Increased EEG gamma power under exposure to drug-related cues: a translational index for cue-elicited craving in METH-dependent individuals.

BACKGROUND: This study explored the feasibility of using EEG gamma-band (30-49 Hz) power as an index of cue-elicited craving in METH-dependent individuals. METHODS: Twenty-nine participants dependent on methamphetamine (METH) and 30 healthy participants were instructed to experience a METH-related virtual reality (VR) social environment. RESULTS: Individuals with METH dependence showed significantly stronger self-reported craving and higher gamma power in a VR environment than healthy individuals. In the METH group, the VR environment elicited a significant increase in gamma power compared with the resting state. The METH group then received a VR counterconditioning procedure (VRCP), which was deemed useful in suppressing cue-induced reactivity. After VRCP, participants showed significantly lower self-reported craving scores and gamma power when exposed to drug-related cues than the first time. CONCLUSIONS: These findings suggest that the EEG gamma-band power may be a marker of cue-induced reactivity in patients with METH dependence.

Virtual-reality-based social cognition and interaction training for patients with schizophrenia: A preliminary efficacy study.

Background: Social cognition and interaction training (SCIT) is a psychosocial intervention program for patients with psychosis, designed to improve their social functioning by improving social cognition. Although the feasibility and efficacy of SCIT have been verified, patients with schizophrenia tend to suffer from motivational deficits and low treatment adherence. It has been suggested that using virtual reality (VR) technology might be effective in addressing these issues. In this study, we aimed to develop a VR-based SCIT and compare its efficacy with that of traditional SCIT. Materials and methods: We developed a novel VR-based social cognition and interaction training (VR-SCIT) that combines traditional SCIT (TR-SCIT) intervention with VR technology. Participants were randomly assigned in a 1:1:1 ratio to the VR-SCIT (n = 28), TR-SCIT (n = 30), or waiting-list groups (n = 29). All treatments were combined with treatment-as-usual. Assessments of social cognition (i.e., Chinese version of Face-Affective Identification Task, Chinese version of Social Cognition Screening Questionnaire) and social functioning (i.e., Chinese version of Personal and Social Performance Scale) were administered from baseline to post-intervention. Results: Patients receiving VR-SCIT and TR-SCIT showed a significantly greater improvement on the assessments of emotion perception (Cohen's d was 1.66, 0.55, and 0.10 for VR-SCIT, TR-SCIT, and Waiting-list, respectively), hostile attributional bias (Cohen's d was 0.48, 0.44, and 0.05 for VR-SCIT, TR-SCIT, and Waiting-list, respectively), metacognition (Cohen's d was 1.66, 0.76, and 0.06 for VR-SCIT, TR-SCIT, and waiting-list, respectively), and social functioning (Cohen's d was 1.09, 0.90, and 0.20 for VR-SCIT, TR-SCIT, and waiting-list, respectively) from baseline to post-intervention, compared to those in waiting-list group. Additionally, VR-SCIT showed an advantage over TR-SCIT in improving emotion perception and metacognition with higher treatment compliance. Conclusion: These preliminary findings indicate that VR-SCIT is a feasible and promising method for improving social cognition and social functioning in patients with schizophrenia.

A virtual reality counterconditioning procedure to reduce methamphetamine cue-induced craving.

The present work developed a virtual reality (VR) counterconditioning procedure (VRCP), and investigated its efficacy in treatment of cue-induced craving in individuals with methamphetamine (METH) dependence. In study 1, thirty-one patients diagnosed with METH dependence received VRCP, while twenty-nine METH-dependent patients in waiting-list group did not. In study 2, the VRCP was computerized as a VR treatment system. Six-hundred and twelve abstinent individuals with a history of METH dependence received the computerized VRCP, while two-hundred seventy-six abstinent individuals with a history of METH dependence in waiting-list group did not. Patients with METH dependence who received VRCP showed a significantly larger decrease on the score of METH-craving and METH-liking from baseline to follow-up assessments, compared to those who did not received VRCP. Participants received VRCP showed a significantly larger decrease in HRV indexes on time domain and non-linear domain from baseline to follow-up assessments during exposure to VR cues, compared to those in waiting-list group. These findings indicate that the counterconditioning procedure under VR environment may be a useful strategy in suppressing cue-induced reactivity for patients with METH dependence.

Epstein-Barr virus-encoded LMP1 regulated Pim1 kinase expression promotes nasopharyngeal carcinoma cells proliferation.

