Research progress on the regulation of bone marrow stem cells by noncoding RNAs in adolescent idiopathic scoliosis.

Adolescent idiopathic scoliosis (AIS) is a common spinal deformity in young women, but its pathogenesis remains unclear. The primary pathogenic factors contributing to its development include genetics, abnormal bone metabolism, and endocrine factors. Bone marrow stem cells (BMSCs) play a crucial role in the pathogenesis of AIS by regulating its occurrence and progression. Noncoding RNAs (ncRNAs) are also involved in the pathogenesis of AIS, and their role in regulating BMSCs in patients with AIS requires further evaluation. In this review, we discuss the relevant literature regarding the osteogenic, chondrogenic, and lipogenic differentiation of BMSCs. The corresponding mechanisms of ncRNA-mediated BMSC regulation in patients with AIS, recent advancements in AIS and ncRNA research, and the importance of ncRNA translation profiling and multiomics are highlighted.

Retrospective analysis of deformed complex vertebral osteotomy in children with severe thoracic post-tubercular angular kyphosis.

BACKGROUND: Many surgical options have been described to manage post-tubercular kyphosis, but the standard approach for treating severe post-tubercular angular kyphosis in children has not been established yet. The present study was performed to evaluate the safety and efficacy of deformed complex vertebral osteotomy (DCVO) for the treatment of severe thoracic post-tubercular angular kyphosis (> 70°) in children. METHODS: Deformed complex vertebrae indicated that multiple deformed and fused vertebrae were usually involved with two or more vertebral bodies and the partial or total fusion of many segments' facet joints and intervertebral discs. Thus, DCVO indicated that a wider posterior wedge-shaped and three-column osteotomy was performed within deformed complex vertebrae to correct a more extensive range of angles. From 2010 to 2017, 15 children who suffered from severe thoracic post-tubercular angular kyphosis underwent DCVO. Deformed complex vertebrae involved two vertebral bodies in 9 patients and three vertebral bodies in 6 patients. The Visual Analogue Scale (VAS) and Oswestry Disability Index (ODI) were assessed preoperatively and at the final follow up. This was a retrospective study analysing the outcome after grade 4/5 spinal osteotomies in deformed complex vertebrae. RESULTS: The mean duration of surgery was 239 ± 37.81 min. The average period of follow-up was 31.6 ± 6.98 months. The preoperative mean kyphosis of deformed complex vertebrae was 83.39° ± 9.04°; the mean thoracic kyphosis (TK) and lumbar lordosis (LL) were 81.09° ± 8.51° and 80.51° ± 7.64°, respectively; the mean sagittal vertical axis (SVA) was 3.83 cm ± 1.43 cm. The postoperative mean kyphosis of deformed complex vertebrae was reduced to 19.98° ± 2.47° (P < 0.001) with a mean kyphosis correction of 63.41°; at the final follow up, it was 18.4° ± 2.29° (P < 0.001) without obvious loss of correction. The postoperative mean TK, LL, and SVA were reduced to 24.05° ± 3.84°, 46.9° ± 3.53°, and 0.6 cm ± 0.34 cm, respectively (P < 0.001 for all); and there was no obvious loss of sagittal alignment and balance at the final follow up (p = 0.982, p = 0.604, p = 0.754). Complicated with neural dysfunction preoperatively, 5 Frankel's grade D cases showed complete neurological recovery at final follow up. VAS score reduced from 3.6 ± 1.18 to 0.87 ± 0.64 (P < 0.001); and ODI score reduced from 22.21 ± 6.93 to 5.02 ± 2.6 (P < 0.001) at the final follow up. CONCLUSIONS: DCVO was an individualized osteotomy for treating severe thoracic post-tubercular angular kyphosis in children and could be safe and effective in reducing the incidence of complications and significantly improving kyphosis correction.

Treatment of ankylosing spondylitis complicated with a thoracolumbar Andersson lesion by posterior closed osteotomy, debridement and fusion through the fracture line.

