Fibroblast growth factor 9 reduces TBHP-induced oxidative stress in chondrocytes and diminishes mouse osteoarthritis by activating ERK/Nrf2 signaling pathway.

Osteoarthritis (OA) is a degenerative and progressive disease that affects joints. Pathologically, it is characterized by oxidative stress-mediated excessive chondrocyte apoptosis and mitochondrial dysfunction. Fibroblast growth factor 9 (FGF9) has been shown to exert antioxidant effects and prevent degenerative diseases by activating ERK-related signaling pathways. However, the mechanism of FGF9 in the pathogenesis of OA and its relationship with anti-oxidative stress and related pathways are unclear. In this study, mice with medial meniscus instability (DMM) were used as the in vivo model whereas TBHP-induced chondrocytes served as the in vitro model to explore the mechanism underlying the effects of FGF9 in OA and its association with anti-oxidative stress. Results showed that FGF9 reduced oxidative stress, apoptosis, and mitochondrial dysfunction in TBHP-treated chondrocytes and promoted the nuclear translocation of Nrf2 to activate the Nrf2/HO1 signaling pathway. Interestingly, silencing the Nrf2 gene or blocking the ERK signaling pathway abolished the antioxidant effects of FGF9. FGF9 treatment reduced joint space narrowing, cartilage ossification, and synovial thickening in the DMM model mice. In conclusion, the present findings demonstrate that FGF9 can inhibit TBHP-induced oxidative stress in chondrocytes through the ERK and Nrf2-HO1 signaling pathways and prevent the progression of OA in vivo.

Study on the Mechanism of Acori Graminei Rhizoma in the Treatment of Alzheimer's Disease Based on Network Pharmacology and Molecular Docking.

Alzheimer's disease is a common neurodegenerative disease in the elderly. This study explored the curative effect and possible mechanism of Acori graminei rhizoma on Alzheimer's disease. In this paper, 8 active components of Acori graminei rhizoma were collected by consulting literature and using the TCMSP database, and 272 targets were screened using the PubChem and Swiss Target Prediction databases. Introduce it into the software of Cytoscape 3.7.2 and establish the graph of "drug-active ingredient-ingredient target." A total of 276 AD targets were obtained from OMIM, Gene Cards, and DisGeNET databases. Import the intersection targets of drugs and diseases into STRING database for enrichment analysis, and build PPI network in the Cytoscape 3.7.2 software, whose core targets involve APP, AMPK, NOS3, etc. GO analysis and KEGG analysis showed that there were 195 GO items and 30 AD-related pathways, including Alzheimer's disease pathway, serotonin synapse, estrogen signaling pathway, dopaminergic synapse, and PI3K-Akt signaling pathway. Finally, molecular docking was carried out to verify the binding ability between Acori graminei rhizoma and core genes. Our results predict that Acori graminei rhizoma can treat AD mainly by mediating Alzheimer's signal pathway, thus reducing the production of Aß, inhibiting the hyperphosphorylation of tau protein, regulating neurotrophic factors, and regulating the activity of kinase to change the function of the receptor.

Metformin Improves Functional Recovery After Spinal Cord Injury via Autophagy Flux Stimulation.

Spinal cord injury (SCI) is a severe neurological disease with few efficacious drugs. Autophagy is a cellular process to confront with stress after SCI and considered to be a therapeutic target of SCI. In this study, we investigated the therapeutic effect of metformin on functional recovery after SCI and its underlying mechanism of autophagy regulation. Using a rat model of traumatic SCI, we found improved function recovery which was paralleled by a reduction of apoptosis after metformin treatment. We further examined autophagy via detecting autophagosomes by transmission electron microscopy and immunofluorescence, as well as autophagy markers by western blot in each groups. The results showed that the number of autophagosomes and expression of autophagy markers such as LC3 and beclin1 were increased in SCI group, while autophagy substrate protein p62 as well as ubiquitinated proteins were found to accumulate in SCI group, indicating an impaired autophagy flux in SCI. But, metformin treatment attenuated the accumulation of p62 and ubiquitinated proteins, suggesting a stimulative effect of autophagy flux by metformin. Blockage of autophagy flux by chloroquine partially abolished the apoptosis inhibition and functional recovery effect of metformin on SCI, which suggested that the protective effect of metformin on SCI was through autophagy flux stimulation. Activation of AMPK as well as inhibition of its downstream mTOR signaling were detected under metformin treatment in vivo and in vitro; inhibition of AMPK signaling by compound C suppressed autophagy flux induced by metformin in vitro, indicating that AMPK signaling was involved in the effect of metformin on autophagy flux regulation. Together, these results illustrated that metformin improved functional recovery effect through autophagy flux stimulation and implied metformin to be a potential drug for SCI therapy.

