Prognostic value and immune landscapes of anoikis-associated lncRNAs in lung adenocarcinoma.

BACKGROUND: Methods for predicting the outcome of lung adenocarcinoma (LUAD) in the clinic are limited. Anoikis is an important route to programmed cell death in LUAD, and the prognostic value of a model constructed with anoikis-related lncRNAs (ARlncRNAs) in LUAD is unclear. METHODS: Transcriptome and basic information for LUAD patients was obtained from the Cancer Genome Atlas. Coexpression and Cox regression analyses were utilized to identify prognostically significant ARlncRNAs and construct a prognostic signature. Furthermore, the signature was combined with clinical characteristics to create a nomogram. Finally, we performed principal component, enrichment, tumor mutation burden (TMB), tumor microenvironment (TME) and drug sensitivity analyses to evaluate the basic research and clinical merit of the signature. RESULTS: The prognostic signature developed with eleven ARlncRNAs can accurately predict that high-risk group patients have a worse prognosis, as proven by the receiver operating characteristic (ROC) curve (AUC: 0.718). Independent prognostic analyses indicated that the risk score is a significant independent prognostic element for LUAD (P<0.001). In the high-risk group, enrichment analysis demonstrated that glucose metabolism and DNA replication were the main enrichment pathways. TMB analysis indicated that the high-risk group had a high TMB (P<0.05). Drug sensitivity analyses can recognize drugs that are sensitive to different risk groups. Finally, 11 ARlncRNAs of this signature were verified by RT-qPCR analysis. CONCLUSIONS: A novel prognostic signature developed with 11 ARlncRNAs can accurately predict the OS of LUAD patients and offer clinical guidance value for immunotherapy and chemotherapy treatment.

circ-ATAD1 as Competing Endogenous RNA for miR-191-5p Forces Non-small Cell Lung Cancer Progression.

The association of circular RNAs (circRNAs) with non-small cell lung cancer (NSCLC) has been recognized extensively. In view of this, our study particularly surveyed the underlying mechanism of circ-ATAD1 in the disease. First, an analysis of the clinical expression of circ-ATPase family AAA domain containing 1 (ATAD1) was performed, followed by further evaluation of the relationship between circ-ATAD1 expression and prognosis. Then, A549 cells were treated with single transfection or combined transfection with the plasmid vectors that interfere with circ-ATAD1 or miR-191-5p. circ-ATAD1 and miR-191-5p levels were detected by reverse transcription quantitative polymerase chain reaction to verify the transfection success. Then, cell proliferation was checked by cell count kit-8 and clonal formation test. Cell apoptosis was analyzed by flow cytometry. Cell migration and invasion were examined by wound healing assay and Transwell. Finally, the targeting of miR-191-5p to circ-ATAD1 or Forkhead Box K1 (FOXK1) was verified by bioinformation website starBase analysis and dual-luciferase reporter assay. circ-ATAD1 was expressed abundantly in tumor tissues of NSCLC patients and had a predictive value in poor prognosis. circ-ATAD1 underexpression or miR-191-5p overexpression could obstruct A549 cells to behave aggressively, while circ-ATAD1 upregulation or miR-191-5p depletion resulted in the promotion of aggressiveness of A549 cells. Interestingly, circ-ATAD1 could decoy miR-191-5p. miR-191-5p negatively regulated FOXK1 expression, and downregulating miR-191-5p or upregulating FOXK1 rescued circ-ATAD1 downregulation-mediated influences on NSCLC cells. circ-ATAD1 accelerates NSCLC progression by absorbing miR-191-5p to upregulate FOXK1 expression.

Factors associated with congenital syphilis: A retrospective study in Jiangxi Province, China.

