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| 1 | 城市自然景区游客环境责任行为影响因素研究显示文摘城市自然景区是城市中不可多得的旅游资源和游憩空间,游客旅游行为对城市自然景区的游憩冲击一直是城市旅游管理亟待解决的棘手问题,研究游客的环境责任行为是控制游憩负面冲击,增强城市自然景区可持续发展能力的有效途径。本研究在国内外文献综述和实践观察基础上,将游客社会责任意识引入游客环境冲击感知和环境责任行为的关系研究中,建立了包含生态环境冲击感知、不友善行为感知、游客冲突感知和设施管理冲击感知四个游憩冲击感知变量,自我约束行为和保护促进行为两个环境责任行为变量的'游憩冲击感知—社会责任意识—环境责任行为'理论模型,应用问卷调查和结构方程模型,以长沙岳麓山国家5A级景区为案例,对城市自然景区游客环境责任行为的影响因素及其相互关系展开定量实证研究。研究发现:(1)游客游憩冲击感知对环境责任行为的直接影响作用较小,生态环境冲击感知对环境保护促进行为具有显著正向影响;(2)游客社会责任意识对环境自我约束行为具有显著正向影响,其在游客环境冲击感知、设施管理冲击感知、游客冲突感知与环境责任行为的影响关系中起中介作用;(3)游客冲击感知对社会责任意识的影响主要表现为游客生态环境冲击感知和设施管理冲击感知对游客社会责任意识具有显著的正向影响,而游客冲突感知对游客社会责任意识具有显著的负向影响。根据研究结论,文章最后指出城市自然景区游客环境责任行为若干管理启示。 | 罗文斌 张小花 钟诚 孟贝 TIMOTHY D J | 2017 | 中国人口·资源与环境2017，27，5： | 30 |
| 2 | Colorectal cancer:Metastases to a single organ显示文摘Colorectal cancer(CRC) is a common malignancy worldwide. In CRC patients, metastases are the main cause of cancer-related mortality. In a group of metastatic CRC patients, the metastases are limited to a single site(solitary organ); the liver and lungs are the most commonly involved sites. When metastatic disease is limited to the liver and/or lungs, the resectability of the metastatic lesions will dictate the management approach and the outcome. Less commonly, the site of solitary organ CRC metastasis is the peritoneum. In these patients, cytoreduction followed by hyperthermic intraperitoneal chemotherapy may improve the outcome. Rarely, CRC involves other organs, such as the brain, bone, adrenals and spleen, as the only site of metastatic disease. There are limited data to guide clinical practice in these cases. Here, we have reviewed the disease characteristics, management approaches and prognosis based on the metastatic disease site in patients with CRC with metastases to a single organ. | Sina Vatandoust Timothy J Price Christos S Karapetis | 2015 | World Journal of Gastroenterology2015，21，41： | 30 |
| 3 | Cardiac rehabilitation and exercise therapy in the elderly: Should we invest in the aged?显示文摘冠的心疾病(CHD ) 是世界范围的死亡的领先的原因并且在病人之中变得逐渐地流行 65 岁以上。老病人在为复杂并发症的更高的风险并且在一个心血管的事件以后加速物理 deconditioning,特别与他们的更年轻的对应物相比。最后几十年是到与 CHD 在病人之中在死亡,锻练能力,心理风险因素,发炎,和肥胖上表明了心脏的康复(CR ) 和锻练治疗的有益的效果的多重研究的厕所。不幸地,这个领域里的可得到的数据的重要部分与更年轻的病人相关。可行解释是更老的病人在为以病人开始并且延长到医生的多重原因的这些节目是非常未被充分代表的。在这篇文章,我们将考察 CR 节目的好处在之中老,以及一些妨碍他们的参予的障碍。 | Arthur R Menezes Carl J Lavie Richard V Milani Ross A Arena Timothy S Church | 2012 | Journal of Geriatric Cardiology2012，9，1： | 25 |
| 4 | Intracellular HMGB1 as a novel tumor suppressor of pancreatic cancer显示文摘尽管有最近的进展, oncogenic K 地岬驾驶的胰腺的 ductal 腺癌(PDAC ) 在最致命的人的癌症之中留在现代医学。PDAC 的致病对内在的染色体不稳定性和外来的发炎激活部分可归因。然而,在在胰腺的 tumorigenesis 的这二个事件之间的分子的连接充分还没被建立了。这里,我们证明(HMGB1 ) 细胞内部的高活动性组盒子 1 显著地压制 oncogenic 由禁止染色体的 K-Ras-driven 胰腺的 tumorigenesis 调停不稳定性的支持 inflammatory nucleosome 版本。任何一个单身者的有条件的基因脱离或在胰的 HMGB1 的两等位基因在出生使老鼠变为极其敏感到先锋损害的 oncogenic K-Ras-driven 开始,包括胰腺的 intraepithelial 瘤, intraductal 乳突的 mucinous 瘤,和 mucinous 膀胱的瘤。在胰的 HMGB1 的损失与染色体重新整理和 telomere 畸形描绘的氧化 DNA 损坏和 chromosomal 不稳定性被联系。这些导致煽动性的 nucleosome 版本并且宣传 K-Ras-driven 胰腺的 tumorigenesis。细胞外的 nucleosomes 支持 interleukin 6 (IL-6 ) 由渗入 macrophages/neutrophils 的分泌物并且提高在胰腺的损害表明激活的 oncogenic K 地岬。到 IL-6 或 histone H3 或为先进 glycation 的受体的大美人的抵销的抗体结束产品都限制表明激活的 K 地岬,阻止癌症开发和转移 / 侵略,并且延长在 Pdx1-Cre 的动物幸存; K 地岬 G12D/+;Hmgb1/ 鼠标。由 glycyrrhizin 的 HMGB1 损失的药理学抑制在煽动性的条件下面在老鼠限制 oncogenic K-Ras-driven tumorigenesis。减少在 PDAC 病人的 HMGB1 的原子、全部的细胞的表示与差的全面幸存相关,在 PDAC 与预示、治疗学的关联作为新奇肿瘤 suppressor 支持细胞内部的 HMGB1。 | Rui Kang Yangchun Xie Qiuhong Zhang Wen Hou Qingping Jiang Shan Zhu Jinbao Liu Dexing Zeng Haichao Wang David L Bartlet Timothy R Billiar Herbert J Zeh III Michael T Lotze Daolin Tang | 2017 | Cell Research2017，27，7： | 22 |
