Critical Review of Synthesis, Toxicology and Detection of Acyclovir.

Acyclovir (ACV) is an effective and selective antiviral drug, and the study of its toxicology and the use of appropriate detection techniques to control its toxicity at safe levels are extremely important for medicine efforts and human health. This review discusses the mechanism driving ACV's ability to inhibit viral coding, starting from its development and pharmacology. A comprehensive summary of the existing preparation methods and synthetic materials, such as 5-aminoimidazole-4-carboxamide, guanine and its derivatives, and other purine derivatives, is presented to elucidate the preparation of ACV in detail. In addition, it presents valuable analytical procedures for the toxicological studies of ACV, which are essential for human use and dosing. Analytical methods, including spectrophotometry, high performance liquid chromatography (HPLC), liquid chromatography/tandem mass spectrometry (LC-MS/MS), electrochemical sensors, molecularly imprinted polymers (MIPs), and flow injection-chemiluminescence (FI-CL) are also highlighted. A brief description of the characteristics of each of these methods is also presented. Finally, insight is provided for the development of ACV to drive further innovation of ACV in pharmaceutical applications. This review provides a comprehensive summary of the past life and future challenges of ACV.

Association between metabolic syndrome and knee osteoarthritis: a cross-sectional study.

BACKGROUND: Osteoarthritis (OA) is the most prevalent chronic joint disease in China. The aim of this study was to examine the association between metabolic syndrome (MetS) and knee OA in a population-based Chinese study. METHODS: Data included in this analysis is from a cross-sectional study, i.e., the Xiangya Hospital Health Management Center Study. MetS was diagnosed according to the criteria defined by the Chinese Diabetes Society. Radiographic knee OA was defined as changes equivalent to Kellgren-Lawrence (K-L) grade 2 or above at least one side. Associations between MetS and its components with OA were evaluated by conducting multivariable adjusted logistic regression. RESULTS: A total of 5764 participants were included in the present study. The unadjusted OR (1.27, 95%CI: 1.10-1.47, P = 0.001), age-sex adjusted OR (1.17, 95%CI: 1.01-1.36, P = 0.041) and multivariable adjusted OR (1.17, 95%CI: 1.01-1.36, P = 0.043) all suggested a positive association between MetS and knee OA. Besides, its components (e.g., overweight, hypertension and dyslipidemia) were also associated with the prevalence of radiographic knee OA respectively, after adjusting for some confounding factors. In addition, with the accumulation of MetS components, the prevalence of knee OA increased. Furthermore, MetS as a whole was associated with the prevalence of knee osteophyte (OSP) (OR = 1.72, 95%CI: 1.42-2.09, P < 0.001), but not joint space narrowing (JSN) (OR = 1.06, 95%CI: 0.91-1.23, P = 0.449). CONCLUSIONS: The findings of the present study indicated that there was a positive association between the prevalence of MetS and knee OA. However, MetS as a whole was associated with the higher prevalence of knee OSP, but not JSN, which should shed light on our understanding the association between MetS and OA.

Visfatin triggers the in vitro migration of osteosarcoma cells via activation of NF-κB/IL-6 signals.

Pulmonary metastasis is the major challenge for clinical treatment of osteosarcoma patients. Recent studies indicated that visfatin, a 52kDa adipocytokine, can trigger the cell motility of various cancers, while its role in the progression of osteosarcoma remains not clear. Our present study revealed that visfatin can significantly promote the in vitro migration and invasion of osteosarcoma MG-63 and HOS cells and up regulate the expression of matrix metalloproteinase-2 (MMP-2) and fibronectin (FN). Furthermore, visfatin treatment also increased the expression of IL-6 in both MG-63 and HOS cells via a time dependent manner, while anti-IL-6 antibody can significantly attenuate visfatin induced cell invasion and up regulation of MMP-2 and FN. It suggested that up regulation of IL-6 mediated visfatin induced in vitro motility of osteosarcoma cells. Visfatin treatment can increase the phosphorylation of both p65 and ERK1/2 in MG-63 and HOS cells, while only the inhibitor of NF-κB, BAY 11-7082, can abolish visfatin induced up regulation of IL-6. BAY 11-7082 also attenuated visfatin induced upregulation of MMP-2 and FN in MG-63 cells. Western blot analysis revealed that visfatin treatment can significantly increase the phosphorylation of IκBα and IKKß in MG-63 cells. ACHP, the inhibitor of IKK-ß, blocked visfatin induced expression of IL-6 mRNA in both MG-63 and HOS cells. Collectively, our data suggested that visfatin can increase the motility of osteosarcoma cells via up regulation of NF-κB/IL-6 signals. It indicated that visfatin might be a potential therapeutic target of osteosarcoma treatment.

