Tourniquet use benefits to reduce intraoperative blood loss in patients receiving total knee arthroplasty for osteoarthritis: An updated meta-analysis with trial sequential analysis.

PURPOSE: The efficacy and safety of tourniquets use during total knee arthroplasty (TKA) in patients with osteoarthritis remain debated. This updated systematic review and meta-analysis aimed to further evaluate the role of tourniquets use in patients undergoing TKA for knee osteoarthritis by introducing trial sequential analysis. METHODS: PubMed, Embase, and the Cochrane Library were searched. We used the Cochrane risk of bias tool for quality assessment. Statistical heterogeneity across studies was evaluated using Cochran's Q and I2 statistic. Meta-analysis was performed using Stata/SE 14.0, and trail sequential analysis was performed using TSA software version 0.9.5.10 Beta. In addition, qualitative summary was also used to describe results. RESULTS: 15 randomized controlled trials (RCTs) involving 1202 patients were included in the meta-analysis. The pooled results showed that tourniquet use during TKA significantly reduced intraoperative blood loss (mean difference (MD)= -123.84, 95% confidence interval (CI): -163.37 to -84.32, p < .001)and shortened operation time (MD = -4.71, 95% CI: -7.6 to -1.82, p = .001), but there were no significant differences in postoperative blood loss, calculated blood loss, total blood loss, transfusion rate (p = .939), and deep venous thrombosis (DVT) rate between the tourniquet and no-tourniquet groups. TSA confirmed that the result of operation time was false positive, but the results of other outcomes were conclusive. The results of qualitative summary showed conflicting findings in terms of pain, range of motion (RoM) and swelling ratio between the two groups. CONCLUSIONS: Tourniquet use in patients receiving TKA for osteoarthritis benefits to reduce intraoperative blood loss but has no effect on postoperative blood loss, calculated blood loss, total blood loss, operation time, transfusion rate, and DVT rate. In addition, it remains unclear the difference between the tourniquet and non-tourniquet groups in terms of pain, RoM and swelling ratio.

LncRNA PCED1B-AS1 knockdown inhibits osteosarcoma via methylation-mediated miR-10a downregulation.

BACKGROUND: LncRNA PCED1B-AS1 (PCED1B-AS1) promotes glioma. This study aimed to investigate its role in osteosarcoma (OS). METHODS: The study included 60 OS patients. Accumulation of miR-10a and PCED1B-AS1 in tissues from OS patients and cell lines was determined by RT-qPCR. Cell transfections were performed for interaction analysis. Participation of PCED1B-AS1 siRNA silencing and miR-10a overexpression in proliferation, invasion, and migration of U2OS and MG-63 cells was analyzed by cell proliferation assay and Transwell assay. RESULTS: PCED1B-AS1 level was increased in OS and positively correlated with miR-10a level. In OS cells, PCED1B-AS1 siRNA silencing downregulated miR-10a. Methylation-specific PCR analysis showed that PCED1B-AS1 siRNA silencing decreased the methylation of miR-10a gene promoter. Moreover, PCED1B-AS1 siRNA silencing suppressed OS cell proliferation, invasion, and migration. In addition, miR-10a overexpression attenuated the effects of PCED1B-AS1 siRNA silencing. CONCLUSION: PCED1B-AS1 knockdown may inhibit OS cell proliferation and movement by regulating miR-10 gene methylation.

LncRNA KCNQ1OT1 promotes the apoptosis and inflammatory response of microglia by regulating the miR-589-5p/NPTN axis after spinal cord injury.

Spinal cord injury (SCI) is a devastating traumatic condition accompanied with excessive inflammatory response and apoptosis of microglia. Long noncoding RNAs (lncRNAs) have been confirmed to be key regulators of cell inflammatory response. Nevertheless, the role of lncRNA KCNQ1OT1 in microglia apoptosis or inflammatory response after SCI remains to be explored. Our study focused on exploring the role and mechanism of KCNQ1OT1 in microglia after SCI. RT-qPCR showed that SCI induced the increase of KCNQ1OT1 level in mice spinal cord. Inhibition of KCNQ1OT1 suppressed the inflammatory response and apoptosis of microglia. In addition, KCNQ1OT1 was proved to bind with miR-589-5p, and NPTN was directly targeted by miR-589-5p. Furthermore, KCNQ1OT1 was negatively correlated with miR-589-5p and positively associated with NPTN. Rescue assays indicated that NPTN overexpression reversed the anti-inflammatory and anti-apoptosis effects of KCNQ1OT1 silencing. In summary, these data revealed that KCNQ1OT1 promoted inflammatory response and apoptosis of microglia by regulating the miR-589-5p/NPTN axis after SCI, which may offer a novel promising therapeutic target for SCI.

