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ndrogen-deprivation therapy in men with metastatic rostate cancer： less may not necessarily be more

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Asian Journal of Andrology 2013年第4期15卷 445-446页

作者： mark ng tang fui Mathis Grossmann Department of Medicine University of Melbourne Austin Health Heidelberg Victoria 3084 Australia and Endocrinology Austin Health Heidelberg Victoria 3084 Australia

In a pivotal phase 3 randomized con trolled trial, Hussain et al. tested thehypothesis that, with respect to survival, intermittent androgen deprivation therapy （ADT） is noninferior to continuous in men with newly diagnosed metastatic prostate cancer. While the trial findings were statis tically inconclusive, the study suggests, but does not prove, that intermittent may do more harm than good, although findings are not definitive. While outcomes of ongoing trials are awaited, the trial by Hussain et al., in conjunction with an ear lier trial in men with nonmetastatic pro state cancer by Crook et al., does provide important new guidance regarding the choice of ADT in men with androgensensitive prostate cancer. ADT is one of the most effective palliat ive therapies for patients with metastatic prostate cancer, but not without drawbacks. While not as toxic as chemotherapy, ADT carries a significant risk of morbidity, including sexual dysfunction, fatigue, ane mia, accelerated bone loss and fractures, sarcopenia, increased risk of diabetes, and possibly, of cardiovascular events.1＇2 In addition, despite an initial response rate of more than 90%, most patients develop res istance to ADT, resulting in a median sur vival of 2.53 years. Predinical data suggest that continuous use of ADT may accelerate the emergence of resistance to this therapy, and that reexposure of prostate cancer stem cells to androgens can reinduce dif ferentiation and increase their apoptotic potential.3 These ADTassociated shortcom ings, in addition to treatment expense, havespurred the development of strategies to min imize the exposure to ADT, including the use of intermittent ADT. While several smaller randomized controlled clinical trials have compared the use of intermittent with con tinuous ADT, no definitive information is available for patients with metastatic prostate cancer. To fill this evidence gap, a large mul tinational randomized controlled trial led by Hussain et al.4 was designed in

关键词： Androgen-deprivation therapy prostate

Testicular volume and clinical correlates of hypothalamic–pituitary–testicular function:A cross-sectional study in obese men

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Asian Journal of Andrology 2020年第4期22卷 354-359页

作者： mark ng tang fui Rudolf Hoermann Gary Wittert Mathis Grossmann Department of Medicine Austin Health University of MelbourneMelbourneVictoria 3084Australia Department of Endocrinology Austin HealthMelbourneVictoria 3084Australia School of Medicine University of AdelaideAdelaideSouth Australia 5005Australia

The aim of this study was to determine whether testicular volume is correlated with clinical and biochemical markers of hypothalamic–pituitary–testicular(HPT)axis *** was a cross-sectional substudy of a larger randomized controlled trial including obese men,body mass index(BMI)≥30 kg m−2,with a total testosterone levelng Males'Symptoms(AMS)score,International Index of Erectile Function-5(IIEF-5),physical function,and handgrip dynamometer ***-nine men participated with a median(interquartile range[IQR])age of 53.1(47.6,59.2)years,BMI of 37.0(34.6,40.5)kg m−2,and a total testosterone of 7.0(6.1,7.9)nmol l−*** testicular volume was 18(IQR:10,20)*** volume was negatively correlated with BMI(τ=−0.1952,P=0.010)and total fat mass(τ=−0.2115,P=0.005)independent of age and *** BMI,testosterone,sex hormone-binding globulin(SHBG),and luteinizing hormone(LH)were present in a multivariable model,only BMI(-0.38 ml change in testicular volume per 1 kg m-2BMI;95%CI:−0.74,−0.02;P=0.04)and LH(-0.92 ml change in testicular volume per 1 IU l-1 LH;95%CI:−1.75,−0.095;P=0.03)remained independent significant predictors of testicular *** volume was positively correlated with IIEF-5(τ=0.2092,P=0.021),but not related to handgrip strength,physical function tests,or *** obese men,testicular volume is inversely and independently associated with measures of adiposity,but not with most clinical or biochemical markers of HPT axis *** a clinical perspective,this suggests that obesity might compromise the reliability of reduced testicular volume as a sign of androgen deficiency in men.

