Metagenome-wide association study of the alterations in the intestinal microbiome composition of ankylosing spondylitis patients and the effect of traditional and herbal treatment.

Introduction. Ankylosing spondylitis (AS) is a systemic progressive disease with an unknown etiology that may be related to the gut microbiome. Therefore, a more thorough understanding of its pathogenesis is necessary for directing future therapy.Aim. We aimed to determine the differences in intestinal microbial composition between healthy individuals and patients with AS who received and who did not receive treatment interventions. In parallel, the pathology of AS in each patient was analysed to better understand the link between AS treatment and the intestinal microbiota of the patients.Methodology. Sixty-six faecal DNA samples, including 37 from healthy controls (HCs), 11 from patients with untreated AS (NM), 7 from patients treated with nonsteroidal anti-inflammatory drugs (e.g. celecoxib; WM) and 11 from patients treated with Chinese herbal medicine (CHM), such as the Bushen-Qiangdu-Zhilv decoction, were collected and used in the drug effect analysis. All samples were sequenced using Illumina HiSeq 4000 and the microbial composition was determined.Results. Four species were enriched in the patients with AS: Flavonifractor plautii, Oscillibacter, Parabacteroides distasonis and Bacteroides nordii (HC vs. NM, P<0.05); only F. plautii was found to be significantly changed in the NM-HC comparison. No additional species were found in the HC vs. CHM analysis, which indicated a beneficial effect of CHM in removing the other three strains. F. plautii was found to be significantly increased in the comparison between the HC and WM groups, along with four other species (Clostridium bolteae, Clostridiales bacterium 1_7_47FAA, C. asparagiforme and C. hathewayi). The patients with AS harboured more bacterial species associated with carbohydrate metabolism and glycan biosynthesis in their faeces. They also had bacterial profiles less able to biodegrade xenobiotics or synthesize and transport vitamins.Conclusion. The gut microbiota of the patients with AS varied from that of the HCs, and the treatment had an impact on this divergence. Our data provide insight that could guide improvements in AS treatment.

Automated tongue diagnosis on the smartphone and its applications.

Tongue features are important objective basis for clinical diagnosis and treatment in both western medicine and Chinese medicine. The need for continuous monitoring of health conditions inspires us to develop an automatic tongue diagnosis system based on built-in sensors of smartphones. However, tongue images taken by smartphone are quite different in color due to various lighting conditions, and it consequently affects the diagnosis especially when we use the appearance of tongue fur to infer health conditions. In this paper, we captured paired tongue images with and without flash, and the color difference between the paired images is used to estimate the lighting condition based on the Support Vector Machine (SVM). The color correction matrices for three kinds of common lights (i.e., fluorescent, halogen and incandescent) are pre-trained by using a ColorChecker-based method, and the corresponding pre-trained matrix for the estimated lighting is then applied to eliminate the effect of color distortion. We further use tongue fur detection as an example to discuss the effect of different model parameters and ColorCheckers for training the tongue color correction matrix under different lighting conditions. Finally, in order to demonstrate the potential use of our proposed system, we recruited 246 patients over a period of 2.5 years from a local hospital in Taiwan and examined the correlations between the captured tongue features and alanine aminotransferase (ALT)/aspartate aminotransferase (AST), which are important bio-markers for liver diseases. We found that some tongue features have strong correlation with AST or ALT, which suggests the possible use of these tongue features captured on a smartphone to provide an early warning of liver diseases.

Treatment of Ankylosing Spondylitis With a Bushen-Qiangdu-Zhilv Decoction: A Case Report With a 3-year Follow-up.

