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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 | Role of ion channels in gastrointestinal cancer显示文摘In their seminal papers Hanahan and Weinberg described oncogenic processes a normal cell undergoes to be transformed into a cancer cell.The functions of ion channels in the gastrointestinal(GI)tract influence a variety of cellular processes,many of which overlap with these hallmarks of cancer.In this review we focus on the roles of the calcium(Ca^2+),sodium(Na^+),potassium(K^+),chloride(Cl^-)and zinc(Zn^2+)transporters in GI cancer,with a special emphasis on the roles of the KCNQ1 K+channel and CFTR Cl-channel in colorectal cancer(CRC).Ca^2+is a ubiquitous second messenger,serving as a signaling molecule for a variety of cellular processes such as control of the cell cycle,apoptosis,and migration.Various members of the TRP superfamily,including TRPM8,TRPM7,TRPM6 and TRPM2,have been implicated in GI cancers,especially through overexpression in pancreatic adenocarcinomas and down-regulation in colon cancer.Voltage-gated sodium channels(VGSCs)are classically associated with the initiation and conduction of action potentials in electrically excitable cells such as neurons and muscle cells.The VGSC NaV1.5 is abundantly expressed in human colorectal CRC cell lines as well as being highly expressed in primary CRC samples.Studies have demonstrated that conductance through NaV1.5 contributes significantly to CRC cell invasiveness and cancer progression.Zn2+transporters of the ZIP/SLC39A and ZnT/SLC30A families are dysregulated in all major GI organ cancers,in particular,ZIP4 up-regulation in pancreatic cancer(PC).More than 70 K+channel genes,clustered in four families,are found expressed in the GI tract,where they regulate a range of cellular processes,including gastrin secretion in the stomach and anion secretion and fluid balance in the intestinal tract.Several distinct types of K+channels are found dysregulated in the GI tract.Notable are hERG1 upregulation in PC,gastric cancer(GC)and CRC,leading to enhanced cancer angiogenesis and invasion,and KCNQ1 down-regulation in CRC,where KCNQ1 expression is associated with enhanced disease-free survival in stage II,III,and IV disease.Cl-channels are critical for a range of cellular and tissue processes in the GI tract,especially fluid balance in the colon.Most notable is CFTR,whose deficiency leads to mucus blockage,microbial dysbiosis and inflammation in the intestinal tract.CFTR is a tumor suppressor in several GI cancers.Cystic fibrosis patients are at a significant risk for CRC and low levels of CFTR expression are associated with poor overall disease-free survival in sporadic CRC.Two other classes of chloride channels that are dysregulated in GI cancers are the chloride intracellular channels(CLIC1,3&4)and the chloride channel accessory proteins(CLCA1,2,4).CLIC1&4 are upregulated in PC,GC,gallbladder cancer,and CRC,while the CLCA proteins have been reported to be down-regulated in CRC.In summary,it is clear,from the diverse influences of ion channels,that their aberrant expression and/or activity can contribute to malignant transformation and tumor progression.Further,because ion channels are often localized to the plasma membrane and subject to multiple layers of regulation,they represent promising clinical targets for therapeutic intervention including the repurposing of current drugs. | Kyle J Anderson Robert T Cormier Patricia M Scott | 2019 | World Journal of Gastroenterology2019，25，38： | 19 |
