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| 1 | Ultra-thin, planar, Babinet-inverted plasmonic metalenses显示文摘We experimentally demonstrate the focusing of visible light with ultra-thin,planar metasurfaces made of concentrically perforated,30-nm-thick gold films.The perforated nano-voids—Babinet-inverted(complementary)nano-antennas—create discrete phase shifts and form a desired wavefront of cross-polarized,scattered light.The signal-to-noise ratio in our complementary nano-antenna design is at least one order of magnitude higher than in previous metallic nano-antenna designs.We first study our proof-of-concept‘metalens’with extremely strong focusing ability:focusing at a distance of only 2.5 mm is achieved experimentally with a 4-mm-diameter lens for light at a wavelength of 676 nm.We then extend our work with one of these‘metalenses’and achieve a wavelength-controllable focal length.Optical characterization of the lens confirms that switching the incident wavelength from 676 to 476 nm changes the focal length from 7 to 10 mm,which opens up new opportunities for tuning and spatially separating light at different wavelengths within small,micrometer-scale areas.All the proposed designs can be embedded on-chip or at the end of an optical fiber.The designs also all work for two orthogonal,linear polarizations of incident light. | Xingjie Ni Satoshi Ishii Alexander V Kildishev Vladimir M Shalaev | 2013 | Light(Science & Applications)2013，2，1： | 20 |
| 2 | Label-free detection of single nanoparticles and biological molecules using microtoroid optical resonators显示文摘Single-molecule detection is one of the fundamental challenges of modern biology.Such experiments often use labels that can be expensive,difficult to produce,and for small analytes,might perturb the molecular events being studied.Analyte size plays an important role in determining detectability.Here we use laser-frequency locking in the context of sensing to improve the signal-to-noise ratio of microtoroid optical resonators to the extent that single nanoparticles 2.5 nm in radius,and 15.5 kDa molecules are detected in aqueous solution,thereby bringing these detectors to the size limits needed for detecting the key macromolecules of the cell.Our results,covering several orders of magnitude of particle radius(100 nm to 2 nm),agree with the‘reactive’model prediction for the frequency shift of the resonator upon particle binding.This confirms that the main contribution of the frequency shift for the resonator upon particle binding is an increase in the effective path length due to part of the evanescent field coupling into the adsorbed particle.We anticipate that our results will enable many applications,including more sensitive medical diagnostics and fundamental studies of single receptor–ligand and protein–protein interactions in real time. | Judith Su Alexander FG Goldberg Brian M Stoltz | 2016 | Light(Science & Applications)2016，5，1： | 20 |
| 3 | Endoscopic transpapillary brush cytology and forceps biopsy in patients with hilar cholangiocarcinoma显示文摘AIM: To evaluate the sensitivity of brush cytology and forceps biopsy in a homogeneous patient group with hilar cholangiocarcinoma.METHODS: Brush cytology and forceps biopsy were routinely performed in patients with suspected malignant biliary strictures. Fifty-eight consecutive patients undergoing endoscopic retrograde cholangio-pancreatography (ERCP) including forceps biopsy and brush cytology in patients with hilar cholangiocarcinoma between 1995-2005.RESULTS: Positive results for malignancy were obtained in 24/58 patients (41.4%) by brush cytology and in 31/58 patients (53.4%) by forceps biopsy. The combination of both techniques brush cytology and forceps biopsy resulted only in a minor increase in diagnostic sensitivity to 60.3% (35/58 patients). In 20/58 patients (34.5%), diagnosis were obtained by both positive cytology and positive histology, in 11/58 (19%) by positive histology (negative cytology) and only 4/58 patients (6.9%) were confirmed by positive cytology (negative histology).CONCLUSION: Brush cytology and forceps biopsy have only limited sensitivity for the diagnosis of malignant hilar tumors. In our eyes, additional diagnostic techniques should be evaluated and should become routine in patients with negative cytological and histological findings. | Andreas Weber Claus von Weyhern Falko Fend Jochen Schneider Bruno Neu Alexander Meining Hans Weidenbach Roland M Schmid Christian Prinz | 2008 | World Journal of Gastroenterology2008，14，7： | 17 |
