Comprehensive analysis of the relationship between competitive endogenous RNA (ceRNA) networks and tumor infiltrating-cells in hepatocellular carcinoma

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.     

Score du risque échocardiographique après un syndrome coronaire aigu

AimsIdentify the predective echocardiographic parameters of major cardiovascular events (death, ischemic recurrence, heart failure and rehospitalization) in-hospital and after six months of follow-up and to establish an echocardiographic prognostic score and to evaluate its prognostic value alone or in association with clinical risk scores.MethodsWe recruited 302 patients in intensive care unit of cardiology for ACS consecutively on admission, patients were assessed by clinical risk scores (GRACE, TIMI, CRUSADE) and resting doppler echocardiography, a follow-up of six months.ResultsThe echocardiographic risk score has four variables: LV-EF (RR = 0.931; 95%CI = 0.885–0.979, P < 0.01), RV-AF (RR = 0.951; 95%CI = 0.903–0.999, P < 0.05), iMAE-M-strain (RR = 1.226; 95%CI = 1.081–1.390, P < 0.01) and ULCs (RR = 1.151; 95%CI = 1.081–1.224, P < 0.01). Its discrimination capacity (AUC = 0.85), greater than that of the clinical risk scores, (GRACE: AUC = 0.72, TIMI: AUC = 0.71 and CRUSADE: AUC = 0.76).DiscussionThe risk stratification can be achieved using echocardiographic score easy to acquire and interpret in the clinical setting, with a stratification power higher than the clinical risk scores. The iconoclinical model makes it possible to select a group of heterogeneous patients by their clinical presentations and iconographic data at high risk but with an echoscore or clinical score weak or intermediate.ConclusionThe developed echocardiographic model could prove very useful in the decision-making process and optimization of the therapeutic strategy in some high-risk patients with acute coronary syndromes following an invasive strategy. It is appropriate for expert interpretation, yet relatively simple because it contains only four simple echocardiographic variables as predictors.     

Getting to Why: Adverse Childhood Experiences' Impact on Adult Health

Exposure to adverse childhood experiences (ACEs) contributes to 7 of the 10 leading causes of death in the United States as well as health risk behaviors, including substance abuse, physical inactivity, and high-risk sex behaviors. ACEs are traumatic childhood events that effect biopsychosocial health across the lifespan. It is vital for health care providers to view individuals from a trauma-informed perspective to guide best practice, but few are aware of ACEs, particularly those who treat adults. A review of the science of ACEs research, feasibility of screening for ACEs, and effective responses to trauma-impacted patients is presented in this report.     

血小板/淋巴细胞比值联合Grace评分对非ST段抬高型急性冠状动脉综合征院内心血管事件的预测价值

目的评估血小板/淋巴细胞比值(PLR)与非ST段抬高型急性冠状动脉综合征(NSTE-ACS)风险分层及院内预后的相关性及PLR联合Grace评分能否提高Grace评分对院内主要不良心血管事件(MACE)的预测价值。方法选取在青岛大学附属医院心内科住院被诊断为NSTE-ACS的患者372例。根据入院时PLR水平,分为低PLR组(PLR97.56)、中PLR组(97.56≤PLR≤133.32)、高PLR组(PLR133.32)各124例。比较三组之间基线临床资料、Grace评分及院内MACE的差异。依据有无MACE分为有MACE组36例,无MACE组336例,比较两组间基线临床资料、PLR、Grace评分的差异,评估PLR及Grace评分与院内MACE的相关性。应用受试者工作特征(ROC)曲线及DELONG方法评估PLR联合Grace评分与单用Grace评分对院内MACE预测价值的大小。结果(1)高、中、低PLR三组在Grace评分、院内MACE及急性心衰发生方面,差异均有统计学意义(P0.001),且高PLR组中PLR组低PLR组。(2)与无MACE组比较,有MACE组在年龄、尿酸、血小板计数、PLR、Gensini评分、Grace评分水平明显升高,舒张压、肌酐清除率及左心室射血分数指标水平明显降低,差异有统计学意义(P0.01)。(3)多因素Logistic回归分析显示PLR为NSTE-ACS患者发生院内MACE的独立预测因子(P0.01)。(4)ROC曲线分析PLR联合Grace评分预测院内MACE发生的AUC为0.828,单用Grace评分预测院内MACE的AUC为0.793;应用MEDCALC的DELONG方法对两者AUC比较发现差异有统计学意义(P0.05)。结论在NSTE-ACS患者中,PLR为发生院内MACE的独立预测因子,PLR联合Grace评分可显著提高Grace评分对院内MACE的预测价值。     

Platelets are important for the development of immune tolerance: Possible involvement of TGF‐β in the mechanism

Platelets have diverse roles in immune processes in addition to their key functions in haemostasis and thrombosis. Some studies imply that platelets may be possibly related to the immune tolerance induction. However, the role of platelets in the development of immune tolerance is not fully understood. The purpose of this study was to investigate the role of platelets in the development of regulatory mechanisms responsible for cutaneous inflammation using a mouse model of low zone tolerance (LZT). Mice were treated with 2,4,6‐trinitro‐1‐chlorobenzene (TNCB) 8 times every other day for tolerance induction with administration of anti‐platelet antibody or control antibody during the tolerance induction phase every 3 days. After the treatment for the tolerance induction, mice were sensitized and then challenged with TNCB. The contact hypersensitivity (CHS) was significantly decreased at 24 hours after challenge in the mice with LZT than in those without LZT. Platelet depletion via administration of anti‐platelet antibody reversed the inhibition of CHS and reduced the frequency of Foxp3⁺ Tregs in the inflamed skin and draining lymph nodes in mice with LZT. In addition, repeated low‐dose skin exposure resulted in elevated plasma levels of transforming growth factor (TGF)‐β1. Interestingly, platelet depletion reduced plasma TGF‐β1 levels of mice with LZT. Furthermore, the CHS response was reduced by administration of recombinant TGF‐β1 during platelet depletion in mice with LZT. Administration of anti‐TGF‐β antibody reversed the inhibition of the CHS responses. These results suggest that platelets are involved in the induction of immune tolerance via the release of TGF‐β1.