[Expert consensus on clinical application of Wangbi Tablets in treating rheumatoid arthritis and knee osteoarthritis].

Wangbi Tablets are widely used in the treatment of rheumatoid arthritis, knee osteoarthritis and other diseases at pre-sent. Long-term clinical application and research have shown that this drug has a good effect in reducing the pain of related diseases and improving symptoms. Due to the lack of guidance in the instructions and currently no relevant norms to guide the clinical application of Wangbi Tablets, in order to further improve clinicians' understanding of the drug and fully tap the clinical advantages of the drug, the Professional Committee of Orthopedics and Traumatology Drug Research of China Association of Chinese Medicine organized experts in the fields of rheumatism, orthopedics, pharmacy and methodology in Chinese and western medicine to develop expert consensus on Chinese patent medicines in accordance with the relevant requirements of the consensus methodology. Based on full consideration of clinical research evidence and expert experience, the clinical issues were summarized in the consensus, and for those clinical problems supported by evidences, the internationally recognized recommendation evaluation and formulation method GRADE was used to evaluate the evidence and form recommendations; for those clinical issues not supported by evidences, a consensus was reached through the nominal group method to form consensus recommendations. The consensus adopted a concise and clear format to form re-commendations or reach consensus suggestions on the medication regimen, medication characteristics, intervention timing, usage and dosage, course of use and safety issues for the treatment of rheumatoid arthritis and knee osteoarthritis with Wangbi Tablets. It is suggested that its application will better improve the efficacy of Wangbi Tablets in the treatment of rheumatoid arthritis and knee osteoarthritis, at the same time provide a reference for clinicians to use Wangbi Tablets in a standardized, reasonable and safe manner.

Piceatannol inhibits proliferation and induces apoptosis of bladder cancer cells through regulation of the PTEN/AKT signal pathway.

This study was aimed to investigate the effect of piceatannol (PIC) on the proliferation and apoptosis of bladder cancer cell line EJ, and the underlying mechanism.   Bladder cancer cell line EJ was incubated with different concentrations of PIC, and CCK-8 method was used to determine the effect of the treatment on cell proliferation. The effect of PIC on cell cycle, apoptosis and the expressions of related signal pathway proteins were determined using Western blotting. Flow cytometry showed that PIC inhibited the proliferation of EJ cells in a concentration- and time-dependent fashion. Moreover, EJ cells were significantly blocked in G0/G1 phase, when compared with the blank control group (p < 0.05). In addition, PIC enhanced apoptosis of EJ cells in a concentration-dependent manner (p < 0.05). Results from western blotting showed that, compared with the control group, PIC upregulated the protein expression of PTEN, but downregulated Akt protein phosphorylation, relative to control cells. PIC significantly inhibits the proliferation of EJ cells and enhances their apoptosis through a mechanism related to the activation of PTEN/Akt signaling pathway.

[Effect of Bushen Qiangdu Recipe on Histomorphology and Wnt Pathway of DBA/1 Mice].