| 4 | Global kinematics of tectonic plates and subduction zones since the late Paleozoic Era显示文摘Detailed global plate motion models that provide a continuous description of plate boundaries through time are an effective tool for exploring processes both at and below the Earth's surface. A new generation of numerical models of mantle dynamics pre-and post-Pangea timeframes requires global kinematic descriptions with full plate reconstructions extending into the Paleozoic(410 Ma). Current plate models that cover Paleozoic times are characterised by large plate speeds and trench migration rates because they assume that lowermost mantle structures are rigid and fixed through time. When used as a surface boundary constraint in geodynamic models, these plate reconstructions do not accurately reproduce the present-day structure of the lowermost mantle. Building upon previous work, we present a global plate motion model with continuously closing plate boundaries ranging from the early Devonian at 410 Ma to present day.We analyse the model in terms of surface kinematics and predicted lower mantle structure. The magnitude of global plate speeds has been greatly reduced in our reconstruction by modifying the evolution of the synthetic Panthalassa oceanic plates, implementing a Paleozoic reference frame independent of any geodynamic assumptions, and implementing revised models for the Paleozoic evolution of North and South China and the closure of the Rheic Ocean. Paleozoic(410-250 Ma) RMS plate speeds are on average ~8 cm/yr, which is comparable to Mesozoic-Cenozoic rates of ~6 cm/yr on average.Paleozoic global median values of trench migration trend from higher speeds(~2.5 cm/yr) in the late Devonian to rates closer to 0 cm/yr at the end of the Permian(~250 Ma), and during the Mesozoic-Cenozoic(250-0 Ma) generally cluster tightly around ~1.1 cm/yr. Plate motions are best constrained over the past 130 Myr and calculations of global trench convergence rates over this period indicate median rates range between 3.2 cm/yr and 12.4 cm/yr with a present day median rate estimated at~5 cm/yr. For Paleozoic times(410-251 Ma) our model results in median convergence rates largely~5 cm/yr. Globally,~90% of subduction zones modelled in our reconstruction are determined to be in a convergent regime for the period of 120-0 Ma. Over the full span of the model, from 410 Ma to 0 Ma,~93% of subduction zones are calculated to be convergent, and at least 85% of subduction zones are converging for 97% of modelled times. Our changes improve global plate and trench kinematics since the late Paleozoic and our reconstructions of the lowermost mantle structure challenge the proposed fixity of lower mantle structures, suggesting that the eastern margin of the African LLSVP margin has moved by as much as ~1450 km since late Permian times(260 Ma). The model of the plate-mantle system we present suggests that during the Permian Period, South China was proximal to the eastern margin of the African LLSVP and not the western margin of the Pacific LLSVP as previous thought. | Alexander Young Nicolas Flament Kayla Maloney Simon Williams Kara Matthews Sabin Zahirovic R.Dietmar Müller | 2019 | Geoscience Frontiers2019，10，3： | 10 |
| 5 | Return to sport following tibial plateau fractures: A systematic review显示文摘AIM To systemically review all studies reporting return to sport following tibial plateau fracture, in order to provide information on return rates and times to sport, and to assess variations in sporting outcome for different treatment methods.METHODS A systematic search of CINAHAL, Cochrane, EMBASE, Google Scholar, MEDLINE, PEDro, Scopus, SPORTDiscus and Web of Science was performed in January 2017 using the keywords 'tibial', 'plateau', 'fractures', 'knee', 'athletes', 'sports', 'non-operative', 'conservative', 'operative', 'return to sport'. All studies which recorded return rates and times to sport following tibial plateau fractures were included. RESULTS Twenty-seven studies were included: 1 was a randomised controlled trial, 7 were prospective cohort studies, 16 were retrospective cohort studies, 3 were case series. One study reported on the outcome of conservative management(n = 3); 27 reported on the outcome of surgical management(n = 917). Nine studies reported on Open Reduction Internal Fixation(ORIF)(n = 193), 11 on Arthroscopic-Assisted Reduction Internal Fixation(ARIF)(n = 253) and 7 on Frame-Assisted Fixation(FRAME)(n = 262). All studies recorded 'return to sport'rates. Only one study