| 5 | Observation of ocean current response to 1998 Hurricane Georges in the Gulf of Mexico显示文摘The ocean current response to a hurricane on the shelf-break is examined. The study area is the DeSoto Canyon in the northeast Gulf of Mexico, and the event is the passage of 1998 Hurricane Georges with a maximum wind speed of 49 m/s. The data sets used for analy- sis consist of the mooring data taken by the Field Program of the DeSoto Canyon Eddy Intrusion Study, and simultaneous winds ob- served by NOAA (National Oceanic and Atmospheric Administration) Moored Buoy 42040. Time-depth ocean current energy density images derived from the observed data show that the ocean currents respond almost immediately to the hurricane with important differ- ences on and off the shelf. On the shelf, in the shallow water of 100 m, the disturbance penetrates rapidly downward to the bottom and forms two energy peaks, the major peak is located in the mixed layer and the secondary one in the lower layer. The response dissipates quickly after external forcing disappears. Off the shelf, in the deep water, the major disturbance energy seems to be trapped in the mixed layer with a trailing oscillation; although the disturbance signals may still be observed at the depths of 500 and 1 290 m. Verti- cal dispersion analysis reveals that the near-initial wave packet generated off the shelf consists of two modes. One is a barotropic wave mode characterized by a fast decay rate of velocity amplitude of 0.020 s-1, and the other is baroclinic wave mode characterized by a slow decay rate of 0.006 9 s-1. The band-pass-filtering and empirical function techniques are employed to the frequency analysis. The results indicate that all frequencies shift above the local inertial frequency. On the shelf, the average frequency is 1.04f in the mixed layer, close to the diagnosed frequency of the first baroclinic mode, and the average frequency increases to 1.07f in the thermocline. Off the shelf, all frequencies are a little smaller than the diagnosed frequency of the first mode. The average frequency decreases from 1.035f in the mixed layer to 1.02f in the thermocline, implying a trend for the shift in frequency of the oscillations towards f with the depth. | ZHENG Quanan LAI Ronald J HUANG Nortlen E PAN Jiayi LIU W Timothy | 2006 | Acta Oceanologica Sinica2006，25，1： | 20 |
| 6 | Irritable bowel syndrome: A microbiome-gut-brain axis disorder?显示文摘Irritable bowel syndrome(IBS) is an extremely prevalent but poorly understood gastrointestinal disorder. Consequently, there are no clear diagnostic markers to help diagnose the disorder and treatment options are limited to management of the symptoms. The concept of a dysregulated gut-brain axis has been adopted as a suitable model for the disorder. The gut microbiome may play an important role in the onset and exacerbation of symptoms in the disorder and has been extensively studied in this context. Although a causal role cannot yet be inferred from the clinical studies which have attempted to characterise the gut microbiota in IBS, they do confirm alterations in both community stability and