Synergistic chemotherapy/PTT/oxygen enrichment by multifunctional liposomal polydopamine nanoparticles for rheumatoid arthritis treatment

Amultifunctional liposomal polydopamine nanoparticle(MPM@Lipo)was designed in this study,to combine chemotherapy,photothermal therapy(PTT)and oxygen enrichment to clear hyperproliferating inflammatory cells and improve the hypoxic microenvironment for rheumatoid arthritis(RA)treatment.MPM@Lipo significantly scavenged intracellular reactive oxygen species and relieved joint hypoxia,thus contributing to the repolarization of M1 macrophages into M2 phenotype.Furthermore,MPM@Lipo could accumulate at inflammatory joints,inhibit the production of inflammatory factors,and protect cartilage in vivo,effectively alleviating RA progression in a rat adjuvant-induced arthritis model.Moreover,upon laser irradiation,MPM@Lipo can elevate the temperature to not only significantly obliterate excessively proliferating inflammatory cells but also accelerate the production of methotrexate and oxygen,resulting in excellent RA treatment effects.Overall,the use of synergistic chemotherapy/PTT/oxygen enrichment therapy to treat RA is a powerful potential strategy.

Research progress of local characteristic drugs for treatment of rheumatoid arthritis in Xinjiang

Rheumatoid arthritis(RA)is a systemic autoimmune disease characterized by synovitis.This disease tends to recur,persist,and is difficult to cure.The pathogenesis of RA is complex.Currently,the commonly used treatments for RA—non-steroidal anti-inflammatory drugs(NSAIDs),disease-modifying anti-rheumatic drugs(DMARDs),glucocorticoids,and immunosuppressants—have notable side effects with long-term use and may be ineffective for some patients.Therefore,it is crucial to find drugs with limited side effects and significant curative effects.Xinjiang's local characteristic drugs have a long history,abundant resources,and are known for their safety and effectiveness in treating RA.In recent years,many studies have reported on the mechanisms of action and therapeutic effects of Xinjiang's local characteristic drugs on RA.This article reviews the pathogenesis of RA,as well as the research progress and treatment characteristics of Xinjiang-featured drugs.

Application of Wax Therapy in Pain Care of Patients with Rheumatoid Arthritis

Objective: To investigate the effect of wax therapy in pain care of patients with rheumatoid arthritis. Methods: Convenience sampling method was used to select inpatients with rheumatoid arthritis admitted to the rheumatology and immunology department of a 3A hospital in Jingzhou City. 75 patients from January 2021 to June 2021 were selected as the control group, and 75 patients from January 2022 to June 2022 were selected as the observation group. The control group was given routine nursing, and the observation group was implemented wax therapy nursing on the basis of the control group. The relief of clinical symptoms (morning stiffness time, pain score) and quality of life score of the two groups were observed. Results: After intervention, there was statistical significance between the two groups (P Conclusion: Wax therapy can improve the time of morning stiffness, the degree of pain and the quality of life of patients with rheumatoid arthritis.

An intra-articular injectable phospholipids-based gel for the treatment of rheumatoid arthritis

Rheumatoid arthritis(RA)is a chronic inflammatory and destructive arthropathy with a high deformity rate.Despite numerous studies and clinical trials,no curative treatment is available for large weight-bearing joints.Intra-articular(IA)injections could deliver high concentrations of drug to the afflicted joint and improve the drug efficacy while reducing systemic toxicity.However,free drugs are rapidly cleared from synovial fluid and do not significantly halt the progression of joint disease.Herein,a phospholipids-based controlledrelease gel was prepared for sustained IA delivery of celastrol(CEL)and the therapeutic efficiencywas evaluated in a rheumatoid arthritis rabbitmodel.The CEL-loaded gel(CEL-gel)contained up to 70%phospholipids yetwas easy to inject.After injecting into the joint cavity,CEL-gel achieved sol to gel phase transition without special stimuli and gelling agent.In vitro release and in vivo pharmacokinetic studies evidenced the stable and sustained release action of CEL-gel.A single IA injection of CEL-gel could maintain therapeutic efficiency for about 25 d and showed much better anti-arthritic efficacy compared to repeated injections of free drug solution(CEL-sol).Furthermore,the IA injection of CEL-gel greatly reduced the systemic toxicity of CEL.With good biocompatibility and biodegradability,CEL-gel might be a promising IA drug delivery system.

