Prevalence of hepatitis E virus and its association with adverse pregnancy outcomes in pregnant women in China.

BACKGROUND: Hepatitis E virus (HEV) infection has become a global concern, especially in pregnant women. However, the association between HEV prevalence and age, gravidity and parity of pregnant women remains unclear. METHODS: Pregnant women (n=19,762) were enrolled for HEV prevalence and associated adverse pregnancy outcomes investigation in Qujing City, Yunnan Province of China from May 2019 to December 2020. RESULTS: The seroprevalence of HEV was 11.6% (2,297/19,762; 95% CI:11.2%-12.1%). About 11.4% (2,247/19,762; 95% CI:10.9%-11.8%) were positive for anti-HEV IgG antibody, 0.1% (22/19,762; 95% CI:0.1%-0.2%) were positive for anti-HEV IgM antibody, and 0.1% (28/19,762; 95% CI:0.1%-0.2%) were positive for both anti-HEV IgM and IgG antibodies. Sixty-one out of 2,297 anti-HEV-antibodies-positive pregnant women were positive for HEV RNA. Phylogenetic analysis revealed that all HEV isolates from pregnant women belong to genotype 4. Age, gravidity and parity are associated with increased prevalence of HEV. Pregnant women positive for HEV-IgG antibody bear a higher risk for an adverse pregnancy history and liver injury with elevated alanine aminotransferase (ALT) and aspartate aminotransferase (AST) levels than anti-HEV-negative pregnant women. Furthermore, seropositive pregnant women suffered a higher adverse maternal outcomes risk (crude odds ratio [cOR]=1.29; 95% CI: 1.16-1.43; adjusted odds ratio [aOR]=1.40, 95% CI: 1.25-1.55 for anti-HEV-IgG-positive pregnant women and cOR=1.38, 95% CI: 1.02-1.86; aOR=1.43, 95% CI: 1.05-1.95 for anti-HEV-IgM-positive pregnant women) and fetal outcomes risk (cOR=1.80, 95% CI: 1.61-2.01; aOR=1.77, 95% CI: 1.57-1.99) than anti-HEV-negative pregnant women. Adverse pregnancy outcomes of HEV infection are aggravated by age, gravidity and parity. CONCLUSION: In this study, we demonstrated high prevalence of HEV in pregnancy women in China, and HEV infection can cause various adverse maternal and neonatal outcomes.

Genotype 4 Hepatitis E virus replicates in the placenta, causes severe histopathological damage, and vertically transmits to fetuses.

BACKGROUND: Hepatitis E virus (HEV) infection in pregnant women causes adverse pregnancy outcomes, including maternal death, premature delivery, stillbirth, and fetal infection. However, the pathogenesis of maternal and fetal HEV infection is unclear. METHODS: Placenta and placental appendixes were collected from HEV-4 infected pregnant women to explore the vertical transmission of HEV from mothers to fetuses. RESULTS: HEV-4 replicated in the placenta, placental membrane, and umbilical cord and was vertically transmitted from mothers to fetuses. HEV-4 placental infection resulted in serious histopathological damage, such as fibrosis and calcification, and severe inflammatory responses. Adverse maternal outcomes were observed in 38.5% of HEV-4 infected pregnant women. The distinct cytokine/chemokine expression patterns of HEV-infected pregnant women and nonpregnant women may contribute to the adverse pregnancy outcomes. Furthermore, the impaired maternal and fetal innate immune responses against HEV-4 facilitated viral replication during pregnancy. CONCLUSION: HEV-4 replicates in the placenta and is vertically transmitted from mothers to fetuses, causing severe histopathological damage.

Protective effects of propofol on experimental neonatal acute lung injury.

The present study aimed to investigate the effects of propofol on neonatal acute lung injury (ALI) in a rat model and to examine the molecular mechanisms underlying propofol function. A rat model of ALI was established by intraperitoneal injection of lipopolysaccharides (LPS). The neonatal rats were treated with various concentrations of propofol and a lung injury score was assessed. The protein expression levels of pro­inflammatory cytokines was detected using ELISA. In the present study, oxidative stress was determined by measuring the level of malondialdehyde (MDA) and the activity of superoxide dismutase (SOD) in lung tissues. Reverse transcription quantitative­polymerase chain reaction and western blot analysis were used to examine the mRNA and protein expression levels of the factors downstream to LPS signaling pathway. Treatment with propofol significantly alleviated LPS­induced lung injury in neonatal rats as suggested by the decreased lung injury score, increased partial pressure of oxygen and decreased lung wet­dry weight ratio. LPS promoted the upregulation of tumor necrosis factor α (TNF­α), interleukin (IL)­6 and IL­1ß in lung tissues and bronchoalveolar lavage fluid from neonatal rats exhibiting ALI. Notably, treatment with propofol decreased the expression levels of these factors. Additionally, LPS caused an increase in the levels of MDA, and a decrease in SOD activity, and treatment with propofol suppressed these effects in a dose­dependent manner. Furthermore, LPS induced the upregulation of phosphorylated (p­)p38, nuclear factor κ­light­chain­enhancer of activated B cells (NF­κB), p­p65, NLR family pyrin domain containing 3 (NLRP3), apoptosis­associated speck­like protein containing CARD and caspase­1 in lung tissues of neonatal rats, and treatment with propofol was able to downregulate these factors in a dose­dependent manner. Propofol alleviated lung injury in neonatal rats with LPS­induced ALI by preventing inflammation and oxidative stress via the regulation of the activity of the p38 mitogen­activated protein kinase/NF­κB signaling pathway and the expression levels of the NLRP3 inflammasome.

Tumor suppressor microRNA­613 inhibits glioma cell proliferation, invasion and angiogenesis by targeting vascular endothelial growth factor A.

MicroRNAs (miRNAs) are small non­coding RNAs which can serve as oncogenes or tumor suppressors in glioma. The present study aimed to investigate the expression of miR­613 in glioma. Reverse transcription­quantitative polymerase chain reaction (RT­qPCR) was used to detect miR­613 in glioma cells and tissues and the relationship between miR­613 and vascular endothelial growth factor (VEGF) A was assessed using a luciferase reporter assay. In addition, glioma cells were transfected with miR­613 mimics and the mRNA and protein expression of VEGFA was detected using RT­qPCR and western blot analysis, respectively. The proliferative, invasive and tube formation capabilities of transfected cells were also assessed in vitro. Furthermore, a nude mouse tumor xenograft model was used to investigate the effects of miR­613 on tumor growth in vivo. The results of the present study demonstrated that the expression of miR­613 was decreased in glioma cell lines, and was associated with the grade of glioma. Ectopic expression of miR­613 markedly suppressed glioma cell proliferation and angiogenesis. Furthermore, the upregulation of miR­613 inhibited tumor angiogenesis and tumor growth in xenografted nude mice in vivo. VEGFA was demonstrated as a direct target of miR­613, as detected by western blot and luciferase reporter assays, and mediated miR­613 induced glioma cell proliferation and angiogenesis inhibition.