Genetic Polymorphism of NQO1 Influences Susceptibility to Coronary Heart Disease in a Chinese Population: A Cross-Sectional Study and Meta-Anaylsis.

Objective: The present study is to explore the association between NQO1 gene polymorphism and coronary heart disease (CHD) risk. Methods: This research were selected 80 CHD patients as the observation group and 130 healthy people who participated in normal physical examination during the same period as the control group. NQO1 gene polymorphism was detected by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) method. In addition, we conducted a meta-analysis to summarize the results of three relevant previously published adult population studies on the association between NQO1 gene polymorphism and coronary heart disease (CHD) risk. Results: There were three genotypes (CC, CT, and TT) for NQO1 C609T polymorphism. The significant associations were found in TT genotype and T allele (all p<0.05). Specifically, People with the TT genotype have 2.06 times CHD risk as those with the CC genotype. And People with the T allele have 1.62 times CHD risk as those with the C allele. No significant association was found by any genetic models in the meta-analysis (all p >0.05). Conclusion: NQO1 gene polymorphism increased the CHD risk in a Chinese population. Combined with individual gene polymorphism, the accuracy of risk assessment for CHD can be improved and individualized health education can be provided for CHD patients by nurses.

Osteogenic differentiation characteristics of hip joint capsule fibroblasts obtained from patients with ankylosing spondylitis.

BACKGROUND: Autoimmune disease are fairly common and one that has an excessive degree of disability is Ankylosing spondylitis (AS). As the main cells in connective tissues, fibroblasts may play important roles in AS ossification. The conducted research aims to establish the osteogenic disparity characteristics of fibroblasts cultured in vitro, obtained via AS patients hip joint capsule, as well as investigating the pathological osteogenic molecular workings of AS. METHODS: AS patients hip joint capsules were acquired and fracture patients as the control with the finite fibroblast line were established by using tissue culture method. AS fibroblast proliferation, cycle and apoptosis, expression of osteogenic marker genes, osteogenic phenotypes, and the activation degree of the bone morphogenetic protein (BMP)/Smads signalling pathway were detected by flow cytometry, western blotting and real-time fluorescent quantitative polymerase chain reaction. RESULTS: Proliferative activity in AS fibroblasts were abnormally high, and the apoptotic rate decreased. Compared with normal fibroblasts, the mRNA expression of osteogenic marker genes, expression of osteogenic phenotypes, protein expression of core-binding factor a1 (Cbfa1), Smad1, Smad4, Smad5, phosphorylated (p) Smad1, and pSmad5 in AS fibroblasts were higher; however, the expression of Smad6 was lower. Moreover, recombinant human bone morphogenetic protein-2(rhBMP-2) stimulated Cbfa1 expression by normal and AS fibroblasts through the BMP/Smads signalling pathway. CONCLUSIONS: The fibroblasts of hip joint capsules in patients with AS cultured in vitro have biologic characteristics of osteogenic differentiation and may be important target cells of AS ossification. The Activated BMP/Smads signalling pathway could potentially be a mechanism relating to fibroblasts differentiating into osteoblasts and an ossification mechanism for AS.

Comparison of combination therapy with methotrexate and sinomenine or leflunomide for active rheumatoid arthritis: A randomized controlled clinical trial.

BACKGROUND: A combination of conventional disease-modifying anti-rheumatic drugs improves the treatment of rheumatoid arthritis but with high side-effects. Methotrexate (MTX) combination therapy that with high therapeutic efficacy and low toxicity is in demand in many countries to replace the use of expensive biological agents. STUDY DESIGN: This study was an open-label, 24-week, parallel randomized controlled trial conducted between November 2015 and December 2017. METHODS: Patients were randomly assigned at a 3:2 ratio to receive MTX combined with sinomenine (SIN) at a dose of 120 mg twice daily, or leflunomide (LEF) at a dose of 20 mg once daily. Efficacy and safety were assessed at weeks 4, 12 and 24. The primary efficacy endpoint was the proportion of patients achieving an American College of Rheumatology (ACR)50 response and a European League Against Rheumatism (EULAR) good response at week 24. RESULTS: A total of 101/120 (84.2%) patients completed 24 weeks of observation. In the intention-to-treat (ITT) analysis, 65.3% of patients treated with MTX + SIN showed improved disease activity as determined by the ACR50 response at week 24 compared to 69.6% of patients treated with MTX + LEF. A similar insignificant pattern was found for the ACR20 and ACR70 responses, as well as the clinical disease activity index, EULAR response, and remission and low disease activity rates between these two treatment groups. The per-protocol analysis showed results consistent with those of the ITT analysis. Notably, significant reductions in gastrointestinal adverse reactions and liver toxicity were found in patients treated with MTX + SIN compared to patients treated with MTX + LEF (p < 0.05). CONCLUSION: Considering the balance of efficacy and toxicity, the current study provides evidence that MTX + SIN combination therapy is probably one of the choices for treating patients with active rheumatoid arthritis in addition to MTX + LEF combination therapy.

