Expression and clinical significance of VISTA, B7-H3, and PD-L1 in glioma.

Immune checkpoint (IC) therapy has led to a breakthrough in cancer treatment. However, the interaction of ICs is controversial in glioma. We detected features of ICs using transcriptome data and a multicolor immunofluorescence assay. We discovered that B7-H3 increased with grade and age and predicted worse overall survival (OS) at the transcriptional and proteomic levels. VISTA and PD-L1 were associated with OS and grade at the RNA level. At the protein level, VISTA was primarily expressed in tumor cells and TAMs. B7-H3 and VISTA were positively correlated with PD-L1. There was a strong correlation between PD-L1 and CD3 and between VISTA and IBA-1. PD-L1 was coexpressed with T cells. VISTA was coexpressed with TAMs. In T cells, we found a strong correlation in ICs, which worsened in TAMs and tumor cells. In conclusion, B7-H3 is a vital prognostic target for immunotherapy. We provided a potential mechanism for the immunosuppressive microenvironment in glioma.

[Correlation of K-ras Gene Mutations with the Protein Expressions of TAK1 and MAP4K2 in Colorectal Cancer].

OBJECTIVE: To analyze the correlation of K-ras gene mutations with the protein expressions of transforming growth factor-ß activating kinase 1 (TAK1) protein and mitogen-activated protein kinase kinase kinase kinase 2 (MAP4K2) protein in colorectal cancer. METHODS: K-ras gene mutations were detected by DNA sequencing analysis, and the expressions of TAK1 protein and MAP4K2 protein were detected by immunohistochemical method in 76 cases of colorectal cancer tissues. RESULTS: In 76 cases of colorectal cancer tissues, the mutation rate of K-ras gene was 32.89% (25 cases), and K-ras gene mutations were correlated with the degrees of cell differentiation ( P<0.05). The positive rates of TAK1 protein and MAP4K2 protein were 48.68% and 46.05%, respectively. The protein expressions of TAK1 and MAP4K2 were positively correlated with the degrees of cell differentiation and lymph node metastases, respectively ( P<0.05). There was no correlation between K-ras gene mutation and either TAK1 protein or MAP4K2 protein expression ( P>0.05). In 25 cases of colorectal cancer with K-ras mutation, the expression of TAK1 protein was positively correlated with the expression of MAP4K2 protein ( P<0.05). CONCLUSION: K-ras gene mutation, TAK1 and MAP4K2 protein expressions were related to the degree of differentiation of colorectal cancer, but not to the depth of invasion. In colorectal cancer with K-ras gene mutation, the expression of TAK1 protein was positively correlated with the expression of MAP4K2 protein.

Reduced hepatic AdipoR2 by increased glucocorticoid mediates effect of psychosocial stress to elevate serum cholesterol.

Understanding the effects of psychosocial stress on serum cholesterol may offer valuable insights into the relationship between psychological disorders and endocrine diseases. However, these effects and their underlying mechanisms have not been elucidated yet. Here we show that serum corticosterone, total cholesterol and low-density lipoprotein cholesterol (LDL-C) are elevated in a mouse model of psychosocial stress. Furthermore, alterations occur in AdipoR2-mediated AMPK and PPARα signaling pathways in liver, accompanied by a decrease in LDL-C clearance and an increase in cholesterol synthesis. These changes are further verified in wild-type and AdipoR2 overexpression HepG2 cells incubated with cortisol and AdipoR agonist, and are finally confirmed by treating wild-type and hepatic-specific AdipoR2 overexpression mice with corticosterone. We conclude that increased glucocorticoid mediates the effects of psychosocial stress to elevate serum cholesterol by inhibiting AdipoR2-mediated AMPK and PPARα signaling to decrease LDL-C clearance and increase cholesterol synthesis in liver.

Male adolescents with Interleukin 10 rs1800872 AA genotype had higher prevalence and slower recoveries of post-traumatic stress disorder at late stage of a follow-up.

