Effect of Synovial Fibroblasts in Rheumatoid Arthritis and Intervention of Chinese Medicine： A Review / 中国实验方剂学杂志

Rheumatoid arthritis （RA） is a common autoimmune disease. Excessive hyperplasia of synovial tissues and osteoclastic bone absorption are two main causes of bone and joint destruction in RA. Synovial fibroblasts in RA （RA-FLS） are important cells in the synovial tissues of RA. The changes in their growth characteristics and inhibition of apoptosis lead to the proliferation of synovial tissues， stimulate inflammatory reactions， damage joint structure， and result in joint dysfunction. Therefore， regulating abnormal proliferation and promoting apoptosis of RA-FLS can interfere with the pathogenesis of RA. At present， there are many studies on the effect of Chinese medicine and its monomer components on the excessive proliferation and apoptosis of RA-FLS. The present study reviewed the effect of RA-FLS in RA and the intervention of Chinese medicinal monomers and compounds by regulating RA-FLS. The results showed that monomer components mainly included terpenoids， flavonoids， alkaloids， and anthraquinones. Despite different types， they can effectively intervene in RA through different approaches. For instance， they can prevent bone and cartilage injury by inhibiting the secretion of inflammatory cytokines and inhibiting the generation of chondrocytes and osteoclasts. They can achieve apoptosis by up-regulating the pro-apoptotic genes B-cell lymphoma 2 （Bcl-2）， Bcl-2-associated X protein （Bax）， and cysteinyl aspartate-specific protease （Caspase） in the Fas/FasL， nuclear factor-κB （NF-κB）， Janus kinase （JAK）/signal transducer and activator of transcription protein （STAT）， and p38 mitogen-activated protein kinase （p38 MAPK） signaling pathways， and down-regulating the anti-apoptotic genes Bcl-xl and Bcl-2. They can also inhibit the proliferation of RA-FLS by inhibiting the protein expression of microtubule-associated protein 1 light chain 3Ⅱ（LC3Ⅱ）/LC3Ⅰ and Beclin-1. Although their molecular mechanisms of action and targets are different， they all exert corresponding roles. The above research results provide a scientific basis for elucidating the multi-component and multi-target characteristics of Chinese medicine in the treatment of RA.

Xinfeng Capsules promotes apoptosis of synovial fibroblasts and attenuates inflammation in rheumatoid arthritis by regulating lncRNA MAPKAPK5-AS1 / 中国中药杂志

To explore the regulatory effects of Xinfeng Capsules(XFC) on the apoptosis of synovial fibroblasts(FLS) and inflammation in rheumatoid arthritis(RA) via lncRNA MAPKAPK5-AS1(MK5-AS1). Thirty healthy people and 30 patients with RA due to spleen deficiency and dampness exuberance were collected for extracting the peripheral blood mononuclear cells(PBMCs) before and after XFC treatment, which were used to observe the correlation between MK5-AS1 and clinical indicators as well as MK5-AS1 expression before and after XFC treatment. Following the establishment of RA-FLS cell line and the preparation of XFC-containing serum, MK5-AS1-overexpression plasmid was constructed and transfected into RA-FLS for investigating the efficacy of XFC-containing serum in regulating inflammation and apoptosis of RA-FLS via MK5-AS1. The expression of MK5-AS1 in PBMCs of patients with RA due to spleen deficiency and dampness exuberance was decreased(P<0.001). The ROC curve analysis revealed the AUC of 83.9%. Correlation analysis showed that MK5-AS1 was negatively correlated with ESR, CRP, RF, CCP, and spleen deficiency and dampness exuberance syndrome score. The expression of MK5-AS1 increased significantly after XFC treatment(P<0.001). As demonstrated by association analysis, XFC decreased MK5-AS1, ESR, CRP, RF, and spleen deficiency and dampness exuberance syndrome score, with the degree of support all greater than 83%, confidence greater than 80%, and lift greater than 1. The results of RT-qPCR showed that the MK5-AS1 RNA expression significantly decreased after TNF-α stimulation(P<0.01), which, however, increased significantly after the intervention with XFC-containing serum(P<0.05). Such expression rose again after the transfection of pcDNA3.1-MK5-AS1(P<0.01). ELISA results showed that TNF-α stimulation elevated the expression of pro-inflammatory factor IL-17 but lowered the expression of anti-inflammatory factor IL-4(P<0.01). After intervention with XFC-containing serum, the expression of IL-17 decreased while that of IL-4 increased(P<0.01). The transfection of pcDNA3.1-MK5-AS1 contributed to the reduction in IL-17 expression but the elevation in IL-4 expression(P<0.01). The immunofluorescence(IF) findings demonstrated that the expression of pro-apoptotic protein Bax was down-regulated, whereas that of the anti-apoptotic protein Bcl-2 was up-regulated after TNF-α stimulation(P<0.01). After the intervention with XFC-containing serum, the Bax expression was increased, while Bcl-2 expression was decreased(P<0.01), which were remarkably collaborated by the transfection of pcDNA3.1-MK5-AS1(P<0.05). The expression of MK5-AS1 is significantly decreased in both RA-PBMCs and RA-FLS, implying that XFC inhibits inflammatory reaction and promotes the apoptosis in RA by regulating the expression of MK5-AS1.

