Intervention effects and related mechanisms of glycyrrhizic acid on zebrafish with Hirschsprung-associated enterocolitis

BACKGROUND The prevention and treatment of Hirschsprung-associated enterocolitis(HAEC)is a serious challenge in pediatric surgery.Exploring the mechanism of HAEC is conducive to the prevention of this disease.AIM To explore the possible mechanism of glycyrrhizic acid(GA)and its therapeutic effect on HAEC.METHODS We developed a model of enteritis induced by trinitrobenzenesulfonic acid(TNBS)in zebrafish,and treated it with different concentrations of GA.We analyzed the effect of GA on the phenotype and inflammation of zebrafish.RESULTS After treatment with TNBS,the area of the intestinal lumen in zebrafish was significantly increased,but the number of goblet cells in the intestinal lumen was significantly reduced,but these did not increase the mortality of zebrafish,indicating that the zebrafish enteritis model was successfully developed.Different concentrations of GA protected zebrafish with enteritis.In particular,high concentrations of GA were important for the prevention and control of HAEC because it significantly reduced the intestinal luminal area,increased the number of goblet cells in the intestinal lumen,and reduced the levels of interleukin(IL)-1βand IL-8.CONCLUSION GA significantly reduced the intestinal luminal area,increased the number of intestinal goblet cells,and decreased IL-1βand IL-8 in zebrafish,and is important for prevention and control of HAEC.

Loss of Wnt5a and Ror2 protein in hepatocellular carcinoma associated with poor prognosis

AIM:To investigate the expression and clinical significance of Wnt member 5a (Wnt5a) and receptor tyrosine kinase-like orphan receptor 2 (Ror2) in hepatocellular carcinoma (HCC).METHODS:In HCC tissues obtained from 85 patients,the protein expressions of Wnt5a,Ror2,β-catenin,and Ki-67 via immunohistochemical staining using the Envision Plus System.The antibody binding was visualized with 3,3'-diaminobenzidine tetrahydrochloride (DAB) before brief counterstaining with Mayer's hematoxylin.The degree of immunohistochemical staining was recorded using a semiquantitative and subjective grading system.The mRNA expression of Ror2 was examined by real-time reverse transcription polymerase chain reaction,including nineteen of the 85 HCC and three normal liver tissues.The ratios of Ror2 to the housekeeping gene GAPDH represented the normalized relative levels of Ror2 expression.To determine the prognostic factor,the outcome of the 82 patients was determined by reviewing their medical charts.The overall and disease-free survival rates were estimated using the Kaplan-Meier method and compared with the log-rank test.The prognostic analysis was carried out with univariate and multivariate Cox regressions models.RESULTS:Compared to nontumorous (hepatitis or cirrhotic) tissues,Ror2 mRNA expression was clearly decreased in HCC.Ror2 and Wnt5a protein expressions in the majority of HCC patients (63% and 77%,respectively) was significantly less in tumor tissues,as compared to adjacent nontumorous tissues,and this reduction was correlated with increasing serum α-fetoprotein and tumor stage.In 68% (58/85) of the HCC cases,the expression of β-catenin in tumor tissues was either downregulated in the cellular membrane,upregulated in the cytoplasm,or both.Survival analysis indicated that Wnt5a and Ror2 protein expressions could be regarded as independent prognostic factors for HCC;HCC patients with decreased Wnt5a or Ror2 protein expression had a poorer prognosis than those with elevated Wnt5a and Ror2 expression (P=0.016,P=0.007,respectively).CONCLUSION:Wnt5a and Ror2 may serve as tumor suppressor genes in the development of HCC,and may serve as clinicopathologic biomarkers for prognosis in HCC patients.

SRY-negative 45,X/46,XY adult male with complete masculinization and infertility:A case report and review of literature

BACKGROUND 45,X/46,XY mosaicism is a rare chromosomal abnormality with a wide range ofphenotypes in both males and females, from normal individuals with differentdegrees of genital ambiguity to those who show signs of Turner’s syndrome.More rarely, cases of 45,X/46,XY mosaicism with a normal-appearing malephenotype are not found until a chromosome test is performed to investigate thecause of male infertility.CASE SUMMARY In this study, a 29-year-old male patient with complete azoospermia is reported.Chromosomal analyses of his lymphocytes revealed the karyotype 45,X[93%]/46,X,+mar(Y)[7%]. In addition, Y chromosome-specific markers, such as SRY,ZFY, AZFa, AZFb and AZFc, were not observed in his blood DNA according tomultiplex polymerase chain reaction test. A literature review identified several45,X/46,XY cases with a normal-appearing male phenotype, most of whom werediagnosed during infertility investigation. However, the present case is the firstSRY-negative 45,X/46,XY male case diagnosed during a premarital medicalexamination.CONCLUSION This finding further suggests that sex determination is a complex processregulated by multiple genetic and environmental factors.