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| 1 | Apoptosis and DNA damage in human spermatozoa显示文摘DNA 损坏经常在 subfertile 男性的精子被遇到并且包括损害授精与不利临床的结果的一个范围被相关,破坏 preimplantation 胚胎的开发,流产的增加的率和在子孙的疾病的提高的风险。在人的精子的 DNA 破碎的病原学密切与氧化的底的外观被相关使内收并且损害精子形式的证据。我们假设那个氧化压力阻碍精子形式,与糟糕改变的染色质导致精子的产生。这些有缺点的房间有一个趋势默认到线粒体与活动性损失, caspase 激活, phosphatidylserine exteriorization 和免费激进的产生的激活联系的一条 apoptotic 小径。后者导致类脂化合物 peroxidation 和氧化 DNA 损坏,它然后导致 DNA 破碎和房间死亡。精子的物理体系结构阻止从获得存取到原子 DNA 并且导致它的破碎由于这 apoptotic 进程激活的任何核酸酶。是为这个原因在人的精子遇到的 DNA 损坏的一个多数似乎氧化。给氧化应力似乎在 DNA 损坏的病原学有的重要角色,应该为在这个条件的处理的抗氧化剂有一个重要角色。如果在精子的氧化 DNA 损坏正在提供全身的氧化应力的敏感读出,这些调查结果的含意能在我们试着作为一篇序言在精子最小化 DNA 损坏到帮助概念治疗的立即的目标以外拉长。 | R John Aitken Adam J Koppers | 2011 | Asian Journal of Andrology2011，13，1： | 46 |
| 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 | Relationship between the exocrine and endocrine pancreas after acute pancreatitis显示文摘AIM:To determine the prevalence and time course of pancreatic exocrine insufficiency in individuals with newly diagnosed prediabetes or diabetes mellitus after acute pancreatitis.METHODS:Relevant literature cited in three major biomedical journal databases(EMBASE,MEDLINE,and Scopus)was reviewed independently by two authors.There were no language constraints but the search was limited to human studies.Studies included were cohort studies of adult patients who were discharged after an attack of acute pancreatitis.Patients were excluded if they were under 18 years of age or had a previous diagnosis of prediabetes or diabetes mellitus,pancreatic exocrine insufficiency,or chronic pancreatitis.The main outcome measure was the prevalence of concomitant pancreatic exocrine insufficiency in patients who were diagnosed with prediabetes and diabetes mellitus after an attack of acute pancreatitis.Subgroup analysis was conducted for patients who were diagnosed with prediabetes only and those who were diagnosed withdiabetes mellitus only.Subgroup analysis looking at the time course of concomitant pancreatic exocrine and endocrine insufficiency was also conducted.Pooled prevalence and corresponding 95%confidence intervals were calculated for all outcome measures and P-values<0.05 were deemed statistically significant.RESULTS:Eight clinical studies comprising of 234patients met all eligibility criteria.The pooled prevalence of newly diagnosed prediabetes or diabetes in individuals after acute pancreatitis was 43%(95%CI:30%-56%).The pooled prevalence of pancreatic exocrine insufficiency in individuals after acute pancreatitis was 29%(95%CI:19%-39%).The prevalence of concomitant pancreatic exocrine insufficiency in individuals with newly diagnosed prediabetes or diabetes was 40%(95%CI:25%-55%).The prevalence of concomitant pancreatic exocrine insufficiency among individuals with prediabetes alone and diabetes mellitus alone was 41%(95%CI:12%-75%)and 39%(95%CI:28%-51%),respectively.Further analysis showed that the prevalence of concomitant pancreatic exocrine insufficiency in individuals with prediabetes or diabetes decreases over time after an attack of acute pancreatitis.CONCLUSION:Pancreatic exocrine insufficiency occurs in 40%of individuals with newly diagnosed prediabetes or diabetes mellitus after acute pancreatitis.Further studies are needed to investigate the pathogenesis of diabetes in this setting. | Stephanie L M Das James I C Kennedy Rinki Murphy Anthony R J Phillips John A Windsor Maxim S Petrov | 2014 | World Journal of Gastroenterology2014，20，45： | 9 |
