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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
2Glypican-3和CD34免疫组化染色在肝细胞癌与良性肝细胞性病变鉴别诊断中的价值显示文摘Coston W M P Loera S Lau S K 黄文斌(摘译) 2008临床与实验病理学杂志2008,24,3:31
3成人、儿童及孕妇特发性血小板减少性紫癜诊治指南显示文摘特发性血小板减少性紫癜(ITP)是一种自体免疫性疾病,以持续性血小板减少为特征(血小板<150×109/L).其发病机理是自身抗体与血小板抗原结合导致它们在未成熟时即被网状内皮系统,特别是在脾脏中被破坏引起血小板减少.Provan D Newland A Norfolk D Bolton-Maggs P Lilleyman J Greer I May A Murphy M Ouwehand W Watson S 李振宇 徐开林 2004国外医学(输血及血液学分册)2004,27,4:25
4Mitogen activated protein (MAP) kinase signal transduction pathways and novel anti-inflammatory targets显示文摘Hommes D W Peppelenbosch M P van Deventer S J 2003Gut2003,52,1:14
5水解蛋白质化学改性(英文)显示文摘从含铬废弃物提取的水解蛋白质与不同量的戊二醛 ,在不同的温度下反应。用聚酰胺凝胶电泳法 (SDS -PAGE)分析了改性蛋白质的分子量及分子量分布。用CanonManning粘度法测定了改性产物的粘度。实验表明改性产物的分子量随戊二醛的用量增加而增加。最佳的戊二醛用量约为水解胶原质量的 12 % ,反应温度大于 6 0℃。同时 ,用改性产物做了皮革的填充实验 ,用萤光标记改性胶原 ,通过扫描电镜研究了填充皮革的纤维结构。研究结果表明 ,改性产物具有较好的填充性能 ,采用适当的应用工艺 ,改性产物可能用作皮革填充剂。陈武勇 Brown E M Taylor M M Cooke P H Marmer W N 2002四川大学学报(工程科学版)2002,34,6:9
6Gastroenteropancreatic neuroendocrine tumours显示文摘Irvin M Modlin Kjell Oberg Daniel C Chung Robert T Jensen Wouter W de Herder Rajesh V Thakker Martyn Caplin Gianfranco Delle Fave Greg A Kaltsas Eric P Krenning Steven F Moss Ola Nilsson Guido Rindi Ramon Salazar Philippe Ruszniewski Anders Sundin 2008Lancet Oncology2008,,1:8
7Nationwide trends and predictors of inpatient mortality in 83884 transjugular intrahepatic portosystemic shunt显示文摘AIM: To evaluate and validate the national trends and predictors of in-patient mortality of transjugular intrahepatic portosystemic shunt(TIPS) in 15 years.METHODS: Using the National Inpatient Sample which is a part of Health Cost and Utilization Project, we identified a discharge-weighted national estimate of 83884 TIPS procedures performed in the United States from 1998 to 2012 using international classification of diseases-9 procedural code 39.1. The demographic, hospital and co-morbility data were analyzed using a multivariant analysis. Using multi-nominal logistic regression analysis, we determined predictive factors related to increases in-hospital mortality. Comorbidity measures are in accordance to the Comorbidity Software designed by the Agency for Healthcare Research and Quality.RESULTS: Overall, 12.3% of patients died during hospitalization with downward trend in-hospitalmortality with the mean length of stay of 10.8 ± 13.1 d. Notable, African American patients(OR = 1.809 vs Caucasian patients, P < 0.001), transferred patients(OR = 1.347 vs non-transferred, P < 0.001), emergency admissions(OR = 3.032 vs elective cases, P < 0.001), patients in the Northeast region(OR = 1.449 vs West, P < 0.001) had significantly higher odds of inhospital mortality. Number of diagnoses and number of procedures showed positive correlations with in-hospital death(OR = 1.249 per one increase in number of procedures). Patients diagnosed with acute respiratory failure(OR = 8.246), acute kidney failure(OR = 4.359), hepatic encephalopathy(OR = 2.217) and esophageal variceal bleeding(OR = 2.187) were at considerably higher odds of in-hospital death compared with ascites(OR = 0.136, P < 