Simulation of 125I-based radioprobing experiments to study DNA quadruplex structure and topology

Purpose: Certain guanine-rich DNA sequences have the capacity to fold into four-stranded structures stabilized by the stacking of square planar arrangements of four hydrogen-bonded guanine bases. However both the overall topology of folding and the more detailed three dimensional structure of these quadruplexes is difficult to determine or predict, and they can be polymorphic, altering radically depending on environmental conditions. Radioprobing experiments, in which Auger electrons emitted during the decay of a ¹²⁵I-containing base induce strand cleavage in a distance- and structure-dependent manner, have provided possible means of determining these details. Here we have used a combination of computer simulation methods to study the information obtained by one such experiment, reported in 2004.

Method: Models were constructed of three quadruplex topologies considered in the experiment, and one other topology proposed more recently. Molecular Dynamics simulations were used to equilibrate these structures and monitor how they evolved over several nanoseconds in solution. Snapshots from the trajectories were then subjected to Monte Carlo track structure prediction, from which theoretical cleavage patterns have been extracted.

Results: The four topologies were found to yield quite different cleavage patterns, which allow the presence of particular conformations in an experiment to be predicted.

Conclusion: Radioprobing, which is usable in biologically relevant environments, is sensitive enough to distinguish with some confidence between alternative folding topologies in a DNA structure. Monte Carlo track structure simulation can reinforce or question conclusions drawn from experiment, and Molecular Dynamics used with various restraints provides a practical means of guiding a model towards one that yields cleavage patterns closer to those found experimentally.     

I125 irradiation stent for treatment of hepatocellular carcinoma with portal vein thrombosis: A meta-analysis

PurposeA meta-analysis aimed to systematically evaluate the safety and efficiency of I¹²⁵ irradiation stent placement for patients with hepatocellular carcinoma (HCC) combined with portal vein tumor thrombosis (PVTT).Materials and methodsThe Cochrane library, PubMed/Medline, EMBASE, CNKI, Wanfang Data and CQVIP were systematically screened out from the earliest to December 2019. The qualities of all included studies were assessed. The primary endpoints were the 6-month, 12-month stent cumulative patency rate and 6-month, 12-month, 24-month overall survival rate while the secondary endpoints were the objective response rate of PVTT, main portal venous pressure changes and treatment-related adverse events. Our meta-analysis was conducted using Stata 12.0 software.ResultsTotally seven studies with 1018 patients were included in the final analysis, in which 602 patients received TACE and I¹²⁵ irradiation stent placement, and 416 patients in control group underwent TACE and stent placement without endovascular brachytherapy (EVBT). Meta-analysis showed that the I¹²⁵ irradiation stent improved the cumulative stent patency rates in 6 months [OR = 1.65, 95% CI (1.32–2.05), P < 0.001] and 12 months [OR = 2.55, 95% CI (1.90–3.42), P < 0.001] and the survival rates in 6 months [OR = 1.77, 95% CI (1.41–2.22), P < 0.001], 12 months [OR = 3.14, 95% CI (2.24–4.40), P < 0.001] and 24 months [OR = 7.39, 95% CI (3.55–15.41), P < 0.001]. However, there was no difference in the objective response rate of PVTT [OR = 1.13, 95% CI (0.87–1.48), P = 0.365], main portal venous pressure and the occurrence adverse event [OR = 0.88, CI = 0.72–1.08, P = 0.212] between two groups.ConclusionI¹²⁵ irradiation stent seems to be more effective in treating hepatocellular carcinoma with portal vein tumor thrombosis. The usage of portal vein stent combined endovascular brachytherapy has the potential to act as an alternative therapy for HCC with PVTT. On account of the limitation of studies included, more studies with high-level evidence, such as RCTs, are requisite to support the above promising results.     

Variation in125i-insulin absorption and blood glucose concentration

Summary The absorption of monocomponent porcine¹²⁵I-insulin Monotard and Isophane was studied in six insulin dependent diabetic patients over a period of 12 days. The absorption of insulin was measured as the disappearance of radioactivity from sites of injection. The daily¹²⁵I-insulin doses ranged from 20 to 48 IU between patients. The insulin absorbed varied considerably within and between patients. The range of individual daily absorbed insulin varied from 19 to 104 per cent of the¹²⁵I-insulin dose. A significant correlation (p<0.05) was found between insulin absorption and blood glucose concentration. Insulin absorption rates were relatively high before all hypoglycaemic episodes and reactive hyperglycaemia was only observed when relatively low insulin absorption rates followed the hypoglycaemic attack. The results show that lability in some insulin dependent diabetics is explained by variation in insulin absorption.     

联合检测ADA、CA125和CEA对结核性与恶性胸腔积液的诊断价值

目的 探讨联合检测胸腔积液中腺苷脱氨酶(ADA)、糖类抗原125(CA125)和癌胚抗原(CEA)对结核性与恶性积液的鉴别诊断价值.方法 采用酶连续监测法和化学发光免疫分析法检测82例结核性积液及56例恶性胸腔积液中ADA、CA125和CEA的水平,并对检测结果进行综合分析.结果 结核性胸腔积液中平均ADA含量明显高于恶性胸腔积液,而CEA和CA125平均水平明显低于恶性胸腔积液(P＜O.05).以ADA＞40U/L为临界值,对结核性积液的敏感性、特异性和准确性分别为82.8％,80.4％和81.7％.以CA125＞35U/ml和CEA＞5μg/L为临界值,对恶性积液诊断的敏感性分别为82.6％和71.7％,特异性分别为58.8％和82.8％,准确性分别为65.4％和76.0％;联合检测CA125和CEA诊断恶性胸腔积液的敏感性和准确性分别为93.5％和81.7％,显著高于单一检测项目(P＜O.05).结论 联合检测胸腔积液中ADA、CEA和CA125对早期鉴别诊断结核性与恶性胸水的有重要参考价值.     

