Resection Activity of the Sgs1 Helicase Alters the Affinity of DNA Ends for Homologous Recombination Proteins in Saccharomyces cerevisiae

The RecQ helicase family is critical during DNA damage repair, and mutations in these proteins are associated with Bloom, Werner, or Rothmund-Thompson syndromes in humans, leading to cancer predisposition and/or premature aging. In the budding yeast Saccharomyces cerevisiae, mutations in the RecQ homolog, SGS1, phenocopy many of the defects observed in the human syndromes. One challenge to studying RecQ helicases is that their disruption leads to a pleiotropic phenotype. Using yeast, we show that the separation-of-function allele of SGS1, sgs1-D664Δ, has impaired activity at DNA ends, resulting in a resection processivity defect. Compromising Sgs1 resection function in the absence of the Sae2 nuclease causes slow growth, which is alleviated by making the DNA ends accessible to Exo1 nuclease. Furthermore, fluorescent microscopy studies reveal that, when Sgs1 resection activity is compromised in sae2Δ cells, Mre11 repair foci persist. We suggest a model where the role of Sgs1 in end resection along with Sae2 is important for removing Mre11 from DNA ends during repair.     

A New Computational Efficient Approach for Trabecular Bone Analysis using Beam Models Generated with Skeletonized Graph Technique

Micro-finite element (FE) analysis is a well established technique for the evaluation of the elastic properties of trabecular bone, but is limited in its application due to the large number of elements that it requires to represent the complex internal structure of the bone. In this paper, we present an alternative FE approach that makes use of a recently developed 3D-Line Skeleton Graph Analysis (LSGA) technique to represent the complex internal structure of trabecular bone as a network of simple straight beam elements in which the beams are assigned geometrical properties of the trabeculae that they represent. Since an enormous reduction of cputime can be obtained with this beam modeling approach, ranging from approximately 1,200 to 3,600 for the problems investigated here, we think that the FE modeling technique that we introduced could potentially constitute an interesting alternative for the evaluation of the elastic mechanical properties of trabecular bone.     

术前TFF1、HSP70、ASPH与原发性肝癌患者手术切除术后早期复发的关系研究

摘要 目的：研究术前三叶因子1（TFF1）、热休克蛋白70（HSP70）、天冬氨酸-天冬酰胺β羟化酶（ASPH）与原发性肝癌（PHC）患者手术切除术后早期复发的关系。方法：选取2018年1月～2019年12月我院收治的83例PHC患者,均行手术切除治疗,术后均随访2年,根据是否复发分为复发组49例以及未复发组34例。比较两组术前TFF1、HSP70、ASPH水平差异,收集患者基线资料,采用多因素Logistic回归分析PHC患者手术切除术后早期复发的危险因素,采用受试者工作特征（ROC）曲线分析术前TFF1、HSP70、ASPH水平预测PHC患者手术切除术后早期复发的效能。结果：复发组术前TFF1、HSP70、ASPH水平均高于未复发组（P＜0.05）。复发组肿瘤直径≥5 cm、肿瘤数目为多发、有血管侵犯的患者比例高于未复发组（P＜0.05）。多因素Logistic回归分析结果显示：肿瘤直径≥5 cm、多发肿瘤、血管侵犯及术前TFF1、HSP70、ASPH高水平是PHC患者手术切除术后早期复发的危险因素（均OR＞1,P＜0.05）。ROC曲线分析结果显示：术前TFF1、HSP70、ASPH联合检测预测PHC患者手术切除术后早期复发的曲线下面积为0.815,明显高于上述三项指标单独检测的0.704、0.713、0.707。结论：术前TFF1、HSP70、ASPH与PHC患者手术切除术后早期复发密切相关,联合检测三项指标水平可能有助于预测PHC患者手术切除术后早期复发。     

DNA end resection is needed for the repair of complex lesions in G1-phase human cells

Repair of DNA double strand breaks (DSBs) is influenced by the chemical complexity of the lesion. Clustered lesions (complex DSBs) are generally considered more difficult to repair and responsible for early and late cellular effects after exposure to genotoxic agents. Resection is commonly used by the cells as part of the homologous recombination (HR) pathway in S- and G2-phase. In contrast, DNA resection in G1-phase may lead to an error-prone microhomology-mediated end joining. We induced DNA lesions with a wide range of complexity by irradiation of mammalian cells with X-rays or accelerated ions of different velocity and mass. We found replication protein A (RPA) foci indicating DSB resection both in S/G2- and G1-cells, and the fraction of resection-positive cells correlates with the severity of lesion complexity throughout the cell cycle. Besides RPA, Ataxia telangiectasia and Rad3-related (ATR) was recruited to complex DSBs both in S/G2- and G1-cells. Resection of complex DSBs is driven by meiotic recombination 11 homolog A (MRE11), CTBP-interacting protein (CtIP), and exonuclease 1 (EXO1) but seems not controlled by the Ku heterodimer or by phosphorylation of H2AX. Reduced resection capacity by CtIP depletion increased cell killing and the fraction of unrepaired DSBs after exposure to densely ionizing heavy ions, but not to X-rays. We conclude that in mammalian cells resection is essential for repair of complex DSBs in all phases of the cell-cycle and targeting this process sensitizes mammalian cells to cytotoxic agents inducing clustered breaks, such as in heavy-ion cancer therapy.     

