This data indicated that altered level of 5 hmC might participate in process of hepatocarcinogenesis. Previous studies demonstrated that the decrease level of 5 hmC in tumors was due to the reduced expression of TET1/2/3 and IDH2 genes or tumor derived IDH1 and IDH2 mutations. In our study, we detected TET1/2/3 protein expression in 20 HCC patient samples by western blotting analysis. Our impulsive atd behaving aggressively result found that only TET1 expression was decreased in HCC tumors, as compared with non-tumor tissues. There were comparable expression of TET2 and TET3 in both of HCC tumors and nontumor tissues. This data indicated that TET1 may play an important role in conversion of 5 mC to 5 hmC in HCC. Recently, Lian et al reported that 5 hmC is lost in melanoma and rebuilding the 5 hmC landscape in melanoma cells by reintroducing active TET2 or IDH2 suppresses melanoma growth and increases tumor-free survival in animal models. It has been shown that different TET family members participate in different types of cancers as the putative tumor suppressor functions. Therefore, our observations provide potential molecular mechanism for the observed underlying global loss of 5 hmC and poor prognosis in human liver cancer. Taken together, our data showed that 5 hmC may be served as a prognostic marker for HCC and the decreased expression of TET1 is likely one of the mechanisms underlying 5 hmC loss in HCC. Animals will readily learn to fear a neutral cue such as a tone, following pairings of that cue with an aversive outcome like footshock. This learned fear of the tone can be reduced by extinction, a process where repeated presentations of the CS alone cause a decline in the fear responses usually elicited by that CS. Because extinction forms the basis of exposure-based therapies, which are the most widely used treatments for anxiety disorders, it is imperative to understand the underlying mechanisms of extinction. Critically, extinction does not completely erase the original learning, but at least in part acts to form a new inhibitory memory which masks expression of the original fear memory and reduces fear responses. As such, a number of factors can lead to retrieval of the original fear memory and the relapse of fear. For example, exposure to the CS outside of the extinction context causes the “renewal” of fear. Understanding the neural mechanisms of such renewal may provide insight into improving the long term outcomes of exposure therapy. The hippocampus is one structure important for contextual learning and memory and is also critical for fear renewal. Although the dorsal hippocampus and the more caudal ventral hippocampus differ substantially in regards to neuronal connectivity and function, both have been implicated in renewal. For example, initial studies demonstrated that reversible inactivation of the DH significantly impairs renewal. More recently the VH has also been implicated in mediating fear renewal, particularly through its direct projections to medial prefrontal cortex and basal amygdala. For example, Herry and colleagues showed that BA neurons active during renewal receive projections from VH, and disconnecting VH from either the mPFC or BA, or lesioning VH, disrupts renewal. Although this basic circuitry of fear renewal has begun to be elucidated, the mechanisms through which this circuit functions remain poorly understood. Recently, there has been increasing interest in the potential therapeutic merit of the kappa opioid receptor system in a range of psychiatric pathologies, including anxiety and depression. This is due in part to studies demonstrating the anxiolytic and antidepressant-like properties of KOR antagonists like norBNI. Furthermore, central norBNI impairs the acquisition of fear conditioning.