Inhibition of TGFß1 activation prevents radiation-induced lung fibrosis.

BACKGROUND: Radiotherapy is the main treatment modality for thoracic tumours, but it may induce pulmonary fibrosis. Currently, the pathogenesis of radiation-induced pulmonary fibrosis (RIPF) is unclear, and effective treatments are lacking. Transforming growth factor beta 1 (TGFß1) plays a central role in RIPF. We found that activated TGFß1 had better performance for radiation pneumonitis (RP) risk prediction by detecting activated and total TGFß1 levels in patient serum. αv integrin plays key roles in TGFß1 activation, but the role of αv integrin-mediated TGFß1 activation in RIPF is unclear. Here, we investigated the role of αv integrin-mediated TGFß1 activation in RIPF and the application of the integrin antagonist cilengitide to prevent RIPF. METHODS: ItgavloxP/loxP ;Pdgfrb-Cre mice were generated by conditionally knocking out Itgav in myofibroblasts, and wild-type mice were treated with cilengitide or placebo. All mice received 16 Gy of radiation or underwent a sham radiation procedure. Lung fibrosis was measured by a modified Ashcroft score and microcomputed tomography (CT). An enzyme-linked immunosorbent assay (ELISA) was used to measure the serum TGFß1 concentration, and total Smad2/3 and p-Smad2/3 levels were determined via Western blotting. RESULTS: Conditional Itgav knockout significantly attenuated RIPF (p < .01). Hounsfield units (HUs) in the lungs were reduced in the knockout mice compared with the control mice (p < .001). Conditional Itgav knockout decreased active TGFß1 secretion and inhibited fibroblast p-Smad2/3 expression. Exogenous active TGFß1, but not latent TGFß1, reversed these reductions. Furthermore, cilengitide treatment elicited similar results and prevented RIPF. CONCLUSIONS: The present study revealed that conditional Itgav knockout and cilengitide treatment both significantly attenuated RIPF in mice by inhibiting αv integrin-mediated TGFß1 activation. HIGHLIGHTS: Activated TGFß1 has a superior capacity in predicting radiation pneumonitis (RP) risk and plays a vital role in the development of radiation-induced pulmonary fibrosis (RIPF). Conditional knock out Itgav in myofibroblasts prevented mice from developing RIPF. Cilengitide alleviated the development of RIPF by inhibiting αv integrin-mediated TGFß1 activation and may be used in targeted approaches for preventing RIPF.

Single-Posterior Revision Surgery for Recurrent Thoracic/Thoracolumbar Spinal Tuberculosis With Kyphosis.

BACKGROUND AND OBJECTIVES: The treatment of thoracic/thoracolumbar spinal tuberculosis (STB) remains challenging. The spinal deformity, long disease history, heterogeneous lesion, and poor drug response make the treatment of recurrent and kyphosis cases even more difficult. This study aims to investigate the efficacy and safety of single-posterior revision surgery in patients with recurrent thoracic/thoracolumbar STB and kyphosis. METHODS: Patients with recurrent thoracic/thoracolumbar STB with kyphosis and treated with single-posterior debridement, osteotomy, correction, bone graft, and fusion in our center from 2009 to 2019 were enrolled. The clinical data, radiographs, and erythrocyte sedimentation rate (ESR) at different stages were collected. ESR, kyphotic angle, Visual Analog Scale, and neurological functions were analyzed. RESULTS: A total of 27 patients (16 male, 11 female) with an average age of 48.4 ± 13.0 years were included. The average surgery time was 320.6 ± 46.4 minutes, and the average estimated blood loss was 1470.6 ± 367.4 mL. From admittance to the latest follow-up, the average Visual Analog Scale significantly reduced from 5.6 ± 1.3 to 0.5 ± 0.7, the average ESR was improved from 69.4 ± 15.8 mm/h to normal, and the average kyphotic angle was corrected from 66.6° ± 11.7° to 34.5° ± 6.6°. For patients with preoperative neurological deficits, their neurological functions were improved to normal. In drug susceptibility tests, 70.5% (11/17) of specimens had bacteria resistant to at least 1 first-line drug. CONCLUSION: Single-posterior debridement, osteotomy, correction, bone graft, and fusion are effective and safe in the treatment of recurrent thoracic/thoracolumbar spinal tuberculosis with kyphosis. The drug treatment of recurrent spinal tuberculosis should be carefully tailored.

