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| 1 | Report of an international workshop to standardize baseline evaluation and response criteria for primary CNS lymphoma.显示文摘 | Abrey LE Batchelor TT Ferreri A J Gospodarowicz M Pulczynski EJ Zucca E Smith JR Korfel A Soussain C DeAngelis LM Neuwelt EA O′Neill BP Thiel E Shenkier T Graus F van den Bent M Seymour JF Poortmans P Armitage JO Cavalli F | 2005 | 中国神经肿瘤杂志2005，3，3： | 53 |
| 2 | MAP沉淀法目标产物最优形成条件及分析方法显示文摘为了确定鸟粪石(MAP:MgNH4PO4.6H2O)形成的最优条件,引入化学剖析法,利用酸溶液将鸟粪石沉淀法中所得沉淀物溶解后进行相应的元素分析;提出一种根据沉淀物中的NH4^+-N含量间接计算确定鸟粪石含量(即纯度)的分析方法.根据这种计算分析方法,分别得出了不同pH条件下以自来水(主要为地下水)和超纯水作为溶剂所合成的鸟粪石纯度,并对pH和Ca^2+在鸟粪石形成过程中的影响进行了评估.结果表明,该计算分析方法能够有效实现对MAP沉淀法目标产物的定量分析,弥补了国内外目前普遍依靠XRD技术定性判断所得沉淀物中鸟粪石是否存在的缺陷.以超纯水作为溶剂时,使鸟粪石纯度〉90%的最佳pH范围在7.5-9.0,而以自来水为溶剂时,获得相同鸟粪石纯度最佳pH范围则是7.0-7.5.实际污水中常常含有相当数量的Ca^2+,实施碱性条件(pH〉8.0)的MAP沉淀势必大幅降低鸟粪石的纯度.因此,对实际污水回收磷而言,MAP沉淀法的最优pH条件应控制在中性范围(〈8.0)以内. | 郝晓地 兰荔 王崇臣 van Loosdrecht M C M | 2009 | 环境科学2009，30，4： | 41 |
| 3 | Challenges in diagnosing mesenteric ischemia显示文摘Early identification of acute mesenteric ischemia (AMI) is challenging. The wide variability in clinical presentation challenges providers to make an early accurate diagnosis. Despite major diagnostic and treatment advances over the past decades, mortality remains high. Arterial embolus and superior mesenteric artery thrombosis are common causes of AMI. Non-occlusive causes are less common, but vasculitis may be important, especially in younger people. Because of the unclear clinical presentation and non-specific laboratory findings, low clinical suspicion may lead to loss of valuable time. During this diagnostic delay, progression of ischemia to transmural bowel infarction with peritonitis and septicemia may further worsen patient outcomes. Several diagnostic modalities are used to assess possible AMI. Multi-detector row computed tomographic angiography is the current gold standard. Although computed tomographic angiography leads to an accurate diagnosis in many cases, early detection is a persistent problem. Because early diagnosis is vital to commence treatment, new diagnostic strategies are needed. A non-invasive simple biochemical test would be ideal to increase clinical suspicion of AMI and would improve patient selection for radiographic evaluation. Thus, AMI could be diagnosed earlier with follow-up computed tomographic angiography or high spatial magnetic resonance imaging. Experimental in vitro and in vivo studies show promise for alpha glutathione S transferase and intestinal fatty acid binding protein as markers for AMI. Future research must confirm the clinical utility of these biochemical markers in the diagnosis of mesenteric ischemia. | Teun C van den Heijkant Bart AC Aerts Joep A Teijink Wim A Buurman Misha DP Luyer | 2013 | World Journal of Gastroenterology2013，19，9： | 31 |
