Return to flight duty (RTFD) after posterior lumbar spine surgery for symptomatic lumbar disc herniation (LDH) and lumbar isthmic spondylolisthesis (LIS) in Chinese military pilots.

BACKGROUND: Symptomatic lumbar disc herniation (LDH) and lumbar isthmic spondylolisthesis (LIS) present significant challenges for military pilots, which may result in grounding if not effectively managed. Surgical treatment for LDH and LIS may offer a pathway to return to flight duty (RTFD), but recent data on this crucial topic is lacking. This study seeks to address this gap by investigating the RTFD outcomes among Chinese military pilots who have undergone lumbar spine surgery for symptomatic LDH and LIS. METHODS: A retrospective review was conducted on active-duty military pilots who underwent isolated decompressive or fusion procedures at an authorized military medical center from March 1, 2007, to March 1, 2023. The analysis utilized descriptive statistics to examine demographic, occupational, surgical, and outcome data, with a particular focus on preoperative flight status, recommended clearance by spine surgeons, and actual RTFD outcomes and time. RESULTS: Among the identified cases of active-duty military pilots with LDH or LIS treated by lumbar surgery (n = 24), 70.8% (17 of 24) consistently maintained RTFD status without encountering surgical complications or medical issues during the follow-up period. Of the seven pilots who did not RTFD, one retired within a year of surgery, two had anterior cruciate ligament injuries, three had residual radicular symptoms, and one had chronic low back pain. Excluding pilots who retired and did not RTFD for reasons unrelated to their lumbar conditions, the RTFD rate stood at 81.0% (17 of 21). The median time for recommended clearance by spine surgeons was 143.0 days (inter-quartile range, 116.5-196.0), while the median duration for actual RTFD attainment was 221.0 days (inter-quartile range, 182.0-300.0). The median follow-up post-lumbar surgery was 1.7 years (inter-quartile range, 0.4-2.9). CONCLUSION: Most military pilots diagnosed with symptomatic LDH and LIS can continue their careers and regain active-duty flight status following lumbar spine surgery, as reflected by the high RTFD rate. Lumbar spine surgery can successfully alleviate the physical constraints associated with spinal conditions, facilitating the return of military pilots to their demanding profession.

MicroRNA-155 suppresses the catabolic effect induced by TNF-α and IL-1ß by targeting C/EBPß in rat nucleus pulposus cells.

AIM: miR-155 is a pro-inflammatory or anti-inflammatory factor depending on the cell type in which it is expressed. miR-155 controls apoptosis and matrix degradation in nucleus pulposus (NP) cells in vitro. The aim of this study is to explore the effect of miR-155 in vivo and further investigate the mechanism of miR-155 in vitro. METHODS: MRI, hematoxylin-eosin staining, or Collagen-II immunochemistry were performed to observe intervertebral disk degeneration in conditional miR-155 overexpression mice and miR-155 knockout mice. In vitro, a dual luciferase reporter assay, real-time PCR and western blot experiments were performed to demonstrate the effect of miR-155 on the expression of catabolic genes induced by inflammatory cytokines and determine the role of ß-catenin and C/EBPß in the miR-155-mediated modulation of the expression of catabolic genes. RESULTS: Degeneration was observed in the lumbar disks of 1-year-old miR-155 knockout mice but not in the conditional miR-155 overexpression mice. miR-155 overexpression repressed the catabolic effect induced by TNF-α or IL-1ß in vitro. Furthermore, specifically in NP cells, miR-155 overexpression suppressed the expression of C/EBPß but not of ß-catenin. Additionally, in the loss-of-function experiments using C/EBPß siRNA, C/EBPß knockdown repressed the expression of catabolic genes induced by TNF-α and IL-1ß, which is consistent with the miR-155 results. CONCLUSION: miR-155 is a sustainable factor for intervertebral disk and suppresses the expression of catabolic genes induced by TNF-α and IL-1ß by targeting C/EBPß in rat NP cells.

Low-level laser irradiation modulates brain-derived neurotrophic factor mRNA transcription through calcium-dependent activation of the ERK/CREB pathway.

