Suppression of YAP Ameliorates Cartilage Degeneration in Ankle Osteoarthritis via Modulation of the Wnt/ß-Catenin Signaling Pathway.

Ankle osteoarthritis is a relatively understudied condition and the molecular mechanisms involved in its development are not well understood. This investigation aimed to explore the role and underlying molecular mechanisms of Yes-associated protein (YAP) in rat ankle osteoarthritis. The results demonstrated that YAP expression levels were abnormally increased in the ankle osteoarthritis cartilage model. In addition, knockdown of YAP expression was shown to hinder the imbalance in ECM metabolism induced by IL-1ß in chondrocytes, as demonstrated by the regulation of matrix metalloproteinase (MMP)-3, MMP-9, and MMP-13, a disintegrin, metalloprotease with thrombospondin motifs, aggrecan, and collagen II expression. Additional studies revealed that downregulation of YAP expression markedly inhibited the overexpression of ß-catenin stimulated by IL-1ß. Furthermore, inhibition of the Wnt/ß-catenin signaling pathway reversed the ECM metabolism imbalance caused by YAP overexpression in chondrocytes. It is important to note that the YAP-specific inhibitor verteporfin (VP) significantly delayed the progression of ankle osteoarthritis. In conclusion, the findings highlighted the crucial role of YAP as a regulator in modulating the progression of ankle osteoarthritis via the Wnt/ß-catenin signaling pathway. These findings suggest that pharmacological inhibition of YAP can be an effective and critical therapeutic target for alleviating ankle osteoarthritis.

Intervertebral Disk Degeneration and Bone Mineral Density: A Bidirectional Mendelian Randomization Study.

This study aimed to investigate the causal relationship between bone mineral density (BMD) and intervertebral disk degeneration (IVDD) using a two-sample bidirectional Mendelian randomization analysis. Summary-level data from the Genome-Wide Association Study (GWAS) were used. Instrumental variables (IVs) for IVDD were selected from the large-scale Genome-Wide Association Study (GWAS) (20,001 cases and 164,682 controls). Bone mineral density (BMD) at five different sites (heel (n = 426,824), total body (TB) (n = 56,284), forearm (FA) (n = 8143), femoral neck (FN) (n = 32,735), and lumbar spine (LS) (n = 28,498)) was used as a phenotype for OP. Bidirectional causality between IVDD and BMD was assessed using inverse variance weighting (IVW) and other methods. Related sensitivity analyses were performed. Myopia was also analyzed as a negative control result to ensure the validity of IVs. Heel bone mineral density (heel BMD), total body bone mineral density (TB-BMD), femoral neck bone mineral density (FN-BMD), and lumbar spine bone mineral density (LS-BMD) have a direct causal relationship on intervertebral disk degeneration (IVDD) [heel BMD-related analysis: beta = 0.06, p = 0.03; TB-BMD-related analysis: beta = 0.18, p = 8.72E-08; FN-BMD-related analysis: beta = 0.15, p = 4.89E-03; LS-BMD-related analysis: beta = 0.16, p = 1.43E-04]. There was no evidence of a significant causal effect of IVDD on BMD. In conclusion, our study found a significant positive causal effect of lower BMD on IVDD, and we identified significant causal effects of heel, TB-, FN-, and LS-BMD on IVDD, but there was no evidence of a significant causal effect of IVDD on BMD.

Hypothyroidism and rheumatoid arthritis: a two-sample Mendelian randomization study.

Background: Meta-analysis of genome-wide association studies (GWAS) data showed that the relationship between hypothyroidism and rheumatoid arthritis (RA) risk remains under debate. This study is conducted to test the causal relationship of hypothyroidism and RA. Methods: A two-sample Mendelian randomization (TSMR) analysis was employed to estimate the causality of hypothyroidism and rheumatoid arthritis in European ancestry and Asian ancestry. Integrating the effects generated by TSMR, functional annotations and noncoding variant prediction framework were applied to analyze and interpret the functional instrument variants (IVs). Results: The results of the inverse variance weighted method showed a strong significant causal relationship between hypothyroidism and risk of RA in European ancestry [odds ratio (OR) = 1.96; 95% confidence interval (CI) 1.49, 2.58; p < 0.001]. The outcomes of MR-Egger, weighted median, weighted mode, and simple mode also showed that hypothyroidism was significantly associated with increased risk of RA in European ancestry. The MR-PRESSO method also showed significant results [Outlier-corrected Causal Estimate = 0.70; standard error (SE) = 0.06; p < 0.001]. An independent dataset and an Asian ancestry dataset were applied to estimate and obtain the coincident results. Furthermore, we integrated the effect of variants in TSMR analysis, functional annotations, and prediction methods to pinpoint the single-nucleotide polymorphism (SNP) rs4409785 as one of the causal variants, which suggested that this variant could impact the binding of CTCF-cohesin and play a vital role in immune cells. Conclusion: In this study, we prove that hypothyroidism is significantly causally associated with increased RA risk, which has not been shown in previous studies. Furthermore, we pinpoint the potential causal variants in RA.