Effect and Mechanism of Yuxuebi Tablet Against Collagen-Induced Arthritis of Rats / 中国实验方剂学杂志

Objective:To explore the intervention effect of Yuxuebi tablet （YXB） on collagen-induced arthritis （CIA） in rats and its anti-inflammatory mechanism. Method:Following CIA modeling， the rats in the drug administration groups were separately treated with intragastric administration of YXB （0.1， 0.2， and 0.4 g·kg^-1） and methotrexate （MTX， 0.4 mg·kg^-1）， once a day. The incidence of CIA， mechanical pain threshold （MPT） and cold pain threshold （CPT） were evaluated once every three days. After continuous administration for 30 days， the peripheral blood of rats was collected for the determination of platelet （PLT） count and fibrinogen （FIB） content. The hematoxylin-eosin （HE） staining was conducted to analyze the pathological changes in joint tissues. The protein expression levels of interleukin （IL）-1<italic>β</italic>， IL-8， nuclear transcription factor-<italic>κ</italic>B （NF-<italic>κ</italic>B） p65， phosphorylated NF-<italic>κ</italic>B （p-NF-<italic>κ</italic>B） p65， Ras， and Raf-1 in joint tissues of CIA rats were detected by immunohistochemistry （IHC） and Western blot. The rheumatoid arthritis fibroblast-like synoviocytes （RA-FLS） were induced by tumor necrosis factor-<italic>α</italic> （TNF-<italic>α</italic>， 10 μg·L^-1） <italic>in vitro</italic> and then subjected to transwell migration/invasion assay， followed by the detection of protein expression levels of Ras， Raf-1， and p-NF-<italic>κ</italic>B p65 in RA-FLS by Western blot. Result:Compared with the control group， the model group exhibited an increased incidence of CIA， significantly decreased MPT （<italic>P</italic><0.05，<italic>P</italic><0.01）， elevated CPT （<italic>P</italic><0.01） and PLT and FIB in the peripheral blood， worsened histopathological score of joints， enhanced RA-FLS migration and invasion， and up-regulated inflammatory factors （<italic>P</italic><0.01）. The comparison with the model group revealed that YXB at different doses obviously reduced the incidence of CIA， increased MPT， down-regulated CPT and PLT and FIB in the peripheral blood （<italic>P</italic><0.05，<italic>P</italic><0.01）， ameliorated the pathological changes like synovial hyperplasia and bone and cartilage destruction （<italic>P</italic><0.05，<italic>P</italic><0.01）， and inhibited RA-FLS migration and invasion. Besides， the low-， medium-， and high-dose YXB reversed the IL-1<italic>β</italic>， IL-8， Ras， Raf-1， and p-NF-<italic>κ</italic>B p65 expression in joint tissues of CIA rats to different extents， as well as the protein expression of Ras， Raf-1 and p-NF-<italic>κ</italic>B p65 in RA-FLS （<italic>P</italic><0.05，<italic>P</italic><0.01）. Conclusion:YXB reduces the incidence of CIA， ameliorates the clinical symptoms of RA and the pathological changes in joint tissues， and inhibits the formation of synovium， which may be attributed to its inhibition against Ras/Raf-1/NF-<italic>κ</italic>B signaling pathway.

Alopecia areata y vitamina D sérica en pacientes iraquíes: un estudio de casos y controles / Alopecia Areata And Serum Vitamin D in Iraqi Patients: a case-control study

Background: Alopecia areata (AA) is a typical hair issue, which may have obliterating mental and social outcomes and is portrayed by the nearness of nonscarring alopecia. Objective: This examination has targets to assess the serum nutrient D levels , with AA; contrast the outcome and clearly sound control; and confirm relationship between AA types and serum nutrient D levels. Patients Also Methods: the examine might have been led clinched alongside Tikrit educating healing facility throughout those time starting with June 2019 of the limit for January 2020. Irrefutably the quantity of subjects associated with the assessment was ninety individuals isolated in two social events; the patients bundle were forty five the people who whimper of AA while the resulting gathering including a forty five age and sex-made solid volunteers were picked as a benchmark gathering. The degree and movement of the alopecia were noted and the patients were meticulously broke down for signs of various ailments. Research center assessments were led to patients and also to those control population, these included serum vitamin D levels were measured as 25-hydroxyvitamin D {25(OH)D} using a chemiluminescence microparticle immunoassay. Blood models were gotten starting with patients and control subjects after totally taught consent was gotten. Results : An essential complexity may have been found for serum 25-OH Vit D levels between patients other than controls. Vitamin D sufficiency were more common in controls than in patients. Serum Vitamin D was deficient in both cases and controls group; but, the deficiency was significantly more throughout AA group (35. 6%) compared to the handle group (11. 1%). Among the list patients gathering, levels associated with nutrient D were totally higher in guys in contrast with females. Conclusions: AA might be related with nutrient D deficiency as mean degrees of nutrient D of patients were seen as fundamentally lower than typical sound controls.