diversity. Moreover, it has been reliably demonstrated that manipulation of the microbiota can influence the key symptoms, including abdominal pain and bowel habit, and other prominent features of IBS. A variety of strategies have been taken to study these interactions, including probiotics, antibiotics, faecal transplantations and the use of germ-free animals. There are clear mechanisms through which the microbiota can produce these effects, both humoral and neural. Taken together, these findings firmly establish the microbiota as a critical node in the gut-brain axis and one which is amenable to therapeutic interventions. | Paul J Kennedy John F Cryan Timothy G Dinan Gerard Clarke | 2014 | World Journal of Gastroenterology2014，20，39： | 20 |
| 7 | Small incision lenticule extraction (SMILE) history, fundamentals of a new refractive surgery technique and clinical outcomes显示文摘This review summarizes the current status of the small incision lenticule extraction(SMILE)procedure.Following the early work by Sekundo et al.and Shah et al.,SMILE has become increasingly popular.The accuracy of the creation of the lenticule with the VisuMax femtosecond laser(Carl Zeiss Meditec)has been verified using very high-frequency(VHF)digital ultrasound and optical coherence tomography(OCT).Visual and refractive outcomes have been shown to be similar to those achieved with laser in situ keratomileusis(LASIK),notably in a large population reported by Hjortdal,Vestergaard et al.Safety in terms of the change in corrected distance visual acuity(CDVA)has also been shown to be similar to LASIK.It was expected that there would be less postoperative dry eye after SMILE compared to LASIK because the anterior stroma is disturbed only by the small incision,meaning that the anterior corneal nerves should be less affected.A number of studies have demonstrated a lower reduction and faster recovery of corneal sensation after SMILE than LASIK.Some studies have also used confocal microscopy to demonstrate a lower decrease in subbasal nerve fiber density after SMILE than LASIK.The potential biomechanical advantages of SMILE have been modeled by Reinstein et al.based on the non-linearity of tensile strength through the stroma.Studies have reported a similar change in Ocular Response Analyzer(Reichert)parameters after SMILE and LASIK,however,these have previously been shown to be unreliable as a representation of corneal biomechanics.Retreatment options after SMILE are discussed.Tissue addition applications of the SMILE procedure are also discussed including the potential for cryo-preservation of the lenticule for later reimplantation(Mohamed-Noriega,Angunawela,Lim et al.),and a new procedure referred to as endokeratophakia in which a myopic SMILE lenticule is implanted into a hyperopic patient(Pradhan et al.).Finally,studies reporting microdistortions in Bowman’s layer and corneal wound healing responses are also described. | Dan Z Reinstein Timothy J Archer Marine Gobbe | 2014 | Eye and Vision2014，1，1： | 12 |