An optimization method for implantation parameters of individualized TKA tibial prosthesis based on finite element analysis and orthogonal experimental design.

BACKGROUND: Individualized and accurate implantation of a tibial prosthesis during total knee arthroplasty (TKA) can assist in uniformly distributing the load and reducing the polyethylene wear to obtain a long-term prosthetic survival rate, but individualized and accurate implantation of a tibial prosthesis during TKA remains challenging. The purpose of this study was to optimize and individualize the positioning parameters of a tibial prosthesis to improve its accurate implantation using a new method of finite element analysis in combination with orthogonal experimental design. METHODS: Ten finite element models of TKA knee joint were developed to optimize the implantation parameters (varus angle, posterior slope angle, and external rotation angle) of tibial prosthesis to reduce the peak value of the contact pressure on the polyethylene liner according to the method of finite element analysis in combination with orthogonal experimental design. The influence of implantation parameters on the peak value of the contact pressure on the polyethylene liner was evaluated based on a range analysis in orthogonal experimental design. RESULTS: The optimal implantation parameters for tibial prosthesis included 0° varus, 1° posterior slope, and 4° external rotation. Under these conditions, the peak value of the contact pressure on the polyethylene liner remained the smallest (16.37 MPa). Among the three parameters that affect the peak value of the contact pressure, the varus angle had the greatest effect (range = 6.70), followed by the posterior slope angle (range = 2.36), and the external rotation angle (range = 2.15). CONCLUSIONS: The optimization method based on finite element analysis and orthogonal experimental design can guide the accurate implantation of the tibial prosthesis, reducing the peak value of the contact pressure on the polyethylene liner. This method provides new insights into the TKA preoperative plan and biomechanical decision-making for accurately implanting TKA prosthesis.

Synthesis of silver @hydroxyapatite nanoparticles based biocomposite and their assessment for viability of Osseointegration for rabbit knee joint anterior cruciate ligament rehabilitation.

In this examination, chitosan-silk fibroin/polyethylene terephthalate (CTS-SF/PET), chitosan-silk fibroin/polyethylene terephthalate/hydroxyapatite (CTS-SF/PET/HAP) and chitosan-silk fibroin/polyethylene terephthalate/Silver @hydroxyapatite (CTS-SF/PET/Ag@HAP) scaffolds were prepared by utilizing the plasma splashing procedure. Field emission scanning electron microscopy (FESEM) results demonstrated that the outside of the PET covered with HAP nanoparticles. The cell viability results demonstrated that the number of Mesenchymal stem cells (MSCs) primarily spread out on CTS-SF/PET/Ag@HAP. RT-PCR results demonstrated that there was an upregulated mRNA articulation of osseous development-related properties in the CTS-SF/PET/Ag@HAP composite. The in vivo rabbit animal assessment scores of the CTS-SF/PET/Ag@HAP composite were significantly better than those of the CTS-SF/PET at 1 to 3 months. Both in-vivo and in-vitro results exhibited in this investigation recommend that the cytocompatibility and osseointegration of CTS-SF/PET/Ag@HAP tendon were fundamentally improved by expanding the multiplication of cells and up-regulating the outflow of tendon development-related properties. In conclusion, the CTS-SF/PET/Ag@HAP tendon is a promising candidate for Anterior Cruciate Ligament (ACL) replacement in the future.

Optimization of parameters for femoral component implantation during TKA using finite element analysis and orthogonal array testing.

