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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 | Ellagic acid induces apoptosis through inhibition of nuclear factor κB in pancreatic cancer cells显示文摘AIM:To determine the effect of ellagic acid on apop-tosis and proliferation in pancreatic cancer cells and to determine the mechanism of the pro-survival effects of ellagic acid. METHODS:The effect of ellagic acid on apoptosis was assessed by measuring Phosphatidylserine externalization,caspase activity,mitochondrial membrane potential and DNA fragmentation;and proliferation by measuring DNA thymidine incorporation. Mitochondrial membrane potential was measured in permeabilized cells,and in isolated mitochondria. Nuclear factor kB(NF-kB) activity was measured by electromobility shift assay(EMSA) . RESULTS:We show that ellagic acid,a polyphenolic compound in fruits and berries,at concentrations 10 to 50 mmol/L stimulates apoptosis in human pancreatic adenocarcinoma cells. Further,ellagic acid decreases proliferation by up to 20-fold at 50 mmol/L. Ellagic acid stimulates the mitochondrial pathway of apoptosis associated with mitochondrial depolarization,cytochrome C release,and the downstream caspaseactivation. Ellagic acid does not directly affect mitochondria. Ellagic acid dose-dependently decreased NF-kB binding activity. Furthermore,inhibition of NF-kB activity using IkB wild type plasmid prevented the effect of ellagic acid on apoptosis. CONCLUSION:Our data indicate that ellagic acid stimulates apoptosis through inhibition of the prosu-rvival transcription factor NF-kB. | Mouad Edderkaoui Irina Odinokova Izumi Ohno Ilya Gukovsky Vay Liang W Go Stephen J Pandol Anna S Gukovskaya | 2008 | World Journal of Gastroenterology2008，14，23： | 30 |
| 3 | Meta-analyses on prevalence of selected Parkinson’s nonmotor symptoms before and after diagnosis显示文摘Background:Nonmotor symptoms are common among patients with Parkinson’s disease(PD)and some may precede disease diagnosis.Methods:We conducted a meta-analysis on the prevalence of selected nonmotor symptoms before and after PD diagnosis,using random-effect models.We searched PubMed(1965 through October/November 2012)for the following symptoms:hyposmia,constipation,rapid eye movement sleep behavior disorder,excessive daytime sleepiness,depression,and anxiety.Eligible studies were publications in English with original data on one or more of these symptoms.Results:The search generated 2,373 non-duplicated publications and 332 met the inclusion criteria,mostly(n=320)on symptoms after PD diagnosis.For all symptoms,the prevalence was substantially higher in PD cases than in controls,each affecting over a third of the patients.Hyposmia was the most prevalent(75.5%in cases vs.19.1%in controls),followed by constipation(50%vs.17.7%),anxiety(39.9%vs.19.1%),rapid eye movement sleep behavior disorder(37.0%vs.7.0%),depression(36.6%vs.14.9%),and excessive daytime sleepiness(33.9%vs.10.5%).We observed substantial heterogeneities across studies and meta-regression analyses suggested that several factors might have contributed to this.However,the prevalence estimates were fairly robust in several sensitivity analyses.Only 20 studies had data on any symptoms prior to PD diagnosis,but still the analyses revealed higher prevalence in future PD cases than in controls.Conclusion:These symptoms are common among PD patients both before and after diagnosis.Further studies are needed to understand the natural history of nonmotor symptoms in PD and their etiological and clinical implications. | Honglei Chen Edward J Zhao Wen Zhang Yi Lu Rui Liu Xuemei Huang Anna J Ciesielski-Jones Michele A Justice Deborah S Cousins Shyamal Peddada | 2015 | Translational Neurodegeneration2015，4，1： | 18 |
