Changes of the Brain Causal Connectivity Networks in Patients With Long-Term Bilateral Hearing Loss.

It remains poorly understood how brain causal connectivity networks change following hearing loss and their effects on cognition. In the current study, we investigated this issue. Twelve patients with long-term bilateral sensorineural hearing loss [mean age, 55.7 ± 2.0; range, 39-63 years; threshold of hearing level (HL): left ear, 49.0 ± 4.1 dB HL, range, 31.25-76.25 dB HL; right ear, 55.1 ± 7.1 dB HL, range, 35-115 dB HL; the duration of hearing loss, 16.67 ± 4.5, range, 3-55 years] and 12 matched normally hearing controls (mean age, 52.3 ± 1.8; range, 42-63 years; threshold of hearing level: left ear, 17.6 ± 1.3 dB HL, range, 11.25-26.25 dB HL; right ear, 19.7 ± 1.3 dB HL, range, 8.75-26.25 dB HL) participated in this experiment. We constructed and analyzed the causal connectivity networks based on functional magnetic resonance imaging data of these participants. Two-sample t-tests revealed significant changes of causal connections and nodal degrees in the right secondary visual cortex, associative visual cortex, right dorsolateral prefrontal cortex, left subgenual cortex, and the left cingulate cortex, as well as the shortest causal connectivity paths from the right secondary visual cortex to Broca's area in hearing loss patients. Neuropsychological tests indicated that hearing loss patients presented significant cognitive decline. Pearson's correlation analysis indicated that changes of nodal degrees and the shortest causal connectivity paths were significantly related with poor cognitive performances. We also found a cross-modal reorganization between associative visual cortex and auditory cortex in patients with hearing loss. Additionally, we noted that visual and auditory signals had different effects on neural activities of Broca's area, respectively. These results suggest that changes in brain causal connectivity network are an important neuroimaging mark of cognitive decline. Our findings provide some implications for rehabilitation of hearing loss patients.

Abnormal neural activities of directional brain networks in patients with long-term bilateral hearing loss.

The objective of the study is to provide some implications for rehabilitation of hearing impairment by investigating changes of neural activities of directional brain networks in patients with long-term bilateral hearing loss. Firstly, we implemented neuropsychological tests of 21 subjects (11 patients with long-term bilateral hearing loss, and 10 subjects with normal hearing), and these tests revealed significant differences between the deaf group and the controls. Then we constructed the individual specific virtual brain based on functional magnetic resonance data of participants by utilizing effective connectivity and multivariate regression methods. We exerted the stimulating signal to the primary auditory cortices of the virtual brain and observed the brain region activations. We found that patients with long-term bilateral hearing loss presented weaker brain region activations in the auditory and language networks, but enhanced neural activities in the default mode network as compared with normally hearing subjects. Especially, the right cerebral hemisphere presented more changes than the left. Additionally, weaker neural activities in the primary auditor cortices were also strongly associated with poorer cognitive performance. Finally, causal analysis revealed several interactional circuits among activated brain regions, and these interregional causal interactions implied that abnormal neural activities of the directional brain networks in the deaf patients impacted cognitive function.

Long noncoding RNA GIHCG promotes hepatocellular carcinoma progression through epigenetically regulating miR-200b/a/429.

Long noncoding RNAs (lncRNAs) have been reported to play pivotal roles in a variety of cancers. However, lncRNAs involved in hepatocellular carcinoma (HCC) initiation and progression remain largely unclear. In this study, we identified an lncRNA gradually increased during hepatocarcinogenesis (lncRNA-GIHCG) using publicly available microarray data. Our results further revealed that GIHCG is upregulated in HCC tissues in comparison with adjacent non-tumor tissues. High GIHCG expression is correlated with large tumor size, microvascular invasion, advanced BCLC stage, and poor survival of HCC patients. Functional experiments showed that GIHCG promotes HCC cells proliferation, migration, and invasion in vitro, and promotes xenografts growth and metastasis in vivo. Mechanistically, we demonstrated that GIHCG physically associates with EZH2 and the promoter of miR-200b/a/429, recruits EZH2 and DNMT1 to the miR-200b/a/429 promoter regions, upregulates histone H3K27 trimethylation and DNA methylation levels on the miR-200b/a/429 promoter, and dramatically silences miR-200b/a/429 expression. Furthermore, the biological functions of GIHCG on HCC are dependent on the silencing of miR-200b/a/429. Collectively, our results demonstrated the roles and functional mechanisms of GIHCG in HCC, and indicated GIHCG may act as a prognostic biomarker and potential therapeutic target for HCC. KEY MESSAGE: lncRNA-GIHCG is upregulated in HCC and associated with poor survival of patients. GIHCG significantly promotes tumor growth and metastasis of HCC. GIHCG physically associates with EZH2. GIHCG upregulates H3K27me3 and DNA methylation levels on the miR-200b/a/429 promoter. GIHCG epigenetically silences miR-200b/a/429 expression.

