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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
2AGNP精神科治疗药物监测共识指南:2011显示文摘治疗药物监测(Therapeutic drug monitoring,TDM),如通过定量测定血清或血浆药物浓度指导用药剂量优化,已经成为对患者进行精神药物治疗的很有价值的工具。在患者用药依从性难以判断、药物耐受性不佳、治疗剂量下无效以及可能存在药代动力学药物-药物相互作用等情况下,测定药物浓度是很有用的。在精神科,有可能明显获益于TDM的主要患者群体包括儿童、孕妇、老年患者、智力障碍患者、涉及司法的患者、已知或怀疑携带药代动力学相关基因变异的患者,以及合并躯体疾病影响药代动力学的患者。然而,只有将TDM充分整合到临床治疗过程中去,才能发挥其优化药物治疗的潜在优势。为了促进TDM的合理应用,神经精神药理学与药物精神病学协会(Arbeitsgemeinschaft für Neuropsychopharmakologie und Pharmakopsychiatrie,AGNP)的TDM专家组在2004年发表了精神药物治疗药物监测指南。之后,随着知识不断更新,又有许多可能需要进行TDM的新药上市。因此,本次更新将神经精神药物的种类扩展到了128种,并将其TDM必要性划分为从'强烈推荐'到'可能有用'的四个等级。经过大量细致且全面的文献检索与分门别类的汇总整理,将基于循证医学理念的'治疗参考浓度范围'和'剂量相关参考浓度范围'呈现给大家。本共识指南引入了'实验室警戒浓度'的新概念,即实验室需要马上告知治疗医生的药物浓度上限。本共识指南还给出了诸如药物作为细胞色素P450酶的底物和抑制剂的性质,代谢物与母药浓度比值的常见范围,以及与结果解释相关的内容,还提供了何时将TDM与遗传药理学检测相结合的建议。遵循本指南,有助于改善许多患者精神药物治疗的效果,特别是那些存在药代动力学异常的患者。TDM是一门交叉学科,有时针对看起来不一致的数据,需要多学科坦诚地讨论,只有这样,患者才能从这种合作中获益。Hiemke C Baumann P Bergemann N Conca A Dietmaier O Egberts K Fric M Gerlach M Greiner C Gründer G Haen E Havemann-Reinecke U Jaquenoud Sirot E Kirchherr H Laux G Lutz UC Messer T Müller MJ Pfuhlmann B Rambeck B Riederer P Schoppek B Stingl J Uhr M Ulrich S Waschgler R Zernig G 李文标(译) 果伟(译) 阮灿军(译) 贺静(译) 汤宜朗(审校) 王传跃(审校) 2016实用药物与临床2016,19,10:37
3腹股沟疝复发的时间分析显示文摘目的假设不同术式疝修补术术后复发的发病过程是不同的,那么疝复发的时间也是不同的。该研究的目的是分析影响初次手术到复发后再次手术时间间隔的危险因素。方法研究数据来自瑞典疝登记注册系统。将5年随访期间的每一年的资料作为亚组分列,后合为大组。对于每个危险因素以再次手术为研究终点,运用Cox回归分析复发时间与危险因素之间的关系。结果共分析了142578例,其中7.7%是女性,年龄平均59岁。5年总体复发率为4.3%。多因素分析显示复发疝修补后再次复发的时间较早(P<0.05);第一次手术后如果发生并发症,则发生复发也较早(P<0.05);缝合修补或腹腔镜修补后的复发要早于开放式补片修补者(P<0.05)。通过单因素分析提示,所有缝合修补的早期复发的危险要高于所有补片修补早期复发的危险(P<0.05)。结论不同术式疝修补术后复发的发病过程是不同的。腹腔镜修补、传统疝修补术(不应用补片)和复发疝修补术后早期复发率高可能是由于手术技术失误率较高。Magnusson N Nordin P Hedberg M Gunnarsson U Sandblom G 2011中国实用外科杂志2011,31,4:20
4Confocal laser endomicroscopy and immunoendoscopy for real-time assessment of vascularization in gastrointestinal malignancies显示文摘Gastrointestinal cancers represent a major cause of morbidity and mortality,with incomplete response to chemotherapy in the advanced stages and poor prognosis.Angiogenesis plays a crucial part in tumor growth and metastasis,with most gastrointestinal cancers depending strictly on the development of a new and devoted capillary network.Confocal laser endomicroscopy is a new technology which allows in vivo microscopic analysis of the gastrointestinal mucosa and its microvascularization during ongoing endoscopy by using topically or systemically administered contrast agents.Targeting markers of angiogenesis in association with confocal laser endomicroscopic examination(immunoendoscopy),as a future challenge,will add functional analysis to the morphological aspect of the neoplastic process.This review describes previous experience in endomicroscopic examination of the upper and lower digestive tract with emphasis on vascularization,resulting in a broad spectrum of potential clinical applications,and also preclinical research that could be translated to human studies.Dan Ionut Gheonea Tatiana Crtnǎ Tudorel Ciurea Carmen Popescu Anca Bǎdǎrǎu Adrian Sǎftoiu 2011World Journal of Gastroenterology2011,17,1:6