关键词： hypothalamic-pituitary-gonadal axis testicular volume testosterone

A Class Effect Network Meta-analysis of Lipid Modulation in Non-alcoholic Steatohepatitis for Dyslipidemia

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Journal of Clinical and Translational Hepatology 2022年第6期10卷 1042-1049页

作者： Jieling Xiao Cheng-Han ng Yip-Han Chin Darren Jun Hao Tan Wen-Hui Lim Grace Lim Jingxuan Quek Ansel Shao Pin tang Kai-En Chan Rou-Yi Soong Nicholas Chew Benjamin Tay Daniel Q.Huang Nobuharu Tamaki Roger Foo mark Y.Chan Mazen Noureddin Mohammad Shadab Siddiqui Arun J.Sanyaland mark D.Muthiah Yong Loo Lin School of Medicine National University of SingaporeSingapore Lee Kong Chian School of Medicine Nan-yang Technological UniversitySingapore Department of Cardiology National University Heart CenterNational University HospitalSingapore Division of Gastroenterology and Hepatology Department of MedicineNational University HospitalSingaporeSingapore National University Center for Organ Transplantation National University Health SystemSingapore NAFLD Research Center Division of Gastroenterology and HepatologyDepartment of MedicineUniversity of California at San DiegoLa JollaCAUSA Department of Gastroenterology and Hepatology Musashino Red Cross HospitalTokyoJapan Cedars-Sinai Fatty Liver Program Division of Digestive and Liver DiseasesDepartment of MedicineComprehen-sive Transplant CenterCedars-Sinai Medical CenterLos AngelesCAUSA Division of Gastroenterology Hepatology and NutritionDepartment of Internal MedicineVirginia Commonwealth UniversityRichmondVAUSA

Background and Aims:Pharmaceutical therapy for NASH is associated with lipid modulation,but the consensus on drug treatment is limited and lacks comparative analysis of effectiveness.A network meta-analysis was conducted to compare NASH drug classes in lipid ***:Online databases were searched for randomized controlled trails(RCTs)evaluating NASH treatments in biopsy-proven NASH *** were classified into four groups:(1)inflammation,(2)energy,(3)bile acids,and(4)fibro-sis based on the mechanism of action.A Bayesian network analysis was conducted with outcome measured by mean difference(MD)with credible intervals(Crl)and surface un-der the cumulative ranking curve(SUCRA).Results:Forty-four RCTs were included in the *** acid modulat-ing treatments(MD:0.05,Crl:0.03-0.07)were the best treatment for improvement in high-density lipid(HDL)cho-lesterol,followed by treatments modulating energy(MD:0.03,Crl:0.02-0.04)and fibrosis(MD:0.01,Crl:−0.12 to 0.14)compared with *** top three treatments for reduction in triglycerides were treatments modulating energy(MD:−0.46,Crl:−0.49 to−0.43),bile acids(MD:−0.22,Crl:−0.35 to−0.09),and inflammation(MD:−0.08,Crl:−0.13 to−0.03)compared with *** found treatment modulating fibrosis(MD:−1.27,Crl:−1.76 to−0.79)was the best treatment for reduction in low-density lipid(LDL)cholesterol followed by treatment modulating in-flammation(MD:−1.03,Crl:−1.09 to−0.97)and energy(MD:−0.37,Crl:−0.39 to−0.34)compared with placebo,but LDL cholesterol was worsened by treatments modulat-ing bile ***:Network analysis comparing the class effects of dyslipidemia modulation in NASH found that treatment targets can include optimization of athero-genic *** studies are required to evaluate the cardiovascular outcomes.

