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| 1 | Intracellular HMGB1 as a novel tumor suppressor of pancreatic cancer显示文摘尽管有最近的进展, oncogenic K 地岬驾驶的胰腺的 ductal 腺癌(PDAC ) 在最致命的人的癌症之中留在现代医学。PDAC 的致病对内在的染色体不稳定性和外来的发炎激活部分可归因。然而,在在胰腺的 tumorigenesis 的这二个事件之间的分子的连接充分还没被建立了。这里,我们证明(HMGB1 ) 细胞内部的高活动性组盒子 1 显著地压制 oncogenic 由禁止染色体的 K-Ras-driven 胰腺的 tumorigenesis 调停不稳定性的支持 inflammatory nucleosome 版本。任何一个单身者的有条件的基因脱离或在胰的 HMGB1 的两等位基因在出生使老鼠变为极其敏感到先锋损害的 oncogenic K-Ras-driven 开始,包括胰腺的 intraepithelial 瘤, intraductal 乳突的 mucinous 瘤,和 mucinous 膀胱的瘤。在胰的 HMGB1 的损失与染色体重新整理和 telomere 畸形描绘的氧化 DNA 损坏和 chromosomal 不稳定性被联系。这些导致煽动性的 nucleosome 版本并且宣传 K-Ras-driven 胰腺的 tumorigenesis。细胞外的 nucleosomes 支持 interleukin 6 (IL-6 ) 由渗入 macrophages/neutrophils 的分泌物并且提高在胰腺的损害表明激活的 oncogenic K 地岬。到 IL-6 或 histone H3 或为先进 glycation 的受体的大美人的抵销的抗体结束产品都限制表明激活的 K 地岬,阻止癌症开发和转移 / 侵略,并且延长在 Pdx1-Cre 的动物幸存; K 地岬 G12D/+;Hmgb1/ 鼠标。由 glycyrrhizin 的 HMGB1 损失的药理学抑制在煽动性的条件下面在老鼠限制 oncogenic K-Ras-driven tumorigenesis。减少在 PDAC 病人的 HMGB1 的原子、全部的细胞的表示与差的全面幸存相关,在 PDAC 与预示、治疗学的关联作为新奇肿瘤 suppressor 支持细胞内部的 HMGB1。 | Rui Kang Yangchun Xie Qiuhong Zhang Wen Hou Qingping Jiang Shan Zhu Jinbao Liu Dexing Zeng Haichao Wang David L Bartlet Timothy R Billiar Herbert J Zeh III Michael T Lotze Daolin Tang | 2017 | Cell Research2017，27，7： | 22 |
| 2 | Methylation-dependent loss of RIP3 expression in cancer represses programmed necrosis in response to chemotherapeutics显示文摘交往受体的蛋白质 kinase-3 (RIP3 或 RIPK3 ) 是执行 “ 的细胞的机械的必要部分; programmed”或 “ regulated”坏死。这里,我们证明那规划坏死响应许多化学疗法的代理人被激活并且贡献导致化疗的房间死亡。然而,我们证明那 RIP3 表情经常在化学疗法的死亡期间由于它的 transcriptional 开始地点, MLKL 的这样 RIP3 依赖的激活和下游地规划的坏死附近的 genomic methylation 是在癌症房间的 silenced 大部分被镇压。不过,有 hypomethylating 代理人的治疗恢复 RIP3 表示,并且从而以一种 RIP3 依赖的方式把敏感提升到 chemotherapeutics。RIP3 表示在 85% 乳癌病人与正常织物相比在肿瘤被减少,建议那 RIP3 缺乏断然在肿瘤生长 / 发展期间被选择。因为 hypomethylating 代理人在病人是相当容忍得好的,我们建议病人们可以从收到 hypomethylating 代理人与常规 chemotherapeutics 在治疗以前导致 RIP3 表示有益于的那 RIP3 缺乏的癌症。 | Gi-Bang Koo Michael J Morgan Da-Gyum Lee Woo-Jung Kim Jung-Ho Yoon Ja Seung Koo Seung I1 Kim Soo Jung Kim Mi Kwon Son Soon Still Hong Jean M Mulcahy Levy Daniel A Pollyea Craig T Jordan Pearlly Yan David Frankhouser Deedra Nicolet Kati Maharry Guido Marcucci Kyeong Sook Choi Hyeseong Cho ndrew Thorbum You-Sun Kim | 2015 | Cell Research2015，25，6： | 20 |
| 3 | Bacterial biota in reflux esophagitis and Barrett's esophagus显示文摘AIM: To identify the bacterial flora in conditions such as Barrett's esophagus and reflux esophagitis to determine if they are similar to normal esophageal flora.METHODS: Using broad-range 16S rDNA PCR,esophageal biopsies were examined from 24 patients [9with normal esophageal mucosa, 12 with gastroesophageal reflux disease (GERD), and 3 with Barrett's esophagus].Two separate broad-range PCR reactions were performed for each patient, and the resulting products were cloned.In one patient with Barrett's esophagus, g9 PCR clones were analyzed.RESULTS: Two separate clones were recovered from each patient (total = 48), representing 24 different species, with 14 species homologous to known bacteria,5 homologous to unidentified bacteria, and 5 were not homologous (<97% identity) to any known bacterial 16S rDNA sequences. Seventeen species were found in the reflux esophagitis patients, 5 in the Barrett's esophagus patients, and 10 in normal esophagus patients.Further analysis concentrating on a single biopsy from an individual with Barrett's esophagus revealed the presence of 21. distinct bacterial species. Members of four phyla were represented, including Bacteroidetes,Firmicutes, Proteobacteria, and Actinobacteria.Microscopic examination of each biopsy demonstrated bacteria in intimate association with the distal esophageal epithelium, suggesting that the presence of these bacteria is not transitory.CONCLUSION: These findings provide evidence for a complex, residential bacterial population in esophageal reflux-related disorders. While much of this biota is present in the normal esophagus, more detailed comparisons may help identify potential disease associations. | Zhiheng Pei Liying Yang Richard M Peek Jr Steven M Levine David T Pride Martin J Blaser | 2005 | World Journal of Gastroenterology2005，11，46： | 11 |
