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.

A three-dimensional measurement study of fracture displacement in Garden I femoral neck fracture: a retrospective study.

BACKGROUND: Garden I femoral neck fractures are nondisplaced femoral neck fractures. Nonoperative treatment and in situ fixation are the preferred treatments. However, the postoperative outcome is not satisfactory and the incidence of complications remains high, which raises doubts about the accuracy of the diagnosis of nondisplaced Garden I fractures. Recently, three-dimensional (3D) reconstruction has been reported as a mature technology for reconstructing the bone structure of patients. We further extended this technique in the measurement of the fracture spatial displacement to verify the accuracy of Garden I femoral neck fractures. METHODS: This was a retrospective study of patients with Garden I femoral neck fractures from January 2013 to December 2018 at our institution, who were included according to specified criteria. A bilateral proximal femur model of each patient was established based on computed tomography (CT) data. The displacement of the deepest portion of the femoral head fovea, the displacement of the center of the femoral head and the rotation of the femoral head were measured in the bilateral model. RESULTS: A total of 102 patients diagnosed with Garden I fractures were included in this study. The cohort included 32 men and 70 women, with an average age of 55.88 ± 15.32 years. In these patients, the average displacement of the deepest portion of the femoral head fovea was 16.43 ± 7.69 mm. The minimum and maximum displacement was 3.58 and 44.32 mm, respectively. The average displacement of the center of the femoral head was 10.39 ± 5.47 mm and ranged from 2.16 to 34.42 mm. The rotational angle was 23.81 ± 10.15 ° and ranged from 3.71 ° to 61.19 °. CONCLUSIONS: Garden I fractures have large spatial displacement and cannot be considered incomplete or nondisplaced fractures. Therefore, we suggest that anatomical reduction should be considered during treatment.

Computer-aided design combined with 3D-printed osteotomy guide-assisted derotational distal femoral osteotomy for treating recurrent patellar dislocation with increased femoral anteversion angle: a retrospective study.

PURPOSE: Derotational distal femoral osteotomy (DDFO) has good clinical outcomes for the treatment of the recurrent patellar dislocation combined with increased femoral anteversion angle (FAA). Currently, there is no uniform surgical technique. The purpose of this study was to evaluate the safety and efficacy of computer-aided design (CAD) combined 3D-printed osteotomy guide-assisted DDFO for treating these patients. METHODS: In a retrospective study of 36 patients with recurrent patellar dislocation (RPD) from December 2017 to December 2020, all patients had increased FAA and underwent DDFO assisted by CAD combined with a 3D-printed osteotomy guide. Patients' radiological parameters were used to assess the correction of increased femoral torsion and preoperative and postoperative subjective scores were recorded to evaluate the knee function. Complications were recorded to determine the safety of the surgery. RESULT: A total of 36 knees were included in this study, with a mean follow-up time of 32.6 ± 8.1 months. The mean age of the patients was 24.9±4.4 years and all patients experienced patellar dislocation preoperatively with a mean of 5.7±3.2 times. The patients' femoral anteversion angle decreased from 35.03±3.05° preoperatively to 14.80±0.87°, and the TT-TG distance decreased from 20.03±1.27 mm preoperatively to 19.22±1.22 mm. The hip-knee-ankle (HKA) angle and Insall-Salvatti index were not significantly different postoperatively compared to preoperatively. The knee function scores and visual analogue scale at the last follow-up were significantly improved compared to the preoperative scores. No major complications such as redislocation, nonunion, fixation or graft failure, or infection were observed in any patients. CONCLUSION: Computer-aided design combined with 3D-printed osteotomy guide-assisted derotational distal femoral osteotomy could correct the increased anterior femoral torsion and demonstrate good results. There were no patients experienced re-dislocation during follow-up period and the overall complication rate is low.

Intra-articular opening wedge osteotomy for varus ankle arthritis with computer-assisted planning and patient-specific surgical guides: a retrospective case series.

