RAD50 germline mutations are associated with poor survival in BRCA1/2–negative breast cancer patients

RAD50 is a highly conserved DNA double‐strand break (DSB) repair gene. However, the associations between RAD50 germline mutations and the survival and risk of breast cancer have not been fully elucidated. Here, we aimed to investigate the clinical impact of RAD50 germline mutations in a large cohort of unselected breast cancer patients. In our study, RAD50 germline mutations were determined using next‐generation sequencing in 7657 consecutive unselected breast cancer patients without BRCA1/2 mutations. We also screened for RAD50 recurrent mutations (L719fs, K994fs, and H1269fs) in 5000 healthy controls using Sanger sequencing. We found that 26 out of 7,657 (0.34%) patients had RAD50 pathogenic mutations, and 16 patients carried one of the three recurrent mutations (L719fs, n = 6 cases; K994fs, n = 5 cases; and H1269fs, n = 5 cases); the recurrent mutation rate was 0.21%. The frequency of the three recurrent mutations in the 5,000 healthy controls was 0.18% (9/5,000). These mutations did not confer an increased risk of breast cancer in the studied patients [odds ratios (OR), 1.16; 95% confidence interval (CI), 0.51–2.63; p = 0.72]. Nevertheless, multivariate analysis revealed that RAD50 pathogenic mutations were an independent unfavourable predictor of recurrence‐free survival (RFS) [adjusted hazard ratio (HR) 2.66; 95% CI, 1.18–5.98; p = 0.018] and disease‐specific survival (DSS; adjusted HR 4.36; 95% CI, 1.58–12.03; p = 0.004) in the entire study cohort. Our study suggested that RAD50 germline mutations are not associated with an increased risk of breast cancer, but patients with RAD50 germline mutations have unfavourable survival compared to patients without these mutations.     

激活素-α在脓毒症患者中的表达水平及临床意义

目的 探讨激活素-α在脓毒症患者中的表达水平及临床意义.方法 前瞻性收集2015年1月至2016年12月鞍山市中心医院收治的脓毒症患者127例,根据患者病情严重程度,将患者分为脓毒症组(n=21)、严重脓毒症组(n=68)和脓毒性休克组(n=38),主要观察指标包括激活素-α、降钙素原、C反应蛋白、APPACHEⅡ评分、序贯器官衰竭(SOFA)评分和乳酸.结果 脓毒症组、严重脓毒症组和脓毒性休克组患者激活素-α分别为(365.57±86.57)、(553.85±108.58)和(974.77±178.54)μg·L-1,三组比较差异有统计学意义(F=19.584,P=0.000);降钙素原分别为(2.46±0.52)、(3.12±0.75)和(3.54±0.78)pg·L-1,三组比较差异有统计学意义(F=2.488,P=0.021),APPACHEⅡ评分分别为(13.57±4.38)、(18.48±5.22)和(24.89±7.12)分,三组比较差异有统计学意义(F=12.577,P=0.000);SOFA评分分别为(4.12±1.28)、(7.88±2.09)和(11.83±4.25)分,三组比较差异有统计学意义(F=9.835,P=0.000);乳酸分别为(2.45±0.54)、(3.98±0.78)和(5.12±1.53)mmol·L-1,三组比较差异有统计学意义(F=11.485,P=0.000).多因素logistic回归分析显示激活素-α、AP-PACHEⅡ评分、SOFA评分和乳酸升高是脓毒症患者死亡的危险因素(P<0.05).结论 激活素-α与脓毒症患者病情严重程度相关,在预测脓毒症患者临床预后中具有一定价值.     