Difficult-to-treat rheumatoid arthritis treated with Abatacept combined with Baricitinib:A case report

BACKGROUND Sporadic cases of rheumatoid arthritis(RA)due to unsatisfactory responses to Abatacept(ABT)have been reported;however,the rescue therapy has not been finalized.Here,we present a case with difficult-to-treat RA(D2T RA)that was resistant to either a single ABT or a Janus kinase(JAK)inhibitor(Tofacitinib),but improved with a combination of ABT and JAK inhibitor(Baricitinib,BAT).CASE SUMMARY A 46-year-old Chinese woman who had RA for ten years that was resistant to Tocilizumab,Etanercept,Adalimumab,and ABT.According to the European League Against Rheumatism definition,the patient was diagnosed with D2T RA.It was then improved with a combination of ABT and a JAK inhibitor BAT.CONCLUSION ABT combined with BAT may be an acceptable strategy for treating D2T RA.

Traditional Chinese Medicine as a Treatment for Rheumatoid Arthritis:From Empirical Practice to Evidence-Based Therapy

Rheumatoid arthritis(RA)is a common autoimmune condition with an elusive etiology.Conventional and biological disease-modifying drugs sometimes fail or produce only partial responses.Traditional Chinese medicine(TCM)has long been used in China as a treatment for RA and is achieving everincreasing acceptance worldwide.TCM treatments are traditionally guided by the theory of treatment based on TCM syndrome differentiation;however,they remain a matter of empirical practice relying on TCM theories and doctors’own experience,which places severe restrictions on worldwide TCM application.Nevertheless,TCM is a treasure trove for drug discovery,particularly as a treatment for complicated human conditions.The discoveries of artemisinin as a treatment for malaria and of TCM–arsenic trioxide(As2O3)combination therapy as a treatment for acute promyelocytic leukemia(APL)are excellent examples of the great value of TCM.Regarding RA treatments,many Chinese medicinal herbs and their formulas,extracts,ingredients,and even single compounds have been used in clinical applications.Several Chinese proprietary medicines(CPMs)derived from TCM formulas or herbal bioactive components,such as the controlled-release ZhengQingFengTongNing(ZQFTN)Tablets,Tripterygium Glycoside Tablets,and Total Glucosides of Peony(TGP)Capsules,have been included in the National Health Insurance Directory of China,and show comparable therapeutic efficacies to those of western chemical drugs with fewer side effects.As TCM research has advanced,particularly in the use of multidisciplinary technologies,the scientific foundations and characteristics of the use of TCM to treat RA have been revealed,and the quality of TCM treatments have been increasingly enhanced.However,TCM generally lacks sufficient clinical and laboratory data to be consistent with international standards for quality,safety,and efficacy in order to support its application worldwide.Therefore,intensive basic and clinical studies on TCM are required.In particular,investigations that use cutting-edge technologies in analytical chemistry,biology,and biomedical sciences,and the development of randomized clinical trials(RCTs)and personalized pragmatic randomized controlled trials(PPRCTs)are necessary.Researchers should also collaborate to advance TCM from empirical practice to evidence-based therapy,thus consistently promoting TCM development and globalization in a vital,beneficial,and contributable manner.

Blood glucose changes surrounding initiation of tumor-necrosis factor inhibitors and conventional disease-modifying anti-rheumatic drugs in veterans with rheumatoid arthritis

