The Effects of Jiang-Zhi-Ning and Its Main Components on Cholesterol Metabolism

To examine how Jiang-Zhi-Ning (JZN) regulates cholesterol metabolism and compare the role of its four main components. We established a beagle model of hyperlipidemia, fed with JZN extract and collected JZN-containing serum 0, 1, 2, 4, and 6 h later. Human liver cells Bel-7402 were stimulated with 10% JZN-containing serum as well as the four main components of JZN and Atorvastatin. The mRNA expression of LDL receptor (LDL-R), 3-hydroxy-3-methyl-glutaryl-CoA reductase (HMG-CoAR), cytochrome P450 7A1 (CYP7A1), and acetyl-Coenzyme A acetyltransferase 2 (ACAT2) was measured by real-time PCR. LDL-R surface expression and LDL-binding and internalization were examined by flow cytometry. The results showed that JZN-containing serum significantly increased the mRNA expression of LDL-R, HMG-CoAR, and CYP7A1 in Bel-7402 cells. All the four components significantly increased the mRNA and protein expression of LDL-R and HMG-CoAR and decreased the mRNA and protein expression of ACAT2 in Bel-7402 cells. Hyperinand chrysophanol also markedly increased the mRNA expression of CYP7A1. Stimulation with stilbene glycosidesignificantly increased the surface expression of LDL-R and the binding and internalization of LDL. In conclusion, JZN and its four components have close relationship with the process of cholesterol metabolism, emphasizing their promising application as new drug candidates in the treatment of hyperlipidemia

In Silico Syndrome Prediction for Coronary Artery Disease in Traditional Chinese Medicine

Coronary artery disease (CAD) is the leading causes of deaths in the world. The differentiation of syndrome (ZHENG) is the criterion of diagnosis and therapeutic in TCM. Therefore, syndrome prediction in silico can be improving the performance of treatment. In this paper, we present a Bayesian network framework to construct a high-confidence syndrome predictor based on the optimum subset, that is, collected by Support Vector Machine (SVM) feature selection. Syndrome of CAD can be divided into asthenia and sthenia syndromes. According to the hierarchical characteristics of syndrome, we firstly label every case three types of syndrome (asthenia, sthenia, or both) to solve several syndromes with some patients. On basis of the three syndromes' classes, we design SVM feature selection to achieve the optimum symptom subset and compare this subset with Markov blanket feature select using ROC. Using this subset, the six predictors of CAD's syndrome are constructed by the Bayesian network technique. We also design Naïve Bayes, C4.5 Logistic, Radial basis function (RBF) network compared with Bayesian network. In a conclusion, the Bayesian network method based on the optimum symptoms shows a practical method to predict six syndromes of CAD in TCM

Metabolomics-Based Study of Clinical and Animal Plasma Samples in Coronary Heart Disease with Blood Stasis Syndrome

The aim of this study is to explore a bridge connecting the mechanism basis and macro syndromes of coronary heart disease with experimental animal models. GC-MS technique was used to detect the metabolites of plasma samples in mini swine models with myocardial infarction (MI) and patients with unstable angina (UA). 30 metabolites were detected in the plasma samples of more than 50 percent of model group and control group in swine, while 37 metabolites were found in the plasma samples of UA patients and healthy control group. 21 metabolites in the plasma samples of swine model and 20 metabolites in patients with UA were found of significant value. Among which, 8 shared metabolites were found of low level expression in both swine model and UA patients. Independent Student's t-test, principal component analysis (PCA), and hierarchicalcluster analysis (HCA) were orderly applied to comprehend inner rules of variables in the data. The 8 shared metabolites could take place of the 21 or 20 metabolites in classification of swine model with MI and UA patients, which could be considered as a bridge connecting the mechanism basis and macrosyndromes of swine model with MI and UA patients

Whole exome sequencing identifies frequent somatic mutations in cell-cell adhesion genes in chinese patients with lung squamous cell carcinoma

