RESUMO
BACKGROUND: The therapeutic efficacy of intra-articular mesenchymal stem cells (MSCs) injection for patients with osteoarthritis (OA) currently exhibits inconsistency, and the underlying mechanism remains elusive. It has been postulated that the immunomodulatory properties and paracrine activity of MSCs might be influenced by the inflammatory micro-environment within osteoarthritic joints, potentially contributing to this observed inconsistency. METHODS: Adipose-derived MSCs (ADSCs) were isolated from SD rats and pre-treated with Toll-like receptor 3 (TLR3) agonist Poly I:C or Toll-like receptor 4 (TLR4) agonist LPS. The pre-treated ADSCs were then co-cultured with IL-1ß-induced osteoarthritic chondrocytes using a Transwell system to analyze the paracrine effect of ADSCs on reversing the osteoarthritic phenotype of chondrocytes. RESULTS: RT-PCR and Western blot analysis revealed that Poly I:C and LPS pre-treatments up-regulated the expression of IL-10 and IL-6 in ADSCs, respectively. Furthermore, only Poly I:C-preconditioned ADSCs significantly promoted proliferation while inhibiting apoptosis in IL-1ß-treated chondrocytes. Additionally, Poly I:C-preconditioned ADSCs downregulated MMP13 expression while upregulating aggrecan and collagen II expression levels in IL-1ß-treated chondrocytes. CONCLUSIONS: TLR3 activation polarizes ADSCs into an immunomodulatory phenotype distinct from TLR4 activation, exerting differential effects on reversing the osteoarthritic phenotype of chondrocytes; thus indicating that MSCs' paracrine effect regulated by TLRs signaling impacts the efficacy of intra-articular MSCs injection.
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Condrócitos , Células-Tronco Mesenquimais , Humanos , Ratos , Animais , Condrócitos/metabolismo , Receptor 4 Toll-Like/metabolismo , Receptor 3 Toll-Like/genética , Receptor 3 Toll-Like/metabolismo , Células Cultivadas , Lipopolissacarídeos/farmacologia , Lipopolissacarídeos/metabolismo , Ratos Sprague-Dawley , Células-Tronco Mesenquimais/metabolismo , Receptores Toll-Like/metabolismo , Fenótipo , Poli I/metabolismo , Poli I/farmacologiaRESUMO
BACKGROUND: The senescence of chondrocytes, which is closely linked to the development of osteoarthritis (OA), has been found to be influenced by the inflammatory environment of joint cavity. However, there remains a lack of comprehensive understanding regarding the specific mechanisms through which cytokine impacts chondrocytes senescence. PURPOSE: To investigate the effects of MIF on the chondrocytes senescence and explore the underlying mechanism. METHODS: Human cytokine array and ELISA were used for the level of MIF in synovium fluid. CCK-8 was used for chondrocytes viability. IF, WB, SA-ß-gal staining and flow cytometry were used for the chondrogenic, apoptotic and senescent phenotype of chondrocytes. RESULTS: The level of MIF was significantly increased in OA patients. MIF significantly reversed the senescent phenotype induced by LPS pretreatment in human chondrocytes. MIF significantly enhanced the expression of Col II, SOX9, and ACAN in LPS pre-treated human chondrocytes. Furthermore, MIF significantly inhibited the apoptosis of LPS-induced senescent chondrocytes. CONCLUSION: Increased level of MIF in osteoarthritic joint cavity might effectively suppress the senescent phenotype and simultaneously improve the chondrogenic phenotype in chondrocytes, the underlying mechanism was likely to be independent of apoptosis.
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Fatores Inibidores da Migração de Macrófagos , Osteoartrite , Humanos , Apoptose , Condrócitos , Lipopolissacarídeos/farmacologia , Fatores Inibidores da Migração de Macrófagos/genética , FenótipoRESUMO
PURPOSE: To compare the outcomes of arthroscopic labral repair using looped type suture with a matched-pair selective labral debridement with a minimum 2-years follow-up. METHODS: We identified 378 patients undergoing primary arthroscopic labral repair using loop-suture and selective labral debridement from January 2, 2018, to December 28, 2020. The labral repair group was matched 1:1 to a selective labral debridement control group by age, sex, body mass index, follow-up period, lateral center-edge angle, Tönnis grade, and preoperative joint space. Before surgery, 3-Tesla radial magnetic resonance imaging with a 3-dimensional double-echo steady-state sequence was obtained following failed nonoperative treatment lasting more than 3 months. Follow-up imaging was conducted at a minimum of 2 years. In both groups, the ratio of positive slices in which a disrupted chondrolabral junction was observed between the 2 o'clock and 11 o'clock positions was measured. Patient-reported outcome scores included the Harris Hip Score, visual analog score, Hip Outcome Score Activities of Daily Living Subscale, and Hip Outcome Score of Sport-Specific Subscale. RESULTS: In total, 76 patients of the repair group were matched to 76 controls with a minimum 2-years follow-up (repair vs control: 2.6 ± 0.4 vs 2.6 ± 0.4 years, P = .775). The repair group experienced a 2-fold improvement (0.6 ± 0.1 to 0.3 ± 0.1, Pï¼.001). Although the selective debridement group experienced a 3-fold improvement (0.3 ± 0.1 to 0.1 ± 0.1, Pï¼.001). Significant improvement of the patient-reported outcome was shown in both groups at final follow-up without significant difference between the 2 groups. CONCLUSIONS: The mid-term clinical outcomes are comparable between the labral repair using looped type suture and selective labral debridement group. Although a gap between the labrum and articular cartilage may appear in 3-dimensional double-echo steady-state magnetic resonance imaging results after labral repair, it does not correspond with clinical outcomes. LEVEL OF EVIDENCE: Level III, retrospective comparative study.
