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Objective:Investigating the distribution of intestinal Akkermansia muciniphila (AKK) and explore abundance-effect in obesity obesity to provide potential dose effect for obesity intervention.Methods:Clinical data of 6 986 subjects including body mass index, waist circumference, and common confounders such as gender, age, diastolic blood pressure, systolic blood pressure, fasting blood glucose, triglyceride, total cholesterol, high density lipoprotein-cholesterol, low density lipoprotein-cholesterol, and uric acid were collected from Guangdong Gut Microbiome Project in 2008. 16S ribosomal RNA (16S rRNA) sequencing data were used to estimate the genus abundance of AKK as well as its operational taxonomic unites (OTUs). Central obesity and overall obesity were diagnosed according to the criteria of China Obesity Working Group in 2002. Multivariate logistic regression was used to analyze the OR (95% CI) of obesity with one-unite elevation of AKK. The dose effect of AKK on obesity was estimated by comparing the trend of ORs from the 1st to the 20th quantile. Results:A total of three AKK OTUs(AKK OTU1, AKK OTU2, AKK OTU3) were identified: AKK OTU1 and AKK OTU2 were distributed in more than 90% of the population, while AKK OTU3 was distributed at 21.7%; All the OTUs showed a"bimodal"distributional pattern and their correlations with common factors were variable. Disparities of the association with obesity were found between the OTUs and the AKK. AKK OTU1, AKK OTU2, and the genus level of AKK showed significant protective effects against obesity; The ORs (95% CI) were 0.95(0.93-0.98), 0.97(0.94-0.99), 0.93(0.91-0.96), respectively for central obesity; And ORs(95% CI) were 0.88(0.80-0.97), 0.98(0.93-1.02), 0.81(0.74-0.89), respectively for overall obesity. The results were similar after adjustment for common confounders. According to the calculation of dose-effect, the protect effects of AKK increased with accumulated abundance and the minimum effective dose on central obesity and overall obesity was 1.83% and 4.98%, respectively. Conclusion:AKK is a protective factor for obesity, but the dose-effect of AKK and the strain-differences should be considered in the future interventional study.
RESUMO
Objective To investigate the radiation induced pulmonary fibrosis with a dose-response mouse model, based on the CT image changes of pulmonary fibrosis.Methods Female C57BL6 mice aged 8-10 weeks were randomly divided into 20 Gy or escalated doses of X-ray whole thoracic irradiation ( WTI) groups. CT scan was performed at different time points before and after radiation. The average lung density and lung volume changes were obtained by three-dimensional segmentation algorithm. After gene chip and pathological validation, the parameters of CT scan were subject to the establishment of logistic regression model. Results At the endpoint of 24 weeks post-irradiation, the lung density in the 20 Gy irradiation group was (-289.81± 12.06) HU, significantly increased compared with (-377.97± 6.24) HU in the control group ( P<0.001) . The lung volume was ( 0.66±0.01) cm3 in the control group, significantly larger than ( 0.44±0.03) cm3 in the irradiated mice ( P<0.001) . The results of quantitative imaging analysis were in accordance with the findings of HE and Mason staining, which were positively correlated with the fibrosis-related biomarkers at the transcriptional level ( all R2=0.75, all P<0.001) . The ED50 for increased lung density was found to be ( 13.64± 0.14) Gy ( R2=0.99, P<0.001) and ( 16.17± 4.36) Gy ( R2=0.89, P<0.001) for decreased lung volume according to the logistic regression model. Conclusions Quantitative CT measurement of lung density and volume are reliable imaging parameters to evaluate the degree of radiation-induced pulmonary fibrosis in mouse models. The dose-response mouse models with pulmonary fibrosis changes can provide experimental basis for comparative analysis of high-dose hypofractioned irradiation-and half-lung irradiation-induced pulmonary fibrosis.