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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 | Review of nonalcoholic fatty liver disease in women with polycystic ovary syndrome显示文摘Polycystic ovary syndrome(PCOS) is the most common endocrine disorder in reproductive-aged women. Women with PCOS frequently have metabolic complications including insulin resistance(IR), early diabetes, hypertension and dyslipidemia. Recent studies have demonstrated an association between PCOS and another metabolic complication: nonalcoholic fatty liver disease(NAFLD). NAFLD occurs as a result of abnormal lipid handling by the liver, which sensitizes the liver to injury and inflammation. It can progress to nonalcoholic steatohepatitis(NASH), which is characterized by hepatocyte injury and apoptosis. With time and further inflammation, NASH can progress to cirrhosis. Thus, given the young age at which NAFLD may occur in PCOS, these women may be at significant risk for progressive hepatic injury over the course of their lives. Many potential links between PCOS and NAFLD have been proposed, most notably IR and hyperandrogenemia. Further studies are needed to clarify the association between PCOS and NAFLD. In the interim, clinicians should be aware of this connection and consider screening for NAFLD in PCOS patients who have other metabolic risk factors. The optimal method of screening is unknown. However, measuring alanine aminotransferase and/or obtaining ultrasound on high-risk patients can be considered. First line treatment consists of lifestyle interventions and weight loss, with possible pharmacologic interventions in some cases. | Carly E Kelley Ann J Brown Anna Mae Diehl Tracy L Setji | 2014 | World Journal of Gastroenterology2014，20，39： | 11 |
| 3 | 如何设计高质量针刺临床研究:基于证据的专家共识显示文摘本针刺随机对照试验(Randomised controlled trials, RCT)专家共识是基于目前针刺试验面临的最普遍、最关键问题,由临床医生、研究人员、从事针灸和外科的临床试验专家、统计专家、临床流行病学和方法学专家以及患者组成的国际临床研究小组联合制订。该共识将有助于临床试验资助者、注册者以及期刊编辑等评估针刺RCT方案及研究结果的相关性、重要性和质量。 | 张誉清 焦睿珉 Claudia M Witt 劳力行 刘建平 Lehana Thabane Karen J Sherman Mike Cummings Dawn P Richards Eun-Kyung Anna Kim Tae-Hun Kim Myeong Soo Lee Michael E Wechsler Benno Brinkhaus Jun J Mao Caroline A Smith 岗卫娟 刘保延 刘志顺 刘岩 郑晖 吴佳霓 AloBSO Carrasco-Labra Mohit Bhandari Philip J Devereaux 景向红 Gordon Guyatt | 2022 | 英国医学杂志中文版2022，25，6： | 7 |
| 4 | Chronic hepatitis C virus infection and atherosclerosis: Clinical impact and mechanisms显示文摘Hepatitis C virus(HCV)infection represents a major health issue worldwide due to its burden of chronic liver disease and extrahepatic manifestations including cardiovascular diseases,which are associated with excess mortality.Analysis of published studies supports the view that HCV infection should be considered a risk factor for the development of carotid atherosclerosis,heart failure and stroke.In contrast,findings from studies addressing coronary artery disease and HCV have yielded conflicting results.Therefore,meta-analytic reviews and prospective studies are warranted.The pathogenic mechanisms connecting HCV infection,chronic liver disease,and atherogenesis are not completely understood.However,it has been hypothesized that HCV may promote atherogenesis and its complications through several direct and indirect biological mechanisms involving HCV colonization and replication within arterial walls,liver steatosis and fibrosis,enhanced and imbalanced secretion of inflammatory cytokines,oxidative stress,endotoxemia,mixed cryoglobulinemia,perturbed cellular and humoral immunity,hyperhomocysteinemia,hypo-adiponectinaemia,insulin resistance,type 2 diabetes and other components of the metabolic syndrome.Understanding these complex mechanisms is of fundamental importance for the development of novel therapeutic approaches to prevent and to treat vascular complications in patients with chronic HCV infection.Currently,it seems that HCV clearance by interferon and ribavirin treatment significantly reduces non-liver-related mortality;moreover,interferon-based treatment appears to decrease the risk of ischemic stroke. | Luigi E Adinolfi Rosa Zampino Luciano Restivo Amedeo Lonardo Barbara Guerrera Aldo Marrone Fabio Nascimbeni Anna Florio Paola Loria | 2014 | World Journal of Gastroenterology2014，20，13： | 6 |
