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| 1 | Dysfunctional stem and progenitor cells impair fracture healing with age显示文摘Successful fracture healing requires the simultaneous regeneration of both the bone and vasculature;mesenchymal stem cells (MSCs) are directed to replace the bone tissue, while endothelial progenitor cells (EPCs) form the new vasculature that supplies blood to the fracture site. In the elderly, the healing process is slowed, partly due to decreased regenerative function of these stem and progenitor cells. MSCs from older individuals are impaired with regard to cell number, proliferative capacity, ability to migrate, and osteochondrogenic differentiation potential. The proliferation, migration and function of EPCs are also compromised with advanced age. Although the reasons for cellular dysfunction with age are complex and multidimensional, reduced expression of growth factors, accumulation of oxidative damage from reactive oxygen species, and altered signaling of the Sirtuin-1 pathway are contributing factors to aging at the cellular level of both MSCs and EPCs. Because of these geriatric-specific issues, effective treatment for fracture repair may require new therapeutic techniques to restore cellular function. Some suggested directions for potential treatments include cellular therapies, pharmacological agents, treatments targeting age-related molecular mechanisms, and physical therapeutics. Advanced age is the primary risk factor for a fracture, due to the low bone mass and inferior bone quality associated with aging;a better understanding of the dysfunctional behavior of the aging cell will provide a foundation for new treatments to decrease healing time and reduce the development of complications during the extended recovery from fracture healing in the elderly. | Diane R Wagner Sonali Karnik Zachary J Gunderson Jeffery J Nielsen Alanna Fennimore Hunter J Promer Jonathan W Lowery M Terry Loghmani Philip S Low Todd O McKinley Melissa A Kacena Matthias Clauss Jiliang Li | 2019 | World Journal of Stem Cells2019，11，6： | 3 |
| 2 | Appropriateness of systemic treatments in unresectable metastatic well-differentiated pancreatic neuroendocrine tumors显示文摘AIM:To evaluate systemic treatment choices in unresectable metastatic well-differentiated pancreatic neuroendocrine tumors(PNETs)and provide consensus treatment recommendations.METHODS:Systemic treatment options for pancreatic neuroendocrine tumors have expanded in recent years to include somatostatin analogs,angiogenesis inhibitors,inhibitors of mammalian target of rapamycinand cytotoxic agents.At this time,there is little data to guide treatment selection and sequence.We therefore assembled a panel of expert physicians to evaluate systemic treatment choices and provide consensus treatment recommendations.Treatment appropriateness ratings were collected using the RAND/UCLA modified Delphi process.After studying the literature,a multidisciplinary panel of 10 physicians assessed the appropriateness of various medical treatment scenarios on a 1-9 scale.Ratings were done both before and after an extended discussion of the evidence.Quantitative measurements of agreement were made and consensus statements developed from the second round ratings.RESULTS:Specialties represented were medical and surgical oncology,interventional radiology,and gastroenterology.Panelists had practiced for a mean of15.5 years(range:6-33).Among 202 rated scenarios,disagreement decreased from 13.2%(26 scenarios)before the face-to-face discussion of evidence to 1%(2)after.In the final ratings,46.5%(94 scenarios)were rated inappropriate,21.8%(44)were uncertain,and30.7%(62)were appropriate.Consensus statements from the scenarios included:(1)it is appropriate to use somatostatin analogs as first line therapy in patients with hormonally functional tumors and may be appropriate in patients who are asymptomatic;(2)it is appropriate to use everolimus,sunitinib,or cytotoxic chemotherapy therapy as first line therapy in patients with symptomatic or progressive tumors;and(3)beyond first line,these same agents can be used.In patients with uncontrolled secretory symptoms,octreotide LAR doses can be titrated up to 60 mg every4 wk or up to 40 mg every 3 or 4 wk.CONCLUSION:Using the Delphi process allowed physician experts to systematically obtain a consensus on the appropriateness of a variety of medical therapies in patients with PNETs. | Jonathan R Strosberg George A Fisher Al B Benson Lowell B Anthony Bulent Arslan John F Gibbs Edward Greeno Renuka V Iyer Michelle K Kim William J Maples Philip A Philip Edward M Wolin Dasha Cherepanov Michael S Broder | 2015 | World Journal of Gastroenterology2015，21，8： | 2 |
