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| 1 | 骨科创伤患者深静脉血栓危险因素的研究显示文摘目的研究骨科创伤患者深静脉血栓(deep vein thrombosis,DVT)的发生率,探讨骨科创伤患者DVT发生的危险因素。方法以2003年11月至2004年10月天津医院收治的新鲜四肢及骨盆骨折患者为研究对象,通过对不同年龄组患者的骨折类型、受伤机制、肿胀程度、既往DVT病史、手术及治疗方法等资料进行统计,并以3次彩色超声多普勒检查为诊断依据。需要手术的患者入院24h内进行第1次静脉多普勒检查,第2次和第3次检查分别在术前2d及术后7d;非手术患者3次检查分别在入院后24h、第5及14天。将需要分析的数据输入临床报告系统数据库1.1版,进行统计学分析及DVT发生率的流行病学分析。结果统计的547例患者中,平均年龄为39.6岁,DVT发生率为12.4%。以股骨干骨折DVT发生率为最高达30.6%,其次为髋部骨折15.7%,膝关节周围骨折14.5%,胫腓骨骨折10.8%。3个部位以上的多部位骨折患者DVT发生率为50%,单部位骨折患者DVT的发生率低于10%。超过半数的DVT(56.7%)发生于受伤3d之内。随着年龄增加DVT发生的风险也随之增大,年龄超过60岁患者的发病风险为184%。吸烟患者发生DVT的危险几乎是非吸烟患者的2倍。结论DVT在骨科创伤患者中具有一定的发生率,其年龄、病史、骨折部位、多发骨折及受伤距手术时间等均与DVT发生相关,须引起骨科临床医生的足够重视,并采取预防措施以降低肺栓塞的发生。 | 陆芸 马宝通 郭若霖 张建国 吴英华 庞贵根 辛景义 叶伟胜 邹玉安 王毅 董强 王学谦 Kerry H Paul C John F | 2007 | 中华骨科杂志2007,27,9: | 244 |
| 2 | 帕博利珠单抗单用或与放疗联用治疗转移性非小细胞肺癌:两个随机试验的汇总分析显示文摘背景放疗可以提高整个机体对免疫治疗的应答。在Ⅱ期PEMBRO-RT研究和Ⅰ/Ⅱ期MDACC研究中,患有转移性非小细胞肺癌(NSCLC)的患者被随机分配入组,接受免疫治疗(帕博利珠单抗)+放疗联合疗法,或免疫治疗单一疗法。当上述2个研究单独分析时,联合疗法组显示出潜在获益。由于每个研究的样本量较小,缓解率和结局并未显示出统计学意义,然而却有显著的临床获益。因此,本研究进行汇总分析,来判断放疗是否会改善转移性NSCLC患者的免疫治疗应答。方法PEMBRO-RT和MDACC研究纳入标准:患者年龄≥18岁,患有转移性NSCLC,且有≥1处未经放疗照射的病灶,以便进行射野外应答监测。PEMBRO-RT研究纳入曾接受过化疗患者,MDACC研究纳入曾接受过治疗或新诊断患者。2个研究中的患者均未接受过免疫治疗。在PEMBRO-RT研究中患者被等比例随机分配入组,并根据吸烟状态进行分层(分为<10年组和≥10年组)。MDACC研究的患者根据放疗计划可行性被等比例随机分配入2个受试组。由于联合治疗组的干预本质,每个研究中的放疗均不适用盲法。在2个研究中,不论是否进行放疗,均静脉滴入帕博利珠单抗(每3周200 mg)。在PEMBRO-RT研究中,在放疗(24 Gy 3次分割照射)结束后1周给予第1剂帕博利珠单抗。在MDACC研究中,在第1次放疗(50 Gy 4次分割照射或45 Gy 15次分割照射)同时给予帕博利珠单抗。仅检测未经照射病灶的应答。本研究的终点为最佳射野外(远隔)应答率(ARR)、最佳射野外疾病控制率(ACR)、12周时ARR、12周时ACR、无进展生存期(PFS)和总生存期(OS)。2个研究的意向治疗(ITT)人群均纳入分析。PEMBRO-RT研究(NCT02492568)和MDACC研究(NCT02444741)均在ClinicalTrials.gov上注册。发现纳入148例患者,76例接受帕博利珠单抗治疗,72例接受帕博利珠单抗+放疗治疗。所有患者随访时间中位数为33个月[四分位距(IQR):32.4~33.6]。148例患者中124例(84%)组织学特征为非鳞癌,111例(75%)患者曾经接受过化疗。组间没有基线特征差异,包括PD-L1表达状态和转移灶体积。最常见的照射部位为肺转移灶(39%,28/72)、胸腔内淋巴结(21%,15/72)和非原发灶(17%,12/72)。帕博利珠单抗组和联合治疗组的最佳ARR分别为19.7%(15/76)和41.7%(30/72),OR=2.96,95%CI:1.42~6.20,P=0.0039;最佳ACR分别为43.4%(33/76)和65.3%(47/72),OR=2.51,95%CI:1.28~4.91,P=0.0071;PFS中位数分别为4.4(IQR:2.9~5.9)和9.0个月(IQR:6.8~11.2),HR=0.67,95%CI:0.45~0.99,P=0.045;OS中位数分别为8.7(IQR:6.4~11.0)和19.2个月(IQR:14.6~23.8),OR=0.67,95%CI:0.54~0.84,P=0.0004。在汇总分析中没有发现新的安全问题。解读帕博利珠单抗免疫疗法+放疗显著提高转移性NSCLC患者的应答和改善治疗结局。这些结果需要在三期临床试验中进行验证。 | 陈大卫(翻译) 于金明(校对) Willemijn S M E Theelen Vivek Verma Brian P Hobbs Heike M U Peulen Joachim G J V Aerts Idris Bahce Anna Larissa N Niemeijer Joe Y Chang Patricia M de Groot Quynh-Nhu Nguyen Nathan I Comeaux George R Simon Ferdinandos Skoulidis Steven H Lin Kewen He Roshal Patel John Heymach Paul Baas James W Welsh | 2021 | 中华肿瘤防治杂志2021,28,24: | 49 |
| 3 | 楔形构造在山前冲断构造位移量消减中的作用——以准噶尔盆地南缘为例显示文摘介于复活的天山造山带与稳定的准噶尔克拉通之间的准噶尔盆地南缘前陆冲断带,是印度板块与欧亚大陆碰撞的远距离效应产物,也是新近纪以来青藏高原隆升并向北推挤的直接结果。前陆冲断带吸收了来自造山带的水平缩短构造位移量后,克拉通一侧构造趋于稳定。准噶尔盆地南缘与世界上多数前陆冲断带构造地质特征相似,通过区域地震剖面的精细构造几何学和运动学解析,发现其中的楔形构造非常典型,是前陆冲断带内部冲断构造位移量消减的主要方式之一,控制着前陆冲断带分布范围和变形方式。准噶尔盆地南缘构造变形主要由南侧的天山造山带向北逆掩冲断,但是大部分冲断构造位移量是通过楔形构造反向传递后消减。紧邻天山北麓的齐古-喀拉扎-昌吉等构造带,山前深部的楔形体沿侏罗系西山窑组煤层向北扩展过程中,部分位移量沿构造楔顶部的反冲断层向南消减,并切割上覆地层形成第一排背斜带,另一部分位移量则继续向北传递,在断坡位置引发褶皱变形,形成霍-玛-吐第二排构造带和安集海-呼图壁第三排背斜带。准噶尔盆地南缘第二、三排构造带中-新生界内部发育多个小型的构造楔型体,这些互相叠置的楔型构造横向延伸不大,加大了构造变形的复杂性和构造圈闭识别的难度。 | 李本亮 管树巍 陈竹新 John H Shaw 雷永良 王丽宁 赵星 | 2012 | 地质学报2012,86,6: | 18 |
