Arthritis Index Scores Research Articles

Effects of dioscin from Dioscorea nipponica on TL1A/DR3 and Th9 cells in a collagen-induced arthritis mouse model.

Rheumatoid arthritis (RA) is a systemic autoimmune disease, and TL1A and its receptor DR3 play important roles in its pathogenesis. Th9 cells are involved in RA development. Dioscin from Dioscorea nipponica (DDN) has a therapeutic effect on RA, but its effect on TL1A/DR3 and Th9 cells remains unclear. A collagen-induced arthritis (CIA) model was established in DBA/1 mice, and the therapeutic effects of DDN were determined using pathological sections and arthritis index scores. Western blotting and PCR were used to detect TL1A, DR3, PU.1, TGF-β and IRF-4. Enzyme-linked immunosorbent assay was used to detect the expression of TL1A and IL-9 in the serum. Immunofluorescence was used to detect the localization and expression of TL1A, DR3, and PU.1 in synovial tissue. Flow cytometry was used to detect TL1A and DR3 expression in different immune cells and Th9 cells. DDN ameliorated bone destruction, inflammatory cell infiltration, synovial inflammation, cartilage tissue destruction, and proteoglycan loss. DDN downregulated TL1A, DR3, and PU.1 in the synovium of the lymph nodes and spleen and TL1A and IL-9 in the serum. DDN decreased the number of TL1A-expressing APCs and macrophages, DR3-expressing CD4+T cells, and Th9 cells. Th9 cell differentiation-related factors TGF-β and IRF-4 were also inhibited by DDN. We conclude that DNN inhibited the expression of TL1A/DR3 in CIA mice and suppressed the expression of the Th9 cell-specific transcription factor PU.1, Th9 cell number, and IL-9 secretion. DDN inhibited the function of Th9 cells by targeting TGF-β and IRF-4 in the TL1A/DR3 pathway, thereby reducing inflammation.

Salicylalazine: A novel therapeutic agent targeting TLR4/NLRP3/GSDMD-mediated pyroptosis in rheumatoid arthritis.

Joint pain and functional impairment are hallmarks of arthritis, a painful inflammatory disease. Salicylalazine (SAZ), an anti-inflammatory compound, has demonstrated promise in modulating inflammation, thereby being selected in the current study to unveil its anti-arthritic potential. The aim behind this study was to assess the anti-arthritic properties of salicylalazine via evaluating its impact on paw volume, arthritic scores, oxidative stress indicators, and significant inflammatory mediators. The arthritic potential of SAZ was estimated first through the formaldehyde (FA) model to screen the most effective dose of SAZ, followed by the Complete Freund's adjuvant (CFA) model. Over a 28-day period, we monitored parameters such as paw edema, arthritic index, body weight, flexion pain, mobility, and stance score. Oxidative stress markers (GSH, CAT, SOD, MDA), serological markers (CRP, RF, anti-CCP), and gene expression of key inflammatory mediators (TLR4, MyD88, NFκB, NLRP3, ASC, IL-1β, IL-18, caspase-1, GSDMD) were assessed. SAZ treatment led to a substantial decrease in paw volume in both arthritis models, with the most pronounced effects observed on day 10 for the formaldehyde model and day 28 for the CFA model (p<0.001). Additionally, SAZ helped to restore the body's weight and considerably relieved the flexion pain, which led to improvements in both mobility and stance. Moreover, SAZ substantially raised the levels of antioxidant enzymes (GSH, CAT, SOD) and decreased MDA levels, suggesting a reduction in oxidative stress. Also with SAZ, there was a substantial (p<0.001) decrease in the expression of pyroptotic mediators. Serological markers of inflammation, including CRP, RF, and anti-CCP levels, were also restored by SAZ administration. In a nutshell, SAZ achieved significant anti-arthritic benefits, most likely via the modulation of the TLR4/NLRP3/GSDMD-mediated pyroptosis pathway, lowering oxidative stress, and improvement of clinical findings. Taking into consideration these findings, it seems that SAZ has the potential to be an effective treatment alternative for the management of arthritis.

Assessing the effectiveness and NSAIDs sparing effect of celery seeds and Boswellia serrata in osteoarthritis management

: This study examines the anti-inflammatory and analgesic properties of Celery seed and extracts as potential alternatives for OA treatment, focusing on their effectiveness in reducing pain and improving joint functionality.Osteoarthritis (OA), a prevalent joint disorder, particularly affects the knees and hips. Current management primarily involves NSAIDs, which can lead to severe side effects, especially in older adults with comorbidities. A multicentre observational study enrolled 394 participants clinically diagnosed with knee osteoarthritis. They continued their usual treatment while taking Celery seeds and extract tablet twice daily for three months. Primary outcomes included Western Ontario and McMaster Universities Arthritis Index (WOMAC) scores and changes in painkiller and NSAID usage. Secondary outcomes included visual analogue scale (VAS) pain scores.The study demonstrated significant improvements in primary outcome measures: WOMAC score improved by 17.07% (p&amp;#60;0.001), WOMAC pain score by 75.00% (p&amp;#60;0.001), WOMAC stiffness score by 72.05% (p&amp;#60;0.001) and WOMAC physical function score by 78.93% (p&amp;#60;0.001). Secondary outcomes showed VAS score reductions at rest by 67.17% (p&amp;#60;0.001) and during movement by 64.28% (p&amp;#60;0.001). There was a notable decrease in NSAID usage from baseline 70.09% to 31.89% (p&amp;#60;0.001).Celery seeds and extract demonstrate promising efficacy as a safer and effective adjunctive therapy for knee osteoarthritis, offering pain relief, enhanced joint functionality and potential reduction in NSAID usage.