| 4 | The enhanced X-ray Timing and Polarimetry mission—eXTP显示文摘In this paper we present the enhanced X-ray Timing and Polarimetry mission—eXTP. eXTP is a space science mission designed to study fundamental physics under extreme conditions of density, gravity and magnetism. The mission aims at determining the equation of state of matter at supra-nuclear density, measuring effects of QED, and understanding the dynamics of matter in strong-field gravity. In addition to investigating fundamental physics, eXTP will be a very powerful observatory for astrophysics that will provide observations of unprecedented quality on a variety of galactic and extragalactic objects. In particular, its wide field monitoring capabilities will be highly instrumental to detect the electro-magnetic counterparts of gravitational wave sources.The paper provides a detailed description of:(1) the technological and technical aspects, and the expected performance of the instruments of the scientific payload;(2) the elements and functions of the mission, from the spacecraft to the ground segment. | ShuangNan Zhang Andrea Santangelo Marco Feroci YuPeng Xu FangJun Lu Yong Chen Hua Feng Shu Zhang Sφren Brandt Margarita Hernanz Luca Baldini Enrico Bozzo Riccardo Campana Alessandra De Rosa YongWei Dong Yuri Evangelista Vladimir Karas Norbert Meidinger Aline Meuris Kirpal Nandra Teng Pan Giovanni Pareschi Piotr Orleanski QiuShi Huang Stephane Schanne Giorgia Sironi Daniele Spiga Jiri Svoboda Gianpiero Tagliaferri Christoph Tenzer Andrea Vacchi Silvia Zane Dave Walton ZhanShan Wang Berend Winter Xin Wu Jean J.M.in't Zand Mahdi Ahangarianabhari Giovanni Ambrosi Filippo Ambrosino Marco Barbera Stefano Basso Jörg Bayer Ronaldo Bellazzini Pierluigi Bellutti Bruna Bertucci Giuseppe Bertuccio Giacomo Borghi XueLei Cao Franck Cadoux Francesco Ceraudo TianXiang Chen Yu Peng Chen Jerome Chevenez Marta Civitani Wei Cui WeiWei Cui Thomas Dauser Ettore Del Monte Sergio Di Cosimo Sebastian Diebold Victor Doroshenko Michal Dovciak YuanYuan Du Lorenzo Ducci QingMei Fan Yannick Favre Fabio Fuschino JoséLuis Ga'lvez Min Gao MingYu Ge Olivier Gevin Marco Grassi QuanYing Gu YuDong Gu DaWei Han Bin Hong Wei Hu Long Ji ShuMei Jia WeiChun Jiang Thomas Kennedy Ingo Kreykenbohm Irfan Kuvvetli Claudio Labanti Luca Latronico Gang Li MaoShun Li Xian Li Wei Li ZhengWei Li Olivier Limousin HongWei Liu XiaoJing Liu Bo Lu Tao Luo Daniele Macera Piero Malcovati Adrian Martindale Malgorzata Michalska Bin Meng Massimo Minuti Alfredo Morbidini Fabio Muleri Stephane Paltani Emanuele Perinati Antonino Picciotto Claudio Piemonte JinLu Qu Alexandre Rachevski Irina Rashevskaya Jerome Rodriguez Thomas Schanz ZhengXiang Shen LiZhi Sheng JiangBo Song LiMing Song Carmelo Sgro Liang Sun Ying Tan Phil Uttley Bo Wang DianLong Wang GuoFeng Wang Juan Wang LangPing Wang YuSa Wang Anna L.Watts XiangYang Wen Jörn Wilms ShaoLin Xiong JiaWei Yang Sheng Yang YanJi Yang Nian Yu WenDa Zhang Gianluigi Zampa Nicola Zampa Andrzej A.Zdziarski AiMei Zhang ChengMo Zhang Fan Zhang Long Zhang Tong Zhang Yi Zhang XiaoLi Zhang ZiLiang Zhang BaoSheng Zhao ShiJie Zheng Yu Peng Zhou Nicola Zorzi J.Frans Zwart | 2019 | Science China(Physics,Mechanics & Astronomy)2019，62，2： | 11 |