| 4 | 氢——一种内源性抗氧化剂(英文)显示文摘最近Ohsawa等报道,呼吸氢气能通过抗氧化作用,减少动物脑和肝缺血再灌注引起的细胞凋亡。实际上,人和动物消化道内许多正常细菌能产生氢气,这些氢气可被消化道吸收进入血液循环。考虑到小鼠部分器官内氢气水平已达到产生抗氧化作用的浓度,我们认为,氢是一种内源性抗氧化物质。 | 孙学军 John H Zhang | 2008 | 第二军医大学学报2008,29,3: | 16 |
| 5 | 内侧固定平台单髁置换术后的冠状面下肢力线是翻修的影响因素显示文摘膝关节单髁置换术(unicompartmental knee arthroplasty,UKA)后患者冠状面的下肢力线被认为是影响手术长期疗效的一个重要因素,但关于最佳的UKA术后下肢力线还没有形成明确共识。一些研究主张术后下肢力线应保持在中立位,而另一些研究认为即使术后下肢力线存在10°的内翻也可获得良好的临床效果。 | Sean E Slaven John P Cody Robert A Sershon Henry Ho Robert H Hopper Jr Kevin B Fricka 李亚坤(整理) 张民(整理) | 2020 | 实用骨科杂志2020,26,12: | 15 |
| 6 | Use of blood-based biomarkers for early diagnosis and surveillance of colorectal cancer显示文摘Early screening for colorectal cancer(CRC) holds the key to combat and control the increasing global burden of CRC morbidity and mortality. However, the current available screening modalities are severely inadequate because of their high cost and cumbersome preparatory procedures that ultimately lead to a low participation rate. People simply do not like to have colonoscopies. It would be ideal, therefore, to develop an alternative modality based on blood biomarkers as the first line screening test. This will allow for the differentiation of the general population from high risk individuals. Colonoscopy would then become the secondary test, to further screen the high risk segment of the population. This will encourage participation and therefore help to reach the goal of early detection and thereby reduce the anticipated increasing global CRC incidence rate. A blood-based screening test is anappealing alternative as it is non-invasive and poses minimal risk to patients. It is easy to perform, can be repeated at shorter intervals, and therefore would likely lead to a much higher participation rate. This review surveys various blood-based test strategies currently under investigation, discusses the potency of what is available, and assesses how new technology may contribute to future test design. | Ganepola AP Ganepola Joel Nizin John R Rutledge David H Chang | 2014 | World Journal of Gastrointestinal Oncology2014,6,4: | 11 |
| 7 | Novel blood-based microRNA biomarker panel for early diagnosis of pancreatic cancer显示文摘AIM:To develop a panel of blood-based diagnostic biomarkers consisting of circulating microRNAs for the detection of pancreatic cancer at an early stage.METHODS:Blood-based circulating microRNAs were profiled by high throughput screening using microarray analysis,comparing differential expression between early stage pancreatic cancer patients(n = 8) and healthy controls(n = 11).A panel of candidate microRNAs was generated based on the microarray signature profiling,including unsupervised clustering and statistical analysis of differential expression levels,and findings from the published literature.The selected candidate microRNAs were then confirmed using TaqMan real-time quantitative reverse transcription polymerase chain reaction(RT-qPCR) to further narrow down to a three-microRNA diagnostic panel.The three-microRNA diagnostic panel was validated with independent experimental proce-dures and instrumentation of RT-qPCR at an independent venue with a new cohort of cancer patients(n = 11),healthy controls(n = 11),and a group of high