Objective To observe the effect of Bushen Qiangdu Recipe (BQR) on the entheses ossification histomorphology of articular ligament of DBA/1 mice with spontaneous ankylosing spondylitis (AS) , and to study its mechanism for prevention and treatment of AS. Methods Thirty 12-week old male DBA/1 mice were randomly divided into the model group, the positive drug group, low, medium, high dose BQR groups, 6 in each group. Another 6 C57BLE mice of the same age were recruited as a blank control group. BQR containing 11. 25, 22. 50, 45.00 g/kg crude drugs was respectively adminis- tered to mice in low, medium, high dose BQR groups by gastrogavage, 0. 2 mL for each mouse, once per day. Celecoxib Capsule (0. 2 mL/0. 8 mg for each mouse, once per day) was administered to mice in the positive drug group by gastrogavage. Equal volume of normal saline was administered to mice in the model group and the blank control group by gastrogavage. All mice were fed and intragastically adminis- tered for 12 successive weeks. Body weight, diet, stools, and hair were routinely observed. Signs of ar- thritis were evaluated once per two weeks. Mice were sacrifice, and then general observation of achilles tendon was performed. The achilles tendon tissue was HE stained. Protein expressions of alkaline phos- phatase (ALP) , bone gamma-carboxyglutamic-acid-containing proteins (BGP) , Dickkopfl (DKK1) , and Wnt5a in the achilles tendon were detected using immunohistochemical method. Results Compared with the blank control group, the scoring of arthritis obviously increased in the model group (P <0. 05). But the scoring of arthritis was obviously lower in the 3 BQR groups and the positive drug group than in the model group (P <0. 05). Histopathological results of achilles tendon tissue showed that no infiltration of inflammatory cells or fibroblasts occurred in the normal group. Their histomorphological structures were normal. Cartilage formation and bone formation at various degrees occurred in the model group. Filtration of fibroblast-like cells occurred in inflammatory cells and attachment points. Scattered lymphocyte infiltra- tion was often seen in the achilles tendon tissue of each medicated group. Cartilage formation and bone formation were rarely seen. Compared with the blank control group, the scoring of arthritis increased in the model group (P <0. 05). Compared with the model group, the scoring of arthritis was decreased in the 3 BQR groups and the positive drug group (P <0. 05). Compared with the blank control group, protein expression of DKK1 decreased and protein expression of Wnt5a increased in the model group (P <0. 05). Compared with the model group, protein expression of DKK1 increased and protein expression of Wnt5a decreased in middle and high dose BQR groups (P <0. 05). Conclusion BQR could delay the occur- rence and development of arthritis and ossification in DBA/1 mice of spontaneous AS model possibly by inhibiting classical Wnt pathway.

[Efficacy and Safety Evaluation of Bushen Shuji Granule in Treating Ankylosing Spondylitis Patients: a Clinical Study].

OBJECTIVE: To evaluate the short-term efficacy and safety of Bushen Shuji Granule (BSG) in treating ankylosing spondylitis (AS) patients. METHODS: A prospective randomized controlled clinical trial was carried out in 62 active stage AS patients with Shen deficiency Du-channel cold syndrome (SDDCS), who were randomly assigned to the BSG group (treated with BSG) and the control group (treated with Celecoxib Capsule). Twelve weeks consisted of one therapeutic course. Therapeutic effects were evaluated by ASAS20 and ASAS40 (set by Assessments in Ankylosing Spondylitis working group) , BASDA150, Chinese medical (CM) syndrome efficacy evaluation standards. BASDAI, the Bath Ankylosing Spondylitis Functional Index (BASFI), the Bath AS Metrology Index (BASMI), scores for spine pain, scores for pain at night, patient global assessment (PGA) , erythrocyte sedimentation rate (ESR) , and C reactive protein (CRP) were observed before and after treatment. RESULTS: After three-month treatment by BSG, ASAS20 standard rate was 63. 33% (19/30 cases) in the BSG group and 66.67% (20/30 cases) in the control group with no significant difference between the two groups (χ2 = 0.073, P > 0.05). The efficacy for CM syndromes was 70.00% (21/30 cases) in the BSG group, higher than that in the control group [40.00% (12/30 cases), χ2 = 5.455, P < 0.05]. Scores for CM syndromes, BASDAI, night pain index, spinal pain index, PGA, CRP were improved in the BSG group (P < 0.05, P < 0.01). The incidence of adverse events in the BSG group was lower than that of the control group. CONCLUSION: BSG based on Shen supplementing, Du-channel strengthening, blood activating, and channels dredging method had good short-term clinical efficacy and safety in treating AS.

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.

[Manifestations of rheumatoid arthritis patients of cold syndrome and heat syndrome using wrist ultrasound].