BACKGROUND: Computer-assisted preoperative planning, combined with PSI has become an effective technique for treating complex limb deformities. The purpose of this study was to evaluate the efficacy and safety of the novel technique in corrective osteotomy for intra-articular varus ankle deformities associated with osteoarthritis and ankle instability. METHODS: Nineteen patients with intra-articular varus ankle arthritis were reviewed between April 2017 and June 2019, including ten men and nine women with a mean age of 58.3 ± 9.9 years (range, 38 to 76 years). All patients underwent intra-articular opening wedge osteotomy assisted by 3D virtual planning and PSI. Weight-bearing radiographs were used to assess the radiographic results, including TAS angle, TT angle, TMM angle, TC angle, TLS angle, opening-wedge angle, and wedge height. Functional outcomes were assessed by the AOFAS score, VAS score, and ROM of the ankle. RESULTS: The average follow-up time was 32.2 ± 9.0 months (range, 22 to 47 months). The average union time was 4.4 ± 0.9 months (range, 3.0 to 6.5 months). The TAS angle significantly changed from 84.1 ± 4.6° preoperatively to 87.7 ± 3.1° at the 1-year follow-up and 86.2 ± 2.6° at the latest follow-up. Similarly, the TT angle, TMM angle and TC angle changed significantly at the 1-year follow-up compared with the preoperative assessment and remained stable until the last follow-up. However, the TLS was not corrected significantly. The postoperative obtained opening-wedge angle, and wedge height showed no significant change with preoperative planning. The overall complication rate was 15.8%. The mean VAS score improved from 5.3 ± 0.6 to 2.7 ± 0.7. The mean AOFAS score improved from 56.2 ± 7.6 to 80.6 ± 4.6. However, the ROM showed no significant change. CONCLUSIONS: Accurate correction and satisfactory functional recovery were attained with computer-assisted planning and PSI in the corrective osteotomy of intra-articular varus ankle deformities.

Practical Three-Factor Authentication Protocol Based on Elliptic Curve Cryptography for Industrial Internet of Things.

Because the majority of information in the industrial Internet of things (IIoT) is transmitted over an open and insecure channel, it is indispensable to design practical and secure authentication and key agreement protocols. Considering the weak computational power of sensors, many scholars have designed lightweight authentication protocols that achieve limited security properties. Moreover, these existing protocols are mostly implemented in a single-gateway scenario, whereas the multigateway scenario is not considered. To deal with these problems, this paper presents a novel three-factor authentication and key agreement protocol based on elliptic curve cryptography for IIoT environments. Based on the elliptic curve Diffie-Hellman problem, we present a protocol achieving desirable forward and backward secrecy. The proposed protocol applies to single-gateway and is also extended to multigateway simultaneously. A formal security analysis is described to prove the security of the proposed scheme. Finally, the comparison results demonstrate that our protocol provides more security attributes at a relatively lower computational cost.

Laser with 10-13 short-term instability for compact optically pumped cesium beam atomic clock.

We realize a high-stability laser by modulation transfer spectroscopy and apply it to implement a high-performance compact optically pumped cesium beam atomic clock. Evaluated by the optical heterodyne method with two identical frequency-stabilized lasers, the frequency instability of the 852 nm laser directly referenced on thermal atoms is 2.6×10-13 at the averaging time of 5 s. Factors degrading the frequency stability of the laser are analyzed, and we will further control it to reduce the frequency noise of the laser. By comparing with a Hydrogen maser, the measured Allan deviation of the high-stability-laser-based cesium beam atomic clock is 2×10-12/τ, dropping to 1×10-14 in less than half a day of averaging time. To our knowledge, the Allan deviation of our cesium clock is better than that of any reported compact cesium beam atomic clocks at the averaging time of half-day. The high-performance atomic clock can promote the fields in metrology and timekeeping, and the high-stability laser additionally possesses great potential to be a compact optical frequency standard.

