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| 1 | HEDGEHOG-GLI1 signaling regulates human glioma growth, cancer stem cell self-renewal, and tumorigenicity显示文摘 | Clement V Sanchez P de Tribolet N Radovanovic I Ruiz i Altaba A | 2007 | 中国神经肿瘤杂志2007，5，2： | 96 |
| 2 | 阿尔泰中蒙边界塔克什肯口岸后造山富碱侵入岩体的形成时代、成因及其地壳生长意义显示文摘塔克什肯口岸富碱侵入岩体是阿尔泰造山带典型的后造山岩体。本次锆石U-Pb定年给出^(206)Pb/^(238)U年龄286±1Ma(MSWD=0.05),代表其形成年龄。这为阿尔泰后造山岩浆作用提供了一个可靠的年代学证据。该岩体主要岩石类型为正长岩、石英二长岩、石英碱长正长岩、正长花岗岩,富钾、富钠、准铝,富集轻稀土、大离子亲石元素,亏损高场强元素,与区内相邻的碱性花岗岩(A型花岗岩)在岩石学、地球化学方面不同。该岩体Sr初始值变化于0.7038~0.7040,ε_(Nd)(t)值为正值(+6.2~+6.3),Nd模式年龄T_(DM)为542~546Ma,与中亚造山带典型的高(正)ε_(Nd)(t)值花岗岩类似。而且,其ε_(Nd)(t)值远高于区内同造山花岗岩,也高于造山带内部同时期的Ⅰ-A型后造山花岗岩。依据岩体构造特征、年代学、地球化学和区域地质背景综合分析,该岩体应为后造山岩体,在时空上可与蒙古南部碱性岩带对比,其形成可能与富集高场强元素的亏损地幔岩浆底侵,导致下地壳重熔,并发生岩浆混合有关。这说明,在阿尔泰造山带后造山阶段,除了可能的俯冲下埋的年轻洋壳或岛弧物质外,还有新的幔源物质加入到地壳。这为中亚造山带后造山阶段陆壳垂向生长提供了一个新证据。同时,也为东北北部-蒙古南部碱性岩带向西沿入阿尔泰造山带提供了证据。 | 童英 王涛 V P Kovach 洪大卫 韩宝福 | 2006 | 岩石学报2006，22，5： | 69 |
| 3 | 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 |
| 4 | 乳腺囊内型乳头状癌显示文摘 | Collins L C Carlo V P Hwang H 魏兵(摘译) 步宏(审校) | 2006 | 临床与实验病理学杂志2006，22，5： | 38 |
| 5 | Use of probiotics for prevention of radiation-induced diarrhea显示文摘AIM: To investigate the efficacy of a high-potency probiotic preparation on prevention of radiation-induced diarrhea in cancer patients. METHODS: This was a double-blind, placebo-controlled trial. Four hundred and ninety patients who underwent adjuvant postoperative radiation therapy after surgery for sigmoid, rectal, or cervical cancer were assigned to either the high-potency probiotic preparation VSL#3 (one sachet t.i.d.,) or placebo starting from the first day of radiation therapy. Efficacy endpoints were incidence and severity of radiation-induced diarrhea, daily number of bowel movements, and the time from the start of the study to the use of loperamide as rescue medication. RESULTS: More placebo patients had radiation-induced diarrhea than VSL#3 patients (124 of 239 patients, 51.8%, and 77 of 243 patients, 31.6%; P < 0.001) and more patients given placebo suffered grade 3 or 4 diarrhea compared with VSL#3 recipients (55.4% and 1.4%, P < 0.001). Daily bowel movements were 14.7 ± 6 and 5.1 ± 3 among placebo and VSL#3 recipients (P < 0.05), and the mean time to the use of loperamide was 86 ± 6 h for placebo patients and 122 ± 8 h for VSL#3 patients (P < 0.001). CONCLUSION: Probiotic lactic acid-producing bacteria are an easy, safe, and feasible approach to protect cancer patients against the risk of radiation-induced diarrhea. | P Delia G Sansotta V Donato P Frosina G Messina C De Renzis G Famularo | 2007 | World Journal of Gastroenterology2007，13，6： | 29 |
| 6 | Risk factors associated with the development of ischemic colitis显示文摘AIM:To ascertain the role of cardiovascular risk factors,cardiovascular diseases,standard treatments and other diseases in the development of ischemic colitis(IC).METHODS:A retrospective,case-control study was designed,using matched data and covering 161 incident cases of IC who required admission to our hospital from 1998 through 2003.IC was diagnosed on the basis of endoscopic findings and diagnostic or compatible his-tology.Controls were randomly chosen from a cohort