recorded a 'return to sport' time. The return rate to sport for the total cohort was 70%. For the conservatively-managed fractures, the return rate was 100%. For the surgically-managed fractures, the return rate was 70%. For fractures managed with ORIF, the return rate was 60%. For fractures managed with ARIF, the return rate was 83%. For fractures managed with FRAME was 52%. The return rate for ARIF was found to be significantly greater than that for ORIF(OR 3.22, 95%CI: 2.09-4.97, P < 0.001) and for FRAME(OR 4.33, 95%CI: 2.89-6.50, P < 0.001). No difference was found between the return rates for ORIF and FRAME(OR 1.35, 95%CI: 0.92-1.96, P = 0.122). The recorded return time was 6.9 mo(median), from a study reporting on ORIF.CONCLUSION Return rates to sport for tibial plateau fractures remain limited compared to other fractures. ARIF provides the best return rates. There is limited data regarding return times to sport. Further research is required to determine return times to sport, and to improve return rates to sport, through treatment and rehabilitation optimisation. | Greg A J Robertson Seng J Wong Alexander M Wood | 2017 | World Journal of Orthopedics2017，8，7： | 10 |
| 6 | Pyrrolidine dithiocarbamate reduces ischemia-reperfusion injury of the small intestine显示文摘AIM: To evaluate whether pyrrolidine dithiocarbamate (PDTC), an enhancer of HO production, attenuates intestinal IR injury.METHODS: Eighteen male rats were randomly allocated into three groups: (a) sham; (b) IR, consisting of 30 min of intestinal ischemia, followed by 2-h period of reperfusion; and (c) PDTC treatment before IR. Intestinal microvascular perfusion (IMP) was monitored continuously by laser Doppler fiowmetry. At the end of the reperfusion, serum samples for lactate dehydrogenase (LDH) levels and biopsies of ileum were obtained. HO activity in the ileum was assessed at the end of the reperfusion period.RESULTS: At the end of the reperfusion in the IR group,IMP recovered partially to 42.5% of baseline (P<0.05vs sham), whereas PDTC improved IMP to 67.3% of baseline (P<0.01 vs IR). There was a twofold increase in HO activity in PDTC group (2 062.66±106.11) as compared to IR (842.3±85.12) (P<0.001). LDH was significantly reduced (P<0.001) in PDTC group (585.6±102.4)as compared to IR group (1 973.8±306.5). Histological examination showed that the ileal mucosa was significantly less injured in PDTC group as compared with IR group.CONCLUSION: Our study demonstrates that PDTC improves the IMP and attenuates IR injury of the intestine possibly via HO production. Additional studies are warranted to evaluate the clinical efficacy of PDTC in the prevention of IR injury of the small intestine. | Ismail H Mallick Wen-Xuan Yang Marc C Winslet Alexander M Seifalian | 2005 | World Journal of Gastroenterology2005，11，46： | 8 |
| 7 | CALCULATION OF ELASTIC DAMPING CHARACTERISTICS OF ROTOR SUPPORT MADE OF METAL RUBBER MATERIAL UNDER VARIABLE LOADS显示文摘金属橡胶(先生) 干燥磨擦更潮湿基于转子支持的负担被设计。为在领前负担下面获得支持的磁滞现象环的一台试验性的仪器被设计。圆形的先生的有弹性抑制的特征更潮湿当在可变负担下面的转子支持被学习磁滞现象环介绍,使用更潮湿。颤动刚硬和精力驱散系数少些从磁滞现象环被计算,基于对有在一种尺寸的简单结构的先生元素的变丑过程的描述坐标系统。计算结果证明精力驱散系数在先生元素并且在边界在之间上内部更潮湿并且转子支持的框架是近似相等的。当时,为领前负担和一个轴的负担的磁滞现象环的比较显示了大差别精力驱散的系数和 MR 的僵硬更潮湿被担心。 | JIANG Hongyuan YAN Hui AO Hongrui ALEXANDER M Ulanov | 2007 | Chinese Journal of Mechanical Engineering2007，20，6： | 8 |
| 8 | Efficacy and safety of tenofovir in chronic hepatitis B: Australian real world experience显示文摘AIM To evaluate the long-term treatment outcomes of tenofovir therapy in patients in a real world Australian tertiary care setting.METHODS We performed a retrospective analysis of treatment outcomes among treatment-na?ve and treatment-experienced patients receiving a minimum 3 mo tenofovir therapy through St Vincent's Hospital Melbourne, Australia. We included patients receiving tenofovir [tenofovir disoproxil fumarate(TDF)] monotherapy, as well as patients treated with TDF in combination with a second antiviral agent. Patients were excluded if they demonstrated human immune-deficiency virus/hepatitis C virus/hepatitis delta virus coinfection or were less than 18 years of age. We considered virological and biochemicalresponse, as well as safety outcomes. Virological response was determined by measurement of hepatitis B virus(HBV) DNA using sensitive assays; biochemical response was determined via serum liver function tests; histological response was determined from liver biopsy and fibroscan; safety analysis focused on glomerular renal function and bone mineral density. The primary efficacy endpoint was complete virological suppression over time, defined by HBV DNA < 20 IU/m L. Secondary efficacy endpoints included rates of biochemical response, and HB e antigen(HBe Ag)/HB surface antigen loss and seroconversion over time.RESULTS Ninety-two patients were identified who fulfilled the enrolment criteria. Median follow-up was 26 mo(range 3-114). Mean age was 46(24-78) years, 64(70%) were male and 77(84%) were of Asian origin. 