0.001). Comorbidity measures with the highest odds of in-hospital death were fluid and electrolyte disorders(OR = 2.823), coagulopathy(OR = 2.016), and lymphoma(OR = 1.842).CONCLUSION: The overall mortality of the TIPS procedure is steadily decreasing, though the length of stay has remained relatively constant. Specific patient ethnicity, location, transfer status, primary diagnosis and comorbidities correlate with increased odds of TIPS in-hospital death.Edward Wolfgang Lee Andrew Kuei Sammy Saab Ronald W Busuttil Francisco Durazo Steven-Huy Han Mohamed M El-Kabany Justin P Mc Williams Stephen T Kee 2016World Journal of Gastroenterology2016,22,25:7
8美白牙膏去除牙外源性色斑的八周效果观察显示文摘目的 :评价含有 1%焦磷酸钠、7%三聚硫酸钠、0 .2 4 3 %氟化钠及 10 %高清洁二氧化硅的牙膏减少外源性牙色斑的效果。方法 :采用双盲、分层、二单位平行观察的临床研究方法。根据改良 L obene色斑指数 (L obene stain in-dex m ethod)均数、性别、吸烟习惯将 91名年龄为 18~ 5 5岁的研究对象平衡地分为两组 ,随机地分配使用试验或对照牙膏。于基线、第 4周及第 8周固定由一名检查者完成研究对象的色斑指数测定。结果 :86人完成了该研究。8周临床研究表明 ,使用美白牙膏的研究对象较对照组的牙齿色斑指数均数降低了 3 7.1% (P=0 .0 0 0 1)。结论 :与对照组牙膏相比 ,使用含有 1%焦磷酸钠、7%三聚硫酸钠、0 .2 4 3 %氟化钠及 10 %高清洁二氧化硅的牙膏可以有效地减少牙外源性色斑。胡德渝 庞若愚 佘晓晴 雷德伦 Volpe A R DeVizio W Petrone M E Zhang Y P Chaknis P Miller S Miller J 1999华西口腔医学杂志1999,17,3:7
9High-density SNP-based genetic maps for the parents of an outcrossed and a selfed tetraploid garden rose cross, inferred from admixed progeny using the 68k rose SNP array显示文摘Dense genetic maps create a base for QTL analysis of important traits and future implementation of marker-assisted breeding.In tetraploid rose,the existing linkage maps include<300 markers to cover 28 linkage groups(4 homologous sets of 7 chromosomes).Here we used the 68k WagRhSNP Axiom single-nucleotide polymorphism(SNP)array for rose,in combination with SNP dosage calling at the tetraploid level,to genotype offspring from the garden rose cultivar‘Red New Dawn’.The offspring proved to be not from a single bi-parental cross.In rose breeding,crosses with unintended parents occur regularly.We developed a strategy to separate progeny into putative populations,even while one of the parents was unknown,using principle component analysis on pairwise genetic distances based on sets of selected SNP markers that were homozygous,and therefore uninformative for one parent.One of the inferred populations was consistent with self-fertilization of‘Red New Dawn’.Subsequently,linkage maps were generated for a bi-parental and a self-pollinated population with‘Red New Dawn’as the common maternal parent.The densest map,for the selfed parent,had 1929 SNP markers on 25 linkage groups,covering 1765.5 cM at an average marker distance of 0.9 cM.Synteny with the strawberry(Fragaria vesca)genome was extensive.Rose ICM1 corresponded to F.vesca pseudochromosome 7(Fv7),ICM4 to Fv4,ICM5 to Fv3,ICM6 to Fv2 and ICM7 to Fv5.Rose ICM2 corresponded to parts of F.vesca pseudochromosomes 1 and 6,whereas ICM3 is syntenic to the remainder of Fv6.Mirjana Vukosavljev Paul Arens Roeland E Voorrips Wendy P C van't Westende G D Esselink Peter M Bourke Peter Cox W Eric van de Weg Richard G F Visser Chris Maliepaard Marinus J M Smulders 2016Horticulture Research2016,3,1:6