Posterior iliac crest vs. proximal tibia: distinct sources of anti-inflammatory and regenerative cells with comparable 6-month clinical outcomes in treatment of osteoarthritis

BackgroundHuman bone marrow is a source of mesenchymal stem cells (MSCs), other progenitor cells, and factors with anti-inflammatory and regenerative capacity. Though the fraction of MSCs out of the nucleated cells is very small, bone marrow aspirate (BMA) for osteoarthritis (OA) has noteworthy effects. BMA is usually collected from the posterior or anterior iliac crest, and rarely from the proximal tibia. We investigated the clinically beneficial concentration of ex vivo MSCs, derived from BM harvested from the posterior iliac crest and proximal tibia by Marrow Cellution™ Aspiration System, and their phenotypic differences, in comparison to autologous Platelet-Rich Plasma (PRP) treatment prepared with a manual, closed system.MethodsA single-center, parallel, randomized controlled study was designed to investigate the efficacy of BMA from the posterior iliac crest compared to BMA from the proximal tibia, against a control group treated with PRP, in knee OA. Thirty patients with knee OA grade I-IV, according to Kellgren-Lawrence (KL), were distributed into each group. Visual Analog Scale (VAS) and Western Ontario & McMaster Universities Arthritis Index (WOMAC) score were used for clinical outcome evaluation.ResultsData from an intermediate analysis of 6-months follow-up, involving 15 patients in each arm, showed that the posterior iliac crest was significantly more densely populated with mononuclear cells, than the proximal tibia (p = 0.005). Flow cytometric analysis on ex vivo BMA showed a significantly greater number of MSCs in the BM-derived from the posterior iliac crest when compared with the proximal tibia (p < 0.001), together with a significantly higher number of platelets (PLTs) (p < 0.001). Surprisingly, despite these differences in cells number, the improvement in early pain and function scores, after each treatment, were statistically significant within each of the three arms. BM from the proximal tibia showed the highest ΔWOMAC, while BM from the posterior iliac crest showed the highest ΔVAS; however, these differences were not statistically significant across the three arms (p > 0.05). A better outcome, in terms of ΔVAS, was observed in patients classified as KL I-II, when treated with BMA from crest (p < 0.001) and PRP (p = 0.004). Moreover, the effect of BMA treatment on ΔVAS depends on MSCs % only in the Tibia Arm (r = -0.59, p = 0.021), where we also found a correlation between ΔWOMAC and monocytes (r = 0.75, p = 0.016).ConclusionThe results indicate that the iliac crest yields a higher concentration of MSCs compared to the proximal tibia, however both BM, independently of the MSCs concentration, show a beneficial clinical outcome in the treatment of knee OA. Furthermore, BMA is not superior to PRP treatment.

High-fat diet stimulated butyric acid metabolism dysbiosis, altered microbiota, and aggravated inflammatory response in collagen-induced arthritis rats.

Research has demonstrated that obesity may be associated with rheumatoid arthritis (RA). In addition, Dysbiosis of intestinal microbiota and their metabolites has been linked to the occurrence and development of RA and obesity. However, the mechanism by which obesity affects RA remains unclear.In this study, we explored the impact of high fat diet(HFD) on collagen-induced arthritis (CIA) rats and revealed its mechanisms based on gut microbiota and metabolomics. Based on diet and modeling, rats were divided into normal group (Con), CIA model group, HFD group (HFD), and HFD + CIA group (HCIA). The effect of HFD on arthritis in CIA rats were investigated based on the arthritis index (AI), weight, blood lipid levels, and inflammatory cytokines. Moreover, HE staining and micro-CT were performed to evaluated the effect of HFD on the pathology of joints and synovial tissues in CIA rats.16S rRNA amplicon sequencing and liquid chromatography-mass spectrometry (LC-MS) were employed to explore changes in gut microbiota and short-chain fatty acids (SCFAs). The AI scores, inflammatory cytokines and bone destruction parameters in the HCIA group were significantly higher than those in the other three groups. The results of 16S rRNA amplicon sequencing and metabolomics showed that compared with the other three groups, the expression of g_Muribaculaceae and butyric acid were reduced in the HCIA group. Spearman and linear correlation analyses revealed a positive correlation between g_Muribaculaceae abundance and butyric acid levels. HFD stimulated butyric acid metabolism dysbiosis, altered microbiota, and aggravated inflammatory response in CIA rats.

