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癌症 2019年第10期38卷 425-435页

作者： chang Zeng emily Kunce Stroup Zhou Zhang Brian c.-H.chiu Wei Zhang Driskill Graduate Program in Life Sciences Northwestern University Feinberg School of MedicineChicagoIL 60611USA Department of Preventive Medicine Northwestern University Feinberg School of Medicine680 N.Lake Shore Dr.Suite 1400ChicagoIL 60611USA Department of Public Health Sciences University of ChicagoChicagoIL 60637USA The Robert H.Lurie comprehensive cancer center Northwestern University Feinberg School of MedicineChicagoIL 60611USA 精准医学研究所济宁医科大学山东济宁272067

将性能稳定且便于临床应用的生物标志物应用于癌症诊断、早期检测和预测预后可提高患者生存率,也是精准医学的关键所在。第二代测序技术可以更加灵敏而全面地分析肿瘤来源的材料的遗传和表观遗传信息。现在,研究人员能够在新的维度上监... 详细信息

将性能稳定且便于临床应用的生物标志物应用于癌症诊断、早期检测和预测预后可提高患者生存率,也是精准医学的关键所在。第二代测序技术可以更加灵敏而全面地分析肿瘤来源的材料的遗传和表观遗传信息。现在,研究人员能够在新的维度上监测肿瘤发生的动态变化,例如使用循环无细胞DNA(circulating cell-free DNA,cf DNA)和循环肿瘤DNA(circulating tumor DNA,ctDNA)。基于突变分析的液体活检通常无法在不同研究中得到一致的结果,部分原因在于肿瘤内和肿瘤间的异质性以及技术的限制。相比之下,患者来源的cf DNA的表观遗传分析是一个很有前景的替代方案,特别是对于早期检测和疾病监测,因为表观遗传修饰是组织特异性的,并且反映了癌症进展的动态过程。因此,基于cf DNA的表观遗传分析正成为癌症诊断和预后预测的高灵敏度且微创的手段,在未来癌症患者的精准护理中具有巨大潜力。然而,应用cf DNA的表观遗传分析的主要障碍是缺乏具有高灵敏度和稳定性的技术。我们在本文中总结了cf DNA中5-羟甲基-胞嘧啶(5-hydroxymethylcytosine,5hmc)的表观基因组分析的研究进展,重点关注其对不同癌症类型的检测方法和作为生物标志物的潜在应用。

关键词：液体活检无细胞DNA 表观遗传学癌症生物标志物 5-羟甲基胞嘧啶

canadian Agility and Movement Skill Assessment(cAMSA):Validity, objectivity, and reliability evidence for children 8–12 years of age

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Journal of Sport and Health Science 2017年第2期6卷 231-240页

作者： Patricia E.Longmuir charles Boyer Meghann Lloyd Michael M.Borghese emily Knight Travis J.Saunders Elena Boiarskaia Weimo Zhu Mark S.Tremblay Healthy Active Living and Obesity Research Group Children's Hospital of Eastern Ontario Research Institute Ottawa Ontario K1H 8L1 Canada Department of Pediatrics Faculty of Medicine and School of Human Kinetics University of Ottawa Ottawa K1H 8M5 Canada Faculty of Health Sciences University of Ontario Institute of Technology Oshawa L1H 7K4 Canada School of Kinesiology and Health Studies Queen 's University Kingston Ontario K7L 3N6 Canada Department of Applied Human Sciences University of Prince Edward Island Charlottetown Prince Edward Island C1A 4P3 Canada Department of Kinesiology and community Health University of Illinois at Urbana-Champaign Urbana IL 61801 USA

Purpose: The primary aim of this study was to develop an assessment of the fundamental, combined, and complex movement skills required to support childhood physical literacy. The secondary aim was to establish the feasibility, objectivity, and reliability evidence for the ***: An expert advisory group recommended a course format for the assessment that would require children to complete a series of dynamic movement skills. criterion-referenced skill performance and completion time were the recommended forms of evaluation. children, 8–12 years of age, self-reported their age and gender and then completed the study assessments while attending local schools or day camps. Face validity was previously established through a Delphi expert(n = 19, 21% female) review process. convergent validity was evaluated by age and gender associations with assessment performance. Inter-and intra-rater(n = 53, 34% female) objectivity and test–retest(n = 60, 47% female) reliability were assessed through repeated test ***: Median total score was 21 of 28 points(range 5–28). Median completion time was 17 s. Total scores were feasible for all 995 children who self-reported age and gender. Total score did not differ between inside and outside environments(95% confidence interval(cI) of difference:-0.7 to 0.6;p = 0.91) or with/without footwear(95%cI of difference:-2.5 to 1.9; p = 0.77). Older age(p ciated with a higher total score. Inter-rater objectivity evidence was excellent(intraclass correlation coefficient(Icc) = 0.99) for completion time and substantial for skill score(Icc = 0.69) for 104 attempts by 53 children(34% female). Intra-rater objectivity was moderate(Icc = 0.52) for skill score and excellent for completion time(Icc = 0.99). Reliability was excellent for completion time over a short(2–4 days; Icc = 0.84) or long(8–14days; Icc = 0.82) interval. Skill score reliability was moderate(