Context • Ankylosing spondylitis (AS) is a refractory rheumatic disease, characterized by sacroiliitis and structural damage, and over decades, it can lead to joint fusion, frequently followed by significant spinal deformity and disability. However, to date, no method has been found to be effective in relieving or blocking structural damage to joints. Objective • The study intended to show that a decoction of Bushen-Qiangdu-Zhilv (BQZ), a therapy used in traditional Chinese medicine (TCM), can provide an alternative treatment for AS patients. Design • The research team performed a case study. Setting • The study was conducted at Guangdong Provincial Hospital of TCM in Guangzhou, China. Participant • The case study involved a 33-y-old male patient with active AS who visited the research team's clinic. Intervention • The patient took the BQZ orally 2 ×/d at 30 min after breakfast and 30 min after dinner. The patient returned to the clinic for consultation monthly. The patient took 2 servings/d for 10 mo and then received continuous BQZ treatment of the maintenance dosage for a period of approximately 3 y until December 2013. The maintenance dosage of BQZ was 3 or 4 decoctions per wk. Outcome Measures • The study used a number of measurements to evaluate the outcomes of treatment: (1) disease activity-the Bath Ankylosing Spondylitis Disease Activity Index (BASDAI); (2) functional condition-the Bath Ankylosing Spondylitis Functional Index (BASFI); (3) inflammation-ratings of morning stiffness and night pain, serum C-reactive protein (CRP) concentration measured by means of particle-enhanced immunonephelometry, and erythrocyte sedimentation rate (ESR) value as detected using the Westergren method; (4) spinal mobility-the Bath Ankylosing Spondylitis Metrology Index (BASMI); and (5) global assessments by patient and physician. Results • The participant showed improvements in inflammatory symptoms and recovery from structural damage after receiving the TCM therapy for 3 y. Conclusions • The study has shown that the long-term use of BQZ not only can lead to an improvement in inflammatory symptoms and quality of life but also can help to restore function after structural damage in AS patients.

Anti-inflammatory activity of extracts of Bushen-Qiangdu-Zhilv decoction, a Chinese medicinal formula, in M1-polarized RAW264.7.

BACKGROUND: Bushen-Qiangdu-Zhilv Decoction (BQZ) is one of famous traditional Chinese medical formula for treating ankylosing spondylitis (AS). However, the mechanisms underlying effects of BQZ remains unknown. Pro-inflammatory cytokines, tumor necrosis factor (TNF)-α and interleukin (IL)-1, play an important role in AS. We therefore evaluated if BQZ could affect the expression of these cytokines. METHODS: Crude extracts were prepared and fractioned with petroleum ether (PE), ethyl acetate (EA), n-butanol (BU) and finally water (ACE). The stability of the extracts was confirmed by high-pressure liquid chromatography (HPLC) analysis. M1-polarized RAW264.7 was induced and subsequently treated with BQZ extracts. Quantitative real-time PCR experiments were performed to measure mRNA expression of TNF-α and IL-1. RESULTS: It was found that TNF-α could be significantly suppressed by ACE extracts, whereas IL-1 was dramatically inhibited by BU extracts, which was further confirmed by dose-dependent experiments. Importantly, MTS assays showed that both ACE and BU extracts had a low cytotoxicity. CONCLUSION: Altogether, our study indicates that BQZ decoction exerts anti-AS effects via its anti-inflammatory activity and may have a low side-effect. Further analysis of the extracts of BQZ decoction could lead to a discovery of some novel drugs adding to therapeutic strategy for AS patients.

Traditional Chinese medicine versus western medicine as used in China in the management of rheumatoid arthritis: a randomized, single-blind, 24-week study.

This study is designed to compare the efficacy and safety of traditional Chinese medicine (TCM) with western medicine (WM) in the management of rheumatoid arthritis (RA). This is a 24-week, randomized, multicenter, single-blind study comparing TCM with WM (as used in China) carried out between June 2002 and December 2004 in nine research centers in China, involving 489 patients. Patients were randomized to receive TCM (n = 247), MTX and SSZ (n = 242). MTX was started at a dose of 5 mg to a final dose of 7.5-15 mg weekly. The maintenance dose was 2.5-7.5 mg weekly. The starting dose of SSZ was 0.25 g bid, increasing by 0.25 g a day once a week to a final dose of 0.5-1 g qid. The maintenance dose was 0.5 g tid to qid. Primary end point was the proportion of patients with response according to the American College of Rheumatology 20 % improvement criteria (ACR20) at weeks 24. At 24 weeks, ACR20 responses were 53.0 % in TCM group and 66.5 % in WM group, (P < 0.001) at 24 weeks. ACR 50 responses were 31.6 % of TCM group and 42.6 % in WM group, (P = 0.01). ACR70 responses were 12.6 % in TCM group and 17.4 % in WM group, (P = 0.14). Side effects were observed more frequently in WM group. In this study, ACR20, ACR50 responses at 24 weeks were significantly better in the WM treated group, by intention to treat (ITT) and per protocol analysis. The ACR 70 response showed no significant difference between the two groups. TCM, while effective in treating RA, appears to be less effective than WM in controlling symptoms, but TCM is associated with fewer side effects.

The extraarticular symptoms influence ACR response in the treatment of rheumatoid arthritis with biomedicine: a single-blind, randomized, controlled, multicenter trial in 194 patients.