Levamisole Ameliorates Rheumatoid Arthritis by Downregulating the PI3K/Akt Pathway in SD Rats.

Background/Objectives: Rheumatoid arthritis (RA) is a systemic chronic autoimmune disease characterized by a protracted course, high rates of morbidity, and disability yet lacks effective therapeutic modalities. Levamisole (LVM), an immunomodulatory drug, has been clinically reported for its potential in RA treatment, while its therapeutic mechanism toward RA remains to be elucidated. Hence, this study provides theoretical support for the application of LVM in the treatment of RA. Methods: This study employed male Sprague-Dawley (SD) rats to construct the adjuvant-induced arthritis (AIA) model, administering LVM orally (5 mg/kg, 15 mg/kg, and 45 mg/kg) for 25 days. An evaluation of LVM's therapeutic effects on RA was conducted through arthritis index scores, paw pad thickness, paw volume, hematoxylin and eosin (H&E) staining, 3D microcomputed tomography (micro-CT) scans, serum levels of pro-/anti-inflammatory cytokines, and serum biochemical indicators. Western blotting and immunohistochemistry staining were utilized to measure the expression levels of phosphatidylinositol 3-kinase/protein kinase B (PI3K/Akt) proteins in synovial and ankle joint tissues. Results: Treatment with the median dose of LVM (15 mg/kg, M-LVM) significantly reduced the arthritis index (p < 0.01), paw pad thickness (p < 0.001), and paw volume (p < 0.01) without affecting body weight. Additionally, M-LVM alleviated inflammatory lesions in the synovium and ankle joints and also normalized serum levels of interleukin-1 beta (IL-1β), tumor necrosis factor-alpha (TNF-α), and transforming growth factor-beta (TGF-β). The Model group exhibited significant increases in serum levels of alkaline phosphatase (ALP) (p < 0.01), creatine kinase (CK) (p < 0.05), and glucose (GLU) (p < 0.001) compared with the Control group; however, M-LVM effectively regulated these parameters to normal levels. Western blotting and immunohistochemistry staining revealed that PI3K-/Akt-related proteins were highly expressed in the synovial and ankle joint tissues of rats in the Model group, while treatment with M-LVM significantly reduced the expression of these proteins. Furthermore, histological examination of major organs (heart, liver, lungs, kidneys, and thymus) showed no significant pathological changes, with the exception of the spleen, where M-LVM ameliorated splenic lesions. Conclusions: We demonstrate that LVM at an optimal dose substantially relieves synovitis and bone erosion in AIA rats by inhibiting the PI3K/Akt signaling pathway.

Burosumab in adults with X-linked hypophosphatemia: real-world experience from a retrospective study in Sydney

Abstract X-linked hypophosphatemia (XLH) is a chronic disabling hereditary musculoskeletal disorder associated with inactivating PHEX mutations and elevated circulating FGF-23 concentrations. In a placebo-controlled trial of adults with XLH, burosumab (anti-FGF-23 antibody) demonstrated durable improvements in phosphate concentrations, and self-reported stiffness and physical limitation. However, real-world data regarding burosumab efficacy and tolerability in adults with XLH is lacking. A retrospective audit was performed of patients (age ≥ 18-years) who commenced four-weekly subcutaneous burosumab for XLH at Royal North Shore and Westmead Hospitals, Sydney, between January 2021 and June 2024. Patients were managed per standard clinical care and burosumab dose adjusted as necessary according to manufacturer instructions. Electronic medical records were reviewed to collate data regarding patient demographics, XLH-related complications and prior treatment, burosumab dosage and side effects, and pre- and post-burosumab biochemistry and Western Ontario and McMaster Universities Arthritis Index (WOMAC) scores. Of thirteen adults with XLH, all had hypophosphatemia before commencing burosumab (mean 0.64 ± 0.08 mmol/L). Mean WOMAC scores demonstrated baseline impairments in stiffness, pain and physical limitation. Burosumab was administered for median 15 months during follow-up (median dose 70 mg). Hypophosphatemia resolved in all patients within three months of burosumab (mean 1.03 ± 0.38 mmol/L). Two patients developed hyperphosphatemia two weeks after commencing burosumab requiring dose reduction. One patient ceased burosumab in the setting of hypercalcaemia and constipation secondary to pre-existing tertiary hyperparathyroidism. Adverse events were mild, including transient musculoskeletal discomfort (n = 4), restless legs (n = 2), injection site reaction (n = 2) and headache (n = 1). Repeat WOMAC within 12 months of commencing burosumab (n = 9) demonstrated clinically meaningful improvements in stiffness (-33.3 ± 12.5, P&amp;lt;.001) and physical function (-14.3 ± 16.2, P=.029). This study reports real-world outcomes of adults with XLH treated with burosumab. Clinical experience from two centres in Sydney support trial findings that burosumab is well-tolerated and associated with improved serum phosphate concentrations and self-reported stiffness and physical function.

