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Objective:To investigate the correlation between morphology of esophageal and gastric mucosal and Helicobacter pylori ( HP) infection under white light gastroscope. Methods:A retrospective analysis was performed on data of 1 339 patients who underwent 13C-urea breath test and white light gastroscopy at the same time in the Southwest Hospital of Army Medical University from September 2018 to August 2019. Chi-square test or Fisher exact probability method was used to analyze the difference on detection rates of 22 indexes of gastroscopic mucosal manifestation between the HP infection group ( n=422) and the non-infection group ( n=917). Then the indexes with difference were further analyzed by binary logistic regression. The receiver operating characteristic (ROC) curve was drawn, and the area under the curve and the sensitivity, specificity, positive predictive value and negative predictive value of prediction of HP infection was calculated. Results:The diffuse redness, spotted redness, mucosal swelling, enlarged folds, sticky mucus, digestive tract ulcer, nodularity, hyperplastic polyp, xanthoma, atrophy, intestinal metaplasia, and depressive erosion were more common in patients with HP infection (all P<0.05). Binary logistic regression analysis showed that diffuse redness ( P<0.001, OR=75.974, 95% CI: 32.551-177.327), spotted redness ( P=0.002, OR=3.360, 95% CI: 1.536-7.349), mucosal swelling ( P<0.001, OR=3.150, 95% CI: 1.654-5.996) were independent risk factors for HP infection. ROC curve analysis showed that the area under ROC curve of diffuse redness, spotted redness, mucosal swelling, enlarged folds, sticky mucus, peptic ulcer, and depressive erosion predicting HP infection were all greater than 0.5 ( P<0.05), among which, the area under curve of diffuse redness, spotted redness and mucosal swelling predicting HP infection were greater than 0.7. The sensitivities corresponding to the three indicators were 0.735, 0.512, and 0.445, the specificities were 0.992, 0.983, and 0.971, the positive predictive values were 0.978, 0.931, and 0.874, and the negative predictive values were 0.890, 0.814, and 0.792, respectively. Conclusion:Morphological manifestations of esophageal and gastric mucosa, especially diffuse redness, spotted redness, and mucosal swelling, are excellent indicators for HP infection under white light gastroscopy.
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Triptolide (TP) is a major active component in Tripterygium root, but its therapeutic window was very narrow due to its severe multi-organ toxicity. In this work, the effect of TP combined with glycyrrhetic acid (GA) on mRNA expression and activity of four cytochrome P450 (CYP) enzymes in rat liver was studied after intragastric administration of TP (0.05, 0.3 and 0.6 mg x kg(-1) x day(-1)) and TP (0.6 mg x kg(-1) x day(-1)) combined with GA (30 mg x kg(-1) x day(-1)) for 7 consecutive days. Compared with the control, the high dose of TP significantly up-regulated the mRNA expression levels of CYP2E1, 1A2, 3A1 and 2C11, the co-administration of TP and GA further up-regulated the mRNA expression levels of CYP3A1, 2C11 and 2E1 as compared with the high dose of TP. Meanwhile, TP at high dose and combined with GA significantly increased CYP3A-associated testosterone 6beta-hydroxylation activity (2.2-fold and 4.1-fold, respectively) as compared with the control. Because TP is mainly metabolized by CYP3A2 in male rats, the present work indicated that TP-induced increase of CYP3A activity might be an important reason for the rapidly metabolic clearance of TP in rat liver, and GA can reduce the hepatotoxicity of TP by promoting its hepatic metabolic clearance. Furthermore, the results also suggest that the drug interactions might be occurred when TP and GA were co-administered with other CYP3A substrate drug.
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Objective To investigate the metabolism of strychnine (STN) and the metabolic interaction between STN and glycyrthetic acid (GA) in vitro.MethodsHuman liver microsomes (HLM) and human recombinant cytochrome P450 (CYP) isoforms were employed to study the metabolism of STN and the metabolic interaction of STN with GA in vitro.ResultsIn HLM,the Km,Vmax,and clearance of STN were 88.50 μmol/L,0.88 nmol/(mg·min),and 9.93 mL/(mg·min),respectively.STN was metabolized mainly by CYP3A4.However,STN noncompetitively inhibited CYP3A4-catalyzed testosterone 6β-hydroxylation with IC50 value of 5.9 μtmol/L and Ki value of 5.5μmol/L.Moreover,GA competitively inhibited STN metabolism with IC5o value of 10.6 μmol/L and Ki value of 17.7 μmol/L.ConclusionAlthough STN is mainly metabolized by CYP3A4 in vitro,STN has noncompetitive inhibition on CYP3A4-catalyzed testosterone 6β-hydroxylation.Moreover,GA could competitively inhibit STN metabolism.The present work is helpful to elucidate the metabolic interaction between STN and GA.
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Licorice root has been frequently used as antitode in traditional Chinese medicine. As the main active component of Licorice root, glycyrrhetic acid (GA) is mainly metabolized in liver. This study was designed to investigate the in vitro metabolism of GA by human liver microsomes (HLM) and human recombinant cytochrome P450 (CYP) isoforms. The results indicated that GA was metabolized mainly by CYP3A4. The K(m), V(max) and CL(int) of GA in HLM were 18.6 micromol x L(-1), 4.4 nmol x mg(-1) (protein) x min(-1) and 0.237 mL x mg(-1) (protein) x min(-1), respectively. At concentration up to 50 micromol x L(-1), GA inhibited CYP2C19, CYP2C9 and CYP3A4 enzyme activities with the inhibitory potencies up to 50%.
