An Assessment of Ankle Function, Oxidative Damage, and Inflammatory Factor Levels in Minimally Invasive Ankle Joint Fusion Surgery for the Treatment of Traumatic Ankle Osteoarthritis

SUMMARY: Traumatic ankle osteoarthritis is a degenerative condition resulting from traumatic injuries. The objective of this study was to evaluate the impact of minimally invasive ankle joint fusion surgery on ankle function, oxidative damage, and inflammatory factor levels in traumatic ankle osteoarthritis patients. A total of 112 traumatic ankle osteoarthritis patients treated in our hospital from January 2022 to January 2023 were enrolled. They were randomly rolled into a control group (Group C) and an experimental group (Group E), with the former undergoing conventional open ankle joint fusion surgery and the latter receiving minimally invasive ankle joint fusion surgery. A comparison was made between the two groups based on American Orthopedic Foot and Ankle Society (AOFAS), bony fusion rates, and visual analog scale (VAS) scores at pre-operation, and at 1, 2, and 3 months post-operation. Additionally, serum oxidative damage indicators and inflammatory factor levels were measured to evaluate the recovery effects in both groups. Relative to Group C, Group E showed drastically increased AOFAS scores and bony fusion rates (P<0.05), as well as greatly decreased VAS scores (P<0.05). Moreover, Group E exhibited more pronounced improvements in oxidative damage indicators and inflammatory factors versus Group C (P<0.05). Minimally invasive ankle joint fusion surgery drastically improves ankle function in traumatic ankle osteoarthritis patients and reduces levels of oxidative damage and inflammatory response. This provides an important clinical treatment option.

La osteoartritis traumática del tobillo es una afección degenerativa resultante de lesiones traumáticas. El objetivo de este estudio fue evaluar el impacto de la cirugía mínimamente invasiva de fusión de la articulación talocrural sobre la función del tobillo, el daño oxidativo y los niveles de factor inflamatorio en pacientes con osteoartritis traumática del tobillo. Se inscribieron un total de 112 pacientes con artrosis traumática de tobillo tratados en nuestro hospital desde enero de 2022 hasta enero de 2023. Fueron divididos aleatoriamente en un grupo de control (Grupo C) y un grupo experimental (Grupo E), donde el primero se sometió a una cirugía de fusión de la articulación talocrural abierta convencional y el segundo recibió una cirugía de fusión de la articulación talocrural mínimamente invasiva. Se realizó una comparación entre los dos grupos según la Sociedad Estadounidense de Ortopedia de Pie y Tobillo (AOFAS), las tasas de fusión ósea y las puntuaciones de la escala visual analógica (EVA) antes de la operación y 1, 2 y 3 meses después de la operación. Además, se midieron los indicadores de daño oxidativo sérico y los niveles de factor inflamatorio para evaluar los efectos de la recuperación en ambos grupos. En relación con el grupo C, el grupo E mostró puntuaciones AOFAS y tasas de fusión ósea drásticamente aumentadas (P <0,05), así como puntuaciones VAS muy disminuidas (P <0,05). Además, el grupo E exhibió mejoras más pronunciadas en los indicadores de daño oxidativo y factores inflamatorios en comparación con el grupo C (P <0,05). La cirugía de fusión de la articulación talocrural mínimamente invasiva mejora drásticamente la función del tobillo en pacientes con osteoartritis traumática del tobillo y reduce los niveles de daño oxidativo y la respuesta inflamatoria. Esto proporciona una importante opción de tratamiento clínico.

Radical surgical approach to chronic suppurative osteomyelitis: Case report / Abordaje quirúrgico radical de una osteomielitis crónica supurativa: reporte de caso

Abstract Diabetes mellitus is a systemic condition potentially related to an increased risk of progression of various infections such as chronic osteomyelitis by accelerating the inflammatory process with bone tissue necrosis and suppuration. Therefore, if there is no proper management of these infections, they can be life-threatening as they spread to deeper spaces in the head and neck. We describe the case of a 52-year-old male patient with a history of diabetes mellitus and grade III osteoarthritis who was diagnosed with chronic suppurative osteomyelitis of the mandible. He underwent a multidisciplinary surgical intervention in which he underwent a hemimandibulectomy with immediate mandibular reconstruction. The present case highlights the importance of early and radical treatment of patients with chronic suppurative osteomyelitis of the mandible and systemic comorbidities. In addition, this case presents a review of diabetes mellitus and the risk of developing odontogenic infections and complications when invading deeper spaces in the head and neck. Therefore, in this population, careful planning is required for early surgical and pharmacological treatment.

Resumen La diabetes mellitus es una condición sistémica potencialmente relacionada con un mayor riesgo de progresión de diversas infecciones como la osteomielitis crónica al acelerar el proceso inflamatorio con necrosis del tejido óseo y supuración. Por lo tanto, si no hay un manejo adecuado de estas infecciones pueden ser potencialmente mortales al llegar a propagarse a espacios más profundos de la cabeza y cuello. Describimos el caso de un paciente varón de 52 años con antecedentes de diabetes mellitus y osteoartrosis grado III a quien se le diagnosticó de osteomielitis crónica supurativa mandibular. Se le realizó una intervención quirúrgica multidisciplinaria en la cual se le realizó una hemimandibulectomía con reconstrucción mandibular inmediata. El presente caso destaca la importancia del tratamiento temprano y radical de los pacientes con osteomielitis mandibular crónica supurativa y comorbilidades sistémicas. Además, en este caso se presenta una revisión sobre la diabetes mellitus y el riesgo de desarrollar infecciones odontogénicas y complicaciones al invadir espacios más profundos de la cabeza y cuello. Por lo tanto, en esta población se requiere de una planificación cuidadosa para realizar un tratamiento quirúrgico y farmacológico temprano.