risk controls(n = 11).Receiver operating characteristic curve analysis was performed to assess the diagnostic capability of the three-microRNA panel.RESULTS:In the initial high throughput screening,1220 known human microRNAs were screened for differential expression in pancreatic cancer patients versus controls.A subset of 42 microRNAs was then generated based on this data analysis and current published literature.Eight microRNAs were selected from the list of 42 targets for confirmation study,and three-microRNAs,miR-642b,miR-885-5p,and miR-22,were confirmed to show consistent expression between microarray and RT-qPCR.These three microRNAs were then validated and evaluated as a diagnostic panel with a new cohort of patients and controls and found to yield high sensitivity(91%) and specificity(91%) with an area under the curve of 0.97(P < 0.001).Compared to the CA19-9 marker at 73%,the three-microRNA panel has higher sensitivity although CA19-9 has higher specificity of 100%.CONCLUSION:The identified panel of three microRNA biomarkers can potentially be used as a diagnostic tool for early stage pancreatic cancer. | Ganepola AP Ganepola John R Rutledge Paritosh Suman Anusak Yiengpruksawan David H Chang | 2014 | World Journal of Gastrointestinal Oncology2014,6,1: | 9 |
| 8 | Near-infrared fluorescence sentinel lymph node detection in gastric cancer: A pilot study显示文摘AIM: To investigate feasibility and accuracy of nearinfrared fluorescence imaging using indocyanine green: nanocolloid for sentinel lymph node(SLN) detection in gastric cancer.METHODS: A prospective, single-institution, phaseI feasibility trial was conducted. Patients suffering from gastric cancer and planned for gastrectomy were included. During surgery, a subserosal injection of 1.6 m L ICG:Nanocoll was administered around the tumor. NIR fluorescence imaging of the abdominal cavity was performed using the Mini-FLARE? NIR fluorescence imaging system. Lymphatic pathways and SLNs were visualized. Of every detected SLN, the corresponding lymph node station, signal-to-background ratio and histopathological diagnosis was determined. Patients underwent standard-of-care gastrectomy. Detected SLNs outside the standard dissection planes were also resected and evaluated.RESULTS: Twenty-six patients were enrolled. Four patients were excluded because distant metastases were found during surgery or due to technical failure of the injection. In 21 of the remaining 22 patients, at least 1 SLN was detected by NIR Fluorescence imaging(mean 3.1 SLNs; range 1-6). In 8 of the 21 patients, tumor-positive LNs were found. Overall accuracy of the technique was 90%(70%-99%; 95%CI), which decreased by higher p T-stage(100%, 100%, 100%, 90%, 0% for respectively Tx, T1, T2, T3, T4 tumors). All NIR-negative SLNs were completely effaced by tumor. Mean fluorescence signal-to-background ratio of SLNs was 4.4(range 1.4-19.8). In 8 of the 21 patients, SLNs outside the standard resection plane were identified, that contained malignant cells in 2 patients.CONCLUSION: This study shows successful use of ICG:Nanocoll as lymphatic tracer for SLN detection in gastric cancer. Moreover, tumor-containing LNs outside the standard dissection planes were identified. | Quirijn RJG Tummers Leonora SF Boogerd Wobbe O de Steur Floris PR Verbeek Martin C Boonstra Henricus JM Handgraaf John V Frangioni Cornelis JH van de Velde Henk H Hartgrink Alexander L Vahrmeijer | 2016 | World Journal of Gastroenterology2016,22,13: | 9 |