OBJECTIVE: The extraarticular symptoms are important in the pattern differentiation of traditional Chinese medicine (TCM), and the present study is designed in an attempt to find the associations between the extraarticular symptoms and American College of Rheumatology (ACR) Response in 194 cases of rheumatoid arthritis (RA) treated with biomedicine. METHODS: The data were obtained from a randomized clinical trial. One hundred ninety-four RA patients were treated with the biomedical therapy (diclofenec, methotrexate and sulfasalazine). ACR20 response in 24 weeks was used for the efficacy evaluation. Eighteen symptoms (including 13 extraarticular symptoms) that TCM practitioners focus on were collected for exploration on the association between the symptoms and the efficacy of the biomedical therapy with association rules method. RESULTS: After 24 weeks, a total of 135 patients receiving biomedicine had achieved an ACR20 response. The association rules analysis on each symptom showed that soreness in the waist was more associated with ACR20 response, but with lower support (selected sample size based, 20.10% and 14.95% respectively); cold intolerance and cold joint were found to be associated with ACR20 response with higher support (48.97% and 53.61% respectively), and the confidences (predicted effective rate) were 73.08% and 71.23% respectively. The associations between combination of symptoms (among them, there was at least one extraarticular symptom) and ACR20 response indicated that cold intolerance or cold joint with higher confidence and support were the most important extraarticular symptoms. CONCLUSION: The RA patients with "cold intolerance" and "cold joints", which are the extraarticular symptoms that TCM practitioners focus on, may show higher ACR20 response when treated with the biomedical approach.

[Principal factor analysis of symptoms of rheumatoid arthritis and their correlations with efficacy of traditional Chinese medicine and Western medicine].

OBJECTIVE: To explore the correlations between symptom-based principal factors of rheumatoid arthritis (RA) and the effect of traditional Chinese medicine or Western medicine on RA after factor analysis of RA symptoms. METHODS: Four hundred and thirteen RA patients from 9 clinical centers were included in the clinical trial. They were randomly divided into Western medicine (WM) treated group with 204 cases and traditional Chinese medicine (CM) treated group with 209 cases. A complete physical examination and 18 common clinical manifestations were recorded before the randomization and after the treatment. The WM therapy included voltaren extended action tablet, methotrexate and sulfasalazine. The CM therapy included glucosidorum Tripterygll totorum tablet and Yishen Juanbi Tablet. The American College of Rheumatology 20 (ACR20) was used for efficacy evaluation. All data were analyzed on SAS 8.2 statistical package. Eighteen symptoms in the RA patients were analyzed by factor analysis and the relationships between the factors and effects were analyzed with Chi-Square test. RESULTS: Four principal factors were obtained from the analysis results of the 18 symptoms. The factors could represent the symptoms related to joints, cold-syndrome, deficiency syndrome and heat-syndrome in traditional Chinese medicine (TCM), respectively. The effect of WM therapy was better than CM therapy. After 12 weeks of treatment, the effect of CM on patients without deficiency-syndrome was better than the patients with deficiency-syndrome. After 24 weeks of treatment, WM therapy showed better effect on patients with cold syndrome than patients without cold syndrome. CONCLUSION: The results based on the factor analysis of RA symptoms are similar to the results of syndrome differentiation of TCM, and the factor-related different categories of symptoms are associated with the curative effect, thus further research on the symptoms is necessary.

[Exploration on relationship between platelet count and efficacy of Chinese medicine and Western medicine in treating rheumatoid arthritis patients].

OBJECTIVE: To explore the correlationship between platelet count and efficacy of traditional Chinese medicine (TCM) or Western medicine (WM) in treating rheumatoid arthritis (RA) patients. METHODS: A total of 356 patients with confirmed diagnosis of active RA from 9 clinical centers were randomly assigned to the TCM group (184 cases) and the WM group (172 cases). The TCM group was treated with basic therapy (administration of glucosidorum tripterygll totorum and Yishen Juanbi Pill) and TCM syndrome differentiation dependent treatment, while the WM group was treated with non-steroidal anti-inflammatory drugs and slow-acting anti-rheumatic drugs. The therapeutic efficacy was assessed with ACR20, the joint damage degree of both hands was evaluated by X-ray. RESULTS: The platelet count was positively correlated to the X- ray grading of joint damage, namely, patients with a more severe joint damage often presented a higher platelet count. After treatment, in patients with joint damage of X-ray grade II or III and effectively treated with TCM, also in patients with joint damage of grade III and effectively treated with WM, the platelet count was lower than that in those treated ineffectively. CONCLUSION: Platelet count is closely correlated to the efficacy of drug therapy, therefore, it may be taken as an important index for judging the curative effect of therapeutic approach in treating RA patients.