BACKGROUND: Epstein-Barr virus-encoded LMP1 plays a critical role in the carcinogenesis of nasopharyngeal carcinoma (NPC), but the mechanism remains elusive. We aimed to analyze the expression and clinical pathological significance of provirus integration site for Moloney murine leukemia virus 1 (Pim1) in clinical NPC, and to elucidate the effect of LMP1 on Pim1 expression and its mechanism. METHODS: Immunohistochemical staining was used to detect the expression of Pim1 in clinical NPC tissues and control nasopharyngeal chronic inflammation (NPI) tissues, and the correlation between Pim1 and clinical parameters of NPC patients was analyzed. The LMP1 stable expression cell line CNE1-LMP1-OV was constructed through infecting the well-differentiated nasopharyngeal carcinoma cells CNE1 with LMP1 overexpressing lentivirus. Then the in vivo experiments were conducted. RESULTS: Among 89 NPC patients, 48 cases (53.93%) were positive for Pim1, while only one case was Pim1 positive in 15 NPI controls (6.67%). Pim1 expression was not correlated with gender, age, smoking status and clinical classification of NPC patients, but positively correlated with T, N and M classification. CNE1-LMP1-OV cell line was successfully established, which displayed a higher cell proliferation ability and Pim1 expression. NF-κB inhibitor PDTC, PKC inhibitor GF109203X and STAT3 inhibitor Stattic significantly attenuated LMP1-induced Pim1 expression, and while AP-1 inhibitor SR11302 showed no inhibitory effect. Interestingly, Pim1 inhibitor quercetagetin significantly inhibited the proliferation of CNE1-LMP1-OV cells. CONCLUSION: LMP1 mediates Pim1 expression through NF-κB, PKC and STAT3 signaling, which promotes the proliferation of NPC cells and participate in the clinical progression of NPC.

Detection of patients with methamphetamine dependence with cue-elicited heart rate variability in a virtual social environment.

In the present study, we developed a methamphetamine (METH)-related virtual social environment to elicit subjective craving and physiological reactivity. Sixty-one male patients who were abstinent from METH use and 45 age-matched healthy males (i.e., normal controls) were recruited. The physiological electrocardiogram (ECG) signals were recorded before (resting-state condition) and during viewing of a METH-cue video in the virtual environment (cue-induced condition). The cue-induced subjective craving was measured with a visual analogue scale (VAS) for patients with METH dependence. The results indicated that the cue-induced condition elicited significant differences in heart rate variability (HRV) between patients with METH dependence and normal controls. The changes of HRV indexes on time domain and non-linear domain from the resting-state condition to the cue-induced condition were positively correlated with the score on VAS of METH craving. Using a supervised machine learning algorithm with the features extracted from HRV changes, our results showed that the discriminant model provided a high predictive power for distinguishing patients with METH dependence from normal controls. Our findings support that immersing subjects with METH dependence in a METH-related virtual social environment can successfully induce physiological reactivity, and cue-induced physiological signal changes may have a potential implication in clinical practice.

Selective impairments of alerting and executive control in HIV-infected patients: evidence from attention network test.

BACKGROUND: Attention ability can be subdivided into three functionally independent networks, i.e., alerting network, orienting network, and executive network. Previous literature has documented that deficits in attention are a common consequence of HIV infection. However, the precise nature of deficits of attention in HIV-infected patients is poorly understood. Accordingly, the aim of the study was to identify whether the HIV-infected patients showed a specific attention network deficit or a general attentional impairment. METHODS: We investigated 27 HIV-infected patients and 31 normal controls with the Attention Network Test (ANT). RESULTS: The patients exhibited less efficient alerting network and executive network than controls. No significant difference was found in orienting network effect between groups. Our results also indicate a tendency for poorer efficiency on alerting attention and executive attention in patients with CD4 ≤ 200. CONCLUSIONS: Our findings suggest that HIV-infected patients exhibited selective impairments of attention network of alerting and executive control. The link between lower CD4 T cell count and poorer attention network function imply the importance of starting antiretroviral therapy earlier to avoid irreversible neurocognitive impairment.

Family history of suicide and high motor impulsivity distinguish suicide attempters from suicide ideators among college students.

Suicide in college students has become an important public health issue in China. The aim of this study was to identify the differences between suicide attempters and suicide ideators based on a cross-sectional survey. Our results indicate that although female gender, positive screening for psychiatric illness, positive family history of suicide, elevated overall impulsivity, and elevated motor impulsivity were correlated with suicidal ideation, only positive family history of suicide and high motor impulsivity could differentiate suicide attempters from suicidal ideators. Future research with a longitudinal and prospective study design should be conducted to confirm these findings.

Theory-of-mind use in remitted schizophrenia patients: The role of inhibition and perspective-switching.

In social interaction, Theory of Mind (ToM) enables us to construct representations of others' mental states, and to use those representations flexibly to explain or predict others' behavior. Although previous literature has documented that schizophrenia is associated with poor ToM ability, little is known about the cognitive mechanisms underlying their difficulty in ToM use. This study developed a new methodology to test whether the difficulty in false-belief-use might be related to deficits in perspective-switching or impaired inhibitory control among 23 remitted schizophrenia patients and 18 normal controls. Patients showed a significantly greater error rate in a perspective-switching condition than a perspective-repeating position in a false-belief-use task, whereas normal controls did not show a difference between the two conditions. In addition, a larger main effect of inhibition was found in remitted schizophrenia patients than normal controls in both a false-belief-use task and control task. Thus, remitted schizophrenia patients' impairment in ToM use might be accounted for, at least partially, by deficits in perspective-switching and impaired inhibitory control.