BACKGROUND: An Andersson lesion (AL) is a fatigue fracture occurring across three columns in ankylosing spondylitis (AS), resulting in spinal pseudarthrosis (SP) formation, most commonly in the thoracolumbar segment. However, there is still great controversy and few reports on the best surgical method for the treatment of AS combined with thoracolumbar AL. The purpose of this study was to investigate the efficacy of posterior closed osteotomy, debridement and fusion through the fracture line for the treatment of this disease. METHODS: The clinical data of 13 patients (male 8, female 5, mean age 50.6 years) with AS combined with thoracolumbar AL treated with posterior closed osteotomy, debridement and fusion through the fracture line were retrospectively analysed. The following parameters of the full-length lateral spine radiographs were measured preoperatively and at the last follow-up: cervical 7 tilt (C7T), global kyphosis (GK), thoracic kyphosis (TK), thoracolumbar kyphosis (TLK), local kyphosis (LK), angle of the fusion levels (AFL), lumbar lordosis (LL), pelvic incidence (PI), pelvic tilt (PT), sacral slope (SS) and sagittal vertical axis (SVA). The visual analog scale (VAS), Oswestry disability index (ODI) and Scoliosis Research Society-22 (SRS-22) scores were recorded preoperatively and at the last follow-up. RESULTS: The mean operation time was 345 min, the mean blood loss was 673 mL, and the mean follow-up time was 21.9 months. Compared with the preoperative values, the C7T, GK, TK, TLK, LK, AFL, PT, SS and SVA values of all patients were significantly improved at the last follow-up (P < 0.05); GK improved from 81.62 ± 16.11 to 50.15 ± 8.55, with an average of 31° of correction (F = 75.945, P<0.001). The VAS, ODI and SRS-22 scores also significantly improved (P < 0.05). At the last follow-up, bone fusion was found in all fracture ends. One patient developed numbness in the lower limbs after surgery and recovered after 3 months of rehabilitation; none of the remaining patients experienced postoperative complications. CONCLUSIONS: Posterior closed osteotomy, debridement and fusion through the fracture line completely removes the necrotic tissue around the SP, relieves symptoms, and corrects kyphosis simultaneously. It reduces the tension behind the fracture line or changes the tension into compressive stress, enabling stable repair of the fracture and avoiding anterior surgery. It is a safe and effective operation.

Posterior-only surgical correction with heavy halo-femoral traction for the treatment of extremely severe and rigid adolescent idiopathic scoliosis (> 130°).

INTRODUCTION: The treatment of extremely severe and rigid spinal deformities was a great surgical challenge. Pulmonary impairment often occurred, which increased the challenges to already daunting surgical approaches. The present study was performed to evaluate the safety and efficacy of posterior-only surgical correction with heavy halo-femoral traction (HFT) for the treatment of extremely severe and rigid adolescent idiopathic scoliosis (AIS) of more than 130°. MATERIALS AND METHODS: From 2010 to 2017, 11 patients suffered from extremely severe and rigid AIS of more than 130° underwent posterior-only surgical correction with HFT. The preoperative mean coronal Cobb angle of major curve was 139.01° ± 5.83°, and the mean flexibility was 17.21% ± 3.33%; the mean angle of thoracic kyphosis (TK) and lumbar lordosis (LL) were 65.02° ± 7.21° and 39.05° ± 4.08°, respectively; the mean trunk shift (TS) and sagittal vertical axis (SVA) were 3.3 ± 0.97 cm and 3.97 ± 1.16 cm, respectively; moreover, the percent forced vital capacity (FVC%) and percent forced expiratory volume in 1 s (FEV1%) were 50.08% ± 6.07% and 53.46% ± 5.96%, respectively; the mean body height and weight were 140.09 ± 4.95 cm and 37 ± 4.34 kg, respectively. RESULTS: The mean duration of surgery was 335.91 ± 48.31 min and blood loss was 1590 ± 520.1 ml. The average period of follow-up was 32.18 ± 8.17 months. After heavy HFT, the mean coronal Cobb angle of major curve was reduced to 82.98° ± 6.91° with correction rate of 40.39%. After posterior-only surgical correction, the mean coronal Cobb angle was further reduced to 51.17° ± 5.4° with correction rate of 63.27%. The postoperative mean TK, LL, TS and SVA were improved to 23.85° ± 5.14°, 44.95° ± 2.26°, 1.32 ± 0.72 cm and 1.42 ± 0.83 cm, respectively. At the final follow-up, the corrective loss rate of Cobb angle was only 0.72%; moreover, the mean FVC% and FEV1% were increased to 65.45% ± 5.29% and 69.08% ± 5.32% with improvement of 15.36% and 15.62%, respectively; the mean body height and weight were increased to 154.45 ± 5.32 cm and 45 ± 4.02 kg with improvement of 14.36 cm and 8 kg, respectively. The spinal cord function was stable, and there were no new neurological symptoms after correction. CONCLUSIONS: Posterior-only surgical correction with heavy HFT could be safe and effective for the treatment of extremely severe and rigid AIS of more than 130° in reducing the incidence of complications and greatly improving curve correction.