Ejercicio terapéutico en la disminución del dolor en pacientes con artrosis de rodilla grado 1: revisión sistemática / Therapeutic exercise to reduce pain in patients with grade 1 knee arthrosis: systematic review / Exercício terapêutico para reduzir a dor em pacientes com artrose grau 1 do joelho: revisão sistemática

La artrosis de rodilla grado 1 es un problema frecuente a escala mundial. La fisioterapia se presenta como una alternativa prometedora para el tratamiento conservador de esta patología, ya que reduce eficazmente la artralgia. Objetivo. Describir la eficacia de los ejercicios terapéuticos para aliviar el dolor en la artrosis de rodilla grado I. Metodología. Se trata de una revisión sistemática, que abarcó una búsqueda exhaustiva en varias bases de datos como Pubmed, Scielo y Elsevier. Los criterios de búsqueda incluyeron ensayos de control aleatorios, experimentales y cuasiexperimentales realizados entre los años 2017 y 2023. Resultados. De un total de 82 documentos se excluyeron 40 al ser estudios secundarios. Posteriormente, se excluyeron 21 estudios adicionales debido a la escasa relación entre las variables del estudio y a su falta de disponibilidad. Finalmente, se seleccionaron 21 artículos que cumplieron con los criterios de evaluación de calidad metodológica mediante la escala CRF-QS. Para evaluar el dolor, la rigidez, la funcionalidad y la calidad de vida, se utilizaron escalas como EVA, NPRS, WOMAC y OXFORD. Los ejercicios isocinéticos resultaron ser los más efectivos, ya que demostraron un aumento de la fuerza y el grosor del cartílago articular, lo que resultó en una disminución de las puntuaciones de EVA de 8,05 a 3,75. Conclusión. El ejercicio terapéutico supervisado centrado en el fortalecimiento de las extremidades inferiores ha demostrado ser una alternativa efectiva para el tratamiento conservador de la artrosis de rodilla grado I. Este enfoque alivia eficazmente el dolor, mejora la calidad de vida e incluso puede detener la progresión de la enfermedad.

Grade 1 knee osteoarthritis is a common problem worldwide. Physiotherapy is presented as a promising alternative for the conservative treatment of this pathology, since it effectively reduces arthralgia. Aim. To describe the effectiveness of therapeutic exercises to relieve pain in grade I knee osteoarthritis. Methodology. This is a systematic review, which included an exhaustive search in several databases such as Pubmed, Scielo and Elsevier. Search criteria included randomized, experimental and quasi-experimental control trials conducted between the years 2017 and 2023. Results. Of a total of 82 documents, 40 were excluded as they were secondary studies. Subsequently, 21 additional studies were excluded due to poor relationships between study variables and lack of availability. Finally, 21 articles were selected that met the methodological quality evaluation criteria using the CRF-QS scale. To evaluate pain, stiffness, functionality and quality of life, scales such as VAS, NPRS, WOMAC and OXFORD were used. Isokinetic exercises were found to be the most effective, demonstrating an increase in articular cartilage strength and thickness, resulting in a decrease in VAS scores from 8.05 to 3.75. Conclusion. Supervised therapeutic exercise focused on strengthening the lower extremities has been shown to be an effective alternative to the conservative treatment of grade I knee osteoarthritis. This approach effectively relieves pain, improves quality of life, and may even stop the progression of osteoarthritis. disease.

A osteoartrite do joelho grau 1 é um problema comum em todo o mundo. A fisioterapia apresenta-se como uma alternativa promissora para o tratamento conservador desta patologia, uma vez que reduz eficazmente a artralgia. Mirar. Descrever a eficácia dos exercícios terapêuticos no alívio da dor na osteoartrite de joelho grau I. Metodologia. Trata-se de uma revisão sistemática, que incluiu uma busca exaustiva em diversas bases de dados como Pubmed, Scielo e Elsevier. Os critérios de pesquisa incluíram ensaios de controle randomizados, experimentais e quase-experimentais realizados entre os anos de 2017 e 2023. Resultados. De um total de 82 documentos, 40 foram excluídos por se tratarem de estudos secundários. Posteriormente, 21 estudos adicionais foram excluídos devido às más relações entre as variáveis do estudo e à falta de disponibilidade. Por fim, foram selecionados 21 artigos que atenderam aos critérios de avaliação da qualidade metodológica pela escala CRF-QS. Para avaliar dor, rigidez, funcionalidade e qualidade de vida foram utilizadas escalas como VAS, NPRS, WOMAC e OXFORD. Os exercícios isocinéticos foram considerados os mais eficazes, demonstrando um aumento na força e espessura da cartilagem articular, resultando em uma diminuição nos escores VAS de 8,05 para 3,75. Conclusão. O exercício terapêutico supervisionado focado no fortalecimento das extremidades inferiores tem se mostrado uma alternativa eficaz ao tratamento conservador da osteoartrite do joelho grau I. Esta abordagem alivia eficazmente a dor, melhora a qualidade de vida e pode até interromper a progressão da osteoartrite.

The rs1477196 SNP of the FTO Gene is Associated with Primary Knee Osteoarthritis in a Female Population from Northern Mexico

ABSTRACT Background: Osteoarthritis is a frequent rheumatic disease. Some single-nucleotide polymorphisms of the gene associated with fat mass and obesity are associated with increased body mass index and knee osteoarthritis. Objective: The objective of this study was to analyze the association of single nucleotide polymorphism rs1477196 of the fat mass and obesity gene with primary knee osteoarthritis. Methods: This observational and cross-sectional study included 347 Mexican participants. We performed the genotypification analysis with TaqMan® probe C_2031262_10 for rs1477196 (Thermo Fisher Scientific). Multivariate analysis included covariables such as age, type 2 diabetes, obesity, and postmenopause. Results: Type 2 diabetes, obesity, and postmenopause were associated with primary knee osteoarthritis in female participants. We did not find an association between rs1477196 and obesity. In the codominant and dominant genetic models, rs1477196 was significantly associated with primary knee osteoarthritis only in the female group, including in the model adjusted by other covariables (odds ratio = 2.517; 1.035-6.123; p = 0.042 and odds ratio = 2.387; 1.054-5.407; p = 0.037, respectively). The interaction between rs1477196 and obesity was significantly associated with primary knee osteoarthritis in female participants (p = 0.039 and p = 0.043). Conclusions: Our findings suggest that the rs1477196 variant of the fat and obesity mass gene may be associated with the risk of primary knee osteoarthritis in women.

