Inhibition of the JAK2/STAT3 signaling pathway exerts a therapeutic effect on osteosarcoma.

Osteosarcoma (OS) is the most common type of malignant bone tumor. Despite aggressive multimodal treatments, including surgical resection, chemotherapy and adjunctive immunotherapies, patients with OS with high-grade malignancy have a poor five-year survival rate that has remained unchanged over the past two decades, highlighting the urgent requirement for novel therapeutic approaches. Signal transducers and activators of transcription 3 (STAT3) has been implicated as an oncogene and therapeutic target in a variety of neoplastic diseases. The aim of the present study was to determine whether inhibition of the janus kinase 2 (JAK2)/STAT3 pathway by FLLL32, a specific JAK2/STAT3 inhibitor, is able to provide a potential therapy for OS. FLLL32 inhibited OS cell growth in vitro and delayed OS growth in an OS xenograft nude mouse model. STAT3 knockdown by short hairpin RNA delayed OS formation in vivo. Thus, the JAK2/STAT3 pathway is important in OS formation. Efficacy of the FLLL32 pharmacological inhibitor in delaying OS growth suggests that targeting JAK2/STAT3 may be a potential therapeutic strategy for patients with OS.

[Clinical outcome of single-bundle versus anatomic double-bundle reconstruction of the anterior cruciate ligament: a meta-analysis].

OBJECTIVE: To evaluate clinical outcome after anterior cruciate ligament (ACL) reconstruction with double-bundle or single-bundle by meta-analysis. METHODS: Randomized controlled trials (RCTs) on differences of clinical outcomes of ACL reconstruction were retrieved in Ovid Medline, PubMed, Embase, Cochrane Library, CBM and VIP database. Relevant journals or conference proceedings were also searched manually. Then extracted the date of KT-1000 arthrometer, pivot-shift testing, Lysholm score and IKDC final score in these researches. RevMan 5.0.23 software was used for data analyses. RESULTS: Eight prospective RCTs met the inclusion criteria. The combined results of meta-analysis indicated that there was statistical difference between two operative procedures on postoperative KT-1000 arthrometer side-to-side [WMD = -0.35, 95%CI (-0.61, -0.08), P = 0.01], Lysholm score [WMD = -1.91, 95%CI (-3.45, -0.37), P = 0.01]. But the difference of KT-1000 arthrometer side-to-side is demonstrated to be clinically insignificant. Others indicated that there was no statistical differences with respect to IKDC final score [OR = 1.80, 95%CI (0.98, 3.31), P = 0.06], having a normal or nearly normal pivot-shift testing [OR = 1.64, 95%CI (0.85, 3.16), P = 0.14]. CONCLUSIONS: Double-bundle reconstruction does not result in clinically significant advantage when compared with single-bundle. The results do not support the theory that double-bundle reconstruction controls knee rotation better.

Vertical weight-bearing MRI provides an innovative method for standardizing Spurling test.

Although Spurling test, a foraminal compression test, is commonly used in clinical practice in patients with a suspected cervical radiculopathy, its protocol is still obscure. In undergoing this test, patients extend, laterally flex and slightly rotate neck to the symptomatic side, and then a pressure is applied on the top of patient's head by examiner. The test is scored as positive if it causes pain or tingling that starts in the shoulder and radiates distally to the elbow. But the range of neck motion and level of load are not clearly defined. Magnetic resonance imaging (MRI) has proved to be an excellent method of assessing the situation of cervical intervertebral foramen. Unfortunately the conventional MRI system is not able to fully achieve this goal because it can only examine patient in supine position while Spurling test needs to be performed in a sitting position. Here we hypothesize that vertical weight-bearing MRI provides an innovative method for researching and standardizing the protocols of Spurling test. The result will provide better knowledge of the mechanism of Spurling test. Standardization of the test will improve its sensitivity and rate of reproducibility.

[A clinical report on arthroscopic reconstruction of posterior cruciate ligament using ligament advanced reinforcement system].