AIM To determine the scope of acute hypoglycemic effects for certain anti-rheumatic medications in a large retrospective observational study. METHODS Patients enrolled in the Veterans Affairs Rheumatoid Arthritis (VARA) registry were selected who, during follow-up, initiated treatment with tumor necrosis factor inhibitors (TNFi's, including etanercept, adalimumab, infliximab, golimumab, or certolizumab), prednisone, or conventional disease-modifying anti-rheumatic drugs(DMARDs), and for whom proximate random blood glucose (RBG) measurements were available within a window 2-wk prior to, and 6 mo following, medication initiation. Similar data were obtained for patients with proximate values available for glycosylated hemoglobin A1C values within a window 2 mo preceding, and 12 mo following, medication initiation. RBG and A1C measurements were compared before and after initiation events using paired t-tests, and multivariate regression analysis was performed including established comorbidities and demographics.RESULTS Two thousands one hundred and eleven patients contributed at least one proximate measurement surrounding the initiation of any examined medication. A significant decrease in RBG was noted surrounding 653 individual hydroxychloroquine-initiation events(-3.68 mg/dL, P = 0.04), while an increase was noted for RBG surrounding 665 prednisone-initiation events(+5.85 mg/d L, P < 0.01). A statistically significant decrease in A1C was noted for sulfasalazine initiation, as measured by 49 individual initiation events(-0.70%, P < 0.01). Multivariate regression analyses, using methotrexate as the referent, suggest sulfasalazine (β =-0.58, P = 0.01) and hydroxychloroquine(β =-5.78, P = 0.01) use as predictors of lower post-medicationinitiation RBG and A1C values, respectively. Analysis by drug class suggested prednisone (or glucocorticoids) as predictive of higher medication-initiation event RBG among all start events as compared to DMARDs, while this analysis did not show any drug class-level effect for TNFi. A diagnosis of congestive heart failure(β = 4.69, P = 0.03) was predictive for higher post-initiation RBG values among all medication-initiation events.CONCLUSION No statistically significant hypoglycemic effects surrounding TNFi initiation were observed in this large cohort. Sulfasalazine and hydroxychloroquine may have epidemiologically significant acute hypoglycemic effects.

Anti-and non-tumor necrosis factor-α-targeted therapies effects on insulin resistance in rheumatoid arthritis,psoriatic arthritis and ankylosing spondylitis

In addition toβ-cell failure with inadequate insulin secretion,the crucial mechanism leading to establishment of diabetes mellitus(DM)is the resistance of target cells to insulin,i.e.insulin resistance(IR),indicating a requirement of beyond-normal insulin concentrations to maintain euglycemic status and an ineffective strength of transduction signaling from the receptor,downstream to the substrates of insulin action.IR is a common feature of most metabolic disorders,particularly type II DM as well as some cases of type I DM.A variety of human inammatory disorders with increased levels of proinflammatory cytokines,including tumor necrosis factor(TNF)-α,interleukin(IL)-6 and IL-1β,have been reported to be associated with an increased risk of IR.Autoimmunemediated arthritis conditions,including rheumatoid arthritis(RA),psoriatic arthritis(PsA)and ankylosing spondylitis(AS),with the involvement of proinflammatory cytokines as their central pathogenesis,have been demonstrated to be associated with IR,especially during the active disease state.There is an increasing trend towards using biologic agents and small molecule-targeted drugs to treat such disorders.In this review,we focus on the effects of anti-TNF-α-and non-TNF-α-targeted therapies on IR in patients with RA,PsA and AS.Anti-TNF-αtherapy,IL-1 blockade,IL-6 antagonist,Janus kinase inhibitor and phosphodiesterase type 4 blocker can reduce IR and improve diabetic hyper-glycemia in autoimmune-mediated arthritis.

Effect of Stereoscopic Comprehensive Therapy of Zhuang Medicine on Inflammatory Factor IL-6 in Patients with Rheumatoid Arthritis

Objective:To study the effect of Stereoscopic Comprehensive of Therapy Zhuang Medicine on IL-6 in serum of patients with rheumatoid arthritis.Methods:Sixty rheumatoid arthritis patients who met the inclusion criteria were selected and randomly divided into a control group and a treatment group using a random number table.Among them,30 cases in the control group were treated with Western medicine,and 30 cases in the treatment group were treated with Western medical and Stereoscopic Comprehensive Therapy of Zhuang Medicine.The observation period was 8 weeks.Results:After 8 weeks of treatment,the level of IL-6 in the treatment group and the control group decreased,and the treatment group was better than the control group(P<0.05).Conclusion:The Stereoscopic Comprehensive of Zhuang Medicine can reduce the level of IL-6 in the serum of patients with rheumatoid arthritis,and has a good regulating effect on the inflammation of rheumatoid arthritis.