MicroRNA-147 suppresses human hepatocellular carcinoma proliferation migration and chemosensitivity by inhibiting HOXC6.

Patients with hepatocellular carcinoma (HCC) experience poor prognosis and low survival rates. In this study, we explored the molecular mechanism of microRNA-147 (miR-147) in regulating human HCC. We firstly used quantitative RT-PCR (qRT-PCR) to compare the expression levels of miR-147 between 7 HCC and two normal liver cell lines, as well as 10 paired primary HCC tissues and their adjacent non-carcinoma tissues. We found miR-147 was down-regulated in both HCC cell lines and primary HCCs tissues. HCC cell lines HepG2 and HuH7 were transfected with lentiviral vector of miR-147 mimics. We found overexpressing miR-147 significantly inhibited HCC in vitro proliferation and migration, increased 5-FU chemosensitivity, and reduced in vivo tumorigenicity. Luciferase, qRT-PCR and western blot assays showed that HOXC6 was the downstream target of miR-147, and both gene and protein levels of HOXC6 were down-regulated by miR-147 in HCC cells. SiRNA mediated HOXC6 knockdown inhibited in vitro proliferation and migration, and increased 5-FU chemosensitivity in HCC. On the other hand, HOXC6 overexpression reversed the inhibitory effect of miR-147 on HCC in vitro proliferation. Therefore, our results suggest that miR-147 can modulates HCC development through the regulation on HOXC6.

[Effects of interferon on hepatic intercellular adhesion molecule-1 expression in patients with chronic hepatitis B].

OBJECTIVE: To investigate the effects of interferon -alpha1b (IFN-alpha1b) on hepatic intercellular adhesion molecule-1 (ICAM-1) expression and serum HBV DNA in patients with chronic hepatitis B. METHODS: Before and 6 months after IFN-alpha1b treatment, liver biopsy was performed in patients with chronic hepatitis B to detect the expression of ICAM-1 in the liver tissues using immunohistochemistry. Serum HBV load was detected with real-time fluorescence polymerase chain reaction. RESULT: CAM-1 expression in the liver tissue was significantly down-regulated after IFN treatment in patients with severe and moderate chronic hepatitis B (P<0.05). No significant variation was noted in the expression of ICAM-1 in the livers of patients with mild chronic hepatitis B after the treatment (P>0.05). In the patients weakly positive for ICAM-1 expression (+), serum HBV DNA varied scarcely after the treatment (P>0.05), while in the patients with strong ICAM-1 positivity (++, +++, or ++++), significant variation of serum HBV DNA occurred after the treatment (P<0.05 or P<0.01). CONCLUSION: The therapeutic effect of IFN-alpha1b is associated with the expression of ICAM-1 in the hepatocytes, and its expression might enhance the effects of IFN on HBV DNA in patients with chronic hepatitis B.

[The protective effect of high density lipoprotein on the lung function of rats with severe burns].