| 5 | Small bowel tumors detected and missed during capsule endoscopy: Single center experience显示文摘AIM:To characterize small bowel(SB)tumors detected by capsule endoscopy(CE),and identify missed tumors.METHODS:The study included 145 consecutive patients in whom 150 CEs were performed.Following CE,the medical records of the study population were reviewed.Results of double-or single-balloon enteroscopy performed after CE and the results of surgery in all patients operated on were retrieved.The patients were contacted through telephone interviews or postal mail.In addition,the national cancer registry and the polish clinical gastrointestinal stromal tumor(GIST)Registry were searched to identify missed neoplasms.RESULTS:Indications for CE included overt and occult obscure gastrointestinal bleeding(n=81,53.7%),anemia(n=19,12.7%),malabsorption(n=18,12%),abnormal CB follow through(n=9,6%),abdominal pain(n=7,5%),celiac disease(n=5,3%),neuroendocrine tumor(n=3,2%),Crohn’s disease(n=2,<2%),Peutz-Jeghers syndrome(n=2,<2%),other polyposes(n=2,<2%),and diarrhea(n=2,<2%).The capsule reached the colon in 115(76.6%)examinations.In 150 investigations,CE identified 15SB tumors(10%),14 of which were operated on or treated endoscopically.Malignancies included metastatic melanoma(n=1),adenocarcinoma(n=2),and GIST(n=3).Benign neoplasms included dysplastic Peutz-Jeghers polyps(n=4).Non-neoplastic masses included venous malformation(n=1),inflammatory tumors(n=2),and a mass of unknown histology(n=1).During the follow-up period,three additional SB tumors were found(2 GISTs and one mesenteric tumor of undefined nature).The National Cancer Registry and Polish Clinical GIST Registry revealed no additional SB neoplasms in the post-examination period(follow-up:range 4.2-102.5 mo,median 39 mo).The sensitivity of CE for tumor detection was 83.3%,and the negative predictive value was 97.6%.The specificity and positive predictive value were both 100%.CONCLUSION:Neoplasms may be missed by CE,especially in the proximal SB.In overt obscure gastrointestinal bleeding,complementary endoscopic and/or radiologic diagnostic tests are indicated. | Edyta S Zagorowicz Anna M Pietrzak Ewa Wronska Jacek Pachlewski Piotr Rutkowski Ewa Kraszewska Jaroslaw Regula | 2013 | World Journal of Gastroenterology2013，19，47： | 10 |
| 6 | Burden of Clostridium difficile infection between 2010 and 2013:Trends and outcomes from an academic center in Eastern Europe显示文摘AIM:To analyze the incidence and possible risk factors in hospitalized patients treated with Clostridium difficile infection(CDI).METHODS:A total of 11751 patients were admitted to our clinic between 1 January 2010 and 1 May2013.Two hundred and forty-seven inpatients were prospectively diagnosed with CDI.For the risk analysis a 1:3 matching was used.Data of 732 patients matched for age,sex,and inpatient care period and unit were compared to those of the CDI population.Inpatient records were collected from an electronic hospital database and comprehensively reviewed.RESULTS:Incidence of CDI was 21.0/1000 admissions(2.1%of all-cause hospitalizations and 4.45%of total inpatient days).The incidence of severe CDI was 12.6%(2.63/1000 of all-cause hospitalizations).Distribution of CDI cases was different according