NF2蛋白518位丝氨酸磷酸化状态对其分子内相互作用机制的结构生物学及生物化学研究

 目的  揭示NF2 (neurofibromatosis type 2)蛋白518位丝氨酸的磷酸化如何对其结构与功能进行调节。  方法  解析野生型NF2^WT(无模拟磷酸化突变)和突变型NF2^S518D(模拟518位丝氨酸被磷酸化的突变体)蛋白的晶体结构,进一步利用体外Pull-down实验及荧光共振能量转移(fluorescence resonance energy transfer,FRET)实验检测了NF2的分子内相互作用。  结果  由于NF2的C-端在结晶过程中降解,未能观察到NF2^WT和NF2^S518D两种蛋白质构象的差异,结构分析发现NF2的N-端FERM(Four-point one,Ezrin,Radixin,Moesin)结构域与已有结构报道的FERM结构域具有相似的空间构象。体外Pull-down实验证明生化实验结果提示,相对NF2^WTC-端蛋白质而言,NF2^S518D的C-端蛋白质与NF2的N-端蛋白质结合更强。FRET实验在波长525 nm处,检测到全长NF2^S518D比全长NF2^WT产生更强的FRET信号。  结论  野生型NF2^WT处于“开放”状态而模拟磷酸化的突变型NF2^S518D处于“闭合”状态。     

盐酸普拉克索B晶型的制备和表征

目的 制备盐酸普拉克索的B晶型并优化制备工艺,同时进行结构表征和稳定性研究。方法 制备盐酸普拉克索的B晶型,采用热重法(TGA)、差示扫描量热法(DSC)、X射线粉末衍射(PXRD)、X射线单晶衍射(SXRD)等分析手段,对盐酸普拉克索B晶型进行表征研究。结果 制备得到了盐酸普拉克索B晶型,其晶型属正交晶系,空间群P2₁2₁2₁,结构中不含溶剂(包括水)。盐酸普拉克索B晶型热处理后晶型不发生转变。结论 盐酸普拉克索B晶型为无水晶型,热稳定性优于一水合物晶型,具有高温稳定性。     

Likelihood‐based dynamic factor analysis for measurement and forecasting

We present new results for the likelihood‐based analysis of the dynamic factor model. The latent factors are modelled by linear dynamic stochastic processes. The idiosyncratic disturbance series are specified as autoregressive processes with mutually correlated innovations. The new results lead to computationally efficient procedures for the estimation of the factors and for the parameter estimation by maximum likelihood methods. We also present the implications of our results for models with regression effects, for Bayesian analysis, for signal extraction, and for forecasting. An empirical illustration is provided for the analysis of a large panel of macroeconomic time series.     

Effect of intermittent versus continuous energy restriction on weight loss,maintenance and cardiometabolic risk: A randomized 1-year trial

Background & aims

Long-term adherence to conventional weight-loss diets is limited while intermittent fasting has risen in popularity. We compared the effects of intermittent versus continuous energy restriction on weight loss, maintenance and cardiometabolic risk factors in adults with abdominal obesity and ≥1 additional component of metabolic syndrome.

In vitro hemopoiesis in human micro long-term bone marrow cultures recharged with either allogeneic,T-cell-depleted allogeneic,or syngeneic bone marrow cells

Summary The production of granulocyte-macrophage colony-forming cells (GM-CFC) and the proliferation period in human long-term bone marrow cultures are inferior to murine cultures. There is also evidence that recharge of the cultures after establishing confluent stromal layers will not greatly improve myelopoiesis. Data in the literature indicate that PHA-responsive T lymphocytes persist for up to 5 weeks in human but not in murine long-term marrow cultures. We therefore analyzed the effects of recharging micro long-term bone marrow cultures with bone marrow cell samples depleted by T lymphocytes. Depletion was performed in a complement-mediated cytotoxicity assay by applying the monoclonal antibody CAMPATH-1. Our data show that regardless of whether T cells were removed only at recharge, at both initiation and recharge, or only at initiation, obvious enhancement could neither be achieved in the GM-CFC production nor in the proliferation period. Furthermore, no advantage was seen when using syngeneic marrow cells. We conclude that in allogeneic long-term marrow cultures hemopoiesis is not limited by immunological incompatibilities.     

