Clinical value of ankle flexion and extension exercises combined with a psychological intervention in knee osteoarthritis.

BACKGROUND: Considering the limited effectiveness of clinical interventions for knee osteoarthritis (KOA), it is necessary to continue to explore appropriate and effective treatment strategies to improve the condition of KOA patients. AIM: To clarify the influence of ankle flexion and extension exercises combined with a psychological intervention on the psychological status and activities of daily living (ADLs) of patients with KOA. METHODS: The research participants were 116 KOA patients admitted to The First Affiliated Hospital of Guizhou University of Traditional Chinese Medicine between May 2019 and May 2022, including 54 patients receiving routine treatment, care and psychological intervention (control group) and 62 patients additionally treated with ankle flexion and extension exercises (research group). The two groups were comparatively analyzed in terms of psychological status (Self-rating Anxiety/Depression Scale, SDS/SAS), ADLs, knee joint function (Lysholm Knee Scoring Scale), pain (Visual Analog Scale, VAS), fatigue (Multidimensional Fatigue Inventory, MFI), and quality of life (QoL; Short-Form 36 Item Health Survey, SF-36). RESULTS: After evaluation, it was found that the postinterventional SDS, SAS, VAS, and MFI scores in the research group were significantly reduced compared with the baseline (before the intervention) values and those of the control group, while the postinterventional Lysholm, ADL and SF-36 scores were markedly elevated. CONCLUSION: Therefore, ankle flexion and extension exercises are highly effective in easing negative psychological status, enhancing ADLs, daily living ability, knee joint function and QoL, and relieving pain and fatigue in KOA patients, thus warranting clinical promotion.

Exploring the active ingredients and potential mechanisms of action of sinomenium acutum in the treatment of rheumatoid arthritis based on systems biology and network pharmacology.

Objective: To investigate and predict the targets and signaling pathways of sinomenium acutum (SA) in the treatment of rheumatoid arthritis (RA) through systems biology and network pharmacology, and to elucidate its possible mechanisms of action. Methods: We screened the active ingredients and corresponding target proteins of SA in Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform (TCMSP), Traditional Chinese Medicines Integrated Database (TCMID) and Bioinformatics Analysis Tool for Molecular mechANism of Traditional Chinese Medicine (BATMAN); and obtained the targets of rheumatoid arthritis diseases in a database of gene-disease associations (DisGeNET), Online Mendelian Inheritance in Man (OMIM) database. The two targets were mapped by Venn diagram and the intersection was taken. The intersecting targets were used to construct protein-protein interaction (PPI) network maps in the String database, and Metascape was used for Gene Ontology (GO) functional annotation and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment. Finally, the molecular docking technique was applied to validate and further clarify the core target of SA for the treatment of rheumatoid arthritis. Results: A total of six active ingredients and 217 potential targets were obtained after screening; 2,752 rheumatoid arthritis-related targets and 66 targets common to RA and SA. GO function and KEGG pathway enrichment analysis yielded 751 GO function entries (652 GO biological processes, 59 GO molecular functions and 40 GO cellular components) and 77 KEGG signaling pathways. It mainly involves pathways related to neural activity ligand-receptor interaction pathways, cancer pathways, calcium signaling channels, Th17 cell differentiation and others, which are mainly classified into four categories, including regulation of immunity, anti-inflammation, regulation of cell growth and apoptosis, and signaling. The molecular docking results showed that the binding energy of PTGS2, CASP3, JUN and PPARG to the key components beta-sitosterol, 16-epi-Isositsirikine, Sinomenine and Stepholidine were ≤ -6.5 kcal/mol, suggesting the existence of molecular binding sites. Conclusion: SA acts on key targets such as PTGS2, CASP3, JUN, and PPARG to modulate signaling pathways such as neural activity ligand-receptor interaction, cancer, calcium ion, NF-κB, and Th17 cell differentiation to regulate immunity, anti-inflammation, modulation of cell cycle, bone metabolism, and signaling for the treatment of RA. It was also confirmed that the treatment of RA with SA has multi-component, multi-target, multi-pathway and multi-mechanism characteristics.

Preference of Orthopedic Practitioners Toward the Use of Topical Medicine for Musculoskeletal Pain Management in China: A National Survey.