Evaluating the Efficacy of Platelet-Rich Plasma in Treating Primary Knee Osteoarthritis: A Prospective Interventional Study.

Knee osteoarthritis (OA) is a prevalent degenerative joint disorder causing pain, stiffness, and reduced function, significantly impacting the quality of life. Current treatments mainly provide symptomatic relief, with limited efficacy in halting disease progression. Platelet-rich plasma (PRP), a biological therapy rich in growth factors, has gained attention as a potential treatment for knee OA due to its regenerative properties. This study evaluates the efficacy of PRP in managing primary knee OA. This prospective interventional study included 100 patients diagnosed with primary knee OA, categorized using the Kellgren-Lawrence grading scale. Leukocyte-reduced PRP was prepared using the double-spin method and injected into the knee joint. The efficacy of PRP was assessed using the Western Ontario and McMaster Universities Arthritis (WOMAC) Index and Visual Analogue Scale (VAS) pain scores at six weeks, three months, and six months post-injection. Statistical analysis was performed using SPSS version 25.0, with significance set at p<0.05. Significant improvements in the WOMAC and VAS scores were observed at all-time points post-PRP injection. The WOMAC score decreased from a baseline of 81.06 to 63.52 at six months (p < 0.001), and the VAS score reduced from 7.53 to 3.09 (p < 0.001). PRP was more effective in patients with lower body mass index (BMI) and less severe OA (Grades 1 and 2). Adverse events were mild, with 18% reporting mild pain or swelling. PRP therapy significantly improves pain and function in patients with primary knee OA, particularly in early-stage disease. The treatment is generally safe, with minor adverse effects. PRP presents a promising non-surgical option, especially for those seeking to delay or avoid knee arthroplasty.

Impact of enhanced recovery after surgery on postoperative blood management following primary total knee arthroplasty: a propensity score-matched analysis.

To evaluate the efficacy of blood management in patients underwent unilateral Total Knee Arthroplasty (TKA)under an enhanced recovery after surgery (ERAS) program. Patients underwent unilateral TKA from January 2019 to October 2023 in a university hospital were retrospectively studied. A total of 200 cases were selected in the analysis. After matching with propensity scoring, 51 patients in each group were included. The postoperative Haemoglobin (Hb), albumin (Alb), C-reactive protein (CRP), total length of stay (LOS), and estimated blood loss after operation were compared between the two groups. Clinical outcomes including Western Ontario and McMaster Universities Arthritis Index (WOMAC), SF-12, and Oxford Knee Score (OKS) were also compared atsixweek and threemonth follow-up. The results showed that the Hb of the ERAS group was significantly higher than those of the non-ERAS group (P < 0.05) on the third postoperative. The mean CRP level was lower, LOS was shorter, and Alb level was higher in the ERAS group compared to that in the non-ERAS group (P < 0.05). The clinical outcomes such as WOMAC and OKS, SF-12 scores were higher in the ERAS group at both follow-up. ERAS protocol effectively minimizes perioperative blood loss and supports optimal nutrient levels in patients. ERAS management significantly contributes to the postoperative recovery of knee function in patients undergoing primary total knee arthroplasty.

Evaluating the Effectiveness of a Structural Allograft in Medial Open Wedge High Tibial Osteotomy in Patients With and Without a Lateral Hinge Fracture.

A lateral hinge fracture is a common complication in medial open wedge high tibial osteotomy (MOWHTO) and is associated with delayed union or nonunion. A comparison of outcomes between patients with or without a lateral hinge fracture after MOWHTO with a structural allograft has not been investigated. To validate the outcomes of MOWHTO with a structural allograft, especially in the presence of a lateral hinge fracture. Case series; Level of evidence, 4. We conducted a single-surgeon cohort study at a tertiary referral hospital between April 2017 and August 2022 and included patients who had undergone MOWHTO with a structural allograft for isolated medial compartment osteoarthritis with genu varum. We compared the incidence of delayed union or nonunion events and functional scores between patients with a lateral hinge fracture and those without using the Fisher exact test and independent t test. A total of 88 MOWHTO procedures (77 patients) were analyzed. The overall incidence of lateral hinge fractures was 29.5% (n = 26), including type I (n = 20 [22.7%]) and type II (n = 6 [6.8%]). Notably, 42.3% (n = 11) of these fractures had not been detected intraoperatively but during the follow-up visits. The overall Knee Society Score (KSS), Knee Society Score-Function (KSS-F), and Western Ontario and McMaster Universities Arthritis Index (WOMAC) scores were 90.0 ± 10.0, 93.4 ± 10.8, and 93.8 ± 7.1 points, respectively. None of the patients had delayed union or nonunion, and none underwent a reoperation because of bony union problems. The functional scores (KSS, KSS-F, and WOMAC) were not different between patients who had a lateral hinge fracture and those who did not (P > .05). The routine use of a structural allograft was associated with satisfactory outcomes after MOWHTO, regardless of whether there was a lateral hinge fracture.

