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| 1 | Cholangiocarcinoma, gone without the Wnt?显示文摘Cholangiocarcinoma(CCA) is a relatively rare malignancy of the intra- or extra-hepatic bile ducts that is classified according to its anatomical localization as intrahepatic, perihilar or distal. Overall, CCA has a dismal prognosis due to typical presentation at an advanced irresectable stage, lack of effective non-surgical treatments, and a high rate of disease recurrence. CCA frequently arises on a background of chronic liver inflammation and cholestasis. Chronic inflammation is accompanied by enhanced cell turnover with generation of additional inflammatory stimuli, and a microenvironment rich in pro-inflammatory mediators and proliferative factors that enable accumulation of mutations, transformation and expansion of mutated cells. A recent study by Boulter et al implicates the Wnt signaling cascade in cholangiocarcinogenesis. Wnt ligands Wnt7 B and Wnt10 A were found to be highly overexpressed in human CCA tissue. Wnt7 B protein was present throughout the tumor stroma, and often co-localized with a subset of CD68+ macrophages. To address in a direct manner whether Wnt signaling is engaged in development of CCA, Boulter et al explored the Wnt signaling pathway in an experimental model that recapitulates the multi-stage progression of human CCA.Wnt ligands found to be elevated in human CCA were also upregulated during the course of CCA development following thioacetamide treatment. Wnt10 a increased during the(pre-cancerous) regenerative phase, while Wnt7 b induction paralleled tumor growth. Along with upregulation of target genes, the findings demonstrate that the canonical Wnt pathway is progressively activated during cholangio-carcinogenesis. Macrophage depletion,eliminating a major source of Wnt7 b, prevented activation of the canonical Wnt cascade, and resulted in reduced number and volume of tumors in this model. Moreover,specific inhibitors of the canonical Wnt pathway(ICG-001 and C-59) caused reduction of tumor area and number,in xenograft and thioacetamide models of CCA. The aggregated findings show that experimental, and presumably human CCA, is a Wnt-driven tumor. Modulation of Wnt signaling, alone or in combination with surgicalor chemotherapy approaches, holds promise in the management of this fatal malignancy. | Anne T R Noll Thorsten Cramer Steven W M Olde Damink Frank G Schaap | 2016 | World Journal of Hepatology2016，8，26： | 3 |
| 2 | 世界家庭医生组织(WONCA)研究论文摘要汇编——帕金森病患者对诊断流程不满意度影响因素的横断面调查研究显示文摘背景帕金森病(PD)的诊断流程通常比较复杂。诊断流程可以影响到患者的自信、就医满意度以及对医务人员的信任情况。尽管诊断结果对患者造成的影响与医务人员无关,但是医务人员可以影响患者在诊断流程中的感受。本研究旨在调查PD患者对诊断流程的不满意度并探究相关影响因素。方法本项横断面研究在902例来自于荷兰帕金森病协会的PD患者中开展。每例患者均被要求书写其诊断流程。采用自行设计的赋值表对数据进行整理。各整理者之间的误差情况采用Cohen's kappa系数进行评价。使用χ~2检验和多因素Logistic回归分析评估患者对诊断流程的不满意度与性别、文化程度、诊断流程时长、患者与全科医生及神经科医生的沟通情况、参与诊断医务人员人数、是否存在二次诊断(包括提出进行二次诊断者)以及延迟诊断(患者认为有人导致了其延迟诊断也考虑在内)之间的关系。采用亚组分析探究不同性别患者对诊断流程不满意度之间的差异。结果 16.4%的PD患者明确表示对诊断流程不满意,4.8%的患者表示对诊断流程很满意。各整理者之间的误差情况Cohen's kappa系数为0.82。患者文化程度较低、参与诊断医务人员超过必要人数1人以上、患者提出进行二次诊断以及由医务人员原因导致的延迟诊断是PD患者对诊断流程不满意的危险因素。当只有全科医生与神经科医生参与诊断时,女性患者对诊断流程的不满意程度超过男性患者。结论 PD患者对诊断流程的不满意度与较低文化程度、患者提出进行二次诊断以及延迟诊断相关。了解这些因素后,如全科医生特别注意与患者进行沟通并且与患者一起进行临床决策,可以减少患者在诊断流程中的不良感受。此举有利于增加患者对医生的信任度,而患者对医生的信任度在以后的治疗过程中极其重要。 | PLOUVIER A O A OLDE HARTMAN T C DE BONT O A 本刊编辑部 | 2017 | 中国全科医学2017，20，29： | 2 |
| 3 | Detection of left ventricular regional relaxation abnormalities and asynchrony in patients with hypertrophic cardiomyopathy with the use of tissue Doppler imaging显示文摘 | Old T Mishiro Y Yamada H | 2000 | Am Heart J2000，139，3： | 1 |
| 4 | Intraepithelial CDS+ tumor-infiltrating lymphocytes and a high CD8+/regnlatory T cell ratio are associated with favorable prognosis in ovarian cancer显示文摘 | Sato E Olson SH Ahn J Bundy B Nishikawa H Qian F Jungbluth AA Frosina D Gnjatic S Ambrosone C Kepner J Odunsi T Ritter G Lele S Chen YT Ohtani H Old LJ Odunsi K | 2005 | Proc Natl Acad Sci USA2005，102，18： | 1 |
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| 10 | Relationships between milk yield and fertility in dairy cattle 显示文摘 | Olds D Cooper T | 1979 | Dairy Sci1979，62，： | 1 |
| 11 | Screenieboppers and extreme screenies: the place of screen time in the time budgets of 10-13 year-old Australian children显示文摘 | Olds T Ridley K Dollman J | 2006 | Aust N Z J Public Health2006，30，2： | 1 |
| 12 | Relationship between left atrial appendage function and plasma concentration of atrial natrinretic peptide 显示文摘 | Tabata T Old T Yamada H | 2000 | EurJ Echocardiogr2000，1，： | 1 |
| 13 | Electronic media use and adolescent health and well-being:cross-sectional community study显示文摘 | Mathers M Canterford L Olds T | 2009 | Acad Pediatr2009，9，5： | 1 |
| 14 | Evolutionary and ecological functional genomics显示文摘 | FEDER M E MITCHELL OLDS T | 2003 | Nature Reviews Genetics2003，4，： | 1 |
| 15 | 'UroMaix' scaffolds:novel collagen matrices for application in tissue engineering of the urinary tract显示文摘 | Becker C Olde Damink L Laeufer T | 2006 | Int J Artif Organs2006，29，8： | 1 |
| 16 | Ceramic sol-gel composite coatings for electrical insulation 显示文摘 | Olding T Sayer M Barrow D | 2001 | Thin Solid Films2001，，： | 1 |
| 17 | Mastitis diagnostics and performance monitoring:a practical approach显示文摘 | LAM T J G M OLDE R R G M SAMPIMON O C | | 0，，： | 1 |
| 18 | Evidence base,quantitation and collaboration:three novel indices for bibliometric content analysis显示文摘 | Wiles L Olds T Williams M | 2010 | Scientometrics2010，85，1： | 1 |
| 19 | Explanatory models of medically unexplained symptoms: a qualitative analysis of the literature 显示文摘 | van Ravenzwaaij J Olde Hartman T van Ravesteijn H | 2010 | Ment Health Fam Med2010，7，4： | 1 |
| 20 | Never enough sleep: a brief history of sleep recommendations for children 显示文摘 | Matricciani L A Olds T S Blunden S | 2012 | Pediatrics2012，129，3： | 1 |
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