肌骨超声对类风湿关节炎疾病分期的评估价值及血清SOD、PCSK9表达的关联性

本研究探讨肌骨超声对类风湿关节炎疾病分期的评估价值及类风湿关节炎与血清超氧化物歧化酶(SOD)、前蛋白转化酶枯草溶菌素9(PCSK9)表达的关系.选取类风湿关节炎患者140例作为观察组,同时选取体检健康者100例作为对照组,检测两组血清SOD、PCSK9的表达水平,给予肌骨超声检查.结果 显示:观察组血清SOD的表达水...     

简化关节超声评分在类风湿关节炎患者中的应用

探讨简化关节超声评分与类风湿关节炎(RA)患者关节炎症、骨破坏的关系及病情转归评估价值。选取112例RA患者作为研究对象,均进行3个月强化治疗,根据病情转归情况分为有效组(n=95)和无效组(n=17)。有效组患者DAS28评分、血沉(ESR)、C-反应蛋白(CRP)、Wnt抑制因子Dickkopf-1、核因子κB受体激活蛋白配体(RANKL)、简化超声评分高于无效组患者,且各指标均为RA病情转归影响因素(P<0.05);RA患者简化关节超声评分与DAS28评分、关节炎症指标(ESR、CRP)、骨破坏指标(Dickkopf-1、RANKL)呈正相关关系(P<0.05);简化关节超声评分项和最终评分评估RA患者病情转归的AUC均高于0.7。简化关节超声评分与RA患者关节炎症、骨破坏有关,且可为RA达标治疗病情转归评估提供有力参考,为及时采取有效、个体化治疗提供依据。     

超声造影参数对宫颈癌新辅助化疗疗效的评估价值

本文对超声造影参数对宫颈癌新辅助化疗疗效的评估价值进行了分析。选取2016年3月~2018年3月本院宫颈癌新辅助化疗患者200例,所有患者均给予紫杉醇+顺铂(TP)方案化疗治疗并行超声造影检查,分析超声造影参数:开始增强时间(AT)、达峰时间(TTP)、峰值强度(PI)、基础强度(BI),以及增强强度(EI)对新辅助化疗疗效的评估价值。结果显示,完全缓解(CR)12例、部分缓解(PR)136例、病情稳定(SD)36例、恶化(PD)16例,化疗无效者148例,有效率74.00%。化疗无效者和有效者BI、EI化疗前后比较,无效者化疗前后AT、TTP、PI比较,差异无统计学意义(P>0.05),有效者化疗后:AT、TTP明显低于化疗前,PI明显高于化疗前;无效者化疗后:AT、TTP明显高于有效者,PI明显低于有效者,有效者AT、TTP下降值及PI升高值明显高于无效,差异有统计学意义(P<0.05)。ROC曲线分析显示评估宫颈癌新辅助化疗有效性的敏感度、特异度、准确度:AT下降值以>1.0 s为临界值时,为87.84%、80.77%、86.00%,TTP下降值以>1.5 s为临界值时,为89.19%、84.62%、88.00%,PI升高值以>2.0 dB为临界值时,为85.14%、76.92%、83.00%,三者联合时为97.30%、96.15%、97.00%,三者联合时明显高于三者单独时,差异有统计学意义(P<0.05)。本文证实了超声造影参数中AT、TTP、PI与宫颈癌新辅助化疗疗效有关,并可作为评估患者化疗有效性的指标,且三者联合时评估效能更佳。     

DCE-MRI检查五项参数与类风湿关节炎疾病活动度关系及临床价值

探究动态增强磁共振成像(DCE-MRI)检查五项参数与类风湿关节炎(RA)患者疾病活动度的相关性及联合预测近期预后的临床价值.选取105例RA患者作为研究对象,均根据治疗6个月后治疗反应情况分为预后良好组(80例)与预后不良组(25例).结果 发现,DCE-MRI检查参数RE、MRE、ME、Slopemax、 AUC随...     

