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Purpose: To characterize profile of cytokines in aqueous humour of common macular diseases during intravitreal anti‐VEGF therapy. Methods: Aqueous humour from eyes with central retinal vein occlusion (CRVO), branch retinal vein occlusion (BRVO), diabetic macular oedema (DME), neovascular age‐related macular degeneration (nAMD) or pathologic myopia associated choroidal neovascularization (pmCNV) was sampled prior to 1st (n = 144) and 2nd (n = 48) intravitreal anti‐VEGF therapy. Cytokines including vascular endothelium growth factor (VEGF), intercellular adhesion molecule 1 (ICAM‐1) and interleukin 6 (IL‐6) were quantitated and analysed along with retinal thickness data by optical coherence tomography (OCT) across two intravitreal injections and five macular disease types. Results: ICAM‐1, IL‐6 and VEGF are positively associated in the aqueous humour of naive eyes (r = 0.39–0.77, p = 0.018 to <0.0001). ICAM‐1, VEGF and IL‐6 were significantly higher in CRVO and DME while lowest in pmCNV (p < 0.0001). Reduction of central retinal thickness (CRT) as a favourable response to anti‐VEGF therapy was in the order of CRVO, BRVO, DME and nAMD/pmCNV (p < 0.0001). The strongest predictor for favourable CRT reduction was baseline CRT (p < 0.0001) followed by baseline ICAM‐1 (p = 0.04). After the 1st intravitreal anti‐VEGF therapy, VEGF in aqueous humour lowered significantly but ICAM‐1 and IL‐6 levels remained unchanged. ICAM‐1 was not predictive for CRT reduction following 2nd anti‐VEGF therapy. Conclusion: Rate of cytokine production is disease‐dependent and higher in CRVO and DME. Anatomical response to intravitreal anti‐VEGF therapy is disease‐specific and best in RVO patients. A combination therapy using both anti‐VEGF and anti‐inflammatory therapeutics may be superior to single anti‐VEGF therapy, at least for RVO and DME. [ABSTRACT FROM AUTHOR]

Summary: Background: The Barcelona Clinic Liver Cancer (BCLC) staging system is the most widely used staging system for hepatocellular carcinoma (HCC). However, the classifications of early (BCLC‐A) and intermediate (BCLC‐B) stage HCC remain controversial. Aim: To refine the staging of BCLC‐A and ‐B. Methods: A total of 986 patients with HCC undergoing liver resection from two institutions formed the training cohort, and 694 from another institution were the validation cohort. Time‐dependent receiver operating characteristic (ROC) curve analysis was performed to evaluate the performance of tumour size in predicting overall survival (OS), and determined the optimised cut‐off. Discriminatory performance was evaluated using Harrell's concordance index (C‐index). Results: Patients with multiple tumours exceeding Milan criteria but within up‐to‐seven criteria had similar OS and disease‐free survival (DFS) to those with multiple tumours meeting Milan criteria, and were assigned to the modified BCLC‐A stage. The area under the ROC curve of tumour size for predicting OS was 0.778, and the diameter of 7 cm was the optimal cut‐off to identify patients with single tumours who had higher OS than BCLC‐B stage patients. Due to the similar OS, patients with single HCCs >7 cm were assigned to the modified BCLC‐B stage. The C‐indexes of the modified BCLC classification for OS and DFS were higher compared to the original version. The findings were supported by the validation cohort. Conclusions: The modified staging of BCLC‐A and ‐B, based on single tumour >7 cm and multiple tumours beyond up‐to‐seven criteria, could be more accurate to predict the prognosis of HCC patients. Liver resection could benefit patients with resectable multifocal HCCs beyond the Milan criteria. [ABSTRACT FROM AUTHOR]

Linked Content This article is linked to Wang et al and Liem and Janssen papers. To view these articles, visit https://doi.org/10.1111/apt.15074 and https://doi.org/10.1111/apt.15121. [ABSTRACT FROM AUTHOR]

LINKED CONTENT: This article is linked to Tong et al papers. To view these articles, visit https://doi.org/10.1111/apt.17263 and https://doi.org/10.1111/apt.17423 [ABSTRACT FROM AUTHOR]

This study aims to clarify the relationship and mechanism between expression of autophagy-related protein P62 and prognosis of patients with hepatocellular carcinoma ( HCC) involving chronic hepatitis B virus ( HBV) infection and aflatoxin B1 ( AFB1) exposure. HCC patients who underwent resection were divided into three groups: HBV(+)/ AFB1(+) ( n = 26), HBV(+)/ AFB1(−) ( n = 68), and HBV(−)/ AFB1(−) ( n = 14). The groups were compared in terms of mRNA and protein levels of P62, disease-free survival ( DFS), and overall survival ( OS) and the expression of NRF2, Nqo1, and AKR7A3 in P62 high-expression and low-expression group. HBV(+)/ AFB1(+) group has lower DFS and OS, and higher P62 expression than in the other two groups. P62 expression generally correlated with elevated NRF2 and Nqo1 expression, and reduced AKR7A3 expression. Patients expressing high levels of P62 showed significantly lower DFS and OS rates than patients expressing low levels. HCC involving HBV infection and AFB1 exposure is associated with relatively high risk of tumor recurrence, and this poor prognosis may relate to high P62 expression. High P62 expression activates the NRF2 pathway, promotes tumor recurrence. The downregulation of AKR7A3 also reduced liver detoxification of aflatoxin B1. [ABSTRACT FROM AUTHOR]

Changhsingian (latest Permian) reefs are reported from the Wubaiti structure, northern Sichuan Basin of southwest China. Here, reefs grew along the platform margins and their tempo-spatial distribution and growth stages were determined based on the integration of detailed seismic profiles, well logs and core data. The Wubaiti reefs experienced two distinct development stages. The first episode of reef development was characterized by the growth of coral and sponge patch reefs during early-middle Changhsingian time. The second episode, the main growth phase of the Wubaiti reefs, occurred in late Changhsingian time when both sponges and algae acted as major reef-builders. These reef-building organisms disappeared in the Permian-Triassic mass extinction. Reef growth coincided with a local transgression event, but ceased due to a fall in local sea-level in the latest Changhsingian time. Dolostones of various parts of the Wubaiti reefs provide considerably high-quality reservoirs for natural gas in the Sichuan Basin. Copyright © 2012 John Wiley & Sons, Ltd. [ABSTRACT FROM AUTHOR]