of patients who were admitted in the same period and required a colonoscopy,excluding those with diagnosis of colitis.Cases were matched with controls(ratio 1:2),by age and sex.A conditional logistic regression was performed.RESULTS:A total of 483 patients(161 cases,322 con-trols)were included;mean age 75.67±10.03 years,55.9%women.The principal indications for colonos-copy in the control group were lower gastrointestinal hemorrhage(35.4%),anemia(33.9%),abdominal pain(19.9%)and diarrhea(9.6%).The endoscopic findings in this group were hemorrhoids(25.5%),diverticular disease(30.4%),polyps(19.9%)and colorectal cancer(10.2%).The following variables were associated with IC in the univariate analysis:arterial hypertension(P= 0.033);dyslipidemia(P<0.001);diabetes mellitus(P =0.025);peripheral arterial disease(P=0.004);heart failure(P=0.026);treatment with hypotensive drugs(P=0.023);angiotensin-converting enzyme inhibitors;(P=0.018);calcium channel antagonists(P=0.028);and acetylsalicylic acid(ASA)(P<0.001).Finally,the following variables were independently associated with the development of IC:diabetes mellitus[odds ratio(OR)1.76,95%confidence interval(CI):1.001-3.077,P=0.046];dyslipidemia(OR 2.12,95%CI:1.26-3.57,P=0.004);heart failure(OR 3.17,95%CI:1.31-7.68,P=0.01);peripheral arterial disease(OR 4.1,95%CI:1.32-12.72,P=0.015);treatment with digoxin(digitalis)(OR 0.27,95%CI:0.084-0.857,P=0.026);and ASA(OR 1.97,95%CI:1.16-3.36,P=0.012).CONCLUSION:The development of an episode of IC was independently associated with diabetes,dyslipid-emia,presence of heart failure,peripheral arterial dis-ease and treatment with digoxin or ASA. | Joaquín Cubiella Fernández Luisa Núez Calvo Elvira González Vázquez Maria Jesús García García Maria Teresa Alves Pérez Isabel Martínez Silva Javier Fernández Seara | 2010 | World Journal of Gastroenterology2010，16，36： | 27 |
| 7 | 急性缺血性卒中的血管内治疗:神经介入外科学学会实践标准委员会的报告显示文摘目的总结采用血管内技术治疗急性缺血性卒中的有关证据并等级分类。方法对美国心脏协会(American Heart Association,AHA)以前发表的推荐意见进行审查并作为当前流程的基础。在此这基础上,进行系统的文献回顾以评估支持急性缺血性卒中血管内治疗的证据。根据AHA卒中委员会和牛津大学循证医学中心提出的循证医学证据分级指南进行评估。对操作安全性、技术效果以及对临床转归的影响进行特别审核。 | K A Blackham P M Meyers T A Abruzzo F C Alberquerque D Fiorella J Fraser D Frei C D Gandhi D V Heck J A Hirsch D P Hsu M Jayaraman S Narayanan C Prestigiacomo J L Sunshine 包元飞(译) 李永坤(译) 刘新峰(译) | 2012 | 国际脑血管病杂志2012，20，12： | 28 |
| 8 | Comparative clinical trial of S-pantoprazole versus racemic pantoprazole in the treatment of gastro-esophageal reflux disease显示文摘AIM: To compare the effi cacy and tolerability of S-pan- toprazole (20 mg once a day) versus racemic Panto- prazole (40 mg once a day) in the treatment of gastro- esophageal reflux disease (GERD). METHODS: This multi-centre, randomized, double-blind clinical trial consisted of 369 patients of either sex suf- fering from GERD. Patients were randomly assigned to receive either one tablet (20 mg) of S-pantoprazole once a day (test group) or 40 mg racemic pantoprazole once a day (reference group) for 28 d. Patients were evaluated for reduction in baseline on d 0, GERD symptom score on d 14 and 28, occurrence of any adverse effect during the course of therapy. Gastrointestinal (GI) endoscopy was performed in 54 patients enrolled