Markers of Inflammation in Rheumatoid Arthritis and Osteoarthritis

Introduction: Rheumatoid arthritis is characterized by local and systemic effects of inflammation while osteoarthritis is aninflammatory degenerative disorder of joints. A wide range of inflammatory markers are implicated in pathogenesis of rheumatoidarthritis and osteoarthritis as a consequence of persistent imbalance between pro- and anti-inflammatory immune mechanisms,leading to chronic inflammation. Hence the present study is an attempt to estimate the levels of serum ceruloplasmin , C-reactiveprotein (CRP) and rheumatoid factor (RF) factor as inflammatory markers in serum of rheumatoid arthritis and osteoarthritispatients and compare them with normal healthy controls. Materials and Methods: Serum ceruloplasmin was estimated byspectrophotometric method while serum C-reactive protein and RA factor were detected using agglutination test in thirty patientsof rheumatoid arthritis ,osteoarthritis and age and sex matched healthy controls each were included in the study. Results:Significant increase in ceruloplasmin was observed (p<0.0001) in rheumatoid arthritis and osteoarthritis as compared to healthycontrols and in that especially ceruloplasmin was more elevated in rheumatoid arthritis than osteoarthritis. C-reactive proteinwas found to be positive in rheumatoid arthritis and osteoarthritis and none of the controls. RF factor was found positive inrheumatoid arthritis and none of the osteoarthritis and controls. Conclusion: There was increased level of serum ceruloplasmin inthe patients with rheumatoid arthritis and osteoarthritis. C-reactive protein and RF factor was found to be positive in rheumatoidarthritis while C-reactive protein was found to be positive in rheumatoid arthritis and osteoarthritis. These findings suggest apossible role of these inflammatory markers in the pathogenesis of rheumatoid arthritis.

Mechanism on moxibustion for rheumatoid arthritis based on PD-1/PD-L1 signaling pathway / 中国针灸

OBJECTIVE@#To explore the mechanism of moxibustion on the treatment of rheumatoid arthritis (RA) in the perspective of programmed cell death-1 and its ligand 1 (PD-1/PD-L1).@*METHODS@#A total of 30 Japanese big ear white rabbits were randomly divided into a control group, a model group and a moxibustion group, 10 rabbits in each one. In the model group and the moxibustion group, RA model was prepared by the injection of Freund's complete adjuvant (FCA) into the hind knee joint cavities of each rabbit. In the control group, 0.9% sodium chloride solution of the same dose was injected. On the 8th day of experiment, in the moxibustion group, moxibustion was applied to "Shenshu" (BL 23) and "Zusanli" (ST 36), 5 cones at each acupoint, on the bilateral sides alternatively, once a day, 6 treatments as one course, with an interval of 1 days between the treatment courses. Totally, 3 courses of treatment were required. On the 1st, 7th, 14th, 21st and 28th days of experiment, successively, the circumference of the bilateral knee joints was measured with the tape. On the 28th day of experiment, H.E. staining was adopted to observe the histopathological morphology and to evaluate the score of knee synovial tissue. ELISA was used to determined the concentrations of soluble PD-1 (sPD-1) and its ligand 1 (sPD-L1), the interleukin 2 (IL-2) and IL-17 in knee synovial fluid and the concentrations of sPD-1 and sPD-L1 in serum. The histochemistry method was used to determine the expressions of membrane PD-1 (mPD-1) and its ligand 1 (mPD-L1) in spleen tissue.@*RESULTS@#On the 14th, 21st and 28th days of experiment, the circumference of both knee joints was increased in each of the rabbits in the model group as compared with the control group (<0.01), and it was reduced significantly in the moxibustion group as compared with the model group (<0.01). Compared with the control group, the hyperplasia of synovial tissue and fibrous tissue, as well as inflammatory cell infiltration were increased obviously in the model group (<0.01), and they were reduced significantly in the moxibustion group as compared with the model group (<0.01, <0.05). Compared with the control group, the concentrations of IL-2 and IL-17 in knee synovial fluid were increased in the rabbits of the model group (<0.01). Compared with the model group, after the intervention with moxibustion, the concentrations of IL-2 and IL-17 in knee synovial fluid were reduced in the rabbits of the moxibustion group (<0.05). Compared with the control group, the concentrations of sPD-1 and sPD-L1 in knee synovial fluid and serum in the rabbits of the model group were all increased (<0.05). Compared with the model group, the concentration of sPD-1 in the knee synovial fluid and serum were reduced in the rabbits of moxibustion group (<0.05). Compared with the control group, the expressions of mPD-1 and mPD-L1 in spleen tissue were increased obviously in the rabbits of the model group (<0.05). Compared with the model group, the expression of mPD-L1 in spleen tissue was up-regulated in the rabbits of the moxibustion group (<0.05).@*CONCLUSION@#Moxibustion could inhibit the over-activation of T cells by enhancing the negative regulation of PD-1/PD-L1 signaling pathway so as to play its effect in treatment of RA.