| 4 | 几种植物提取物和天然产物对马铃薯晚疫病菌的抑制作用(英文)显示文摘大蒜和木贼提取物以及生物洁净剂和香茅油被用来测定对马铃薯晚疫病菌的孢子萌发、菌丝生长以及对叶片侵染的抑制作用 ,百菌清和清水用作对照。生物洁净剂和大蒜提取物对晚疫病菌孢子萌发具有最好的抑制作用。随着提取物浓度的提高 ,抑制效果也相应提高直到抑制率 10 0 %。生物洁净剂和大蒜提取物的所有浓度处理均完全抑制了游动孢子的萌发。木贼提取物也显示了抑菌特性 ,但程度较低。香茅油对孢子囊的萌发未显示抑制作用但对游动孢子的萌发有一定抑制作用。新鲜大蒜提取物比半干燥大蒜提取物有更强的抑菌作用。新制备的提取物与在 4℃条件下放置 1周的提取物相比在抑菌作用上没有显著差异 ,然而 ,来自新鲜木贼茎叶的提取物比干燥茎叶的提取物对游动孢子萌发抑制作用更强。无论经过灭菌与否 ,0 .12 5 %的生物洁净剂能完全抑制晚疫菌菌落的形成 ,说明它对高温不敏感。大蒜提取物在经高温处理后抑菌作用显著下降。对菌丝生长抑制效果从高到低排列依次为 :生物洁净剂 ,大蒜 ,木贼和香茅油。所有提取物和天然产物对马铃薯叶片上的病菌不表现治疗作用。0 12 5 %的生物洁净剂在接种前 3d和接种同时都显著地抑制了病原菌的侵染 ,其效果等同于百菌清。 2 %的大蒜提取物在接种前 | 曹克强 Ariena H C van Bruggen | 2001 | 河北农业大学学报2001，24，2： | 33 |
| 5 | NLRP3炎症小体对急性胰腺炎小鼠全身炎症反应及代偿性抗炎反应综合征的调节作用显示文摘【据《Gastroenterology》2019年10月报道】题:NLRP3炎症小体对急性胰腺炎小鼠全身炎症反应及代偿性抗炎反应综合征的调节作用(作者Sendler M等)胰腺炎开始时主要是无菌的局部炎症,其引起全身性炎症反应综合征(SIRS),然后是代偿性抗炎反应综合征(CARS)。来自德国格赖夫斯瓦尔德大学的Sendler等通过研究探讨了小鼠和人类血清中该过程的机制。 | 李德钊 郭晓林 SENDLER M van den BRANDT C GLAUBITZ J | 2020 | 临床肝胆病杂志2020，36，3： | 24 |
| 6 | Trastuzumab in combination with chemotherapy versus chemotherapy alone for treatment of HER2-positive advanced gastric or gastro-oesophageal junction cancer (ToGA): a phase 3, open-label, randomised controlled trial显示文摘 | Yung-Jue Bang Eric Van Cutsem Andrea Feyereislova Hyun C Chung Lin Shen Akira Sawaki Florian Lordick Atsushi Ohtsu Yasushi Omuro Taroh Satoh Giuseppe Aprile Evgeny Kulikov Julie Hill Michaela Lehle Josef Rüschoff Yoon-Koo Kang | 2010 | The Lancet2010，，9742： | 20 |
| 7 | 神经网络补偿机床热变形误差的机器学习技术显示文摘研究了以神经网络(NN)为模型的软件补偿不同机床热误差。提出知识获取是神经网络建模的关键环节。两种数控机床被用来研究分析热变形,通过测量实验获取学习数据,特别是温度测量和传感器数目的选取。介绍了机器学习技术和学习数据组织方法,包括归纳学习和推理学习。给出了预报补偿的结果和精度评价。 | 杨庆东 Van Den Bergh C Venherck P KruthJP | 2000 | 机械工程学报2000，36，1： | 15 |
| 8 | 焦炭特性及其在高炉下部的变化过程显示文摘气化、石墨化和溶解是影响焦炭从高炉软熔带至炉缸间行为的三个主要过程。过去几年在一些专题项目中对这些过程进行了研究。简要叙述并讨论了这些过程的相互作用及其与焦炭特性的关系。对焦炭的气化反应进行了实验室测试研究,用以评价高炉条件下焦炭的特性。用高炉条件下的气化测试装置测试了几种焦炭试样,考查的质量指标包括反应性、结构变化和强度等。用实际尺寸的焦炭块对块状焦炭试样的高温行为进行了评估,将不同种类的焦炭试样加热到2 000℃,以鉴别其在高温下的行为。高温下焦炭将发生石墨化,对高温反应后的强度进行了评定,并作了显微观察,发现了一些现象和组织结构的变化。焦炭与液态渣铁相互作用的研究结果对焦炭在高炉下部的行为有了更好的理解。通过试验研究了焦炭抗液态铁水溶解的性能,对入炉前的焦炭和经高温反应的焦炭分别进行了试验。分析讨论了焦炭的抗气化、抗石墨化和抗铁水溶解性能与其结构、化学成分和强度的关系。 | B van der Velden C J Atkinson T Bakker J R H Stuurwold G J Tijhuis 徐万仁 | 2014 | 世界钢铁2014，，2： | 11 |
| 9 | Inflammatory bowel disease serology in Asia and the West显示文摘AIM:To study serological antibodies in Caucasians and Asians,in health and inflammatory bowel disease(IBD),in Australia and Hong Kong(HK).METHODS:Anti-glycan antibodies[anti-chitobioside(ACCA),anti-laminaribioside(ALCA)],and anti-mannobioside(AMCA),anti-Saccharomyces cervisiae(gASCA);and atypical perinuclear anti-neutrophil cytoplasmic antibody(pANCA)were tested in IBD patients,their unaffected relatives,and healthy controls in Australia and HK(China).Antibody status(positive or negative)and titre was compared between subjects of different geography,ethnicity and disease state.RESULTS:Ninety subjects were evaluated:21 Crohn’s disease(CD),32 ulcerative colitis(UC),29 healthy controls,and 8 IBD patient relatives.Forty eight subjects were Australian(29 Caucasian and 19 ethnic Han Chinese)and 42 were from HK(all Han Chinese).Caucasian CD patients had a significantly higher antibody prevalence of gASCA(67%vs 