at one of the study centers at baseline and on d 28. RESULTS: Signifi cant reduction in the scores (mean and median) for heart burn (P < 0.0001), acid regurgitation (P < 0.0001), bloating (P < 0.0001), nausea (P < 0.0001) and dysphagia (P < 0.001) was achieved in both groups on d 14 with further reduction on continuing the therapy till 28 d. There was a statistically signifi cant difference in the proportion of patients showing improvement in acid regurgitation and bloating on d 14 and 28 (P = 0.004 for acid regurgitation; P = 0.03 for bloating) and heart burn on d 28 (P = 0.01) between the two groups, with a higher proportion in the test group than in the refer- ence group. Absolute risk reductions for heartburn/acid regurgitation/bloating were approximately 15% on d 14 and 10% on d 28. The relative risk reductions were 26%-33% on d 14 and 15% on d 28. GI endoscopy showed no signifi cant difference in healing of esophagitis (P = 1) and gastric erosions (P = 0.27) between the two groups. None of the patients in either group reported any adverse effect during the course of therapy.CONCLUSION: In GERD, S-pantoprazole (20 mg) is more effective than racemic pantoprazole (40 mg) in improving symptoms of heartburn, acid regurgitation, bloating and equally effective in healing esophagitis and gastric erosions. The relative risk reduction is 15%-33%. Both drugs are safe and well tolerated. | Vikas G Pai Nitin V Pai Hemant P Thacker Jaisingh K Shinde Vijay P Mandora Subhash S Erram | 2006 | World Journal of Gastroenterology2006，12，37： | 19 |
| 9 | Spontaneous transformation of human adult non-tumorigenic stem cells to cancer stem cells is driven by genomic instability in a human model of glioblastoma显示文摘 | Shims A Chettiar S Shepal V Rajendran G Prasad R Shastry P | 2007 | 中国神经肿瘤杂志2007，5，1： | 16 |
| 10 | Antihyperglycemic activity,antihyperlipedemic activity,haematological effects and histopathological analysis of Sapindus mukorossi Gaerten fruits in streptozotocin induced diabetic rats显示文摘Objective:To investigate the antihyperglycemic and antihyperlipidemie properties of hydroalcoholic extract of fruits of Sapindus mukorossi Caerlen and its beneficial effect on haeniatological parameters with histopathological analysis in streptpzotocin induced diabetic rats.Methods:Sapindus mukorossi fruits extract(250 and 500 mg/kg body weight) and standard drug glybenclamide(0.5 mg/kg body weight) were administered to diabetic rats.Effect of extract on hyperglycemia,hyperlipidemia and hematological parameters was studied in diabetic rats.Histopathological changes in diabetic rat pancreas were also observed after extract and glybenclamide treatment.Results:Daily oral administration of Sapindus mukorossi fruits extract(250 and 500 mg/kg body weight) and glybenclamide for 20 days showed beneficial effects on blood glucose level(P<0.01) and lipid level.The extract has a favorable effect on the histopathological changes of the pancreas in streptozotocin induced diabetes.Conclusions: These findings reveal that the hydroalcoholic extract of Sapindus mukorossi fruits extract possesses antihyperglycemic and antihyperlipidemie properties.In addition.the extract can prevent various complications of diabetes and improve some haeniatological parameters. | Neeraj Verma G Amresh P K Sahu Neelam Mishra Anil P Singh Ch V Rao | 2012 | Asian Pacific Journal of Tropical Medicine2012，5，7： | 14 |
