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Abbreviations: ALT, alanine transaminase; aOR, adjusting odds ratio; APOs, adverse pregnancy outcomes; BMI, body mass index; CI, confidence interval; DAGs, directed acyclic graphs;ELISA, enzyme-linked immunosorbent assay; FDR, false discovery rate; GDM, gestational diabetes mellitus; HBeAg, hepatitis B e antigen; HBsAg, Serum hepatitis B surface antigen; HBV, hepatitis B virus; HDP, hypertensive disorders of pregnancy; ICP, intrahepatic cholestasis pregnancy; LGA, large for gestational age; PROM, premature rupture of the membranes; PW, pregnant women; SGA, small for gestational age; TNF-a, tumour necrosis factor alpha. AbstractIt is not clear whether chronic hepatitis B virus (HBV) infection during pregnancy can increase the risk of adverse pregnancy outcomes for both mothers and neonates. We conducted a hospital-based prospective cohort study on pregnant women (PW) andused an analysis strategy that was guided by directed acyclic graphs (DAGs). Maternal characteristics and major adverse pregnancy outcomes were collected both from questionnaires and hospital-based electronic medical records. Serum hepatitis B surface antigen (HBsAg) and hepatitis B e antigen (HBeAg) status were determined. In total, 3329 of the 3416 pregnant women who received routine antenatal care in a hospital setting at baseline, including 346 HBsAg carriers, were available for analysis.Maternal HBsAg carrier status was associated with an increased risk of intrahepatic cholestasis pregnancy [aOR (adjusting odds ratio) = 1.70; 95% CI (confidence interval) = 1.16-2.49], premature rupture of the membranes (aOR = 1.38; 95% CI = 1.00-1.89) and large for gestational age birth aOR = 1.67; 95% CI = 1.17-2.39).The risk of intrahepatic cholestasis remained in pregnant women with either HBeAgpositive (aOR = 2.96; 95% CI = 1.33-6.62) or HBeAg-negative (aOR = 1.52; 95% CI =1.00-2.32)] status; notably, only maternal HBeAg-negative status was associated with a higher risk of large for gestational age birth (aOR = 1.91; 95% CI = 1.33-2.76).Our results implied that chronic HBV infection during pregnancy may increase the risk of intrahepatic cholestasis of pregnancy, premature rupture of membranes and large for gestational age pregnancies. K E Y W O R D Shepatitis B virus infection, intrahepatic cholestasis during pregnancy, large for gestational age, pregnancy outcomes, premature rupture of the membranes

Anti-GABAB receptor encephalitis is an uncommon autoimmune disease, which has been known to be often associated with cancer. Generally, patients associated with GABABR GABA-B receptor antibody encephalitis respond well to immunotherapy, especially if started early.

ObjectivesWe aimed to evaluate the relation of total homocysteine (tHcy) concentrations with systolic blood pressure (SBP) and diastolic blood pressure (DBP) levels, and examine the possible modifiers in the association among a general population of Chinese adults.DesignA cross-sectional study.SettingThe study was conducted within 21 communities in Lianyungang of Jiangsu province, China.ParticipantsA total of 26 648 participants aged ≥35 years and with no antihypertensive drug use were included in the final analysis.ResultsOverall, there was a positive association between tHcy concentrations and SBP (per 5 μmol/L tHcy increase: adjusted β=0.45 mm Hg; 95% CI 0.29 to 0.61) or DBP levels (per 5 μmol/L tHcy increase: adjusted β=0.47 mm Hg; 95% CI 0.35 to 0.59). Compared with participants with tHcy <10 μmol/L, significantly higher SBP levels were found in those with tHcy concentrations of 10 to <15 (adjusted β=0.80 mm Hg; 95% CI 0.32 to 1.28) and ≥15 µmol/L (adjusted β=1.79 mm Hg; 95% CI 1.20 to 2.37; p for trend <0.001). Consistently, significantly higher DBP levels were found in participants with tHcy concentrations of 10 to <15 (adjusted β=0.86 mm Hg; 95% CI 0.49 to 1.22) and ≥15 µmol/L (adjusted β=2.01 mm Hg; 95% CI 1.57 to 2.46; p for trend <0.001), respectively as compared with those with <10 μmol/L. Furthermore, a stronger association between tHcy and SBP (p for interaction=0.009) or DBP (p for interaction=0.067) was found in current alcohol drinkers.ConclusionSerum tHcy concentrations were positively associated with both SBP and DBP levels in a general Chinese adult population. The association was stronger in current alcohol drinkers.

BackgroundChronic hepatitis B (CHB) infection during pregnancy is associated with insulin resistance. A meta-analytic technique was used to quantify the evidence of an association between CHB infection and the risk of gestational diabetes (GDM) among pregnant women.MethodsWe searched PubMed for studies up to September 5th 2013. Additional studies were obtained from other sources. We selected studies using a cohort-study design and reported a quantitative association between CHB infection during pregnancy and risk of GDM. A total of 280 articles were identified, of which fourteen publications involving 439,514 subjects met the inclusion criteria. A sequential algorithm was used to reduce between-study heterogeneity, and further meta-analysis was conducted using a random-effects model.ResultsTen out of the fourteen studies were highly homogeneous, indicating an association of 1.11 [the adjusted odds ratio, 95% confidence interval 0.96 - 1.28] between CHB infection during pregnancy and the risk of developing GDM. The heterogeneity of the additional four studies may be due to selection bias or possible aetiological differences for special subsets of pregnant women.ConclusionsThese results indicate that CHB infection during pregnancy is not associated with an increased risk of developing GDM among pregnant women except those from Iran.

Glucocorticoids are the primary anti-inflammatory therapy for asthma, but their effects are characterized by some interindividual variability that might have a genetic basis.We aimed to determine the relationship between pulmonary function change and the variant of the glucocorticoid-induced transcript 1 (GLCCI1) gene in patients with asthma receiving long-term ICS treatment, the association of GLCCI1 genotypes and the level of GLCCI1 expression and cytokines production.A total of 418 patients with asthma, including 25 individuals from 11 families with a history of asthma, were enrolled. The effects of single-nucleotide polymorphisms (SNPs) in GLCCI1 on changes in lung function in response to inhaled glucocorticoids were assessed. The expression levels of GLCCI1 mRNA and cytokines were also measured.The SNP rs37973 in GLCCI1 was independently associated with changes in forced expiratory volume at one second (FEV1) and FEV1%pred. Individuals homozygous for the wild-type allele who had a percent FEV1 change greater than 5% were more common than individuals homozygous for the rare allele. When patients were stratified according to genotype, GLCCI1 expression was enhanced upon administration of low-dose dexamethasone among patients with the rs37973 A allele; however, GG homozygotes required high-dose dexamethasone to achieve enhanced GLCCI1 expression. Furthermore, the levels of some cytokines were significantly reduced after glucocorticoid treatment in individuals with the AA and AG genotypes.The genetic variant rs37973 in GLCCI1 is associated with poorer clinical therapeutic response to inhaled glucocorticoids in a Chinese asthma population.

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