3%,P<0.001),ALCA(44%vs 6%,P=0.005),and AMCA(67%vs 15%,P=0.002),whereas HK CD patients had a higher prevalence of only AMCA(58%vs 25%,P=0.035),when compared with UC and healthy subjects in both countries.Caucasian CD had significantly higher gASCA prevalence(67%vs 0%,P<0.001)and titre(median59 vs 9,P=0.002)than HK CD patients.Prevalence and titres of ALCA,ACCA and AMCA did not differ between CD in the two countries.Presence of at least one antibody was higher in Caucasian than HK CD patients(100%vs 58%,P=0.045).pANCA did not differ between countries or ethnicity.CONCLUSION:Serologic CD responses differ between HK Asian and Australian Caucasian patients.Different genetic,environmental or disease pathogenic factors may account for these differences. | Lani Prideaux Michael A Kamm Peter De Cruz Daniel R van Langenberg Siew C Ng Iris Dotan | 2013 | World Journal of Gastroenterology2013，19，37： | 10 |
| 10 | Near-infrared fluorescence sentinel lymph node detection in gastric cancer: A pilot study显示文摘AIM: To investigate feasibility and accuracy of nearinfrared fluorescence imaging using indocyanine green: nanocolloid for sentinel lymph node(SLN) detection in gastric cancer.METHODS: A prospective, single-institution, phaseI feasibility trial was conducted. Patients suffering from gastric cancer and planned for gastrectomy were included. During surgery, a subserosal injection of 1.6 m L ICG:Nanocoll was administered around the tumor. NIR fluorescence imaging of the abdominal cavity was performed using the Mini-FLARE? NIR fluorescence imaging system. Lymphatic pathways and SLNs were visualized. Of every detected SLN, the corresponding lymph node station, signal-to-background ratio and histopathological diagnosis was determined. Patients underwent standard-of-care gastrectomy. Detected SLNs outside the standard dissection planes were also resected and evaluated.RESULTS: Twenty-six patients were enrolled. Four patients were excluded because distant metastases were found during surgery or due to technical failure of the injection. In 21 of the remaining 22 patients, at least 1 SLN was detected by NIR Fluorescence imaging(mean 3.1 SLNs; range 1-6). In 8 of the 21 patients, tumor-positive LNs were found. Overall accuracy of the technique was 90%(70%-99%; 95%CI), which decreased by higher p T-stage(100%, 100%, 100%, 90%, 0% for respectively Tx, T1, T2, T3, T4 tumors). All NIR-negative SLNs were completely effaced by tumor. Mean fluorescence signal-to-background ratio of SLNs was 4.4(range 1.4-19.8). In 8 of the 21 patients, SLNs outside the standard resection plane were identified, that contained malignant cells in 2 patients.CONCLUSION: This study shows successful use of ICG:Nanocoll as lymphatic tracer for SLN detection in gastric cancer. Moreover, tumor-containing LNs outside the standard dissection planes were identified. | Quirijn RJG Tummers Leonora SF Boogerd Wobbe O de Steur Floris PR Verbeek Martin C Boonstra Henricus JM Handgraaf John V Frangioni Cornelis JH van de Velde Henk H Hartgrink Alexander L Vahrmeijer | 2016 | World Journal of Gastroenterology2016，22，13： | 9 |