对211例类风湿关节炎患者微量元素的测定

用同位素激发Ｘ射线荧光分析对２１１例类风湿关节炎患者发中１０种常量及微量元素测定，以探索类风湿关节病与微量元素之间的关系．结果表明：全部女性患者发锌含量明显降低，除３０～３９岁及５０～５９岁年龄组Ｐ＜０．０５外，其余各组均Ｐ＜０．０１。而２０～２９岁男性组患者发锌含量也低，Ｐ＜０．０１。男女患者各组发锶含量较对照组均低，且有明显差异（除男性２０～２９岁组及５０￣５９岁组Ｐ＜０．０５，其余各组均ｐ＜０．０１）。提示类风湿关节病患者发中锌、锶含量较正常人低。因此，如临床上补充锌和锶元素，可能是有效治疗类风湿关节病的新途径．     

以琼脂凝胶固定热聚IgG制备类风湿关节炎免疫吸附剂的研究

以环氧氯丙烷对琼脂凝胶珠进行活化反应后键联热聚ＩｇＧ,制成一种新型类风湿关节炎免疫吸附剂。确定了最佳制备条件,使凝胶上环氧基的含量达１１０μｍｏｌ／ｇ,对热苯ＩｇＧ的固定量达６ｍｇ／ｇ。在体外条件下吸附剂对三种类风湿因子ＩｇＭＲＦ,ＩｇＧＲＦ及ＩｇＡＲＦ的吸附量分别达３４００,２２５０和２４００ＩＵ／ｇ,具有良好的应用前景。     

京尼平衍生物的合成及其抗类风湿关节炎活性

以京尼平(Genipin, GEP)为先导物,设计并合成了4个C-10位含螺环氨甲酸酯片段的GEP衍生物(6a～6d),其结构经HR-MS(ESI),¹H NMR和¹³C NMR确证。采用CCK-8法测试了目标化合物对人类风湿关节炎成纤维滑膜细胞(MH7A)增殖的抑制作用。结果表明：化合物6a的抗增殖活性最强,在200μmol/L下的抑制率为75.81%,具有进一步结构优化的价值。     

类风湿关节炎免疫吸附剂载体-碳化树脂的制备及性能研究

以苯乙烯、丙烯腈为单体,二乙烯苯为交联剂,添加一定量的致孔剂,在水相中采用分步聚合工艺制成高分子树脂,再经高温碳化制备碳化树脂.研究结果表明,单体交联度为35%时,碳化树脂比表面积达到601m2/g.用该碳化树脂包埋DNA后对类风湿因子IgG、IgM、IgA的吸附清除率达到了52.9%、58.5%、37.0%.     

抗-CCP和RF联合检测对RA的临床诊断价值探讨

目的分析抗环瓜氨酸肽抗体与类风湿因子联合检测对类风湿性关节炎的临床诊断效果。方法选2014年10月至2016年12月在广东省茂名市电白区中医院就诊的类风湿性关节炎患者100例(研究组),及同时期健康体检者100例(对照组)为研究对象,观察抗环瓜氨酸肽抗体与类风湿因子阳性检出率。结果研究组患者抗环瓜氨酸肽抗体与类风湿因子的阳性检出率均要高于对照组患者,两组数据之间进行比较,差异有统计学意义(P0.05)。结论抗环瓜氨酸肽抗体与类风湿因子联合检测的灵敏度、特异度较高,是作为鉴别类风湿性关节炎疾病的重要指标,值得临床推广及应用。     

麻醉前快速超声评估及术中经食道超声心动图监测对急危重患者手术麻醉的临床指导作用

本文探讨麻醉前快速超声评估及术中经食道超声心动图监测对急危重患者的手术麻醉管理是否有临床指导意义.60例急危重手术患者根据随机数字表法分为对照组(麻醉医生经验评估处理)和观察组(经胸超声和经食道超声扫查评估处理).比较两组患者液体出入量、血管活性药物使用种类及剂量、术后拔管时间等情况.研究发现,观察组患者术中使用血管活...     