MiR-125b inhibits stromal cell proliferation in giant cell tumor of bone by targeting parathyroid hormone 1 receptor.

OBJECTIVES: miR-125b has been identified as a tumor suppressor in many tumors, but its role in giant cell tumor (GCT) of bone remains poorly understood. The current study aimed to investigate the potential role and mechanism of miR-125b in GCT. MATERIALS AND METHODS: Expression levels of miR-125b in GCT tissues were determined using RT-PCR. The cell proliferation was surveyed by direct cell counting, MTS and CCK-8, and the apoptotic cells were evaluated by Annexin V-FITC and propidium iodine staining assay. The target gene expression was determined using RT-PCR and western blot. Parathyroid hormone 1 receptor (PTH1R) 3'-UTR was cloned into luciferase reporter plasmid to confirm direct targeting. RESULTS: We found that miR-125b was significantly down-regulated in GCT tissues. Using both gain- and loss-of-function analyses, we further revealed that miR-125b suppressed GCT stromal cell proliferation and induced cell apoptosis. Furthermore, we revealed that PTH/PTHrP type 1 receptor is a direct and functional target of miR-125b. CONCLUSION: Our results suggest that miR-125b acts as a tumor suppressor through suppression of the PTH1R/RANKL signaling pathway. These findings contribute to our understanding of the functions of miR-125b in GCT.

Benefit of degenerative posterior longitudinal ligament removal during anterior decompression in cervical spondylotic myelopathy.

It remains controversial whether degenerative posterior longitudinal ligaments should be removed during anterior decompression procedures for cervical spondylotic myelopathy. Few data are available from studies that have compared removing and retaining the degenerative posterior longitudinal ligament. The goal of this retrospective study was to evaluate the benefit of degenerative posterior longitudinal ligament removal during such operations. Clinical data on 130 patients with confirmed degenerative posterior longitudinal ligament who underwent anterior cervical decompression surgery were retrospectively reviewed. All procedures were performed by the same senior orthopedic surgeon at the authors' spinal surgery center. The degenerative posterior longitudinal ligament was removed in 62 patients (group A) and retained in 68 patients (group B). The 130 patients were followed for 36 months. The Japanese Orthopedic Association score improved from 9.0±2.7 to 14.7±1.5 in group A and from 9.4±2.6 to 14.1±1.7 in group B (P=.028). The recovery rate for spinal cord neurologic function was 66.7% in group A and 61.3% in group B (P=.031). Operating time was longer (P=.002) and the sagittal median diameter of the vertebral canal was enhanced in group A (P<.001). Narrowing of previously enlarged canals occurred at a significantly higher rate in group B (P=.044). No significant difference was found in the rates of common complications between groups. Removal of the degenerative posterior longitudinal ligament in anterior decompression procedures for cervical spondylotic myelopathy appeared to be beneficial and provided more complete decompression and better postoperative outcomes than surgery without removal of the ligament. Although this procedure was generally safe, it required longer operating times, was more technically challenging, and required more experienced surgeons than surgery without removal of the ligament.

RANK pathway in giant cell tumor of bone: pathogenesis and therapeutic aspects.

Giant cell tumor is a relatively uncommon but painful tumor of bone, which can metastasize to the lungs. The RANK pathway is often reported to be involved in the pathogenesis of giant cell tumor of bone (GCTB). This pathway is a key signaling pathway of bone remodeling that plays a critical role in differentiation of precursors into multinucleated osteoclasts, and activation of osteoclasts leading to bone resorption. Dysregulation of RANK ligand (RANKL)-RANK-osteoprotegerin (OPG) signaling cascade induces the imbalance between bone formation and bone resorption, which leads to the changes in bone mass, increases osteoclast-mediated bone destruction, bone metastasis, and the progression of existing skeletal tumors. Recent evidences have shown that targeting the components of RANKL-RANK-OPG signaling pathway is a promising approach in the treatment of GCTB. This review study has focused on the association of RANKL-RANK-OPG pathway in the pathogenesis and progression of GCTB as well as discussed the possible therapeutic strategies by targeting this pathway.

