OBJECTIVESTo study the relationship between intra-hepatic levels of regulated on activation, normal T-cell expressed and secreted (RANTES) and the disease severity and liver inflammatory degrees in patients with chronic hepatitis B and the possible mechanism of the changes of intra-hepatic levels of RANTES.

METHODSThe expression of RANTES of the livers was studied using immunohistochemical stainings and morphometric quantitative measurements in liver specimens from 10 normal subjects and 64 patients with chronic hepatitis B with different degrees of liver inflammation and different clinical severity. The expressions of RANTES protein and mRNA in cell line HepG2, HepG2.2.15 and HepG2 treated with 10 ng/ml TNFa at different times were quantified by ELISA and one-step RT-PCR.

RESULTSThe expression of RANTES of the livers in patients was significantly higher than that in the normal controls. Hepatic RANTES levels increased significantly and the increases were parallel to the increases of the severity of the hepatitis, from mild, moderate to severe hepatitis (the positive units were 3.7+/-1.5, 15.6+/-6.9, 24.0+/-4.0, 37.9+/-11.1, respectively) and from G0 degree to G4 degrees of liver inflammation (the positive units were 3.7+/-1.5, 15.0+/-5.7, 21.6+/-5.9, 30.3+/-8.2, 40.9+/-12.3, respectively). The expressions of RANTES protein and mRNA of HepG2.2.15 were higher than that of HepG2. RANTES protein and mRNA were induced in HepG2 by TNFa.

CONCLUSIONRANTES may have an important role in the pathogenesis of chronic hepatitis B. The elevation of hepatic RANTES may be caused by hepatitis B virus and TNFa.

Adolescent ; Adult ; Case-Control Studies ; Chemokine CCL5 ; metabolism ; Female ; Hep G2 Cells ; Hepatitis B virus ; Hepatitis B, Chronic ; metabolism ; Humans ; Liver ; metabolism ; Male ; Middle Aged ; Tumor Necrosis Factor-alpha ; Young Adult

OBJECTIVE It's known that post-retrieval extinction but not extinction alone could erase fear memory.However,whether the coding pattern of original fear engrams is remod-eled or inhibited remains largely unclear.Here we try to investigate whether the coding pattern of memory engrams is altered during post-retrieval extinction induced memory updating.METHODS To answer the question,by using activity-depen-dent neuronal-tagging technology,neuronal trac-ing technique combined with optogenetic manipu-lation and in vivo calcium imaging,we identified the fear and extinction cells in PrL and BLA and investigated the dynamic encoding of memory engram ensembles in the PrL and BLA during CS versus US initiated memory updating.RESULTS We found increased reactivation of engram cells in the prelimbic cortex and basolat-eral amygdala during memory updating.More-over,conditioned stimulus and unconditioned stimulu sinitiated memory updating depend on the engram cells reactivation in the prelimbic cor-tex or basolateral amygdala respectively.Finally,we found memory updating causes increased overlapping between fear and extinction cells and the original fear engrams encoding was altered during memory updating.CONCLUSION Our data provide the first evidence to show the overlapping ensembles between fear and extinc-tion cells and functional reorganization of original engrams underlying conditioned stimulus and unconditioned stimulus initiated memory updating.