Circular RNA circZFR Promotes Hepatocellular Carcinoma Progression by Regulating miR-375/HMGA2 Axis.

BACKGROUND: Mounting evidence indicates that circular RNAs (circRNAs) have vital roles in human diseases, especially in cancers. AIMS: The aim of this study was to explore the biological functions and underlying mechanism of circRNA zinc finger RNA binding (circZFR) in hepatocellular carcinoma (HCC). METHODS: The expression levels of circZFR, microRNA-375 (miR-375) and high mobility group A2 (HMGA2) were detected by qRT-PCR or western blot assay. Glycolytic metabolism was examined via the measurement of extracellular acidification rate, oxygen consumption rate, glucose uptake, lactate production, and ATP level. MTT assay and flow cytometry were used to assess cell proliferation and cell apoptosis, respectively. The interaction between miR-375 and circZFR or HMGA2 was verified by dual-luciferase reporter and RNA Immunoprecipitation (RIP) assays. The mice xenograft model was established to investigate the role of circZFR in vivo. RESULTS: CircZFR and HMGA2 were upregulated while miR-375 was downregulated in HCC tissues and cells. CircZFR silence inhibited HCC progression by inhibiting cell proliferation, glycolysis and tumor growth and promoting apoptosis. MiR-375 was a direct target of circZFR and its knockdown reversed the inhibitory effect of circZFR silence on the progression of HCC cells. Moreover, HMGA2 was a downstream target of miR-375, and miR-375 suppressed proliferation and glycolysis and induced apoptosis by targeting HMGA2 in HCC cells. Besides, circZFR acted as a molecular sponge of miR-375 to regulate HMGA2 expression. CONCLUSION: Knockdown of circZFR suppressed the progression of HCC by upregulating miR-375 and downregulating HMGA2, providing new insight into the pathogenesis of HCC.

[Alterations of brain network efficiency in patients with post-concussion syndrome].

OBJECTIVE: To discuss the alterations of brain network efficiency in patients with post-concussion syndrome. METHODS: A total of 23 patients from Anhui Provincial Hospital in the period from 2013/6 to 2014/3 who have had the concussion for 3 months were enrolled and 23 volunteers paired in sex, age and education were also enrolled as healthy controls. Comparisons of selective attention of both groups were conducted using Stroop Word-Color Test. The data of resting-state functional magnetic resonance imaging (fMRI) in both groups were collected and the data were dealt with Network Construction which is a part of GRETNA software to obtain the Matrix of brain network. Network analysis was used to obtain Global and Nodal efficiency, then independent t-test was used for statistical analyses of the value of Global and Nodal efficiency. RESULTS: The difference in Global efficiency of two groups in every threshold value had no statistical significance. Compared with healthy controls, the Nodal efficiencies in patients with post-concussion syndrome were significantly different in the brain regions as below: left orbital middle frontal gyrus, left posterior cingulate, left lingual, left thalamus, left superior temporal gyrus, right anterior cingulate, right posterior cingulate, right supramarginalgyrus. CONCLUSIONS: Compared with healthy controls, there is no significant changes of Globe efficiency in patients with post-concussion syndrome, and the brain function deficits in these patients may be caused by changes of Nodal efficiency in their brain network.

Comparison of efficacy and safety between transarterial chemoembolization (TACE) combined with lenvatinib versus TACE combined with sorafenib in the treatment of intermediate and advanced hepatocellular carcinoma.