The feasibility and radiological features of sacral alar iliac fixation in an adult population: a 3D imaging study.

BACKGROUND: Surgical treatments for adult spinal deformities often include pelvic fixation, and the feasibility of sacral-2 alar iliac (S2AI) screw fixation has been shown previously. However, sometimes S2AI screw fixation cannot be applied due to the presence of an osteolytic lesion or trauma or because the biomechanical properties of only an S2AI screw is insufficient. Therefore, we questioned the feasibility of using sacral AI screws in other segments and determined whether S3AI and S4AI screws have the potential to be used for sacral fractures. The aim of this study was to investigate the feasibility and radiological features of sacral AI fixation in S1-S4 in an adult population using 3D imaging techniques. METHODS: Computed tomography (CT) scans were taken of 45 patients and were imported into Mimics (Version 10.01, Materialise, Belgium) software to reconstruct the 3D digital images. Next, a cylinder (radius of 3.5 mm) was drawn to imitate the screw trajectory of a S1-4 AI screw, and every imitated screw in each segment was adjusted to a maximum upward and downward angle to acquire the feasible region. The parameters of the S1-4AI screw trajectories were measured. RESULTS: Sacral AI screws could be successfully imitated using 3D digital imaging. The S4AI screw trajectory could be obtained in 19 of 45 patient images (42.2%), while the feasibility rates of S1AI, S2AI, and S3AI screw fixation were 100%, 100%, and 91.1% (41/45), respectively. The feasible regions of S1AI, S2AI, and S3AI screw trajectories were wide enough, while the adjustable angle of S4AI screws was very small. CONCLUSION: It is feasible to place S1-2AI screws in the entire adult population and S3-4AI screws in some of the adult population. Furthermore, our study suggested that 3D digital images are suitable to study the feasibility of new screw fixation.

Comparison of Pediatric Forearm Fracture Fixation Between Single- and Double-Elastic Stable Intramedullary Nailing.

The purpose of this study was to evaluate and compare the outcome of single- and double-elastic stable intramedullary nailing (ESIN) for the treatment of pediatric both-bone forearm fractures. We retrospectively analyzed 49 children with both-bone forearm fractures treated with ESIN. Twenty-four patients were treated with single-ESIN (S-ESIN) to fixate the radius only, and the other 25 patients were treated with double-ESIN (D-ESIN) to fixate the radius and ulna. The duration of surgery, times of fluoroscopy, cost of hospitalization, period of castoff, union time, radiographic outcomes, clinical results, and postoperative complications were compared. The duration of surgery, times of fluoroscopy, and cost of hospitalization were significantly lower in the S-ESIN group; however, the average period of castoff was longer in the S-ESIN group. The incidence of delayed union of the ulna was significantly higher in the D-ESIN than in the S-ESIN group. Although the mean angulation deformity of the ulna in the S-ESIN group was significantly larger than in the D-ESIN group, both of them were acceptable (<10 degrees). Despite this, there was no difference in the loss of forearm motion and complication rates between the 2 groups. In conclusion, our data suggest that S-ESIN to fixate the radius alone remains an equally effective fixation method in the pediatric population compared with both-bone fixation and is our treatment of choice.

Percutaneous posterior transdiscal oblique screw fixation with lateral interbody fusion: a radiological and cadaveric study.

PURPOSE: To design and investigate a novel technique of percutaneous posterior transdiscal oblique screw fixation with lateral interbody fusion. METHODS: CT scans of 45 patients were collected and imported into Mimics software for three-dimensional (3D) reconstruction. Cylinders were drawn to simulate the trajectory of the oblique screw. Six measurements were obtained for each unit to design a right size cage: a the distance between the intersection of the simulated trajectory of the screw with the inferior border of the upper vertebra and its anteroinferior corner; b the distance between the intersection of the simulated trajectory of the screw with the superior border of the inferior vertebra and its anterosuperior corner; h the height of the intervertebral space; θ the angle between simulated trajectory of screw and the upper endplate of inferior vertebra; uw: the width of the inferior endplate of upper vertebra; iw: the width of upper endplate of inferior vertebra. Three intact adult fresh-frozen cadaveric specimens were obtained, percutaneous posterior transdiscal oblique screw fixation was performed under X-ray apparatus, and interbody cage was implanted by assistance with special self-retaining retractor system and endoscope. RESULTS: According to the results of data measured from 3D images, trapezoid shape interbody cages with suitable size were designed. Percutaneous posterior oblique screw fixation with lateral interbody fusion was performed on three cadaveric specimens successfully. CONCLUSION: Using specially designed trapezoid shape interbody cages, assisted by intra-operative image intensification and endoscope, it is feasible to perform percutaneous posterior transdiscal oblique screw fixation with lateral interbody fusion technique.