Screening and bioinformatics of rheumatoid arthritis markers based on GEO chip / 西安交通大学学报(医学版)

Objective To perform bioinformatics analysis of the genetic chip data of rheumatoid arthritis (RA) in order to search for the characteristic gene expression profiles. Methods Differential expression analysis of RA Gene chip data in GEO database was performed using GEO2R, and GO and KEGG enrichment analysis of functional annotation and pathway analysis of differentially expressed genes (DEGs) were conducted by DAVID6.8 and R language. Protein-protein interaction (PPI) and target genes acquisition were realized by String-database and software Cytoscape3.7.1. Results The 1 184 DEGs in synovial tissues isolated from the knee joints of RA patients were statistically significant. Among them 664 were up-regulated and 520 were down-regulated. DEGs were enriched to 70 different GOterms, and the most significant terms were signal transduction, plasma membrane and protein binding. DEGs were enriched to 62 different signal pathways, including cytokine-cytokine receptor interaction, osteoclast differentiation, rheumatoid arthritis, Th17 cell differentiation, and IL17 signal pathway. PPI analysis screened out 19 pivotal target genes, namely, NKG7, BCL6, SEMA4D, NFIL3, RAC2, MLIP, SEL1L3, GUSBP11, IGLV1-44, IGLJ3, IGLC1, IGKV1OR2-118, IGKV1OR2-108, IGKC, IGHV4-31, IGHV3-23, IGHM, IGHD and CYAT1. Conclusion Partial DEGs screened out by analyzing the expression profiles are involved in the key links affecting the development of synovial inflammation in RA, which may provide an important theoretical basis for early diagnosis and treatment of this disease and development of targeted drugs.

Correlation analysis of platelet-lymphocyte ratio with system involvement and disease activity in rheumatoid arthritis / 医学研究生学报

ObjectiveIt is very important to monitor the disease activity and complications of patients in the treatment of rheumatoid arthritis (RA). In this paper, we evaluated the level of platelet-lymphocyte ratio (PLR) of peripheral blood in patients with rheumatoid arthritis and discussed the relationship between PLR and the system involvement, laboratory indexes, and disease activity in patients with rheumatoid arthritis.MethodsFrom September 2013 to May 2017, 123 patients with rheumatoid arthritis who were first diagnosed in the General Hospital of Eastern Theater Command were analyzed retrospectively. 123 healthy persons(healthy control group) and 123 patients with other autoimmune diseases(disease control group) were matched according to the sex and age in a ratio of 1:1. According to the disease activity score 28 joints C-reactive protein (DAS28-CRP), RA patients were divided into the high activity group and the low activity group, and the PLR levels of high-activity and low-activity patients, healthy control group and disease control group were compared, respectively. To evaluate the relationship between system involvement and PLR level in RA patients; to analyze the correlation between PLR and DAS28-CRP and traditional inflammatory indexes by Spearman; to evaluate the application effect of receiver operating characteristic curve(ROC) in the diagnosis of RA and the differentiation of disease activity of RA patients.ResultsThe PLR level of RA patients was significantly higher than that of healthy people [133.63 (103.17, 140.99)] and disease control group [159.83(104.22, 203.55)], and the difference was statistically significant(P0.05]. There was a significant positive correlation between PLR and DAS28 CRP, C-reactive protein (CRP), ESR (r=0.433, 0.501, 0.592, P all <0.01）. The AUC of PLR in diagnosing RA and evaluating RA was 0.68 and 0.73 respectively. When cut off value was 134.47 and 147.61 respectively, sensitivity was 74.8% and 77.5%, specificity was 56.5% and 63.2%.ConclusionThe level of PLR of peripheral blood in patients with RA is increased, especially in patients with circulatory system involvement, infectious diseases or RF positive, and related to disease activity. PLR is expected to be an effective supplement for RA disease diagnosis and disease activity assessment and has potential application value.

Research progress of mechanism of IL-37 in rheumatoid arthritis / 上海交通大学学报（医学版）

Rheumatoid arthritis (RA) is a chronic progressive autoimmune disorder, the mechanism of which is not clear yet. Cytokines play a key role in the pathogenesis of RA. Recent studies on cytokine involvement in autoimmune diseases have found that, as a new member of interleukin-1 (IL-1) family, IL-37 can participate in the regulation of signaling pathway and play its anti-inflammatory role by extracellular binding to membrane receptor and intracellular complex formation. Studies have shown that the expression level of IL-37 in healthy people is extremely low and overexpressed in RA patients, and the serum level of IL-37 in RA patients is positively correlated with the level of pro-inflammation cytokines such as tumor necrosis factor-α (TNF-α), IL-6 and IL-1α, the level of C reactive protein and 28-joint disease activity score (DAS28). However, IL-37 treatment can alleviate the inflammation and pathological symptoms of collagen-induced arthritis (CIA) mice, which indicates that IL-37 has anti-inflammatory effect via negative feedback. The specific anti-inflammatory mechanism may be related to mothers against decapentaplegic homolog 3 (SMAD3) pathway and nuclear factor kappa-B (NF-κB) pathway. This article reviews the structure and expression of IL-37, the receptor and its signal pathway and the function and its mechanism in RA, which provides references for the further study of IL-37 and RA.