| 11 | 肽酰基精氨酸脱亚氨酶4和中性粒细胞胞外诱捕网形成在实验性动脉粥样硬化和动脉损伤中的作用:浅表糜烂的影响显示文摘中性粒细胞可能促进人类动脉粥样硬化的血栓并发症的发生。特别是中性粒细胞胞外诱捕网(neutrophil extracellular traps,NETs)可加剧局部炎症,并放大和加剧动脉内膜损伤和血栓形成。肽酰基精氨酸脱亚氨酶4(peptidyl arginine deiminase 4,PAD4)参与NET的形成,但对该酶在动脉粥样硬化血栓形成中的作用的认识仍然不足。 | 刘青 叶鹏 Franck G Mawson TL Folco EJ Molinaro R Ruvkun V Engelbertsen D Liu X Tesmenitsky Y Shvartz F Sukhova GK Michel JB Nicoletti A Lichtman AH Wagner DD Croce KJ Libby P | 2018 | 中华高血压杂志2018，26，5： | 13 |
| 12 | 通过TFE-3融合变异体分析Xp11易位癌之间的临床病理关系显示文摘Xp11易位癌包括Xp11易位性肾细胞癌(RCC)、Xp11易位性血管周上皮样细胞肿瘤(PEComa)以及色素性Xp11易位肾癌。在Xp11易位癌中,TFE3与一些不同基因伴侣的融合,从而激活TFE3致癌基因;然而不同的融合变异体对Xp11易位癌的临床病理特点影响尚不清楚。本文使用定制的细菌人工染色体探针来建立TFE3融合基因伴侣,采用原位荧光杂交对60例Xp11易位癌进行分析。5例通过RNA测序进一步分析其融合转录体的特点。60例Xp11易位癌包括47例Xp11易位性RCC、8例Xp11易位性PEComas以及5例色素性Xp11易位肾癌。60例患者中有53例(88%)确定了融合基因伴侣,包括18例SFPQ(PSF)、16例PRCC、12例ASPSCR1(ASPL)、6例NONO及1例DVL2。 | Argani P Zhong M Reuter V E 魏建国 刘勇 | 2016 | 临床与实验病理学杂志2016，32，9： | 13 |
| 13 | Mucinous cystadenoma of the appendix associated with adenocarcinoma of the sigmoid colon and hepatocellular carcinoma of the liver:Report of a case显示文摘附录的粘蛋白的包囊腺瘤是一个稀罕条件并且与附录的普通名字粘液囊肿代表三个实体之一。它被腔的膀胱的膨胀在它内与粘液的壅滞描绘。组织病理学说地,粘液囊肿被划分成三个组:焦点或弥漫的粘膜增生,粘蛋白的包囊腺瘤和粘蛋白的包囊腺癌。这个条件经常与另外的瘤形成被联系,特别冒号和卵巢的腺癌。我们这里描述与腹的不快,便秘,在凳子的新鲜的血和经常的泌尿介绍了的 57 岁男性病人。他有与结肠的腺癌和肝的肝细胞癌联系的附录的一个大包囊腺瘤。病人经历了正确 haemicolectomy, S 字形的冒号切除术和肝的部分切除术。现在, 3 年以后,他没有疾病恶化的证据。根据这,我们在这些病人强调精确外科手术前的诊断的需要和整个腹部的 intraoperative 探索。 | Srdjan P Djuranovic Milan M Spuran Nada V Kovacevic Milenko B Uqliesic Dragutin M Kecmanovic Marian T Micev | 2006 | World Journal of Gastroenterology2006，12，12： | 12 |
| 14 | 烟酰胺磷酸核糖基转移酶促进肺血管重塑,是肺动脉高压的治疗靶点显示文摘肺动脉高压(pulmonary arterial hypertension,PAH)是一种严重的进行性疾病,其标志之一是肺血管重塑。烟酰胺磷酸核糖基转移酶(nicotinamide phosphoribosyl transferase,NAMPT)是调节细胞内烟酰胺腺嘌呤二核苷酸水平、细胞氧化还原状态,调节组蛋白脱乙酰酶,促进细胞增殖和抑制凋亡的一种细胞酶。研究人员假设NAMPT可促进肺血管重塑, | Chen J Sysol JR Singla S Zhao S Yamamura A Valdez-Jasso D Abbasi T Shioura KM Sahni S Reddy V Sridhar A Gao H Torres J Camp SM Tang H Ye SQ Comhair S Dweik R Hassoun P Yuan JX Garcia JG Machado RF 刘莉 叶鹏 | 2017 | 中华高血压杂志2017，25，2： | 10 |
| 15 | Pancreatic cancer and its stroma: A conspiracy theory显示文摘Pancreatic cancer is characterised by a prominent desmoplastic/stromal reaction that has received little attention until recent times. Given that treatments focusing on pancreatic cancer cells alone have failed to significantly improve patient outcome over many decades, research efforts have now moved to understanding the pathophysiology of the stromal reaction and its role in cancer progression. In this regard, our Group was the first to identify the cells(pancreatic stellate cells, PSCs) that produced the collagenous stroma of pancreatic cancer and to demonstrate that these cells interacted closely with cancer cells to facilitate local tumour growth and distant metastasis. Evidence is accumulating to indicate that stromal PSCs may also mediate angiogenesis, immune evasion and the well known resistance of pancreatic cancer to chemotherapy and radiotherapy. This review will summarise current knowledge regarding the critical role of pancreatic stellate cells and the stroma in pancreatic cancer biologyand the therapeutic approaches being developed to target the stroma in a bid to improve the outcome of this devastating disease. | Zhihong Xu Srinivasa P Pothula Jeremy S Wilson Minoti V Apte | 2014 | World Journal of Gastroenterology2014，20，32： | 10 |
