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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 | Molecular targets of cancer chemoprevention by garlic-derived organosulfides显示文摘瞀或蒜之类蔬菜的药用的好处,特别大蒜,在整个记录历史被注意了。瞀或蒜之类蔬菜和他们的成分的已知的健康好处包括心血管的保护的效果,有免疫力的功能的刺激,血葡萄糖水平的减小,辐射防护,记忆损失的改进,对微生物引起、病毒、真菌的感染的保护,象反癌症一样, 基于effects.Population 的盒子控制研究包括大蒜建议了在瞀或蒜之类蔬菜的饮食的吸入和瞀或蒜之类蔬菜的不同类型 ofcancers.The anticarcinogenic 效果的风险之间的反的关联被归因 toorganosulfur 混合物(振荡),它在在许多化学致癌物劝诱的动物模特儿对癌症负担得起保护是高度有效的。更最近的研究证明了某些自然地发生的振荡类似物能在文化并且在在房间经常是的癌症的增长的导致振荡的变化在房间周期前进和 G2/M 阶段拘捕的正式就职与不安联系了的 vivo.The 压制癌症房间的增长。振荡也被表明了由在房间文化并且在改变蛋白质的 Bc1-2 家庭的比率经由内在的小径导致 apoptosis 在 vivo models.Anti-angiogenic,为 garlic-derivedOSC 的活动也被记录了。这篇文章由振荡在癌症 chemoprevention 的分子的目标上总结当前的知识。 | Anna HERMAN-ANTOSIEWICZ Anna A POWOLNY Shivendra V SINGH | 2007 | Acta Pharmacologica Sinica2007，28，9： | 6 |
| 3 | Contribution of functional KIR3DL1 to ankylosing spondylitis显示文摘Increasing evidence points to a role for killer immunoglobulin-like receptors(KIRs)in the development of autoimmune diseases.In particular,a positive association of KIR3DS1(activating receptor)and a negative association of KIR3DL1(inhibitory receptor)alleles with ankylosing spondylitis(AS)have been reported by several groups.However,none of the studies analyzed these associations in the context of functionality of polymorphic KIR3DL1.To better understand how the KIR3DL1/3DS1 genes determine susceptibility to AS,we analyzed the frequencies of alleles and genotypes encoding functional(KIR3DL1*F)and non-functional(KIR3DL1*004)receptors.We genotyped 83 AS patients and 107 human leukocyte antigen(HLA)-B27-positive healthy controls from the Russian Caucasian population using a two-stage sequence-specific primer PCR,which distinguishes KIR3DS1,KIR3DL1*F and KIR3DL1*004 alleles.For the patients carrying two functional KIR3DL1 alleles,those alleles were additionally genotyped to identify KIR3DL1*005 and KIR3DL1*007 alleles,which are functional but are expressed at low levels.KIR3DL1 was negatively associated with AS at the expense of KIR3DL1*F but not of KIR3DL1*004.This finding indicates that the inhibitory KIR3DL1 receptor protects against the development of AS and is not simply a passive counterpart of the segregating KIR3DS1 allele encoding the activating receptor.However,analysis of genotype frequencies indicates that the presence of KIR3DS1 is a more important factor for AS susceptibility than the absence of KIR3DL1*F.The activation of either natural killer(NK)or T cells via the KIR3DS1 receptor can be one of the critical events in AS development,while the presence of the functional KIR3DL1 receptor has a protective effect.Nevertheless,even individuals with a genotype that carried two inhibitory KIR3DL1 alleles expressed at high levels could develop AS. | Ivan V Zvyagin Ilgar Z Mamedov Olga V Britanova Dmitriy B Staroverov Evgeni L Nasonov Anna G Bochkova Anna V Chkalina Alexei A Kotlobay Dmitriy O Korostin Denis V Rebrikov Sergey Lukyanov Yuri B Lebedev Dmitriy M Chudakov | 2010 | Cellular & Molecular Immunology2010，7，6： | 5 |
| 4 | Steatosis and steatohepatitis in postmortem material from Northwestern Greece显示文摘AIM: To determine the prevalence of steatosis and steatohepatitis in a series of autopsies in Northwestern Greece. METHODS: Liver biopsy material from a total of 600 autopsies performed over a period of 2 years (2006-2008) to def ine the cause of death was subjected to histological examination. Patient demographic data were also collected. Tissue sections were stained with different dyes for the evaluation of liver architecture, degree of fibrosis and other pathological conditions when necessary. RESULTS: Satisfactory tissue samples for histological evaluation were available in 498 cases (341 male, 157 female) with