55(60%) patients were treatment-na?ve and 62 patients(67%) were HBe Ag-negative. Complete virological suppression was achieved by 45/65(71%) patients at 12 mo, 37/46(80%) at 24 mo and 25/28(89%) at 36 mo. Partial virological response(HBV DNA 20-2000 IU/m L) was achieved by 89/92(96.7%) of patients. Multivariate analysis showed a significant relationship between virological suppression at end of follow-up and baseline HBV DNA level(OR = 0.897, 95%CI: 0.833-0.967, P = 0.0046) and HBe Ag positive status(OR = 0.373, 95%CI: 0.183-0.762, P = 0.0069). There was no difference in response comparing treatment-na?ve and treatment-experienced patients. Three episodes of virological breakthrough occurred in the setting of noncompliance. Tenofovir therapy was well tolerated.CONCLUSION Tenofovir is an efficacious, safe and well-tolerated treatment in an Australian real-world tertiary care setting. Our data are similar to the reported experience from registration trials. | Grace C Lovett Tin Nguyen David M Iser Jacinta A Holmes Robert Chen Barbara Demediuk Gideon Shaw Sally J Bell Paul V Desmond Alexander J Thompson | 2017 | World Journal of Hepatology2017，9，1： | 7 |
| 9 | Lower limb stress fractures in sport:Optimising their management and outcome显示文摘Stress fractures in sport are becoming increasing more common,comprising up to 10%of all of sporting injuries.Around 90%of such injuries are located in the lower limb.This articles aims to define the optimal management of lower limb stress fractures in the athlete,with a view to maximise return rates and minimise return times to sport.Treatment planning of this condition is specific to the location of the injury.However,there remains a clear division of stress fractures by'high'and'low'risk.'Low risk'stress fractures are those with a low probability of fracture propagation,delayed union,or non-union,and so can be managed reliably with rest and exercise limitation.These include stress fractures of the PosteroMedial Tibial Diaphysis,Metatarsal Shafts,Distal Fibula,Medial Femoral Neck,Femoral Shaft and Calcaneus.'High risk'stress fractures,in contrast,have increased rates of fracture propagation,displacement,delayed and non-union,and so require immediate cessation of activity,with orthopaedic referral,to assess the need for surgical intervention.These include stress fractures of the Anterior Tibial Diaphysis,Fifth Metatarsal Base,Medial Malleolus,Lateral Femoral Neck,Tarsal Navicular and Great Toe Sesamoids.In order to establish the optimal methods for managing these injuries,we present and review the current evidence which guides the treatment of stress fractures in athletes.From this,we note an increased role for surgical management of certain high risk stress fractures to improve return times and rates to sport.Following this,key recommendations are provided for the management of the common stress fracture types seen in the athlete.Five case reports are also presented to illustrate the application of sportfocussed lower limb stress fracture treatment in the clinical setting. | Greg A J Robertson Alexander M Wood | 2017 | World Journal of Orthopedics2017，8，3： | 7 |
| 10 | Risk stratification for ST segment elevation myocardial infarction in the era of primary percutaneous coronary intervention显示文摘Acute coronary syndromes presenting with ST elevation are usually treated with emergency reperfusion/revascularisation therapy. In contrast current evidence and national guidelines recommend risk stratification for non ST segment elevation myocardial infarction(NSTEMI) with the decision on revascularisation dependent on perceived clinical risk. Risk stratification for STEMI has no recommendation. Statistical risk scoring techniques in NSTEMI have been demonstrated to improve outcomes however their uptake has been poor perhaps due to questions over their discrimination and concern for application to individuals who may not have been adequately represented in clinical trials. STEMI is perceived to carry sufficient risk to warrant emergency coronary intervention [by primary percutaneous coronary intervention(PPCI)] even