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| 1 | Pancreatic cancer: A review of clinical diagnosis, epidemiology, treatment and outcomes显示文摘This review aims to outline the most up-to-date knowledge of pancreatic adenocarcinoma risk, diagnostics, treatment and outcomes, while identifying gaps that aim to stimulate further research in this understudied malignancy. Pancreatic adenocarcinoma is a lethal condition with a rising incidence, predicted to become the second leading cause of cancer death in some regions. It often presents at an advanced stage, which contributes to poor five-year survival rates of 2%-9%, ranking firmly last amongst all cancer sites in terms of prognostic outcomes for patients. Better understanding of the risk factors and symptoms associated with this disease is essential to inform both health professionals and the general population of potential preventive and/or early detection measures. The identification of high-risk patients who could benefit from screening to detect pre-malignant conditions such as pancreatic intraepithelial neoplasia, intraductal papillary mucinous neoplasms and mucinous cystic neoplasms is urgently required, however an acceptable screening test has yet to be identified. The management of pancreatic adenocarcinoma is evolving, with the introduction of new surgical techniques and medical therapies such as laparoscopic techniques and neo-adjuvant chemoradiotherapy, however this has only led to modest improvements in outcomes. The identification of novel biomarkers is desirable to move towards a precision medicine era, where pancreatic cancer therapy can be tailored to the individual patient, while unnecessary treatments that have negative consequences on quality of life could be prevented for others. Research efforts must also focus on the development of new agents and delivery systems. Overall, considerable progress is required to reduce the burden associated with pancreatic cancer. Recent, renewed efforts to fund large consortia and research into pancreatic adenocarcinoma are welcomed, but further streams will be necessary to facilitate the momentum needed to bring breakthroughs seen for other cancer sites. | Andrew McGuigan Paul Kelly Richard C Turkington Claire Jones Helen G Coleman R Stephen McCain | 2018 | World Journal of Gastroenterology2018，24，43： | 140 |
| 2 | Skeletal muscle mitochondrial remodeling in exercise and diseases显示文摘 | Zhenji Gan Tingting Fu Daniel R Kelly Rick B. Vega | 2018 | Cell Research2018，28，10： | 25 |
| 3 | Sitagliptin in patients with non-alcoholic steatohepatitis: A randomized, placebo-controlled trial显示文摘AIM To evaluate the effect of sitagliptin vs placebo on histologic and non-histologic parameters of nonalcoholic steatohepatitis(NASH).METHODS Twelve patients with biopsy-proven NASH were randomized to sitagliptin(100 mg daily)(n=6)or placebo(n=6)for 24 wk.The primary outcome was improvement in liver fibrosis after 24 wk.Secondary outcomes included evaluation of changes in NAFLD activity score(NAS),individual components of NAS(hepatocyte ballooning,lobular inflammation,and steatosis),glycemic control and insulin resistance[including measurements of glycated hemoglobin(Hb A1C)and adipocytokines],lipid profile including free fatty acids,adipose distribution measured using magnetic resonance imaging(MRI),and thrombosis markers(platelet aggregation and plasminogen activator inhibitor 1 levels).We also sought to determine the correlation between changes in hepatic fat fraction(%)[as measured using the Iterative Decomposition of water and fat with Echo Asymmetry and Least-squares estimation(IDEAL)MRI