The increasing evidences suggest that Immunoscore(IS), a combinatorial density analysis of CD8+ and CD3+ cells in the centre and invasive margin of tumour (CT and IM), has an advantage over the currently used tumour staging methods in a variety of tumours; however, IS in hepatocellular carcinoma remains unreported. In this study, IS was performed on serial sections from two HCC cohorts (total 449) and compared with current tumour staging systems. Kaplan–Meier curves illustrate a positive association between a higher IS (IS≥2) and longer survival of HCC patients. Although the IS was highly related to the outcome of patients, however, IS seems not to be the optimal prognostic factor when compared with the CD8CT. As noted, among CD8CT, CD8IM, CD3CT, CD3IM and IS, CD8CT, as an independent indicator, demonstrated the highest prognostic impact on both DFS and OS in our Cox multivariate regression analysis (P< 0.0001). In our study, the minimum cut-off value was 93 CD8CT cells per mm2, to be used to divide the patients into CD8CTHi group and CD8CTLo group in clinical settings. Our results suggest that CD8CT densities analysis notably improved the accuracy of survival prediction with convenience of clinical manipulation in HCC.

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Objectives: Several studies have investigated the association between serum uric acid (SUA) and the risks of coronary artery disease (CAD) but have yielded inconsistent results. The aim of this study was to assess whether there is an independent association of SUA with all-cause and cardiovascular disease (CVD) mortality in Chinese patients with CAD. Methods: A prospective cohort study of 1,799 patients was conducted. Cox regression models were used to estimate the association of SUA with the risk of death. Results: During a median follow-up of 3.9 years, 177 deaths were recorded and 126 of these were due to CVD. Patients in the highest SUA quartile had a 2.43-fold risk of all-cause mortality and a 2.44-fold risk of CVD mortality compared with those in the lowest quartile. In the subpopulation analysis, the association between SUA and mortality remained similar when participants were stratified by age, gender, body mass index and type of CAD. In contrast, we found a significant interaction with estimated glomerular filtration rate (eGFR). There was a stronger association between SUA and the risk of all-cause and CVD mortality among patients with an eGFR ≥60 ml/min/1.73 m², but no significant association was found in the population with an eGFR <60 ml/min/1.73 m². Conclusions: Elevated SUA levels were positively associated with an increased risk of all-cause and CVD mortality among CAD patients.

The pathogenesis of diabetic retinopathy (DR) is complicated, and there is no effective drug. Oxidative stress-induced human retinal microvascular endothelial cells (HRMECs) injury is one of the pathogenic factors for DR. Molecular switches are considered high-risk targets in disease progression. Identification of molecular switch is crucial to interpret the pathogenesis of disease and screen effective ingredients. In this study, a systematic process was executed to discover therapeutic candidates for DR based on HRMECs injury. First of all, the molecular mechanism of HRMECs oxidative stress injury was revealed by transcriptomics and network pharmacology. We found that oxidative stress was one of the pivotal pathogenic factors, which interfered with vascular system development, inflammation, cell adhesion, and cytoskeleton damaged HRMECs through crosstalk. Then, network topology analysis was used to recognize molecular switches. The results indicated that the Keap1-Nrf2-ARE signaling pathway was the molecular switch in HRMECs oxidative stress injury. On this basis, the HEK293-ARE overexpression cell line was applied to obtain 18 active traditional Chinese medicine (TCM) ingredients. Furthermore, andrographolide, one of the 18 candidates, was applied in the HRMECs oxidative stress model to evaluate the accuracy of the systematic process. The efficacy evaluation results showed that andrographolide could regulate oxidative stress, vascular system development, inflammation, adhesion, and skeleton tissue to inhibit HRMECs injury cooperatively. And its mechanism was related to the Nrf2 signaling pathway. Overall, our data suggest that the Nrf2 signaling pathway is the molecular switch in the HRMECs oxidative stress injury. 18 potential Nrf2 agonists are likely to be promising DR candidates.

Objective To investigate the association between serum cholesterol efflux capacity and all-cause and cardiovascular mortality in patients with coronary artery disease. Design Prospective cohort study. Setting Guangdong Coronary Artery Disease Cohort, established in 2008-2011. Participants 1 765 patients with coronary artery disease were followed-up for a median of 3.9 years. Main outcome measures Primary outcome was the association of baseline serum cholesterol efflux capacity with the risks of all-cause and cardiovascular mortality. Results: During 6 778 person-years of follow-up, 170 deaths were registered, 126 of which were caused by cardiovascular diseases. After multivariate adjustment for factors related to cardiovascular diseases, the hazard ratios (95% confidence intervals) across quartiles of serum cholesterol efflux capacity were 1.00, 0.75 (0.51-1.10), 0.51 (0.33-0.81) and 0.43 (0.25-0.73) for all-cause mortality ( P = 0.003), and 1.00, 0.76 (0.49-1.18), 0.37 (0.21-0.65), and 0.25 (0.12-0.52) for cardiovascular mortality ( P < 0.001). Adding serum cholesterol efflux capacity to a model containing traditional cardiovascular risk factors significantly increases its discriminatory power and predictive ability for all-cause (area under receiver operating characteristic curve 0.68 versus 0.61, P < 0.001; net reclassification improvement 14.5%, P = 0.001) and cardiovascular (area under receiver operating characteristic curve 0.71 versus 0.63, P < 0.001; net reclassification improvement 18.4%, P < 0.001) death, respectively. Conclusions: Serum cholesterol efflux capacity may serve as an independent measure for predicting all-cause and cardiovascular mortality in patients with coronary artery disease.