[Fuyu Decoction ameliorates myocardial fibrosis in rat model of heart failure by regulating Nrf2/GPX4-mediated ferroptosis].

This study aims to investigate the effect and mechanism of Fuyu Decoction(FYD) in the treatment of myocardial fibrosis in the rat model of heart failure(HF). Sixty Wistar rats were randomized into a modeling group(n=50) and a sham group(n=10). A post-myocardial infarction HF model was established by ligating the left anterior descending coronary artery in rats. The successfully modeled rats were assigned into model, low-dose(2.5 g·kg~(-1)) FYD(FYD-L), high-dose(5.0 g·kg~(-1)) FYD(FYD-H), and FYD+Nrf2 inhibitor(ML385, 30 mg·kg~(-1)) groups(n=10). FYD was administrated by gavage and ML385 by intraperitoneal injection. The rats in the sham and model groups were administrated with equal amounts of normal saline by gavage. After 8 weeks of intervention, the cardiac function indicators were measured, and the myocardial tissue morphology and collagen deposition were observed. The positive expression of collagens Ⅰ and Ⅲ, apoptosis, and oxidative stress were examined, and the levels of Fe~(2+) and reactive oxygen species(ROS) were determined. The protein levels of nuclear factor erythroid 2-related factor 2(Nrf2), solute carrier family 7 member 11(SLC7A11), glutathione peroxidase 4(GPX4), and acyl-coenzyme A synthase long chain family member 4(ACSL4) in the myocardial tissue were determined. Compared with sham group, the model group showed decreased left ventricular ejection fraction(LVEF) and left ventricular fractional shortening(LVFS), increased left ventricular end internal dimension in systole(LVIDs), left ventricular internal diameter in diastole(LVIDd), and myocardial collagen deposition, positive expression of collagens Ⅰ and Ⅲ, elevated apoptosis rate and malondialdehyde(MDA), Fe~(2+), and ROS levels, lowered superoxide dismutase(SOD) and glutathione peroxidase(GSH) levels, down-regulated protein levels of Nrf2, SLC7A11, and GPX4, and up-regulated protein level of ACSL4. Compared with the model group, the above indicators were restored by FYD. Moreover, ML385 reversed the protective effect of FYD on myocardial fibrosis in HF rats. In conclusion, FYD can inhibit ferroptosis by activating the Nrf2/GPX4 pathway, thereby ameliorating myocardial fibrosis in HF rats.

[Association between maternal age and adverse pregnancy outcome in twin pregnancy].

OBJECTIVE: To study the association between maternal age and adverse pregnancy outcome in twin pregnancy. METHODS: The clinical data of 2 363 women with twin pregnancy from January 2006 to June 2016 were retrospectively reviewed. According to the age, the women were divided into six groups: <20 years (n=15), 20-24 years (n=158), 25-29 years (n=894), 30-34 years (n=936), 35-39 years (n=320), and ≥40 years group (n=40). The above groups were compared in terms of related baseline features and incidence rates of adverse pregnancy outcomes (preterm birth, birth defect, stillbirth in late pregnancy and small-for-gestational-age birth). A generalized estimating equation was used to investigate the risk of adverse pregnancy outcomes in different age groups. RESULTS: After control for the factors including place of residence, primipara, pregnancy pattern, and gestational diseases, the incidence rates of very preterm birth and moderately preterm birth in the ≥40 years group were 2.60 and 1.99 times than those in the 25-29 years group respectively (P<0.05). The incidence rates of very preterm birth and late preterm birth in the 20-24 years group were 1.99 and 1.33 times than those in the 25-29 years group respectively (P<0.05). The incidence rates of stillbirth in late pregnancy in the <20 years group, the 20-24 years group, and the ≥40 years group were 9.10, 2.88 and 3.97 times than those in the 25-29 years group respectively (P<0.05). The incidence rates of small-for-gestational-age birth in the <20 years group and the 35-39 years group were 2.70 and 0.73 times than those in the 25-29 years group respectively (P<0.05). CONCLUSIONS: In twin pregnancy, pregnant women, aged <20 years, have a higher risk of smaller-for-gestational-age birth and stillbirth in late pregnancy, those aged ≥40 years have a higher risk of very preterm birth, moderately preterm birth and stillbirth in late pregnancy, and those aged 20-24 years have a higher risk of very preterm birth, late preterm birth and stillbirth in late pregnancy.

