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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 | 内侧固定平台单髁置换术后的冠状面下肢力线是翻修的影响因素显示文摘膝关节单髁置换术(unicompartmental knee arthroplasty,UKA)后患者冠状面的下肢力线被认为是影响手术长期疗效的一个重要因素,但关于最佳的UKA术后下肢力线还没有形成明确共识。一些研究主张术后下肢力线应保持在中立位,而另一些研究认为即使术后下肢力线存在10°的内翻也可获得良好的临床效果。 | Sean E Slaven John P Cody Robert A Sershon Henry Ho Robert H Hopper Jr Kevin B Fricka 李亚坤(整理) 张民(整理) | 2020 | 实用骨科杂志2020，26，12： | 15 |
| 3 | 诊断性试验和策略的证据质量和推荐强度的分级显示文摘GRADE系统能对诊断性试验或策略的证据质量和推荐强度进行分级。本文旨在阐释在此过程中如何考虑患者的重要结局, | Holger J Schünemann Andrew D Oxman Jan Brozek Paul Glasziou Roman Jaeschke Gunn E Vist John W Williams Jr Regina Kunz Jonathan Craig Victor M Montori Patrick Bossuyt Gordon H Guyatt 李晓 黄程 陈耀龙 李幼平 | 2009 | 中国循证医学杂志2009，9，5： | 7 |
| 4 | Sofosbuvir and ledipasvir fixed-dose combination with and without ribavirin in treatment-naive and previously treated patients with genotype 1 hepatitis C virus infection (LONESTAR): an open-label, randomised, phase 2 trial显示文摘 | Eric Lawitz Fred F Poordad Phillip S Pang Robert H Hyland Xiao Ding Hongmei Mo William T Symonds John G McHutchison Fernando E Membreno | 2013 | The Lancet2013，，： | 5 |
| 5 | Guidelines for the Management of Aneurysmal Subarachnoid Hemorrhage: A Statement for Healthcare Professionals From a Special Writing Group of the Stroke Council, American Heart Association显示文摘 | Joshua B. Bederson E Sander Connolly H Hunt Batjer Ralph G. Dacey Jacques E. Dion Michael N. Diringer John E. Duldner Robert E. Harbaugh Aman B. Patel Robert H. Rosenwasser | 2009 | Stroke2009，，3： | 4 |
| 6 | ACC/AHA guidelines for the management of patients with unstable angina and non–st-segment elevation myocardial infarction显示文摘 | Eugene Braunwald Elliott M Antman John W Beasley Robert M Califf Melvin D Cheitlin Judith S Hochman Robert H Jones Dean Kereiakes Joel Kupersmith Thomas N Levin Carl J Pepine John W Schaeffer Earl E Smith David E Steward Pierre Theroux Raymond J Gibbons J | 2000 | Journal of the American College of Cardiology2000，，3： | 4 |
| 7 | 每日1次利拉鲁肽与每日2次艾塞那肽治疗2型糖尿病比较:一项为期26周的随机、平行组、多国开放标记试验(LEAD-6)显示文摘背景与大多数抗高血糖药物不同,胰高血糖素样肽-1(GLP-1)受体激动剂的药理作用依赖于葡萄糖水平,并且有助于减轻患者体重。本研究比较了利拉鲁肽(一种人GLP-1类似物)与艾塞那肽(一种基于醋酸艾塞那肽的GLP-1受体激动剂)治疗2型糖尿病的疗效和安全性。方法对于用最大耐受剂量二甲双胍或(和)磺脲仍控制不良的2型糖尿病成年患者,根据之前服用的抗糖尿病药物进行分层,并随机分配这些患者额外接受利拉鲁肽1.8mg每El1次(n=233)或艾塞那肽10μg每日2次(n=231),进行为期26周的开放标记、平行组、多国(15个国家)研究。主要终点是糖化血红蛋白(HbA1c)水平的变化,疗效分析采用意向性治疗分析。本试验在Clinical Trial.gov注册,注册号为NCT00518882。结果受试者的HbA1c平均基线水平为8.2%。与艾塞那肽相比,利拉鲁肽能显著降低HbA1c平均水平[-1.12%(s=0.08%)vs-0.79%(s=0.08%);疗效差异估计值为-0.33%,95%CI-0.47%~-0.18%;P〈0.0001],并且利拉鲁肽组有更多患者HbA1c水平低于7%(54%vs543%;OR 2.02,95%CI 1.31~3.11;P=0.0015)。利拉鲁肽降低平均空腹血糖的能力也显著优于艾塞那肽[-1.61mmol/Lb=0.20)vs-0.60mmol/L(s=0.20);疗效差异估计值为-1.01mmol/L,95%CI-1.37—-0.65;P〈0.0001],但是其降低早餐和晚餐后血糖的能力较艾塞那肽差。两种药物促进患者体重减轻的作用相似(利拉鲁肽组~3.24kg vs艾塞那肽组-2.87地)。耐受性均较好,但与艾塞那肽组相比,利拉鲁肽组患者恶心的持续时间较短(估计的治疗相关事件率比值为0.448,P〈0.0001),轻度低血糖的发生率也较低(每患者每年的事件发生数为1.93vs2.60;发生率比值为0.55,95%C10.34~0.88:P=0.0131;轻度低血糖的发生率为25.5%掷33.6%)。2例同时注射艾塞那肽和一种磺脲类药物的患者发生了严重的低血糖。结论相对于艾塞那肽每日2次,利拉鲁肽每日1次能显著改善血糖控制水平,且患者的耐受性更好。研究结果提示利拉鲁肽或许是2型糖尿病的一种治疗选择,特别是在减轻体重和低血糖风险作为主要考虑因素的情况下。 | John B Buse Julia Rosenstock Giorgio Sesti Wolfgang E Schmidt Eduard Montanya Jason H Brett Marcin Zychma Lawrence Blonde 赵乐(译) | 2009 | 世界临床医学2009，，11： | 3 |
| 8 | Sofosbuvir with pegylated interferon alfa-2a and ribavirin for treatment-naive patients with hepatitis C genotype-1 infection (ATOMIC): an open-label, randomised, multicentre phase 2 trial显示文摘 | Kris V Kowdley Eric Lawitz Israel Crespo Tarek Hassanein Mitchell N Davis Michael DeMicco David E Bernstein Nezam Afdhal John M Vierling Stuart C Gordon Jane K Anderson Robert H Hyland Hadas Dvory-Sobol Di An Robert G Hindes Efsevia Albanis William T Symo | 2013 | The Lancet2013，，9883： | 3 |
| 9 | Aerosol size distributions of elemental and organic carbon in urban and over-water atmospheres显示文摘 | John H Offenberg Joel E Baker | 2000 | Atmospheric Environment2000，，10： | 2 |
