ABSTRACT
Background The optimal model method for estimation of benchmark dose (BMD) does not consider the uncertainty of model selection. There is a lack of studies on using Bayesian model averaging (BMA) to estimate BMD. Objective To apply BMA to the exposure assessment of cadmium pollution in China, discuss the role of BMA in estimating BMD based on dose-response models, and to provide methodological support for health risk assessment of hazardous substances. Methods The parameters of five dose-response models (Gamma, Log-logistic, Log-probit, Two-stage, and Weibull models) estimated from the data from a cadmium-contaminated area in Baiyin City of Gansu Province and the urinary cadmium ranges in five cadmium-contaminated areas in China were used to simulate the data of varied correct models with different numbers of dosage groups (5 and 8) and different sample sizes (50, 100, and 200), then the performance of BMA and traditional optimal model were compared. The case analysis used the cadmium exposure data in Baiyin, Gansu Province. All analyses set urinary cadmium as the indicator of cadmium exposure, the abnormal rate of β2-microglobulin as the effect indicator, and the benchmark response to 10%. The correct model (the model used when simulating data), optimal model [the model with smallest Akaike information criterion (AIC)], and BMA were used to estimate BMD and lower confidence limit of benchmark dose (BMDL); the BMDs, BMDLs, and relative deviations from different methods were compared. Results In the simulation study, with increasing sample size or the number of dosage groups, the intervals of the 5th percentile and the 90th percentile of BMD tended to be narrower; when the correct model was a single model, the relative deviation of BMD estimation by BMA was greater than that of the traditional optimal model; when the correct model was an equal weight mixed model, the relative deviation of BMD estimation by BMA was less than that by the traditional optimal model. For the data of cadmium-contaminated areas, the optimal model was a Log-probit model (AIC=1814.46), followed by a Log-logistic model (AIC=1814.57); the BMDs (BMDLs) estimated by the Log-probit model, the Log-logistic model, and BMA were 3.46 (2.68), 3.16 (2.33), and 2.92 (2.07) μg·g−1, respectively. Conclusion The traditional optimal model is still recommended when the correct model is known. However, when the dose-response relationship of a hazardous substance is uncertain or with different sources or exposure grouping, compared with the traditional optimal model, BMA theoretically provides more stable estimation of BMD and BMDL by considering multiple possible alternative models.
ABSTRACT
Objective To evaluate the association of gastric hyperplastic polyps with colorectal neo-plasia.Methods Data of consecutive patients who underwent esophagogastroduodenoscopy (EGD)and colonoscopy between January 2011 and December 2013 were reviewed retrospectively.They were compared with patients without gastric polyps who also underwent EGD in the same period.The relationship between gastric polyps and colorectal neoplasia was analyzed.Results The incidence of colorectal neoplasia in gas-tric hyperplastic polyps group was higher than that of the control group [24.0% (46 /192)VS 10.4%(40 /384),P =0.000].An increased incidence of colorectal adenomas in gastric hyperplastic polyps group was found,but there was no difference in the incidence of colorectal cancer in gastric hyperplastic polyps group and control group[2.1%(4 /192)VS 2.3%(9 /384),P =1.000].Stratification analysis suggested that the incidence of colorectal neoplasia in gastric hyperplastic polyps group who aged over 50 was signifi-cantly higher than that in the control group[28.5%(43 /151)VS 10.6%(29 /274),P =0.017],regard-less of different genders and the number of gastric hyperplastic polyps.Conclusion The incidence of color-ectal neoplasia in gastric hyperplastic polyps has significantly increased,especially in those aged over 50 years,regardless of different genders and the number of gastric hyperplastic polyps.Such patients should undergo colonoscopy to detect colorectal neoplasia.
ABSTRACT
Objective To investigate the effects of berberine on tumor-associated macrophages (TAM)and the expression of cyclooxygenase-2 (COX-2)of intestinal polyps in Apc(Min/+) mice.Methods A total of 20 Apc(Min/+) mice,four weeks old,were equally divided into the control group and the berberine group,10 in each group.The mice of the control group drank plain water,while the mice of berberine group drank water with 0.1 % berberine.After 12 weeks,all the mice were sacrificed.The intestine and colon were isolated,and the numbers of polyps were counted.The expression of F4/80,inducible nitric oxide synthase-2 (iNOS),macrophage mannose receptor (MR)and COX-2 was detected by immunohisto-chemistry method.The relative expression of COX-2 at protein level was measured by Western blotting. The t test was performed for comparison between two independent groups.Results The total number of intestinal polyps,the number of small intestinal polyps and the number of colon polyps of the berberine group (11 .50±2.05 ,10.50±1 .77 and 1 .00±0.46,respectively)were all less than those of the control group (30.63±1 .69,28.00±2.00 and 2.63±0.74,respectively),and the differences were statistically significant (t=16.727,16.952 and 3.162,P =0.001 ,0.001 and 0.010,respectively).The percentage of F4/80 positive cells in the stroma of polyps of the berberine group ((17.40 ±4.23 )%)was less than that of the control group ((31 .24±6.34)%),and the difference was statistically significant (t =5 .327, P =0.043).The percentage of iNOS positive cells in the stroma of polyps of the berberine group ((7.43± 1 .78 )%) was higher than that of the control group ((2.72±0.68)%), and the difference was statistically significant (t=7.335 ,P =0.004).The percentage of MR positive cells in stroma of polyps of the berberine group ((19.52±1 .54)%)was less than that of the control group ((12.63±0.68)%),and the difference was statistically significant (t=5 .634,P =0.016).The percentage of COX-2 positive cells in stroma of polyps of berberine group ((3.38 ± 0.51 )%)was less than that of the control group ((7.60±0.57 )%),and the difference was statistically significant (t = 7.234,P = 0.001 ).The relative expression of COX-2 at protein level of polyps of the berberine group was lower than that of the control group. Conclusion Berberine may take the role in inhibiting the growth of intestinal polyps in Apc(Min/+) mice through interfering the differentiation of TAM in polyps and suppression the expression of COX-2.