| 4 | 地理信息系统技术在伤寒发热监测中应用显示文摘目的运用地理信息系统(GIS)技术,了解各居民点发热流行率和评价以医疗机构为哨点的伤寒发热监测系统的敏感性。方法收集医学人口普查数据、疾病监测系统信息数据、现场采集居民居住点全球卫星定位数据等资料,建立GIS系统和以人口为基数的发热监测系统;对所有发热就诊病人进行身份和居住地址确认,并制作各居民点年发热就诊率GIS分布图。结果共采集3776个居民居住的全球定位系统(GPS)定位点,人群发热就诊率为1.11‰,发热就诊人次占总门诊人次的16.3%,监测区内的发热就诊病人占所有发热就诊病人的83.5%。在3种类型的医疗机构中,门诊量以个体门诊类最多,但其发热就诊人次占总门诊人次的比率最低(12.6%)。监测区内发热1d或以上的病人地址和身份(ADDRESS-ID)确认率达到95%。根据居民点年发热就诊率GIS分布图,发热就诊率最高的居民点达到17.81‰,最低为0;发热就诊率高的居民点多集中在城市。结论利用GIS技术可直观准确的了解疾病流行率的分布,可迅速直观的寻找出监测系统中的薄弱环节和推断出可能存在的问题。 | 杨进 董柏青 张杰 廖和壮 梁大斌 吴兴华 司国爱 杨宏徽 Jin Kyung Park R Leon Ochiai Camilo J Acosta Moharmmad Ali John D Clemens | 2007 | 中国公共卫生2007，23，9： | 8 |
| 5 | 导致儿童期肥胖的生命早期危险因素:队列研究显示文摘目的确定早年(3岁以内)导致英国儿童肥胖的危险因素。设计前瞻性队列研究。方法Avon英国父母及儿童纵向调查研究。参与者参与队列研究的8234名年龄为7岁的儿童以及亚组的909名重点儿童,后者需额外提供与早期发育有关并涉及可能导致肥胖的各种资料。诊断标准7岁儿童体重指数≥95百分位确定为肥胖,参考1990年英国人口调查的诊断标准。结果经过最终验证,在假设的25项危险因素中有8项与肥胖有关:父母肥胖(父母双方校正后的相对危险度10.44,95%可信区间5.11~21.32);最早期(43个月内)的体重指数或体重反弹升高(校正后的相对危险度15.00,95%可信区间5.32~42.30);3岁时每周看电视的时间超过8小时(校正后的相对危险度1.55,95%可信区间1.13~2.12);追赶性生长(校正后的相对危险度2.60,95%可信区间1.09~6.16);8个月(校正后的相对危险度3.13,95%可信区间1.43~6.85)和18个月(校正后的相对危险度2.65,95%可信区间1.25~5.59)时体重的标准差值;1岁时体重增加值(校正后的相对危险度1.06,95%可信区间1.02~1.10,体重每增加100g);出生体重,每100g(校正后的相对危险度1.05,95%可信区间1.03~1.07);3岁时睡眠不足(<10.5小时,校正后的相对危险度1.45,95%可信区间1.10~1.89)。结论儿童期肥胖可能与8项危险因素有关。 | John J Reilly Julie Amstrong Ahmad R Dorosty Pauline M Emmett A Ness I Rogers Colin Steer Andrea Sherriff Children Study Team 冯凯 | 2005 | 英国医学杂志中文版2005，8，5： | 8 |
| 6 | Dietary advanced glycation end-products aggravate non-alcoholic fatty liver disease显示文摘AIM To determine if manipulation of dietary advanced glycation end product(AGE), intake affects nonalcoholic fatty liver disease(NAFLD) progression and whether these effects are mediated via RAGE. METHODS Male C57Bl6 mice were fed a high fat, high fructose, high cholesterol(HFHC) diet for 33 wk and compared with animals on normal chow. A third group were given a HFHC diet that was high in AGEs. Another group was given a HFHC diet that was marinated in vinegar to prevent the formation of AGEs. In a second experiment, RAGE KO animals were fed a HFHC diet or a high AGE HFHC diet and compared with wildtype controls. Hepatic biochemistry, histology, picrosirius red morphometry and hepatic mR NA were determined. RESULTS Long-term consumption of the HFHC diet generated significant steatohepatitis and fibrosis after 33 wk. In this model, hepatic 4-hydroxynonenal content(a marker of chronic oxidative stress), hepatocyte ballooning, picrosirius red staining, α-smooth muscle actin and collagen type 1A gene expression were all significantly increased. Increasing the AGE content of the HFHC diet by baking further increased these markers of liver damage, but this was abrogated by pre-marination in acetic acid. In response to the HFHC diet, RAGE-/-animals developed NASH of similar severity to RAGE+/+ animals but were protected from the additional harmful effects of the high AGE containing diet. Studies in isolated Kupffer cells showed that AGEs increase cell proliferation and oxidative stress, providing a likely mechanism through which these compounds contribute to liver injury. CONCLUSION In the HFHC model of NAFLD, manipulation of dietary AGEs modulates liver injury, inflammation, and liver fibrosis via a RAGE dependent pathway. This suggests that pharmacological and dietary strategies targeting the AGE/RAGE pathway could slow the progression of NAFLD. | Christopher Leung Chandana B Herath Zhiyuan Jia Sof Andrikopoulos Bronwyn E Brown Michael J Davies Leni R Rivera John B Furness Josephine M Forbes Peter W Angus | 2016 | World Journal of Gastroenterology2016，22，35： | 7 |