Low-level laser (LLL) irradiation has been reported to promote neuronal differentiation, but the mechanism remains unclear. Brain-derived neurotrophic factor (BDNF) has been confirmed to be one of the most important neurotrophic factors because it is critical for the differentiation and survival of neurons during development. Thus, this study aimed to investigate the effects of LLL irradiation on Bdnf messenger RNA (mRNA) transcription and the molecular pathway involved in LLL-induced Bdnf mRNA transcription in cultured dorsal root ganglion neurons (DRGNs) using Ca2+ imaging, pharmacological detections, RNA interference, immunocytochemistry assay, Western blot, and qPCR analysis. We show here that LLL induced increases in the [Ca2+] i level, Bdnf mRNA transcription, cAMP-response element-binding protein (CREB) phosphorylation, and extracellular signal-regulated kinase (ERK) phosphorylation, mediated by Ca2+ release via inositol triphosphate receptor (IP3R)-sensitive calcium (Ca2+) stores. Blockade of Ca2+ increase suppressed Bdnf mRNA transcription, CREB phosphorylation, and ERK phosphorylation. Downregulation of phosphorylated (p)-CREB reduced Bdnf mRNA transcription triggered by LLL. Furthermore, blockade of ERK using PD98059 inhibitor reduced p-CREB and Bdnf mRNA transcription induced by LLL. Taken together, these findings establish the Ca2+-ERK-CREB cascade as a potential signaling pathway involved in LLL-induced Bdnf mRNA transcription. To our knowledge, this is the first report of the mechanisms of Ca2+-dependent Bdnf mRNA transcription triggered by LLL. These findings may help further explore the complex molecular signaling networks in LLL-triggered nerve regeneration in vivo and may also provide experimental evidence for the development of LLL for clinical applications.

Oxymatrine induces mitochondria dependent apoptosis in human osteosarcoma MNNG/HOS cells through inhibition of PI3K/Akt pathway.

The cytostatic drug from traditional Chinese medicinal herb has acted as a chemotherapeutic agent used in treatment of a wide variety of cancers. Oxymatrine, classified as a quinolizidine alkaloid, is a phytochemical product derived from Sophora flavescens, and has been reported to possess anticancer activities. However, the cancer growth inhibitory effects and molecular mechanisms in human osteosarcoma MNNG/HOS cell have not been well studied. In the present study, the cytotoxic effects of oxymatrine on MNNG/HOS cells were examined by MTT and bromodeoxyuridine (BrdU) incorporation assays. The percentage of apoptotic cells and the level of mitochondrial membrane potential (Δψ m) were assayed by flow cytometry. The levels of apoptosis-related proteins were measured by Western blot analysis or enzyme assay Kit. Our results showed that treatment with oxymatrine resulted in a significant inhibition of cell proliferation and DNA synthesis in a dose-dependent manner, which has been attributed to apoptosis. Furthermore, we found that oxymatrine considerably inhibited the expression of Bcl-2 whilst increasing that of Bax. This promoted mitochondrial dysfunction, leading to the release of cytochrome c from the mitochondria to the cytoplasm, as well as the activation of caspase-9 and -3. Moreover, addition of oxymatrine to MNNG/HOS cells also attenuated phosphatidylinositol 3-kinase (PI3K) /Akt signaling pathway cascade, evidenced by the dephosphorylation of P13K and Akt. Likewise, oxymatrine significantly suppressed tumor growth in female BALB/C nude mice bearing MNNG/HOS xenograft tumors. In addition, no evidence of drug-related toxicity was identified in the treated animals by comparing the body weight increase and mortality. Therefore, these findings should be useful for understanding the apoptotic cellular mechanism mediated by oxymatrine and might offer a therapeutic potential advantage for human osteosarcoma chemoprevention or chemotherapy.

Effect of Zoledronic Acid on the Vertebral Body Bone Mineral Density After Instrumented Intervertebral Fusion in Postmenopausal Women With Osteoporosis.

