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| 1 | Cell cycle-related kinase reprograms the liver immune microenvironment to promote cancer metastasis显示文摘The liver is an immunologically tolerant organ and a common metastatic site of multiple cancer types.Although a role for cancer cell invasion programs has been well characterized,whether and how liver-intrinsic factors drive metastatic spread is incompletely understood.Here,we show that aberrantly activated hepatocyte-intrinsic cell cycle-related kinase(CCRK)signaling in chronic liver diseases is critical for cancer metastasis by reprogramming an immunosuppressive microenvironment.Using an inducible liverspecific transgenic model,we found that CCRK overexpression dramatically increased both B16F10 melanoma and MC38 colorectal cancer(CRC)metastasis to the liver,which was highly infiltrated by polymorphonuclear-myeloid-derived suppressor cells(PMNMDSCs)and lacking natural killer T(NKT)cells.Depletion of PMN-MDSCs in CCRK transgenic mice restored NKT cell levels and their interferon gamma production and reduced liver metastasis to 2.7% and 0.7%(metastatic tumor weights)in the melanoma and CRC models,respectively.Mechanistically,CCRK activated nuclear factor-kappa B(NF-κB)signaling to increase the PMN-MDSC trafficking chemokine C-X-C motif ligand 1(CXCL1),which was positively correlated with liver-infiltrating PMN-MDSC levels in CCRK transgenic mice.Accordingly,CRC liver metastasis patients exhibited hyperaaivation of hepatic CCRK/NF-κB/CXCL1 signaling,which was associated with accumulation of PMN-MDSCs and paucity of NKT cells compared to healthy liver transplantation donors.In summary,this study demonstrates that immunosuppressive reprogramming by hepatic CCRK signaling undermines antimetastatic immunosurveillance.Our findings offer new mechanistic insights and therapeutic targets for liver metastasis intervention. | Xuezhen Zeng Jingying Zhou Zhewen Xiong Hanyong Sun Weiqin Yang Myth T.S.Mok Jing Wang Jingqing Li Man Liu Wenshu Tang Yu Feng Hector Kwong-Sang W ang Shun-Wa Tsang King-Lau Chow Philip Chun Yeung John Wong Paul Bo-San Lai Anthony Wing-Hung Chan Ka Fai To Stephen Lam Chan Qiang Xia Jing Xue Xiao Chen Jun Yu Sui Peng Joseph Jao-Yiu Sung Ming Kuang Alfred Sze-Lok Cheng | 2021 | Cellular & Molecular Immunology2021，18，4： | 5 |
| 2 | Randomised controlled trial comparing modified Sano's and narrow band imaging international colorectal endoscopic classifications for colorectal lesions显示文摘AIM To assess the utility of modified Sano′s(MS) vs thenarrow band imaging international colorectal endoscopic(NICE) classification in differentiating colorectal polyps.METHODS Patients undergoing colonoscopy between 2013 and 2015 were enrolled in this trial.Based on the MS or the NICE classifications,patients were randomised for real-time endoscopic diagnosis.This was followed by biopsies,endoscopic or surgical resection.The endoscopic diagnosis was then compared to the final(blinded) histopathology.The primary endpoint was the sensitivity(Sn),specificity(Sp),positive predictive value(PPV) and negative predictive value(NPV) of differentiating neoplastic and non-neoplastic polyps(MSⅡ/Ⅱo/Ⅲa/Ⅲb vs I or NICE 1 vs 2/3).The secondary endpoints were 'endoscopic resectability'(MSⅡ/Ⅱo/Ⅲa vs Ⅰ/Ⅲb or NICE 2 vs 1/3),NPV for diminutive distal adenomas and prediction of post-polypectomy surveillance intervals.RESULTS