[Imaging measurement of anterior internal fixation for the cervicothoracic junction and its clinical significance].

OBJECTIVE: To measure important parameters of anterior internal fixation for the cervicothoracic junction by us-ing imaging measurement, and provide reference for cervicothoracic junction surgery and design of steel plate screw internal fixation. METHODS: From June to November 2012, 120 health people's median sagittal plane MRI of cervical spine were ran-domly collected. Of the 120 cases, there were 58 males and 62 females with an average age of 48.3 +/- 13.7, ranging the age of 20 to 78 years old. The anterior,middle and posterior height of vertebral, anterior, upper, medium and lower sagittal diameter, an-terior height of different segments and Cobb angle were measured by measuring machine in the PACS system. RESULTS: The an-terior, middle and posterior height of vertebral, medium and lower sagittal diameter gradually increased from cranial to caudal of cervicothoracic junction (P < 0.01). For single vertebral,posterior> anterior>middle height (P < 0.01), lower > upper>medium sagittal diameter (P < 0.01). The lower sagittal diameter of upper vertebral body was close to upper sagittal diameter of lower vertebral body. Cobb angle of male was (7.61 +/- 3.85) degrees, while female's was (5.58 +/- 2.59) degrees . CONCLUSION: During the anterior in-ternal fixation of cervicothoracic junction, it is suggested that the entry points of upper vertebral body should locate on the lower and middle 1/3 of vertebral body, and screws could slightly incline towards cranial,the entry points of lower vertebral body should locate on the upper and middle 1/3 of vertebral body, while screws could slightly incline towards caudal, also can be prebent according to Cobb angle of health.

A biomechanical study on the interosseous membrane and radial head in cadaveric forearms.

OBJECTIVE: Our aim was to evaluate the biomechanical properties of the interosseous membrane (IOM) and radial head and investigate the pathomechanics of the Essex-Lopresti injury. METHODS: Twelve adult fresh frozen upper limbs of human cadavers were chosen for test. First, the 12 intact specimens were mounted onto a materials testing machine to carry out biomechanical tests in pronation, supination and neutral positions, respectively. An axial load of 100 N was applied along the longitudinal axis of the forearm for 30 seconds in each position. Then, the twelve specimens were randomly divided into two groups. The radial head was resected in 6 specimens. And the central band of IOM was severed in another 6 specimens. Each group was tested by the same method. Finally, both the radial head and the IOM were excised in all specimens and biomechanical tests were performed. RESULTS: The rotational position of the forearm or simple severance of the IOM had no effect on longitudinal displacement. The radial longitudinal displacement increased significantly after resection of the radial head. The severance of the IOM had no effect on compressive stiffness of the radius. However, compressive stiffness of the radius decreased significantly after resection of the radial head. CONCLUSION: The radial head fracture combined with the IOM injury was the most important cause of the Essex-Lopresti injury, and the radial head fracture was the major factor. The IOM was the major structure to maintain the longitudinal stability of the forearm after resection of the radial head.

Mini-open anterior approach to the cervicothoracic junction: a cadaveric study.

PURPOSE: To investigate the feasibility of mini-open anterior approach to the cervicothoracic junction (CTJ) in cadaveric specimens. METHODS: Four adult fresh-frozen cadaveric specimens were used for this study. On the cadaveric specimen, an osteotomy window was made in manubrium sterni to remove the bony obstacle. To bypass the vital vascular and neural structures over the operative field, we used the surgical corridor which was located medially by the brachiocephalic artery and laterally by the right brachiocephalic vein, or in combination with another surgical corridor between the ascending aorta and the superior vena cava. And we used a special self-retaining retractor system and an endoscope to facilitate the procedures. RESULTS: Surgical procedures performed on the four fresh-frozen cadaveric specimens to expose the CTJ through mini-open anterior approach were successful. The anterior surface of C6-T5 could be exposed, allowing complete decompression and application of locking plate and screws. The most caudal accessible vertebral body was T5 vertebral body in our study. CONCLUSION: It is feasible to expose the CTJ through this mini-open anterior approach.