复方半枝莲防治二乙基亚硝胺诱发大鼠肝癌的研究

目的 :研究复方半枝莲 (SBC)对二乙基亚硝胺 (DEN)诱发大鼠肝癌的防治作用。方法 :利用免疫组化、流式细胞仪、血清和组织生化等检测方法 ,分别在第 14周和第 2 4周观察 SBC对 DEN诱发的肝癌形成过程的影响。结果 :中药组 14周时大鼠肝脏异型性增生灶明显较模型组少 ,2 4周时形成的肝癌结节小而少 ,模型组、中药组肝癌发生率分别为 75 .0 %、5 0 .0 % ;免疫组化显示中药组大鼠肝组织谷胱甘肽 - S-转移酶胎盘型阳性灶面积明显低于模型组 ;肝组织匀浆上清液谷胱甘肽 - S-转移酶含量以及血清 λ-谷氨酰转移酶、碱性磷酸酶、谷丙转氨酶含量也明显低于模型组 ;流式细胞仪检测结果显示 ,中药组大鼠肝细胞 G0 - G1 期比例下降 ,G2 - M期比例升高。结论 :SBC能抑制癌前病变 ,延缓肝癌的形成 ,降低肝癌发病率 ,其作用机制之一可能为阻滞 G2 - M期细胞进展 ,从而抑制DEN引起的肝细胞的去分化和恶性增殖     

62例成人脊髓型结核性脑膜炎临床分析

目的探讨成人脊髓型结核性脑膜炎（结脑）的临床特点和治疗方法。方法对1999—2004年收治确诊的62例成人脊髓型结脑进行回顾性分析。结果脊髓型结脑占同期住院结脑13.9%,除具有发热及脑膜刺激征外,以截瘫、尿便障碍和传导束型感觉障碍为主要表现。脑脊液循环通路存在不同程度梗阻,脑脊液常规生化并非完全符合蛋白细胞分离现象,ADA活性明显升高,虽然细胞学呈混合性细胞反应,但是嗜中性粒细胞比例较低,平均仅为17.7%,尿便障碍较截瘫恢复早,治愈率为61.3%,病死率为3.2%,后遗症发生率为35.5%,复发率为1.6%。结论脊髓型结脑治愈率低,后遗症发生率高。结脑早期发现和有效治疗可有效预防一部分脊髓型结脑的发生,以H、R、S（E）、Z为主的四联18～24个月抗结核治疗方案适用于脊髓型结脑,适宜剂量地塞米松和长疗程的放脑脊液并鞘内注药治疗可以提高脊髓型结脑的治愈率。     

消化科危重病人SBAR模式标准化交班报告表使用体验的质性研究

目的 通过对消化科危重患者SBAR模式标准化交班报告表使用体验的质性研究来探讨该表在消化科危重患者中的使用效果。方法 将根据消化科危重患者病情特点设计的SBAR模式交班报告表用于2016年11月至2017年4月在南京医科大学第一附属医院消化科住院的危重患者的交班中,使用6个月后通过对18名护士进行半结构式深入访谈评价SBAR模式标准化交班报告表的使用效果。结果 SBAR模式标准化交班报告表的使用减轻了护士在护理危重患者时的心理压力,提高了护士自身的沟通能力和临床思维能力。但在过程中存在使用依从性还不全现象,同时希望能与医生也进行SBAR沟通模式交流。结论 运用SBAR模式标准化交班报告表能有效避免由于护士自身能力原因而造成的交班信息缺失,对于防范护理差错、保证患者安全有重要作用。但对临床经验缺乏的护士,需要较长时间培训才能适应该模式。     

Medical Rehabilitation: Guidelines to Advance the Field With High-Impact Clinical Trials

The purpose of this Special Communication is to summarize guidelines and recommendations stemming from an expert panel convened by the National Institutes of Health, National Center for Medical Rehabilitation Research (NCMRR) for a workshop entitled The Future of Medical Rehabilitation Clinical Trials, held September 29-30, 2016, at the NCMRR offices in Bethesda, Maryland. The ultimate goal of both the workshop and this summary is to offer guidance on clinical trials design and operations to the medical rehabilitation research community, with the intent of maximizing the effect of future trials.