to the unit type,with highest incidence rates in hematology,gastroenterology and nephrology units(32.9,25 and24.6/1000 admissions,respectively) and lowest rates in 1.4%(33/2312) in endocrinology and general internal medicine(14.2 and 16.9/1000 admissions)units.Recurrence of CDI was 11.3%within 12 wk after discharge.Duration of hospital stay was longer in patients with CDI compared to controls(17.6 ± 10.8d vs 12.4 ± 7.71 d).CDI accounted for 6.3%of allinpatient deaths,and 30-d mortality rate was 21.9%(54/247 cases).Risk factors for CDI were antibiotic therapy[including third-generation cephalosporins or fluoroquinolones,odds ratio(OR) = 4.559;P < 0.001],use of proton pump inhibitors(OR = 2.082,P< 0.001),previous hospitaiization within 12 mo(OR = 3.167,P < 0.001),previous CDI(OR = 15.32;P < 0.001),while presence of diabetes mellitus was associated with a decreased risk for CDI(OR = 0.484;P< 0.001).Treatment of recurrent cases was significantly different from primary infections with more frequent use of vancomycin alone or in combination(P < 0.001),and antibiotic therapy duration was longer(P < 0.02).Severity,mortality and outcome of primary infections and relapsing cases did not significantly differ.CONCLUSION:CDI was accounted for significant burden with longer hospitaiization and adverse outcomes.Antibiotic,PPI therapy and previous hospitaiization or CDI were risk factors for CDI. | Zsuzsanna Kurti Barbara D Lovasz Michael D Mandel Zoltan Csima Petra A Golovics Bence D Csako Anna Mohas Lorant Gnczi Krisztina B Gecse Lajos S Kiss Miklos Szathmari Peter L Lakatos | 2015 | World Journal of Gastroenterology2015，21，21： | 6 |
| 7 | Risk factors for resistance to ceftriaxone and its impact on mortality in community, healthcare and nosocomial spontaneous bacterial peritonitis显示文摘 | Xavier Ariza José Castellote Jaime Lora-Tamayo Anna Girbau Sílvia Salord Rosa Rota Javier Ariza Xavier Xiol | 2011 | Journal of Hepatology2011，，4： | 5 |
| 8 | Economic impact of minimally invasive lumbar surgery显示文摘Cost effectiveness has been demonstrated for traditional lumbar discectomy, lumbar laminectomy as well as for instrumented and noninstrumented arthrodesis. While emerging evidence suggests that minimally invasive spine surgery reduces morbidity, duration of hospitalization, and accelerates return to activites of daily living, data regarding cost effectiveness of these novel techniques is limited. The current study analyzes all available data on minimally invasive techniques for lumbar discectomy, decompression, short-segment fusion and deformity surgery. In general, minimallyinvasive spine procedures appear to hold promise in quicker patient recovery times and earlier return to work. Thus, minimally invasive lumbar spine surgery appears to have the potential to be a cost-effective intervention. Moreover, novel less invasive procedures are less destabilizing and may therefore be utilized in certain indications that traditionally required arthrodesis procedures. However, there is a lack of studies analyzing the economic impact of minimally invasive spine surgery. Future studies are necessary to confirm the durability and further define indications for minimally invasive lumbar spine procedures. | Christoph P Hofstetter Anna S Hofer Michael Y Wang | 2015 | World Journal of Orthopedics2015，6，2： | 4 |
