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, Rot2, 13-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 Rot2 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 diseasefree survival rates were estimated using the Kaplan-Meier method and compared with the logrank test. The prognostic analysis was carried out with univariate and multivariate Cox regressions models.RESULTS： Compared to nontumorous （hepatitis or cirrhotic） tissues, Rot2 mRNA expression was clearly decreased in HCC. Rot2 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 IB-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.

Quantitative assessment of myocardial blush grade in patients with coronary artery disease and in cardiac transplant recipients

Quantitative assessment of myocardial perfusion by myocardial blush grade(MBG) is an angiographic computer-assisted method to assess myocardial tissue-level reperfusion in patients with acute coronary syndromes and microvascular integrity in heart transplant recipients with suspected cardiac allograft vasculopathy. This review describes the ability of quantitative MBG as a simple, fast and cost effective modality for the prompt diagnosis of impaired microvascular integrity during routine cardiac catheterization. Herein, we summarize the existing evidence, its usefulness in the clinical routine, and compare this method to other techniques which can be used for the assessment of myocardial perfusion.

Could Labor Be Considered Outside of a Medical Environment in Africa? Case of the Maternity Hospital in Yopougon Attié/Abidjan/Ivory Coast/West Africa

Introduction: Developing countries are characterized by a high maternal mortality rate, particulary related to the management of childbirth. The author describes in this work 588 childbirth labors that took place without any medical supervision. Method: All patients who reached the hospital with a full cervix dilation were included in the study. The outcomes of those childbirth labors without medical supervision were evaluated at the maternal and neonatal level. Results and Discussion: The average age of the patients was 28.1 ± 13 years with 47% nulliparous and 30% pauciparous. These patients represented 14% of all births;59% of the patients had had three and five prenatal consultations. 71% of them came straight from home and had meconium-stained amniotic fluid. The APGAR score was greater than 6 in 94% of newborns, and 66.7 of them weighed between 2500 and 3500 g. Only 0.9% of patients coming from home needed a caesarean section. Conclusion: Home birth is not yet possible in Africa because it is not supervised by professionals who know the risks of childbirth, its complications and recognize the warning signs;however, the results of this preliminary study show that the issue of home childbirth in Côte d’Ivoire can be reconsidered subject to greater involvement of medical staffs.

Expression and Regulatory Network Analysis of Function of Small Nucleolar RNA Host Gene 4 in Hepatocellular Carcinoma

Background and Aims:Long non-coding RNA small nucleolar RNA host genes(SNHGs)play a critical role in the occurrence and development of tumors.In this study,we aimed to investigate the role of SNHG4 in hepatocellular carcinoma(HCC)and its underlining mechanism.Methods:Datasets were acquired from The Cancer Genome Atlas(TCGA)database.lncLocator 2.0 was used to identify the distribution of SNHG4 in HCC cells.Gene expression,Kaplan-Meier survival,microRNA and transcription factor target analyses were performed with the University of Alabama Cancer(UALCAN)Database,Kaplan-Meier Plotter,LinkedOmics,WebGestalt and gene set enrichment analysis,respectively.Gene Ontology and pathway enrichment analyses and assessment of RNA binding proteins were performed by R software,circlncRNAnet and Encyclopedia of RNA Interactomes(EN-CORI).In addition,CirclncRNAnet and ENCORI were used to find the correlation between SNHG4 and important proteins,while the prognostic value was assessed with the Human Protein Atlas database and Kaplan-Meier Plotter.Results:Expression of SNHG4 in HCC is higher in HCC tissue than in normal healthy liver tissues and is mainly distributed in the nucleus.SNHG4 positively correlated with poor prognosis(p<0.01 for overall survival and recurrence-free survival).Functional enrichment analysis revealed SNHG4 involve-ment with regulation of ribosomal RNA synthesis and the RNA processing and surveillance pathway.SNHG4 is closely associated with miR-154 and miR-206,transcription factor target E2F family and the signaling pathway for MAPK/ERK and mTOR.U2 auxiliary factor 2(U2AF2)showed strong correlation with SNHG4,while low-expression of U2AF2 showed good prognosis.Conclusions:Based on our find-ings,we infer SNHG4 may play a role in the formation of HCC via regulation of tumor-related pathways.