[The correlation between reflux esophagitis and Helicobacter pylori infection based on natural population].

Objective: Reflux esophagitis (RE) may be negatively correlated with Helicobacter pylori (H. pylori) infection, but the conclusion and relevant mechanism is still controversial. This study proposed to explore the correlation between RE and H. pylori infection based on natural population. Methods: From July 2013 to December 2014, 3 940 residents aged 40-69 years were recruited in Linqu County of Shandong Province and Hua County of Henan Province by the whole sampling method. All the subjects underwent gastroscopy, and gastric mucosa biopsy specimens were collected for pathological diagnosis and Warthin-Starry (WS) staining to identify H. pylori infection. Venous blood samples of some subjects were collected for H. pylori immunoglobulin G (H. pylori-IgG) detection. Also, demographic and sociological data were collected. Chi-square test and logistic regression were used to analyze the correlation between RE and H. pylori infection. Results: A total of 359 cases of RE were detected. Excluding RE and other upper gastrointestinal organic diseases, 3 382 cases were considered as controls. Chi-square test showed that WS staining positive rate in RE group was significantly lower than that in control group (P=0.023), but there was no significant difference in the positive rate of H. pylori-IgG between the two groups (P=0.281). There were significant differences between RE group and control group in gender composition, age, body mass index (BMI), smoking, alcohol consumption, education level and mucosal active inflammation. Multivariate regression analysis showed that RE was negatively correlated with gastric mucosa active inflammation [OR=0.754 (95%CI 0.600-0.949), P=0.016], and positively correlated with male [OR=4.231 (95%CI 3.263-5.486), P<0.001], age ≥60 years, BMI≥24 kg/m2 [OR=1.540 (95%CI 1.220-1.945), P<0.001]. Compared to those aged 40-49 years and 50-59 years, the odds ratio (OR) of RE in these aged ≥60 years were 1.566 (95%CI 1.144-2.143, P=0.005) and 1.405 (95%CI 1.093-1.805, P=0.008). Conclusion: RE is more closely related to H. pylori present infection. Multivariate analysis showed that RE is negatively correlated with active inflammation of gastric mucosa caused by H. pylori infection, and positively correlated with male, overweight and aged ≥60 years.

[Overexpression of NAT10 induced platinum drugs resistance in breast cancer cell].

Objective: To observe the platinum drugs resistance effect of N-acetyltransferase 10 (NAT10) overexpression in breast cancer cell line and elucidate the underlining mechanisms. Methods: The experiment was divided into wild-type (MCF-7 wild-type cells without any treatment) group, NAT10 overexpression group (H-NAT10 plasmid transfected into MCF-7 cells) and NAT10 knockdown group (SH-NAT10 plasmid transfected into MCF-7 cells). The invasion was detected by Transwell array, the interaction between NAT10 and PARP1 was detected by co-immunoprecipitation. The impact of NAT10 overexpression or knockdown on the acetylation level of PARP1 and its half-life was also determined. Immunostaining and IP array were used to detect the recruitment of DNA damage repair protein by acetylated PARP1. Flow cytometry was used to detect the cell apoptosis. Results: Transwell invasion assay showed that the number of cell invasion was 483.00±46.90 in the NAT10 overexpression group, 469.00±40.50 in the NAT10 knockdown group, and 445.00±35.50 in the MCF-7 wild-type cells, and the differences were not statistically significant (P>0.05). In the presence of 10 µmol/L oxaliplatin, the number of cell invasion was 502.00±45.60 in the NAT10 overexpression group and 105.00±20.50 in the NAT10 knockdown group, both statistically significant (P<0.05) compared with 219.00±31.50 in wild-type cells. In the presence of 10 µmol/L oxaliplatin, NAT10 overexpression enhanced the binding of PARP1 to NAT10 compared with wild-type cells, whereas the use of the NAT10 inhibitor Remodelin inhibited the mutual binding of the two. Overexpression of NAT10 induced PARP1 acetylation followed by increased PARP1 binding to XRCC1, and knockdown of NAT10 expression reduced PARP1 binding to XRCC1. Overexpression of NAT10 enhanced PARP1 binding to LIG3, while knockdown of NAT10 expression decreased PARP1 binding to LIG3. In 10 µmol/L oxaliplatin-treated cells, the γH2AX expression level was 0.38±0.02 in NAT10 overexpressing cells and 1.36±0.15 in NAT10 knockdown cells, both statistically significant (P<0.05) compared with 1.00±0.00 in wild-type cells. In 10 µmol/L oxaliplatin treated cells, the apoptosis rate was (6.54±0.68)% in the NAT10 overexpression group and (12.98±2.54)% in the NAT10 knockdown group, both of which were statistically significant (P<0.05) compared with (9.67±0.37)% in wild-type cells. Conclusion: NAT10 overexpression enhances the binding of NAT10 to PARP1 and promotes the acetylation of PARP1, which in turn prolongs the half-life of PARP1, thus enhancing PARP1 recruitment of DNA damage repair related proteins to the damage sites, promoting DNA damage repair and ultimately the survival of breast cancer cells.

Pharmacokinetics of ceftizoxime in renal failure patients without dialysis.

AIM: To investigate the pharmacokinetics of ceftizoxime (Cef) in renal failure patients without any dialysis and supply the basis for a suitable clinical regimen. METHODS: Cef in plasma and urine was assayed by HPLC. RESULTS: After injecting Cef 16.7 mg kg-1, Cef concentration in blood was described as a 2-compartment open model. The main pharmacokinetic parameters were Vd 0.55 +/- 0.17 L kg-1; AUC 879 +/- 460 mg L-1 h; Cl 27 +/- 11 mL kg-1 h-1. T1/2 beta was 15 +/- 4 h. CONCLUSION: T1/2 beta in renal failure patients was about 10 times longer than that in normal volunteers. The clinical regimen should be adjusted in renal failure patients with infection, either prolonging the interval between Cef administration, or decreasing Cef dosage.

Lysine substitution increases mu-selectivity of potent di- and tri-peptide enkephalin analogs.

A general trend toward increased mu-selectivity has been reported in two classes of minimal structure enkephalin analogs which contain the essential structural and functional information for potent enkephalin-like biological activity. A single Lys residue added to the amino terminal of several tripeptide amides, and to the potent dipeptide amide Tyr-DAla-phenylpropylamide, causes a further increase in mu-selectivity as determined in the stimulated guinea pig ileum (GPI) and mouse vas deferens (MVD) assays, and in receptor binding studies in homogenates of guinea pig brain. The effect of Lys substitution was a significant decrease in the delta-related MVD potencies.

Selectivity of minimum structure enkephalins.

The biological activity of 45 deletion tetrapeptide-, tripeptide- and dipeptide enkephalin analogs has been determined in the stimulated mouse vas deferens (MVD) and guinea pig ileum (GPI) assays. A comparison of the GPI and MVD activities of these 45 minimum structure analogs indicates a high degree of mu receptor specificity. The greatest selectivity is found in the dipeptide amide Tyr-DAla-benzylamide, while high selectivity was also found in the tetrapeptides Tyr-DAla-Trp-Leu-NH2 and Tyr-Aib-Phe-Leu-NH2, and in two tripeptides Tyr-DTrp-Phe-NH2 and Tyr-Pro-Phe-NH2. The dipeptide amide Tyr-DAla-(3-phenyl-1-propyl)-amide (DAPPA), which has been shown to possess high in vitro potency (on the stimulated GPI) and in vivo potency (analgesia in mice after icv administration), is shown to have 60 times the activity in the GPI assay relative to its activity on the stimulated MVD, further indicating the correlation between mu-receptor activity and analgesia.