Electro-acupuncture modulated miR-214 expression to prevent chondrocyte apoptosis and reduce pain by targeting BAX and TRPV4 in osteoarthritis rats

Osteoarthritis (OA) is a highly prevalent joint disorder characterized by progressive degeneration of articular cartilage, subchondral bone remodeling, osteophyte formation, synovial inflammation, and meniscal damage. Although the etiology of OA is multifactorial, pro-inflammatory processes appear to play a key role in disease pathogenesis. Previous studies indicate that electroacupuncture (EA) exerts chondroprotective, anti-inflammatory, and analgesic effects in preclinical models of OA, but the mechanisms underlying these potential therapeutic benefits remain incompletely defined. This study aimed to investigate the effects of EA on OA development in a rat model, as well as to explore associated molecular mechanisms modulated by EA treatment. Forty rats were divided into OA, EA, antagomiR-214, and control groups. Following intra-articular injection of monosodium iodoacetate to induce OA, EA and antagomiR-214 groups received daily EA stimulation at acupoints around the knee joint for 21 days. Functional pain behaviors and chondrocyte apoptosis were assessed as outcome measures. The expression of microRNA-214 (miR-214) and its downstream targets involved in apoptosis and nociception, BAX and TRPV4, were examined. Results demonstrated that EA treatment upregulated miR-214 expression in OA knee cartilage. By suppressing pro-apoptotic BAX and pro-nociceptive TRPV4, this EA-induced miR-214 upregulation ameliorated articular pain and prevented chondrocyte apoptosis. These findings suggested that miR-214 plays a key role mediating EA's therapeutic effects in OA pathophysiology, and represents a promising OA treatment target for modulation by acupuncture.

Quality of Life of Patients submitted to Total Knee Arthroplasty / Qualidade de vida de pacientes submetidos à artroplastia total do joelho

Objective: the aim of this study was to evaluate the quality of life between patients who have already undergone the TKA surgery and those who have not. Methodology: 118 patients [60 undergoing TKA (G1) and the remaining 58 awaiting the procedure (G2)] answered questions about QoL using the WOMAC and SF-36 protocols. The comparison was performed using the chi-square test and Student's t-test, with a significance level of 0.05. Results: with regard to clinical aspects, there was a higher level of pain in Group G2, as well as greater frequency in the use of medications, especially for pain relief. In the QoL evaluation, significant difference was observed in all the domains of the generic questionnaire SF-36 and in WOMAC, estando a capacidade functional do G2 reduzida e abaixo do nível observado nos pacientes do G1. Conclusion: patients with advanced knee arthrosis who underwent TKA, compared to those who did not undergo the procedure, had better quality of life in all domains assessed by both the general SF-36 questionnaire and the WOMAC questionnaire.

Objetivo: o objetivo deste estudo foi avaliar a qualidade de vida entre pacientes que já se submeteram à cirurgia de ATJ e aqueles que ainda não passaram pelo procedimento. Metodologia: 118 pacientes [60 submetidos à ATJ (G1) e os 58 restantes aguardando o procedimento (G2)] responderam perguntas sobre QV usando os protocolos WOMAC e SF-36. A comparação foi realizada usando o teste qui-quadrado e o teste t de Student, com um nível de significância de 0,05. Resultados: em relação aos aspectos clínicos, houve um maior nível de dor no Grupo G2, bem como maior frequência no uso de medicamentos, especialmente para alívio da dor. Na avaliação da QV, foi observada diferença significativa em todos os domínios do questionário genérico SF-36 e no WOMAC, estando a capacidade funcional do G2 reduzida e abaixo do nível observado nos pacientes do G1. Conclusão: pacientes com artrose avançada de joelho que se submeteram à ATJ, em comparação com aqueles que não passaram pelo procedimento, apresentaram melhor qualidade de vida em todos os domínios avaliados tanto pelo questionário geral SF-36 quanto pelo questionário WOMAC.

Effect of Tongluo Juanbi Granules on Inflammatory Injury and Apoptosis of Osteoarthritis Based on TLR4/MyD88/NF-κB Signaling Pathway / 中国实验方剂学杂志

ObjectiveTo investigate the effects of Tongluo Juanbi granules on chondrocyte apoptosis and Toll-like receptor 4 （TLR4）/myeloid differentiation factor 88 （MyD88）/nuclear factor-κB （NF-κB） signaling pathway of rabbits with knee osteoarthritis （KOA） and study the mechanism of Tongluo Juanbi granules in the prevention and treatment of KOA. MethodThirty New Zealand rabbits were randomly assigned to the following five groups （n=6）： sham group， model group， low-dose and high-dose groups of Tongluo Juanbi granules （4.1 and 8.2 g·kg-1·d-1）， and celecoxib group （10.9 mg·kg-1·d-1）. The KOA model was established by destabilization of the medial meniscus （DMM） for six weeks. Six weeks after the modeling， the drug was given once a day for eight weeks. The pathological changes of cartilago articularis were observed by hematoxylin-eosin （HE） staining and Safranin O-Fast Green staining. Terminal deoxynucleotidyl transferase dUTP nick end labeling （TUNEL） staining was performed to detect chondrocyte apoptosis. Enzyme-linked immunosorbent assay （ELISA） was used to detect the contents of interleukin-1β （IL-1β） and tumor necrosis factor-α （TNF-α） in synovial fluid. The mRNA and protein expression levels of genes related to the TLR4/MyD88/NF-κB signaling pathway were detected by real-time fluorescence quantitative polymerase chain reaction （Real-time PCR） and Western blot， respectively. ResultCompared with the sham group， the cartilago articularis of the model group significantly degenerated. Mankin's score was increased （P<0.01）， and the contents of IL-1β and TNF-α in synovial fluid were increased （P<0.01）. The number of apoptosis of chondrocytes was increased （P<0.01）. The mRNA and protein expressions of TLR4， MyD88， and NF-κB p65 in cartilage tissue were up-regulated （P<0.01）， while the mRNA and protein expressions of Bcl-2 were down-regulated （P<0.01）. Compared with the model group， chondrocyte degeneration in both low-dose and high-dose groups of Tongluo Juanbi granules was improved， and Mankin's score was decreased （P<0.01）. The contents of IL-1β and TNF-α were decreased （P<0.01）， and the number of apoptosis of chondrocytes was decreased （P<0.01）. The mRNA and protein expressions of TLR4， MyD88， and NF-κB p65 in cartilage tissue were down-regulated （P<0.01）， while the mRNA and protein expressions of Bcl-2 were up-regulated （P<0.01）. In addition， in the above observation indicators， the high-dose group of Tongluo Juanbi granules was significantly superior to the low-dose group of Tongluo Juanbi granules. ConclusionTongluo Juanbi granules could inhibit chondrocyte apoptosis in rabbits with KOA and improve cartilage degeneration， which may be related to inhibiting inflammatory responses mediated by TLR4/MyD88/NF-κB signaling pathway.

