Identification of immune feature genes and intercellular profiles in diabetic cardiomyopathy

BACKGROUND Diabetic cardiomyopathy(DCM)is a multifaceted cardiovascular disorder in which immune dysregulation plays a pivotal role.The immunological molecular mechanisms underlying DCM are poorly understood.AIM To examine the immunological molecular mechanisms of DCM and construct diagnostic and prognostic models of DCM based on immune feature genes(IFGs).METHODS Weighted gene co-expression network analysis along with machine learning methods were employed to pinpoint IFGs within bulk RNA sequencing(RNA-seq)datasets.Single-sample gene set enrichment analysis(ssGSEA)facilitated the analysis of immune cell infiltration.Diagnostic and prognostic models for these IFGs were developed and assessed in a validation cohort.Gene expression in the DCM cell model was confirmed through real time-quantitative polymerase chain reaction and western blotting techniques.Additionally,single-cell RNA-seq data provided deeper insights into cellular profiles and interactions.RESULTS The overlap between 69 differentially expressed genes in the DCM-associated module and 2483 immune genes yielded 7 differentially expressed immune-related genes.Four IFGs showed good diagnostic and prognostic values in the validation cohort:Proenkephalin(Penk)and retinol binding protein 7(Rbp7),which were highly expressed,and glucagon receptor and inhibin subunit alpha,which were expressed at low levels in DCM patients(all area under the curves>0.9).SsGSEA revealed that IFG-related immune cell infiltration primarily involved type 2 T helper cells.High expression of Penk(P<0.0001)and Rbp7(P=0.001)was detected in cardiomyocytes and interstitial cells and further confirmed in a DCM cell model in vitro.Intercellular events and communication analysis revealed abnormal cellular phenotype transformation and signaling communication in DCM,especially between mesenchymal cells and macrophages.CONCLUSION The present study identified Penk and Rbp7 as potential DCM biomarkers,and aberrant mesenchymal-immune cell phenotype communication may be an important aspect of DCM pathogenesis.

The expression of HER-2/neu gene in colon cancer tissues and its clinical significance

Objective：The article aims to detect the expression of HER-2/neu gene in colon cancer tissues and adjacent tissues, to analyze the relationship between dif erent pathologic types and clinical features, also to invest the distribution of patients with positive expression of HER-2 gene. Methods：The expression of HER-2 gene in the 223 samples with colon can-cer was detected by immunochemical approach. The expression of HER-2 gene in colon cancer tissues and adjacent tissues and dif erent pathologic types was analyzed byχ2 test. The correlation between the expression of HER-2 gene and clinical features was analyzed by Spearman. Results：The number of positive expression of HER-2 gene in colon cancer tissues and adjacent tissues were 74 and 0 respectively, the dif erence has statistical significance. The number of papil ary or tubular adenocarcinoma was 182, among them, 60 cases were positive expression. The number of mucinous adenocarcinoma was 41, among them, 14 cases were positive expression. The expression of HER-2/neu gene has no correlation with sex, age, the maximum diameter, general classification, degree of dif erentiation and depth of invasion, which has no statistical significance. However, the expression of HER-2/neu gene has correlation with metastasis of lymph node and Dukes stage, which has statistical significance. The expression of HER-2/neu gene was positive correlation with metastasis of lymph node and Dukes stage. The correlated coef icient index was 0.320 and 0.320 respectively. In the 74 patients with positive expression of HER-2 gene, 59.4%of them were 60-74 years old. And there was 97.3%of the patients without family history of adenocarcinoma. Conclusion：The expression of HER-2/neu gene in colon cancer tissues was higher than in adjacent tissues. The expression of HER-2/neu gene has no correlation with sex, age, the maximum diameter, general classification, degree of dif erentiation and depth of invasion, but has correlation with metastasis of lymph node and Dukes stage. The expression of HER-2/neu gene was positive correlation with metastasis of lymph node and Dukes stage. The expression of HER-2/neu gene with age of 60-74 years old and without family history of adenocarcinoma was higher than other groups.

Gene selection in class space for molecular classification of cancer

Gene selection (feature selection) is generally pertormed in gene space(feature space), where a very serious curse of dimensionality problem always existsbecause the number of genes is much larger than the number of samples in gene space(G-space). This results in difficulty in modeling the data set in this space and the lowconfidence of the result of gene selection. How to find a gene subset in this case is achallenging subject. In this paper, the above G-space is transformed into its dual space,referred to as class space (C-space) such that the number of dimensions is the verynumber of classes of the samples in G-space and the number of samples in C-space isthe number of genes in G-space. it is obvious that the curse of dimensionality in C-spacedoes not exist. A new gene selection method which is based on the principle of separatingdifferent classes as far as possible is presented with the help of Principal ComponentAnalysis (PCA). The experimental results on gene selection for real data set areevaluated with Fisher criterion, weighted Fisher criterion as well as leave-one-out crossvalidation, showing that the method presented here is effective and efficient.

The clinical and genetic characteristics in children with mitochondrial disease in China

Mitochondrial disease was a clinically and genetically heterogeneous group of diseases, thus the diagnosis was very difficult to clinicians. Our objective was to analyze clinical and genetic characteristics of children with mitochondrial disease in China. We tested 141 candidate patients who have been suspected of mitochondrial disorders by using targeted next-generation sequencing(NGS), and summarized the clinical and genetic data of gene confirmed cases from Neurology Department, Beijing Children's Hospital, Capital Medical University from October 2012 to January 2015. In our study, 40 cases of gene confirmed mitochondrial disease including eight kinds of mitochondrial disease, among which Leigh syndrome was identified to be the most common type, followed by mitochondrial encephalomyopathy, lactic acidosis, and stroke-like episodes(MELAS). The age-of-onset varies among mitochondrial disease, but early onset was common. All of 40 cases were gene confirmed, among which 25 cases(62.5%)with mitochondrial DNA(mtDNA) mutation, and 15 cases(37.5%) with nuclear DNA(nDNA) mutation. M.3243A>G(n=7)accounts for a large proportion of mtDNA mutation. The nDNA mutations include SURF1(n=7),PDHA1(n=2),and NDUFV1,NDUFAF6, SUCLA2, SUCLG1, RRM2 B, and C12orf65, respectively.