Systematic narrative review of modalities in physiotherapy for managing pain in hip and knee osteoarthritis: A review.

Osteoarthritis (OA) affects 528 million individuals globally, predominantly in knee and hip joints, with a notable impact on females aged over 55, resulting in a substantial economic burden. However, the efficacy of modalities used in physiotherapy to manage OA pain for reducing the need for joint replacement remains an open question, and guidelines differ. Our systematic narrative review, drawing from reputable databases (e.g., PubMed, Cochrane, and CINAHL) with specific Mesh terms investigated evidence from 23 Randomized Controlled Trials (that included a control or a sham group in 30 different protocols) using therapeutic modalities like ultrasound, diathermy, and electrical stimulation for knee and hip OA pain, involving a total of 1055 subjects. We investigated the attainment of minimal clinically important differences in pain reduction, operationalized through a 20% decrement in the Western Ontario and McMaster University Arthritis Index or Visual Analog Scale (VAS) score. Our results indicated that 15 protocols out of 30 reach that level, but there were no statistical differences among modalities. Half of the protocol presented in the literature reached clinical efficiency but studies on hip remains scarce. We recommend a comprehensive, sequential, and multimodal intervention plan for individuals with joint OA with initial transcutaneous electrical nerve stimulation and progressing to a 2-week protocol of continuous ultrasound, potentially combined with deep microwave diathermy. Long-term intervention involves the use of pulsed electrical stimulation. For hip OA, a cautious approach and discussions with healthcare providers about potential benefits of spinal cord nerve stimulation.

Early gait analysis after total knee arthroplasty based on artificial intelligence dynamic image recognition

To explore early postoperative gait characteristics and clinical outcomes after total knee arthroplasty (TKA). From February 2023 to July 2023, 26 patients with unilateral knee osteoarthritis (KOA) were treated with TKA, including 4 males and 22 females, aged from 57 to 85 years old with an average of (67.58±6.49) years old;body mass index (BMI) ranged from 18.83 to 38.28 kg·m-2 with an average of (26.43±4.15) kg·m-2;14 patients on the left side, 12 patients on the right side;according to Kellgren-Lawrence(K-L) classification, 6 patients with grade Ⅲ and 20 patients with grade IV;the courses of disease ranged from 1 to 14 years with an average of (5.54±3.29) years. Images and videos of standing up and walking, walking side shot, squatting and supine kneeling were taken with smart phones before operation and 6 weeks after operation. The human posture estimation framework OpenPose were used to analyze stride frequency, step length, step length, step speed, active knee knee bending angle, stride length, double support phase time, as well as maximum hip flexion angle and maximum knee bending angle on squatting position. Western Ontario and McMaster Universities (WOMAC) arthritis index and Knee Society Score (KSS) were used to evaluate clinical efficacy of knee joint. All patients were followed up for 5 to 7 weeks with an average of (6.00±0.57) weeks. The total score of WOMAC decreased from (64.85±11.54) before operation to (45.81±7.91) at 6 weeks after operation (P<0.001). The total KSS was increased from (101.19±9.58) before operation to (125.50±10.32) at 6 weeks after operation (P<0.001). The gait speed, stride frequency and stride length of the affected side before operation were (0.32±0.10) m·s-1, (96.35±24.18) steps·min-1, (0.72±0.14) m, respectively;and increased to (0.48±0.11) m·s-1, (104.20±22.53) steps·min-1, (0.79±0.10) m at 6 weeks after operation (P<0.05). The lower limb support time and active knee bending angle decreased from (0.31±0.38) s and (125.21±11.64) ° before operation to (0.11±0.04) s and (120.01±13.35) ° at 6 weeks after operation (P<0.05). Eleven patients could able to complete squat before operation, 13 patients could able to complete at 6 weeks after operation, and 9 patients could able to complete both before operation and 6 weeks after operation. In 9 patients, the maximum bending angle of crouching position was increased from 76.29° to 124.11° before operation to 91.35° to 134.12° at 6 weeks after operation, and the maximum bending angle of hip was increased from 103.70° to 147.25° before operation to 118.61° to 149.48° at 6 weeks after operation. Gait analysis technology based on artificial intelligence image recognition is a safe and effective method to quantitatively identify the changes of patients' gait. Knee pain of KOA was relieved and the function was improved, the supporting ability of the affected limb was improved after TKA, and the patient's stride frequency, stride length and stride speed were improved, and the overall movement rhythm of both lower limbs are more coordinated.

Effect of knee strengthening exercises and lifestyle modifications through mobile phone support in people suffering from knee osteoarthritis.