technique]and changes in hepatic steatosis on liver biopsy.RESULTS Sitagliptin was not significantly better than placebo at reducing liver fibrosis score as measured on liver biopsy(mean difference between sitagliptin and placebo arms,0.40,P=0.82).There were no significant improvements evident with the use of sitagliptin vs placebo for the secondary histologic outcomes of NAS total score as well as for the individual components of NAS.Compared to baseline,those patients who received sitagliptin demonstrated improved Hb A1C(6.7%±0.4%vs 7.9%±1.0%,P=0.02),and trended towards improved adiponectin levels(4.7±3.5μg/m L vs 3.9±2.7μg/m L,P=0.06)and triglyceride levels(1.26±0.43 mmol/L vs 2.80±1.64 mmol/L,P=0.08).However,when compared with placebo,sitagliptin did not cause a statistically significant improvement in Hb A1C(mean difference,-0.7%,P=0.19)nor triglyceride levels(mean difference-1.10mmol/L,P=0.19)but did trend towards improved adiponectin levels only(mean difference,0.60μg/m L,P=0.095).No significant changes in anthropometrics,liver enzymes,other adipocytokines,lipid profile,thrombosis parameters,or adipose distribution were demonstrated.The MRI IDEAL procedure correlated well with steatosis scores obtained on liver biopsy in both groups at baseline and post-treatment,and the Spearman correlation coefficients ranged from r=0.819(baseline)to r=0.878(post-treatment),P=0.002.CONCLUSION Sitagliptin does not improve fibrosis score or NAS after 24 wk of therapy.The MRI IDEAL technique may be useful for non-invasive measurement of hepatic steatosis. | Tisha R Joy Charles A McKenzie Rommel G Tirona Kelly Summers Shannon Seney Subrata Chakrabarti Neel Malhotra Melanie D Beaton | 2017 | World Journal of Gastroenterology2017，23，1： | 18 |
| 4 | 在血压控制不良的高血压患者中使用数字化干预的家庭和在线血压管理:随机对照试验显示文摘HOME BP试验(The home and online management and evaluation of blood pressure)的目的是评估在初级预防中结合自我监测和自我管理的数字化干预在高血压管理中的作用。研究者纳入英国76个治疗中心经过治疗但血压控制不好(>140/90 mm Hg, 1 mm Hg=0.133 kPa)并能上网的患者622例,进行自动确定主要终点的公开随机对照试验。 | McMa-nus RJ Little P Stuart B Morton K Raftery J Kelly J Bradbury K Zhang J Zhu S Murray E May CR Mair FS Michie S Smith P Band R Ogburn E AllenJ Rice C Nut-tall J Williams B Yardley L 陈嘉睿(译) 叶鹏(审校) | 2021 | 中华高血压杂志2021，29，5： | 15 |
| 5 | The wonders of BMP9:From mesenchymal stem cell differentiation,angiogenesis,neurogenesis,tumorigenesis,and metabolism to regenerative medicine显示文摘Although bone morphogenetic proteins(BMPs)initially showed effective induction of ectopic bone growth in muscle,it has since been determined that these proteins,as members of the TGF-b superfamily,play a diverse and critical array of biological roles.These roles include regulating skeletal and bone formation,angiogenesis,and development and homeostasis of multiple organ systems.Disruptions of the members of the TGF-b/BMP superfamily result in severe skeletal and extra-skeletal irregularities,suggesting high therapeutic potential from understanding this family of BMP proteins.Although it was once one of the least characterized BMPs,BMP9 has revealed itself to have the highest osteogenic potential across numerous experiments both in vitro and in vivo,with recent studies suggesting that the exceptional potency of BMP9 may result from unique signaling pathways that differentiate it from other BMPs.The effectiveness of BMP9 in inducing bone formation was recently revealed in promising experiments that demonstrated efficacy in the repair of critical sized cranial defects as well as compatibility with bone-inducing bio-implants,revealing the great translational promise of BMP9.Furthermore,emerging evidence indicates