18氟-胸腺嘧啶核苷正电子发射体层-CT显像在胸部肿瘤上的初步研究

目的：评价^18氟-胸腺嘧啶核苷（^18F-FLT）正电子发射体层（PET）-CT显像对胸部肿瘤定性诊断的价值。方法：对17例做了^18氟-脱氧葡萄糖（^18F-FDG）PET-CT检查，但定性诊断困难的患者，在第2～3天进行了^18F-FLITPET-CT显像。分析病变在两种不同显像剂PET-CT上的表现，分别测量二者的最大标准摄取值（maxSUV）。结果：8例恶性病变（5例肺癌、1例纵隔淋巴瘤、1例胸椎恶性肿瘤、1例胸椎转移瘤），其中7例见FLT异常摄取，5例肺癌平均maxSUV为4．2（鳞癌2例、腺癌2例、肺泡癌1例）；9例良性病变（5例肺结核、1例肺炎、3例纵隔淋巴结结核）无或轻度摄取FLT，其中6例肺内良性病变平均maxSUV为1．6；9例良性病变中8例见FDG异常浓聚，其中6例肺内良性病灶平均maxSUV为3．9，3例纵隔淋巴结结核也见FDG明显摄取，平均maxSUV为11．0。11例肺内病灶FDG和FLT显像的敏感性、特异性、准确性分别为100．0％（5／5）、16．7％（1／6）、54．5％（6／11）和80．0％（4／5）、66．7％（4／6）、72．7％（8／11）。结论：胸部肿瘤^18F-FLT显像的特异性较高，在^18F-FDG显像阳性，难以确定病变性质时，FLIT可以作为FDG的有益补充，二者联合显像有助于提高胸部肿瘤诊断的准确性。     

结直肠癌组织TP、DPD不同表达水平与XELOX化疗效果的关系及意义?

【目的】探讨胸腺嘧啶磷酸化酶(TP)、二氢吡啶脱氢酶(DPD)在结直肠癌组织中的表达情况及其与 XELOX化疗效果的相关性。【方法】用 ELISA 双抗体夹心法检测58例结直肠癌患者癌组织中 TP 和DPD的表达量,以 TP 和 DPD的中位数为分界,将患者分为高表达组和低表达组,患者术后均接受 XELOX方案进行化疗,4个疗程后,比较不同TP和DPD的表达水平患者的早期疗效。对所有患者进行随访12~36个月,行Kaplan-Meier生存分析,比较比较不同TP和DPD的表达水平患者的预后生存情况。【结果】TP 高表达组和低表达组行 XELOX化疗方案的短期临床疗效相比差异无显著性(P >0.05);TP 高表达组中位生存时间显著高于低表达组(P <0.05)。DPD高表达组 XELOX化疗方案早期有效率及中位生存时间均低于于低表达组,差异具有统计学意义(P <0.05)。各组患者的并发症发生情况无显著性差异(P >0.05)。【结论】结直肠癌组织TP、DPD表达水平对XELOX化疗方案的临床疗效有关,可以作为预测XELOX化疗方案疗效的重要指标之一。     

采用BOC前体提高18F-FLT合成产率

目的：通过对BAThy前体和BOC前体合成肿瘤增值示踪剂 3’-脱氧-3’-[18F]氟胸腺嘧啶（18F-FLT）合成产率的研究,探讨BOC前体在提高18F-FLT合成产率中的价值。方法：联合国内7家PET中心按照国内多中心研究的统一标准进行正电子示踪剂18F-FLT合成研究方面的合作,回旋加速器（MINItrace,GE Healthcare）,全自动合成系统（TRACERlab FX F-N;GE Healthcare）。BAThy前体：5’-氧-苯甲酰基-2,3’-胸苷;BOC前体：3-N-t-叔丁氧羰基-1-[5’-O-（4,4’-二甲氧基三苯甲基）-2’-脱氧-3’-O-（4-硝基苯磺酰基）-β-D-苏型-呋喃戊糖基]胸腺嘧啶,通过18O（p,n）18F反应生产的18F-离子分别与两种前体进行标记反应并水解,用HPLC进行纯化得到18F-FLT,放化纯度>95%。结果：采用BAThy前体合成18F-FLT,平均合成产率为10.1%。采用BOC前体合成18F-FLT,平均合成产率为23.2%。结论：研究发现BOC前体更容易被18F-离子标记,平均产率比BAThy前体提高了130%。我们还研究了各个因素对于18F-FLT合成的影响,包括碱量与前体量的比、前体的溶剂、水解方式以及操作方法。由于参与的单位分布在国内各个不同的地区,基本能够消除地域因素对合成产率的影响,所得出的结果对于今后的研究有很好的指导意义。     

