目的基于网络药理学初步预测大黄素治疗乳腺癌合并高脂血症的作用靶点及信号通路,通过分子对接和体外实验验证探讨其可能的作用机制。方法通过中药系统药理学数据库及分析平台(Traditional Chinese Medicine Systems Pharmacology Datab...目的基于网络药理学初步预测大黄素治疗乳腺癌合并高脂血症的作用靶点及信号通路,通过分子对接和体外实验验证探讨其可能的作用机制。方法通过中药系统药理学数据库及分析平台(Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform,TCMSP)、Swiss Target Prediction数据库查询大黄素的作用靶点;通过GeneCards、OMIM数据库获取乳腺癌、高脂血症的相关靶点;通过在线Veny软件获得大黄素-乳腺癌-高脂血症的共同靶点,并将共同靶点导入STRING数据库构建靶点蛋白质相互作用(protein-protein interaction,PPI)网络,再利用Cytoscape 3.9.1软件进行可视化处理,筛选核心靶点。通过Metascape在线基因功能注释分析工具进行基因本体(gene ontology,GO)生物学过程和京都基因与基因组百科全书(Kyoto encyclopedia of genes and genomes,KEGG)通路富集分析。选取关键靶点与大黄素通过AutoDock Vina等软件进行分子对接验证。在乳腺癌4T1细胞和肿瘤相关巨噬细胞(tumor-associated macrophage,TAM)中检测大黄素在抑制乳腺癌发展中的作用。以CCK-8法检测大黄素对4T1细胞生长的影响并筛选最佳药物作用浓度,分别采用Real-time PCR及ELISA检测基质金属蛋白酶9(matrix metalloproteinase,MMP9)、白细胞介素-1β(interleukin-1 beta,IL-1β)及转化生长因子β1(transforming growth factor beta 1,TGF-β1)的表达水平。结果共筛选得到43个大黄素-乳腺癌合并高脂血症共同靶点,核心靶点有肿瘤抗原p53(tumor protein p53,TP53)、肿瘤坏死因子(tumor necrosis factor,TNF)、髓细胞增生原癌基因(myelocytomatosis oncogene,MYC)、表皮生长因子受体(epidermal growth factor receptor,EGFR)、90 kDa热休克蛋白AA1(heat shock protein 90 kDa alpha1,HSP90AA1)、半胱氨酸天冬氨酸蛋白酶3(caspase 3,CASP3)等。涉及癌症通路、化学致癌作用-受体激活、脂质与动脉粥样硬化、膀胱癌、结肠直肠癌、癌症中的蛋白多糖、白细胞介素17(interleukin-17,IL-17)信号通路等。分子对接提示大黄素与核心靶点能较好地结合。实验结果显示,大黄素可显著下调乳腺癌4T1细胞MMP9和TGF-β1的表达。TAM与脂多糖(lipopolysaccharides,LPS)共培养可诱导IL-1β表达,大黄素组可明显下调IL-1β的表达。结论大黄素治疗乳腺癌合并高脂血症的作用机制可能与抑制肿瘤细胞增殖、转移,诱导肿瘤细胞凋亡及调控肿瘤和高脂血症相关炎性微环境有关。展开更多
目的探讨住院2型糖尿病患者经皮下胰岛素泵降糖后给予不同治疗方案日内血糖变异情况。方法选取2型糖尿病患者165例,均给予皮下胰岛素泵强化降糖,血糖达标后给予撤泵,随机分为地特+门冬胰岛素组(对照组)和门冬胰岛素30注射液组(试验组)...目的探讨住院2型糖尿病患者经皮下胰岛素泵降糖后给予不同治疗方案日内血糖变异情况。方法选取2型糖尿病患者165例,均给予皮下胰岛素泵强化降糖,血糖达标后给予撤泵,随机分为地特+门冬胰岛素组(对照组)和门冬胰岛素30注射液组(试验组)。比较2组撤泵当日的血糖变异指标:撤泵当日最小血糖值(minimum blood glucose before removing the subcutaneous pump,bminGlu)、撤泵当日血糖水平的标准差(standard deviation of blood glucose before removing the subcutaneous pump,bSDBG)、撤泵当日餐后血糖波动幅度(postprandial glucoseexcursion before removing the subcutaneous pump,bPPGE)、撤泵当日最大血糖波动幅度(largest amplitudeof glycemic excursions before removing the subcutaneous pump,bLAGE)、撤泵当日胰岛素总量(total insulin before removing the subcutaneous pump,bTins)。比较2组皮下注射胰岛素后第4天的血糖变异指标:皮下注射胰岛素后第4天最小血糖值(minimum blood glucose after removing the subcutaneous pump,aminGlu)、皮下注射胰岛素后第4天血糖水平的标准差(standard deviation of blood glucose after removing the subcutaneous pump,aSDBG)、皮下注射胰岛素后第4天餐后血糖波动幅度(postprandial glucoseexcursion after removing the subcutaneous pump,aPPGE)、皮下注射胰岛素后第4天最大血糖波动幅度(largest amplitudeof glycemic excursions after removing the subcutaneous pump,aLAGE)、皮下注射胰岛素后第4天胰岛素总量(total insulin after removing the subcutaneous pump,aTins)。结果2组患者bminGlu、bSDBG、bPPGE、bLAGE、bTins、aminGlu、aSDBG、aPPGE、aLAGE、aTins差异均无统计学意义(P>0.05)。结论住院2型糖尿病患者使用皮下胰岛素泵强化降糖后更换为门冬胰岛素30注射液2次/d与餐时门冬胰岛素+地特胰岛素注射液均能较好的控制血糖、减少血糖波动。展开更多
The impact of sea surface temperature(SST)on winter haze in Guangdong province(WHDGD)was analyzed on the interannual scale.It was pointed out that the northern Indian Ocean and the northwest Pacific SST play a leading...The impact of sea surface temperature(SST)on winter haze in Guangdong province(WHDGD)was analyzed on the interannual scale.It was pointed out that the northern Indian Ocean and the northwest Pacific SST play a leading role in the variation of WHDGD.Cold(warm)SST anomalies over the northern Indian Ocean and the Northwest Pacific stimulate the eastward propagation of cold(warm)Kelvin waves through the Gill forced response,causing Ekman convergence(divergence)in the western Pacific,inducing abnormal cyclonic(anticyclonic)circulation.It excites the positive(negative)Western Pacific teleconnection pattern(WP),which results in the temperature and the precipitation decrease(increase)in Guangdong and forms the meteorological variables conditions that are conducive(not conducive)to the formation of haze.ENSO has an asymmetric influence on WHDGD.In El Niño(La Niña)winters,there