LncRNA TSIX knockdown restores spinal cord injury repair through miR-30a/SOCS3 axis.

Spinal cord injury (SCI) is a serious injury to the central nervous system. Previous studies have discovered that the development of SCI is associated with gene expression. The purpose of this study was to explore the significance of lncRNA TSIX in SCI and its underlying mechanism involved. An in vivo SCI mice model and an in vitro hypoxia-treated HT22 cells model were applied in this study. TSIX and SOCS3 expression in SCI tissues was measured by qRT-PCR, western blot and FISH assay. LV-sh-TSIX was injected into SCI mice intrathecally or subjected to HT22 cells to access the consequent alteration in inflammation response, cell apoptosis and functional recovery through ELISA, immunohistochemistry, TUNEL, flow cytometry assays and BMS scores. Then, the underlying mechanism of TSIX was analyzed by bioinformatics analysis and then confirmed by RIP, RNA pull-down and dual-luciferase reporter assay. It was identified that TSIX was up-regulated in HT22 cells under hypoxia operation and spinal cord tissues of SCI mice. TSIX knockdown improved the lesion size and BMS score and inhibited inflammation and cell apoptosis. MiR-30a was identified as a target for TSIX and SOCS3, and TSIX binds to miR-30a by competing with SOCS3, thereby counteracting miR-30a-mediated SOCS3 inhibition. In addition, LV-sh-TSIX effects were significantly overturned by miR-30a inhibition or SOCS3 over-expression. Knockdown of TSIX improved functional recovery and attenuated the inflammation response and cell apoptosis via miR-30a/SOCS3 axis. These results may provide a potential novel insight for SCI treatment.

LncRNA prostate androgen-regulated transcript 1 (PART 1) functions as an oncogene in osteosarcoma via sponging miR-20b-5p to upregulate BAMBI.

BACKGROUND: Osteosarcoma (OS) is an aggressive bone cancer that most commonly affects adolescents and children. Emerging studies have shown that long noncoding RNA (lncRNA) performs essential roles in the occurrence and development of many tumors. Prostate androgen-regulated transcript 1 (PART 1) has been reported as a tumor oncogene; despite this, the mechanisms underlying its involvement in OS are unclear. METHODS: OS and paired normal tissue samples were obtained, and gene expressions were detected by real time-quantitative polymerase chain reaction (RT-qPCR). The functions of PART 1 in OS cell proliferation, invasion, and migration were determined by Cell Counting Kit-8 (CCK-8) and Transwell assays. Furthermore, the binding sites of PART 1 and miR-20b-5p as well as those between miR-20b-5p and bone morphogenic protein and activin membrane-bound inhibitor homolog (BAMBI) were verified by bioinformatics analysis and dual-luciferase reporter assay. RESULTS: Our study found obvious overexpression of PART 1 in OS tissues and cells. Furthermore, PART 1 overexpression facilitated OS cell proliferation, invasion, and migration. Further mechanistic investigations revealed that PART 1 could sponge to miR-20b-5p, which was expressed at a low level in OS tissues and cells. Importantly, miR-20b-5p overexpression inhibited OS cell proliferation, invasion, and migration. Additionally, BAMBI was confirmed as a downstream gene of miR-20b-5p, and its expression was reversely modulated by miR-20b-5p and positively modulated by PART 1. Rescue experiments suggested that BAMBI was involved in PART 1-mediated promotion of OS progression. CONCLUSIONS: PART 1 serves as a competing endogenous RNA to promote OS tumorigenesis via its regulation of the miR-20b-5p/BAMBI axis, which may provide a promising therapeutic biomarkers for OS patients.

The three-dimensional printed template guided technique for S2 alar iliac screw placement and a comparison with freehand technique.

PURPOSE: Sacropelvic fixation continues to present challenges when involved in the adult spinal deformity correction. The S2 alar iliac (S2AI) fixation is commonly used in sacropelvic fixation. Several techniques, including intraoperative navigation and freehand technique, were used for S2AI screws placement. The aim of this study is to analyze the anatomic parameters for S2AI screw trajectory in Asian population and introduce a novel technique described as a three-dimensional printed template guided technique (TGT). Meanwhile, the accuracy and safety of this technique were compared with the conventional freehand technique. METHODS: The S2AI trajectory parameters were measured in 100 Asian adult volunteers. Parameters were compared between different genders. Forty-eight adult patients who underwent S2AI screw placement were reviewed: 28 patients received freehand technique and 20 patients received TGT technique. Postoperative computed tomography was used to assess the accuracy of screw trajectory and cortex violation-related complications were recorded. RESULTS: The cephalocaudal angles (CAs), maximal length of screw pathway, narrowest width of pathway within the iliar teardrop, distance from the center of teardrop to sciatic notch, and distance of the start point distal to S1 dorsal foramen showed significant gender-related difference (p < 0.05). All 48 patients were placed S2AI screws bilaterally (40 screws in TGT vs. 56 screws in freehand). One screw penetrated iliac cortex in the TGT group but 10 screws penetrated iliac cortex in the freehand group (3% vs. 17.9%) (p < 0.05). CONCLUSION: Approximately 30-35° of CA and 39° mediolateral angle are appropriate for S2AI screw placement in Asian patients. Either freehand or TGT technique is safe for S2AI screw placement. TGT technique is more accurate compared with the conventional freehand technique. TRIAL REGISTRATION: This is a retrospective study.