BACKGROUND: There are a lack of studies about factors influencing congenital syphilis (CS) in economically underdeveloped areas, such as Jiangxi Province, China. METHODS: A retrospective study was conducted based on the information system of prevention of mother-to-child transmission of syphilis management in Jiangxi Province, China. Pregnant women with syphilis infection who delivered ≥28 gestational weeks and registered in this system from 1 January 2013 to 2030 June 2018 were enrolled. Maternal characteristics and treatment regimens associated with CS were evaluated using multivariable regression analysis. RESULTS: 1196 syphilis infected mothers and their 1207 infants were included in the analyses, and 116 infants were diagnosed with CS, providing an overall incidence of 9.61% (116/1207). Multivariable logistic regression analysis showed that increasing maternal age was barely associated with the risk of CS (adjusted odds ratio (aOR) = 0.97, 95% CI, 0.93-1.00, p = .047). Women with a high nontreponemal serum test titer (≥1:8) had a 126% increased risk of delivering an infant with CS than those with a low titer (<1:8) (aOR = 2.26, 95% CI, 1.51-3.39, p < .001). The risk for CS decreased significantly in infants born to mothers receiving adequate treatment than those receiving no treatment (aOR = 0.36, 95% CI, 0.21-0.61, p < .001). CONCLUSIONS: Adequate treatment is critical for the prevention of CS. Further strategies focusing on early diagnosis and adequate treatment among syphilis infected pregnant women, particularly among those with younger age and high nontreponemal titer, should be strengthened to prevent CS.

Theaflavin ameliorates renal ischemia/reperfusion injury by activating the Nrf2 signalling pathway in vivo and in vitro.

Studies have demonstrated that oxidaive stress-induced apoptosis may be the main pathogenic mechanism of renal ischemia/reperfusion (I/R) injury. Theaflavin, a polyphenolic compound extracted from black tea, has been proven to exert strong antioxidant biological function. The objective of the present study was to investigate the potential role of theaflavin on renal I/R injury and its potential molecular mechanism both in vitro and in vivo. C57/BL6 J mice were used to create a model of I/R injury wherein mice were ligated with bilateral renal pedicles for 45 min, and then reperfused for 24 h. A hypoxia/reoxygenation (H/R) model of TCMK-1 cells was used to simulate I/R in vitro. Theaflavin were administered to the treatment group first and then established the model. Kidney Injury Molecule-1 (KIM-1), serum creatinine, urea nitrogen, and 24-h urinary protein levels were evaluated and changes in mitochondrial membrane potential and the ultrastructure of mitochondria were observed. Cell viability, oxidative stress damage, and apoptosis were assessed. The expression levels of nuclear factor erythroid 2-related factor 2 (Nrf2) and its downstream target genes HO-1 and NQO1 were evaluated. Our results revealed that pretreatment with theaflavin significantly inhibited I/R- and H/R-induced renal injury and cell apoptosis. Theaflavin improved mitochondrial dysfunction by attenuating mitochondrial damage and promoting mitochondrial membrane potential. Theaflavin pretreatment significantly reduced malondialdehyde content, while enhancing superoxide dismutase activity in vivo and in vitro. It also reduced oxidative stress and apoptosis mainly by upregulating Nrf2 and its downstream targets in TCMK-1 cells. Thus, theaflavin exerted a protective effect against renal I/R injury by inhibiting oxidative stress and apoptosis via activation of the Nrf2-NQO1/HO-1 pathway as well as correcting mitochondrial dysfunction, thereby presenting its potential as a clinical therapeutic in cases of acute kidney injury.

circITGA7 Acts as a miR-370-3p Sponge to Suppress the Proliferation of Prostate Cancer.

Prostate cancer (PCa) refers to one of the most common tumors in male's genitourinary system. Emerging research has confirmed that circRNAs play an important role in the occurrence and development of tumors. However, the correlation between circular RNA circITGA7 and PCa still remains unclear. Here, the role of circITGA7 in PCa was explored and the underlying mechanism was investigated as well. The circRNA expression profiles in PCa and the paracancerous tissues were established by high-throughput sequencing. The expression levels of circITGA7 in PCa tissues and cells were detected by qRT-PCR. Cell Counting Kit-8, colony formation, EdU, and flow cytometry assays were used to detect the effects of circITGA7 on PCa cell proliferation. To further explore the underlying mechanisms, bioinformatics analysis on downstream target genes was carried out. RNA immunoprecipitation and dual-luciferase reporter assays were used to verify the direct relationship between miR-370-3p and circITGA7 or P21CIP1. The present results demonstrated that circITGA7 was downregulated in PCa tissues and cells. Gain- or loss-of-function assays showed that circITGA7 inhibited the proliferation of PCa cells in vivo and in vitro. Mechanically, circITGA7 served as a sponge for miR-370-3p, and miR-370-3p could target P21CIP1 in PCa cells. The inhibition of cell proliferation induced by circITGA7 could be reversed by transfecting miR-370-3p mimic. Collectively, our data indicated that circITGA7 played an important role in inhibiting tumor proliferation in PCa and might be a potential therapeutic target.

