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Ischemic stroke causes irreversible damage to the brain. The hippocampus is a vulnerable region and plays an important role in cognition and locomotor activity. Puerarin is a phytoestrogen that has beneficial effects in treating neurological disorders. How puerarin protects against hippocampal injury and its molecular mechanisms remain to be elucidated. Transient global brain ischemia was induced by 4-vessel occlusion in adult male Sprague-Dawley rats. The rats were pretreated with puerarin alone or together with LY294002 (an PI3K inhibitor) before ischemia/reperfusion (I/R). The open- and closed-field tasks and Morris water maze (MWM) test were used to assess the effects of puerarin on anxiety-like behavioral and cognitive impairment following I/R. Hematoxylin-eosin staining(HE) was used to examine the survival of hippocampal CA1 pyramidal neurons, and immunoblotting was performed to examine the expression of the related proteins. By using the rat model for transient I/R, we demonstrated that puerarin pretreatment significantly increased the travelling distance and number of crossings in the open- and closed-field tests, reduced latency and increased the proportion of distance and time in zone IV in the MWM. The number of live cells in the hippocampus is sharply increased by puerarin pretreatment.We further observed that the levels of phosphorylated Akt1, GSK-3β and MCL-1were elevated and those of cleaved-caspase-3 were reduced in the puerarin-treatment group. Notably, the PI3K inhibitor LY294002 counteracted all of the effects of puerarin. Our findings suggest that puerarin protects the hippocampus from I/R damage by activating the PI3K/Akt1/GSK-3β/MCL-1 signaling pathway.

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BackgroundThere are estimated 20% of mechanically ventilated patients having difficulty in weaning from the ventilators, and the weaning process accounts for 40% of the whole ventilation time. Reliable tools are urgently needed to estimate the weaning outcome. Diaphragmatic ultrasonography, as a relatively good predictive method for the adults, was measured in this study, assessing the value of each indicator of diaphragmatic ultrasonography to predict the outcomes of ventilator weaning from mechanically ventilated children of 1–3 years old.MethodsBetween November 2018 and November 2019, children who were mechanically ventilated and ready for weaning in the pediatric intensive care unit (PICU) were enrolled in the study. Diaphragmatic ultrasonography was performed to the children to measure the right diaphragm excursion (DE), contraction velocity, thickness, and diaphragm thickening fraction (DTF), which were recorded followed by spontaneous breathing trial (SBT). The receiver operator characteristic (ROC) curves were also used to assess the value of each indicator to predict the weaning outcome.ResultsDuring this study period, a total of 72 children were enrolled, and of them, 56 children passed the weaning process, while 16 children failed. There were significant differences in DE, contraction velocity, thickness, and DTF parameters between the weaning success group and the failure group. The areas under the ROC curves (AUC) and the optimal threshold of the above indicators were as follows: 0.72 and 8.08 mm for DE, 0.71 and 26.1% for right DTF (DTFR), 0.71 and 20.7% for left DTF (DTFL), 0.78 and 14.8% for minimum DTF (DTFMIN), 0.79 and 26.1% for maximum DTF (DTFMAX), 0.71 and 1.24 mm for maximum diaphragm thickness at the end of inspiration (DteiMAX), and 0.65 and 10.0 mm/s for contraction velocity.ConclusionDiaphragmatic ultrasonography is feasible in guiding ventilator weaning, and the indicators of DE, DTF, and DteiMAX guide the weaning more accurately. Among them, DTF may act as a more reliable predictor of weaning by avoiding the influence of diaphragm development in children.

The present study reported the complete mitochondrial genome of Alticorpus geoffreyi for the first time. The mitochondrial genome of A. geoffreyi possesses 16,578 bp in length, involving 22 transfer RNA genes, 2 ribosomal RNA, 13 protein-coding genes and one control region. In addition, its GC content is 45.82% that is similar to that of Astatotilapia calliptera (the GC content of 45.90%). Based on the complete mitochondrial genomes of 14 closely related species, the phylogenetic tree was further made to show their phylogenic relationship. The results will serve as a useful dataset for studying the evolution of Cichlidae mitochondrial genome.

The aim of this study was to establish the population pharmacokinetics (PK) model of Vancomycin for Chinese pediatric patients which can extrapolate to whole age periods by bridging the published adult population PK model and the established pediatric population PK model. The final consolidated population PK model was used to explore the correlation of pharmacokinetics/pharmacodynamics (PK/PD) indices and efficacy of vancomycin and to provide evidence for the optimized regimen of vancomycin in Chinese pediatric patients with Gram-positive bacterial infection. 108 pediatric patients with Gram-positive infections from 2 pediatric hospitals in China in the first period of the prospective multi-center vancomycin clinical observational study were enrolled to establish the population PK model. A one-compartment population PK model was established and validated. The correlation between vancomycin PK/PD indices [trough concentration (Cmin), peak concentration (Cmax), 0–24 h area under the curve (AUC0–24) and the area under the curve to minimum inhibitory concentration ratio (AUC0–24/MIC)] and the overall clinical outcomes (clinical efficacy and microbiological efficacy) in Chinese pediatric patients were evaluated. There is no significant correlation between PK/PD indices and clinical efficacy or microbiological efficacy. Considering the high clinical effective rate (>90%) and median AUC0–24/MIC values of 200–300, Chinese pediatric patients with Gram-positive bacterial infection may be suitable for lower AUC0–24/MIC target value compared to the target value of 400–600 recommended by IDSA guideline. Different optimal dose regimen of vancomycin for Chinese pediatric patients should be considered. Further evaluation in more prospective studies will be needed.

Background: Severe pneumonia due to lower respiratory tract infections (LRTIs) is a significant cause of morbidity and mortality in children. Noninfectious respiratory syndromes resembling LRTIs can complicate the diagnosis and may also make targeted therapy difficult because of the difficulty of identifying LRTI pathogens. In the present study, a highly sensitive metagenomic next-generation sequencing (mNGS) approach was used to characterize the microbiome of bronchoalveolar lavage fluid (BALF) in children with severe lower pneumonia and identify pathogenic microorganisms that may cause severe pneumonia.Methods: In total, 126 BALF samples were collected from children admitted to the pediatric intensive care unit (PICU) with severe pneumonia, and mNGS was performed at the DNA and/or RNA level. The pathogenic microorganisms in BALF were identified and correlated with serological inflammatory indicators, lymphocyte subtypes, and clinical symptoms.Results: mNGS of BALF identified potentially pathogenic bacteria in children with severe pneumonia in the PICU. An increased BALF bacterial diversity index was positively correlated with serum inflammatory indicators and lymphocyte subtypes. Children with severe pneumonia in the PICU had the potential for coinfection with viruses including Epstein–Barr virus, Cytomegalovirus, and Human betaherpesvirus 6B, the abundance of which was positively correlated with immunodeficiency and pneumonia severity, suggesting that the virus may be reactivated in children in the PICU. There was also the potential for coinfection with fungal pathogens including Pneumocystis jirovecii and Aspergillus fumigatus in children with severe pneumonia in the PICU, and an increase in potentially pathogenic eukaryotic diversity in BALF was positively associated with the occurrence of death and sepsis.Conclusions: mNGS can be used for clinical microbiological testing of BALF samples from children in the PICU. Bacterial combined with viral or fungal infections may be present in the BALF of patients with severe pneumonia in the PICU. Viral or fungal infections are associated with greater disease severity and death.