A comparative study of axis-line-distance technique and Cobb method on assessing the curative effect on scoliosis.

PURPOSE: To compare the axis-line-distance technique (ALDT) and Cobb method for therapeutic evaluation of scoliosis. METHODS: Fifty-seven patients with scoliosis were treated in our hospital, 47 underwent conservative bracing therapy and 10 underwent surgery. Based on 171 full-spine X-ray images obtained from these 57 cases before treatment, during conservative treatment or surgery, and at final follow-up after removing the brace or after surgery, two radiologists independently measured and calculated the correction rate during treatment and at final follow-up and the rate of correction loss after treatment with the ALDT and Cobb methods. Paired t-test and correlation analysis were performed. RESULTS: Based on the ALDT, the lateral deviations of the apical vertebrae before treatment, during treatment, and at final follow-up were 31 ± 14 mm, 16 ± 8 mm, and 20 ± 8 mm, respectively; the correction rates during treatment and at final follow-up were 48.7 ± 21.2% and 37.6 ± 14.2%, respectively, and the rate of correction loss after treatment was 11.3 ± 6.5%. The Cobb angles of scoliosis before treatment, during treatment, and at final follow-up were 34 ± 14°, 19 ± 7°, and 22 ± 6°, respectively; the correction rates during treatment and at final follow-up were 44.4 ± 17.3% and 33.9 ± 14.4%, respectively, and the rate of correction loss after treatment was 11.4 ± 4.3%. Calculation of the correction rate during treatment differed significantly between the two radiologists when using the Cobb method (P < 0.05); their calculations of the correction rate and rate of correction loss were not different (P > 0.05). The measurement data of the two radiologists using the Cobb method showed a weak to moderate correlation (r = 0.49, 0.57, and 0.51, respectively). When using the ALDT, there were no significant differences between the radiologists in their measurements of the correction rate during and after treatment (P > 0.05) or in the rate of correction loss. The measurement data of the two radiologists using the ALDT showed a good to excellent correlation (r = 0.92, 0.93, and 0.90, respectively). CONCLUSION: The ALDT is better than the Cobb method for therapeutic evaluation of scoliosis during treatment and at follow-up visits.

Percutaneous pedicle screw fixation for neurologic intact thoracolumbar burst fractures.

STUDY DESIGN: Prospective consecutive series. OBJECTIVE: To evaluate the efficacy and safety of percutaneous pedicle screw fixation (PPSF) for thoracolumbar AO type A3 fractures with a specially designed surgical instrument system. SUMMARY OF BACKGROUND DATA: Minimally invasive surgery including PPSF is becoming increasingly widespread in the spine surgery. The technique of PPSF was mostly used as supplemental fixation combined with minimally invasive posterior or anterior lumbar interbody fusion in management of lumbar degenerative disorders. There are fewer studies available in literature regarding PPSF without additional kyphoplasty or vertebroplasty for management of thoracolumbar burst fractures. METHODS: Thirty-six adult patients, who had single thoracolumbar AO type A3 fractures and the load-sharing score of 6 or less, underwent application of percutaneous short-segment pedicle screw fixation. Radiologic parameters including kyphotic angle and vertebral height loss were assessed before and after surgery, and functional outcome was evaluated by Prolo questionnaire. RESULTS: All patients were successfully managed with percutaneous minimal invasive procedures. The average operative time was 78 minutes (range 62 to 117 min). The average intraoperative blood loss was 75 mL (range 50 to 220 mL). After a mean follow-up of 48.5 months (range 32 to 63 mo), 31 of 36 (86.1%) patients had a satisfactory result (19 excellent and 12 good) and 5 of them fair. CONCLUSIONS: Our clinical results suggest that PPSF can be an alternative for management of thoracolumbar AO type A3 fractures that have no neurologic deficits. With a specially designed percutaneous instrument and pedicle screw system, the procedure has been proved as relatively safe and a minimally invasive approach for the management of thoracolumbar burst fracture without neurologic deficit.

Anterior approaches to the cervicothoracic junction: a study on the surgical accessibility of three different corridors based on the CT images.