The role of ageing and oxidative stress in intervertebral disc degeneration.

Intervertebral disc degeneration (IDD) is the primary cause of intervertebral disc (IVD) disease. With the increased ageing of society, an increasing number of patients are plagued by intervertebral disc disease. Ageing not only accelerates the decreased vitality and functional loss of intervertebral disc cells but also increases intracellular oxidative stress. Moreover, the speed of intervertebral disc ageing is also linked to high levels of reactive oxygen species (ROS) production. Not only is the production of ROS increased in ageing intervertebral disc cells, but antioxidant levels in degenerative intervertebral discs also decrease. In addition to the intervertebral disc, the structural components of the intervertebral disc matrix are vulnerable to oxidative damage. After chronic mitochondrial dysfunction, ROS can be produced in large quantities, while autophagy can eliminate these impaired mitochondria to reduce the production of ROS. Oxidative stress has a marked impact on the occurrence of IDD. In the future, IDD treatment is aiming to improve oxidative stress by regulating the redox balance in intervertebral disc cells. In summary, ageing and oxidative stress promote the degeneration of IVD, but further basic and clinical trials are needed to determine how to treat oxidative stress. At present, although there are many in-depth studies on the relationship between oxidative stress and degeneration of intervertebral disc cells, the specific mechanism has not been elucidated. In this paper, the main causes of intervertebral disc diseases are studied and summarized, and the impact of oxidative stress on intervertebral disc degeneration is studied.

Posterior Surgery in the Treatment of Craniovertebral Junction Deformity with Torticollis.

OBJECTIVE: To investigate the clinical effect of posterior surgery in the treatment of craniovertebral junction (CVJ) deformities with torticollis and methods for preventing and treating complications in order to obtain a reasonable treatment strategy. METHODS: From January 2007 to December 2017, 78 patients who suffered from CVJ deformities with torticollis treated by posterior surgery were analyzed. The surgical techniques were all posterior correction and fusion to restore the anatomical alignment of the craniovertebral junction. The visual analog score (VAS) and Short Form-36 (SF-36) health survey questionnaire were utilized to evaluate preoperative and postoperative neck pain, and changes in the torticollis angle and atlas-dens interval (ADI) were evaluated through anteroposterior X-ray and computed tomography. Intra- and postoperative complications were all recorded. One-way ANOVA, LSD-t test, and χ2 test were performed to evaluate the difference between the preoperative and postoperative data. RESULTS: The mean follow-up time was 37.4 ± 15.7 months, the average operation time was 115.6 ± 12.8 min, and the average blood loss was 170.8 ± 26.3 mL. According to the deformity site, the range of posterior correction and fusion was as follows: 38 cases of C1 -C2 , 33 cases of C0 -C2 , and seven cases of C0 -C3 . The preoperative SF-36, VAS, torticollis angle, and ADI were 42.6 ± 8.8, 4.8 ± 1.1, 37.2 ± 11.2°, and 4.9 ± 2.3 mm, respectively. The difference was significant at 3 months post operation (p < 0.05), and there was no significant difference at the final follow-up compared with 3 months post operation (p > 0.05). CONCLUSION: It can objectively achieve favorable correction and satisfactory clinical effects under posterior correction and fixation for CVJ deformities with torticollis. Intra- and postoperative complications can be settled by proper management.

C1-ring osteosynthesis versus C1-2 fixation fusion in the treatment of unstable atlas fractures: a multicenter, prospective, randomized controlled study with 5-year follow-up.

OBJECTIVE: The aim of the present study was to compare the long-term effects of posterior C1-ring osteosynthesis and C1-2 fixation fusion in the treatment of unstable atlas fractures. METHODS: A multicenter, prospective, randomized controlled trial was conducted to analyze 73 patients with atlas fractures who underwent posterior fixation. The intervention group was treated with C1-ring osteosynthesis, and the control group was treated with C1-2 fixation fusion. The patients were followed up for 6 months, 1 year, 2 years, and 5 years after the operation. RESULTS: Fifty-two patients had complete data at the last follow-up. The visual analog scale (VAS) score for neck pain in the intervention group was lower than that in the control group (p < 0.001). The operation time, intraoperative blood loss, radiation dose, bedridden period, hospital stay, and cost in the intervention group were significantly lower than those in the control group (p < 0.001). At the last follow-up, the Neck Disability Index in the intervention group was higher than that of the control group, and the angle of flexion-extension and axial rotation in the intervention group were greater than those in the control group (p < 0.001). CONCLUSIONS: In this study, the authors found that posterior C1-ring osteosynthesis is superior to C1-2 fixation fusion in terms of long-term relief of neck pain and preservation of the physiological function of the cervical vertebrae. This technique is a reliable choice for the treatment of unstable C1 fractures.