| 9 | Redox therapeutics in hepatic ischemia reperfusion injury显示文摘Ischemia-reperfusion plays a major role in the injury experienced by the liver during transplantation. Much work has been done recently investigating the role of redox species in hepatic ischemia-reperfusion. As animal models are better characterized and developed, and more insights are gained into the pathophysiology of hepatic ischemia reperfusion injury in humans the questions into exactly how oxidants participate in this injury are becoming more refined. These questions include effects of cellular location, timing of injury, and ability of therapeutics to access this site are increasing our appreciation of the complexity of ischemia reperfusion and improving attempts to ameliorate its effects. In this review, we aim to discuss the various methods to alter redox chemistry during ischemia reperfusion injury and future prospects for preventing organ injury during hepatic ischemia reperfusion. | Rakesh P Patel John D Lang Alvin B Smith Jack H Crawford | 2014 | World Journal of Hepatology2014,6,1: | 9 |
| 10 | 氧合血红蛋白对培养的血管平滑肌细胞形态及增殖的作用显示文摘目的观察不同浓度氧合血红蛋白(oxyhemoglobin,OxyHb)对培养的血管平滑肌细胞(vascualrsmoothmusclecell,VSMC)的作用。方法将培养的VSMC根据OxyHb浓度分为1μmol/L、10μmol/L、100μmol/L、200μmol/L及正常对照组,通过观察形态学改变、MTT比色法分析评估其损害和增殖状况。结果与对照组比较,OxyHb组VSMC出现明显的病理形态学改变,MTT比色显示各浓度组OxyHb作用后OD值-时间曲线呈现双向性特点,在作用初期较对照组呈现明显的下降趋势,此后出现大幅上升,在24h内OxyHb组OD值均明显低于对照组。高浓度组(100μmol/L、200μmol/L)各时间点OD值均显著低于低浓度组(1μmol/L、10μmol/L。各浓度组相互比较有显著差异性。结论OxyHb作用下的VSMC其增殖活性呈现双向性改变,与临床经过相一致,抗VSMC增殖可能在慢性脑血管痉挛治疗中具有一定意义。 | 唐卫华 朱刚 John H Zhang 陈志 刘智 王宪荣 冯华 | 2005 | 中华神经外科杂志2005,21,7: | 8 |
| 11 | Assessment of lymph node involvement in colorectal cancer显示文摘Lymph node metastasis informs prognosis and is a key factor in deciding further management, particularly adjuvant chemotherapy. It is core to all contemporary staging systems, including the widely used tumor node metastasis staging system. Patients with nodenegative disease have 5-year survival rates of 70%-80%, implying a significant minority of patients with occult lymph node metastases will succumb to disease recurrence. Enhanced staging techniques may help to identify this subset of patients, who might benefit from further treatment. Obtaining adequate numbers of lymph nodes is essential for accurate staging. Lymph node yields are affected by numerous factors, many inherent to the patient and the tumour, but others related to surgical and histopathological practice. Good lymph node recovery relies on close collaboration between surgeon and pathologist. The optimal extent of surgical resection remains a subject of debate. Extended lymphadenectomy, extra-mesenteric lymph node dissection, high arterial ligation and complete mesocolic excision are amongst the surgical techniques with plausible oncological bases, but which are not supported by the highest levels of evidence. With further development and refinement, intra-operative