[Predictive role of diagnostic information in treatment efficacy of rheumatoid arthritis based on neural network model analysis].

OBJECTIVE: To analyze the indications of the therapies for rheumatoid arthritis (RA) with neural network model analysis. METHODS: Three hundred and ninety-seven patients were included in the clinical trial from 9 clinical centers. They were randomly divided into Western medicine (WM) treated group, 194 cases; and traditional Chinese herbal medicine (CM) treated group, 203 cases. A complete physical examination and 18 common clinical manifestations were prepared before the randomization and after the treatment. The WM therapy included voltaren extended action tablet, methotrexate and sulfasalazine. The CM therapy included Glucosidorum Tripterygii Totorum Tablet and syndrome differentiation treatment. The American College of Rheumatology 20 (ACR20) was taken as efficacy evaluation. All data were analyzed on SAS 8.2 statistical package. The relationships between each variable and efficacy were analyzed, and the variables with P<0.2 were included for the data mining analysis with neural network model. All data were classified into training set (75%) and verification set (25%) for further verification on the data-mining model. RESULTS: Eighteen variables in CM and 24 variables in WM were included in the data-mining model. In CM, morning stiffness, swollen joint number, peripheral immunoglobulin M (IgM) level, tenderness joint number, tenderness, rheumatoid factor (RF), C-reactive protein (CRP) and joint pain were positively related to the efficacy, and disease duration and more urination at night negatively related to the efficacy. In WM, erythrocyte sedimentation rate (ESR), weak waist, white fur in tongue, joint pain, joint stiffness and swollen joint were positively related to the efficacy, and yellow fur in tongue, red tongue, white blood negatively related to the efficacy. In the analysis with the neural network model in the patients of verification set, the predictive response rates of 20% patients would be 100% and 90% in the treatment with CM and WM, respectively. CONCLUSION: Neural network model analysis, based on the full clinical trial data with collection of both traditional Chinese medicine and modern medicine diagnostic information, shows a good predictive role for the information in the efficacy in rheumatoid arthritis.

[Comparative study on characteristics of Chinese and Western medicine for treatment of rheumatoid arthritis regarding cartilage erosion related blood biochemical and immunological factors].

OBJECTIVE: To analyse the cartilage erosion related blood biochemical and immune factors in rheumatoid arthritis (RA) and to explore the special influences of Chinese medicine (CM) and Western medicine (WM) on these factors. METHODS: Three hundred and ninety-seven patients, with confirmed diagnosis of active RA, were randomly assigned to the WM group (194 patients) and the CM group (203 patients). The WM applied covered non-steroid anti-inflammatory agents and slow acting medicine; and the CM given included basic remedy and syndrome differentiating medication. Related blood biochemical and immunological indexes were determined before and after treatment to screen out the cartilage erosion related factors and to compare the influence of CM and WM on them. RESULTS: Patients' peripheral red blood cell (RBC) and platelet (PLT) count were changed closely along with their degree of cartilage erosion. RBC count increased in the CM group and PLT count lowered in the WM group after treatment, all showed statistical significance; comparison of the two indexes between the two groups showed that statistical difference presented in RBC but not in PLT count. CONCLUSION: Both WM and CM can ameliorate the cartilage erosive factor in RA, but they are acting in different ways.

[Correlations between diagnostic information and therapeutic efficacy in rheumatoid arthritis analyzed with decision tree model].

OBJECTIVE: To explore the correlations between diagnostic information and therapeutic efficacy in rheumatoid arthritis (RA) with decision tree model analysis. METHODS: Three hundred and ninety seven patients came from 9 clinical centers were randomly divided into the Western medicine (WM) group (n=194) treated with non-steroidal anti-inflammatory drugs and slow-acting antirheumatic drug and the Chinese medicine (CM) group (n=203) with basic therapy and syndrome-differentiation dependant TCM treatment. TCM and WM diagnostic information were collected. The ACR 20 was used for efficacy evaluation and the information of patients before treatment was analyzed by SAS 8.2 statistical package. Through single-factor exploratory analysis, odds ratio of efficacy and variable was calculated taken P < 0.2 as the including criteria for data mining analysis with decision tree model. All data were classified into the training set (75%) and verifying set (25%) with efficacy as the variable for layering to make further verification of the data-mining analysis. RESULTS: Twenty variables were included in the CM group and 26 in the WM group in the data-mining model. In the former, 9 variables were positively correlated to the efficacy, including degree of arthralgia, tenderness and morning stiffness, number of swollen joint, and joint with tenderness, levels of IgM, rheumatoid factor (RF), C-reactive protein (CRP), and total assessment from doctor; and disease duration and degree of nocturnal polyuria were negatively correlated to that. While in the latter, 8 were positively correlated to the efficacy, including erythrocyte sedimentation rate (ESR), sour and weak waist and knees, white fur in tongue, joint ache and stiffness, swollen joint, and total assessment from doctor and patient, and red tongue with yellow fur and leucocyte count negatively correlated to it. Data mining with decision tree analysis revealed that different combinations of morning stiffness, slight red tongue, joint tenderness and nocturnal polyuria in the CM group, and those of white fur in tongue, CRP level, leucocyte count and morning stiffness in the WM group showed different efficacy, which were also verified in the randomly chosen verifying set. CONCLUSION: To analyze the correlations between diagnostic information and therapeutic efficacy with decision tree analysis is conformed to the theory of TCM in applying treatment according to syndrome differentiation individually, thus it would contribute to elevate the accuracy of therapy.