Minimum 5-year follow-up outcomes for one-stage posterior instrumentation without neurosurgery intervention for correction of scoliosis associated with Chiari I malformation and syringomyelia.

INTRODUCTION: Traditionally, the common belief has been that, all patients with Chiari I malformation (CM-1) and syringomyelia (SM) undergoing a neurosurgical procedure even if they are neurologically asymptomatic. As the pathology of CM-1 and SM has become better understood, the traditional concepts have been challenged. The objective of this study was to investigate the minimum 5-year follow-up clinical outcomes of surgical treatment of patients with scoliosis associated with CM-1 and SM and to evaluate the necessity of neurosurgical intervention before corrective surgery. METHODS: This retrospective study was performed from May 2009 to September 2014. We enrolled 35 patients with scoliosis associated with CM-1 and SM who were undergoing spinal correction surgery without neurosurgical intervention. During the surgery, spinal cord monitor and wake-up test were used. Preoperative, postoperative, and final follow-up major curve coronary Cobb angle, correction rate, apical vertebral rotation (AVR), apical vertebral translation (AVT), thoracic kyphosis angle (T5-T12), lumbar lordosis angle (L1-S1) were analyzed on radiographs. RESULTS: The mean follow-up period was 82.5 months. The preoperative and postoperative mean curve coronary Cobb angle was from 55.7 ± 7.5° to 20.1 ± 5.8°, correction rate was 63.9%, AVR from 2.8 ± 0.6° to 1.3 ± 0.5°, AVT from 5.1 ± 1.4 to 1.7 ± 0.7 cm, thoracic kyphosis angle from 18.7 ± 4.0° to 32.2 ± 2.7°, lumbar lordosis angle from 36.3 ± 4.1° to 43.8 ± 3.2°. No neurological deficits occurred during the operation and follow-up. CONCLUSIONS: Our minimum 5-year follow-up outcomes showed that in a distinct patient population of neurologically asymptomatic individuals with CM-1, SM and progressive scoliosis, posterior instrumented spinal deformity surgery can be safely done without neurosurgical interverventions with the help of preoperative flexibility evaluation and intraoperative neuromonitoring.

Halo traction combined with posterior-only approach correction for cervical kyphosis with Neurofibromatosis-1: minimum 2 years follow-up.

BACKGROUND: Surgical management of cervical kyphosis in patients with NF-1 is a challenging task. Presently, anterior-only (AO), posterior-only (PO) and combined anterior-posterior (AP) spinal fusion are common surgical strategies. However, the choice of surgical strategy and application of Halo traction remain controversial. Few studies have shown and recommended posterior-only approach for cervical kyphosis correction in patients with NF-1. The aim of this study is to evaluate the safety and the effectiveness of halo Traction combined with posterior-only approach correction for treatment of cervical kyphosis with NF-1. METHODS: Twenty-six patients with severe cervical kyphosis due to NF-1 were reviewed retrospectively between January 2010 and April 2018. All the cases underwent halo traction combined with posterior instrumentation and fusion surgery. Correction result, neurologic status and complications were analyzed. RESULTS: In this study, cervical kyphosis Cobb angle decreased from initial 61.3 ± 19.7 degrees to postoperative 10.6 ± 3.7 degrees (P<0.01), with total correction rate of 82.7%, which consist of 45.8% from halo traction and 36.9% from surgical correction. JOA scores were improved from preoperative 13.3 ± 1.6 to postoperative 16.2 ± 0.7 (P<0.01). Neurological status was also improved. There was no correction loss and the neurological status was stable in mean 43 months follow-up. Three patients experienced minor complications and one patient underwent a second surgery. CONCLUSION: Halo traction combined with PO approach surgery is safe and effective method for cervical kyphosis correction in patients with NF-1. A satisfied correction result, and successful bone fusion can be achieved via this procedure, even improvement of neurological deficits can also be obtained. Our study suggested that halo traction combined with PO approach surgery is another consideration for cervical kyphosis correction in patients with NF-1.

Posterior-only debridement, internal fixation, and interbody fusion using titanium mesh in the surgical treatment of thoracolumbar tuberculosis with spinal epidural abscess: a minimum 5-year follow-up.