Exploration and Evaluation of Therapeutic Efficacy of Drug‐Free Macromolecular Therapeutics in Collagen‐Induced Rheumatoid Arthritis Mouse Model

Monoclonal antibodies (mAbs) against B cell antigens are extensively used in the treatment of rheumatoid arthritis (RA). The B cell depletion therapy prevents RA symptoms and/or alleviates existing inflammation. The previously established two‐step drug‐free macromolecular therapeutics (DFMT) is applied in the treatment of collagen‐induced rheumatoid arthritis in a collagen‐induced rheumatoid arthritis mouse model. DFMT is a B cell depletion strategy utilizing Fab′ fragment of anti‐CD20 mAb for biorecognition and receptor crosslinking to induce B cell apoptosis. DFMT is composed from two nanoconjugates: 1) bispecific engager, Fab′‐MORF1 (anti‐CD20 Fab′ fragment conjugated with morpholino oligonucleotide MORF1), and 2) a crosslinking (effector) component P‐(MORF2)_X (N‐(2‐hydroxypropyl)methacrylamide copolymer grafted with multiple copies of complementary morpholino oligonucleotide MORF2). The absence of Fc fragment has the potential to avoid development of resistance and infusion‐related reactions. DFMT produces B cell depletion, keeps the RA score low for more than 100 days, and shows minimal cartilage and bone erosion and inflammatory cell infiltration. Further improvements will be explored to optimize DFMT strategy in autoimmune disease treatment.     

Towards Better Sinomenine-Type Drugs to Treat Rheumatoid Arthritis: Molecular Mechanisms and Structural Modification

Sinomenine is the main component of the vine Sinomenium acutum. It was first isolated in the early 1920s and has since attracted special interest as a potential anti-rheumatoid arthritis (RA) agent, owing to its successful application in traditional Chinese medicine for the treatment of neuralgia and rheumatoid diseases. In the past few decades, significant advances have broadened our understanding of the molecular mechanisms through which sinomenine treats RA, as well as the structural modifications necessary for improved pharmacological activity. In this review, we summarize up-to-date reports on the pharmacological properties of sinomenine in RA treatment, document their underlying mechanisms, and provide an overview of promising sinomenine derivatives as potential RA drug therapies.     

Functional Analysis of Autoantibody Signatures in Rheumatoid Arthritis

For the identification of antigenic protein biomarkers for rheumatoid arthritis (RA), we conducted IgG profiling on high density protein microarrays. Plasma IgG of 96 human samples (healthy controls, osteoarthritis, seropositive and seronegative RA, n = 24 each) and time-series plasma of a pristane-induced arthritis (PIA) rat model (n = 24 total) were probed on AIT’s 16k protein microarray. To investigate the analogy of underlying disease pathways, differential reactivity analysis was conducted. A total of n = 602 differentially reactive antigens (DIRAGs) at a significance cutoff of p < 0.05 were identified between seropositive and seronegative RA for the human samples. Correlation with the clinical disease activity index revealed an inverse correlation of antibodies against self-proteins found in pathways relevant for antigen presentation and immune regulation. The PIA model showed n = 1291 significant DIRAGs within acute disease. Significant DIRAGs for (I) seropositive, (II) seronegative and (III) PIA were subjected to the Reactome pathway browser which also revealed pathways relevant for antigen presentation and immune regulation; of these, seven overlapping pathways had high significance. We therefore conclude that the PIA model reflects the biological similarities of the disease pathogenesis. Our data show that protein array analysis can elucidate biological differences and pathways relevant in disease as well be a useful additional layer of omics information.     

Breathing Micelles for Combinatorial Treatment of Rheumatoid Arthritis

Breathing process involves inhalation and exhalation of different gases in animals. The gas exchange of the breathing process plays a critical role in maintaining the physiological functions of living organisms. Although artificial breathing materials exhibiting volume expansion and contraction upon alternate exposure to different gases have been well explored, those being able to realize the gas exchange remain elusive. Herein, we report breathing micelles (BM) capable of inhaling nitric oxide (NO) and exhaling carbon monoxide (CO), both of which are endogenous gaseous signaling molecules. We demonstrate that BM can simultaneously scavenge overproduced NO and attenuate proinflammatory cytokines in lipopolysaccharide (LPS)-challenged macrophage cells. In vivo studies revealed that BM outperformed conventional nonsteroidal anti-inflammatory drugs such as dexamethasone (Dexa) in treatment of rheumatoid arthritis (RA) in adjuvant-induced arthritis (AIA) rats, likely due to the combinatorial effect of NO depletion, CO-mediated deactivation of inducible NO synthase (iNOS) and activation of heme oxygenase-1 (HO-1). This work provides new insights into artificial BM for potential biomedical applications.     