Reinforcement strategy for medial open-wedge high tibial osteotomy: a finite element evaluation of the additional opposite screw technique and bone grafts.

BACKGROUND AND OBJECTIVE: bone grafts (bgs) and the opposite screw insertion technique are reported to enhance initial stability after medial open-wedge high tibial osteotomy (OWHTO); however, it is unclear how the general and local biomechanical stability of the proximal tibia is affected by these reinforcement strategies. In this study, we aimed to assess the biomechanical differences among different fixation configurations for OWHTO under two loading conditions using finite element analysis, and to assess the biomechanical contribution of an opposite screw insertion. METHODS: Models of the proximal tibia with three different gap defects were created to simulate different distraction heights in OWHTO. Four groups of models were then assembled with different fixation configurations, including the no BG (NBG) group, BG group, partially threaded screw (PT) group, and fully threaded screw (FT) group. Testing loads were applied to simulate the static forces on the knee joint during double-limb and single-limb standing. For each group, the stresses of the lateral hinge area (LHA) and the medial implant area (MIA), the maximum displacement of the tibia and the relative displacement (RD) of the medial gap were evaluated. RESULTS: Compared to NBG group, bone block grafting effectively reduced the stress of the tibia and implant, as well as the maximum displacement of the tibia and the RD of the medial gap. The opposite screw group showed similar trends in alleviating the stress concentration on the LHA and MIA, and contributing to the maintaining the medial gap reduction, especially in the FT group; however, additional stresses were concentrated on the opposite screw itself, which indicated the potential risk of screw breakage. CONCLUSIONS: Compared to NBG group, the BG group bone graft showed superior biomechanical advantages in decreasing the risk of implant failure and lateral hinge fracture, and maintaining the reduction in OWHTO. The additional opposite screw provided an extra support to the proximal tibia, with similar contributions to improve the structural stability after osteotomy, especially in the FT group.

Efficacy and safety of tanezumab administered as a fixed dosing regimen in patients with knee or hip osteoarthritis: a meta-analysis of randomized controlled phase III trials.

This study aims to evaluate the efficacy and safety of tanezumab administered as a fixed dosing regimen in patients with knee or hip osteoarthritis. Randomized controlled phase III trials (RCTs) that evaluated the efficacy and safety associated with tanezumab for knee or hip OA were systematically identified by searching electronic databases, including Cochrane Library, PubMed, and Embase, for 30 years from December 1990 up to July 2020. Ten relevant studies were included in our meta-analysis. The research was reported based on the preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines to ensure the reliability and verity of results. Our study showed that the tanezumab groups were more effective than the placebo groups in terms of mean change from the baseline in Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) pain (P < .00001), WOMAC physical functional (P < .00001), and patient's global assessment (PGA) (P < .00001). Discontinued due to adverse events (AEs) (P < .00001), serious AEs (P = .02), abnormal peripheral sensations (both P < .00001), and peripheral neuropathy (P < .002) in tanezumab groups were significantly higher than that in control groups. Compared with placebo, tanezumab can effectively relieve pain and improve WOMAC physical function and patient's global assessment (PGA) in knee and hip osteoarthritis. Meanwhile, adverse events are transient in nature and generally well-tolerated. However, we still need large-sample, high-quality studies to investigate the long-term safety of tanezumab to give the conclusion.

Biomechanical efficacy of four different dual screws fixations in treatment of talus neck fracture: a three-dimensional finite element analysis.

