类风湿性关节炎膝关节病变的X线影像学研究

目的 :分析类风湿性关节炎(RA)膝关节病变的X线影像学特征,以提高诊断正确率。方法 :收集2015年2月至2017年2月收治的RA患者52例和骨关节炎患者45例,进行X线摄片,分析两组膝关节病变的影像学特征。结果 :RA组中,关节间隙呈均匀性狭窄47例(90.4%),髌上囊肿胀41例(78.8%),关节面毛糙、关节面不同程度侵蚀破坏22例,关节周缘轻度骨质增生43例,明显重度增生、骨赘形成5例,未见明显骨质增生4例,52例均有不同程度骨质疏松。OA组中,关节间隙呈均匀性狭窄5例(11.1%),髌上囊肿胀16例(35.6%),关节面下小囊性改变7例,45例有不同程度骨质增生、骨赘形成改变。两组关节间隙均匀狭窄及髌上囊肿胀改变发生率差异有统计学意义(P<0.05)。结论 :RA膝关节病变的X线影像学表现具有一定特征性,尤其是关节间隙均匀性狭窄、髌上囊肿胀及关节面侵蚀的改变在鉴别RA和OA的诊断中有重要价值。

雷公藤总萜片治疗类风湿性关节炎106例临床分析

雷公藤总萜片为雷公藤经改进工艺流程研制而成。临床应用暂时缓解及显效率分别为6.6％、28.3％,总有效率95.3％。与同类雷公藤片疗效相似。副作用发生率仅28.13％,对照组雷公藤片为75％,两者有显著差异(P<0.001),尤其是消化道反应发生率低,症状轻、症状单一。是临床治疗RA值得推荐的药物。

Elucidating the therapeutic mechanism of Cang Zhu and Huang Bai in rheumatoid arthritis: a comprehensive analysis integrating network pharmacology and GEO data

In the present study, we explored the therapeutic potential of Cang Zhu-Huang Bai (CZ-HB) against rheumatoid arthritis (RA) and elucidated the associated mechanisms. The approach involved a systematic examination of the chemical ingredients of CZ-HB using TCMSP database. Subsequently, we predicted the targets corresponding to the active ingredients through the SwissTargetPrediction database. We constructed a comprehensive drug-ingredient-target network using Cytoscape (v 3.8.0), with the main ingredients of the drugs identified based on their degree values. We conducted a meticulous search across GEO, GeneCards, Therapeutic Target Database (TTD), and PharmGkb databases to identify target proteins associated with RA. The intersection of targets corresponding to the drugs' active ingredients and those associated with RA provided crucial insights. Functional analysis, including GO and KEGG pathway enrichment analyses, was performed on the intersecting targets using R (v 4.2.2). Additionally, a protein-protein interaction (PPI) network of the intersecting targets was constructed using the String platform. The resulting drug-ingredient-target-disease topology network was visualized using Cytoscape (v 3.8.0), and the Cytohubba plugin facilitated the identification of hub genes. The study revealed 35 active ingredients of CZ-HB and their corresponding 673 targets. We identified 14 major active ingredients crucial to the drug’s effects by focusing on the degree values. Furthermore, our investigation uncovered 784 targets associated with RA. Through the intersection of drug and disease targets, we pinpointed 34 active ingredients of CZ-HB capable of acting on 126 targets implicated in RA. The topological network analysis of the intersected genes identified five hub genes. The binding affinity of these hub genes to the 14 primary active ingredients of the drug was confirmed through molecular docking. The enrichment results of the intersecting genes suggested that CZ-HB exerted its anti-RA effects through a multi-component, multi-target, and multi-pathway approach.