关键词： Lipid modulation NASH Dyslipidemia

P13K、P38MAPK及ERK1／2抑制剂对EGF诱导的血管平滑肌细胞迁移的实验研究

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中国医师杂志 2009年第6期11卷 742-744页

作者：张复贵闵新文曾秋棠陈龙菊姜铧郧阳医学院附属东风总医院心内科湖北十堰442000 华中科技大学附属协和医院心内科郧阳医学院解剖学教研室郧阳医学院附属太和医院血液内科

目的探讨P13K抑制剂Wortmannin、P38MAPK抑制剂SB202190及ERK1／2抑制剂PD98059对表皮生长因子（EGF）诱导的大鼠主动脉平滑肌细胞（VSMCs）迁移的影响。方法以1％FCS血清孵育为对照，用EGF（10ng／ml）刺激，平行加入PD98059（PD组）、... 详细信息

目的探讨P13K抑制剂Wortmannin、P38MAPK抑制剂SB202190及ERK1／2抑制剂PD98059对表皮生长因子（EGF）诱导的大鼠主动脉平滑肌细胞（VSMCs）迁移的影响。方法以1％FCS血清孵育为对照，用EGF（10ng／ml）刺激，平行加入PD98059（PD组）、SB202190（SB组）和Wortmannin（WT），划痕损伤实验分析VSMCs迁移情况。结果划痕后24h，EGF组VSMCs迁移较对照组明显（P〈0．01），WT组、SB组及PD纽与EGF组相比都明显抑制VSMCs迁移（P〈0．01），但三个抑制剂组之间差异无统计学意义（P〉0．05）；划痕后30h，EGF组VSMCs迁移仍较对照组明显（P〈0．01），WT组、SB组及PD组与EGF组相比则明显抑制VSMCs迁移（P〈0．叭），且三个抑制剂组之间差异有统计学意义，其中sB组较WT组和PD组抑制VSMCs的迁移更明显（P〈0．01）。结论EGF诱导VSMCs迁移可能通过P13K、P38MAPK及ERK1／2途径起作用，且P38MAPK途径作用更明显。

关键词： 1-磷脂酰肌醇3-激酶/拮抗剂和抑制剂 p38丝裂原活化蛋白激酶类/拮抗剂和抑制剂肌细胞平滑肌/药物作用表皮生长因子

军用电子PCBA三防涂层耐湿热性能的影响因素

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电子工艺技术 2015年第1期36卷 29-31,54页

作者：杨唐绍钟付先张红兵中国电子科技集团公司第三十研究所四川成都610041

军用电子设备需要在恶劣的环境中工作。PCBA涂覆后在耐湿热加速老化试验中,常出现涂层脱落、气泡、失光、发白等失效现象。通过对空气湿度、涂覆前处理、机箱结构形式、阻焊膜选择、涂料选择五方面因子进行验证及分析,提出了相应的解决... 详细信息

军用电子设备需要在恶劣的环境中工作。PCBA涂覆后在耐湿热加速老化试验中,常出现涂层脱落、气泡、失光、发白等失效现象。通过对空气湿度、涂覆前处理、机箱结构形式、阻焊膜选择、涂料选择五方面因子进行验证及分析,提出了相应的解决措施,为军事电子PCBA防护工艺提供参考。

关键词： PCBA 三防涂层空气湿度涂覆前处理机箱结构阻焊膜涂料

橙皮素对转化生长因子-β_1诱导心肌成纤维细胞增殖的影响

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疑难病杂志 2015年第4期14卷 376-379页

作者：胡哲夫唐其柱刘源李金张文斌武汉大学人民医院心血管内科 430060

目的探讨橙皮素(HES)对转化生长因子-β_1(TGF-β_1)诱导心肌成纤维细胞增殖的影响,并探讨其可能的机制。方法取SD大鼠30只,取其心肌组织进行成纤维细胞的培养。而后采用TGF-β_1(10 ng/ml)刺激成纤维细胞,采用4种不同浓度梯度的HES(25... 详细信息