The effect of a methyl‐deficient diet on the global DNA methylation and the DNA methylation regulatory pathways

Methyl‐deficient diets are known to induce various liver disorders, in which DNA methylation changes are implicated. Recent studies have clarified the existence of the active DNA demethylation pathways that start with oxidization of 5‐methylcytosine (5meC) to 5‐hydroxymethylcytosine by ten‐eleven translocation (Tet) enzymes, followed by the action of base–excision–repair pathways. Here, we investigated the effects of a methionine–choline‐deficient (MCD) diet on the hepatic DNA methylation of mice by precisely quantifying 5meC using a liquid chromatography–electrospray ionization–mass spectrometry and by investigating the regulatory pathways, including DNA demethylation. Although feeding the MCD diet for 1 week induced hepatic steatosis and lower level of the methyl donor S‐adenosylmethionine, it did not cause a significant reduction in the 5meC content. On the other hand, the MCD diet significantly upregulated the gene expression of the Tet enzymes, Tet2 and Tet3, and the base–excision–repair enzymes, thymine DNA glycosylase and apurinic/apyrimidinic‐endonuclease 1. At the same time, the gene expression of DNA methyltransferase 1 and a, was also significantly increased by the MCD diet. These results suggest that the DNA methylation level is precisely regulated even when dietary methyl donors are restricted. Methyl‐deficient diets are well known to induce oxidative stress and the oxidative‐stress‐induced DNA damage, 8‐hydroxy‐2′‐deoxyguanosine (8OHdG), is reported to inhibit DNA methylation. In this study, we also clarified that the increase in 8OHdG number per DNA by the MCD diet is approximately 10 000 times smaller than the reduction in 5meC number, suggesting the contribution of 8OHdG formation to DNA methylation would not be significant. Copyright © 2015 John Wiley & Sons, Ltd.     

Bismuth UPD on the modified Au(1 1 1) electrode

The bismuth UPD was studied on Au(1 1 1) electrodes modified by silver intermediates and adsorbed thymine. Cyclic voltammetry, potential step experiments and X-ray photoelectron spectroscopy were used for investigation. The results were compared to the results of the analogous experiments performed on bare Au(1 1 1) and on bulk silver. In the first part it is shown that the Bi UPD on Ag_ML/Au(1 1 1) differs completely from the UPD on Au(1 1 1) as well as on bulk Ag due to changed electronic properties of the substrate. The 2nd part focuses on the Bi UPD in presence of the nucleobase thymine. Thymine undergoes a reorientation from the chemisorbed state to the physisorbed state on Au(1 1 1) at potentials where the Bi UPD takes place. During the UPD adsorbed thymine is replaced by Bi species on the electrode surface. It does not re-adsorb on top of the deposited Bi layer. An energetic advantage due to re-adsorption on topmost layer as described for the Cu UPD on thymine modified Au(1 1 1) does not occur.     

糖基化产物对牛视网膜微血管周细胞增生和胞浆[Ca~(2 )]i水平的影响

目的　探讨糖基化产物对牛视网膜周细胞 (pericyte ,PC)增生和胞浆 [Ca2 ]i水平的影响。　方法　采用细胞计数结合噻唑蓝比色测定 ,氚标胸腺嘧啶核苷 (3H thymidine ,3H TdR)掺入和钙荧光探剂 (Fu ra 2Acetoxymethylester,Fura 2AM) ,研究PC在牛血清白蛋白早期糖基化产物 (earlyglycationpro ductsofbovineserumalbumin ,EG BSA)和牛血清白蛋白糖基化终产物 (advancedglycationendproductsofbovineserumalbumin ,AGE BSA)培养下 ,PC增生数、DNA合成量及胞浆 [Ca2 ]i水平的改变。　结果　培养 4d后 ,细胞计数法 :EG BSA和AGE BSA组PC数分别为 17.87± 2 .36 ,14 .77± 3 .72 ,较其对照组 (2 0 .5 4± 0 .82 ,2 0 .31± 0 .93)减少13 .0 0 %和 2 7.0 0 % (P <0 .0 1) ;MTT法 :EG BSA和AGE BSA组分别为 0 .46 19± 0 .0 946 ,0 .3884± 0 .10 13 ,较其对照组 (0 .5 2 36± 0 .0 5 39,0 .5 2 2 7± 0 .0 5 19)减少 12 .0 0 %和 2 5 .70 % (P <0 .0 1) ;3H TdR掺入量 :EG BSA和AGE BSA组分别为 3945 0 .16± 8870 .6 8,336 6 7.85± 10 5 81.70 ,较其对照组 (5 6 373 .6 3± 2 317.97,5 6 5 42 .0 4±196 1 2 3)减少 30 .0 0 %和 40 46 % (P <0 0 1) ;胞浆 [Ca2 ]i水平 :EG BSA和AGE BSA组分别为 (12 9.     