Maternal syphilis treatment and pregnancy outcomes: a retrospective study in Jiangxi Province, China.

BACKGROUND: Studies investigating the associations of maternal syphilis treatment with birth outcomes mainly concentrated in economically developed areas. Limited data are available in economically underdeveloped areas, such as Jiangxi Province. The study aims to investigate the impact of maternal treatment on birth outcomes in Jiangxi Province, China. METHODS: Data were obtained from the China's Information System of Prevention of Mother-to-Child Transmission in Jiangxi Province. All syphilis infected pregnant women who delivered ≥28 gestational weeks and were registered in this system between 1 January 2013 and 31 December 2019 were enrolled. Pregnancy outcomes were evaluated by group-specific analyses according to their treatment status, adequacy and initiation time. RESULTS: 4210 syphilis infected pregnant women were included in the analyses. Infants born to untreated mothers (n = 1364) were at significantly higher risk for stillbirth (adjusted odds ratio (aOR) = 1.74, 95% CI, 1.01-3.00, P = 0.045), preterm birth (aOR = 1.27, 95% CI, 1.02-1.59, P = 0.034) and low birth weight (LBW) (aOR = 1.44; 95% CI, 1.11-1.86, P = 0.006) than those born to treated mothers (n = 2846) after adjustment for confounding factors. A significantly higher risk of stillbirth (aOR = 3.68; 95% CI, 1.62-8.34, P = 0.002), preterm birth (aOR = 2.26; 95% CI, 1.71-3.00, P < 0.001), LBW (aOR = 2.23; 95% CI, 1.59-3.14, P < 0.001) and congenital syphilis (CS) (aOR = 3.63; 95% CI, 1.80-7.31, P < 0.001) was found in infants exposed to mothers treated inadequately (n = 1299) than those treated adequately (n = 1547). No pregnant women who initiated the treatment in the first trimester (n = 682) delivered a neonatal CS case. Compared with mothers who initiated treatment in the first trimester (n = 682), those initiated in the third trimester (n = 1234) suffered an increased risk of stillbirth (aOR = 4.48; 95% CI, 1.31-15.30, P = 0.017), preterm birth (aOR = 2.34; 95% CI, 1.61-3.40, P < 0.001) and LBW (aOR = 3.25; 95% CI, 1.97-5.37, P < 0.001). CONCLUSIONS: Maternal treatment, especially early and adequate treatment, plays a crucial role in mitigating adverse pregnancy outcomes among syphilis infected women.

Quantitative Hepatitis B Surface Antigen Predicts Hepatitis B Transmission in Infants Born to e Antigen-positive Mothers.

GOALS: This study aimed to explore whether quantitative surface antigen [hepatitis B surface antigen (HBsAg)] can be used as a surrogate marker of hepatitis B virus (HBV) DNA to predict hepatitis B transmission before the first hepatitis vaccine dose in infants born to hepatitis B e antigen (HBeAg)-positive pregnant women. BACKGROUND: Currently, HBV transmission persistently occurs worldwide, especially in infants born to e antigen (HBeAg)-positive highly viremic mothers. However, due to high cost, the extensive use of viral load testing to identify these high-risk mothers is limited. MATERIALS AND METHODS: In total of 275 HBeAg-positive pregnant women paired with 280 infants were enrolled in this study. Quantitative HBsAg and HBV DNA levels were measured in the third trimester. Spearman rank correlation was used to assess the correlation between HBsAg levels and viral load, and multivariate logistic regression to identify factors related to HBV transmission in infants. RESULTS: Among 280 infants included, 15 (5.4%) infants were infected with HBV. In this study, we observed that quantitative HBsAg was positively correlated with maternal viral load (r=0.70, P<0.001) and highly predicted HBV transmission in infants born to HBeAg-positive mothers with area under the curve of 0.76 (95% confidence interval, 0.71-0.81). The optimum threshold HBsAg levels above 4.6 log10 IU/mL to predict HBV transmission in infants had a sensitivity of 80.0%, specificity of 67.9%. CONCLUSIONS: Quantitative HBsAg could be used as a surrogate marker of HBV DNA levels to predict hepatitis B transmission occurring before the injection of first-dose vaccine in infants born to e antigen-positive mothers.