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Atividades Cotidianas , Impacto Femoroacetabular , Humanos , Seguimentos , Estudos Retrospectivos , Desbridamento , Resultado do Tratamento , Satisfação do Paciente , Artroscopia/métodos , Articulação do Quadril/diagnóstico por imagem , Articulação do Quadril/cirurgia , Medidas de Resultados Relatados pelo Paciente , Impacto Femoroacetabular/cirurgiaRESUMO
BACKGROUND: Currently, hidden blood loss (HBL) has been paid more and more attention by spine surgeons. Simultaneously, it has been the effort of spine surgeons to explore more advantages of minimally invasive surgery. More and more articles have compared unilateral biportal endoscopic lumbar interbody fusion (BE-LIF) and minimally invasive transforaminal lumbar interbody fusion (MIS-TLIF). But so far, there is no HBL comparison between BE-LIF and MIS-TLIF. This study aims to compare the surgical invasiveness, hidden blood loss, and clinical outcome of BE-LIF and MIS-TLIF and to provide insight regarding minimally invasive surgery for lumbar degenerative disease (LDD). METHODS: We enrolled 103 eligible patients with LDD who underwent BE-LIF (n = 46) and MIS-TLIF (n = 57) during August 2020-March 2021. We collected data, including demographics, perioperative haematocrit, operative and postoperative hospital times, serum creatine kinase (CK) and C-reactive protein (CRP) levels, and hospitalization costs. Total and hidden blood loss was calculated. Clinical outcomes were assessed using a visual analogue scale (VAS) score for back and leg pain, Oswestry Disability Index (ODI), modified MacNab criteria, fusion rate, and complications. RESULTS: Basic demographics and surgical data were comparable. The CRP and CK levels were generally lower in the BE-LIF than in the MIS-TLIF group, especially CRP levels on postoperative day (POD) three and CK levels on POD one. True total blood loss, postoperative blood loss, and hidden blood loss were significantly reduced in the BE-LIF group compared with the MIS-TLIF group. Postoperative hospital times was statistically significantly shorter in the BE-LIF group. The VAS pain and ODI scores improved in both groups. At three days and one month, the VAS lower back pain scores were significantly better after BE-LIF. Clinical outcomes did not otherwise differ between groups. CONCLUSIONS: Compared with MIS-TLIF, BE-LIF has similar medium and short-term clinical outcomes. However, it is better regarding surgical trauma, early lower back pain, total and hidden blood loss, and recovery time. BE-LIF is an adequate option for selected LDD.
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Dor Lombar , Fusão Vertebral , Humanos , Dor Lombar/cirurgia , Vértebras Lombares/cirurgia , Procedimentos Cirúrgicos Minimamente Invasivos/efeitos adversos , Estudos Retrospectivos , Resultado do Tratamento , Fusão Vertebral/efeitos adversosRESUMO
It is still a clinical challenge to sustain the remission of rheumatoid arthritis (RA); thus, identifying more effective and safer agents for RA treatment remains an urgent demand. We investigated the anti-arthritic activity and potential mechanism of action of sodium Danshensu (SDSS), a structurally representative water-soluble derivative of Danshen, on collagen-induced arthritis (CIA) mice. Our results showed that paw edema, synovium hyperplasia, bone destruction, and the serum levels of both IL-1ß and IL-6 were ameliorated by SDSS (40 mg/kg·d) in CIA mice. In addition, there was no difference between SDSS and methotrexate (MTX, 2 mg/kg·3d) treatment in the above indicators. Further mechanism studies illustrated that SDSS inhibited IL-1ß secretion by downregulating the HIF-1α/STAT3/NLRP3 pathway in macrophages. On the other hand, HIF-1α accumulation and HIF-1α/STAT3/NLRP3 pathway activation by IOX4 stimulation reduced the therapeutic effect of SDSS. These findings demonstrate that SDSS displays anti-arthritic activity in CIA mice and prevents proinflammatory cytokines secretion in macrophages by suppressing the HIF-1α/STAT3/NLRP3 pathway.