OBJECTIVE: To investigate the clinical efficacy and feasibility of posterior-only debridement, internal fixation, and interbody fusion using titanium mesh in the surgical treatment of thoracolumbar tuberculosis (TB) with spinal epidural abscess. METHODS: From January 2008 to January 2014, a total of 45 patients (27 male and 18 female) were reviewed. The patients were diagnosed with thoracolumbar TB with spinal epidural abscess. The patients underwent posterior-only debridement, internal fixation, and interbody fusion using titanium mesh. Hence, we assessed the intraoperative and postoperative complications, disease recurrences, kyphosis deformity correction, and neurological improvement following the American Spinal Injury Association (ASIA). We used SPSS 22.0 for the statistical analyses. An independent Student's t-test was used for the analysis of preoperative and postoperative continuous variables. The value of P (P < 0.05) was considered statistically significant. RESULTS: The mean age of patients was 37.76 ± 10.94 years (17-59 years). The mean follow-up time was 82.76 ± 12.56 months (60-128 months). The mean kyphosis Cobb angle preoperative was 29.36 ± 13.29° (5-55°) and postoperative was 3.58 ± 5.44° (- 6-13°), given the value of P (P < 0.001). According to the neurological score by the ASIA scale, there were 3 cases of grade B, 11 cases of grade C, 16 cases of grade D, and 15 cases of grade E preoperatively. The neurological score improved by 1 ~ 2 grades. All patients achieved pain relief and the VAS score significantly reduced at the last follow-up (P<0.05). While 1 patient had cerebrospinal fluid leakage, 1 had a neurological complication, 1 had delayed surgical wound healing, and 1 had a disease recurrence. No pseudoarthrosis or implant failure occurred in our patients. All patients achieved solid bone graft fusion. CONCLUSION: For thoracolumbar TB patients with spinal epidural abscess, posterior-only debridement, internal fixation, and interbody fusion using titanium mesh are safe and effective surgical treatments.

High methylation of lysine acetyltransferase 6B is associated with the Cobb angle in patients with congenital scoliosis.

BACKGROUND: The etiology of congenital scoliosis (CS) is complex and uncertain. Abnormal DNA methylation affects the growth and development of spinal development. In this study, we investigated the role of DNA methylation in CS. METHODS: The target region DNA methylation level in the peripheral blood of patients with CS was analyzed. Through in-depth analysis, genes closely related to the growth and development of the vertebra were identified. EdU staining was performed to verify the role of differentially expressed genes in chondrocyte proliferation. RESULTS: The hypermethylated KAT6B gene was observed in patients with CS, and was positively correlated with the Cobb angle. KAT6B was primarily expressed on chondrocytes. The promoter of KAT6B in CS patients was hypermethylated, and its expression was significantly reduced. Further mechanistic studies revealed that EZH2 mediated trimethylation of lysine 27 on histone H3 of the KAT6B promoter. Overexpression of KAT6B in CS-derived primary chondrocytes can significantly promote chondrocyte proliferation, which may be related to activation of the RUNX2/Wnt/ß-catenin signaling pathway. CONCLUSION: Epigenetic modification of KAT6B may be a cause of CS. If similar epigenetic modification abnormalities can be detected through maternal liquid biopsy screening, they may provide useful biomarkers for early screening and diagnosis of CS.

Analyzing mode index mismatch and field overlap for light guidance in negative-curvature fibers.

We numerically investigate the role of cladding geometries in two widely used anti-resonant hollow-core fiber designs with negative curvatures, the tubular negative-curvature fiber and ice-cream-cone negative-curvature fiber. The confinement loss governed by the inhibited coupling between the modes in the core and cladding is thoroughly examined systematically against the core-cladding curvature for both types. We show that, in addition to the mode-index mismatch, the mode-field overlap also plays a key role in determining the loss. Simultaneously, we find the ice-cream-cone negative-curvature fiber can exhibit better loss performance than the tubular design within a specific range of the curvature. This enhancement is achieved without sacrificing the transmission bandwidth and is relatively robust against the fabrication error.

Band-edge mediated frequency down-conversion in a gas-filled anti-resonant hollow-core fiber.

We demonstrate frequency down-conversions of femtosecond pulses through dispersive wave generation and degenerate four-wave mixing in a gas-filled anti-resonant hollow-core fiber. These are achieved by exploiting the rapid variation of the dispersion in the fiber's transmission band edge. In this approach, the wavelength of the down-shifted radiation is governed solely by the thickness of the dielectric wall at the core-cladding interface, while other system parameters are accountable only for inducing sufficient nonlinear phase shifts. With the right choice of cladding wall thickness, the concept can be applied directly for generating high-power mid-infrared femtosecond pulses.

Functional role of hedgehog pathway in osteoarthritis.