5健康领域的文化能力显示文摘1背景 尽管人类对其他社会的兴趣纵贯历史的各个阶段,但是检验不同文化概念对人类健康实践的影响从20世纪才开始,当时是伴随着长期的人类学田野调查产生的,这些田野调查揭露了不同文化之间相关卫生实践的多样性、复杂性和连续性。Napier A D Ancarno C Butler B Calabrese j Chater A Chatterjee H Guesnet F Home R Jacyna S Jadhav S Macdonald A Neuendorf U Parkhurst A Reynolds R Scambler G Shamdasani S Smith S Z Stougaard-Nielsen J Thomson L Tyler N Volkmann A M Walker T Watson J Williams AC Willott C Wilson J Woolf K 2016中国卫生政策研究2016,9,2:5
6Evolution of plasma parameters in an Ar-N2/He inductive plasma source with magnetic pole enhancement显示文摘Magnetic pole enhanced inductively coupled plasmas(MaPE-ICPs) are a promising source for plasma-based etching and have a wide range of material processing appUcations.In the present study Langmuir probe and optical emission spectroscopy were used to monitor the evolution of plasma parameters in a MaPE-ICP Ar-N_2/He mixture plasma.Electron density(n_e) and temperature(T_e),excitation temperature(T_(exc)),plasma potential(V_p),skin depth(δ) and the evolution of the electron energy probability function(EEPF) are reported as a function of radiofrequency(RF) power,pressure and argon concentration in the mixture.It is observed that n_e increases while T_e decreases with increase in RF power and argon concentration in the mixture.The emission intensity of the argon line at 750.4 nm is also used to monitor the variation of the 'high-energy tail' of the EEPF with RF power and gas pressure.The EEPF has a'bi-Maxwellian' distribution at low RF powers and higher pressure in a pure N_2 discharge.However,it evolves into a 'Maxwellian' distribution at RF powers greater than 70 W for pure N_2,and at 50 W for higher argon concentrations in the mixture.The effect of argon concentration on the temperatures of two electron groups in the 'bi-Maxwellian' EEPF is examined.The temperature of the low-energy electron group T_L shows a decreasing trend with argon addition until the 'thermalization' of the two temperatures occurs,while the temperature of high-energy electrons T_H decreases continuously.Maria YOUNUS N U REHMAN M SHAFIQ M NAEEM M ZAKA-UL-ISLAM M ZAKAULLAH 2017Plasma Science and Technology2017,19,2:2
7Landsat TM image forward/reverse scan banding: characterization and correction 显示文摘Fuseo L Frei U Treverse D Blonda P N Pasquariello G and Milillo G 1986International Journal of Remote Sensing1986,7,:2
8Performance and limitations of MoS2/Ti composite coated inserts显示文摘Renevier N M Oosterling H Konig U 2003Surface and Coatings Technology2003,172,:2
9文化、不平等性与卫生服务提供显示文摘1动态不平等性对基层医疗卫生人力的影响 政治、社会、文化、专业群体皆建立在一致且常规的人类行为之上。当遭受巨大变革和内外压力时,这些群体会变得十分脆弱。尤其在动荡时期,这些群体往往更关注社会和文化的差异性,而非二者的一致性。尽管社会中的个体思维和行为会呈现较大的差异,但对健康的感知具有统一性,并在更广范围人群内尤为突出,这主要归因于文化价值观的作用。广义的文化心态会随着时间和地理位置的不同而不同,就像健康的社会决定因素也会因文化类型的不同而产生差异。Napier A D Ancarno C Butler B Calabrese J Chater A Chatterjee H Guesnet F Horne R Jacyna S Jadhav S Macdonald A Neuendorf U Parkhurst A Reynolds R Scambler G Shamdasani S Smith S Z Stougaard-Nielsen J Thomson L Tyler N Volkmann A M Walker T Watson J Williams A C Willott C Wilson J Woolf K 2016中国卫生政策研究2016,9,3:2
10Clinical evaluation of submucosal colonic lipomas: Decision making显示文摘甚至脂肪瘤是胃肠道的最普通的间充质的良性瘤,征兆的结肠的表示是稀罕的。此处,我们评估了受不了结肠的脂肪瘤的各种各样的尺寸的四个病人并且由不同治疗学的形式来临了。Oge Tascilar Güldeniz Karadeniz Cakmak Banu Dogan Gün Bülent Hamdi U(?)an Hakan Balbaloglu Ali Cesur Ali Ugur Emre Mustafa Comert Lütfü Oktay Erdem Selim Aydemir 2006World Journal of Gastroenterology2006,12,31:2
