Network-Based Gene Expression Biomarkers for Cold and Heat Patterns of Rheumatoid Arthritis in Traditional Chinese Medicine

In Traditional Chinese Medicine (TCM), patients with Rheumatoid Arthritis (RA) can be classified into two main patterns: cold-pattern and heat-pattern. This paper identified the network-based gene expression biomarkers for both cold- and heat-patterns of RA. Gene expression profilings of CD4+ T cells from cold-pattern RA patients, heat-pattern RA patients, and healthy volunteers were obtained using microarray. The differentially expressed genes and related networks were explored using DAVID, GeneSpring software, and the protein-protein interactions (PPI) method. EIF4A2, CCNT1, and IL7R, which were related to the up-regulation of cell proliferation and the Jak-STAT cascade, were significant gene biomarkers of the TCM cold pattern of RA. PRKAA1, HSPA8, and LSM6, which were related to fatty acid metabolism and the I-κB kinase/NF-κB cascade, were significant biomarkers of the TCM heat-pattern of RA. The network-based gene expression biomarkers for the TCM cold- and heat-patterns may be helpful for the further stratification of RA patients when deciding on interventions or clinical trials

Xiaoqinglong granules as add-on therapy for asthma: latent class analysis of symptom predictors of response.

Xiaoqinglong granules (XQLG) has been shown to be an effective therapy in asthma animal models. We reviewed the literature and conducted this study to assess the impact of XQLG as an add-on therapy to treatment with fluticasone/salmeterol (seretide) in adult patients with mild-to-moderate, persistent asthma. A total of 178 patients were randomly assigned to receive XQLG and seretide or seretide plus placebo for 90 days. Asthma control was assessed by asthma control test (ACT), symptoms scores, FEV(1), and PEF. Baseline patient-reported Chinese medicine (CM)-specific symptoms were analyzed to determine whether the symptoms may be possible indicators of treatment response by conducting latent class analysis (LCA). There was no statistically significant difference in ACT score between two groups. In the subset of 70 patients with symptoms defined by CM criteria, XQLG add-on therapy was found to significantly increase the levels of asthma control according to global initiative for asthma (GINA) guidelines (P = 0.0329). There was no significant difference in another subset of 100 patients with relatively low levels of the above-mentioned symptoms (P = 0.1291). Results of LCA suggest that patients with the six typical symptoms defined in CM may benefit from XQLG

A traditional Chinese medicine versus Western combination therapy in the treatment of rheumatoid arthritis: two-stage study protocol for a randomized controlled trial

<p>Abstract</p> <p>Background</p> <p>The common randomized controlled trial design has distinct limitations when applied to Chinese medicine, because Chinese medicine identifies and treats 'Chinese medicine patterns' rather than diagnosed diseases. Chinese medicine patterns are a group of associated symptoms, tongue appearances and pulse characteristics. These limitations could be overcome by developing new strategies to evaluate the effect of Chinese medicine. The idea behind pattern-based efficacy evaluations may optimize clinical trial design by identifying the responsiveness-related Chinese medicine patterns.</p> <p>Methods/Design</p> <p>This is a two-stage multi-center trial of Chinese herbal medicine for the management of rheumatoid arthritis. The stage one trial is an open-label trial and aims to explore what groups of Chinese medicine information (such as symptoms) correlates with better efficacy, and the stage two trial is a randomized, controlled, double-blind, double-dummy clinical trial that incorporates the efficacy-related information identified in the stage-one trial into the inclusion criteria.</p> <p>Discussion</p> <p>The indication of a Chinese herbal formula is a specific Chinese medicine pattern and not a single disease and stratifying a disease into several patterns with a group of symptoms is a feasible procedure in clinical trials. This study is the first to investigate whether this approach in the design of Chinese herbal medicine trials can improve responses.</p> <p>Trial registration</p> <p>ChiCTR-TRC-10000989</p

Facile Two-Step Deposition of Calcium Oxalate Film on Dolomite to Improve Acid Rain Resistance

The deposition of a calcium oxalate layer on dolomite demonstrates potential application in stone culture heritage conservation. However, due to insufficient coverage and the presence of cracks, the film’s usefulness is restricted. In this investigation, we used a simple two-step procedure to create a cohesive and uncracked film. The findings show that the protective layer provides better coverage of the dolomite surface without causing cracks and significantly improves acid resistance. Furthermore, after the simple two-step treatment, the color and adhesive strength of dolomite substrates remained nearly unchanged

Facile Two-Step Deposition of Calcium Oxalate Film on Dolomite to Improve Acid Rain Resistance