| 9 | Glycoprotein biomarkers for the detection of pancreatic ductal adenocarcinoma显示文摘Pancreatic cancer(Pa C) shows a clear tendency to increase in the next years and therefore represents an important health and social challenge. Currently, there is an important need to find biomarkers for PaC early detection because the existing ones are not useful for that purpose. Recent studies have indicated that there is a large window of time for PaC early detection, which opens the possibility to find early biomarkers that could greatly improve the dismal prognosis of this tumor. The present manuscript reviews the state of the art of the existing PaC biomarkers. It focuses on the anomalous glycosylation process and its role in PaC. Glycan structures of glycoconjugates such as glycoproteins are modified in tumors and these modifications can be detected in biological fluids of the cancer patients. Several studies have found serum glycoproteins with altered glycan chains in PaC patients, but they have not shown enough specificity for PaC. To find more specific cancer glycoproteins we propose to analyze the glycan moieties of a battery of glycoproteins that have been reported to increase in PaC tissues and that can also be found in serum. The combination of these new candidate glycoproteins with their aberrant glycosylation together with the existing biomarkers could result in a panel, which would expect to give better results as a new tool for early diagnosis of PaC and to monitor the disease. | Esther Llop Pedro E Guerrero AdriàDuran Sílvia Barrabés Anna Massaguer María JoséFerri Maite Albiol-Quer Rafael de Llorens Rosa Peracaula | 2018 | World Journal of Gastroenterology2018，24，24： | 4 |
| 10 | Lamivudine therapy for children with chronic hepatitis B显示文摘瞄准:为了估计,为失败到的有长期的肝炎 B (CHB ) 的孩子的 lamivudine 治疗的有效性和副作用对作出回应或有禁止徵候到 interferon-alpha (IFN-alpha ) 治疗。方法:有 CHB 的 59 个孩子被对待, 100 片 mg lamivudine 药片每天为 12 瞬间口头上地给一次。丙氨酸 aminotransferase (中高音) 活动在它的中止以后在治疗和每 3 瞬间期间每月被评估。HBe 抗原, anti-HBe 抗体,在浆液的 HBV DNA 水平在基线和每六个月被评估在期间并且在 lamivudine 治疗以后。对 lamivudine 治疗的持续病毒的反应(SVR ) 被定义为永久(比在治疗的结束以后的 6 瞬间不短) ,也就是中高音活动正规化,到 anti-HBe 抗体的 HBeAg 的 seroconversion,和在浆液的无法发现的病毒的 HBV-DNA (比 200 个拷贝低每 mL ) 。lamivudine 治疗的副作用的分析有关测试在治疗以后在治疗,和每 3 瞬间期间每月在临床的访问期间执行了的主观、客观的症状,临床的考试,和实验室用一张问询表在病人和他们的父母的会见之上被基于。结果:中高音 normalisation 发生在 47 (79.7%) 病人在之间第一和 11 (th ) 治疗的瞬间(吝啬的 4.4+/-2.95 瞬间,中部 4.0 瞬间) ,并且在 18 (30.5%) 他们在治疗的 2 瞬间以后。在中高音正规化和孩子们的年龄的时间之间没有关联, HBV 感染的年龄, HBV 感染的持续时间,发炎活动分数(分级) ,阶段,在治疗前的中高音活动,浆液 HBV DNA 水平,和 lamivudine 每体重的 kg 开。HBeAg/anti HBe seroconversion 在 27.1% 盒子中被完成。seroconversion 的更高的率与更低的浆液 HBV DNA 水平和 HBV 感染的更长的持续时间被连接。在 HBeAg/anti HBeAb seroconversion 和孩子们之间没有连接,分级是年龄, HBV 感染的年龄,阶段,在治疗前的中高音活动,和 lamivudnie 每体重的 kg 开。没有抱怨或临床的症状在 lamivudine 治疗期间被观察。肾的功能或骨髓中毒的效果的缺陷病人在没有被注意。结论:为有长期的肝炎 B 的孩子的一年 lamivudine 治疗有效、很好容忍。HBeAg/HBeAb 和 SVR 的 Seroconversion 与更低的预告的处理浆液 HBV DNA 水平被连接。 | Anna Liberek Anna Szaflarska-Poplawska Maria Korzon Gra(?)yna (?)uczak Magdalena Góra-Gebka Ewa (?)o(s|')-Rycharska Wanda Bako Mieczyslawa Czerwionka-Szaflarska | 2006 | World Journal of Gastroenterology2006，12，15： | 4 |
