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1.  Arsenic trioxide induces apoptosis of human gastrointestinal cancer cells 
AIM: To investigate the changes in apoptosis in gastrointestinal cancer cells from patients with gastrointestinal cancers treated with arsenic trioxide (As2O3); and to study the possible molecular mechanisms of such changes by detecting the expression levels of p53 and Bcl-2.
METHODS: Twenty patients with gastrointestinal adenocarcinoma based on endoscopic and biopsy findings (ten patients with gastric cancer and ten patients with colorectal cancer) who received treatment in our hospital between August 2007 and December 2008 were included in this study. None of the patients had received anti-tumour agents prior to As2O3 treatment. As2O3 was administered intravenously at a dose of 0.01 g/d diluted with 5% glucose in normal saline for 2-3 h for 3 consecutive days before surgery. Morphological changes associated with apoptosis of gastrointestinal cancer cells were observed by light microscopy. Changes in the apoptotic index induced by As2O3 were investigated using the terminal deoxynucleotidyl transferase dUTP nick end labelling method. Expression levels of p53 and Bcl-2 proteins in gastrointestinal cancer tissues were determined by immunohistochemistry.
RESULTS: The apoptotic index of human gastrointestinal cancer cells was higher in cells from patients treated with As2O3 than in those not treated (P < 0.05). p53 protein expression in gastrointestinal tissues was unchanged by As2O3 (P > 0.05). However, Bcl-2 protein expression in gastrointestinal tissues was down-regulated by As2O3 (P < 0.01).
CONCLUSION: These results demonstrate that As2O3 treatment in patients with gastrointestinal cancers can induce apoptosis in gastrointestinal cancer cells and down-regulate Bcl-2 protein expression.
PMCID: PMC4017065  PMID: 24833880
Gastrointestinal cancer; Arsenic trioxide; Apoptosis; p53; Bcl-2
2.  Rheumatoid Arthritis with Deficiency Pattern in Traditional Chinese Medicine Shows Correlation with Cold and Hot Patterns in Gene Expression Profiles 
In our precious study, the correlation between cold and hot patterns in traditional Chinese medicine (TCM) and gene expression profiles in rheumatoid arthritis (RA) has been explored. Based on TCM theory, deficiency pattern is another key pattern diagnosis among RA patients, which leads to a specific treatment principle in clinical management. Therefore, a further analysis was performed aiming at exploring the characteristic gene expression profile of deficiency pattern and its correlation with cold and hot patterns in RA patients by bioinformatics analysis approach based on gene expression profiles data detected with microarray technology. The TCM deficiency pattern-related genes network comprises 7 significantly, highly connected regions which are mainly involved in protein transcription processes, protein ubiquitination, toll-like receptor activated NF-κB regulated gene transcription and apoptosis, RNA clipping, NF-κB signal, nucleotide metabolism-related apoptosis, and immune response processes. Toll-like receptor activated NF-κB regulated gene transcription and apoptosis pathways are potential specific pathways related to TCM deficiency patterns in RA patients; TCM deficiency pattern is probably related to immune response. Network analysis can be used as a powerful tool for detecting the characteristic mechanism related to specific TCM pattern and the correlations between different patterns.
PMCID: PMC3794642  PMID: 24174973
3.  Expression Profiling and Proteomic Analysis of JIN Chinese Herbal Formula in Lung Carcinoma H460 Xenografts 
Many traditional Chinese medicine (TCM) formulae have been used in cancer therapy. The JIN formula is an ancient herbal formula recorded in the classic TCM book Jin Kui Yao Lue (Golden Chamber). The JIN formula significantly delayed the growth of subcutaneous human H460 xenografted tumors in vivo compared with the growth of mock controls. Gene array analysis of signal transduction in cancer showed that the JIN formula acted on multiple targets such as the mitogen-activated protein kinase, hedgehog, and Wnt signaling pathways. The coformula treatment of JIN and diamminedichloroplatinum (DDP) affected the stress/heat shock pathway. Proteomic analysis showed 36 and 84 differentially expressed proteins between the mock and DDP groups and between the mock and JIN groups, respectively. GoMiner analysis revealed that the differentially expressed proteins between the JIN and mock groups were enriched during cellular metabolic processes, and so forth. The ones between the DDP and mock groups were enriched during protein-DNA complex assembly, and so forth. Most downregulated proteins in the JIN group were heat shock proteins (HSPs) such as HSP90AA1 and HSPA1B, which could be used as markers to monitor responses to the JIN formula therapy. The mechanism of action of the JIN formula on HSP proteins warrants further investigation.