Isolation and characteristics of autoreactive T cells specific to aggrecan G1 domain from rheumatoid arthritis patients

Our previous work showed that the cartilage proteoglycan aggrecan could induce an erosive polyarthritis and spondylitis in BALB/c mice and the GI globular domain of the aggrecan (GI) contained the arthritogenic region. To elucidate whether autoreactive T cells to G1 are expressed in rheumatoid arthritis patients, we analyzed the frequency of human G1-specific T cells in the peripheral blood of five rheumatoid arthritis patients and tried to establish G1-reactive T cell lines from these rheumatoid arthritis patients. The results showed that the G1-specific T cells in PBL were detectable at the range of 4.97 ±0.5 ×10-6 in peripheral blood lymphocytes. We have also generated 15 G1-specific T lymphocyte lines from these pateints with a standard split-well method. All these cells expressed fine specificity to human recombinant G1, but not to unrelated antigen. All the 15 lines expressed a panT cell marker and 13 of them selectively used the αβ T cell receptor. Two of them used rye T cell receptor. The 13 of these T cell lines was CD4 positive. One line expressed CD8. One line expressed both CD4 and CD8. Moreover, 14 out of 15 lines expressed the Th-1 cytokine profile, characterized by interferon-γpositivity and IL-4 negativity. No Th-2 type cell line was generated. These data provide strong evidence in favor of the presence of autoreactive T cells in the rheumatoid arthritis pateints. What is the mechanism(s) that these autoreactive T cells attack self-target and whether these G1-specific, Th-1 type T cell lines can induce arthritis in immune deficiency mice are currently under investigation.

Analysis of the action mechanism of Fang Ji Huang Qi decoction in treating rheumatoid arthritis by network pharmacology

Objective:To explore the pharmacological action mechanism of Fang Ji Huang Qi decoction(FHD)in the treatment of rheumatoid arthritis(RA)by network pharmacology.Methods:The chemical compositions and functional targets of the TCM were retrieved using the systematic pharmacological analysis platform TCMSP,and the gene name of each target protein was obtained from the UniProtKB network platform.The targets of RA were queried through the CTD database.The protein–protein interaction network was constructed in the STRING database,and the network visualization analysis was performed in Cytoscape.The Gene Ontology and Kyoto Gene and Genomic Encyclopedia pathways enrichment analyses of key target proteins were performed using the DAVID data platform.Results:A total of 472 drug active ingredients were screened from the TCMSP database.Seventy-five disease targets from the CTD database were screened.The compound-target network map contained further screened out 98 components and corresponding 75 targets.The key compounds included quercetin and kaempferol.The key targets were prostaglandin G/H synthase 2 and nitric oxide synthase 2.The protein-protein interaction network consisted of 75 proteins,of which 37 were key proteins,including tumor protein 53,JUN and interleukin-6.There were 260 Gene Ontology entries,of which 246 were biological processes.Fifty-five Kyoto Gene and Genomic Encyclopedia pathways were enriched,mainly the cancer pathway,NOD-like receptor signaling pathway,and Toll-like receptor signaling pathway,which are involved in the action mechanism of FHD.Conclusion:The results of this study preliminarily verified the basic pharmacological action mechanism of FHD in the treatment of RA,laying a foundation for elucidating its mechanism of action.

Serum Levels of Interleukin-1 Beta, Interleukin-6 and Melatonin over Summer and Winter in Kidney Deficiency Syndrome in Bizheng Rats

