53BP1 regulates cell cycle arrest in esophageal cancer model.

OBJECTIVE: This study aims to investigate effects of checkpoint kinase, mediator of DNA damage checkpoint 1 (MDC1) and p53-binding protein 1 (53BP1) silencing on p53, checkpoint kinase 1 and 2 (CHK1 and CHK2), and CHK2-T68 expression. MATERIALS AND METHODS: Eca109 cells were divided into untransfected Eca109, Blank-vector, MDC1-RNAi transfection, and 53BP1-RNAi transfection group. Streptavidin-peroxidase (SP) immunohistochemical assay was used to examine CHK2-T68 expression. About 4 groups were used to establish esophageal carcinoma nude-mouse models, and assigned as Eca-109 control (or Eca-109 plus 15 Gy γ-rays irradiation, Eca-109+IR), Blank-vector (or Blank-vecor+IR), 53BP1-RNAi (or 53BP1-RNAi+IR), and MDC1-RNAi group (or MDC1-RNAi+IR group) by injecting. The expression of p53, CHK1, CHK2 were evaluated using SP immunohistochemical assay. RESULTS: 53BP1 and MDC1 down-regulation significantly inhibited expression of CHK2-T68 in Eca-109 cells compared to untreated group (p<0.05). There were significant differences for CHK2-T68 expressions in different time and groups (p<0.05). 53BP1 down-regulation significantly reduced p53 and enhanced CHK1 and CHK2 expression compared to that of Eca-109 control group (p<0.05) in Eca-109 cells. 53BP1 down-regulation significantly regulated CHK1, CHK2, and p53 in xenograft nude mice models exposed to γ-ray irradiation compared to that of untreated group (p<0.05). p53 was negatively correlated with CHK1 and CHK2 in xenograft nude mice models. CONCLUSIONS: 53BP1 regulated the cell cycle arrest by modulating p53, CHK1, and CHK2 expression in both Eca-109 cells and xenograft nude mice models.

[Distribution of electroencephalograph power density in patients with severe obstructive sleep apnea during different sleep stages].

Objective: To investigate the variation of electroencephalograph(EEG) power density during different sleep stages in OSA for understanding of the mechanisms underlying the brain dysfunction in OSA as well as its earlier diagnosis and treatment. Methods: Sixteen-channel EEGs from OSA patients and normal controls in stage wake, sleep stage 1, sleep stage 2, sleep stage 3 and rapid eye movement stage were analyzed by time-frequency analysis method. The EEG power density in different frequency bands (including δ, θ, α, σ, ß and γ) was respectively compared between the 2 groups. The correlation between the variation in the EEG power and primary indices of polysomnography was further analyzed. Results: The EEG power density in δ band in stage wake [OSA: (0.82±0.13) µV(2)/Hz, Control: (0.66±0.02) µV(2)/Hz, t=4.309, P<0.05], stage 1 [OSA: (1.28±0.07) µV(2)/Hz, Control: (0.92±0.04) µV(2)/Hz, t=-3.369, P<0.05] and stage 3 [OSA: (2.74±0.22) µV(2)/Hz, Control: (2.04±0.07) µV(2)/Hz, t=-2.669, P<0.05] was significantly higher in OSA, compared with that in the control. Statistical analysis showed that the EEG power density was significantly higher in frontal and central regions in stage wake [frontal: OSA: (0.90±0.02) µV(2)/Hz, Control: (0.66±0.02) µV(2)/Hz, t=8.539, P<0.01; central: OSA: (1.15±0.06) µV(2)/Hz, Control: (0.72±0.02) µV(2)/Hz, t=6.669, P<0.01] and stage 1 [frontal: OSA: (1.23±0.03) µV(2)/Hz, Control: (0.99±0.03) µV(2)/Hz, t=5.983, P<0.01; central: OSA: (1.52±0.05) µV(2)/Hz, Control: (1.14±0.04) µV(2)/Hz, t=5.714, P<0.01], as well as central region in stage 3 [OSA: (3.24±0.17) µV(2)/Hz, Control: (2.71±0.08) µV(2)/Hz, t=2.707, P<0.05]. The correlation analysis showed that the power density in central region in stage 1 and stage 3 was positively correlated with arousal index (r=0.877 in stage 1, 0.656 in stage 3), implying that sleep fragmentation was closely related to the variation of EEG power density during nocturnal sleep in OSA. Conclusions: The feature stages for OSA are stage wake, stage 1 and stage 3. The EEG power density in OSA (δ band) was significantly higher than that in the control. The EEG power density in OSA and the control shows differences in frontal and central regions in stage wake and stage 1, as well as in central region in stage 3. The results indicate that low-frequency EEG power density giving priority to frontal area and central area has improved in severe OSA, which may be related to the neurologic deficits in corresponding brain areas.

Epidemiology, disease burden and outcomes of cirrhosis in a large secondary care hospital in South Auckland, New Zealand.

BACKGROUND: Liver cirrhosis is an important cause of morbidity and mortality; however, little is known about its impact in New Zealand. AIMS: We aim to determine the disease burden, epidemiology and outcomes of cirrhotic patients. METHODS: This is a retrospective study of cirrhosis patients under secondary public hospital care in a geographically defined region, between the years 2000 and 2011. Cirrhosis complications and mortality was recorded. Poisson log-linear regression analysis was performed for incidence rate ratio (IRR) and Cox regression analysis was used to analyse time-related events. RESULTS: Seven hundred and forty-six cirrhotic patients were analysed; most were European/Other (39.9%), Pacific islanders (21.6%), Southeast Asian/Chinese (17.8%) and Maori (12.3%). 68.4% were male. The common primary aetiologies for cirrhosis were chronic hepatitis B (CHB) cirrhosis (37.3%), alcoholic liver disease (ALD) cirrhosis (24.1%), chronic hepatitis C (CHC) cirrhosis (22.3%) and non-alcoholic fatty liver disease (NAFLD) cirrhosis (16.4%). The hepatocellular carcinoma (HCC) mortality rates were highest in NAFLD and CHB cirrhosis groups (3.0 and 3.1 per 100 patient-year respectively), compared with ALD and CHC groups (2.2 and 1.4 per 100 patient-year, all P < 0.05 respectively). Patients with ALD and NAFLD cirrhosis had the highest all-cause and non-HCC mortality rate compared with viral hepatitis cirrhosis groups. The IRR for HCC incidence, liver-related mortality and HCC mortality were 1.087, 1.098 and 1.114, respectively (all P < 0.001), suggesting increasing incidence and disease burden over the study period. CONCLUSION: The number of cirrhotic patients in secondary care is increasing steadily. Cirrhosis complications and mortality rates are also rising, particularly the incidence and mortality of HCC.