关键词：技能评估复杂运动客观性加拿大儿童活性证据完成时间

Drinking Water Quality in the Sagarmatha National Park, Nepal

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Journal of Geoscience and Environment Protection 2016年第4期4卷 43-53页

作者： Kirsten Nicholson emily Hayes Klaus Neumann carolyn Dowling Subodh Sharma Department of Geological Sciences Ball State University Muncie USA Department of Environmental Science & Engineering Kathmandu University Dhulikhel Nepal

In 2014 we began the first systematic study of water quality, specifically fecal contamination of drinking water in the Khumbu Valley, Sagarmatha National Park (SNP, Mt. Everest region), Nepal. Our goal was to identify coliform bacteria and E. coli in drinking water and groundwater-fed springs to generate a data set that will function as a base for potable water supplies and further monitoring. Sampling occurred in May (pre-monsoon summer) and early November (post-monsoon early winter) 2014. Sample sites were selected based on proximity to villages and primary use as a drinking water source. Overall, the data presented a predictable correlation between fecal contamination and both elevation and increasing population/tourist traffic. Drinking water within the study area met current World Health Organization drinking water standards for the physical properties of temperature (2.8°c - 13°c), pH (5.27 - 7.24), conductivity (14.5 - 133 mS) and TDS (7.24 - 65.5 ppm). Samples from the more populated, lower altitude areas had higher levels of E. coli. Samples collected and analyzed in May (pre-monsoon summer) had a higher level of E. coli and coliform bacteria than samples collected in November (post-monsoon early winter) suggesting a seasonal dependence overlaid on the population signature. Surface water typically had higher E. coli values than groundwater-fed springs. Temperature, total dissolved solids and conductivity generally decreased with increasing elevation, whereas pH increased with increasing elevation. There appears to be significant presence of fecal contamination of water sources due to a combination of tourism, elevation and seasons.

关键词： Fecal coliform E. coli Mt. Everest Drinking Water

TLR4 signaling and the inhibition of liver hepcidin expression by alcohol

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World Journal of Gastroenterology 2014年第34期20卷 12161-12170页

作者： emily Zmijewski Sizhao Lu Duygu Dee Harrison-Findik Department of Internal Medicine University of Nebraska Medical CenterOmahaNE 68198-5820United States

AIM:To understand the role of toll-like receptor 4(TLR4)signaling in the regulation of iron-regulatory hormone,hepcidin by chronic alcohol ***:For chronic alcohol intake studies,TLR4mutant mice on c3H/HeJ background and wildtype counterpart on c3H/HeOuJ background were pair-fed with regular(control)and ethanol-containing Lieber De carli liquids *** expression was determined by real-time quantitative ***-protein interactions and protein expression were determined by co-immunoprecipitation and western *** occupancy of hepcidin gene promoter was determined by chromatin immunoprecipitation ***:chronic alcohol intake suppressed hepcidin mRNA expression in the livers of wildtype,but not TLR4 mutant,*** phosphorylation and nuclear translocation of nuclear factor(NF)-κB p65 subunit protein was observed in alcohol-fed wildtype,but not in alcohol-fed TLR4 mutant,***,alcohol induced the binding of NF-κB p50 subunit protein to hepcidin gene promoter in wildtype,but not in TLR4mutant,*** contrast,the phosphorylation of Stat3in the liver was stronger in alcohol-treated TLR4 mutant mice compared to alcohol-treated wildtype *** occupancy of hepcidin gene promoter by Stat3was observed in alcohol-fed mutant,but not in wildtype,*** interaction between NF-κB p65 subunit protein and small heterodimer partner protein(SHP)was observed in the livers of both wildtype and TLR4mutant mice fed with the control diet,as shown by coimmunoprecipitation *** intake elevated cytosolic SHP expression but attenuated its interaction with NF-κB in the liver,which was more prominent in the livers of wildtype compared to TLR4 mutant ***:Activation of TLR4 signaling and NF-кB are involved in the suppression of hepcidin gene transcription by alcohol in the presence of inflammation in the liver.

