Perinatal maternal depression and the risk of childhood asthma in offspring: A meta-analysis.

BACKGROUND: Previous studies have yielded conflicting results regarding the link between maternal perinatal depression and asthma in children. To provide a clearer understanding of this relationship, a comprehensive meta-analysis was carried out to evaluate the association mentioned above. METHODS: A comprehensive review of observational studies was conducted by searching electronic databases including Medline, Embase, and Web of Science. The data were combined using a randomized-effects model taking into account potential variations. Subgroup analyses were performed to evaluate the possible impact of study characteristics on outcomes. RESULTS: Ten cohort studies, which included 833,230 mother-child pairs, were examined in the analysis. Maternal depressive symptoms during the perinatal period were associated with an increased risk of asthma in offspring (risk ratio [RR]: 1.24, 95% confidence interval [CI]: 1.19 to 1.30, p < 0.001; I2 = 0%). Further sensitivity analyses restricted to multivariate studies (RR: 1.24, 95% CI: 1.19 to 1.30, p < 0.001; I2 = 0%) or studies where asthma was diagnosed in children aged three years or older (RR: 1.24, 95% CI: 1.19 to 1.30, p < 0.001; I2 = 0%) revealed consistent outcomes. Subgroup analyses according to study design, methods for the diagnosis of maternal depression, timing for the evaluation of maternal depression, methods for the validation of asthma in offspring, adjustment of maternal smoking during pregnancy and of maternal asthma, or study quality score showed similar results (p for subgroup difference all > 0.05). CONCLUSIONS: Maternal perinatal depression appears to be significantly linked to a higher occurrence of childhood asthma in children.

Inflammatory cytokines and their potential role in Sjogren's syndrome risk: insights from a mendelian randomization study.

AIM: This study aimed to investigate the causal impact of inflammatory cytokines on Sjogren's Syndrome (SS) and to identify potential biomarkers for SS clinical management using Mendelian Randomization (MR). MATERIALS AND METHODS: Leveraging GWAS summary data of inflammatory cytokines and SS, we executed the first two-sample MR analysis. Genetic variants from prior GWASs associated with circulating inflammatory cytokines served as instrumental variables (IVs). Data regarding cytokines were analyzed using the Olink Target-96 Inflammation panel, synthesizing data from 14,824 participants. GWAS summary statistics for SS were procured from the UK Biobank, focusing on samples of European ancestry. To discern the causal relationship between inflammatory cytokines and SS, several MR methodologies, including inverse variance weighted (IVW) and MR-Egger regression, were applied. RESULTS: After rigorous IV quality control, 91 cytokines were incorporated into the MR analysis. The IVW analysis identified 8 cytokines with a positive association to SS: Axin-1 (OR 2.56, 95% CI 1.07-6.10), T-cell surface glycoprotein CD5 (OR 1.81, 95% CI 1.08-3.02), CUDP1 (OR 1.61, 95% CI 1.00-2.58), CXCL10 (OR 1.92, 95% CI 1.25-2.95), IL-4 (OR 2.18, 95% CI 1.22-3.91), IL-7 (OR 2.35, 95% CI 1.27-4.33), MCP-2 (OR 1.27, 95% CI 1.05-1.54), and TNFRSF9 (OR 1.83, 95% CI 1.03-3.24), suggesting their potential in increasing SS risk. CONCLUSION: Our study conducted through MR, identified various inflammatory cytokines associated with SS risk, validating some previous research results and offering some new potential biomarkers for SS. However, these findings necessitate further research for validation and exploration of their precise role in the onset and progression of SS.

[Expression of nuclear factor-kappaB and its inhibitor in alveolar macrophages of patients with neonatal hyaline membrane disease].