| 3 | Tooth loss and alveolar remodeling in Sinosaurus triassicus (Dinosauria: Theropoda) from the Lower Jurassic strata of the Lufeng Basin, China显示文摘Pathological or traumatic loss of teeth often results in the resorption and remodeling of the affected alveoli in mammals. However, instances of alveolar remodeling in reptiles are rare. A remodeled alveolus in the maxilla of the Chinese theropod Sinosaurus (Lower Jurassic Lower Lufeng Formation) is the first confirmed example of such dental pathology in a dinosaur. Given the known relationship between feeding behavior and tooth damage in theropods (teeth with spalled enamel, tooth crowns embedded in bone) and the absence of dentary, maxillary, and premaxillary osteomyelitis, traumatic loss of a tooth is most likely the cause of alveolar remodeling. Based on the extent of remodeling, the injury and subsequent tooth loss were non-fatal in this individual. | XING LiDa BELL Phil R ROTHSCHILD Bruce M RAN Hao ZHANG JianPing DONG ZhiMing ZHANG Wei CURRIE Philip J | 2013 | Chinese Science Bulletin2013，58，16： | 2 |
| 4 | The effect of celecoxib,a cyclooxygenase-2 inhibitor,in familial adenomatous polyposis显示文摘 | Steinbach G Lynch P M Philips R | 2000 | N Engl J Med2000，342，26： | 1 |
| 5 | Zinc oxide varistors-A review 显示文摘 | Levinson L M Philip H R | 1986 | Am Ceram Soc Bull1986，65，4： | 1 |
| 6 | The effect of hydrogen peroxide on a CST under cesium ion exchange conditions显示文摘 | KIN S H PHILIP M ANTHONY R G | 2003 | Separation Science and Technology2003，38，1213： | 1 |
| 7 | Drying and rewetting effects on soil microbial community composition and nutrient leaching显示文摘 | Gordon H Philip M H Bardgett R D | 2008 | Soil Biology & Biochemistry2008，40，： | 1 |
| 8 | Voriconazole - Associated Phototoxicity 显示文摘 | Ryan R Riahi B S Philip R Cohen M D | 2011 | Dermatology Online Journal2011，17，2： | 1 |
| 9 | Exploratory analysis of the safety climate and safety behavior relationship显示文摘 | Cooper M D Philips R | 2004 | Journal of Safety Research2004，35，5： | 1 |
| 10 | Topical phenylephrine increases anal canal resting pressure in patients with fecal incontinence 显示文摘 | CHEETHAM M J KAMM M A PHILIPS R K S | 2001 | Gut2001，48，： | 1 |
| 11 | Activated Kras, but not Hras or Nras, may initiate tumors of endodermal origin via stem cell expansion显示文摘 | Nlan M P Quatela S E Philips M R | 2008 | Mol Cell Biol2008，28，8： | 1 |
| 12 | Methotrexate and Ras methylation:A new trick for an old drug?显示文摘 | Philips M R | 2004 | Sci STKE2004，2004，225： | 1 |
| 13 | Physical properties of directly expanded extrudates formulated from partially defatted peanut flour and different types of starch显示文摘 | Suknard K Philips R D Chinnan M S | 1997 | Food Res Int1997，，： | 1 |
| 14 | Introduction: STS and neoliberal science 显示文摘 | Lave R Philip M Samuel R | 2010 | Social Studies of Science2010，40，： | 1 |
| 15 | Relative position and attitude estimation and control schemes for the final phase of an autonomous docking mission of spacecraft 显示文摘 | Philip N K Ananthasayanam M R | 2003 | ActaAstronautica2003，52，7： | 1 |
| 16 | Discussion “Stabilization of networked control systems with data packet dropout and transmission delays: continuous-time case” 显示文摘 | PHILIPS S M TILBURY D M MOYNE J R | 2005 | European Journal of Control2005，11，1： | 1 |
| 17 | Application of a numerical model for simulating water flow, isotope transport and heat transfer in the unsaturated zone 显示文摘 | SHURBAJI A R M PHILIPS F M CAMPBELL A R | 1995 | Hydrol1995，171，： | 1 |
| 18 | Surviving Sepsis Campaign: International guidelines for management of severe sepsis and sep- tic shock:2008显示文摘 | Philip R D Carlet J M Masure H | 2008 | Intensive Care Med2008，34，： | 1 |
| 19 | Evaluation of chemical coagulation-flocculation aids for the removal of suspended solids and phosphorus from intensive recirculating aquaculture effluent discharge显示文摘 | James M Philip L Sarah R | | 0，，： | 1 |
| 20 | Relative Position and Attitude Estimation and Control Schemes for The Final Phase of an Autonomous Docking Mission of Spacecraft 显示文摘 | Philip N K Ananthasayanam M R | 2003 | Acta Astronautica2003，52，7： | 1 |
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