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Artrite Experimental , Artrite Reumatoide , Camundongos , Animais , Artrite Experimental/tratamento farmacológico , Proteína 3 que Contém Domínio de Pirina da Família NLR/metabolismo , Ativação de Macrófagos , Membrana Sinovial/metabolismo , Artrite Reumatoide/tratamento farmacológico , Metotrexato/farmacologia , Subunidade alfa do Fator 1 Induzível por Hipóxia/metabolismoRESUMO
Arthroscopic superior capsular reconstruction is an innovative technique for the irreparable rotator cuff tears, but spontaneous pneumothorax after surgery is very rare. The present case was a 66-year-old female with irreparable rotator cuff tears of the right shoulder, treated with the arthroscopic shoulder superior capsular reconstruction. The general anesthesia and operation went smoothly, but the patient experienced stuffiness in the chest and shortness of breath after recovery from anesthesia. Thoracic CT scans showed spontaneous pneumothorax in the right side, which was successfully treated by the conservative treatments (oxygen therapy) according to multidisciplinary team. Prompt and accurate early-stage diagnosis is necessary in controlling postoperative complications and standardized treatment is the key to relieve the suffering. Spontaneous pneumothorax after arthroscopic shoulder surgery has been rarely reported in previous literatures.
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Pneumotórax , Lesões do Manguito Rotador , Articulação do Ombro , Idoso , Artroscopia/efeitos adversos , Artroscopia/métodos , Feminino , Humanos , Pneumotórax/etiologia , Pneumotórax/cirurgia , Amplitude de Movimento Articular , Lesões do Manguito Rotador/cirurgia , Ombro , Resultado do TratamentoRESUMO
Prosthetic infection is one of the severe postoperative complications of arthroplasty. Mixed bacterial-fungal prosthetic infection is rare but can be disastrous. This case was a 76-year-old female suffered from prosthetic infection following total hip replacement due to femoral neck fracture and underwent multiple debridements. The culture of periprosthetic tissue was bacteriologically sterile following the first debridement, while the Staphylococcus hominis was identified in the second debridement in the previous hospitalization where fungal infection had not been considered. Thus the pathogen spectrum of anti-infection therapy failed to contain fungus. Ultimately, the culture result of our sampled periprosthetic tissue during the third debridement was Candida albicans without bacterium in our hospital. The fungal prosthetic infection was successfully treated by a two-stage revision with antifungal drugs. Accurate diagnosis and standardized treatment is the key to the therapy of infection after hip arthroplasty, especially for mixed bacterial-fungal prosthetic infection.
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Artroplastia de Quadril , Prótese de Quadril , Micoses , Infecções Relacionadas à Prótese , Idoso , Antibacterianos/uso terapêutico , Artroplastia de Quadril/efeitos adversos , Desbridamento , Feminino , Fungos , Prótese de Quadril/efeitos adversos , Humanos , Micoses/tratamento farmacológico , Infecções Relacionadas à Prótese/terapia , Reoperação , Estudos Retrospectivos , Resultado do TratamentoRESUMO
Hippo signaling pathway is involved in many biological processes including the fate decision of embryonic stem cells (ESCs). Yes-associated protein (Yap) function as a key effector of Hippo pathway, but its role in ESCs is still controversial. So far, only two isoforms of Yap have been identified and they have both overlapping and distinct functions. Here, we identify six novel isoforms of mouse Yap, bringing the total number of isoforms to eight. According to the differences in the first exon, they are divided into two subtypes (a and b). Isoform-a and isoform-b exhibit different subcellular localizations. Moreover, isoform-a can fully reverse the impaired self-renewal phenotype induced by Yap knockout (KO). Upon overexpression, isoform-a moderately promotes mESCs self-renewal and markedly delays differentiation. On the contrary, no significant pro-self-renewal phenotype is observed when isoform-b overexpressed in wildtype (WT) mESCs or re-expressed in Yap KO cell lines. These finding not only help to clarify the role of Yap in mESCs, but also lay the foundation for advancing functional researches of Yap in other processes.