BACKGROUND: Pathophysiological mechanisms of post-traumatic stress disorder (PTSD) are elusive and heterogeneous relationships have been reported among PTSD, Interleukin 10 (IL-10), and other factors after stresses. The present study aimed to longitudinally investigate associations of PTSD with environmental factors and genetic variation of rs1800872 at IL-10 gene. METHODS: Symptoms of PTSD were measured by PTSD Checklist-Civilian Version (PCL-C) in 462 high school students at 6, 12, and 18 months after Wenchuan earthquake in China. Genotypes of IL-10 rs1800872 were identified by polymerase chain reaction-restriction fragment length polymorphism analysis and verified by DNA sequencing. RESULTS: AA homozygotes had higher PTSD prevalence than C allele carriers only at 18 months in male, but not female subjects. PTSD prevalence at 18 months was lowered in all subjects except male AA homozygotes when compared to that at 6 months, and only in female C allele carriers when compared to that at 12 months. PCL-C scores at 18 months were decreased in all students but not in male AA homozygotes when compared to those at 6 months. IL-10 rs1800872 was associated with PTSD at 18 months. Patterns of predictors of PCL-C scores were different between AA homozygotes and C allele carriers at different times during the follow-up. CONCLUSION: There were different reciprocal actions of IL-10 rs1800872 with other potential factors or predictors on PTSD in a time-course and gender-dependent manner. Male students with IL-10 rs1800872 AA genotype had higher prevalence and slower recoveries of PTSD at late stage of the follow-up, suggesting requirements of special psychiatric care or drug supplementation at this stage.

Alpha spectral power and coherence in the patients with mild cognitive impairment during a three-level working memory task / 浙江大学学报（英文版）（B辑：生物医学和生物技术）

<p><b>OBJECTIVE</b>The functional relationship between calculated alpha band spectral power and inter-/intra-hemispheric coherence during a three-level working memory task of patients with mild cognitive impairment (MCI) was investigated.</p><p><b>METHODS</b>Subjects included 35 MCI patients according to the DSM-IV criteria (mean age: 62.3, SD: 6.5) and 34 healthy controls (mean age: 57.4, SD: 4.0) were selected from the community at large. All subjects performed a simple calculation and recall task with three levels of working memory load while electroencephalograph (EEG) signal was recorded. The spectral EEG power was computed over alpha1 (8.0-10.0 Hz) and alpha2 (10.5-13.0 Hz) frequency bands and was compared between rest stage and working memory processing stage by two-way ANOVA. Post hoc testing analyzed the differences between each two levels of working memory load during task processing. The inter-hemisphere EEG coherence of frontal (F3-F4), central (C3-C4), parietal (P3-P4), temporal (T5-T6) as well as occipital (O1-O2) was compared between MCI patients and normal controls. The EEG signals from F3-C3, F4-C4, C3-P3, C4-P4, P3-O1, P4-O2, T5-C3, T6-C4, T5-P3 and T6-P4 electrode pairs resulted from the intra-hemispheric action for alpha1 and alpha2 frequency bands.</p><p><b>RESULT</b>There was significantly higher EEG power from MCI patients than from normal controls both at rest and during working memory processing. Significant differences existed between rest condition and three-level working memory tasks (P<0.001). The inter- and intra-hemispheric coherence during working memory tasks showed a "drop to rise" tendency compared to that at rest condition. There was significantly higher coherence in MCI patients than in the controls. When task difficulties increased, the cortical connectivity of intra-hemispheric diminished while the inter-hemispheric connectivity dominantly maintained the cognitive processing in MCI patients.</p><p><b>CONCLUSION</b>The results of the present study indicate that the alpha frequency band may be the characteristic band in distinguishing MCI patients from normal controls during working memory tasks. MCI patients exhibit greater inter-hemispheric connectivity than intra-hemispheric connectivity when memory demands increase. MCI patients mobilize a compensatory mechanism to maintain the processing effectiveness while the processing efficiency is reduced.</p>

Inter- and intra-hemispheric EEG coherence in patients with mild cognitive impairment at rest and during working memory task / 浙江大学学报（英文版）（B辑：生物医学和生物技术）

<p><b>OBJECTIVE</b>To assess functional relationship by calculating inter- and intra-hemispheric electroencephalography (EEG) coherence at rest and during a working memory task of patients with mild cognitive impairment (MCI).</p><p><b>METHODS</b>The sample consisted of 69 subjects: 35 patients (n=17 males, n=18 females; 52-71 years old) and 34 normal controls (n=17 males, n=17 females; 51~63 years old). Mini-mental state examination (MMSE) of two groups revealed that the scores of MCI patients did not differ significantly from those of normal controls (P>0.05). In EEG recording, subjects were performed at rest and during working memory task. EEG signals from F3-F4, C3-C4, P3-P4, T5-T6 and O1-O2 electrode pairs are resulted from the inter-hemispheric action, and EEG signals from F3-C3, F4-C4, C3-P3, C4-P4, P3-O1, P4-O2, T5-C3, T6-C4, T5-P3 and T6-P4 electrode pairs are resulted from the intra-hemispheric action for delta (1.0-3.5 Hz), theta (4.0-7.5 Hz), alpha-1 (8.0-10.0 Hz), alpha-2 (10.5-13.0 Hz), beta-1 (13.5-18.0 Hz) and beta-2 (18.5-30.0 Hz) frequency bands. The influence of inter- and intra-hemispheric coherence on EEG activity with eyes closed was examined using fast Fourier transformation from the 16 sampled channels.</p><p><b>RESULTS</b>During working memory tasks, the inter- and intra-hemispheric EEG coherences in all bands were significantly higher in the MCI group in comparison with those in the control group (P<0.05). However, there was no significant difference in inter- and intra-hemispheric EEG coherences between two groups at rest.</p><p><b>CONCLUSION</b>Experimental results comprise evidence that MCI patients have higher degree of functional connectivity between hemispheres and in hemispheres during working condition. It suggests that MCI may be associated with compensatory processes during working memory tasks between hemispheres and in hemispheres. Moreover, failure of normal cortical connections may exist in MCI patients.</p>