| 8 | Management of borderline and locally advanced pancreatic cancer:Where do we stand?显示文摘Many patients with pancreas cancer present with locally advanced pancreatic cancer(LAPC).The principle tools used for diagnosis and staging of LAPC include endoscopic ultrasound,axial imaging with computed tomography and magnetic resonance imaging,and diagnostic laparoscopy.The definition of resectability has historically been vague,as there is considerable debate and controversy as to the definition of LAPC.For the patient with LAPC,there is some level of involvement of the surrounding vascular structures,which include the superior mesenteric artery,celiac axis,hepatic artery,superior mesenteric vein,or portal vein.When feasible,most surgeons would recommend possible surgical resection for patients with borderline LAPC,with the goal of an R0 resection.For initially unresectable LAPC,neoadjuvant should be strongly considered.Specifically,these patients should be offered neoadjuvant therapy,and the tumor should be assessed for possible response and eventual resection.The efficacy of neoadjuvant therapy with this approach as a bridge to potential curative resection is broad,ranging from 3%-79%.The different modalities of neoadjuvant therapy include sin-gle or multi-agent chemotherapy combined with radiation,chemotherapy alone,and chemotherapy followed by chemotherapy with radiation.This review focuses on patients with LAPC and addresses recent advances and controversies in the field. | Jin He Andrew J Page Matthew Weiss Christopher L Wolfgang Joseph M Herman Timothy M Pawlik | 2014 | World Journal of Gastroenterology2014，20，9： | 11 |
| 9 | Passive expansion of sub-maximally dilated transjugular intrahepatic portosystemic shunts and assessment of clinical outcomes显示文摘AIM To assess for passive expansion of sub-maximally dilated transjugular intrahepatic portosystemic shunts(TIPS) and compare outcomes with maximally dilated TIPS.METHODS Polytetrafluoroethylene covered TIPS(Viatorr) from July 2002 to December 2013 were retrospectively reviewed at two hospitals in a single institution. Two hundred and thirty patients had TIPS maximally dilated to 10 mm(m TIPS), while 43 patients who were at increased risk for hepatic encephalopathy(HE), based on clinical evaluation or low pre-TIPS portosystemic gradient(PSG), had 10 mm TIPS sub-maximally dilated to 8 mm(sm TIPS). Group characteristics(age, gender, Model for End-Stage Liver Disease score, post-TIPS PSG and clinical outcomes were compared between groups, including clinical success(ascites or varices), primary patency,primary assisted patency, and severe post-TIPS HE. A subset of fourteen patients with sm TIPS underwent follow-up computed tomography imaging after TIPS creation, and were grouped based on time of imaging(< 6 mo and > 6 mo). Change in diameter and crosssectional area were measured with 3D imaging software to evaluate for passive expansion.RESULTS Patient characteristics were similar between the sm TIPS and m TIPS groups, except for pre-TIPS portosystemic gradient, which was lower in the sm TIPS group(19.4 mm Hg ± 6.8 vs 22.4 mm Hg ± 7.1, P = 0.01). Primary patency and primary assisted patency between sm TIPS and m TIPS was not significantly different(P = 0.64 and 0.55, respectively). Four of the 55 patients(7%) with sm TIPS required TIPS reduction for severe refractory HE, while this occurred in 6 of the 218 patients(3%) with m TIPS(P = 0.12). For the 14 patients with follow-up computed tomography(CT) imaging, the median imaging follow-up was 373 d. There was an increase in median TIPS diameter, median percent diameter change, median area, and median percent area change in patients with CT follow-up greater than 6 mo after TIPS placement compared to follow-up within 6 mo(8.45 mm, 5.58%, 56.04 mm^2, and 11.48%, respectively, P = 0.01).CONCLUSION Passive expansion of sm TIPS does occur but clinical outcomes of sm TIPS and m TIPS were similar. Sub-maximal dilation can prevent complications related to overshunting in select patients. | Michael C Hsu Charles N Weber S William Stavropoulos Timothy W Clark Scott O Trerotola Richard D Shlansky Goldberg Michael C Soulen Gregory J Nadolski | 2017 | World Journal of Hepatology2017，9，12： | 11 |
