Predicting risk of severe neonatal outcomes in preterm infants born from mother with prelabor rupture of membranes.

BACKGROUND: Perinatal complications are common burdens for neonates born from mother with pPROM. Physicians and parents sometimes need to make critical decisions about neonatal care with short- and long-term implications on infant's health and families and it is important to predict severe neonatal outcomes with high accuracy. METHODS: The study was based on our prospective study on 1001 preterm infants born from mother with pPROM from August 1, 2017, to March 31, 2018 in three hospitals in China. Multivariable logistic regression analysis was applied to build a predicting model incorporating obstetric and neonatal characteristics available within the first day of NICU admission. We used enhanced bootstrap resampling for internal validation. RESULTS: One thousand one-hundred pregnancies with PROM at preterm with a single fetus were included in our study. SNO was diagnosed in 180 (17.98%) neonates. On multivariate analysis of the primary cohort, independent factors for SNO were respiratory support on the first day,, surfactant on day 1, and birth weight, which were selected into the nomogram. The model displayed good discrimination with a C-index of 0.838 (95%CI, 0.802-0.874) and good calibration performance. High C-index value of 0.835 could still be reached in the internal validation and the calibration curve showed good agreement. Decision curve analysis showed if the threshold is > 15%, using our model would achieve higher net benefit than model with birthweight as the only one predictor. CONCLUSION: Variables available on the first day in NICU including respiratory support on the first day, the use of surfactant on the first day and birthweight could be used to predict the risk of SNO in infants born from mother with pPROM with good discrimination and calibration performance.

Latency period of PROM at term and the risk of neonatal infectious diseases.

To find the risk of time thresholds of PROM for infectious diseases of term neonates. A multi-center prospective cohort study including pregnancies with PROM at term with a single fetus were conducted. Time thresholds of the duration from PROM to delivery were examined in 2-h increments to assess the rates of infectious neonatal diseases. 7019 pregnancies were included in the study. Neonatal pneumonia and sepsis were most frequent infectious diseases in neonates born from mother with PROM at term. Rates of early-onset pneumonia varied significantly when comparing length of time of PROM greater than 16 h vs. less than 16 h (for EOP in 3 days of life, adjusted OR 1.864, 95% CI 1.159 ~ 2.997, p = 0.010; for EOP in 7 days of life, adjusted OR 1.704, 95% CI 1.104 ~ 2.628, p = 0.016). Neonates born from mother of whom the length of time from PROM to delivery ≥ 16 h were at a higher risk of acquiring EOP.

The correlation between prelabour rupture of the membranes and neonatal infectious diseases, and the evaluation of guideline implementation in China: a multi-centre prospective cohort study.

BACKGROUND: The aim of this study was to describe the epidemiology of prelabour rupture of membranes (PROM) in China and to assess the association between clinical practice following the guidelines and early neonatal infections. METHODS: We conducted a prospective cohort study of 15926 deliveries in ShenZhen Baoan Women's and Children's Hospital, Xibei Women's and Children's Hospital and Chengdu Women's and Children's Hospital between August 1, 2017, to March 31, 2018. Clinical data were collected for each participant. The epidemiology of PROM was described. The association between PROM with early neonatal infectious outcomes and the influence of the implementation of the guideline on early neonatal infectious outcomes were assessed. FINDINGS: The incidence of PROM was 18•7%. PROM was showed to be a risk factor for neonatal infectious diseases (adjusted OR 1•92, 95%CI 1•49~2•49, p<0•0001), early-onset pneumonia (EOP) (adjusted OR 1•81, 95%CI 1•29~2•53, p=0•0006) and early-onset sepsis(EOS) (adjusted OR 14•56, 95%CI 1•90~111•67, p=0•01) for term neonates. For term neonates born from mother with PROM, induction of labor according to the guideline was a protective factor for neonatal diseases(adjusted OR 0•50, 95%CI 0•25~1•00, p=0•00498) and EOP(adjusted OR 0•32, 95%CI 0•11~0•91, p=0•03). For preterm neonates born from mother with PROM, using antibiotics according to the guideline showed to be protective for neonatal infectious diseases (adjusted OR 0•14, 95%CI 0•09~0•23, p<0•0001) and EOP (adjusted OR 0•08, 95%CI 0•04~0•14, p<0•0001). INTERPRETATION: Our study showed the risk of PROM for infectious diseases (including EOP and EOS) and the benefit of the usage of antibiotics according to the guideline for infectious diseases and EOP for preterm neonates. FUNDING: National Natural Science Foundation of China, Capital Medical Development Research Fund of Beijing.