lymphatic mapping and sentinel lymph node biopsy may provide a guide to the optimum extent of lymphadenectomy, but in its present form, it is beset by false negatives, skip lesions and failures to identify a sentinel node. Once resected, histopathological assessment of the surgical specimen can be improved by thorough dissection techniques, step-sectioning of tissue blocks and immunohistochemistry. More recently, molecular methods have been employed. In this review, we consider the numerous factors that affect lymph node yields, including the impact of the surgical and histopathological techniques. Potential future strategies, including the use of evolving technologies, are also discussed. | Mark L H Ong John B Schofield | 2016 | World Journal of Gastrointestinal Surgery2016,8,3: | 8 |
| 12 | Parallel effects of β-adrenoceptor blockade on cardiac function and fatty acid oxidation in the diabetic heart: Confronting the maze显示文摘Diabetic cardiomyopathy is a disease process in which diabetes produces a direct and continuous myocardial insult even in the absence of ischemic, hypertensive or valvular disease. The β-blocking agents bisoprolol, carvedilol and metoprolol have been shown in large-scale randomized controlled trials to reduce heart failure mortality. In this review, we summarize the results of our studies investigating the effects of β-blocking agents on cardiac function and metabolism in diabetic heart failure, and the complex inter-related mechanisms involved. Metoprolol inhibits fatty acid oxidation at the mitochondrial level but does not prevent lipotoxicity; its benefi cial effects are more likely to be due to prosurvival effects of chronic treatment. These studies have expanded our understanding of the range of effects produced by β-adrenergic blockade and showhow interconnected the signaling pathways of function and metabolism are in the heart. Although our initial hypothesis that inhibition of fatty acid oxidation would be a key mechanism of action was disproved, unexpected results led us to some intriguing regulatory mechanisms of cardiac metabolism. The fi rst was upstream stimulatory factor-2-mediated repression of transcriptional master regulator PGC-1α, most likely occurring as a consequence of the improved function; it is unclear whether this effect is unique to β-blockers, although repression of carnitine palmitoyltransferase (CPT)-1 has not been reported with other drugs which improve function. The second was the identif ication of a range of covalent modifications which can regulate CPT-1 directly, mediated by a signalome at the level of the mitochondria. We also identif ied an important interaction between β-adrenergic signaling and caveolins, which may be a key mechanism of action of β-adrenergic blockade. Our experience with this labyrinthine signaling web illustrates that initial hypotheses and anticipat-ed directions do not have to be right in order to open up meaningful directions or reveal new information. | Vijay Sharma John H McNeill | 2011 | World Journal of Cardiology2011,3,9: | 8 |
| 13 | 太赫兹折叠波导行波管再生反馈振荡器非线性理论与模拟显示文摘行波管再生反馈振荡器是一种新型太赫兹源器件.基于560GHz折叠波导慢波结构,对此类器件的工作原理与物理模型进行分析阐述.采用非线性互作用模型对行波管再生反馈振荡器进行详细振荡过程模拟.模拟结果显示,在550—600GHz频率下可以获得稳态振荡频率,并在560GHz处获得最大单频输出功率.结果同时表明,振荡频率随电子注电压发生跳变现象,并简要分析了其产生原因. | 高鹏 John H Booske 杨中海 李斌 徐立 何俊 宫玉彬 田忠 | 2010 | 物理学报2010,59,12: | 7 |
