核因子红细胞2相关因子2在毒死蜱毒性机制中的作用

毒死蜱(chlorpyrifos,CPF)是一种广泛使用的有机磷农药,其对人类健康和生态系统的潜在风险已引起广泛关注。CPF主要通过抑制乙酰胆碱酯酶(AChE)发挥杀虫作用,但越来越多的研究表明,CPF的毒性作用远不止于此,也与氧化应激、炎症反应、 细胞死亡等多种生物学过程密切相关,因而可能导致神经退行性疾病、生殖发育障碍以及其他慢性健康问题。核因子红细胞2相关因子2(Nrf2)作为一种关键的抗氧化应激调节因子,具有显著的保护作用。本文旨在综述Nrf2在调节CPF诱导的氧化应激、神经毒性、细胞死亡和炎症反应中的作用机制,探讨其作为潜在治疗靶点的前景,以为开发新的CPF中毒治疗策略提供理论基础。     

EGFR mutation types and abundance were associated with the overall survival of advanced lung adenocarcinoma patients receiving first-line tyrosine kinase inhibitors

BackgroundEpidermal growth factor receptor tyrosine kinases inhibitors (EGFR-TKIs) are currently recognized as the standard treatment for advanced non-small cell lung cancer (NSCLC) patients with EGFR mutations. Clinically found patients with different EGFR mutational status have different prognosis.MethodsA retrospective cohort study was performed to explore the relationship between EGFR mutations and abundance with patient survival by using patient data from the Affiliated Cancer Hospital of Zhengzhou University between January 2013 and November 2016. All patients involved in the present study had sensitive EGFR mutations [either exon 19 deletion (DEL) or exon 21 L858R] and treated by EGFR-TKIs. They were followed up every three months until lost or dead. Mutation abundance was calculated as the copies of EGFR mutation divided by copies of EGFR locus, and the cut-off values for 19DEL and L858R were 4.9% and 9.5%, respectively.ResultsTotal of 236 patients were included, comprising 116 (49.2%) patients with 19DEL mutation and 120 (50.8%) patients with L858R mutation. The median follow-up duration was 23.2 months (95% CI: 14.9–26.7 months). Overall survival (OS) was significantly longer in patients with 19DEL mutation (20.9 months, 95% CI: 17.7–24.1 months versus 17.0 months, 95% CI: 14.4–19.6 months in patients with L858R; P=0.008) and in patients with high mutation abundance (20.9 months, 95% CI: 18.3–23.5 months versus 13.0 months, 95% CI: 10.3–15.7 months in patients with low mutation abundance; P<0.001). Multivariate Cox regression including age, performance status and tumor stage revealed that longer OS was independently associated with 19DEL mutation (HR: 0.48, 95% CI: 0.39–0.67, P=0.033) and high mutation abundance (HR: 0.62, 95% CI: 0.50–0.79, P=0.027).ConclusionsEGFR mutation types and abundance was associated with the patients’ survival which might be used to predict the efficacy of targeted therapy by EGFR-TKIs.     

Ogilvie’s syndrome: a case report

Objective Ogilvies syndrome (OS) is a rare condition in obstetrics but occurs most commonly after caesarean section. Mortality rates from OS can be as high as 36–50% when bowel perforation or ischemia develops which highlights the early recognition of this condition. Early diagnosis is therefore essential to prevent serious morbidity and mortality. Conclusion We, therefore report a case of OS after caesarean section in which early detection by senior clinicians resulted in successful management of the condition and an excellent outcome.     

Identification of potential prognostic biomarkers for hepatocellular carcinoma

BackgroundThe incidence of liver cancer is increasing every year. Hepatocellular carcinoma (HCC) accounts for nearly 90% of liver cancer, and the overall 5-year survival rate of become of Hepatocellular carcinoma patients less than 20%. However, the molecular mechanism of HCC progression and prognosis still requires further exploration.MethodsIn this study, we downloaded the gene expression data from the Cancer Genome Atlas (TCGA) Genomic Data and the official website of GEO database. Weighted gene co-expression network analysis (WGCNA) and Pearson’s correlation coefficient were utilized to detect the gene modules. The shared differentially-expressed genes (DEGs) were screened out by a Venn diagram, and the hub genes were identified through protein-protein interaction (PPI) network analyses. GO and KEGG enrichment analyses were constructed for these hub genes. Overall survival (OS) and correlation analysis were conducted to investigate the relationship between the hub genes and clinical features.ResultsWe screened out 27 shared DEGs, and the mainly enriched GO terms were mitotic nuclear division, chromosomal region, and tubulin binding. Furthermore, the top three enriched KEGG pathways were “cell cycle”, “oocyte meiosis”, and “p53 signaling pathway”. According to the Maximal Clique Centrality (MCC) algorithm, the top 10 candidate hub genes were MYC, MCM3, CDC20, CCNB1, BIRC5, UBE2C, TOP2A, RRM2, TK1, and PTTG1, among which BIRC5, CDC20, and UBE2C showed a strong correlation with the OS.ConclusionsThree hub genes (BIRC5, CDC20, and UBE2C) were identified and found to be correlated to the progression and prognosis of HCC. These may become potential targets for HCC therapy.     

