Momordicine I alleviates isoproterenol-induced cardiomyocyte hypertrophy through suppression of PLA2G6 and DGK-ζ

This study aimed to observe the protective effect of momordicine I, a triterpenoid compound extracted from momordica charantia L., on isoproterenol (ISO)-induced hypertrophy in rat H9c2 cardiomyocytes and investigate its potential mechanism. Treatment with 10 μM ISO induced cardiomyocyte hypertrophy as evidenced by increased cell surface area and protein content as well as pronounced upregulation of fetal genes including atrial natriuretic peptide, β-myosin heavy chain, and α-skeletal actin; however, those responses were markedly attenuated by treatment with 12.5 μg/ml momordicine I. Transcriptome experiment results showed that there were 381 and 447 differentially expressed genes expressed in comparisons of model/control and momordicine I intervention/model, respectively. GO enrichment analysis suggested that the anti-cardiomyocyte hypertrophic effect of momordicine I may be mainly associated with the regulation of metabolic processes. Based on our transcriptome experiment results as well as literature reports, we selected glycerophospholipid metabolizing enzymes group VI phospholipase A 2 (PLA2G6) and diacylglycerol kinase ζ (DGK-ζ) as targets to further explore the potential mechanism through which momordicine I inhibited ISO-induced cardiomyocyte hypertrophy.Our results demonstrated that momordicine I inhibited ISO-induced upregulations of mRNA levels and protein expressions of PLA2G6 and DGK-ζ. Collectively, momordicine I alleviated ISO-induced cardiomyocyte hypertrophy, which may be related to its inhibition of the expression of glycerophospholipid metabolizing enzymes PLA2G6 and DGK-ζ.

Relationship between the chemical properties of drinking water and the prevalence of dental fluorosis based on the principal component regression model in Bijie City, Guizhou Province / 中华地方病学杂志

Objective:To study the relationship between the relevant chemical elements in the original surface drinking water sources and the prevalence of dental fluorosis in Bijie City, Guizhou Province, and to provide a scientific basis for further studying the distribution of dental fluorosis patients, clarifying the mechanism of endemic fluorosis, and scientifically adjusting relevant prevention and treatment policies.Methods:From August 2021 to March 2022, based on the local census data of endemic fluorosis in Guizhou Province, 385 samples of original surface drinking water sources were collected in 214 townships (towns) of Bijie City. The pH value, and contents of fluorine (F), calcium (Ca), magnesium (Mg), aluminum (Al), titanium (Ti), manganese (Mn), copper (Cu), zinc (Zn), nickel (Ni), arsenic (As), molybdenum (Mo), cadmium (Cd), barium (Ba), lead (Pb), chromium (Cr), iron (Fe), and selenium (Se) in the drinking water were determined. Taking the dental fluorosis index representing the prevalence of dental fluorosis as the dependent variable, a principal component multiple regression model was constructed based on the above chemical elements of drinking water to study the related factors affecting the prevalence of dental fluorosis, and its contribution rate was calculated.Results:The median of dental fluorosis index in 214 townships (towns) of Bijie City was 1.460. The average of pH values and contents of F, Ca, Mg, Al, Ti, Cr, Mn, Fe, Ni, Cu, Zn, As, Se, Mo, Cd, Ba and Pb of 385 drinking water samples were 6.369, and 0.209, 179.706, 16.198, 0.163, 0.987, 0.015, 0.073, 0.176, 0.027, 0.014, 0.191, 0.007, 0.005, 0.003, 0.001, 0.155, 0.005 mg/L, respectively. Six principal components ( F1 - F6) were extracted by principal component regression analysis, and the cumulative contribution rate was 72.05%. After multiple linear regression analysis, the chemical elements in drinking water were positively correlated with the prevalence of dental fluorosis in the order of Se, Fe, Cr, Mn, Ni, Cd and Cu, and negatively correlated with the prevalence of dental fluorosis in the order of Ba, F, Ti, Mo, Zn, Al, Pb, Ca, As and Mg. Conclusions:The chemical properties in drinking water of endemic fluorosis areas in Bijie City have obvious synergistic or antagonistic effects on the occurrence and prevalence of dental fluorosis in this area. The F in the drinking water may not play a decisive role in the occurrence and prevalence of local dental fluorosis.

