通过建立比例1∶5的物理模型,分别研究了吹气流量、吹气孔数、浸渍管插入深度以及真空室内液面高度等参数对210 t RH内钢液混匀过程的影响。同时,研究了不同吹气孔堵塞方式对RH内混匀的影响。结果表明:增大吹气流量使得RH内混匀时间逐...通过建立比例1∶5的物理模型,分别研究了吹气流量、吹气孔数、浸渍管插入深度以及真空室内液面高度等参数对210 t RH内钢液混匀过程的影响。同时,研究了不同吹气孔堵塞方式对RH内混匀的影响。结果表明:增大吹气流量使得RH内混匀时间逐渐降低直至趋于稳定,与吹气流量0.41 m^(3)/h相比,混匀时间降低比例由5.5%增加至37.9%,此后基本保持不变,对应的最佳吹气流量为0.76 m^(3)/h;增加吹气孔数、浸渍管插入深度以及提高真空室内液面高度均能促进RH内钢液的混匀,缩短混匀时间。在8孔吹气条件下,采用下层吹气方式时,混匀时间最短,较单侧吹气方式下混匀时间降低幅度为37.7~56.8 s;在12孔吹气条件下,采用上层堵4孔吹气方式时,混匀时间最短,较单侧吹气方式下混匀时间降低幅度为5.5~21.3 s。展开更多
目的:探讨人参皂苷Rh1对糖尿病(DM)小鼠肾损伤的保护作用,并阐明其作用机制。方法:应用高脂高糖饲养佐以腹腔注射链脲佐菌素(STZ)法制备糖尿病肾脏疾病(DKD)模型。将48只C57/BL6成模小鼠随机分为模型组、核因子红细胞2相关因子2(Nrf2)...目的:探讨人参皂苷Rh1对糖尿病(DM)小鼠肾损伤的保护作用,并阐明其作用机制。方法:应用高脂高糖饲养佐以腹腔注射链脲佐菌素(STZ)法制备糖尿病肾脏疾病(DKD)模型。将48只C57/BL6成模小鼠随机分为模型组、核因子红细胞2相关因子2(Nrf2)抑制剂ML385组(ML385组)(30 mg·kg^(-1)ML385)、人参皂苷Rh1组(G-Rh1组)(30 mg·kg^(-1)人参皂苷Rh1)和G-Rh1+ML385组(30 mg·kg^(-1)人参皂苷Rh1+30 mg·kg^(-1)ML385),每组12只,另外12只C57/BL6小鼠作为对照组。作用8周后,全自动分析仪检测各组小鼠血清中空腹血糖(FBG)、尿素氮(BUN)和血肌酐(Scr)水平及尿液中24 h尿蛋白(24 h UP)水平,并计算肾脏指数。试剂盒检测各组小鼠肾组织中超氧化物歧化酶(SOD)和乳酸脱氢酶(LDH)活性及丙二醛(MDA)水平,Western blotting法检测各组小鼠肾组织中Nrf2和血红素加氧酶1(HO-1)蛋白表达水平。结果:与对照组比较,模型组、ML385组和G-Rh1+ML385组小鼠血清中FBG水平和肾脏指数均明显升高(P<0.01),G-Rh1组小鼠血清中FBG水平明显升高(P<0.01);与模型组比较,ML385组小鼠肾脏指数明显升高(P<0.05),G-Rh1组小鼠FBG水平和肾脏指数均明显降低(P<0.05或P<0.01);与G-Rh1组比较,G-Rh1+ML385组小鼠FBG水平和肾脏指数均明显升高(P<0.01)。与对照组比较,模型组、ML385组、G-Rh1组和G-Rh1+ML385组小鼠血清中BUN和Scr水平及尿液中24 h UP水平均明显升高(P<0.01);与模型组比较,ML385组小鼠血清中BUN水平及尿液中24 h UP水平均明显升高(P<0.05),G-Rh1组小鼠血清中BUN和Scr水平及尿液中24 h UP水平均明显降低(P<0.01);与G-Rh1组比较,G-Rh1+ML385组小鼠血清中BUN和Scr水平及尿液中24 h UP水平均明显升高(P<0.01)。与对照组比较,模型组、ML385组、G-Rh1组和G-Rh1+ML385组小鼠肾组织中SOD活性均明显降低(P<0.01),MDA水平和LDH活性均明显升高(P<0.01);与模型组比较,ML385组小鼠肾组织中SOD活性明显降低(P<0.05),MDA水平明显升高(P<0.05),G-Rh1组小鼠肾组织中SOD活性明显升高(P<0.01),MDA水平和LDH活性均明显降低(P<0.01);与G-Rh1组比较,G-Rh1+ML385组小鼠肾组织中SOD活性明显降低(P<0.01),MDA水平和LDH活性均明显升高(P<0.01)。与对照组比较,模型组、ML385组、G-Rh1组和G-Rh1+ML385组小鼠肾组织中Nrf2和HO-1蛋白表达水平均明显降低(P<0.05或P<0.01);与模型组比较,ML385组和G-Rh1+ML385组小鼠肾组织中Nrf2和HO-1蛋白表达水平均明显降低(P<0.05),G-Rh1组小鼠肾组织中Nrf2和HO-1蛋白表达水平均明显升高(P<0.01);与G-Rh1组比较,G-Rh1+ML385组小鼠肾组织中Nrf2和HO-1蛋白表达水平均明显降低(P<0.01)。结论:人参皂苷Rh1可降低氧化应激,改善肾功能,对DM小鼠肾脏损伤具有保护作用,其作用机制可能与激活Nrf2/HO-1信号通路有关。展开更多