BACKGROUND: Current there are different screws fixation methods used for fixation of the talar neck fracture. However, the best method of screws internal fixation is still controversial. Few relevant studies have focused on this issue, especially by finite element analysis. The purpose of this study was to explore the mechanical stability of dual screws internal fixation methods with different approaches and the best biomechanical environment of the fracture section, so as to provide reliable mechanical evidence for the selection of clinical internal fixation. METHODS: The computed tomography (CT) image of the healthy adult male ankle joint was used for three-dimensional reconstruction of the ankle model. Talus neck fracture and screws were constructed by computer-aided design (CAD). Then, 3D model of talar neck fracture which fixed with antero-posterior (AP) parallel dual screws, antero-posterior (AP) cross dual screws, postero-anterior (PA) parallel dual screws, and postero-anterior (PA) cross dual screws were simulated. Finally, under the condition of 2400N vertical load, finite element analysis (FEA) were carried out to compare the outcome of the four different internal fixation methods. The results of Von Mises stress, displacement of four groups which contain talus fracture fragments and screws internal fixations were analyzed. RESULTS: Compared with the other three groups, postero-anterior (PA) parallel dual screws had better results in the stress peak, stress distribution, and displacement of talus and internal fixation. CONCLUSIONS: To sum up, the Von Mises stress of fracture section was the smallest, the stress distribution of screws were the most scattered, and the peak value was the smallest in posterior to anterior parallel double screws fixation, which was obviously better than that in the other three groups. When using screws internal fixation, the method of posterior to anterior screws fixation is better than that of anterior to posterior screws fixation, and the peak value and stress distribution of parallel double screws fixation is better than that of cross double screws fixation. Thus, for the talar neck fracture, the use of posterior to anterior parallel double screws fixation is recommended in clinical surgery.

The efficacy of dexamethasone reducing postoperative pain and emesis after total knee arthroplasty: A systematic review and meta-analysis.

BACKGROUND: Total knee arthroplasty (TKA) is gradually emerging as the treatment of choice for end-stage osteoarthritis. In the past, Perioperative dexamethasone treatment is still a controversial subject in total knee arthroplasty. Therefore, we write this systematic review and meta-analysis to evaluate the efficacy of dexamethasone on pain and recovery after Total knee Arthroplasty. MATERIALS AND METHODS: Embase, Pubmed, and Cochrane Library were comprehensively searched. Randomized controlled trials, cohort studies were included in our meta-analysis. Eight studies that compared dexamethasone groups with placebo groups were included in our meta-analysis. The research was reported according to the preferred reporting items for systematic reviews and meta-analysis (PRISMA) guidelines. Randomized controlled trials were included in our meta-analysis. RESULTS: Our study demonstrated that the dexamethasone group was more effective than the placebo group in term of VAS score at 24 h(P < 0.00001), 48 h(P = 0.0002); Opioid consumption (P < 0.00001); postoperative nausea (P < 0.00001); and Inflammatory factors of CPR at 24 h (P = 0.003). CONCLUSION: Our meta-analysis demonstrated that dexamethasone decreased postoperative pain, the incidence of POVN, and total opioid consumption effectively which played a critical role in rapid recovery to TKA. However, we still need large sample size, high quality studies to explore the relationship between complications and dose response to give the final conclusion.

The efficacy of dexamethasone on pain and recovery after total hip arthroplasty: A systematic review and meta-analysis of randomized controlled trials.

BACKGROUND: Total hip arthroplasty (THA) perioperative dexamethasone treatment is still a controversial subject. We write this systematic review and meta-analysis to evaluate the efficacy of dexamethasone on pain and recovery after THA. METHODS: Two researchers searched the relevant studies from Pubmed, Cochrane, and Embase. The research was reported according to the preferred reporting items for systematic reviews and meta-analysis (PRISMA) guidelines. Randomized controlled trials (RCTs) were included in our meta-analysis. At the same time, the assessment of the risk of bias was conducted according to the Cochrane Handbook for Systematic Reviews of Interventions version. The pooled data are processed by software RevMan 5.3. RESULT: In accordance with inclusion and exclusion, 3 studies with 207 patients were eligible and accepted into this meta-analysis. For RCTs, the risk of bias was evaluated by Cochrane Collaboration tool. Only one study did not have detection bias. Our study demonstrated that the dexamethasone group was more effective than the placebo group in term of visual analogue scale (VAS) score at 24 hours (P < .001), 48 hours (P = .04); opioid consumption (P < .001); length of stay (LOS, P < .001); and postoperative nausea (P = .001). CONCLUSION: Dexamethasone not only reduces postoperative pain scores and postoperative opioids consumption within 48 hours, but also reduces postoperative vomiting and effectively reduces LOS. However, we still need large sample size and high quality studies to explore the relationship between complications and dose response to give the final conclusion.

Sliding hip screw versus cannulated cancellous screws for fixation of femoral neck fracture in adults: A systematic review.