Inhibition of miR-9-5p suppresses prostate cancer progress by targeting StarD13.

BACKGROUND: This study aims to investigate the effects of inhibiting microRNA-9-5p (miR-9-5p) on the expression of StAR-related lipid transfer domain containing 13 (StarD13) and the progress of prostate cancer. METHODS: The mRNA expression levels of miR-9-5p and StarD13 were determined in several prostate cancer cell lines. We chose DU145 and PC-3 cells for further research. The CCK8 assay was used to measure the cell viability. The cell invasion and wound-healing assays were respectively applied to evaluate invasion and migration. The expression of E-cadherin (E-cad), N-cadherin (N-cad) and vimentin were measured via western blot. DU145 and PC-3 cells overexpressing StarD13 were generated to investigate the variation in proliferation, invasion and migration. A luciferase reporter assay was used to identify the target of miR-9-5p. RESULTS: Our results show that miR-9-5p was highly expressed and StarD13 was suppressed in prostate cancer cells. MiR-9-5p inhibition repressed the cells' viability, invasion and migration. It also increased the expression of E-cad and decreased that of N-cad and vimentin. StarD13 overexpression gave the same results as silencing of miR-9-5p: suppression of cell proliferation, invasion and migration. The bioinformatics analysis predicted StarD13 as a target gene of miR-9-5p. Quantitative RT-PCR, western blot analysis and the dual-luciferase reporter assay were employed to confirm the prediction. CONCLUSION: Our results show that miR-9-5p plays a powerful role in the growth, invasion, migration and epithelial-mesenchymal transition (EMT) of prostate cancer cells by regulating StarD13. A therapeutic agent inhibiting miR-9-5p could act as a tumor suppressor for prostate cancer.

Maternal hepatitis B surface antigen carrier status increased the incidence of gestational diabetes mellitus.

BACKGROUND: The relationship between chronic hepatitis B virus (HBV) infection with gestational diabetes mellitus (GDM) remains unclear. This study aimed to identify the association between maternal HBsAg-positive status and GDM. METHODS: A retrospective cohort study was performed on the pregnant women who delivered from June 2012 to May 2016 at Wuhan Medical Care Center for Women and Children, Wuhan, China. We compared the incidence of GDM between HBsAg-positive pregnant women and HBsAg-negative controls. A multivariate regression model was used to measure the independent association between maternal HBsAg carrier and the risk of developing GDM. RESULTS: In total, 964 HBsAg-positive pregnant women and 964 HBsAg-negative women were included into the study. We observed maternal HBsAg carrier (OR 1.47, 95% CI 1.06-2.03), age (OR 1.05, 95% CI 1.00-1.10) and family history of diabetes (OR 3.97, 95% CI 2.05-7.67) had an independent risk for GDM in multivariable logistical regression model. However, no significant association was found between HBeAg carrier status, other HBV markers or viral load in pregnancy and the incidence of GDM. CONCLUSIONS: Our results indicated that maternal HBsAg carriage is an independent risk factor for GDM, but viral activity indicated by HBeAg status and viral load is not the main reason for this phenomenon. Further studies are warranted to clarify the possible mechanisms behind such association of HBV infection and the additional risk of GDM.

Incidence and Risk Factors of Intrauterine Transmission Among Pregnant Women With Chronic Hepatitis B Virus Infection.