PMCID: PMC3770002  PMID: 24066008
4.  TGFA and IRF6 Contribute to the Risk of Nonsyndromic Cleft Lip with or without Cleft Palate in Northeast China 
PLoS ONE  2013;8(8):e70754.
Nonsyndromic cleft lip with or without cleft palate (NSCL/P) are common birth defects with a complex etiology. Multiple interacting loci and possible environmental factors influence the risk of NSCL/P. 12 single nucleotide polymorphisms (SNPs) in 7 candidate genes were tested using an allele-specific primer extension for case-control and case-parent analyses in northeast China in 236 unrelated patients, 185 mothers and 154 fathers, including 128 complete trios, and 400 control individuals. TGFA and IRF6 genes showed a significant association with NSCL/P. In IRF6, statistical evidence of an association between rs2235371 (p = 0.003), rs2013162 (p<0.0001) and NSCL/P was observed in case-control analyses. Family based association tests (FBATs) showed over-transmission of the C allele at the rs2235371 polymorphism (p = 0.007). In TGFA, associations between rs3771494, rs3771523 (G3822A), rs11466285 (T3851C) and NSCL/P were observed in case-control and FBAT analyses. Associations between other genes (BCL3, TGFB3, MTHFR, PVRL1 and SUMO1) and NSCL/P were not detected.
PMCID: PMC3735505  PMID: 23940636
5.  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, FEV1, 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.
PMCID: PMC3574648  PMID: 23431348
6.  Ganoderma lucidum polysaccharides counteract inhibition on CD71 and FasL expression by culture supernatant of B16F10 cells upon lymphocyte activation 
Immune responses to tumor-associated antigens are often detectable in tumor-bearing hosts, but they fail to eliminate malignant cells or prevent development of metastases. Tumor cells produce factors such as interleukin-10, transforming growth factor-β1 and vascular endothelial growth factor (VEGF) that suppress the function of immune cells or induce apoptosis of immune cells. Culture supernatant of tumor cells may contain these immunosuppressive factors which suppress lymphocyte activation. CD71 and FasL are two important molecules that are expressed upon lymphocyte activation. Counteraction against suppression CD71 and FasL expression upon lymphocyte activation may benefit tumor control. A potential component with this effect is Ganoderma lucidum polysaccharides (Gl-PS). In this study, Gl-PS was used on lymphocytes incubating with culture supernatant of B16F10 melanoma cells (B16F10-CS) in the presence of phytohemagglutinin. Following induction with phytohemagglutinin, B16F10-CS suppressed CD71 expression in lymphocytes (as detected by immunofluorescence and flow cytometry), proliferation in lymphocytes (as detected by MTT assay), and FasL expression in lymphocytes (as detected by immunocytochemistry and western blot analysis), while Gl-PS fully or partially counteracted these suppressions. Gl-PS showed counteractive effects against suppression induced by B16F10-CS on CD71 and FasL expression upon lymphocyte activation, suggesting the potential of Gl-PS to facilitate cancer immunotherapy.
PMCID: PMC3628224  PMID: 23596479
tumor; lymphocyte activation; Ganoderma lucidum; polysaccharides; FasL; CD71
7.  Traditional Chinese Medicine-Based Network Pharmacology Could Lead to New Multicompound Drug Discovery 
Current strategies for drug discovery have reached a bottleneck where the paradigm is generally “one gene, one drug, one disease.” However, using holistic and systemic views, network pharmacology may be the next paradigm in drug discovery. Based on network pharmacology, a combinational drug with two or more compounds could offer beneficial synergistic effects for complex diseases. Interestingly, traditional chinese medicine (TCM) has been practicing holistic views for over 3,000 years, and its distinguished feature is using herbal formulas to treat diseases based on the unique pattern classification. Though TCM herbal formulas are acknowledged as a great source for drug discovery, no drug discovery strategies compatible with the multidimensional complexities of TCM herbal formulas have been developed. In this paper, we highlighted some novel paradigms in TCM-based network pharmacology and new drug discovery. A multiple compound drug can be discovered by merging herbal formula-based pharmacological networks with TCM pattern-based disease molecular networks. Herbal formulas would be a source for multiple compound drug candidates, and the TCM pattern in the disease would be an indication for a new drug.