OBJECTIVE: Musculoskeletal pain is having growing impacts worldwide with clinical challenge in pain management. The purpose of the present study is to investigate the preferences of orthopedic surgeons of China for using medicine in musculoskeletal pain. METHODS: A questionnaire was developed, including the following domains, personal information, medication preference for pain treatment, and perceptions of topical medicine. Ten participants were selected to confirm the consistency of questionnaire. A cross-sectional survey was conducted in orthopedic physicians with different specialties in different regions of China via the online survey platform. The participants' survey results were analyzed one-way and multi-way using chi-square test and logistic regression. RESULTS: The pre-survey analysis results of 10 randomly selected investigators were a mean weighted kappa coefficient of 0.76 (range 0.61-0.89), which indicated the substantial consistency of the present questionnaire. A total of 1099 orthopedic surgeons (mean age, 41.67 ± 8.31 years) responded to our survey, most of whom were male (90.72%), and most of whom worked in level III hospitals (63.24%) and trained in modern medicine (71.43%). Most surgeons who participated in the survey had used topical analgesics in their clinical work (95.81%), and most preferred to use topical analgesics (39.50%) or a combination of oral analgesics (28.87%). Primary reasons for preferring topical analgesics were as follows: less adverse reactions (68.01%); ease of use (60.90%); and not interfering with other oral medications (49.60%). The preference for prescribing topical analgesics increased with the education level of the respondent, where statistically significant differences were seen (P < 0.05). In addition, the level of the respondent's hospital, type of hospital, the respondent's profession, and their participation in surgical work influenced their preferences for topical analgesics (P < 0.05). CONCLUSION: Orthopedic surgeons across China have different medication preferences in the treatment of musculoskeletal pain. The educational background of the physician largely influences the preference when selecting medications. To better improve the treatment of musculoskeletal pain, there is a need to improve the overall medical education of practitioners and to disseminate clinical practice guidelines.

Traditional Chinese medicine classification of knee osteoarthritis with proteomics analysis.

BACKGROUND: Osteoarthritis (OA) is a heterogeneous disease caused by the pathology of the synovial joint. About 10-12% of adults have symptomatic OA. In this study, the proteomics method was used to find differentially expressed proteins and to explore the material basis of traditional Chinese medicine (TCM) classification in knee OA patients. METHODS: Fifteen patients of the treatment group with knee OA of three different classifications were divided into three groups according to the dialectical classification of TCM: kidney deficiency type (5 cases), Yang deficiency type (5 cases), blood stasis type (5 cases). Also, five patients with traumatic synovitis were enrolled as the control group. The joint fluids were drawn separately. The joint fluids before treatment were Aa, Ba, and Ca groups. After one week of medication, the three joint fluid types were drawn again, and they were Ab group, Bb, and Cb groups. Liquid from the control group was named group D. Quantitative analysis of protein expression was conducted to find out the differently expressed proteins. The treatment group was treated with prescriptions for syndromes according to the TCM classification. RESULTS: The proteomics analysis identified 251 differentially expressed protein groups, and the number of groups with quantitative information for all seven channels was 246. The three treatment groups and the control group had 32 differential proteins (P<0.01), of which nine might be differential proteins between OA and traumatic synovitis. Histone H4, histone H2A, S100 calbindin A8, fibrinogen γ, fiber protein α, cDNA (FLJ92148), C4b binding protein, and partial transketolase variants were down-regulation, and basement membrane glycan was up-regulation in the treatment group compared with the control group (P<0.01). HIST1H2BC and myeloperoxidase levels in the Aa group were less than those in the D and Ab groups. The serum amyloid P and apolipoprotein CI variants in the Ba group were less than those in the D and Bb groups. Histone H2A and C-reactive protein, Fibrinogen α levels in the Ca group were less than those in the D and Cb groups. CONCLUSIONS: Nine proteins are closely related to OA of different TCM classification.

Valgus malalignment and prevalence of lateral compartmental radiographic knee osteoarthritis (OA): The Wuchuan OA study.

AIM: To evaluate whether knee alignment explains the higher prevalence of lateral compartment tibiofemoral radiographic osteoarthritis (TFROA) among rural Chinese compared with that among Whites. METHODS: The Wuchuan OA Study is a population-based longitudinal study of risk factors for knee OA. At baseline 1030 participants had home interviews, clinical examinations and weight-bearing posteroanterior semi-flexed radiographs of the tibiofemoral joints. Anatomic knee alignment was measured using an e-film workstation and divided into three categories: normal (182°-184°), valgus (> 184°), and varus (< 182°) alignment. A knee was defined as having medial or lateral compartmental ROA if its Kellgren and Lawrence grade was ≥ 2 and joint space narrowing ≥ 1 in the medial or lateral compartment, respectively. We examined the association between knee alignment with prevalent medial or lateral knee ROA separately using multiple logistic regression. RESULTS: Among 1030 participants, the proportions of knees with normal, valgus and varus alignment were 29.9%, 56.5% and 13.7%, respectively. The prevalence of medial and lateral ROA was 16.0% and 4.3%, respectively. Valgus alignment was associated with prevalence of lateral compartment ROA (odds ratio [OR] = 5.0, 95% CI: 2.4-10.5), while varus alignment was associated with medial compartment ROA (OR = 6.1, 95% CI: 4.4-8.6). The ratio of prevalence of lateral versus medial compartment TFROA was greater in Wuchuan than that in the Framingham OA Study and valgus malalignment was more common in Wuchuan than in the Rotterdam study. CONCLUSIONS: The prevalence of compartment-specific TFROA differs between rural Chinese and Whites. This difference is likely due to relatively high prevalence of valgus malalignment in rural Chinese compared with that in Whites.

Intra-articular Hyaluronic Acid in Treating Knee Osteoarthritis: a PRISMA-Compliant Systematic Review of Overlapping Meta-analysis.