| 7 | Highly efficient derivation of ventricular cardiomyocytes from induced pluripotent stem cells with a distinct epigenetic signature显示文摘从 pluripotent 干细胞导出的 Cardiomyocytes 能在药测试,疾病建模和基于房间的治疗被使用。没有 procardiogenic 生长因素,然而,从 pluripotent 干细胞的 cardiomyogenesis 的效率通常是低的,产生 cardiomyocyte 人口是异构的。这里,我们证明导致的 pluripotent 干细胞( iPSCs )能从鼠科的室的 myocytes ( VM )被导出,并且与从各种各样的体的房间类型导出的 iPSCs 的另外的报告一致,自发地作为与遗传上匹配的胚胎的干细胞(转换字符)或 iPSCs 相比区分 cardiomyocytes 进跳动的显著地更高的倾向从尾巴尖端成纤维细胞导出的 导出VM 的 iPSCs ( ViPSCs )展览。惊人地,导出 ViPSC 的 cardiomyocytes 显示的多数室的显型。在 ViPSCs 的提高的室的 myogenesis 在区别的早阶段经由心血管的祖先的增加的数字被调停。以便从 ViPSCs 调查提高的室的 myogenesis 的机制,我们执行了全球基因表示和 DNA methylation 分析,它揭示了可以涉及在 pluripotent 干细胞指定 VM 命运的不同 epigenetic 签名。 | Huansheng Xu B Alexander Yi Hao Wu Christoph Bock Hongcang Gu Kathy O Lui Joo-Hye C Park Ying Shao Alyssa K Riley Ibrahim J Domian Erding Hu Robert Willette John Lepore Alexander Meissner Zhong Wang Kenneth R Chien | 2012 | Cell Research2012，22，1： | 7 |
| 8 | Factors predicting adverse short-term outcomes in patients with acute cholangitis undergoing ERCP: A single center experience显示文摘AIM: To identify potential factors that can predict adverse short-term outcomes in patients with acute cholangitis undergoing endoscopic retrograde cholangiopancreatography(ERCP). METHODS: Retrospective analysis of consecutive patients admitted to our center for acute cholangitis and underwent ERCP from 2001 to 2012. Involvement of two or more organ systems was termed as organ failure(OF). Cardiovascular failure was defined based on a systolic blood pressure of < 90 mmHg despite fluid replacement and/or requiring vasopressor treatment; respiratory failure if the Pa02 /Fi02 ratio was < 300 mmHg and/or required mechanical ventilation; coagulopathy if the platelet count was < 80; and renal insufficiency if serum creatinine was > 1.9 mg/dL. Variables associated with short term adverse clinical outcomes defined as persistent OF and/or 30-d mortality was determined. RESULTS: A total of 172 patients(median age 62 years, 56.4% female) were included. The median door to ERCP time was 17 h. Bile duct stones were the most common etiology(n = 67, 39.2%). In multivariate analysis, factors that were independently associated with persistent OF and/or 30-d mortality included American Society of Anesthesiology(ASA) physical classification score > 3(OR = 7.70; 95%CI: 2.73-24.40), presence of systemic inflammatory response syndrome(OR = 3.67; 95%CI: 1.34-10.3) and door to ERCP time greater than 72 h(OR = 3.36; 95%CI: 1.12-10.20). Door to ERCP time greater than 72 h was also associated with 70% increase in the mean length of stay(P < 0.001). Every one point increase in the ASA physical classification and every 1 mg/dL increase in the preERCP bilirubin level was associated with a 34% and 2% increase in the mean length of hospital stay, respectively. Transfer status did not impact clinical outcomes. CONCLUSION: Higher ASA physical classification and delays in ERCP are associated with adverse clinical outcomes and prolonged length of hospital stay in patients with acute cholangitis undergoing ERCP. | Udayakumar Navaneethan Norma G Gutierrez Ramprasad Jegadeesan Preethi GK Venkatesh Madhusudhan R Sanaka John J Vargo Mansour A Parsi | 2014 | World Journal of Gastrointestinal Endoscopy2014，6，3： | 7 |