10Osteoprotegerin: A Novel Secreted Protein Involved in the Regulation of Bone Density显示文摘W.S Simonet D.L Lacey C.R Dunstan M Kelley M.-S Chang R Lüthy H.Q Nguyen S Wooden L Bennett T Boone G Shimamoto M DeRose R Elliott A Colombero H.-L Tan G Trail J Sullivan E Davy N Bucay L Renshaw-Gegg T.M Hughes D Hill W Pattison P Campbell S Sander G Van 1997Cell1997,,2:6
11Long-term irritable bowel syndrome symptom control with reintroduction of selected FODMAPs显示文摘AIM To investigate the long-term effect of dietary education on a low fermentable oligosaccharide, disaccharide and polyol(FODMAP) diet on irritable bowel syndrome(IBS) symptoms and quality of life(Qo L).METHODS Participants with IBS(Rome III) were randomized to two groups. Group I commenced a low FODMAP diet at baseline. At three months, group II, so far a comparator group, crossed over to a low FODMAP diet while group I started re-challenging foods. All patients completed the IBS SSS(IBS symptom severity scoring system, 0-500 points increasing with severity), IBS Qo L questionnaire(0-100 increasing with Qo L), a FODMAP specific food frequency questionnaire and provided a stool sample at baseline, three and six months for microbiome analysis.RESULTS Fifty participants were enrolled into group I(n = 23) or group II(n = 27). Participants in both groups were similar in baseline values but with more men in group I. There was a significantly lower IBS SSS(275.6 ± 63.6 to 128.8 ± 82.5 vs 246.8 ± 71.1 to 203.6 ± 70.1)(P < 0.0002) and increased Qo L(68.5 ± 18.0 to 83 ± 13.4 vs 72.9 ± 12.8 to 73.3 ± 14.4)(P < 0.0001) in group I vs group II at 3 mo. The reduced IBS SSS was sustained at 6 mo in group I(160 ± 102) and replicated in group II(124 ± 76). Fiber intake decreased on the low FODMAP diet(33 ± 17 g/d to 21 ± 8 g/d)(P < 0.01) and after re-introducing FODMAP containing foods increased again to 27 ± 9 g/d. There was no change seen in the intestinal microbiome when participants adopted a low FODMAP diet.CONCLUSION This study demonstrated that a reduction in FODMAPs improves symptoms in IBS and this improvement can be maintained while reintroducing FODMAPs.Ruth M Harvie Alexandra W Chisholm Jordan E Bisanz Jeremy P Burton Peter Herbison Kim Schultz Michael Schultz 2017World Journal of Gastroenterology2017,23,25:5
12多糖和寡糖的体外发酵特性及其对鸡盲肠微生物菌群的影响显示文摘本研究采用体外累积发酵产气法和16SrDNA指纹图谱鉴定技术研究了来自香菇、银耳和黄芪的天然免疫活性多糖(LenE,TreE和AstE)及酵母胞壁甘露寡糖(MOS)对鸡肠道微生物菌群及其发酵特性的影响。结果表明,三种多糖提取物的总糖含量均占干物质的60%以上,而MOS总糖含量在90%以上。多糖和寡糖具有不同的发酵模式;MOS、AstE和LenE三种糖的发酵模式相似,呈一阶段发酵模式;TreE呈两阶段的发酵模式。三种糖中,MOS和AstE发酵速度较TreE快。MOS和AstE在发酵后总VFA产量最高,pH最低;黄芪多糖发酵后产生较多的直链脂肪酸和较低的氨。这些多糖和寡糖提取物影响肠道微生物的活性和组成成分,体现在发酵模式和发酵终产物的显著改变上。以上研究结果表明,来自香菇、银耳和黄芪的天然免疫活性多糖(LenE,TreE和AstE)及酵母胞壁甘露寡糖(MOS)在体外发酵后,均具有显著改变鸡盲肠微生物发酵终产物的含量和盲肠微生物活性的作用。李万坤 郭福存 赵兴绪 Williams B A Kwakkel R P Verstegen M W A 2007动物营养学报2007,19,3:5