BACKGROUND: Individualized and accurate implantation of a femoral component during total knee arthroplasty (TKA) is essential in achieving equal distribution of intra-articular stress and long-term survival of the prosthesis. However, individualized component implantation remains challenging. This study aimed to optimize and individualize the positioning parameters of a femoral component in order to facilitate its accurate implantation. METHODS: Using computer-simulated TKA, the positioning parameters of a femoral component were optimized individually by finite element analysis in combination with orthogonal array testing. Flexion angle, valgus angle, and external rotation angle were optimized in order to reduce the peak value of the pressure on the polyethylene liner of the prosthesis. RESULTS: The optimal implantation parameters of the femoral component were as follows: 1° flexion, 5° valgus angle, and 4° external rotation. Under these conditions, the peak value of the pressure on the polyethylene liner surface was minimized to 16.46 MPa. Among the three parameters, the external rotation angle had the greatest effect on the pressure, followed by the valgus angle and the flexion angle. CONCLUSION: Finite element analysis in combination with orthogonal array testing can optimize the implantation parameters of a femoral component for TKA. This approach would possibly reduce the wear of the polyethylene liner and prolong the survival of the TKA prosthesis, due to its capacity to minimize stress. This technique represents a new method for preoperative optimization of the implantation parameters that can achieve the best possible TKA outcome.

Increasing UCP2 expression and decreasing NOX1/4 expression maintain chondrocyte phenotype by reducing reactive oxygen species production.

The aim of this study is to demonstrate that improving the mitochondrial function can inhibite the loss of chondrocyte phenotype by regulating the expression of uncoupling protein 2(UCP2) and NADPH oxidase1/4(NOX1/4) to reduce the production of reactive oxygen species(ROS). The effects of mitochondrial biogenesis "master regular" peroxisome proliferator-activated receptor gamma coactivator-1α (PGC-1α), mitochondrial transcriptional factor A (TFAM), UCP2, and NOX1/4 on chondrocyte phenotype was examined. It was found that when the chondrocyte phenotype was lost, PGC-1α, UCP2, and TFAM expression decreased, while NOX1/4 expression increased. Inhibiting UCP2 expression promoted the loss of chondrocyte phenotype, and inhibiting NOX1/4 relieved the loss of the chondrocyte phenotype. After activating the PGC-1α-TFAM pathway, UCP2 increased and NOX1/4 decreased, which suppressed loss of the chondrocyte phenotype. After inhibiting NOX1/4, UCP2 expression increased. Increasing and decreasing UCP2 and NOX1/4 expression, respectively, helps maintain the chondrocyte phenotype and improve mitochondrial functioning by reducing reactive oxygen species production.

Accurate movement of jaw segment in virtual 3D orthognathic surgery.

In traditional virtual 3D orthognathic surgery, after repositioning the maxillary segment to the desired position, surgeons usually roughly rotate or adjust the mandibular segment to obtain a relatively good relationship with maxillary dentition to calculate the virtual terminal occlusion splint. However, surgeons are not easy to avoid penetrability, overlap, or an overly large space existing between the maxillary and mandibular dentitions during this process. The present report offered a new method to obtain a suitable virtual terminal occlusal splint that could avoid penetrability, overlap, or an overly large space between the maxillary and mandibular dentitions, and simultaneously accurately moving the maxillary or mandibular segment to the desired position utilizing the planned terminal occlusion plaster models in virtual orthognathic surgery. For double jaw surgery, after aligning the planned plaster models to the 3D maxilla and mandible, we could simultaneously move the maxillary and mandibular segment as a whole that maintain the planned terminal occlusion to the desired position. This present method may enhance the accuracy of 3D virtual orthognathic surgery and save plenty of time spend on virtual surgery simulation, which also offers a useful educational method for training junior surgeons and students.

Bioinformatic analysis of Msx1 and Msx2 involved in craniofacial development.

