OBJECTIVE To investigate the dynamic changes in urine metabolic profiles in rats induced by D-galactose (D-Gal),and to study the correlations between the differential metabolites and behavior indicators using the proton nuclear magnetic resonance (1H-NMR)-based metabonomics.METHODS Subcutaneous injection of D-Gal 100 mg· kg-1 for 10 weeks was adopted in the model group.The sample of urine was collected at day 0 (dO),d14,d28,d42,d56 and d70.NMR metabonomics technique was used for acquisition of data,which was analyzed by multivariate statistical analysis.The ability of learning and memory were measured by Morris water maze test from d70.After the behavioral test,the rats were sacrificed and the hippocampus was observed by hematoxylin-eosin staining.RESULTS Principal component analysis (PCA) results revealed that there was considerable difference between the model group and the normal control group at d70.According to the varible importance plot (VIP) calculation and S-plot scores,a total of 12 metabolites were screened and identified as potential biomarkers at d70.The differences of metabolites and Morris water maze test were subjected to correlation analysis,and the results showed that the levels of choline,lactate and dimethylglycine in the model group were significantly increased and negatively correlated with the times of crossing the platform (r =-0.90,-0.50 and-0.52;n=10).Formate was significantly negatively correlated with the time spent in the target area (r =-0.51,n=10),but choline and formate were significantly positively correlated with the escape latency (r =0.72 and 0.53;n=10).However,the levels of creatine and taurine decreased in the model group,which was significantly positively correlated to the times of acrossing platforms (r =0.89 and 0.71;n=10),while alanine was significantly positively correlated to the time spent in the target area(r =0.74,n=10).Taurine,alanine and creatine were significantly negatively correlated with the escape latency (r =-0.66,-0.50 and-0.85;n=10).The correlations between the differential metabolites and the behavioral indicators were further proved.CONCLUSION The metabolic profile changes in urine from D-Gal induced aging model rats are significantly correlated with impairement of ability in learning and memory.1H-NMR metabonomics in urinary metabolic profile changes may be used as an evaluation index in the D-Gal induced aging rats model.

OBJECTIVE: To observe the effects of probiotics supplementation on the natural killer T cell (NKT cell) and inflammatory factors in children with sepsis and its protective effect on long-term lung function. METHODS: A total of 100 children with sepsis admitted to the department of pediatric intensive care unit (PICU) of Henan Provincial People's Hospital from March 2021 to May 2022 were selected as the research objects. The children were randomly divided into placebo group and probiotic group, 50 cases in each group. In addition to the conventional treatment, the probiotic group was given oral or nasal administration of 0.5 g probiotics, three times a day for 30 days, and the placebo group received oral placebo. 40 healthy children were selected as the healthy control group. The levels of interleukins (IL-4, IL-10), interferon-γ (IFN-γ) and immunoglobulin E (IgE), percentages of NKT cell in blood and induced sputum, lung function of the two groups of children with sepsis were measured before treatment, 7 days after treatment, and during follow-up. All these data were compared with those of healthy children. Kaplan-Meier analysis was used to compare the incidence of cough varied cough (CVA) between the two septic groups. Multiple linear regression analysis was used to explore the influence of various factors on the proportion of NKT cells in induced sputum. RESULTS: In the placebo group, 2 cases died and 4 cases were lost to follow-up. In the probiotics group, 3 cases died and 5 cases were lost to follow-up. All the inflammatory factors of two groups decreased slowly after 7 day after treatment. There was no significance in the parameters of the two groups, but the levels of probiotic group declined more evidently. During the follow-up, a further decrease of inflammatory factors in probiotic group could be found, the levels of IL-4 and IL-10 were significantly different from those in the placebo group [IL-4 (ng/L): 20.3±9.3 vs. 27.6±11.9, IL-10 (ng/L): 23.1±6.8 vs. 14.4±4.4, both P < 0.05], with a significant decrease in IgE level (μg/L: 53.0±15.6 vs. 64.2±16.9, P < 0.05]. The results of flow cytometry showed that the percentage of NKT cell in peripheral blood in two septic groups decreased gradually, and the proportion of peripheral blood NKT cells in the probiotics group was significantly lower than that in the placebo group after 7 days of treatment [(4.2±0.9)% vs. (5.3±1.2)%, P < 0.05]. In the follow-up, the level of NKT cell in peripheral blood and induced sputum in probiotic group were lower than the placebo group [peripheral blood: (0.024±0.009)% vs. (0.029±0.008)%, induced sputum: (0.025±0.008)% vs. (0.035±0.01)%, both P < 0.05], which were similar to those in the healthy control group. Meanwhile, the percentage of predicted peak expiratory (PEF%) and ratio of forced expiratory volume in one second/forced vital capacity (FEV1/FVC) of probiotic group were higher than those in the placebo group [PEF%: (91.3±4.8)% vs. (85.8±8.6)%, FEV1/FVC ratio: (91.8±4.7)% vs. (87.2±7.4)%, both P < 0.05]. Although there was no significance in the incidence of CVA between two septic groups according to the Kaplan-Meier curve analysis, multiple linear regression analysis showed mechanical ventilation and allergic history were the risk factors for the increase of NKT cells [β values were 0.584, 0.601, 95% confidence interval (95%CI) were 0.069 to 1.099, 0.011 to 1.192, P = 0.027, 0.046], and probiotics was an independent protective factor for the relieve of increase in NKT cells (β value was -0.984,95%CI was -1.378 to -0.591, P = 0.001). CONCLUSIONS Application of probiotics to septic children early could promote the recovery of NKT cell and inflammatory factors, and alleviate the lung function injury induced by them during follow-up, which is helpful to improve the long-term prognosis of the patients.
Child ; Humans ; Interleukin-10 ; Interleukin-4 ; Sepsis ; Probiotics/therapeutic use* ; Lung ; Cough ; Immunoglobulin E

Community acquired pneumonia(CAP)has a high morbidity and mortality rate, and can bring a heavy social and economic burden.Its etiology is complex.How to identify high-risk children, early diagnosis, prognosis prediction are the focus of clinical research.Early identification and active intervention of high-risk children who need hospitalization or admission to pediatric intensive care unit by using score scales and biomarkers are crucial to improve the survival rate.This review summarized the assessment of severity and prognosis of CAP in children by different score scales and biomarkers.