a mean age of 64.51 ± 17.78 years. In total, 144 (28.9%) had normal liver histology, 156 (31.3%) had evidence of steatosis, and 198 (39.8%) had typical histological findings of steatohepatitis. The most common causes of death were ischemic heart disease with or without myocardial infarction (43.4%), and traffic accidents (13.4%). CONCLUSION: A high prevalence of steatosis and steatohepatitis was detected in postmortem biopsies from Northwestern Greece. Since both diseases can have serious clinical consequences, they should be considered as an important threat to the health of the general population in Greece. | Christos D Zois Gerasimos H Baltayiannis Anna Bekiari Anna Goussia Peter Karayiannis Michalis Doukas Demetrios Demopoulos Antigoni Mitsellou Theodoros Vougiouklakis Vasiliki Mitsi Epameinondas V Tsianos | 2010 | World Journal of Gastroenterology2010，16，31： | 4 |
| 5 | 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 |
| 6 | Fecal calprotectin measurement is a marker of shortterm clinical outcome and presence of mucosal healing in patients with inflammatory bowel disease显示文摘AIM To evaluate the utility of fecal calprotectin(FC) in predicting relapse and endoscopic activity during follow-up in an inflammatory bowel disease(IBD) cohort.METHODS All FC measurements that were obtained during a 3-year period from patients with inflammatory bowel disease in clinical remission were identified. Data regarding the short-term(6 mo) course of the disease were extracted from the medical files. Exclusion criteria were defined as:(1) An established flare of the disease at the time of FC measurement,(2) Loss to follow up within 6 mo from baseline FC measurement, and,(3) Insufficient data on file. Statistical analysis was performed to evaluate whether baseline FC measurement could predict the short term clinical relapse and/or the presence of mucosal healing.RESULTS We included 149 [Crohn's disease(CD) = 113, Ulcerative colitis(UC) = 36, male = 77] IBD patients in our study. Within the determined 6-month period post-FC measurement, 47(31.5%) had a disease flare. Among 76 patients who underwent endoscopy, 39(51.3%) had mucosal healing. Baseline FC concentrations were significantly higher in those who had clinical relapse compared to those who remained in remission during follow up(481.0 μg/g, 286.0-600.0 vs 89.0, 36.0-180.8, P < 0.001). The significant predictive value of baseline median with IQR FC for clinical relapse was confirmed by multivariate Cox analysis [HR for 100μg/g: 1.75(95%CI: 1.28-2.39), P = 0.001]. Furthermore, lower FC baseline values significantly correlated to the presence of mucosal healing in endoscopy(69.0 μg/g, 30.0-128.0 vs 481.0, 278.0-600.0, in those with mucosal inflammation, median with IQR, P < 0.001). We were able to extract cut-off values for FC concentration with a high sensitivity and specificity for predicting clinical relapse(261 μg/g with AUC = 0.901, sensitivity 87.2%, specificity 85.3%, P < 0.001) or mucosal healing(174 μg/g with AUC = 0.956, sensitivity 91.9%, specificity 87.2%, P < 0.001). FC was better than CRP in predicting either outcome; nevertheless, having a pathological CRP(> 5 mg/L) in addition to the cutoffs for FC, significantly enhanced the specificity for predicting clinical relapse(95.1% from 85.3%) or endoscopic activity(100% from 87.2%). CONCLUSION Serial FC measurements may be useful in monitoring IBD patients in remission, as FC appears to be a reliable predictor of short-term relapse and endoscopic activity. | Athanasios Kostas Spyros I Siakavellas Charalambos Kosmidis Anna Takou Joanna Nikou Georgios Maropoulos John Vlachogiannakos George V Papatheodoridis Ioannis Papaconstantinou Giorgos Bamias | 2017 | World Journal of Gastroenterology2017，23，41： | 2 |
