A Novel Target and Approach for Identifying Antivirals against Molluscum Contagiosum Virus

The dermatological disease molluscum contagiosum (MC) presents as lesions restricted solely to the skin. The poxvirus molluscum contagiosum virus (MCV) is responsible for this skin disease that is easily transmitted through casual contact among all populations, with greater frequency in children and immunosuppressed individuals. In addition, sexual transmission of MCV in adolescents and adults is a health concern. Although the skin lesions ultimately resolve in immunocompetent individuals, they can persist for extended periods, be painful, and result in scarring. Treatment is problematic, and there is no drug that specifically targets MCV. The inability of MCV to propagate in cell culture has impeded drug development. To overcome these barriers, we integrated three new developments. First, we identified a new MCV drug target (mD4) that is essential for processive DNA synthesis in vitro. Second, we discovered a small chemical compound that binds to mD4 and prevents DNA synthesis in vitro. Third, and most significant, we engineered a hybrid vaccinia virus (mD4-VV) in which the natural vaccinia D4 (vD4) gene is replaced by the mD4 target gene. This hybrid virus is dependent on mD4 for viral growth in culture and is inhibited by the small compound. This target system provides, for the first time, a platform and approach for the discovery and evaluation of new therapeutics that can be used to treat MC.     

N-乙酰半胱氨酸联合抗坏血酸对大鼠重症急性胰腺炎时急性肺损伤的作用

目的:探讨N-乙酰半胱氨酸(NAC)联合抗坏血酸对大鼠重症急性胰腺炎(SAP)时急性肺损伤(ALI)的作用及机制.方法:40只SD大鼠随机分为假手术(SO)组、SAP+ALI组、NAC治疗组、NAC+抗坏血酸治疗组4组.采用胰胆管逆行注射4%的牛磺胆酸钠(0.1 ml/100 g)诱导SAP+ALI模型,NAC治疗组于...     

Extensive X-linked adaptive evolution in central chimpanzees

Surveying genome-wide coding variation within and among species gives unprecedented power to study the genetics of adaptation, in particular the proportion of amino acid substitutions fixed by positive selection. Additionally, contrasting the autosomes and the X chromosome holds information on the dominance of beneficial (adaptive) and deleterious mutations. Here we capture and sequence the complete exomes of 12 chimpanzees and present the largest set of protein-coding polymorphism to date. We report extensive adaptive evolution specifically targeting the X chromosome of chimpanzees with as much as 30% of all amino acid replacements being adaptive. Adaptive evolution is barely detectable on the autosomes except for a few striking cases of recent selective sweeps associated with immunity gene clusters. We also find much stronger purifying selection than observed in humans, and in contrast to humans, we find that purifying selection is stronger on the X chromosome than on the autosomes in chimpanzees. We therefore conclude that most adaptive mutations are recessive. We also document dramatically reduced synonymous diversity in the chimpanzee X chromosome relative to autosomes and stronger purifying selection than for the human X chromosome. If similar processes were operating in the human-chimpanzee ancestor as in central chimpanzees today, our results therefore provide an explanation for the much-discussed reduction in the human-chimpanzee divergence at the X chromosome.     

CT引导下脑内血肿穿刺引流术治疗基底节区脑出血疗效分析

目的观察分析CT引导下脑内血肿微创穿刺引流术治疗基底节区脑出血的临床疗效。方法选择2010-09—2012-09于我院就诊的基底节区脑出血患者80例,随机均分为微创穿刺引流组和保守治疗组各40例,分别比较2组患者的血肿残存体积及神经功能、日常生活能力的预后恢复情况。结果微创组的血肿体积由术前的(36.33±8.04)mL至术后的3d的(18.28±5.25)mL及术后14d的(12.38±4.25)mL,而保守治疗组则从术前至术后3d、7d分别为(35.31±7.06)mL、(30.56±6.35)mL、(26.52±5.27)mL,2组术后比较差异有统计学意义(P<0.05),微创组的血肿体积下降更明显;从评分结果可以看出,微创组与保守治疗组相比,神经功能及日常生活能力恢复更好,2组比较差异有统计学意义(P<0.05)。结论采用CT引导下的微创穿刺引流术治疗基底节区脑出血疗效满意。     

干燥综合征患者唇腺的免疫病理学研究

目的研究干燥综合征（Ｓｊｏｇｒｅｎ′ｓｓｙｎｄｒｏｍｅ，ＳＳ）的发病机理及病因，为ＳＳ的治疗提供理论依据。方法采用卵白素－生物素过氧化酶复合物技术（ａｖｉｄｉｎ－ｂｉｏｔｉｎ－ｐｅｒｏｘｉｄａｓｅｃｏｍｐｌｅｘｔｅｃｈｎｉｑｕｅ，ＡＢＣ）对２０例ＳＳ的唇腺中浸润的淋巴细胞进行分析。结果ＳＳ唇腺浸润淋巴细胞中以Ｔ细胞为主。而在Ｔ细胞中，辅助Ｔ细胞（ＣＤ４）增多，抑制Ｔ细胞（ＣＤ８）明显减少，ＣＤ＋４／ＣＤ＋８比值明显高于正常对照组。结论ＳＳ外分泌腺免疫功能亢进是导致本病的直接原因，进一步证实ＳＳ是自身免疫性疾病。     