| 5 | 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 |
| 6 | Rates and risk factors for suicidal ideation,suicide attempts and suicide deaths in persons with HIV:a systematic review and meta-analysis显示文摘Background People living with HIV/AIDS(PLWHA)must contend with a significant burden of disease.However,current studies of this demographic have yielded wide variations in the incidence of suicidality(defined as suicidal ideation,suicide attempt and suicide deaths).Aims This systematic review and meta-analysis aimed to assess the lifetime incidence and prevalence of suicidality in PLWHA.Methods Publications were identified from PubMed(MEDLINE),SCOPUS,OVID(MEDLINE),Joanna Briggs Institute EBP and Cochrane Library databases(from inception to before 1 February 2020).The search strategy included a combination of Medical Subject Headings associated with suicide and HIV.Researchers independently screened records,extracted outcome measures and assessed study quality.Data were pooled using a random-effects model.Subgroup and meta-regression analyses were conducted to explore the associated risk factors and to identify the sources of heterogeneity.Main outcomes were lifetime incidence of suicide completion and lifetime incidence and prevalence of suicidal ideation and suicide attempt.Results A total of 185199 PLWHA were identified from 40 studies(12 cohorts,27 cross-sectional and 1 nested case-control).The overall incidence of suicide completion in PLWHA was 10.2/1000 persons(95%CI:4.5 to 23.1),translating to 100-fold higher suicide deaths than the global general population rate of 0.11/1000 persons.The lifetime prevalence of suicide attempts was 158.3/1000 persons(95%CI:106.9 to 228.2)and of suicidal ideation was 228.3/1000 persons(95%CI:150.8 to 330.1).Meta-regression revealed that for every 10-percentage point increase in the proportion of people living with HIV with advanced disease(AIDS),the risk of suicide completion increased by 34 per 1000 persons.The quality of evidence by Grading of Recommendations,Assessment,Development and Evaluations for the suicide deaths was graded as‘moderate’quality.Conclusions The risk of suicide death is 100-fold higher in people living with HIV than in the general population.Lifetime incidence of suicidal ideation and attempts are substantially high.Suicide risk assessments should be a priority in PLWHA,especially for those with more advanced disease. | Matt Pelton Matt Ciarletta Holly Wisnousky Nicholas Lazzara Monica Manglani Djibril M Ba Vernon M Chinchillli Ping Du Anna E Ssentongo Paddy Ssentongo | 2021 | General Psychiatry2021，34，2： | 3 |
| 7 | Deletion or underexpression of the Y-chromosome genes CDY2 and HSFY is associated with maturation arrest in American men with nonobstructive azoospermia显示文摘成熟拘捕(麻省) 指导致临床的 nonobstructive 精子缺乏的细菌房间开发的失败。尽管人的 Y 染色体的 azoospermic 因素(AZF ) 区域清楚地在一些情况中被含有,因此,远,很,很少对哪个个人, Y 染色体基因为完全的男细菌房间开发是重要的被知道。我们寻求了在可以在在美国人口与麻省联系的 nonobstructive 精子缺乏的致病被含有的 Y 染色体上识别单个基因。有 Y 染色体 microdeletions 的 132 个人的遗传型显型分析被执行。与麻省联系的编码蛋白质的基因被一张遗传型显型地图的视觉分析识别。与麻省联系的基因在 Y 染色体的一个片断以内作为那些基因被选择完全或部分删除了,总是与可恢复的阴囊的精子的麻省和缺席被联系。每个识别基因抄本的表示然后与自发的麻省和妨碍的精子缺乏从病人的分开的队在阴囊的织物与量的 RT-PCR 被测量。为有麻省的协会的十候选人基因在重叠的 Y 染色体的一个 8.4-Mb 片断以内被识别 AZFb 区域。CDY2 和 HSFY 是唯一的识别了在表示的差别在麻省和妨碍的精子缺乏队之间为被观察的基因。有妨碍的精子缺乏的人有 12 褶层 CDY2 抄本的更高相对的表示(1.33 ± 0.40 对 0.11 ± 0.04;P=0.0003 ) 并且 16 褶层 HSFY 抄本的更高的表示(0.78 ± 0.32 对 0.05 ± 0.02;P=0.0005 ) 与有麻省的人相比。CDY2 和 HSFY 也仅仅是在有 Sertoli 房间的病人的 underexpressed 症候群。这些数据显示 CDY2 和 HSFY 位于为精子成熟是重要的,并且是在与麻省从人导出的阴囊的织物的 underexpressed 的 Y 染色体的一个片断以内。这些观察建议在 CDY2 或 HSFY 表示的缺陷能在麻省的致病被含有。 | Peter J Stahl Anna N Mielnik Christopher E Barbieri Peter N Schlegel Darius A Paduch | 2012 | Asian Journal of Andrology2012，14，5： | 3 |
| 8 | Inhibiting Cxcr2 disrupts tumor-stromal interactions and improves survival in a mouse model of pancreatic ductal adenocarcinoma显示文摘 | Ijichi Hideaki Chytil Anna Gorska Agnieszka E Aakre Mary E Bierie Brian Tada Motohisa Mohri Dai Miyabayashi Koji Asaoka Yoshinari Maeda Shin Ikenoue Tsuneo Tateishi Keisuke Wright Christopher V E Koike Kazuhiko Omata Masao Moses Harold L | 2011 | Journal of Clinical Investigation2011，，10： | 3 |
