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| 1 | 大气二氧化氮与每日总死亡率、心血管和呼吸系统疾病死亡率的短期关联:398个城市的多中心分析显示文摘目的:采用统一的分析方案,评估全球多个国家/地区的二氧化氮(NO_(2))与总死亡率、心血管和呼吸系统疾病死亡率之间的短期关联。研究设计:采用两阶段的时间序列分析方法、过度离散的广义线性模型和多水平meta分析。研究地点:22个低到高收入国家/地区的398个城市。主要结局指标:1973—2018年逐日总死亡人数(6280万人)、心血管疾病死亡人数(1970万人)和呼吸系统疾病死亡人数(550万人)。结果:平均而言,NO_(2)浓度在滞后1天(前1天)每增加10μg/m^(3),会导致总死亡率、心血管和呼吸系统疾病死亡率分别增加0.46%(95%可信区间0.36%~0.57%)、0.37%(0.22%~0.51%)、0.47%(0.21%~0.72%)。在对共污染物(PM_(10)、PM_(2.5)、臭氧、二氧化硫和一氧化碳)进行调整后,这些关联仍然很稳定。所有3种死因的暴露-反应曲线几乎是线性的,没有明显的阈值。在398个城市中,可归因于高过假定零水平的NO_(2)浓度造成的死亡比例为1.23%(95%可信区间0.96%~1.51%)。结论:这项多中心研究提供了关于NO_(2)短期暴露与总死亡率、心血管和呼吸系统死亡风险之间的独立和线性关联的关键证据,说明通过加强NO_(2)的控制和监管限制标准,可获得人群水平的健康收益。 | 孟夏 刘聪(校) 陈仁杰 郑湃(译) 阚海东(校) Francesco Sera Ana Vicedo-Cabrera Ai Milojevic Maria Guo Yuming Tong Shilu Micheline de Sousa Zanotti Stagliorio Coelh Paulo Hilario Nascimento Saldiva Eric Lavigne Patricia Matus Correa Nicolas Valdes Ortega Samuel Osorio Garcia Jan Kysely Ales Urban Hans Orru Marek Maasikmets Jouni J K Jaakkola Niilo Ryti Veronika Huber Alexandra Schneider Klea Katsouyanni Antonis Analitis Masahiro Hashizume Yasushi Honda Chris Fook Sheng Ng Baltazar Nunes João Paulo Teixeira Iulian Horia Holobaca Simona Fratianni Ho Kim Aurelio Tobias Carmeníniguez Bertil Forsberg ChristoferÅström Martina S Ragettli Yue-Liang Leon Guo Shih-Chun Pan Shanshan Li Michelle L Bell Antonella Zanobetti Joel Schwartz Tangchun Wu Antonio Gasparrini | 2021 | 英国医学杂志中文版2021，24，8： | 7 |
| 2 | Arachidyl amido cholanoic acid improves liver glucose and lipid homeostasis in nonalcoholic steatohepatitis via AMPK and mTOR regulation显示文摘BACKGROUND Arachidyl amido cholanoic acid(Aramchol)is a potent downregulator of hepatic stearoyl-CoA desaturase 1(SCD1)protein expression that reduces liver triglycerides and fibrosis in animal models of steatohepatitis.In a phase IIb clinical trial in patients with nonalcoholic steatohepatitis(NASH),52 wk of treatment with Aramchol reduced blood levels of glycated hemoglobin A1c,an indicator of glycemic control.AIM To assess lipid and glucose metabolism in mouse hepatocytes and in a NASH mouse model[induced with a 0.1%methionine and choline deficient diet(0.1MCD)]after treatment with Aramchol.METHODS Isolated primary mouse hepatocytes were incubated with 20μmol/L Aramchol or vehicle for 48 h.Subsequently,analyses were performed including Western blot,proteomics by mass spectrometry,and fluxomic analysis with 13C-uniformly labeled glucose.For the in vivo part of the study,male C57BL/6J mice were randomly fed a control or 0.1MCD for 4 wk and received 1 or 5 mg/kg/d Aramchol or vehicle by intragastric gavage for the last 2 wk.Liver metabolomics were assessed using ultra-high-performance liquid chromatography-time of flight-MS for the determination of glucose metabolism-related metabolites.RESULTS Combination of proteomics and Western blot analyses showed increased AMPK activity while the activity of nutrient sensor mTORC1 was decreased by Aramchol in hepatocytes.This translated into changes in the content of their downstream targets including proteins involved in fatty acid(FA)synthesis and oxidation[PACCα/β(S79),SCD1,CPT1A/B,HADHA,and HADHB],oxidative phosphorylation(NDUFA9,NDUFB11,NDUFS1,NDUFV1,ETFDH,and UQCRC2),tricarboxylic acid(TCA)cycle(MDH2,SUCLA2,and SUCLG2),and ribosome(P-p70S6K[T389]and P-S6[S235/S236]).Flux experiments with 13Cuniformely labeled glucose showed that TCA cycle cataplerosis was reduced by Aramchol in hepatocytes,as indicated by the increase in the number of rounds that malate remained in the TCA cycle.Finally,liver metabolomic analysis showed that glucose homeostasis was improved by Aramchol in 0.1MCD fed mice in a dose-dependent manner,showing normalization of glucose,G6P,F6P,UDP-glucose,and Rbl5P/Xyl5P.CONCLUSION Aramchol exerts its effect on glucose and lipid metabolism in NASH through activation of AMPK and inhibition of mTORC1,which in turn activate FAβ-oxidation and oxidative phosphorylation. | David Fernández-Ramos Fernando Lopitz-Otsoa Laura Delacruz-Villar Jon Bilbao Martina Pagano Laura Mosca Maider Bizkarguenaga Marina Serrano-Macia Mikel Azkargorta Marta Iruarrizaga-Lejarreta Jesús Sot Darya Tsvirkun Sebastiaan Martijn van Liempd Felix M Goni Cristina Alonso María Luz Martínez-Chantar Felix Elortza Liat Hayardeny Shelly C Lu JoséM Mato | 2020 | World Journal of Gastroenterology2020，26，34： | 5 |