OBJECTIVE: To compare the clinical effect and safety of transcatheter arterial chemoembolization (TACE) combined with lenvatinib versus TACE combined with sorafenib in the treatment of intermediate-advanced hepatocellular carcinoma. METHODS: In this retrospective study, 84 patients with intermediate-advanced hepatocellular carcinoma admitted to the First Affiliated Hospital of Anhui Medical University and the First Affiliated Hospital of USTC from June 2019 to June 2021 were enrolled. The control group was given TACE combined with sorafenib, and the experimental group was given TACE combined with lenvatinib. The clinical efficacy, tumor markers, liver function indexes, and occurrence of toxic and side effects were compared between the two groups. RESULTS: The disease control rate (DCR) and the objective remission rate (ORR) of the experimental group was higher than that of the control group, and the difference was statistically significant (P<0.05). Before treatment, there were no significant differences in the levels of alpha fetoprotein (AFP) and des-gamma carboxyprothrombin (DCP) between the two groups (both P>0.05); after the treatment, the levels of AFP and DCP in both groups decreased, and those in the experimental group were lower than the control group (all P<0.05). Before treatment, there were no significant differences in the levels of alanine aminotransferase (ALT), aspartate aminotransferase (AST) or lactate dehydrogenase (LDH), bilirubin (BIL) between the two groups (all P>0.05); after treatment, the levels of ALT, AST and LDH, BIL in both groups decreased, with the experimental group lower than the control group (all P<0.05). The overall survival (OS) and progression-free survival (PFS) in the experimental group were significantly higher than in the control group (both P<0.05). The incidences of symptoms of diarrhea, hand-foot syndrome, hypertension and rash in the experimental group were higher than those in the control group (all P<0.05). Fatigue, digestive tract reaction, bone marrow suppression and abnormal liver function of the two groups were similar (all P>0.05). CONCLUSION: Compared with TACE plus sorafenib, TACE plus lenvatinib can better control disease progression, reduce the levels of tumor markers, and stabilize the liver function of patients with intermediate-advanced hepatocellular carcinoma.

[A voxel-based morphometric analysis of brain gray matter in online game addicts].

OBJECTIVE: To explore the possible brain mechanism of online game addiction (OGA) in terms of brain morphology through voxel-based morphometric (VBM) analysis. METHODS: Seventeen subjects with OGA and 17 age- and gender-matched healthy controls (HC group) were recruited from Department of Psychology at our hospital during February-December 2011. The internet addiction scale (IAS) was used to measure the degree of OGA tendency. Magnetic resonance imaging (MRI) scans were performed to acquire 3-dimensional T1-weighted images. And FSL 4.1 software was employed to confirm regional gray matter volume changes. For the regions where OGA subjects showed significantly different gray matter volumes from the controls, the gray matter volumes of these areas were extracted, averaged and regressed against the scores of IAS. RESULTS: The OGA group had lower gray matter volume in left orbitofrontal cortex (OFC), left medial prefrontal cortex (mPFC), bilateral insula (INS), left posterior cingulate cortex (PCC) and left supplementary motor area (SMA). Gray matter volumes of left OFC and bilateral INS showed a negative correlation with the scores of IAS (r = -0.65, r = -0.78, P < 0.05). CONCLUSION: Gray matter volume changes are present in online game addicts and they may be correlated with the occurrence and maintenance of OGA.

[Impulsive decision-making behaviors in heroin addicts: a study of functional magnetic resonance imaging].

OBJECTIVE: To explore the brain regions associated with impulsive decision-making behaviors and interpret the nervous mechanism for addiction and relapse in heroin abusers. METHODS: Using the paradigms of psychological experiment, the subjects in both heroin addiction group (HA group) and normal control group (HC group) performed Iowa gambling task (IGT) and simultaneously underwent functional magnetic resonance imaging (fMRI) scan. All the above data were gathered and then analyzed by SPM5 software to explore both the brain regions and their functional changes correlated with impulsive decision-making. RESULTS: Evidence by IGT behavioral consequences demonstrated that the net scores in HC group increased with numbers of decision-making whereas no increment (fluctuating between-1 and 0) was observed in HA group. Based on the results of fMRI analysis, right orbitofrontal cortex (OFC), dorsolateral prefrontal cortex (DLPFC), left ventromedial prefrontal cortex (MPFC) and anterior cingulate cortex (ACC) were activated in both groups. But the right OFC was more active while the right DLPFC and left MPFC were weaker in HA group versus the HC group. Meanwhile, activation of right lenticular nucleus, right thalamus, right insula, hippocampus and left caudate nucleus were observed in HA group. CONCLUSION: Heroin abusers are incapable of impulsive decision-making in behavioral studies. Such a brain region as prefrontal cortex participates in the decision-making performance and control of impulsiveness. Functionally abnormal brain regions correlated with impulsive decision-making may be one cause of genesis, maintenance and relapse of heroin addiction.