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Fenômenos Biológicos , Células-Tronco Embrionárias Murinas , Proteínas de Sinalização YAP/genética , Proteínas Adaptadoras de Transdução de Sinal/genética , Proteínas Adaptadoras de Transdução de Sinal/metabolismo , Animais , Células-Tronco Embrionárias/metabolismo , Camundongos , Células-Tronco Embrionárias Murinas/metabolismo , Isoformas de Proteínas/genética , Isoformas de Proteínas/metabolismoRESUMO
The mortality of conservative treatment and the risk resulting from operation for elderly patients with femoral intertrochanteric fractures are high. Safety in the perioperative period and quicker recovery should be placed at the top priority for elderly patients with hip fractures. We reported a case of 109-year-old female patient with intertrochanteric fracture who has undergone the hemiarthroplasty in our center recently. With sciatic nerve and lateral cutaneous nerve block anesthesia, she was offered the artificial femoral head replacement in the lumbar plexus block after sufficient preoperative preparation. The surgery went well with minimally invasive cut, and the patient's recovery was satisfactory.
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Hemiartroplastia/métodos , Fraturas do Quadril/cirurgia , Idoso de 80 Anos ou mais , Feminino , Humanos , Bloqueio NervosoRESUMO
PURPOSE: The purpose of this study was to investigate the relation between isolated discoid lateral meniscus (DLM) tears and the presence of articular cartilage lesions. METHODS: From January 2010 to January 2012, 252 consecutive patients diagnosed with an isolated DLM tear during an arthroscopic procedure were included in this study. Demographic variables, including gender, age, body mass index (BMI), traumatic history, time course, and date of the DLM tear, were recorded. The relation between DLM tears and the presence of articular cartilage lesions was analyzed by the χ(2) test. Logistic regression analysis was used to analyze the relation between these variables and articular cartilage lesions. RESULTS: Of the patients with DLM tears, 67 (26.6%) also had articular cartilage lesions. The most common type of DLM tear was the complex tear (46.8%). The most common location of articular cartilage lesions was the lateral tibial plateau (11.6%). Lesions on the opposing articular surfaces of the lateral compartment and patellofemoral joint of the knee were found in 12 patients (4.8%) and 11 patients (4.4%), respectively. There were no significant differences in the incidences of articular cartilage lesions in patients with different types of DLM tears (P > .05). Gender (odds ratio [OR], 2.289; P = .012), BMI (OR, 1.991; P = .023), and time course (OR, 2.050; P = .034) were significantly associated with articular cartilage lesions. CONCLUSIONS: DLM tears were more common in the context of degenerative tears. There was no significant difference in the incidence of articular cartilage lesions among patients with different types of DLM tears. Female patients, patients with a BMI greater than 23.0 kg/m(2), or patients with a time course of greater than 6 months were more frequently observed to also have articular cartilage lesions. LEVEL OF EVIDENCE: Level IV, therapeutic case series.
Assuntos
Cartilagem Articular/lesões , Lesões do Menisco Tibial , Adolescente , Adulto , Fatores Etários , Artroscopia , Índice de Massa Corporal , Distribuição de Qui-Quadrado , Criança , Feminino , Humanos , Articulação do Joelho , Masculino , Pessoa de Meia-Idade , Análise de Regressão , Tíbia/lesões , Adulto JovemRESUMO
In total hip arthroplasty for the treatment of developmental dysplasia of the hip (DDH) with high hip dislocation, it can be technically challenging to locate the true acetabulum and restore limb length without subtrochantric femoral shortening osteotomy. We explored and described total hip arthroplasty without subtrochanteric femoral shortening osteotomy in 28 hips with Crowe type III and IV dislocation by intravenous injection of rocuronium at 0.9mg/kg 1minute before reduction and hip reduction combined with continuous strong traction of the affected limb with patients in a position with hip and knee flexion. All patients did not show dislocation, prosthesis loosening, and other severe complications. It is thus a safe and feasible reduction technique for arthroplasty of Crowe type III or IV dislocation of DDH.