13CYP24A1 inhibition facilitates the anti-tumor effect of vitamin D3 on colorectal cancer cells显示文摘AIM:The effects of vitamin D3 have been investigated on various tumors, including colorectal cancer (CRC). 25-hydroxyvitamin-D3-24-hydroxylase (CYP24A1), the enzyme that inactivates the active vitamin D3 metabolite 1,25-dihydroxyvitamin D3 (1,25-D3), is considered to be the main enzyme determining the biological halflife of 1,25-D3. During colorectal carcinogenesis, the expression and concentration of CYP24A1 increases significantly, suggesting that this phenomenon could be responsible for the proposed efficacy of 1,25-D3 in the treatment of CRC. The aim of this study was to investigate the anti-tumor effects of vitamin D3 on the human CRC cell line Caco-2 after inhibition of the cytochrome P450 component of CYP24A1 activity. METHODS:We examined the expression of CYP24A1 mRNA and the effects of 1,25-D3 on the cell line Caco-2 after inhibition of CYP24A1. Cell viability and proliferation were determined by means of sulforhodamine-B staining and bromodeoxyuridine incorporation, respectively, while cytotoxicity was estimated via the lactate dehydrogenase content of the cell culture supernatant. CYP24A1 expression was measured by realtime reverse transcription polymerase chain reaction. A number of tetralone compounds were synthesized to investigate their CP24A1 inhibitory activity. RESULTS:In response to 1,25-D3, CYP24A1 mRNA expression was enhanced significantly, in a time- and dose-dependent manner. Caco-2 cell viability and proliferation were not influenced by the administration of 1,25-D3 alone, but were markedly reduced by coadministration of 1,25-D3 and KD-35, a CYP24A1-inhibiting tetralone. Our data suggest that the mechanism of action of co-administered KD-35 and 1,25-D3 does not involve a direct cytotoxic effect, but rather the inhibition of cell proliferation. CONCLUSION:These findings demonstrate that the selective inhibition of CYP24A1 by compounds such as KD-35 may be a new approach for enhancement of the anti-tumor effect of 1,25-D3 on CRC.János P Kósa Péter Horváth János Wlfling Dóra Kovács Bernadett Balla Péter Mátyus Evelin Horváth Gábor Speer István Takács Zsolt Nagy Henrik Horváth Péter Lakatos 2013World Journal of Gastroenterology2013,19,17:5
14Correlation of serum insulin like growth factor-I with retinopathy in Malaysian pregnant diabetics显示文摘AIM:To study the association of serum insulin-like growth factor-I(IGF-I) with diabetic retinopathy.· METHODS:Serum IGF-1 levels were measured in 25 pregnant diabetic patients and 25 pregnant non-diabetic patients who were matched for age,ethnicity,parity and period of gestation.Fundus examination was performed in both groups at 28,32 and 36 weeks of gestation.RESULTS:The serum IGF-I level was significantly elevated in pregnant diabetics compared to pregnant non-diabetics(366±199μg/L vs 184±89μg/L,(P=0.0001) at 24 weeks,535±251μg/L vs 356±89μg/L,(P=0.007) at 32 weeks and 404±166μg/L vs 264±113μg/L,(P=0.003) at 36 weeks of gestation).The pregnant diabetics with established diabetes had significantly higher IGF-1 level than gestational diabetes at 28,32 and 36 weeks of gestation.The serum IGF-I level in pregnant diabetics with retinopathy was significantly higher than in those without retinopathy at all periods of gestation.· CONCLUSION:Increased serum IGF-1 in pregnancy may increase the risks for retinopathy.S Adzura M Muhaya M Normalina A M Zaleha W P Sharifa Ezat I Tajunisah 2011International Journal of Ophthalmology(English edition)2011,4,1:4