Rh血型系统是输血医学中重要的常规检测血型系统,因RhD血型不合引起的溶血性输血反应及新生儿溶血病一直以来倍受临床重视。本研究报道了2例罕见的RHD基因变异型RHD*DEL37个体的血清学和基因特征,这2例个体的血液样本经血清学方法(试管...Rh血型系统是输血医学中重要的常规检测血型系统,因RhD血型不合引起的溶血性输血反应及新生儿溶血病一直以来倍受临床重视。本研究报道了2例罕见的RHD基因变异型RHD*DEL37个体的血清学和基因特征,这2例个体的血液样本经血清学方法(试管法和微柱凝胶法)鉴定为RhD阴性。采用聚合酶链反应-序列特异性引物(polymerase chain reaction-sequence specific prime,PCR-SSP)对样本进行RHD基因分型和合子型分析,基因分型结果为RHD基因阳性,并排除了常见的几种RHD基因变异体的可能。RHD基因合子型检测阳性,证明其中一条RHD等位基因1~10外显子全部缺失。进一步对样本RHD基因1~10外显子基因进行Sanger法测序,测序结果显示在另一条等位基因第8内含子上的第1154-31号碱基发生了T>C突变,国际输血协会(International Society of Blood Transfusion,ISBT)将该突变等位基因命名为RHD*DEL37,表型为RhD放散型(D-elute,Del)。本研究中,2例血清学初筛RhD阴性的样本通过分子生物学检测,其基因型为RHD*DEL37/RHD-(RHD*01N.01)。由于这2例个体无血缘关系,提示我国可能存在携带该基因突变的人群。本研究提示分子生物学方法可辅助鉴别血清学初筛为阴性的RhD变异体样本,联用分子生物学方法和血清学方法在准确鉴定血型、保障患者输血安全方面有重要意义。展开更多
Liposomes hold great potential in anti-cancer drug delivery and the targeting treatment of tumors.However,the clinical therapeutic efficacy of liposomes is still limited by the complexity of tumor microenvironment(TME...Liposomes hold great potential in anti-cancer drug delivery and the targeting treatment of tumors.However,the clinical therapeutic efficacy of liposomes is still limited by the complexity of tumor microenvironment(TME)and the insufficient accumulation in tumor sites.Meanwhile,the application of cholesterol and polyethylene glycol(PEG),which are usually used to prolong the blood circulation and stabilize the structure of liposomes respectively,has been questioned due to various disadvantages.Herein,we developed a ginsenoside Rh2-based multifunctional liposome system(Rh2-lipo)to effectively address these challenges once for all.Different with the conventional’wooden’liposomes,Rh2-lipo is a much more brilliant carrier with multiple functions.In Rh2-lipo,both cholesterol and PEG were substituted by Rh2,which works as membrane stabilizer,long-circulating stealther,active targeting ligand,and chemotherapy adjuvant at the same time.Firstly,Rh2 could keep the stability of liposomes and avoid the shortcomings caused by cholesterol.Secondly,Rh2-lipo showed a specifically prolonged circulation behavior in the blood.Thirdly,the accumulation of the liposomes in the tumor was significantly enhanced by the interaction of glucose transporter of tumor cells with Rh2.Fourth,Rh2-lipo could remodel the structure and reverse the