| 16 | Malignant schwannoma of the pancreas involving transversal colon treated with en-bloc resection显示文摘Pancreatic schwannoma is a very uncommon tumor of the pancreas,with only 27 cases reported.Most pancreatic schwannomas are benign,with only four malignant tumors reported.We describe a case of giant malignant schwannoma of the pancreatic body and tail,which involved the transverse colon.The tumor was treated successfully with en bloc distal splenopancreatectomy and colon resection.This is believed to be the first reported radical operation for malignant schwannoma of the pancreatic body,with infiltration of the transverse colon,with excellent longterm results.The patient is alive and well 28 mo after the operation.The authors conclude that pancreatic schwannomas should be considered in the differential diagnosis of cystic neoplasms of the pancreas,although the diagnosis can only be confirmed by microscopic examination.In the case of the benign tumors,local excision is adequate,but in the case of malignant schwannoma,oncological standards must be fulfilled. | Miroslav P Stojanovic Milan Radojkovic Ljiljana M Jeremic Aleksandar V Zlatic Goran Z Stanojevic Milan A Jovanovic Milos S Kostov Vuka P Katic | 2010 | World Journal of Gastroenterology2010，16，1： | 8 |
| 17 | Evaluation of brain tumor metabolism with [^(11)C] choline PET and ~1H-MRS.显示文摘BACKGROUND:The signal of choline containing compounds(Cho)in proton magnetic resonance spectroscopy(1H-MRS)is elevated in brain tumors.[11C]choline uptake as assessed using positron emission tomography(PET)has also been suggested to be higher in brain tumors than in the normal brain.We examined whetherquantitative analysis of choline accumulation and content using these 1wo novel techniques would be helpful innon-invasive,preoperative evaluation of suspected brain tumors and tumor malignancy grade.METHODS:12patients with suspected brain tumor were studied using[11C]choline PET,gadolinium enhanced 3-D magneticresonance imaging and1H-MRS prior to diagnostic biopsy or resection.Eleven normal subjects served as | Utriainen M Komu M Vuorinen V Lehikoinen P Sonninen P Kurki T Utriainen T Roivainen A Kalimo H Minn H | 2003 | 中国神经肿瘤杂志2003，1，2： | 8 |
| 18 | Gastroenteropancreatic neuroendocrine tumours显示文摘 | Irvin M Modlin Kjell Oberg Daniel C Chung Robert T Jensen Wouter W de Herder Rajesh V Thakker Martyn Caplin Gianfranco Delle Fave Greg A Kaltsas Eric P Krenning Steven F Moss Ola Nilsson Guido Rindi Ramon Salazar Philippe Ruszniewski Anders Sundin | 2008 | Lancet Oncology2008，，1： | 8 |
| 19 | 室内TDR试验监测石灰矿渣加固粘性土的物理化学反应过程(英文)显示文摘石灰矿渣和水泥矿渣常用于加固道路基层的粘性土。目前现场一般采用未加固土的最大干密度和最优含水率来评价加固土的压实施工质量。但是粘性土掺加了石灰后,发生了复杂的物理化学反应,使得其压实特性与未加固土有很大的不同。采用时域反射计监测石灰加固土内的物理化学反应过程。试验时将不同石灰矿渣掺和量和含水率的Orchard粘土通过标准击实试验夯实于击实筒中,用TDR监测其中的物理化学反应,针式贯入仪监测强度的增长。试验发现,电导率和介电常数的变化反应了土中的离子交换和硬化反应的过程。初始电导率(1d之内)的减小揭示了石灰矿渣的掺和量的大小,而长期电导率的减小揭示了强度的增长。试验表明,时域反射计技术可用于评价石灰加固土的施工质量。 | 陈仁朋 DAITA R K DRNEVICH V P KIM D H | 2006 | 岩土工程学报2006，28，2： | 7 |