Objective To observe the seasonal changes in serum levels of interleukin-1 beta(IL-1β), interleukin-6(IL-6) and melatonin(MT) in Bizheng rat model, and explore the relationship between MT and the pathogenesis of rheumatoid arthritis. Methods One hundred and sixty Sprague-Dawley rats were randomly divided into four groups in summer(n=80) and winter(n=80) respectively: normal group, collagen-induced arthritis(CIA) model group, operation group, and sham-operation group(n=20 in each group). The CIA model group was injected with collagen emulsion at the base of the tail to induce arthritis. The rats in the operation group received pineal gland resection, and 7 days after the first operation, underwent testectomy or oophorectomy. The rats in the sham-operation group were operated to ligature the sagittal sinus, without extracting the pineal gland. After the operations, the operation group and the sham-operation group both were immunized as the CIA group was. The serum levels of IL-1β, IL-6 and MT in different groups were measured by radioimmunoassay. Results Compared with the normal group, the serum levels of IL-1β and IL-6 increased in the CIA model, operation, and sham-operation groups both in summer and in winter(IL-1β in summer, P=0.008, P<0.01, P=0.012; IL-1β in winter, P=0.019, P<0.01, P=0.027; IL-6 in summer, P=0.028, P<0.01, P=0.024; IL-6 in winter, P=0.006, P<0.01, P=0.008). In the operation group, the serum levels of IL-1β and IL-6 in winter were higher than in summer, but with no statistically significant differences(P=0.844, 0.679). Compared with the normal group, the serum level of MT significantly increased in summer and winter in both the CIA model group(P=0.002, 0.008) and the sham-operation group(P=0.003, 0.007), while significantly decreased in the operation group(P=0.023, 0.003). There was no significant difference in MT level in the operation group between summer and winter(P=0.947). Conclusions The increase of serum levels of IL-1β and IL-6 may exacerbate the inflammatoryreaction and cause a more severe condition in the rheumatoid arthritis. The concentrations of IL-1β, IL-6, and MT correspond with the change of seasons, confirming that there are connections between nature and human body.

Studies on Thermodynamic Properties of Some Imidazolinone Derivatives in DMF at 308.15 K

Density,ultrasonic velocity and viscosity of imidazolinone derivatives are studied in dimethyl formamide(DMF) at 308.15 K.From the experimental data,various acoustical parameters,such as specific impedance Z,isentropic compressibilityκs,Rao's molar sound function Rm,van der Waals constant b,relaxation strength r,intermolecular free length Lf,internal pressureπ,solvation number Sn,relative association RA,etc.are evaluated,which helps in understanding the molecular interactions occurring in these solutions.

Role of Acetylated p53 in Regulating the Expression of map2 in Retinoic Acid-induced P19 Cells

Objective To investigate the regulatory mechanisms of acetylated p53 in the expression of microtubule-associated protein-2(MAP2) in neuronal differentiation of P19 cells induced by all-trans retinoic acid(RA).Methods Neuronal differentiation of P19 cells was initiated with 4-day RA treatment.Immunofluorescence,real-time reverse transcription-polymerase chain reaction(RT-PCR) assay,and map2 promoter driven luciferase assay were performed to detect the expression and relative promoter activity of MAP2 in those RA-treated cells.Real-time PCR-based chromatin immunoprecipitation assay(ChIP) was carried out to reveal the specific recruitment of acetylated p53 onto its binding sites on map2 promoter.Results The expression of MAP2 was markedly increased in RA-induced P19 cells.The map2 mRNA increased 34-fold after 4 days of RA treatment and 730-fold 2 days after the treatment,compared with the cells without RA treatment(control).p53 was recruited to the promoter of map2 gene in acetylated form and thereby enhanced its promoter activity.p300/CBP associated factor(PCAF) was found induced in RA-treated cells and enriched in the nucleus,which might contribute to the acetylation of p53 in the regulation of map2 gene.Conclusions Acetylated p53 may participate in regulating the expression of map2 in RA-induced differentiation of P19 cells.PCAF is possibly involved in this process by mediating the acetylation of p53.

In silico prediction of phytoconstituents from Ehretia laevis targeting TNF-αin arthritis

Objective Rheumatoid arthritis(RA)is an autoimmune disease involving the synovial lining of the major joints.Current therapies have noteworthy side effects.Our study involved in silico evaluation of Ehretia laevis(E.laevis)phytoconstituents targeting tumor necrosis factor-α(TNF-α).Methods Molecular docking studies performed to investigate the binding pattern of the plant E.laevis phytoconstituents along with the crystal structure of TNF-α(PDB ID:2 AZ5)using AutoDock Vina followed by a study of interacting amino acid residues and their influence on the inhibitory potentials of the active constituents.Further the pharmacokinetic profile and toxicity screening carried out using Swiss ADME and pk CSM.Results The docked results suggest that lupeol(-9.4 kcal/mol)andα-amyrin(-9.4 kcal/mol)has best affinity towards TNF-αcompared to standard drug thalidomide(-7.4 kcal/mol).The active chemical constituents represents better interaction with the conserved catalytic residues,leading to the inhibition/blockade of the TNF-α-associated signaling pathway in RA.Furthermore,pharmacokinetics and toxicity parameters of these phytochemicals were within acceptable limits according to ADMET studies.Conclusion The binding potential of phytoconstituents targeting TNF-αshowed promising results.Nonetheless,it encourages the traditional use of E.laevis and provides vital information on drug development and clinical treatment.