STUDY DESIGN: Retrospective cohort study. OBJECTIVES: To evaluate the effect of zoledronic acid, an anti-osteoporosis treatment, during the perioperative period on vertebral body bone mineral density (BMD) after spinal fusion surgery in postmenopausal women with osteoporosis. METHODS: The medical records of postmenopausal patients with osteoporosis who underwent instrumented intervertebral fusion for lumbar degenerative disease between July 2016 and May 2018 were reviewed. Patients with comorbidities or condition which might affect bone metabolism were excluded. Forty-six patients did not receive anti-osteoporosis treatment before surgery and during the postoperative follow-up (untreated group). Another 46 patients who was treated with zoledronic acid perioperatively were matched for age and body mass index to patients in the untreated group. Preoperative and postoperative dual-energy X-ray absorptiometry (DEXA) records and lumbar BMD values of the involved spinal segments and of the cephalad levels, as well as of the femoral neck were recorded. RESULTS: A significant decrease of cephalad vertebral BMD values was observed in the untreated group (-11.47%, P < 0.001), with a slight decrease of the femoral neck (-1.28%, P > 0.05). Zoledronic acid prevented rapid bone loss after instrumented intervertebral fusion surgery, with a bone loss in the cephalad levels of -0.76 ± 4.71% compared to -11.47 ± 16.45% in the untreated group (P < 0.001). while the change in BMD of the femoral neck in the treated group was 1.52 ± 5.88% compared to -1.28 ± 6.58% in the untreated group (P = 0.036). CONCLUSIONS: Perioperative zoledronic acid treatment may offer protection against a significant decrease in BMD of cephalad vertebrae after spinal fusion surgery among postmenopausal women with osteoporosis.

Comparison of the Clinical Efficacy of Two Reduction Methods for the Treatment of Irreducible Unilateral Subaxial Cervical Facet Joint Dislocation.

OBJECTIVE: To compare the clinical efficacy of the minimally invasive technique and the open method in the treatment of irreducible unilateral subaxial cervical facet joint dislocation (SCFD). METHODS: From March 2015 to September 2018, 62 patients with unilateral SCFD were studied. The cases were divided into 2 groups based on different surgery strategies. Thirty-one patients were enrolled in the minimally invasive surgery (MIS) group, and 31 patients were enrolled in the open surgery group. The duration of prone position operation, blood loss, and total hospitalization costs were recorded. The clinical effects were evaluated using visual analogue scale scores, the Oswestry Disability Index, and Japanese Orthopedic Association scores at each follow-up. In addition, the segmental Cobb angle and intervertebral height were recorded and compared. RESULTS: The amount of intraoperative blood loss, prone position operation duration, and total hospital costs in the MIS group were significantly lower than in the open surgery group. The visual analogue scale, Oswestry Disability Index, and Japanese Orthopedic Association scores of the 2 groups significantly improved after the operation. A satisfactory fusion rate was obtained in both groups, and the segmental Cobb angle and intervertebral height scores in both groups improved significantly. CONCLUSIONS: Minimally invasive reduction had equal clinical efficacy to posterior open surgery. However, MIS was less invasive and had lower costs. Therefore, it is a potential option in the treatment of SCFD.

Outcome of lumbar lateral recess stenosis with percutaneous endoscopic transforaminal decompression in patients 65 years of age or older and in younger patients.