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Artroplastia de Quadril/métodos , Fêmur/cirurgia , Luxação Congênita de Quadril/cirurgia , Acetábulo/cirurgia , Adulto , Artroplastia de Quadril/efeitos adversos , Feminino , Colo do Fêmur/cirurgia , Prótese de Quadril , Humanos , Masculino , Pessoa de Meia-Idade , Osteotomia/métodos , Adulto JovemRESUMO
OBJECTIVE: To observe autograft of femoral head for acetabular reconstruction in total hip arthroplasty(THA)without shortening femoral osteotomy for developmental dysplasia of the hip (DDH) with complicated deformity. METHODS: A case series of 18 Crowe type-III-IV DDH patients (19 hips) with osteoarthritis between December 2004 and October 2010 was reported. There were 2 male and 16 female patients. Mean age was 34.3 years (19-44 years) and limb shortening 4.5 cm (3.0-6.2 cm), and preoperative Harris score was 40 ± 17. All cases were accomplished through posterolateral approach by the same surgeon and underwent the procedure of acetabular reconstruction using a bulk femoral head autograft and periarticular soft tissue releases(dissection of the entire articular capsule, scar tissues and osteophytes), but had no procedure of shortening by subtrochanteric transverse osteotomy. Design data through paired t-test compared the preoperative and postoperative Harris scores, also the radiographic observation, in order to asses the clinical efficacy of acetabular reconstruction, while observing the length of limb lengthening, complications and function. RESULTS: Graft coverage of cases in the group were 16%-47% (mean, 26%), with 17 mm of the socket uncovered during operative evaluation. All patients were followed-up for 14-56 months (mean, 34.6 months). The lengthening of the affected limb was 2.9-4.6 cm (mean, (3.6 ± 0.7)cm). The limb-length discrepancy was 0-1.2 cm (mean, (0.6 ± 0.3)cm) after THA. The offset of the affected limbs was 26.4-34.3 cm(mean, (30.5 ± 1.6)cm). The postoperation radiography showed good position of the prosthetic components and coverage of the socket after bone graft was full. All patients had no static contraction abnormality of muscle in the affected limb. Three patients with numbness in lateral leg after the procedure recovered completely in one months. No other complication was observed except heterotopic ossification in 1 case. At the last follow-up examination, Harris hip score was 86 ± 11. There was statistical significance compared with the preoperative score (t = 5.86, P < 0.01) , and no revision was needed in all patients. CONCLUSION: Autograft of femoral head for acetabular reconstruction in THA without shortening femoral osteotomy for developmental dysplasia of the hip (DDH) is an effective procedure to reconstruct acetabulum and improve the socket bone coverage.
Assuntos
Acetábulo/cirurgia , Artroplastia de Quadril , Cabeça do Fêmur/transplante , Luxação Congênita de Quadril/cirurgia , Procedimentos de Cirurgia Plástica , Adulto , Feminino , Humanos , Masculino , Estudos Retrospectivos , Adulto JovemRESUMO
BACKGROUND: The distally fixed stem used in revision total hip arthroplasty (rTHA) with extended trochanteric osteotomy (ETO) is subject to periprosthetic fracture, stem subsidence, and stress shielding. The prospective multicentric study aimed to assess the clinical and radiographic outcomes, and complications of using the Corail revision stem in rTHA with ETO. METHODS: Sixty-four patients undergoing rTHA with ETO using the Corail revision stem between 2019 and 2020 were enrolled in the study. We performed a postoperative follow-up of the patient and obtained radiographs and Harris hip scores (HHSs). These results were used to analyze ETO union, Engh scores, bone remodeling, stem stability and hip function. RESULTS: The mean follow-up duration was 34 months (range 23-41). Sixty-two patients who underwent ETOs achieved complete healing at the final follow-up. Fifty-nine hips had bony ingrowth from the osteotomy fragment to the stem without radiolucent lines. The postoperative Engh score was 21.3 ± 3.59 (range 15.5-27.0). Forty-three hips had regeneration in the proximal femur. Two patients had transient thigh pain postoperatively. The postoperative HHS improved from 40.7 ± 16.67 (range 0-67) preoperatively to 82.1 ± 6.83 (range 73-93). CONCLUSION: Corail revision stems are a viable and reliable option in rTHA with ETO. This stem had excellent clinical and radiographic outcomes, resulting in a high rate of ETO union and stem survival. The revision stem enabled restoration of proximal bone stock in femurs with prerevision bone defects, which were prepared for the next revision operation. Level of evidence Level IIb, Prospective self-control study.