The Effectiveness and Safety of Tripterygium wilfordii Hook. F Extracts in Rheumatoid Arthritis: A Systematic Review and Meta-Analysis.

Objective: To conduct a meta-analysis of the effectiveness and safety of Tripterygium wilfordii Hook. F (TwHF) extracts for the treatment of rheumatoid arthritis (RA). Methods: A systematic literature search was conducted in PubMed, EMBASE, Cochrane, Medline, CNKI, SinoMed and WanFang Library till 12 July 2017. All included studies were analyzed with the use of the Review Manager 5.2 software according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) Statement protocol. Results: Fourteen randomized controlled trials (RCTs) were identified. TwHF extracts provided a statistically significant improvement in grip strength (GS), swelling joint count (SJC) and morning stiffness (MS) compared with placebo (P < 0.001). The meta-analysis showed significant differences between TwHF extract-treated group and the DMARDs group in GS, MS, C-reactive protein (CRP), and tender joint count (TJC) (P < 0.05), aside from ESR and SJC (P > 0.05). The pooled results also displayed significant differences between the combination of TwHF extracts with DMARDs and the DMARDs alone group in ESR, CRP, SJC, and TJC (P ≤ 0.05). For the safety analysis, two trials favored TwHF extract-treatment and one trial favored non-TWHF extract-treatment in AEs (P < 0.05). Eleven trials showed no statistically significant differences between TwHF extract-treated group and the DMARDs group (P > 0.05). Conclusions: The findings of this systematic review with meta-analysis indicate that TwHF extracts provides statistically significant and clinically important improvement in RA symptoms and has an acceptable safety profile.

Bushen Qiangji Granule () medicated serum inhibits osteogenic differentiation of fibroblasts in ankylosing spondylitis by inhibiting the BMP/Smads signal pathway in vitro.

OBJECTIVE: To explore the mechanism of Bushen Qiangji Granule (, BSQJ) in restraining the osteogenic differentiation of ankylosing spondylitis (AS) fifibroblasts. METHODS: Hip joint capsules were obtained from AS patients (n=10) receiving total hip replacement and healthy hip joint capsules from patients with hip fracture (n=10) receiving surgery as a control. Finite fifibroblast lines were established from these tissue samples to observe the effect of BSQJ on suppressing osteogenic differentiation of fifibroblasts. The expression of osteogenic marker gene corebinding factor a1 (Cbfa1) and Smad family proteins were examined by Western blot and real-time quantitative polymerase chain reaction (qPCR). RESULTS: The mRNA expression level of Cbfa1 was significantly higher in AS fibroblasts than that in normal fibroblasts and the expression of pSmad1, pSmad5, Smad4 and Cbfa1 in AS fibroblasts was also higher, demonstrating the activation of the BMP/Smads signal pathway in AS fifibroblasts. BSQJ-medicated serum not only restrained the mRNA and protein expression levels of Cbfa1 and inhibited protein expression level of Smad4 but also decreased the expression quantities of pSmad1 and pSmad5. CONCLUSIONS: BSQJ can inhibit osteogenic differentiation of AS fifibroblasts in vitro by suppressing the activation of the BMP/Smads signal pathway. This may be the important molecular mechanism of BSQJ in regulating AS ossifification.

Bushen-Qiangdu-Zhilv decoction inhibits osteogenic differentiation of rat fibroblasts by regulating connexin 43.

Bushen-Qiangdu-Zhilv (BQZ) decoction is a traditional Chinese medicinal compound widely used for treating ankylosing spondylitis (AS). However, the mechanisms underlying effects of BQZ remain largely unknown. Osteoblast differentiation of fibroblasts plays an important role in heterotopic ossification (HO) of AS, and connexin 43 (Cx43) is crucially involved in the osteoblast differentiation of fibroblasts. The aim of the present study was to evaluate the effects of BQZ on the osteogenic differentiation of fibroblasts by regulating Cx43. Rat fibroblasts were treated with freeze-dried powder of BQZ, in the presence or absence of recombinant human bone morphogenetic protein-2 (rhBMP-2). MTS assays were performed to examine the inhibitory effects of BQZ on fibroblast proliferation. Western blot assays were conducted to detect the protein expression of core-binding factor alpha 1 (Cbfα1), Cx43 and phosphorylated Cx43 (pCx43). BQZ appeared to inhibit fibroblast proliferation in a dose-dependent manner. Furthermore, the expression of Cbfα1 and Cx43/pCx43 was significantly suppressed by BQZ, with or without rhBMP-2 stimulation. Therefore, the present results indicate that BQZ may exert an anti-AS effect by suppressing the osteogenic differentiation of fibroblasts via Cx43 regulation.