IGF-1、IGFBP-3、CEA和CA125联合检测对肺癌的诊断价值

目的 探讨胰岛素样生长因子1(insulin-like growth factor-1,IGF-1)、胰岛素样生长因子结合蛋白-3(insulin-like growth factor binding protein-3,IGFBP-3)、CEA及CA125联合检测对肺癌诊断的临床价值.方法 采用化学发光法分别对77例肺癌患者和41名健康体检者血清IGF-1、IGFBP-3、CEA和CA125水平进行检测,并对检测结果进行对比分析.结果 肺癌组血清IGF-1水平明显高于健康对照组(P＜0.01),血清IGFBP-3水平明显低于健康对照组(P＜0.05);单项检测时IGF-1灵敏性为28.57％,CEA灵敏性为44.16％,CA125灵敏性为40.26％;三项指标联合检测时灵敏性为75.33％.结论 IGF-1有助于肺癌的诊断,IGF-1、CEA及CA125联合检测可显著提高肺癌检出率.     

血清人附睾分泌蛋白4在卵巢上皮性癌中的临床价值

目的 研究血清人附睾蛋白4(HE4)在卵巢恶性肿瘤中的诊断价值.方法 用酶联疫吸附试验方法对卵巢上皮性癌组(54例)、盆腔良性疾病组(60例)、正常组(60例)妇女血清中HE4和CA125进行双盲检测,结果以中位数表示,分析比较两者单独检测诊断卵巢恶性肿瘤的价值.血清HE4和CA125的正常值分别为0～ 140pmol/L和0～ 35KU/L,其中任一指标高于正常即为阳性.结果 ①卵巢上皮性癌组血清HE4和CA125水平分别为142.72pmol/L和136.07KU/L,分别与盆腔良性疾病组(分别为63.72pmol/L和72.20KU/L)和正常组(分别为57.82pmol/L和57.42KU/L)比较,差异均有统计学意义(P＜0.01).②以盆腔良性疾病组作参照人群时,HE4和CA125单独检测的受试者工作特征曲线下面积(ROC-AUC)分别为0.958和0.886,两者比较,差异有统计学意义(P＜0.001).③以ROC曲线最左上方的点130 pmol/L、正常组95％参考值80pmol/L和正常值的上限140pmol/L为界值点,比较HE4单项检测对卵巢上皮性恶性肿瘤的诊断能力,结果显示,界值点为80pmol/L的特异度和阳性预测值均为88％,明显低于界值点为130(分别为93％和90％)和140pmol/L(分别为93％和95％)时的特异度和阳性预测值(P＜0.01).结论 HE4单项检测诊断卵巢上皮性恶性肿瘤的特异度优于CA125单项检测.以140pmol/L为界值点,对卵巢上皮性恶性肿瘤的早期诊断准确率更高,而以130pmol/L为界值点有利于卵巢上皮性恶性肿瘤的筛查、降低漏诊率.     

CA125单项与多项肿瘤指标联合检测在卵巢癌诊断中的比较

目的:探讨血清糖类抗原125(CA125)及CA125联合CA199、CA153、癌胚抗原(CEA)检测在卵巢癌诊断中的意义。方法:采用化学发光微粒子免疫检测法测定71例卵巢癌患者、10例卵巢交界性肿瘤患者和42例卵巢良性肿瘤患者血清中CA125、CA199、CA153和CEA的含量,阳性诊断标准分别为:CA12535 k U/L,CA19937 k U/L,CA15330 k U/L,CEA5μg/L。结果:在单项肿瘤标记物中,CA125的阳性率最高(84.5%),敏感度、特异度和准确度指标平稳。在不同的联合检测方案中CA199、CA153与CA125联合检测方案最优,较CA125单项检测敏感度和准确度均有提高。晚期卵巢癌(Ⅲ~Ⅳ期)患者的CA153、CA125含量高于早期卵巢癌(Ⅰ~Ⅱ期)患者(P0.001)。结论:CA199、CA153、CEA与CA125在卵巢癌鉴别诊断中均有一定价值,并可以根据CA153、CA125含量判断患者卵巢癌的分期,CA199、CA153与CA125联合检测是诊断卵巢癌较为理想的标记物组合。     

碘125粒子组织间植入治疗癌性疼痛的疗效与安全性

目的:探讨碘125粒子组织间植入治疗肿瘤患者癌性疼痛的临床效果与不良反应.方法:将200例中晚期恶性肿瘤癌痛患者随机分作观察组与对照组,观察组予以碘125粒子组织间植入治疗,对照组予以药物治疗,观察与比较两组患者疼痛视觉模拟评分(VAS)、疼痛缓解率、平均镇痛时间及不良反应.结果:治疗后观察组与对照组VAS评分均明显减少,治疗后1d两组VAS无统计学差异(P＞0.05),治疗后7、30 d观察组VAS显著低于对照组(P＜0.05);观察组疼痛缓解率(88.0％)明显高于对照组(64.0％),有统计学差异(x2=5.908,P＜0.05);治疗后观察组平均疼痛时间显著较对照组短(￡=7.342,P＜0.05);观察组不良反应发生率(3.0％)明显低于对照组(11.0％).结论:碘125粒子组织间植入治疗癌性疼痛的效果确切,具有迅速与持久的镇痛效果,不良反应少,值得临床借鉴.