11Performance and limitation of hybrid PECVD (hard coating)-PVD magnetron sputtering (MoS2/Ti composite) coated inserts tested for dry high speed milling of steel and grey cast iron显示文摘Renevier N M Oosterling H Konig U Surface and Coatings Techno0,,:2
12Bayesian probabilistic network modeling of remifentanil and propofol interaction on wakeup time after close-loop controlled anesthesia显示文摘Bothner U Milne S E Kenny G N C 2002J Clin Monit2002,17,:2
13Instantaneous frequency and wave mode identification in a magnetosheath using few spatial points显示文摘Observational data such as those obtained from the magnetosheath in the downstream of Earth's bow shock have waveforms that differ from those of sinusoidal signals. In practice, they are not even aggregates of sinusoidal signals. Therefore, the frequency decomposition for the data requires technique that will account for the time-varying features of the data that will lead to deduction of physical meaning of the observations. The combination of empirical mode decomposition (EMD) and Hilbert transform has been used for extracting the various contributing oscillatory modes (EMDs) and the instantaneous frequency determination (Hilbert transform) of every physically meaningful mode called intrinsic mode function (IMF). The resulting instantaneous frequencies are used to determine instantaneous wave vectors. The combination of the instantaneous frequencies and wave vectors is useful in the identification of wave modes based on the characteristics of the waves. The results show that EMD-Hilbert can be more reliable than simple Hilbert transform alone.Nathaniel E U Beloff N George N J 2013Chinese Physics B2013,22,8:2
14Toxicity of complex chemical mixturees: acute and long-term effects on different life stages of zebrafish(Brachydanio rerio)显示文摘Ensenbach U Roland N 1995Ecotoxicity and Environmental Safety1995,30,2:2
15Structural, electronic, and optical properties of ZnO_(1-x)Se_x alloys using first-principles calculations显示文摘The structural, electronic, and optical properties of binary ZnO, ZnSe compounds, and their ternary ZnO 1-x Se x alloys are computed using the accurate full potential linearized augmented plane wave plus local orbital (FP-LAPW + lo) method in the rocksalt (B1) and zincblende (B3) crystallographic phases. The electronic band structures, fundamental energy band gaps, and densities of states for ZnO 1-x Se x are evaluated in the range 0 ≤ x ≤ 1 using Wu-Cohen (WC) generalized gradient approximation (GGA) for the exchange-correlation potential. Our calculated results of lattice parameters and bulk modulus reveal a nonlinear variation for pseudo-binary and their ternary alloys in both phases and show a considerable deviation from Vegard's law. It is observed that the predicted lattice parameter and bulk modulus are in good agreement with the available experimental and theoretical data. We establish that the composition dependence of band gap is semi-metallic in B1 phase, while a direct band gap is observed in B3 phase. The calculated density of states is described by taking into account the contribution of Zn 3d, O2p, and Se 4s, and the optical properties are studied in terms of dielectric functions, refractive index, reflectivity, and energy loss function for the B3 phase and are compared with the available experimental data.Muhammad Rashid Fayyaz Hussain Muhammad Imran S A Ahmad N A Noor M U Sohaib S M Alay-e-Abbas 2013Chinese Physics B2013,22,8:2
