Interaction studies of muts and mutl with DNA containing the major cisplatin lesion and its mismatched counterpart under equilibrium and nonequilibrium conditions

The DNA mismatch repair (MMR) system participates in cis‐diamminedichloroplatinum (II) (cisplatin) cytotoxicity through signaling of cisplatin DNA lesions by yet unknown molecular mechanisms. It is thus of great interest to determine whether specialized function of MMR proteins could be associated with cisplatin DNA damage. The major cisplatin 1,2‐d(GpG) intrastrand crosslink and compound lesions arising from misincorporation of a mispaired base opposite either platinated guanine of the 1,2‐d(GpG) adduct are thought to be critical lesions for MMR signaling. Previously, we have shown that cisplatin compound lesion with a mispaired thymine opposite the 3′ platinated guanine triggers new Escherichia coli MutS ATP‐dependent biochemical activities distinguishable from those encountered with DNA mismatch consistent with a role of this lesion in MMR‐dependent signaling mechanism. In this report, we show that the major cisplatin 1,2‐d(GpG) intrastrand crosslink does not confer novel MutS postrecognition biochemical activity as studied by surface plasmon resonance spectroscopy. A fast rate of MutS ATP‐dependent dissociation prevents MutL recruitment to the major cisplatin lesion in contrast to cisplatin compound lesion which authorized MutS‐dependent recruitment of MutL with a dynamic of ternary complex formation distinguishable from that encountered with DNA mismatch substrate. We conclude that the mode of cisplatin DNA damage recognition by MutS and the nature of MMR post‐recognition events are lesion‐dependent and suggest that MMR signaling through the major cisplatin lesion is unlikely to occur. © 2013 Wiley Periodicals, Inc. Biopolymers 99: 636–647, 2013.     

人乳头瘤病毒与宫颈癌前病变的相关性研究

目的：探讨人乳头瘤病毒感染与宫颈癌前病变两者之间的相关性。方法：选择2009年11月～2011年12月来我院就诊的220例宫颈病变患者为研究对象,将患者分成4组,即炎症组、CINl组、CIN2组和CIN3组,各组进行人乳头瘤病毒检出率及病毒载量的比较。结果：炎症组、CINl、CIN2和CIN34组人乳头瘤病毒的检出率分别为67．2％、80％、87．3％和91．4％且4组之间比较差异有显著统计学意义（P〈O．001）。炎症组HPV感染的阳性率与CIN组比较显著降低（P〈0．005）,宫颈癌前病变各组HPV感染呈阳性的病毒载量差异有统计学意义（P〈0．05）。结论：宫颈癌前病变的严重程度和感染高危型HPV病毒载量呈正相关,随着感染高危型HPV病毒载量越高,宫颈癌前病变的程度越严重。     

Prediction of reduction in aggressive behaviour of growing pigs using skin lesion traits as selection criteria

Aggression at regrouping is a common issue in pig farming. Skin lesions are genetically and phenotypically correlated with aggression and have been shown to have a significant heritable component. This study predicts the magnitude of reduction in complex aggressive behavioural traits when using lesion numbers on different body regions at two different time points as selection criteria, to identify the optimum skin lesion trait for selection purposes. In total, 1146 pigs were mixed into new social groups, and skin lesions were counted 24 h (SL24h) and 3 weeks (SL3wk) post-mixing, on the anterior, centre and posterior regions of the body. An animal model was used to estimate genetic parameters for skin lesion traits and 14 aggressive behavioural traits. Estimated breeding values (EBVs) and phenotypic values were scaled and standardised to allow direct comparison across multiple traits. Individuals with SL24h and SL3wk EBVs in the least aggressive 10% of the population were compared with the population mean to predict the expected genetic and phenotypic response in aggressive behaviour to selection. At mixing, selection for low anterior lesions was predicted to affect substantially more behavioural traits of aggressiveness than lesions obtained on other body parts, with EBVs between −0.21 and −1.17 SD below the population mean. Individuals with low central SL24h EBVs also had low EBVs for aggressive traits (−0.33 to −0.55). Individuals with high SL3wk EBVs had low EBVs for aggression at mixing (between −0.24 and −0.53 SD below the population mean), although this was predicted to affect fewer traits than selection against SL24h. These results suggest that selection against anterior SL24h would result in the greatest genetic and phenotypic reduction in aggressive behaviour recorded at mixing. Selection for increased SL3wk was predicted to reduce aggression at mixing; however, current understanding about aggressive behaviour under stable social conditions is insufficient to recommend using this trait for selection purposes.     