[Correlations of clinical symptoms and treatment efficacy in patients with rheumatoid arthritis treated with Chinese herbal drugs or Western medicine].

OBJECTIVE: To evaluate the correlations between clinical symptoms and treatment efficacy in patients with rheumatoid arthritis (RA). METHODS: Four hundred and thirteen patients were included in the clinical trial from 9 clinical centers. They were randomly divided into Western medicine-treated group with 204 cases and Chinese herbal drug-treated group with 209 cases. Eighteen clinical symptoms were evaluated before and after treatment. The Western medicine therapy included voltaren extended release tablets, methotrexate and sulfasalazine. The Chinese herbal drug therapy included glucosidorum Tripterygii totorum tablets and Yishen Juanbi Tablets combined with treatment based on syndrome differentiation. The American College of Rheumatology 20 (ACR20) was used as efficacy evaluation criteria. RESULTS: In the Chinese herbal drug-treated group, clinical symptoms such as arthralgia and tenderness of joints were positively correlated with the efficacy after 12-week treatment, while frequent urination at night was negatively correlated. In the same group, tenderness of joints and fever were positively correlated with the efficacy after 24-week treatment, while deep-colored and turbid urine was negatively correlated. In the Western medicine-treated group, tenderness of joints and thirst were positively correlated with the efficacy after 12-week treatment, while vertigo was negatively correlated. And in the same group, tenderness of joints was positively correlated with the efficacy after 24-week treatment, while heaviness of limbs was negatively correlated to the efficacy. The statistical results showed that the treatment efficacy was improved when the correlated symptoms were included in the indications. CONCLUSION: The treatment efficacy of RA is correlated with some symptoms, so further studies should proceed on these correlations in order to achieve better treatment outcome.

[Analysis on symptomatic factors of rheumatoid arthritis and its correlation with therapeutic efficacy].

OBJECTIVE: To analyze the symptomatic factors of rheumatoid arthritis (RA), and to explore the correlations between these factors and the efficacy of TCM herbal and western medicinal therapies. METHODS: Four hundred and thirteen patients with confirmed diagnosis as active RA came from 9 clinical centers were randomly divided into the Western medicine (WM) treated group (n=204) and the traditional herbal medicine (CM) treated group (n=209). The scheme of WM therapy included administration of voltaren extended action tablet, methotrexate and sulfasalazine. That of CM therapy included basic treatment and medication by syndrome differentiation. Eighteen items of often seen symptoms of the patients were collected before and after treatment. The therapeutic effect was evaluated by the American College of Rheumatology 20% improvement (ACR 20) and all data were analyzed using SAS 8.2 statistical software package. The category of symptoms was analyzed by factor analysis. The correlation of changes of various common factors with the therapeutic efficacy were analyzed by one-way ANOVA test. RESULTS: Four common factors were obtained from the 18 items of symptoms, which could better reflect respectively the local status of arthritis, and symptoms of Cold-syndrome, Asthenia-syndrome and Heat-syndrome in traditional Chinese medicine (TCM). Both CM and WM therapies showed consistent effect on the common factors that reflects the state of RA, but CM therapy showed superior effect on the common factors to improve Asthenia-syndrome to that of WM therapy. CONCLUSION: Factor analysis could be used to categorize and study the important factor symptoms in the syndrome differentiation of TCM, and the results of factor analysis were in accord with the category of TCM syndrome differentiation. The exploration on the correlation of common factor and therapeutic efficacy could better exhibit the characteristics of TCM efficacy.