Lung squamous cell carcinoma (SQCC) accounts for about 30% of all lung cancer cases. Understanding of mutational landscape for this subtype of lung cancer in Chinese patients is currently limited. We performed whole exome sequencing in samples from 100 patients with lung SQCCs to search for somatic mutations and the subsequent target capture sequencing in another 98 samples for validation. We identified 20 significantly mutated genes, including TP53, CDH10, NFE2L2 and PTEN. Pathways with frequently mutated genes included those of cell-cell adhesion/Wnt/Hippo in 76%, oxidative stress response in 21%, and phosphatidylinositol-3-OH kinase in 36% of the tested tumor samples. Mutations of Chromatin regulatory factor genes were identified at a lower frequency. In functional assays, we observed that knockdown of CDH10 promoted cell proliferation, soft-agar colony formation, cell migration and cell invasion, and overexpression of CDH10 inhibited cell proliferation. This mutational landscape of lung SQCC in Chinese patients improves our current understanding of lung carcinogenesis, early diagnosis and personalized therapy

Retrospective evaluation of whole exome and genome mutation calls in 746 cancer samples

Funder: NCI U24CA211006Abstract: The Cancer Genome Atlas (TCGA) and International Cancer Genome Consortium (ICGC) curated consensus somatic mutation calls using whole exome sequencing (WES) and whole genome sequencing (WGS), respectively. Here, as part of the ICGC/TCGA Pan-Cancer Analysis of Whole Genomes (PCAWG) Consortium, which aggregated whole genome sequencing data from 2,658 cancers across 38 tumour types, we compare WES and WGS side-by-side from 746 TCGA samples, finding that ~80% of mutations overlap in covered exonic regions. We estimate that low variant allele fraction (VAF < 15%) and clonal heterogeneity contribute up to 68% of private WGS mutations and 71% of private WES mutations. We observe that ~30% of private WGS mutations trace to mutations identified by a single variant caller in WES consensus efforts. WGS captures both ~50% more variation in exonic regions and un-observed mutations in loci with variable GC-content. Together, our analysis highlights technological divergences between two reproducible somatic variant detection efforts

Study on the Differences between Traditional Chinese Medicine Syndromes in NYHA I–IV Classification of Chronic Heart Failure

Objectives. This study investigated the distribution of characteristics of traditional Chinese medicine syndromes and their association with symptoms in 1027 patients with chronic heart failure (CHF). Methods. An observational study was performed by researchers, collecting data from 1036 patients with CHF from 24 Chinese medicine hospitals from May 2009 to December 2014. Due to incomplete information from nine patients, 1027 patients with CHF were analysed. The distribution of syndromes in CHF and association between high-frequency syndromes and symptoms were investigated. Results. The primary syndromes were qi deficiency, blood stasis, fluid retention, yin deficiency, phlegm turbidity, and yang deficiency. The primary sites of disease were the heart, kidney, lung, and spleen. In patients with CHF of differing cardiac function, there was no significant difference in the frequency of yin deficiency (P>0.05). The distribution of yang deficiency was significantly different between New York Heat Association (NYHA) classes II, III, and IV and between classes I+II and III+IV (P<0.05). The frequency of phlegm turbidity was significantly different between NYHA classes II and III, between classes III and IV, and between classes I+II and III+IV (P<0.05). The frequency of fluid retention was significantly different between NYHA classes I and IV, between classes II, III, and IV, and between classes I+II and III+IV (P<0.05). Regarding associations between syndromes and symptoms, qi deficiency was diagnosed in 87.43% of patients with insomnia and spiritlessness; blood stasis in 84.85% of patients with spontaneous sweating + cyanosis of the lips; fluid retention in 75% of patients with a hard pulse and oedema; and yin deficiency in 72.92% of patients with feverish sensation in the chest, palms, and soles and spontaneous sweating. Conclusions. The frequency of yang deficiency and fluid retention was higher and that of phlegm turbidity was lower in classes III and IV than in classes I and II