The study aimed to evaluate the effectiveness of mobile phone-based support in improving exercise adherence and outcomes in knee OA. A prospective comparative cohort study was conducted with a follow-up at 3, 6, and 12 weeks, involving 210 participants allocated into intervention and control groups. The intervention group received knee exercise flyers and mobile phone-based adherence support, while the control group received only standard instructions after physiotherapy. Outcome measures included Western Ontario and McMaster Universities Arthritis Index (WOMAC) scores, numeric rating scale pain scores, and quality of life assessments at baseline and follow-ups at 3, 6 and 12 weeks. The intervention group exhibited significant reductions in WOMAC scores, pain scores and improvement in quality of life over the 12-week follow-up compared to baseline. The intervention group exhibited significantly greater improvements in the outcomes as compared to control group. A combined intervention of knee exercises leaflets and SMS/phone-call adherence support led to significant improvements in pain, functional outcomes and quality of life among individuals with knee OA. These findings underscore the potential of mobile phone-based interventions as effective adjuncts to traditional therapies for knee OA.

Screening bioactive compounds from Fangji Huangqi decoction for treating rheumatoid arthritis via COX-2 magnetic ligand fishing combined with in vivo validation

Ethnopharmacological relevanceFangji Huangqi Decoction (FHD) is a classical Chinese compound formula for treating rheumatoid arthritis (RA) with satisfactory effects. FHD is reputed for its ability to tonify qi with strengthening exterior, and dispel wind while removing dampness, but its mechanisms and bioactive compounds for treating RA remain unclear. Aim of the studyThe aim of this study was to explore the key target and bioactive compounds that were responsible for FHD-mediated improvements in RA. Materials and methodsUsing network pharmacology, we discovered that cyclooxygenase-2 (COX-2) was the key target of FHD against RA. We utilized a ligand fishing technique with COX-2 immobilized magnetic beads to recognize the bioactive components that act on COX-2. Then we carried out an in vitro assay of COX-2 enzyme inhibition and in vivo assay of carrageenan-induced inflammation and collagen-induced arthritis (CIA) to validate the bioactive effects of these captured ingredients. In the CIA assay, micro-CT, hematoxylin‒eosin staining and safranin-O/fast green staining were employed to assess the influence of the captured ligand on bone damage, pathological injury and cartilage destruction, respectively. Immunohistochemistry (IHC) and enzyme-linked immunosorbent assays (ELISAs) were used to detect the expression of COX-2 target in the ankle joint. interleukin-6 (IL-6) levels in the serum were also detected by ELISA. Molecular docking was used to reveal the binding mechanism of the COX-2 protein and the captured ligand. ResultsEleven ligands, including tetrandrine, fangchinoline, cyclanoline, licochalcone B, ononin, calycosin and liquiritin, were specifically bound to the COX-2 protein, as determined by ultrahigh-performance liquid chromatography–mass spectrometry (UPLC–MS), seven of which were present at high levels. One ligand, tetrandrine, not only had a great inhibitory effect on COX-2 enzyme activity but also significantly reduced carrageenan-induced inflammation. In the CIA assay, middle- and high-dose tetrandrine (25 and 50 mg/kg) had effects comparable to those of FHD and celecoxib on ameliorating RA symptoms in CIA mice via the COX-2 target. Furthermore, compared with the low-dose tetrandrine group (12.5 mg/kg), the FHD group exhibited significantly lower arthritis index scores and serum IL-6 expression, although the content of tetrandrine in FHD extract solution was approximately 0.1% of that in the low-dose tetrandrine group. ConclusionsHence, we inferred that tetrandrine was the main bioactive component responsible for the effects of FHD against RA by suppressing the expression of the COX-2 protein and inhibiting the enzyme catalytic activity of COX-2. The reason for these effects may be that tetrandrine can interact with the residue Tyr385 of COX-2, the enzymatic catalytic site of COX-2 to transform arachidonic acid (AA) to prostaglandin E2 (PGE2), and thereby reduce the production of prostaglandins and inflammatory metabolites. Moreover, in addition to tetrandrine, FHD contains other compounds that could supplement the activity of tetrandrine when FHD was used to treat RA, which is manifested the “multi-component” characteristic of how Traditional Chinese Medicine formulas treat diseases.

Tujia medicine Toddalia asiatica improves synovial pannus in rats with collagen-induced arthritis through the PI3K/Akt signaling pathway