| 11 | Optical disassembly of cellular clusters by tunable ‘tug-of-war’ tweezers显示文摘Bacterial biofilms underlie many persistent infections,posing major hurdles in antibiotic treatment.Here we design and demonstrate‘tug-of-war’optical tweezers that can facilitate the assessment of cell–cell adhesion—a key contributing factor to biofilm development,thanks to the combined actions of optical scattering and gradient forces.With a customized optical landscape distinct from that of conventional tweezers,not only can such‘tug-of-war’tweezers stably trap and stretch a rod-shaped bacterium in the observing plane,but,more importantly,they can also impose a tunable lateral force that pulls apart cellular clusters without any tethering or mechanical movement.As a proof of principle,we examined a Sinorhizobium meliloti strain that forms robust biofilms and found that the strength of intercellular adhesion depends on the growth medium.This technique may herald new photonic tools for optical manipulation and biofilm study,as well as other biological applications. | Anna S Bezryadina Daryl C Preece Joseph C Chen Zhigang Chen | 2016 | Light(Science & Applications)2016，5，1： | 4 |
| 12 | Determination of drug,excipients and coating distribution in pharmaceutical tablets using NIR-CI显示文摘The growing interest of the pharmaceutical industry in Near Infrared-Chemical Imaging (NIR-CI) is a result of its high usefulness for quality control analyses of drugs throughout their production process (particularly of its non-destructive nature and expeditious data acquisition).In this work,the concentration and distribution of the major and minor components of pharmaceutical tablets are determined and the spatial distribution from the internal and external sides has been obtained.In addition,the same NIR-CI allowed the coating thickness and its surface distribution to be quantified.Images were processed to extract the target data and calibration models constructed using the Partial Least Squares (PLS) algorithms.The concentrations of Active Pharmaceutical Ingredient (API) and excipients obtained for uncoated cores were essentially identical to the nominal values of the pharmaceutical formulation.But the predictive ability of the calibration models applied to the coated tablets decreased as the coating thickness increased. | Anna Palou Jordi Cruz Marcelo Blanco Jaume Tomàs Joaquín de los Ríos Manel Alcalà | 2012 | Journal of Pharmaceutical Analysis2012，2，2： | 4 |
| 13 | Beta-blocker therapy in elderly patients with renal dysfunction and heart failure显示文摘OBJECTIVE To assess the role of beta-blockers(BB)in patients with chronic kidney disease(CKD)aged≥75 years.METHODS AND RESULTS From January 2008 to July 2014,we included 390 consecutive patients≥75 years of age with ejection fraction≤35%and glomerular filtration rate(GFR)≤60 m L/min per 1.73 m^2.We analyzed the relationship between treatment with BB and mortality or cardiovascular events.The mean age of our population was 82.6±4.1 years.Mean ejection fraction was 27.9%±6.5%.GFR was 60-45 m L/min per 1.73 m^2 in 50.3%of patients,45-30 m L/min per 1.73 m^2 in 37.4%,and<30 m L/min per 1.73 m^2 in 12.3%.At the conclusion of follow-up,67.4%of patients were receiving BB.The median follow-up was28.04(IR:19.41-36.67)months.During the study period,211 patients(54.1%)died and 257(65.9%)had a major cardiovascular event(death or hospitalization for heart failure).BB use was significantly associated with a reduced risk of death(HR=0.51,95%CI:0.35-0.74;P<0.001).Patients receiving BB consistently showed a reduced risk of death across the different stages of CKD:stage IIIa(GFR=30-45 m L/min per 1.73 m^2;HR=0.47,95%CI:0.26-0.86,P<0.0001),stage IIIb(GFR 30-45 m L/min per 1.73 m^2;HR=0.55,95%CI:0.26-1.06,P=0.007),and stages IV and V(GFR<30 m