Y型聚乙二醇干扰素琢-2b注射液治疗HCV基因2/3型慢性丙型肝炎患者疗效和安全性的多中心随机对照试验研究

目的以标准剂量的聚乙二醇干扰素(Peg IFN)α-2a联合利巴韦林作为阳性对照,评价新型试验药物Y型Peg IFNα-2b注射液联合利巴韦林治疗2型/3型慢性丙型肝炎(CHC)患者的疗效和安全性。方法采用多中心、随机开放、阳性药对照的Ⅲ期临床试验,筛选符合要求的2型/3型CHC患者,按照2:1的比例随机分配到Y型Peg IFNα-2b组和Peg IFNα-2a组,同时口服利巴韦林,疗程24 w,停药随访24 w。采用Abbott Real Time HCV Genotype II检测HCV基因型,采用Cobas Taq Man实时定量PCR法检测血清HCV RNA水平。详细记录不良事件。主要疗效指标为持续病毒学应答(SVR),并进行非劣效检验。结果本试验实际入组2型/3型CHC患者255例,实际治疗241例。全分析集(FAS)数据显示,158例试验组和83例对照组患者SVR分别为85.4%(95%CI 79.94%~90.94%)和79.5%(95%CI 70.84%~88.20%,P=0.2402);对符合方案分析集(PPS)人群分析显示,试验组和对照组患者SVR分别为87.9%(95%CI 82.45%~93.27%)和85.9%(95%CI 77.82%~94.01%,P=0.7060),率差的95%可置信区间均符合非劣效标准;对PPS人群分析显示,85.8%受试者获得了早期病毒学应答(RVR),RVR的阳性预测值为90.1%;试验组和对照组不良事件发生率相似,分别为95.6%和95.2%,严重不良事件发生率分别为3.8%和3.6%。结论应用Peg IFNα联合利巴韦林治疗2型/3型CHC患者,新型试验药物Y型Peg IFNα-2b具有与对照药物Peg IFNα-2a相似的疗效和安全性。国家科技部“十二五”重大专项(编号:2012ZX10002-003)；“重大新药创制”十二五科技重大专项(编号:2012ZX09303019)

城市老年人的生活和心理状况及其增龄变化

目的研究我国城市老年人的生活和心理状况及其增龄变化。方法以《中脉老年生活质量指数调查问卷》为依据,对七个城市2 225位60~99岁老年人的调查数据进行分析。结果大多数老年人的教育程度和经济收入偏低,但能保持较好的心情,生活满意度和主观幸福感较高;随着年龄的增高,参加活动的人数减少,孤独寂寞的人数增加,家庭精神生活满意度降低,人际关系的广度和深度也有所下降,但更多的高龄老年人仍能保持平静满足的心态。结论大多数老年人的社会经济状况偏低,但心理状况较好;随着年龄的增高,更多人的心情趋于平静满足,少数老年人的生活和心理状况需要社会积极关注

Comparison of life and psychological status of the elderly between families with children absent and families with children

目的　比较研究城市空巢老人与非空巢老人的生活和心理状况。方法　以《中脉老年生活质量指数调查问卷》为材料,对7个城市2 225位独居、夫妻同住和非空巢老人的调查数据进行分析。结果　大多数老年人的经济收入偏低,非空巢老人给予子女经济支持和体力付出的压力较大;大多数老年人的心情较好,但超过1 /4的独居老人心情较差;老年人的主观幸福感居中上水平,但独居老人的主观幸福感、与家人交流满意度较低;在养老依靠问题上空巢老人(尤其是独居老人)对于家人的期望较低;对于第三方赡养和老年人再婚的问题,夫妻同住老人比较理解和支持。 结论　夫妻同住老人的生活和心理状况均较好,独居老人的心理状况较差,非空巢老人的经济和体力付出的压力较大

Development of a Stereoselective Approach for the Synthesis of Allo Bile Acids

Bile acids are natural products that are located within a variety of organisms through metabolism of cholesterol. The less common allo bile acids contain a trans AB ring fusion and are designated as the C5α diastereomers. Although Iqbal, and Tochtrop have described synthetic approaches to the 5α stereocenter, there still remain issues of stereoselectivity and chemoselectivity when forging the AB trans ring. We have established a general approach to the synthesis of allo bile acids by applying a recently developed manganese catalyzed hydrogen atom transfer reduction. This key tactic enabled us to successfully synthesize allolithocholic acid over seven steps in 26% yield and 97% diastereomer purity, starting with the commercially available lithocholic acid. Notably, this is the first reported synthesis of allolithocholic acid. Derivatives of lithocholic acid were also synthesized to explore the hydrogen atom transfer reaction in order to develop an understanding of the reaction outcome in terms of stereoselectivity. Finally, this synthetic tactic was also applied to the synthesis of other allo bile acid derivatives such as deoxycholic, chenodeoxycholic, and hyodeoxycholic acids. The later chapter in this thesis describes a synthetic endeavor to develop a general approach toward the eudesmane carbon skeleton through a double addition strategy. This strategy was effective in forming the C10 quaternary center and the C6–C7 bond in the eudesmane skeleton albeit with modest stereoselectivity as a 1:1 mixture of uncharacterized diastereomers

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