| 9 | Clinical outcomes following salvage Gamma Knife radiosurgery for recurrent glioblastoma显示文摘Glioblastoma multiforme(GBM) is the most common malignant primary brain tumor with a survival prognosis of 14-16 mo for the highest functioning patients. Despite aggressive, multimodal upfront therapies, the majority of GBMs will recur in approximately six months. Salvage therapy options for recurrent GBM(r GBM) are an area of intense research. This study compares recent survival and quality of life outcomes following Gamma Knife radiosurgery(GKRS) salvage therapy. Following a Pub Med search for studies usingGKRS as salvage therapy for malignant gliomas, nine articles from 2005 to July 2013 were identified which evaluated rG BM treatment. In this review, we compare overall survival following diagnosis, overall survival following salvage treatment, progression-free survival, time to recurrence, local tumor control, and adverse radiation effects. This report discusses results for rG BM patient populations alone, not for mixed populations with other tumor histology grades. All nine studies reported median overall survival rates(from diagnosis, range:16.7-33.2 mo; from salvage, range:9-17.9 mo). Three studies identified median progression-free survival(range:4.6-14.9 mo). Two showed median time to recurrence of GBM. Two discussed local tumor control. Six studies reported adverse radiation effects(range:0%-46% of patients). The greatest survival advantages were seen in patients who received GKRS salvage along with other treatments, like resection or bevacizumab, suggesting that appropriately tailored multimodal therapy should be considered with each rG BM patient. However, there needs to be a randomized clinical trial to test GKRS for rG BM before the possibility of selection bias can be dismissed. | Erik W Larson Halloran E Peterson Wayne T Lamoreaux Alexander R MacKay Robert K Fairbanks Jason A Call Jonathan D Carlson Benjamin C Ling John J Demakas Barton S Cooke Christopher M Lee | 2014 | World Journal of Clinical Oncology2014，5，2： | 5 |
| 10 | Genetic association and epistatic interaction of the interleukin-10 signaling pathway in pediatric inflammatory bowel disease显示文摘AIM To study the genetic association and epistatic interaction of the interleukin(IL)-10 and IL-10/STAT3 pathways in pediatric inflammatory bowel disease(IBD). METHODS A total of 159 pediatric inflammatory IBD patients(Crohn's disease,n = 136; ulcerative colitis,n = 23) and 129 matched controls were studied for genetic association of selected single nucleotide polymorphisms(SNPs) of the IL-10 gene and the genes IL10 RA,IL10 RB,STAT3,and HO1,from the IL-10/STAT3 signaling pathway. As interactions between SNPs from different loci may significantly affect the associated risk for disease,additive(a) and dominant(d) modeling of SNP interactions was also performed to examine highorder epistasis between combinations of the individual SNPs. RESULTS The results showed that IL-10 rs304496 was associated with pediatric IBD(P = 0.022),but no association was found for two other IL-10 SNPs,rs1800872 and rs2034498,or for SNPs in genes IL10 RA,IL10 RB,STAT3,and HO1. However,analysis of epistatic interaction among these genes showed significant interactions:(1) between two IL-10 SNPs rs1800872 and rs3024496(additive-additive P = 0.00015,Bonferroni P value(Bp) = 0.003);(2) between IL-10 RB rs2834167 and HO1 rs2071746(dominant-additive,P = 0.0018,Bp = 0.039); and(3) among IL-10 rs1800872,IL10 RB rs2834167,and HO1 rs2071746(additivedominant-additive,P = 0.00015,Bp = 0.005),as well as weak interactions among IL-10 rs1800872,IL-10 rs3024496,and IL-10RA(additive-additive-additive,P = 0.003; Bp = 0.099),and among IL10 RA,IL10 RB,and HO1 genes(additive-dominant-additive,P = 0.008,Bp = 0.287).CONCLUSION These results indicate that both the IL-10 gene itself,and through epistatic interaction with genes within the IL-10/STAT3 signaling pathway,contribute to the risk of pediatric IBD. | Zhenwu Lin Zhong Wang John P Hegarty Tony R Lin Yunhua Wang Sue Deiling Rongling Wu Neal J Thomas Joanna Floros | 2017 | World Journal of Gastroenterology2017，23，27： | 5 |
| 11 | Hypothetical model of dynamic biomarkers of the Alzheimer’s pathological cascade显示文摘 | Clifford R Jack David S Knopman William J Jagust Leslie M Shaw Paul S Aisen Michael W Weiner Ronald C Petersen John Q Trojanowski | 2010 | Lancet Neurology2010，，1： | 4 |
| 12 | Failure of P-selectin blockade alone to protect the liver from ischemia-reperfusion injury in the isolated blood-perfused rat liver显示文摘AIM:To determine if blockade of P-selectin in the isolated blood-perfused cold ex vivo rat liver model protects the liver from ischemia-reperfusion injury. METHODS:The effect of P-selectin blockade was assessed by employing an isolated blood-perfused cold ex vivo rat liver with or without P-selectin antibody treatment before and after 6 h of cold storage in University of Wisconsin solution. RESULTS:In our isolated blood-perfused rat liver model,pre-treatment with P-selectin antibody failed to protect the liver from ischemia-reperfusion injury,as judged by the elevated aspartate aminotransferase activity. In addition,P-selectin antibody treatment did not significantly reduced hepatic polymorphonuclear leukocyte accumulation after 120 min of perfusion. Histological evaluation of liver sections obtained at 120 min of perfusion showed significant oncotic necrosis in liver sections of both ischemic control and P-selectin antibody-treated groups. However,total bile production after 120 min of perfusion was signifi cantly greater in P-selectin antibody-treated livers,compared to control livers. No signifi cant difference in P-selectin and ICAM-1 mRNAs and proteins,GSH,GSSG,and nuclear NF-κB was found between control and P-selectin antibody-treated livers. CONCLUSION:In conclusion,we have shown that blockade of P-selectin alone failed to reduced polymorphonuclear leukocyte accumulation in the liver and protect hepatocytes from ischemia-reperfusion injury in the isolated blood-perfused cold-ex vivo rat liver model. | Samuel Wyllie Neal R Barshes Saul J Karpen John A Goss | 2008 | World Journal of Gastroenterology2008，14，44： | 4 |
| 13 | Differential response of tomato genotypes to Xanthomonas-specific pathogen-associated molecular patterns and correlation with bacterial spot (Xanthomonas perforans) resistance显示文摘Plants depend on innate immune responses to retard the initial spread of pathogens entering through stomata,hydathodes or injuries.These responses are triggered by conserved patterns in pathogen-encoded molecules known as pathogen-associated molecular patterns(PAMPs).Production of reactive oxygen species(ROS)is one of the first responses,and the resulting‘oxidative burst’is considered to be a first line of defense.In this study,we conducted association analyses between ROS production and bacterial spot(BS;Xanthomonas spp.)resistance in 63 genotypes of tomato(Solanum lycopersicum L.).A luminol-based assay was performed on leaf