The combination of forskolin and VPA increases gene expression efficiency to the hypoxia/neuron-specific system.

BACKGROUND: Spinal cord injury (SCI) tends to damage neural tissue and generate a hypoxic environment. Studies have confirmed that single therapy with gene or stem cells is inefficient, but research into combining stem cells and gene therapy in treating tissue damage has been undertaken to overcome the related limitations, which include low gene delivery efficiency and therapeutic outcome. Thus, a combination of stem cells, gene therapy, and a hypoxia-specific system may be useful for the reconstruction of SCI. METHODS: To synergistically treat SCI, a combined platform using a hypoxia/neuron-inducible gene expression system (HNIS) and human induced-neural stem cells (hiNSCs) produced by direct reprogramming was designed. Sox2- or nestin-positive hiNSCs were differentiated to Tuj1-, MAP2-, or NeuN-positive neurons. RESULTS: HNIS showed consistent hypoxia/neuron-specific gene expression in hiNSCs cultured under hypoxia. In particular, the HNIS-hiNSC combined platform revealed a complex pattern with higher gene expression compared with a single platform. In addition, we found that an optimal combination of small molecules, such as CHIR99021, valproic acid (VPA), glycogen synthase kinase-3ß (GSK3ß), and histone deacetylase (HDAC) inhibitors, could significantly enhance gene expression with HNIS-hiNSCs in the hypoxic environment. CONCLUSIONS: This experiment demonstrated that HNIS-hiNSCs combined with GSK3 and HDAC inhibitors may present another promising strategy in the treatment of SCI.

Salmonella Enteritidis Effector AvrA Suppresses Autophagy by Reducing Beclin-1 Protein.

Autophagy is a cellular process to clear pathogens. Salmonella enterica serovar Enteritidis (S.E) has emerged as one of the most important food-borne pathogens. However, major studies still focus on Salmonella enterica serovar Typhimurium. Here, we reported that AvrA, a S. Enteritidis effector, inhibited autophagy to promote bacterial survival in the host. We found that AvrA regulates the conversion of LC3 I into LC3 II and the enrichment of lysosomes. Beclin-1, a key molecular regulator of autophagy, was decreased after AvrA expressed strain colonization. In S.E-AvrA--infected cells, we found the increases of protein levels of p-JNK and p-c-Jun and the transcription level of AP-1. AvrA-reduction of Beclin-1 protein expression is through the JNK pathway. The JNK inhibitor abolished the AvrA-reduced Beclin-1 protein expression. Moreover, we identified that the AvrA mutation C186A abolished its regulation of Beclin-1 expression. In addition AvrA protein was found interacted with Beclin-1. In organoids and infected mice, we explored the physiologically related effects and mechanism of AvrA in reducing Beclin-1 through the JNK pathway, thus attenuating autophagic responses. This finding not only indicates an important role of S. Enteritidis effector in reducing host protein as a strategy to suppress autophagy, but also suggests manipulating autophagy as a new strategy to treat infectious diseases.

Extensor muscle-preserving laminectomy in treating multilevel cervical spondylotic myelopathy compared with laminoplasty.