Effect of partial and complete posterior cruciate ligament transection on medial meniscus: A biomechanical evaluation in a cadaveric model.

BACKGROUND: The relationship between medial meniscus tear and posterior cruciate ligament (PCL) injury has not been exactly explained. We studied to investigate the biomechanical effect of partial and complete PCL transection on different parts of medial meniscus at different flexion angles under static loading conditions. MATERIALS AND METHODS: TWELVE FRESH HUMAN CADAVERIC KNEE SPECIMENS WERE DIVIDED INTO FOUR GROUPS: PCL intact (PCL-I), anterolateral bundle transection (ALB-T), posteromedial bundle transection (PMB-T) and PCL complete transection (PCL-T) group. Strain on the anterior horn, body part and posterior horn of medial meniscus were measured under different axial compressive tibial loads (200-800 N) at 0°, 30°, 60° and 90° knee flexion in each groups respectively. RESULTS: Compared with the PCL-I group, the PCL-T group had a higher strain on whole medial meniscus at 30°, 60° and 90° flexion in all loading conditions and at 0° flexion with 400, 600 and 800 N loads. In ALB-T group, strain on whole meniscus increased at 30°, 60° and 90° flexion under all loading conditions and at 0° flexion with 800 N only. PMB-T exihibited higher strain at 0° flexion with 400 N, 600 N and 800 N, while at 30° and 60° flexion with 800 N and at 90° flexion under all loading conditions. CONCLUSIONS: Partial PCL transection triggers strain concentration on medial meniscus and the effect is more pronounced with higher loading conditions at higher flexion angles.

Effects of a selective cyclooxygenase-2 inhibitor (celecoxib) on fracture healing in rats.

BACKGROUND: Several studies suggested that celecoxib interferes with bone healing while others contradict these findings. This study was conducted to investigate the effects of celecoxib on bone healing in rats femur mold with a dose based on body surface area conversion. MATERIALS AND METHODS: 72 adult female Sprague Dawley rats were randomly divided into three groups after the internal fixation operation of nondisplaced transverse mid diaphyseal fractures of the right femurs. Each group was treated with 1% methylcellulose, celecoxib (21 mg/kg/d) for 1 week, or celecoxib (21 mg/kg/d) for 4 weeks after surgeries respectively. Bone healing scores and callus formation were evaluated by radiographs at 3, 4, 6 weeks after surgeries. Half of these rats were sacrificed for histological analysis at 4 weeks after surgery. The remaining fractured femurs were evaluated by biomechanical tests at 6 weeks after surgery. RESULTS: The mean radiographic scores for fracture healing of both short and long term groups were lower than that of the control group and the differences among the three groups were statistically significant (P < 0.05) at 3, 4, 6 weeks after surgery. The mean bone trabecula density of both groups was smaller than that of the control group and the differences were also statistically significant (P < 0.05) at 4 week. The maximum load, total energy and stiffness in both the short term and long term groups were significantly decreased compared with those in the control group (P < 0.05) at 6 week. CONCLUSION: Both short term and long term sustained use of celecoxib in rat models has significantly inhibitory effects on rat fracture healing.

Relationship between the migratory, metabolic and proliferative ability of fibrochondrocytes and the meniscal fragment size: an in vivo study.

OBJECTIVE: To investigate the migratory, metabolic and proliferative ability of rabbit fibrochondrocytes in meniscal fragments of different sizes under an in vivo subcutaneous environment. METHODS: Adult, male, New Zealand white rabbit menisci were harvested and the inner two-thirds of each were minced into different sizes: 0.5 × 0.5 × 0.5 mm (group A); 1.0 × 1.0 × 1.0 mm (group B); 2.0 × 2.0 × 2.0 mm (group C). Meniscal fragments were packed into a fascia sheath, then implanted subcutaneously. At weeks 1, 2 and 3 postimplantation, meniscal fragments were harvested; cell migration and viability were then evaluated by confocal laser scanning microscopy and haematoxylin and eosin staining. Aggrecan was detected using Safranin O and Fast Green staining, and protein levels of types I and II collagen, and proliferating cell nuclear antigen (PCNA), were evaluated by immunohistochemistry. RESULTS: Protein levels of types I and II collagen and PCNA, and fibrochondrocyte migration, were highest in group A compared with groups B and C, but aggrecan staining remained the same across the groups. CONCLUSION: There was an inverse relationship between the migratory, metabolic and proliferative abilities of rabbit fibrochondrocytes and meniscal fragment size.