| 7 | Metal-organic frameworks based surface-enhanced Raman spectroscopy technique for ultra-sensitive biomedical trace detection显示文摘Metal-organic frameworks(MOFs)have attracted widespread interest due to their unique and unprecedented advantages in microstructures and properties.Besides,surface-enhanced Raman scattering(SERS)technology has also rapidly developed into a powerful fingerprint spectroscopic technique that can provide rapid,non-invasive,non-destructive,and ultra-sensitive detection,even down to single molecular level.Consequently,a considerable amount of researchers combined MOFs with the SERS technique to further improve the sensing performance and broaden the applications of SERS substrates.Herein,representative synthesis strategies of MOFs to fabricate SERS-active substrates are summarized and their applications in ultra-sensitive biomedical trace detection are also reviewed.Besides,relative barriers,advantages,disadvantages,future trends,and prospects are particularly discussed to give guidance to relevant researchers. | Yuna Zhang Cuili Xue Yuli Xu Shengsheng Cui Alexander A.Ganeev Kistenev Yury V Anna Gubal Victoria Chuchina Han Jin Daxiang Cui | 2023 | Nano Research2023，16，2： | 2 |
| 8 | Reducing intrathecal pressure after traumatic spinal cord injury: a potential clinical target to promote tissue survival显示文摘Spinal cord injury(SCI)is an unexpected event that is both devastating and debilitating,resulting in not just motor and sensory loss,but also autonomic dysfunction of the bladder,bowel and sexual organs.Currently,there are no treatments available to improve outcome following SCI,leaving individuals with permanent and lifelong physical disability.Worldwide it is estimated that | Anna V Leonard Robert Vink | 2015 | Neural Regeneration Research2015，10，3： | 2 |
| 9 | Pharmacological properties of Anagallis arvensis L. (“scarlet pimpernel”) and Anagallis foemina Mill. (“blue pimpernel”) traditionally used as wound healing remedies in Navarra (Spain)显示文摘 | Víctor López Anna K. J?ger Silvia Akerreta Rita Yolanda Cavero Maria Isabel Calvo | 2011 | Journal of Ethnopharmacology2011，，3： | 2 |
| 10 | 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 |
| 11 | Accurnulation of an endogenous in hibitors of nitric oxide synthesis in chronic renalfailure显示文摘 | Patric V Anna L Alison C | 1992 | Lancet1992，339，8795： | 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 | Analysis of chloride diffusion into partially saturated concrete 显示文摘 | Anna V S Roberto V S | 1993 | ACI Material Journal1993，，5： | 1 |
| 14 | The catecholamine biosynthesis route in potato is affected by stress显示文摘 | Anna W V Katarzyna L K Aleksandra S | 2004 | Plant Physiology and Biochemistry2004，42，： | 1 |
| 15 | 2-D model for carbonation and moisture-heat flow in porous materials显示文摘 | Anna V Bernhard A Schrefler Renato V Vitaliani | 1995 | Cement and Concrete Research1995，25，8： | 1 |
| 16 | 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 |
| 17 | Stress analysis of concrete structures subjected to variable thermal loads 显示文摘 | Anna S Roberto S Renato V | 1995 | Journal of Structural Engineering1995，121，3： | 1 |
| 18 | Membrane concentration of liquid foods by forward osmosis : process and quality view 显示文摘 | SANT' ANNA V MARCZAK L D F TESSARO I C | 2012 | Journal of Food Engineering2012，111，3： | 1 |
| 19 | Manipulation of DET1 expression in tomato results in photomorphogenic phenotypes caused by post-transcriptional gene silencing显示文摘 | Ganga R D Ageeth V T Anna C M | 2004 | The Plant Journal2004，，： | 1 |
| 20 | Atom transfer radical polymerization of methyl acrylate from a multifunctional initiator at ambient temperature显示文摘 | ANNA C ROBERT V EVA M J | 2002 | Polymer2002，43，： | 1 |
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