高危型HPV 感染对宫颈病变组织IFN-r、IL-10表达的影响

目的：探讨高危型人乳头瘤病毒（HPV）感染对宫颈病变组织干扰素-r(IFN-r)、白细胞介素-10(IL-10)的影响。方法：收集我 院2013 年1 月到2015 年1 月妇科门诊行宫颈活检患者150 例,根据病理检查结果,将患者分为观察组（宫颈癌33 例、CINⅠ期 26 例、CINⅡ期28 例、CINⅢ期23 例）110 例,对照组（慢性宫颈炎患者）40 例。提取两组患者宫颈组织标本,检测观察组 HPV-DNA、HPV 分型,及两组IFN-r、IL-10 蛋白及mRNA 表达,分析高危型HPV感染与宫颈病变组织IFN-r、IL-10 表达的关系。 结果：观察组HPV-DNA阳性87 例（79.1%）,其中HPV16 型47 例（42.7%）、HPV18 型20 例（18.2%）感染率最高;且HPV16、18 感 染率在CINⅠ期、CINⅡ期、CINⅢ期以及宫颈癌组中的感染率差异均有统计学意义（P<0.05）,Spearman相关性分析显示,HPV16、 18 与宫颈病变程度均呈现正相关关系（r=0.896,0.786;均P<0.05）。IFN-r、IL-10 表达水平在CINⅠ期、CINⅡ期、CINⅢ期、宫颈 癌、对照组表达水平差异均具有统计学意义（P<0.05）,Spearman 相关性分析显示,IFN-r与宫颈病变程度呈现负相关关系（r=-0. 567,P<0.05）,IL-10 呈现正相关关系（r=0.678,P<0.05）。且HPV16、HPV18 感染率与IFN-r表达呈现负相关关系（rHPV16/18=-0. 678,-0.675,均P<0.05）,与IL-10 呈现正相关关系（rHPV16/18=0.582,0.778,均P<0.05）。结论：IFN-r表达随着宫颈病变加重或者 HPV16、HPV18 感染率升高逐渐降低,IL-10 则逐渐升高。     

阴式全子宫切除术和腹腔镜下全子宫切除术的临床对比分析

目的:比较阴式全子宫切除术与腹腔镜下全子宫切除术的临床治疗效果。方法:回顾性分析2014年6月-2015年6月我院收治的137例子宫良性病变患者的临床病历资料,按照手术方式将其分为阴式组(行阴式全子宫切除术)和腹腔镜组(行腹腔镜下全子宫切除术),比较两组患者的术中、术后临床指标及术后并发症情况。结果:阴式组手术时间及术中出血量均少于腹腔镜组,差异有统计学意义(P0.05)。阴式组肛门排气时间、下床活动时间以及住院时间均短于腹腔镜组,住院总费用低于腹腔镜组,差异有统计学意义(P0.05)。两组患者并发症发生情况差异无统计学意义(P0.05)。结论:阴式全子宫切除术较腹腔镜下全子宫切除术而言,具有手术创伤小、术后恢复快的特点,值得临床推广。     

早发冠心病患者的危险因素及冠脉病变特点研究

目的:探讨早发冠心病(PCAD)患者的危险因素及冠脉病变特点。方法:收集2014年8月至2015年2月北京安贞医院急诊科行冠状动脉造影的1000例患者为研究对象,根据冠状动脉造影结果和临床资料分为早发冠心病(PCAD)组(男55岁,女65岁,n=340)、晚发冠心病组(n=300)和对照组(非冠心病者,n=360)。对三组患者的临床资料进行统计学分析,采用logistic回归分析PCAD患者的危险因素,并比较PCAD组与晚发冠心病组的冠状动脉病变特点。结果:Logistic回归分析结果提示:吸烟、早发冠心病家族史、高血压病及2型糖尿病是PCAD的独立危险因素(P0.001)。PCAD组单支病变比例显著高于晚发冠心病组(P0.05);回旋支、右冠状动脉病变比例低于晚发冠心病组(P0.05)。结论:吸烟、早发冠心病家族史、高血压病及2型糖尿病是PCAD的独立危险因素。早发冠心病患者冠脉病变主要累及前降支,单支病变多于晚发冠心病患者。     