OBJECTIVE: To explore the protective effect of high density lipoprotein on the lung function of rats with severe burns. METHODS: One hundred and thirty-five Wistar rats were employed in the study and were randomly divided into control (n = 15, without injury), burn (n = 60, with 30% TBSA full-thickness burn on the back) and experimental [(n = 60, with the injection of HDL (80 mg/kg) via the caudal vein immediately after burns)] groups. The rats in the latter two groups were resuscitated with intraperitoneal isotonic saline (50 ml/kg) 30 minutes after burns. The serum content of ICAM-1 and TNF-alpha as well as the blood content of PCO2 and PO2 of the rats in burn and experimental groups were determined at 12, 24, 48 and 72 post-burn hours (PBH) and in control group. The pathological changes in the lung tissue of the rats in all groups were observed under light microscope and electronic microscope at 48 PBH. RESULTS: PCO2 and the contents of ICAM-1 and TNF-alpha in burn group were significantly higher, but the PO2 was lower than those in control group at each time-point (P < 0.05 or P < 0.01). There were no obvious differences in the above indices between the experimental and control groups (P > 0.05), but the ICAM-1 and TNF-alpha levels in experimental group were markedly decreased than those in burn group at each time-point (P < 0.05 or P < 0.01). The ICAM-1 and TNF-alpha contents in burn group at 48 PBH were (3.42 +/- 0.25) microg/L and (4. 04 +/- 0.28) ng/L, respectively, which were markedly higher than those in experimental group [(2.24 +/- 0.14) microg/L, (3.35 +/- 0.22) ng/L, P < 0.05 or P < 0.01]. Dilation of capillaries, congestion and inflammatory infiltration in the pulmonary capillaries, and loosening of conjunction between pulmonary capillary vascular endothelial cells and endothelial swelling were observed in burn group at 48 PBH. Compared with the burn group, the injury was markedly alleviated in the experiment group, and the pulmonary capillary endothelial cells showed tighter junction. CONCLUSION: HDL exhibits a protective effect on the lung function of rats with severe burns via reducing the expression of ICAM-1 and TNF-alpha.

[The protective effect of high density lipoprotein on the cardiac function of rats with severe burns].

OBJECTIVE: To investigate the protective effect of high density lipoprotein on the cardiac function of rats with severe burns. METHODS: One hundred and thirty-five Wistar rats were employed in the study and were randomly divided into control (n = 15, without treatment), burn (n = 60, with 30% TBSA full-thickness burn on the back) and experimental (n = 60, with the injection of HDL (80 mg/kg) via the caudal vein immediately after burns) groups. The rats in the groups with burn injury were resuscitated with intraperitoneal isotonic saline (50 ml/kg) 30 minutes after burn (PBM). The serum contents of CK, ICAM-1 and TNF-alpha of the rats of all the three groups were determined with corresponding methods. The histological changes in the cardiac muscle tissue of the rats in all groups were observed under light microscope and electronic microscope. RESULTS: The serum contents of CK, ICAM-1 and TNF-alpha in the control group were obviously lower than those in burn group (P < 0.01), while those in experimental group were also markedly lower than those in control group (P < 0.05 or 0.01). The average reduction rate was 36.5%, 32.0% and 12.6%, respectively. The size and the structure of the cardiac muscular fiber in the control group were even and normal. Compared with the burn group, degeneration, inflammatory infiltration and mitochondrial swelling were found to be less marked in the experimental group at 48 PBH, and no focal lysis and necrosis were found, which were observed in the burn group. CONCLUSION: High density lipoprotein can be beneficial to the protection of cardiac tissue in protecting from secondary injury in rats with severe burns.

[Expression of IGF-I and IGF-IR in bladder cancer].

BACKGROUND & OBJECTIVE: Insulin-like growth factors (IGF) is one of polypeptide growth factors that stimulate proliferation, survival, and differentiation in many cell types; their signal pathways implicate development and progression of many kinds of malignant tumor, while less study were undergone on the roles of IGF-I and IGF-IR in bladder cancer genesis. This study was designed to investigate the expression of IGF-I and IGF-IR and proliferation cell nuclear antigen (PCNA) in human normal and carcinomatous bladder cancer, and to explore the mechanism of IGF-I and IGF-IR in cellular proliferation and tumorigenesis of bladder cancer. METHODS: Immunohistochemical methods were adopted to examine expression of IGF-I, IGF-IR, and PCNA in 88 cases with bladder cancer and 12 cases with normal bladder tissues. The relationship of expression of IGF-I and IGF-IR with various clinicopathological parameters and PCNA were analyzed. RESULTS: The protein expression rates of IGF-I and IGF-IR in bladder cancer were 73.9% and 59.1%, significantly higher than 33.3% and 16.7% in normal tissues, respectively(P< 0.05). Both two protein expression were association with PCNA indexes in bladder cancer (P< 0.05). There were close relationship among IGF-I expression and tumor recurrence (P< 0.05), IGF-IR and tumor grade, stage and recurrence (P< 0.05). CONCLUSION: Abnormality of IGF-I-IGF-IR autocrine loop play an important role in development and progression of bladder cancer by promoting abnormal cellular proliferation. IGF-IR may be a marker for evaluating tumor biological behaviors.