| 3 | Orally administered extract from Prunella vulgaris attenuates spontaneous colitis in mdr1a^(-/-) mice显示文摘AIM: To investigate the ability of a Prunella vulgaris(P. vulgaris) ethanolic extract to attenuate spontaneous typhlocolitis in mdr1a-/- mice. METHODS: Vehicle(5% ethanol) or P. vulgaris ethanolic extract(2.4 mg/d) were administered daily by oral gavage to mdr1a-/- or wild type FVBWT mice from 6 wk of age up to 20 wk of age. Clinical signs of disease were noted by monitoring weight loss. Mice experiencingweight loss in excess of 15% were removed from the study. At the time mice were removed from the study, blood and colon tissue were collected for analyses that included histological evaluation of lesions, inflammatory cytokine levels, and myeloperoxidase activity. RESULTS: Administration of P. vulgaris extracts to mdr1a-/- mice delayed onset of colitis and reduced severity of mucosal inflammation when compared to vehicle-treated mdr1a-/- mice. Oral administration of the P. vulgaris extract resulted in reduced(P < 0.05) serum levels of IL-10(4.6 ± 2 vs 19.4 ± 4), CXCL9(1319.0 ± 277 vs 3901.0 ± 858), and TNFα(9.9 ± 3 vs 14.8 ± 1) as well as reduced gene expression by more than two-fold for Ccl2, Ccl20, Cxcl1, Cxcl9, IL-1 α, Mmp10, VCAM-1, ICAM, IL-2, and TNFα in the colonic mucosa of mdr1a-/- mice compared to vehicle-treated mdr1a-/-mice. Histologically, several microscopic parameters were reduced(P < 0.05) in P. vulgaris-treated mdr1a-/-mice, as was myeloperoxidase activity in the colon(2.49 ± 0.16 vs 3.36 ± 0.06, P < 0.05). The numbers of CD4+ T cells(2031.9 ± 412.1 vs 5054.5 ± 809.5) and germinal center B cells(2749.6 ± 473.7 vs 4934.0 ± 645.9) observed in the cecal tonsils of P. vulgaris-treated mdr1a-/- were significantly reduced(P < 0.05) from vehicle-treated mdr1a-/- mice. Vehicle-treated mdr1a-/- mice were found to produce serum antibodies to antigens derived from members of the intestinal microbiota, indicative of severe colitis and a loss of adaptive tolerance to the members of the microbiota. These serum antibodies were greatly reduced or absent in P. vulgaris-treated mdr1a-/- mice. CONCLUSION: The anti-inflammatory activity of P. vulgaris ethanolic extract effectively attenuated the severity of intestinal inflammation in mdr1a-/- mice. | Kelley MK Haarberg Meghan J Wymore Brand Anne-Marie C Overstreet Catherine C Hauck Patricia A Murphy Jesse M Hostetter Amanda E Ramer-Tait Michael J Wannemuehler | 2015 | World Journal of Gastrointestinal Pharmacology and Therapeutics2015，6，4： | 8 |