| 4 | Photonic gas sensors exploiting directly the optical properties of hybrid carbon nanotube localized surface plasmon structures显示文摘Weinvestigate the modification of the optical properties of carbon nanotubes(CNTs)resulting from a chemical reaction triggered by the presence of a specific compound(gaseous carbon dioxide(CO_(2)))and show this mechanism has important consequences for chemical sensing.CNTs have attracted significant research interest because they can be functionalized for a particular chemical,yielding a specific physical response which suggests many potential applications in the fields of nanotechnology and sensing.So far,however,utilizing their optical properties for this purpose has proven to be challenging.We demonstrate the use of localized surface plasmons generated on a nanostructured thin film,resembling a large array of nano-wires,to detect changes in the optical properties of the CNTs.Chemical selectivity is demonstrated using CO_(2) in gaseous form at room temperature.The demonstrated methodology results additionally in a new,electrically passive,optical sensing configuration that opens up the possibilities of using CNTs as sensors in hazardous/explosive environments. | Thomas Allsop Raz Arif Ron Neal Kyriacos Kalli Vojtěch Kundrát Aleksey Rozhin Phil Culverhouse David J Webb | 2016 | Light(Science & Applications)2016，5，1： | 3 |
| 5 | The Importance of Medial Support in Locked Plating of Proximal Humerus Fractures显示文摘 | Michael J Gardner Yoram Weil Joseph U Barker Bryan T Kelly David L Helfet Dean G Lorich | 2007 | Journal of Orthopaedic Trauma2007，，3： | 2 |
| 6 | CD133 expression is not restricted to stem cells, and both CD133^sup +^ and CD133^sup -^ metastatic colon cancer cells initiate tumors显示文摘 | Shmelkov Sergey V Butler Jason M Hooper Andrea T Hormigo Adilia Kushner Jared Milde Till Clair Ryan St Baljevic Muhamed White Ian Jin David K Chadburn Amy Murphy Andrew J Valenzuela David M Gale Nicholas W Thurston Gavin Yancopoulos George | 2008 | Journal of Clinical Investigation2008，，： | 2 |
| 7 | Therapeutic drug monitoring in patients with inflammatory bowel disease显示文摘Thiopurine analogs and anti-tumor necrosis factor(TNF)agents have dramatically changed the therapeutics of inflammatory bowel diseases(IBD),improving short and long-term outcomes.Unfortunately some patients do not respond to therapy and others lose response over time.The pharmacokinetic properties of these drugs are complex,with high inter-patient variability.Thiopurine analogs are metabolized through a series of pathways,which vary according to the patients’pharmacogenetic profile.This profile largely determines the ratios of metabolites,which are in turn associated with likelihoods of clinical efficacy and/or toxicity.Understanding these mechanisms allows for manipulation of drug dose,aiming to reduce the development of toxicity while improving the efficacy of treatment.The efficacy of anti-TNF drugs is influenced by many pharmacodynamic variables.Several factors may alter drug clearance,including the concomitant use of immunomodulators(thiopurine analogs and methotrexate),systemic inflammation,the presence of anti-drug antibodies,and body mass.The treatment of IBD has evolved with the understanding of the pharmacologic profiles of immunomodulating and TNF-inhibiting medications,with good evidence for improvement in patient outcomesobserved when measuring metabolic pathway indices.The role of routine measurement of metabolite/drug levels and antibodies warrants further prospective studies as we enter the era of personalized IBD care. | Andres J Yarur Maria T Abreu Amar R Deshpande David H Kerman Daniel A Sussman | 2014 | World Journal of Gastroenterology2014，20，13： | 2 |