Impact of a Tailored Self-Management Education Programme for Older Adults with Knee Osteoarthritis in a Multi-Ethnic Country / Jurnal Sains Kesihatan Malaysia

@#Self-management education program (SMEP) is essential in the knee osteoarthritis (OA) management. While the benefits of tailored SMEP have been highlighted in the literature, evidence on the effects of tailored knee OA SMEP for multiethnic populations, such as in Malaysia, remains limited. Therefore, the aim of this study was to conduct an intervention study on a tailored SMEP among Malaysian older adults who aged 60 years and above with knee OA. Participants aged 60 years and over with a diagnosis of knee OA were recruited. The intervention comprised four weekly structured group SMEP which was developed specifically for the multicultural population in Malaysia. Symptom’s severity and functional performance were assessed at baseline and six-week follow-up using the Knee Injury and Osteoarthritis Outcome Score questionnaire (KOOS), 30 seconds sit to stand (30sST), time up and go (TUG), chair sit and reach (CSR), back stretch (BS), handgrip strength (HGS) and two-minute walk (2MW) tests. Of the 32 individuals recruited, 30 participants, mean age of 66.77 (±6.42) years, completed the post-intervention assessment. Improvements in mean KOOS domains scores were observed by between 1.3% - 8.6% from baseline to follow-up. Significant differences between baseline and followup scores were identified for 30sST (p < 0.05), TUG ( p < 0.001) and 2MW (p < 0.001) tests. A 4-week tailored SMEP delivered face to face by a physiotherapist, improved lower limb muscle strength, mobility, balance and endurance. Larger randomized controlled trials regarding the long-term effects of SMEP for older adults with OA is warranted.

Improvement effect and mechanism of “Layers adjusting external application”paste on synovial fibrosis in rats with knee osteoarthritis / 中国药房

OBJECTIVE To investigate the improvement effect and potential mechanism of “Layers adjusting external application” paste on synovial fibrosis （SF） in rats with knee osteoarthritis （KOA）. METHODS Male SD rats were randomly divided into sham operation group， KOA group and Layers adjusting external application group， with 8 rats in each group. KOA model was induced by the anterior cruciate ligament disruption method in KOA group and Layers adjusting external application group. Fourteen days after modeling， the Layers adjusting external application group was given “Layers adjusting external application” paste [Sanse powder （8 g for every 100 cm2）， Compound sanhuang ointment （5 g for every 100 cm2）] on the knee joint， 8 h every day， for 28 d in total. After the last administration， the degree of synovitis and fibrosis in rats was observed， and Krenn scoring was performed in each group. The expressions of collagen Ⅰ， high mobility group protein B1 （HMGB1） and phosphorylated nuclear factor-κB p65 （p-NF-κB p65） were detected in the synovial membrane； the contents of interleukin-1β （IL- 1β）， IL-6 and tumor necrosis factor-α （TNF-α） in serum as well as the expressions of fibrosis-related and HMGB1/Toll-like receptor 4 （TLR4）/NF-κB signaling pathway-related proteins and mRNA were detected in synovial tissue. RESULTS Compared with the sham operation group， the synovial lining cells in the KOA group showed significant proliferation and disordered arrangement， the inflammatory cell infiltration and collagen fiber deposition were obvious； the positive expressing cells of collagen Ⅰ， HMGB1 and p-NF-κB p65 were increased significantly； the contents of IL-1β， IL-6 and TNF-α in serum， the expressions of fibrosis-related protein （transforming growth factor-β， collagen Ⅰ， tissue inhibitor of metalloproteinase 1， α-smooth muscle actin） and their mRNA as well as theexpressions of HMGB1， TLR4 protein and their mRNA， the expressions of p-NF-κB p65 protein and NF-κB p65 mRNA were all increased significantly in synovial tissues of rats （P＜0.01）. Compared with the KOA group， the pathological changes in the synovial tissue of rats in Layers adjusting external application group were significantly improved， and the above quantitative indicators were significantly reversed （P＜0.05 or P＜0.01）. CONCLUSIONS “Layers adjusting external application” paste could significantly improve SF in KOA rats， the mechanism of which may be associated with the inhibition of the activation of HMGB1/ TLR4/NF-κB signaling pathway.

Traditional Chinese Medicine Regulates Autophagy to Prevent and Treat Osteoarthritis： A Review / 中国实验方剂学杂志

Osteoarthritis （OA） is a common chronic， highly prevalent， painful， and disabling degenerative joint disease. It has imposed a heavy burden on social healthcare and patients' psychology and economy due to its clinical symptoms such as impaired joint mobility and severe joint pain and the immature therapies. Studies have shown that OA is closely associated with articular cartilage dysfunction， synthesis and degradation disorders of chondrocyte extracellular matrix （ECM）， and joint inflammation. Moderate autophagy can restore the function of damaged chondrocytes， regulate chondrocyte apoptosis， and promote the synthesis and metabolism of ECM to alleviate the inflammation of joints and delay the onset and progression of OA. According to the clinical symptoms， OA can be classified into the category of impediment in traditional Chinese medicine. With the theories of holistic conception， treatment based on syndrome differentiation， and individualised diagnosis and treatment， traditional Chinese medicine has demonstrated definite effects in the treatment of OA in thousands of years of practice. Moreover， traditional Chinese medicine causes mild adverse reactions， and the patients have high tolerance and acceptance. This paper briefly explains the roles of autophagy and the related regulatory proteins， such as Unc-51-like autophagy-activated kinase 1 （ULK1）， Beclin-1， and microtubule-associated protein light chain 3 （LC3）， and details the latest research achievements in the prevention and control of OA by traditional Chinese medicines and its related markers via the regulation of autophagy， so as to provide a idea for the in-depth research in this field and the clinical application of traditional Chinese medicine in preventing and treating OA.