Retraction notice to "Melatonin alleviates acute spinal cord injury in rats through promoting on progenitor cells proliferation" [Saudi Pharm. J. 25 (2017) 570-574].

[This retracts the article DOI: 10.1016/j.jsps.2017.04.025.].

Correlation between the progression of cancer and the expression of matrix metalloproteinase-9 in metastatic spinal tumor.

PURPOSE: To explore whether the expression levels of matrix metalloproteinase-9 (MMP-9) are related to spinal metastasis of gastric carcinoma. METHODS: Fifty tissue specimens were collected from gastric carcinoma with spinal metastasis and set as test group A; 30 tissue specimens of primary gastric carcinoma were collected and set as control group B; 30 healthy paracancerous gastric tissue specimens were collected and set as control group C. The expression levels of MMP-9 and vascular endothelial growth factor (VEGF) in the specimens were analyzed by immunohistochemistry. RESULTS: The positive expression rates of MMP-9 in the three groups were 82.0, 63.33 and 16.67% respectively, and the positive expression rates of VEGF were 78.00, 56.67 and 13.33%, respectively. The positive expression rates of MMP-9 and VEGF in the test group A were statistically significantly higher than those of control group B and C (p<0.05). These findings suggest a positive correlation between MMP-9 and VEGF expression. CONCLUSION: Increased expression of MMP-9 is associated with the spinal metastasis of gastric carcinoma.

Anterior versus posterior surgical approach for lumbosacral tuberculosis.

Objective To compare two different approaches for the treatment of lumbosacral tuberculosis. Patients and Methods In total, 115 patients who were surgically treated in our department from July 2010 to July 2014 were included in this retrospective study. They were divided into the anterior and posterior approach groups. Intraoperative hemorrhage; the surgery time; the Cobb angle preoperatively, postoperatively, and at the follow-up visit (2 years postoperatively); visual analog scale (VAS) pain scores before and after surgery; and Oswestry Disability Index (ODI) scores before and after surgery were compared between the two groups. Results The Cobb angle and VAS and ODI scores were significantly improved in both groups after surgery. Significant differences were found in the operation time, intraoperative hemorrhage, Cobb angle correction, and loss of correction at the last follow-up. No significant differences were found in the VAS and ODI scores between the groups. Conclusions The posterior approach is superior to the anterior approach with respect to the surgery time, intraoperative hemorrhage, and Cobb angle postoperatively and at the last follow-up. When both approaches can be carried out for a patient with lumbosacral tuberculosis, the posterior approach should be favored over the anterior approach.

ACDF vs TDR for patients with cervical spondylosis - an 8 year follow up study.

BACKGROUND: ACDF has been considered as the gold standard in the treatment of single level cervical disk protrusion. However, it may cause adjacent level degeneration due to regional biomechanical changes. TDR has been applied with satisfactory results for over a decade, but there is no consensus if TDR is safer and more efficient than ACDF. The current study was carried out to compare the efficiency and safety of TDR and ACDF in the treatment of patients with single level cervical disk protrusion. METHODS: One hundred forty-five consecutive patients who underwent either TDR or ACDF in our center were included in the current study. Time of surgery, intraoperative blood loss, VAS arm and neck pain scores, ROM, ODI, SF36 and Patient satisfaction were compared before the surgery, after the surgery, and during follow up 1, 3, 5, 8 years after the surgery. RESULTS: The time of surgery was 64.6 ± 20.7 min in the ACDF group and 69.4 ± 19.3 min in the TDR group; intraoperative hemorrhage was 67.2 ± 14.3 ml in ACDF group and 70.7 ± 18.6 ml in TDR group. There were no significant differences between two groups concerning time of surgery and intraoperative blood loss. No differences were found concerning patient satisfaction between the two groups during the follow up (P > 0.05). Significant differences were found between the groups concerning VAS arm and neck pain scores, ROM, ODI and SF36 after the surgery and during the 8 year follow up. CONCLUSION: TDR may be a more effective approach than ACDF for treating patients with single level cervical disk protrusion.