Msx1 and Msx2 were revealed to be candidate genes for some craniofacial deformities, such as cleft lip with/without cleft palate (CL/P) and craniosynostosis. Many other genes were demonstrated to have a cross-talk with MSX genes in causing these defects. However, there is no systematic evaluation for these MSX gene-related factors. In this study, we performed systematic bioinformatic analysis for MSX genes by combining using GeneDecks, DAVID, and STRING database, and the results showed that there were numerous genes related to MSX genes, such as Irf6, TP63, Dlx2, Dlx5, Pax3, Pax9, Bmp4, Tgf-beta2, and Tgf-beta3 that have been demonstrated to be involved in CL/P, and Fgfr2, Fgfr1, Fgfr3, and Twist1 that were involved in craniosynostosis. Many of these genes could be enriched into different gene groups involved in different signaling ways, different craniofacial deformities, and different biological process. These findings could make us analyze the function of MSX gens in a gene network. In addition, our findings showed that Sumo, a novel gene whose polymorphisms were demonstrated to be associated with nonsyndromic CL/P by genome-wide association study, has protein-protein interaction with MSX1, which may offer us an alternative method to perform bioinformatic analysis for genes found by genome-wide association study and can make us predict the disrupted protein function due to the mutation in a gene DNA sequence. These findings may guide us to perform further functional studies in the future.

The effect of meniscal tears and resultant partial meniscectomies on the knee contact stresses: a finite element analysis.

Knee osteoarthritis (OA) is believed to result from high levels of contact stresses on the articular cartilage and meniscus after meniscal damage. This study investigated the effect of meniscal tears and partial meniscectomies on the peak compressive and shear stresses in the human knee joint. An elaborate three-dimensional finite element model of knee joint including bones, articular cartilages, menisci and main ligaments was developed from computed tomography and magnetic resonance imaging images. This model was used to model four types of meniscal tears and their resultant partial meniscectomies and analysed under an axial 1150 N load at 0° flexion. Three different conditions were compared: a healthy knee joint, a knee joint with medial meniscal tears and a knee joint following partial meniscectomies. The numerical results showed that each meniscal tear and its resultant partial meniscectomy led to an increase in the peak compressive and shear stresses on the articular cartilages and meniscus in the medial knee compartment, especially for partial meniscectomy. Among the four types of meniscal tears, the oblique tear resulted in the highest values of the peak compressive and shear stresses. For the four partial meniscectomies, longitudinal meniscectomy led to the largest increase in these two stresses. The lateral compartment was minimally affected by all the simulations. The results of this study demonstrate meniscal tear and its resultant partial meniscectomy has a positive impact on the maintenance of high levels of contact stresses, which may improve the progression of knee OA, especially for partial meniscectomy. Surgeons should adopt a prudent strategy to preserve the greatest amount of meniscus possible.

A novel method to determine the potential rotational axis of the mandible during virtual three-dimensional orthognathic surgery.

During virtual three-dimensional orthognathic surgery in cases where an overlap or penetrability occurs between the 2 jaws due to the repositioning of the maxillary segment, it is necessary to establish a vertical opening of the mandible to obtain a relatively good relationship with the maxillary segment for the fabrication of an intermediate occlusal splint. However, there are few reports that address the precise definition of the rotational axis of the mandible during virtual surgery. Here, we present the idea that the mandible's movement during virtual three-dimensional orthognathic surgery is similar to hinge movement in vivo and developed a method for locating the geometric center of the three-dimensional condyle using Hypermesh software combined with Mimics software. Subsequently, we defined the rotational axis of the mandible based on the located geometric centers of the bilateral condyles, and the mandible was then rotated around the defined axis from the retruded contact position to mimic the hinge movement. Preliminary results indicated that the presented method could approximately mimic the hinge movement of the mandible with a relatively high accuracy in a three-dimensional environment, which may improve the accuracy of virtual intermediate occlusal splint.

Three-dimensional reconstruction of subject-specific knee joint using computed tomography and magnetic resonance imaging image data fusions.

Three-dimensional reconstruction of human body from a living subject can be considered as the first step toward promoting virtual human project as a tool in clinical applications. This study proposes a detailed protocol for building subject-specific three-dimensional model of knee joint from a living subject. The computed tomography and magnetic resonance imaging image data of knee joint were used to reconstruct knee structures, including bones, skin, muscles, cartilages, menisci, and ligaments. They were fused to assemble the complete three-dimensional knee joint. The procedure was repeated three times with respect to three different methods of reference landmarks. The accuracy of image fusion in accordance with different landmarks was evaluated and compared with each other. The complete three-dimensional knee joint, which included 21 knee structures, was accurately developed. The choice of external or anatomical landmarks was not crucial to improve image fusion accuracy for three-dimensional reconstruction. Further work needs to be done to explore the value of the reconstructed three-dimensional knee joint for its biomechanics and kinematics.

