Mesenchymal Stem Cells Injection Is More Effective Than Hyaluronic Acid Injection in the Treatment of Knee Osteoarthritis With Similar Safety: A Systematic Review and Meta-Analysis.

PURPOSE: To evaluate the efficacy and safety of intra-articular injection of mesenchymal stem cells (MSCs) versus hyaluronic acid (HA) in the treatment of knee osteoarthritis (KOA). METHODS: Eligible randomized controlled trials (RCTs) were identified through a search of PubMed, Embase, the Cochrane Library, Web of Science, SinoMed, and CNKI databases from inception to March 2024. For meta-analysis, data on clinical outcomes were measured using visual analog scale (VAS) and the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC), and data on cartilage repair were measured using the Whole-Organ Magnetic Resonance Imaging Score (WORMS); data on safety were evaluated by the incidence of adverse events. Two researchers independently read the included literature, extracted data and evaluated the quality, used the Cochrane risk bias assessment tool for bias risk assessment, and used RevMan5.3 software for meta-analysis. RESULTS: Ten RCTs involving 818 patients with KOA ranging from I to Ⅲ on the Kellgren-Lawrence grading scale were included in this meta-analysis. Meta-analysis results showed that at 12 months, the WOMAC total score (mean difference [MD] = -10.22, 95% confidence interval [CI]: -14.86 to -5.59, P < .0001, Z = 4.32), VAS score (MD = -1.31, 95% CI: -1.90 to -0.73, P < .0001, Z = 4.40); and WORMS score (MD = -26.01, 95% CI: -31.88 to -20.14, P < .001, Z = 8.69) of the MSCs group all decreased significantly (P < .05) compared with the HA control group and reached the minimal clinically important differences. Furthermore, there was no significant difference in the incidence of adverse events (relative risk = 1.54, 95% CI: 0.85-2.79, P = .16, I2 = 0) between the 2 groups (P > .05). CONCLUSIONS: Compared with HA, intra-articular injection of MSCs therapy appears to alleviate joint pain effectively, improving clinical function of KOA patients. These benefits are observed to last for at least 12 months without an increase in adverse events. Due to limited, varied, and lacking minimal clinically important differences results in existing literature, further research is needed. LEVEL OF EVIDENCE: Level I, meta-analysis of Level I studies.

1,25-Dihydroxyvitamin D3 attenuates disease severity and induces synoviocyte apoptosis in a concentration-dependent manner in rats with adjuvant-induced arthritis by inactivating the NF-κB signaling pathway.

An aggressive proliferation of synoviocytes is the hallmark of rheumatoid arthritis (RA). Emerging evidence shows that inhibiting the NF-κB signaling pathway with 1,25-dihydroxyvitamin D3 [1,25(OH)2D3] may be a therapeutic approach for controlling inflammatory diseases. In this study, we demonstrated the protective effects of three different 1,25(OH)2D3 concentration on adjuvant-induced arthritis (AA) rats through the NF-κB signaling pathway and their pro-apoptotic roles in cultured adjuvant-induced arthritis synoviocytes (AIASs). AA rats were prepared by injecting complete Freund's adjuvant and independently given daily intraperitoneal injection of 1,25(OH)2D3 at concentrations of 50, 100, and 300 ng/day/kg. Subsequently, AIASs were isolated from the inflamed joints of AA rats to test the effects of 1,25(OH)2D3 on AIASs in vitro. Intraperitoneal injection of 1,25-(OH)2D3 was found to induce a concentration- and time-dependent improvement in relieving the symptoms of AA. We found an increased paw withdrawal thermal latency (PWTL) in the affected paw of AA rats as the concentration of 1,25-(OH)2D3 increased. 1,25-(OH)2D3 treatment reduced levels of inflammatory factors in synovial tissues of AA rats. In the case of cultured AIASs, 1,25-(OH)2D3 was shown to inhibit cell proliferation and induce cell apoptosis in a concentration-dependent manner. Additionally, 1,25-(OH)2D3 inhibited the activation of the NF-κB signaling pathway. In conclusion, our study provides evidence emphasizing that 1,25(OH)2D3 has the potential to attenuate disease severity in RA potentially due to its contributory role in synoviocyte proliferation and apoptosis. The protective role of 1,25(OH)2D3 against RA depends on the NF-κB signaling pathway.