Interleukins and interleukin receptors in rheumatoid arthritis: Research, diagnostics and clinical implications

Rheumatoid arthritis(RA) is an autoimmune disease, resulting in a chronic, systemic inflammatory disorder. It may affect many tissues and organs, but it primarily affects the flexible joints. In clinical practice patient care generates many questions about diagnosis, prognosis, and treatment. It is challenging for health care specialists to keep up to date with the medical literature. This review summarizes the pathogenesis, the polymorphisms of interleukin and interleukin genes and the standard available and possible future immunologictargets for RA treatment. The identification of diseaseassociated interleukin and interleukin receptor genes can provide precious insight into the genetic variations prior to disease onset in order to identify the pathways important for RA pathogenesis. The knowledge of the complex genetic background may prove useful for developing novel therapies and making personalized medicine based on the individual's genetics.

Perioperative management of the patient with rheumatoid arthritis

A multidisciplinary approach is required to care for patients with rheumatoid arthritis(RA)in the perioperative period.In preparation for surgery,patients must have a cardiovascular risk assessment performed due to the high risk of heart disease in patients with RA.Treatment of RA is with immunomodulatory medications,which present unique challenges for the perioperative period.Currently,there is no consensus on how to manage disease modifying antirheumatic drug(DMARD)therapy in the perioperative setting.Much of the data to guide therapy is based on retrospective cohort data.Choices regarding DMARDs require an individualized approach with collaboration between surgeons and rheumatologists.Consensus regarding biologic therapy is to hold the therapy in the perioperative period with the length of time dictated by the half-life of the medication.Special attention is required at the time of surgery for potential need for stress dose steroids.Further,there must be close communication with anesthesiologists in terms of airway management particularly in light of the risk for cervical spine disease.There are no consensus guidelines regarding the requirement for cervical spine radiographs prior to surgery.However,history and exam alone cannot be relied upon toidentify cervical spine disease.Patients with RA who undergo joint replacement arthroplasty are at higher risk for infection and dislocation compared to patients with osteoarthritis,necessitating particular vigilance in postoperative follow up.This review summarizes available evidence regarding perioperative management of patients with RA.

Targeting the resolution pathway of inflammation using Ac2–26 peptide-loaded PEGylated lipid nanoparticles for the remission of rheumatoid arthritis

Rheumatoid arthritis(RA)is a common autoimmune disease characterized by joint inflammation and immune dysfunction.Although various therapeutic approaches have been utilized for the treatment of RA in clinical applications,the low responsiveness of RA patients and undesired systemic toxicity are still unresolved problems.Targeting the resolution pathway of inflammation with pro-resolving mediators would evoke the protective actions of patient for combating the inflammation.Ac2–26,a 25-amino acid peptide derived from Annexin A(a pro-resolving mediator),has shown good efficacy in the treatment of inflammatory disorders.However,the low bioavailability of Ac2–26 peptides hinders their efficacy in vivo.In this paper,we formed PEGylated lipid nanoparticles(LDNPs)by the co-assembly of l-ascorbyl palmitate(L-AP)and N-(carbonyl methoxypolyethylene glycol-2000)-1,2-distearoyl-sn–glycero-3-phosphoethanolamine(DSPE-PEG 2 k)to encapsulate and deliver Ac2–26 peptides to the arthritic rats.They showed good stability and biocompatibility.After being intravenously administrated,Ac2–26 peptide-loaded PEGylated lipid nanoparticles(ADNPs)showed the prolonged in vivo circulation time and enhanced accumulation in inflamed sites.In vivo therapeutic evaluations revealed that ADNPs could attenuate synovial inflammation and improve joint pathology.Therefore,the pro-resolving therapeutic strategy using ADNPs is effective in RA treatment.

Is non-biological treatment of rheumatoid arthritis as good as biologics?