BACKGROUND: Laminectomy and laminoplasty are popularly used in posterior cervical spine surgery but still have involved complications. We aimed to compare the clinical outcomes of microscope-assisted extensor muscle-preserving laminectomy (MA-EMPL) and open-door laminoplasty (ODLP) in treating multilevel cervical spondylotic myelopathy (MCSM). METHODS: A prospective study was designed to enroll twenty patients with MCSM underwent MA-EMPL, and recruit twenty-four patients with MCSM received ODLP (control). Radiographic measurements, outcome indicators including Japanese Orthopedic Association (JOA) score and visual analogue score (VAS) were used to evaluate technical effectiveness. Surgical complications were documented to assess technical safety. RESULTS: Postoperative cervical curvature index and range of neck motion (ROM) were not significantly changed except ROM in ODLP group. Postoperative JOA score and VAS in both groups showed improvements at final follow-up. There was no statistical difference in postoperative neurological recovery rates between two groups (67.6%±17.8% vs. 70.15%±19.6%, P=0.632). However, VAS was significantly lower at postoperative 1 month in MA-EMPL group compared with ODLP group (P<0.001). The incidences of C5 palsy were 0 vs. 16.7% between MA-EMPL group and ODLP group. There was no axial symptom occurred in MA-EMPL group while six patients in ODLP group (0 vs. 25%, P=0.049). In addition, the mean blood loss and hospital stay were lesser in MA-EMPL group compared with ODLP group (P<0.001, P=0.002, respectively). CONCLUSIONS: MA-EMPL is an effective, safe and minimally invasive method in treatment of MCSM. Compared with ODLP, MA-EMPL has advantage to decrease intraoperative blood loss, hospital stay, postoperative VAS and axial symptom, as well as preserve postoperative ROM.

Independent Correlation of the C1-2 Cobb Angle With Patient-Reported Outcomes After Correcting Chronic Atlantoaxial Instability.

OBJECTIVE: To investigate three-planar radiographic results and patient-reported outcomes (PROs) after correcting chronic atlantoaxial instability (AAI) by translaminar screw (TLS) and pedicle screw (PS) fixation, and to explore the potential association of atlantoaxial realignment with PRO improvements. METHODS: Twenty-three patients who underwent C1 lateral mass screw (LMS)-C2 TLS and 29 who underwent C1 LMS-C2 PS with ≥ 2 years of follow-up were retrospectively analyzed. Three-planar (sagittal, coronal, and axial) radiographic parameters were measured. PROs including the Neck Disability Index (NDI), Japanese Orthopaedic Association (JOA) score and the Short Form 36 Physical Component Summary (SF-36 PCS) were documented. Factors potentially associated with PROs were identified. RESULTS: The radiographic parameters significantly changed postoperatively except the C1-2 midlines' intersection angle in the TLS group (p = 0.073) and posterior atlanto-dens interval in both groups (p = 0.283, p = 0.271, respectively). The difference in bilateral odontoid lateral mass interspaces at last follow-up was better corrected in the TLS group than in the PS group (p = 0.010). Postoperative PROs had significantly improved in both groups (all p < 0.05). Thereinto, NDI at last follow-up was significantly lower in the TLS group compared with PS group (p = 0.013). In addition, blood loss and operative time were obviously lesser in TLS group compared with PS group (p = 0.010, p = 0.004, respectively). Multivariable regression analysis revealed that a change in C1-2 Cobb angle was independently correlated to PROs improvement (NDI: ß = -0.435, p = 0.003; JOA score: ß = 0.111, p = 0.033; SF-36 PCS: ß = 1.013, p = 0.024, respectively), also age ≤ 40 years was independently associated with NDI (ß = 5.40, p = 0.002). CONCLUSION: Three-planar AAI should be reconstructed by C1 LMS-C2 PS fixation, while sagittal or coronal AAI could be corrected by C1 LMS-C2 TLS fixation. PROs may improve after atlantoaxial reconstruction in patients with chronic AAI. The C1-2 Cobb angle is an independent predictor of PROs after correcting chronic AAI, as is age ≤ 40 years for postoperative NDI.

The risk factors associated with delirium after lumbar spine surgery in elderly patients.

BACKGROUND: To prospectively explore the incidence and risk factors for postoperative delirium in elderly patients following lumbar spine surgery. METHODS: This prospective study enrolled 148 consecutive patients over the age of 65 who were scheduled to undergo spine surgery. Patients were screened for delirium using the short Confusion Assessment Method (CAM) postoperatively. Patient demographics and relevant medical information were collected. Logistic regression analysis was used to identify the risk factors associated with postoperative delirium. RESULTS: Eighty-three patients (56.1%) who underwent lumbar spine surgery (not coexisting with cervical or thoracic spine surgery) were enrolled in our study. Post-operative delirium was noted in 14.5% of patients over 65 years old. The presence of preoperative Parkinsonism was significantly higher in the delirium group (41.7% vs. 8.5%, P=0.002), as was a higher preoperative C-reactive protein (CRP) (7.0±15.2 vs. 1.3±2.3 mg/L, P=0.017) when compared with the non-delirium group. Of the risk factors, male sex [odds ratio (OR) =0.10, 95% confidence interval (CI): 0.01-0.66, P=0.017], Parkinsonism (OR =5.83, 95% CI: 1.03-32.89, P=0.046), and lower baseline MMSE score (OR =0.71, 95% CI: 0.52-0.97, P=0.032) were independently associated with postoperative delirium in elderly patients undergoing lumbar spine surgery. CONCLUSIONS: Post-operative delirium occurred in 14.5% of elderly patients who underwent lumbar spine surgery. Male sex, Parkinsonism, and lower baseline MMSE score were identified as independent risk factors for postoperative delirium in elderly patients following lumbar surgery.

