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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 | Intestinal microbiota in health and disease: Role of bifidobacteria in gut homeostasis显示文摘The pool of microbes inhabiting our body is known as 'microbiota' and their collective genomes as 'microbiome'. The colon is the most densely populated organ in the human body, although other parts, such as the skin, vaginal mucosa, or respiratory tract, also harbour specific microbiota. This microbial community regulates some important metabolic and physiological functions of the host, and drives the maturation of the immune system in early life, contributing to its homeostasis during life. Alterations of the intestinal microbiota can occur by changes in composition(dysbiosis), function, or microbiota-host interactions and they can be directly correlated with several diseases. The only disease in which a clear causal role of a dysbiotic microbiota has been demonstrated is the case of Clostridium difficile infections. Nonetheless, alterations in composition and function of the microbiota have been associated with several gastrointestinal diseases(inflammatory bowel disease, colorectal cancer, or irritable bowel syndrome), as well as extra-intestinal pathologies, such as those affecting the liver, or the respiratory tract(e.g., allergy, bronchial asthma, and cystic fibrosis), among others. Species of Bifidobacterium genus are the normal inhabitants of a healthy human gut and alterations in number and composition of their populations is one of the most frequent features present in these diseases. The use of probiotics, including bifidobacteria strains, in preventive medicine to maintain a healthy intestinal function is well documented. Probiotics are also proposed as therapeutic agents for gastrointestinal disorders and other pathologies. The World Gastroenterology Organization recently published potential clinical applications for several probiotic formulations, in which species of lactobacilli are predominant. This review is focused on probiotic preparations containing Bifidobacterium strains, alone or in combination with other bacteria, which have been tested in human clinical studies. In spite of extensive literature on and research into this topic, the degree of scientific evidence of the effectiveness of probiotics is still insufficient in most cases. More effort need to be made to design and conduct accurate human studies demonstrating the efficacy of probiotics in the prevention, alleviation, or treatment of different pathologies. | Rafael Tojo Adolfo Suárez Marta G Clemente Clara G de los Reyes-Gavilán Abelardo Margolles Miguel Gueimonde Patricia Ruas-Madiedo | 2014 | World Journal of Gastroenterology2014，20，41： | 33 |
| 3 | 从附睾到卵子:CRISP蛋白在哺乳动物受精过程中的作用显示文摘哺乳动物的受精过程涉及精卵结合的很多步骤,是一个非常复杂的过程,其分了机制亟待阐明。此篇综述主要论述了CRISP(富含半胱氨酸的分泌蛋白)作为模型分子在哺乳动物受精过程中的价值。大量的体外实验和基因敲出模型研究显示,附睾内的CRISP1以两种不同的亲和力结合于精子表面,参与精子获能、精子-透明带结合、精卵融合的调控。这些研究成果可以延伸至人类。我们住研究中发现,人类具有与啮齿类同源的CRISP(hCRISP1),同样参与受精过样。CRISP家族的其他成员(睾丸内CRISP2、附挈内CRISP3—4、射精时的CRISP3)也参与了精卵结合的过程,提示同源分子间的相互协同有助于受精的成功。另外,我们的研究显示,CRISP蛋白伴随精子穿越男性及女性生殖管道的全过程。我们推测CRISP不仅参与了受精过程,而且可能成为不育和避孕研究的新靶点。 | Vanina G Da Ros Mariana Weigel Munoz Maria A Battistone Nicolas G Brukman Guillermo Carvajal Ludmila Curci Matlas D Gomez-Elias Debora J Cohen Patricia S Cuasnicu | 2015 | Asian Journal of Andrology2015，17，5： | 5 |
| 4 | Interplay between post-translational cyclooxygenase-2 modifications and the metabolic and proteomic profile in a colorectal cancer cohort显示文摘BACKGROUND Colorectal cancer(CRC) is the second most common cause of cancer death worldwide. It is broadly described that cyclooxygenase-2(COX-2) is mainly overexpressed in CRC but less is known regarding post-translational modifications of this enzyme that may regulate its activity, intracellular localization and stability. Since metabolic and proteomic profile analysis is essential for cancer prognosis and diagnosis, our hypothesis is that the analysis of correlations between