L/min per 1.73 m~2;HR=0.29,95%CI:0.11-0.76;P=0.047).CONCLUSIONS The use of BB in elderly patients with HFr EF and renal impairment was associated with a better prognosis.Use of BB should be encouraged when possible. | Juan Martínez-Milla Marcelino Cortés García Julia Anna Palfy Mikel Taibo Urquía Marta López Castillo Ana Devesa Arbiol Ana Lucía Rivero Monteagudo María Luisa Martín Mariscal Inés Jiménez-Varas Sem Briongos Figuero Juan Antonio Franco-Pelaéz JoséTuñón | 2021 | Journal of Geriatric Cardiology2021，18，1： | 3 |
| 14 | New genes emerging for colorectal cancer predisposition显示文摘Colorectal cancer(CRC)is one of the most frequent neoplasms and an important cause of mortality in the developed world.This cancer is caused by both genetic and environmental factors although 35%of the variation in CRC susceptibility involves inherited genetic differences.Mendelian syndromes account for about5%of the total burden of CRC,with Lynch syndrome and familial adenomatous polyposis the most common forms.Excluding hereditary forms,there is an important fraction of CRC cases that present familial aggregation for the disease with an unknown germline genetic cause.CRC can be also considered as a complex disease taking into account the common diseasecommom variant hypothesis with a polygenic model of inheritance where the genetic components of common complex diseases correspond mostly to variants of low/moderate effect.So far,30 common,low-penetrance susceptibility variants have been identified for CRC.Recently,new sequencing technologies including exomeand whole-genome sequencing have permitted to add a new approach to facilitate the identification of new genes responsible for human disease predisposition.By using whole-genome sequencing,germline mutations in the POLE and POLD1 genes have been found to be responsible for a new form of CRC genetic predisposition called polymerase proofreading-associated polyposis. | Clara Esteban-Jurado Pilar Garre Maria Vila Juan José Lozano Anna Pristoupilova Sergi Beltrán Anna Abulí Jenifer Muoz Francesc Balaguer Teresa Ocaa Antoni Castells Josep M Piqué Angel Carracedo Clara Ruiz-Ponte Xavier Bessa Montserrat Andreu Luis Bujanda Trinidad Caldés Sergi Castellví-Bel | 2014 | World Journal of Gastroenterology2014，20，8： | 3 |
| 15 | Hedgehog signaling regulates epithelial-mesenchymal transition during biliary fibrosis in rodents and humans显示文摘 | Omenetti Alessia Porrello Alessandro Jung Youngmi Yang Liu Popov Yury Choi Steve S Witek Rafal P Alpini Gianfranco Venter Juliet Vandongen Hendrika M Syn Wing-Kin Baroni Gianluca Svegliati Benedetti Antonio Schuppan Detlef Diehl Anna Mae | 2008 | Journal of Clinical Investigation2008，，10： | 3 |
| 16 | Is early limited surgery associated with a more benign disease course in Crohn's disease?显示文摘AIM:To analyze the difference in disease course and need for surgery in patients with Crohn’s disease(CD).METHODS:Data of 506 patients with incident CD were analyzed(age at diagnosis:31.5±13.8 years).Both hospital and outpatient records were collected prospectively with a complete clinical follow-up and comprehensively reviewed in the population-based Veszprem province database,which includes incident CD patients diagnosed between January 1,1977 and December 31,2008.Follow-up data were collected until December 31,2009.All patients included had at least 1year of follow-up available.Patients with indeterminate colitis