Novel insights into whey protein among Yak, Yellow Cattle, and Cattle-Yak milk.

This study identified characteristic whey proteins from Zhongdian Yak (ZY), Diqing Yellow Cattle (DYC), and Cattle Yak (CY), revealing insights into their potential functions and released peptides. A total of 118 whey proteins were quantified in milk obtained from the three breeds of cattle, including seven characteristic proteins (IGL@ protein, 40S ribosomal protein S9, calreticulin, etc.) in CY milk and two characteristic proteins (RNA helicase and uncharacterized protein (A0A3Q1LFQ2)) in ZY milk. These characteristic proteins are involved in the phagosome and Fc gamma R-mediated phagocytosis pathways, exhibiting immunoprotective activities, verified through molecular docking. Furthermore, the molecular docking results showed five whey proteins (IGL@ protein, rho GDP-dissociation inhibitor 1, small monomeric GTPase, action-like protein 3, and adenylyl cyclase-associated protein) interacted with TLR4 through multiple hydrogen and hydrophobic bonds. Therefore, these proteins may exert immunomodulatory functions by inhibiting TLR4. Meanwhile, whey proteins produced bioactive peptides, such as antioxidant peptides and ACE inhibitory peptides after simulated gastrointestinal digestion (SGID). The whey proteins and bioactive peptides from CY exhibited more types and activities than the ZY and DYC whey proteins. This study provides a theoretical basis for promoting formula milk powder production.

The Osteoarthritis Natural Progress and Changes in Intraosseous Pressure of the Guinea Pig Model in Different Degeneration Stages.

OBJECTIVE: Articular cartilage and subchondral bone changes during the pathological progress of knee osteoarthritis (KOA) is a key event marking the development of the disease. The age varying alteration patterns within entire osteochondral unit remains poorly understood. The purpose of this study was to find a reasonable age range of the Dunkin-Hartley guinea pig model for the studying of KOA pathological process, and to investigate Intraosseous pressure (IOP) in the process during different degeneration stages of KOA. METHODS: Male Dunkin-Hartley guinea pigs were selected and divided into groups of 3, 6, 9, 12, 18 months old by age, 10 in each group. All knees underwent imaging examination including X-ray, Micro-CT and MRI. Observed the imaging findings with the use of Kellgren-Lawrence (K-L) classification and knee osteoarthritis MRI scores. Measured the IOP of distal femur (DF) and proximal tibia (PT) in each group, and observed the differences of bilateral tibiofemoral articular cartilage in histological and immunohistochemistry, staining results were evaluated by using Mankin's score. Analysis of variance (ANOVA) and t-tests were used to compare the differences indicators between groups. RESULTS: With the increase of age, changes in X-ray, Micro-CT and MRI imaging findings and pathological staining results of articular cartilage in all stages were consistent with the changing of degenerative KOA process. The IOP of DF and PT increased gradually with age, and reached its peak in 12-month age group, and then gradually decreased, there was a statistically significant difference of IOP between each group. The IOP of DF was slightly higher than that of PT, but the difference was not statistically significant. CONCLUSION: Dunkin-Hartley guinea pigs can be used as an animal model to study different pathological stages of KOA. There might be a correlation between the changes of IOP and the pathological progress of articular cartilage and subchondral bone in DF and PT.

Computer-aided Design of Distal Femoral Osteotomy for the Valgus Knee and Effect of Correction Angle on Joint Loading by Finite Element Analysis.