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Artroplastia de Quadril , Prótese de Quadril , Humanos , Artroplastia de Quadril/efeitos adversos , Artroplastia de Quadril/métodos , Durapatita , Estudos Prospectivos , Fêmur/diagnóstico por imagem , Fêmur/cirurgia , Osteotomia/métodos , Reoperação/métodos , Estudos Retrospectivos , Desenho de Prótese , SeguimentosRESUMO
Background: Yishen-Tongbi Decoction (YSTB), a traditional Chinese prescription, has been used to improve syndromes of rheumatoid arthritis (RA) for many years. Previous research has shown that YSTB has anti-inflammatory and analgesic properties. However, the underlying molecular mechanism of the anti-RA effects of YSTB remains unclear. Purpose and study design: The purpose of this research was to investigate how YSTB affected mice with collagen-induced arthritis (CIA) and RAW264.7 cells induced with lipopolysaccharide (LPS). Results: The findings show that YSTB could significantly improve the clinical arthritic symptoms of CIA mice (mitigate paw swelling, arthritis score, thymus and spleen indices, augment body weight), downregulated expression of pro-inflammatory cytokines like tumor necrosis factor-alpha (TNF-α), interleukin-1ß (IL-1ß), IL-6 and IL-17, while upregulated the level of anti-inflammatory like IL-10 and transforming growth factor-ß (TGF-ß). Meanwhile, YSTB inhibits bone erosion and reduces inflammatory cell infiltration, synovial proliferation, and joint destruction in CIA mice. In addition, we found that YSTB was able to suppress the LPS-induced inflammation of RAW264.7 cells, which was ascribed to the suppression of nitric oxide (NO) production and reactive oxygen species formation (ROS). YSTB also inhibited the production of inducible nitric oxide synthase and reduced the releases of pro-inflammatory cytokines TNF-α, IL-1ß, and IL-6 in LPS-induced RAW264.7 cells. Furthermore, the phosphorylation expression of JAK2, JAK3, STAT3, p38, ERK and p65 protein could be suppressed by YSTB, while the expression of SOCS3 could be activated. Conclusion: Taken together, YSTB possesses anti-inflammatory and prevention bone destruction effects in RA disease by regulating the JAK/STAT3/SOCS3 signaling pathway.
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Artrite Experimental , Artrite Reumatoide , Medicamentos de Ervas Chinesas , Janus Quinases , Fator de Transcrição STAT3 , Transdução de Sinais , Proteína 3 Supressora da Sinalização de Citocinas , Animais , Camundongos , Medicamentos de Ervas Chinesas/farmacologia , Medicamentos de Ervas Chinesas/uso terapêutico , Artrite Reumatoide/tratamento farmacológico , Artrite Reumatoide/metabolismo , Células RAW 264.7 , Fator de Transcrição STAT3/metabolismo , Proteína 3 Supressora da Sinalização de Citocinas/metabolismo , Proteína 3 Supressora da Sinalização de Citocinas/genética , Artrite Experimental/tratamento farmacológico , Artrite Experimental/patologia , Artrite Experimental/metabolismo , Transdução de Sinais/efeitos dos fármacos , Janus Quinases/metabolismo , Masculino , Citocinas/metabolismo , Anti-Inflamatórios/farmacologia , Anti-Inflamatórios/uso terapêutico , Inflamação/tratamento farmacológico , Camundongos Endogâmicos DBA , Modelos Animais de DoençasRESUMO
Introduction: Rheumatoid arthritis (RA) is a globally challenging and refractory autoimmune disease, constituting a serious menace to human health. RA is characterized by recurrent pain and is difficult to resolve, necessitating prolonged medication for control. Yishen Tongbi decoction is a traditional Chinese herbal compound prescribed for treating RA. We have completed a 3-year RCT study that confirmed the clinical efficacy of Yishen Tongbi decoction for RA. Notably, we observed a faster clinical remission rate compared to MTX by week 4 of treatment. In our forthcoming study, we intend to conduct a comprehensive assessment of the efficacy and safety of Yishen Tongbi decoction in the real-world treatment of RA through a prospective study. Methods and analysis: This prospective, multicenter, real-world observational study will be conducted at two designated centers in China from October 2023 to August 2025. The study will include 324 patients with active rheumatoid arthritis. One group will receive Yishen Tongbi decoction combined with conventional synthetic disease-modifying antirheumatic drugs (csDMARDs). The other group will receive standard treatment. Standard treatment can be further divided into subgroups: csDMARDs, targeted synthetic disease-modifying antirheumatic drugs (tsDMARDs), and biologic disease-modifying antirheumatic drugs (bDMARDs). In each group, the number of tender joints, number of swollen joints, pain score, patient global assessment, physician global assessment, disease activity index (DAS28-ESR or DAS28-CRP), clinical disease activity index (cDAI), simplified disease activity index (sDAI) and relevant laboratory data will be compared. Clinical indicators and disease activity of the patients will be assessed at baseline, week 4 and week 12 after the initiation of treatment. The primary outcome will be the American College of Rheumatology 20% improvement criteria (ACR20) attainment rate among patients at week 12 after treatment. Every adverse event will be reported. Ethics and dissemination: This study has been approved by the Ethics Committee of the first affiliated Hospital of Guangzhou University of traditional Chinese Medicine (NO.K-2023-009). The results of the study will be published in national and international peer-reviewed journals and at scientific conferences. The researchers will inform participants and other RA patients of the results through health education. Clinical Trial Registration: https://www.chictr.org.cn/index.html, identifier ChiCTR2300076073.