Vosaroxin induces mitochondrial dysfunction and apoptosis in cervical cancer HeLa cells: Involvement of AMPK/Sirt3/HIF-1 pathway.

Vosaroxin is a quinolone-derivative anticancer agent with inhibitory activity on type II DNA topoisomerases (TOP2). The aim of the present study was to investigate its cytotoxic effect and potential molecular mechanisms in human cervical cancer HeLa cells. Vosaroxin decreased cell viability and increased lactate dehydrogenase (LDH) release in a dose- and time-dependent manner in HeLa cells, but not in normal cervical epithelial cells. Vosaroxin also induced apoptosis and increased caspase-3 activity in HeLa cells. These effects were accompanied by increased mitochondrial reactive oxygen species (ROS) generation, lipid peroxidation, mitochondrial swelling and reduced ATP production. Western blot analysis showed that vosaroxin significantly reduced hypoxia-inducible factor 1α (HIF-1α) protein levels. However, it had no effect on HIF-1α protein degradation and HIF-1α mRNA levels. The results showed that vosaroxin inhibited the synthesis of HIF-1α protein and interfered with the dimerization of HIF-1α and aryl hydrocarbon receptor nuclear translocator (ARNT). In addition, vosaroxin stimulated mitochondrial enzyme activities and superoxide dismutase 2 (SOD2) deacetylation via activating (Sir2 like protein 3) Sirt3. More importantly, vosaroxin-induced inhibition on HIF-1α and its cytotoxic effects, as measured by cell viability, LDH release and apoptosis, were partially prevented by Sirt3 knockdown or the AMP-activated protein kinase (AMPK) inhibitor compound C. Overall, vosaroxin is demonstrated to be a chemotherapeutic agent targeting the Sirt3/HIF-1 pathway and could be beneficial for inducing cytotoxicity in human cervical cancer cells.

[Relationship between the expression of human leukocyte antigen G and preeclampsia].

OBJECTIVES: To detect the expression of human leukocyte antigen-G (HLA-G) in tissues from pregnant women with preeclampsia and discuss the relationship between HLA-G and preeclampsia. METHODS: Pregnant women with preeclampsia in Maternal and Child Health Hospital of Shaanxi Province from March 2009 to December 2009 were included. Eight were included into mild preeclampsia groups and 22 were included into severe preeclampsia group. And 30 age-matched normal pregnancies were referred as the control group. All women in the three groups received cesarean section. The soluble HLA-G (sHLA-G) levels in peripheral blood, umbilical blood and amniotic fluid were examined by ELISA; the expressions of HLA-G protein in placenta, fetal membrane and umbilical cord were examined by western blot. RESULTS: (1) The sHLA-G levels in peripheral blood, umbilical blood and amniotic fluid in each group. The sHLA-G levels in peripheral blood in mild and severe preeclampsia group were (50 ± 14) and (30 ± 6) µg/L respectively, and the sHLA-G levels in umbilical blood were (34 ± 10) and (26 ± 8) µg/L respectively. All were significantly lower than those in the control group (P < 0.01), which were (100 ± 16) and (70 ± 9) µg/L respectively. There was also statistical difference between mild and severe preeclampsia group (P < 0.01). Although the sHLA-G level in umbilical blood of severe preeclampsia group was lower than that in mild preeclampsia group, there was no statistical difference (P > 0.05). The sHLA-G levels in amniotic fluid in mild and severe preeclampsia groups were (26 ± 7) and (25 ± 5) µg/L respectively, which were lower than that in the control group (27 ± 6) µg/L, but the differences were not significant (P > 0.05). There was no statistical difference between mild and severe preeclampsia groups (P > 0.05). (2) The expression levels of HLA-G protein in placenta, fetal membrane and umbilical cord in each group. The expression levels of HLA-G in placenta and fetal membrane in the control group were 1.59 ± 0.36 and 0.42 ± 0.09 respectively. The expression of HLA-G in placenta was significantly higher than that in fetal membrane (P < 0.05). The expression level of HLA-G in umbilical cord in the control group was 0.24 ± 0.17, statistically different from those in placenta and fetal membrane, respectively (P < 0.01). The expression levels of HLA-G in placenta in mild and severe preeclampsia groups were 0.78 ± 0.21 and 0.29 ± 0.17 respectively, significantly different from the control group (P < 0.01). There was no expression of HLA-G in fetal membrane and umbilical cord in mild and severe preeclampsia groups. CONCLUSIONS: The expressions of HLA-G in the peripheral blood, umbilical blood and placenta in women with preeclampsia are significantly lower than those in normal pregnant women. The abnormal expression of HLA-G might be associated with the pathogenesis of preeclampsia.