The hedgehog signalling pathway is one of the key regulators of metazoan development, and it plays an important role in the regulation of a variety of developmental and physiological processes. But it is aberrantly activated in many human diseases, including osteoarthritis (OA). In this study, we have reviewed the association of hedgehog signalling pathway in the development and progression of OA and evaluated the efforts to target this pathway for the prevention of OA. Usually in OA, activation of hedgehog induces up-regulation of the expression of hypertrophic markers, including type X collagen, increases production of nitric oxide and prostaglandin E2, several matrix-degrading enzymes including matrix metalloproteinase and a disintegrin and metalloproteinase with thrombospondin motifs in human knee joint cartilage leading to cartilage degeneration, and thus contributes in OA. Targeting hedgehog signalling might be a viable strategy to prevent or treat OA. Chemical inhibitors of hedgehog signalling is promising, but they cause severe side effects. Knockdown of HH gene is not an option for OA treatment in humans because it is not possible to delete HH in larger animals. Efficient knockdown of HH achieved by local delivery of small interfering RNA in future studies utilizing large animal OA models might be a more efficient approach for the prevention of OA. However, it remains a major problem to develop one single scaffold due to the different physiological functions of cartilage and subchondral bones possess. More studies are necessary to identify selective inhibitors for efficiently targeting the hedgehog pathway in clinical conditions.

Posterior-only surgical correction with heavy halo-femoral traction for the treatment of rigid congenital scoliosis associated with split cord malformation.

BACKGROUND: Whether or not, prophylactic neurosurgical interventions of split cord malformation (SCM) before undertaking corrective surgery was the focus of debate. The present study was performed to evaluate the safety and efficacy of posterior-only surgical correction with heavy halo-femoral traction for the treatment of rigid congenital scoliosis (RCS) associated with SCM. METHODS: From 2011 to 2017, 24 patients suffered from RCS associated with SCM underwent posterior-only surgical correction with heavy halo-femoral traction. The apex of the deformity was lumbar (n = 9), thoracic (n = 11), and thoracolumbar (n = 4). There were 13 cases of failure of segmentation; 4 cases of failure of formation and 7 cases of mixed defects. Based on SCM classification, there were 14 patients with SCM type 1 and 10 patients with SCM type 2. The Scoliosis Research Society (SRS)-22 and modified Japanese Orthopaedic Association (mJOA) scores were assessed preoperatively and at the final follow up. RESULTS: The mean duration of surgery was 327.08 ± 43.99 min and the mean blood loss was 1303.33 ± 526.86 ml. The mean follow-up period was 20.75 ± 8.29 months. The preoperative mean coronal Cobb angle was 80.38° ± 13.55°; on the bending radiograph of the convex side, the mean Cobb angle was 68.91° ± 15.48°; the mean flexibility was 15.04% ± 7.11%. After heavy halo-femoral traction, the mean coronal Cobb angle was reduced to 56.89° ± 13.39°. After posterior-only surgical correction, postoperative mean coronal Cobb angle was further reduced to 32.54° ±11.33°. The postoperative mean correction rate was 60.51% ± 7.79%. At the final follow up, the corrective loss rate of Cobb angle was only 3.17%. The SRS-22 total score improved at the final follow-up evaluation compared with the preoperative SRS-22 total score. The spinal cord function was stable and there were no new neurological symptoms after correction. There were no significant differences between final follow-up and preoperative mJOA total scores. CONCLUSIONS: Without prophylactic neurosurgical intervention and spine-shortening osteotomy, posterior-only surgical correction with heavy halo-femoral traction could be safe and effective for the treatment of RCS associated with SCM.

Matrix metalloproteinase-1 promoter -1607 bp 1G/2G polymorphism associated with increased risk of spinal tuberculosis in Southern Chinese Han population.

BACKGROUND: Spinal tuberculosis is the most common form of musculoskeletal tuberculosis. The expression of matrix metalloproteinase-1 (MMP-1) is increased in cells with Mycobacterium tuberculosis infection. MMP-1 plays a curial role in extracellular matrix degradation during the progression of tuberculosis. Although the 1G/2G polymorphism in MMP-1-1607 influences its transcription, its role in spinal tuberculosis remains unknown. METHODS: Healthy controls and patients with spinal tuberculosis of Han ethnicity were recruited between January 2010 and May 2016. The MMP-1-1607 1G/2G polymorphism was genotyped using the Sequenom mass Array polymorphism analysis system. RESULTS: The genotypes of 1G/1G, 1G/2G, and 2G/2G were found in 13.7%, 53.6%, and 32.8% of patients, and 12.2%, 37.4%, and 50.4% of controls, respectively. The 1G/2G genotype were more common in cases than in controls (P=2.05E-04). The 1G allele showed an association with an increased risk for spinal tuberculosis when compared to 2G allele (P=.004). 1G genotypes, having at least one 1G allele, were associated with the risk of developing spinal tuberculosis (1G/1G+1G/2G vs 2G/2G: OR=2.084, 95%CI=1.401-3.100, P=2.65E-04). CONCLUSION: 1G genotypes of the MMP-1-1607 may be associated with susceptibility to spinal tuberculosis in Southern Chinese Han population.