| 14 | 诊断性试验和策略的证据质量和推荐强度的分级显示文摘GRADE系统能对诊断性试验或策略的证据质量和推荐强度进行分级。本文旨在阐释在此过程中如何考虑患者的重要结局, | Holger J Schünemann Andrew D Oxman Jan Brozek Paul Glasziou Roman Jaeschke Gunn E Vist John W Williams Jr Regina Kunz Jonathan Craig Victor M Montori Patrick Bossuyt Gordon H Guyatt 李晓 黄程 陈耀龙 李幼平 | 2009 | 中国循证医学杂志2009,9,5: | 7 |
| 15 | Hematological disorders and pulmonary hypertension显示文摘Pulmonary hypertension(PH),a serious disorder with a high morbidity and mortality rate,is known to occur in a number of unrelated systemic diseases.Several hematological disorders such as sickle cell disease,thalassemia and myeloproliferative diseases develop PH which worsens the prognosis.Associated oxidant injury and vascular inflammation cause endothelial damage and dysfunction.Pulmonary vascular endothelial damage/dysfunction is an early event in PH resulting in the loss of vascular reactivity,activation of proliferative and antiapoptotic pathways leading to vascular remodeling,elevated pulmonary artery pressure,right ventricular hypertrophy and premature death.Hemolysis observed in hematological disorders leads to free hemoglobin which rapidly scavenges nitric oxide(NO),limiting its bioavailability,and leading to endothelial dysfunction.In addition,hemolysis releases arginase into the circulation which converts L-arginine to ornithine,thus bypassing NO production.Furthermore,treatments for hematological disorders such as immunosuppressive therapy,splenectomy,bone marrow transplantation,and radiation have been shown to contribute to the development of PH.Recent studies have shown deregulated iron homeostasis in patients with cardiopulmonary diseases including pulmonary arterial hypertension(PAH).Several studies have reported low iron levels in patients with idiopathic PAH,and iron deficiency is an important risk factor.This article reviews PH associated with hematological disorders and its mechanism:and iron homeostasis and its relevance to PH. | Rajamma Mathew Jing Huang Joseph M Wu John T Fallon Michael H Gewitz | 2016 | World Journal of Cardiology2016,8,12: | 6 |
| 16 | 氧合血红蛋白诱导神经细胞Caspase-3表达的研究显示文摘 | 王睿智 师蔚 孙建军 王芳茹 刘重霄 周乐 白斌 John H Zhang | 2004 | 中华实验外科杂志2004,21,7: | 6 |
| 17 | Tolvaptan, an oral vasopressin antagonist, in the treatment of hyponatremia in cirrhosis显示文摘 | Andrés Cárdenas Pere Ginès Paul Marotta Frank Czerwiec John Oyuang Mónica Guevara Nezam H Afdhal | 2011 | Journal of Hepatology2011,,3: | 6 |
| 18 | Simulation of multiple scattering of seismic waves by spatially distributed inclusions显示文摘A 2D elastodynamic boundary element method (BEM) is used to solve multiple scattering of elastic waves. The method is based on the integral representation of an elastic wave-field by assuming a fictitious source distribution on the scattering objects or inclusions, i.e. a mathematical description of Huygens’ principle, and the fictitious source distribution can be found by matching appropriate boundary conditions at the boundary of the inclusions. Numerical studies show that in the presence of cracks, spatial and scale-length distributions are important and different spatial arrangements of the same scatters lead to profound differences in scattering characteristics, in particular the frequency contents of the transmitted wave-fields. The frequency characteristics, such as the frequency of peak attenuation , can be related to spatial size parameters of the model. | 刘恩儒 QUEEN John H 张中杰 陈东 | 2000 | Science China(Technological Sciences)2000,43,4: | 6 |