超声内镜辅助下内镜黏膜下切除术对食管癌前病变患者肿瘤标志物及应激反应指标的影响

目的:探讨超声内镜(EUS)辅助下内镜黏膜下切除术(EMR)对食管癌前病变患者肿瘤标志物及应激反应指标的影响。方法:选择山东大学齐鲁医院青岛院区消化内科于2016年3月至2018年4月期间收治的食管癌前病变患者137例,采用随机数字表法将患者分为常规组(n=68,常规胃镜下行EMR)和EUS组(n=69,EUS辅助下行EMR),比较两组患者临床指标,比较两组术前、术后血清肿瘤标志物及应激反应指标水平,比较两组术前、术后1周相关遗传学分子水平。结果:EUS组手术时间、术后流质饮食时间均短于常规组(P0.05),并发食管黏膜小穿孔例数、使用钛夹止血例数均少于常规组(P0.05)。两组患者术后肿瘤特异性生长因子(TSGF)、细胞角蛋白19血清片段21-1(CYFRA21-1)、鳞状上皮细胞癌抗原(SCC-Ag)均较术前升高,但EUS组低于常规组(P0.05)。两组患者术后肾上腺素(E)、去甲肾上腺素(NE)、肾素(R)、血管紧张素Ⅱ(AngⅡ)、醛固酮均较术前升高,但EUS组低于常规组(P0.05)。两组患者术后1周细胞周期素E(Cyclin E)、转化生长因子-α(TGF-α)均较术前降低,且EUS组低于常规组(P0.05)。结论:相比于常规胃镜,经EUS辅助下EMR治疗食管癌前病变可有效改善患者的临床指标,减轻患者应激反应,有利于降低血清肿瘤标志物及遗传学分子水平。     

‘Tailception’: using neural networks for assessing tail lesions on pictures of pig carcasses

Tail lesions caused by tail biting are a widespread welfare issue in pig husbandry. Determining their prevalence currently involves labour intensive, subjective scoring methods. Increased societal interest in tail lesions requires fast, reliable and cheap systems for assessing tail status. In the present study, we aimed to test the reliability of neural networks for assessing tail pictures from carcasses against trained human observers. Three trained observers scored tail lesions from automatically recorded pictures of 13 124 pigs. Nearly all pigs had been tail docked. Tail lesions were classified using a 4-point score (0=no lesion, to 3=severe lesion). In addition, total tail loss was recorded. Agreement between observers was tested prior and during the assessment in a total of seven inter-observer tests with 80 pictures each. We calculated agreement between observer pairs as exact agreement (%) and prevalence-adjusted bias-adjusted κ (PABAK; value 1=optimal agreement). Out of the 13 124 scored pictures, we used 80% for training and 20% for validating our neural networks. As the position of the tail in the pictures varied (high, low, left, right), we first trained a part detection network to find the tail in the picture and select a rectangular part of the picture which includes the tail. We then trained a classification network to categorise tail lesion severity using pictures scored by human observers whereby the classification network only analysed the selected picture parts. Median exact agreement between the three observers was 80% for tail lesions and 94% for tail loss. Median PABAK for tail lesions and loss were 0.75 and 0.87, respectively. The agreement between classification by the neural network and human observers was 74% for tail lesions and 95% for tail loss. In other words, the agreement between the networks and human observers were very similar to the agreement between human observers. The main reason for disagreement between observers and thereby higher variation in network training material were picture quality issues. Therefore, we expect even better results for neural network application to tail lesions if training is based on high quality pictures. Very reliable and repeatable tail lesion assessment from pictures would allow automated tail classification of all pigs slaughtered, which is something that some animal welfare labels would like to do.     

Global DNA methylation (LINE-1) associated with exposure to arsenic-contaminated environment and with type of arsenical skin lesions in Thailand

The effects of chronic arsenic exposure mode on DNA methylation and skin lesion type are unclear. These relationships were investigated in an arsenic-contaminated area of southern Thailand. Cases with arsenical skin lesions (n = 131) and lesion-free controls (n = 163) were selected from an arsenic-contaminated sub-district, as well as 105 controls from a non-contaminated area. Type and severity of skin lesions and salivary global DNA methylation (LINE-1) were determined. Arsenic exposure was characterized as occupational, domestic and current (toe-nail arsenic). Associations were explored using logistic regression. Cases and controls had lower LINE-1 methylation and higher toenail arsenic than external controls (74.65% and 74.61% vs 76.05%, p < 0.001 for each). Cases were more likely to have been exposed domestically (OR_total 1.76, 95% ci 1.00, 3.11; and 2.22, 95% ci 1.22, 4.03; P_trend = 0.005 for exposure <36 and ≥36 years). More severe spotty hyperpigmentation was related to higher LINE-1 methylation (P_trend=0.006). LINE-1 methylation was positively associated with toenail arsenic only among non-symptomatic exposed subjects (OR 1.31, 95% ci 1.06, 1.64; p = 0.014). Exposure to an arsenic-contaminated environment results in global DNA hypomethylation. However, among symptomatic subjects, increased global DNA methylation was associated with increased severity of spotty hyperpigmentation.