OBJECTIVE: To explore distinctive manifestations of rheumatoid arthritis (RA) patients of cold syndrome and heat syndrome using wrist joints ultrasound. METHOD: s Totally 65 RA patients were syndrome typed as cold syndrome (29 cases, cold-damp blockage syndrome) and heat syndrome (36 cases, damp-heat obstruction syndrome). Grey-scale synovitis, power doppler (PD) signals, tenosynovitis, and bone erosion were observed using wrist ultrasound. Distinctive manifestations of cold syndrome and heat syndrome were analyzed using wrist ultrasound. RESULTS: In RA patients of cold syndrome, the positive rate of synovitis, PD, tenosynovitis, and bone erosion was 51.72%, 20.68%, 51.72%, and 37.93%, respectively, while they were 97.22%, 91.67%, 75.0%, and 63.89%, respectively in RA patients of heat syndrome. Compared with patients of cold syndrome, the positive rate of synovitis, PD, and bone erosion increased in patients of heat syndrome (P < 0.01, P < 0.01, P < 0.05). There was no statistical difference in the positive rate of tenosynovitis between the two groups (P > 0.05). Compared with the cold syndrome group, there was statistical difference in the constituent ratio of synovitis, PD, and bone erosion in the heat syndrome group (P < 0.01, P < 0.01, P < 0.05), but with no statistical difference in the constituent ratio of tenosynovitis (P > 0.05). Results of the ROC curve showed that the sensitivity was 86.1% and the specificity was 62.1% in judging heat syndrome, when the total score of synovitis in two wrists was more than 1.5; the sensitivity was 80.0% and the specificity was 93.1% in judging heat syndrome, when the total score of PD in two wrists was more than 1.5. CONCLUSIONS: Positive rates of synovitis, PD, and bone erosion were significantly higher in RA patients of heat syndrome than those of cold syndrome. Especially serious manifestations were more often seen in RA patients of heat syndrome. The total score of synovitis or PD in the two wrist joints higher than 1.5 was characteristic manifestations of heat syndrome using wrist ultrasound.

[The re-evaluation of 140 patients diagnosed as ankylosing spondylitis and nonradiographic axial spondyloarthritis].

OBJECTIVE: To re-evaluate the diagnoses of ankylosing spondylitis (AS) and nonradiographic axial spondyloarthritis (nr-axSpA) and analyze the incidence and reason of misdiagnosis. METHODS: Patients who were previously diagnosed as AS and nr-axSpA before referrals to Peking Union Medical College Hospital (PUMCH) were re-evaluated by three rheumatologists of PUMCH according to the modified New York criteria for AS and Assessment of SpondyloArthritis international Society (ASAS) axial SpA classification criteria for nr-axSpA. RESULTS: Totally 87 prior AS patients and 53 prior nr-axSpA patients were enrolled in this study. After re-evaluation, 57 patients were still diagnosed as AS and 16 patients were still diagnosed as nr-axSpA. The misdiagnosis incidences were 34.48% and 69.81%, respectively. The misdiagnosis incidence of nr-axSpA was higher than that of AS (P < 0.01). CONCLUSIONS: The misdiagnosis of AS were mainly due to the misjudgment of sacroiliac joints by CT. The misdiagnosis of nr-axSpA were mainly due to the misjudgment of sacroiliac joints by magnetic resonance imaging. Moreover, the misuse of ASAS axial SpA classification criteria contributed to the misdiagnosis also.

[Treatment of ankylosing spondylitis by modified bushen zhuanggu recipe: a clinical observation].