Effect of nerve growth factor on elderly degenerative knee osteoarthritis pain / 中国骨伤

OBJECTIVE@#To explore effect of nerve growth factor (NGF) antibody on knee osteoarthritis (KOA) pain model was evaluated by in vitro model.@*METHODS@#Thirty male SPF rats aged 28-week-old were divided into blank group (10 rats with anesthesia only). The other 20 rats were with monoiodoacetate (MIA) on the right knee joint to establish pain model of OA, and were randomly divided into control group (injected intraperitoneal injection of normal saline) and treatment group (injected anti-NGF) intraperitoneal after successful modeling, and 10 rats in each group. All rats were received retrograde injection of fluorogold (FG) into the right knee joint. Gait was assessed using catwalk gait analysis system before treatment, 1 and 2 weeks after treatment. Three weeks after treatment, right dorsal root ganglia (DRG) were excised on L4-L6 level, immunostained for calcitonin gene-related peptide (CGRP), and the number of DRGS was counted.@*RESULTS@#In terms of gait analysis using cat track system, duty cycle, swing speed and print area ratio in control and treatment group were significantly reduced compared with blank group (P<0.05). Compared with control group, duty cycle and swing speed of treatment group were significantly improved (P<0.05), and there was no significant difference in print area ratio between treatment group and blank group (P>0.05). The number of FG-labeled DRG neurons in control group was significantly higher than that in treatment group and blank group (P<0.05). The expression of CGRP in control group was up-regulated, and differences were statistically significant compared with treatment group (P<0.05).@*CONCLUSION@#Intraperitoneal injection of anti-NGF antibody inhibited gait injury and upregulation of CGRP in DRG neurons. The results suggest that anti-nerve growth factor therapy may be of value in treating knee pain. NGF may be an important target for the treatment of knee OA pain.

Effects of VX765 on osteoarthritis and chondrocyte inflammation in rats / 中国修复重建外科杂志

OBJECTIVE@#To investigate the effects and underlying mechanisms of VX765 on osteoarthritis (OA) and chondrocytes inflammation in rats.@*METHODS@#Chondrocytes were isolated from the knee joints of 4-week-old Sprague Dawley (SD) rats. The third-generation cells were subjected to cell counting kit 8 (CCK-8) analysis to assess the impact of various concentrations (0, 1, 5, 10, 20, 50, 100 μmol/L) of VX765 on rat chondrocyte activity. An in vitro lipopolysaccharide (LPS) induced cell inflammation model was employed, dividing cells into control group, LPS group, VX765 concentration 1 group and VX765 concentration 2 group without obvious cytotoxicity. Western blot, real-time fluorescence quantitative PCR, and ELISA were conducted to measure the expression levels of inflammatory factors-transforming growth factor β 1 (TGF-β 1), interleukin 6 (IL-6), and tumor necrosis factor α (TNF-α). Additionally, Western blot and immunofluorescence staining were employed to assess the expressions of nuclear factor erythroid 2-related factor 2 (Nrf2) and heme oxygenase 1 (HO-1). Thirty-two SD rats were randomly assigned to sham surgery group (group A), OA group (group B), OA+VX765 (50 mg/kg) group (group C), and OA+VX765 (100 mg/kg) group (group D), with 8 rats in each group. Group A underwent a sham operation with a medial incision, while groups B to D underwent additional transverse incisions to the medial collateral ligament and anterior cruciate ligament, with removal of the medial meniscus. One week post-surgery, groups C and D were orally administered 50 mg/kg and 100 mg/kg VX765, respectively, while groups A and B received an equivalent volume of saline. Histopathological examination using HE and safranin-fast green staining was performed, and Mankin scoring was utilized for evaluation. Immunohistochemical staining technique was employed to analyze the expressions of matrix metalloproteinase 13 (MMP-13) and collagen type Ⅱ.@*RESULTS@#The CCK-8 assay indicated a significant decrease in cell viability at VX765 concentrations exceeding 10 μmol/L ( P<0.05), so 4 μmol/L and 8 μmol/L VX765 without obvious cytotoxicity were selected for subsequent experiments. Following LPS induction, the expressions of TGF-β 1, IL-6, and TNF-α in cells significantly increased when compared with the control group ( P<0.05). However, intervention with 4 μmol/L and 8 μmol/L VX765 led to a significant decrease in expression compared to the LPS group ( P<0.05). Western blot and immunofluorescence staining demonstrated a significant upregulation of Nrf2 pathway-related molecules Nrf2 and HO-1 protein expressions by VX765 ( P<0.05), indicating Nrf2 pathway activation. Histopathological examination of rat knee joint tissues and immunohistochemical staining revealed that, compared to group B, treatment with VX765 in groups C and D improved joint structural damage in rat OA, alleviated inflammatory reactions, downregulated MMP-13 expression, and increased collagen type Ⅱ expression.@*CONCLUSION@#VX765 can improve rat OA and reduce chondrocyte inflammation, possibly through the activation of the Nrf2 pathway.

Mechanism of Traditional Chinese Medicine Intervening in Pyroptosis to Prevent and Treat Bone and Joint Related Diseases： A Review / 中国实验方剂学杂志

Osteoarthritis （OA）， rheumatoid arthritis （RA）， gouty arthritis （GA）， and intervertebral disc degeneration （IVDD） are the most common bone and joint-related diseases in clinical practice. They can all affect related joints， leading to joint pain， swelling， dysfunction， and other symptoms. The difference is that OA is mainly caused by joint wear and age-related degradation and is manifested as joint pain， stiffness， and limited movement. RA is an autoimmune disease， manifested as joint pain， swelling， morning stiffness， and systemic symptoms. GA is caused by abnormal uric acid metabolism， manifested as acute arthritis， and IVDD is caused by intervertebral disc degeneration. Studies have shown that the mechanism of the occurrence and development of these bone and joint diseases is extremely complex. Pyroptosis is closely related to these bone and joint-related diseases by participating in bone and joint inflammation， cartilage metabolism imbalance， extracellular matrix degradation， and pathological damage of bone and joint. Inhibition of bone and joint-related pyroptosis will effectively prevent and treat bone and joint-related diseases. At the same time， many studies have confirmed that traditional Chinese medicine （TCM） has a prominent curative effect and obvious advantages in the prevention and treatment of bone and joint-related diseases. TCM can reduce the inflammatory reaction of bone and joints， improve the pathological damage of bone and joint diseases， and relieve bone and joint pain by inhibiting pyroptosis. Therefore， this article aims to briefly explain the relationship between pyroptosis and the occurrence and development of bone and joint-related diseases and summarize the latest research reports on the intervention of pyroptosis in the treatment of bone and joint-related diseases by TCM monomers， TCM extracts， and TCM compounds. It offers new ideas for the in-depth study of the pathogenesis and drug treatment of bone and joint diseases and provides a basis for the clinical use of TCM to prevent and treat bone and joint diseases.