Construction of a predictive nomogram for functional recovery after Bernese periacetabular osteotomy.

Background and purpose: Surgical indications for Bernese periacetabular osteotomy (PAO) are well-established. However, the extent of postoperative functional recovery varies widely, as observed in clinical follow-ups. Thus, preoperative evaluation is crucial. This study aims to identify factors that influence functional recovery post-PAO and to develop a predictive nomogram. Patients and methods: Retrospective data were collected between December 2016 and March 2022 at The First Affiliated Hospital of Shandong First Medical University. The dataset included demographic and imaging data of patients who underwent PAO. The least absolute shrinkage and selection operator (LASSO) regression was utilized to identify influencing factors, which were further analyzed using multivariate logistic regression to construct a predictive nomogram for post-PAO functional recovery. Result: The analysis identified critical factors affecting functional recovery post-PAO, namely, the preoperative distance from the innermost surface of the femoral head to the ilioischial line, the surgical approach, preoperative acetabular depth, and the continuity of the preoperative Calve line. A nomogram was developed using these significant predictors. The model's validity was demonstrated by the receiver operating characteristic curve, with an area under the curve of 0.864. Additionally, the calibration curve confirmed the nomogram's accuracy, showing a strong correlation between observed and predicted probabilities, indicating high predictive accuracy. Conclusion: This predictive nomogram effectively identifies patients most suitable for PAO, providing valuable guidance for selecting surgical candidates and determining the appropriate surgical approach.

Early results of high tibial osteotomy versus combined arthroscopic surgery.

Objective: To investigate the early effect of high tibial osteotomy (HTO) compared with combined arthroscopic surgery. Methods: A retrospective study was conducted on patients who underwent HTO at The First Affiliated Hospital of Shandong First Medical University from January 2018 to January 2022. 138 patients (163 knees) with knee osteoarthritis (KOA) treated with HTO were selected. The medial proximal tibial angle (MPTA), joint line convergence angle (JLCA), femoral tibial angle (FTA), hip-knee-ankle (HKA) angle, weight-bearing line (WBL) ratio of the knee joint, opening gap, opening angle, American Knee Society score (KSS), US Hospital for Special Surgery (HSS) score, and Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) score were measured to determine the different effects between HTO and HTO combined with arthroscopic by logistic regression analysis. Results: Patients with HTO combined with arthroscopic surgery have improved functional scores as well as imaging perspectives compared to preoperative. By multivariate logistic analysis, it was concluded that arthroscopic surgery and gender are influential factors in the outcome of HTO surgery. The postoperative KSS score was 2.702 times more likely to be classified as excellent in the HTO combined with arthroscopy group than in the HTO group [Exp (ß) = 2.702, 95% CI (1.049-6.961), P = 0.039]; the postoperative KSS score was 0.349 times more likely to be classified as excellent in women than in men [Exp (ß) = 0.349, 95% CI (0.138-0.883), P = 0.026]. Conclusion: Better results with HTO combined with arthroscopic surgery. HTO combined with arthroscopy is a better choice in the surgical treatment of KOA.

Arthroscopic ankle arthrodesis in hemophilic arthropathy.

BACKGROUND: Ankle arthrodesis is an accepted treatment for patients with advanced disabling tibiotalar arthritis, mostly in osteoarthritis, rheumatoid, and posttraumatic arthritis. No detailed reports have been published regarding the use of arthroscopy for the treatment of the end-stage hemophilic ankle. The purpose of this article is to report the results of arthroscopic ankle arthrodesis in hemophilic arthropathy of the ankle. METHODS: Ten patients (10 ankle joints) who underwent arthroscopically assisted ankle arthrodesis for the treatment of end-stage hemophilic A arthritis were enrolled in this study. The rate of ankle fusion, incidence of complications, and clinical rating by the Morgan system were analyzed. RESULTS: In this series, the fusion rate was 100%, and patients achieved bone fusion as shown by radiographs. The average time to fusion was 10.5 weeks. Superficial wound infection occurred in 1 patient. According to the Morgan system, there were 8 (80%) good to excellent results and 2 (20%) fair results. All patients were satisfied with the outcome of the operation. CONCLUSIONS: Arthroscopic ankle arthrodesis was an effective alternative to open technique with established advantages in hemophilic arthropathy. LEVEL OF CLINICAL EVIDENCE: Level IV, retrospective case series.