OBJECTIVE: Inflammatory reaction and injury in immature lungs are associated with activation of nuclear factor-kappa B (NF-kappaB) to trigger proinflammatory cytokine release, but the mechanism thereof is not fully understood. The present study was conducted to understand possible relationship between expression of NF-kappaB and its inhibitor and severity and outcome of neonates with hyaline membrane disease (HMD). METHODS: Serial samples of bronchoalveolar lavage fluid (BALF) were obtained during mechanical ventilation from 31 preterm infants with HMD. These infants were divided into two groups: survivors group [n = 22, birth weight (1500 +/- 320) g and gestational age (31.2 +/- 1.8) weeks] and nonsurvivors group [birth weight (1340 +/- 280) g, gestational age (30.8 +/- 2.1) weeks]. Nineteen preterm infants [birth weight (1470 +/- 280) g, gestational age (30.6 +/- 1.9) weeks] without respiratory disorders were enrolled as control subjects. Alveolar macrophages (AM) were isolated by differential adherence. AM was cultured and treated with lipopolysaccharide (LPS) for 1 hr. Then, nuclear extracts of AM were analyzed by electrophoretic mobility shift assay (EMSA) for NF-kappaB expression. NF-kappaB inhibitor (IkappaB-alpha protein) in cytoplasmic extracts was detected by using Western blotting and IL-1beta and IL-8 in BALF by enzyme-linked immunosorbent assay (ELISA). RESULTS: NF-kappaB complexes were observed by EMSA, they were characterized by competition with cold oligonucleotide and p65-specific antibodies. The addition of an excess of cold oligonucleotide, corresponding to the NF-kappaB binding site, turned off the signal of the band, showing that the band was specific. An excess of an irrelevant oligonucleotide (corresponding to the SP-1) did not show any effect. The addition of an anti-p65 antibody caused the supershift of the two upper bands. After EMSA, the NF-kappaB complexes were quantified by using a ImageQuant software. NF-kappaB expression in AM at 24 hrs was higher in all the patients with HMD as compared with control subjects (survives/control, 34.1 vs 11.4 RDU, P < 0.01; nonsurvivors/control, 55.2 vs 11.4 RDU, P < 0.01). The NF-kappaB expression in AM at 72 hrs was higher than that in control subjects but not for nonsurvivors (survivors/control, 47.8 vs 25.6 RDU, P < 0.01; nonsurvivors/control, 21.8 vs 25.6, P > 0.05). The NF-kappaB expression in AM from nonsurvivors was depressed at 72 hrs as compared to 24 hrs (21.8 vs 55.2, P < 0.01), whereas the NF-kappaB expression in AM from survivors was still higher at 72 hrs than that at 24 hrs (47.8 vs 34.1, t = 4.43, P < 0.01). CONCLUSION: Altered NF-kappaB activation in AM of BALF of neonates with HMD was observed, and it may be mediated by decreased IkappaB synthesis, increased IkappaB degradation, or both. In HMD nonsurvivors NF-kappaB translocation was hampered upon LPS activation.

[Significance of soluble intercellular adhesion molecule-1 and procalcitonin in diagnosis of neonatal septicemia].