The management of rheumatoid arthritis(RA) in the past three decades has undergone a paradigm shift from symptomatic relief to a "treat-to-target" approach. This has been possible through use of various conventional and biologic disease modifying anti-rheumatic drugs(DMARDs) which target disease pathogenesis at a molecular level. Cost and infection risk preclude regular use of biologics in resource-constrained settings. In therecent years, evidence has emerged that combination therapy with conventional DMARDs is not inferior to biologics in the management of RA and is a feasible cost-effective option.

THERAPEUTIC EFFECT OF NEEDLE WARMING THROUGH MOXIBUSTION AT TWELVE SHU POINTS ON RHEUMATOID ARTHRITIS

Rheumatoid arthritis is a chronic andgeneral immunologic disease,mainlyinvolving the joints.Clinically,it is manifestedby morning ankylosis,arthroncus,jointdeformity and dysfunction.It falls into thecategory of arthralgia syndrome in traditionalChinese medicine(TCM).The authors havetreated 55 cases of rheumatoid arthritis byneedle warming through moxibustion

A Clinical Study of Suogudan Granule (索骨丹颗粒) in the Treat ment of Rheumatoid Arthritis

Objective： To study the clinical efficacy of Suogudan Granule （SGDG, 索骨丹颗粒） in the treatment of rheumatoid arthritis （RA）. Methods： Ninety patients with RA were randomly divided into the treated group and the control group. The treated group was administered orally with SGDG 6 g each time, thrice a day, while the control group with the combined therapy of Fenbid Oapsules 0.3 g each time, twice a day and Tripterygium tablet 20 mg each time, thrice a day. The treatment course for both groups was 6 weeks. The changes of clinical symptoms and signs, and laboratory indices such as erythrocyte sedimentation rate （ESR）, rheumatoid factor （RF）, antistreptolysin O （ASO）, routine examination of blood and urine, liver and kidney function, etc. before and after treatment were observed. Results： （1） The total effective rate in the treated group （88.0 %） was obviously higher than that in the control group （67.5 %） with significant difference （P〈0.05）. （2） The improvement in arthralgia, joint swelling, time of morning stiffness, 15-meter walking, analgesia initiation and persistence in the treated group was better than that in the control group （P〈0.05, P〈0.01）, but there was no obvious difference in improvement of joint tenderness, range of joint motion, grip strength, and initiating detumescence time （P〉0.05）. （3） The improvement in ESR and RF in the treated group was better than that in the control group with significant difference （P〈0.05）. The negative-conversion rate of ASO in the treated group was also higher than that in the control group （P〈0.01）. （4） No evident abnormality in blood, urine, liver or kidney function was found in either group. Conclusion： SGDG is effective and safe for the treatment of RA.

Advances in TCM Symptomatology of Rheumatoid Arthritis

In view of the rich experiences and new advances in TCM treatment of rheumatoid arthritis, it is very promising to find a further breakthough in the field of traditional Chinese medicine (TCM). Treating the disease by means of differentiation of symptoms and signs is a distinctive feature of TCM, however the difficult and also the major point would be the research of mechanism of its symptomatology. The following is a summary of the advances in the study of symptomatology, especially its epidemiology, the role of immune system and blood rheology made since 1987 when the ARA criteria1 was published.……

Intermediate and Late Rheumatoid Arthritis Treated by Tonifying the Kidney, Resolving Phlegm and Removing Blood Stasis

Eighty-seven cases of intermediate and late rheumatoid arthritis were treated with Instant Shu GuanWen Jing Granules(疏关温经冲剂 Relaxing Joints by Warming Channels)and Instant Shu GuanQing Luo Granules(疏光清络冲剂 Relaxing Joints by Removing Heat from the Lung Channel)totonify the kidney resolve phlegm and remove blood stasis,and compared with 41 cases treated withInstant Wang Bi Granules(尪痹冲剂 Prescription for Arthralgia-syndrome).The treatment produceda clinical cure rate of 54.0% and a total effective rate of 90.8% as in against 29.3% and 73.2%respectively in the control group.The difference was significant(P<0.01).Improvement in mainsymptoms and laboratory findings in the treatment group was all more marked than that in thecontrol group (P<0.05 or P<0.01),with no side effects observed.