GOALS: To identify the potential risk factors of hepatitis B virus (HBV) intrauterine transmission and predict the incidence of HBV intrauterine transmission among hepatitis B surface antigen-positive pregnant women with diverse viral load. BACKGROUND: The intrauterine transmission of HBV significantly contributes to the persistence of a high number of patients infected with HBV. However, its risk factors remain unclear. MATERIALS AND METHODS: A prospective study was performed on hepatitis B surface antigen-positive pregnant women who delivered from June 2012 to December 2016 at Wuhan Medical Care Center for Women and Children, Wuhan, China. RESULTS: In total, 1200 women paired with 1219 infants were enrolled. In total, 11 (0.9%) infants were identified with intrauterine transmission. We observed that all infants with intrauterine transmission were born to hepatitis B e antigen-positive mothers who had serum HBV DNA levels >7 log10 copies/mL. Our study suggested that the HBV DNA levels (for each log10 copies/mL increase, odds ratio=5.43; 95% confidence interval, 1.31-22.43; P=0.019) had independent effects on HBV intrauterine transmission in a multivariate logistic regression model. Moreover, cesarean section (odds ratio=0.18; 95% confidence interval, 0.04-0.74; P=0.018) was associated with a reduced risk of HBV intrauterine transmission. The predictive rates of intrauterine transmission were 0.06%, 0.50%, 2.81%, 8.89% in infants with maternal HBV DNA levels of 10, 10, 10, 10 copies/mL, respectively. CONCLUSIONS: Our data confirmed that increasing maternal viral load has the ability to predict intrauterine HBV transmission. Vaginal delivery increased risk of HBV transmission in infants compared with cesarean section. Further studies are warranted to clarify the possible mechanism underlying these associations.

G protein-coupled receptor kinase 2 inhibition improves erectile function through amelioration of endothelial dysfunction and oxidative stress in a rat model of type 2 diabetes.

Type 2 diabetes mellitus (T2DM) is a common cause of erectile dysfunction (ED). It has been demonstrated that G protein-coupled receptor kinase 2 (GRK2) overexpression contributes to diabetic endothelial dysfunction and oxidative stress, which also underlies ED in T2DM. We hypothesized that GRK2 overexpressed and attenuated endothelial function of the cavernosal tissue in a rat model of T2DM. T2DM rats were established by feeding with a high-fat diet (HFD) for 2 weeks and then administering two intraperitoneal (IP) injections of a low dose of streptozotocin (STZ), followed by continuous feeding with a HFD for 6 weeks. GRK2 was inhibited by IP injection of paroxetine, a selective GRK2 inhibitor, after STZ injection. Insulin challenge tests, intracavernous pressure (ICP), GRK2 expression, the protein kinase B (Akt)/endothelial nitric oxide synthase (eNOS) pathway, nicotinamide adenine dinucleotide phosphate (NADPH) oxidase subunit gp91phox, nitric oxide (NO), reactive oxygen species (ROS) production, and apoptosis in cavernosal tissue were examined. Less response to insulin injection was observed in T2DM rats 2 weeks after HFD. Markedly increased GRK2 expression, along with impaired Akt/eNOS pathway, reduced NO production, increased gp91phox expression and ROS generation, increased apoptosis and impaired erectile function were found in T2DM rats. Inhibition of GRK2 with paroxetine ameliorated Akt/eNOS signaling, restored NO production, downregulated NADPH oxidase, subsequently inhibited ROS generation and apoptosis, and ultimately preserved erectile function. These results indicated that GRK2 upregulation may be an important mechanism underlying T2DM ED, and GRK2 inhibition may be a potential therapeutic strategy for T2DM ED.

Cesarean section reduces the risk of early mother-to-child transmission of hepatitis B virus.

AIMS: To evaluate the effects of cesarean section (CS) on the prevention of mother-to-child transmission (MTCT) of hepatitis B virus (HBV) among hepatitis B surface antigen (HBsAg) positive pregnant women. METHODS: A prospective cohort study was performed on HBsAg-positive pregnant women who delivered from June 2012 to March 2017 at Wuhan Medical Care Center for Women and Children in Wuhan, China. Logistic regression models were used to examine the associations between mode of delivery and the presence of HBV MTCT. RESULTS: A total of 1384 women paired with 1407 infants were enrolled. Our study showed that the incidence of HBV MTCT was 1.0% (14/1407) in infants born to HBsAg-positive pregnant women. We observed that the infants born by CS had a smaller percentage of HBV infection than those born by vaginal delivery (VD) (0.5% vs 1.7%, P = 0.043). In the fully adjusted model, CS was significantly associated with a decreased risk of HBV MTCT (OR = 0.26; 95% CI: 0.07-0.95; P = 0.042). CONCLUSION: Our data confirmed that CS has a protective effect on early MTCT of HBV. CS for HBeAg-positive mothers with high viral load could reduce risk of MTCT and may become a new preventive measure of HBV MTCT through research on its risk-benefit assessment.