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Background: Osteoarthritis (OA) is a debilitating degenerative joint disease, leading to significant pain and disability. Despite advancements, current regenerative therapies, such as mesenchymal stem cells (MSCs), face challenges in clinical efficacy and ethical considerations. This study aimed to evaluate the therapeutic potential of stromal vascular fraction gel (SVF-gel) in comparison to available treatments like hyaluronic acid (HA) and adipose-derived stem cells (ADSCs) and to assess the enhancement of this potential by incorporating tropoelastin (TE). Methods: We conducted a comparative laboratory study, establishing an indirect co-culture system using a Transwell assay to test the effects of HA, ADSCs, SVF-gel, and TE-SVF-gel on osteoarthritic articular chondrocytes (OACs). Chondrogenic and hypertrophic markers were assessed after a 72-hour co-culture. SVF-gel was harvested from rat subcutaneous abdominal adipose tissue, with its mechanical properties characterized. Cell viability was specifically analyzed for SVF-gel and TE-SVF-gel. The in vivo therapeutic effectiveness was further investigated in a rat model of OA, examining MSCs tracking, effects on cartilage matrix synthesis, osteophyte formation, and muscle weight changes. Results: Cell viability assays revealed that TE-SVF-gel maintained higher cell survival rates than SVF-gel. In comparison to the control, HA, and ADSCs groups, SVF-gel and TE-SVF-gel significantly upregulated the expression of chondrogenic markers COL 2, SOX-9, and ACAN and downregulated the hypertrophic marker COL 10 in OACs. The TE-SVF-gel showed further improved expression of chondrogenic markers and a greater decrease in COL 10 expression compared to SVF-gel alone. Notably, the TE-SVF-gel treated group in the in vivo OA model exhibited the most MSCs on the synovial surface, superior cartilage matrix synthesis, increased COL 2 expression, and better muscle weight recovery, despite the presence of fewer stem cells than other treatments. Discussion: The findings suggest that SVF-gel, particularly when combined with TE, provides a more effective regenerative treatment for OA by enhancing the therapeutic potential of MSCs. This combination could represent an innovative strategy that overcomes limitations of current therapies, offering a new avenue for patient treatment. Further research is warranted to explore the long-term benefits and potential clinical applications of this combined approach.
RESUMO
In this study, the regulatory role and mechanisms of tantalum (Ta) particles in the bone tissue microenvironment are explored. Ta particle deposition occurs in both clinical samples and animal tissues following porous Ta implantation. Unlike titanium (Ti) particles promoting M1 macrophage (MÏ) polarization, Ta particles regulating calcium signaling pathways and promoting M2 MÏ polarization. Ta-induced M2 MÏ enhances bone marrow-derived mesenchymal stem cells (BMSCs) proliferation, migration, and osteogenic differentiation through exosomes (Exo) by upregulating miR-378a-3p/miR-221-5p and downregulating miR-155-5p/miR-212-5p. Ta particles suppress the pro-inflammatory and bone resorption effects of Ti particles in vivo and in vitro. In a rat femoral condyle bone defect model, artificial bone loaded with Ta particles promotes endogenous MÏ polarization toward M2 differentiation at the defect site, accelerating bone repair. In conclusion, Ta particles modulate MÏ polarization toward M2 and influence BMSCs osteogenic capacity through Exo secreted by M2 MÏ, providing insights for potential bone repair applications.
Assuntos
Diferenciação Celular , Exossomos , Macrófagos , Células-Tronco Mesenquimais , MicroRNAs , Osteogênese , Tantálio , Animais , Células-Tronco Mesenquimais/metabolismo , Células-Tronco Mesenquimais/efeitos dos fármacos , Células-Tronco Mesenquimais/citologia , Exossomos/metabolismo , Tantálio/química , Tantálio/farmacologia , Osteogênese/efeitos dos fármacos , Macrófagos/metabolismo , Macrófagos/efeitos dos fármacos , Macrófagos/citologia , Ratos , Diferenciação Celular/efeitos dos fármacos , MicroRNAs/metabolismo , Ratos Sprague-Dawley , Humanos , Masculino , Proliferação de Células/efeitos dos fármacos , Osso e Ossos/metabolismoRESUMO
OBJECTIVE: Cytokines are implicated in the pathogenesis of osteoarthritis (OA), and this study aims to assess the therapeutic potential of an IL-8 neutralizing monoclonal antibody (mAb) for OA intervention. DESIGN: The study employed a rabbit model of OA induced by anterior cruciate ligament transection (ACLT) surgery to investigate the effects of an interleukin (IL)-8 neutralizing mAb, with hyaluronic acid (HA) used as a positive control. Primary outcomes assessed in the rabbits included cartilage repair, synovitis, joint effusion, changes in footprints, and lower limb loading conditions. RESULTS: Compared to HA, intra-articular injection of the IL-8 neutralizing mAb demonstrated a more pronounced attenuation of OA progression and enhancement of cartilage repair. We observed a reduction in synovitis and joint effusion, indications of bone marrow edema, as well as improvements in lower limb function. In knees treated with the neutralizing IL-8 mAb, there was a significant decrease in IL-8 levels within the synovial tissues. CONCLUSIONS: The IL-8 neutralizing mAb exhibits promising therapeutic potential in the management of OA by attenuating inflammation and facilitating cartilage repair. However, further investigations are warranted to comprehensively elucidate the underlying mechanisms, optimize treatment protocols, and ensure the long-term safety and efficacy of this innovative therapeutic approach.