| 11 | Dietary and metabolomic determinants of relapse in ulcerative colitis patients: A pilot prospective cohort study显示文摘AIM To identify demographic, clinical, metabolomic, and lifestyle related predictors of relapse in adult ulcerative colitis(UC) patients.METHODS In this prospective pilot study, UC patients in clinical remission were recruited and followed-up at 12 mo to assess a clinical relapse, or not. At baseline information on demographic and clinical parameters was collected. Serum and urine samples were collected for analysis of metabolomic assays using a combined direct infusion/liquid chromatography tandem mass spectrometry and nuclear magnetic resolution spectroscopy. Stool samples were also collected to measure fecal calprotectin(FCP). Dietary assessment was performed using a validated self-administered food frequency questionnaire. RESULTS Twenty patients were included(mean age: 42.7 ± 14.8 years, females: 55%). Seven patients(35%) experienced a clinical relapse during the follow-up period. While 6 patients(66.7%) with normal body weight developed a clinical relapse, 1 UC patient(9.1%) who was overweight/obese relapsed during the follow-up(P = 0.02). At baseline, poultry intake was significantly higher in patients who were still in remission during follow-up(0.9 oz vs 0.2 oz, P = 0.002). Five patients(71.4%) with FCP > 150 μg/g and 2 patients(15.4%) with normal FCP(≤ 150 μg/g) at baseline relapsed during the follow-up(P = 0.02). Interestingly, baseline urinary and serum metabolomic profiling of UC patients with or without clinical relapse within 12 mo showed a significant difference. The most important metabolites that were responsible for this discrimination were trans-aconitate, cystine and acetamide in urine, and 3-hydroxybutyrate, acetoacetate and acetone in serum. CONCLUSION A combination of baseline dietary intake, fecal calprotectin, and metabolomic factors are associated with risk of UC clinical relapse within 12 mo. | Ammar Hassanzadeh Keshtel iFloris F van den Brand Karen L Madsen Rupasri Mandal Rosica ValchevaKaren I Kroeker Beomsoo Han Rhonda C Bell Janis Cole Thomas Hoevers David S Wishart Richard N Fedorak Levinus A Dieleman | 2017 | World Journal of Gastroenterology2017，23，21： | 9 |
| 12 | α-葡萄糖苷酶抑制剂治疗2型糖尿病的系统评价(英文)显示文摘目的评价α-葡萄糖苷酶抑制剂治疗2型糖尿病患者的效果。方法检索Cochrane图书馆、MEDLINE、EMBASE、CurrentContents、LILACS在研试验数据库,主题为α-葡萄糖苷酶抑制剂的综述的参考文献,并联系纳入试验的专家与实施者。最近检索日期为2003年月12月(CurrentContents)和2003年4月(其他数据库)。纳入α-葡萄糖苷酶抑制剂单一疗法与其它干预比较,治疗2型糖尿病疗程至少12周的随机对照试验,并且试验至少包括以下结局之一:病死率、患病率、生活质量、血糖控制、血脂、胰岛素水平、体重、不良事件。两名评价者独立阅读所有摘要,评价质量并提取数据,分歧通过协商解决或由第三位评价者裁决。由一位统计学家在对提取数据输入数据库时进行检查。我们尽量联系所有作者以核实数据。结果共纳入41个试验、8130例受试者,其中30个针对阿卡波糖,7个针对米格列醇,1个针对优格列波糖,还有3个为不同α-葡萄糖苷酶抑制剂间的比较。绝大多数研究疗程为24周,仅有2个研究超过1年。与安慰剂相比,阿卡波糖血糖控制效果更好:糖化血红蛋白–0.8%[95%CI(–0.9,–0.7)],空腹血糖–1.1mmol/L[95%CI(–1.4,–0.9)],负荷血糖–2.3mmol/L[95%CI(–2.7,–1.9)],阿卡波糖对糖化血红蛋白的作用呈非剂量依赖。我们发现其可降低负荷胰岛素,但对血脂和体重未见临床相关的作用。不良反应主要来自胃肠道且与剂量相关。相对于磺脲,阿卡波糖将空腹和负荷胰岛素水平分别降低至–24.8pmol/L[95%CI(–43.3,–6.3)]和–133.2pmol/L[95%CI(–184.5,–81.8)],但阿卡波糖引起的不良反应更多。结论关于α-葡萄糖苷酶抑制剂是否影响2型糖尿病患者的病死率和患病率仍不清楚。相反,其对血糖控制或胰岛素水平作用明显,对血脂和体重的作用差异无统计学意义。α-葡萄糖苷酶抑制剂更长疗程的效果仍不确定。阿卡波糖剂量超过50mg(TID)时不能进一步影响糖化血红蛋白水平,不良反应反而更多,与磺脲相比,α-葡萄糖苷酶抑制剂降低了空腹和负荷胰岛素水平,但在血糖控制和不良反应方面存在不利影响。 | VandeLaarFA Lucassen PLBJ Akkermans RP Van de Lisdonk EH Rutten GEHM Van Weel C 陈耀龙(译) 孙丁(审校) | 2006 | 中国循证医学杂志2006，6，5： | 9 |