Development and Promotion of Concrete Strength at Initial 24 Hours.

Knowing and promoting the strength development of concrete at an earlier age is essential for accelerating formwork circulation of the on-site construction and precast product manufacture. The strength development rate at earlier ages of less than the initial 24 h was investigated. The effect of measures of adding silica fume, calcium sulfoaluminate cement, and early strength agent on the strength development of earlier concrete at ambient temperatures of 10, 15, 20, 25, and 30 °C was studied. The microstructure and long-term properties were further tested. It is shown that the strength increases exponentially first and then logarithmically, different from what is commonly recognized. Increasing cement content exhibited a certain effect only above 25 °C. When the cement content increased from 420 to 460 kg/m3, the strength only increased from 6.2 to 6.7 MPa after 12 h at 25 °C. The early strength agent could increase the strength significantly, the strength could be increased from 6.4 to 10.8 MPa after 20 h at 10 °C and from 7.2 to 20.6 MPa after 14 h at 20 °C. All measures for promoting earlier strength did not have an evident negative effect. The results could be potentially referred for the formwork removal at a suitable moment.

The effectiveness and influencing factors of the "Y" line technique in reducing the leg length discrepancy after total hip arthroplasty.

Objective: To introduce a surgical technique (the "Y" line technique) that will control leg length discrepancy (LLD) after total hip arthroplasty and to observe its effectiveness and influencing factors. Methods: According to the inclusion and exclusion criteria, a total of 350 patients were selected in this study; 134 patients in whom used the "Y" line technique was used to control lower limb length were included in Group A and 166 patients treated with freehand methods to control lower limb length were included in Group B. A total of 50 patients in whom the standard anteroposterior x-ray of bilateral hips was taken preoperatively and in whom the "Y" line technique was used during the operation were included in Group C. Results: The postoperative LLD of Group A was 4.74 mm (3.93), that of Group B was 5.85 mm (4.60), and that of Group C was 2 mm (1.00)-the difference was statistically significant (p < 0.001). There were significant statistical differences when comparisons were made between any two groups (p < 0.01). The distribution of postoperative LLD in Group A was better than that in Group B, and this factor was better in Group C than in Group A-the difference was statistically significant (p < 0.001). Severe unequal length rates of the lower extremities (LLD > 10 mm) were 5.97% (8/134) in Group A, 14.3% (24/166) in Group B, and 0% (0/50) in Group C-the difference was statistically significant (p < 0.001). There were significant differences between Group A and Group B and between Group B and Group C (p < 0.05), but there was no significant difference between Group A and Group C (p = 0.078). Conclusion: The "Y" line technique, which does not increase the operating time and patient cost, can effectively reduce postoperative LLD. Insufficient internal rotation of the healthy lower extremity and the low projection position in the preoperative anteroposterior x-ray of the bilateral hips were important factors affecting the accuracy of the "Y" line technique.

Analysis of Factors Affecting Early Functional Recovery of Bernese Periacetabular Osteotomy.