紫草素与胸腺嘧啶相互作用的理论研究

目的：对紫草素与胸腺嘧啶形成的复合物进行了结构优化,比较它们的稳定性和活性,为实验设计合成活性更高的紫草素类抗癌药物指明方向。方法：采用密度泛函理论的M06方法在6-311＋＋G＊＊基组水平下对研究对象进行计算,同时我们还应用了分子中的原子（AIM）理论和自然键轨道（NBO）理论对得到的这些稳定复合物中的氢键的性质和特征进行了分析。结果：得到了14个稳定的紫草素-胸腺嘧啶复合物.发现复合物2的结构是最稳定的。结论：计算结果与临床试验结果一致,该方法用于指导该类化合物的设计合成是可行的。     

淋巴瘤细胞株Raji摄取18F-氟脱氧葡萄糖和18F-氟脱氧胸腺嘧啶核苷的体外实验研究

目的研究测定人淋巴瘤细胞株Raji摄取18F-氟脱氧葡萄糖（18F—FDG）和18F-氟脱氧胸腺嘧啶核苷（18F—FLT）的方法并比较两者的差异。方法在不同条件下测定淋巴瘤细胞株Raji对18F—FDG和18F—FLT的细胞结合率：细胞数量1×10^5-1×10^7/瓶;18F-FDG和18F—FLT的放射性活度1．85—29．6kBq;反应时间20—120min;葡萄糖浓度0～11．1mmol／L。结果每瓶1×10^7个细胞、加入3．7kBq18F．FDG、葡萄糖浓度在0—2．78mmol／L、作用100min,18F-FDG细胞结合率达到（50．42×1．07）％;每瓶1×10^7个细胞、加入3．7kBq 18F—FLT、作用100min,18F—FLT细胞结合率达到（59．48±0．77）％;18F—FDG和18F-FLT的细胞结合率之间具有统计学差异（F=1192．805,P〈0．001）。结论Raji细胞与18F—FDG的结合率与细胞数量、作用时间及葡萄糖浓度有关,与18F-FDG的放射性活度无关;Raji细胞与18F-FLT的结合率与细胞数量和作用时间有关,与18F-FLT的放射性活度及葡萄糖浓度无关;同等条件下,Raji细胞对18F-FLT的细胞结合率高于18F—FDG。     

Reactions of the nitro radical anion of metronidazole in aqueous and mixed solvent: a cyclic voltammetric study

Cyclic voltammetry was used to investigate the electrochemical reduction of metronidazole (2-methyl-5-nitro-1H-imidazole-1-ethanol) at glassy carbon and gold electrodes at different pHs in aqueous solution as well as in mixed solvent viz., aqueous dimethyl formamide. The electrogenerated nitro radical anion undergoes a disproportionation reaction, the rate constant of which is dependent on the pH, solvent composition and electrode material. The interactions of the nitro radical anion with thymine and cytosine were also investigated using a cyclic voltammetric technique. Both the bases were found to react with metronidazole nitro radical anion. The rate constants for such reactions in aqueous solutions were 3.5 × 10³ and 3.0 × 10³ dm³ mol^?1 s^?1 for thymine and cytosine, respectively.     

Cytotoxic constituents of the octocoralDendronephthya gigantea

A known monoalkyl glycerol ether, (+/-)-1-nonadecyloxy-2,3-propanediol (1) was isolated from the ethyl acetate extract of a soft coral Dendronephthya gigantea as a weakly cytotoxic constituent against four human cancer cell lines, A549, HT-29, HT-1080, and SNU-638. In addition, a known ceramide, (2S,3R,4E,8E)-N-hexadecanoyl-2-amino-4,8-octadecadiene-1,3-diol (2), was also isolated as an inactive constituent. This is the first report on the isolation of the compounds 1 and 2 from the octocoral, Dendronephthya species.