Lateral recess stenosis is a common pathology causing clinical syndromes in the elderly population, and there is some concern regarding the number of comorbidities that can occur when performing surgery for this condition in the elderly. However, little research has focused on the issues related to older age, and limited data is available to help the clinician counsel elderly patients undergoing percutaneous endoscopic transforaminal decompression. The present study aimed to explore the safety and efficacy of percutaneous endoscopic transforaminal decompression for lumbar degenerative disease in elderly patients with lumbar lateral recess stenosis and to determine whether age and comorbidity affect the outcome and complication rate.We identified 117 patients in our patient database who underwent percutaneous endoscopic transforaminal decompression for single-level lumbar lateral recess stenosis. Data regarding the Oswestry Disability Index and visual analog scale for back and leg pain were collected preoperatively, postoperatively, and at the last follow-up. Other data, including preoperative comorbidities, operation time, and intraoperative and postoperative complications, were recorded.The average follow-up period was 29.9 ±â€Š5.5 months, with a mean age of 69.8 ±â€Š5.4 years in elderly patients (group A) and 50.4 ±â€Š6.4 years in younger patients (group B). Group A had a higher percentage of comorbidity than group B (83.9% vs 18.0%, P < .001). Both visual analog scale scores for leg pain and Oswestry Disability Index were significantly improved in the 2 groups, and no difference was found between the groups regarding both parameters (P >.05). The elderly patients had the same high rate of favorable outcomes as group B (P > .05). Moreover, there was no difference in surgical complications, recurrence, and neurologic deficit recovery rate between both groups. No major complications or perioperative deaths occurred in both groups.The present study demonstrates that percutaneous endoscopic transforaminal decompression for lateral recess stenosis in elderly patients may be a reasonable treatment associated with substantial benefit.

Management for lumbar spinal stenosis: Protocol for a network meta-analysis and systematic review.

INTRODUCTION: Lumbar spinal stenosis (LSS) is caused by structural changes of the spine, which lead to several severe symptoms, including back pain, leg pain, numbness and tingling in the legs, as well as reduced physical function. However, there is little evidence suggesting whether a patient with LSS should be treated with surgery. If surgery is recommended, which type of surgery benefits the patient most? To answer these questions, we will conduct a network meta-analysis and a systematic review to compare surgical and nonsurgical interventions in terms of efficacy as well as safety in adult patients with LSS. METHODS AND ANALYSIS: We will search the PubMed, Cochrane library, and EMBASE databases for articles published prior to October 10, 2019. We will search for randomized controlled trials assessing surgical and nonsurgical interventions for adult patients with degenerative LSS without any language restrictions. The primary outcome measures will be pain and disability. The secondary outcomes will include adverse events (number of events or number of people with each type of adverse event), reoperations, complications, blood loss and operation time. We will obtain the full texts of the potentially relevant studies and independently assess them. The quality of evidence will be evaluated according to the Grading of Recommendations Assessment, Development and Evaluation framework. A random-effects network meta-analysis will be performed to analyze all the evidence under the frequentist framework, and the ranking results will be presented. We will generate plots depicting the network geometry using Stata. The network meta-analysis will be performed according to the Bayesian framework. Ethics and dissemination Ethics approval is not required. The research will be published in a peer-reviewed journal.

Silencing of calpain expression reduces the metastatic potential of human osteosarcoma cells.

Osteosarcoma, the most common primary bone tumor in young adults, is characterized by local invasion and distant metastasis. But detailed mechanisms of tumorigenicity and metastasis of osteosarcoma are not well known. We report the involvement of calpains, a family of calcium-activated, cysteine proteases, in the invasive and metastatic processes of human osteosarcoma cells. By using siRNA treatment, the expression of mu- and m-calpains were downregulated in human Saos-2 osteosarcoma cells. Both the adhesive and invasive potentials were significantly attenuated in calpain siRNA-transfected human Saos-2 osteosarcoma cells. MMPs are the main factors involved in malignant tumor invasion and metastasis. siRNA of calpains also significantly inhibited the secretion of MMP-2 in Saos-2 cells. These results suggest that mu- and m-calpains are important in the invasion and metastasis of human osteosarcoma cells, and calpains might be targeted to reduce tumor progression.

miR-640 aggravates intervertebral disc degeneration via NF-κB and WNT signalling pathway.

