The association between Helicobacter pylori virulence factor genotypes and gastroduodenal diseases in children / 中华儿科杂志

Objective: To investigate the association between Helicobacter pylori (Hp) virulence factor genotypes and the degree and activity of gastric mucosa pathological changes in pediatric gastroduodenal diseases. Methods: This retrospective cohort study was conducted from May 2020 to October 2020. The frozen strains of Hp, which were cultured with the gastric mucosa of 68 children with gastroscopy confirmed gastroduodenal diseases who visited the children's hospital of Zhejiang University School of Medicine from April 2012 to December 2014, were resuscitated. After extracting DNA from these Hp strains, PCR amplification and agarose gel electrophoresis were performed to determine the detection rate of cytotoxin-associated protein A (cagA),vacuolating cytotoxin A (vacA)(s1a、s1b/s2,m1/m2), outer inflammatory protein A (oipA),blood group antigen binding adhesin (babA),duodenal ulcer promoting protein A (dupA) genes; oipA genes were sequenced to determine the gene status. The patients were divided into different groups according to the findings of gastroscopy and gastric mucosa pathology. The detection rates of various virulence factor genotypes among different groups were compared using χ2 tests or Fisher's exact tests. Results: The 68 Hp strains all completed genetic testing. According to the diagnostic findings of gastroscopy, the 68 cases were divided into 47 cases of superficial gastritis and 21 cases of peptic ulcer. Regarding the pathological changes of gastric mucosa, 8 cases were mild, and 60 cases were moderate and severe according to the degree of inflammation; 61 cases were active and 7 cases inactive according to the activity of inflammation. The overall detection rates of cagA, vacA, vacA s1/m2, functional oipA, babA2, and dupA virulence factor genes were 100% (68/68), 100% (68/68), 94% (64/68), 99% (67/68), 82% (56/68), and 71% (48/68), respectively. In the superficial gastritis group, their detection rates were 100% (47/47), 100% (47/47), 96% (45/47), 98% (46/47), 81% (38/47), and 70% (33/47), respectively; in the peptic ulcer group, their detection rates were 100% (21/21), 100% (21/21), 90% (19/21), 100% (21/21), 86% (18/21), and 71% (15/21), respectively. There was no statistically significant difference between the two groups (all P>0.05). In the mild gastric mucosa inflammation group, the detection rates of the above six genotypes were 8/8, 8/8, 8/8, 7/8, 7/8, and 5/8, respectively; and in the moderate to severe inflammation groups, the detection rates were 100% (60/60), 100% (60/60), 93% (56/60), 100% (60/60), 82% (49/60), and 72% (43/60), respectively, with no statistically significant difference between the two groups (all P>0.05). In the active inflammation group, the detection rate of six genotypes were 100% (61/61), 100% (61/61), 93% (57/61), 98% (60/61), 82% (50/61), and 72% (44/61), respectively; and in the inactive inflammation group, they were 7/7, 7/7, 7/7, 7/7, 6/7, and 4/7, respectively. Again, there was no statistically significant difference between the two groups (all P>0.05). There was no statistically significant difference in the detection rate of combinations of 4 or 5 virulence factor genes among the different groups (all P>0.05). Conclusions: CagA, vacA, vacA s1/m2, functional oipA, babA2, and dupA genes are not associated with superficial gastritis and peptic ulcer in children, or with the degree and activity of gastric mucosa pathological inflammation. Different gene combinations of cagA, vacA, oipA, babA2, and dupA have no significant effects on predicting the clinical outcome of Hp infection in children.

Effect of NBED on decorporation of uranium and protective effect on HK-2 cellular damage / 中国药理学通报

Aim To study the effect of NBED on the decorporation of uranium and the protective effect on HK-2 cellular damage.Methods ICR mice were divided into control group, uranium exposure group(0.03 mg), DTPA-CaNa3(300 mg·kg-1)and NBED(300, 150, 75 mg·kg-1)treatment groups.After injection of uranyl acetate, mice were given different doses of decorporation agents immediately.After 24 h the content of uranium in kidney, bone, liver, spleen and muscle was determined by ICP-MS.HK-2 cells were divided into control group, uranium model group(80 μmol·L-1), DTPA-CaNa3(80 μmol·L-1)and NBED(80, 40, 20 μmol·L-1)treatment group interacted with uranium for 48h.CCK-8 method was used to detect the cell survival rate; light microscope was used to observe the cell morphology; ICP-MS method was used to detect the ratio of uranium endocytosis and uranium efflux; biochemical method was employed to determine SOD, GSH and LDH levels; flow cytometry was applied to determine ROS, apoptosis and cell cycle.Results 300 mg·kg-1 NBED reduced the content of uranium in kidney and bone by 44.3% and 18.8% respectively.Compared with model group, NBED reduced uranium entry into cells by 11%42%, increased uranium emission by 18%48%, increased the survival rate of HK-2 cells, thelevels of SOD and GSH, decreased the expression levels of ROS and LDH, and decreased the apoptotic rate and S phase arrest.DTPA-CaNa3 could significantly reduce the content of uranium and the amount of uranium endocytosis in kidney of mice, but the effect of promoting excretion was significantly lower than that of NBED, and it had no protective effect on the acute injury of HK-2 cells caused by uranium.Conclusions NBED is an effective uranium decorporation agent, which is superior to DTPA-CaNa3 approved by FDA.It could reduce the production of ROS and LDH, increase the content of SOD and GSH, and reduce the arrest and apoptosis of S phase, thus protecting HK-2 cells from uranium induced damage.