| 8 | Keeping an eye on the diabetic foot: The connection between diabetic eye disease and wound healing in the lower extremity显示文摘Diabetic eye disease is strongly associated with the development of diabetic foot ulcers(DFUs).DFUs are a common and significant complication of diabetes mellitus(DM)that arise from a combination of micro-and macrovascular compromise.Hyperglycemia and associated metabolic dysfunction in DM lead to impaired wound healing,immune dysregulation,peripheral vascular disease,and diabetic neuropathy that predisposes the lower extremities to repetitive injury and progressive tissue damage that may ultimately necessitate amputation.Diabetic retinopathy(DR)is caused by cumulative damage to the retinal microvasculature from hyperglycemia and other diabetes-associated factors.The severity of DR is closely associated with the development of DFUs and the need for lower extremity revascularization procedures and/or amputation.Like the lower extremity,the eye may also suffer end-organ damage from macrovascular compromise in the form of cranial neuropathies that impair its motility,cause optic neuropathy,or result in partial or complete blindness.Additionally,poor perfusion of the eye can cause ischemic retinopathy leading to the development of proliferative diabetic retinopathy or neovascular glaucoma,both serious,visionthreatening conditions.Finally,diabetic corneal ulcers and DFUs share many aspects of impaired wound healing resulting from neurovascular,sensory,and immunologic compromise.Notably,alterations in serum biomarkers,such as hemoglobin A1c,ceruloplasmin,creatinine,low-density lipoprotein,and highdensity lipoprotein,are associated with both DR and DFUs.Monitoring these parameters can aid in prognosticating long-term outcomes and shed light on shared pathogenic mechanisms that lead to end-organ damage.The frequent cooccurrence of diabetic eye and foot problems mandate that patients affected by either condition undergo reciprocal comprehensive eye and foot evaluations in addition to optimizing diabetes management. | David J Ramsey James T Kwan Arjun Sharma | 2022 | World Journal of Diabetes2022，13，12： | 2 |
| 9 | Mutifactorial analysis of risk factors for reduced bone mineral density in patients with Crohn’s disease显示文摘AIM: To determine the prevalence of osteoporosis in a cohort of patients with Crohn’s disease (CD) and to identify the relative significance of risk factors for osteoporosis. METHODS: Two hundred and fifty-eight unselected patients (92 M, 166 F) with CD were studied. Bone mineral density (BMD) was measured at the lumbar spine and hip by dual X-ray absorptiometry. Bone formation was assessed by measuring bone specific alkaline phosphatase (BSAP) and bone resorption by measuring urinary excretion of deoxypyridinoline (DPD) and N-telopeptide (NTX). RESULTS: Between 11.6%-13.6% patients were osteoporotic (T score < -2.5) at the lumbar spine and/or hip. NTX levels were significantly higher in the patients with osteoporosis (P < 0.05) but BSAP and DPD levels were not significantly different. Independent risk factors for osteoporosis at either the lumbar spine or hip were a low body mass index (P < 0.001), increasing corticosteroid use (P < 0.005), and male sex (P < 0.01). These factors combined accounted for 23% and 37% of the reduction in BMD at the lumbar spine and hip respectively. CONCLUSION: Our results confirm that osteoporosis is common in patients with CD and suggest that increased bone resorption is the mechanism responsible for thebone loss. However, less than half of the reduction in BMD can be attributed to risk factors such as corticosteroid use and low BMI and therefore remains unexplained. | Sarah A Bartram Robert T Peaston David J Rawlings David Walshaw Roger M Francis Nick P Thompson | 2006 | World Journal of Gastroenterology2006，12，35： | 2 |
