Establishment of a prognostic model of Wnt signaling pathway related genes in gastric cancer / 西安交通大学学报(医学版)

【Objective】 To confirm the role of Wnt signaling pathway in the occurrence and development of gastric cancer （GC）， establish a prognostic model composed of Wnt pathway related genes， and then evaluate the predictive value of the model. 【Methods】 We downloaded the gene expression data and survival data of GC in TCGA database， and used GSEA enrichment analysis to verify the enrichment of Wnt pathway in GC and para-cancer samples. In this study， univariable COX regression analysis and survival curve analysis were used to select the prognosis-related genes of GC. Then the multivariate COX proportional hazard regression model was used to obtain the prognostic model of Wnt signaling pathway related genes. Then， receiver operating characteristic （ROC） curve and forest plot were used to verify the clinical predictive value of the model. The model was then validated in GEO external database. Finally， by utilizing quantitative real-time PCR （qPCR）， we detected the expressions of Wnt signaling pathway related genes in 8 pairs of clinical GC and para-cancer samples. 【Results】 We downloaded 32 samples of normal para-cancer samples and 375 cancer samples and their corresponding clinical data. GSEA enrichment showed that compared with normal samples， Wnt pathway was significantly enriched in GC samples （P<0.05）. The results of univariate COX analysis showed that 13 Wnt pathway genes were closely related to the prognosis of GC patients. Multivariate COX determined that the model was multiplied and accumulated by ETV2， SERPINE1， CPZ， VPS35 and IGFBP1 and their corresponding coefficient β. The survival curve and ROC curve showed that the model could accurately predict the prognosis of GC patients， and the 1-year， 3-year， and 5-year areas under the curve （AUC） were 68.0%， 69.4% and 78.5%， respectively. Clinical univariate and multivariate COX analyses showed that the model could become an independent prognostic factor other than TNM system of GC. The external data set （GSE84437） validation results of GC showed that the model could better predict the prognosis of GC patients. qPCR results indicated that ETV2， SERPINE1， CPZ， VPS35 and IGFBP1 expressions were upregulated in GC samples compared with para-cancer samples. 【Conclusion】 This study further confirmed that Wnt pathway plays an important role in the progress of GC from the perspective of bioinformatics， and we have established a prognosis-related risk model， providing a new perspective for clinical genetic testing， targeted therapy and individualized therapy.

Relationship of intestinal microecology with infantile cholestatic liver disease / 临床肝胆病杂志

Intestinal microecology is an important and complex biological system essential to human health. Intestinal microecology and the liver are closely related in anatomical structure and function. Infantile cholestatic liver disease lead to abnormal bile secretion, abnormal excretion, and reduced bile release into the intestinal tract. As a result, the intestinal mucosa barrier is damaged and intestinal microecology changes; at the same time, pathogenic bacteria and endotoxin translocation cause liver injury and aggravate cholestasis. Therefore, a close relationship of intestinal microecology with infantile cholestatic liver disease can be found. In this article, the relationship of intestinal microecology with the development and progression of infantile cholestatic liver disease is illustrated and it is concluded that probiotics should be given as a supplement when infantile cholestatic liver disease occurs, because it promotes bile secretion, blocks intestinal inflammatory reactions, and improves prognosis of the disease. It is recommended to provide microecological agents routinely as a method to prevent and treat infantile cholestatic liver disease.

Study on the Relationship between susceptibility of stomach neoplasm cancer and polymorphism of inducible nitric oxide synthase gene / 中华流行病学杂志

