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| 1 | Non-alcoholic fatty liver disease and the metabolic syndrome:An update显示文摘Sedentary lifestyle and poor dietary choices are leading to a weight gain epidemic in westernized countries, subsequently increasing the risk for developing the metabolic syndrome and nonalcoholic fatty liver disease (NAFLD). NAFLD is estimated to affect approximate 30% of the general US population and is considered the hepatic manifestation of the metabolic syndrome. Recent findings linking the components of the metabolic syndrome with NAFLD and the progression to nonalcoholic steatohepatitis (NASH) will be reviewed; in particular, the role of visceral adipose tissue, insulin resistance, and adipocytokines in the exacerbation of these conditions. While no therapy has been proven effective for treating NAFLD/NASH, common recommendations will be discussed. | R Scott Rector John P Thyfault Yongzhong Wei Jamal A Ibdah | 2008 | World Journal of Gastroenterology2008，14，2： | 60 |
| 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 | Current oncologic applications of radiofrequency ablation therapies显示文摘Radiofrequency ablation (RFA) uses high frequency alternating current to heat a volume of tissue around a needle electrode to induce focal coagulative necrosis with minimal injury to surrounding tissues. RFA can be performed via an open, laparoscopic, or image guided percutaneous approach and be performed under general or local anesthesia. Advances in delivery mechanisms, electrode designs, and higher power generators have increased the maximum volume that can be ablated, while maximizing oncological outcomes. In general, RFA is used to control local tumor growth, prevent recurrence, palliate symptoms, and improve survival in a subset of patients that are not candidates for surgical resection. It's equivalence to surgical resection has yet to be proven in large randomized control trials. Currently, the use of RFA has been well described as a primary or adjuvant treatment modality of limited but unresectable hepatocellular carcinoma, liver metastasis, especially colorectal cancer metastases, primary lung tumors, renal cell carcinoma, boney metastasis and osteoid osteomas. The role of RFA in the primary treatment of early stage breast cancer is still evolving. This review will discuss the general features of RFA and outline its role in commonly encountered solid tumors. | Dhruvil R Shah Sari Green Angelina Elliot John P McGahan Vijay P Khatri | 2013 | World Journal of Gastrointestinal Oncology2013，5，4： | 33 |
| 4 | Nonalcoholic fatty liver disease and mitochondrial dysfunction显示文摘Nonalcoholic fatty liver disease (NAFLD) includes hepatic steatosis, nonalcoholic steatohepatitis (NASH), fibrosis, and cirrhosis. NAFLD is the most common liver disorder in the United States and worldwide. Due to the rapid rise of the metabolic syndrome, the prevalence of NAFLD has recently dramatically increased and will continue to increase. NAFLD has also the potential to progress to hepatocellular carcinoma (HCC) or liver failure. NAFLD is strongly linked to caloric overconsumption, physical inactivity, insulin resistance and genetic factors. Although significant progress in understanding the pathogenesis of NAFLD has been achieved in years, the primary metabolic abnormalities leading to lipid accumulation within hepatocytes has remained poorly understood. Mitochondria are critical metabolic organelles serving as 'cellular power plants'. Accumulating evidence indicate that hepatic mitochondrial dysfunction is crucial to the pathogenesis of NAFLD. This review is focused on the significant role of mitochondria in the development of NAFLD. | Yongzhong Wei R Scott Rector John P Thyfault Jamal A Ibdah | 2008 | World Journal of Gastroenterology2008，14，2： | 32 |