Endoscopic Characteristics of Diminutive and Small Colorectal Polyps With Advanced Histology / 胃肠病学

Background: Diminutive (≤5 mm) and small (6-9 mm) polyps are the most common colorectal polyps seen clinically, and a tiny percentage of them contain advanced histology. Aims: To clarify the endoscopic characteristics of diminutive and small colorectal polyps with advanced histology. Methods: A retrospective analysis was conducted in patients undergoing colonoscopic polypectomy in Ningbo First Hospital from June 2016 to September 2021, and the clinical, endoscopic and pathological data were collected. Propensity score matching (1: 1) was performed to select the non - advanced histology controls comparable with diminutive and small polyps with advanced histology. The endoscopic characteristics related to advanced histology was identified by univariate and multivariate analyses. Results: A total of 3 631 diminutive and small adenomatous polyps were detected in 2 950 patients, among them, 14 (1.2%) diminutive polyps and 114 (4.6%) small polyps were diagnosed as advanced histology pathologically, with 14 high - grade intraepithelial neoplasia (HGIN) in diminutive polyps, and 109 HGIN and 5 submucosal invasive carcinoma in small polyps. For serrated lesions, 755 polyps less than 10 mm in diameter were detected in 504 patients, but no advanced histology was diagnosed. Multivariate Logistic regression analysis showed that chicken skin mucosa (OR=3.790, 95% CI: 1.767-8.128), congestion (OR=2.802, 95% CI: 1.450 - 5.415), hemorrhage (OR=5.074, 95% CI: 1.511 - 17.035), lobular changes (OR=2.522, 95% CI: 1.247 - 5.098) and relative depression (OR=5.317, 95% CI: 1.376-20.550) were independent risk factors for advanced histology in diminutive and small polyps, while no correlations were found between JNET classification type 2B and type 3, Paris endoscopic classification type 0 - I and advanced histology. Conclusions: When endoscopic characteristics including chicken skin mucosa, congestion, hemorrhage, lobular changes and relative depression are found in diminutive and small colorectal polyps, advanced histology should be suspected.

Construction of a computer-assisted polyp detection system under colonoscopy / 中华消化杂志

Objective To set up a computer-assisted polyp detection system under colonoscopy,and to preliminarily verify its effectiveness.Methods Based on Faster R-CNN algorithm and the open source implementation of the open source framework tensorflow and Faster R-CNN,a computer-assisted polyp detection system under colonoscopy was constructed.According to the size and difficulty of the training set,five test groups were set up:test group one,two,three and four contained 1 000,2 000,4 000 and 6 000 training samples,respectively.Test group five increased the probability of selecting the difficult samples based on 6 000 training samples.In different training sets,the sensitivity,specificity,other classification evaluation parameters,and the evaluation parameters of target detection such as recall and precision of this polyps detection system were calculated.Results Classification evaluation parameters showed that the sensitivities of test group one,two,three,four and five were 90.1％,93.3％,93.3％,93.3 ％ and 93.5 ％,respectively,and the difference was statistically significant (x2 =25.324,P＜0.01).The sensitivities of test group two,three,four and five were all higher than that of test group one,and the differences were statistically significant (x2 =13.964,13.508,13.508 and 13.386,all P＜ 0.006 25).There were no significant differences in specificity and positive predictive value among test groups (both P＞0.05).The negative predictive values of test group one,two,three,four and five were 90.4％,93.3％,93.3％,93.3％ and 93.5％,respectively,and the differences were statistically significant (x2 =21.862,P＜0.01).The negative predictive values of test group two,three,four and five were higher than that of test group one,and the differences were statistically significant (x2=11.447,11.564,11.755,13.760;all P＜0.006 25).As the training sample size increased from 1 000 to 2 000,the area under curve (AUC) increased by 2％,and further increased the sample size to 6 000,AUC increased by less than 1 ％.At this point maintaining the same sample size while increasing the proportion of difficult samples,AUC increased by 0.4％.The results of evaluation parameters of target detection showed that the recall rate of each test group was 73.6％,79.8％,79.5％,79.8％ and 83.3％,respectively,and the differences were statistically significant (x2 =71.936,P＜0.01).Among them,the recall rates of test group two,three and four were higher than that of test group one,and the differences were statistically significant (x2 =25.960,23.492 and 25.960,all P＜0.006 25),and the recall rate of test group five was higher than those of test group one,two,three and four,and the differences were statistically significant (x2=67.361,9.899,11.527 and 9.899;all P＜0.006 25).In addition,the precision rates of test group one,two,three,four and five were 87.9％,85.3％,90.2％,91.4％ and 89.2％,respectively,and the difference was statistically significant (x2=48.194,P＜0.01).The precision rates of test group three and five were higher than that of test group two,and the differences were statistically significant (x2 =24.508 and 15.223,both P＜0.006 25),and the precision rate of test group four was higher than those of test group one and two,and the differences were statistically significant (x2=13.524 and 39.120,both P＜0.006 25).As samples size and training difficulty increased,the values of F1-score and mean average precision increased steadily.Conclusions This study initially constructed a computer-assisted polyp detection system under colonoscopy.Currently the maximum sensitivity reached 93.5％,and the maximum recall rate reached 83.3％.Increasing the training set size may improve the polyp detection result to a certain degree,however it will reach a bottleneck.At this time,increasing the training difficulty can further improve the detection scores,especially the recall rate.