Accuracy and Safety of Lateral Vertebral Notch-Referred Technique Used in Subaxial Cervical Pedicle Screw Placement.

BACKGROUND: Biomechanical studies revealed that pedicle screw instrumentation has a superior stabilizing effect compared with other internal fixations in reconstructing the subaxial cervical spine. However, severe neurovascular risks preclude surgeons from routinely conducting pedicle screw manipulation in cervical spine. OBJECTIVE: To evaluate the accuracy and safety of the lateral vertebral notch (LVN)-referred technique used in subaxial cervical pedicle screw (CPS) placement. METHODS: One hundred thirty-five consecutive retrospective patients with cervical disorders underwent the LVN-referred technique for CPS placements in 3 spine centers. Postoperative pedicle perforations were confirmed by CT scans to assess the technical accuracy. Neurovascular complications derived from CPS misplacements were recorded to evaluate the technical safety. RESULTS: A total of 718 CPSs were inserted into subaxial cervical spine. Postoperative CT scans revealed that the accuracy of CPS placement was superior. Neither vertebral artery injury nor spinal cord injury occurred. One radiculopathy was from a unilateral C6 nerve root compression. A screw-related neurovascular injury rate of 0.7% occurred in this cohort. Additionally, there was no significant difference in the accuracy of CPS placement among 3 surgeons (H = 1.460, P = .482). The relative standard deviation values revealed that technical reproducibility was acceptable. Furthermore, there was no significant difference between the patients' pedicle transverse angles and inserted CPS transverse angles from C3 to C7 (all P > .05). CONCLUSION: The LVN is a reliable and consistent anatomic landmark for CPS placement. The accuracy and safety of subaxial CPS placement by using LVN-referred technique are highly acceptable, which may endow this technique to be practicably performed in selected patients.

The modified transforaminal endoscopic technique in treating intracanalicular combining foraminal and/or extraforaminal lumbar disc herniations.

BACKGROUND: To develop a modified transforaminal endoscopic spine system (TESSYS®) technique for treating intracanalicular combining foraminal and/or extraforaminal lumbar disc herniation (ICFE-LDH), and evaluate the technical efficacy and safety. METHODS: Twenty-three patients with ICFE-LDH underwent the modified TESSYS technique were enrolled. Magnetic resonance imaging (MRI) was used to verify the reduction of herniated disc. Pre- and post-operative neurological functions were compared by visual analogue scale (VAS) score, Oswestry disability index (ODI) and the modified MacNab criteria. The technical safety was evaluated by surgical complications. RESULTS: MRI demonstrated reductions of disc herniations in 22 patients (95.7%) after surgeries. The VAS scores were significantly improved at 1 year follow-up (low back: P=0.001, lower limbs: P<0.001), as well as ODI scores (P<0.001). 22 patients had achieved excellent and good recovery postoperatively according to the modified MacNab criteria. One patient (4.3%) underwent a reoperation due to postoperative recurrence of disc herniation. Another patient complained postoperative causalgia in 8 weeks, the symptom alleviated after conservative treatment at 1 year follow-up (VAS: back, 3, lower limbs, 0; ODI: 20%). The incidence rate of surgical complication was 8.7%. CONCLUSIONS: The modified TESSYS technique is a minimally-invasive, effective and safe surgery for treating ICFE-LDHs in selected patients.

Postoperative Cervical Sagittal Realignment Improves Patient-Reported Outcomes in Chronic Atlantoaxial Anterior Dislocation.