Metabolomics analysis reveals perturbations of cerebrocortical metabolic pathways in the Pahenu2 mouse model of phenylketonuria.

AIMS: Phenylketonuria (PKU), which is caused by mutations in the phenylalanine hydroxylase (PAH) gene, is one of the most common inherited diseases of amino acid metabolism. Phenylketonuria is characterized by an abnormal accumulation of phenylalanine and its metabolites in body fluids and brain tissues, subsequently leading to severe brain dysfunction. Various pathophysiological and molecular mechanisms underlying brain dysfunction in PKU have been described. However, the metabolic changes and their impacts on the function of cerebral cortices of patients with PKU remain largely unknown. METHODS: We measured the levels of small molecule metabolites in the cerebrocortical tissues of PKU mice and wild-type control mice using liquid chromatography-mass spectrometry (LC-MS)-based metabolome analysis. Differential metabolites were further subjected to metabolic pathway and enrichment analysis. RESULTS: Metabolome analysis revealed 35 compounds among 143 detected metabolites were significantly changed in PKU mice as compared to those in their wild-type littermates. Metabolic pathway and enrichment analysis of these differential metabolites showed that multiple metabolic pathways, including phenylalanine, tyrosine, and tryptophan biosynthesis; valine, leucine, and isoleucine biosynthesis; alanine, aspartate, and glutamate metabolism; purine metabolism; arginine and proline metabolism and methionine metabolism, were impacted in the cerebral cortices of PKU mice. CONCLUSIONS: The data revealed that multiple metabolic pathways in cerebral cortices of PKU mice were disturbed, suggesting that the disturbances of the metabolic pathways might contribute to neurological or neurodevelopmental dysfunction in PKU, which could thus provide new insights into brain pathogenic mechanisms in PKU as well as mechanistic insights for better understanding the complexity of the metabolic mechanisms of the brain dysfunction in PKU.

[Changes in epidermal growth factor concentrations in neonates with late-onset breast milk jaundice after stopping breast feeding].

OBJECTIVE: To investigate the changes in epidermal growth factor (EGF) concentrations in infants' serum and breast milk in neonates with late-onset breast milk jaundice after stopping breast feeding. METHODS: Thirty full-term infants with late-onset breast milk jaundice were included in the study. Infants' serum and breast milk were collected before and 72 hours after stopping breast feeding, and the total bilirubin and EGF concentrations in infants' serum and EGF concentration in breast milk were measured respectively. RESULTS: At 72 hours after stopping breast feeding, the total bilirubin and EGF concentrations in infants' serum were significantly decreased (P<0.05), but the EGF concentration in breast milk did not show significant change (P>0.05). CONCLUSIONS: After stopping breast feeding, the neonates with late-onset breast milk jaundice show significant decreases in serum EGF concentration, but the EGF concentration in breast milk shows no significant change. The role and action mechanism of EGF in late-onset breast milk jaundice need further study.

[Application of regionalized critical neonatal emergency transport system].

OBJECTIVE: To study the application of the regional critical neonatal emergency transport system (NETS) to provide evidence for the optimization of NETS in Beijing. METHODS: All the transported neonates in four hospitals in Haidian District, Beijing, between January 2009 and September 2010 were enrolled. The relevant clinical information of two referral hospitals was analyzed. RESULTS: The top three conditions requiring transport were pre-term delivery, diseases requiring surgical treatment, and respiratory diseases, which accounted for 33.1%, 18.3%, and 14.8%, respectively. Active transport was performed in 95 cases (66.9%) and passive transport in 47 cases (33.1%). The age distribution of the neonates requiring transport was as follows: <6 hrs after birth (24.1%); 6-12 hrs (9.3%); 12-24 hrs (25.9%); and >24 hrs (40.8%). The mean time for transport from the hospital to a referral ward by ambulance was 28.0±11.1 minutes. Diseases requiring emergency surgical treatment were the leading cause of death, accounting for 53.8% of total deaths. The mortality rate was not significantly different between the neonates aged <6 hrs and ≥6 hrs groups. CONCLUSIONS: Active transport remains the main transport pattern among these four hospitals. Neonates requiring surgical treatment have a high mortality rate, and thus special attention should be paid to their transport.