if this results in a delay to reperfusion with immediate thrombolysis. Immediate thrombolysis may be as effective in patients presenting early, or at low risk, but physicians are poor at assessing clinical and procedural risks and currently are not required to consider this. Inadequate data on risk stratification in STEMI inhibits the option of immediate fibrinolysis, which may be cost-effective. Currently the mode of reperfusion for STEMI defaults to emergency angiography and percutaneous coronary intervention ignoring alternative strategies. This review article examines the current risk scores and evidence base for risk stratification for STEMI patients. The requirements for an ideal STEMI risk score are discussed. | Richard A Brogan Christopher J Malkin Philip D Batin Alexander D Simms James M McLenachan Christopher P Gale | 2014 | World Journal of Cardiology2014，6，8： | 6 |
| 11 | Clinical outcomes following salvage Gamma Knife radiosurgery for recurrent glioblastoma显示文摘Glioblastoma multiforme(GBM) is the most common malignant primary brain tumor with a survival prognosis of 14-16 mo for the highest functioning patients. Despite aggressive, multimodal upfront therapies, the majority of GBMs will recur in approximately six months. Salvage therapy options for recurrent GBM(r GBM) are an area of intense research. This study compares recent survival and quality of life outcomes following Gamma Knife radiosurgery(GKRS) salvage therapy. Following a Pub Med search for studies usingGKRS as salvage therapy for malignant gliomas, nine articles from 2005 to July 2013 were identified which evaluated rG BM treatment. In this review, we compare overall survival following diagnosis, overall survival following salvage treatment, progression-free survival, time to recurrence, local tumor control, and adverse radiation effects. This report discusses results for rG BM patient populations alone, not for mixed populations with other tumor histology grades. All nine studies reported median overall survival rates(from diagnosis, range:16.7-33.2 mo; from salvage, range:9-17.9 mo). Three studies identified median progression-free survival(range:4.6-14.9 mo). Two showed median time to recurrence of GBM. Two discussed local tumor control. Six studies reported adverse radiation effects(range:0%-46% of patients). The greatest survival advantages were seen in patients who received GKRS salvage along with other treatments, like resection or bevacizumab, suggesting that appropriately tailored multimodal therapy should be considered with each rG BM patient. However, there needs to be a randomized clinical trial to test GKRS for rG BM before the possibility of selection bias can be dismissed. | Erik W Larson Halloran E Peterson Wayne T Lamoreaux Alexander R MacKay Robert K Fairbanks Jason A Call Jonathan D Carlson Benjamin C Ling John J Demakas Barton S Cooke Christopher M Lee | 2014 | World Journal of Clinical Oncology2014，5，2： | 5 |
| 12 | Lrp1 in osteoblasts controls osteoclast activity and protects against osteoporosis by limiting PDGF–RANKL signaling显示文摘Skeletal health relies on architectural integrity and sufficient bone mass, which are maintained through a tightly regulated equilibrium of bone resorption by osteoclasts and bone formation by osteoblasts. Genetic studies have linked the gene coding for low-density lipoprotein receptor-related protein1(Lrp1) to bone traits but whether these associations are based on a causal molecular relationship is unknown. Here, we show that Lrp1 in osteoblasts is a novel regulator of osteoclast activity and bone mass.Mice lacking Lrp1 specifically in the osteoblast lineage displayed normal osteoblast function but severe osteoporosis due to highly increased osteoclast numbers and bone resorption. Osteoblast Lrp1 limited receptor activator of NF-κB ligand(RANKL) expression in vivo and in vitro through attenuation of platelet-derived growth factor(PDGF-BB) signaling. In co-culture, Lrp1-deficient osteoblasts stimulated osteoclastogenesis in a PDGFRβ-dependent manner and in vivo treatment with the PDGFR tyrosine kinase inhibitor imatinib mesylate limited RANKL production and led to complete remission of the osteoporotic phenotype. These results identify osteoblast Lrp1 as a key regulator of osteoblast-to-osteoclast communication and bone mass through a PDGF–RANKL signaling axis in osteoblasts and open perspectives to further explore the potential of PDGF signaling inhibitors in counteracting bone loss as well as to evaluate the importance of functional LRP1 gene variants in the control of bone mass in humans. | Alexander Bartelt Friederike Behler-Janbeck F.Timo Beil Till Koehne Brigitte Müller Tobias Schmidt Markus Heine Laura Ochs Tayfun Yilmaz Martin Dietrich Jan P.Tuckermann Michael Amling Joachim Herz Thorsten Schinke Joerg Heeren Andreas Niemeier | 2018 | Bone Research2018，6，1： | 5 |
