The roles of Qishen granules recipes, Qingre Jiedu, Wenyang Yiqi and Huo Xue, in the treatment of heart failure.

ETHNOPHARMACOLOGICAL RELEVANCE: Recipes (Qingre Jiedu (QJ), Wenyang Yiqi (WYYQ) and Huo Xue (HX)) in Qishen granules (QSG) are believed to synergistically exert cardio-protective effects. However, the underlying pattern of each decomposed recipe in QSG and their synergistic effects in the treatment of heart failure (HF) are not clear. OBJECTIVE: The purpose of this study is to explore the biological contributions of decomposed recipes to therapeutic effects of QSG and reveal the pharmacological mechanism of QSG in treating HF. MATERIALS AND METHODS: The therapeutic effects of QSG or its recipes on heart failure were examined in wet-lab at both transcription and phenotypic level using HF Sprague-Dawley rats. Sequencing and transcriptome analyses were performed using in silico approaches including identification of differentially expressed genes, pathway enrichment and protein-protein interaction network studies. Specially, an optimized in silico quantitative pathway analysis that maximally extracted gene expression information was developed to reveal differentially expressed pathways (DEPs) among various groups, and is publicly available as R package QPA on GitHub (https://github.com/github-gs/QPA). Finally, the HF-related genes predicted using DEP approach were validated by quantitative real-time polymerase chain reaction and western blot. RESULTS: Multiple key genes and the associated signaling pathways were shown to be highly relevant for the therapeutic effect of QSG. Decreased expression of Spp1 gene required for inflammatory signaling and profibrotic signaling were observed in failing hearts treated with QJ, WYYQ and HX. Decreased expression of Cx3cr1 gene required for inflammatory signaling was observed in failing hearts treated with WYYQ and HX. Decreased expression of Myc gene required for oxidative stress and Fgfr2 gene required for profibrotic signaling were observed in failing hearts treated with HX and WYYQ, respectively. Increased expression of Adcy1 gene required for cAMP-PKA signaling cascade was observed in failing hearts treated with WYYQ and HX. CONCLUSIONS: Our study suggests that QJ, WYYQ and HX recipes in QSG achieve synergistic and complementary therapeutic effects through alleviating inflammatory responses, attenuating ventricular remodeling and enhancing myocardial energy supply.

Gut microbiota contributes to the distinction between two traditional Chinese medicine syndromes of ulcerative colitis.

BACKGROUND: Ulcerative colitis (UC) is considered to be closely associated with alteration of intestinal microorganisms. According to the traditional Chinese medicine (TCM) theory, UC can be divided into two disease syndromes called Pi-Xu-Shi-Yun (PXSY) and Da-Chang-Shi-Re (DCSR). The relationships among gut microbiota, TCM syndromes, and UC pathogenesis have not been well investigated. AIM: To investigate the role of gut microbiota in UC and the distinction of microbiota dysbiosis between PXSY and DCSR syndromes. METHODS: From May 2015 to February 2016, UC patients presenting to LongHua Hospital who met the established inclusion and exclusion criteria were enrolled in this retrospective study. Fresh stool specimens of UC patients with PXSY or DCSR were collected. The feces of the control group came from the health examination population of Longhua Hospital. The composition of gut bacterial communities in stool samples was determined by the pyrosequencing of 16S ribosomal RNA. The high-throughput sequencing reads were processed with QIIME, and biological functions were predicted using Phylogenetic Investigation of Communities by Reconstruction of Unobserved States. RESULTS: The composition of gut bacterial communities in 93 stool samples (30 healthy controls, 32 patients with PXSY syndrome, and 31 patients with DCSR syndrome) was determined by the pyrosequencing of 16S ribosomal RNA. Beta diversity showed that the composition of the microbiota was different among the three groups. At the family level, Porphyromonadaceae, Rikeneliaceae, and Lachnospiraceae significantly decreased while Enterococcus, Streptococcus, and other potential pathogens significantly increased in UC patients compared to healthy subjects. At the genus level, Parabacteroides, Dorea, and Ruminococcus decreased while Faeca-libacterium showed increased abundance in UC compared to healthy controls. Five differential taxa were identified between PXSY and DCSR syndromes. At the genus level, a significantly increased abundance of Streptococcus was observed in DCSR patients, while Lachnoclostridium increased in PXSY patients. The differential functional pathways of the gut microbiome between the PXSY and DCSR groups mainly included lipid metabolism, immunity, and the metabolism of polypeptides. CONCLUSION: Our study suggests that the gut microbiota contributes to the distinction between the two TCM syndromes of UC.

An eight-miRNA signature expression-based risk scoring system for prediction of survival in pancreatic adenocarcinoma.

PURPOSE: The purpose of this study was to establish a risk scoring system based on miRNAs to evaluate the prognosis in pancreatic adenocarcinoma. METHODS: Using a miRNA microarray dataset (179 pancreatic adenocarcinoma specimens and 4 normal control specimens) from TCGA, differentially expressed miRNAs were identified. Cox proportional hazards regression analysis was used to identify significant prognostic miRNAs, with which a risk scoring system was established and tested on a validation set. Cox regression analysis was performed to identify independent predictors of survival from clinical characteristics. Stratified Cox regression analyses were conducted to unravel the associations of clinical characteristics with survival. Differentially expressed genes (DEGs) were screened followed by functional annotation of the DEGs. RESULTS: Eight miRNAs (miR-1301, miR-598, miR-1180, miR-155, miR-496, miR-203, miR-193b, miR-135b) were independent predictors for survival. A risk scoring system was established with the 8 signature miRNAs. Upon Cox multivariate regression analysis, risk score, new tumor and targeted molecular therapy were independent predictors of prognosis. Stratified Cox regression analyses found that targeted molecular therapy and new tumor are associated with survival of patients. Survival-related DEGs were significantly enriched with regulation of transforming growth factor beta receptor, potassium ion transport and MAPK signaling pathway. CONCLUSIONS: The study proposes 8-miRNA expression-based risk scoring system to predict prognosis in pancreatic adenocarcinoma. New tumor and targeted molecular therapy were independent predictors of prognosis. Transforming growth factor beta receptor, potassium ion transport and MAPK signaling pathway may be related to prognosis in pancreatic adenocarcinoma.