The effect of impurity on miscible CO2 displacement mechanism

International audienceThe CO2 displacement is one of the gasflooding Enhanced Oil Recovery (EOR) methods. The application from volatile oil to black oil is popular mainly because CO2 requires a relatively low miscibility pressure, which is suitable to most reservoir conditions. However, CO2 always contains some impurity, such as CH4, H2S and N2, leading to the change of phase behavior and flooding efficiency. Whether the gasflooding achieves successfully miscible displacement depends on the reservoir pressure and temperature, injected solvent and crude oil compositions. So three different types of oil samples from the real field are selected and mixtures of CH4, H2S and N2 with various CO2 concentrations as the solvent are considered. After a series of experimental data are excellently matched, three nine-pseudocomponent models are generated based on the thermodynamic Equation-of-State (EoS), which are capable of accurately predicting the complicated phase behavior. Three common tools of pressure–temperature (P–T), pressure–composition (P–X) and pseudoternary diagrams are used to display and analyze the alteration of phase behavior and types of displacement mechanism. Simulation results show that H2S is favorable to attain miscibility while CH4 and N2 are adverse, and the former can reduce the Multiple Contact Miscibility (MCM) pressure by the maximum level of 1.675 MPa per 0.1 mol. In addition, the phase envelope of the mixtures CO2/H2S displacing the reservoir oil on the pseudoternary diagram behaves a triangle shape, indicating the condensing-dominated process. While most phase envelopes of CO2/CH4 and CO2/N2 exhibit the trump and bell shapes, revealing the MCM of vaporization

Chinese Herbal Medicine in the Treatment of Chronic Heart Failure: Three-Stage Study Protocol for a Randomized Controlled Trial

Background. Chinese herbal medicine (CHM) has been used in the treatment of chronic heart failure (CHF) for a long time. Treatment based on syndrome differentiation and the main characteristic of TCM is the fundamental principle of TCM practice. In this study protocol, we have designed a trial to assess the efficacy and safety of CHM on CHF based on syndrome differentiation. Methods/Design. This is a three-stage trial of CHM in the treatment of CHF. The first stage is a literature review aiming to explore the common syndromes of CHF. The second is a multicentral, randomized, placebo-controlled trial to evaluate the efficacy and safety of CHM for the treatment of CHF. The third is a multicentral, randomized controlled clinical trial aiming to make cost-effectiveness analysis and evaluate the feasibility, compliance, and universality of CHM on CHF. Discussion. This trial will evaluate the efficacy, safety, feasibility, compliance, and universality of CHM on CHF. The expected outcome is to provide evidence-based recommendations for CHM on CHF and develop a prescription of CHM in the treatment of CHF. This trial is registered with NCT01939236 (Stage Two of the whole trial)

Plasma metabolomics combined with personalized diagnosis guided by Chinese medicine reveals subtypes of chronic heart failure

Background: Chronic heart failure (CHF) is characterized by insufficient blood supply from heart to meet the body's metabolic demands. Integrating Western and traditional Chinese medicine to treat CHF has proved a validated therapeutic approach. In recent years, metabolomics has been regarded as a potential platform to provide biomarkers for disease-subtypes. Objective: To examine 38 patients, combined NMR plasma metabolomics and traditional Chinese medicine diagnosis in order to identify diagnostic biomarkers for two CHF syndrome subtypes. Methods: After processing the spectra, orthogonal partial least square discriminant analysis was performed, and the contributing NMR signals were analyzed using Y-scrambling statistical validation with good reliability. Results: Plasma metabolic patterns of yin deficiency and yang deficiency patients were clearly discriminated. The yin-deficiency group had increased level of lactate, glycoprotein, lipoprotein and lower levels of glucose, valine and proline. The yang-deficiency group had higher levels of lactate, glycoprotein and pyruvic acid, and lower levels of glucose and lipoprotein. Potential biomarkers of CHF based on the two traditional Chinese medicine syndromes indicated alternative modes of metabolites and metabolic pathways in the disease, e.g. dysfunction of energy utilization and disturbance in fatty acids, amino acids. Conclusion: This study suggests that combining metabolomics with traditional Chinese medicine diagnosis can reveal metabolic signatures for CHF syndrome subtypes. The plasma metabolites identified might be of special clinical relevance for subtypes of CHF, which could lead to further understanding of mechanisms involved and an improvement in personalized treatment for CHF