关键词： Iron Small heterodimer partner protein Nuclear fac

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明尼苏达蓝天湖水的北星之州

旅游世界 2016年第10期 33-41页

作者： emily Wang Ever Liu Elliott c.Mei

在即将结束明尼苏达的旅程的某一天清晨，我和朋友们坐在窗明几净的JW万豪酒店餐厅，阳光透过雅白色的落地窗帘洒进来，洒在我们丰盛的早餐和透亮的盛满气泡水的玻璃杯上，我的朋友突然提议，让我们每人用一个词语来形容自己对明尼苏达... 详细信息

在即将结束明尼苏达的旅程的某一天清晨，我和朋友们坐在窗明几净的JW万豪酒店餐厅，阳光透过雅白色的落地窗帘洒进来，洒在我们丰盛的早餐和透亮的盛满气泡水的玻璃杯上，我的朋友突然提议，让我们每人用一个词语来形容自己对明尼苏达的感受。这真是一个难题，因为明尼苏达实在有太多难以言尽的美丽，只用一个词语来概括，未免有点单薄。但我们还是绞尽脑汁在记忆中搜寻着那个最合适的词汇。

关键词：明尼苏达湖水万豪酒店玻璃杯朋友词语

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圣地亚哥美国人心目中最美的阳光海岸

旅游世界 2016年第10期 23-32页

作者： emily Wang Ever Liu Elliott c.Mei

圣地亚哥，在有些地方也被翻译为“圣迭戈”（SanDiego）,位于美国本土的西南角，是美国的第七大城市，与墨西哥的小镇蒂华纳接壤，以温暖的气候和美丽的沙滩著名，是美国人心目中的度假胜地，这里有蔚蓝的太平洋和细软的沙滩，可以冲... 详细信息

圣地亚哥，在有些地方也被翻译为“圣迭戈”（SanDiego）,位于美国本土的西南角，是美国的第七大城市，与墨西哥的小镇蒂华纳接壤，以温暖的气候和美丽的沙滩著名，是美国人心目中的度假胜地，这里有蔚蓝的太平洋和细软的沙滩，可以冲浪、潜水、钓鱼、骑马、慢跑等。像我这样挑剔又爱好“慢旅行”的人，这样一个风景优美，游客不至于拥挤，户外活动众多的海边度假地，好像是独一无二的香氛一样令我垂爱。

关键词：圣地亚哥美国人心海岸阳光度假胜地户外活动大城市

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行走美国,梦中之境

旅游世界 2016年第10期 20-22页

作者： emily Wang Ever Liu Elliott c.Mei

每次去美国，都会得到不一样的收获。不管是充满着浓厚学术氛围与优雅气息的新英格兰地区，还是历史古迹众多，白宫所在地的首都地区，又或者是南部热情似火的佛罗里达，又或者是墨西哥湾畔狂野不羁的德克萨斯，抑或是娱乐产业发达，一... 详细信息

每次去美国，都会得到不一样的收获。不管是充满着浓厚学术氛围与优雅气息的新英格兰地区，还是历史古迹众多，白宫所在地的首都地区，又或者是南部热情似火的佛罗里达，又或者是墨西哥湾畔狂野不羁的德克萨斯，抑或是娱乐产业发达，一半海水一半戈壁的加利福尼亚……这些年，我的足迹从东岸到西岸，从北部到南部，每一次前往美国的旅途，都令我兴奋不已，因为我知道，地广物博的美国有太多的迷人之境值得我去探寻，而每一次的旅程结束，我都能或多或少获得一些成长和感悟，在这个梦想国度，无所不能，只要你敢上路，终点便由你说了算。

关键词：美国加利福尼亚新英格兰学术氛围历史古迹佛罗里达墨西哥湾娱乐产业

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三例遗传性白内障家系的分子诊断

三例遗传性白内障家系的分子诊断

Hepatocellular carcinoma with biliary and neuroendocrine differentiation: A case report

第八次全国医学遗传学学术会议(中华医学会2009年医学...

作者：郑芳刘媛媛陈强饶艳 emily 武汉大学中南医院

先天性白内障是儿童常见的致盲眼病,可以是家族聚集或散发,可以是单眼或双眼发病,可以伴眼部或全身其他先天性异常,也可以只表现为晶状体混浊,其中遗传性单纯性(非综合征性)白内障占绝大多数。遗传性白内障的遗传方式有常染色体显性遗传...