BACKGROUND: Chronic atlantoaxial anterior dislocation (AAD) not only results in myelopathy, but dislocation-related kyphosis also results in cervical malalignment, which permanently affects neck function and patient-reported outcomes (PROs). OBJECTIVE: To investigate the effect of kyphotic correction on realigning cervical spine and independent cervical alignment parameters, which may be correlated with an improvement of PROs. METHODS: The study included 21 patients with chronic AAD-related kyphosis who underwent C1-2 reduction and correction surgery. Radiographic parameters were measured to assess cervical realignment preoperatively and postoperatively. Neck disability index (NDI), short form 12 physical component summary (SF-12 PCS), and Japanese Orthopaedic Association (JOA) scores were recorded to reveal changes in PROs. The independent parameters correlated with the improvements of PROs were analyzed. RESULTS: Of the radiographic parameters, the C1-2 Cobb angle, the C2-7 Cobb angle, thoracic inlet angle, cervical tilt, and T1 slope were significantly changed from -4.0° ± 16.2°, -29.2° ± 11.2°, 73.1° ± 13.3°, 30.4° ± 8.5°, and 29.1° ± 8.8° preoperatively to -13.5° ± 8.1° (P = .005), -18.0° ± 12.0° (P < .001), 67.1° ± 11.6° (P = .042), 23.1° ± 10.3° (P = .007), and 24.0° ± 7.0° (P = .011) at last follow-up, respectively. NDI, JOA, and SF-12 PCS scores were significantly improved postoperatively. The C1-2 Cobb angle was an independent parameter correlated with the improvements in SF-12 PCS, NDI, and JOA scores. CONCLUSION: Correction and reduction surgery can realign cervical spine in chronic AAD patients. The C1-2 Cobb angle was an independent parameter correlated with the improvements of PROs.

The change of cervical spine alignment along with aging in asymptomatic population: a preliminary analysis.

STUDY DESIGN: A cross-sectional study. OBJECTIVE: To investigate the correlation of cervical spine alignment changes with aging in asymptomatic population. BACKGROUND: Previous studies demonstrated the influence of lumbar and thoracic spine on cervical spine alignment, but few has reported the cervical spine alignment change along with aging in asymptomatic population. METHODS: Asymptomatic population were divided into four groups according to different ages (Group A: ≤20 years; Group B: 21-40 years; Group C: 41-60 years; Group D: ≥61 years). Each group was composed of 30 subjects. The following parameters were measured: C0-1 Cobb angle, C1-2 Cobb angle, C2-7 Cobb angle, C1-7 sagittal vertical axis (C1-7 SVA), C2-7 SVA, central of gravity to C7 sagittal vertical axis (CG-C7 SVA), Thoracic Inlet Angle (TIA), Neck Tilt (NT), cervical tilt, cranial tilt, T1 slope (TS), TS-CL, and ANOVA statistical method was used to analyze the differences among four groups, and then, linear regression analysis was performed to analyze correlation of the cervical spine alignment with the aging. RESULTS: C1-7 SVA, C2-7 SVA, CG-C7 SVA, TIA, NT, TS, and cranial tilt were found statistically different among four groups (P < 0.01). From Group A to Group D, the mean C1-7 SVA were 30.7, 26.0, 21.8, and 36.9 mm, the mean C2-7 SVA were 18.7, 14.7, 11.9, and 24.7 mm, and the mean CG-C7 SVA were 19.6, 16.6, 9.4, and 26.7 mm. The mean TIA were 62.4°, 65.0°, 71.8°, and 76.9°, the mean NT were 39.4°, 43.8°, 46.3°, and 48.2°, the mean TS were 23.0°, 21.1°, 25.5°, and 28.7°, and the mean cranial tilt were 5.7°, 4.8°, 3.0°, and 9.5°. Further linear regression indicated that TIA (r = 0.472; P < 0.0001), NT (r = 0.337; P = 0.0006), and TS (r = 0.299; P = 0.0025) were positively correlated with aging. CONCLUSION: A gradual increase of TIA, NT, and TS, accompanied with an increased CL, is found along with aging in asymptomatic population, among which TIA, NT, and TS are significantly correlated with physiological nature of aging.

Coronal Multiplane Reconstructed Computed Tomography Image Determining Lateral Vertebral Notch-Referred Pedicle Screw Entry Point in Subaxial Cervical Spine: A Preclinical Study.

OBJECTIVE: To evaluate feasibility of computed tomography (CT) coronal multiplane reconstruction image (CMRI) to determine subaxial cervical pedicle screw (PS) entry point and guide lateral vertebral notch (LVN)-referred technique for subaxial cervical PS insertion. METHODS: Cervical CT scans were performed in 40 volunteers. PS entry point was determined by quantitating PS entry point related to LVN on CMRI. Pedicle mediolateral angle (α) and cephalocaudad angle (ß) were also measured to guide the trajectory of PS insertion. Based on these quantitations, 12 human cadaveric subaxial cervical pedicles were inserted with PS referring to LVN. Cortical integrity of each pedicle was evaluated after dissecting the cadaveric vertebrae one by one and confirmed by radiography and CT. The cortical penetration and PS position were classified into 4 grades: 0 (excellent position), I (good position), II (fair position), and III (poor position). RESULTS: On CT CMRI, PS entry point was consistently located approximately 2.2 mm medial to LVN from C3 to C7 and approximately 1.4 mm lower to LVN from C3 to C6, but 1.2 mm higher at C7. Bilateral α angle and ß angle showed substantial decrease from cranial to caudal. Cortical integrity of PS positions was excellent and good in 88.33%, fair in 8.33%, and poor in 3.33%. CONCLUSIONS: CMRI is reliable for determining subaxial cervical PS entry point. LVN is a consistent landmark for the notch-referred technique, which is a practical and easy to master technique for subaxial cervical spine PS insertion.

