地磷莫斯的免疫抑制效果及机制的研究

目的临床上已应用多种免疫抑制剂,但是因为其价格昂贵,毒副作用强等等原因阻碍了其在临床的应用,雷帕霉素在临床上的应用已得到公认。但是由于雷帕霉素的水溶性小,半衰期长,水溶性较弱,化学稳定性较弱,限制了其在临床的应用。雷帕霉素的的衍生物地磷莫斯具有高溶解性、高稳定性、高生物利用度等优点。地磷莫斯的诸多优点已得到FDA以快速通道方式批准,应用于软组织与骨肉瘤的治疗。关于治疗血液癌(淋巴瘤和白血病)的二期临床试验已经完成,子宫内膜癌的二期临床试验也已展开。为了研究其在免疫抑制方面的作用机制,我们进行一系列体外实验,观察其免疫抑制效果,研究其免疫抑制机制,为地磷莫斯进一步进行体内试验打下基础,为其能顺利扩大临床应用做好铺垫。方法我们首先采用淋巴细胞转化实验来观察地磷莫斯对淋巴细胞与T细胞增殖的抑制作用,确定地磷莫斯的免疫抑制作用及其免疫抑制发挥的浓度,再用凋亡实验、克隆无能实验等探讨地磷莫斯的免疫抑制作用机制。结果我们运用淋巴细胞转化实验确定了地磷莫斯可以抑制淋巴细胞的增殖;我们用流式检测术,发现地磷莫斯不会引起淋巴细胞/T细胞的凋亡;克隆无能实验证明了克隆无能是地磷莫斯诱导免疫耐受的机制之一。结论通过本课题的研究,我们首次证实了地磷莫斯在体外通过抑制淋巴细胞/T细胞增殖,诱导克隆无能等方法发挥免疫抑制作用,为地磷莫斯应用于器官移植领域奠定了基础,促进了地磷莫斯从基础研究向临床器官移植的转化

JUNO Sensitivity on Proton Decay p→νˉK+p\to \bar\nu K^+ Searches

The Jiangmen Underground Neutrino Observatory (JUNO) is a large liquid scintillator detector designed to explore many topics in fundamental physics. In this paper, the potential on searching for proton decay in $p\to \bar\nu K^+$ mode with JUNO is investigated.The kaon and its decay particles feature a clear three-fold coincidence signature that results in a high efficiency for identification. Moreover, the excellent energy resolution of JUNO permits to suppress the sizable background caused by other delayed signals. Based on these advantages, the detection efficiency for the proton decay via $p\to \bar\nu K^+$ is 36.9% with a background level of 0.2 events after 10 years of data taking. The estimated sensitivity based on 200 kton-years exposure is $9.6 \times 10^{33}$ years, competitive with the current best limits on the proton lifetime in this channel

JUNO sensitivity on proton decay p → ν K + searches*

The Jiangmen Underground Neutrino Observatory (JUNO) is a large liquid scintillator detector designed to explore many topics in fundamental physics. In this study, the potential of searching for proton decay in the $p\to \bar{\nu} K^+$ mode with JUNO is investigated. The kaon and its decay particles feature a clear three-fold coincidence signature that results in a high efficiency for identification. Moreover, the excellent energy resolution of JUNO permits suppression of the sizable background caused by other delayed signals. Based on these advantages, the detection efficiency for the proton decay via $p\to \bar{\nu} K^+$ is 36.9% ± 4.9% with a background level of $0.2\pm 0.05({\rm syst})\pm$$0.2({\rm stat})$ events after 10 years of data collection. The estimated sensitivity based on 200 kton-years of exposure is $9.6 \times 10^{33}$ years, which is competitive with the current best limits on the proton lifetime in this channel and complements the use of different detection technologies