| 13 | Hip hemi-arthroplasty for neck of femur fracture:What is the current evidence?显示文摘This editorial reviews and summarises the current evidence(meta-analyses and Cochrane reviews) relating to the use of hip hemi-arthroplasty for neck of femur fractures. Regarding the optimal surgical approach,two recent meta-analyses have found that posterior approaches are associated with: higher rates of dislocation compared to lateral and anterior approaches; and higher rates of re-operation compared to lateral approaches. Posterior approaches should therefore be avoided when performing hip hemi-arthroplasty procedures. Assessing the optimal prosthesis head component,three recent meta-analyses and one Cochrane review have found that while unipolar hemiarthroplasty can be associated with increased rates of acetabular erosion at short-term follow-up(up to 1 year),there is no significant difference between the unipolar hemi-arthroplasty and bipolar hemi-arthroplasty for surgical outcome,complication profile,functional outcome and acetabular erosion rates at longer-term follow-up(2 to 4 years). With bipolar hemi-arthroplasty being the more expensive prosthesis,unipolar hemi-arthroplasty is the recommended option. With regards to the optimal femoral stem insertion technique,three recent metaanalyses and one Cochrane Review have found that,while cemented hip hemi-arthroplasties are associated with a longer operative time compared to uncemented Hip Hemi-arthroplasties,cemented prostheses have lower rates of implant-related complications(particularly peri-prosthetic femoral fracture) and improved postoperative outcome regarding residual thigh pain and mobility. With no significant difference found between the two techniques for medical complications and mortality,cemented hip hemi-arthroplasty would appear to be the superior technique. On the topic of wound closure,one recent meta-analysis has found that,while staples can result in a quicker closure time,there is no significant difference in post-operative infections rates or wound healing outcomes when comparing staples to sutures. Therefore,either suture or staple wound closure techniques appear equally appropriate for hip hemiarthroplasty procedures. | Greg AJ Robertson Alexander M Wood | 2018 | World Journal of Orthopedics2018，9，11： | 4 |
| 14 | Molecular markers(PECAM-1,ICAM-3,HLA-DR)determine prognosis in primary non-Hodgkin's gastric lymphoma patients显示文摘瞄准:与主要 non-Hodgkin 的胃的淋巴瘤在病人调查 PECAM-1, ICAM-3 和 HLA 医生抗原的预示的意义。方法:我们免疫组织化学地在 36 个 B 房间麦芽类型主要胃的淋巴瘤病人学习了 PECAM-1, ICAM-3 和 HLA 医生抗原表示。十非恶意并且十个健康胃的织物标本被用作控制。Clinicopathological 和幸存数据与染色的结果被相关。结果:HLA 医生抗原表示在 33 个胃的淋巴瘤病人(91.7%) 和 6 个非恶意的病人(54.5%) 被检测。PECAM-1 染色了 10 个病人(27.8%) 的肿瘤房间, 9 个病人(25%) 的 endothelial 并且煽动性有良性的胃的疾病的 4 个病人(40%) 渗入。ICAM-3 表示在 17 个病人(47.2%) 的肿瘤房间上被观察,当 5 个非恶意的病人(50%) 被染色时积极也。任何一个都没为任何学习的基因健康控制被染色。在里面多,变量分析, HLA 医生抗原和 PECAM-1 被证明是与联系的统计上重要的独立预示的因素一赞成并且不利预后分别地(P=0.009 和 P=0.003 ) 。在 univariate 分析, PECAM-1 (+)/ICAM-3 (-) 和 HLA 医生(-)/ICAM-3 (-) 病人与确切相反的基因表示模式与那些相比展出了显著地减少的全面幸存(P=0.0041 和 P=0.0091,分别地) 。是 HLA 医生(+)/ICAM-3 (+)/PECAM-1 (-)(n=8 ) 的那些病人让显著地更高的幸存与这个组(n=24 )(P=0.0289 ) 的其余部分相比评价。结论:PECAM-1, ICAM-3 和 HLA 医生分别地是肿瘤扩大潜力和主人免疫者监视的代表性的标记。他们的联合使用可以帮助我们识别能得益于更好攻击的治疗学的协议的高风险的病人。 | Alexander Darom Ilias P Gomatos Emmanuel Leandros Emmu Chatzigianni Dimitris Panousopoulos Manousos M Konstadoulakis George Androulakis | 2006 | World Journal of Gastroenterology2006，12，12： | 4 |
| 15 | Role of nanotopography in the development of tissue engineered 3D organs and tissues using mesenchymal stem cells显示文摘Recent regenerative medicine and tissue engineering strategies(using cells, scaffolds, medical devices and gene therapy) have led to fascinating progress of translation of basic research towards clinical applications. In the past decade, great deal of research has focused on developing various three dimensional(3D) organs, such as bone, skin, liver, kidney and ear,using such strategies in order to replace or regenerate damaged organs for the purpose of maintaining or restoring organs' functions that may have been lost due to aging, accident or disease. The surface properties of a material or a device are key aspects in determining the