these specific parameters and COX-2 state in tumors of a high number of CRC patients could be useful for the understanding of the basis of this cancer in humans.AIM To analyze COX-2 regulation in colorectal cancer and to perform a detailed analysis of their metabolic and proteomic profile.METHODS Biopsies from both healthy and pathological colorectal tissues were taken under informed consent from patients during standard colonoscopy procedure in the University Hospital of Bellvitge(Barcelona, Spain) and Germans Trias i Pujol University Hospital(Campus Can Ruti)(Barcelona, Spain). Western blot analysis was used to determine COX-2 levels. Deglycosylation assays were performed in both cells and tumor samples incubating each sample with peptide N-glycosidase F(PNGase F). Prostaglandin E2(PGE2) levels were determined using a specific ELISA. 1 H high resolution magic angle spinning(HRMAS) analysis was performed using a Bruker AVIII 500 MHz spectrometer and proteomic analysis was performed in a nano-liquid chromatography-tandem mass spectrometer(nano LC-MS/MS) using a QExactive HF orbitrap MS.RESULTS Our data show that COX-2 has a differential expression profile in tumor tissue of CRC patients vs the adjacent non-tumor area, which correspond to a glycosylated and less active state of the protein. This fact was associated to a lesser PGE2 production in tumors. These results were corroborated in vitro performing deglycosylation assays in HT29 cell line where COX-2 protein profile was modified after PNGase F incubation, showing higher PGE2 levels. Moreover,HRMAS analysis indicated that tumor tissue has altered metabolic features vs non-tumor counterparts, presenting increased levels of certain metabolites such as taurine and phosphocholine and lower levels of lactate. In proteomic experiments, we detected an enlarged number of proteins in tumors that are mainly implicated in basic biological functions like mitochondrial activity,DNA/RNA processing, vesicular trafficking, metabolism, cytoskeleton and splicing.CONCLUSION In our colorectal cancer cohort, tumor tissue presents a differential COX-2 expression pattern with lower enzymatic activity that can be related to an altered metabolic and proteomic profile. | Patricia Prieto Rafael I Jaén Daniel Calle María Gómez-Serrano Estefanía Nú?ez María Fernández-Velasco Paloma Martín-Sanz Sergio Alonso Jesús Vázquez Sebastián Cerdán Miguel ángel Peinado Lisardo Boscá | 2019 | World Journal of Gastroenterology2019，25，4： | 4 |
| 5 | 中文迁延悲伤量表修订版的效度和信度显示文摘目的:评价中文迁延悲伤量表修订版(PG-13-R)的效度和信度。方法:招募符合DSM-5-TR迁延悲伤障碍(PGD)诊断标准的患者200例为研究对象,进行迁延悲伤量表修订版评定,计算组内相关系数(ICC)评价评定者之间的一致性;计算Cronbachα系数评价量表的内部一致性,采取主成份方法计算条目的因子载荷考评量表的结构效度。通过计算PG-13-Revised量表的评分与社会适应量表(WSAS)评分和自评抑郁量表(SDS)的相关性来考察PG-R-13效标效度。以DSM-5-TR诊断标准为依据,计算受试者可接受曲线下面积(AUC)来判断量表的区分效度以及划定量表的划界分。结果:评定者一致性系数ICC为0.97;各个分条目之间的相关系数在0.85~0.99之间。量表总Cronbachα系数为0.85。在PG-13-R的13个条目中,采用主成分分析法算出1个主因子,贡献率达78.98%,高于结构效度检验的标准50%。以临床评估标准为参考,在区分轻度迁延悲伤障碍时划界分为≥25时灵敏度和特异度最好,分别为93.3%和78.2%,AUC为0.82,区分中度迁延悲伤障碍,划界分≥37时灵敏度和特异度最高,分别为92.5%、90.7%,AUC为0.92;在区分重度迁延悲伤障碍时,划界分≥46时灵敏度和特异度最高,分别为95.47%、92.18%,AUC为0.96。结论:中文迁延悲伤量表修订版(PG-13-R)有良好的效度和信度,能够早期测评迁延悲伤障碍的严重程度。 | 霍平乐 李然立 孙芸 陈新英 PRIGERSON Holly G CHOU S Patricia 陈光东 禚传君 黄春海 | 2022 | 中国心理卫生杂志2022，36，5： | 4 |
| 6 | 含有加州杏仁皮的酸面团发酵面条的剪切质构特性研究显示文摘本实验主要在传统的面条工艺基础上,研究影响含有加州杏仁皮的经自然发酵酸面团(发酵剂)发酵的风味面条剪切质构特性的关键因素。结果表明,发酵剂的发酵时间和添加量及杏仁皮添加量对酸面团发酵面条的最大剪切力的影响显著。应用响应面分析法建立了描述各因素与最大剪切力之间关系的回归模型,最大剪切力的回归方程的R2为0.9562,说明响应面法可以作为推测研究发酵剂的发酵时间和添加量及杏仁皮添加量各因素以及它们之间的交互作用对酸面团发酵面条品质(剪切质构特性)影响效果的适宜方法。最后,通过岭脊分析得到制备含有加州杏仁皮的酸面团发酵面条的最佳工艺条件是发酵剂发酵时间33h、发酵剂量5%、杏仁皮量3%。 | 靳翔 黄卫宁 RAYAS-DUARTE Patricia HUANG G SAITAMA Kristi | 2008 | 食品科学2008，29，3： | 4 |