Study of Prognostic Significance of Anti Cyclic Citrullinated Peptide Antibodies in Patients with Rheumatoid Arthritis

Background: Rheumatoid arthritis is a chronic autoimmune inflammatory disease with articular and extra-articular manifestation that affects 0.5 to 1 % of total population. Aim and Objectives: To correlate Rheumatoid factor (RF) and Anti-CCP antibody in RA, to evaluate prognostic value of RF and Anti-CCP antibody in RA. Materials and methods: Retrospective study of total 50 patients admitted to our hospital from January 2018 to December 2018 was done. All patients were diagnosed as rheumatoid arthritis as per diagnostic criteria of American College of Rheumatology. All patients had symptom duration of at least one Year. Anti-CCP and lgM-RF were evaluated in all patients. Disease activity score 28 was calculated in all patients. Radiological Damage was assessed by Larsen Score. Results: Anti-CCP and RF were significantly correlated with each other and both were seen as significant independent predictors of radiological outcomes (p value 0.01 and <0.05 respectively). Combination of these two had highest risk for erosive joint damage. Conclusion: RA is more common in female. Anti-CCP antibody and RF both in combination were associated with higher probabilities of erosive disease.

Analysis of B cell subsets in rhumatoid arthritis patients and the effect of epigallocatechingallate on B cell subsets / 上海交通大学学报（医学版）

Objective:To explore the characteristics of B cell subsets in rheumatoid arthritis (RA) patients and the regulation of epigallocatechingallate (EGCG) on B cell subsets in RA patients. Methods:Twenty-nine age- and sex-matched RA patients and 29 healthy controls were selected, and the difference of B cell subsets in peripheral blood between the two groups was analyzed by paired t-test. According to the value of disease activity score in 28 joints (DAS28), RA patients were divided into active group (2.6 ≤ DAS28 0.05). There was no significant difference in the numbers and the proportions of total B cells and B cell subsets (except CD19+ IL-10+ Breg) between 10 RA patients of active group and 19 RA patients of highly active group (P>0.05). There was no significant difference in the number and the proportion of CD19+ IL-10+ Breg in lymphocytes between 6 RA patients of active group and 12 RA patients of highly active group (P>0.05). The proportion of total B cells was weakly positively correlated with IgG type rheumatoid factor (r=0.308). EGCG could significantly increase the proportion of CD19+ IL-10+ Breg (P0.05). Conclusion:B cells may play an auxiliary role in the development of RA. The number of CD19+ IL-10+ Breg in RA patients increases as a feedback. EGCG can promote Breg proliferation and suppress BAFF-R mRNA expression.

Comparison of comorbidities between rheumatoid and psoriatic arthritis in a tertiary care rheumatic center

Introduction: Rheumatoid arthritis (RA) and psoriatic arthritis (PsA) have key differences in clinical presentation, radiographic findings, comorbidities and pathogenesis to distinguish between these common forms of chronic inflammatory arthritis Joint involvement is typically, but not always, asymmetric in PsA, while it is predominantly symmetric in RA Bone erosions, without new bone growth, and cervical spine involvement are distinctive of RA, while axial spine involvement, psoriasis, and nail dystrophy are distinctive of PsA Aim of the study: To Compares the comorbidities between Rheumatoid Arthritis (RA) and Psoriatic Arthritis (PSA) Materials and methods: This was a prospective observational study conducted for a period of 6 months at Institute of Rheumatology, Government KAPV Medical College and MGM Government Hospital Totally 241 patients who were fulfilling inclusion criteria has been included Patients diagnosed with and treated for PsA on the basis of clinical, radiological and laboratory findings and expert opinion was monitored using standardized examination methods and jointly prepared forms Clinical status, accompanying systemic diseases and surgical history was recorded Routine clinical examination and basic comorbid findings have been assessed by standardized methods

Effects of moxibustion at different time points on foot swelling, serum level of TNF-α and circadian rhythm in rats with rheumatoid arthritis / 中国针灸

OBJECTIVE@#To study the effects of moxibustion at different time points on serum level of tumor necrosis factor-α (TNF-α) in rats with rheumatoid arthritis (RA), and to explore its regulation mechanism on circadian rhythm.@*METHODS@#A total of 96 Sprague-Dawley (SD) adult rats were randomly assigned into a blank group, a model group, a moxibustion at 5-7 AM group and a moxibustion at 5-7 PM group, 24 rats in each group, half male and half female. Each group was further divided into a 0 AM group, a 6 AM group, a 12 N group and a 6 PM group, 6 rats in each group. All rats were treated with the 12 h/12 h light-dark cycle in the whole process of experiment. Except for the blank group, all rats were treated with intracutaneous injection of freund's complete adjuvant (FCA) at right foot pad to establish the RA model. The rats at the two moxibustion groups were treated with grain-sized moxibustion at "Shenshu" (BL 23) and "Zusanli" (ST 36) at 5-7 AM and 5-7 PM, respectively, one side per treatment, once a day; six treatments were taken as one course and 3 courses were given with an interval of one day between courses. The rats in the remaining groups were treated with identical fixation but without moxibustion intervention. The right foot volume was measured before model establishment, after model establishment and after treatment. The blood samples were collected after treatment and the serum level of TNF-α was measured by ELISA. The SPSS 21.0 software and Halberg Cosinor were adopted to analyze the experiment data.@*RESULTS@#After treatment, compared with the blank group, the foot swelling severity was significantly increased in the model group, moxibustion at 5-7 AM group and moxibustion at 5-7 PM group (all <0.01); compared with the model group, the foot swelling severity was significantly reduced in the moxibustion at 5-7 AM group and moxibustion at 5-7 PM group (both <0.01). Compared with the blank group, the serum level of TNF-α was increased significantly in the model group and moxibustion at 5-7 AM group (both <0.05); compared with the model group, the serum level of TNF-α was reduced significantly in the moxibustion at 5-7 AM group and moxibustion at 5-7 PM group (both <0.05). The serum level of TNF-α showed circadian rhythm in all the groups (all <0.05), and the peak appeared at night phase; compared with the blank group, the median value of TNF-α was increased significantly in the model group (<0.05), the peak phase was delayed and the amplitude was increased (<0.05); compared with the model group, the median value of TNF-α was significantly reduced in the moxibustion at 5-7 AM group and moxibustion at 5-7 PM group (<0.01), the peak phase was advanced and the amplitude was reduced (<0.05).@*CONCLUSION@#Moxibustion could effectively reduce the serum level of TNF-α to relieve the foot swelling severity in RA rats. Moxibustion could regulate the circadian rhythm of TNF-α to play its effects on the inhibition of the synthesis of TNF-α. No efficacy is observed between the treatment at 5-7 AM and 5-7 PM.