Débridement and Reconstruction Improve Postoperative Sagittal Alignment in Kyphotic Cervical Spinal Tuberculosis.

BACKGROUND: Cervical spinal tuberculosis is relatively common in some developing countries. It erodes vertebrae and discs, which sometimes results in cervical kyphosis and myelopathy. However, to our knowledge, no studies have evaluated improvements to patient-reported outcomes among patients who undergo surgical cervical sagittal realignment after kyphotic cervical spinal tuberculosis has been treated by débridement and reconstruction. QUESTIONS/PURPOSES: (1) Can a spine with kyphotic cervical spinal tuberculosis be returned to normal alignment and fused successfully? (2) Will patient-reported outcomes be improved with this intervention? (3) Are patient-reported outcomes correlated with realignment? METHODS: Forty-six patients with kyphotic cervical spinal tuberculosis were evaluated in this retrospective study. We generally performed surgery on patients with this condition when patients with cervical spinal tuberculosis presented with cervical kyphosis with or without neurologic deficits. Patients who did not meet these criteria were treated with other surgical procedures during the study period. Study patients were evaluated with cervical imaging, patient-reported outcomes questionnaires (Neck Disability Index [NDI], and the Japanese Orthopaedic Association [JOA] score), and physical examinations. Scores were collected by fellows preoperatively and at followup. No patient died during the followup. The mean followup was 26.8 months (range, 20-35 months). Preoperative and 2-year followup radiologic parameters were measured, including C0-2 Cobb angle, C2-7 Cobb angle, C2-7 sagittal vertical axis, center of gravity (CG) to C7 sagittal vertical axis (CG-C7 sagittal vertical axis), thoracic inlet angle, T1 slope, and neck tilt. The correlations between cervical alignment and the NDI and JOA score were analyzed. Factors correlated with the NDI and JOA score improvements were identified by multiple stepwise regression analysis. CT was used to assess bone fusion after surgery. RESULTS: All 46 patients showed bone fusion on CT scans. The preoperative C0-2 Cobb angle improved after surgery (mean difference, 5.0°; 95% CI, 2.3°-7.7°; p = 0.0068), as did C2-7 Cobb angle (mean difference, -33°; 95% CI, -35° to -31°; p = 0.0074), C2-7 sagittal vertical axis (mean difference, -28 mm; 95% CI, -30 mm to -26 mm; p = 0.0036), CG-7 sagittal vertical axis (mean difference, -26 mm; 95% CI, -28 mm to -24 mm; p = 0.0049), T1 slope (mean difference, 6.0°; 95% CI, 3.7°-8.3°; p = 0.0053) and the thoracic inlet angle (mean difference, 8.0°; 95% CI, 3.7°-12°; p = 0.0072). With the numbers available, the neck tilt angle did not improve (mean difference, -0.2°; 95% CI, -1.0° to 0.6°; p = 0.079). The preoperative NDI of 34 ± 5.1 decreased to 17 ± 4.6 (p = 0.0096) at followup. Improvements in NDI were correlated with the magnitude of correction of the cervical deformities, including C0-2 Cobb angle (r = -0.357, p = 0.007), C2-7 Cobb angle (r = 0.410, p = 0.002), T1 slope (r = -0.366, p = 0.006, thoracic inlet angle (r = -0.376, p = 0.005), C2-7 sagittal vertical axis (r = 0.450, p = 0.001), and CG-C7 sagittal vertical axis (r = 0.361, p = 0.007). The JOA score improved to 13 ± 2.6 from 7.2 ± 1.9, which did not correlate with postoperative cervical realignment. After controlling for potential confounding variables like Cobb angles and T1 slope, we found C2-7 sagittal vertical axis was the most influential factor correlated with NDI improvement (r = 0.450, p = 0.002). CONCLUSION: When treating kyphotic cervical spinal tuberculosis by débridement, decompression, and reconstruction, more attention should be drawn to realigning the cervical spine, in particular to restoring the C2-7 sagittal vertical axis. However, how best to restore the C2-7 sagittal vertical axis and cervical alignment in a kyphotic cervical spine needs further study. LEVEL OF EVIDENCE: Level III, therapeutic study.