One-stage posterior focus debridement, interbody grafts, and posterior instrumentation and fusion in the surgical treatment of thoracolumbar spinal tuberculosis with kyphosis in children: a preliminary report.

PURPOSE: The purpose of this study was to determine the efficacy and feasibility of surgical management of children with thoracolumbar spine tuberculosis with kyphosis by using one-stage posterior focus debridement, interbody grafts, and posterior instrumentation and fusion. METHODS: From October 2010 to September 2013, 21 children with thoracolumbar spinal tuberculosis accompanied by kyphosis were treated with one-stage posterior decompression, interbody grafts, and posterior instrumentation and fusion. There were 13 males and 8 females, aged from 7 to 13 years old (average age 9.9 years). The mean follow-up was 34 months (range26-48 months). Patients were evaluated before and after surgery in terms of ESR, neurologic status, pain, and kyphotic angle. RESULTS: Spinal tuberculosis was completely cured, and the grafted bones were fused in all 21 patients. There was no recurrent tuberculous infection. ESR got normal within 3 months in all patients. The ASIA neurologic classification improved in all cases. Pain relief was obtained in all patients. The average preoperative kyphosis was 29.7° (range 12-42°) and decreased to 5.5° (range 2-10°), postoperatively. There was no significant loss of the correction at the latest follow-up. CONCLUSIONS: Our results show that one-stage posterior decompression, interbody grafts, and posterior instrumentation and fusion were an effective treatment for children with thoracolumbar spinal tuberculosis. It is characterized as minimum surgical trauma, good neurologic recovery, good correction of kyphosis, and prevention of progressive kyphosis.

One-stage posterior focus debridement, interbody graft using titanium mesh cages, posterior instrumentation and fusion in the surgical treatment of lumbo-sacral spinal tuberculosis in the aged.

PURPOSE: Aged patients represent a high risk group for acquiring spinal tuberculosis, and it still remains a leading cause of kyphosis and paraplegia in developing nations. Aged patients often combined with cardiovascular and respiratory disease and single lung ventilation via anterior approach surgery could result in more post-operative complications. We aimed to analyze the efficacy and feasibility of surgical management of aged patients with lumbo-sacral spine tuberculosis using one-stage posterior focus debridement, interbody graft using titanium mesh cages, posterior instrumentation, and fusion. METHODS: From March 2009 and July 2012, 17 aged patients with lumbo-sacral spinal tuberculosis were treated with one-stage posterior focus debridement, interbody graft using titanium mesh cages, posterior instrumentation, and fusion. There were eight male and nine female with a mean age of 63.3 years (range: 60-71 years). The mean follow-up was 46.5 months (range 38-70 months). Patients were evaluated before and after surgery in terms of ESR, neurological status, visual analog scale (VAS), and lumbosacral angle. RESULTS: Spinal tuberculosis was completely cured and the grafted bones were fused in all 17 patients. There were no recurrent tuberculous infections. ESR became normal within three months in all patients. The ASIA neurological classification and VAS scores improved in all cases. The average preoperative lumbosacral angle was 20.6° (range 18.1°-22.5°) and became 29.4° (range 27.1°-32.5°) at final follow-up. CONCLUSIONS: Our results showed that one-stage posterior focus debridement, interbody graft using titanium mesh cages, posterior instrumentation, and fusion was an effective treatment for aged patients with lumbo-sacral spinal tuberculosis. It is characterized with minimum surgical trauma, good pain relief, good neurological recovery, and good reconstruction of the spinal stability.

A Zanamivir-protein conjugate mimicking mucin for trapping influenza virion particles and inhibiting neuraminidase activity.