Production of Gel with Menthol, Benzocaine and Procaine HCl for Topical Application in Rheumatoid Arthritis Patients

Antirheurnatic and analgesics drugs are the most commonly prescribed medications for treatment of acute and chronic pain. Frequent application of these agents often causes adverse effects. So, in order to avoid the incidence of side effects, topical analgesics are treatment of choice for localized muscle pain. Topical analgesics offer the potential to provide the same analgesic relief provided by oral analgesics but with minimal adverse systemic effects. The aim of this study is to present the preparation and characterization of topical analgesic gel named ＂Russian water＂. Gel is composed of Menthol, Benzocaine, Procaine HCl as topical analgesic agents indicated for temporary relief of pain. Obtained results showed prolonged analgesic effect compared with liquid ethanol solution composed of the same components.

Leflunomide-induced acute liver failure: a case report

A 27-year-old male patient with rheumatoid arthritis was diagnosed with acute liver failure when he was taking leflunomide, a new immunosuppressant. This case illustrates the risk that leflunomide may lead to severe hepatotoxicity.

Effects of the Overall Alkaloid of a Traditional Chinese Medicine “Tongbiling” on the Cytokine Expression in Th1 and Th2 Cells of Rheumatoid Arthritis and Their Signaling Pathway

To investigate the effects of overall alkali of a traditional Chinese medicine “Tongbiling” (brucine and strychnine alkaloids in main) on the cytokines expression in Th1 and Th2 cells in the synovial fluid of patients with rheumatism arthritis and their signal pathway, the mononuclear cells in the synovial fluid (SFMC) of patients were isolated by Ficoll-Hypaque gradient centrifugation, and the CD3 + CD69 + and CD3 + HLA-DR antigen were analyzed by flow cytometry in comparison with those of the peripheral blood. The rest of cells were cultured after resuspension with RPMI 1640 culture medium. Phorbol 12,13-dibutyrate (PDB) and ionomycin were added successively into the culture with various concentration of overall alkali Tongbiling (TBL). After 4 h of cultivation, the expression of IFN-γ and IL-4 in CD3 + cells were analyzed by flow cytometry. The influence of overall alkali TBL (100?mg/L) on the intracellular calcium was investigated after Fluo-3/AM labeling and stimulation with PDB and ionomycin at 1, 2, 4 and 10?min, and the influence of TBL on the expression of CD3 + CD69 + cells were determined with stimulation of PDB for 24?h in the whole blood lymphocytes culture. It was found that the percentage of T cells bearing CD69 was significantly up-regulated (77%), while that of T cells bearing HLA-DR was 44% in the synovial mononucleated cells. After PDB and ionomycin stimulation, the expression of IFN-γ in CD3 + cells were up-regulated, but there was no change on the expression of IL-4 in CD3 + cells, indicating that ratio of Th1/Th2 was significantly increased and Th cells differentiate to Th1 cells in mainly. Four concentrations of overall alkaloid of TBL (200?mg/L, 100?mg/L, 50?mg/L, 25?mg/L) could down-regulated the expression of IFN-γ in CD3 + cells and the Th1/Th2 ratio obviously, but all the concentrations of the overall alkaloids had no effect on the expression of IL-4 in CD3 + cells. 100?mg/L concentration of the overall alkaloid did not down-regulate the intracellular calcium level. Each concentration of the overall alkaloid could down-regulated the expression CD69 obviously on the PDB-activated mouse T cells. It concluded from the above observations that the overall alkaloid of TBL could relieve the inflammatory and immune damages by suppressing the expression of Th1 type cytokines and Th1 cell differentiation, regulating the imbalance of Th1/Th2 cells and inhibiting the early activation of the T lymphocytes bearing CD69. There was no remarkable influence on the intracellular calcium signaling transduction pathway. The inhibitory effected on T cells to express IFN-γ might be due to the suppression of PKC-MAPK signaling pathway. From the standpoint of traditional Chinese medicine, this might be due to the regulation of “Yin” and “Yang” imbalance of joints to modify the pathological status in rheumatoid arthritis. This study provided an experimental basis for the application of overall alkaloids of TBL in the treatment of rheumatoid arthritis.