Impact of Partial and complete rupture of anterior cruciate ligament on medial meniscus: A cadavaric study.

BACKGROUND: The clinical relationship between medial meniscus tear and anterior cruciate ligament (ACL) rupture has been well documented. However, the mechanism of this clinical phenomenon is not exactly explained. Our aim is to investigate the biomechanical impact of partial and complete ACL rupture on different parts of medial meniscus. MATERIALS AND METHODS: TWELVE FRESH HUMAN CADAVERIC KNEE SPECIMENS WERE DIVIDED INTO FOUR GROUPS: ACL intact (ACL-I), anteromedial bundle transection (AMB-T), posterolateral bundle transection (PLB-T), and ACL complete transection (ACL-T) group. Strain on the anterior horn, body part, and posterior horn of medial meniscus were measured under 200 N axial compressive tibial load at 0°, 30°, 60°, and 90° of knee flexion, respectively. RESULTS: Compared with the control group (ACL-I), the ACL-T group had a higher strain on whole medial meniscus at 0°, 60°, and 90° of flexion. But at 30°, it had a higher strain on posterior horn of meniscus only. As to PLB-T group, strain on whole meniscus increased at full extension, while strain increased on posterior horn at 30° and on body of meniscus at 60°. However, AMB-T only brought about higher strain at 60° of flexion on body and posterior horn of meniscus. CONCLUSIONS: Similar to complete rupture, partial rupture of ACL can also trigger strain concentration on medial meniscus, especially posterior horn, which may be a more critical reason for meniscus injury associated with chronic ACL deficiency.

[Raman spectroscopy analysis of carbon structural evolution of diesel particulate matters with the treatment of nonthermal plasma].

Original and nonthermal plasma treated particulate matters (PM) samples of a diesel were obtained and characterized by Raman spectroscopy. A five-bands model was adopted for Raman spectrum curve fitting. As parameters involving most information about carbon structure, variation of FWHM of D1 band and D3 relative intensity were analyzed. It was found that original PM presented higher graphical structural order and lower chemical heterogeneity with the increase in the diesel load. After the treatment of NTP, the graphical structural order and chemical heterogeneity of PM kept at a relative stable level, affected very slightly by diesel load. Meanwhile, the amount of molecular carbon in PM increased. Further study for relation between structural evolution and chemical reactivity of PM with chemical kinetics would make Raman spectroscopy of great promise to become an important method for PM characterization, which could provide basis for more effective removal.

Which treatment is the best for giant cell tumors of the distal radius? A meta-analysis.

BACKGROUND: Intralesional excision and en bloc resection are used to treat giant cell tumors (GCTs) of the distal radius. However, it is unclear whether one provides lower rates of recurrences and fewer complications, and whether the use of polymethylmethacrylate (PMMA) after curettage reduces the risk of recurrence. QUESTIONS/PURPOSES: We examined whether curettage was associated with lower rates of recurrence and fewer major complications compared with en bloc excision, and whether PMMA resulted in lower rates of recurrence compared with a bone graft. METHODS: We systematically searched the literature using the criteria, "giant cell tumor" AND "curettage" OR "intralesional excision" OR "resection". Six relevant articles were identified that reported data for 80 curettage cases (PMMA, n = 49; bone graft, n = 26; no PMMA or bone grafts, n = 5) and 59 involving en bloc excision. A meta-analysis was performed using these data. RESULTS: Overall, patients in the intralesional excision group had a higher recurrence rate (relative risk [RR], 2.80; 95% CI, 1.17-6.71), especially for Campanacci grade 3 GCTs (RR, 4.90; 95% CI, 1.36-17.66), yet fewer major complications (RR, 0.21; 95% CI, 0.09-0.54) than the en bloc resection group. The use of PMMA versus bone graft did not affect the recurrence rate (RR, 0.98; 95% CI, 0.44-2.17). CONCLUSIONS: Based on data obtained from the limited number of studies available, intralesional excision appears to be more appropriate for the treatment of local lesions (e.g., grades 1 and 2) than grade 3 GCTs of the distal radius. Moreover, PMMA was not additionally effective as an adjuvant. LEVEL OF EVIDENCE: Level III, therapeutic study (systematic review). See Guidelines for Authors for a complete description of levels of evidence.

