Atractylenolide-III attenuates osteoarthritis by repolarizing macrophages through inactivating TLR4/NF-κB signaling.

BACKGROUND: As a common chronic musculoskeletal condition, osteoarthritis (OA) presently lacks particular treatment strategies. The aim of this study was to examine how AT-III therapies affected macrophage repolarity in order to slow down the advancement of OA. METHODS: RAW264.7 macrophages were polarized to M1 subtypes then administered with different concentrations of AT-III. Immunofluorescence, qRT-PCR and flow cytometry were used to assess the polarization of the macrophages. The mechanism of AT-III repolarize macrophages was evaluated by western blot. Furthermore, the effects of macrophage conditioned media (CM) on the migration, proliferation, and chondrogenic differentiation of bone marrow mesenchymal stem cells (BMSCs) were investigated using CCK-8 assays, the scratch test, and alcian blue staining. The effects of macrophage CM on chondrocyte proliferation and degeneration were investigated using CCK-8 and qRT-PCR. In vivo micro-CT and histological observations were performed on rats with anterior cruciate ligament transection and partial medial meniscectomy, either with or without AT-III treatment. RESULTS: AT-III repolarized M1 macrophages to M2 phenotype. Mechanistically, AT-III reduced the expression of Toll-like receptor(TLR) 4 induced by lipopolysaccharide in RAW264.7 and lowered nuclear factor-κB (NF-κB) signaling molecules p-p65 and p-IκBα. The TLR4 agonist RS09 reversed the effects of AT-III on macrophage repolarization. AT-III-induced macrophages CM stimulated BMSCs migration, proliferation and chondrogenic differentiation. AT-III-treated macrophage CM promoted chondrocyte proliferation while inhibiting chondrocyte degeneration. In vivo, AT-III treatment alleviated the degree of synovitis, inhibited subchondral bone remodeling and reduced cartilage destruction in the rat OA model. CONCLUSIONS: AT-III attenuates OA by repolarizing macrophages through inactivating TLR4/NF-κB signaling. These data suggest that AT-III may be an effective therapeutic candidate for OA treatment.

[New external spinal skeletal fixation combined with percutaneous injury vertebra bone grafting for the treatment of two-segment thoracolumbar fractures].

OBJECTIVE: To investigate the clinical results of new external spinal skeletal fixation combined with percutaneous injury vertebra bone grafting in the treatment of two-segment thoracolumbar fractures without neural dysfunction. METHODS: The clinical data of 28 patients with two-segment thoracolumbar fractures without neural dysfunction treated from January 2013 to August 2015 were retrospectively analyzed. There were 17 males and 11 females, with a mean age of(37.5±10.3) years (ranging from 19 to 55 years). According to fracture AO classification, all 28 cases were type A, including 2 cases of T10,11, 3 cases of T11,12, 9 cases of T12-L1, 4 cases of L1,2, 5 cases of L2,3, 4 cases of L3,4, 1 case of L4,5. All 28 patients received treatment of new external spinal skeletal fixation and percutaneous injury vertebra bone grafting. Operation time, intraoperative bleeding and related complications were recorded. The informations of vertebral anterior border height percentage and bone fusion were observed by radiography before and after operation, before removed external fixation and final follow-up. Visual analogue scale(VAS) was used to evaluate the clinical effects. RESULTS: All the patients were followed up for 13 to 32 months with an average of (24.5±3.5) months. There was significant difference by the time of 3 days postoperatively, before removed external fixation, final follow-up comparing with the preoperative in vertebral anterior border height percentage and VAS score(P<0.05). There was no significant difference in vertebral anterior border height percentage by the time of 3 days postoperatively, before removed external fixation comparing with final follow-up(P>0.05). While the VAS score showed a gradually declining trend, screw lossening ocurred in 2 cases and nail tracker infection occurred in 1 case after operation, and no other complications were found. CONCLUSIONS: New external spinal skeletal fixation and percutaneous injury vertebra bone grafting can got satisfactory clinical effect in treating two-segment thoracolumbar fractures without neural dysfunction, which is an effective method of minimally invasive surgery.

Clinical effect evaluation of percutaneous vertebroplasty combined with the spinal external fixator for the treatment of osteoporotic compressive fractures with posterior vertebral defect.

PURPOSE: The purpose of this study is to report a new technique and assess clinical outcome of compressive fractures with posterior vertebral defect treated by percutaneous vertebroplasty combined with the spinal external fixator. METHOD: 80 patients (32 males and 48 females), ranging from 62 to 88 years old with the mean age of 71.5 years, underwent surgery for the compressive fractures with posterior vertebral defect by percutaneous vertebroplasty combined with the spinal external fixator. All patients were diagnosed to have fresh compressive fractures with osteoporosis and posterior vertebral defect shown on roentgenograms, computed tomography scans or magnetic resonance imaging preoperatively. They underwent spinal external fixation firstly to be fixed and restored, then to be carried out percutaneous vertebroplasty. The mean follow-up was 24 months (16-42 months). Spinal canal encroachment, spinal cobb angle and vertebral body height loss were measured to assess clinical outcome before and after surgery, at the final follow-up. The Visual Analogue Scale and Oswestry Disability Index were used for pain and functional assessment. In all cases, preoperative and postoperative radiographs and magnetic resonance imaging were obtained. RESULTS: The average time of surgery was 88 min (75-115 min). The mean blood loss was 10 ml (6-12 ml) during surgery. The anterior height loss of vertebral body decreased significantly from 79.3 ± 11% before surgery to 8.0 ± 5.2% after surgery, and 7.6 ± 6.0% at the final follow-up. The spinal canal encroachment significantly reduced from 19.9 ± 2.6 % preoperatively to 4.0 ± 0.7% postoperatively, 4.1 ± 0.7% at the final follow-up. The Cobb angle was corrected from 25.8 ± 7.9° primarily to 8.2 ± 4.1° postoperatively, 7.8 ± 3.1° at the final follow-up. There were significant differences (p < 0.05) among them before and after the surgery. Postoperative VAS and Oswestry scores were both significantly different from the preoperative and follow-up (p < 0.05). CONCLUSION: The preliminary results are encouraging, showing that the spinal external fixator combined with percutaneous vertebroplasty was a safe and effective method to treat the osteoporotic compressive fractures with posterior vertebral defect.