| 10 | 绿地免费开放对不同收入居民休闲行为和地方情感的影响研究显示文摘基于824份居民有效问卷数据,通过评价绿地空间免费开放对不同收入水平居民休闲行为和地方情感的影响,探讨绿地空间免费开放的意义和必要性.研究揭示:1)大样本数据支持休闲参与在居民对绿地空间免费开放感知和地方依恋间的中介作用,绿地空间免费开放显著影响居民的休闲参与行为,同时影响居民对整个城市的地方依恋.2)收入变量显著干扰休闲参与中介模型,中、高收入组地方依恋的形成直接来自于居民对绿地空间免费开放政策的正面感知,而对于低收入群体,免费开放将有效推动居民绿地空间的休闲活动,并因此形成对城市的情感依恋.3)收入干扰模型验证了收入水平是影响居民绿地空间利用和地方依恋中介模型的干扰因素. | 史春云 杨旸 Timothy J Fik 姚晓蔚 赵桃桃 方星 李晨 | 2017 | 江苏师范大学学报(自然科学版)2017，35，3： | 8 |
| 11 | Notch signaling controls chondrocyte hypertrophy via indirect regulation of Sox9显示文摘RBPjk-dependent Notch signaling regulates both the onset of chondrocyte hypertrophy and the progression to terminal chondrocyte maturation during endochondral ossification. It has been suggested that Notch signaling can regulate Sox9 transcription, although how this occurs at the molecular level in chondrocytes and whether this transcriptional regulation mediates Notch control of chondrocyte hypertrophy and cartilage development is unknown or controversial. Here we have provided conclusive genetic evidence linking RBPjk-dependent Notch signaling to the regulation of Sox9 expression and chondrocyte hypertrophy by examining tissuespecific Rbpjk mutant(Prx1Cre;Rbpjkf/f), Rbpjk mutant/Sox9 haploinsufficient(Prx1Cre;Rbpjkf/f;Sox9f/1),and control embryos for alterations in SOX9 expression and chondrocyte hypertrophy during cartilage development. These studies demonstrate that Notch signaling regulates the onset of chondrocyte maturation in a SOX9-dependent manner, while Notch-mediated regulation of terminal chondrocyte maturation likely functions independently of SOX9. Furthermore, our in vitro molecular analyses of the Sox9 promoter and Notch-mediated regulation of Sox9 gene expression in chondrogenic cells identified the ability of Notch to induce Sox9 expression directly in the acute setting, but suppresses Sox9 transcription with prolonged Notch signaling that requires protein synthesis of secondary effectors. | Anat Kohn Timothy P Rutkowski Zhaoyang Liu Anthony J Mirando Michael J Zuscik Regis J O'Keefe Matthew J Hilton | 2015 | Bone Research2015，3，3： | 8 |
| 12 | Drug eluting biliary stents to decrease stent failure rates:Areview of the literature显示文摘Biliary stenting is clinically effective in relieving both malignant and non-malignant obstructions. However, there are high failure rates associated with tumor ingrowth and epithelial overgrowth as well as internally from biofilm development and subsequent clogging. Within the last decade, the use of prophylactic drug eluting stents as a means to reduce stent failure has been investigated. In this review we provide an overview of the current research on drug eluting biliary stents. While there is limited human trial data regarding the clinical benefit of drug eluting biliary stents in preventing stent obstruction, recent research suggests promise regarding their safety and potential efficacy. | Joseph Shatzel Jisoo Kim Kartik Sampath Sharjeel Syed Jennifer Saad Zilla H Hussain Kabir Mody J Marc Pipas Stuart Gordon Timothy Gardner Richard I Rothstein | 2016 | World Journal of Gastrointestinal Endoscopy2016，8，2： | 6 |