Effect of epimedium pubescen flavonoid on bone mineral status and bone turnover in male rats chronically exposed to cigarette smoke.

BACKGROUND: Epimedii herba is one of the most frequently used herbs in formulas that are prescribed for the treatment of osteoporosis in China and its main constituent is Epimedium pubescen flavonoid (EPF). However, it is unclear whether EPF during chronic exposure to cigarette smoke may have a protective influence on the skeleton. The present study investigated the effect of EPF on bone mineral status and bone turnover in a rat model of human relatively high exposure to cigarette smoke. METHODS: Fifty male Wistar rats were randomized into five groups: controls, passive smoking groups and passive smoking rats administered EPF at three dosage levels (75, 150 or 300 mg/kg/day) in drinking water for 4 months. A rat model of passive smoking was prepared by breeding male rats in a cigarette-smoking box. Bone mineral content (BMC), bone mineral density (BMD), bone turnover markers, bone histomorphometric parameters and biomechanical properties were examined. RESULTS: Smoke exposure decreased BMC and BMD, increased bone turnover (inhibited bone formation and stimulated its resorption), affected bone histomorphometry (increased trabecular separation and osteoclast surface per bone surface; decreased trabecular bone volume, trabecular thickness, trabecular number, cortical thickness, bone formation rate and osteoblast surface per bone surface), and reduced mechanical properties. EPF supplementation during cigarette smoke exposure prevented smoke-induced changes in bone mineral status and bone turnover. CONCLUSION: The results suggest that EPF can prevent the adverse effects of smoke exposure on bone by stimulating bone formation and inhibiting bone turnover and bone resorption.

Effect of Epimedium pubescen flavonoid on bone mineral density and biomechanical properties of femoral distal end and femoral diaphysis of passively smoking male rats.

BACKGROUND: Based on a rat model of human relatively high exposure to cigarette smoke, this study aimed to estimate whether Epimedium pubescen flavonoid (EPF) may prevent a smoke-induced decrease in bone mineral density (BMD) and weakening of the biomechanical properties of bone. METHODS: Fifty male Wistar rats were randomized into five groups: controls, passively smoking groups and passively smoking rats administered EPF at three dosage levels (75, 150 or 300 mg/kg/day) in drinking water for 4 months. A rat model of passive cigarette smoking was prepared by breeding male rats in a cigarette-smoking box for 4 months. Bone metabolic makers, BMD and biomechanical properties of the femoral distal end and femoral diaphysis were examined. RESULTS: Exposure to cigarette smoke decreased the BMD, affected bone turnover (inhibited bone formation and stimulated its resorption) and weakened the biomechanical properties of the femur at its distal end and diaphysis. EPF supplementation during cigarette smoke exposure prevented the decrease in BMD, accelerated bone turnover and weakened the biomechanical properties of bone. CONCLUSION: Our data suggest that EPF supplementation can prevent the adverse effects of smoke exposure on BMD and biomechanical properties by inhibiting bone turnover and preventing bone resorption, and in this way it can decrease the risk of bone fractures.

Could nonunion tissue be transformed capable of bone formation by negative pressure: a new alternative to treat bone nonunion?

Despite substantial advances in orthopaedic surgery, bone nonunion is still a matter of debate for orthopaedic surgeon to provide optimal options on treatment of nonunion. Negative pressure therapy has already been successfully used in dealing with complex kinds of soft tissue healing. Some studies show that negative pressure can induce mesenchymal stem cells to differentiate into osteoblasts and others suggest that there are some mesenchymal-like cells existing in the nonunion tissue which can be re-activated and transformed into osteoblasts under some circumstance. We hypothesized that under negative pressure the mesenchymal-like cells can be transformed into osteoblasts in nonunion site. Under negative pressure, both "seeds" and "soils" can be made for new bone formation. If our hypothesis is proved to be corrected, it could be an innovative method to treat the bone nonunion.

Biomechanical evaluation of tenodesis reconstruction in ankle with deltoid ligament deficiency: a finite element analysis.