| 5 | Is cardiac resynchronisation therapy feasible, safe and beneficial in the very elderly?显示文摘ObjectiveTo evaluate 心脏的同一时刻治疗(CRT ) 培植是否与经历 CRT 培植的 symptoms.MethodsConsecutive 病人一起在 octogenarians 和协会可行、安全,从二个英国中心被招募。根据年龄组织的病人:<80 &≥80 年。基线人口分布,复杂并发症和结果在 439 个病人的那些 groups.ResultsA 总数之间被比较在这研究, 26%≥ 是谁被包括;80 年。Octogenarians 更经常与心脏的同一时刻治疗使用高压脉冲来消减心脏相比收到了心脏的再同步治疗心律调整器。从心律调整器的升级在两个组是普通的(16%<80 年对 22%≥80 年, P = NS ) 。合作病态在两个组是同样普通的(全面糖尿病:25% , atrial 纤维性颤动:23% ,高血压:45%) 。更耐心的年龄 ≥80 年有重要的长期的肾疾病(CKD,估计的 glomerular 过滤率 <45 mL/min 每 1.73 m 2,44% 对 22% , P <0.01 ) 。全面复杂并发症率(任何东西) 在两个组是类似的(16% 对 17% , P = NS ) 。两个组表明了征兆的利益。一个年死亡率作为与更年轻的队相比是在 octogenarians 更大的几乎四褶层(13.9% 对 3.7% , P <0.01 ).ConclusionsCRT 看起来安全在尽管有广泛的合作病态老、特别地经常严重 CKD。征兆的改进看起来有意义。增加的策略是 CRT 的潜在的候选人的有 CHF 的老病人的适当鉴定被要求。 | Bartosz Olechowski Rebecca Sands Donah Zachariah Neil P Andrews Richard Balasubramaniam Mark Sopher John Paisey Paul R Kalra | 2015 | Journal of Geriatric Cardiology2015，12，5： | 5 |
| 6 | 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 |
| 7 | FibroSURE^(TM) and FibroScan~ in relation to treatment response in chronic hepatitis C virus显示文摘AIM:To compare histological endpoint assessment using noninvasive alternatives to biopsy during treatment in a chronic hepatitis C virus(HCV)cohort.METHODS:Patients with chronic HCV were randomized to receive interferon-based therapy for 24(genotypes 2/3)or 48(genotype 1)wk.FibroSURE~TM(FS)was assessed at baseline and at week-12 post-treatment follow-up.Baseline biopsy for METAVIR was assessed by a single pathologist.FibroScan~ transient elastogra-phy(TE)was performed during treatment in a patient subset.RESULTS:Two thousand and sixty patients(n = 253 in Asia)were classif ied as METAVIR F0-1(n = 1682)or F2-4(n = 378).For F2-4,FS(n = 2055)had sensitiv-ity and specif icity of 0.87 and 0.61,respectively,with area under the receiver-operating curve of 0.82;corre-sponding values for TE(n = 214)and combined FS/TE(n = 209)were 0.77,0.88 and 0.88,and 0.93,0.68 and 0.88.Overall FS/TE agreement for F2-4 was 71%(κ = 0.41)and higher in Asians vs non-Asians(κ = 0.86 vs 0.35;P < 0.001).Combined FS/TE had 97% accuracy in Asians(n = 33).Baseline FS(0.38 vs 0.51,P < 0.001)and TE(8.0 kPa vs 11.9 kPa,P = 0.006)scores were lower in patients with sustained virological response than in nonresponders,and were maintained through follow-up.CONCLUSION:FS and TE may reliably differentiate mild from moderate-advanced disease,with a potential for high diagnostic accuracy in Asians with chronic HCV. | Keyur Patel Mireen Friedrich-Rust Yoav Lurie Mircea Grigorescu Carol Stanciu Chuan-Mo Lee Eugene R Schiff Dieter Hussinger Michael P Manns Guido Gerken Isabelle Colle Michael Torbenson Erik Pulkstenis G Mani Subramanian John G McHutchison Stefan Zeuzem | 2011 | World Journal of Gastroenterology2011，17，41： | 4 |
| 8 | Th1 cytokines promote T-cell binding to antigen-presenting cells via enhanced hyaluronan production and accumulation at the immune synapse显示文摘Hyaluronan(HA)production by dendritic cells(DCs)is known to promote antigen presentation and to augment T-cell activation and proliferation.We hypothesized that pericellular HA can function as intercellular‘glue’directly mediating T cell–DC binding.Using primary human cells,we observed HA-dependent binding between T cells and DCs,which was abrogated upon pre-treatment of the DCs with 4-methylumbelliferone(4-MU),an agent which blocks HA synthesis.Furthermore,T cells regulate HA production by DCs via T cell-derived cytokines in a T helper(Th)subset-specific manner,as demonstrated by the observation that cell-culture supernatants from Th1 but not Th2 clones promote HA production.Similar effects were seen upon the addition of exogenous Th1 cytokines,IL-2,interferon c(IFN-c)and tumor necrosis factor a(TNF-a).The critical factors which determined the extent of DC–T cell binding in this system were the nature of the pre-treatment the DCs received and their capacity to synthesize HA,as T-cell clones which were pre-treated with monensin,added to block cytokine secretion,bound equivalently irrespective of their Th subset.These data support the existence of a