Numerous meta-analyses have been conducted aiming to compare hyaluronic acid (HA) and placebo in treating knee osteoarthritis (OA). Nevertheless, the conclusions of these meta-analyses are not in consistency. The purpose of the present study was to perform a systematic review of overlapping meta-analyses investigating the efficacy and safety of HA for Knee OA and to provide treatment recommendations through the best evidence. A systematic review was conducted based on the PRISMA guidelines. The meta-analyses and/or systematic reviews that compared HA and placebo for knee OA were identified. AMSTAR instrument was used to evaluate the methodological quality of individual study. The information of heterogeneity within each variable was fetched for the individual studies. Which meta-analyses can provide best evidence was determined according to Jadad algorithm. Twelve meta-analyses met the eligibility requirements. The Jadad decision making tool suggests that the highest quality review should be selected. As a result, a high-quality Cochrane review was included. The present systematic review of overlapping meta-analyses demonstrates that HA is an effective intervention in treating knee OA without increased risk of adverse events. Therefore, the present conclusions may help decision makers interpret and choose among discordant meta-analyses.

Osteoarthritis and all-cause mortality in worldwide populations: grading the evidence from a meta-analysis.

The objective of this study is to investigate the association between osteoarthritis (OA) and all-cause mortality in worldwide populations and to develop recommendations according to GRADE evidence levels. Literature search through Nov 2015 was performed using the electronic databases (including MEDLINE, EMBASE, EBSCO and Cochrane library). The prospective cohort trials that investigated the association between the symptomatic OA (SxOA) or radiological OA (ROA) and all-cause mortality were identified. Hazard ratios (HR) of all-cause mortality in patients with RxOA or ROA were pooled respectively. The evidence quality was evaluated using the GRADE system, while the recommendations were taken according to the quality. Nine of the published literature met the eligible criteria. Meta-analysis revealed that there was no significant difference in the association between SxOA and all-cause mortality (HR = 0.91, 95% CI: 0.68-1.23) and between ROA and all-cause mortality (HR = 1.13, 95% CI: 0.95-1.35). The overall GARDE evidence quality was very low, which will lower our confidence in taking recommendations. To summarize, there was no reliable and confident evidence existed currently in respect of the association between OA and all-cause mortality. Due to the very low level of evidence quality currently, high-quality studies are still required.

The role of MCP-1-CCR2 ligand-receptor axis in chondrocyte degradation and disease progress in knee osteoarthritis.

BACKGROUND: Osteoarthritis (OA) is a common arthritic disease and multifactorial whole-joint disease. Interactions of chemokines and OA is inadequately documented. RESULTS: In vivo and in vitro studies were conducted to investigate monocyte chemoattractant protein 1 (MCP-1) and receptor chemokine (C-C motif) receptor 2 (CCR2) in chondrocyte degradation and cartilage degeneration. Chondrocytes from 16 OA patients and 6 normal controls were involved in this study. After stimulation of MCP-1, the expression of MCP-1 and CCR2 increased significantly (P < 0.001) and the expression of MMP-13 also increased (P < 0.05). MCP-1 stimulation also induced (or enhanced) the apoptosis of OA chondrocytes (P < 0.05). Additionally, the degradation of cartilage matrix markers (metalloproteinase 3 and 13, MMP3 and MMP13) in the culture medium of normal chondrocytes was also assessed. Furthermore, intra-articular injection of MCP-1 in mouse knees induced cartilage degradation and the CCR2 antagonist did not impede cartilage destroy in rats knees of monosodium iodoacetate (MIA) model. CONCLUSIONS: The results of this study demonstrate that the MCP-1-CCR2 ligand-receptor axis plays a special role in the initiation and progression of OA pathology. Patients with ambiguous etiology can gain some insight from the MCP-1-CCR2 ligand-receptor axis.

The role of MCP-1-CCR2 ligand-receptor axis in chondrocyte degradation and disease progress in knee osteoarthritis

BACKGROUND: Osteoarthritis (OA) is a common arthritic disease and multifactorial whole-joint disease. Interactions of chemokines and OA is inadequately documented. RESULTS: In vivo and in vitro studies were conducted to investigate monocyte chemoattractant protein 1 (MCP-1) and receptor chemokine (C-C motif) receptor 2 (CCR2) in chondrocyte degradation and cartilage degeneration. Chondrocytes from 16 OA patients and 6 normal controls were involved in this study. After stimulation of MCP-1, the expression of MCP-1 and CCR2 increased significantly (P < 0.001) and the expression of MMP-13 also increased (P < 0.05). MCP-1 stimulation also induced (or enhanced) the apoptosis of OA chondrocytes (P < 0.05). Additionally, the degradation of cartilage matrix markers (metalloproteinase 3 and 13, MMP3 and MMP13) in the culture medium of normal chondrocytes was also assessed. Furthermore, intra-articular injection of MCP-1 in mouse knees induced cartilage degradation and the CCR2 antagonist did not impede cartilage destroy in rats knees of monosodium iodoacetate (MIA) model. CONCLUSIONS: The results of this study demonstrate that the MCP-1-CCR2 ligand-receptor axis plays a special role in the initiation and progression of OA pathology. Patients with ambiguous etiology can gain some insight from the MCP-1-CCR2 ligand-receptor axis.