The accuracy of the lateral vertebral notch-referred pedicle screw insertion technique in subaxial cervical spine: a human cadaver study.

STUDY DESIGN: This is a cadaver specimen study to confirm new pedicle screw (PS) entry point and trajectory for subaxial cervical PS insertion. OBJECTIVE: To assess the accuracy of the lateral vertebral notch-referred PS insertion technique in subaxial cervical spine in cadaver cervical spine. BACKGROUNDS: Reported morphometric landmarks used to guide the surgeon in PS insertion show significant variability. In the previous study, we proposed a new technique (as called "notch-referred" technique) primarily based on coronal multiplane reconstruction images (CMRI) and cortical integrity after PS insertion in cadavers. However, the PS position in cadaveric cervical segment was not confirmed radiologically. Therefore, the difference between the pedicle trajectory and the PS trajectory using the notch-referred technique needs to be illuminated. METHODS: Twelve cadaveric cervical spines were conducted with PS insertion using the lateral vertebral notch-referred technique. The guideline for entry point and trajectory for each vertebra was established based on the morphometric data from our previous study. After 3.5-mm diameter screw insertion, each vertebra was dissected and inspected for pedicle trajectory by CT scan. The pedicle trajectory and PS trajectory were measured and compared in axial plane. The perforation rate was assessed radiologically and was graded from ideal to unacceptable: Grade 0 = screw in pedicle; Grade I = perforation of pedicle wall less than one-fourth of the screw diameter; Grade II = perforation more than one-fourth of the screw diameter but less than one-second; Grade III = perforation more than one-second outside of the screw diameter. In addition, pedicle width between the acceptable and unacceptable screws was compared. RESULTS: A total of 120 pedicle screws were inserted. The perforation rate of pedicle screws was 78.3% in grade 0 (excellent PS position), 10.0% in grade I (good PS position), 8.3% in grade II (fair PS position), and 3.3% in grade III (poor PS position). The overall accepted accuracy of pedicle screws was 96.7% (Grade 0 + Grade I + Grade II), and only 3.3% had critical breach. There was no statistical difference between the pedicle trajectory and PS trajectory (p > 0.05). Compared to the pedicle width (4.4 ± 0.7 mm) in acceptably inserted screw, the unacceptably screw is 3.2 ± 0.3 mm which was statistically different (p < 0.05). CONCLUSION: The accuracy of the notch-referred PS insertion in cadaveric subaxial cervical spine is satisfactory.

Increased sorbitol levels in the hypertrophic ligamentum flavum of diabetic patients with lumbar spinal canal stenosis.

The pathomechanism of the ligamentum flavum (LF) hypertrophy in diabetic patients with lumbar spinal canal stenosis (LSCS) remains unclear. A cross-sectional study was undertaken to investigate the mechanism of LF hypertrophy in these patients. Twenty-four diabetic and 20 normoglycemic patients with LSCS were enrolled in the study. The structure of the LF in the study subjects was evaluated using histological and immunohistochemical methods, and the levels of sorbitol, pro-inflammatory cytokines, and the fibrogenic factor, TGF-ß1, in the LF were analyzed. In vitro experiments were performed using NIH3T3 fibroblasts to evaluate the effect of high-glucose conditions and an aldose reductase inhibitor on the cellular production of sorbitol, pro-inflammatory factors, and TGF-ß1. We found that the LF of diabetic patients exhibited significantly higher levels of sorbitol and pro-inflammatory cytokines, TGF-ß1 and of CD68-positive staining than that of the normoglycemic subjects. The diabetic LF was significantly thicker than that of the controls, and showed evidence of degeneration. The high glucose-cultured fibroblasts exhibited significantly higher levels of sorbitol, pro-inflammatory factors, and TGF-ß1 compared to the low glucose-cultured cells, and these levels were dose-dependently reduced by treatment with the aldose reductase inhibitor. Taken together, our data suggests that increased sorbitol levels in the LF of diabetic patients results in increased production of pro-inflammatory and fibrogenic factor, which contribute to LF hypertrophy, and could increase the susceptibility of diabetic patients to LSCS. Furthermore, aldose reductase inhibition effectively reduced the levels of sorbitol and sorbitol-induced pro-inflammatory factor expression in high glucose-cultured fibroblasts. © 2017 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 35:1058-1066, 2017.

Efficacy of Transforaminal Endoscopic Spine System (TESSYS) Technique in Treating Lumbar Disc Herniation.