Comparative Functional and Isokinetic Analysis between Implants with Posterior Stabilization and Rotating Hinge Total Knee Arthroplasty / Análise funcional e isocinética comparativa entre implantes com estabilização posterior e rotatórios constritos (hinge) em artroplastias do joelho

Abstract Objective: To compare the function and muscle strength of the limb between patients undergoing knee arthroplasties using primary implants with posterior stabilization (control group) and patients with rotating hinge implants (Hinge group). Methods: Function assessment was performed using the Knee Society Score (KSS) and muscle strength using an isokinetic dynamometer using a speed of 60°/s. Results: 43 patients were analyzed, who underwent 51 surgeries, with the Hinge group comprising 25 surgeries and the control group comprising 26 primary surgeries. We did not observe significant differences between the Hinge and control groups in the values of functional KSS (p = 0.54), objective KSS (p = 0.91), peak flexor torque (p = 0.25) and peak extensor torque (p = 0.08). Patients in the Hinge group who underwent primary arthroplasties had a higher peak flexor torque (0.76 Nm/kg) than those who used the implant in revision after septic failure (0.33 Nm/kg) (p <0.05). The constrained implant was indicated in arthroplasty revision surgeries with severe ligament instability and in cases of complex primary arthroplasties with bone destruction or severe coronal deformity in the coronal plane. Conclusion: The use of constrained implants enables joint function and muscle strength comparable to patients who underwent primary arthroplasty using conventional implants with posterior stabilization. Patients undergoing septic revision with a rotating Hinge prosthesis exhibit lower flexor muscle strength compared to those undergoing primary arthroplasty with a constrained implant.

Resumo Objetivo: Comparar a função e a força muscular do membro entre pacientes submetidos a artroplastias do joelho que utilizaram implantes primários com estabilização posterior (grupo controle) e pacientes com implantes constritos rotatórios (grupo Hinge). Métodos: A avaliação da função foi feita por meio do Knee Society Score (KSS) e da força muscular por um dinamômetro isocinético utilizando a velocidade de 60°/s. Resultados: Foram analisados 43 pacientes, que realizaram 51 cirurgias, sendo o grupo Hinge composto por 25 cirurgias e o grupo controle por 26 cirurgias primárias. Não observamos diferenças significativas entre os grupos Hinge e controle nos valores do KSS funcional (p = 0,54), KSS objetivo (p = 0,91), pico de torque flexor (p = 0,25) e pico de torque extensor (p =0,08). Os pacientes do grupo Hinge que realizaram artro-plastias primárias apresentaram um pico de torque flexor maior (0,76 Nm/kg) que aqueles que utilizaram o implante em revisão após falha séptica (0,33 Nm/kg) (p < 0,05). O implante constrito foi indicado em cirurgias de revisão de artroplastia com instabilidade ligamentar grave e em casos de artroplastias primárias complexas com destruição óssea ou deformidade coronal grave no plano coronal. Conclusão: O uso de implantes bloqueados possibilita função articular e força muscular comparáveis a dos pacientes que realizaram artroplastia primária utilizando implantes convencionais com estabilização posterior. Pacientes submetidos à revisão séptica com prótese Hinge rotatória apresentam menor força da musculatura flexora em relação àqueles submetidos a artroplastia primária com implante constrito.

Minimally Invasive Tibiotalocalcaneal Arthrodesis with Blocked Retrograde Intramedullary Nail - Report of Three Cases / Artrodese tibiotalocalcaneana minimamente invasiva com haste intramedular retrógrada bloqueada - Relato de três casos

Abstract Ankle osteoarthritis (AOA) is associated with pain and variable functional limitation, demanding clinical treatment and possible surgical indication when conservative measures are ineffective - arthrodesis has been the procedure of choice, because it reduces pain, restores joint alignment and makes the segment stable, preserving gait. The present study reports 3 cases (3 ankles) of male patients between 49 and 63 years old, with secondary AOA, preoperative American Orthopaedic Foot and Ankle Society Ankle-Hindfoot Scale (AOFAS AHS) of 27 to 39 points, treated by minimally invasive tibiotalocalcaneal arthrodesis using blocked retrograde intramedullary nail. Hospital stay was of 1 day, and the patients were authorized for immediate loading with removable ambulation orthotics, as tolerated. The physical therapy treatment, introduced since hospitalization, was maintained, prioritizing gait training, strength gain, and proprioception. Clinical and radiographic follow-up was performed at weeks 1, 2, 6, 12 and 24. After evidence of consolidation (between the 6th and 10th weeks), the orthotics were removed. One patient complained of pain in the immediate postoperative period and, at the end of the 1st year, only one patient presented pain during rehabilitation, which was completely resolved with analgesics. Currently, the patients do not present complaints, returning to activities without restrictions - one of them, to the practice of soccer and rappelling. The postoperative AOFAS AHS was from 68 to 86 points.