OBJECTIVE: To observe the clinical effect and safety of modified Bushen Zhuanggu Recipe (BZR) in treating ankylosing spondylitis (AS). METHODS: Recruited were 96 AS outpatients of Shen deficiency induced cold-dampness syndrome (SDCDS) or Shen deficiency dampness-heat syndrome (SDDHS) at clinics of China-Japan Friendship Hospital from May 2010 to May 2011. They were randomly assigned to the traditional Chinese medicine (TCM) treatment group and the Western medicine (WM) treatment group in the ratio of 1:1. Those in the TCM treatment group were syndrome typed as the SDCDS group (group A, 22 cases, treated by Bushen Zhuanggu Quhan Decoction + WM placebos) and the SDDHS group (group B, 26 cases, treated by Bushen Zhuanggu Qinghua Decoction +WM placebos). Those in the WM treatment group were syndrome typed as SDCDS group (group C, 27 cases, treated by SASP + TCM placebos) and the SDDHS group (group D, 21 cases, treated by SASP +TCM placebos). Totally 12 weeks consisted of one therapeutic course. BAS-G, BASFI, BASDAI, spine pain, pain at night, TCM symptom score, distance between occipital and wall, distance between finger and ground, thoracic activity, spine activity, Schober test, ESR, CRP were observed as the observing indices; ASAS20, ASAS50, ASAS70, BASDAI50, and criteria of TCM were explored for clinical evaluation and safety evaluation. RESULTS: In comparison with the same group before treatment,BAS-G, BASFI, BASDAI, spine pain, pain at night, TCM syndrome score,distance between finger and ground, Schober test, ESR, and CRP were improved after treatment (P < 0.01, P < 0.05). In group A and C, thoracic activity and spine activity were getting better (P < 0.01, P < 0.05). In group B distance between occipital and wall and spine activity were getting better (P < 0.01, P < 0.05). In comparison with group C, BAS-G, BASFI, BASDAI, spine pain, distance between finger and ground,thoracic activity,spine activity, Schober test, ESR, CRP were getting better in group A after treatment (P < 0.01, P < 0.05). In comparison with group D, BASFI, BASDAI, spine pain, pain at night,distance between finger and ground, distance between occipital and wall, spine activity, Schober test, and ESR were getting better in group B after treatment (P < 0.01, P < 0.05). The total effective rate, ASAS20, ASAS50, ASAS70, and BASDAI50 were higher in the TCM treatment group than in the WM treatment group (P < 0.05). CONCLUSION: Modified BZR was more effective than SASP method in relieving clinical symptoms and signs, TCM syndrome scores, and inflammatory activity indicators of AS patients.

[Treating rheumatoid arthritis patients of Shen deficiency and cold invading syndrome by bushen quhan zhiwang decoction combined methotrexate: an evaluation of clinical efficacy and safety].

OBJECTIVE: To evaluate the clinical efficacy and safety of bushen quhan zhiwang decoction (BQZD) combined methotrexate (MTX) in treating rheumatoid arthritis (RA). METHODS: A prospective, randomized controlled study was carried out. RA patients of Shen deficiency and cold invading syndrome in the treatment group (120 cases) were treated with BQZD and MTX (10 mg/week), while those in the control group (120 cases) were treated with MTX (10 mg/week) alone. The therapeutic course for all was 24 weeks. The efficacy and safety indices were evaluated at the baseline and 24 weeks after treatment, including clinical signs and symptoms, condition assessment, Health Assessment Questionnaire (HAQ), disease activity index 28 (DAS28), laboratory parameters of erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP), safety indicators, and Chinese medical syndrome integrals. RESULTS: The total effective rate was 80. 0% in the treatment group, better than that of the control group (66.7%), showing statistical difference (P <0.01). In the two groups significant improvement of clinical signs and symptoms, ESR, CRP, visual analogue scale (VAS) by both physicians and patients, HAQ, DAS28, and Chinese medical syndrome integrals after treatment were shown (P <0.01). Better effects were obtained in the treatment group in lessening tender joint numbers and swollen joint numbers, VAS by both physicians and patients, DAS28, and Chinese medical syndrome integrals (P < 0.05). Besides, adverse reactions occurred less in the treatment group than in the control group (P < 0.05). CONCLUSIONS: BQZD had roles in relieving symptoms, improving joint functions, signs, ESR, and CRP. It was an effective herb for RA patients of Shen deficiency and cold invading syndrome. It could enhance the efficacy and reduce adverse reactions of MTX through synergistic effects with MTX.

[Optimization of formulas of Quban gel by uniform design].