lncRNA DNM3OS在喉鳞状细胞癌组织和细胞中的表达及其临床和生物学意义

目的:检测lncRNA DNM3OS在喉鳞状细胞癌(laryngeal squamous cell carcinoma,LSCC)组织和LSCC细胞株中的表达及其临床意义,探讨其对LSCC TU177细胞体外增殖、迁移及侵袭的影响,并分析DNM3OS与EMT的关系.方法:从河北医科大学第四医院生物标本库选取2014年3...     

Is OSNA better than imprint cytology for intraoperative diagnosis of cancer involvement of axillary sentinel node in breast cancer?

ObjectiveThe study aim was to establish Sensitivity, Specificity, Positive Predictive Value, Negative Predictive Value (NPV), and Accuracy Values of both imprint cytology (IC) and the OSNA assay for intraoperative assessment of axillary sentinel node (SN) cancer involvement in breast cancer. Specifically, we wished to find out if true positive and false negative results of IC were associated to axillary lymphadenectomy (ALND). Also, we addressed a comparative cost analysis between techniques.Methods244 patients treated for breast cancer in the Breast Unit of Hospital Germans Trias i Pujol from 2011 to 2015 were prospectively included. A transversal, consecutive design was applied to assess IC compared to the reference test (OSNA). Inclusion criteria were: T1 and T2 tumors with negative nodes, both clinically and on ultrasound.ResultsSensitivity of IC for macrometastases was 70%. The NPV of IC for macrometastases was 95,75%. Accuracy of IC was 96,12%. In the comparative cost analysis, the release time of results for OSNA doubled that of IC and was associated with an increased cost of € 370.ConclusionsIC has been stated as a good technique for intraoperative cancer involvement SN with high sensitivity and NPV compared to the OSNA assay. It allows keeping the whole node tissue and thus the possibility of improved histopathological evaluation, which can be useful for adjuvant, and offers the advantage of being less time consuming. Cost analysis shows a higher cost for OSNA, which may exceed the benefit of sorting out false negatives from IC.     

Smoking and FGFR2 rs2981582 variant independently modulate male breast cancer survival: A population-based study in Tuscany,Italy

AimMale breast cancer (MBC) is a rare disease and recommendations for its clinical management are often extrapolated from those for female breast cancer, even if breast cancer (BC) has different characteristics in the two sexes. The purpose of this study was to assess the influence of several individual characteristics including clinico-pathological, lifestyle and genetic factors on overall survival (OS) of a relatively large and well characterized population-based series of 166 MBCs enrolled in Tuscany.MethodsWe genotyped MBC cases at BRCA1/2 genes and at 9 candidate BC susceptibility SNPs. Kaplan-Meier method and multivariate Cox regression, adjusted for several individual characteristics were used. To reduce a possible selection bias related to the interval between diagnosis and enrolment of MBC cases into the study, we used the date of blood donation as the date of the start of observation for survival analysis.ResultsOnly smoking habits had a significant effect on OS at 10 years (for current smokers, HR: 3.34; 95% CI 1.45–7.68; p = 0.004), while lymph node status fell short of reaching statistical significance (for pN positive, HR: 2.07; 95% CI 0.93–4.55; p = 0.07). In the same multivariate analysis we found a significantly higher OS in cases with FGFR2 rs2981582 variant in the dominant transmission model (HR: 0.29; 95% CI: 0.13–0.62; p = 0.028). A sensitivity analysis with left truncation showed similar results.ConclusionsOur results may contribute to shed light on factors influencing MBC survival suggesting an important role for cigarette smoking and FGFR2 rs2981582 variant, and provide clues for better patient management.     