| 7 | Effect of electrical stimulation of the lower esophageal sphincter in gastroesophageal reflux disease patients refractory to proton pump inhibitors显示文摘AIM: To evaluate the efficacy of lower esophageal sphincter(LES)-electrical stimulation therapy(EST) in a subgroup of patients that reported only partial response to proton pump inhibitors(PPIs) therapy, compared to a group of patient with complete response.METHODS: Bipolar stitch electrodes were laparoscopically placed in the LES and connected to an implantable pulse generator(EndoS tim BV, the Hague, the Netherlands), placed subcutaneously in the anterior abdominal wall. Stimulation at 20 Hz, 215 μsec, 3-8 m Amp in 30 min sessions was delivered starting on day 1 post-implant. Patients were evaluated using gastroesophageal reflux disease(GERD)-HRQL, symptom diaries; esophageal p H and esophageal manometry before and up to 24 mo after therapy and results were compared between partial and complete responders.RESULTS: Twenty-three patients with GERD on LESEST were enrolled and received continuous per-protocol stimulation through 12 mo and 21 patients completed 24 mo of therapy. Of the 23 patients, 16(8 male, mean age 52.1 ± 12 years) had incomplete response to PPIs prior to LES-EST, while 7 patients(5 male, mean age 52.7 ± 4.7) had complete response to PPIs. In the sub-group with incomplete response to PPIs, median(IQR) composite GERD-HRQL score improved significantly from 9.5(9.0-10.0) at baseline on-PPI and 24.0(20.8-26.3) at baseline off-PPI to 2.5(0.0-4.0) at 12-mo and 0.0(0.0-2.5) at 24-mo follow-up(P < 0.05 compared to on-and off-PPI at baseline). Median(IQR) % 24-h esophageal pH < 4.0 at baseline in this sub-group improved significantly from 9.8%(7.8-11.5) at baseline to 3.0%(1.9-6.3) at 12 mo(P < 0.001) and 4.6%(2.0-5.8) at 24 mo follow-up(P < 0.01). At their 24-mo follow-up, 9/11 patients in this sub-group were completely free of PPI use. These results were comparable to the sub-group that reported complete response to PPI therapy at baseline. No unanticipated implantation or stimulation-related adverse events, or any untoward sensation due to stimulation were reported in either group and LES-EST was safely tolerated by both groups. CONCLUSION: LES-EST is safe and effective in controlling symptoms and esophageal acid exposure in GERD patients with incomplete response to PPIs. These results were comparable to those observed PPI responders. | Edy Soffer Leonardo Rodríguez Patricia Rodriguez Beatriz Gómez Manoel G Neto Michael D Crowell | 2016 | World Journal of Gastrointestinal Pharmacology and Therapeutics2016，7，1： | 4 |
| 8 | Intestinal microbiota determines development of non-alcoholic fatty liver disease in mice显示文摘 | Tiphaine Le Roy Marta Llopis Patricia Lepage Aurélia Bruneau Sylvie Rabot Claudia Bevilacqua Patrice Martin Catherine Philippe Francine Walker André Bado Gabriel Perlemuter Anne-Marie Cassard-Doulcier Philippe Gérard | 2013 | Gut2013，，12： | 3 |
| 9 | Stemflow contribution to the ‘fertile island’ effect in creosotebush, Larrea tridentata显示文摘 | Walter G Whitford John Anderson Patricia M Rice | 1997 | Journal of Arid Environments1997，，3： | 2 |
| 10 | Human acute myelogenous leukemia stem cells are rare and heterogeneous when assayed in NOD/SCID/IL2R[gamma]c-deficient mice显示文摘 | Sarry Jean-Emmanuel Murphy Kathleen Perry Robin Sanchez Patricia V Secreto Anthony Keefer Cathy Swider Cezary R Strzelecki Anne-Claire Cavelier Cindy Récher Christian Mansat-De Mas Véronique Delabesse Eric Danet-Desnoyers G Carroll Martin | 2011 | Journal of Clinical Investigation2011，，1： | 2 |
| 11 | Electrical stimulation therapy of the lower esophageal sphincter is successful in treating GERD: final results of open-label prospective trial显示文摘 | Leonardo Rodríguez Patricia Rodriguez Beatriz Gómez Juan C. Ayala Jorge Saba Alberto Perez-Castilla Manoel Galvao Neto Michael D. Crowell | 2013 | Surgical Endoscopy2013，，4： | 2 |
| 12 | Comparison of Topical Cyclosporine, Punctal Occlusion, and a Combination for the Treatment of Dry Eye显示文摘 | Calvin W Roberts Patricia E Carniglia Brian G Brazzo | 2007 | Cornea2007，，7： | 2 |