正常人与Sjogren''s Syndrome患者球结膜免疫细胞的研究

目的 研究正常人与干燥综合征(Sjogren’s Syndrome,SS)患者球结膜HLA-DR+细胞、朗格罕斯细胞(LC)、T淋巴细胞亚群的变化特征。方法 采用链菌素-过氧化物酶法检测正常人与SS患者球结膜组织。结果 (1)SS患者球结膜大量T淋巴细胞浸润,抑制性T淋巴细胞(CD~(+8))较辅助性T淋巴细胞(CD~(+4))为多。CD~(+4)/CD~(+8)比值升高。(2)SS球结膜中LC数量减少,且鳞状上皮化生明显。(3)SS球结膜中HLA-DR~+细胞较正常人明显增加。结论 SS患者球结膜有显著的病理改变和免疫细胞异常。     

Postmortem diagnosis of fatal hypothermia/hyperthermia by spectrochemical analysis of plasma

Postmortem diagnosis of extreme-weather-related deaths is a challenging forensic task. Here, we present a state-of-the-art study that employed attenuated total reflection (ATR) Fourier transform infrared (FTIR) spectroscopy in combination with Chemometrics for postmortem diagnosis of fatal hypothermia/hyperthermia by biochemical investigation of plasma in rats. The results of principal component analysis (PCA) and spectral analysis revealed that plasma samples from the fatal hypothermia, fatal hyperthermia, and control groups, are substantially different from each other based on the spectral variations associated with the lipid, carbohydrate and nucleic acid components. Two partial least squares-discriminant analysis (PLS-DA) classification models (hypothermia-nonhypothermia and hyperthermia-nonhyperthermia binary models) with a 100% accuracy rate were constructed. Subsequently, internal cross-validation was performed to assess the robustness of these two models, which resulted in 98.1 and 100% accuracy. Ultimately, classification predictions of 42 unknown plasma samples were performed by these two models, and both models achieved 100% accuracy. Additionally, our results demonstrated that hemolysis and postmortem hypothermic/hyperthermic effects did not weaken the prediction ability of these two classification models. In summary, this work demonstrates ATR-FTIR spectroscopy’s great potential for postmortem diagnosis of fatal hypothermia/hyperthermia.     

Automated synthesis of 2'-deoxy-2'-[18F]fluoro-5-methyl-1-β-D-arabinofuranosyluracil ([18F]-FMAU) using a one reactor radiosynthesis module

2'-Deoxy-2'-[(18)F]fluoro-5-methyl-1-β-D-arabinofuranosyluracil ([(18)F]-FMAU) is an established PET probe used to monitor cellular proliferation. For clinical applications, a fully automated cGMP-compliant radiosynthesis would be preferred. However, the current synthesis of [(18)F]-FMAU requires a multistep procedure, making the development of an automated protocol difficult and complicated. Recently, we have developed a significantly simplified one-pot reaction condition for the synthesis of [(18)F]-FMAU in the presence of Friedel-Crafts catalysts. Here, we report a fully automated synthesis of [(18)F]-FMAU based on a one reactor radiosynthesis module using our newly developed synthetic method. The product was purified on a semi-preparative high-performance liquid chromatography integrated with the synthesis module using 6% EtOH in 10 mM phosphate buffer or 8% MeCN/water. [(18)F]-FMAU was obtained in 12±3% radiochemical yield (decay corrected overall yield based on [(18)F]-F(-), n=4) with 383±33 mCi/μmol specific activity at the time of injection. The α/β anomer ratio was 4:6. The overall reaction time was about 150 min from the end of bombardment and the radiochemical purity was >99%. This automated synthesis should also be suitable for the production of other 5-substituted thymidine analogues.     

肺气虚证患者T淋巴细胞相关基因的表达研究

目的：通过基因芯片技术研究肺气虚证患者T淋巴细胞基因表达的差异。方法：采集肺气虚证和肺阴虚证患者、正常人的外周血作为实验血样和对照血样。采用Fieoll技术分离外周血淋巴细胞、流式细胞仪分选并纯化T淋巴细胞，一步法提取总RNA，逆转录合成双链cDNA，体外转录合成生物素标记的cRNA，片断化后，采用人类全基因表达谱芯片进行芯片杂交，扫描后筛选出差异表达基因。结果：肺气虚证患者／正常人外周血T淋巴细胞相关差异表达基因45条，其中上调41条，下调4条；肺气虚证／肺阴虚证患者外周血T淋巴细胞相关差异表达基因43条，其中上调27条，下调16条；肺气虚证组／肺阴虚证组、正常人组均高表达的差异基因15条。结论：基因芯片技术能有效地研究中医证的基因表达谱，筛查出肺气虚证患者T淋巴细胞相关差异表达基因。