| 10 | Modeling of lithium-ion batteries显示文摘 | JOHN N KAREN E HOOMAN H | 2003 | Journal of Power Sources2003，119，： | 2 |
| 11 | Liraglutide once a day versus exenatide twice a day for type 2 diabetes: a 26-week randomised, parallel-group, multinational, open-label trial (LEAD-6)显示文摘 | John B Buse Julio Rosenstock Giorgio Sesti Wolfgang E Schmidt Eduard Montanya Jason H Brett Marcin Zychma Lawrence Blonde | 2009 | The Lancet2009，，9683： | 2 |
| 12 | 由地震简正模式观测得到的内核各向异性区域变化显示文摘地球的固体内核被对流的液体外核包围,由此创建了驱动地球磁场的地核发电机。用压缩体波研究地震显示出内核各向异性结构的半球性变化,但由于受地震和接收器分布状况所限,这一结论还不够充分。本文中,利用大地震的简正模式分裂函数测定结果,并基于扩展交叉耦合理论,我们观测到了区域变化和内核中东、西两半球的各向异性。这一模式与地球磁场的相似性说明在固化或组构演变过程中由Maxwell应力引起的晶体排列的凝入是产生各向异性的根源。这些观测结果限制了内核超速旋转的总量,但与振荡相符。 | Arwen Deuss Jessica C E Irving John H Woodhouse 洪启宇(译) 左玉玲(校) | 2010 | 国际地震动态2010，，10： | 2 |
| 13 | Enhanced caveolin-1 expression in smooth muscle cells: Possible prelude to neointima formation显示文摘AIM: To study the genesis of neointima formation in pulmonary hypertension(PH), we investigated the role of caveolin-1 and related proteins. METHODS: Male Sprague Dawley rats were given monocrotaline(M, 40 mg/kg) or subjected to hypobaric hypoxia(H) to induce PH. Another group was given M and subjected to H to accelerate the disease process(M + H). Right ventricular systolic pressure, right ventricular hypertrophy, lung histology for medial hypertrophy and the presence of neointimal lesions were examined at 2 and 4 wk. The expression of caveolin-1 and its regulatory protein peroxisome proliferator-activated receptor(PPAR) γ, caveolin-2, proliferative and antiapoptotic factors(PY-STAT3, p-Erk, Bcl-x L), endothelial nitric oxide synthase(e NOS) and heat shock protein(HSP) 90 in the lungs were analyzed, and the results from M + H group were compared with the controls, M and H groups. Double immunofluorescence technique was used to identify the localization of caveolin-1 in pulmonary arteries in rat lungs and in human PH lung tissue. RESULTS: In the M + H group, PH was more severe compared with M or H group. In the 4 wk M+H group, several arteries with reduced caveolin-1 expression in endothelial layer coupled with an increased expression in smooth muscle cells(SMC), exhibited neointimal lesions. Neointima was present only in the arteries exhibiting enhanced caveolin-1 expression in SMC. Lung tissue obtained from patients with PH also revealed neointimal lesions only in the arteries exhibiting endothelial caveolin-1 loss accompanied by an increased caveolin-1 expression in SMC. Reduction in e NOS and HSP90 expression was present in the M groups(2 and 4 wk), but not in the M + H groups. In both M groups and in the M + H group at 2 wk, endothelial caveolin-1 loss was accompanied by an increase in PPARγ expression. In the M + H group at 4 wk, increase in caveolin-1 expression was accompanied by a reduction in the PPARγ expression. In the H group, there was neither a loss of endothelial caveolin-1, eNOS or HSP 90, nor an increase in SMC caveolin-1 expression; or any alteration in PPARγ expression. Proliferative pathways were activated in all experimental groups. CONCLUSION: Enhanced caveolin-1 expression in SMC follows extensive endothelial caveolin-1 loss with subsequent neointima formation. Increased caveolin-1 expression in SMC, thus, may be a prelude to neointima formation. | Jing Huang John H Wolk Michael H Gewitz James E Loyd James West Eric D Austin Rajamma Mathew | 2015 | World Journal of Cardiology2015，7，10： | 2 |
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| 19 | Liraglutide once a day versus exenatide twice a day for type 2 diabetes: a 26-week randomised, parallel-group, multinational, open-label trial (LEAD-6)显示文摘 | John B Buse Julio Rosenstock Giorgio Sesti Wolfgang E Schmidt Eduard Montanya Jason H Brett Marcin Zychma Lawrence Blonde | 2009 | The Lancet . 2009 (9683)2009，，9683： | 1 |
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