A DOUBLE BLIND OBSERVATION FOR THERAPEUTIC EFFECTS OF THE TONG LUO KAI BI TABLETS ON RHEUMATOID ARTHRITIS

The therapeutic effects of the Tong Luo Kai Bi Tablets [symbol: see text] in 120 patients with rheumatoid arthritis were observed in this clinical trial by the randomized double blind method. Both the observed group and the control group each had 60 patients. In the observed group treated with the Tong Luo Kai Bi Tablets, 1 case (1.7%) was cured clinically, 27 cases (45.0%) improved markedly, 26 cases (43.3%) improved, with a total effective rate of 90.0%. In the control group treated with Rheumatic Semen Strychni Tablets [symbol: see text], no case was cured, 16 cases (26.7%) improved markedly, 33 cases (55.0%) improved, with a total effective rate of 81.7%. Statistical data showed the Tong Luo Kai Bi Tablets had much better therapeutic effectiveness clinically than the Rheumatic Semen Strychni Tablets (P

Association Between IL-6 （Interleukin-6） and Iron Status in Rheumatoid Arthritis Patients

The study was performed to determine whether the srum concentrations of IL （interleukin）-6 are elevated in patients with RA （rheumatoid arthritis） and to investigate the relationship between IL-6 levels and iron status in RA patients. 95 serum samples were obtained, 70 of them from patients with RA who had visited the department of Rheumatology at Al-Sadder medical city in Najaf governorate （Iraq） and 25 age and sex-matched healthy controls. The authors assessed the clinical parameters of the disease, including ESR （erythrocyte sedimentation rate）, CRP （C-reactive protein）, and RF （rheumatoid factor）. Serum levels of iron and TIBC （total iron binding capacity） were measured spectrophotometrically, while TS% （transferrin saturation percentage） and transferrin concentration were calculated mathematically. Serum concentrations of IL-6 （interleukin-6） and ferritin were measured using an ELISA （enzyme-linked immunosorbent assay）. The results of serum concentration of IL-6 （interleukin-6） and ferritin were significantly elevated （P 〈 0.0001） in patients with RA compared to those of healthy controls. On the other hand, serum concentrations of iron, TIBC （total iron binding capacity）, TS% （transferrin saturation percentage） and transferrin concentration were significantly decreased in patients with RA compared with those of healthy controls. These findings suggest that anemia is the most frequent observations in patients with RA and mostly associative with increasing level of interleukin-6.

A Novel Design of a Metacarpal/MetatarsaI-Phalangeal Total Joint Replacement

Arthritis, most notably rheumatoid arthritis, can destroy the surfaces of the bones; the ideal solution for this is T JR （total joint replacement）, which would restore joint functionality, maintain correct aesthetics and eradicate pain for the patient. Current metacarpophalangeal TJR do not provide the normal biomechanical range of motion and functionality. The proposed design attempts to correct this through the use of design geometry and functional anatomy. Numerical analysis is used in conjunction with computational solid modeling to compare a one-piece silicone implant with the proposed T JR. Peak stresses during flexion for the proposed design did not exceed 1.2 MPa, where as soft implants approach 100 MPa to 1,000 MPa for peak stress values. The proposed design, due to high stress tolerances with low deformation, along with functionality and biomechanics, seems to be an appropriate replacement for one-piece silicone implant.