| 13 | 超声心动图对左心发育不良综合征术前诊断及术后评价的意义显示文摘目的 总结 1998年在美国贝勒医学院工作期间 ,左心发育不良综合征 (HLHS)患者改良NorwoodⅢ期心脏重建手术前后超声心动图诊断的资料和经验 ,评价其价值并为国内同行借鉴。方法 HLHS患者 18例 ,NorwoodⅠ期手术 10例 ,Ⅱ期手术 6例 ,Ⅲ期手术 2例。术前超声心动图结果与术中外科诊断比较 ,分诊断符合、诊断不符和轻微差别。结果 NorwoodⅠ期手术 10例患者均无术前心导管检查 ,超声心动图术前诊断与术中外科诊断达到 10 0 %的诊断符合。Ⅱ期手术患者 6例 ,超声心动图对Ⅰ期手术术后评价的诊断符合率为10 0 % ,分支肺动脉的评价 33 .3 %诊断符合 ,6 6 .7%有轻微差别。Ⅲ期手术的 2例病患者超声心动图与术中诊断均相符。结论 单靠超声心动图能够确立HLHS的诊断并为NorwooⅠ期手术提供足够的信息 ,对NorwoodⅡ期和Ⅲ期术前及术后诊断超声心动图能够提供大量正确的信息 。 | 吴进 Ricardo H Pignatelli Louis I Bezold J Timothy Bricker | 2001 | 中华超声影像学杂志2001，10，9： | 6 |
| 14 | Management of gastric cancer in Asia: resource-stratified guidelines显示文摘 | Lin Shen Yan-Shen Shan Huang-Ming Hu Timothy J Price Bhawna Sirohi Kun-Huei Yeh Yi-Hsin Yang Takeshi Sano Han-Kwang Yang Xiaotian Zhang Sook Ryun Park Masashi Fujii Yoon-Koo Kang Li-Tzong Chen | 2013 | Lancet Oncology2013，，12： | 5 |
| 15 | 饮食、营养及癌症风险:已知与前景显示文摘几十年来科学家们就认为,营养在癌症发展中起着重要的作用。早在20世纪60年代就有流行病学研究显示,不同人群的癌症发病率差别非常大,而且从癌症低发国家移民到高发国家后,移民们的癌症发病率可能上升到与移民国家原住民的癌症发病率相当,甚至更高1-2。这些观察结果提示环境是导致癌症发生的重要因素。 | Timothy J Key Kathryn E Bradbury Aurora Perez-Comago Rashmi Sinha Konstantinos K Tsilidis Shoichiro Tsugane 徐欣悦(译) 严雪敏(校) | 2020 | 英国医学杂志中文版2020，23，7： | 5 |
| 16 | Distribution of pericellular matrix molecules in the temporomandibular joint and their chondroprotective effects against inflammation显示文摘The objectives of this study were to(1) determine the distribution and synthesis of pericellular matrix(PCM) molecules(collagen VI, collagen IV and laminin) in rat temporomandibular joint(TMJ) and(2) investigate the effects of PCM molecules on chondrocytes against inflammation in osteoarthritis. Four zones(fibrous, proliferating, mature and hypertrophic) of condylar cartilage and three bands(anterior, intermediate and posterior) of disc were analysed by immunohistochemistry for the presence of PCM molecules in rat TMJs. Isolated chondrocytes were pre-treated with PCM molecules before being subjected to interleukin(IL)-1β treatment to stimulate inflammation. The responses of the chondrocytes were analysed using gene expression, nitric oxide release and matrix metalloproteinase(MMP)-13 production measures. Histomorphometric analyses revealed that the highest areal deposition of collagen VI(67.4%), collagen IV(45.7%) and laminin(52.4%) was in the proliferating zone of TMJ condylar cartilage. No significant difference in the distribution of PCM molecules was noted among the three bands of the TMJ disc. All three PCM molecules were expressed intracellularly by chondrocytes cultured in the monolayer. Among the PCM molecules, pre-treatment with collagen VI enhanced cellular proliferation, ameliorated IL-1β-induced MMP-3, MMP-9, MMP-13 and inducible nitric oxide synthase gene expression, and attenuated the downregulation of cartilage matrix genes, including collagen I, aggrecan and cartilage oligomeric matrix protein(COMP). Concurrently, collagen VI pretreatment inhibited nitric oxide and MMP-13 production. Our study demonstrates for the first time the distribution and role of PCM molecules, particularly collagen VI, in the protection of chondrocytes against inflammation. | Wern Cui Chu Shipin Zhang Timothy J Sng Yu Jie Ong Wen-Li Tan Vivien Y Ang Casper B Foldager Wei Seong Toh | 2017 | International Journal of Oral Science2017，9，1： | 5 |