To determine the location of left brachiocephalic vein (BCV) and tracheal bifurcation (TB) relative to the vertebral levels, and to ascertain the accessibility of three different corridors (C1: between the esophagus and trachea medially and the carotid sheath laterally, C2: between the right BCV and the brachiocephalic artery, and C3: between the ascending aorta and superior vena cava) for preoperative planning. From August 2008 to April 2009, normal chest CT scans of 150 subjects ranging in age from 18 to 78 years were selected. According to our definition, of the 150 studies, 132 T2 vertebral bodies (VBs) could be accessed through C1 (88.0%), 100 T3 VBs could be reached through C2 (66.7%), and 110 T4 VBs could be exposed through C3 (73.3%). The results suggest that the surgical accessibility of three different corridors is different and we conclude that T2, T3, and T4 are, respectively, readily accessible through C1, C2, and C3.

Three-dimensional reconstruction of the superior mediastinum from Chinese Visible Human Female.

PURPOSE: This research aimed to construct three-dimensional (3D) visible models of the superior mediastinum for anatomic study and surgical approaches to the superior mediastinum. METHOD: Sectional images of the superior mediastinum were acquired through the Chinese Visible Human Female (VCHF) database. One hundred eighty images of the superior mediastinum were imported into Photoshop CS and the images were converted into a JPEG format. Surface and volume reconstruction were performed by 3D Doctor 3.5 and Amira 4.0 software programs on an ordinary personal computer, respectively. RESULT: The surface and volume reconstruction of the superior mediastinum were successful. The surface reconstruction model allowed rotation and magnification of the superior mediastinum structures as well as displayed the contours of reconstructed structures individually or as a composite with any other selected structure. Volume reconstruction displayed abundant internal detail of reconstructed images in transverse, coronal, sagittal, and random oblique sections. CONCLUSION: Three-dimensional, visible models of the superior mediastinum based on the sectional images of VCHF can provide unique insight into the anatomy of superior mediastinum. These models provide an excellent adjunct to the anatomy curriculum in medical schools and an invaluable tool for the practicing surgeon planning an operation in this complex anatomic region.

[CT imaging study of anterior approaches to the upper thoracic spine].

OBJECTIVE: There are small smount of literatures on the study of the anterior surgical approaches to the upper thoracic spine (UTS). Moreover, there are many differences among the results of these studies. This study is to investigate the exposure ranges of different anterior surgical approaches to the UTS for making the preoperative plan by means of CT images analysis. METHODS: From October to December in 2008, 120 CT images of normal chests were chosen. These subjects (58 males, 62 females) ranged in age from 16 to 75 years (mean 40.3 +/- 12.3 years). By using the X-ray positioning images of these CT images,following indexes were studied: the location of the superior margin of the left brachiocephalic vein on the sagittal plane, the confluence of the bilateral brachiocephalic veins, and the vertebrae level of the tracheal bifurcation. The caudal access of E1 (the interval between the tracheo esophageal sheath and the bilateral carotid sheath), E2 (the interval between the right brachiocephalic vein and the brachiocephalic artery), and E3 (the interval between the ascending aorta and superior caval vein) were respectively defined as the above mentioned three points. RESULTS: Among the 120 studies, 105 T2 vertebral bodies could be exposed through E1 (87.5%), 82 T3 vertebral bodies could be exposed through E2 (68.3%), and 89 T4 vertebral bodies could be exposed through E3 (74.2%). CONCLUSION: The exposure ranges of three different anterior surgical approaches to the upper thoracic spine are different. Proper surgical approaches could be selected according to the chest CT images of the patients.

[Study on the three-dimensional reconstruction and visualization of the anatomical structures of the anterior approach to the upper thoracic spine].

OBJECTIVE: To establish the three-dimensional (3D) visible models of the anatomical structures of the anterior approach to the upper thoracic spine (UTS) for anatomic study and preoperative planning of the UTS. METHODS: Sectional images from the superior margin of the first thoracic vertebral body to the inferior margin of the fifth thoracic vertebral body were acquired through the Chinese Visible Human Female (VCHF) database which was collected by the Third Military Medical University. These images were imported into Photoshop CS, cut automatically and converted into a JPEG format. Surface and volume reconstruction were performed by 3D Doctor 3.5 and Amira 4.0 software programs on an ordinary personal computer respectively. RESULTS: The surface reconstruction model could be rotated at any angle and observed from any direction. And the reconstructed structures of the anterior approach to the UTS could be displayed individually or as a composite with any other selected structure. The volume reconstruction displayed abundant internal details of the reconstructed images in transverse, coronal, sagittal, and random oblique sections. CONCLUSION: Three-dimensional visible models of the anatomical structures of the anterior approach to the UTS based on the sectional images of VCHF can clearly display the morphology, spatial orientation and adjacent relationship of every structure. These models are very helpful to the anatomy study and preoperative planning of this complex anatomic region.