| 4 | Leukocyte driven-decidual angiogenesis in early.pregnancy显示文摘成功的怀孕并且长期,出生后母亲并且后代心脏、脉管、新陈代谢的健康在怀孕期上要求关键母亲的心血管的改编。在怀孕 decidualizing 子宫以内,协调了脉管,免疫学的和 stromal 房间变化发生。可观的注意在开始蜕膜的螺线被给了房间到子宫的生来的杀手(uNK ) 的角色动脉的改变,通常完成由的一个过程在老鼠并且在人中间怀孕期。然而,白血球角色在早得多,区域特定,蜕膜的脉管的改变现在正在被定义。对免疫者的兴趣支持房间的脉管的改变被在象不孕,周期性的自发的流产, preeclampsia (PE ) 和胎儿的生长限制那样的人的 gestational 复杂并发症被报导的脉管的错误驾驶。适当母亲的心血管的回答在怀孕期间保护母亲和他们的孩子免受以后的心血管的疾病风险举起的伤害。对在有 hemochorial 胎座式的种类的怀孕的最早子宫的回答之一是 stromal 细胞 decidualization,它为 angiogenesis 和白血球招募创造唯一的壁龛。在早蜕膜 basalis,将抱发展中的胎盘并且提供主要的血容器支持成熟胎盘的功能的培植地点的方面,白血球极大地被充实并且显示专业化性质。UNK 房间,在早蜕膜 basalis 的最丰富的白血球子集,有 angiogenic 能力并且为正常早蜕膜的 angiogenesis 是必要的。在决定的 uNK 房间和他们的角色的规定母亲并且子孙在怀孕上的心血管的健康并且产后被讨论。 | Patricia DA Lima Jianhong Zhang Caroline Dunk Stephen J Lye B Anne Croy | 2014 | Cellular & Molecular Immunology2014，11，6： | 8 |
| 5 | 大气二氧化氮与每日总死亡率、心血管和呼吸系统疾病死亡率的短期关联:398个城市的多中心分析显示文摘目的:采用统一的分析方案,评估全球多个国家/地区的二氧化氮(NO_(2))与总死亡率、心血管和呼吸系统疾病死亡率之间的短期关联。研究设计:采用两阶段的时间序列分析方法、过度离散的广义线性模型和多水平meta分析。研究地点:22个低到高收入国家/地区的398个城市。主要结局指标:1973—2018年逐日总死亡人数(6280万人)、心血管疾病死亡人数(1970万人)和呼吸系统疾病死亡人数(550万人)。结果:平均而言,NO_(2)浓度在滞后1天(前1天)每增加10μg/m^(3),会导致总死亡率、心血管和呼吸系统疾病死亡率分别增加0.46%(95%可信区间0.36%~0.57%)、0.37%(0.22%~0.51%)、0.47%(0.21%~0.72%)。在对共污染物(PM_(10)、PM_(2.5)、臭氧、二氧化硫和一氧化碳)进行调整后,这些关联仍然很稳定。所有3种死因的暴露-反应曲线几乎是线性的,没有明显的阈值。在398个城市中,可归因于高过假定零水平的NO_(2)浓度造成的死亡比例为1.23%(95%可信区间0.96%~1.51%)。结论:这项多中心研究提供了关于NO_(2)短期暴露与总死亡率、心血管和呼吸系统死亡风险之间的独立和线性关联的关键证据,说明通过加强NO_(2)的控制和监管限制标准,可获得人群水平的健康收益。 | 孟夏 刘聪(校) 陈仁杰 郑湃(译) 阚海东(校) Francesco Sera Ana Vicedo-Cabrera Ai Milojevic Maria Guo Yuming Tong Shilu Micheline de Sousa Zanotti Stagliorio Coelh Paulo Hilario Nascimento Saldiva Eric Lavigne Patricia Matus Correa Nicolas Valdes Ortega Samuel Osorio Garcia Jan Kysely Ales Urban Hans Orru Marek Maasikmets Jouni J K Jaakkola Niilo Ryti Veronika Huber Alexandra Schneider Klea Katsouyanni Antonis Analitis Masahiro Hashizume Yasushi Honda Chris Fook Sheng Ng Baltazar Nunes João Paulo Teixeira Iulian Horia Holobaca Simona Fratianni Ho Kim Aurelio Tobias Carmeníniguez Bertil Forsberg ChristoferÅström Martina S Ragettli Yue-Liang Leon Guo Shih-Chun Pan Shanshan Li Michelle L Bell Antonella Zanobetti Joel Schwartz Tangchun Wu Antonio Gasparrini | 2021 | 英国医学杂志中文版2021，24，8： | 7 |
| 6 | Enzymatic vitrectomy for diabetic retinopathy and diabetic macular edema显示文摘The aim of this paper is to determine the role of enzymatic vitrectomy performed by intravitreal injection of autologous plasmin enzyme(APE)in the management of diabetic retinopathy and diabetic macular edema(DME).Diabetic patients with proliferative diabetic retinopathy or DME and evident posterior hyaloid adherence to the retinal surface were included.All cases were treated with an initial intravitreal injection of APE and reevaluated one month later,measuring changes in best-corrected visual acuity(BCVA),macular thickness and the status of the posterior hyaloid.A second APE injection was performed in cases with no evident posterior vitreous detachment(PVD)after the initial treatment.Sixty-three eyes were included in the present review.A complete PVD appeared in 38%of cases(24 eyes)after one injection of plasmin and the total increased to 51%(32 eyes)after the second