OBJECTIVES: To explore factors affecting the efficacy of Bernese periacetabular osteotomy for the treatment of hip dysplasia. METHODS: A retrospective study was conducted on 44 patients with hip dysplasia who underwent Bernese periacetabular osteotomy with a modified Smith-Peterson approach between January 2017 and November 2019. Among them, 40 were women and four were men. The average age was 31.2 ± 9.4. Preoperative and postoperative imaging parameters were measured. The acetabular top tilt angle, lateral central edge angle, acetabular abduction angle, femoral head extrusion index, sphericity index of femoral head, Shenton line, Tonnis grade of osteoarthritis, joint congruency, p/a ratio, acetabular anteversion angle, Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) scale scores, and modified Harris hip score (MHHS) were observed. MHHS were divided into three clinically relevant categories: poor (<70 points), good (70-85 points), and excellent (86-91 points). Patient demographic data, as well as preoperative and postoperative radiographic parameters, were subjected to univariate logistic regression analysis. Multiple regression analysis was used to determine factors influencing postoperative MHHS. RESULTS: The follow-up time was 1.0-3.9 years after surgery, with an average of 1.6 years. By the last follow-up, MHHS increased from 70 points before surgery to 91 points after surgery (P < 0.001), WOMAC pain score decreased from 4 points before surgery to 0 points after surgery (P < 0.001). WOMAC functional score decreased (Preoperative: 18.0 [4.0]; Postoperative: 4.0 [0], P = 0.004). Six patients had sensory disturbance of the lateral femoral cutaneous nerve, four of which recovered completely during follow-up. No other complications related to surgical approach, osteotomy, acetabular displacement, acetabular fixation, and postoperative stage were found. There was no significant vascular, nerve, or visceral injuries in any of the patients. On multiple regression analysis, the probability of the postoperative modified Harris hip score of a hip joint with a preoperative lateral center edge angle ≥4.5° being classified as excellent was six times that of angles <4.5° (Exp[ß]: 6.249, 95% CI: 1.03-37.85, P = 0.046). Regression analysis of other factors found no significant correlation with postoperative functional scores. CONCLUSION: Overall functional scores post-PAO significantly improved, and pain symptoms were significantly reduced. Patients with a preoperative lateral center edge angle ≥4.5° had better joint function after surgery.

Additive Effects of VDBP and 1,25(OH)2D3 on the Viability and Apoptosis of Rheumatoid Arthritis Synovial Fibroblasts.

Aim: This study is to investigate the additive effect of Vitamin D-binding protein (VDBP) and 1,25(OH)2D3 on the viability and apoptosis of synovial cells from patients with rheumatoid arthritis (RA). Methods: Synovial tissues and synovial fluid of patients with RA and osteoarthritis (OA) were collected. The expression of VDBP was analyzed with immunohistochemistry and ELISA. CCK-8 assay was applied to detect cell viability. Flow cytometry was used to analyze cell cycle and apoptosis. Results: Immunohistochemical results showed that the expression of VDBP in the synovium of RA patients was significantly lower than that of OA (P<0.05). Similarly, ELISA results presented a lower expression of VDBP in the synovial fluid of RA patients. The results of CCK-8 assay showed that both 1,25(OH)2D3 and VDBP significantly inhibited the viability of rheumatoid arthritis synovial fibroblasts (RASF) (P<0.05). The treatment with 1,25(OH)2D3+VDBP led to more significantly inhibited viability of RASF, compared with 1,25(OH)2D3 alone (P<0.05). The results of flow cytometry showed that 1,25(OH)2D3 and VDBP both promoted the apoptosis of RASF (P<0.05) and 1,25(OH)2D3+VDBP led to a higher proportion of RASF apoptosis, compared with 1,25(OH)2D3 alone (P<0.05). However, 1,25(OH)2D3 and VDBP had no significant effect on the cell cycle of RASF. Additionally, 1,25(OH)2D3 promoted the expression of VDBP in RASF, but not concentration-dependently. Conclusion: VDBP is reduced in the synovial tissue and synovial fluid of RA patients and can inhibit viability of RASF and promote the apoptosis of RASF. The 1,25(OH)2D3 can upregulate the expression of VDBP in RASF. Additionally, VDBP can enhance the effects of 1,25(OH)2D3 on viability and apoptosis of RASF.

IgM+CD27+ B cells possessed regulatory function and represented the main source of B cell-derived IL-10 in the synovial fluid of osteoarthritis patients.