success of the implant in biomedicine, as the majority of biological reactions in human body occur on surfaces or interfaces. Furthermore, it has been established in the literature that cell adhesion and proliferation are, to a great extent, influenced by the micro- and nanosurface characteristics of biomaterials and devices. In addition, it has been shown that the functions of stem cells, mesenchymal stem cells in particular, could be regulated through physical interaction with specific nanotopographical cues. Therefore, guided stem cell proliferation, differentiation and function are of great importance in the regeneration of 3D tissues and organs using tissue engineering strategies. This review will provide an update on the impact of nanotopography on mesenchymal stem cells for the purpose of developing laboratory-based 3D organs and tissues, as well as the most recent research and case studies on this topic. | Shima Salmasi Deepak M Kalaskar Wai-Weng Yoon Gordon W Blunn Alexander M Seifalian | 2015 | World Journal of Stem Cells2015，7，2： | 4 |
| 16 | Role of interleukin-1 and its antagonism of hepatic stellate cell proliferation and liver fibrosis in the Abcb4^(-/-) mouse model显示文摘AIM: To study the interleukin-1(IL-1) pathway as a therapeutic target for liver fibrosis in vitro and in vivo using the ATP-binding cassette transporter b4^(-/-)(Abcb4^(-/-)) mouse model.METHODS: Female and male Abcb4^(-/-) mice from 6 to 13 mo of age were analysed for the degree of cholestasis(liver serum tests), extent of liver fibrosis(hydroxyproline content and Sirius red staining) and tissue-specific activation of signalling pathways such as the IL-1 pathway [quantitative polymerase chain reaction(q PCR)]. For in vivo experiments, murine hepatic stellate cells(HSCs) were isolated via pronasecollagenase perfusion followed by density gradient centrifugation using female mice. Murine HSCs were stimulated with up to 1 ng/m L IL-1β with or without 2.5 μg/m L Anakinra, an IL-1 receptor antagonist, respectively. The proliferation of murine HSCs was assessed via the Brd U assay. The toxicity of Anakinra was evaluated via the fluorescein diacetate hydrolysis(FDH) assay. In vivo 8-wk-old Abcb4^(-/-) mice with an already fully established hepatic phenotype were treated with Anakinra(1 mg/kg body-weight daily intraperitoneally) or vehicle and liver injury and liver fibrosis were evaluated via serum tests, q PCR, hydroxyproline content and Sirius red staining. RESULTS: Liver fibrosis was less pronounced in males than in female Abcb4^(-/-) animals as defined by a lower hydroxyproline content(274 ± 64 μg/g vs 436 ± 80 μg/g liver, respectively; n = 13-15; P < 0.001; MannWhitney U-test) and lower m RNA expression of the profibrogenic tissue inhibitor of metalloproteinase-1(TIMP)(1 ± 0.41 vs 0.66 ± 0.33 fold, respectively; n = 13-15; P < 0.05; Mann-Whitney U-test). Reduced liver fibrosis was associated with significantly lower levels of F4/80 m RNA expression(1 ± 0.28 vs 0.71 ± 0.41 fold, respectively; n = 12-15; P < 0.05; Mann-Whitney U-test) and significantly lower IL-1β m RNA expression levels(1 ± 0.38 vs 0.44 ± 0.26 fold, respectively; n = 13-15; P < 0.001; Mann-Whitney U-test). No gender differences in the serum liver parameters [bilirubin; alanine aminotransferase(ALT); aspartate aminotransferase and alkaline phosphatase(AP)] were found. In vitro, the administration of IL-1β resulted in a significant increase in HSC proliferation [0.94 ± 0.72 arbitrary units(A.U.) in untreated controls, 1.12 ± 0.80 A.U. at an IL-1β concentration of 0.1 ng/m L and 1.18 ± 0.73 A.U. at an IL-1β concentration of 1 ng/m L in samples from n = 6 donor animals; P < 0.001; analyses of variance(ANOVA)]. Proliferation was reduced significantly by the addition of 2.5 μg/m L Anakinra(0.81 ± 0.60 A.U. in untreated controls, 0.92 ± 0.68 A.U. at an IL-1β concentration of 0.1 ng/m L, and 0.91 ± 0.69 A.U. at an IL-1β concentration of 1 ng/m L; in samples from n = 6 donor animals; P < 0.001; ANOVA) suggesting an anti-proliferative effect of this clinically approved IL-1 receptor antagonist. The FDH assay showed this dose to be non-toxic in HSCs. In vivo, Anakinra had no effect on the hepatic hydroxyprolinecontent, liver serum tests(ALT and AP) and profibrotic(collagen 1α1, collagen 1α2, transforming growth factor-β, and TIMP-1) and anti-fibrotic [matrix metalloproteinase 2(MMP2), MMP9 and MMP13 ] gene expression after 4 wk of treatment. Furthermore, the hepatic IL-1β and F4/80 m RNA expression levels were unaffected by Anakinra treatment.CONCLUSION: IL-1β expression is associated with the degree of liver fibrosis in Abcb4^(-/-) mice and promotes HSC proliferation. IL-1 antagonism shows antifibrotic effects in vitro but not in Abcb4^(-/-) mice. | Florian P Reiter Ralf Wimmer Lena Wottke Renate Artmann Jutta M Nagel Manuel O Carranza Doris Mayr Christian Rust Peter Fickert Michael Trauner Alexander L Gerbes Simon Hohenester Gerald U Denk | 2016 | World Journal of Hepatology2016，8，8： | 3 |