Signal Alteration of Substantia Nigra on 3.0T Susceptibility-weighted Imaging in Parkinson's Disease and Vascular Parkinsonism.

Recent researches have found that 7 Tesla SWI can detect the alteration of substantia nigra hyperintensity in Parkinson's disease (PD), multiple system atrophy (MSA), and progressive supranuclear palsy (PSP). The aim of this study was to investigate whether 3 Tesla SWI (3T SWI) can visualize anatomical alterations occurring in a hyperintense structure of the substantia nigra in PD and vascular parkinsonism (VP), and whether the evaluation of abnormal signal can be used as a factor in the differential diagnosis of PD and VP. Using 3 Tesla MRI, we evaluated 38 healthy subjects, 33 patients with PD and 34 patients with VP. Two blinded readers independently assessed the images. We found that the dorsolateral nigral hyperintensity was absent in 31 of 33 patients with PD and 15 of 34 patients with VP. The dorsolateral nigral hyperintensity was present in 19 of 34 patients with VP and 35 of 38 healthy controls. Group comparisons of absence of dorsolateral nigral hyperintensity revealed significant differences between the patients with PD and those with VP (P<0.001). The sensitivity of SWI for PD was 93.9% and the specificity was 92.1%. Visual assessment of dorsolateral nigral hyperintensity on high-field SWI scans may serve as a new simple diagnostic imaging marker for PD. And our study results indicate that 3T SWI can be used as a tool to identify PD and VP.

Electrical stimulation reduces smokers' craving by modulating the coupling between dorsal lateral prefrontal cortex and parahippocampal gyrus.

Applying electrical stimulation over the prefrontal cortex can help nicotine dependents reduce cigarette craving. However, the underlying mechanism remains ambiguous. This study investigates this issue with functional magnetic resonance imaging. Thirty-two male chronic smokers received real and sham stimulation over dorsal lateral prefrontal cortex (DLPFC) separated by 1 week. The neuroimaging data of the resting state, the smoking cue-reactivity task and the emotion task after stimulation were collected. The craving across the cue-reactivity task was diminished during real stimulation as compared with sham stimulation. The whole-brain analysis on the cue-reactivity task revealed a significant interaction between the stimulation condition (real vs sham) and the cue type (smoking vs neutral) in the left superior frontal gyrus and the left middle frontal gyrus. The functional connectivity between the left DLPFC and the right parahippocampal gyrus, as revealed by both psychophysical interaction analysis and the resting state functional connectivity, is altered by electrical stimulation. Moreover, the craving change across the real and sham condition is predicted by alteration of functional connectivity revealed by psychophysical interaction analysis. The local and long-distance coupling, altered by the electrical stimulation, might be the underlying neural mechanism of craving regulation.

Changes in the default mode network in the prefrontal lobe, posterior cingulated cortex and hippocampus of heroin users.

The default mode network is associated with senior cognitive functions in humans. In this study, we performed independent component analysis of blood oxygenation signals from 14 heroin users and 13 matched normal controls in the resting state through functional MRI scans. Results showed that the default mode network was significantly activated in the prefrontal lobe, posterior cingulated cortex and hippocampus of heroin users, and an enhanced activation signal was observed in the right inferior parietal lobule (P < 0.05, corrected for false discovery rate). Experimental findings indicate that the default mode network is altered in heroin users.