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| 1 | 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 |
| 2 | Visceral hypersensitivity and electromechanical dysfunction as therapeutic targets in pediatric functional dyspepsia显示文摘Functional gastrointestinal disorders(FGID) are common clinical syndromes diagnosed in the absence of biochemical,structural,or metabolic abnormalities. They account for significant morbidity and health care expenditures and are identifiable across variable age,geography,and culture. Etiology of abdominal pain associated FGIDs,including functional dyspepsia(FD),remains incompletely understood,but growing evidence implicates the importance of visceral hypersensitivity and electromechanical dysfunction. This manuscript explores data supporting the role of visceral hypersensitivity and electromechanical dysfunction in FD,with focus on pediatric data when available,and provides a summary of potential therapeutic targets. | John M Rosen Jose T Cocjin Jennifer V Schurman Jennifer M Colombo Craig A Friesen | 2014 | World Journal of Gastrointestinal Pharmacology and Therapeutics2014，5，3： | 16 |
| 3 | Bemisia tabaci Phylogenetic Groups in India and the Relative Transmission Efficacy of Tomato leaf curl Bangalore virus by an Indigenous and an Exotic Population显示文摘Bemisia tabaci adults from various host-plant species were collected from 31 regions across India.266 B.tabaci samples were first screened by RAPD-PCR to examine molecular variability and to select individuals with different fingerprints.Host-plant and region of collection were then used to select 25 individuals for PCR amplification and sequencing of their partial mitochondrial cytochrome oxidase subunit one(mtCOI)genes.Pairwise comparisons with mtCOI consensus sequences showed that the majority of these samples had <3.5% sequence divergence from groups currently termed Asia I,Asia II-5,Asia II-7,and Asia II-8.The biotype-B B.tabaci from India clustered into the Middle East-Asia Minor 1 group.A new group of B.tabaci from Coimbatore,collected from pumpkin,was related most closely to the Asia I group(6.2% sequence divergence from the consensus Asia I sequence).To increase our understanding of the epidemiology of tomato leaf curl disease(ToLCD)and the key B.tabaci genetic groups involved in virus spread,the indigenous Asia I and the exotic biotype-B population from South India were used to carry out transmission experiments using Tomato leaf curl Bangalore virus(ToLCBV).The acquisition access periods(AAP),inoculation access periods(IAP),latent periods(LP),and ToLCBV transmission efficiencies of the two populations were compared and the biotype-B had the more efficient transmission characteristics.These results are discussed in relation to recent changes in the epidemiology of tomato leaf curl disease in South India. | R V Chowda-Reddy M Kirankumar Susan E Seal V Muniyappa Girish B Valand M R Govindappa John Colvin | 2012 | Journal of Integrative Agriculture2012，11，2： | 8 |
| 4 | Association between thyroid function and gallstone disease显示文摘AIM: To investigate those associations using data of the population-based Study of Health in Pomerania.METHODS: A study population of 3 749 residents aged 20-79 years without previously diagnosed thyroid disease was available for analyses. Serum TSH was used to assess thyroid function. Cholelithiasis was defined by either a prior history of cholecystectomy or the presence of gallstones on ultrasound. Logistic regression was performed to analyze independent associations between thyroid function and cholelithiasis.RESULTS: There were 385 persons (10.3%) with low (<0.3 mIU/L), 3 321 persons (88.6%) with normal and 43 persons (1.2%) with high serum TSH levels (>3 mIU/L).The proportion of cholelithiasis among males and females was 14.4% and 25.3%, respectively. Among males, there was an independent relation between high serum TSH and cholelithiasis (OR 3.77; 95%-CI 1.06-13.41; ,P<0.05). zAlso among males, there was a tendency towards an elevated risk of cholelithiasis in persons with low serum TSH (OR 1.40; 95%-CI 0.96-2.02; P = 0.07). In the female population, no such relation was identified.CONCLUSION: There is an association between thyroid and gallstone disease with a gender-specific relation between hypothyroidism and cholelithiasis. | Henry Vlzke Daniel M Robinson Ulrich John | 2005 | World Journal of Gastroenterology2005，11，35： | 8 |