TCM Treatment for 40 Cases of Rheumatoid Arthritis with Channel Blockage due to Yin Deficiency

To verify the therapeutic effects of the method of softening and lubricating the joints,and calming the endogenous wind in case of rheumatoid arthritis (RA) with the syndrome of channel blockage due to yin deficiency,60 RA patients with the syndrome of channel blockage due to yin deficiency were randomly divided into a treatment group (40 cases) and a control group (20 cases) and treated respectively by the above method for the former and with Zheng Qing Feng Tong Ning Tablets (正清风痛宁片) for the latter. The result turned out to be that the effect in the treatment group was very satisfying.The treatment group obtained a better result in the accumulated points of syndrome and RA,morning rigidity of the joints,grip strength,20m walking time and erythrocyte sedimentation rate (ESR) (P<0.01 or P<0.05).The above indicates that channel blockage due to yin deficiency is an important pathogenesis of RA,and calming the endogenous wind is a method of choice for treating RA.

Hepatitis B virus reactivation in rheumatoid arthritis

Rheumatoid arthritis(RA)is an autoimmune disease characterized by proliferative synovitis,which can cause cartilage and bone damage as well as functional limitations.Disease-modifying anti-rheumatic drugs have significantly improved the prognosis of RA patients.However,people with RA,when combined with hepatitis B virus(HBV)infection,may experience reactivation of HBV during treatment with anti-rheumatic drugs.The outcome of HBV reactivation(HBVr)varies from liver inflammation to liver failure,while insufficient HBV screening in RA patients has been reported in various countries.Therefore,it is necessary to identify patients at high risk before starting immunosuppressive therapy.The immune response plays an important role in anti-HBV infection.However,most anti-rheumatic drugs exert an inhibitory effect on the body’s immune system,resulting in HBVr.Therefore,it is necessary to conduct a comprehensive evaluation based on host factors,viral factors,and drug factors.In this paper,we summarize the mechanism of HBVr,the risk of HBVr caused by anti-rheumatic drugs,and the appropriate diagnosis and treatment process for RA patients so that clinicians can have a more comprehensive understanding of HBVr in RA patients.

Systematic Review and Meta-Analysis on the Effect of Transdermal Preparations of Sinomenium Acutum on Rheumatoid Arthritis

Objective:We evaluated the efficacy and safety of transdermal preparations of Sinomenium acutum(SA)for rheumatoid arthritis(RA).Methods:Randomized controlled trials(RCTs)of SA transdermal preparations for RA were extracted from relevant databases and screened in accordance with the inclusion criteria.The Cochrane System Evaluation Manual(version 5.1.0)was used to assess the quality of the included trials.We used the Cochrane Review Manager(version 5.4)to conduct the meta-analysis.Results:Six trials comprising 436 patients(220 patients in the treatment group and 216 patients in the control group)were analyzed.The meta-analysis indicated that SA transdermal preparations in combination with disease-modifying antirheumatic drugs(DMARDs)enhanced the overall effect(odds ratio[OR]3.97,95%confidence interval[CI][2.25,7.00],P<0.00001),decreased visual analogue scale(VAS)results(mean difference[MD]-0.64,95%CI[-1.20,-0.09],P=0.02),decreased laboratory indexes including the erythrocyte sedimentation rate(ESR)(MD-4.36,95%CI[-5.63,-3.08],P<0.00001)and C-reactive protein(CRP)(MD-3.6,95%CI[-3.99,-3.21,P<0.00001]),and decreased the Disease Activity Score-28(DAS28)(MD-0.41,95%CI[-0.78,-0.03],P=0.03).The results suggest that combination therapy did not shorten the duration of morning stiffness(DMS;standardized MD[SMD]-6.13,95%CI[-17.33,5.06],P=0.28)or reduce rheumatoid factor(RF)laboratory indexes(SMD-0.85;95%CI[-2.19,0.49],P=0.21).Only one study reported adverse reactions,and thus,it was difficult to determine whether adverse drug reactions in the combination therapy group were significantly different from those in the control group.Conclusion:We found that SA transdermal preparations combined with DMARDs may have greater clinical efficacy than DMARDs for RA.More well-designed and high-quality RCTs are required to verify the findings and determine whether transder-mal preparations cause fewer adverse events.