OBJECTIVE: To optimize formulas of Quban gel. METHOD: The U6 (6(2) x 3) uniform design was adopted to optimize gel formulas, with rheological parameters, such as viscosity and yield value in room temperature, viscosity and yield value in average temperature of skin, thixlotropy. RESULT: The optimum proportion of matrix was made of 1.0 g carbomer 940, 5 mL glycerin and pH value 5-6. CONCLUSION: The regression model for gel matrix quality and gel rheological parameters was established to directly reflect the impacting effect of various factors, and provide certain preference basis for the screening of gel matrix formulas. Quban gel prepared by the method was evenly distributed, moderately viscous and highly thixotropic

[Study on acute toxicity test of different processed products of Radix polygalae].

OBJECTIVE: To study the acute toxicity of the water extracts (ERWE) and 60% ethanol extracts (EREE) from different processed products of Radix Polygalae (crude Radix Polygalae, licorice, and honey processed Radix Polygalae), thus providing scientific evidence for toxicity study of Radix Polygalae and its safe clinical application. METHODS: The ERWE and EREE were prepared from different processed products of Radix Polygalae. Their contents of saponins were respectively determined. The poisoning condition and death of the mice administered with ERWE and EREE by gastrogavage were observed within fourteen days. The modified Karber's method was used to calculate LD50 and 95% confidence interval (CI). RESULTS: The EREE of licorice processed Radix Polygalae had the maximum toxicity with highest content of saponins, while the ERWE of honey processed Radix Polygalae had the minimum toxicity with lowest content of saponins. CONCLUSIONS: Different processing methods have effects on the contents of saponins in Radix Polygalae. The experiment showed that the toxicity of Radix Polygalae is in direct proportion to the content of saponins. The higher the saponins contents, the higher the toxicity.

[Effects of Bushen Shuji Granule on IL-6 in the culture fluid sample of fibroblast cells from the synovial liquid of the ankylosing spondylitis patients].

OBJECTIVE: To explore the effects of Bushen Shuji Granule (BSG) on inhibiting the interleukin 6 (IL-6) level in the synovial fluid sample of fibroblast cells from the ankylosing spondylitis (AS) patients. METHODS: Using serum pharmacologic method, the IL-6 level in the culture fluid sample of fibroblast cells was observed by ELISA method with different concentrations of medicated serum containing BSG. The IL-6 level at the mRNA level was detected using reverse transcriptase-polymerase chain reaction (RT-PCR). The vehicle serum and sulfasalazine (SSZ) serum were taken as controls. RESULTS: Results of ELISA showed the IL-6 level in the AS group was more than that in the vehicle serum group with obvious statistical difference. BSG could obviously inhibited the IL-6 level, showing statistical difference when compared with the vehicle serum group. Besides, obvious dose-dependent correlation existed between BSG and its inhibition on fibroblast proliferation. And the IL-6 level at the mRNA level in the AS group was higher than that in the vehicle serum group, showing statistical difference by semi-quantitative analysis. CONCLUSION: BSG could play its clinical role of anti-inflammation and anti-fibrosis through inhibiting the IL-6 level in the culture fluid sample of fibroblast cells.

[Effect of bushen qiangdu recipe on osteoporosis and bone loss of patients with ankylosing spondylitis].

OBJECTIVE: To observe the therapeutic effect of Bushen Qiangdu Recipe (BSQDR) on osteoporosis and bone loss in patients with ankylosing spondylitis (AS). METHODS: Patients with AS were randomly assigned to two groups. The 288 patients in the treatment group received BSQDR (consisting of cibotii rhizoma, antler, prepared rehmannia root, epimedium herb, rhizoma drynariae, teasel root, eucommia bark, pangolin scales, etc., one dose daily, taken in two portions, once in the morning and once in the evening). The 72 patients in the control group received SIDSM and sulfasalazine. The therapeutic course for both was six months. Clinical symptoms, pillow distance from the wall, hand distance from the ground, jaw distance from the handle, chest mobility, Schober test, spinal mobility and other signs of disease activity indices (ESR and CRP) were observed in patients before and after treatment. The bone mineral density (BMD) testing was performed in the lumbar spine, the femur, the forearm, and the heels, etc. Osteocalcin (BGP), calcitonin, parathyroid hormone (PTH), etc. bone metabolic indices were detected. RESULTS: BASFI, BASDAI, the overall assessment, the spinal pain, pillow distance from the wall, hand distance from the ground, jaw distance from the handle, chest mobility, Schober test, spinal mobility, and so on were all improved to some extent when compared with before treatment in the treatment group (P<0.05). The ESR and CRP decreased to various degrees, showing statistical significance when compared with before treatment (P <0.01). BGP increased and PTH decreased, showing statistical difference when compared with before treatment (P<0.05). The BMD in patients' lumbar spine, femoral neck, Ward's triangle, femoral trochanter increased to various degrees. The calcaneal intensity index, blood uric acid (BUA) and SOS values also increased more than before treatment, showing statistical significance (P<0.05). Long-term oral administration of BSQDR was safe, with no obvious adverse reaction. CONCLUSIONS: BSQDR showed significant effect in treatment of AS. It could regulate the bone metabolic level in patients, attenuate the immune inflammatory response, improve the spine and joint activities functions, increase bone formation, reduce bone resorption, thereby, enhancing the BMD, showing significant therapeutic effect on osteoporosis in AS patients.