[Analysis of the clinical effects of the modified halo pelvic frame for the treatment of severe scoliosis with rigidity].

OBJECTIVE: To evaluate the clinical curative effect of the modified Halo pelvic frame and surgery for the treatment of severe scoliosis with rigidity. METHODS: From January 2004 to May 2010,50 patients with severe scoliosis patients with rigidity were treated in our hospital. Twenty-three patients were male and 27 patients were female, with a mean age of 10.8 years old, ranging from 4 to 16 years. Twenty-four patients were congenital scoliosis and 26 patiens were idiopathic scoliosis. The mean body height were (152.1 +/- 11.1) cm and the average Cobb angle of scoliosis and kyphosis were (91.8 +/- 14.5) degrees and (69.5 +/- 14.0) degrees respectively. All the patients were treated with three-stages modified Halo pelvic traction, the second stage anterior release and the third stage posterior correction. The amount of correction was determined by measuring the change of body height, the Cobb angles and correction rate of scoliosis as well as kyphosis before and after the operation. RESULTS: The mean body height were correct to (158.5 +/- 10.5) cm. The average Cobb angle of scoliosis were correct to (30.8 +/- 7.9) degrees. The average Cobb angle of kyphosis were correct to (31.6 +/- 10.1) degrees. After the first stage, the average Cobb angle of scoliosis and kyphosis were changed with the mean of (30.4 +/- 6.6)% correction and (22.3 +/- 5.2)% respectively; after the second stage, the average Cobb angle of scoliosis and kyphosis were changed with the mean (26.7 -/+ 5.1)% correction and (21.2 -/+ 6.0)% respectively; the third stage, above data were (33.7 -/+ 7.2)% and (27.1 +/- 5.3)%. Correction rate of scoliosis and kyphosis were (66.5 +/- 7.2)% and (55.1 +/- 6.4)% respectively by the modified Halo pelvic frame traction and surgery. Body height, the Cobb angles and correction rate of scoliosis and kyphosis on radiographs were different in all stages (P<0.05). CONCLUSION: Operative complications of severe scoliosis with rigidity can be reduced and better deformity correction and trunk balance achieved by the modified Halo pelvic frame traction and surgery.

External spinal skeletal fixation combination with percutaneous injury vertebra bone grafting in the treatment of thoracolumbar fractures.

STUDY DESIGN: A technical report of thoracolumbar fractures managed by percutaneous external pedicular fixation and intracorporeal bone grafting. OBJECTIVE: To develop a new technique by combining simplified percutaneous external pedicular fixator with intracorporeal bone grafting to treat thoracolumbar fractures and assess its technical safety and clinical efficacy. SUMMARY OF BACKGROUND DATA: For surgical treatment of thoracolumbar fractures, the classical techniques are beneficial in decompression, restoration, fixation, and graft fusion, but they are also hugely invasive procedures. The earlier external spinal fixation procedures are good at indirect restoration, decompression, and elastic fixation of spinal fracture. However, they are limited by remains of a large external frame and inability of vertebral reconstruct. Therefore, the minimally invasive techniques combining simplified percutaneous external pedicular fixation and intracorporeal bone grafting might be a useful alternative. METHODS: There were 50 consecutive patients who had thoracolumbar fractures with or without associated incomplete neurologic deficit. They underwent percutaneous external pedicle fixation and intracorporeal bone grafting surgery within 7 days of admission, had their implants removed after 3 months, and were prospectively followed for at least 12 months. American Spine Injury Association grading, spinal canal encroachment, spinal Cobb angle, and vertebral body height were calculated before and after surgery to assess clinical outcome. RESULTS: A minimum of 12-month follow-up was achieved in 50 patients. The average operative time was 90 minutes (range, 50-160 minutes). The mean bone graft volume was 4.8 cm (range, 3.2-10.6 cm). The intraoperative mean blood loss was 100 mL (range, 50-180 mL). Forty-two patients all had at least one American Spine Injury Association grade neurologic improvement on final follow-up observation; there were no surgery-related complications. The mean anterior height of vertebral body was 53.2% (range 25%-78%) before surgery, 93.6% (range 78%-104%) after surgery, and 94% (range 79%-103%) at final follow-up. The preoperative Cobb angle of the primary curve averaged 30.7° (range 8°-67°), and corrected to 4.5° (range 0°-12.0°) immediately after surgery, There were statistically significant (P < 0.01) among them before and after operation. There was no instrumentation failure or measurable loss of sagittal curve and vertebral height correction in any cases. CONCLUSION: The new technique by combination of percutaneous external transpedicular fixation and transpedicular bone grafting is a feasible, safe, useful, efficient, and minimally invasive method to treat thoracolumbar fractures. It is a reasonable alternative method to other minimally invasive techniques of surgical management of the thoracolumbar fractures.