先天性白内障是儿童常见的致盲眼病,可以是家族聚集或散发,可以是单眼或双眼发病,可以伴眼部或全身其他先天性异常,也可以只表现为晶状体混浊,其中遗传性单纯性(非综合征性)白内障占绝大多数。遗传性白内障的遗传方式有常染色体显性遗传(autosomal dominance,AD),常染色体隐性遗传(autosomal recessive,AR)以及X连锁隐性遗传(X-linked recessive, XR)等,多为单基因显性遗传。在临床工作中,我们随访到湖北地区三个先天性遗传性白内障大家系,均呈常染色体显性遗传,分别命名为ADcc-1、ADcc-2、ADcc-3。ADcc-1家系成员涉及四代73人,其中先天性白内障患者20人,正常人53人。家系中受累者均为双眼同时发病,表现为粉尘状白内障。据家系中患病成员回忆,在7岁学龄期左右开始出现视物的异常,视力逐渐下降,不伴有其他先天异常。通过对遗传性白内障致病基因的分析,发现家系中所有患者均携带有缝隙连接蛋白cx50基因氨基酸保守区的突变,而这个突变不存在于正常对照中,这一个c/T的碱基突变导致了cx50氨基酸序列276位丝氨酸至苯丙氨酸(S/F)的改变。同时利用生物信息学的方法,预测突变蛋白质的二级结构,发现突变蛋白发生明显的二级结构变化。采用激光共聚焦显微镜,观察突变型cx50和野生突变杂合型cx50与野生型cx50在Hela细胞中的定位,发现突变型cx50和野生突变杂合型cx50与野生型cx50均定位于细胞膜上,呈斑片状分布,无明显定位差异。通过对ADcc-2家系进行基因筛查发现在该(四代共23人,患者9人)常染色体显性遗传的核性白内障家系中发现了一个位于cRYAB基因上的R11H新突变。将人αB-晶状体蛋白基因成功地克隆到的原核表达载体pET 28a(+)上并表达出相应大小的目的蛋白,蛋白以可溶性形式表达。通过Ni-NTA纯化出重组表达的αB-晶状体蛋白。Western Blot结果显示所表达的αB-晶状体蛋白能够特异性地与相应抗体结合。圆二色光谱、内部色氨酸荧光光谱分析表明R11H突变导致了αB-晶状体蛋白构象和结构的改变。疏水性分析表明突变型表面疏水性增加。分子伴侣活性测定显示突变型蛋白分子伴侣活性下降。细胞实验表明突变型蛋白在细胞核和胞浆均有分布,而野生型蛋白主要在胞浆分布。说明αB-晶状体蛋白R11H突变导致其结构变化,分子伴侣功能的下降和在细胞内的分布异常,这些改变可能是促使白内障发生的原因。ADcc-3家系成员25人(包括患者11人,非患者14人)发现cRYBB1基因上第六外显子的一个新的终止突变Q227X,蛋白二级和三级结构预测异常。功能分析正在进行中。

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World Journal of clinical Oncology 2021年第4期12卷 262-271页

作者： Yiannis Petros Dimopoulos emily R Winslow Aiwu Ruth He Metin Ozdemirli Department of Pathology and Laboratory Medicine Medstar Georgetown University HospitalWashingtonDC 20007United States Medstar center for Liver and Pancreas Surgery Medstar Georgetown University HospitalWashingtonDC 20007United States Lombardi comprehensive cancer center Medstar Georgetown University HospitalWashingtonDC 20007United States

BAcKGROUND Liver tumors with dual differentiations[combined hepatocellular carcinoma(Hcc)and cholangiocarcinoma]are ***,liver tumors that exhibit hepatocellular,biliary,and neuroendocrine differentiation are exceedingly rare,with only three previous case reports in the *** SUMMARY A 65-year-old female with a previous history of hepatitis c and a distant history of low grade,well-differentiated rectal neuroendocrine tumor was found to have two liver lesions in segment 4 and segment 7 on *** alpha-fetoprotein and chromogranin A were *** of the larger lesion in segment 4 revealed a high-grade tumor,with morphologic and immunohistochemical features of a neuroendocrine *** the previous history of rectal neuroendocrine tumor,imaging investigation,serologic markers,and biopsy findings,metastatic neuroendocrine tumor was *** regional resection of these hepatic lesions revealed the segment 4 lesion to be a Hcc with additional biliary and neuroendocrine differentiation and the segment 7 lesion to be a cholangiocarcinoma with neuroendocrine ***-up of the patient revealed disease recurrence in the dome of the liver and metastasis in retro-pancreatic lymph *** patient eventually expired due to complications of *** Hcc cases with additional biliary and neuroendocrine differentiation are exceedingly rare,posing a diagnostic challenge for clinicians and pathologists.

关键词： Mixed liver tumor Hepatocellular Biliary Neuroendocrine Triple differentiation case report