肺癌根治术后并发症危险因素分析及其生活质量变化研究

摘要 目的：探讨肺癌根治术后并发症的危险因素,并分析其生活质量的变化。方法：纳入我院2018年9月～2020年7月收治的行肺癌根治术患者104例,对患者的临床资料进行回顾性分析。根据患者术后3个月的并发症发生情况,分成并发症组（n=32）和非并发症组（n=72）,分析肺癌根治术后并发症发生的影响因素,利用癌症病人生活质量测定量表（QLQ-C30）评估患者术前及术后3个月的生活质量。结果：肺癌根治术后32例出现并发症,其中切口感染6例,肺炎7例,肺不张9例,心律失常6例,脓胸4例。并发症组年龄≥60岁、烟龄≥10年、传统开胸术、慢性阻塞性肺疾病史人数占比高于非并发症组（P＜0.05）。多因素Logistic回归分析显示,年龄≥60岁（OR=2.978,95%CI：1.415-6.267）、烟龄≥10年（OR=3.847,95%CI：1.869-7.918）、传统开胸术（OR=3.065,95%CI：1.544-6.084）、慢性阻塞性肺疾病史（OR=2.848,95%CI：1.481-5.477）是肺癌根治术后患者发生并发症的危险因素（P＜0.05）。非并发症组术后3个月的总体生活质量量表、角色功能、躯体功能、情绪功能、社会功能评分高于术前与并发症组,且恶心呕吐、疲乏、疼痛、便秘、呼吸困难、食欲下降、睡眠障碍、腹泻评分较术前与并发症组明显降低（P＜0.05）。结论：肺癌根治术后并发症的发生主要与患者年龄、烟龄、手术方式、慢性阻塞性肺疾病史有关,且并发症对患者术后生活质量影响较大。     

盐酸右美托咪定联合盐酸罗哌卡因胸椎旁神经阻滞对肺癌根治术患者血清炎性因子和免疫学指标的影响

摘要 目的：探讨盐酸右美托咪定联合盐酸罗哌卡因胸椎旁神经阻滞（TPVB）对肺癌根治术患者血清炎性因子和免疫学指标的影响。方法：选取2018年4月~2020年4月期间于我院行肺癌根治术的患者400例,根据信封抽签法分为对照组和观察组,各200例,对照组给予盐酸罗哌卡因TPVB,观察组在对照组基础上联合盐酸右美托咪定,对比两组疼痛、炎性因子、免疫学指标、血流动力学及不良反应。结果：观察组术后6 h（T5）~术后48h（T8）时间点视觉模拟评分法（VAS）评分均低于对照组（P<0.05）。对照组插管后5 min（T1）~术毕（T3）时间点心率（HR）及平均动脉压（MAP）较麻醉诱导前（T0）时间点升高（P<0.013）,观察组T1~T3时间点HR、MAP低于对照组（P<0.05）。两组T8时间点白介素-6（IL-6）、C反应蛋白（CRP）、肿瘤坏死因子-α（TNF-α）均较T0下降,且观察组低于对照组（P<0.05）。两组T8时间点CD4⁺、CD4⁺/CD8⁺均较T0时间点下降,但观察组高于对照组（P<0.05）,CD8⁺均较T0时间点升高,但观察组低于对照组（P<0.05）。观察组不良反应总发生率低于对照组（P<0.05）。结论：盐酸右美托咪定联合盐酸罗哌卡因TPVB用于肺癌根治术患者,可稳定血流动力学,且可获得较好的镇痛效果,降低不良反应发生率,减轻术后炎性损伤及免疫抑制。     

腔镜下腺体切除术对早期乳腺癌患者血清免疫球蛋白及TNF-α、IL-10水平变化的影响

摘要 目的：分析腔镜下腺体切除术对早期乳腺癌患者血清免疫球蛋白及TNF-α、IL-10水平的影响,从而对其优势评估。方法：选择2017年2月-2020年2月于本院实施乳腺癌手术患者100例,根据其选择手术方式的不同分为2组：A组（腔镜下腺体切除术,59例）和B组（开放乳房皮下腺体切除术,41例）,分别统计患者手术时间、术后拔管时间以及住院时间;术后1个月,取患者外周血,离心取血清,采用免疫比浊法检测患者血清免疫功能相关指标IgM和IgG含量、采用人酶联免疫吸附实验（ELISA）试剂盒检测患者血清中炎症反应指标TNF-α和IL-10含量、统计术后两组患者出现术野皮下出血、皮下积液、乳头乳晕坏死等并发症的例数;术后一年,统计两组患者出现复发和淋巴结转移等现象的例数。结果：A组患者手术时间显著长于B组,而其拔管时间和住院时间均显著短于B组（P＜0.05）。A组并发症发生率（5.00 %）显著高于B组（25.71%）（P<0.05）。术前1 d,两组患者血清免疫指标IgM和IgG水平和炎症反应指标TNF-α和IL-10水平相比差异无统计学意义（P＞0.05）,而术后3 d~术后1 m,A组患者血清免疫指标IgM和IgG水平以及抗炎因子IL-10水平均显著高于B组,促炎因子TNF-α水平显著低于B组（P＜0.05）。A组患者术后1年内乳腺癌复发率（3.3%）与B组（10.0%）相比差异不具有统计学意义（P＞0.05）。结论：腔镜下腺体切除术治疗早期乳腺癌具有拔管时间以及术后住院时间短、并发症发生率低等优势,其原因可能与该手术对患者血清免疫球蛋白IgM和IgG及炎症因子TNF-α、IL-10水平影响程度较小、术后恢复较快有关。