Melatonin alleviates acute spinal cord injury in rats through promoting on progenitor cells proliferation.

The previous studies have shown that melatonin is beneficial for nervous system after spinal cord injury (SCI). After SCI, the endogenous neural stem/progenitor cells (eNSPCs) proliferate and differentiate into neurons and glial cells. In the present study, we examined the effect of melatonin on eNSPCs proliferation and differentiation in SCI rat model. SCI rat model was established by dropping a 10 g rod from the height of 25 mm. Then, the rats were randomly divided into the control group, the melatonin treated group, and the G3335 treated group. The Basso-Beattie-Bresnahan locomotor rating scale (BBB scale) was used to evaluate the recovery of locomotor function after SCI. Flow cytometry was used to evaluate eNSPCs proliferation and differentiation. The rats in the melatonin treated group demonstrated significantly faster locomotor function recovery and more eNSPCs proliferation and differentiation. However, these effects were abolished in the G3335 treated group. Melatonin can effectively promote locomotor function recovery via improving eNSPCs proliferation and differentiation after SCI.

Transforaminal lumbar interbody fusion versus posterolateral fusion in degenerative lumbar spondylosis: A meta-analysis.

OBJECTIVE: The aim of the study was to evaluate the efficacy and safety of transforaminal lumbar interbody fusion (TLIF) versus posterolateral fusion (PLF) in degenerative lumbar spondylosis. METHODS: A systematic literature review was performed to obtain randomized controlled trials (RCTs) and observational studies (OSs) of TLIF and PLF for degenerative lumbar spondylosis. Trials performed before November 2015 were retrieved from the Medline, EMBASE, Cochrane library, and Chinese databases. Data extraction and quality evaluation of the trials were performed independently by 2 investigators. A meta-analysis was performed using STATA version 12.0. RESULTS: Two RCTs and 5 OSs of 630 patients were included. Of these subjects, 325 were in the TLIF and 305 were in the PLF group. Results showed that TLIF did not increase the fusion rate based on RCTs (relative risk [RR] = 1.06; 95% confidence interval [CI]: 0.95-1.18; P = 0.321), but increased it based on OSs (RR = 1.14; 95% CI: 1.07-1.23; P = 0.000) and overall (RR = 1.11; 95% CI: 1.05-1.18; P = 0.001) as compared with PLF. TLIF was able to improve the clinical outcomes based on 1 RCT (RR = 1.33; 95% CI: 1.11-1.59, P = 0.002) and overall (RR = 1.19; 95% CI: 1.07-1.33; P = 0.001), but not based on OSs (RR = 1.11; 95% CI: 0.97-1.27; P = 0.129) as compared with PLF. There were no differences between TLIF and PLF in terms of visual analogue scale, Oswestry Disability Index, reoperation, complications, duration of surgical procedure, blood loss, and hospitalization. CONCLUSIONS: In conclusion, evidence is not sufficient to support that TLIF provides higher fusion rate than PLF, and this poor evidence indicates that TLIF might improve only clinical outcomes. Higher quality, multicenter RCTs are needed to better define the role of TLIF and PLF.

Treating Huge Tear-Drop Fracture of Axis With Trapezoidal Bone: A Case Report and Literature Review.

STUDY DESIGN: Case report and review of relevant literature. OBJECTIVE: To discuss the surgical strategies and clinical outcome of managing huge tear drop fracture of axis. SUMMARY OF BACKGROUND DATA: Teardrop fracture of axis is rarely seen, especially the huge type. The surgical technique is demanding because of the special anatomical structure and difficulty with bone grafting. Moreover, the surgical approach is controversial in the literature. METHODS: A 51-year-old male patient suffered from neck pain after falling from the bicycle, neck movement was limited with no neurological compromise. X-ray suggested huge tear-drop fracture of anterior-inferior corner of axis, narrowing of C2/3 intervertebral disc. Fusion with self-designed tricortical trapezoidal iliac bone was performed. RESULTS: Treating huge teardrop fracture of axis by anterior bone grafting with self-designed tricortical trapezoidal iliac bone is effective and stable. A 3-month follow-up showed fusion was achieved, upper cervical curvature was restored, and neck pain disappeared. CONCLUSION: Self-designed tricortical trapezoidal iliac bone provided adequate fusion area of bone grafting, restoring the normal intervertebral height and cervical alignment, and the midterm outcome is satisfactory. LEVEL OF EVIDENCE: 5.