| 3 | Generation of superparamagnetic liposomes revealed as highly efficient MRI contrast agents for in vivo imaging 显示文摘 | MARTINA M S FORTIN J P MENAGER C | 2005 | J Am Chem Soc2005，127，10： | 1 |
| 4 | Mouse cardiac surgery: Comprehensive techniques for the generation of mouse models of human diseases and their application for genomic studies显示文摘 | OLEG T JULIE R M MARTINA S | 2004 | Physiol Genomies2004，16，1： | 1 |
| 5 | Ozone-induced oxidative burst in the ozone bicmonitor plant tobacco BelWs显示文摘 | Martina S Wolfgang M Cosima W | 1998 | The Plant J1998，，16： | 1 |
| 6 | The value of ultrasound in acute ankle injury: comparison with MR显示文摘 | PETRA M MARTINA S IVAN Z L | 2009 | Eur J Trauma Emerg Surg2009，35，2： | 1 |
| 7 | Ozone- in- duced oxidat ive burnt in the ozone biem onitor plant to- bacco BelWs显示文摘 | Martina S Wol - ang M Cosima W | | 0，，16： | 1 |
| 8 | Magnetic Targeting of Magnetoliposomes to Solid Tumors with MR Imaging Monitoring in Mice : Feasibility 显示文摘 | Fortin-Ripoche J Martina M S Gazeau F | 2006 | Radiology2006，239，2： | 1 |
| 9 | Product Market Competition and Organizational Slack under Profit-Target Contracts显示文摘 | PICCOLO S D' Amato M MARTINA R | 2008 | International Journal of Industrial Organiza- tion2008，，26： | 1 |
| 10 | Exploring laser-induced breakdown spectroscopy for nuclear materials analysis and in-situ applications显示文摘 | M Z Martina S Allmana D J Brice | 2011 | Spectrochimica Acta Part B: Atomic Spectroscopy2011，74，75： | 1 |
| 11 | Expression of bacterial biphenyl-chlorobiphenyl dioxygenase genes in tobacco plants 显示文摘 | Mohammadi M Chalavi V Martina S N | 2007 | Biotechnology and Bioengineering2007，97，3： | 1 |
| 12 | Generation of superparamagnetic liposomes revealed as highly efficient MRI contrast agents for in vivo imaging显示文摘 | Martina M S Fortin J P Menager C | 2005 | J Am Chem Soc2005，127，10： | 1 |
| 13 | Anthocyanin content and antioxidam activity of various red fruit juices显示文摘 | LIDIJA J MARUAN S MARTINA M K | 2007 | Dtsoh Lebensm- Rundsch2007，103，2： | 1 |
| 14 | 2001 censensus guidelines for the management of women with cervical intraepithelial neoplasia显示文摘 | Hpffman M S Martina M A | 2004 | Am J Obstet Gynecol2004，191，： | 1 |
| 15 | Generation of superparamagnetic liposomes revealed as highly efficient MRI contrast agents for in vivo imaging显示文摘 | Martina M S Fortin J P Menager C | 2005 | J Am Chem Soc2005，127，10： | 1 |
| 16 | Evaluating environmental influences of zoning in urban ecosystems with remote sensing 显示文摘 | Wilson J S Clay M Martina E et at | 2003 | Remote Sensing of Environment2003，86，2： | 1 |
| 17 | The effect of magnetic targeting on the uptake of magnetic -fluid - loaded liposomes by human prostatic adenocarcinoma cells 显示文摘 | Martina M S Claire W Lesieur S | 2008 | Biomaterials2008，29，： | 1 |
| 18 | Drug-induced apoptosis in hepatoma cells is mediated by the CD95 (APO-1/Fas) receptor/Ligand system and involves activation of wild-type p53 显示文摘 | Martina M Susanne S Hubert H | 1997 | J Clin Invest1997，99，3： | 1 |
| 19 | Anthocyanin content and antioxidant activity of various red fruit juices 显示文摘 | Lidija J Marijan S Martina M K | 2007 | Dtsch Lebensm Rundsch2007，103，2： | 1 |
| 20 | New poly ether ether ketones containing phosphorus for membrane preparation显示文摘 | TROTTA F CERESA M S MARTINA K | 2010 | Asia-Pac J Chem Eng2010，5，1： | 1 |
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