Novel quinolone CHM‐1 induces apoptosis and inhibits metastasis in a human osterogenic sarcoma cell line

Novel 2‐phenyl‐4‐quinolone compounds have potent cytotoxic effects on different human cancer cell lines. In this study, we examined anticancer activity and mechanisms of 20‐fluoro‐6,7‐methylenedioxy‐2‐phenyl‐4‐quinolone (CHM‐1) in human osterogenic sarcoma U‐2 OS cells. CHM‐1‐induced apoptosis was determined by flow cytometric analysis, DAPI staining, Comet assay, and caspase inhibitors. CHM‐1‐inhibited cell migration and invasion was assessed by a wound healing assay, gelatin zymography, and a Transwell assay. The mechanisms of CHM‐1 effects on apoptosis and metastasis signaling pathways were studied using Western blotting and gene expression. CHM‐1 induced G2/M arrest and apoptosis at an IC₅₀ (3 µM) in U‐2 OS cells and caspase‐3, ‐8, and ‐9 were activated. Caspase inhibitors increased cell viability after exposure to CHM‐1. CHM‐1‐induced apoptosis was associated with enhanced ROS generation, DNA damage, decreased ΔΨ_m levels, and promotion of mitochondrial cytochrome c release. CHM‐1 stimulated mRNA expression of caspase‐3, ‐8, and ‐9, AIF, and Endo G. In addition, CHM‐1 inhibited cell metastasis at a low concentration (<3 µM). CHM‐1 inhibited the cell metastasis through the inhibition of MMP‐2, ‐7, and ‐9. CHM‐1 also decreased the levels of MAPK signaling pathways before leading to the inhibition of MMPs. In summary, CHM‐1 is a potent inducer of apoptosis, which plays a role in the anticancer activity of CHM‐1. © 2009 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 27:1637–1644, 2009     

Endocrine therapy for hormone treatment-naïve advanced breast cancer

A proportion of patients with hormone receptor-positive locally advanced or metastatic breast cancer will not have received prior endocrine therapy. However, there are limited clinical data specifically in these patients. We conducted a review of randomized phase II and III clinical studies of anastrozole, letrozole, exemestane, palbociclib, and fulvestrant to determine the evidence base supporting use of specific endocrine therapies in this patient population. From our findings, there is a paucity of clinical studies in patients with endocrine therapy-naïve disease; however, it appears that first-line treatment effects are consistent between patients who have and have not received prior endocrine treatment.     

PET／CT用于评估弥漫大B细胞淋巴瘤预后的Meta分析

目的 评价PET／CT在预测弥漫大B细胞淋巴瘤（DLBCL）预后中的价值。方法计算机检索PubMed、万方、Cochrane Library、EMBASE、中国知网、Medline等数据库中关于PET／CT评价DLBCL预后的研究,检索年限均为2000年1月至2015年3月。采用STATA11.0统计学软件进行Meta分析,各效应量均以95％可信区间（CI）表示。分析治疗中期PET／CT参数最大标准摄取值（SUVmax）、治疗末期SUVmax和肿瘤代谢体积（MTV）,并应用Meta分析合并风险比（HR）来评价DLBCL患者治疗后的预后与PET/CT参数的关系。分析各纳入研究结果间的异质性,采用随机效应模型对各研究结果进行Meta分析。评价指标包括无进展生存期（PFS）和总生存期（OS）的HR。结果 共纳入11项研究,包括1068例初诊的DLBCL患者。Meta分析结果显示：（1）治疗中期（2～4化疗周期后）PET／CT SUVmax评价DLBCL 患者PFS的HR为1.50 （95％CI：1.12～2.01,P=0.007）;（2）治疗末期（6～8化疗周期后）PET／CT SUVmax评价DLBCL患者PFS的HR为1.30 （95％CI：0.74～2.29,P=0.369）,评价DLBCL患者OS的HR为1.75 （95％CI：0.74～4.17,P=0.204）;（3） 治疗末期PET／CT MTV评价DLBCL患者PFS的HR为2.17 （95％CI：1.46～3.24,P=0.000）,评价DLBCL患者OS的HR为2.99 （95％CI 1.91～4.69,P=0.000）。结论 治疗中期PET／CT的SUVmax可以预测患者的PFS;治疗末期PET／CT的MTV可以预测患者的PFS、OS,而SUVmax则不能预测患者的PFS、OS。