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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 | 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 |
| 3 | Development of a quantum-dot-labelled magnetic immunoassay method for circulating colorectal cancer cell detection显示文摘AIM:To detect of colorectal cancer(CRC) circulating tumour cells(CTCs) surface antigens,we present an assay incorporating cadmium selenide quantum dots(QDs) in these paper.METHODS:The principle of the assay is the immunomagnetic separation of CTCs from body fluids in conjunction with QDs,using specific antibody biomarkers:epithelial cell adhesion molecule antibody,and monoclonal cytokeratin 19 antibody.The detection signal was acquired from the fluorescence signal of QDs.For the evaluation of the performance,the method under study was used to isolate the human colon adenocarcinoma cell line(DLD-1) and CTCs from CRC patients' peripheral blood.RESULTS:The minimum detection limit of the assay was defined to 10 DLD-1 CRC cells/mL as fluorescence was measured with a spectrofluorometer.Fluorescenceactivated cell sorting analysis and Real Time RT-PCR,they both have also been used to evaluate the performance of the described method.In conclusion,we developed a simple,sensitive,efficient and of lower cost(than the existing ones) method for the detection of CRC CTCs in human samples.We have accomplished these results by using magnetic bead isolation and subsequent QD fluorescence detection.CONCLUSION:The method described here can be easily adjusted for any other protein target of either the CTC or the host. | Maria Gazouli Anna Lyberopoulou Pericles Pericleous Spyros Rizos Gerassimos Aravantinos Nikolaos Nikiteas Nicholas P Anagnou Efstathios P Efstathopoulos | 2012 | World Journal of Gastroenterology2012，18，32： | 6 |
| 4 | 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 |
| 5 | Pregnancy and inflammatory bowel disease: Do we provide enough patient education? A British study of 1324 women显示文摘AIM To examine patient knowledge and factors influencing knowledge about pregnancy in British women with inflammatory bowel disease(IBD).METHODS This is a post hoc analysis of a study of female members of Crohn's and Colitis United Kingdom, aged 18-45 years who were sent an online questionnaire recording patient demographics, education, employment, marital status, and disease characteristics. Disease related pregnancy knowledge was recorded using Crohn's and colitis pregnancy knowledge score(CCPKnow).RESULTS Of 1324 responders, 776(59%) suffered from Crohn's disease, 496(38%) from ulcerative colitis and 52(4%) from IBD-uncategorised. CCPKnow scores were poor(0-7) in 50.8%, adequate(8-10) in 23.6%, good(11-13) in 17.7% and very good(≥ 14) in 7.8%. Multiple linear regression analysis revealed that higher CCPKnow scores were independently associated with higher educational achievement(P < 0.001), younger age at diagnosis(P = 0.003) and having consulted a health care professional about pregnancy and IBD(P = 0.001). CONCLUSION Knowledge was poor in 50%. Speaking with healthcare professionals was a modifiable factor associated with better knowledge. This illustrates the importance of disease related pregnancy | Isabel Carbery Jihane Ghorayeb Anna Madill Christian P Selinger | 2016 | World Journal of Gastroenterology2016，22，36： | 4 |