RESUMO
OBJECTIVE: To study the correlation between the expression of Fcgamma receptor II b (FcgammaRII b) on B cells and rheumatoid arthritis (RA) patients of Shen deficiency syndrome (SDS). METHODS: There were 43 RA patients, including 26 of SDS and 17 of non-SDS. The expression levels of FcgammaRII b on naive B cells, memory B cells, and plasma blasts in the peripheral blood were detected by flow cytometry. The numbers of tender joints, numbers of swollen joints, erythrocyte sedimentation rate (ESR), rheumatoid factor (RF), and disease activity score (DAS28), the correlation between the distribution of B cells and the expression level of FcgammaRII b in RA patients were analyzed. Besides, another 21 healthy volunteers were recruited as the control group. RESULTS: The expression level of FcgammaRII b was 49.65% +/- 15.86% on memory B cells and 43.69% +/- 22.57% on plasma blasts in RA patients of SDS, significantly down-regulated when compared with those of the control group (64.03% +/- 6.01%, 66.59% +/- 10.18%, P < 0.01). The expression level of FcgammaRII b on memory B cells of RA patients of non-SDS was down-regulated more obviously when compared with that of the control group (52.70% +/- 9.52% versus 64.03% +/- 6.01%, P < 0.01). The expression level of FcgammaRII b on plasma blasts was obviously lower in RA patients of SDS than in RA patients of non-SDS (56.10% +/- 17.05%, P < 0.05). The expression level of FcgammaRII b on memory B cells was not correlated with numbers of tender joints, numbers of swollen joints, ESR, RF, or DAS28. CONCLUSIONS: The defective immunological tolerance of B cells in RA patients of SDS might be closely correlated with down-regulation of FcgammaRII b on memory B cells and plasma blasts. There might exist genetic abnormality of FcgammaRII b gene in RA patients of SDS, thus inducing loss of autoimmunity tolerance.
Assuntos
Artrite Reumatoide/sangue , Artrite Reumatoide/imunologia , Linfócitos B/metabolismo , Receptores de IgG/metabolismo , Adulto , Artrite Reumatoide/diagnóstico , Linfócitos B/imunologia , Estudos de Casos e Controles , Feminino , Humanos , Masculino , Medicina Tradicional Chinesa , Pessoa de Meia-Idade , Receptores de IgG/imunologiaRESUMO
OBJECTIVE: To investigate the correlation between auto-immune antibodies and rheumatoid arthritis (RA) patients of Shen deficiency syndrome (SDS), thus providing clinical evidence for further researches on molecular biological mechanisms of RA patients of SDS. METHODS: Totally 451 RA patients were assigned to the SDS group and the non-SDS group. Their general conditions (including gender, age, duration, and age of onset), C reactive protein (CRP), erythrocyte sedimentation rate (ESR), platelet (PLT), disease activities (DAS28), auto-antibodies [rheumatoid factor (RF), anti-CCP antibodies, anti-nuclear antibody (ANA)] were compared between the two groups. RESULTS: (1) The scores for EST, PLT, and DAS28 were obviously higher in the SDS group than in the non-SDS group (P < 0.05, P <0. 01). (2) The level of average RF was (697.32 +/-1 061.38 IU/mL) in the SDS group, higher than that in the non-SDS group (439.91 +/- 672.24 IU/mL, P <0.01). There was no statistical difference in anti-CCP antibody between the two groups (P >0.05).(3) The ANA positive rate of RA patients was 29. 63% (120/405). It was 37.19% (74/199) in RA patients of SDS and 22. 33% (46/206) in RA patients of non-SDS, showing statistical difference between the two groups (P <0.01). (4) The odds ratio for high level RF positive and ANA positive was 1. 574 and 2. 059 folds in RA patients of SDS as high as that in RA patients of non-SDS. CONCLUSIONS: RA patients of SDS would have higher risk of having auto-immune antibodies, fastened development, more worsen joint damage, and more poor prognosis. Its mechanisms might be closely associated with autoimmune tolerance.