| 10 | Adipocyte iron regulates adiponectin and insulin sensitivity显示文摘 | Gabrielsen J Scott Gao Yan Simcox Judith A Huang Jingyu Thorup David Jones Deborah Cooksey Robert C Gabrielsen David Adams Ted D Hunt Steven C Hopkins Paul N Cefalu William T McClain Donald A | 2012 | EN2012，，10： | 2 |
| 11 | Differential diagnosis in patients with suspected bile acid synthesis defects显示文摘AIM: To investigate the clinical presentations associated with bile acid synthesis defects and to describe identification of individual disorders and diagnostic pitfalls. METHODS: We describe semiquantitative determination of 16 urinary bile acid metabolites by electrospray ionization-tandem mass spectrometry. Sample preparation was performed by solid-phase extraction. The total analysis time was 2 min per sample. We determined bile acid metabolites in 363 patients with suspected defects in bile acid metabolism. RESULTS: Abnormal bile acid metabolites were found in 36 patients. Two patients had bile acid synthesis defects but presented with atypical presentations. In 2 other patients who were later shown to be affected by biliary atresia and cystic fibrosis the profile of bile acid metabolites was initially suggestive of a bile acid synthesis defect. Three adult patients suffered from cerebrotendinous xanthomatosis. Nineteen patients had peroxisomal disorders, and 10 patients had cholestatic hepatopathy of other cause. CONCLUSION: Screening for urinary cholanoids should be done in every infant with cholestatic hepatopathy as well as in children with progressive neurological disease to provide specific therapy. | Dorothea Haas Hongying Gan-Schreier Claus-Dieter Langhans Tilman Rohrer Guido Engelmann Maura Heverin David W Russell Peter T Clayton Georg F Hoffmann Jürgen G Okun | 2012 | World Journal of Gastroenterology2012，18，10： | 2 |
| 12 | Remote Sensing of Complex Permittivity by Multipole Resonances in RCS显示文摘 | DAVID J BURR YUEN T LO | 1973 | IEEE Transactions on Antennas and Propagation1973，21，4： | 1 |
| 13 | Relations among sprinkler uniforrnity measures显示文摘 | Beale J G David T H | 1966 | Journal of Irrigation and Drainage Division1966，92，1： | 1 |
| 14 | The Implications of Debt Heterogeneity for R and D Investment and Firm Performance 显示文摘 | David P O'Brien J P Yoshikawa T | 2008 | Academy of Management Journal2008，51，： | 1 |
| 15 | Recombinant human interleukin-6 (IL-6/ BSF-2/HSF) regulates the synthesis of acute phase proteins in human hepatocytes 显示文摘 | Casted JV Gomez-Lechon M J David M Hirano T Kishimoto T Heinrich PC | 1988 | FEBS Lett1988，232，2： | 1 |
| 16 | The effects of system and geometric parameters on abrasive water jet nozzle wear显示文摘 | MADHUSARATHI N DAVID G T THOMAS J K | 2002 | International Jour- nal of Machine Tools b- Manufacture2002，42，： | 1 |
| 17 | Enhancement of metal dispersion and selective acetylene hydrogenation catalytic properties of a supported Pd catalyst 显示文摘 | Feng J T Ma X Y David G E | 2011 | Industrial Engineering Chemical Research2011，50，4： | 1 |
| 18 | Late Glacial temperature and precipitation changes in tile lowland Neotropics by tandem measurement of lSO in biogenic carbonate and gypsum hydration water显示文摘 | DAVID A H ALEXANDRA V T CAMILLA J W | 2012 | Geochimica et Cosmochimica Acta2012，77，： | 1 |
| 19 | Climate change and international tourism: A simulation study显示文摘 | Jacqueline M H David J M Richard S J T | 2005 | Global Environ-mental Change Part A2005，15，3： | 1 |
| 20 | Geographic Information System, Decision Support System, and Urban Storm-Water Management 显示文摘 | David J Sample James P Heaney Leonard T Wright | 2001 | Journal of Water Resources Planning and Management2001，127，3： | 1 |
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