PMCID: PMC3541710  PMID: 23346189
8.  Effect of Combining Therapy with Traditional Chinese Medicine-Based Psychotherapy and Herbal Medicines in Women with Menopausal Syndrome: A Randomized Controlled Clinical Trial 
This multicenter, randomized, controlled clinical study was designed to address the effectiveness of combined traditional-Chinese-medicine- (TCM-) based psychotherapy and Chinese herbal medicine (CHM) in the treatment of menopausal syndrome. Altogether 424 eligible women diagnosed as menopausal syndrome and categorized as Kidney-Yin/Kidney-Yang deficiency pattern in TCM were randomly assigned into 4 groups and accepted TCM-based psychotherapy (PSY), CHM, PSY + CHM, or placebo therapies, respectively, for 12 weeks, and another 12 weeks were taken as the followup. Kupperman Index (KI) and the Menopause-Specific Quality of Life (MENQOL) with its four subscales (vasomotor, physical, psychosocial, and sexual) were employed for efficacy assessment. Results showed that 400 participants completed 12-week treatment, of which 380 finished the record of KI and MENQOF at week 24. The average adjusted number of KI score decreased between baseline and 12 weeks in all groups. Statistically significant differences were detected in the average adjusted change between the PSY + CHM group and placebo at overall time points (P < 0.05). No severe adverse events occurred in each group and no significant differences were indicated between any of the three groups and placebo in adverse event proportion. We concluded that TCM psychotherapy combined with CHM has a favorable outcome in treating menopausal syndrome.
PMCID: PMC3523610  PMID: 23304198
9.  Inhibition of β-catenin Signaling by Nongenomic Action of Orphan Nuclear Receptor Nur77 
Oncogene  2011;31(21):2653-2667.
Dysregulation of β-catenin turnover due to mutations of its regulatory proteins including APC and p53 is implicated in the pathogenesis of cancer. Thus, intensive effort is being made to search for alternative approaches to reduce abnormally activated β-catenin in cancer cells. Nur77, an orphan member of the nuclear receptor superfamily, plays a role in the growth and apoptosis of cancer cells. Here, we reported that Nur77 could inhibit transcriptional activity of β-catenin by inducing β-catenin degradation via proteasomal degradation pathway that is GSK3β and Siah-1 independent. Nur77 induction of β-catenin degradation required both the N-terminal region of Nur77, which was involved in Nur77 ubiquitination, and the C-terminal region, which was responsible for β-catenin binding. Nur77/ΔDBD, a Nur77 mutant lacking its DNA-binding domain, resided in the cytoplasm, interacted with β-catenin, and induced β-catenin degradation, demonstrating that Nur77-mediated β-catenin degradation was independent of its DNA-binding and transactivation and might occur in the cytoplasm. In addition, we reported our identification of two digitalis-like compounds (DLCs), H-9 and ATE-i2-b4, which potently induced Nur77 expression and β-catenin degradation in SW620 colon cancer cells expressing mutant APC protein in vitro and in animals. DLC-induced Nur77 protein was mainly found in the cytoplasm, and inhibition of Nur77 nuclear export by the CRM1-dependent nuclear export inhibitor leptomycin B or Jun N-terminal kinase inhibitor prevented the effect of DLC on inducing β-catenin degradation. Together, our results demonstrate that β-catenin can be degraded by cytoplasmic Nur77 through their interaction and identify H-9 and ATE-i2-b4 as potent activators of the Nur77-mediated pathway for β-catenin degradation.
PMCID: PMC3257393  PMID: 21986938
Nur77; β-catenin; Nongenomic; Cardenolide; Cancer
10.  Ophiopogonin B-induced autophagy in non-small cell lung cancer cells via inhibition of the PI3K/Akt signaling pathway 
Oncology Reports  2012;29(2):430-436.