| 13 | Anti-hypertensive drugs in children and adolescents显示文摘Worldwide the prevalence of essential hypertension inchildren and adolescents continues to increase. Tradi-tionally providers have used 'off-label' drugs to treatpediatric hypertension, meaning that rigorous clinicaltrials of these drugs have not been specifically per-formed in pediatric patient populations. Consequentlyproviders have extrapolated dosing, safety and efficacyfrom trials in adults. This practice is sub-optimal as chil-dren demonstrate unique differences in drug metabo-lism and response. Use of unstudied or understudieddrugs increases risk of adverse events and/or can leadto sub-optimal efficacy. Recognizing these concerns,regulatory agencies have created financial incentivesfor industry to conduct pediatric clinical trials. Theseincentives, coupled with the emerging pediatric hyper-tension epidemic, have spurred over 30 clinical trialsof anti-hypertensive drugs over the past 15 years andhave resulted in labeling of 10 new drugs by the UnitedStates Food and Drug Administration for treatment ofhypertension in children and adolescents. Unfortunatelythe financial incentive structures focus on newer drugsand drug classes. Consequently there is now a relativedearth of trial data for older but sometimes commonlyprescribed pediatric antihypertensive drugs. This article reviews recent pediatric antihypertensive drug trials with a focus on trial design and endpoints, drug dosing, safety, efficacy and specific drug indications. We also review the available data and experience for some of the more commonly prescribed, but less well studied 'older' pediatric antihypertensive drugs. | Patricia Y Chu Michael J Campbell Stephen G Miller Kevin D Hill | 2014 | World Journal of Cardiology2014，6，5： | 2 |
| 14 | MicroRNAs in biliary diseases显示文摘Cholangiopathies are a group of diseases primarily or secondarily affecting bile duct cells, and result in cholangiocyte proliferation, regression, and/or transformation. Their etiopathogenesis may be associated with a broad variety of causes of different nature, which includes genetic, neoplastic, immune-associated, infectious, vascular, and drug-induced alterations, or being idiopathic. miRNAs, small non-coding endogenous RNAs that post-transcriptionally regulate gene expres sion, have been associated with pathophysiological processes in different organs and cell types, and are postulated as potential targets for diagnosis and therapy. In the current manuscript, knowledge regarding the role of miRNAs in the development and/or progression of cholangiopathies has been reviewed and the most relevant findings in this promising field of hepatology have been highlighted. | Patricia Munoz-Garrido Maite García-Fernández de Barrena Elizabeth Hijona Miguel Carracedo JoséJ G Marín Luis Bujanda Jesús M Banales | 2012 | World Journal of Gastroenterology2012，18，43： | 2 |
| 15 | Thymosin-beta4 modulates corneal matrix metalloproteinase levels and polymorphonuclear celt infiltration after alkali injury 显示文摘 | Sosne G Patricia L Christopherson P L | 2005 | Invest Ophthalmol Vis Sci2005，46，7： | 1 |
| 16 | Confidence in linear spectral unmixing of single pixels显示文摘 | Petrou Maria Foschi Patricia G | 1999 | IEEE Transactions on Geoscience and Remote Sensing1999，37，1： | 1 |
| 17 | Quality of Life in Long - Term, Disease- Free Survivors of Breast Cancer: a Follow - up Study 显示文摘 | Patricia A G Katherine A D Beth L | 2002 | J Natl Cancer Inst2002，94，1： | 1 |
| 18 | Online Communication and Adolescent Relationships 显示文摘 | Subrahmanyam K Patricia G | 2008 | The Future of Children2008，18，1： | 1 |
| 19 | LIGHT, a New Member of the TNF Superfamily, and Lymphotoxin α Are Ligands for Herpesvirus Entry Mediator显示文摘 | Davide N Mauri Reinhard Ebner Rebecca I Montgomery Kristine D Kochel Timothy C Cheung Guo-Liang Yu Steve Ruben Marianne Murphy Roselyn J Eisenberg Gary H Cohen Patricia G Spear Carl F Ware | 1998 | Immunity1998，，： | 1 |
| 20 | Advances in the manufacture, purification and applications of xylo-oligosaccharides as food additives and nutraceuticals显示文摘 | Andres Moure Patricia G ullon Herminia Dominguez | 2006 | Process Biochemistry2006，，41： | 1 |
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