Resumo A osteoartrite do tornozelo (OAT) está associada a quadro álgico e limitação funcional variável, demandando tratamento clínico e eventual indicação cirúrgica quando as medidas conservadoras são inefetivas - a artrodese tem sido o procedimento de escolha, por reduzir a dor, restaurar o alinhamento articular e tornar o segmento estável, preservando a marcha. O presente estudo relata 3 casos (3 tornozelos) de pacientes do sexo masculino, com entre 49 e 63 anos de idade, portadores de OAT secundária, American Orthopaedic Foot and Ankle Society Ankle-Hindfoot Scale (AOFAS AHS, na sigla em inglês) pré-operatória de 27 a 39 pontos, tratados mediante artrodese tibiotalocalcaneana minimamente invasiva utilizando haste intramedular retrógrada bloqueada. A permanência hospitalar foi de 1 dia, e os pacientes foram autorizados para carga imediata com órteses removíveis para deambulação, conforme tolerado. O tratamento fisioterápico, introduzido desde o internamento, foi mantido, priorizando-se treino de marcha, ganho de força e propriocepção. Foi realizado acompanhamento clínico e radiográfico nas semanas 1, 2, 6, 12 e 24. Após evidências de consolidação (entre a 6ª e a 10ª semanas), as órteses foram retiradas. Um paciente queixou-se de dor no pós-operatório imediato e, ao final do 1° ano, apenas 1 paciente apresentou dor durante a reabilitação, resolvida completamente com analgésicos. Atualmente, os pacientes não apresentam queixas, retornando às atividades sem restrições - um deles, à prática de futebol e rapel. A AOFAS AHS pós-operatória foi de 68 a 86 pontos.

Transtibial Femoral Tunnel Technique in ACL Reconstruction and Osteoarthritis Incidence / Técnica do túnel femoral transtibial na reconstrução do LCA e incidência de osteoartrite

Abstract Objective: Evaluate osteoarthritis incidence in patients that undergone ACL reconstruction using the transtibial technique, with a minimum of 5 years of follow up, with isolated ACL injury. Methods: Patients who underwent ACL reconstruction by the same surgeon using the transtibial technique with hamstrings graft and with a minimum of 5 years of follow-up, without other injuries during the surgical procedure, were selected to undergo imaging exams of the operated knee to assess the incidence of osteoarthritis. The obtained data were evaluated by descriptive statistics. Results: Forty-two patients (44 knees) were evaluated, with a mean age of 31 years old (SD: 8), being 23 right knees and 28 male patients. Mean time from surgery to imaging evaluation was 94.1 months (ranging from 60 to 154 months; SD: 28). Of the evaluated knees, 37 did not have osteoarthritis (83.3%) and 7 had (16.7%). Conclusion: ACL reconstruction with femoral tunnel performed through the transtibial technique in patients without other associated injuries in the operated knee, using hamstrings graft, with a minimum of 5 years of follow up, showed an osteoarthritis incidence of 16.7% in a mean follow-up of 94.1 months. Level Of Evidence V; Case Series.

Resumo Objetivo: Avaliar a incidência de osteoartrite em pacientes submetidos à reconstrução do LCA pela técnica transtibial, com seguimento mínimo de 5 anos, com lesão isolada do LCA. Métodos: Pacientes que passaram por reconstrução LCA pelo mesmo cirurgião usando a técnica transtibial com enxerto de tendão dos músculos isquiotibiais e que foram acompanhados por no mínimo 5 anos, sem outras lesões durante o procedimento cirúrgico, foram selecionados para realizar exames de imagem do joelho operado a fim de avaliar a incidência de osteoartrite. Os dados obtidos foram avaliados por meio de estatísticas descritivas.. Resultados: Foram avaliados 42 pacientes (44 joelhos), com idade média de 31 anos (DP: 8), sendo 23 joelhos direitos e 28 pacientes do sexo masculino. O tempo médio entre a cirurgia e a avaliação por imagem foi de 94,1 meses (variando de 60 a 154 meses; DP: 28). Dos joelhos avaliados, 37 não apresentavam osteoartrite (83,3%) e 7 apresentavam (16,7%). Conclusão: A reconstrução do LCA com túnel femoral realizado por meio da técnica transtibial em pacientes sem outras lesões associadas no joelho operado, utilizando enxerto dos tendões isquiotibiais, com um acompanhamento mínimo de 5 anos, apresentou uma incidência de osteoartrite de 16,7% em um acompanhamento médio de 94,1 meses. Level of Evidence V; Case Series. Nível de Evidência V; Série de casos

Bone protective effect of sinomenine against monosodium iodoacetate induced knee and hip injury in rat model: an inflammatory pathway

Purpose: Osteoarthritis (OA) is a degenerative joint disease which is categorized via destruction of joint cartilage and it also affects the various joints, especially knees and hips. Sinomenine active phytoconstituents isolated from the stem of Sinomenium acutum and already proof anti-inflammatory effect against the arthritis model of rodent. In this experimental protocol, we scrutinized the anti-osteoarthritis effect of sinomenine against monosodium iodoacetate (MIA) induced OA in rats. Methods: MIA (3 mg/50 µL) was used for inducing the OA in the rats, and rats received the oral administration of sinomenine (2.5, 5 and 7.5 mg/kg body weight) up to the end of the experimental study (four weeks). The body and organs weight were estimated. Aggrecan, C-terminal cross-linked telopeptide of type II collagen (CTX-II), glycosaminoglycans (GCGs), monocyte chemoattractant protein-1 (MCP-1), Interferon gamma (IFN-γ), antioxidant, inflammatory cytokines, inflammatory mediators and matrix metalloproteinases (MMP) were analyzed. Results: Sinomenine significantly (P < 0.001) boosted the body weight and reduced the heart weight, but the weight of spleen and kidney remain unchanged. Sinomenine significantly (P < 0.001) reduced the level of nitric oxide, MCP-1 and improved the level of aggrecan, IFN-γ and GCGs. Sinomenine remarkably upregulated the level of glutathione, superoxide dismutase and suppressed the level of malonaldehyde. It effectually modulated the level of inflammatory cytokines and inflammatory mediators and significantly (P < 0.001) reduced the level of MMPs, like MMP-1, 2, 3, 9 and 13. Conclusions: Sinomenine is a beneficial active agent for the treatment of OA disease.