immunosuppressive environment in TME.When tested in a 4T1 breast carcinoma xenograft model,the paclitaxel-loaded Rh2-lipo realized high efficient tumor growth suppression.Therefore,Rh2-lipo not only innovatively challenges the position of cholesterol as a liposome component,but also provides another innovative potential system with multiple functions for anti-cancer drug delivery.展开更多
文摘目的:探讨人参皂苷Rh1对糖尿病(DM)小鼠肾损伤的保护作用,并阐明其作用机制。方法:应用高脂高糖饲养佐以腹腔注射链脲佐菌素(STZ)法制备糖尿病肾脏疾病(DKD)模型。将48只C57/BL6成模小鼠随机分为模型组、核因子红细胞2相关因子2(Nrf2)抑制剂ML385组(ML385组)(30 mg·kg^(-1)ML385)、人参皂苷Rh1组(G-Rh1组)(30 mg·kg^(-1)人参皂苷Rh1)和G-Rh1+ML385组(30 mg·kg^(-1)人参皂苷Rh1+30 mg·kg^(-1)ML385),每组12只,另外12只C57/BL6小鼠作为对照组。作用8周后,全自动分析仪检测各组小鼠血清中空腹血糖(FBG)、尿素氮(BUN)和血肌酐(Scr)水平及尿液中24 h尿蛋白(24 h UP)水平,并计算肾脏指数。试剂盒检测各组小鼠肾组织中超氧化物歧化酶(SOD)和乳酸脱氢酶(LDH)活性及丙二醛(MDA)水平,Western blotting法检测各组小鼠肾组织中Nrf2和血红素加氧酶1(HO-1)蛋白表达水平。结果:与对照组比较,模型组、ML385组和G-Rh1+ML385组小鼠血清中FBG水平和肾脏指数均明显升高(P<0.01),G-Rh1组小鼠血清中FBG水平明显升高(P<0.01);与模型组比较,ML385组小鼠肾脏指数明显升高(P<0.05),G-Rh1组小鼠FBG水平和肾脏指数均明显降低(P<0.05或P<0.01);与G-Rh1组比较,G-Rh1+ML385组小鼠FBG水平和肾脏指数均明显升高(P<0.01)。与对照组比较,模型组、ML385组、G-Rh1组和G-Rh1+ML385组小鼠血清中BUN和Scr水平及尿液中24 h UP水平均明显升高(P<0.01);与模型组比较,ML385组小鼠血清中BUN水平及尿液中24 h UP水平均明显升高(P<0.05),G-Rh1组小鼠血清中BUN和Scr水平及尿液中24 h UP水平均明显降低(P<0.01);与G-Rh1组比较,G-Rh1+ML385组小鼠血清中BUN和Scr水平及尿液中24 h UP水平均明显升高(P<0.01)。与对照组比较,模型组、ML385组、G-Rh1组和G-Rh1+ML385组小鼠肾组织中SOD活性均明显降低(P<0.01),MDA水平和LDH活性均明显升高(P<0.01);与模型组比较,ML385组小鼠肾组织中SOD活性明显降低(P<0.05),MDA水平明显升高(P<0.05),G-Rh1组小鼠肾组织中SOD活性明显升高(P<0.01),MDA水平和LDH活性均明显降低(P<0.01);与G-Rh1组比较,G-Rh1+ML385组小鼠肾组织中SOD活性明显降低(P<0.01),MDA水平和LDH活性均明显升高(P<0.01)。与对照组比较,模型组、ML385组、G-Rh1组和G-Rh1+ML385组小鼠肾组织中Nrf2和HO-1蛋白表达水平均明显降低(P<0.05或P<0.01);与模型组比较,ML385组和G-Rh1+ML385组小鼠肾组织中Nrf2和HO-1蛋白表达水平均明显降低(P<0.05),G-Rh1组小鼠肾组织中Nrf2和HO-1蛋白表达水平均明显升高(P<0.01);与G-Rh1组比较,G-Rh1+ML385组小鼠肾组织中Nrf2和HO-1蛋白表达水平均明显降低(P<0.01)。结论:人参皂苷Rh1可降低氧化应激,改善肾功能,对DM小鼠肾脏损伤具有保护作用,其作用机制可能与激活Nrf2/HO-1信号通路有关。
文摘Rh血型系统是输血医学中重要的常规检测血型系统,因RhD血型不合引起的溶血性输血反应及新生儿溶血病一直以来倍受临床重视。本研究报道了2例罕见的RHD基因变异型RHD*DEL37个体的血清学和基因特征,这2例个体的血液样本经血清学方法(试管法和微柱凝胶法)鉴定为RhD阴性。采用聚合酶链反应-序列特异性引物(polymerase chain reaction-sequence specific prime,PCR-SSP)对样本进行RHD基因分型和合子型分析,基因分型结果为RHD基因阳性,并排除了常见的几种RHD基因变异体的可能。RHD基因合子型检测阳性,证明其中一条RHD等位基因1~10外显子全部缺失。进一步对样本RHD基因1~10外显子基因进行Sanger法测序,测序结果显示在另一条等位基因第8内含子上的第1154-31号碱基发生了T>C突变,国际输血协会(International Society of Blood Transfusion,ISBT)将该突变等位基因命名为RHD*DEL37,表型为RhD放散型(D-elute,Del)。本研究中,2例血清学初筛RhD阴性的样本通过分子生物学检测,其基因型为RHD*DEL37/RHD-(RHD*01N.01)。由于这2例个体无血缘关系,提示我国可能存在携带该基因突变的人群。本研究提示分子生物学方法可辅助鉴别血清学初筛为阴性的RhD变异体样本,联用分子生物学方法和血清学方法在准确鉴定血型、保障患者输血安全方面有重要意义。