OBJECTIVE: To explore the operative techniques and preliminary clinical effect of arthroscopic reconstruction of posterior cruciate ligament (PCL) using ligament advanced reinforcement system (LARS). METHODS: From June 2006 to July 2007, 9 patients with PCL rupture were treated with LARS under arthroscopic observation. There were 8 males and 1 female, aged 23-49 years old. The left knee was involved in 3 cases and the right knee in 6 cases. The main causes of injuries were sports in 5 cases, falling in 1 case and traffic accident in 3 cases. The time from injury to reconstruction was 6-20 days (13.6 days on average). There were 2 cases with associated medial meniscus injury and 1 with lateral meniscus injury. X-ray films showed no avulsion fracture of tibial plateau was found. The preoperative Lysholm score was 40-55 (50 on average). According to the preoperative international knee documentation committee (IKDC) grading, 1 case was graded as C and 8 as D. The Lachman test showed that there was 1 case (+), 6 cases (++) and 2 cases (+++). The operation was performed under arthroscopic observation. The tibial isometric point and tunnel were drilled with the help of a drill bit guide, while the femoral isometric point and tunnel were drilled under the C-arm X-ray machine. The diameter of the bone tunnels was 6 mm, while the diameters of LARS artificial ligaments and cannulated interference screws were 7 mm. RESULTS: All the patients were regularly followed up for 8-16 months (10.5 months on average). The postoperative Lysholm score was 70-95 (85 on average). There were 5 cases of excellent, 3 of good and 1 of fair, with the choiceness rate of 88%. The postoperative IKDC grading showed that 7 cases were graded as A and 2 as B. The Lachman test showed that no case was positive. Complications such as infection, spontaneous rupture or laxity of graft were not observed. CONCLUSION: PCL arthroscopic reconstruction with the use of LARS artificial ligaments leads to a good anatomic reconstruction and knee function with minor injury, rapid recovery and satisfactory clinical effect.

[Diagnosis and operative treatment of far lateral lumbar disc herniation].

OBJECTIVE: To discuss the characteristics and operative selection of far lateral lumbar disc herniation (FLLDH). METHODS: Twenty-three cases of FLLDH, 14 were foraminal, and 9 were extraforaminal lumbar disc herniation. Of the 23 cases, low back pain was observed in 8 cases (31%), severe lower leg pain in 21 cases (91%) and Lasegue sign in 10 cases (43%). CT and MRI showed the protruded disc in and outside of the foramen clearly. Three surgical procedures were performed, including hemilaminotomy with medial facetectomy, facetectomy with pedicle screw fixation and fusion with posteolateral bone grafting, and the transmuscular approaches. RESULTS: Twenty-two cases were followed up for an average of 3.6 years. According to the Macnab criteria, 15 patients achieved excellent results, good 4, fair 3 and poor 0. Excellent and good rate was 86%. CONCLUSIONS: The symptoms and signs of FLLDH mainly result from injury of upper nerve segments with the dominant symptom of severe lower leg pain. CT and MRI appearance are not only sensitive but also specific for the diagnosis of FLLDH. In foraminal lumbar disc herniation, the hemilaminotomy with medial facetectomy is recommended. While in extraforaminal lumbar disc herniation, either facetectomy with pedicle screw fixation and fusion with posterolateral bone grafting or transmuscular approaches for removal of nucleus pulposus can be chosen. Microendoscopic discectomy is a new, safe and efficient method for the disease, however, a skillful microendoscopic technique should be mastered prior.

Effects of spinal cord injury on c-fos expression in hypothalamic paraventricular nucleus and supraoptic nucleus in rats.

The effects of spinal cord injury (SCI) on c-fos expression in hypothalamic paraventricular nucleus (PVN) and supraoptic nucleus (SON) in rats were investigated. As hypothesized, SCI has a significant effect on neuronal responses in the PVN and SON. A significant increase in c-fos in the PVN was found at 1, 6, 12 and 24 h following SCI, implying that the neurons in the PVN can be activated soon after SCI and persist for at least 24 h. However, in contrast to the PVN, SCI did not induce a significant increase in c-fos expression in the SON until 12 h following SCI. The highest expression of c-fos in the SON was found at the end point of this study (24 h) following SCI. The data demonstrated that SCI can significantly activate neurons in the PVN and SON. The activated neurons might involve in the initiation of a variety biochemical, ischemic and other injury processes. The area-specific effects of SCI on the PVN and SON suggest that these nuclei might play their roles in different stages in the prolonged time course following SCI.