injection,separated at least by one month.The central macular thickness improved in all cases(100%)and BCVA in89%.Finally,in 50%of eyes with proliferative diabetic retinopathy,a high reduction of new vessels regression was observed.Enzymatic vitrectomy could be considered a good therapeutic alternative in diabetic retinopathy and macular edema. | Manuel Diaz-Llopis Patricia Udaondo Jose Maria Millán J Fernando Arevalo | 2013 | World Journal of Diabetes2013，4，6： | 6 |
| 7 | 癌症的时间生物学:治疗癌症的时间重要吗?(英文)显示文摘我们周围的世界是一个已知有生命进化的世界,一个在不停变化的世界.这些变化多数是周期性的.这些周期性动态变化起源于地球、太阳和月亮之间有规律的时空关系,这种关系正是节律产生的本质.日夜的交替、日照时间的季节性变化以及由于过强或过弱的寻常节律导致的突发性气候变化,所有这些使得地球生命节律得以产生(火星生命尚未深入研究).这些近乎完美的节律变化引起了每日两次(昼夜)和每月一次(月经)的生命节律及相呼应的复杂生理变化.这些信息均已被深深地编入在我们的基因密码中.还有更低频率的节律,如:反映太阳黑子活动的规律(周期为10.5年)及世纪性周期或更长周期的节律,如气候的变更.所有这些节律都具有生物学意义.过去30年中,这些节律对健康、对疾病和宿主间平衡的影响已日显明朗.这些概念早在三世纪前的西方医学中就已经发现,在几千年前的中国传统医学中就有描述和应用.中医的因时施治和时令用药等正合此理.该文通过深入的理论探讨和详实的实验数据阐述了在认识、预防、诊断和治疗癌症时要仔细地考虑时间的科学基础,也为这方面的中医理论提供了现代科学的依据.时间生物学(chronobiology)是一门研究生物现象节律性变化的科学.这种动态生物学研究揭示的是在生物物理和生物化学过程中,以时间为基础的变化规律.最常见的生物节律按其周期的长短有3种:以(24±4)h为周期的昼夜节律,以(30±7)d为周期的月节律,和以(12±2)月为周期的年节律.目前,对昼夜生物节律现象研究的最多,对其生物学意义了解也最深.生物节律最基本的特性有:①内源性和遗传性;②外界刺激可调节生物节律;③在没有外界时间相关信息提示时仍可保持节律性.机体内的生物钟是维持这些节律的基本结构,下丘脑的视交叉上核是这个时间中枢的所在.外界环境,如光线或日照每天都对这个时间中枢进行调整,并进而影响机体的许多生理功能,如睡眠、体温、激素分泌及细胞增殖周期等,使得健康机体中这些生理过程都维持着显著的昼夜周期性节律.不适当外界环境刺激,尤其是长期在夜间暴露于强光之下(如从事护士和娱乐业的人员),可导致机体生物钟的持续紊乱.这种持续的紊乱可导致睡眠紊乱、激素分泌失衡、精神状态失调及冠心病等.近来流行病学调查还发现这种紊乱和乳腺癌、结肠癌的发病有关.生物体内存在维持时间节律的分子机制,这就是生物钟基因.它存在于生物钟中枢及每一个外周组织中.机体的时间节律正是由这些生物钟基因及受其调控的相关基因(钟控基因,约占人基因的10%~15%)的协同表达所致.目前已知正常增生活跃的组织中,DNA合成和细胞分裂都具有明显的昼夜周期性节律.其中以对骨髓、肠道粘膜研究得最多,因为这两个组织对许多细胞毒化疗药物都很敏感,造成它们损伤的程度是许多化疗药物及放疗应用受限的原因.癌组织也有昼夜时间节律,这表现在:①它在宿主体内的生长有时间节律;②癌细胞的增生和凋亡受生物钟基因调控;③同一种抗癌药物,在某些时间给药可能是有效的,而在另外一些时间给药则不仅无效反而造成对正常组织损伤.临床的随机抽样调查表明只要用药时间适当,细胞毒化疗药物的毒性可以减弱,药物的剂量可以加大,治疗效果可以改善,癌症病人的生存可以延长.对人体癌细胞在一天中某一时刻、处于某一细胞周期阶段的细胞比例的研究,目前仍需要系列地采集一天内不同时段的组织标本来完成.我们曾对一例恶性表皮癌及周边正常皮肤进行了系列的、跨24小时的研究.结果表明病人在日常光照环境中,其癌症及正常表皮细胞的分裂都是有规律的、时多时少的过程.这种动态的昼夜变化节律毫无疑问在癌症的化疗和放疗中有很大应用价值. 动物和临床实验已证明调整用药时间的重要性和可行性.有一个典型的动物实验可证明药物毒性和用药时间的关系.如果连续6 d在白天或其睡眠期给小鼠注射一定剂量的阿拉伯糖苷(arcC),只有15%的小鼠会因药物毒性而死亡;而如果在晚上或其活动期注射同样剂量的药物,则小鼠的死亡率会增加至75%.用表阿霉素(doxorubicin)和顺铂(cisplatin)治疗晚期卵巢癌的临床研究是另一个例子.对病人采用晚间注射表阿霉素和早晨注射顺铂的治疗方案产生副作用的机率明显高于采用早晨注射表阿霉素和晚间注射顺铂的方案.5氟尿嘧啶(5-Fu)的抗癌疗效和副作用的产生也有很强的时间依赖性.对这种时间依赖性的机制现已有所了解.二氢嘧啶脱氢酶(DPD)是氟嘧啶代谢的限速酶,它可以将5-Fu及代谢衍生物转化成无细胞毒性的产物而排出体外.研究表明DPD在大鼠肝脏中的表达是有昼夜节律的,正是DPD在肝脏有节律地代谢、清除5-Fu及代谢衍生物才使得5-Fu的疗效和副作用有很强的时间依赖性.抗癌药物的发展是一个复杂、代价高昂和充满冒险的过程.许多化合物或衍生物被设计、合成或生产,这些备选药物可能针对细胞周期的不同阶段或机制,其中很多备选药物在层层筛选中因为毒性、特异性或有效性等问题而被弃用.如果一个备选药物被证明有效或完全无效,则取舍的结果将是完全不同的,此时请别忘记考虑用药时间的因素.我们的研究表明人体和癌症之间的平衡存在着日、月或季节的节律性变化.了解和承认这些日、月或季节性变化可帮助我们更好地预防、诊断,更安全、有效地治疗人类的癌症.在我们这个以24/7(24小时/日,7日/周)为时间周期单位的世界里,一个现代化、工业化的世界,不适当的环境污染,包括光的污染(如夜间强光照射)日渐增多.它所造成的人的生物钟节律的紊乱是显著的.遗憾的是只有少数医学科学家重视和正在从事这方面的研究.理解生物时间节律的概念可以更好地预防、诊断和治疗人类癌症.我们邀请更多的中国医学科学研究人员和机构加入到我们这个研究行列,运用时间生物学的概念,为更有效地预防癌症、更早期地诊断癌症、更好地控制和治疗癌症而努力. | William J M Hrushesky Jovelyn Du-Quiton Masami Ohmori Patricia A.Wood | 2005 | 基础医学与临床2005，25，4： | 5 |