at diagnosis were excluded from the analysis.RESULTS:Overall,73 patients(14.4%)required resective surgery within 1 year of diagnosis.Steroid exposure and need for biological therapy were lower in patients with early limited surgery(P<0.001 and P=0.09).In addition,surgery rates during follow-up in patients with and without early surgery differed significantly after matching on propensity scores(P<0.001,HR=0.23).The need for reoperation was also lower in patients with early limited resective surgery(P=0.038,HR=0.42)in a Kaplan-Meier and multivariate Cox regression(P=0.04)analysis.However,this advantage was not observed after matching on propensity scores(PLogrank=0.656,PBreslow=0.498).CONCLUSION:Long-term surgery rates and overall exposure to steroids and biological agents were lower in patients with early limited resective surgery,but reoperation rates did not differ. | Petra Anna Golovics Laszlo Lakatos Attila Nagy Tunde Pandur Istvan Szita Mihaly Balogh Csaba Molnar Erzsebet Komaromi Barbara Dorottya Lovasz Michael Mandel Gabor Veres Lajos S Kiss Zsuzsanna Vegh Peter Laszlo Lakatos | 2013 | World Journal of Gastroenterology2013，19，43： | 3 |
| 17 | Accuracy of Magnetic Resonance Enterography in Assessing Response to Therapy and Mucosal Healing in Patients With Crohn’s Disease显示文摘 | Ingrid Ordás Jordi Rimola Sonia Rodríguez José M. Paredes María J. Martínez-Pérez Esther Blanc Juan A. Arévalo Marta Aduna Montserrat Andreu Alexander Radosevic Anna M. Ramírez-Morros Susana Pinó Marta Gallego Aranzazu Jauregui-Amezaga Elena Ricart Julián | 2013 | Gastroenterology2013，，： | 3 |
| 18 | Susceptibility Genetic Variants Associated With Colorectal Cancer Risk Correlate With Cancer Phenotype显示文摘 | Anna Abulí Xavier Bessa Juan Ramón González Clara Ruiz–Ponte Alejandro Cáceres Jenifer Mu?oz Victoria Gonzalo Francesc Balaguer Ceres Fernández–Rozadilla Dolors González Luisa de Castro Juan Clofent Luís Bujanda Joaquín Cubiella Josep M a Re?é Juan Diego | 2010 | Gastroenterology2010，，3： | 2 |
| 19 | 小型腐殖质湖泊的碳收支:湖泊对北方集水区有机物质循环重要性的一个实例显示文摘由于通常是大范围的细菌呼吸作用和沉积物中有机碳的有效埋藏,湖泊在北方景观有机物质循环中发挥着重要作用。为了评估碳收支对与有机物有关的放射性核素在环境中迁移的潜在影响,我们基于一种质量平衡方法,计算了瑞典的一个小腐殖质湖的碳收支,该湖位于一个放射性废料潜在最后埋藏点的附近。我们发现该湖是一个净异养的生态系统,从集水区和现有大型植物生产物中补充得到有机碳输入。有机碳最大的汇点是水生细菌的呼吸作用和随后向大气释放CO_2。虽然每年埋藏在沉积物中的有机碳是一个比较小的汇,但它却导致湖中最大碳库的形成。因此,湖泊也许同时分散和聚集从最后埋藏点中泄漏的有机伴生的放射性核素。 | Sebastian Sobek Bjrn Sderbck Sara Karlsson Eva Andersson Anna Kristina Brunberg 李四海 | 2006 | AMBIO-人类环境杂志2006，35，8： | 2 |
| 20 | Bulbocavernosus muscle area measurement: a novel method to assess androgenic activity显示文摘浆液睾丸激素不与雄激素织物活动相关,并且优化工具在男性评估如此的活动是批评的。bulbocavernosus 肌肉(BCM ) 的超声测量被用来在雄激素受体(AR ) 和 BCM 尺寸估计在 CAG 重复(CAGn ) 的数字之间的关系;在 CAGn 超龄的数字的变化也被评估。BCM 的 Transperineal 超声测量也被执行。AR CAGn 被高效液体层析,和早上荷尔蒙决定层次用免疫分析被决定。48 个人让 CAG 重复分析。25 是 < 30 岁,平均数 23.7 年(s.d = 3.24 ) 并且 23 是 > 45 岁,平均数 53 年(s.d = 5.58 ) 。中部的 CAGn 是 21 (13-29 ) 。当 CAGn 的数字是 < 时, BCM 区域更大; 18 作为与 CAGn > 的数字相比; 24 (P = 0.04 ) 。在 CAGn 和 BCM 区域 R 2= 的数字之间有线性关联 16%(P = 0.01 ) 。在 45 到 65-years-old 组,强壮得多的否定关联(R 2=29% , P = 0.01 ) 被注意。在 19,到 29-years-old 组,,没有如此的关联被发现(R 2=4% , P = 0.36 ) 。在老人, CAGn 的数字与年龄增加了(R 2=32% , P = 0.01 ) 。在 AR 的 CAGn 的数字与 BCM 的区域相关。对 BCM 的超声评价是一个有效代理人评估雄激素的结束器官活动。CAGn 的数字可以与年龄增加。 | Ali A Dabaja Matthew S Wosnitzer Anna Mielnik Alexander Bolyakov Peter N Schlegel Darius A Paduch | 2014 | Asian Journal of Andrology2014，16，4： | 2 |
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