Clinical and functional evaluation of wrists and hands of spinal cord injured patients / Avaliação clínica e funcional de mãos e punhos de pacientes lesados medulares

ABSTRACT Introduction: The inability of the spinal cord to propagate sensory and motor stimuli as a result of the disruption of the nerve tracts is called spinal cord injury. Objective: This study analyzes clinically and radiologically the hands and wrists of spinal cord injured patients, evaluating their motor and sensitive functionality, in order to determine if these patients are more likely to develop degenerative alterations. Methods: 14 patients (8 paraplegics and 6 tetraplegics) were evaluated, undergoing anamnesis and clinical examination - a scale of muscular strength (MRC - Medical Research Council) and the amplitude measurement of the movement with a manual goniometer (ROM), were used for objective evaluation - and x-ray exams. The results were compared with pre-existing data from other studies. Results: When asked, only one of the 14 observed patients complained about constant wrist pain, described as level 3 (weak to moderate), based on the visual analog scale (VAS). The motor evaluation, MRC and ROM divided the group of patients into two subgroups: paraplegic and tetraplegic patients. The x-ray analysis showed, based on Kellgren and Lawrence classification, that all exam images fit grades 1 or 2 of osteoarthritis and osteoarthrosis. Conclusion: In conclusion, spinal cord injured patients showed none or minimal clinical and radiological signs of osteoarthritis on hands or wrists. Overall, the hands and wrists of spinal cord-injured patients behave similarly to noninjured patients. Level of Evidence III; Retrospective Comparative Study.

RESUMO Introdução: A incapacidade da medula espinhal de propagar estímulos sensoriais e motores como resultado do rompimento das vias nervosas é chamada de lesão da medula espinhal. Objetivo: Este estudo analisa clínica e radiograficamente mão e punhos de pacientes lesados medulares, avaliando função motora e sensitiva, a fim de determinar se estes pacientes estariam mais propensos a alterações degenerativas. Métodos: 14 pacientes (8 paraplégicos e 6 tetraplégicos) foram avaliados, passando por anamnese e exame clínico - sendo escala de força muscular (MRC - Medical Research Council) e a medição da amplitude de movimento com um goniômetro manual (ROM) foram utilizados para análise objetiva - e radiografias. Os dados obtidos foram comparados com literatura preexistente. Resultados: Quando questionados, apenas um dos 14 pacientes observados referiu dor crônica nos punhos, descrita como nível 3 (fraca a moderada), baseada na escala visual analógica. A avaliação motora, MRC e ROM dividiram os pacientes em 2 subgrupos: pacientes paraplégicos e tetraplégicos. A análise radiográfica mostrou, baseada na classificação de Kellgren e Lawrence, que todas as imagens se encaixam nos graus 1 ou 2 de osteoartrite e osteoartrose. Conclusão: Conclui-se, então, que pacientes lesados medulares apresentam nenhuma ou mínimas alterações clínicas e radiológicas para osteoartrite ou osteoartrose de punhos ou mãos. Ou seja, no geral, mãos e punhos de pacientes lesados medulares comportam-se como os pacientes sem lesão medular. Nível de Evidência III; Estudo Retrospectivo Comparativo.

Role of Interleukin-17 family cytokines in disease severity of patients with knee osteoarthritis

Abstract Background Interleukin-17 (IL-17) family plays a role in the pathogenesis of knee osteoarthritis (KOA) by contributing to the inflammatory and destructive processes in the affected joint. This study aimed to measure levels of IL-17 A and IL-25 (IL-17E) in serum of KOA patients and determine their roles in the disease severity of patients. Methods In this, 34 patients with KOA and 30 age and sex-matched healthy subjects (HS) were enrolled. Patients were categorized based on their Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC), Visual Analog Scale (VAS), and Body Mass Index (BMI) scores. The enzyme-linked immunosorbent assay (ELISA) technique was employed to measure serum levels of IL-17 A and IL-25. Results Level of IL-25 was significantly higher (P < 0.0001) in the KOA subjects than HS. IL-17 A level was significantly higher in KOA cases with WOMAC < 40 (P < 0.0001) in comparison to HS. IL-25 level was significantly higher in the KOA cases with WOMAC < 40 (P < 0.0001) and with WOMAC ≥ 40 (P < 0.0001) compared to HS. IL-17 A concentration was significantly higher in the KOA cases with VAS < 5 (P < 0.0001) compared to HS. IL-25 level was significantly higher in the KOA cases with VAS < 5 (P < 0.0001) and with VAS ≥ 5 (P < 0.0001) in comparison to HS. KOA patients with BMI ≥ 30 had significantly higher IL-17 A and IL-25 concentration in comparison to HS. Conclusions The serum level of IL-25 in KOA patients is increased probably due to negative controlling feedback on inflammatory responses, which can be associated with obesity and disease activity.

Genetic polymorphism of WNT9A is functionally associated with thumb osteoarthritis in the Chinese population

Abstract Background In a recent genome-wide association study, novel genetic variations of WNT9A were reported to be involved in the etiopathogenesis of thumb osteoarthritis (TOA) in Caucasians. Our purposes were to replicate the association of WNT9A with the development of TOA in the Chinese population and to further unveil the functional role of the risk variants. Methods SNP rs11588850 of WNT9A were genotyped in 953 TOA patients and 1124 healthy controls. The differences of genotype and allele distributions between the patients and healthy controls were evaluated using the Chi-square test. Luciferase Reporter Assay was performed to investigate the influence of variant on the gene expression. Results There was significantly lower frequency of genotype AA in TOA patients than in the controls 74.9% vs. 81.9%, p < 0.001). The frequency of allele A was remarkably lower in the patients than in the controls (86.3% vs. 90.5%, p < 0.001), with an odds ratio of 0.66 (95% CI = 0.54-0.80). Luciferase Reporter Assay showed that the construct containing mutant allele G of rs11588850 displayed 29.1% higher enhancer activity than the wild allele A construct (p < 0.05). Conclusions Allele G of rs11588850 was associated with the increased risk of TOA possibly via up-regulation of WNT9A expression. Further functional analysis into the regulatory role of rs11588850 in WNT9A expression can shed new light on the genetic architecture of TOA. Key Points Genetic variants of WNT9A were associated with the incidence and severity of TOA. Allele G of rs11588850 was associated with an increased transcriptional activity of WNT9A promoter. Allele G of rs11588850 may add to the risk of TOA possibly via up-regulation of WNT9A expression. Further functional analysis into the regulatory role of rs11588850 in WNT9A expression can shed new light on the genetic architecture of TOA.