Influenza viruses contribute significantly to the global health burden, necessitating the development of strategies against transmission as well as effective antiviral treatments. The present study reports a biomimetic strategy inspired by the natural antiviral properties of mucins. A bovine serum albumin (BSA) conjugate decorated with the multivalent neuraminidase inhibitor Zanamivir (ZA-BSA) was synthesized using copper-free click chemistry. This synthetic pseudo-mucin exhibited potent neuraminidase inhibitory activity against several influenza strains. Virus capture and growth inhibition assays demonstrated its effective absorption of virion particles and ability to prevent viral infection in nanomolar concentrations. Investigation of the underlying antiviral mechanism of ZA-BSA revealed a dual mode of action, involving disruption of the initial stages of host-cell binding and fusion by inducing viral aggregation, followed by blocking the release of newly assembled virions by targeting neuraminidase activity. Notably, the conjugate also exhibited potent inhibitory activity against oseltamivir-resistant neuraminidase variant comparable to the monomeric Zanamivir. These findings highlight the application of multivalent drug presentation on protein scaffold to mimic mucin adsorption of viruses, together with counteracting drug resistance. This innovative approach has potential for the creation of antiviral agents against influenza and other viral infections.

Cervical Sagittal Alignment and Related Factor Analysis and Prediction Model in Patients Undergoing Revision Surgery After Anterior Cervical Fusion.

INTRODUCTION: Patients with myelopathy or radiculopathy commonly undergo anterior cervical fusion surgery (ACFS), which has a notable failure rate on occasion. The goal of this study was to compare revision and nonrevision surgery patients in cervical sagittal alignment (CSA) subsequent to ACFS; additionally, to identify the best CSA parameters for predicting clinical outcome after ACFS; and furthermore, to create an equation model to assist surgeons in making decisions on patients undergoing ACFS. METHODS: The data of 99 patients with symptomatic cervical myelopathy/radiculopathy who underwent ACFS were analyzed. Patients were divided into group A (underwent revision surgery after the first surgery failed) and group B (underwent only the first surgery). We measured and analyzed both preoperative and postoperative CSA parameters, including C2 slope, T1 slope, cervical lordosis C2-C7 (CL), C2-C7 sagittal vertical axis (C2C7 SVA), occiput-C2 lordosis angle (C0-C2), and chin brow vertical angle, and we further computed the correlation between the CSA parameters and created a prediction model. RESULTS: The (T1S-CL)-C2S mismatch differed significantly between groups A and B ([9.95 ± 9.95] 0 , [3.79 ± 6.58] 0 , P < 0.05, respectively). A significant correlation was observed between C2 slope and T1CL in group B relative to group A postoperatively (R 2 = 0.42 versus R 2 = 0.09, respectively). Compared with group B, patients in group A had significantly higher C2C7SVA values, more levels of fusion, and more smokers. The sensitivity, specificity, accuracy, and discrimination of the model were, respectively, 73.5%, 84%, 78.8%, and 85.65%. CONCLUSION: The causes of revision surgery in cervical myelopathic patients after anterior cervical corpectomy and fusion/anterior cervical diskectomy and fusion are multifactorial. (T1S-CL)-C2S mismatch and high C2C7SVA are the best cervical sagittal parameters that increase the odds of revision surgery, and the effect is more enhanced when comorbidities such as smoking, low bone-mineral density, and increased levels of fusion are taken into account.

The use of posterior vertebral column resection in the management of severe posttuberculous kyphosis: a retrospective study and literature review.

PURPOSE: We present a retrospective study of 15 cases with severe posttuberculous kyphosis of thoracolumbar region that underwent posterior vertebral column resection. METHODS: From 2004 to 2009, 15 consecutive patients with posttubercular kyphotic deformity underwent posterior vertebral resection osteotomy. Six subjects were females and nine were males with an average age of 35.8 years (range 20-60 years) at the time of surgery. None of the patients had neurological deficits. The mean preoperative visual analogue scale was 8.7 (range 3-9), and the average preoperative Oswestry Disability Index was 46.5 (range 40-56). RESULTS: The average duration of postoperative follow-up was 36.1 ± 10.7 months (range 24-62 months). The number of vertebra resected was 1.3 (range 1-2) on average. There were ten patients with one-level osteotomy and five patients with two-level osteotomy. The average operation time was 446.0 ± 92.5 min (range 300-640 min) with an average blood loss of 1,653.3 ± 777.9 ml (range 800-3000 ml). The focal kyphosis before surgery averaged 92.3 ± 8.9° (range 74-105°), and the kyphotic angle decreased to 34.5 ± 8.7° on average after the surgical correction. The average kyphotic angle at the last follow-up was 36.9 ± 8.5°, loss of correction was 2.4 ± 1.4° on average. All patients postoperatively received bony fusion within 6-9 months. CONCLUSIONS: Our results showed that although posterior vertebral resection is a highly technical procedure, it can be used safely and effectively in the management of severe posttuberculous kyphosis. It is imperative that operations be performed by an experienced surgical team to prevent operation-related complications.

