Multiomics to Characterize the Molecular Events Underlying Impaired Glucose Tolerance in FXR-Knockout Mice.

The prevalence of different metabolic syndromes has grown globally, and the farnesoid X receptor (FXR), a metabolic homeostat for glucose, lipid, and bile acid metabolisms, may serve an important role in the progression of metabolic disorders. Glucose intolerance by FXR deficiency was previously reported and observed in our study, but the underlying biology remained unclear. To investigate the ambiguity, we collected the nontargeted profiles of the fecal metaproteome, serum metabolome, and liver proteome in Fxr-null (Fxr-/-) and wild-type (WT) mice with LC-HRMS. FXR deficiency showed a global impact on the different molecular levels we monitored, suggesting its serious disruption in the gut microbiota, hepatic metabolism, and circulating biomolecules. The network and enrichment analyses of the dysregulated metabolites and proteins suggested the perturbation of carbohydrate and lipid metabolism by FXR deficiency. Fxr-/- mice presented lower levels of hepatic proteins involved in glycogenesis. The impairment of glycogenesis by an FXR deficiency may leave glucose to accumulate in the circulation, which may deteriorate glucose tolerance. Lipid metabolism was dysregulated by FXR deficiency in a structural-dependent manner. Fatty acid ß-oxidations were alleviated, but cholesterol metabolism was promoted by an FXR deficiency. Together, we explored the molecular events associated with glucose intolerance by impaired FXR with integrated novel multiomic data.

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.

Effects of Exercise Training on Cognitive Function in Individuals With Heart Failure: A Meta-Analysis.

OBJECTIVE: Cognitive function is critical for disease self-management; however, it is poorer in individuals with heart failure (HF) than in age-matched people who are healthy. Aging and disease progression collectively threaten the cognitive function of individuals with HF. Exercise has been shown to improve the mobility and mortality risk factors of this population, but the effects of exercise on the cognitive function of individuals with HF are unclear. This meta-analysis aimed to examine these potential effects. METHODS: A systematic literature search was conducted in PubMed, MEDLINE, CINAHL, Cochrane Library, Physiotherapy Evidence Database, and ClinicalKey on literature published until January 2022. Studies examining the effects of exercise training on cognitive function in individuals with HF were included. Characteristics of participants and details of interventions were extracted. Effects of exercise training on global cognitive function, attention, and executive function were analyzed using the Comprehensive Meta-Analysis software. RESULTS: Six studies were included. Individuals with chronic HF were examined in most studies. The average ejection fraction of participants was 23 to 46%. Aerobic exercise was used in most studies. All included studies had exercise frequency of 2 to 3 times per week and a duration of 30 to 60 minutes per session for 12 to 18 weeks. Compared with the control group, exercise training benefited the global cognitive function of individuals with HF and cognitive impairments (standardized mean difference = 0.44; 95% CI = 0.01-0.87). The attention of individuals with HF improved after exercise training compared with that before the intervention. CONCLUSION: Exercise may improve cognitive function in individuals with HF and cognitive impairments. However, due to large heterogeneity in the study design, more studies are needed to support clinical application. IMPACT: These findings should raise clinicians' awareness about the role of exercise on the cognitive function of individuals with HF, in addition to benefits in physical domains.

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.