Synovial inflammation is observed in patients with osteoathritis (OA) and likely contributed to its exacerbation. Regulatory B (Breg) cells are shown to suppress inflammation in various diseases, including rheumatoid arthritis (RA). To examine whether Breg cells also participated in OA, we examined the synovial fluid from OA patients, and compared with that in RA patients. In OA synovial fluid, IL-10-producing B cells were present directly ex vivo and were increased upon stimulation, indicating that B cells were a source of IL-10 directly at the affected site of OA patients. Interestingly, the frequency of IL-10+ cells in synovial B cells was higher in OA patients than in RA patients, but the total number of IL-10+ B cells in OA was lower than that in RA, suggesting that OA patients presented lower B cell infiltration than RA patients. Phenotypical analysis demonstrated that the IL-10+ B cells were IgM+ and CD27+, but not CD24hi or CD38hi. To allow functional analysis of IgM+CD27+ B cells, the IgM+CD27+ B cells in the blood of OA patients were examined. These blood IgM+CD27+ B cells expressed more IL-10, but less CD80 and CD86 than non-IgM+CD27+ B cells. Blood IgM+CD27+ B cells suppressed the proliferation and IFN-γ expression of autologous T cells, and this effect could be reverted if IL-10 was inhibited. Furthermore, we found that patients with more severe OA presented lower levels of IL-10+ B cells in the synovial fluid. Together, our study described an IgM+CD27+ B cell subset in OA patients, which represented the major IL-10-secreting B cell type in the synovial fluid of OA patients and possessed regulatory function.

The barbed suture of deep fascia walks away and pierces through skin far from the incision - a case report.

Barbed suture has been widely used in surgeries. However, this technique may raise many problems. Here, we report that the barbed suture of deep fascia walks away and pierces through skin far from the incision in a 61-year-old male 6 weeks after total hip arthroplasty.

Tim3+ Foxp3 + Treg Cells Are Potent Inhibitors of Effector T Cells and Are Suppressed in Rheumatoid Arthritis.

Rheumatoid arthritis (RA) is a chronic autoimmune disorder. Earlier studies have demonstrated that regulatory T (Treg) cells, the main cell type mediating immune tolerance, appeared to be enriched in the inflamed synovial tissues. It is still unclear why the Treg cells in RA patients are unable to limit exacerbated inflammation. Here, we found that the frequency of Tim3+Foxp3+ Treg cells, which were potent suppressors of proinflammatory responses, was downregulated in RA patients. Reduction in Tim3+Foxp3+ Treg frequency was correlated with increased RA disease activity. Furthermore, we observed that Tim3+Foxp3+ Tregs were expressed more interleukin (IL)-10 than Tim3-Foxp3+ Tregs. CD4+CD25+Tim3+ T cells had higher capability of inhibiting interferon (IFN)-γ and tumor necrosis factor (TNF)-α secretion from T cells and peripheral blood mononuclear cells (PBMCs) than CD4+CD25+Tim3- T cells. Compared to that in healthy individuals, CD4+CD25+ T cells in RA patients were less potent in suppressing IFN-γ and TNF-α production from PBMCs. Blocking Tim3 on CD4+CD25+ T cells from healthy controls resulted in an elevation of IFN-γ and TNF-α production from PBMCs, suggesting that Tim3 expression on CD4+CD25+ T cells was required for optimal Treg function. However, this phenomenon was not observed in RA patients. In conclusion, our study suggested that the CD4+CD25+Foxp3+ Treg cells from RA patients demonstrated a reduction of Tim3 and were less functional than Treg cells from healthy controls in a Tim3-related manner.

Exposing the transverse acetabular ligament in the presence of large floor osteophytes in primary total hip arthroplasty.

BACKGROUND/OBJECTIVE: The transverse acetabular ligament (TAL) can be used to position the acetabular cup and may help to improve the accuracy of primary total hip arthroplasty (THA). However, because the TAL may be covered by osteophytes, the ability to find the TAL varies greatly in the reported literature. In the present study, we introduce 2 methods and make a comparison between them to identify the easier procedure for finding an osteophyte-covered TAL. METHODS: During primary THA operations conducted from January 2012 to June 2015, a total of 100 patients (100 hips) were confirmed to have an osteophyte-covered TAL following the exposure of the acetabulum and removal of all soft tissues covering the TAL. These 100 patients were enrolled in this study. 2 methods were used to identify the TAL: the use of a bone chisel or a small reamer, and patients were allocated randomly to 1 of these 2 methods. The proportion of patients in whom TAL was identified was compared between the 2 methods using the chi-square test. RESULTS: The percentage of patients in whom the TAL was found using a bone chisel was 54.1% (26/48), whereas the percentage was 94.2% (49/52) in patients for whom a small reamer was used. The difference between the 2 methods was statistically significant (chi-square test, p<0.05). CONCLUSIONS: The TAL can be found more easily with a small reamer than with a bone chisel.