| 13 | 地氯雷他定对变应性鼻炎动物模型鼻腔灌洗液中血栓素B_2和白三烯的影响显示文摘目的:观察豚鼠变应性鼻炎动物模型的鼻腔灌洗液(NLF)中血栓素(TX)B2和白三烯(LTs)水平及地氯雷他定对这些递质的影响。方法:将36只豚鼠分为阳性对照组、地氯雷他定(desloratadine)治疗组和阴性对照组,每组12只。阴性对照组未予抗原致敏和激发,阳性对照组和地氯雷他定治疗组经卵白蛋白局部致敏,卵白蛋白溶液反复局部激发后,收集并测定各组NLF中TXB2和LTs水平。结果:NLF中,阳性对照组TXB2水平[(271.8±36.5)pg/1mlNLF]较地氯雷他定治疗组[(156.4±34.0)pg/1mlNLF]及阴性对照组[(62.1±16.0)pg/1mlNLF]高,差异均有统计学意义(均P<0.01);地氯雷他定治疗组较阴性对照组高(P<0.01)。阳性对照组LTs水平[(114.5±40.0)pg/1mlNLF]较地氯雷他定治疗组[(66.0±16.7)pg/1mlNLF]及阴性对照组[(12.4±2.3)pg/1mlNLF]高,差异均有统计学意义(P<0.05和P<0.01);地氯雷他定治疗组较阴性对照组高(P<0.05)。结论:在豚鼠变应性鼻炎动物模型中,其NLF中的TXB2和LTs水平在抗原激发后显著升高;地氯雷他定能显著抑制TXB2和LTs水平,提示地氯雷他定的治疗机制与抑制TXB2和LTs的产生或释放有关。 | 赵宇 Van Hasselt C A 吴港生 黄约爱 梁秉中 | 2005 | 临床耳鼻咽喉科杂志2005，19，8： | 8 |
| 14 | How to Make Capsules Containing Rejuvenators for Their Use in Asphalt Concrete显示文摘Rejuvenators are products designed to restore original properties to oxidized asphalt binders by restoring the original ratio of asphaltenes to maltenes. But,for a rejuvenator to be successful,it must penetrate the pavement surface. Besides,application of a rejuvenator will also reduce the skid resistance of the pavement. To solve this,these rejuvenators can be encapsulated and mixed in asphalt concrete. Once the stress in the capsules reaches a certain threshold,the particles break and the rejuvenator is released,giving back the original properties of the pavement. The objective of this paper is to show how these capsules behave and define the most appropriate testing methods to find their effect on asphalt concrete. For this,two different types of rejuvenators will be encapsulated and their effect on the properties of the capsules investigated. Besides,the release mechanisms of the capsules will be unravelled. | GARCIA A SCHLANGEN E VAN DE VEN M F C | 2010 | 武汉理工大学学报2010，32，17： | 7 |
| 15 | Pineal clock gene oscillation is disturbed in Alzheimer's disease, due to functional disconnection from the "master clock"显示文摘 | Wu YH Fischer DF Kalsbcck A Garidou-Boof ML van der Vliet J van Heijningen C Liu RY Zhou JN Swaab DE | 2006 | 中国生物学文摘2006，20，9： | 7 |
| 16 | Trastuzumab in combination with chemotherapy versus chemotherapy alone for treatment of HER2-positive advanced gastric or gastro-oesophageal junction cancer (ToGA): a phase 3, open-label, randomised controlled trial显示文摘 | Yung-Jue Bang Eric Van Cutsem Andrea Feyereislova Hyun C Chung Lin Shen Akira Sawaki Florian Lordick Atsushi Ohtsu Yasushi Omuro Taroh Satoh Giuseppe Aprile Evgeny Kulikov Julie Hill Michaela Lehle Josef Rüschoff Yoon-Koo Kang | 2010 | The Lancet . 2010 (9742)2010，，9742： | 6 |