基金supported by National Natural Science Foundation of China(Nos.81773911,81690263 and 81573616)the Development Project of Shanghai Peak Disciplines-Integrated Medicine(No.20150407)。
文摘Liposomes hold great potential in anti-cancer drug delivery and the targeting treatment of tumors.However,the clinical therapeutic efficacy of liposomes is still limited by the complexity of tumor microenvironment(TME)and the insufficient accumulation in tumor sites.Meanwhile,the application of cholesterol and polyethylene glycol(PEG),which are usually used to prolong the blood circulation and stabilize the structure of liposomes respectively,has been questioned due to various disadvantages.Herein,we developed a ginsenoside Rh2-based multifunctional liposome system(Rh2-lipo)to effectively address these challenges once for all.Different with the conventional’wooden’liposomes,Rh2-lipo is a much more brilliant carrier with multiple functions.In Rh2-lipo,both cholesterol and PEG were substituted by Rh2,which works as membrane stabilizer,long-circulating stealther,active targeting ligand,and chemotherapy adjuvant at the same time.Firstly,Rh2 could keep the stability of liposomes and avoid the shortcomings caused by cholesterol.Secondly,Rh2-lipo showed a specifically prolonged circulation behavior in the blood.Thirdly,the accumulation of the liposomes in the tumor was significantly enhanced by the interaction of glucose transporter of tumor cells with Rh2.Fourth,Rh2-lipo could remodel the structure and reverse the immunosuppressive environment in TME.When tested in a 4T1 breast carcinoma xenograft model,the paclitaxel-loaded Rh2-lipo realized high efficient tumor growth suppression.Therefore,Rh2-lipo not only innovatively challenges the position of cholesterol as a liposome component,but also provides another innovative potential system with multiple functions for anti-cancer drug delivery.
