ABSTRACT
ObjectiveMetabolomics was used to reveal the mechanism of Aconiti Lateralis Radix Praeparata（ALRP） in attenuating toxicity by processing from the aspects of amino acid metabolism， oxidative stress and energy metabolism by analyzing multiple metabolic pathways. MethodTwenty-four rats were randomly divided into control group， raw group and processed group， 8 rats in each group. The raw and processed group were given with 0.64 g·kg-1 of raw ALRP and processed ALRP respectively every day， the control group was given with an equal amount of normal saline once a day. After continuous administration for 7 days， the urine， serum and heart tissue of rats were collected. Pathological examination of the heart was carried out using hematoxylin-eosin（HE） staining， and the activities of lactate dehydrogenase（LDH） and creatine kinase-MB（CK-MB） in serum and cardiac tissues were detected by microplate assay and immunoinhibition assay. The effects of ALRP on rat heart before and after processing were compared and analyzed. Ultra performance liquid chromatography-quadrupole-time-of-flight mass spectrometry（UPLC-Q-TOF-MS） was used to perform urine metabolomics analysis， and multivariate statistical analysis was used to screen for differential metabolites related to ALRP in attenuating toxicity by processing， and pathway enrichment analysis was carried out to explore the processing mechanism. ResultHE staining showed that no obvious pathological changes were observed in the heart tissue of the control group， while obvious infiltration of inflammatory cells such as plasma cells and granulocytes was observed in the heart tissue of the raw group， indicating that the raw ALRP had strong cardiotoxicity. There was no significant difference in HE staining of heart tissue between the processed group and the control group， indicating that the toxicity of ALRP was significantly reduced after processing. Compared with the control group， the activities of LDH and CK-MB were significantly increased in serum and heart tissue of the raw group， and those were significantly decreased in serum and heart tissue of the processed group， suggesting that the myocardial toxicity of processed ALRP was reduced. A total of 108 endogenous differential metabolites associated with the raw ALRP were screened using multivariate statistical analysis in positive and negative modes， of which 51 differential metabolites were back-regulated by the processed ALRP. Biological analysis of the key regulatory pathways and associated network changes showed that the pathways related to toxicity of ALRP mainly included tryptophan metabolism， arginine and proline metabolism， phenylalanine metabolism， aminoacyl-tRNA biosynthesis， alanine， aspartate and glutamate metabolism， etc. The metabolic pathways related to the attenuation of processed ALRP mainly included aminoacyl-tRNA biosynthesis， tryptophan metabolism， phenylalanine， tyrosine and tryptophan biosynthesis， phenylalanine metabolism and caffeine metabolism. ConclusionThe processing technology of ALRP in Guilingji can significantly attenuate the cardiotoxicity of raw products， the mechanism mainly involves amino acid metabolism， oxidative stress and energy metabolism， which can provide experimental bases for the research related to the mechanism of toxicity reduction of ALRP by processing and its clinical safety applications.
ABSTRACT
Objective:To summarize and analyze the clinical features and risk factors of acute focal bacterial nephritis (AFBN) in children.Methods:It was a retrospective cohort study. The clinical data of patients diagnosed with upper urinary tract infection in Children's Hospital Affiliated to Capital Institute of Pediatrics from July 1, 2016 to July 31, 2021 were collected, and the patients all received abdominal enhanced CT examination. According to the imaging examination results, the patients were divided into AFBN group and acute pyelonephritis (APN) group, and the clinical manifestations, laboratory and imaging examination between the two groups were compared. Logistic regression model and receiver operating characteristic curve were used to analyze the risk factors of AFBN.Results:A total of 135 patients with upper urinary tract infection were enrolled in this study, with age of 2.5 (0.5, 3.7) years old, and 68 males (50.4%). There were 67 patients (49.6%) in AFBN group and 68 patients (50.4%) in APN group. There were statistically significant differences in the highest fever temperature, duration of fever after treatment, proportion of lower urinary tract irritation symptoms, proportion of urinary tract malformation or abnormality, white blood cell count, neutrophil count, procalcitonin, C-reactive protein, proportion of pyuria, urinary β2 microglobulin and proportion of using carbapenem antibiotics between the two groups (all P<0.05). Multivariate logistic regression analysis result showed that urinary tract malformation/abnormality ( OR=3.34, 95% CI 1.23-9.10) and leukocytosis ( OR=1.25, 95% CI 1.03-1.51) were the independent risk factors of AFBN. Conclusions:The children with urinary tract infection who have high peak fever, long duration, obvious increase of inflammatory indexes and urinary β2 microglobulin may suggest AFBN. Urinary tract malformation/abnormality and high white blood cells are risk factors of AFBN.
ABSTRACT
Objective:To investigate the expression of Mucosal-associated invariant T (MAIT) cells in the salivary gland of primary Sj?gren′s syndrome (pSS) patients, and to analyze its clinical significance.Methods:Thirty-two pSS patients and 27 non-pSS controls who had salivary gland biopsies were enrolled. The expression of MAIT cells was detected by immunofluorescence and then analyzed based on clinical data. T test, variance analysis and Spearman correlation analysis were used for statistical analysis. Results:The expression of MAIT cells in the salivary gland of pSS patients was significantly higher than in controls [(2.40±0.33)/gland and (0.79±0.13)/gland respectively, t=4.24, P<0.01]. In pSS patients with mouth dryness ( n=26), MAIT cells in the sali-vary gland were significantly increased compared with those without [(2.73±0.38)/gland vs (0.95±0.15)/gland, t=2.24, P=0.03]. In patients with dental caries ( n=17), MAIT cells in the salivary gland were also significantly increased [(3.13±0.54)/gland vs (1.57±0.20)/gland, t=2.57, P=0.02]. The expression of MAIT cells in the salivary gland of pSS patients was positively correlated with erythrocyte sedimentation rate (ESR) and European League Against Rheumatism Sj?gren′s Syndrome Disease Activity Index (ESSDAI) scores ( r=0.37, P=0.04 and r=0.65, P<0.01 respectively). In pSS patients with positive SSA antibody ( n=23), the amount of MAIT cells was more than controls [(2.89±0.40)/gland vs (1.13±0.32)/gland, t=2.61, P=0.01]. The level of MAIT cells in the salivary gland was higher in pSS patients with more lymphocytic foci [one foci: (1.50±0.49)/gland, two foci: (2.29±0.52)/gland, three foci(3.66±0.59)/gland; F=4.22, P=0.02]. Conclusion:The expression of MAIT cells in the salivary gland of pSS patients is significantly higher than non-pSS controls, and is correlated with oral symptoms, disease activity and the production of autoantibodies. This may suggest that MAIT cells may participate in the local inflammation response and play a role in the pathogenesis of pSS.