Expression of CC Chemokine Ligand 5 in Patients with Rheumatoid Arthritis and Its Correlation with Disease Activity and Medication

Objective To determine the levels of CC chemokine ligand 5 (CCL5) in serum and synovial fluid (SF) from patients with rheumatoid arthritis (RA) and their relations with disease activity and medication. Methods CCL5 in serum and SF was quantified by enzyme-linked immunosorbent assay (ELISA) in 28 RA patients and 21 osteoarthritis (OA) patients. In RA patients, the correlations of CCL5 levels in serum and SF with disease activity were analyzed. Meanwhile, the serum CCL5 levels among RA patients treated with disease-modifying antirheumatic drugs (DMARDs), Tripterygium Glucosides, and other Chinese herbs without disease-modifying effects were also compared. Results CCL5 levels in both serum and SF of RA patients were significantly higher than those of OA patients (P<0.05). Moreover, the level of CCL5 was higher in SF than that in serum of RA patients (P<0.01). Serum CCL5 level was correlated significantly with the number of swollen joints (r=0.3329, P<0.05), erythrocyte sedimentation rate (r=0.4001, P<0.05), and C reactive protein (r=0.3735, P<0.01). In addition, the level of CCL5 had a trend of lower in patients treated with DMARDs or Tripterygium Glucosides than those treated with other Chinese herbs, although the difference was not significant among those patients due to the small number of patients in each group. Conclusions In RA patients, the expression of CCL5 increases and correlates with some clinical and laboratory parameters of RA, which indicate that CCL5 plays an important role in RA and may serve as a useful marker of disease activity. DMARDs and Tripterygium Glucosides might exert their clinical effects through reducing CCL5 production in RA.

MODIFICATION OF TRYPTOPHAN RESIDUES OF IgGRF AND ITS EFFECT ON THE ADSORPTION CAPACITY

Tryptophan residues of IgGRF from rheumatoid arthritis patient were modified with N-Bromosuccinimide (NBS) and the product of modification was characterized by UV-spectrum、Fluorescence emission spectrum and CD-spectrum. The corresponding adsorption capacity of immobilized ssDNA immunoadsorbent for IgGRF was enhanced from 46% to 86%, This result indicates the tryptophan residue is essential for the interaction between ssDNA and IgGRF .and ionic-bonding plays an important role in adsorption.

Rheumatoid arthritis and ankylosing spondylitis occurring together: a case report

Ankylosing spondylitis (AS) and rheumatoid arthritis (RA) are two different rheumatoid immune diseases. It is not common that the two diseases occur simultaneously in the same patient in clinical practice. Here, we reported a case of meeting the diagnostic criteria for both AS and RA, who was treated with integrated traditional Chinese and Western medicine and received apparent improvement.

Bayesian Variable Selection via Perfect Gibbs Coupler Using Approximate Bounds

Variable selection is one of the most fundamental problems in regression analysis. By sampling from the posterior distributions of candidate models, Bayesian variable selection via MCMC （Markov chain Monte-Carlo） is effective to overcome the computational burden of all-subset variable selection approaches. However, the convergence of the MCMC is often hard to determine and one is often not sure about if obtained samples are unbiased. This complication has limited the application of Bayesian variable selection in practice. Based on the idea of CFTP （coupling from the past）, perfect sampling schemes have been developed to obtain independent samples from the posterior distribution for a variety of problems. Here the authors propose an efficient and effective perfect sampling algorithm for Bayesian variable selection of linear regression models, which independently and identically sample from the posterior distribution of the model space and can efficiently handle thousands of variables. The effectiveness of the authors＇ algorithm is illustrated by three simulation studies, which have up to thousands of variables, the authors＇ method is further illustrated in SNPs （single nucleotide polymorphisms） association study among RA （rheumatoid arthritis） patients.