Involvement of IL-17 in Secondary Brain Injury After a Traumatic Brain Injury in Rats

The pro-inflammatory activity of interleukin 17, which is produced by the IL-23/IL-17 axis, has been associated with the pathogenesis of traumatic brain injury (TBI). The study investigated the potential role of IL-17 in secondary brain injury of TBI in a rat model. Our data showed that the levels of IL-17 increased from 6 h to 7 days and peaked at 3 days, in both the CNS and serum, which were consistent with the severity of secondary brain injury. The IL-23 inhibitor suberoylanilide hydroxamic acid (SAHA) treatment markedly decreased the expressions of IL-17 and apoptosis-associated proteins cleaved caspase-3 and increased the protein ratio of Bcl-2 (B cell lymphoma/leukemia-2)/Bax (Bcl-2-associated X protein). Meanwhile, neuronal apoptosis was reduced, and neural function was improved after SAHA treatment. This study suggests that IL-17 is involved in secondary brain injury after TBI. Administering an IL-23 inhibitor and thereby blocking the IL-23/IL-17 axis may be beneficial in the treatment of TBI.     

中国医院感染监测工作的发展及变化趋势

目的总结三十年来我国医院感染监测活动所取得的成效，探索医院感染监测的变化趋势，寻找适合我国医院感染监测的新模式。方法抽取13个省（自治区、直辖市）及军队系统综合性医院194所，采用问卷调查的方式调查其医院感染监测工作开展情况。结果194所医院审核后数据可用医院为184所(94.85%)。二级、三级医院医院感染发病率分别为0.78%、1.58%，两组比较，差异有统计学意义（P＜0.01）。以2006年为界线分为两个阶段，2006年以前、2006—2016年开展各项监测的医院累计比率：环境卫生学监测分别为73.91%、100.00%，消毒效果监测分别为69.57%、97.28%，全面综合性监测分别为64.67%、98.91%，手术部位感染监测分别为13.04%、94.57%，ICU医院感染监测分别为4.89%、87.50%，新生儿医院感染监测分别为1.75%、60.82%，多重耐药菌监测分别为5.43%、95.65%，手卫生依从性监测分别为2.17%、93.48%，抗菌药物监测分别为15.22%、87.50%。三级医院医院感染暴发事件报告的比率为33.33%（37所），高于二级医院16.44%（12所），差异有统计学意义（P=0.01）。结论我国医院感染监测起步较晚，但发展较快。我国医院感染监测系统仍然存在缺陷，医院感染病例漏报率仍较高，医院感染暴发报告率低。     

VitC对兔慢性高同型半胱氨酸血症氧化应激导致内皮功能损伤的保护作用

目的　探讨高同型半胱氨酸血症 (HHcy)导致内皮功能损伤时 ,兔血中一氧化氮 (NO)以及谷胱甘肽过氧化物酶 (GSH PX)活性的改变 ,从而观察氧化应激在活体内皮功能损伤中的作用以及抗氧化剂VitC的保护作用。方法　将兔随机分为 3组 ,每组 9只 ,分别喂食正常饲料 (N组 ) ,L 蛋氨酸 (0 .8g·kg-1·d-1)饲料 (M组 ) ,L 蛋氨酸加VitC(1.0g·kg-1·d-1)饲料 (MC组 ) ,然后于第 0、2 0、40、60、80天取血检测NO、GSH PX的活性 ,同时利用高分辨率超声检测其内皮依赖性舒张功能 (EDD)、内皮非依赖性舒张功能 (EID)。结果　慢性HHcy时 ,MC组和M组的EDD均较对照组明显降低 ,P <0 .0 1,而且两组之间也差异显著 ,P <0 .0 1;MC组和M组的EID亦较对照组明显降低 ,P <0 .0 5 ,但两组之间无显著差异。同时 ,M组血浆NO、GSH PX活性较对照组和MC组明显降低 ,P <0 .0 5 ;而MC组和对照组之间无显著差异。结论　HHcy可导致兔血浆NO及GSH PX的活性降低 ,而抗氧化剂VitC可以保护Hcy对兔血管内皮功能的损伤 ,减少NO的灭活 ,而且对GSH PX的活性具有一定的保护作用