16Management of Recurrent Malignant Pleural Effusion with Chemical Pleurodesis显示文摘Dalokay Kilic Hadi Akay ?evket Kavuk?u Hakan Kutlay Ayten Kayi Cangir Serkan En?n Cem Kadilar 2005Surgery Today2005,,8:2
17Competition between fusion-evaporation and multifragmentation in central collisions in ^(58)Ni+^(48)Ca at 25A MeV显示文摘The experimental data concerning the58Ni+48Ca reaction at Elab(Ni)=25A MeV,collected by using the CHIMERA 4π device,have been analyzed in order to investigate the competition among different reaction mechanisms for central collisions in the Fermi energy domain.As a main criterion for centrality selection we have chosen the flow angle(flow) method,making an event-by-event analysis that considers the shape of events,as it is determined by the eigenvectors of the experimental kinetic-energy tensor.For the selected central events(flow >60°) some global variables,good to characterize the pattern of central collisions have been constructed.The main features of the reaction products were explored by using different constraints on some of the relevant observables,like mass and velocity distributions and their correlations.Much emphasis was devoted,for central collisions,to the competition between fusion-evaporation processes with subsequent identification of a heavy residue and a possible multifragmentation mechanism of a well defined(if any) transient nuclear system.Dynamical evolution of the system and pre-equilibrium emission were taken into account by simulating the reactions in the framework of transport theories.Different approaches have been envisaged(dynamical stochastic BNV calculations + sequential SIMON code,QMD,CoMD,etc.).Preliminary comparison of the experimental data with BNV calculations shows reasonable agreement with the assumption of sequential multifragmentation emission in the mass region of IMFs close to the heavy residues.Possible deviations from sequential processes were found for those IMFs in the region of masses intermediate between the mass of heavy residues and the mass of light IMFs.Further simulations are in progress.The experimental analysis will be enriched also by information obtained inspecting the IMF-IMF correlation function,in order to elucidated the nature of space-time decay property of the emitting source associated with events having the largest IMF multiplicity.FRANCALANZA L ABBONDANNO U AMORINI F BARLINI S BINI M BOUGAULT R BRUNO M CARDELLA G CASINI G AGOSTINO M D' De FILIPPO V De SANCTIS J GERACI E GIUSSANI A GRAMEGNA F GUIOT B KRAVCHUK V La GUIDARA E LANZALONE G Le NEINDRE N MAIOLINO C MARINI P MORELLI L OLMI A PAGANO A PAPA M PIANTELLI S PIRRONE S POLITI G POGGI G PORTO F RUSSOTTO P RIZZO F VANNINI G VANNUCCI L 2013Nuclear Science and Techniques2013,24,5:2
18Helv Chim Acta显示文摘Ruegg R Gliir U Goel R N 195942:2616-26201959,42,:1
19Intravenous transfusion of endothelial progeni- tor cells reduces neointima formation after vaseular injury显示文摘Werner N Junk S Lads U 2003Cite Res2003,93,2:1
20Compartment-specific expression and function of the chemokine IP-10/CXCL10 in a model of renal endothelial microvascular injury显示文摘Panzer U Steinmetz O M Reinking R R Meyer T N Fehr S Schneider A 2006J Am Soc Nephrol2006,17,:1
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