feedforward loop wherein T-cell cytokines influence DC production of HA,which in turn affects the extent of DC–T cell binding.We also document the presence of focal deposits of HA at the immune synapse between T-cells and APC and on dendritic processes thought to be important in antigen presentation.These data point to a pivotal role for HA in DC–T cell interactions at the IS. | Paul L Bollyky Stephen P Evanko Rebecca P Wu Susan Potter-Perigo S Alice Long Brian Kinsella Helena Reijonen Kelly Guebtner Brandon Teng Christina K Chan Kathy R Braun John A Gebe Gerald T Nepom Thomas N Wight | 2010 | Cellular & Molecular Immunology2010，7，3： | 3 |
| 9 | 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 |
| 10 | Impact of androgen deprivation therapy on sexua function显示文摘有雄激素剥夺治疗(ADT ) 为被显示的前列腺癌症的许多病人是年轻的并且需要仍然保持性活跃。在如此的病人,性功能上的雄激素治疗的副作用能是在生活的全面质量的严肃的减小的来源。在这张耐心的人口提供适当治疗选择因此是必要的。不过,对待如此的病人是挑战性的,性生理学和 pathophysiology 的内在的机制的理解对最佳的耐心的照顾关键。在这份报纸,我们考察了什么在动物模型在性功能上关于 ADT 的效果被知道,我们也在人和它的治疗在性健康上在 ADT 的效果上提供了详细评论。 | Clarisse R Mazzola John P Mulhall | 2012 | Asian Journal of Andrology2012，14，2： | 3 |
| 11 | Treating to New Targets (TNT) Study: does lowering low-density lipoprotein cholesterol levels below currently recommended guidelines yield incremental clinical benefit?显示文摘 | David D Waters John R Guyton David M Herrington Mary P McGowan Nanette K Wenger Charles Shear | 2004 | The American Journal of Cardiology2004，，2： | 2 |
| 12 | Risk for esophageal neoplasia in B arrett’s esophagus patients with mucosal changes indefinite for dysplasia显示文摘 | Bela Horvath Prabhdeep Singh Hao Xie Prashanthi N Thota Daniela S Allende Rish K Pai Deepa T Patil Thomas P Plesec John R Goldblum Xiuli Liu | 2015 | J Gastroenterol Hepatol2015，，： | 2 |
| 13 | Assessment of erosion haz- ard with the USLE and GIS A ease study of the Upper Ewaso Nglro North basin of Kenya显示文摘 | Bancy M Mati Royston P C Morgan Francis N Gichuki John N Quinton Tim R Brewer Hans P l iniger | 2000 | lnternation Journal of Applied Earth Ob- servation and Geoinformation2000，2，2： | 1 |
| 14 | Relationship of superficial scald development and ct-Farnesene oxidation to re- actions of diphenylamine and diphenylamine derivatives in CV, Granny Smith apple peel 显示文摘 | David R R James P M John K F | 2005 | J Agric Food Chem2005，，53： | 1 |
| 15 | Analysis of joint action of insecticides against housefly显示文摘 | Sun Y P John E R | 1960 | Journal of Economic Entomology1960，53，5： | 1 |
| 16 | No Significant Association of 14 Candidate Genes With Schizophrenia in a Large European Ancestry Sample: Implications for Psychiatric Genetics显示文摘 | Sanders Alan R Duan Jubao Levinson Douglas F Shi Jianxin He Deli Hou Cuiping Burrell Gregory J Rice John P Nertney Deborah A Olincy Ann Rozic Pablo Vinogradov Sophia Buccola Nancy G Mowry Bryan J Freedman Robert Amin Farooq Black Donald W | 2008 | The American Journal of Psychiatry2008，，4： | 1 |
| 17 | Adaptation of HIV-1to human leukocyte antigen class I显示文摘 | Kawashima Y Pfafferott K Frater J Matthews P Payne R Addo M Gatanaga H Fujiwara M Hachiya A Koizumi H Kuse N Oka S Duda A Prendergast A Crawford H Leslie A Brumme Z Brumme C Allen T Brander C Kaslow R Tang J Hunter E Allen S Mulenga J Branch S Roach T John M Mallal S Ogwu A Shapiro R Prado J G Fidler S Weber J Pybus O G Klenerman P Ndung'u T Phillips R Heckerman D Harrigan P R Walker B D Takiguchi M Goulder P | 2009 | Nature2009，458，7238： | 1 |
| 18 | Effects of nitrogen and phosphorus on blue grama growth and mycorrhizal infection 显示文摘 | Hays R Reid C C P John T V St Coleman D C | 1982 | Oecologia1982，54，： | 1 |
| 19 | Uncertainty quantification using evidence theory in multidisciplinary design optimization 显示文摘 | Harish A John E R Evan L P | 2004 | Reliability Engineering and System Safety2004，85，13： | 1 |
| 20 | Increase in tropospheric nitrogen dioxide over China observed from space显示文摘 | Andreas R John P B Hendrik N | 2005 | Nature2005，437，： | 1 |
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