OBJECTIVES: Low back pain becomes a common orthopaedic disease today. It is mainly induced by the degeneration of the intervertebral disc. In this study, we tried to reveal the pathogenesis of the degeneration and the relative therapeutic strategy, which are still elusive. MATERIALS AND METHODS: We collected 15 degenerative intervertebral tissues and five healthy donors. Nucleus pulposus and annulus fibrosus cells were subcultured. miR-640 expression was determined by qPCR. Computer analysis and luciferase reporter assay were used to confirm miR-640 target genes. Immunohistochemical and immunocytochemical staining was used to trace the proinflammatory cytokines and key transductor of signalling pathways. We also used ß-galactosidase staining, flow cytometry, and cell viability assay to monitor the degenerative index. RESULTS: miR-640 overexpressed in patients derived degenerative nucleus pulposus tissues and cells. The inflammatory environment promoted miR-640 expression via NF-κB signalling pathway. In addition, miR-640 targeted to LRP1 and enhances NF-κB signal activity, which built a positive feedback loop. miR-640 inhibited the expression of ß-catenin and EP300, therefore, restrained WNT signal and induced the degeneration in nucleus pulposus cells. miR-640 inhibitor treatment exhibited the effects of anti-inflammation, reverse WNT signalling pathway exhaustion, and remission of degenerative characteristics in vitro. CONCLUSIONS: miR-640 plays an important role in the degeneration of intervertebral disc and the relative inflammatory microenvironment. It is a promising potential therapeutic target for the low back pain biotherapy.

Transcription factor 7-like 2 controls matrix degradation through nuclear factor κB signaling and is repressed by microRNA-155 in nucleus pulposus cells.

AIM: TCF7L2, a key transcription factor in the canonical Wnt pathway, plays a vital role in the matrix degradation of chondrocytes. However, it is unknown whether TCF7L2 is important in the matrix metabolism of inner gel-like nucleus pulposus (NP) cells; thus, the aim of this study was to explore the effect and mechanism of TCF7L2 in this process. METHODS: Western blotting and immunofluorescence analyses were used to observe TCF7L2 expression in rat and human NP tissues. Real-time PCR and western blotting were performed to detect the expression of TCF7L2 stimulated by inflammatory cytokines. Dual luciferase reporter assay, real-time PCR, western blotting and knockdown experiments were performed to demonstrate the role of NF-κB signaling in matrix regulation by TCF7L2 and the regulation of TCF7L2 by miR-155 in intervertebral disc degeneration. KEY FINDINGS: TCF7L2 is present in rat and human NP tissues and is expressed in the nucleus of NP cells. TCF7L2 is refractory to stimulation of rat and human NP cells with the inflammatory cytokines TNF-α and IL-1ß, in contrast to the results in other cell types. Loss-of-function experiments using TCF7L2 siRNA or lentiviral shTCF7L2 showed that TCF7L2 knockdown suppresses matrix degradation through p65/NF-κB signaling in the absence and presence of TNF-α. In addition, TCF7L2 expression is repressed by miR-155 overexpression and promoted by miR-155 inhibition. SIGNIFICANCE: Overall, these results demonstrate that the suppression of TCF7L2, which is modulated by miR-155, inhibits matrix degradation through p65/NF-κB signaling. TCF7L2 suppression may have therapeutic potential in intervertebral disc degeneration.

Treatment of complicated tibial plateau fractures with dual plating via a 2-incision technique.

The operative treatment of complicated bicondylar fractures of the tibial plateau remains a challenge to most surgeons. This retrospective study was designed to evaluate the clinical and radiological outcomes of dual plating via a 2-incision technique for the repair of complicated bicondylar tibial plateau fractures. A series of consecutive patients with bicondylar tibial plateau fractures treated by open reduction and internal fixation with a double buttress plate or a combination of locking plate and buttress plate via a 2-incision technique between March 2004 and March 2008 were retrospectively analyzed. Radiological and clinical results and complications of the 2 different fixation methods were compared. Seventy-nine patients matching the criteria of this study were followed up for at least 24 months. All of the fractures healed, with 3 cases of deep infection, 7 cases of secondary loss of reduction, 3 cases of secondary loss of alignment, and 10 cases of knee instability. At 24-month follow-up, mean Hospital for Special Surgery scores were 77.8±9.4 and 79.0±7.9 in the double buttress plate group and combination group, respectively. No significant differences in clinical or radiographic outcomes were found between the 2 groups, except that the combination group needed less bone graft. Dual plating with 2 incisions provided good exposition for the reduction and fixation of complicated bicondylar tibial plateau fractures. Using a combination of locking plate and buttress plate reduced the amount of bone graft compared with the double buttress plate technique.