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.

Role of gut microbiome in ankylosing spondylitis: an analysis of studies in literature.

OBJECTIVE: Gut microbiome is considered to be involved in the pathogenesis of ankylosing spondylitis (AS). We conducted a comprehensive literature review in this area to facilitate future research. METHODS: We searched all literature in the PubMed database from inception to July 2016. Relevant articles were chosen and analyzed by three independent investigators. RESULTS: The composition of gut microbiome in patients with AS has been identified to be different from healthy populations; however, specific profiles of gut microbiome are not yet clearly known. Through the host-bacteria dynamic interactions in general, intestinal dysbiosis impairs the gut mucosal barrier and leads to the disorder of intestinal mucosal immunity, resulting in increased pro-inflammatory cytokines and subsequent chronic inflammatory phenotype of AS. Moreover, colonization with specific AS gut microbiome could induce effective animal models, which will aid studies of pathogenesis of AS. CONCLUSION: This analysis underscores the role of gut microbiome in chronic inflammation of AS and its possible underlying mechanisms. Intestinal dysbiosis is undoubtedly involved in the disease progression of AS, and the discovery of a specific profile of gut microbiome in AS will help reveal new therapeutic targets and diagnosis markers.

Elemene, the essential oil of Curcuma wenyujin, inhibits osteogenic differentiation in ankylosing spondylitis.

OBJECTIVE: To explore the effects of Elemene, the essential oil of Curcuma wenyujin, on Bone morphogenetic protein/drosophila mothers against decapentaplegic proteins (BMP/SMADs) signal pathway in ankylosing spondylitis (AS) fibroblasts. METHODS: Hip joint capsules were obtained from AS patients (n=10) receiving total hip replacement. Healthy hip joint capsules from patients with hip fracture (n=10) receiving surgery were included as a control. Primary fibroblast cell lines were established from these tissue samples. Fibroblasts were incubated with Elemene for 48 hours. The protein expression was detected by Western blot. The mRNA expression was detected by real-time fluorescent quantitative polymerase chain reaction (PCR). RESULTS: The results showed that the expression of proteins including SMAD1, pSMAD1, SMAD4 and Runt-related transcription factor 2 (RUNX2), and mRNA of RUNX2, which were over-expressed in AS fibroblasts were decreased in the AS fibroblasts cultured in medium with Elemene. CONCLUSIONS: Ele could have a hand in anti-osteogenic differentiation of AS fibroblasts by inhibiting the BMP/SMADs signal pathway and subsequently blocking expression of ossification marker genes RUNX2 that initiate the osteogenic differentiation.

Determination of role of thromboxane A2 in rheumatoid arthritis.

INTRODUCTION: To date, the etiology of rheumatoid arthritis (RA) remains largely unknown, and the therapies are still unsatisfactory. The biosynthesis of thromboxane A2 (TxA2) is increased in RA patients, suggesting a role of TxA2 in RA pathology. METHODS: RA patients were divided into two groups, DMARDs and non-DMARDs, according to their use of disease-modifying antirheumatic drugs (DMARDs). Sera from RA patients and healthy controls were extracted and subjected to enzyme immunoassays for measurement of the thromboxane B2 (TxB2) level. The statistical correlations between serum TxB2 levels and disease activity score of 28 joints (DAS28), C-reactive protein (CRP), or erythrocyte sedimentation rate (ESR) were calculated. Moreover, the effects of dual TxA2 modulator BM567 on cell proliferation as well as protein expression of α-actinin and NF-κB2 in RA fibroblast-like synovial (FLS) cells MH7A were determined by MTS assays and Western blot analysis, respectively. The effects of BM567 on mRNA expression of cyclooxygenase (COX)-2, a downstream product of NF-κB2 and an upstream enzyme of TxA2, was examined by real-time quantitative PCR experiments. RESULTS: Serum TxB2 level was significantly higher in RA patients as compared to healthy controls. Both DAS28 score and serum TxB2 levels were slightly lower in the DMARDs group than the non-DMARDs group, without statistical significance, and there was positive correlation between these two factors. BM567 significantly suppressed cell proliferation as well as expression of α-actinin, NF-κB2, p52, and COX-2 in MH7A. CONCLUSION: TxA2 plays an important role in RA pathology, synovial cell proliferation in particular, through an auto-regulatory feedback loop. Thus, targeting TxA2 may represent a promising add-on therapy in the treatment of RA.

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.