15初级医疗排除肺栓塞:格式塔理论(Gestalt)和威尔斯规则(Wells Rule)的诊断表现对比显示文摘目的威尔斯规则等诊断预测模式可以安全排除疑似肺栓塞。然而,医生的自主可能性评估(格式塔理论)的利用也很常见。评估这两种方法在初级医疗中的诊断表现。方法家庭医生以0—100%的格式塔理论评分对肺栓塞的可能性进行评估,并计算转诊至二级医疗机构进行确诊的疑似肺栓塞患者598例的威尔斯评分。对比两种方法的识别能力(C统计量值)。之后,根据肺栓塞风险类别,将患者分层。对于格式塔理论,低于20%和D-二聚体试验阴性被视为低风险;对于威尔斯规则,4分及以下和D-二聚体试验阴性被视为低风险。对比灵敏度、特异度、有效率(在整个群组中的低风险患者比例)和失败率(被列入低风险的肺栓塞患者)。结果在随访3个月内,73例(12%)患者被确诊为静脉血栓栓塞(基线肺栓塞替代)。格式塔理论与威尔斯规则的C统计量值分别为0.77[95%CI(0.70,0.83)]和0.80[95%CI(0.75,0.86)]。通过格式塔理论识别的152例低风险患者中,有2例患者被遗漏,失败率为1.3%[95%CI(0.2%,4.7%)],有效率为25%[95%CI(22%,29%)];通过威尔斯规则识别的272例低风险患者中,有4例患者被遗漏,失败率为1.5%[95%CI(0.4%,3.7%)],有效率为45%[95%CI(41%,50%)]。结论在初级医疗中,结合D-二聚体试验,格式塔理论分数低于20%和威尔斯规则分数为4分及以下的患者可排除肺栓塞的可能。且威尔斯规则更加有效,可以排除更大比例的疑似患者。HENDRIKSEN J M LUCASSEN W A ERKENS P M 本刊编辑部 2016中国全科医学2016,19,19:4
16Small interfering RNA inhibits SARS-CoV nucleocapsid gene expression in cultured cells and mouse muscles显示文摘Zhao P Qin ZL Ke JS Lu Y Liu M Pan W Zhao LJ Cao J Qi ZT 2005第二军医大学学报2005,26,10:4
17动态88小时:美国地质调查局国家地震信息中心对2011年3月11日M_W9.0日本地震的响应显示文摘引言 2011年3月11日日本本州岛东海岸附近海域发生的M9.0地震(Tohoku earthquake,以下称“东日本大地震”——译者注)及其引发的海啸造成数以万计的人员死亡,造成的财产损失可能超过1万亿美元,这是有历史记录以来最严重的自然灾害之一。Gavin P Hayes Paul S Earle Harley M Benz David J Wald Richard W Briggs 左玉玲(译) 郑需要(校) 2011国际地震动态2011,,8:4
18Inducing embryonic stem cells to differentiate into pancreatic beta cells by a novel three-step approach with activin A and all-trans retinoic acid显示文摘Shi Y Hou L Tang F Jiang W Wang P Ding M Deng H 2006中国生物学文摘2006,20,7:4
19生物素——抗结核药物新研究方向(英文)显示文摘耐药菌的出现对全球公共卫生构成了巨大的挑战,结核分枝杆菌(TB)是结核病的病原菌,是临床上最重要的病原体之一。新抗生素的研发用以治疗耐药性结核病已成为临床及公共卫生管理亟待解决的重要问题。生物素(维生素B7)在结核杆菌的代谢途径如脂肪酸合成和三羧酸循环中发挥重要作用,通过生物素蛋白连接酶连接活性辅助因子而被激活。生物素蛋白连接酶及其相关生物合成通路是微生物合成生物素过程中必不可或缺的关键分子,因而有可能成为新的药物靶点。遗传研究表明,结核杆菌需要由菌体进行生物素的全程合成,因此,生物素合成酶在在结核杆菌代谢过程中起着至关重要的作用,引起了抗结核药物研究者的高度重视。本文论述了结核杆菌生物素合成通路,并重点分析了生物素合成过程中可能成为药物靶点的关键酶,旨在为结核病的治疗提供新思路,具有重要的临床意义。THOMPSON Andrew P STERNICKI Louise M WEGENER Kate L 陆伟 竺丽梅 BOOKER Grant W POLYAK Steven W 李燕 2016江苏预防医学2016,27,3:4
20Parvovirus B19 induced hepatic failure in an adult requiring liver transplantation显示文摘Parvovirus B19 induced acute hepatitis and hepatic failure have been previously reported, mainly in children. Very few cases of parvovirus induced hepatic failure have been reported in adults and fewer still have required liver transplantation. We report the case of a 55-year-old immunocompetent woman who developed fulminant hepatic failure after acute infection with Parvovirus B19 who subsequently underwent orthotopic liver transplantation. This is believed to be the first reported case in the literature in which an adult patient with fulminant hepatic failure associated with acute parvovirus B19 infection and without hematologic abnormalities has been identified prior to undergoing liver transplantation. This case suggests that Parvovirus B19 induced liver disease can affect adults, can occur in the absence of hematologic abnormalities and can be severe enough to require liver transplantation.Darin S Krygier Urs P Steinbrecher Martin Petric Siegfried R Erb Stephen W Chung Charles H Scudamore Andrzej K Buczkowski Eric M Yoshida 2009World Journal of Gastroenterology2009,15,32:3
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