Downregulation of IL-10 secretion by Treg cells in osteoarthritis is associated with a reduction in Tim-3 expression.

Knee osteoarthritis (OA) is the most common cause of musculoskeletal pain and disability in the knee. Though traditionally thought a mechanical wear-and-tear disease, in recent years, knee OA as a low-grade, chronic inflammatory disease has been increasingly recognized. In this study, we examined the Treg responses in non-obese knee OA patients at different stages. Significantly elevated frequencies of CD4(+)CD25(+)Foxp3(+) Tregs were found in OA patients, while on the other hand, lower IL-10 secretion from Tregs in OA patients was observed. Importantly, this decrease in IL-10 was associated with reduced Tim-3 expression on Tregs. Although both Tim-3(-) and Tim3(+) Tregs could secrete IL-10, the majority of IL-10 was observed in Tim-3(+) Tregs. Reduction of Tim-3(+) Tregs in OA patients resulted in less IL-10-producing Tregs. Interestingly, the OA patients in more advanced stages showed further reductions in IL-10 and Tim-3 expression. In conclusion, our results revealed an immunoregulatory disorder in OA independent of obesity, and demonstrated a potential mechanism in establishing the proinflammatory status of OA patients.

TIM-3 Genetic Variations Affect Susceptibility to Osteoarthritis by Interfering with Interferon Gamma in CD4+ T Cells.

Osteoarthritis (OA) is the most common type of arthritis, in which T cell responses and cytokines may play critical roles in the development of the disease. TIM-3 may affect immune responses and is correlated with decreased expression of interferon gamma (INF-γ) in CD4+ T cells. In the current study, we investigated the association between polymorphisms in the TIM-3 gene and susceptibility to OA. Two polymorphisms in TIM-3, -574G/T and +4259T/G polymorphisms, were identified in OA cases and healthy donors by polymerase chain reaction-restriction fragment length polymorphism method. Data revealed that the prevalence of TIM-3 +4259T/G genotype was significantly elevated in OA patients than in the healthy donors after adjustment (Odds ratio [OR] = 2.67, 95% confidence interval [CI] 1.32-5.11, P < 0.001). Similarly, the TIM-3 +4259G allele presented a positive association with the risk of OA after adjustment (OR = 2.58, 95% CI 1.29-4.82, P = 0.003). The TIM-3 -574G/T polymorphism did not show any correlation with the disease. We further examined whether the two TIM-3 polymorphisms could affect INF-γ expression in CD4+ T cells. Data revealed that subjects carrying polymorphic +4259TG genotype had significantly higher mRNA and protein levels of INF-γ in CD4+ T cells compared to wild-type GG genotype (P < 0.001 and P < 0.01). These results indicated that TIM-3 polymorphism is associated with increased susceptibility to OA possibly by upregulating INF-γ expression in CD4+ T cells.

Expression of TIM-3 on CD4+ and CD8+ T cells in the peripheral blood and synovial fluid of rheumatoid arthritis.

Rheumatoid arthritis (RA) is characterized by a chronic inflammatory process that targets the synovial lining of diarthrodial joints. TIM-3 plays a key role in the negative regulation of the immune response. In this study, we investigated the expression of TIM-3 on CD4+ and CD8+ T cells from systemic (peripheral blood) and local (synovial fluid) perspectives of RA. Level of TIM-3+ cells from peripheral blood and synovial fluid of patients as well as peripheral blood of healthy controls was measured by flow cytometry. Results showed that TIM-3 expression was significantly increased in both CD4+ and CD8+ T cells in the peripheral blood of RA (p < 0.001 and p < 0.001, respectively). Furthermore, patients revealed even higher expression of TIM-3 in CD4+ and CD8+ T cells in synovial fluid than in peripheral blood. When comparing TIM-3 level with the severity of RA, we identified that the percentage of TIM-3 on both peripheral CD4+ and peripheral CD8+ T cells was negatively correlated with disease activity score 28 (DAS28) of the patients. Similarly, TIM-3 on synovial fluid CD4+ and CD8+ T cells also revealed inverse correlation with DAS28 of the cases. Our data demonstrate a negative correlation between TIM-3 and the disease progression of RA.