Genetic variations in LTA gene and PDCD1 gene and intrauterine infection of hepatitis B virus: a case-control study in China.

Intrauterine infection with hepatitis B virus (HBV) has been suggested to accounting for most cases of chronic HBV infection, which cannot be blocked by combined immunoprophylaxis. The fact that the genetic background might impact the susceptibility to intrauterine infection of HBV has been identified by recent researches. A case-control study included sixty-nine HBsAg-positive mother-newborn pairs with intrauterine infection as cases compared to 138 mother-newborn pairs without intrauterine infection as controls. We studied the correlations between HBV intrauterine transmission and 15 maternal SNPs in eight genes (LTA, LTBR, TNFSF14, PDCD1, APOBEC3B, CD274, CD40 and CD40LG). There was a substantially significantly decreased risk of intrauterine infection of HBV in mothers with the rs2227981 TT genotype in PDCD1 gene compared to those with the rs2227981 GG genotype (OR 0.11, 95% CI 0.01-0.95, P = 0.045). Under recessive model (OR 0.51, 95% CI 0.26-1, P = 0.050) and additive model (OR 0.50, 95% CI 0.28-0.88, P = 0.017), we also found a marginally significantly decreased risk of intrauterine infection of HBV. Furthermore, under additive model, maternal genotype for rs2239704 in LTA gene was marginally significantly related to an increased risk of intrauterine HBV infection (OR 1.62, 95% CI 1-6.66, P = 0.055). However, there were no statistically significant associations among the remaining 13 SNPs and the risk of intrauterine infection of HBV. The examination implied that hereditary variants of PDCD1 and LTA genes were associated with intrauterine infection of HBV.

Amelioration of Cavernosal Fibrosis and Erectile Function by Lysyl Oxidase Inhibition in a Rat Model of Cavernous Nerve Injury.

BACKGROUND: Cavernous nerve injury (CNI) causes fibrosis and loss of smooth muscle cells (SMCs) in the corpus cavernosum and leads to erectile dysfunction, and lysyl oxidase (LOX) activation has been found to play an important role in fibrotic diseases. AIM: To evaluate the role of LOX in penile fibrosis after bilateral CNI (BCNI). METHODS: Rats underwent BCNI or a sham operation and were treated with vehicle or ß-aminopropionitrile, a specific LOX activity inhibitor. 30 days after BCNI, rats were tested for erectile function before penile tissue harvest. LOX and extracellular matrix component expression levels in the corpus cavernosum, including matrix metalloproteinases (MMPs), tissue inhibitors of metalloproteinases (TIMPs), fibronectin (FN), collagen (COL) I, and COL IV, were evaluated by real-time quantitative polymerase chain reaction and western blot. Corporal fibrosis was evaluated by Masson trichrome staining. Localization of LOX and SMC content in the corpus cavernosum were assessed by immunohistochemistry. OUTCOMES: Ratio of intracavernous pressure to mean arterial blood pressure; LOX, MMPs, TIMPs, COL I, COL IV, and FN expression; penile fibrosis; penile SMC content. RESULTS: After BCNI, there was an increase in penile LOX expression and activity, increased penile fibrosis, decreased SMC content, and impaired erectile function. TIMP1, TIMP2, COL I, COL IV, and FN expression was markedly upregulated, whereas the enzyme activity of MMPs was decreased after BCNI. ß-Aminopropionitrile treatment, at least in part, prevented a decrease in the ratio of intracavernous pressure to mean arterial blood pressure, decreased penile expression of TIMP1, TIMP2, COL I, COL IV, and FN, increased MMP activity, prevented corporal fibrosis, and preserved SMC content. CLINICAL TRANSLATION: LOX over-activation contributes to penile fibrosis and LOX inhibition could be a promising strategy in preventing the progression of CNI-induced erectile dysfunction. STRENGTHS AND LIMITATIONS: This is the 1st study to demonstrate the role of LOX activation in penile fibrosis. However, the exact mechanism of how LOX influences extracellular matrix protein synthesis and SMC content preservation awaits further investigation. CONCLUSION: CNI induced LOX over-activation in cavernous tissue, and inhibition of LOX preserved penile morphology and improved erectile function in a rat model of BCNI. Wan Z-H, Li G-H, Guo Y-L, et al. Amelioration of Cavernosal Fibrosis and Erectile Function by Lysyl Oxidase Inhibition in a Rat Model of Cavernous Nerve Injury. J Sex Med 2018;15:304-313.