Expressions of vascular endothelial growth factor-C,-D and vascular endothelial growth factor receptor-3 correlates with lymph node micrometastasis of patient with pN0 early gastric cancer / 中华消化杂志

Objective To investigate the expressions of vascular endothelial growth factor (VEGF)-C,-D and VEGF receptor-3 (VEGFR-3/Flt-4) in pN0 early gastric cancer (ECG) and their relationship with lymph node micrometastasis.Methods From January 2005 to January 2010,the paraffin-embedded specimens of 61 pN0 ECG were collected.The expressions of VEGF-C,VEGF-D and VEGFR-3 in 61 pN0 early gastric cancer tissue,25 adjacent tissue and CAM5.2 expression in 868 hematoxylin-eosin staining negative lymph nodes were detected by immunohistochemical assay.The rate of lymph node micrometastasis of 61 pN0 ECG was evaluated.According to the data type,t test,x2 test or Fisher exact probability were performed for the relationship analysis between the expressions of VEGF-C,VEGF-D and VEGFR-3 in pN0 stage ECG and lymph node micrometastasis.Results The high expressions of VEGF-C,VEGF-D and VEGFR-3 in the 61 pN0 ECG were 34.4％ (21/61),34.4％ (21/61) and 44.3％ (27/61) respectively,which were higher than those of adjacent tissues [12.0％ (3/25),8.0％ (2/25) and 16.0％ (4/25) respectively] (x2=4.433,6.321 and 6.144 respectively,all P＜0.05).There were 10 cases (16.4％) of pN0 ECG with lymph node micrometastasis.In pN0 ECG,the low expressions of VEGF-C and VEGFR-3 in negative Flt-4 vascular invasion (FVI) were common than positive FVI (x2 =15.828,6.879 and 9.244,all P＜0.05).The high expressions of VEGF-C and VEGFR-3 were related to the depth of tumor invasion (x2 =5.561 and 5.678,both P＜0.05),the density of VEGFR 3 positive vascular (FVD) (t=2.987and 5.652,both P＜0.01) and lymph node micrometastasis (x2 =6.705 and 6.192,both P＜0.05),but not related to the degree of differentiation (P＞0.05).However,the high expression of VEGF-D was not related to depth of tumor invasion,FVD and lymph node micrometastasis (all P＞0.05),but related to the degree of differentiation (x2 =8.472,P =0.004).The high expressions of VEGF-C,VEGF-D and VEGFR-3 were not related to gender,age,tumor location,macroscopic type and tumor size (all P＞0.05).Conclusions The high expressions of VEGF-C,VEGFR-3 were related to lymph node micrometastasis in pN0 ECG.Although the high expression of VEGF-D was not related to lymph node micrometastasis,it could indirectly affect lymph node micrometastasis through VEGF-C-VEGFR-3 axis in pN0 ECG.