| 6 | Ibutilide and novel indexes of ventricular repolarization in persistent atrial fibrillation patients显示文摘AIM: To examine the effect of ibutilide on novel indexes of repolarization in patients with persistent atrial fibrillation (AF). METHODS: We studied consecutive patients scheduled for elective electrical cardioversion. Intravenous ibutilide (1+1mg) was administered before the electrical cardioversion while close electrocardiographic (ECG) monitoring was performed. ECG indexes such as corrected QT interval (QTc), the interval from the peak until the end of T wave (Tpe), and the Tpe/QT ratio were measured before ibutilide infusion and 10 min after the end of infusion. RESULTS: The final study population consisted of 20 patients (mean age: 67.1±9.9 years, 10 men). Six patients were cardioverted pharmacologically and did not proceed to electrical cardioversion. Two patientsdeveloped short non-sustained episodes of torsades de pointes ventricular tachycardia. All but one of the aforementioned ECG indexes increased significantly after ibutilide administration. In specific, the QTc interval increased from 442 ± 29 to 471 ± 37 ms (P=0.037), the Tpe interval in precordial leads from 96 ms (range 80-108 ms) to 101 ms (range 91-119 ms) (P=0.021), the Tpe interval in lead Ⅱ from 79 ms (range 70-88 ms) to 100 ms (range 87-104 ms) (P<0.001), the Tpe/QT ratio in precordial leads from 0.23 ms (range 0.18-0.26 ms) to 0.26 ms (range 0.23-0.28 ms) (P=0.028), and the Tpe interval dispersion from 25 ms (range 23-30 ms) to 35 ms (range 27-39 ms) (P=0.012). However, the Tpe/QT ratio in lead II did not change significantly. CONCLUSION: Ibutilide increases the duration and dispersion of ventricular repolarization. The prognostic value of Tpe and Tpe/QT in the setting of drug-induced proarrhythmia needs further study. | Panagiotis Korantzopoulos Konstantinos P Letsas Anna Kotsia Giannis Baltogiannis Kallirroi Kalantzi Konstantinos Kyrlas John A Goudevenos | 2013 | World Journal of Cardiology2013，5，7： | 3 |
| 7 | 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 |
| 8 | Empagliflozin alleviates podocytopathy and enhances glomerular nephrin expression in db/db diabetic mice显示文摘BACKGROUND Modern guidelines recommend sodium-glucose cotransporter-2(SGLT2)inhibitors as the preferred antihyperglycemic agents for patients with type 2 diabetes and chronic kidney disease.However,the mechanisms underlying the renal protective effect of SGLT2 inhibitors are not fully understood.structure of podocytes and nephrin expression in glomeruli in db/db diabetic mice.METHODS We treated 8-wk-old male db/db mice with EMPA(10 mg/kg/d)or vehicle for 8 wk.Age-matched male db/+mice were included as non-diabetic controls.Parameters of body composition,glycemic and lipid control,and plasma concentrations of leptin,insulin and glucagon were assessed.We evaluated renal hypertrophy as kidney weight adjusted to lean mass,renal function as plasma levels of creatinine,and albuminuria as the urinary albumin-to-creatinine ratio(UACR).Renal structures were studied by light and transmission electron microscopy with a focus on mesangial volume and podocyte structure,respectively.Glomerular nephrin and transforming growth factor beta(TGF-β)were assessed by immunohistochemistry.RESULTS Severe obesity and hyperglycemia developed in db/db mice prior to the start of the experiment;increased plasma concentrations of fructosamine,glycated albumin,cholesterol,leptin,and insulin,and elevated UACR were detected.Mesangial expansion,glomerular basement membrane thickening,and increased area of TGF-βstaining in glomeruli were revealed in vehicle-treated mice.Podocytopathy was manifested by effacement of foot processes;nephrin-positive areas in glomeruli were reduced.EMPA decreased the levels of glucose,fructosamine and glycated albumin,UACR,kidney hypertrophy,mesangial expansion,glomerular basement membrane thickening,and glomerular TGF-βstaining,alleviated podocytopathy and restored glomerular staining of nephrin.CONCLUSION These data indicate that EMPA attenuates podocytopathy in experimental diabetic kidney disease.The anti-albuminuric effect of EMPA could be attributed to mitigation of podocyte injury and enhancement of nephrin expression. | Vadim V Klimontov Anton I Korbut Iuliia S Taskaeva Nataliya P Bgatova Maksim V Dashkin Nikolai BOrlov Anna S Khotskina Evgenii L Zavyalov Thomas Klein | 2020 | World Journal of Diabetes2020，11，12： | 2 |