The effect of overexpression of Dlx2 on the migration, proliferation and osteogenic differentiation of cranial neural crest stem cells.

Craniofacial skeleton mainly originate from the cranial neural crest stem cells (CNCCs), which is a subpopulation of neural crest stem cells (NCCs). Dlx2, a member of the homeodomain family of transcription factors, plays crucial roles in the development of the CNCCs derived craniofacial skeleton. Previous reports reveal that Dlx2-targeted null mutation resulted in anomalies in the skeletal derivatives of CNCCs in mice. Dlx2 overexpression in ova disturbed the migration and differentiation of affected CNCCs and induced the development of ectopic skeleton elements. However, whether Dlx2 overexpression can impair the morphogenesis of CNCCs derived craniofacial skeleton in vivo has not been explored. Here, we generated a transgenic mouse overexpressing Dlx2 in NCCs (Wnt1Cre::iZEG-Dlx2). The Wnt1Cre::iZEG-Dlx2 embryos showed decreased cell proliferation, increased cell apoptosis, abnormal chondrogenesis and impaired osteogenesis within the CNCCs population, resulting in obvious craniofacial defects that ranged from a cleft lip and midfacial clefts to neural tube defects and exencephaly. Adult Wnt1Cre::iZEG-Dlx2 mice showed nasal and premaxillary hypoplasia and spinal deformities. These findings reveal that Dlx2 overexpression in NCCs may be a new pathogenesis of facial cleft and spinal kyphosis in mammals, and may offer us a useful model organism to find suitable therapy methods for these genetic defects that may be different from the traumatic defect and resected defect.

CBCT combining with plaster models: application in virtual three-dimensional subapical segmental osteotomy to obtain more precise occlusal splint.

Anterior subapical segmental osteotomy is considered to be an important surgical technique to obtain functional occlusion and improve the facial profile for patients with maxillary and mandibular protrusion or retrusion, and some complications, such as ischemic necrosis of the distal segment, devitalization of the teeth adjacent to the osteotomy site, and inadequate movement space of segment for obtaining a good occlusion or facial profile, usually exist during surgery. Imprecise measurement of root length, interradicular distance, and intertooth distance based on traditional panoramic radiography that demonstrated existing horizontal distortion and vertical distortion may play an important role in resulting in these problems. In addition, the root is invisible for surgical simulation in traditional plaster models. The recently developed cone-beam computed tomography (CBCT) presents a higher spatial resolution with a lower radiation dose, simultaneously with excellent accuracy and without magnification of images. The presented technique was used to obtain a precise occlusal splint in virtual 3D subapical segmental osteotomy by combining CBCT with plaster models that could guarantee the measurement accuracy of root length, interradicular distance, and intertooth distance, followed by the result of fewer tooth root damage and more precise forecasting of available movement space of jaw segment. Combining with other advantages of virtual 3D surgery, such as precise teeth surface of plaster models, soft tissue simulation, genoplasty simulation, and zygoma plasty simulation, this presented technique may offer a preferable method to patients who need subapical segmental osteotomy.

Merging the computed tomography and magnetic resonance imaging images for the visualization of temporomandibular joint disk.

Computed tomography (CT) depicts intricate bony details well, whereas magnetic resonance imaging (MRI) offers excellent contrast to the anatomy of soft tissues. This technical report offers a method to merge the CT and MRI images using Photoshop software and yield hybrid images that combine the key features of both CT and MRI. In this hybrid image, the temporomandibular joint (TMJ) disk was clearly displayed, and the relationship between the TMJ disk and surrounding skeleton structures, including glenoid fossa and condyle, also was finely demonstrated. Although the merging process is not absolutely accurate, the method presented in this article can be applied as a supplementary way to help the physicians to read the image of TMJ in an even better fashion and also may offer a useful method to help the junior physicians to quickly identify the TMJ disk.