Firebird and cypher sirolimus-eluting stents and bare metal stents in treatment of very long coronary lesions.

BACKGROUND: As a kind of sirolimus-eluting stent (SES) made in China, Firebird SES is more effective than bare metal stent (BMS) and not inferior to Cypher SES for short coronary lesions in terms of reduction of restenosis and revascularization. However, Firebird SES does not show any benefits in patients with a very long coronary lesion (VLCL). The present study was undertaken to evaluate the safety and efficacy of Firebird SES for VLCL by comparison of Cypher SES and BMS. METHODS: In this prospective, nonrandomized and comparative study, eligible patients with de novo coronary lesion (> or = 30 mm) between January 2005 and June 2006 were allocated into Firebird SES group, Cypher SES group or BMS group. They were subjected to an angiographic follow-up of 6 months and a clinical follow-up of 12 months. The primary endpoints constitute the in-stent and in-segment restenosis rates at 6 months. The secondary endpoint was defined as a major adverse cardiovascular event (MACE) that was a 12-month combined endpoint of all-cause deaths, reinfarction or in-stent thrombosis, and target-lesion revascularization. The 12-month in-stent thrombosis was also evaluated to address the safety of Firebird SES implantation exceptionally. RESULTS: A total of 468 patients were assessed for eligibility. Of 113 patients who were finally included according to the prior inclusion and exclusion criteria, 39 (41 lesions) were treated with Firebird SES, 37 (39 lesions) with Cypher SES, and 37 (37 lesions) with BMS. There were no significant differences in the baseline characteristics between the three groups; but there were longer lesions, more frequent use of overlapping stent in the Firebird SES group and the Cypher SES group. Angiographic follow-up showed that the rates of binary stenosis were similar between the Firebird SES group and the Cypher SES group (in-segment: 14.6% vs 12.8%, relative risk (RR) 1.14, P = 0.81; in-stent: 9.8% vs 10.3%, RR 0.95, P = 0.94), and significantly lower than those in the BMS group (in-segment: vs. 36.1%, RR 0.41 or 0.36, P = 0.04 or 0.03, respectively; in-stent: vs 30.6%, RR 0.32 or 0.34, P = 0.03 or 0.04, respectively). The total MACE rate up to 12 months was also similar in both SES groups (7.7% vs 5.4%, P = 1.000), and significantly lower than that in the BMS group (27.0%, P = 0.034 or 0.024, respectively). The in-stent thrombosis rate in the follow-up period was 2.6% in the Firebird SES group, not higher in the Cypher SES and BMS groups (2.7% and 2.7%, respectively, P = 1.000). CONCLUSIONS: In the treatment of VLCL, Firebird SES would be safer and more effective than BMS. Firebird SES may be not inferior to Cypher SES in terms of restenosis and MACE.

[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.

[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.

[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.

Long-term outcomes of device closure of very large secundum atrial septal defects: a comparison of transcatheter vs intraoperative approaches.