| 17 | Control of stem cell fate by engineering their micro and nanoenvironment显示文摘Stem cells are capable of long-term self-renewal and differentiation into specialised cell types, making them an ideal candidate for a cell source for regenerative medicine. The control of stem cell fate has become a major area of interest in the field of regenerative medicine and therapeutic intervention. Conventional methods of chemically inducing stem cells into specific lineages is being challenged by the advances in biomaterial technology, with evidence highlighting that material properties are capable of driving stem cell fate. Materials are being designed to mimic the clues stem cells receive in their in vivo stem cell niche including topographical and chemical instructions. Nanotopographical clues that mimic the extracellular matrix(ECM) in vivo have shown to regulate stem cell differentiation. The delivery of ECM components on biomaterials in the form of short peptides sequences has also proved successful in directing stem cell lineage. Growth factors responsible for controlling stem cell fate in vivo have also been delivered via biomaterials to provide clues to determine stem cell differentiation. An alternative approach to guide stem cells fate is to provide genetic clues including delivering DNA plasmids and small interfering RNAs via scaffolds. This review, aims to provide an overview of the topographical, chemical and molecular clues that biomaterials can provide to guide stem cell fate. The promising features and challenges of such approaches will be highlighted, to provide directions for future advancements in this exciting area of stem cell translation for regenerative medicine. | Michelle F Griffin Peter E Butler Alexander M Seifalian Deepak M Kalaskar | 2015 | World Journal of Stem Cells2015，7，1： | 3 |
| 18 | PI 3-kinase pathway is responsible for antiapoptotic effects of atrial natriuretic peptide in rat liver transplantation显示文摘AIM:To investigate the in vivo effect of atrial natriureticpeptide(ANP)and its signaling pathway during ortho-topic rat liver transplantation.METHODS:Rats were infused with NaCl,ANP(5 μg/kg),wortmannin(WM,16 μg/kg),or a combination ofboth for 20 min.Livers were stored in UW solution(4°C)for 24 h,transplanted and reperfused.Apoptosis wasexamined by caspase-3 activity and TUNEL staining.Phosphorylation of Akt and Bad was visualized by West-ern blotting and phospho-Akt-localization by confocalmicroscopy.RESULTS:ANP-pretreatment decreased caspase-3activity and TUNEL-positive cells after cold ischemia,indicating antiapoptotic effects of ANP in vivo.The an-tiapoptotic signaling of ANP was most likely caused byphosphorylation of Akt and Bad,since pretreatment withPI 3-kinase inhibitor WM abrogated the ANP-inducedreduction of caspase-3 activity.Interestingly,analysis ofliver tissue by confocal microscopy showed translocationof phosphorylated Akt to the plasma membrane of hepa-tocytes evoked by ANP.CONCLUSION:ANP activates the PI-3-kinase pathwayin the liver in vivo leading to phosphorylation of Bad, an event triggering antiapoptotic signaling cascade inischemic liver. | Uwe Grutzner Melanie Keller Michael Bach Alexandra K Kiemer Herbert Meissner Manfred Bilzer Stefan Zahler Alexander L Gerbes Angelika M Vollmar | 2006 | World Journal of Gastroenterology2006，12，7： | 3 |
| 19 | Heart rate deceleration runs for postinfarction risk prediction显示文摘 | Przemyslaw Guzik Jaroslaw Piskorski Petra Barthel Axel Bauer Alexander Müller Nadine Junk Kurt Ulm Marek Malik Georg Schmidt | 2012 | Journal of Electrocardiology2012，，1： | 3 |
| 20 | A striking local esophageal cytokine expression profile in eosinophilic esophagitis显示文摘 | Carine Blanchard Emily M. Stucke Beatriz Rodriguez-Jimenez Karen Burwinkel Margaret H. Collins Annette Ahrens Eileen S. Alexander Bridget K. Buckmeier Butz Sean C. Jameson Ajay Kaul James P. Franciosi Jonathan P. Kushner Philip E. Putnam J. Pablo Abonia M | 2010 | The Journal of Allergy and Clinical Immunology2010，，1： | 3 |
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