| 8 | 从附睾到卵子:CRISP蛋白在哺乳动物受精过程中的作用显示文摘哺乳动物的受精过程涉及精卵结合的很多步骤,是一个非常复杂的过程,其分了机制亟待阐明。此篇综述主要论述了CRISP(富含半胱氨酸的分泌蛋白)作为模型分子在哺乳动物受精过程中的价值。大量的体外实验和基因敲出模型研究显示,附睾内的CRISP1以两种不同的亲和力结合于精子表面,参与精子获能、精子-透明带结合、精卵融合的调控。这些研究成果可以延伸至人类。我们住研究中发现,人类具有与啮齿类同源的CRISP(hCRISP1),同样参与受精过样。CRISP家族的其他成员(睾丸内CRISP2、附挈内CRISP3—4、射精时的CRISP3)也参与了精卵结合的过程,提示同源分子间的相互协同有助于受精的成功。另外,我们的研究显示,CRISP蛋白伴随精子穿越男性及女性生殖管道的全过程。我们推测CRISP不仅参与了受精过程,而且可能成为不育和避孕研究的新靶点。 | Vanina G Da Ros Mariana Weigel Munoz Maria A Battistone Nicolas G Brukman Guillermo Carvajal Ludmila Curci Matlas D Gomez-Elias Debora J Cohen Patricia S Cuasnicu | 2015 | Asian Journal of Andrology2015，17，5： | 5 |
| 9 | Opioid growth factor and the treatment of human pancreatic cancer:A review显示文摘Opioid growth factor(OGF),chemically termed[Met5]-enkephalin,and its receptor,OGF receptor(OGFr),form a biological axis that tonically regulates cell proliferation by delaying the G1/S interface of the cell cycle under homeostatic conditions or in neoplasia.Modulation of the OGF-OGFr pathway mediates the course of pancreatic cancer,with exogenous OGF or upregulation of OGFr repressing growth of human pancreatic cancer cells in culture and in nude mice.OGF therapy alone or in combination with standard chemotherapies such as gemcitabine and 5-fluorouracil results in enhanced inhibition of DNA synthesis and tumor growth.Molecular manipulation of OGFr confirms that the receptor is specific for OGF’s inhibitory action.Preclinical studies have warranted PhaseⅠand PhaseⅡclinical trials using OGF infusions as a treatment for patients with advanced,unresectable pancreatic cancers.OGF,an endogenous neuropeptide,is a safe,non-toxic,and effective biotherapy that utilizes the OGF-OGFr axis to mediate pancreatic tumor progression. | Ian S Zagon Patricia J McLaughlin | 2014 | World Journal of Gastroenterology2014，20，9： | 4 |
| 10 | Outcomes of critically ill cancer patients with Acinetobacter baumannii infection显示文摘AIM: To describe the intensive care unit(ICU) outcomes of critically ill cancer patients with Acinetobacter baumannii(AB) infection.METHODS: This was an observational study that included 23 consecutive cancer patients who acquired AB infections during their stay at ICU of the National Cancer Institute of Mexico(INCan), located in Mexico City. Data collection took place between January 2011, and December 2012. Patients who had AB infections before ICU admission, and infections that occurred during the first 2 d of ICU stay were excluded. Data were obtained by reviewing the electronic health record of each patient. This investigation was approved by the Scientific and Ethics Committees at INCan. Because of its observational nature, informed consent of the patients was not required.RESULTS: Throughout the study period, a total of 494 critically ill patients with cancer were admitted to the ICU of the INCan, 23(4.6%) of whom developed AB infections. Sixteen(60.9%) of these patients had hematologic malignancies. Most frequent reasons for ICU admission were severe sepsis or septic shock(56.2%) and postoperative care(21.7%). The respiratory tract was the most frequent site of AB infection(91.3%). The most common organ dysfunction observed in our group of patients