A total of 348 patients were evaluated.The Sn,Sp,PPV and NPV in differentiating neoplastic polyps from non-neoplastic polyps were,98.9%,85.7%,98.2% and 90.9% for MS;and 99.1%,57.7%,95.4% and 88.2% for NICE,respectively.The area under the receiver operating characteristic curve(AUC) for MS was 0.92(95%CI:0.86-0.98);and AUC for NICE was 0.78(95%CI:0.69,0.88).The Sn,Sp,PPV and NPV in predicting 'endoscopic resectability' were 98.9%,86.1%,97.8% and 92.5% for MS;and 98.6%,66.7%,94.7% and 88.9% for NICE,respectively.The AUC for MS was 0.92(95%CI:0.87-0.98);and the AUC for NICE was 0.83(95%CI:0.75-0.90).The AUC values were statistically different for both comparisons(P = 0.0165 and P = 0.0420,respectively).The accuracy for diagnosis of sessile serrated adenoma/polyp(SSA/P) with high confidence utilizing MS classification was 93.2%.The differentiation of SSA/P from other lesions achieved Sp,Sn,PPV and NPV of 87.2%,91.5%,89.6% and 98.6%,respectively.The NPV for predicting adenomas in diminutive rectosigmoid polyps(n = 150) was 96.6% and 95% with MS and NICE respectively.The calculated accuracy of post-polypectomy surveillance for MS group was 98.2%(167 out of 170) and for NICE group was 92.1%(139 out of 151).CONCLUSION The MS classification outperformed the NICE classification in differentiating neoplastic polyps and predicting endoscopic resectability.Both classifications met ASGE PIVI thresholds. | Leonardo Zorrón Cheng Tao Pu Kuan Loong Cheong Doreen Siew Ching Koay Sze Pheh Yeap Amanda Ovenden Mahima Raju Andrew Ruszkiewicz Philip W Chiu James Y Lau Rajvinder Singh | 2018 | World Journal of Gastrointestinal Endoscopy2018，10，9： | 4 |
| 3 | 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 |
| 4 | Factor analysis identifies subgroups of constipation显示文摘AIM:To determine whether distinct symptom groupings exist in a constipated population and whether such grouping might correlate with quantifiable pathophysiological measures of colonic dysfunction.METHODS:One hundred and ninety-one patients presenting to a Gastroenterology clinic with constipation and 32 constipated patients responding to a newspaper advertisement completed a 53-item,wide-ranging selfreport questionnaire.One hundred of these patients had colonic transit measured scintigraphically.Factor analysis determined whether constipation-related symptoms grouped into distinct aspects of symptomatology.Cluster analysis was used to determine whether indi-vidual patients naturally group into distinct subtypes.RESULTS:Cluster analysis yielded a 4 cluster solution with the presence or absence of pain and laxative unresponsiveness providing the main descriptors.Amongst all clusters there was a considerable proportion of patients with demonstrable delayed colon transit,irritable bowel syndrome positive criteria and regular stool frequency.The majority of patients with these characteristics also reported regular laxative use.CONCLUSION:Factor analysis identified four constipation subgroups,based on severity and laxative unresponsiveness,in a constipated population.However,clear stratification into clinically identifiable groups remains imprecise. | Philip G Dinning Mike Jones Linda Hunt Sergio E Fuentealba Jamshid Kalanter Denis W King David Z Lubowski Nicholas J Talley Ian J Cook | 2011 | World Journal of Gastroenterology2011，17，11： | 3 |