Maternal Hepatitis B Virus Infection and Pregnancy Outcomes: A Hospital-based Case-control Study in Wuhan, China.

GOALS: To examine the impact of maternal hepatitis B virus infection on pregnancy outcomes. BACKGROUND: Studies regarding hepatitis B virus infection and pregnancy outcomes are limited with inconsistent results, and none of them have evaluated the effect of maternal viral load in pregnancy on pregnancy outcomes. STUDY: A hospital-based case-control study was conducted. In total, 1728 hepatitis B surface antigen (HBsAg)-positive women who delivered consecutively at Wuhan Women and Children Medical and Healthcare Center, Wuhan, China, from June 2008 to May 2015, were compared with 1497 HBsAg-negative women giving birth in the same hospital during the same period who were randomly identified and selected from the computerized medical record database in parallel. Univariate and multivariate logistic regression models were constructed. RESULTS: After adjusting for confounding variables, maternal HBsAg carriage was associated with increased risk of pregnancy-induced hypertension [adjusted odds ratio (aOR)=2.20; 95% confidence interval (CI), 1.30-3.73], fetal distress (aOR=1.40; 95% CI, 1.09-1.78), cesarean delivery (aOR=1.70; 95% CI, 1.45-1.99), and macrosomia (aOR=1.68; 95% CI, 1.19-2.37). Moreover, maternal viral load in the second trimester was significantly associated with risk of preterm birth (aOR for each log10 copy/mL increase, 1.18; 95% CI, 1.01-1.39) among HBsAg carriers after adjustment for maternal age, employment, parity, history of abortion, and prenatal body mass index. CONCLUSIONS: Maternal HBsAg carriage was associated with several adverse pregnancy outcomes. Furthermore, hepatitis B viral activity in pregnancy might have certain effects on pregnancy outcomes. Careful surveillance of maternal HBsAg status as well as viral activity in the second trimester among HBsAg carriers is warranted.

Associations of phthalates exposure with attention deficits hyperactivity disorder: A case-control study among Chinese children.

Researches on associations between phthalates exposure and child attention deficit hyperactivity disorder (ADHD) are inconsistent. This study aimed to evaluate the associations of urinary phthalates with ADHD, co-occurring oppositional defiant disorder (ODD), related symptoms and behavior problems among Chinese children. We enrolled 225 ADHD cases and 225 healthy controls aged 6-13 years old in Liuzhou, China. Each child provided repeated urine samples at 4 visits. Eight phthalate metabolites were measured by high-performance liquid chromatography and tandem mass spectrometry. Child ADHD symptoms and related behaviors were assessed using Swanson, Nolan, and Pelham Version IV scale and child behavior checklist. Higher urinary concentrations of mono(2-ethyl-5-hydroxyhexyl) phthalate (MEHHP), mono(2-ethyl-5-oxohexyl) phthalate (MEOHP), mono-(2-ethyl)-hexyl phthalate (MEHP) were dose-dependently associated with ADHD [odds ratios (ORs) ranged from 2.35 to 3.04 for the highest vs. the lowest tertile] and co-occurring ODD (ORs ranged from 3.27 to 4.44 for the highest vs. the lowest tertile) in the multivariable logistic regression models (all p for trend ≤ 0.01), which were consistent with positive trends of increased scores of inattention domain, hyperactive domain and ODD symptoms (all p for trend ≤ 0.01). Besides, the monomethyl phthalate (MMP) concentration was associated with higher scores of inattention domain and ODD symptoms (both p < 0.05). Additionally, the MEHHP, MEOHP and MEHP concentrations were related to child attention problems, aggressive behaviors and externalizing behaviors (all p < 0.05). We also observed positive associations of the MEHP concentration with depressed behaviors and internalizing behaviors (all p < 0.05). Our results indicate that child exposure to phthalates may contribute to ADHD, ODD and externalizing and internalizing behavior problems.