| 17 | BNIP3 is essential for mediating 6-thioguanine- and 5-fluorouracil-induced autophagy following DNA mismatch repair processing显示文摘DNA 失配修理(MMR ) 与象 6-thioguanine (6-TG ) 和 5 氟尿嘧啶(5-FU ) 那样的临床上重要的 nucleoside 类似物处理化学上导致的错误对追随者处理。这些药处理的 MMR 为不可弥补的 DNA 损坏为修理和 apoptosis 或 autophagy 的以后的正式就职在延长 G2/M 房间周期拘捕的激活被含有。在这研究,我们在 autophagy,和在 G2/M 房间周期拘捕之间的时间的关系的激活和 6-TG 和 5-FU 处理的调停 BNIP3 的 autophagy 追随者 MMR 的激活调查了 Bcl2 和侵入人体气管粘膜的病菌 E1B Nineteen-kilodalton 交往蛋白质(BNIP3 ) 的角色。我们发现 BNIP3 蛋白质层次是在一个 MLH1 (MMR+) 依赖者的 upregulated 方式追随者 6-TG 和 5-FU 处理。随后的小介入的 RNA (siRNA ) 调停了 BNIP3 击倒废除 6-TG-induced autophagy。我们也发现击倒的 p53 或由 rapamycin cotreatment 的 mTOR 活动的抑制损害 6-TG- 和 BNIP3 蛋白质层次和 autophagy 的 5-FU-induced upregulation。而且,检查点 kinase 的抑制 1 (Chk1 ) 有在由 Chk1 siRNA 的 6-TG-induced G2/M 房间周期拘捕的随后的减小的表示支持 6-TG-induced autophagy 的程度。这些调查结果建议 BNIP3 调停以一种 p53 依赖、 mTOR 依赖的方式的 6-TG- 和 5-FU-induced autophagy。另外,激活 Chk1 的 G2/M 房间周期拘捕的持续时间决定这些 nucleoside 类似物处理的 autophagy 追随者 MMR 的水平。 | Xuehuo Zeng | 2010 | Cell Research2010，20，6： | 4 |
| 18 | Refining pathological evaluation of neoadjuvant therapy for adenocarcinoma of the esophagus显示文摘AIM:To assess tumour regression grade(TRG)and lymph node downstaging to help define patients who benefit from neoadjuvant chemotherapy.METHODS:Two hundred and eighteen consecutive patients with adenocarcinoma of the esophagus or gastro-esophageal junction treated with surgery alone or neoadjuvant chemotherapy and surgery between 2005and 2011 at a single institution were reviewed.Triplet neoadjuvant chemotherapy consisting of platinum,fluoropyrimidine and anthracycline was considered for operable patients(World Health Organization performance status≤2)with clinical stage T2-4 N0-1.Response to neoadjuvant chemotherapy(NAC)was assessed using TRG,as described by Mandard et al.In addition lymph node downstaging was also assessed.Lymph node downstaging was defined by cN1 at diagnosis:assessed radiologically(computed tomography,positron emission tomography,endoscopic ultrasonography),then pathologically recorded as N0 after surgery;ypN0 if NAC given prior to surgery,or pN0if surgery alone.Patients were followed up for 5 years post surgery.Recurrence was defined radiologically,with or without pathological confirmation.An association was examined between t TRG and lymph node downstaging with disease free survival(DFS)and a comprehensive range of clinicopathological characteristics.RESULTS:Two hundred and eighteen patients underwent esophageal resection during the study interval with a mean follow up of 3 years(median follow up:2.552,95%CI:2.022-3.081).There was a 1.8%(n=4)inpatient mortality rate.One hundred and thirty-six(62.4%)patients received NAC,with 74.3%(n=101)of patients demonstrating some signs of pathological tumour regression(TRG 1-4)and 5.9%(n=8)having a complete pathological response.Forty four point one percent(n=60)had downstaging of their nodal disease(cN1 to ypN0),compared to only 15.9%(n=13)that underwent surgery alone(pre-operatively overstaged:cN1 to pN0),(P<0.0001).Response to NAC was associated with significantly increased DFS(mean DFS;TRG 1-2:5.1years,95%CI:4.6-5.6 vs TRG 3-5:2.8 years,95%CI:2.2-3.3,P<0.0001).Nodal down-staging conferred a significant DFS advantage for those patients with a poor primary tumour response to NAC(median DFS;TRG 3-5 and nodal down-staging:5.533 years,95%CI:3.558-7.531 vs TRG 3-5 and no nodal down-staging:1.114 years,95%CI:0.961-1.267,P<0.0001).CONCLUSION:Response to NAC in the primary tumour and in the lymph nodes are both independently associated with improved DFS. | Fergus Noble Luke Nolan Adrian C Bateman James P Byrne Jamie J Kelly Ian S Bailey Donna M Sharland Charlotte N Rees Timothy J Iveson Tim J Underwood Andrew R Bateman | 2013 | World Journal of Gastroenterology2013，19，48： | 4 |