To investigate the therapeutic mechanism of Tujia medicine Toddalia asiatica alcohol extract (TAAE) for synovial pannus formation in rats with college-induced arthritis (CIA). Sixty male SD rats were randomized into normal control group, CIA model group, TGT group, 3 TAAE treatment groups at low, medium and high doses (n=10). Except for those in the normal control group, all the rats were subjected to CIA modeling using a secondary immunization method and treatment with saline, TGT or TAAE by gavage once daily for 35 days. The severity of arthritis was assessed using arthritis index (AI) score, and knee joint synovium pathologies were examined with HE staining. Serum levels of TNF-α, IL-6, and IL-1β were detected with ELISA; the protein expressions of PI3K, Akt, p-PI3K, p-Akt, VEGF, endostatin, HIF-1α, MMP1, MMP3, and MMP9 in knee joint synovial tissues were determined using Western blotting, and the mRNA expressions of TNF‑α, IL-6, IL-1β, VEGF, HIF-1α, PI3K, and Akt were detected with RT-PCR. Treatment of CIA rat models with TAAE and TGT significantly alleviated paw swelling, lowered AI scores, and reduced knee joint pathology, neoangiogenesis, and serum levels of inflammatory factors. TAAE treatment obviously increased endostatin protein expression, downregulated p-PI3K, p-Akt, MMP1, MMP3, MMP9, VEGF, and HIF-1α proteins, and reduced TNF‑α, IL-6, IL-1β, PI3K, Akt, VEGF, and HIF-1α mRNA levels in the synovial tissues, and these changes were comparable between high-dose TAAE group and TGT group. TAAE can improve joint symptoms and inhibit synovial pannus formation in CIA rats by regulating the expressions of HIF-1α, VEGF, endostatin, MMP1, MMP3, and MMP9 via the PI3K/Akt signalling pathway.

Assessing the Value of Imaging Data in Machine Learning Models to Predict Patient-Reported Outcome Measures in Knee Osteoarthritis Patients.

Knee osteoarthritis (OA) affects over 650 million patients worldwide. Total knee replacement is aimed at end-stage OA to relieve symptoms of pain, stiffness and reduced mobility. However, the role of imaging modalities in monitoring symptomatic disease progression remains unclear. This study aimed to compare machine learning (ML) models, with and without imaging features, in predicting the two-year Western Ontario and McMaster Universities Arthritis Index (WOMAC) score for knee OA patients. We included 2408 patients from the Osteoarthritis Initiative (OAI) database, with 629 patients from the Multicenter Osteoarthritis Study (MOST) database. The clinical dataset included 18 clinical features, while the imaging dataset contained an additional 10 imaging features. Minimal Clinically Important Difference (MCID) was set to 24, reflecting meaningful physical impairment. Clinical and imaging dataset models produced similar area under curve (AUC) scores, highlighting low differences in performance AUC < 0.025). For both clinical and imaging datasets, Gradient Boosting Machine (GBM) models performed the best in the external validation, with a clinically acceptable AUC of 0.734 (95% CI 0.687-0.781) and 0.747 (95% CI 0.701-0.792), respectively. The five features identified included educational background, family history of osteoarthritis, co-morbidities, use of osteoporosis medications and previous knee procedures. This is the first study to demonstrate that ML models achieve comparable performance with and without imaging features.

Functional Outcome after Direct Anterior Approach Total Hip Arthroplasty (DAA-THA) for Coxa Profunda and Protrusio Acetabuli-A Retrospective Study.

Objective: The direct anterior approach (DAA) is a recognized technique for total hip arthroplasty (THA) that spares soft tissue. Functional and clinical outcomes following THA via the DAA in patients with complex acetabular deformities, specifically coxa profunda (CP) and protrusio acetabuli (PA), have yet to be determined. Methods: A retrospective analysis was conducted on 188 primary THA cases, including 100 CP hips and 88 PA hips, performed via the DAA. Functional and clinical outcomes were evaluated by means of the Western Ontario and McMaster Universities Arthritis Index (WOMAC) and Harris Hip Score (HHS) preoperatively and at a mean follow-up of 46 ± 14 months. Furthermore, potential complications were assessed. Results: From the preoperative to the latest postoperative visit, a significant improvement in the WOMAC total score was observed (CP: -34.89 ± 20.66; PA: -40.38 ± 21.11). The length of stay (LOS) was the only parameter predictive of the postoperative WOMAC total score, with each day of LOS increasing the postoperative WOMAC by a mean of 1.77 points (p < 0.01). The HHS improved by 38.37 ± 14.23 (PA-group) and 32.79 ± 14.89 points (CP-group). No significant difference in the patient-reported outcome measures (PROMs) between the CP- and PA-group was found. The survival rate for any revision was 97.70% (PA-group) and 92.80% (CP-group). Conclusion: The results of this study indicate that the minimally invasive DAA was not predictive of the functional and clinical outcome following DAA-THA in patients with CP and PA. Improvements in the mean WOMAC and HHS scores were above or within the reported MCID. Additionally, revision rates were well below those reported in the literature for short and intermediate follow-up periods.

Fu-zi decoction attenuate rheumatoid arthritis in vivo and in vitro by modulating RANK/RANKL signaling pathway.