| 19 | The immunology of human cytomegalovirus latency: could latent infection be cleared by novel immunotherapeutic strategies?显示文摘当跟随主要人的 cytomegalovirus (HCMV ) 感染的主人免疫者反应在停止病毒复制和传播通常是有效的时,病毒从来没被主人并且象所有 herpesviruses 一样清除,永久坚持。至少部分地,这坚持被知道被 HCMV 的能力便于在感染是实质上沉默的与的 myeloid 在房间建立潜伏,重要地新病毒生产的全部的缺乏。然而,尽管病毒的抄写计划很在潜伏期间被压制,很多病毒的基因在蛋白质水平在潜伏的感染期间被表示,这些中的许多被显示了在潜伏的房间和它的环境上有深刻效果。有趣地,许多也在 lysin 的感染期间这些联系潜伏的基因被表示。因此,一样的有势力主人免疫者回答为什么在 lysin 的感染期间产生了到这些病毒的基因产品,没在潜伏期间被认出,从而允许隐而不见地的感染的房间的清理,是远非清楚的。从潜伏的复活也是调停 HCMV 的疾病的一个主要原因,特别地在损害的免疫者和免疫者天真,并且也是可能的是在被建议了与象动脉粥样硬化和一些瘤形成那样的长期的疾病被联系的长期的无临床症状的 HCMV 感染的病毒的主要来源。因而,理解潜伏并且隐而不见地的感染的房间为什么看起来是 immunoprivileged,为 HCMV 的致病的理解是关键的并且可以帮助设计策略消除潜伏的病毒水库,至少在某些临床的背景。 | Mark R Wills Emma Poole Betty Lau Ben Krishna John H Sinclair | 2015 | Cellular & Molecular Immunology2015,12,2: | 6 |
| 20 | Histone modifications:Targeting head and neck cancer stem cells显示文摘Head and neck squamous cell carcinoma(HNSCC) is the sixth most common cancer worldwide, and is responsible for a quarter of a million deaths annually. The survival rate for HNSCC patients is poor, showing only minor improvement in the last three decades. Despite new surgical techniques and chemotherapy protocols, tumor resistance to chemotherapy remains a significant challenge for HNSCC patients. Numerous mechanisms underlie chemoresistance, including genetic and epigenetic alterations in cancer cells that may be acquired during treatment and activation of mitogenic signaling pathways, such as nuclear factor kappa-light-chain-enhancer-of activated B cell, that cause reduced apoptosis. In addition to dysfunctional molecular signaling, emerging evidence reveals involvement of cancer stem cells(CSCs) in tumor development and in tumor resistance to chemotherapy and radiotherapy. These observations have sparked interest in understanding the mechanisms involved in the control of CSC function and fate. Post-translational modifications of histones dynamically influence gene expression independent of alterations to the DNA sequence. Recent findings from our group have shown that pharmacological induction of posttranslational modifications of tumor histones dynamically modulates CSC plasticity. These findings suggest that a better understanding of the biology of CSCs in response to epigenetic switches and pharmacological inhibitors of histone function may directly translate to the development of a mechanism-based strategy to disrupt CSCs. In this review, we present and discuss current knowledge on epigenetic modifications of HNSCC and CSC response to DNA methylation and histone modifications. In addition, we discuss chromatin modifications and their role in tumor resistance to therapy. | John M Le Cristiane H Squarize Rogerio M Castilho | 2014 | World Journal of Stem Cells2014,6,5: | 6 |