Elevated homocysteine levels in mothers with neural tube defects: a systematic review and meta-analysis.

PURPOSE: To find the real relationship between maternal total homocysteine (tHcy) level and risk of neural tube defects (NTDs). MATERIALS AND METHODS: A systematic review and meta-analysis were conducted. The literature search was conducted with the use of PubMed and EMBASE databases and weighted mean difference (WMD) with 95% confidence interval (CI) was applied to measure the difference in tHcy level between case and control group. Seventeen articles involving 3237 subjects were included according to the inclusion criteria. RESULTS: Pooled result showed that mothers with NTDs offspring demonstrated significantly a higher mean log plasma tHcy level than mothers with normal offspring (log WMD: 0.06; 95%CI: 0.02-0.09, p = 0.001), corresponding to an increase of 6% (2-9%) in the geometric mean. Subgroup analyses also displayed this difference in subjects who were detected during pregnancy or without folate supplementation before sampling. However, in the mandatory folate fortification countries, we did not find this association. CONCLUSIONS: A slightly higher tHcy level in mothers with NTDs was indicated, but potential confounders could not be ruled out completely. Further larger or cohort studies are needed to confirm this association.

Genetic variant in CXCL13 gene is associated with susceptibility to intrauterine infection of hepatitis B virus.

Intrauterine infection of hepatitis B virus (HBV), which accounts for the majority of mother-to-child transmission, is one of the main reasons for the failure of combined immunoprophylaxis against the transmission. Recent studies have identified that genetic background might influence the susceptibility to intrauterine infection of HBV. We conducted this study to investigate the associations between 10 genetic variants in 9 genes (SLC10A1, HLA-DP, HLA-C, CXCR5, CXCL13, TLR3, TLR4, TLR9 and UBE2L3) of mothers and their neonates and HBV intrauterine infection. A significantly decreased risk of HBV intrauterine transmission were found among mothers who carried the rs355687 CT genotypes in CXCL13 gene compared to those with CC genotypes (OR = 0.25, 95% CI, 0.08-0.82, P = 0.022); and a marginally significantly decreased risk was also observed under the dominant model (OR = 0.34, 95% CI, 0.11-1.01, P = 0.052). Besides, neonatal rs3130542 in HLA-C gene was found to be marginally significantly associated with decreased risk of HBV intrauterine infection under the additive model (OR = 0.55, 95% CI, 0.29-1.04, P = 0.064). However, we found no evidence of associations between the remaining 8 SNPs and risk of HBV intrauterine infection among mothers and their neonates. In conclusion, this study suggested that genetic variant in CXCL13 gene was associated with susceptibility to intrauterine infection of HBV.

Relationships between plasma leptin levels, leptin G2548A, leptin receptor Gln223Arg polymorphisms and gestational diabetes mellitus in Chinese population.

The purposes of this study were to examine concentrations of leptin and biochemical parameters in gestational diabetes mellitus (GDM) patients and normal glucose tolerance (NGT) individuals, and also to explore the links of leptin (LEP) G2548A and leptin receptor (LEPR) Gln223Arg polymorphisms with leptin levels and GDM risk among Chinese. Our study included 357 GDM and 355 NGT individuals who were at 24~30 gestational weeks. Plasma leptin and insulin levels were analyzed by ELISA. Gene polymorphisms were genotyped using TaqMan real-time polymerase chain reaction assay. The results showed that plasma leptin levels were significantly higher in the impaired fasting glucose (IFG) group than NGT group (34.35 (26.54, 56.48) ng/mL vs 26.31 (17.99, 37.87) ng/mL, P < 0.05). Plasma leptin levels correlated with plasma fasting insulin levels, pre-pregnant body mass index, homeostasis model assessment-insulin resistance and quantitative insulin sensitivity check index both in GDM and NGT group (P < 0.05). However, neither LEP G2548A nor LEPR Gln223Arg polymorphisms were significantly associated with GDM risk and plasma leptin levels (P > 0.05). Our findings showed that high leptin level was associated with GDM. And larger and more rigorous researches were needed to further explore the association of LEP and LEPR gene polymorphisms and GDM among Chinese population.