Could local deliver of bisphosphonates be a new therapeutic choice for Gorham-Stout syndrome?

The Gorham-Stout Syndrome is a rare condition in which spontaneous, progressive resorption of bone occurs. Even though the prognosis of the condition is generally considered to be good, Gorham-Stout syndrome can cause severe debilitation. In approximately 13% of recorded cases, death ensues. The treatment modalities for Gorham-Stout Syndrome include surgery, radiation therapy, anti-osteoclastic medications, however there is no known successful treatment. To date, the etiology of Gorham-Stout Syndrome is still controversial. However, general consensus on the importance of the derangement of osteoclastic activity and angiomatosis of blood vessels. Thus, local deliver of anti-osteoclastic and anti-angiogenic agents may be of great interest for the treatment of Gorham-Stout Syndrome. Bisphosphonates are potent in inhibiting osteoclast activity and promoting apoptosis, which has been widely used for the treatment of osteoporosis and osteolysis diseases and proved to be able to decrease the speed of bone destruction in Gorham-Stout Syndrome through systemic administration. In addition to its anti-osteolytic effect, bisphosphonates are currently shown to be capable of anti-angiogenesis and induction of apoptosis in tumor cells. Furthermore biocompatible calcium phosphate which is widely used for bone reconstruction in clinical has also been reported to be a suitable carrier for loading and releasing of bioactive bisphosphonates. Therefore, we hypothesis that local deliver of bisphosphonates by calcium phosphate may be a potential treatment of Gorham-Stout Syndrome.

Application of locking plate in long-bone atrophic nonunion following external fixation.

The treatment of atrophic fracture nonunion continues to represent a therapeutic challenge. Large segmental osteopenia is often seen in patients who received uniplanar or hybrid external fixators as the definitive method of fixation for high-energy fractures, and this adds more difficulties to the treatment of fracture nonunion. This retrospective study was designed to assess the outcome of locking compression plating with autologous bone grafting in patients with long-bone atrophic nonunion following external fixation.From January 2004 to December 2009, a series of consecutive patients with atrophic nonunion of the long bone following external fixation were treated with this method in our institution. The clinical outcomes and complications of these patients were retrospectively analyzed. Twenty-seven patients with 28 fracture nonunions were involved in this study. Mean follow-up was 14.2±3.4 months. Bony union was achieved in all 27 patients within a mean 18.6±4.8 weeks after revision surgery. Two patients developed superficial wound infections. No deep infections were found, and no implant failure was seen. Three patients reported minor pain in the donor site of the bone graft, and no other donor site complications were found.Revision osteosynthesis of long-bone atrophic nonunion following external fixation by locking compression plating with autologous iliac crest bone grafting represents a safe and efficacious modality for the treatment of these challenging conditions.

Two-stage flexor tendon reconstruction in zone II using Hunter's technique.

Tendon injuries in the digital flexor sheath area (zone II) are the most difficult to treat and remain a focus of both clinical attention and basic investigations. Although some new techniques have been developed, the clinical results are still not satisfying, especially in old injuries. This retrospective study was designed to investigate the results of delayed zone II flexor tendon repair using Hunter rods. Between July 1974 and June 1998, 81 patients at our institution underwent 2-stage reconstruction using Hunter's technique. Sixty-one patients with 106 fingers were included in this study. Digital flexor tendon resection and Hunter rod implantation were performed in the first-stage operation. Combined digital nerve injuries and damaged pulleys were repaired or reconstructed at the same time. Plaster was used to immobilize the hand for 3 weeks. During the second-stage operation, performed 2 to 6 months later, palmaris longus or plantaris were grafted into the pseudosheath formed surrounding the Hunter rods. The proximal end of the transplanted tendon was fixated with flexor digitorum profundus tendon using the Pulvertaft method, and the distal end was fixated to the distal phalanx using Bunnell's pullout wire method. Early controlled motion was performed in all cases. Evaluation based on total active motion was good to excellent in 84%, fair in 12%, and poor in 4% of patients. Flexor tendon reconstruction using Hunter technique is an effective way to restore digital function in delayed zone II flexor tendon injuries.