OBJECTIVE: Lateral open-wedge distal femoral osteotomy (DFO) has been used to treat valgus deformity of the knee, with good clinical outcomes. However, there is a lack of biomechanical studies regarding the angle of correction. The objective of this study was to apply computer-aided design (CAD) for osteotomy planning in a three-dimensional (3D) anatomical model and to assess the biomechanical differences among the varying correction angles on joint loading by finite element analysis (FEA). METHODS: To model different angles of lateral open-wedge DFO correction, the CAD software package Mimics 21.0 was used to accurately simulate the operated knee. The femur was cut to 0°, 2°, 4°, 6°, 8°, and 10° of varus (equivalent to hip-knee-ankle angles of 180°, 178°, 176°, 174°, 172°, and 170°, respectively). The original knee model and the corrected models were processed by FE software. Then, the FE models were subjected to an axial force to obtain the von Mises stress (VMS) and shear stress distributions within the femoral cartilages and menisci. RESULTS: Under a compressive load of 740 N, the highest VMS in lateral and medial compartments of the intact knee model was 3.418 and 3.303 MPa. The maximum value of both the VMS and the shear stress in the lateral compartment decreased as the varus angle increased, but the corresponding values in the medial compartment increased. When the hip-knee-ankle (HKA) angle was 180°, the VMS in the lateral and medial compartments was balanced (3.418 and 3.303 MPa, respectively). Meanwhile, when the HKA angle was 178° (3.488 and 3.625 MPa, respectively), the shear stress in the lateral and medial compartments was balanced. In addition, the magnitude of change in the stress was significantly higher in the medial compartment (90.9%) than in the lateral compartment (19.3%). CONCLUSION: The optimal correction angle of the valgus knee is close to neutral alignment or slightly varus (0° - 2°). Overcorrection is not recommended, as it can result in a steep increase of the stress within the medial compartment and may accelerate the process of medial compartment OA.

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.

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.

The efficacy of pregabalin for the management of postoperative pain in primary total knee and hip arthroplasty: a meta-analysis.

OBJECTIVE: A systematic review of randomized controlled trials (RCTs) was conducted to evaluate the efficacy of pregabalin for the management of postoperative pain in patients undergoing primary total knee arthroplasty (TKA) and primary total hip arthroplasty (THA). METHOD: The PubMed, Embase, Cochrane Central Register of Controlled Trials, and Google Scholar databases were searched for related articles using search strategy. RevMan 5.3 software was selected to conduct the meta-analysis. RESULTS: Seven RCTs were included in our meta-analysis. There were significant differences in visual analogue scale (VAS) at 24 and 48 h with rest, knee flexion degree, mean morphine consumption, and postoperative side effects (nausea, vomiting, pruritus, and dizziness) when comparing the pregabalin group to the placebo group after TKA and THA. However, the differences in VAS at 72 h with rest and at 24 h on movement were not significant between the two groups. CONCLUSIONS: Pregabalin was found to improve pain control at 24 and 48 h with rest, reduce morphine consumption, improve the knee flexion degree, decrease the incident rate of nausea, vomiting, and pruritus, and increase the incident rate of dizziness after TKA and THA but could not improve the pain control at 72 h with rest. In summary, the use of pregabalin may be a valuable asset in pain management within the first 48 h after TKA and THA. However, future studies regarding doses and pregabalin medication are required.

Effectiveness of surgery versus conservative treatment for lumbar spinal stenosis: A system review and meta-analysis of randomized controlled trials.

PURPOSE: Lumbar spinal stenosis (LSS) was a common degenerative disease that affected the lumbar spine function and quality of life, which can be treated both surgery and conservative treatment. We did this study to compare the effectiveness of surgery versus conservative treatment for LSS. METHODS: We searched PubMed as well as other databases in September.18th.2016. Randomized controlled trials compared surgery versus conservative treatment for patients with LSS were enrolled. Outcomes and complications were collected with data selection criteria and analyzed with Review Manager Version 5.3. RESULTS: Nine RCTs (14 articles) and 1658 patients were included, and three of them were high-quality studies. At first 6 months after treatment, there were no significant differences for ODI scores between two therapeutic groups (P > 0.05), however, surgery group showed significant higher ODI scores at one year (P < 0.05) and two years (P < 0.05). Two studies reported no significant difference between laminectomy and conservative treatment for the SF-36 physical function scores at 3 months, 6 months, 12 months and 24 months (P > 0.05) and two studies reported patients were satisfied with X-STOP implanted at six weeks, six months, and one year. No statistical differences for the adverse events intra-operation or within 72 h (P > 0.05) between surgery and non-surgery groups. Moreover, subgroup analysis showed there were no safety differences between laminectomy and conservative treatment, X-STOP and conservative treatment at early stage of duration. However, the surgical groups had higher complication rates than non-surgery groups throughout the follow-up duration. CONCLUSION: Surgery groups showed better late clinical outcomes after one year and higher complication rate throughout the follow-up duration, although it had no significant differences compared with conservative groups in the first six months post-treatment. However, there was no evidence that a definitive method could be firmly recommended to LSS patients. Further researches were needed to achieve high quality and credible results.