Inhibition of miR-182-5p Targets FGF9 to Alleviate Osteoarthritis.

Background: The pathogenesis of osteoarthritis (OA) is complex and there is no specific drug for treatment. The aim of this study was to identify the molecular targets of OA therapy, focusing on the expression and biological functions of miR-182-5p and its target genes in OA. Methods: miR-182-5p and fibroblast growth factor 9 (FGF9) were overexpressed or knocked down in IL-1ß-induced chondrocytes. An OA knee model was performed by surgically destroying the medial meniscus. The gene expression of miR-182-5p and FGF9 was calculated. The protein FGF9 was tested by western blotting. Cell counting kit-8 (CCK8), plate cloning assay, and flow cytometry were conducted to evaluate cell proliferation and apoptosis. The expression of inflammatory factors, tumor necrosis factor-alpha (TNF-α), interleukin (IL)-6, and interleukin (IL)-8, was evaluated using enzyme-linked immunosorbent assay (ELISA). Dual-luciferase reporter assays validated the targeting relationship between miR-182-5p and FGF9. Hematoxylin-eosin (HE) and safranin O-fast Green (S-O) staining were utilized to access cartilage damage. Ki67 expression in cartilage was detected using immunohistochemistry (IHC). TdT-mediated dUTP nick-end labeling (TUNEL) assays were used to calculate the apoptosis rate of cartilage. Results: The expression of miR-182-5p was upregulated, and FGF9 was downregulated in the IL-1ß-induced chondrocytes. OA chondrocytes proliferation ability in the miR-182-5p mimics group was decreased, and the apoptosis rate and inflammatory factor were increased. Transfection with miR-182-5p inhibitor increased the proliferative ability and decreased the apoptosis rate in the IL-1ß-induced chondrocytes. Transfection with miR-182-5p inhibitor reversed IL-1ß-induced inflammatory factor release in chondrocytes. Targeted binding sites existed between miR-182-5p and FGF9. After overexpression of FGF9, the miR-182-5p effect on OA chondrocytes was reversed. The hyaline cartilage thickness and proteoglycan content decreased in OA rats, and this was reversed by miR-182-5p inhibitor treatment. Conclusions: miR-182-5p expression levels were increased in OA chondrocytes and regulated chondrocyte proliferation, apoptosis, and inflammation by targeting FGF9. miR-182-5p is a potential gene for OA treatment.

Promotion effect of FGF23 on osteopenia in congenital scoliosis through FGFr3/TNAP/OPN pathway.

BACKGROUND: Congenital scoliosis (CS) is a complex spinal malformation of unknown etiology with abnormal bone metabolism. Fibroblast growth factor 23 (FGF23), secreted by osteoblasts and osteocytes, can inhibit bone formation and mineralization. This research aims to investigate the relationship between CS and FGF23. METHODS: We collected peripheral blood from two pairs of identical twins for methylation sequencing of the target region. FGF23 mRNA levels in the peripheral blood of CS patients and age-matched controls were measured. Receiver operator characteristic (ROC) curve analyses were conducted to evaluate the specificity and sensitivity of FGF23. The expression levels of FGF23 and its downstream factors fibroblast growth factor receptor 3 (FGFr3)/tissue non-specific alkaline phosphatase (TNAP)/osteopontin (OPN) in primary osteoblasts from CS patients (CS-Ob) and controls (CT-Ob) were detected. In addition, the osteogenic abilities of FGF23-knockdown or FGF23-overexpressing Ob were examined. RESULTS: DNA methylation of the FGF23 gene in CS patients was decreased compared to that of their identical twins, accompanied by increased mRNA levels. CS patients had increased peripheral blood FGF23 mRNA levels and decreased computed tomography (CT) values compared with controls. The FGF23 mRNA levels were negatively correlated with the CT value of the spine, and ROCs of FGF23 mRNA levels showed high sensitivity and specificity for CS. Additionally, significantly increased levels of FGF23, FGFr3, OPN, impaired osteogenic mineralization and lower TNAP levels were observed in CS-Ob. Moreover, FGF23 overexpression in CT-Ob increased FGFr3 and OPN levels and decreased TNAP levels, while FGF23 knockdown induced downregulation of FGFr3 and OPN but upregulation of TNAP in CS-Ob. Mineralization of CS-Ob was rescued after FGF23 knockdown. CONCLUSIONS: Our results suggested increased peripheral blood FGF23 levels, decreased bone mineral density in CS patients, and a good predictive ability of CS by peripheral blood FGF23 levels. FGF23 may contribute to osteopenia in CS patients through FGFr3/TNAP / OPN pathway.