To identify susceptibility variants for hepatitis B virus (HBV)-related hepatocellular carcinoma (HCC), we conducted a genome-wide association study by genotyping 440,794 SNPs in 355 chronic HBV carriers with HCC and 360 chronic HBV carriers without HCC, all of Chinese ancestry. We identified one intronic SNP (rs17401966) in KIF1B on chromosome 1p36.22 that was highly associated with HBV-related HCC and confirmed this association in five additional independent samples, consisting of 1,962 individuals with HCC, 1,430 control subjects and 159 family trios. Across the six studies, the association with rs17401966 was highly statistically significant (joint odds ratio = 0.61, P = 1.7 x 10(-18)). In addition to KIF1B, the association region tagged two other plausible causative genes, UBE4B and PGD. Our findings provide evidence that the 1p36.22 locus confers susceptibility to HBV-related HCC, and suggest that KIF1B-, UBE4B- or PGD-related pathways might be involved in the pathogenesis of this malignancy.

Previous research has shown that type 2 diabetes mellitus (T2DM) is associated with an increased risk of cognitive impairment. Patients with impaired cognition often show decreased spontaneous brain activity on resting-state functional magnetic resonance imaging (rs-fMRI). This study used rs-fMRI to investigate changes in spontaneous brain activity among patients with T2DM and to determine the relationship of these changes with cognitive impairment. T2DM patients (n = 29) and age-, sex-, and education-matched healthy control subjects (n = 27) were included in this study. Amplitude of lowfrequency fluctuation (ALFF) and regional homogeneity (ReHo) values were calculated to represent spontaneous brain activity. Brain volume and cognition were also evaluated among these participants. Compared with healthy control subjects, patients with T2DM had significantly decreased ALFF and ReHo values in the occipital lobe and postcentral gyrus. Patients performed worse on several cognitive tests; this impaired cognitive performance was correlated with decreased activity in the cuneus and lingual gyrus in the occipital lobe. Brain volume did not differ between the two groups. The abnormalities of spontaneous brain activity reflected by ALFF and ReHo measurements in the absence of structural changes in T2DM patients may provide insights into the neurological pathophysiology underlying diabetes-associated cognitive decline.

Angiopoietin-like protein 4 (ANGPTL4) plays complex and often contradictory roles in vascular biology and tumor metastasis, but little is known about its function in hepatocellular carcinoma (HCC) metastasis. In the present study, we showed that hypoxia-inducible factor 1a (HIF-1a) directly up-regulates ANGPTL4, and its stableness positively correlates with ANGPTL4 expression in HCC tissue. Overexpression of ANGPTL4 significantly increased HCC cell transendothelial migration in vitro and intrahepatic and distal pulmonary metastasis in vivo, whereas silencing ANGPTL4 expression or treatment with a neutralizing antibody specific for ANGPTL4 protein resulted in a reduced transendothelial migration. We also found that serum ANGPTL4 is higher in HCC patients, compared to healthy control, and correlates with intrahepatic metastasis and histological grade. Further, secreted ANGPTL4 promotes transendothelial migration and metastasis of HCC cells in vitro and in vivo through the up-regulation of vascular cell adhesion molecule-1 (VCAM-1) of human umbilical vein endothelial cells and the activation of the VCAM-1/ integrin b1 axis. Conclusion: ANGPTL4 is a target gene of HIF-1a and acts as an important regulator in the metastasis of HCC. Serum ANGPTL4 correlates with tumor progression and metastasis and might be used to indicate prognosis in HCC patients. (HEPATOLOGY 2011;54:910-919) Abbreviations: 2ME2, 2-methoxyestradiol; AFP, alpha-fetoprotein; ANGPTL4, angiopoietin-like protein 4; ChIP, chromatin immunoprecipitation; CM, conditioned medium; DFO, deferoxamine mesylate; HBV, hepatitis B virus; HCC, hepatocellular carcinoma; HIF-1a, hypoxia-inducible factor 1a; HREs, hypoxia-responsive elements; HUVECs, human umbilical vein endothelial cells; IgG, immunoglobulin G; IL-1b, interleukin-1 beta; IjB-b, inhibitor of nuclear factor kappa B beta; kb, kilobase; LPS, lipopolysaccharide; NF-jB, nuclear factor kappa light-chain enhancer of activated B cells; shRNA, short-hairpin RNA; VCAM-1, vascular cell adhesion molecule-1.From the

BackgroundDepression during pregnancy can be detrimental to both maternal and fetal health outcomes. A cross-sectional study was undertaken, with the goal of determining the prevalence and predicting factors associated with antenatal depressive symptoms during late pregnancy among Chinese women.MethodsParticipants were recruited during bookings for antenatal care at a maternal and child health hospital’s outpatient care clinics. Measurements included the Chinese version of Self-rating Depression Scale, Eysenck Personality Questionnaire, Social Support Rating Scale, and Simplified Coping Strategies Questionnaire.ResultsA total of 292 women participated in this study, with 28.5% prevalence of depressive symptoms. Significant protective predictors were: a younger age (OR = 0.85; 95% Confidence Interval-CI 0.76-0.95), good partner relationship (OR = 0.40; 95% CI 0.17-0.93), preparedness for delivery (OR = 0.36; 95% CI 0.20-0.63), active coping (OR = 0.92; 95% CI 0.89-0.96), and social support (OR = 0.92; 95% CI 0.88-0.97). In contrast, significant risk factors were: a history of miscarriage (OR = 1.86; 95% CI 1.30-2.66), irregular menstrual history (OR = 2.98; 95% CI 1.64-5.40), and financial worries (OR = 2.33; 95% CI 1.27-4.30). Psychosocial risk factors include psychoticism and neuroticism personality traits (OR = 1.06; 95% CI 1.02-1.10 and OR = 1.07; 95% CI 1.04-1.10, respectively), and pregnancy pressures (OR = 1.04; 95% CI 1.02-1.07).ConclusionDepressive symptoms are common in third trimester antenatal clinic attendees. Interventions for early recognition of depression should target older women with a history of miscarriage and financial worries. Intervention strategies could be by providing more social support and promoting active coping strategies. Findings support a recommendation that antenatal services consider integrating screening for depression in routine antenatal care.

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