Ophiopogonin B (OP-B) is a bioactive component of Radix Ophiopogon Japonicus, which is often used in Chinese traditional medicine to treat pulmonary disease. However, whether or not OP-B has any potential antitumor activity has not been reported. Here, we show that the non-small cell lung cancer (NSCLC) cell lines NCI-H157 and NCI-H460 treated with OP-B grow more slowly and accumulate vacuoles in their cytoplasm compared to untreated control cells. Flow cytometric analysis showed that the cells were arrested in G0/G1 phase. Nuclear morphology, Annexin-V/PI staining, and expression of cleaved caspase-3 all confirm that OP-B does not induce apoptosis. Instead, based on results from both transmission electron microscopy (TEM) and the expression of microtubule-associated protein 1 light chain 3-II (LC3-II), we determined that OP-B treatment induced autophagy in both cell lines. Next, we examined the PI3K/Akt/mTOR signaling pathway and found that OP-B inhibited phosphorylation of Akt (Ser473, Thr308) in NCI-H157 cells and also inhibited several key components of the pathway in NCI-H460 cells, such as p-Akt(Ser473, Thr308), p-p70S6K (Thr389). Additionally, insulin-mediated activation of the PI3K/Akt/mTOR pathway provides evidence that activation of this pathway may correlate with induction of autophagy in H460 cells. Therefore, OP-B is a prospective inhibitor of PI3K/Akt and may be used as an alternative compound to treat NSCLC.
PMCID: PMC3583607  PMID: 23151908
autophagy; natural medicines; non-small cell lung cancer; Ophiopogonin B; PI3K/Akt/mTOR
11.  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.
PMCID: PMC3480696  PMID: 23118783
12.  The Effect of the WIC Program on the Health of Newborns 
Health Services Research  2010;45(4):1083-1104.
To determine the effect of the Special Supplemental Nutrition Program for Women, Infants, and Children (WIC) on birth outcomes.
Data Source
The Child Development Supplement (CDS) of the Panel Study of Income Dynamics (PSID). The PSID provides extensive data on the income and well-being of a representative sample of U.S. families from 1968 to present. The CDS collects information on the children in PSID families ranging from cognitive, behavioral, and health status to their family and neighborhood environment. The first two waves of the CDS were conducted in 1997 and 2002, respectively. We use information on 3,181 children and their mothers.
Study Design
We use propensity score matching with multiple imputations to examine whether WIC program influences birth outcomes: birth weight, prematurity, maternal report of the infant's health, small for gestational age, and placement in the neonatal intensive care unit. Furthermore, we use a fixed-effects model to examine the above outcomes controlling for mother-specific unobservables.
Principal Findings
After using propensity scores to adjust for confounding factors, WIC shows no statistically significant effects for any of six outcomes. Fixed-effects models, however, reveal some effects that are statistically significant and fairly substantial in size. These involve preterm birth and birth weight.
Overall, the WIC program had moderate effects, but findings were sensitive to the estimation method used.
PMCID: PMC2910570  PMID: 20459450
WIC; birth outcomes; propensity score; multiple imputations; fixed-effects model
13.  Traditional Chinese Medicine Zheng in the Era of Evidence-Based Medicine: A Literature Analysis 
Zheng, which is also called a syndrome or pattern, is the basic unit and a key concept of traditional Chinese medicine (TCM) theory. Zheng can be considered a further stratification of patients when it is integrated with biomedical diagnoses in clinical practice to achieve higher efficacies. In an era of evidence-based medicine, confronted with the vast and increasing volume of TCM data, there is an urgent need to explore these resources effectively using techniques of knowledge discovery in databases. The application of effective data mining in the analysis of multiple extensively integrated databases can supply new information about TCM Zheng research. In this paper, we screened the published literature on TCM Zheng-related studies in the SinoMed and PubMed databases with a novel data mining approach to obtain an overview of the Zheng research landscape in the hope of contributing to a better understanding of TCM Zheng in the era of evidence-based medicine. In our results, contrast was found in Zheng in different studies, and several determinants of Zheng were identified. The data described in this paper can be used to assess Zheng research studies based on the title and certain characteristics of the abstract. These findings will benefit modern TCM Zheng-related studies and guide future Zheng study efforts.