were the respiratory(100%), cardiovascular(100%), hepatic(73.9%) and renal dysfunction(65.2%). The ICU mortality of patients with 3 or less organ system dysfunctions was 11.7%(2/17) compared with 66.6%(4/6) for the group of patients with 4 or more organ system dysfunctions(P = 0.021). Multivariate analysis identified blood lactate levels(BLL) as the only variable independently associated with inICU death(OR = 2.59, 95%CI: 1.04-6.43, P = 0.040). ICU and hospital mortality rates were 26.1% and 43.5%, respectively.CONCLUSION: The mortality rate in critically ill patients with both HM, and AB infections who are admitted to the ICU is high. The variable most associated with increased mortality was a BLL ≥ 2.6 mmol/L in the first day of stay in the ICU. | Silvio A ?amendys-Silva Paulina Correa-García Francisco J García-Guillén María O González-Herrera Américo Pérez-Alonso Julia Texcocano-Becerra Angel Herrera-Gómez Patricia Cornejo-Juárez Abelardo Meneses-García | 2015 | World Journal of Critical Care Medicine2015，4，3： | 3 |
| 11 | Non-steroidal anti-inflammatory drugs and risk of neoplastic progression in Barrett’s oesophagus: a prospective study显示文摘 | Thomas L Vaughan Linda M Dong Patricia L Blount Kamran Ayub Robert D Odze Carissa A Sanchez Peter S Rabinovitch Brian J Reid | 2005 | Lancet Oncology2005，，12： | 2 |
| 12 | Anti-hypertensive drugs in children and adolescents显示文摘Worldwide the prevalence of essential hypertension inchildren and adolescents continues to increase. Tradi-tionally providers have used 'off-label' drugs to treatpediatric hypertension, meaning that rigorous clinicaltrials of these drugs have not been specifically per-formed in pediatric patient populations. Consequentlyproviders have extrapolated dosing, safety and efficacyfrom trials in adults. This practice is sub-optimal as chil-dren demonstrate unique differences in drug metabo-lism and response. Use of unstudied or understudieddrugs increases risk of adverse events and/or can leadto sub-optimal efficacy. Recognizing these concerns,regulatory agencies have created financial incentivesfor industry to conduct pediatric clinical trials. Theseincentives, coupled with the emerging pediatric hyper-tension epidemic, have spurred over 30 clinical trialsof anti-hypertensive drugs over the past 15 years andhave resulted in labeling of 10 new drugs by the UnitedStates Food and Drug Administration for treatment ofhypertension in children and adolescents. Unfortunatelythe financial incentive structures focus on newer drugsand drug classes. Consequently there is now a relativedearth of trial data for older but sometimes commonlyprescribed pediatric antihypertensive drugs. This article reviews recent pediatric antihypertensive drug trials with a focus on trial design and endpoints, drug dosing, safety, efficacy and specific drug indications. We also review the available data and experience for some of the more commonly prescribed, but less well studied 'older' pediatric antihypertensive drugs. | Patricia Y Chu Michael J Campbell Stephen G Miller Kevin D Hill | 2014 | World Journal of Cardiology2014，6，5： | 2 |