Nano-Based Co-Delivery System for Treatment of Rheumatoid Arthritis

A systemic autoimmune condition known as rheumatoid arthritis (RA) has a significant impact on patients’ quality of life. Given the complexity of RA’s biology, no single treatment can totally block the disease’s progression. The combined use of co-delivery regimens integrating various diverse mechanisms has been widely acknowledged as a way to make up for the drawbacks of single therapy. These days, co-delivery systems have been frequently utilized for co-treatment, getting over drug limitations, imaging of inflammatory areas, and inducing reactions. Various small molecules, nucleic acid drugs, and enzyme-like agents intended for co-delivery are frequently capable of producing the ability to require positive outcomes. In addition, the excellent response effect of phototherapeutic agents has led to their frequent use for delivery together with chemotherapeutics. In this review, we discuss different types of nano-based co-delivery systems and their advantages, limitations, and future directions. In addition, we review the prospects and predicted challenges for the combining of phototherapeutic agents with conventional drugs, hoping to provide some theoretical support for future in-depth studies of nano-based co-delivery systems and phototherapeutic agents.     

Gene Interaction Network Analysis Reveals IFI44L as a Drug Target in Rheumatoid Arthritis and Periodontitis

Simple SummaryIn spite of substantial investigation, the biological link between periodontitis and rheumatoid arthritis remains unexplained. This study intended to correlate periodontitis and rheumatoid arthritis gene expression patterns to find shared targets for both the disease. We identified the differentially expressed genes (DEGs) in periodontitis and rheumatoid arthritis. The network was built by integrating DEGs and ranking the genes using GeneMANIA. FINDSITEcomb2.0 was used to find a possible inhibitor for the top-ranked gene. Further, the binding effectiveness and protein-ligand complex stability were then determined by molecular docking and molecular dynamics. The network analysis showed IFI44L as a highly ranking gene implicated in most immunological pathways. A virtual screening of 6507 compounds revealed vemurafenib as the best candidate for the IFI44L target. Molecular docking and molecular dynamics modelling revealed the stability of the IFI44L-vemurafenib complex, which suggest IFI44L is potential target and vemurafenib could be the better candidate to treat both diseases.AbstractObjective: Despite extensive research on periodontitis and rheumatoid arthritis, the underlying molecular connectivity between these condition remains largely unknown. This research aimed to integrate periodontitis and rheumatoid arthritis gene expression profiles to identify interconnecting genes and focus to develop a common lead molecule against these inflammatory conditions. Materials and Methods: Differentially expressed genes (DEGs) of periodontitis and rheumatoid arthritis were identified from the datasets retrieved from the Gene Expression Omnibus database. The network was constructed by merging DEGs, and the interconnecting genes were identified and ranked using GeneMANIA. For the selected top ranked gene, the potential inhibitor was searched using FINDSITE^comb2.0. Subsequently, the molecular docking and molecular dynamics were performed to determine the binding efficiency and protein-ligand complex stability, respectively. Results: From the network analysis, IFN-induced protein 44-like (IFI44L) was identified as a top ranked gene involved in most of the immunological pathway. With further virtual screening of 6507 molecules, vemurafenib was identified to be the best fit against the IFI44L target. The binding energy and stability of IFI44L with vemurafenib were investigated using molecular docking and molecular dynamics simulation. Docking results show binding energy of −7.7 Kcal/mol, and the simulation results show stability till 100 ns. Conclusions: The identified IFI44L may represent a common drug target for periodontitis and rheumatoid arthritis. Vemurafenib could be a potent anti-inflammatory drug for both diseases.     