that,besides its osteogenic activity,BMP9 exerts a broad range of biological functions,including stem cell differentiation,angiogenesis,neurogenesis,tumorigenesis,and metabolism.This review aims to summarize our current understanding of BMP9 across biology and the body. | Sami Mostafa Mikhail Pakvasa Elam Coalson Allen Zhu Alex Alverdy Hector Castillo Jiaming Fan Alex Li Yixiao Feng Di Wu Elliott Bishop Scott Du Mia Spezia Alissa Li Ofir Hagag Alison Deng Winny Liu Mingyang Li Sherwin S·Ho Aravind Athiviraham Michael J·Lee Jennifer Moriatis Wolf Guillermo A·Ameer Hue H·Luu Rex C·Haydon Jason Strelzow Kelly Hynes Tong-Chuan He Russell R·Reid | 2019 | Genes & Diseases2019，6，3： | 15 |
| 6 | Platelet thromboxane(11-dehydro-Thromboxane B_2) and aspirin response in patients with diabetes and coronary artery disease显示文摘Aspirin(ASA) irreversibly inhibits platelet cyclooxygenase-1(COX-1) leading to decreased thromboxane-mediated platelet activation. The effect of ASA ingestion on thromboxane generation was evaluated in patients with diabetes(DM) and cardiovascular disease. Thromboxane inhibition was assessed by measuring the urinary excretion of 11-dehydro-thromboxane B2(11dhTxB2), a stable metabolite of thromboxane A2. The mean baseline urinary 11dhTxB2 of DM was 69.6% higher than healthy controls(P = 0.024): female subjects(DM and controls) had 50.9% higher baseline 11dhTxB2 than males(P = 0.0004), while age or disease duration had no influence. Daily ASA ingestion inhibited urinary 11dhTxB2 in both DM(71.7%) and controls(75.1%, P < 0.0001). Using a pre-established cut-off of 1500 pg/mg of urinary 11dhTxB2, there were twice as many ASA poor responders(ASA 'resistant') in DM than in controls(14.8% and 8.4%, respectively). The rate of ASA poor responders in two populations of acute coronary syndrome(ACS) patients was 28.6 and 28.7%, in spite of a significant(81.6%) inhibition of urinary 11dhTxB2(P < 0.0001). Both baseline 11dhTxB2 levels and rate of poor ASA responders were significantly higher in DM and ACS compared to controls. Underlying systemic oxidative inflammation may maintain platelet function in atherosclerotic cardiovascular disease irrespective of COX-1 pathway inhibition and/or increase systemic generation of thromboxane from non-platelet sources. | Luis R Lopez Kirk E Guyer Ignacio Garcia De La Torre Kelly R Pitts Eiji Matsuura Paul RJ Ames | 2014 | World Journal of Diabetes2014，5，2： | 13 |
| 7 | 儿童期应用吸入性糖皮质激素治疗对成年身高的影响显示文摘背景在青春期前儿童中,应用吸入性糖皮质激素治疗持续性哮喘可引起生长速度暂时减慢。目前认为开始吸入性糖皮质激素治疗后1~4年所致的身高降低不会降低成年后所达到的身高。方法在儿童哮喘管理计划(试验)的1 041名受试者中,我们测量了943名(90.6%)受试者的成年身高,测量成年身高时的平均年龄为(24.9±2.7)岁。从5~13岁时开始,受试者被随机分配接受每日布地奈德400μg、奈多罗米16 mg或者安慰剂治疗4~6年。我们采用对(受试者在)试验入选时人口学特性、哮喘特点以及身高进行校正的多因素线性回归方法,计算了每个治疗组的成年身高(分别)与安慰剂组相比的差异。结果布地奈德组成年平均身高较安慰剂组低1.2 cm〔95%CI(-1.9,-0.5)〕,奈多罗米组成年平均身高较安慰剂组低0.2cm〔95%CI(-0.9,0.5),P=0.61〕。最初2年内吸入性糖皮质激素的日剂量较大,与成年身高较低相关(剂量每增大1 mg/kg体质量,身高就降低0.1 cm,P=0.007)。布地奈德组与安慰剂组相比成年身高降低与治疗了2年后的身高降低情况相似〔-1.3 cm,95%CI(-1.7,-0.9)〕。在最初的2年内,布地奈德组的生长速度减慢主要发生在青春期前的受试者中。结论青春期前儿童中最初出现的、与应用吸入性糖皮质激素治疗相关的身高降低在成年时仍持续存在,不过身高的降低不是进行性的,也不具有累积性。 | Kelly HW Sternberg AL Lescher R | 2012 | 中国全科医学2012，15，36： | 9 |