| 5 | Sofosbuvir with pegylated interferon alfa-2a and ribavirin for treatment-naive patients with hepatitis C genotype-1 infection (ATOMIC): an open-label, randomised, multicentre phase 2 trial显示文摘 | Kris V Kowdley Eric Lawitz Israel Crespo Tarek Hassanein Mitchell N Davis Michael DeMicco David E Bernstein Nezam Afdhal John M Vierling Stuart C Gordon Jane K Anderson Robert H Hyland Hadas Dvory-Sobol Di An Robert G Hindes Efsevia Albanis William T Symo | 2013 | The Lancet2013，，9883： | 3 |
| 6 | Appropriateness of systemic treatments in unresectable metastatic well-differentiated pancreatic neuroendocrine tumors显示文摘AIM:To evaluate systemic treatment choices in unresectable metastatic well-differentiated pancreatic neuroendocrine tumors(PNETs)and provide consensus treatment recommendations.METHODS:Systemic treatment options for pancreatic neuroendocrine tumors have expanded in recent years to include somatostatin analogs,angiogenesis inhibitors,inhibitors of mammalian target of rapamycinand cytotoxic agents.At this time,there is little data to guide treatment selection and sequence.We therefore assembled a panel of expert physicians to evaluate systemic treatment choices and provide consensus treatment recommendations.Treatment appropriateness ratings were collected using the RAND/UCLA modified Delphi process.After studying the literature,a multidisciplinary panel of 10 physicians assessed the appropriateness of various medical treatment scenarios on a 1-9 scale.Ratings were done both before and after an extended discussion of the evidence.Quantitative measurements of agreement were made and consensus statements developed from the second round ratings.RESULTS:Specialties represented were medical and surgical oncology,interventional radiology,and gastroenterology.Panelists had practiced for a mean of15.5 years(range:6-33).Among 202 rated scenarios,disagreement decreased from 13.2%(26 scenarios)before the face-to-face discussion of evidence to 1%(2)after.In the final ratings,46.5%(94 scenarios)were rated inappropriate,21.8%(44)were uncertain,and30.7%(62)were appropriate.Consensus statements from the scenarios included:(1)it is appropriate to use somatostatin analogs as first line therapy in patients with hormonally functional tumors and may be appropriate in patients who are asymptomatic;(2)it is appropriate to use everolimus,sunitinib,or cytotoxic chemotherapy therapy as first line therapy in patients with symptomatic or progressive tumors;and(3)beyond first line,these same agents can be used.In patients with uncontrolled secretory symptoms,octreotide LAR doses can be titrated up to 60 mg every4 wk or up to 40 mg every 3 or 4 wk.CONCLUSION:Using the Delphi process allowed physician experts to systematically obtain a consensus on the appropriateness of a variety of medical therapies in patients with PNETs. | Jonathan R Strosberg George A Fisher Al B Benson Lowell B Anthony Bulent Arslan John F Gibbs Edward Greeno Renuka V Iyer Michelle K Kim William J Maples Philip A Philip Edward M Wolin Dasha Cherepanov Michael S Broder | 2015 | World Journal of Gastroenterology2015，21，8： | 2 |
| 7 | Survival after inflammatory bowel disease-associated colorectal cancer in the Colon Cancer Family Registry显示文摘AIM: To investigate the survival of individuals with colorectal cancer (CRC) with inflammatory bowel disease (IBD-associated CRC) compared to that of individuals without IBD diagnosed with CRC. METHODS: Epidemiologic, clinical, and follow-up data were obtained from the Colon Cancer Family Registry (Colon CFR). IBD-associated cases were identified from self-report of physician diagnosis. For a subset of participants, medical records were examined to confirm self-report of IBD. Cox proportional hazards regression was applied to