| 5 | 一种房颤风险评分系统的建立(Framingham心脏研究):基于社区的队列研究显示文摘背景房颤导致了发病率和病死率的显著上升。本研究旨在建立一种预测个体罹患房颤绝对风险的风险评分系统,并提供研究人员评价新危险因素的流程。方法作者评估了Framingham心脏研究中于1968年6月至1987年9月间进行了8044次检测的4764例参与者(55%为女性,年龄45~95岁)。此后,参与者被随访至房颤首发,随访期最长达10年。多变量Coxi回归确认出1(1年内罹患房颤的临床危险因素。次级分析纳入了常规超声心动图检测指标(5152例4参与者,7156次检测)对房颤风险进行再分层评估,并评价超声检测指标能否提高风险预测能力。结果4764例参与者中的457例4(10%)罹患房颤。年龄、性别、体重指数、收缩压、降压治疗、PR间期、有临床意义的心脏杂音及心力衰竭与房颤相关,并被纳入了风险评分模型(除体重指数P=0.08外,其余均为P〈0.05),模型的C统计量为0.78(95%CI0.76~0.80)。10年房颤风险随年龄变化:年龄〈65岁的人群中53例(1%)风险高于15%,而〉65岁的人群中为783例(27%)。为提高预测能力而纳入超声检测指标仅使模型C统计量略微增高,由0.78(95%C10.75~0.80)增至0.79(95%CI0.77~0.82:P=0.005)。超声心动图检测指标并不能改善风险再分层评估(P=0.18)。结论基于社区医疗中易得的临床因素建立的风险评分系统,有助于确认社区个体罹患房颤的风险,评估技术或标志物能否改善风险预测,以及针对高危个体采取预防措施。 | Renate B Schnabel Lisa M Sullivan Daniel Levy Michael J Pencina Joseph M Massaro Ralph B D'Agostino Sr Christopher Newton-Cheh Jennifer F Yamamoto Jared W Magnani Thomas M Tadros William B Kannel Thomas J Wang Patrick T Ellinor Philip A Wolf Ramachanclran S Vasan Emelia J Benjamin 黄刚(译) | 2009 | 世界临床医学2009，，9： | 2 |
| 6 | Sphincter Preservation in Low Rectal Cancer is Facilitated by Preoperative Chemoradiation and Intersphincteric Dissection显示文摘 | Martin R. Weiser Hak-Mien Quah Jinru Shia José G. Guillem Philip B. Paty Larissa K. Temple Karyn A. Goodman Bruce D. Minsky W Douglas Wong | 2009 | Annals of Surgery2009，，2： | 2 |
| 7 | Public Sector Technical Inefficiency in Large U.S. Cities显示文摘 | Philip J Grossman Panayiotis Mavros Robert W Wassmer | 1999 | Journal of Urban Economics1999，，2： | 2 |
| 8 | Incorporation of esterified soybean isoflavones with antioxidant activity into low density lipoprotein显示文摘 | Meng Q H Philip L Kristiina W | 1999 | Biochim Biophys Acta1999，1438，3： | 1 |
| 9 | Stability of Networked Control Systems显示文摘 | Zhang W Branicky M S Philips S M | 2001 | IEEE Control Magazine2001，21，1： | 1 |
| 10 | Stability of networked control systems显示文摘 | Zhang W Branicky M S Philips S M | 2001 | IEEE Control Systems Magazine2001，21，2： | 1 |
| 11 | Proteome analysis and its impact on the discovery of serological tumor markers显示文摘 | Ference C W Philip J J | 2001 | Clinica Chimica Acta2001，13，： | 1 |
| 12 | Impact of iron salts on activated sludge and interaction with nitrite or nitrate显示文摘 | Philips S Rabaey K Verstraete W | | 0，，03： | 1 |
| 13 | Effect of repeated addition of nitrite to semi-continuous activated sludge reactors显示文摘 | S Philips W Verstraete | 2001 | Bio-resource Technology2001，80，： | 1 |
| 14 | Stability of Networked Control Systems显示文摘 | Zhang W Branicky M S V Philips S M | 2001 | IEEE Control Systems Magazine2001，21，2： | 1 |
| 15 | An application of Bayesian methods in SPC显示文摘 | Philip W W | 1993 | TheStatistican1993，42，4： | 1 |
| 16 | Vascular endothelial growth factor in normal human corneal epithelium:Detection and physiological importance显示文摘 | Philip W | 2000 | Invest Ophthalmol Vis Sci2000，41，3： | 1 |
| 17 | A Comparison of Four Hybrid Block/Object Image Coders显示文摘 | Philips W | 1996 | Signal Processing1996，54，10： | 1 |
| 18 | Nitrification denitrification process and technologies in new contexts显示文摘 | VERSTRAETE W PHILIPS S | 1998 | Environmental Pollution1998，102，： | 1 |
| 19 | q-Profile Measurement in Tokomaks Using Fueling Pellets显示文摘 | Durst R D Philips P E Rowan W L | | 0，，： | 1 |
| 20 | Automatic Registration of SAR Images显示文摘 | Hie Q L Gautama S Philips W | 2004 | IEEE International Geoscience and Remote Sensing Symposium2004，，6： | 1 |
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