| 8 | Acute inflammatory demyelinating polyneuropathy associated with pegylated interferon α 2a therapy for chronic hepatitis C virus infection显示文摘The combination of pegylated interferon (Peg-IFN) and ribavirin is the standard of care for chronic hepatitis C virus (HCV) infection treatment. In general, common side effects related to this combination therapy are mild and are very well tolerated. However, peripheral neuropathy including demyelinating polyneuropathy related to Peg-IFN is extremely rare. We present the first case of an acute inflammatory demyelinating polyneuropathy (AIDP) associated with Peg-IFN-α 2a (Pegasys) after 16 wk of a combination therapy with Pegasys and ribavirin in a 65-year-old woman with chronic HCV infection. She developed tingling, numbness, and weakness of her upper and lower extremities and was hospitalized for acute neurological deficits. Her clinical course, neurological findings, an electromyogram (EMG), nerve conductions studies (NCS), muscle biopsy, and a sural nerve biopsy were all consistent with AIDP likely related to Pegasys use. The patient recovered completely with the use of intravenous immunoglobulin (IVIG) including physical therapy and neurological rehabilitation. It is very important that gastroenterologists and/or hepatologists recognize this rare neurological complication related to Peg-IFN treatment very early, since it requires a prompt discontinuation of therapy including an immediate referral to a neurologist for the confirmation of diagnosis, management, and the prevention of long-term neurological deficits. | Vijay Khiani Thomas Kelly Adeel Shibli Donald Jensen Smruti R Mohanty | 2008 | World Journal of Gastroenterology2008，14，2： | 7 |
| 9 | Hematopoietic stem cell-derived adipocytes and fibroblasts in the tumor microenvironment显示文摘The tumor microenvironment(TME) is complex and constantly evolving. This is due, in part, to the crosstalk between tumor cells and the multiple cell types that comprise the TME, which results in a heterogeneous population of tumor cells and TME cells. This review will focus on two stromal cell types, the cancerassociated adipocyte(CAA) and the cancer-associated fibroblast(CAF). In the clinic, the presence of CAAs and CAFs in the TME translates to poor prognosis in multiple tumor types. CAAs and CAFs have an activated phenotype and produce growth factors, inflammatory factors, cytokines, chemokines, extracellular matrix components, and proteases in an accelerated and aberrant fashion. Through this activated state, CAAs and CAFs remodel the TME, thereby driving all aspects of tumor progression, including tumor growth and survival, chemoresistance, tumor vascularization, tumor invasion, and tumor cell metastasis. Similarities in the tumorpromoting functions of CAAs and CAFs suggest that a multipronged therapeutic approach may be necessary to achieve maximal impact on disease. While CAAs and CAFs are thought to arise from tissues adjacent to the tumor, multiple alternative origins for CAAs and CAFs have recently been identified. Recent studies from our lab and others suggest that the hematopoietic stem cell, through the myeloid lineage, may serve as a progenitor for CAAs and CAFs. We hypothesize that the multiple origins of CAAs and CAFs may contribute to the heterogeneity seen in the TME. Thus, a better understanding of the origin of CAAs and CAFs, how this origin impacts their functions in the TME, and thetemporal participation of uniquely originating TME cells may lead to novel or improved anti-tumor therapeutics. | Ying Xiong Lindsay T Mc Donald Dayvia L Russell Ryan R Kelly Katie R Wilson Meenal Mehrotra Adam C Soloff Amanda C LaRue | 2015 | World Journal of Stem Cells2015，7，2： | 6 |
| 10 | 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 |