OBJECTIVE: Femoral neck fracture is considered a difficult fracture to treat and often gives rise to unsatisfactory treatment results. Cannulated cancellous screws (CCS) or a sliding hip screw (SHS) are the mainstream internal fixations used for osteosynthesis of femoral neck fractures. There is a need to integrate existing data through a meta-analysis to investigate the safety and effectiveness of CCS and SHS in the treatment of femoral neck fractures. METHOD: According to the Cochrane Handbook for Systematic Reviews of Interventions, we screened for the relevant studies by searching Google Scholar, the Cochrane Controlled Trials Register, the Cochrane Library, Web of Science, EMBASE, and PubMed. The PICOS criteria was used to make sure the included studies fulfilled the inclusion criteria. RESULTS: Pooled data showed that there were no significant differences between the SHS and CCS groups for the Harris Hip Score. Significant differences were found between the SHS and CCS groups in terms of union time, postoperative complications, blood loss, operation time, incision length and length of hospital stay. CONCLUSIONS: Although the SHS and CCS groups showed similar functional recovery in treatment of femoral neck fracture in terms of the Harris Hip Score, the SHS group showed fewer postoperative complications and faster union time for patients with femoral neck fractures. Therefore, compared with CCS, the use of SHS may be a more effective treatment of femoral neck fractures.

Custom-made Prosthesis for Reconstruction after Radical Resection for Chondrosarcoma of Manubrium.

The clinical incidence of tumors in the manubrium is not high. Regardless of whether the tumor is primary or metastatic, the tumor should be completely removed as long as the patient is able to tolerate the surgery. This procedure can lead to sternal defects. Deciding on the method of defect reconstruction is a critical problem that clinicians face. In this , to reduce the limitations of the patient's upper body movement after surgery due to the inflexibility in the connections of the sternal prosthesis, we created a prosthesis using a computer-assisted design method and a 3-D technique, to completely preserve the agility of the sternum and maximize the patient's post-operational movement. The method used in the present study takes into consideration the individual's chest anatomy, sternum stress, and many other biological characteristics. Care is taken to measure the sternum size accurately, to provide personalized treatment, to accomplish precise results, and to reduce potential future damage. The patient's shoulder function was improved following the procedure.

Comparison of clinical outcomes with InterTan vs Gamma nail or PFNA in the treatment of intertrochanteric fractures: A meta-analysis.

Intertrochanteric fractures are common injuries in the elderly. Conventional intramedullary nails including Gamma 3 locking nail and proximal femoral nail antirotation (PFNA) were designed for unstable intertrochanteric fractures. The InterTan (IT) nail system, introduced in 2005, has been reported superior biomechanical and clinical outcomes compared with 1-screw nailing system. However, some recent studies have reported that IT did not improve functional recovery in patients with intertrochanteric fractures. Randomized controlled trials (RCTs) or prospective cohort studies were included in our meta-analysis. We used the PRISMA guidelines and Cochrane Handbook to evaluate the quality of included studies to ensure that the pooled data of our meta-analysis were reliable and veritable. Our pooled data analysis demonstrated that IT was as effective as the control group in terms of Harris Hip Score (HHS), blood loss, total complications, union time, length of hospital stay, revision rate, and fluoroscopy time. IT shows less implant cut-out rate and femoral fractures when compared with control groups.

The efficacy of tranexamic acid using oral administration in total knee arthroplasty: a systematic review and meta-analysis.

BACKGROUND: Total knee arthroplasty (TKA) is gradually regarded as an effective choice for end-stage osteoarthritis or rheumatic arthritis. In the past, the management of tranexamic acid (TXA) using intravenous injection or topical application has been extensively researched. However, several studies have reported that oral TXA has an effect on blood loss. Therefore, a meta-analysis should be performed to determine whether oral TXA helps to prevent blood loss. METHODS: Randomized controlled trials or retrospective cohort studies about relevant studies were searched in PubMed (1996-April 2017), Embase (1980-April 2017), and the Cochrane Library (CENTRAL, April 2017). Six studies that compared oral TXA to non-TXA were included in our meta-analysis. Meta-analyses (PRISMA) guidelines, the Cochrane Handbook, and the Jadad scale were used to evaluate the included studies and the results to ensure that the meta-analysis was viable. RESULTS: In accordance with inclusion and exclusion, six studies with 2553 patients (oral TXA = 1386, without TXA = 1167) were eligible and accepted into this meta-analysis. Pooled data indicated that the oral TXA group was effective compared to the without TXA group in terms of hemoglobin (Hb) drop (P < 0.05), blood loss at 24 h (P < 0.05), total blood loss (P < 0.05), and the transfusion rate (P < 0.05). No significant differences were found in the length of hospital stay (P = 0.96) and complications (P = 0.39). CONCLUSION: Compared to the non-TXA group, the oral TXA group showed effects of blood sparing. Considering the cost and effectiveness, oral TXA is useful for TKA.