Elevated HMGB1 and sRAGE levels in cerebrospinal fluid of aneurysmal subarachnoid hemorrhage patients.

BACKGROUND: Neuroinflammation after aneurysmal subarachnoid hemorrhage (aSAH) leads to poor outcome of patients. High mobility group box 1 (HMGB1) contributes to inflammation through binding to receptors for advanced glycation end-products (RAGE) in various diseases. We aimed to determine the production of these two factors after aSAH and their relationship with clinical features. METHODS: HMGB1 and soluble RAGE (sRAGE) levels in cerebrospinal fluid (CSF) of aSAH patients and controls were measured, and their temporal courses were observed. The correlation between early concentrations (days 1-3) and clinical symptoms assessed by disease severity scores, neuroinflammation estimated by CSF IL-6 levels, as well as prognosis evidenced by delayed cerebral ischemia (DCI) and 6-month adverse outcome was investigated. Finally, combined analysis of early levels for predicting prognosis was confirmed. RESULTS: CSF HMGB1 and sRAGE levels were higher in aSAH patients than in controls (P < 0.05), and the levels decreased from higher early to lower over time. Their early concentrations were positively associated with disease severity scores, IL-6 levels, DCI and 6-month poor outcome (P < 0.05). HMGB1 ≥ 6045.5 pg/ml (OR = 14.291, P = 0.046) and sRAGE ≥ 572.0 pg/ml (OR = 13.988, P = 0.043) emerged as independent predictors for DCI, while HMGB1 ≥ 5163.2 pg/ml (OR = 7.483, P = 0.043) and sRAGE ≥ 537.3 pg/ml (OR = 12.653, P = 0.042) were predictors for 6-month poor outcome. Combined analysis of them improved predictive values of adverse prognosis. CONCLUSION: CSF HMGB1 and sRAGE levels of aSAH patients were increased early and then varied dynamically, which might act as potential biomarkers for poor outcome, especially when co-analyzed.

Relationship between Maternal PBMC HBV cccDNA and HBV Serological Markers and its Effect on HBV Intrauterine Transmission.

OBJECTIVE: To investigate the relationship between maternal peripheral blood mononuclear cells (PBMC) hepatitis B virus (HBV) covalenty closed circular deoxyribonucleic acid (cccDNA) and other HBV serological markers and its effects on HBV intrauterine transmission. METHODS: We enrolled 290 newborns and their hepatitis B surface antigen (HBsAg) positive mothers. HBV cccDNA in PBMC and HBV DNA in serum were detected by a real-time PCR-TaqMan probe while HBV serological markers were detected with an electrochemiluminescence immunoassay. RESULTS: There was a positive correlation between the levels of PBMC HBV cccDNA and serum HBV DNA and HBeAg (r = 0.436 and 0.403, P < 0.001). The detection rate of pattern A ['HBsAg (+), HBeAg (+), and anti-HBc (+)'] was significantly higher in the PBMC HBV cccDNA positive group than in the control group (χ2 = 48.48, P < 0.001). There was a significant association between HBV intrauterine transmission and PBMC HBV cccDNA (χ2 = 9.28, P = 0.002). In the presence of serum HBV DNA, HBeAg, and PBMC HBV cccDNA, the risk of HBV intrauterine transmission was three times higher (OR = 3.69, 95% CI: 1.30-10.42) than that observed in their absence. The risk of HBV intrauterine transmission was the greatest (OR = 5.89, 95% CI: 2.35-14.72) when both PBMC HBV cccDNA and pattern A were present. A Bayesian network model showed that maternal PBMC HBV cccDNA was directly related to HBV intrauterine transmission. CONCLUSION: PBMC HBV cccDNA may be a direct risk factor for HBV intrauterine transmission. Our study suggests that serological markers could be combined with PBMC-related markers in prenatal testing.

[Comprehensive study on the risk factors of hepatitis B virus intrauterine infection].

OBJECTIVE: To study the risk factors of hepatitis B virus (HBV) intrauterine infection. METHODS: Risk factors of HBV intrauterine infection were analyzed by nested case control study. RESULTS: Data from univariate analysis revealed that risk factors of HBV intrauterine infection were positive results on HLA-DR3 (OR = 4.71, 1.62-13.66), HBV DNA (OR = 6.59, 2.72-15.97) and HBeAg (OR = 4.53, 1.93-10.64) in pregnant women, HLA-DR3 (OR = 3.91, 1.18-12.94) in newborn, HLA-I) R3 (OR = 5.96, 1.14-31.15) both in pregnant women and her newborns and HBV infection in placentas (OR = 2.51,1.12-5.60). Results from Multivariate unconditional logistics regression analysis showed that the risk factors of HBV intrauterine infection were positive in both HLA-DR3 (OR = 4.65, 1.44-15.05) and HBV DNA (OR = 6.56, 2.65-16.23) in pregnant women. However, there was no interaction between the two factors. The exposure rate of other factors did not reveal the difference in the two groups. With the increase of HBV DNA in pregnant women, the risk of HBV intrauterine infection was rising (chi2 = 16.74, P < 0.05). CONCLUSION: Risk factors of HBV intrauterine infection were HLA-DR3 positive and HBV DNA positive in pregnant women but there was no interaction between the two factors. The risk of HBV intrauterine infection was increased along with the increase of HBV DNA in pregnant women.

[Study on hepatitis B virus intrauterine infection state and its correlation factors].

OBJECTIVE: To investigate the correlation factors of hepatitis B virus (HBV) intrauterine infection and the influence factors of HBV infection in peripheral blood mononuclear cells (PBMC) and placentas. METHODS: HBeAg and HBsAg in 151 pregnant women and their newborns were determined by enzyme linked immunoadsorbent assay (ELISA). HBV DNA in serum and PBMC of pregnant women and their newborns were determined by polymerase chain reaction. HBsAg in 151 placentas were detected by immunohistochemistry ABC. The correlation risk factors were analyzed by non-condition logistic regression model. RESULTS: HBV DNA positive in serum, HBV DNA positive in PBMC of pregnant women and HBsAg positive in placentas were the risk factors for HBV intrauterine infection. Their odds ratio (OR) and 95% confidence interval were 2.25 (1.08-4.72), 2.69 (1.26-5.73) and 4.63 (1.70-12.62), respectively. The influence factors of HBV infection in placenta included antepartum injection of hepatitis B immunoglobulin (HBIG) over thrice and HBV DNA positive in serum of pregnant women with OR 0.08 (0.01-0.69) and 4.24 (1.22-14.69). The risk factor for HBV DNA positive in PBMC of newborns was HBV DNA positive in PBMC of their mothers with OR 24.53 (7.92-76.01). CONCLUSIONS: HBV infection in placentas, HBV DNA positive in PBMC and serum of pregnant women are the risk factors for HBV intrauterine infection. Antepartum injection of HBIG over thrice can protect placentas from being infected by HBV to some extent. PBMC HBV DNA positive in pregnant women is probably the independent risk factor for PBMC HBV intrauterine infection in newborns.