Hepatocellular carcinoma (HCC) is one of the fastest‐rising causes of cancer‐related death worldwide, but its deficiency of specific biomarkers and therapeutic targets in the early stages lead to severe inadequacy in the early diagnosis and treatment of HCC. Covalently closed circular RNA (circRNA), which was once considered an aberrant splicing by‐product, is now drawing new interest in cancer research because of its remarkable functionality. Beneath the surface of the dominant functional proteins events, a hidden circRNA‐centric noncoding regulatory RNAs network active in the very early stage of HCC is here revealed by a genome‐wide analysis of mRNA, circRNA, and microRNA (miRNA) expression profiles. Circ‐CDYL (chromodomain Y like) is specifically up‐regulated in the early stages of HCC and therefore contributes to the properties of epithelial cell adhesion molecule (EPCAM)‐positive liver tumor‐initiating cells. Circ‐CDYL interacts with mRNAs encoding hepatoma‐derived growth factor (HDGF) and hypoxia‐inducible factor asparagine hydroxylase (HIF1AN) by acting as the sponge of miR‐892a and miR‐328‐3p, respectively. Subsequently, activation of the phosphoinositide 3‐kinase (PI3K)‐AKT serine/threonine kinase‐mechanistic target of rapamycin kinase complex 1/β‐catenin and NOTCH2 pathways, which promote the expression of the effect proteins, baculoviral IAP repeat containing 5 (BIRC5 or SURVIVIN) and MYC proto‐oncogene, is influenced by circ‐CDYL. A treatment incorporating circ‐CDYL interference and traditional enzyme inhibitors targeting PI3K and HIF1AN demonstrated highly effective inhibition of stem‐like characteristics and tumor growth in HCC. Finally, we demonstrated that circ‐CDYL expression or which combined with HDGF and HIF1AN are both independent markers for discrimination of early stages of HCC with the odds ratios of 1.09 (95% confidence interval [CI], 1.02‐1.17) and 124.58 (95% CI, 13.26‐1170.56), respectively. Conclusion: These findings uncover a circRNA‐centric noncoding regulatory RNAs network in the early stages of HCC and thus provide a possibility for surveillance and early treatment of HCC.

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Citation: Wang W S, Jin J L, Ding J, et al. A new approach to water resources system assessment --set pair analysis method.Most traditional assessment methods, which have complicated mathematic formulas, are difficult for calculation and application in water resources system assessment. A new approach to water resources system assessment, the set pair analysis method (SPAM), has been proposed based on the principle of set pair analysis (SPA). The basic ideals and steps of SPAM are discussed. The proposed method can take fuzzy property of threshold values for grade standards into full account and avoid determining the discrepancy uncertainty coefficient i or i 1 , i 2 , i 3 , … in SPA. The presented method is simple in concept, convenient to calculate and feasible for application. Two case studies of water resources assessment have been made. The results show that the proposed method is satisfactory.water resources, assessment, set pair analysis, connection degree Regional water resources system assessment is a complex dynamic system [1] because of the influence of many factors, such as regional physical geography, socioeconomy and so on. For this assessment two key issues must be addressed. One is the reasonable determination of its index systems and standard grades; the other is development of its method or model based on the relationship between the values of various indexes' standard grades and those of sample's indexes. Concerning the current methods of water resources system assessment, there are mainly principal component method, grey method [2] , fuzzy method [3] , projection pursuit method [4] , matter element method [5] and so on. Though these methods can be applied in practice to a certain degree, common defects may exist such as their complexity, a lot of mathematical knowledge required, implementation difficulty and inconvenient application. Based on the point of view in unity and opposition, the Chinese scholar ZHAO KeQin has first put forward set pair analysis (SPA), which has been used widely in many fields of mathematics, physics, information management, economy, resources and environment [6] . The results from our researches have fully indicated that SPA may be considered as a new uncertainty analysis approach and can be used to analyze the internal relationship of a given system from both its whole and part. During recent years, we have introduced SPA into hydrology and water resources field and carried out a systematic study on its application [7] in many aspects such as computation, forecast, assessment and so on, in which the applications to water resources system assessment have made some progress [7][8][9][10][11] . However, so far as the method for assessment based on SPA is concerned, there is not a reasonable, systematic and acceptable framework. Moreover, its simplicity and effectiveness in practice may not be fully exhibited. In this paper we attempt to develop a new approach to water resources system assessment for the framework based on SPA. The proposed approach, namely the set pair...

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MWA results in lower DFS rates than RES for HCC conforming to Milan criteria. However, the OS rates are comparable between the two therapies. For solitary HCC ≤ 3 cm, MWA is as effective as RES.