PURPOSE: Isolated deltoid ligament injuries are relatively uncommon but can be a significant source of pain and disability. Several approaches to deltoid reconstruction have been reported. However, there is no previous comparative study of Wiltberger, Deland, Kitaoka and Hintermann procedures with respect to biomechanical characteristics such as kinematics, ligaments and grafts stresses using finite element analysis. The purpose of this study was to evaluate the biomechanical results of those deltoid ligament reconstructions using finite element analysis. METHODS: A three-dimensional finite element model of the ankle including six bony structures, cartilage and nine principal ligaments surrounding the ankle joint complex was developed and validated. In addition to the intact model, superficial deltoid-deficient, deltoid-deficient, Wiltberger reconstruction, Deland reconstruction, Kitaoka reconstruction and Hintermann reconstruction models were simulated. Then, the forces in the ligaments and grafts and the kinematics of talus and calcaneus were predicted for an eversional or external torque through the range of ankle flexion. RESULTS: No reconstructions could completely restore the values for ankle flexibility and the stresses of the lateral ligaments to normality. The Kitaoka procedure was the most effective technique in eliminating external rotation displacement. The Deland procedure restored better the talar tilt than the other three reconstructions. CONCLUSION: This study showed that Kitaoka and Deland procedures have advantages with regard to rotational stabilities as well as ligaments stress in comparison with other methods.

Lipoic acid prevents steroid-induced osteonecrosis in rabbits.

The objective of this study was to investigate in vivo effects of lipoic acid (LA) in preventing steroid-induced osteonecrosis and the possible pathway in a rabbit model. Sixty rabbits were divided into 2 groups: rabbits were intraperitoneally injected with LA aqueous solution at 36 mg/kg of body weight per day for 4 weeks in Group A and rabbits were injected with physiologic saline (PS) as a control in Group B. At 2 weeks after starting treatment, they were intramuscularly injected once with 20 mg/kg of methylprednisolone acetate (MPSL). The femora were histopathologically examined for the presence of osteonecrosis. The plasma levels of total cholesterol (TC), low-density lipoprotein (LDL), high-density lipoprotein (HDL), glutathione (GSH), endothelin (ET) and malondialdehyde (MDA) were assayed at 2 weeks after the injection of MPSL. The incidence of osteonecrosis was significantly higher in Group B (73.1%) than in Group A (20.8%). The GSH level was higher in Group A than in Group B after the LA injection. The plasma MDA and ET levels were lower in Group A than in Group B at 2 weeks after the MPSL administration. Lipoic acid can prevent the development of steroid-induced osteonecrosis in rabbits. Inhibited oxidative stress and amendment of vascular endothelial dysfunction is a possible mechanism for this effect.

Effect of posterior cruciate ligament rupture on biomechanical features of the medial femoral condyle.

OBJECTIVE: To investigate the biomechanical impact of rupture of the posterior cruciate ligament (PCL) and its various bundles on the medial femoral condyle. METHODS: Twelve fresh human cadaveric knee specimens were divided into four groups: PCL intact, anterolateral band (ALB) rupture, posteromedial band (PMB) rupture and PCL complete rupture groups according to the purpose and order of testing. Strain in the middle of the medial femoral condyle was measured under different loads (200-800N) at 0°, 30°, 60°, and 90° of knee flexion. RESULTS: At 0° of knee flexion, compared with the PCL intact and ALB rupture groups, strain on the medial femoral condyle increased in the PMB rupture and PCL complete rupture groups under all loading conditions. There was no statistical difference between the PMB rupture and PCL complete rupture groups. At 30°, 60° and 90° of knee flexion, compared with the PCL intact group, increase in strain on the medial femoral condyle was noted in the ALB rupture group under higher loading conditions (600N and 800N) and PCL complete rupture group under all loading conditions. The PCL complete rupture group had higher strain on the medial femoral condyle than did the ALB rupture group under most loading conditions. CONCLUSION: At 0° of knee flexion, PMB rupture or PCL complete rupture can cause increase in strain on the medial femoral condyle. However, at 30°, 60° and 90° of knee flexion, ALB rupture or PCL complete rupture can cause increase in strain on the medial femoral condyle.

WITHDRAWN: Biomechanical Comparison of Lumbar Total Disc Arthroplasty, Discectomy and Fusion: Effect on Adjacent-Level Disc Pressure and Facet Joint Force.

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