The effect of co-culturing costal chondrocytes and dental pulp stem cells combined with exogenous FGF9 protein on chondrogenesis and ossification in engineered cartilage.

Dental pulp stem cells (DPSCs), which arise from cranial neural crest cells, are multipotent, making them a candidate for use in tissue engineering that may be especially useful for craniofacial tissues. Costal chondrocytes (CCs) can be easily obtained and demonstrate higher initial cell yields and expansion than articular chondrocytes. CCs have been found to retain chondrogenic capacity that can effectively repair articular defects. In this study, human CCs were co-cultured with human DPSCs, and the results showed that the CCs were able to supply a chondro-inductive niche that promoted the DPSCs to undergo chondrogenic differentiation and to enhance the formation of cartilage. Although CCs alone could not prevent the mineralization of chondro-differentiated DPSCs, CCs combined with exogenous FGF9 were able to simultaneously promote the chondrogenesis of DPSCs and partially inhibit their mineralization. Furthermore, FGF9 may activate this inhibition by binding to FGFR3 and enhancing the phosphorylation of ERK1/2 in DPSCs. Our results strongly suggest that the co-culture of CCs and DPSCs combined with exogenous FGF9 can simultaneously enhance chondrogenesis and partially inhibit ossification in engineered cartilage.

Two- and three-dimensional models for the visualization of jaw tumors based on CT-MRI image fusion.

PURPOSE: The objective of this study was to demonstrate the feasibility of two- and three-dimensional (2D and 3D) models based on computed tomography-magnetic resonance imaging (CT-MRI) image fusion for the visualization of jaw tumors. METHODS: Seven patients with proved jaw tumors were involved in this study. Both preoperative CT and MRI image data were acquired in DICOM format and imported into Surgicase CMF software, respectively. Then, the structures of interest, including tumor, muscle, and vascular, and so on, were segmented based on different thresholds and reconstructed in 3D texture. Finally, CT-MRI image fusion was semiautomatically performed to obtain the fused 2D images and 3D models for the visualization of jaw tumors. The qualities of the fused 2D images and 3D models together with their potential applications in surgical management of jaw tumors were qualitatively assessed. Besides, the importance of this imaging technique in terms of training junior surgeons was also discussed in detail. RESULTS: Computed tomography-MRI image fusion clearly showed the relationship between tumors and adjacent structures. The qualitative assessment of fused images was satisfied. CONCLUSIONS: Although there are some limitations, the 2D images and 3D models based on CT-MRI image fusion can provide a powerful tool for the visualization of jaw tumors. It may offer surgeons an assisted tool for the subject-specific preoperative planning, surgical simulation, and intraoperative guidance for jaw tumors. Furthermore, it also may offer valuable 2D and 3D models for training junior surgeons or provide a useful tool for surgeons to communicate well with patients.

Three-dimensional reconstruction of extremity tumor regions by CT and MRI image data fusion for subject-specific preoperative assessment and planning.

This study was conducted to demonstrate the feasibility of three-dimensional (3D) reconstruction of extremity tumor regions for patient-specific preoperative assessment and planning by using CT and MRI image data fusion. The CT and MRI image data of five patients with solid tumors were fused to construct 3D models of the respective tumor regions. The reconstruction time and image fusion accuracy were measured, and the tumor features and spatial relationships were analyzed to enable subject-specific preoperative assessment and planning as guidance for tumor resection. The 3D models of the tumor regions, including skin, fat, bones, tumor, muscles, internal organs, nerves and vessels, were created with a mean reconstruction time of 103 minutes and fusion accuracy of 2.02 mm. The 3D reconstruction clearly delineated the tumor features, and provided a vivid view of spatial relationships within the tumor region. Based on this intuitional information, the subject-specific preoperative assessment and planning were easily accomplished, and all tumor resections were performed as planned preoperatively. Three-dimensional reconstruction using CT/MRI image fusion is feasible for accurate reproduction of the complex anatomy of the tumor region with high efficiency, and can help surgeons improve the preoperative assessment and planning for effective removal of tumors.