Heparanase promotes human gastric cancer cells migration and invasion by increasing Src and p38 phosphorylation expression.

Gastric cancer is one of the most common cancers and it remains difficult to cure, primarily because most cancer stem like cells possess higher capability of invasion and metastasis. Heparanase acts as a master regulator of the aggressive tumor phenotype in part by enhancing expression of proteins and activating signaling molecules. There were less associated with heparanase of molecular biology mechanism in human gastric cancer. We first evaluated the endogenous expression of heparanase in human gastric cancer cell lines and found Heparanase expression higher in SGC-7901 than MGC-803. Using the technology of RNAi in SGC-7901 cells down regulated heparanase gene, and reduced SGC-7901 cells migration and invasion. On the other hand, recombinant heparanase protein added in MGC-803 cells enhanced MGC-803 cell migration and invasion. The elevated cell migration and invasion were impaired by treatment of Src inhibitor pp2 or p38 inhibitor SB 203580. We further found that Stable knockdown of heparanase in SGC-7901 cells decreased phosphorylation of Src and p38. The phosphorylation of p38 was inhibited in response to pp2 treatment while the addition of SB 203580 to SGC-7901 cells did not change phosphorylation of Src. These data suggest that heparanase facilitates invasion and migration of human gastric cancer cells probably through elevating phosphorylation of Src and p38.

Inhibition of Pim-1 attenuates the proliferation and migration in nasopharyngeal carcinoma cells.

OBJECTIVE: To explore the role of proto-oncogene Pim-1 in the proliferation and migration of nasopharyngeal carcinoma (NPC) cells. METHODS: Pim-1 expressions in NPC cell lines CNE1, CNE1-GL, CNE-2Z and C666-1 were examined by RT-PCR, western blotting and immunoflucesence, respectively. After CNE1, CNE1-GL and C666-1 cells were treated with different concentrations of Pim-1 special inhibitor, quercetagetin, the cell viability, colony formation rate and migration ability were analyzed. RESULTS: Pim-1 expression was negative in well-differentiated CNE1 cells, whereas expressed weakly positive in poor-differentiated CNE-2Z cells and strongly positive in undifferentiated C666-1 cells. Interestingly, CNE1-GL cells that derived from CNE1 transfected with an Epstein Barr virus latent membrane protein-1 over-expression plasmid displayed stronger expression of Pim-1. Treatment of CNE1-GL and C666-1 cells with quercetagetin significantly decreased the cell viability, colony formation rate and migration ability but not the CNE1 cells. CONCLUSIONS: These findings suggest that Pim-1 overexpression contributes to NPC proliferation and migration, and targeting Pim-1 may be a potential treatment for anti-Pim-1-expressed NPCs.

[Impact of up-regulating Ezrin expression by Epstein-Barr virus latent membrane protein 1 on metastasis ability of nasopharyngeal carcinoma cells].

BACKGROUND & OBJECTIVE: Ezrin, a cytoskeleton-related protein, contributes to the invasion and metastasis of tumors; our previous study had also shown that Epstein-Barr virus latent membrane protein 1 (EBV-LMP1) can promote the metastasis of nasopharyngeal carcinoma (NPC) cells. This study was to investigate whether EBV-LMP1 could change the expression of Ezrin and the role of Ezrin on the metastasis of NPC cells. METHODS: The expression of EBV-LMP1 and Ezrin in NPC cell lines CNE1 (well differentiated NPC cell line) and CNE1-GL (CNE1 cells stably transfected with EBV-LMP1) were detected by SP immunohistochemistry and Western blot. The adhesive abilities of CNE1, CNE1-GL and AntiEzrin-CNE1-GL (CNE1-GL cells pretreated with Ezrin antibody) cells were assessed by cell-matrix adhesion assay. The invasion and migration of these cell lines were investigated by Transwell method. RESULTS: Ezrin was not expressed in CNE1 cells while strongly expressed in CNE1-GL cells. The adhesive ability of CNE1-GL cells with matrix was significantly higher than those of CNE1 and AntiEzrin-CNE1-GL cells [adhesive rate: (89.38+/-6.12)% vs. (49.42+/-5.37)% and (56.94+/-4.08)%, P<0.001, P<0.05]. The invasion and migration of CNE1-GL cells were significantly higher than those of CNE1 and AntiEzrin-CNE1-GL cells (invasive cells: 107+/-11 vs. 27+/-3 and 38+/-4, P<0.001; migratory cells: 179+/-25 vs. 46+/-6 and 51+/-5, P<0.001). CONCLUSION: EBV-LMP1 contributes to the metastasis ability of CNE1 cells by up-regulating the expression of Ezrin.