BACKGROUND: Transcatheter device closure (TCDC) and intraoperative device closure (IODC) have emerged as minimally invasive methods in the treatment of secundum atrial septal defects (ASDs), but the long-term safety and efficacy remains uncertain for the large ASDs. HYPOTHESIS: TCDC may be as safe and efficacious as IODC for closure of large ASDs in terms of long-term clinical outcomes. METHODS: Ninety-two patients who had ASDs with a defect diameter of ≥30 mm were included in this study. The patients received either TCDC (n = 42) or IODC (n = 50). An Amplatzer septal occluder was used in both groups. The dumbbell-like device deploying technique was introduced in the TCDC group. Physical exams, electrocardiography, and echocardiography were performed preprocedurally and postprocedurally at the index follow-up visits. RESULTS: The procedural immediate success rate was 97.6% for TCDC and 98.0% for IODC (P = 0.328). The rate of periprocedural complications was 9.5% for TCDC and 28.0% for IODC (P = 0.026). The mean hospital stay was 7.5 ± 2.7 days for TCDC and 11.9 ± 3.8 days for IODC (P < 0.001). For the mean follow-up of 5.4 ± 0.5 years, there were no cardiac deaths and late complications in either group. No significant residual shunts were documented, and symptoms were significantly improved in both groups. Right and left ventricular diameter, pulmonary artery diameter, and pulmonary systolic pressure were all significantly decreased in both groups (P < 0.05). CONCLUSIONS: The present study confirmed the long-term safety and efficacy for closing a large ASD either by TCDC or IODC. Either of them could become an effective alternative to the surgery for large ASD closure. The authors have no funding, financial relationships, or conflicts of interest to disclose.

[Effects of Bushen qiangdu decoction on MMP-9 and TIMP-1 produced by peripheral blood mononuclear cells in patients with ankylosing spondylitis].

OBJECTIVE: In order to investigate the roles of metalloproteinase in inflammatory bone destruction in ankylosing spondylitis (AS), and analyze the mechanism of preventing inflammatory bone destruction of Bushen Qiangdu decoction (BSQDD) in AS cases. Comparisons were made on the expressions of matrix metalloproteinase 9 (MMP-9) and tissue inhibitor of metalloproteinase 1 (TIMP-1) by peripheral blood mononuclear cells (PBMC) between AS patients and healthy controls. The effect of BSQDD was investigated on the expression and of MMP-9 and TIMP-1 produced by PBMC in AS patients. METHODS: From March 2005 to March 2006, 30 active AS cases of Kidney-asthenia, Du-cold and blood-stasis syndrome were selected as patients group in the China-Japan Friendship Hospital. There are 27 male patients and 3 female patients. The age range is from 16 to 45, averaging (30.8 +/- 8.8) years. Disease duration is from 0.5 to 10 years. Cases received three-month BSQDD treatment were considered as the treatment group. Twenty healthy persons were included in the control group. Serum and PBMC were separated. The PBMC were stimulated by PHA and PMA, and the supernatant was collected. The mRNA expression of MMP-9 and TIMP-1 in PBMC was analyzed by RT-PCR. The content of MMP-9 and TIMP-1 in serum and culture supernatant of PBMC were detected by ELISA. RESULTS: Compared with health control group, the serum concentration of MMP-9 and TIMP-1 in patients group before treatment increased (P<0.01, P<0.05), but the level of MMP-9 and TIMP-1 in the serum of patients after treatment decreased compared with pre-treatment cases (P<0.05). Furthermore,compared with health control group, PBMC of patients group before treatment expressed higher levels of MMP-9 and TIMP-1 both on transcript level and at protein level (P<0.01, P<0.05), and the expression levels of MMP-9 and TIMP-1 in PBMC in patients after treatment both on transcript level and at protein level was down-regulated compared with pre-treatment (P<0.01, P<0.05). CONCLUSION: PBMC of AS patients had a higher potential capacity for MMP-9 and TIMP-1. BSQDD possibly prevented inflammatory bone destruction of AS through inhibiting production of MMP-9 and TIMP-1 produced by PBMC.