| 9 | Metabolomic and elemental profiling of blood serum in bladder cancer显示文摘Bladder cancer(BC)is one of the most frequently diagnosed types of urinary cancer.Despite advances in treatment methods,no specific biomarkers are currently in use.Targeted and untargeted profiling of metabolites and elements of human blood serum from 100 BC patients and the same number of normal controls(NCs),with external validation,was attempted using three analytical methods,i.e.,nuclear magnetic resonance,gold and silver-109 nanoparticle-based laser desorption/ionization mass spectrometry(LDI-MS),and inductively coupled plasma optical emission spectrometry(ICP-OES).All results were subjected to multivariate statistical analysis.Four potential serum biomarkers of BC,namely,isobutyrate,pyroglutamate,choline,and acetate,were quantified with proton nuclear magnetic resonance,which had excellent predictive ability as judged by the area under the curve(AUC)value of 0.999.Two elements,Li and Fe,were also found to distinguish between cancer and control samples,as judged from ICP-OES data and AUC of 0.807(in validation set).Twenty-five putatively identified compounds,mostly related to glycans and lipids,differentiated BC from NCs,as detected using LDI-MS.Five serum metabolites were found to discriminate between tumor grades and nine metabolites between tumor stages.The results from three different analytical platforms demonstrate that the identified distinct serum metabolites and metal elements have potential to be used for noninvasive detection,staging,and grading of BC. | Krzysztof Ossolinski Tomasz Ruman Valerie Copie Brian P.Tripet Leonardo B.Nogueira Katiane O.P.C.Nogueira Artur Kołodziej Aneta Płaza-Altamer Anna Ossolinska Tadeusz Ossolinski Joanna Nizioł | 2022 | Journal of Pharmaceutical Analysis2022，12，6： | 2 |
| 10 | Sludge dewatering and stabilization in drying reed beds:characterization of three full-scale systems in Catolonia,Spain显示文摘 | ENRICA U ESTHER L ANNA P | 2009 | Bioresource Technology2009，100，17： | 1 |
| 11 | Ceramic precursor in flame retardant systems显示文摘 | Marosi G Ma' rton A Anna P | 2002 | Polym Degrad Stab2002，77，2： | 1 |
| 12 | Impact of testosterone on body fat composition 显示文摘 | CHIARA DE M STELLA V ANNA P | 2012 | J Cell Physiol2012，227，12： | 1 |
| 13 | Choline and phosphatidylcholine fluorescent derivatives localization in carcinoma ceils studied by laser scanning confocal fluorescence microscopy 显示文摘 | Anna M V Elvira C Antonio P | 2005 | Eur J Cancer2005，41，10： | 1 |
| 14 | Human fear conditioning is related to dopaminergic and serotonergic biological markers显示文摘 | Garpenstrand H Annas P Ekblom J | 2001 | Behav Neurosci2001，115，2： | 1 |
| 15 | Apoptosis induced in neuronal cells by oxidative stress:role played by caspases and intracellular calcium ions显示文摘 | Lucio A Salvatore A Anna P | 2003 | Toxicol Lett2003，139，： | 1 |
| 16 | Synthesis of phosphorus-based flame retardant systems and their use in an epoxy resin显示文摘 | TOLDY A TTH N ANNA P | 2006 | Polymer Degradation and Stability2006，91，3： | 1 |
| 17 | Development of a black carbon-inclusive multi-media model: Application for PAHs in Stockholm显示文摘 | Prevedouros K Anna P C Gustafsson ? | 2008 | Chemosphere2008，70，4： | 1 |
| 18 | Antioxidant activity applying an improved ABTS radical cation decolorization assay 显示文摘 | Re R Pellegrini N Anna P A | 1999 | Free Radical Biology and Medicine1999，26，910： | 1 |
| 19 | Drafting the Genetic Privacy Act: Science, Policy and Practical Considerations显示文摘 | Annas G J Glantz L H Roche P A | 1995 | The Journal of Law Medicine and Ethics1995，23，4： | 1 |
| 20 | Treatment of Fourteen Chronic Active HBSAg^+ ,HBeAg^+ Hepatitis Patients with Low Dose Nature Human Interferon Alpha Administered Orally 显示文摘 | Wladyslawa Z Jacek P Anna K | 1993 | Arch lmmunol Ther Exp1993，41，： | 1 |
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