基于多色探针熔解曲线分析技术的华法林个体化用药相关基因多态性快速检测方法

华法林是一种广泛使用的抗凝剂，其治疗窗口较窄，患者间达到抗凝所需剂量的变异性大。已有研究表明CYP2C9*3 (rs1057910)、CYP2C9 IVS3-65G>C (rs9332127)、VKORC1 c.-1639G>A (rs9923231)和CYP4F2*3 (rs2108622)的单核苷酸多态性（SNP）是影响中国人群华法林敏感性的主要遗传因素。该研究利用多色探针熔解曲线（MMCA）技术，建立可同时检测4个华法林敏感性基因多态性的单管PCR反应体系，可在2.5 h内完成检测，能检测低至50 pg/反应的人基因组DNA。对218份厦门地区随机人群各SNP进行筛查结果及部分样本测序结果表明，MMCA体系有极高的准确性，厦门地区各SNP的发生频率与此前报道的中国汉族人群相近，其中rs1057910的等位基因A和C的频率分别为96.3%和3.7%；rs9332127的等位基因G和C的频率分别为96.3%和3.7%；rs9923231的等位基因G和A的频率分别为92.2%和7.8%；rs2108622等位基因G和A的频率分别为75.7%和24.3%。基于MMCA技术的SNP分型体系具有快速、简便、准确、低成本等优点，适合在临床实验室推广使用。厦门市科技计划项目（3502Z20179044）;;\n福建省高校杰出青年科研人才培育计划项

基于多色探针熔解曲线分析技术的华法林个体化用药相关基因多态性快速检测方法

华法林是一种广泛使用的抗凝剂,其治疗窗口较窄,患者达到抗凝所需剂量的变异性大.已有研究表明CYP2C9*3 (rs1057910)、CYP2C9IVS3-65G>C(rs9332127)、VKORC1 c.-1639G>A (rs9923231)和CYP4F2*3 (rs2108622)的单核苷酸多态性(SNPs)是影响中国人群华法林敏感性的主要遗传因素.该研究利用多色探针熔解曲线分析(MMCA)技术,建立可同时检测4个华法林敏感性基因多态性位点的单管PCR反应体系,可在2.5h内完成检测,每个反应能检测低至0.05ng的人基因组DNA.对218份厦门市随机人群的4类SNPs进行筛查及其中40份样本测序的结果表明,MMCA体系准确性高,厦门市人群的4类SNPs发生频率与此前报道的中国汉族人群的相近,其中rs1057910的等位基因A和C的频率分别为96.4%和3.6%,rs9332127的等位基因G和C的频率分别为96.4%和3.6%,rs9923231的等位基因G和A的频率分别为7.8%和92.2%,rs2108622的等位基因G和A的频率分别为75.7%和24.3%.上述基于MMCA技术的SNP分型体系具有快速、简便、准确、低成本等优点,适合在临床上推广用于指导华法林用药剂量.福建省高校杰出青年科研人才培育计划项目厦门市科技计划项目（3502Z20179044

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