Abnormal cortical functional connections in Alzheimer's disease: analysis of inter- and intra-hemispheric EEG coherence / 浙江大学学报（英文版）（B辑：生物医学和生物技术）

To investigate inter- and intra-hemispheric electroencephalography (EEG) coherence at rest and during photic stimulation of patients with Alzheimer's disease (AD). Thirty-five patients (12 males, 23 females; 52 to approximately 64 y) and 33 sex- and age-matched controls (12 males, 21 females; 56 to approximately 65 y) were recruited in the present study. EEG signals from C3-C4, P3-P4, T5-T6 and O1-O2 electrode pairs resulted from the inter-hemispheric action, and EEG signals from C3-P3, C4-P4, P3-O1, P4-O2, C3-O1, C4-O2, T5-O1 and T6-O2 electrode pairs resulted from the intra-hemispheric action. The influence of inter- and intra-hemispheric coherence on EEG activity with eyes closed was examined, using fast Fourier transformation from the 16 sampled channels. The frequencies of photic stimulation were fixed at 5, 10 and 15 Hz, respectively. The general decrease of AD patients in inter- and intra-hemispheric EEG coherence was more significant than that of the normal controls at the resting EEG, with most striking decrease observed in the alpha-1 (8.0-9.0 Hz) and alpha-2 (9.5-12.5 Hz) bands. During photic stimulation, inter- and intra-hemispheric EEG coherences of the AD patients having lower values in the alpha (9.5-10.5 Hz) band than those of the control group. It suggests that under stimulated and non-stimulated conditions, AD patients had impaired inter- and intra-hemispheric functional connections, indicating failure of brain activation in alpha-related frequency.

Study on EEG power and coherence in patients with mild cognitive impairment during working memory task / 浙江大学学报（英文版）（B辑：生物医学和生物技术）

To investigate the features of electroencephalography (EEG) power and coherence at rest and during a working memory task of patients with mild cognitive impairment (MCI). Thirty-five patients (17 males, 18 females; 52-71 years old) and 34 sex- and age-matched controls (17 males, 17 females; 51-63 years old) were recruited in the present study. Mini-Mental State Examination (MMSE) of 35 patients with MCI and 34 normal controls revealed that the scores of MCI patients did not differ significantly from those of normal controls (P>0.05). Then, EEGs at rest and during working memory task with three levels of working memory load were recorded. The EEG power was computed over 10 channels: right and left frontal (F3, F4), central (C3, C4), parietal (P3, P4), temporal (T5, T6) and occipital (O1, O2); inter-hemispheric coherences were computed from five electrode pairs of F3-F4, C3-C4, P3-P4, T5-T6 and O1-O2 for delta (1.0-3.5 Hz), theta (4.0-7.5 Hz), alpha-1 (8.0-10.0 Hz), alpha-2 (10.5 -13.0 Hz), beta-1 (13.5-18.0 Hz) and beta-2 (18.5-30.0 Hz) frequency bands. All values of the EEG power of MCI patients were found to be higher than those of normal controls at rest and during working memory tasks. Furthermore, the values of EEG power in the theta, alpha-1, alpha-2 and beta-1 bands of patients with MCI were significantly high (P<0.05) in comparison with those of normal controls. Correlation analysis indicated a significant negative correlation between the EEG powers and MMSE scores. In addition, during working memory tasks, the EEG coherences in all bands were significantly higher in the MCI group in comparison with those in the control group (P<0.05). However, there was no significant difference in EEG coherences between two groups at rest. These findings comprise evidence that MCI patients have higher EEG power at rest, and higher EEG power and coherence during working conditions. It suggests that MCI may be associated with compensatory processes at rest and during working memory tasks. Moreover, failure of normal cortical connections may be exist in MCI patients.