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61.
Jun Zhu Liang Wang Yifan Zhou Jun Hao Shuai Wang Lei Liu Jipeng Li 《Journal of gastrointestinal oncology.》2020,11(6):1381
BackgroundThe innovation of immune checkpoint blockade (ICB) represents a promising shift in the treatment of advanced hepatocellular carcinoma (HCC). However, response to ICB has varied largely due to the high tumor heterogeneity and complex tumor microenvironment (TME). The competitive endogenous RNA (ceRNA) network also plays an important role in tumor occurrence and progression, but its relation with tumor-infiltrating immune cells (TICs) remains largely unexplored in HCC. The overriding objective of our study was thus to construct a prognosis-related risk model and to further evaluate the relationship between ceRNA networks and TICs.MethodsDifferentially expressed gene (DEG) analysis was performed to identify the differentially expressed RNAs. Lasso and multivariable Cox regression analyses were used to construct risk models, which were assessed by the area under the receiver operating characteristic curve (AUC of ROC) and Kaplan-Meier (K-M) curves. Then, a single-sample gene set enrichment analysis (ssGSEA) algorithm was adopted to dissect the TICs in HCC samples. Nomograms were constructed and calibration curves were used to verify the discrimination and accuracy of the nomograms. Finally, integration analysis was performed to validate the correlation of ceRNA and TICs.ResultsIn the study, 7 differentially expressed RNAs [5 messenger RNA s (mRNAs) and 2 micro RNAs (miRNAs)] were incorporated to construct a ceRNA risk model. The AUC of the 1-, 3-, and 5-year overall survival (OS) were 0.784, 0.685, and 0.691 respectively. Likewise, 7 types TICs were in the TICs signature model and the AUC of the 1-, 3-, and 5-year OS were 0.706, 0.731, and 0.721 respectively. The integration analysis showed that 7 pairs of mRNA-TICs and 1 pair of miRNA-TICs had a close relation (all correlation coefficients >0.2, P<0.001).ConclusionsThrough constructing two risk models based on ceRNA network and TICs, we identified the hub RNAs and key TICs in the progression and prognosis of HCC, and further explored the relationship between ceRNA and TME. Importantly, targeting these hub RNAs may facilitate the remodeling of the TME and be a potential therapeutic alternative to enhancing the response to ICB, thus improving the prognosis of HCC patients. 相似文献
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Xiaofan Guo Zhao Li Ying Zhou Shasha Yu Hongmei Yang Liqiang Zheng Yamin Liu Yingxian Sun 《Journal of stroke and cerebrovascular diseases》2019,28(4):1062-1069
Background
Stroke burden is extremely high in Chinese hypertensive population. Novel biomarkers for cardiovascular diseases can be detected by metabolomic profiling of human fluids. We aim to find a panel of distinctive plasma metabolites for predicting incident ischemic stroke in hypertensive patients.Methods
This is a nested case-control study from a prospective cohort design. Baseline plasma samples were collected from 66 newly developed ischemic stroke cases and 66 matched controls. Untargeted metabolomics was performed by ultra-high performance liquid chromatography-tandem mass spectrometry, and data were analyzed by multivariate and univariate statistics.Results
Plasma metabolite profiles clearly differed between hypertensive patients with incident ischemic stroke and without. A total of 12 metabolites were screened and identified as potential biomarkers. The altered metabolic pathways included retinol metabolism, sphingolipid metabolism, glycerophospholipid metabolism, lysine degradation, tyrosine metabolism, and tryptophan metabolism. For prediction of hypertensive ischemic stroke, the panel of specific metabolomics-based biomarkers provided area under the curve of 0.848 (95% confidence interval: 0.783-0.913).Conclusions
Our study identified a metabolic signature of incident ischemic stroke in hypertension. Differences in small-molecule metabolites hold translational value in prediction and provide insights into potential new mechanisms of this condition. 相似文献64.
目的探讨对鼓膜大穿孔病例应用耳内镜下单纯鼓膜成形术的疗效。方法选取2015年9月-2018年1月收治的鼓膜大穿孔患者43例(46耳),耳内镜下采取耳屏软骨-软骨膜进行鼓膜成形术,对鼓膜愈合及听力情况进行评价。结果 43耳鼓膜愈合,3耳未愈合,愈合率93.5%,听力改善患者满意,1例出现迟发性面瘫,药物治疗后恢复,其余均无并发症出现。结论耳内镜下应用耳屏软骨-软骨膜修补鼓膜大穿孔操作相对简单,能抵近观察,手术成功率高,比显微镜下手术更具优势,利于年轻医师上手,值得临床推广。 相似文献
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S. Xing X. Zhang J. H. Liu X. Huang P. Zhou 《Clinical and experimental immunology》2019,195(1):121-131
Recent experimental strategies to reduce graft-versus-host disease (GVHD) have focused largely on modifying innate immunity. Toll-like receptor (TLR)-driven myeloid differentiation primary response 88 (MyD88)-dependent signalling pathways that initiate adaptive immune function are also critical for the pathogenesis of GVHD. This study aimed to delineate the role of host MyD88 in the development of acute GVHD following fully major histocompatibility complex-mismatched allogeneic bone marrow transplantation (BMT). When myeloablated BALB/c MyD88 knock-out recipients were transplanted with C57BL/6 (B6) donor cells, they developed significantly more severe GVHD than wild-type (WT) BALB/c hosts. The increased morbidity and mortality in MyD88–/– mice correlated with increased serum levels of lipopolysaccharide and elevated inflammatory cytokines in GVHD target organs. Additionally, MyD88 deficiency in BMT recipients led to increased donor T cell expansion and more donor CD11c+ cell intestinal infiltration with apoptotic cells but reduced proliferation of intestinal epithelial cells compared with that in WT BMT recipients. Decreased expression of tight junction mRNA in epithelial cells of MyD88–/– mice suggested that MyD88 contributes to intestinal integrity. Cox-2 expression in the GVHD-targeted organs of WT mice is increased upon GVHD induction, but this enhanced expression was obviously inhibited by MyD88 deficiency. The present findings demonstrate an unexpected role for host MyD88 in preventing GVHD after allogeneic BMT. 相似文献
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