Fu-zi decoction (FZD) has a long history of application for treating Rheumatoid arthritis (RA) as a classic formulation. However, its underlying mechanisms have not been fully elucidated. This study aimed to decipher the potential mechanism of FZD in treating RA, with a specific focus on receptor activator of nuclear factor κB/receptor activator of nuclear factor κB ligand (RANK/RANKL) signaling pathway. The impact of FZD on RA was investigated in collagen-induced arthritis rats (CIA), and the underlying mechanism was investigated in an osteoclast differentiation cell model. In vivo, the antiarthritic effect of FZD at various doses (2.3, 4.6, 9.2g/kg/day) was evaluated by arthritis index score, paw volume, toe thickness and histopathological examination of inflamed joints. Additionally, the ankle joint tissues were determined with micro-CT and safranin O fast green staining to evaluate synovial hyperplasia and articular cartilage damage. In vitro, osteoclast differentiation and maturation were evaluated by TRAP staining in RANKL-induced bone marrow mononuclear cells. The levels of pro- and anti-inflammatory cytokines as well as RANKL and OPG were evaluated by ELISA kits. In addition, Western blotting was used to investigate the effect of FZD on RANK/RANKL pathway activation both in vivo and in vitro. FZD significantly diminished the arthritis index score, paw volume, toe thickness and weigh loss in CIA rats, alleviated the pathological joint alterations. Consistent with in vivo results, FZD markedly inhibited RANKL-induced osteoclast differentiation by decreasing osteoclast numbers in a dose-dependent manner. Moreover, FZD decreased the levels of pro-inflammatory cytokines IL-6, IL-1β and TNF-α, while increasing anti-inflammatory cytokine IL-10 level both in serum and culture supernatants. Treatment with FZD significantly reduced serum RANKL levels, increased OPG levels, and decreased the RANKL/OPG ratio. In both in vivo and in vitro settings, FZD downregulated the protein expressions of RANK, RANKL, and c-Fos, while elevating OPG levels, further decreasing the RANKL/OPG ratio. In conclusion, FZD exerts a therapeutic effect in CIA rats by inhibiting RANK/RANKL-mediated osteoclast differentiation, which suggested that FZD is a promising treatment for RA.

Femorotibial angle scan-rescan reproducibility: A high-precision calculation on a large cohort.

Femorotibial angle (FTA) is a convenient measure of coronal knee alignment that can be extracted from a short knee radiograph, avoiding the additional radiation exposure and specialist equipment required for full-leg radiographs. While intra- and inter-reader reproducibility from the same image has been reported, the full scan-rescan reproducibility across images, as calculated in this study, has not. In this study, 4589 FTA measurement pairs from 2586 subjects acquired a year apart were used to estimate FTA scan-rescan reproducibility using data from the Osteoarthritis Initiative. Subjects with radiographic progression of osteoarthritis or other conditions that may cause a change in coronal knee alignment were excluded. Measurement pairs were analysed using paired-samples tests to detect differences and compared to symptomatic changes in Western Ontario and McMaster Universities Arthritis Index scores for joint pain, stiffnessand physical function to detect correlations. The 95% limit of agreement and the paired-samplescorrelation were calculated with high precision to be [-1.76°, +1.78°] and 0.938, considerably worse than the corresponding figures for intra- and inter-reader reproducibility, without relation to symptomatic or radiographic changes in knee condition. This error will weakly attenuate and values from their true values in correlative studies involving FTA. The realistic maximum value for is 87%and for Pearson's is 93%. The scan-rescan reproducibility in FTAis almost double the intra- and inter-reader reliability from a single scan. At almost ±2° accuracy, FTA is inappropriate for surgical use, but it is sufficiently reproducible to produce good correlations in studies predicting disease incidence and progression. Level II, retrospective study.

Predictors and Prevalence of Persistent Pain after Total Knee Arthroplasty in One-Year Follow-up.

Total knee arthroplasty (TKA) is one of the most common surgeries performed to reduce pain and disability in knee arthritis. Comprehension of the etiology and prevalence of persistent postoperative knee pain can help reduce this pain and identify the predictive factors leading to it. This study aimed to investigate the predictive factors and the prevalence of persistent pain after total knee arthroplasty in one-year follow-up. This was a prospective cohort study. Demographic data including age, sex, body mass index (BMI), hospital anxiety and depression scale (HADS), and comorbidities were collected. In 242 patients, preoperative and postoperative Western Ontario and McMaster Universities Arthritis Index (WOMAC) scores were measured before and immediately after surgery and in 3-, 6-, and 12-month intervals during follow-up. Loosening of the prosthesis was also investigated by radiographic imaging in every postoperative visit. WOMAC pain decreased from a mean (standard deviation) of 49 before surgery to 18 at 6 months and 13 at 12 months. Despite this, the prevalence of moderate-to-severe persistent postoperative pain (PPP) was 13.22% (n = 32) and 9.09% (n = 22) at 6 and 12 months lower preoperative WOMAC (odd's ratio:2.8), loosening of the prosthesis (odd's ratio:1.9), higher HADS (odd's ratio:2.1) were main predictors for PPP in TKA patients as in rheumatoid arthritis (odd's ratio:1.2). Loosening of the prosthesis and higher preoperative WOMAC scores are key factors in persistent post-TKA pain. Depression and anxiety are more popular among patients with more pain after TKA. RA is more prevalent in patients with PPP after TKA.