| 13 | Predictors of progression in Barrett’s esophagus III: baseline flow cytometric variables显示文摘 | Peter S Rabinovitch Gary Longton Patricia L Blount Douglas S Levine Brian J Reid | 2001 | The American Journal of Gastroenterology2001，，11： | 2 |
| 14 | Predictors of progression in Barrett’s esophagus II: baseline 17p (p53) loss of heterozygosity identifies a patient subset at increased risk for neoplastic progression显示文摘 | Brian J Reid Laura J Prevo Patricia C Galipeau Carissa A Sanchez Gary Longton Douglas S Levine Patricia L Blount Peter S Rabinovitch | 2001 | The American Journal of Gastroenterology2001，，10： | 2 |
| 15 | MicroRNAs in biliary diseases显示文摘Cholangiopathies are a group of diseases primarily or secondarily affecting bile duct cells, and result in cholangiocyte proliferation, regression, and/or transformation. Their etiopathogenesis may be associated with a broad variety of causes of different nature, which includes genetic, neoplastic, immune-associated, infectious, vascular, and drug-induced alterations, or being idiopathic. miRNAs, small non-coding endogenous RNAs that post-transcriptionally regulate gene expres sion, have been associated with pathophysiological processes in different organs and cell types, and are postulated as potential targets for diagnosis and therapy. In the current manuscript, knowledge regarding the role of miRNAs in the development and/or progression of cholangiopathies has been reviewed and the most relevant findings in this promising field of hepatology have been highlighted. | Patricia Munoz-Garrido Maite García-Fernández de Barrena Elizabeth Hijona Miguel Carracedo JoséJ G Marín Luis Bujanda Jesús M Banales | 2012 | World Journal of Gastroenterology2012，18，43： | 2 |
| 16 | Clinical presentation and pre-mortem diagnosis of variant Creutzfeldt-Jakob disease associated with blood transfusion: a case report显示文摘 | Stephen J Wroe Suvankar Pal Durrenajaf Siddique Harpreet Hyare Rebecca Macfarlane Susan Joiner Jacqueline M Linehan Sebastian Brandner Jonathan DF Wadsworth Patricia Hewitt John Collinge | 2006 | The Lancet2006，，9552： | 1 |
| 17 | Perception of Diesel Engine Gear Rattle Noise显示文摘 | BRANDON S PATRICIA D BOLTON J S | 2015 | SAE2015，，1： | 1 |
| 18 | LIGHT, a New Member of the TNF Superfamily, and Lymphotoxin α Are Ligands for Herpesvirus Entry Mediator显示文摘 | Davide N Mauri Reinhard Ebner Rebecca I Montgomery Kristine D Kochel Timothy C Cheung Guo-Liang Yu Steve Ruben Marianne Murphy Roselyn J Eisenberg Gary H Cohen Patricia G Spear Carl F Ware | 1998 | Immunity1998，，： | 1 |
| 19 | Casts of Aporrectodea caliginosa (Savigny) and Lumbricus rubellus (Hoffmeister) differ in microbial activity,nutrient availability and aggregate stability显示文摘 | Richard J H Patricia M F Jacqueline E P | 2003 | Pedobiologia2003，47，： | 1 |
| 20 | Phenylpropanoid derivatives and biflavones at different stages of differentiation and development of Araucaria angustifolia 显示文摘 | Fabiana N F Ari J S F Patricia S | 2000 | Phytochemistry2000，55，6： | 1 |
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