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.

"Meridian-sinew Acupuncture Method"Improves Deformity Joint Dysfunction in Rheumatoid Arthritis

Joint deformity and dysfunction are common and serious complications in the late stage of rheumatoid arthritis,which seriously affect the quality of life of patients.Traditional Chinese medicine(TCM)believes that joint deformity and dysfunction in some patients with rheumatoid arthritis are closely related to the apraxia of meridians and tendons due to enduring illness.Based on the theory of meridians and tendons circulation,using the local and nearby therapeutic effect of acupoints as the treatment method in clinical practice,we conducted penetration needling of Houxi,Baxie,Wailaogong as well as Ashi points of interphalangeal joints of both hands through bilateral Sanjian,and used the uniform reinforcing-reducing method to soothe tendons and meridians,thus effectively improving the dysfunction of deformed joints.

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.

THE EFFECT OF WARM ACUPUNCTURE ON RHEUMATOID ARTHRITIS OF 434 CASES

Clinical observation on 434 cases of rheumatoid arthritis shows that the warmingneedle method is markedly effective for rheumatoid arthritis (RA). It also helps to reveal the mecha-nism and function of acupuncture and moxibustion (AM) in curing diseases. Laboratory observationconfirms that the warming needle method can modulate the body’s immunity function significantly. Inthe future, more attention should be paid to point selection and manipulation method so that the bestresult can be obtained.

Rules of acupuncture point selection in the treatment of rheumatoid arthritis through data mining

Objective:To explore the rules of acupuncture point selection in thetreatment of rheumatoid arthritis by applying data mining and modern Statistical software.Methods:We retrieved literature from China hownet(CNKI),VIP database(VIP),Wanfang,PubMed,MEDLINE,Embase database from the founding of the database to February 1,2020.The main information of meridians and acupoints were entered into Excel,SPSS22.0 was used to extract data and do clustering analysis.Results:Quchi,Zusanli,Hegu,Yanglingquan,Xiyan were often chosen for electropuncture treatment of rheumatoid arthritis.Most of the acupoints are located in the large intestine channel of hand yangming bladder meridian or bladder channel of foot Taiyang,Shaoyang gallbladder channel of foot,stomachmeridian of foot Yangming,the energizer meridian and concentrated in the upper and lower extremities.The frequency of use of five Shu points,crossing point,source point,lowerconfluent and eight meeting points acupoints is higher.Cluster analysis can divide the included acupoints into 5 clusters.Conclusion:Quchi,Zusanli,Hegu,Yanglingquan,Xiyan are often chosen for electropuncture treatment of rheumatoid arthritis.Most of the selected acupoints aremostly distributed in the acupoints which are located in the large intestine channel of hand yangming bladder meridian or bladder channel of foot Taiyang,Shaoyang gallbladder channel of foot,Stomach meridian of foot Yangming,and the energizer meridian.

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.

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.

Effect of Electro-acupuncture on Rat Joint Pathomorpnology of Chronic Adjuvant Arthritis Model

Objective:To study the effect of electro-acupuncture (EA) on pathomorphological changes of joints in rat model of chronic adjuvant arthritis. Methods: The rat chronic adjuvant arthritis model was established by subcutaneous injection of 0.1 ml of complete Freund’s adjuvant to the left hind sole. Forty Wistar rats were randomly divided into the model group, the low frequency (2 Hz) EA group, the high frequency EA (100 Hz) group and the body acupuncture group. After being modeled except the model group, the other three groups were treated with EA or body acupuncture in Yanglingquan points (bilateral) for 3 weeks, the left ankle joints and metatarsal joints of rats were taken for pathological examination by fixing with 10% formalin and embedding in paraffin, sectioning and staining with HE. Results: Obvious inflammatory cell infiltration, loosened synovial tissue, damage of articular cartilage and proliferation of synovial cells and granulation tissue were observed in the sections of joints in model rats.

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.

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

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.

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.

Comparative Clinical Trial of Antibodies to Interferon-Gamma (IFN-γ) and Tumor Necrosis Factor-Alpha (TNF-α) in the Treatment of Rheumatoid Arthritis

In 1974, in Nature, one of us has proposed a radically new idea that led to the development of anticytokine therapy which is now used around the world for the treatment of autoimmune diseases. We were the first to use antibodies to IFN-γ and were some of the first to suggest using antagonists of TNF-α in the treatment of autoimmune and inflammatory diseases as well. Our method suppresses one of the main pathogenetic mechanisms of these diseases. Antibodies to IFN-γ and TNF-α exhibit dramatic effects on clinical manifestations of rheumatoid arthritis (RA). However, in our trial ultrasound assessment of the synovial membrane thickness in RA patients showed that only anti-IFN-γ exerted pronounced anti-inflammatory effect. Some patients who underwent treatment with antibodies to TNF-α developed a number of complications. Anticytokine therapy (mono- and poly-) alone or in combination with other drugs can possibly be used not only in the treatment of autoimmune diseases, but also in other pathologies with cytokine synthesis disturbances (a number of neurological, psychiatric, endocrine, and other diseases).

The Influence of Health Qigong on the Subjectively Expressed Psychophysical State of Patients with Rheumatoid Arthritis,Rheum,Osteoporosis,Osteopenia

This study assesses the impact of exercise on the health of the Qigong(Jibengong,Health Qigong Ba Duan Jin and Health Qigong Yi Jin Jing)in patients with rheumatoid arthritis,rheumatism,osteoporosis,osteopenia.Through the given questionnaire we have come up with data showing how and how much health qigong affects the patients with rheumatoid arthritis,rheumatism,osteoporosis,osteopenia according to the subjective assessment.