estimate adjusted hazard ratios (aHR) and 95%CI of mortality, comparing IBD-associated to non-IBD-associated CRC, adjusted for age at CRC diagnosis, sex, Colon CFR phase, and number of prior endoscopies. Following imputation to complete CRC stage information, adjustment for CRC stage was examined. RESULTS: A total of 7202 CRC cases, including 250 cases of IBD-associated CRC, were analyzed. Over a twelve year follow-up period following CRC diagnosis, 2013 and 74 deaths occurred among non-IBD associated CRC and IBD-associated CRC patients, respectively. The difference in survival between IBD-associated and non-IBD CRC cases was not statistically significant (aHR = 1.08; 95%CI: 0.85-1.36). However, the assumption of proportional hazards necessary for valid inference from Cox regression was not met over the entire follow-up period, and we therefore limited analyses to within five years after CRC diagnosis when the assumption of proportional hazards was met. Over this period, there was evidence of worse prognosis for IBD-associated CRC (aHR = 1.36; 95%CI: 1.05-1.76). Results were similar when adjusted for CRC stage, or restricted to IBD confirmed in medical records. CONCLUSION: These results support the hypothesis that IBD-associated CRC has a worse prognosis than non-IBD-associated CRC. | Scott V Adams Dennis J Ahnen John A Baron Peter T Campbell Steven Gallinger William M Grady Loic LeMarchand Noralane M Lindor John D Potter Polly A Newcomb | 2013 | World Journal of Gastroenterology2013，19，21： | 2 |
| 8 | Personalising pancreas cancer treatment:When tissue is the issue显示文摘The treatment of advanced pancreatic cancer has not moved much beyond single agent gemcitabine until recently when protocols such as FOLFIRINOX(fluorouracil,leucovorin,irinotecan and oxaliplatin)and nab-paclitaxelgemcitabine have demonstrated some improved outcomes.Advances in technology especially in massively parallel genome sequencing has progressed our understanding of the biology of pancreatic cancer especially the candidate signalling pathways that are involved in tumourogenesis and disease course.This has allowed identification of potentially actionable mutations that may be targeted by new biological agents.The heterogeneity of pancreatic cancer makes tumour tissue collection important with the aim of being able to personalise therapies for the individual as opposed to a one size fits all approach to treatment of the condition.This paper reviews the developments in this area of translational research and the ongoing clinical studies that will attempt to move this into the everyday oncology practice. | Katrin M Sjoquist Venessa T Chin Lorraine A Chantrill Chelsie O'Connor Chris Hemmings David K Chang Angela Chou Marina Pajic Amber L Johns Adnan M Nagrial Andrew V Biankin Desmond Yip | 2014 | World Journal of Gastroenterology2014，20，24： | 2 |
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| 12 | Enhanced protective immune responses against Salmonella Enteritidis infection by Salmonella secreting an Escherichia coli heat-labile enterotoxin B subunit protein显示文摘 | Rahul M Nandre Chetan V Jawale John Hwa Lee | 2013 | Comparative Immunology Microbiology and Infectious Diseases2013，36，： | 1 |
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| 15 | Exploring the potential of fimctionally graded materials concept for the development of fiber cement显示文摘 | Dias C M R Savastano Jr H John V M | 2010 | Construction and Building Materials2010，24，： | 1 |
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| 17 | Prehabilitation Before Total Knee Arthroplasty Increases Strength and Function in Older Adults With Severe Osteo- arthritis 显示文摘 | Ann M Swank Joseph B Kachelman Wendy Bibeau Peter M Quesada John Nyland Arthur Malkani Robert V Topp | 2011 | Journal of Strength and Conditioning Re- search2011，2，2： | 1 |
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| 19 | Pore size distribution of hydrated cement pastes modified with polymers 显示文摘 | SILVA D A JOHN V M RIBEIRO J L D | 2001 | Cem Concr Res2001，31，8： | 1 |
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