High-Throughput Metabolomics Integrated Network Pharmacology Reveals the Underlying Mechanism of Paeoniae Radix Alba Treating Rheumatoid Arthritis

Objective: The mechanism of action and potential targets of Paeoniae Radix Alba (Baishao, B) in the treatment of adjuvant-induced arthritis (AIA) rats are explained using metabolomics and network pharmacology techniques, and the research evidence for the development of anti-rheumatoid arthritis (RA) drugs is enriched. Methods: The rats were injected with Freund’s complete adjuvant (CFA) to induce arthritis. We then measured the general physical characteristics, examined their X-rays and histopathology to evaluate the pathological condition of the inflammation models, and conducted metabolomics studies on the change in urine metabolism caused by CFA. The lyophilized powder of B at a dose of 2.16 g/kg was orally administered to the rats continuously for 28 days, and the therapeutic effect was evaluated. Network pharmacology prediction shows that B contains the target action of the ingredient, and the simulation of the target molecular docking, in combination with the metabolomics analysis results, shows that B has a potential role in the treatment of AIA rats. Results: B can reduce the paw swelling and pathological changes in rats caused by CFA, reverse the levels of 12 urine biomarkers, and regulate histidine metabolism, phenylalanine metabolism, arginine, proline metabolism, pyrimidine metabolism, etc. The prediction of the active ingredient target in B indicates that it may act as an inflammatory signaling pathway in anti-RA, among them being paeoniflorin, palbinone, beta-sitosterol, kaempferol, and catechin, which are the significant active ingredients. Conclusion: The metabolomics results revealed the markers and metabolic mechanisms of urinary metabolic disorders in rats with AIA, demonstrated the efficacy of the therapeutic effect of B, and identified the key ingredients in B, providing theoretical support for the subsequent development and utilization of B.     

The Novel Role of MIF in the Secretion of IL-25, IL-31, and IL-33 from PBMC of Patients with Rheumatoid Arthritis

Rheumatoid arthritis (RA) is an autoimmune inflammatory joint disease with complex pathogenesis associated with cytokine dysregulation. Macrophage migration inhibitory factor (MIF) plays a role in systemic inflammation and joint destruction in RA and could be associated with the secretion of other immune-modulatory cytokines such as IL-25, IL-31, and IL-33. For the above, our main aim was to evaluate the IL-25, IL-31, and IL-33 secretion from recombinant human MIF (rhMIF)-stimulated peripheral blood mononuclear cells (PBMC) of RA patients. The rhMIF and lipopolysaccharide (LPS) plus rhMIF stimuli promote the secretion of IL-25, IL-31, and IL-33 (p < 0.05) from PBMC of RA patients. The study groups, the different stimuli, and the interaction between both showed a statistically significant effect on the secretion of IL-25 (p < 0.05) and IL-31 (p < 0.01). The study of the effect of the RA patient treatments and their interaction with the effect of stimuli did not show an interaction between them. In conclusion, our study generates new evidence for the role of MIF in the secretion of IL-25, IL-31, and IL-33 and its immunomodulatory effect on RA.     

Formulation of Topical Dosage Forms Containing Synthetic and Natural Anti-Inflammatory Agents for the Treatment of Rheumatoid Arthritis

Topical anti-inflammatory and analgesic effect for the treatment of rheumatoid arthritis is of major interest because of their fewer side effects compared to oral therapy. The purpose of this study was to prepare different types of topical formulations (ointments and gels) containing synthetic and natural anti-inflammatory agents with different excipients (e.g.,: surfactants, gel-forming) for the treatment of rheumatoid arthritis. The combination of Non-Steroidal Anti-Inflammatory Drugs (NSAIDs), diclofenac sodium, a topical analgesic agent methyl salicylate, and a lyophilized extract of Calendula officinalis with antioxidant effect were used in our formulations. The aim was to select the appropriate excipients and dosage form for the formulation in order to enhance the diffusion of active substances and to certify the antioxidant, analgesic, and anti-inflammatory effects of these formulations. To characterize the physicochemical properties of the formulations, rheological studies, and texture profile analysis were carried out. Membrane diffusion and permeability studies were performed with Franz-diffusion method. The therapeutic properties of the formulations have been proven by an antioxidant assay and a randomized prospective study that was carried out on 115 patients with rheumatoid arthritis. The results showed that the treatment with the gel containing diclofenac sodium, methyl salicylate, and lyophilized Calendula officinalis as active ingredients, 2-propenoic acid homopolymer (Synthalen K) as gel-forming excipient, distilled water, triethanolamine, and glycerol had a beneficial analgesic and local anti-inflammatory effect.