The clinical observation of Compound Xuanju Capsules Combined with methotrexate treating rheumatoid arthritis / 中成药

AIM To evaluate the clinical effects of Compound Xuanju Capsules (CXC,Polyrhachis vicina Roger,Epimedii Folium,Lycii Fructus,Cnidii Fructus) combined with methotrexate (MTX) on patients with moderate or severe rheumatoid arthritis (RA).METHODS One hundred and eighty RA patients were randomized into 3 groups:CXC group,MTX group and combined group (dosed with both CXC and MTX) for a 48-week intervention.The clinical observation on the changes of the signs and symptoms,erythrocyte sedimentation rate (ESR),C-reactive protein (CRP),health assessment questionnaire (HAQ),visual analogue scale (VAS) and disease active score (DAS) 28 were performed before and after each treatment.ACR20,American College of Rheumatology 20％ improvement criteria was taken as the primary end point,and ACR50 and ACR70 as the secondary end points to standardize the patients' response measurement,and all adverse reactions were recorded as well.RESULTS At the time point right after the 12th week,the ACR20 response rate of the combined group (41.5％) was significantly higher than that of the CXC group (19.6％,P ＜ 0.05) and the MTX group (24.1％,P＜0.05).The respective ACR50 (2.1％) and ACR70 (20.8％) response rate of the combined group were significantly higher than those of CXC group and MTX group (P ＜ 0.05).At the time point right after the 24th week,the combined group still demonstrated its significantly higher ACR20 response rate (81.1％) to the CXC group (30.4％,P ＜ 0.05) and the MTX group (68.5％,P ＜ 0.05).The similar superiority in ACRS0 (60.4％) and ACR70 (54.7％) response rate of the combined group to the CXC group and the MTX group were found (P ＜0.05).After the 48th week,the combined group displayed its significantly higher ACR70 response rate (75.7％) to CXC group and MTX group (P ＜ 0.05).Given the reduction of DAS28,HAQ and VAS from the12thweek's5.26±0.83),(22.2±10.3),(6.0±0.4) to the 24thweek's (4.21 ±0.91),(17.1±10.3),(2.4±2.2),andthe48thweek's (2.19±0.56),(10.4±5.0),(0.8±0.9),the combined group's more outstanding performance compared to CXC group and MTX group started right after the 24th week (P ＜ 0.05).Generally,no difference in adverse events was detected between the combined group and MTX group (P ＞ 0.05).CONCLUSION The combined use of CXC and MTX can be an effective and safe treatment for moderate and severe rheumatoid arthritis.

Meta-analysis on efficacy and safety of combination therapy of Aconitum and Western medicine in treatment of rheumatoid arthritis / 中国中药杂志

To analyze the efficacy and safety of the combination therapy of Aconitum and Western medicine in the treatment of rheumatoid arthritis (RA) by Meta-analysis, and provide evidence for its clinic application for RA. The random clinical trials (RCTs) regarding the combination therapy for treating RA were retrieved in the database of China National Knowledge Infrastructure database, China Science and Technology Journal database, WanFang, Chinese Biomedical Medical Database, PubMed, and Cochrane Library up to July 2017. According to the given inclusion criteria, 8 RCTs involving 659 participants were included, and the included RCTs could be further divided into three subgroups according to the herb type, which were Aconiti Radix (Chuanwu) subgroup (6RCTs), Aconiti Kusnezoffii Radix (Caowu) subgroup (1RCT), and Chuanwu-Caowu subgroup (1RCT). The Meta-analysis results indicated that as compared with Western medicine, the combined use of Aconitum and Western medicine, no matter Chuanwu, Caowu or Chuanwu-Caowu subgroups, could improve the total effective rate of RA (6RCTs, RR=1.19, 95%CI [1.10, 1.28], <0.000 01), (1 RCT, RR=1.43, 95%CI [1.18, 1.73], =0.000 2), (1 RCT, RR=1.27, 95%CI [1.02, 1.58], =0.03) respectively. The combined use of Aconitum and Western medicine was also effective on the number of joint swelling, duration of morning stiffness, patients' handgrip, and the erythrocyte sedimentation rate, C-reactive protein and rheumatoid factor. However, its action was not significant on joint tenderness. And also, in the included RCTs, there were 34 cases of adverse drug reactions/events (ADR/ADE) in the Chuanwu subgroup, while 86 cases in the Western medicine control group. The ADR/ADE incidence was even more lower in Chuanwu-Caowu subgroup, but no difference between Caowu subgroup and Western medicine group. Based on the included RCTs, the combined use of Aconitum and Western medicine could achieve more satisfying efficacy and lower ADRs incidence for RA as compared with Western medicine alone. However, due to the limitation in the not-high quality of included RCTs and the lack of large-scale multi-center research, the results still need to be further validated in the clinic application.