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Advanced studying doctors play important roles in the clinical services, and how to train them to improve training quality is worth investigating. We classified them into three types such as the clinical skills-improved, the special skills-trained and clinical knowledge eextensively-spread, then employed the individual teaching methods and emphasized the medical ethics during the training, which is not only beneficial to us, but also of great importance and necessity to advanced studying doctors themselves.
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Objective To investigate the relationship between the expression of eonnexin 43 (Cx43) and clinicopathologieal characteristics of gastric cancer, and to study the role of Cx43 in peritoneal metastasis of gastric cancer. Methods Thirty-two patients who had gastric cancer and with peritoneal metastasis had been admitted to Southwest Hospital from January 2000 to December 2008. Gastric cancer tissues, adjacent tissues and metastatic peritoneal tissues were obtained postoperatively, and the expression of Cx43 was detected by immunohistochemistry. The relationship between Cx43 expression and clinicopathological characteristics of gastric cancer was analyzed. All data were analyzed via Spearman rank correlation coefficient, Fisher exact probability and chi-square test. Results The expression of Cx43 was mainly detected in the cell membrane and cytoplasm. The positive expres-sion rates of Cx43 in gastric cancer tissues, adjacent tissues and metastatic peritoneal tissues were 34% (11/32), 100% (32/32) and 94% (30/32), respectively. There were significant differences in the Cx43 expression between gastric cancer tissues and adjacent tissues (X~2=28.350, P < 0.01), and between gastric cancer tissues and metastatic peritoneal tissues (X~2 = 21.989, P < 0.01). The expression of Cx43 did not correlate with age and sex of patients (r = -0.030, - 0.169, P > 0.05), but with tumor differentiation, histological type and lymph node metastasis (r = 0.750, 0.642, - 0.357, P < 0.05). Conclusions There is a decreased expression of Cx43 in gastric cancer tissues and a up-regulated expression of Cx43 in metastatic peritoneal tissues. Cx43 may play a positive role in the peritoneal metastasis.
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Objective The C-terminal domain of rodent Muc3 is proteolytically cleaved.This study is to explore the relationship between N-linked oligosaccharides in SEA module and the proteolytic cleavage within C-terminal domain of rodent Muc3.Methods Truncated rodent Muc3 C-terminal domains with complete SEA module(p20SEA) were produced by site-directed mutagenesis to insert a stop code in the required place.Proteins were detected by pulse/chase and immunoprecipitation method,or SDS/PAGE and Western blot.Inhibition of glycosylation of the expressed protein was performed by using tunicamycin.Results Muc3 C-terminal domain was posttranslationally cleaved to produce a V5-tagged 30 000 extracellular glycopeptide and a Myc-tagged 49 000 membrane-associated glycopeptide.Treatment with tunicamycin to transfected COS-1 cells led to the abundant production of 60 000 uncleaved and whole-length Muc3 C-terminal domain,the 30 000 N-terminal fragment shifted to 22 000 and 49 000 C-terminal fragment shifted to 41 000 after deglycosylation.The truncated Muc3 C-terminal domain containing complete SEA module but without the following residues led to production of 36 000 uncleaved and whole-length protein,and 30 000 cleaved product shifted to 22 000 after deglycosylation.Conclusion Proteolytic cleavage in both complete rodent C-terminal domain and complete SEA module without the following residues were partially inhibited by tunicamycin.
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Objective To explore the correlation between membrane targeting of rodent Muc3 C-terminal domain and proteolytic cleavage blockage within its SEA module and N-linked oligosaccharides inhibition.Methods COS-1 cells were transfected with three different expression vectors containing rodent Muc3 C-terminal domain,namely p20,p20t and p20s/a by lipofectAMINE reagent.Inhibition of N-glycosylation of the expressed protein was performed by using tunicamycin.The transfected COS-1 cells(fixed or unfixed) were detected by immunolocalization experiments(anti-V5 and anti-Myc antibody) for the protein expression.Results In fixed COS-1 cells,the expressed product of p20 transfectant detected using both anti-Myc and anti-V5 antibodies was found to localize in perinuclear position and on the plasma membrane.While in the unfixed cells,immunostaining was only confined on cell surface using anti-V5 antibody.The expressed product of p20t transfectant was detected by anti-V5 antibody to localize only in perinuclear region,as observed in a few fixed cells.The distribution of p20s/a fluorescence resembled that of p20 transfectant.Plasma membrane targeting of the non-glycosylated products due to tunicamycin treatment still occurred in transfected COS-1 cells and resembled the glycosylated products.Conclusions The blockage of proteolytic cleavage within C-terminal domain of rodent Muc3 and its inhibition of N-linked oligosaccharides in SEA module cannot affect its membrane targeting.The only apparent requirement for membrane targeting is the transmembrane and/or cytoplasmic tail segments which exist in the C-terminal domains of rMuc3.