tissues that had been treated with a flagellin 22(flg22),flagellin 28 and a Xanthomonas-specific flg22(flg22-Xac)peptide,to measure PAMP-induced ROS production in each genotype.These genotypes were also assessed for BS disease response by inoculation with Xanthomonas perforans,race T4.Although there was no consistent relationship between peptides used and host response to the BS,there was a significant negative correlation(r=−0.25,P<0.05)between foliar disease severity and ROS production,when flg22-Xac was used.This response could potentially be used to identify the Xanthomonas-specific PRR allele in tomato,and eventually PAMP-triggered immunity loci could be mapped in a segregating population.This has potential significance in tomato improvement. | Krishna Bhattarai Frank J Louws John D Williamson Dilip R Panthee | 2016 | Horticulture Research2016，3，1： | 3 |
| 14 | Evidence for the involvement of NOD2 in regulating colonic epithelial cell growth and survival显示文摘AIM: To investigate the function of NOD2 in colonic epithelial cells (CEC). METHODS: A combination of in vivo and in vitro analyses of epithelial cell turnover in the presence and absence of a functional NOD2 protein and, in response to enteric Salmonella typhimurium infection, were used. shRNA interference was also used to investigate the consequences of knocking down NOD2 gene expression on the growth and survival of colorectal carcinoma cell lines. RESULTS:In the colonic mucosa the highest levels of NOD2 expression were in proliferating crypt epithelial cells. Muramyl dipeptide (MDP), that is recognized by NOD2, promoted CEC growth in vitro . By contrast,the growth of NOD2-deficient CECs was impaired. In vivo CEC proliferation was also reduced and apoptosis increased in Nod2-/- mice, which were also evident following enteric Salmonella infection. Furthermore, neutralization of NOD2 mRNA expression in human colonic carcinoma cells by shRNA interference resulted in decreased survival due to increased levels of apoptosis. CONCLUSION: These findings are consistent with the involvement of NOD2 protein in promoting CEC growth and survival. Defects in proliferation by CECs in cases of CD may contribute to the underlying pathology of disrupted intestinal homeostasis and excessive inflammation. | Sheena M Cruickshank Louise Wakenshaw John Cardone Peter D Howdle Peter J Murray Simon R Carding | 2008 | World Journal of Gastroenterology2008，14，38： | 3 |
| 15 | Efficacy of boceprevir, an NS3 protease inhibitor, in combination with peginterferon alfa-2b and ribavirin in treatment-naive patients with genotype 1 hepatitis C infection (SPRINT-1): an open-label, randomised, multicentre phase 2 trial显示文摘 | Paul Y Kwo Eric J Lawitz Jonathan McCone Eugene R Schiff John M Vierling David Pound Mitchell N Davis Joseph S Galati Stuart C Gordon Natarajan Ravendhran Lorenzo Rossaro Frank H Anderson Ira M Jacobson Raymond Rubin Kenneth Koury Lisa D Pedicone Clifford | 2010 | The Lancet2010，，9742： | 3 |