| 9 | Ureteroscopy and stones:Current status and future expectations显示文摘Urolithaisis is becoming an ever increasing urological,nephrological and primary care problem.With a lifetime prevalence approaching 10% and increasing morbidity due to stone disease,the role of ureteroscopy and stone removal is becoming more important.We discuss the current status of stone disease and review the ever increasing role that ureteroscopy has to play in its management.We discuss technological advances that have been made in stone management and give you an overview of when,how and why ureteroscopy is the most common treatment option for stone management.We touch on the role of robotic ureteroscopy and the future of ureteroscopy in the next 10 years. | Anna E Wright Nicholas J Rukin Bhaskar K Somani | 2014 | World Journal of Nephrology2014，3，4： | 2 |
| 10 | 2007 Guidelines for the Management of Arterial Hypertension: The Task Force for the Management of Arterial Hypertension of the European Society of Hypertension (ESH) and of the European Society of Cardiology (ESC)显示文摘 | Giuseppe Mancia Guy De Backer Anna Dominiczak Renata Cifkova Robert Fagard Giuseppe Germano Guido Grassi Anthony M Heagerty Sverre E Kjeldsen Stephane Laurent Krzysztof Narkiewicz Luis Ruilope Andrzej Rynkiewicz Roland E Schmieder Harry AJ Struijker Boudi | 2007 | Journal of Hypertension2007，，6： | 2 |
| 11 | 2007 Guidelines for the Management of Arterial Hypertension: The Task Force for the Management of Arterial Hypertension of the European Society of Hypertension (ESH) and of the European Society of Cardiology (ESC)显示文摘 | Giuseppe Mancia Guy De Backer Anna Dominiczak Renata Cifkova Robert Fagard Giuseppe Germano Guido Grassi Anthony M Heagerty Sverre E Kjeldsen Stephane Laurent Krzysztof Narkiewicz Luis Ruilope Andrzej Rynkiewicz Roland E Schmieder Harry AJ Struijker Boudi | 2007 | Journal of Hypertension2007，，6： | 2 |
| 12 | 向在人的察觉到钙的受体的 allosteric 药的结构的理解显示文摘allosterically 指向人的察觉到钙的受体(CaSR ) 的药有实质的治疗学的潜力,但是当前被限制。给 CaSR 的高分辨率的结构的缺席,我们把 mutagenesis 与一条新奇分析途径并且开发 “ 的分子的建模相结合; enriched”为在 Ca 2+ 在 CaSRs 7 transmembrane (7TM ) 以内的 o 和 allosteric 调节的人领域。修改多重有约束力的地点以适应在结构上的一个扩大的洞多样的 ligands 被识别。Phenylalkylamines 绑在与通常认为的 Ca 2+ o -binding 地点并且向一个细胞外的门厅延长。相反,在结构上和 pharmacologically 不同的 AC-265347 在 7TM 领域以内更深绑。而且,不同氨基酸网络被发现调停由不同调节的人的 cooperativity。这些调查结果可以与不同、潜在地偏导小径的药理学效果便于 allosteric 调节的人的合理设计。 | Katie Leach Karen J Gregory Irina Kufareva Elham Khajehali Anna E Cook Ruben Abagyan Arthur D Conigrave Patrick M Sexton Arthur Christopoulos | 2016 | Cell Research2016，26，5： | 2 |
| 13 | Evaluation of benzo(a)pyrene-induced DNA damage in human endothelial cells using alkaline single cell gel electrophoresis显示文摘 | Annas A Brittebo E Hellman B | 2000 | Mutat Res2000，471，12： | 2 |
| 14 | Delayed neuronal death following perinatal asphxia in rat显示文摘 | Dell' Anna E ChenY Engidawork E | 1997 | Exp Brain Res1997，115，1： | 1 |
| 15 | A comparative study of fuzzy rough sets显示文摘 | Anna Maria Radzikowska Etienne E Kerre | 2002 | Fuzzy Sets and Systems2002，，126： | 1 |
| 16 | Discarding heparins as treatment for progressive stroke in Sweden 2001 to 2008显示文摘 | Marie E Anna S Eva-Lotta G | | 0，，11： | 1 |
| 17 | Accidental hypothermia显示文摘 | Epstein E Anna K | 2006 | BMJ2006，332，7543： | 1 |
| 18 | Wireless capsule endoscopy for obscure small-bowel disorders: Final results of the first pediatric controlled trial显示文摘 | Ana Maria Guilhon de Araujo Sant’Anna Josée Dubois Marie-Claude Miron Ernest G. Seidman | 2005 | Clinical Gastroenterology and Hepatology2005，，3： | 1 |
| 19 | Alternative nuclear functions for NF-KB family members显示文摘 | Llufs E Anna B Maria C M | 2011 | Am J Cancer Res2011，1，4： | 1 |
| 20 | Ultrastructural organization and micromechanical properties of shark tooth enameloid显示文摘 | Joachim E Anna M J Dierk R | 2014 | Acta Biomaterialia2014，10，9： | 1 |
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