Pedicle screw fixation with translaminar facet joint screws for the treatment of thoracolumbar fracture.

OBJECTIVE: To evaluate the efficacy of Cotrel-Dubeusset (CD) instrumentation combined with translaminar facet joint screw (TLS) in the treatment of thoracolumbar fracture. METHODS: A total of six L(2)-L(4) spines were used to establish unstable fracture model with three-dimensional range of motion (ROM) of the spines measured. Fixation with CD and fixation with CD combined with translaminar facet joint screw were achieved to compare their stability. Thirty cases of thoracolumbar fracture, in whom the anterior edge of vertebral body was compressed to 59% and the posterior edge compressed to 88%, were treated by pedicle screw fixation combined with TLS. Among them, 19 received posterolateral or anterior-posterior bone grafting. RESULTS: There was significant difference in ROM between the two techniques except that in extension. In Group CD+TLS, ROM was 5.38% lower, lateral bending 4.91% lower and axial rotation 11.85% lower than those in Group CD respectively. In the clinical group, the average anterior edge restored to 97% and posterior edge to 98%. The duration of follow-up was 5-24 months (mean, 10 months). The rate of correction loss on the anterior edge was 4.5%. Among the 19 cases of bone grafting, all of them achieved bony fusion (mean fusion time, 4.3 month) with a correction loss rate of 3.4%. CONCLUSIONS: In the treatment of thoracolumbar fracture, pedicle screw fixation combined with TLS can strengthen the stability of pedicle screws, especially anti-rotation stability and enhance fusion rate and reduce correction loss.

Screw placement of pedicle of vertebral arch--pay great attention to segmental differences of the pedicle.

OBJECTIVE: To investigate appropriate ways for screw placement of pedicle of vertebral arch in the horizontal plane. METHODS: Fifteen preserved thoracolumbar spine specimens (T(11)-L(5)) were used and divided into three groups at random. Firstly four anatomic parameters indicating screw positions in the horizontal plane were measured. Secondly the methods of Roy-camille, Magerl, and authors' segmental differences were used to place successively the screws of the pedicles with 5 mm, 6 mm, and 7 mm in diameter. Coincidences between the drilling point, drilling direction and pedicle axis, and ruptures of the pedicle as well as the length of the screw in the vertebral body were observed. RESULTS: Four anatomic parameters at various segments showed significant differences (P<0.05). The drilling point by the Roy-camille's method deviated medial to pedicle axis in most segments, and its drilling direction did not coincide well with most E-angles of the pedicles. The drilling point by Magerl's method coincided relatively well with pedicle axis in lumbar vertebrae, but there were still some differences between its drilling direction and E-angles of the pedicles. The method of segmental differences coincided the best with the pedicle axis. The lengths of screw in the vertebra were relatively long by both Magerl and segmental difference methods. When 5 mm diametral screw was used by the three methods, the rupture rate was very low. When 6 mm and 7 mm diametral screws were placed, the rupture rate was accordingly increased. Of the three methods, Roy-camille's method showed a relatively high rupture rate, while the method of segmental differences a comparatively low rupture rate. Various degrees of rupture of the pedicle of vertebral arch were found at the juncture of the thoracic and lumbar vertebrae when 6 mm or 7 mm diametral screws was used by any screw placement method. In contrast, the rupture was seldom seen at the lower lumbar vertebrae when 7 mm diametral screws were used. CONCLUSIONS: The segmental difference method is proved to have the anatomic safety and screw biomechanical stability. It is appropriate to choose different diametral screws, different drilling points and directions according to different segments of the vertebra.