BACKGROUND To compare efficacy and safety of percutaneous transforaminal endoscopic spine system (TESSYS) and traditional fenestration discectomy (FD) in treatment of lumbar disc herniation (LDH). MATERIAL AND METHODS A total of 106 LDH patients were divided into TESSYS group (n=48) and FD group (n=58). Visual analogue scale (VAS), Oswestry disability index (ODI), Japanese Orthopedic Association (JOA), and modified MacNab criteria were used for efficacy evaluation. Post-operative responses were compared by enzyme-linked immunosorbent assay (ELISA) based on detection of serum IL-6, CRP, and CPK levels. RESULTS In the TESSYS group, compared with the FD group, we observed, shorter incision length, less blood loss, shorter hospital stay, lower hospitalization cost, shorter recovery time, lower complication rate (all P<0.001), and lower VAS scores of lumbago and skelalgia at 3 days and 1, 3, and 6 months postoperatively (all P<0.05). At 24 and 48 h postoperatively, CRP level was remarkably higher in the FD group compared to the TESSYS group (P<0.001). Further, comparison of IL-6 levels at 6, 12, 24, and 48 h postoperatively revealed significantly higher levels in the FD group than in the FESSYS group (all P<0.001). CONCLUSIONS TESSYS had clinical advantages over FD and entails less trauma and quicker postoperative recovery, suggesting that TESSYS is well tolerated by patients and is a better approach than FD in surgical treatment of LDH.

Treatment of Femoral Head Necrosis With Bone Marrow Mesenchymal Stem Cells Expressing Inducible Hepatocyte Growth Factor.

Our study assessed the effect of bone marrow mesenchymal stem cells (BMSCs) expressing inducible hepatocyte growth factor (HGF) on the recovery of femoral head necrosis (FHN). BMSCs were isolated by density gradient centrifugation. A recombinant AdTRE-HGF was constructed as the response plasmid and Adeno-X Tet-on as the regulator vector. The regulator and the response vectors were coinfected into BMSCs and induced at 0, 200, 500, 1000, and 1200 ng/mL doxycycline (Dox). After 3 days, the concentration of HGF was determined using enzyme-linked immunosorbent assay. Forty rabbits were selected to establish the FHN model and divided into 4 experimental groups. After the rabbits were killed by ketamine overdose, the restoration of FHN was assessed. The distribution of HGF-positive cells was observed by immunohistochemical method. Enzyme-linked immunosorbent assay results showed that 1000 ng/mL Dox induced the highest HGF expression level, even higher than the 1200 ng/mL Dox induction. The highest osteonecrosis incidence and empty lacunae percentage were found in group A compared with all the other groups (all P < 0.05). Furthermore, dramatically lower osteonecrosis incidence and empty lacunae percentage were found in group C compared with those of groups B and D (all P < 0.05). A significantly higher level of HGF protein was detected in group C compared with the other groups (all P < 0.05). Our study successfully developed the AdTRE-HGF, a recombinant adenovirus carrying HGF gene, for high expression of HGF in BMSCs. Importantly, introduction of BMSCs expressing HGF successfully produced the desired therapeutic effect in reversing FHN, in a Dox-dependent manner.

Emodin prevents intima thickness via Wnt4/Dvl-1/ß-catenin signaling pathway mediated by miR-126 in balloon-injured carotid artery rats.

Neointimal proliferation after vascular injury is a key mechanism of restenosis, a major cause of percutaneous transluminal angioplasty failure and artery bypass occlusion. Emodin, an anthraquinone with multiple physiological activities, has been reported to inhibit proliferation of vascular smooth muscle cells (VSMCs) that might cause intimal arterial thickening. Thus, in this study, we established a rat model of balloon-injured carotid artery and investigated the therapeutic effect of emodin and its underlying mechanism. Intimal thickness was analyzed by hematoxylin and eosin staining. Expression of Wnt4, dvl-1, ß-catenin and collagen was determined by immunohistochemistry and/or western blotting. The proliferation of VSMC was evaluated by MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) assay and electron microscopy. MicroRNA levels were quantified by real-time quantitative PCR. Emodin relieved injury-induced artery intimal thickness. Results of western blots and immunohistochemistry showed that emodin suppressed expression of signaling molecules Wnt4/Dvl-1/ß-catenin as well as collagen protein in the injured artery. In addition, emodin enhanced expression of an artery injury-related microRNA, miR-126. In vitro, MTT assay showed that emodin suppressed angiotensin II (AngII)-induced proliferation of VSMCs. Emodin reversed AngII-induced activation of Wnt4/Dvl-1/ß-catenin signaling by increasing expression of miR-126 that was strongly supported by transfection of mimic or inhibitor for miR-126. Emodin prevents intimal thickening via Wnt4/Dvl-1/ß-catenin signaling pathway mediated by miR-126 in balloon-injured carotid artery of rats.