<p><b>OBJECTIVE</b>To study the relationship between polymorphism of inducible Nitric Oxide Synthase (iNOS) gene and the susceptibility of intestinal type stomach cancer and stomach cardia cancer in Chinese people.</p><p><b>METHODS</b>A community-based case-control study was designed. Ninety-three intestinal type of stomach cancer and 50 stomach cardia cancer patients with endoscopy and pathology diagnosis were identified as cases. Two hundred and forty-six controls served as controls.</p><p><b>RESULTS</b>C-->T polymorphism was found in exon 16 of iNOS gene, which changed the coding amino acid from serine to leucine, and formed a recognition site identified by Tsp 509 I restriction enzyme (we called it C-->T polymorphism). The T allele gene frequency in the control group was 13.21%. No statistically significant difference was found between C-->T polymorphism alone and the increased susceptibility to intestinal stomach cancer or stomach cardia cancer. A significant type 2 multiplicative interaction was found in increasing both the risk of intestinal stomach cancer and stomach cardia cancer when both C-->T polymorphism and tobacco smoking exposure existed. An additive interaction model, which showed statistically significant difference, was found to increase only the risk of stomach cardia cancer when CagA antibody shared negative but C-->T polymorphism occurred.</p><p><b>CONCLUSION</b>C-->T polymorphism of iNOS gene was considered as one of the possible susceptible genes, which specifically increased the risk of tobacco-related but CagA negative types of intestinal stomach cancer and stomach cardia cancer.</p>

Linkage disequilibrium study of microsatellite markers on chromosome 6 and schizophrenia / 中华医学遗传学杂志

<p><b>OBJECTIVE</b>To explore the relationship between the microsatellite markers on chromosome 6 and schizophrenia by linkage disequilibrium analysis.</p><p><b>METHODS</b>Twenty-eight microsatellite markers on chromosome 6 were evaluated in 115 affected-sib-pair and trios families. Linkage disequilibrium analysis was conducted according to diagnostic categories, Positive and Negative Syndrome Scale (PANSS) and other clinical data by XDT and MAPMAKER/SIBS software system.</p><p><b>RESULTS</b>Significant P value (P<0.005) was found in all the four diagnostic categories. Only the locus of D6S1960 showed positive P value (P<0.05) in all the subgroups divided by PANSS scale and the age of onset.</p><p><b>CONCLUSION</b>The area around D6S1960 in short arm of chromosome 6 may contain susceptibility gene of schizophrenia.</p>

A linkage disequilibrium study of methylenetetrahydrofolate reductase C677T and schizophrenia / 中华医学遗传学杂志

<p><b>OBJECTIVE</b>To explore the relationship between the methylenetetrahy drofolate reductase (MTHFR) C677T missense mutation and schizophrenia by linkage disequilibrium study.</p><p><b>METHODS</b>Linkage disequilibrium analys is was conducted bet ween MTHFR C677T and schizophrenia in 115 affected-sib-pair (105) and trios (10) families by XDT and MAPMAKER/SIBS soft system. The analyses were performed in different diagnostic categories and combined with the age of onset as well.</p><p><b>RESULTS</b>No positive results were found in the analysis in all the family in all the four diagnostic categories. Significant P values, which were P<0.05, P<0.01 respectively, were observed in the families with the affected individual's onset age less than 25 years in all the four diagnostic categories.</p><p><b>CONCLUSION</b>The missense mutation of MTHFR C677T or other gene structure around this mutation may be one of the susceptibility gene of schizophrenia.</p>

The distributive features of three kinds of metabolic genes polymorphisms in population of Han nationality in south area of China / 中华医学遗传学杂志

<p><b>OBJECTIVE</b>To find out the distributive features of some metabolic genes polymorphisms in Han population of south area of China.</p><p><b>METHODS</b>Study population was obtained from the controls of a community based case-control study, which included 290 blood relatives (inner control) and 404 non-blood relatives (outer control).</p><p><b>RESULTS</b>Frequencies of CYP1A1, GSTM1 and GSTT1 polymorphisms had no significant difference among confounding factors, such as sex, living areas, stomach cancer family history and history of tobacco smoking etc. Some controls showed significant difference in age group and alcohol drinking which would be adjusted in analysis of the relationship between polymorphisms and cancers. CYP1A1 Ile/Val and Val/Val genotypes were 33.43% and 5.62% respectively, which were similar to other results from Chinese and Japanese, but higher than those from Caucasians in American, Europe and African-Americans. GSTM1 null allele frequency was 53.48% in our population, which showed difference even among Chinese in different areas. GSTT1 null allele frequency was 45.78%, which was significantly higher than that in Caucasians and African-American.</p><p><b>CONCLUSION</b>The frequencies of CYP1A1 Ile/Val, Val/Val and GSTT1 null in Han population in south area of China are significantly higher than those in other races, while the ethnic difference of frequency of GSTM1 null is less.</p>