OBJECTIVE: Neonatal septicemia is a critical disease in neonatal period. Its incidence among live births is between 1 per thousand and 8 per thousand. Mortality of neonatal septicemia may be as high as 50% for infants who are not treated. The early signs of septicemia in the newborn are generally nonspecific. Blood culture and the other clinical diagnostic measures are not sufficiently sensitive. The present study aimed at evaluating potential use of soluble intercellular adhesion molecule-1 (sICAM-1), procalcitonin (PCT) and C-reactive protein (CRP) in diagnosis of septicemia. METHODS: The experimental group consisted of 50 newborns with septicemia who were treated in Hebei Provincial Children's Hospital from April 1, 2002 to December 30, 2002. Thirty of the 50 cases had positive blood culture. The control group included 35 healthy newborns. Fasting blood samples were taken for bacterial cultures and sICAM-1, CRP, PCT determination. PCT and CRP contents were determined immediately after the specimens were collected. Analyses of sICAM-1 were done after inclusion of the last patient. Serum was separated from each specimen and stored at -20 degrees C within 2 hours. The analyses of sICAM-1 were performed by ELISA technique. CRP was analyzed by immunoturbidimetry assay (ITA). Immunochromatographic test was performed for detection of PCT from 200 ul serum. SPSS 10.0 was used to process the data. P values < 0.05 was considered to be statistically significant. One way analysis of variance (ANOVA), multiple comparison, chi-square test, paired-samples T test, linear correlation, Spearman correlation analysis, ROC curve were used for statistical analysis. The sensitivity, specificity, positive and negative predictive values, accuracy, Youden's index for sICAM-1, PCT, CRP and WBC count were calculated. These values were compared with each other. RESULTS: (1) The content of sICAM-1 in control group varied widely from 79 to 1252 ng/ml. Comparison of the data indicated that there was significant difference among the three groups in the content of sICAM-1, CRP and PCT (P < 0.05), but not in WBC count. These markers are considered positive if sICAM-1 >or= 300 ng/ml, CRP >or= 8 mg/l, PCT >or= 2 ng/ml. Their sensitivity was higher than WBC (P < 0.05). Among these indices, PCT has the highest specificity (94.3%), positive predictive (95.6%), negative predictive (82.5%), accuracy (89.4%), and Youden's index (80.3%). (2) No significant difference was found in sICAM-1 between pre- and post-treatment (P > 0.05); however, there was significant difference in CRP and PCT. (3) sICAM-1 was in direct proportion to CRP (r = 0.339,P < 0.01). PCT is correlated with sICAM-1, CRP (the spearman correlation coefficient 0.569, 0.482, P < 0.01). CONCLUSION: Different individual is in different immune status; The level of sICAM-1 is related with neonatal septicemia. sICAM-1 concentration may be used as a diagnostic tool with high sensitivity (85%) and moderate specificity (54.3%) in neonates suspected of infection. The sensitivity and specificity of CRP (>or= 8 mg/l) were accordingly 87.5% and 54.3%. WBC count had low sensitivity for diagnosis (30.0%); Among these indices, PCT had the highest specificity (94.3%), positive predictive (95.6%), negative predictive (82.5%) Values, accuracy (89.4%), Youden's index (80.3%); No correlation was found between sICAM-1 concentration and their ages in day accordingly. CRP, PCT may be used to estimate the effect of therapy. The correlation of the infectious indices indicates that the body may mobilize many organs at the same time to resist the invasion of organism.

Nuclear factor-kappa B expression in alveolar macrophages of mechanically ventilated neonates with respiratory distress syndrome.

BACKGROUND: Inflammatory reaction and injury in mature lungs are associated with activation of nuclear factor-kappaB (NF-kappaB) to trigger proinflammatory cytokine release. In preterm infants with immature lungs, this mechanism is not yet fully understood, therefore we investigated this mechanism in mechanically ventilated neonates with respiratory distress syndrome (RDS). METHODS: Serial samples of the airway aspirates (AA) were obtained during mechanical ventilation from 21 preterm infants with RDS, of which 12 were survivors (birth weight 1.48 +/- 0.32 kg and gestational age 31 +/- 1.5 weeks) and 9 nonsurvivors (1.34 +/- 0.31 kg and 30 +/- 2 weeks). Seven neonates matched for age and birth weight without respiratory disorders served as controls. Alveolar macrophages (AM) of AA were isolated by differential adherence, some were cultured with lipopolysaccharide (LPS) for 1 h. Then, nuclear extracts of AM were analyzed by electrophoretic mobility shift assay for NF-kappaB expression. The NF-kappaB inhibitor (IkappaB-alpha protein) in cytoplasmic extracts was detected by Western blot, and concentrations of IL-1beta and IL-8 in AA by enzyme-linked immunosorbent assay (ELISA). RESULTS: On day 2 NF-kappaB expression in AM was significantly increased in the survivors and nonsurvivors at 33.3 +/- 9 and 54.8 +/- 10.2 relative density units (RDU) compared to control infants (11.1 +/- 6.7; p < 0.01). Expression of IkappaB-alpha was significantly higher in controls than that in the survivors and nonsurvivors on days 2 and 4. Moreover, in the nonsurvivors of RDS, expression of NF-kappaB was decreased following LPS stimulation in vitro on day 4. IL-1beta and IL-8 levels in the AA supernatant were higher in the survivors than in controls on days 2 and 4, but lower than those of the nonsurvivors on day 2. There were close correlations between the expression of NF-kappaB and levels of IL-1beta (r = 0.78, p < 0.01), and IL-8 (r = 0.81, p < 0.01) in AA. CONCLUSION: There were alterations in NF-kappaB activity in the AM of mechanically ventilated preterm neonates with RDS, mediated by decreased synthesis and increased degradation of IkappaB.