Use of palmar dermatoglyphics in rheumatoid arthritis – A case-control study

Background: The susceptibility and severity of Rheumatoid arthritis are determined by both genetic and environmental factors. Dermatoglyphic patterns of individuals which are formed early in the fetal life are also determined by both genetic and environmental factors. Since both are genetically acquired and environmentally modified, it has been shown that there are particular dermatoglyphic patterns associated with Rheumatoid arthritis. If it is so, dermatoglyphics can serve as an additional tool in the early diagnosis and management of such a disabling disease like rheumatoid arthritis. Although there are some studies which mentioned dermatoglyphic pattern variation in the disease, the results are contradicting. Therefore, the present study was undertaken to find out a possible correlation of some quantitative and qualitative dermatoglyphic variables with Rheumatoid Arthritis. Aim of the study: To study the dermatoglyphic patterns in patients with Rheumatoid Arthritis and control population and to study the correlation between dermatoglyphic patterns and Rheumatoid Arthritis. Materials and methods: We studied 60 patients with Rheumatoid arthritis and 60 controls. All were subjected to detailed medical history and clinical examination. Both quantitative (finger ridge count and pattern intensity) and qualitative (fingerprint pattern) dermatoglyphic parameters were studied and the same were compared with age, sex and disease matched controls. Results: Out of the total 60 cases 12(20%) were male and 48(80%) were females. Of the total 60 controls, 12(20%) were males and 48(80%) were females. Analysis of the qualitative parameters revealed: Significant increase in the number of whorls in both the hands of female patients cases compared to the controls (p-value for right hand 0.001, p-value for left hand 0.004). The decrease in the number of radial loops in both the hands of male and female patients and the decrease was more in the left hand in males and right hand in females (p-value male left hand 0.002, female right hand Saritha K. Narayanan, Christopher C. Pais, Pradeep Kumar Shenoy. Use of palmar dermatoglyphics in rheumatoid arthritis - A case-control study. IAIM, 2017; 4(12): 70-76. Page 71 0.003). Decrease in the number of arches in the left hand of female patients compared to the controls (p-0.10). Analysis of the quantitative parameters showed: A statistically significant increase in the finger ridge count of individual hand and the total finger ridge count in both male and female patients compared to the controls (p-value males: right hand 0.003, left hand 0.004, right plus left hand 0.002; p-value females right hand.0000, left hand 0.000, right plus left hand 0.000). A statistically significant increase in the pattern intensity of fingers in female patients compared to the controls (p-value: right hand 0.006, left hand 0.001, right plus left hand 0.000). Conclusion: The findings of this work demonstrate the association between some of the qualitative and quantitative parameters of dermatoglyphics and Rheumatoid arthritis suggesting that dermatoglyphics can represent an anatomical, non-invasive, inexpensive tool for screening high-risk population and thus facilitate early detection and management.

Clinical efficacy of Chenshi Qingfei Decoction on rheumatoid arthritis and interstitial lung disease / 中成药

AIM To explore the efficacy of Chenshi Qingfei Decoction (Pseudostellariae Radix,Ophiopogonis Radix,Adenophorae Radix,etc.) against rheumatoid arthritis and interstitial lung disease (RA-ILD).METHODS Based on Prednisolone,RA-ILD patients were randomly divided into control group and observation group by random number table and randomized block design.The observation group took Chenshi Qingfei Decoction.The treatment course was three months for both groups.Before the treatment,the activity of the disease (DAS28) was assessed and ESR,CRP,RF,CCP were measured.Before and after the treatment,high resolution-CT (HRCT) was conducted and graded,and symptoms and signs were graded.RESULTS After the treatment,the effective rate of cough,expectoration and breath hard in the syndromes of Chinese traditional medicine was 71％ in the observation group and 23％ in the control group (P ＜0.01).The effective rate of improved lung imaging by HRCT was 68％ in the observation group but 13％ in the control group (P ＜0.01).CONCLUSION Based on the immunosuppressive agents therapy in RA,Chenshi Qingfei Decoction can relieve clinical symptoms of cough,expectoration and breath hard,and reduce area and degree of interstitial lung disease by HRCT.

Research progress of TNF-α and its receptors in rheumatoid arthritis / 药学实践杂志

The TNF-α signaling pathway is a valuable target in the therapy of autoimmune diseases.TNF-α binds to two different receptors and exerts anti-inflammatory and anti-rheumatic effects.The drugs of anti-TNF-α are widely used in rheumatoid arthritis, such as infliximab, adalimumab etc.These TNF blockers have become invaluable tools to reduce damages induced by inflammation and allow recovery of the affected tissues.Unfortunately, this therapy has some drawbacks, such as increasing the risk of infection, malignancy and the incidence rate of new auto-immune diseases.Some of these effects are caused by the unwanted abrogation of beneficial TNF signaling.Therefore, elective antagonism of TNFR is an important approach to alleviate the side effects of TNF-α antibody.The medications specifically targeting the TNFR might have better applicability and safety.In this article, research progresses of TNF-α and its receptors in the therapy of rheumatoid arthritis were reviewed.