The deposition of a calcium oxalate layer on dolomite demonstrates potential application in stone culture heritage conservation. However, due to insufficient coverage and the presence of cracks, the film&rsquo;s usefulness is restricted. In this investigation, we used a simple two-step procedure to create a cohesive and uncracked film. The findings show that the protective layer provides better coverage of the dolomite surface without causing cracks and significantly improves acid resistance. Furthermore, after the simple two-step treatment, the color and adhesive strength of dolomite substrates remained nearly unchanged

Understanding the Molecular Mechanism of Interventions in Treating Rheumatoid Arthritis Patients with Corresponding Traditional Chinese Medicine Patterns Based on Bioinformatics Approach

Better effectiveness would be achieved when interventions are used in treating patients with a specific traditional Chinese medicine (TCM) pattern. In this paper, the effectiveness in treating rheumatoid arthritis (RA) patients in a randomized clinical trial as reanalyzed after the patients were classified into different TCM patterns and the underlying mechanism of how the TCM pattern influences the clinical effectiveness of interventions (TCM and biomedicine therapy) was explored. The pharmacological networks of interventions were builtup with protein and protein interaction analyses based on all the related targeted proteins obtained from PubChem. The underlying mechanism was explored by merging the pharmacological networks with the molecular networks of TCM cold and hot patterns in RA. The results show that the TCM therapy is better in treating the RA patients with TCM hot pattern, and the biomedical therapy is better in the RA patients with cold pattern. The pharmacological network of TCM intervention is merged well with the molecular network of TCM hot pattern, and the pharmacological network of biomedical therapy is merged well with the network of cold pattern. The finding indicates that molecular network analysis could give insight into the full understanding of the underlying mechanism of how TCM pattern impacts the efficacy

Cold and heat pattern of rheumatoid arthritis in traditional Chinese medicine: distinct molecular signatures indentified by microarray expression profiles in CD4-positive T cell

The research is aimed to explore the distinct molecular signatures in discriminating the rheumatoid arthritis patients with traditional Chinese medicine (TCM) cold pattern and heat pattern. Twenty patients with typical TCM cold pattern and heat pattern were included. Microarray technology was used to reveal gene expression profiles in CD4+ T cells. The signal intensity of each expressed gene was globally normalized using the R statistics program. The ratio of cold pattern to heat pattern in patients with RA at more or less than 1:2 was taken as the differential gene expression criteria. Protein–protein interaction information for these genes from databases was searched, and the highly connected regions were detected by IPCA algorithm. The significant pathways were extracted from these subnetworks by Biological Network Gene Ontology tool. Twenty-nine genes differentially regulated between cold pattern and heat pattern were found. Among them, 7 genes were expressed significantly more in cold pattern. Biological network of protein–protein interaction information for these significant genes were searched and four highly connected regions were detected by IPCA algorithm to infer significant complexes or pathways in the biological network. Particularly, the cold pattern was related to Toll-like receptor signaling pathway. The following related pathways in heat pattern were included: Calcium signaling pathway; cell adhesion molecules; PPAR signaling pathway; fatty acid metabolism. These results suggest that better knowledge of the main biological processes involved at a given pattern in TCM might help to choose the most appropriate treatment

Plasma metabonomics study of rheumatoid arthritis and its Chinese medicine subtypes by using liquid chromatography and gas chromatography coupled with mass spectrometry

Rheumatoid arthritis (RA) is the most severe type of chronic inflammatory disease and has always been a research hotspot in different fields. In this study, a non-targeted metabonomics approach was carried out to profile metabolic characteristics of RA and its Chinese medicine subtypes by using liquid chromatography-mass spectrometry (LC-MS) and gas chromatography-mass spectrometry (GC-MS). Plasma samples of 57 RA patients and 23 healthy controls were collected. On the basis of the traditional Chinese medicine (TCM), RA patients were classified into two main patterns, the cold pattern and the heat pattern. By using univariate and multivariate data analysis, we found that the RA patients presented diverse dysfunctions in inositol phosphate metabolism, lipid metabolism, amino acid metabolism, glucose metabolism, ascorbate metabolism, glyoxylate and dicarboxylate metabolism. The metabolic phenotypes were different between the RA cold pattern and the RA heat pattern. Compared with the RA cold pattern, the RA heat pattern showed elevated plasma concentrations of glycochenodeoxycholate, proline, saturated and mono-unsaturated phosphatidylcholine (PC) but decreased levels of urea, free fatty acid (FFA) and polyunsaturated PC. Our data show that metabonomics is a valuable tool in disease and TCM subtype research