| 19 | Development of minimally invasive techniques for management of medically-complicated obesity显示文摘The field of bariatric surgery has been rapidly growing and evolving over the past several decades. During the period that obesity has become a worldwide epidemic, new interventions have been developed to combat this complex disorder. The development of new laparoscopic and minimally invasive treatments for medically-complicated obesity has made it essential that gastrointestinal physicians obtain a thorough understanding of past developments and possible future directions in bariatrics. New laparoscopic advancements provide patients and practitioners with a variety of options that have an improved safety profile and better efficacy without open, invasive surgery. The mechanisms of weight loss after bariatric surgery are complex and may in part be related to altered release of regulatory peptide hormones from the gut. Endoscopic techniques designed to mimic the effects of bariatric surgery and endolumenal inter-ventions performed entirely through the gastrointestinal tract offer potential advantages. Several of these new techniques have demonstrated promising, preliminary results. We outline herein historical and current trends in the development of bariatric surgery and its transition to safer and more minimally invasive procedures designed to induce weight loss. | Farzin Rashti Ekta Gupta Suzan Ebrahimi Timothy R Shope Timothy R Koch Christopher J Gostout | 2014 | World Journal of Gastroenterology2014，20，37： | 4 |
| 20 | Radial artery access site complications during cardiac procedures,clinical implications and potential solutions: The role of nitric oxide显示文摘Percutaneous coronary intervention for the treatment of coronary artery disease is most commonly performed in the UK through the radial artery,as this is considered to be safer than the femoral approach.However,despite improvements in technology and techniques,complications can occur.The most common complication,arterial spasm,can cause intense pain and,in some cases,procedural failure.The incidence of spasm is dependent on several variables,including operator experience,artery size,and equipment used.An antispasmolytic cocktail can be applied to reduce spasm,which usually includes an exogenous nitric oxide(NO)donor(glyceryl trinitrate).NO is an endogenous local vasodilator and therefore is a potential target for anti-spasm intervention.However,systemic administration can result in unwanted side-effects,such as hypotension.A method that adopts local delivery of NO might be advantageous.This review article describes the mechanisms involved in radial artery spasm,discusses the advantages and disadvantages of current strategies to reduce spasm,and highlight the potential of NO-loaded nanoporous materials for use in this setting. | Emma M Coghill Timothy Johnson Russell E Morris Ian L Megson Stephen J Leslie | 2020 | World Journal of Cardiology2020，12，1： | 4 |
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