Identification and validation of aging-related gene signatures and their immune landscape in diabetic nephropathy.

Background: Aging and immune infiltration have essential role in the physiopathological mechanisms of diabetic nephropathy (DN), but their relationship has not been systematically elucidated. We identified aging-related characteristic genes in DN and explored their immune landscape. Methods: Four datasets from the Gene Expression Omnibus (GEO) database were screened for exploration and validation. Functional and pathway analysis was performed using Gene Set Enrichment Analysis (GSEA). Characteristic genes were obtained using a combination of Random Forest (RF) and Support Vector Machine Recursive Feature Elimination (SVM-RFE) algorithm. We evaluated and validated the diagnostic performance of the characteristic genes using receiver operating characteristic (ROC) curve, and the expression pattern of the characteristic genes was evaluated and validated. Single-Sample Gene Set Enrichment Analysis (ssGSEA) was adopted to assess immune cell infiltration in samples. Based on the TarBase database and the JASPAR repository, potential microRNAs and transcription factors were predicted to further elucidate the molecular regulatory mechanisms of the characteristic genes. Results: A total of 14 differentially expressed genes related to aging were obtained, of which 10 were up-regulated and 4 were down-regulated. Models were constructed by the RF and SVM-RFE algorithms, contracted to three signature genes: EGF-containing fibulin-like extracellular matrix (EFEMP1), Growth hormone receptor (GHR), and Vascular endothelial growth factor A (VEGFA). The three genes showed good efficacy in three tested cohorts and consistent expression patterns in the glomerular test cohorts. Most immune cells were more infiltrated in the DN samples compared to the controls, and there was a negative correlation between the characteristic genes and most immune cell infiltration. 24 microRNAs were involved in the transcriptional regulation of multiple genes simultaneously, and Endothelial transcription factor GATA-2 (GATA2) had a potential regulatory effect on both GHR and VEGFA. Conclusion: We identified a novel aging-related signature allowing assessment of diagnosis for DN patients, and further can be used to predict immune infiltration sensitivity.

Metabolite Comparison between Spleen-Deficiency and Healthy Children.

Objective: From the perspective of metabolomics, this study compares the metabolomics characteristics of feces and urine between children with spleen-deficiency and healthy children to explain the scientific connotation of children with spleen-deficiency susceptibility to digestive system diseases from the metabolic level and provide a scientific basis for further research. Methods: This study included 20 children with spleen-deficiencies and 17 healthy children. Children's symptom scores, height, and weight were recorded in groups, and feces and urine samples were collected. The samples were detected using ultrahigh-performance liquid chromatography-mass spectrometry. The data were analyzed using multivariate statistical analysis such as principal component analysis (PCA) and partial least squares discriminant analysis (PLS-DA). Related differential metabolites were identified through database comparisons between two groups based on the MS and KEGG. Results: Compared to healthy children, the metabolites glucuronic acid, xanthine, and indole-3-acetaldehyde tend to be reduced in children with spleen-deficiency. Moreover, these children showed an increase in metabolites such as quinic acid, adenine, 4-methyl-5-thiazole-ethanol, 3-formyl indole, and 5-hydroxy indole-3-acetic acid. The condition affected many of the critical metabolic pathways, including the metabolism of tryptophan, cysteine, methionine, and pentose phosphate. Conclusion: The children with spleen-deficiency had disorders at the metabolic level, which might be due to factors such as diet, personal preferences, and genes, leading to various symptoms, making spleen-deficiency children more prone to suffer from digestive diseases than healthy children. The results set a basis for the research on children's TCM constitution, which can be a reference to further studies to deal with the spleen-deficiency.

Exploration of microRNA profiles in human colostrum.

BACKGROUND: Colostrum is well known to have excellent nutritional value for newborns. The aim of this study was to investigate the dynamic expression pattern of microRNA in human colostrum and mature milk. Furthermore, we identified the specific microRNA in human colostrum and analyzed the regulatory function of human colostrum. METHODS: We collected breast milk samples from 18 lactating volunteers. The expression of microRNA in breast milk was detected by microarray analysis. The expression differences were characterized by log2FC (|log2fold change| >1.58) and associated P values (P<0.05). Furthermore, the prediction of microRNA targets, bioinformatics analysis and network generation were carried out using network database. RESULTS: Our results showed that during the human lactation process, the composition of microRNAs in human milk changes dynamically. Compared to the microRNA expression profile in human mature milk, the expression levels of 49 microRNAs were significantly different and 67 microRNAs were specifically expressed in human colostrum. Based on the results of Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis, the predicted target mRNAs of the identified colostrum-specific microRNAs were involved in the regulation of distinct biological processes, such as signal transduction, positive regulation of GTPase activity, and protein phosphorylation. Moreover, the predicted mRNA targets were from large spectrums of signaling pathways, such as the MAPK, Ras, Hippo, Wnt, and mTOR signaling pathways, as well as the longevity regulating pathway. CONCLUSIONS: Our study illuminates the landscape of microRNA expressions in human colostrum and mature milk, and emphasizes the value of microRNAs as nutritional additives in milk-related commercial products.

[Feasibility of treatment of cesarean scar pregnancy with dilatation and curettage under ultrasound guidance].

OBJECTIVE: The present study sought to investigate the predictors of successful dilatation and curettage (D&C) in treatment of cesarean scar pregnancy (CSP). METHODS: Retrospective analysis was conducted in 84 CSP patients undergoing D&C from January 2013 to December 2014. Failure was defined as D&C followed by transcatheter uterine arterial embolization due to uncontrolled hemorrhage. Sub-stratification of success group as residue group or non-residue group was performed according to the residues at the site of cesarean scar after D&C. The univariate logistic regression and linear regression were used to assess the predictors of the failure and residues. ROC curve was used to assess the cut-off values of the predictors. RESULTS: D&C under ultrasound guidance succeeded in 75 patients (89.3%) and 36 patients had residues at the site of cesarean scar among them (48%), 9 patients failed in D&C (10.7%). High Serum human chorionic-gonadotropin (hCG), small gestation sac (GS), thin cesarean scar myometrium thickness (CSM) and low peritrophoblastic flow resistance index (RI) were risk factors of D&C failure in treatment of CSP. That serum hCG>97 006 U/L was prime predictor of failure (predictive value 100%, 95% CI 94.9%-100%). High success ratio was observed in patients with serum hCG<58 076 U/L, GS≤19 mm, CSM>2.7 mm, and RI>0.25. And days of menopause≤41 d, GS≤15 mm, CSM>3.7 mm, RI>0.4 and serum hCG<3 935 U/L were predictors of complete success of D&C. The postponed restoration of menstruation was observed in patients with residues, which did not induce amenorrhea and disappeared in 1-3 months after procedures. CONCLUSION: Early diagnosis and treatment is associated with successful D&C in treatment of CSP. HCG, GS, CSM and RI are valuable in predicting the prognosis of D&C in treatment of CSP.