are strong(weak)coordinated variations between the northern Indian Ocean,the northwest Pacific,and the eastern Pacific,which stimulate the negative(positive)phase of WP teleconnection.In El Niño winters,the enhanced moisture is attributed to the joint effects of the horizontal advection from the surrounding ocean,vertical advection from the moisture convergence,and the increased atmospheric apparent moisture sink(Q2)from soil evaporation.The weakening of the atmospheric apparent heat source(Q1)in the upper layer is not conducive to the formation of inversion stratification.In contrast,in La Niña winters,the reduced moisture is attributed to the reduced upward water vapor transport and Q2 loss.Due to the Q1 increase in the upper layer,the temperature inversion forms and suppresses the diffusion of haze.展开更多
文摘目的探讨住院2型糖尿病患者经皮下胰岛素泵降糖后给予不同治疗方案日内血糖变异情况。方法选取2型糖尿病患者165例,均给予皮下胰岛素泵强化降糖,血糖达标后给予撤泵,随机分为地特+门冬胰岛素组(对照组)和门冬胰岛素30注射液组(试验组)。比较2组撤泵当日的血糖变异指标:撤泵当日最小血糖值(minimum blood glucose before removing the subcutaneous pump,bminGlu)、撤泵当日血糖水平的标准差(standard deviation of blood glucose before removing the subcutaneous pump,bSDBG)、撤泵当日餐后血糖波动幅度(postprandial glucoseexcursion before removing the subcutaneous pump,bPPGE)、撤泵当日最大血糖波动幅度(largest amplitudeof glycemic excursions before removing the subcutaneous pump,bLAGE)、撤泵当日胰岛素总量(total insulin before removing the subcutaneous pump,bTins)。比较2组皮下注射胰岛素后第4天的血糖变异指标:皮下注射胰岛素后第4天最小血糖值(minimum blood glucose after removing the subcutaneous pump,aminGlu)、皮下注射胰岛素后第4天血糖水平的标准差(standard deviation of blood glucose after removing the subcutaneous pump,aSDBG)、皮下注射胰岛素后第4天餐后血糖波动幅度(postprandial glucoseexcursion after removing the subcutaneous pump,aPPGE)、皮下注射胰岛素后第4天最大血糖波动幅度(largest amplitudeof glycemic excursions after removing the subcutaneous pump,aLAGE)、皮下注射胰岛素后第4天胰岛素总量(total insulin after removing the subcutaneous pump,aTins)。结果2组患者bminGlu、bSDBG、bPPGE、bLAGE、bTins、aminGlu、aSDBG、aPPGE、aLAGE、aTins差异均无统计学意义(P>0.05)。结论住院2型糖尿病患者使用皮下胰岛素泵强化降糖后更换为门冬胰岛素30注射液2次/d与餐时门冬胰岛素+地特胰岛素注射液均能较好的控制血糖、减少血糖波动。
基金Guangdong Basic and Applied Basic Research Foundation(2019A1515011808)Science and Technology Planning Program of Guangdong Province(2021B1212020016)。
文摘The impact of sea surface temperature(SST)on winter haze in Guangdong province(WHDGD)was analyzed on the interannual scale.It was pointed out that the northern Indian Ocean and the northwest Pacific SST play a leading role in the variation of WHDGD.Cold(warm)SST anomalies over the northern Indian Ocean and the Northwest Pacific stimulate the eastward propagation of cold(warm)Kelvin waves through the Gill forced response,causing Ekman convergence(divergence)in the western Pacific,inducing abnormal cyclonic(anticyclonic)circulation.It excites the positive(negative)Western Pacific teleconnection pattern(WP),which results in the temperature and the precipitation decrease(increase)in Guangdong and forms the meteorological variables conditions that are conducive(not conducive)to the formation of haze.ENSO has an asymmetric influence on WHDGD.In El Niño(La Niña)winters,there are strong(weak)coordinated variations between the northern Indian Ocean,the northwest Pacific,and the eastern Pacific,which stimulate the negative(positive)phase of WP teleconnection.In El Niño winters,the enhanced moisture is attributed to the joint effects of the horizontal advection from the surrounding ocean,vertical advection from the moisture convergence,and the increased atmospheric apparent moisture sink(Q2)from soil evaporation.The weakening of the atmospheric apparent heat source(Q1)in the upper layer is not conducive to the formation of inversion stratification.In contrast,in La Niña winters,the reduced moisture is attributed to the reduced upward water vapor transport and Q2 loss.Due to the Q1 increase in the upper layer,the temperature inversion forms and suppresses the diffusion of haze.