目的探讨橙皮素(HES)对转化生长因子-β_1(TGF-β_1)诱导心肌成纤维细胞增殖的影响,并探讨其可能的机制。方法取SD大鼠30只,取其心肌组织进行成纤维细胞的培养。而后采用TGF-β_1(10 ng/ml)刺激成纤维细胞,采用4种不同浓度梯度的HES(25μmol/L、50μmol/L、75μmol/L、100μmol/L)干预成纤维细胞24 h,以台盼蓝染色检测其对细胞活性的影响;荧光酶标仪检测法用于检测细胞内活性氧(ROS)的水平;活细胞计数试剂盒(CCK-8)用以检测成纤维细胞的增殖情况。结果台盼蓝染色结果提示,HES对成纤维细胞的细胞活性无显著影响,各组活性值分别为空白对照组:100%,HES 25μmol/L组:95%,HES 50μmol/L组:94%,HES 75μmol/L组:93%,HES100μmol/L组:93%。酶标仪检测结果表明,与空白对照组相比,TGF-β_1可增加成纤维细胞内ROS的水平(P<0.01),当HES与TGF-β_1同时作用时,ROS水平随着HES浓度的增加逐渐降低,均存在统计学意义(P<0.05);TGF-β_1可刺激成纤维细胞增殖(P<0.01),当HES(100μmol/L)或N-乙酰半胱氨酸(NAC)(1 mmol/L)与TGF-β_1同时作用时,可明显抑制成纤维细胞增殖(P<0.01)。结论 HES可通过抑制TGF-β_1诱导的氧化应激进而抑制心肌成纤维细胞增殖,提示其对于预防心肌纤维化可能具有潜在效果。

关键词：橙皮素转化生长因子-β_1 成纤维细胞细胞活性

生肌玉红复合胶原改善脂肪干细胞功能的实验研究

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辽宁中医杂志 2018年第6期45卷 1121-1125,I0001页

作者：唐甜陈绪许岩磊薛静娴王聪冯泽宇姚昶南京中医药大学江苏南京210029 南京中医药大学附属医院江苏南京210029

目的：探索生肌玉红复合胶原改善脂肪干细胞功能及其作用机制。方法：首先,将生肌玉红膏提取液分0.0125 g·L^-1、0.025 g·L^-1、0.05 g·L^-1、0.1 g·L^-1各浓度,以细胞增殖实验筛选生肌玉红膏提取液促进脂肪干细胞增殖的最佳浓度;... 详细信息

目的：探索生肌玉红复合胶原改善脂肪干细胞功能及其作用机制。方法：首先,将生肌玉红膏提取液分0.0125 g·L^-1、0.025 g·L^-1、0.05 g·L^-1、0.1 g·L^-1各浓度,以细胞增殖实验筛选生肌玉红膏提取液促进脂肪干细胞增殖的最佳浓度;将筛选的最佳浓度生肌玉红膏提取液、胶原及最佳浓度生肌玉红膏提取液复合胶原,分别以transwell小室实验刺激脂肪干细胞迁移;增殖培养48 h后提取脂肪干细胞蛋白,以免疫蛋白印迹法（Western blot）测定各组细胞外调节蛋白激酶类（extracellular regulated protein kinases,ERK）蛋白表达,同时以酶联免疫吸附法（ELISA）测定细胞培养液中血管内皮生长因子（vascular endothelial growth factor,VEGF）含量。结果：在给药培养后24 h、48 h及72 h后,0.05 g·L^-1生肌玉红膏提取液增殖效果最为明显,均优于各时间观测点其他浓度的生肌玉红膏提取液,培养48 h后,生肌玉红复合胶原组相对于对照组增殖了46%,显著高于生肌玉红膏提取液组27.4%及胶原组27.6%,差异有显著统计学意义（P〈0.05）;提高脂肪干细胞迁移率约220%,显著高于生肌玉红膏提取液组140%及胶原组50%;提高脂肪干细胞外调节蛋白激酶（ERK）蛋白表达40%左右,显著高于生肌玉红膏提取液组15%及胶原组10%;同时刺激脂肪干细胞分泌VEGF达411.4 ng·L^-1,显著高于生肌玉红膏提取液组207.5 ng·L^-1及胶原组240.8 ng·L^-1。结论：生肌玉红复合胶原可以通过mark/ERK通路信号通路显著促进脂肪干细胞功能并刺激血管内皮生长因子分泌,与脂肪干细胞结合可进一步提升促血管新生功效。

关键词：生肌玉红膏胶原脂肪干细胞血管内皮生长因子