PMCID: PMC3375182  PMID: 22719784
14.  Gastrodia elata Blume (tianma) mobilizes neuro-protective capacities 
Tianma (Gastrodia elata Blume) is a traditional Chinese medicine (TCM) often used for the treatment of headache, convulsions, hypertension and neurodegenerative diseases. Tianma also modulates the cleavage of the amyloid precursor protein App and cognitive functions in mice. The neuronal actions of tianma thus led us to investigate its specific effects on neuronal signalling. Accordingly, this pilot study was designed to examine the effects of tianma on the proteome metabolism in differentiated mouse neuronal N2a cells using an iTRAQ (isobaric tags for relative and absolute quantitation)-based proteomics research approach. We identified 2178 proteins, out of which 74 were found to be altered upon tianma treatment in differentiated mouse neuronal N2a cells. Based on the observed data obtained, we hypothesize that tianma could promote neuro-regenerative processes by inhibiting stress-related proteins and mobilizing neuroprotective genes such as Nxn, Dbnl, Mobkl3, Clic4, Mki67 and Bax with various regenerative modalities and capacities related to neuro-synaptic plasticity.
PMCID: PMC3388733  PMID: 22773961
Aging; tianma; neuron; neurodegeneration; metabolism; signalling; TCM
15.  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.
PMCID: PMC3318903  PMID: 22536280
16.  Tianma Modulates Blood Vessel Tonicity 
Tianma is a traditional Chinese medicine (TCM) often used for the treatment of hypertension and heart diseases. To elucidate the function of tianma at the molecular level, we investigated the effect of tianma on vascular functions and aortic protein metabolism. We found that long-term treatment with tianma (~2.5g/kg/day for three months) in one-year-old rats could enhance acetylcholine (ACh)-induced vasorelaxation in endothelium-intact thoracic aortic rings against both KCl (80 mM)- and phenylephrine (PE)-induced contraction. By using the iTRAQ (isobaric tag for relative and absolute quantification) technique, we confirmed from the functional data at the proteome level that tianma treatment down-regulated the expressions of contractile proteins (e.g. Acta2) and other related structural proteins (e.g. desmin), and up-regulated the expressions of extracellular matrix (ECM) glycoproteins (e.g. Fbln5) and anti-thrombotic proteins (e.g. Anxa2) in aortic tissue. By inductive reasoning, tianma could perform its vasodilatory effect not only by inhibiting vascular smooth muscle contraction, but also by enhancing blood vessel elasticity and stabilizing the arterial structure. Thus, tianma might become a novel therapeutic herbal medicine for cardiovascular diseases by regulating the aortic proteome metabolism.
PMCID: PMC3391654  PMID: 22787517
Tianma; Vascular disease; Aorta; TCM.
17.  Discrete derivative: a data slicing algorithm for exploration of sharing biological networks between rheumatoid arthritis and coronary heart disease 
BioData Mining  2011;4:18.
One important concept in traditional Chinese medicine (TCM) is "treating different diseases with the same therapy". In TCM practice, some patients with Rheumatoid Arthritis (RA) and some other patients with Coronary Heart Disease (CHD) can be treated with similar therapies. This suggests that there might be something commonly existed between RA and CHD, for example, biological networks or biological basis. As the amount of biomedical data in leading databases (i.e., PubMed, SinoMed, etc.) is growing at an exponential rate, it might be possible to get something interesting and meaningful through the techniques developed in data mining.
Based on the large data sets of Western medicine literature (PubMed) and traditional Chinese medicine literature (SinoMed), by applying data slicing algorithm in text mining, we retrieved some simple and meaningful networks. The Chinese herbs used in treatment of both RA and CHD, might affect the commonly existed networks between RA and CHD. This might support the TCM concept of treating different diseases with the same therapy.
First, the data mining results might show the positive answer that there are biological basis/networks commonly existed in both RA and CHD. Second, there are basic Chinese herbs used in the treatment of both RA and CHD. Third, these commonly existed networks might be affected by the basic Chinese herbs. Forth, discrete derivative, the data slicing algorithm is feasible in mining out useful data from literature of PubMed and SinoMed.
PMCID: PMC3141583  PMID: 21696640
18.  A traditional Chinese medicine versus Western combination therapy in the treatment of rheumatoid arthritis: two-stage study protocol for a randomized controlled trial 
Trials  2011;12:137.
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.
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.
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.
Trial registration
PMCID: PMC3123562  PMID: 21639923
19.  Cold and heat pattern of rheumatoid arthritis in traditional Chinese medicine: distinct molecular signatures indentified by microarray expression profiles in CD4-positive T cell 
Rheumatology International  2010;32(1):61-68.
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.
PMCID: PMC3253282  PMID: 20658292
Protein and protein interaction; Genomics; Pathway; Rheumatoid arthritis; Traditional Chinese medicine

Results 1-19 (19)