| 16 | Immune checkpoint inhibitor-mediated colitis in gastrointestinal malignancies and inflammatory bowel disease显示文摘Immune checkpoint inhibitors(ICI)have markedly changed the landscape of cancer therapy.By re-invigorating the immune system against tumors,ICI provide novel therapeutic options for a broad variety of malignancies,including many gastrointestinal(GI)cancers.However,these therapies can also induce autoimmune-like side effects in healthy tissue across the body.One of the most common of these side effects is ICI-mediated colitis and diarrhea(IMC).Here,we review the incidence and risk of IMC in ICI therapy,with a focus on what is known regarding IMC in patients with GI malignancies.We also discuss data available on the use of ICI and risk of IMC in patients with pre-existing inflammatory bowel disease,as these patients may have increased risk of IMC due to their underlying intestinal pathology. | Alexa R Weingarden Samuel J S Rubin John Gubatan | 2021 | World Journal of Gastrointestinal Oncology2021，13，8： | 3 |
| 17 | Hyperspectral vegetation indices and novel algorithms for predicting green LAI of crop canopies: Modeling and validation in the context of precision agriculture显示文摘 | Driss Haboudane John R Miller Elizabeth Pattey Pablo J Zarco-Tejada Ian B Strachan | 2004 | Remote Sensing of Environment2004，，3： | 3 |
| 18 | Reinterpretation of histology of proximal colon polyps called hyperplastic in 2001显示文摘AIM: To evaluate how proximal colon polyps interpreted as hyperplastic polyps in 2001 would be interpreted by expert pathologists in 2007. METHODS: Forty consecutive proximal colon polyps ≥ 5 mm in size, removed in 2001, and originally interpreted as hyperplastic polyps by general pathologists at Indiana University, were reviewed in 2007 by 3 GI pathologists. RESULTS: The gastrointestinal (GI) pathologists interpreted 85%, 43% and 30% of the polyps as sessile serrated polyps (sessile serrated adenomas). The overall Kappa was 0.16. When diagnoses were compared in pairs, Kappa values were 0.38 and 0.25 (fair agreement) and 0.14 (slight agreement). CONCLUSION: Many polyps interpreted as hyperplastic in 2001 were considered sessile serrated lesions by GI pathologists in 2007, but there is substantial inter-observer variation amongst GI pathologists. | Omer Khalid Sofyan Radaideh Oscar W Cummings Michael J O'Brien John R Goldblum Douglas K Rex | 2009 | World Journal of Gastroenterology2009，15，30： | 3 |
| 19 | Antimicrobial peptides and the gut microbiome in inflammatory bowel disease显示文摘Antimicrobial peptides(AMP)are highly diverse and dynamic molecules that are expressed by specific intestinal epithelial cells,Paneth cells,as well as immune cells in the gastrointestinal(GI)tract.They play critical roles in maintaining tolerance to gut microbiota and protecting against enteric infections.Given that disruptions in tolerance to commensal microbiota and loss of barrier function play major roles in the pathogenesis of inflammatory bowel disease(IBD)and converge on the function of AMP,the significance of AMP as potential biomarkers and novel therapeutic targets in IBD have been increasingly recognized in recent years.In this frontier article,we discuss the function and mechanisms of AMP in the GI tract,examine the interaction of AMP with the gut microbiome,explore the role of AMP in the pathogenesis of IBD,and review translational applications of AMP in patients with IBD. | John Gubatan Derek R Holman Christopher J Puntasecca Danielle Polevoi Samuel JS Rubin Stephan Rogalla | 2021 | World Journal of Gastroenterology2021，27，43： | 3 |
| 20 | Reproducibility of the diagnosis of dysplasia in Barrett esophagus: A reaffirmation显示文摘 | Elizabeth Montgomery Mary P Bronner John R Goldblum Joel K Greenson Marian M Haber John Hart Laura W Lamps Gregory Y Lauwers Audrey J Lazenby David N Lewin Marie E Robert Alicia Y Toledano Yu Shyr Kay Washington | 2001 | Human Pathology2001，，4： | 3 |
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