Remission is not maintained over 2 years with hematopoietic stem cell transplantation for rheumatoid arthritis:A systematic review with meta-analysis

BACKGROUND Hematopoietic stem cell(HSC)transplantation(HSCT)is being accepted as a standard of care in various inflammatory diseases.The treatment of rheumatoid arthritis(RA)has been closely evolving with the understanding of disease pathogenesis.With the rising resistance to the traditional disease-modifying antirheumatic drugs and targeted biological therapy,researchers are in pursuit of other methods for disease management.Since the ultimate goal of the ideal treatment of RA is to restore immune tolerance,HSCT attracts much attention considering its reparative,paracrine,and anti-inflammatory effects.However,a systematic review of studies on HSCT in RA is lacking.AIM To investigate the role of HSCT in the management of RA.METHODS A detailed search of PubMed,Scopus,EMBASE,Cochrane,and the Web of Science databases was made to identify the relevant articles till September 2020 following Cochrane and PRISMA guidelines.We extracted data including the number of patients,source of hematopoietic stem cells,their mobilization and conditioning regimens,results,and complications from the eligible studies.Results were dichotomized into success(ACR 50/70)and failure(ACR 20)based on the improvement from baseline characteristics.The methodological quality of the included studies was also assessed.Analysis was performed using OpenMeta[Analysis]software.RESULTS We included 17 studies(1 randomized controlled trial,11 prospective,and 5 retrospective studies)with 233 patients for analysis.HSCT provided a significantly beneficial overall improvement in the clinical grades of ACR criteria(Z=11.309,P<0.001).However,the remission was noted only till 24 mo and later on the significance of the result was lost(Z=1.737,P=0.082).A less than 1%treatmentrelated mortality was noted from the included studies.No major drug-related toxicities were noted in any of the included studies.All patients who underwent allogeneic HSCT received immunosuppression in the conditioning regimen to counteract the graft-vs-host reaction which made them vulnerable to infections.It is noted that the source of hematopoietic stem cells did not play a role in altering the functional outcome and both autologous(Z=9.972,P<0.001)and allogenic(Z=6.978,P<0.001)sources produced significant improvement in the outcome compared to the pre-operative state despite having a significant heterogeneity among the studies reporting them(I2=99.4,P<0.001).CONCLUSION Although the available literature is encouraging towards the use of HSCT in refractory cases with significant improvement from baseline till 2 years,the inclusion of HSCT into the standard of care of RA needs further exploration.

Photodynamic therapy for arthritis: A promising therapeutic strategy

Photodynamic therapy(PDT)is a novel therapy that combines photosensitizers,light,and oxygen molecules to treat diseases such as joint lesions and microbial infections through photodynamic reactions.The photosensitizers are activated under specific wavelengths of laser radiation to generate reactive oxygen species,which alter the microenvironment of the diseased tissue,cause ischemia and target cell death,and thus effectively treat cancer.Now that there is growing evidence that nonlethal doses of PDT reduce inflammation and treat infections in multiple animal models of arthritis,PDT should be considered as a new option for the treatment of arthritis.This article presents a literature review of published original articles and review articles concerning photodynamic therapy and arthritis.We conducted a comprehensive literature search in PubMed,Web of Science and Google Scholar databases,excluding duplicated and irrelevant studies.In cases of duplicated research,we selected articles with higher impact factors for the review.In this review,we summarize the application and progress of PDT in the treatment of rheumatoid arthritis,osteoarthritis,psoriatic arthritis,and infectious arthritis,and clarify the advantages and limitations of PDT for arthritis.PDT offers therapeutic value for patients with inflammatory and infectious arthritis through promoting vascular occlusion,cell death,and antibacterial therapy.

Metrology of clinical literature on acupuncture for rheumatoid arthritis in China in recent five years

Objective To conduct metrological study on clinical literature on acupuncture in treatment of rheumatoid arthritis（RA） at home in recent five years, providing reference basis and train of thought for clinical scientific research. Methods CNKI was retrieved based on the following search words： acupuncture and moxibustion, acupuncture, electroacupuncture, filiform needle, hand acupuncture, body acupuncture, and rheumatoid arthritis. The general information, diagnostic criteria, treatment principles, treatment methods, amount of stimulation, reinforcing/reducing methods, and efficacy criteria were analyzed. Results Fifty papers were obtained after strict screening, and most clinical reports were randomized controlled trials; there were differences among the diagnostic criteria, treatment principles and efficacy criteria in different reports; there were few literature on acupuncture in treatment of RA simply, most of the literature were about acupuncture combining other therapies. Conclusion The acupoint selection of acupuncture in treatment of RA should be studied further.

Acupuncture combined with vesiculating cupping for 110 patients with rheumatoid arthritis

Objective To explore the clinical efficacy of acupuncture combined with vesiculating cupping in treatment of rheumatoid arthritis（RA）. Methods A total of 110 patients with RA were randomly divided into an acupuncture combined with vesiculating cupping group（group A） and an acupuncture combined with non-vesiculating cupping group（group B）. Treatment was conducted once a day in two groups, and ten days were considered as one course of treatment. The total effective rate was observed after treatment for three courses. Results The difference in cured and markable effective rate of group A and group B was obviously significant [81.82%（45/55） vs 18.18%（10/55）, P〈0.01], the difference in total effective rate of group A and group B was significant [96.36%（53/55） vs 69.09%（38/55）, P〈0.05], indicating that the efficacy in group A was significantly superior to that of group B. Conclusion Acupurcture combined with vesiculating cupping therapy achieves more satisfactory efficacy on RA compared with acupuncture combined with nonvesiculating cupping therapy.