| 20 | Aging related methylation influences the gene expression of key control genes in colorectal cancer and adenoma显示文摘AIM To analyze colorectal carcinogenesis and age-related DNA methylation alterations of gene sequences associated with epigenetic clock CpG sites. METHODS In silico DNA methylation analysis of 353 epigenetic clock Cp G sites published by Steve Horvath was performed using methylation array data for a set of 123 colonic tissue samples [64 colorectal cancer(CRC), 42 adenoma, 17 normal; GEO accession number: GSE48684]. Among the differentially methylated agerelated genes, secreted frizzled related protein 1(SFRP1) promoter methylation was further investigated in colonic tissue from 8 healthy adults, 19 normal children, 20 adenoma and 8 CRC patients using bisulfite-specific PCR followed by methylation-specific high resolution melting(MS-HRM) analysis. m RNA expression of age-related 'epigenetic clock' genes was studied using Affymetrix HGU133 Plus2.0 whole transcriptome data of 153 colonic biopsy samples(49 healthy adult, 49 adenoma, 49 CRC, 6 healthy children)(GEO accession numbers: GSE37364, GSE10714, GSE4183, GSE37267). Whole promoter methylation analysis of genes showing inverse DNA methylationgene expression data was performed on 30 colonic samples using methyl capture sequencing.RESULTS Fifty-seven age-related Cp G sites including hypermethylated PPP1R16 B, SFRP1, SYNE1 and hypomethylated MGP, PIPOX were differentially methylated between CRC and normal tissues(P < 0.05, ?β≥ 10%). In the adenoma vs normal comparison, 70 CpG sites differed significantly, including hypermethylated DKK3, SDC2, SFRP1, SYNE1 and hypomethylated CEMIP, SPATA18(P < 0.05, ?β≥ 10%). In MS-HRM analysis, the SFRP1 promoter region was significantly hypermethylated in CRC(55.0% ± 8.4 %) and adenoma tissue samples(49.9% ± 18.1%) compared to normal adult(5.2% ± 2.7%) and young(2.2% ± 0.7%) colonic tissue(P < 0.0001). DNA methylation of SFRP1 promoter was slightly, but significantly increased in healthy adults compared to normal young samples(P < 0.02). This correlated with significantly increased SFRP1 m RNA levels in children compared to normal adult samples(P < 0.05). In CRC tissue the mR NA expression of 117 agerelated genes were changed, while in adenoma samples 102 genes showed differential expression compared with normal colonic tissue(P < 0.05, logF C > 0.5). The change of expression for several genes including SYNE1, CLEC3 B, LTBP3 and SFRP1, followed the same pattern in aging and carcinogenesis, though not for all genes(e.g., MGP). CONCLUSION Several age-related DNA methylation alterations can be observed during CRC development and progression affecting the m RNA expression of certain CRC- and adenoma-related key control genes. | Orsolya Galamb Alexandra Kalmár Barbara Kinga Barták árpád V Patai Katalin Leiszter Bálint Péterfia Barnabás Wichmann Gábor Valcz Gábor Veres Zsolt Tulassay Béla Molnár | 2016 | World Journal of Gastroenterology2016，22，47： | 7 |
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