| 11 | Nat Genet:单基因突变导致过敏性皮炎的发生显示文摘最近,研究者们鉴定出了一类导致神经性皮炎发生的关键基因突变:CARDll。来自美国NIH过敏与传染病研究所的研究者们通过对四个没有血缘关系的患病家庭进行分析,发现了这一导致疾病产生的基因、 | Chi A Ma, Yuan Zhang, Michael A Weinreich, Jonathan J Lyons, Celeste G Nelson, Thomas DiMaggio, Kelly D Stone, Joshua D Milner Jeffrey R Stinson, Elisa Ruffo, Batsukh Dorjbal, Swadhinya Arjunaraja, Kelsey Voss, Andrew L Snow Jordan K Abbott, Pia J Hauk, Paul R Reynolds, Erwin W Gelfand Elisa Ruffo Salomé Glauzy, Natsuko Yamakawa, Eric Meffre Jennifer Stoddard, Julie Niemela, Sergio D Rosenzweig Yu Zhang, Helen F Matthews Joshua J McElwee Nina Jones Alejandro Palma, Matías Oleastro, Emma Prieto, Andrea R Bernasconi, Geronimo Dubra, Silvia Danielian, Jonathan Zaiat, Marcelo A Marti Brian Kim Megan A Cooper Neil Romberg | 2017 | 现代生物医学进展2017，17，27： | 3 |
| 12 | Th1 cytokines promote T-cell binding to antigen-presenting cells via enhanced hyaluronan production and accumulation at the immune synapse显示文摘Hyaluronan(HA)production by dendritic cells(DCs)is known to promote antigen presentation and to augment T-cell activation and proliferation.We hypothesized that pericellular HA can function as intercellular‘glue’directly mediating T cell–DC binding.Using primary human cells,we observed HA-dependent binding between T cells and DCs,which was abrogated upon pre-treatment of the DCs with 4-methylumbelliferone(4-MU),an agent which blocks HA synthesis.Furthermore,T cells regulate HA production by DCs via T cell-derived cytokines in a T helper(Th)subset-specific manner,as demonstrated by the observation that cell-culture supernatants from Th1 but not Th2 clones promote HA production.Similar effects were seen upon the addition of exogenous Th1 cytokines,IL-2,interferon c(IFN-c)and tumor necrosis factor a(TNF-a).The critical factors which determined the extent of DC–T cell binding in this system were the nature of the pre-treatment the DCs received and their capacity to synthesize HA,as T-cell clones which were pre-treated with monensin,added to block cytokine secretion,bound equivalently irrespective of their Th subset.These data support the existence of a feedforward loop wherein T-cell cytokines influence DC production of HA,which in turn affects the extent of DC–T cell binding.We also document the presence of focal deposits of HA at the immune synapse between T-cells and APC and on dendritic processes thought to be important in antigen presentation.These data point to a pivotal role for HA in DC–T cell interactions at the IS. | Paul L Bollyky Stephen P Evanko Rebecca P Wu Susan Potter-Perigo S Alice Long Brian Kinsella Helena Reijonen Kelly Guebtner Brandon Teng Christina K Chan Kathy R Braun John A Gebe Gerald T Nepom Thomas N Wight | 2010 | Cellular & Molecular Immunology2010，7，3： | 3 |
| 13 | Synthetic seismograms,a finite difference approach显示文摘 | Kelly K R Ward R W Treiter S | 1976 | Geophysics1976，41，1： | 2 |
| 14 | Staging of brain pathology related to sporadic Parkinson’s disease显示文摘 | Heiko Braak Kelly Del Tredici Udo Rüb Rob A.I de Vos Ernst N.H Jansen Steur Eva Braak | 2002 | Neurobiology of Aging2002，，2： | 2 |
| 15 | Synthetic seismograms, a finite difference approach显示文摘 | Kelly K R Ward R W Treitel S | 1976 | Geophysics1976，41，： | 2 |
| 16 | Ceramics in Dentistry: Historical Roots and Current Perspectives显示文摘 | Kelly J R Nishimura I Campbell S D | 1996 | J Prosthet Dent1996，75，： | 1 |
| 17 | Endocrine regulation of menstruation 显示文摘 | Jabbour H N Kelly R W Fraser H M | 2006 | Endocr Rew2006，27，1： | 1 |
| 18 | Structural testing of concurrent programs显示文摘 | Taylor R N Levine D L Kelly C D | 1992 | IEEE Trans Softw Eng1992，18，3： | 1 |
| 19 | A third-generation lentivirus vector with a conditional packaging system显示文摘 | Dull T Zufferey R Kelly M | 1998 | J Virol1998，72，11： | 1 |
| 20 | Magnetron sputtering;a review of recent development and applications显示文摘 | Kelly P J Arnell R D | 2000 | Vacuum2000，56，： | 1 |
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