A meta-analysis of external fixation versus open reduction and internal fixation for complex tibial plateau fractures.

PURPOSE: Both external fixation (ExFx) and open reduction and internal fixation(ORIF) were used to treat complex tibial plateau fractures, but it was not sure which one was better. So we did this meta-analysis to evaluate the outcomes of ExFx and ORIF in managing complex tibial plateau fractures. METHODS: Articles published before August 5, 2016 were selected from PubMed, Cochrane library, and some other electronic database. Relevant journals were also searched manually with no language limited. Two independent reviewers searched and assessed the literature. A fixed effect model was initially used for meta-analyses with RevMan 5.3. RESULTS: When compared with ORIF, cases undergoing ExFx were more likely to return to the preinjury state at the early stage, but no difference in the later period of follow-up. However, ExFx group had higher infection rate (OR 1.98, 95% CI 1.08-3.63, P = 0.03), higher venous thromboembolism rate (OR 1.56, 95% CI 0.49-4.96, P = 0.45), higher re-operation rate (OR 0.87, 95% CI 0.47-1.62, P = 0.66) and lower compartment syndrome rate (OR 0.61, 95% CI 0.12-3.22, P = 0.56), lower TKA rate (OR 0.51, 95% CI 0.20-1.34, P = 0.17). There were no statistically significant differences in the rate of deep infection, venous thromboembolism, compartment syndrome and VTE between the two groups. CONCLUSION: Although external fixation may offer some advantages, both were acceptable strategies in managing complex tibial plateau fractures. According to our analysis results, we strongly recommend that selection of definitive fixators should base on the fracture patterns, soft-tissue condition as well as the injury stages in clinical practice. More important, further multicentered, randomized controlled studies should be implemented to get a more reliable and clear result.

Interspinous process devices(IPD) alone versus decompression surgery for lumbar spinal stenosis(LSS): A systematic review and meta-analysis of randomized controlled trials.

BACKGROUND: and purpose: Interspinous process devices (IPD) were widely used for the treatment of lumbar spinal stenosis (LSS). However, whether IPD was superior to bony decompression was still debated. We aimed to compare the clinical outcomes of IPD to bony decompression for LSS. METHODS: PubMed, Cochrane library, Cochrane Central Register of Controlled Trials (CCTR), Ovid Medline, China national knowledge internet database, Wan Fang database were searched in August.8th.2016. Studies were identified using selection criteria and analysed was performed with Review Manager Version 5.3. RESULTS: Four RCTs (seven articles) were included, with 200 patients in the interspinous process devices (IPD) group and 200 patients in bony decompression (DP) group. There was no significant difference in hospital stay time (P = 0.36), VAS leg pain scores (P = 0.83), and complication rates (P = 0.20) for IPD alone versus bony decompression. However, IPD alone showed higher VAS low back pain scores (P = 0.03) and reoperation rates (P < 0.0001) between the two therapy groups. Two studies' results showed the IPD group had lower cost-effectiveness. CONCLUSIONS: Although patients who received IPD may obtain several benefits in the short term, it was associated with higher costs, reoperation rates. Both IPD and bony decompression were acceptable strategies for LSS, but the risks, indications, and costs of IPD should be carefully taken into account before surgery.