Diagnostic Value and Significance of the HLA-DR53,Anti-Sa and Anti-CCP Antibody Factors Combination in Rheumatoid Arthritis / 现代检验医学杂志

Objective To explore the value of human leucocyte antigen-DR53 (HLA-DR53),anti-Sa antibody and anti-cyclic citrullinated peptide antibody(anti-CCP) factors combination in rheumatoid arthritis.Methods 170 patients with rheumatoid arthritis and 50 healthy individuals in the hospital were chosen.The levels of HLA-DR53 by PCR-SSP,the levels of anti-Sa and anti-CCP by ELISA,compared their diagnostic value by consistency analysis and joint detection analysis.Results The sensibility of anti-Sa,HLA-DR53 and anti-CCP in RA were 44.07％ (P =0.00,x2 =165.214),68.65 ％ (P =0.00,x2 =9.837) and 79.45 ％ (P=0.00,x2=48.028).Consistency analysis in RA,HLA DR53,anti-CCP and anti-Sa highly consistent,OR were 3.94,38.6 and 184.52.The sensitivity and Youden index of anti-CCP were the highest.The sensitivity of anti Sa and anti-CCP parallelled was 88.51 ％.The sensitivity of HLA-DR53 and anti-CCP parallelled was 93.56％,and the spe cificity of anti-Sa and anti-CCP of RA were 100％.Conclusion There is a certain correlation between HLA-DR53,anti-Sa and anti-CCP antibody,which are related risk factors of RA,co-detection will improve the diagnosis of RA.

Effects of moxibustion on Treg/Th17 cell and its signal pathway in mice with rheumatoid arthritis / 中国针灸

<p><b>OBJECTIVE</b>To observe the effects of moxibustion on Treg/Th17 imbalance and related signal pathway in mice with rheumatoid arthritis (RA), so as to explore the action mechanism of moxibustion on RA.</p><p><b>METHODS</b>Twenty-four DBA/1J male mice were randomly divided into a normal group, a model group, a sham moxibustion group and a moxibustion group, 6 mice in each one. RA model was induced by subcutaneous injection of typeⅡcollagen and adjuvant at tail in mice other than the normal group. The mice in the moxibustion group were treated with moxibustion at"Zusanli" (ST 36) and "Shenshu" (BL 23), 1 mg per cone, 6 cones per acupoint. The consecutive 6-day treatment was taken as one course, and totally 2 courses were given with an interval of 2 d between courses. The mice in the sham moxibustion group were treated with immobilization as the moxibustion group. The effects of moxibustion on joint swelling was evaluated by RA scale of collagen induced arthritis (CIA); the pathological changes of joint inflammation were observed by HE staining; the cell count of Th17 and Treg in spleen was analyzed by flow cytometry; the content of cytokine IL-1β, IL-6, IL-10, IL-17, IL-23, TGF-β and Galectin-9 were analyzed by ELISA; the mRNA and protein expression of Foxp3, Galectin-9, RORγt, CARMA1, NF-κB were analyzed by Real-time PCR and Western Blotting method.</p><p><b>RESULTS</b>Ten to 12 d after the secondary immune, red and swelling of ankle joint, feet and toe joint were observed, indicating successful establishment of RA model. 15 d into moxibustion treatment, the joint swelling was improved in the moxibustion group and the sham moxibustion group, which was superior in the moxibustion group (<0.05). As for pathological changes, compare with the normal group, the articular surface was rougher and synovial layer thinner in the model group, which was recovered to a certain extent in the sham moxibustion group; the articular surface was smooth and synovial layer was thicker in the moxibustion group, which was similar to the normal group. The results of flow cytometry test indicated the cell count of Treg in the model group was reduced but that of Th17 was increased than the normal group (both<0.01); the moxibustion could increase significantly the cell count of Treg (<0.05), but no effect was observed on Th17 (>0.05). The results of ELISA test indicated the differences of increasing of IL-1β, IL-6, IL-17, IL-23, TGF-βas well as the reducing of IL-10 were not significant between the sham moxibustion group and the moxibustion group (all>0.05); moxibustion treatment could increase the content of Galectin-9 which was reduced in RA mice (<0.05). The results of RT-PCR and Western blotting test indicated the mRNA and protein expression of Foxp3, Galectin-9 were reduced in the model group (all<0.01), which could be up-regulated by moxibustion treatment (<0.05,<0.01); the mRNA and protein expression of RORγt, CARMA1, NF-κB was increased (all<0.01), which could be down-regulated by moxibustion treatment (<0.05,<0.01).</p><p><b>CONCLUSION</b>Moxibustion could improve the swelling of joint and inflammatory reaction of joint synovial in RA mice; the mechanism may be related to the regulation of Treg cells number in spleen and the expression of Foxp3, Galectin-9, RORγt, CARMA1, NF-κB, mRNA and protein expression.</p>