migration assays to characterise the composition and function of the hepatocyte SASP.RESULTS:Senescent hepatocytes induced classical markers of senescence(p21,heterochromatin protein1β,and senescence-associated-β-galactosidase activity);and downregulated the proliferation marker,Ki67.Hepatocyte senescence induced a 4.6-fold increase in total secreted protein(P=0.06)without major alterations in the protein profile.Senescence-induced genes were identified by microarray(Benjamini Hochbergcorrected P<0.05);and,consistent with the increase in secreted protein,gene ontology analysis revealed a significant enrichment of secreted proteins among inducible genes.The hepatocyte SASP included characteristic factors such as interleukin(IL)-8 and IL-6,as well as novel components such as SAA4,IL-32and Fibrinogen,which were validated by q PCR and/or chemokine protein array.Senescent hepatocyteconditioned medium elicited migration of inflammatory(granulocyte-macrophage colony stimulating factor,GM-CSF-derived),but not non-inflammatory(CSF-1-derived)human macrophages(P=0.022),which could contribute to a pro-inflammatory microenvironment in vivo,or facilitate the clearance of senescent cells.CONCLUSION:Our novel model of hepatocyte senescence provides insights into mechanisms by which senescent hepatocytes may promote chronic liver disease pathogenesis.Katharine M Irvine Richard Skoien Nilesh J Bokil Michelle Melino Gethin P Thomas Dorothy Loo Brian Gabrielli Michelle M Hill Matthew J Sweet Andrew D Clouston Elizabeth E Powell 2014World Journal of Gastroenterology2014,20,47:2
19Direct control of the grid point distribution in meshs generated by elliptic equations显示文摘P D Thomas J F Middlecoff 1980AIAA Journal1980,18,6:2
20Treatment of relapsing autoimmune pancreatitis with immunomodulators and rituximab: the Mayo Clinic experience显示文摘Phil A Hart Mark D Topazian Thomas E Witzig Jonathan E Clain Ferga C Gleeson Robin R Klebig Michael J Levy Randall K Pearson Bret T Petersen Thomas C Smyrk Aravind Sugumar Naoki Takahashi Santhi S Vege Suresh T Chari 2013Gut2013,,11:2
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