| 17 | High-density SNP-based genetic maps for the parents of an outcrossed and a selfed tetraploid garden rose cross, inferred from admixed progeny using the 68k rose SNP array显示文摘Dense genetic maps create a base for QTL analysis of important traits and future implementation of marker-assisted breeding.In tetraploid rose,the existing linkage maps include<300 markers to cover 28 linkage groups(4 homologous sets of 7 chromosomes).Here we used the 68k WagRhSNP Axiom single-nucleotide polymorphism(SNP)array for rose,in combination with SNP dosage calling at the tetraploid level,to genotype offspring from the garden rose cultivar‘Red New Dawn’.The offspring proved to be not from a single bi-parental cross.In rose breeding,crosses with unintended parents occur regularly.We developed a strategy to separate progeny into putative populations,even while one of the parents was unknown,using principle component analysis on pairwise genetic distances based on sets of selected SNP markers that were homozygous,and therefore uninformative for one parent.One of the inferred populations was consistent with self-fertilization of‘Red New Dawn’.Subsequently,linkage maps were generated for a bi-parental and a self-pollinated population with‘Red New Dawn’as the common maternal parent.The densest map,for the selfed parent,had 1929 SNP markers on 25 linkage groups,covering 1765.5 cM at an average marker distance of 0.9 cM.Synteny with the strawberry(Fragaria vesca)genome was extensive.Rose ICM1 corresponded to F.vesca pseudochromosome 7(Fv7),ICM4 to Fv4,ICM5 to Fv3,ICM6 to Fv2 and ICM7 to Fv5.Rose ICM2 corresponded to parts of F.vesca pseudochromosomes 1 and 6,whereas ICM3 is syntenic to the remainder of Fv6. | Mirjana Vukosavljev Paul Arens Roeland E Voorrips Wendy P C van't Westende G D Esselink Peter M Bourke Peter Cox W Eric van de Weg Richard G F Visser Chris Maliepaard Marinus J M Smulders | 2016 | Horticulture Research2016，3，1： | 6 |
| 18 | 中国北京和长岛大气颗粒物中铅的同位素丰度比测定(英文)显示文摘采用高分辨电感耦合等离子体质谱技术(HRICPMS)分析了48个不同季节大气气溶胶颗粒样品中铅同位素丰度(A)比值,为中国城市铅污染源研究提供数据。样品采自中国北京和山东长岛地区(2002~2003年期间不同季节)。A(206Pb/207Pb)和A(208Pb/207Pb)的10次测定精密度为0.05%~0.19%RSD。 | 李冰 刘咸德 董树屏 Veerle Van Lierde Frank Vanhaecke Freddy C Adams | 2005 | 岩矿测试2005，24，1： | 5 |
| 19 | TAT-Gap19通过抑制啮齿动物星形胶质细胞的连接蛋白43半通道发挥抗惊厥作用显示文摘越来越多的证据表明,星形胶质细胞连接蛋白43(Cx43)信号在癫痫中发挥至关重要的作用。但是,由于通过实验方法鉴别Cx43间隙连接通道(GJCs)和半通道(HCs)的技术尚不成熟,导致目前尚无法确定哪个通道在癫痫的发生中发挥更重要的作用。因此,本研究观察TAT-Gap19(Cx模拟肽)是否通过抑制Cx43半通道而非Cx43间隙连接通道影响实验诱导的啮齿动物癫痫发作。急性海马切片小鼠染料摄取实验表明,星形胶质Cx43半通道响应化学惊厥毛果芸香碱的作用而开放,并且可被TAT-Gap19抑制。体内实验中,毛果芸香碱诱导的癫痫发作及相伴随的D-丝氨酸微透析液的增长水平被Cx43半通道的抑制所抑制。此外,TAT-Gap19的抗惊厥作用被外源性D-丝氨酸给药逆转,这表明,抑制Cx43半通道可以通过降低细胞外D-丝氨酸水平来防止癫痫发作。抑制Cx43半通道的抗惊厥特性在电癫痫小鼠模型(如急性6 Hz难治性癫痫发作模型和慢性6 Hz角膜点燃模型)中得到了进一步的证实。总而言之,这些结果表明,Cx43半通道在癫痫发作中可以起到一定作用,并且有成为癫痫治疗中新型用药靶点的潜力。 | Walrave L Pierre A Albertini G Aourz N De Bundel D Van Eeckhaut A Vinken M Giaume C Leybaert L Smolders I 聂昊 | 2018 | 神经损伤与功能重建2018，13，6： | 5 |
| 20 | 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 |
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