A comparative study of one-stage posterior unilateral limited laminectomy vs. bilateral laminectomy debridement and bone grafting fusion combined with internal fixation for the treatment of aged patients with single-segment spinal tuberculosis.

STUDY DESIGN: This is a retrospective study. BACKGROUND: To assess and compare the clinical outcomes of posterior unilateral limited laminectomy (ULL) or bilateral laminectomy (BL) debridement and bone grafting fusion combined with internal fixation among aged patients with single-segment thoracic and lumbar tuberculosis (SST/LTB). MATERIALS AND METHODS: We performed a retrospective study on aged patients (age > 65 years old) with SST/LTB from January 2010 to October 2018. We reviewed 36 aged patients who were treated with BL and 31 aged patients treated with ULL. All participants had undergone and finished a three-year follow-up. The outcomes were evaluated by the improvement of neurological function, correction Cobb angle, bone fusion time, and back pain, as well as operative time, blood loss, hospital stay, and postoperative complications. RESULTS: The operative time, blood loss volume, and incidence of complications in group B were significantly less than those in group A (P < 0.01). The postoperative kyphotic angle in both groups was reduced significantly compared to the preoperative status (P < 0.01). The percentage of neurological improvement was 92.9% in group A and 90.9% in group B. All patients achieved solid bone fusion after surgery. At three-year follow-up, the angle loss in group B was significantly less than that in group A (P < 0.01); Furthermore, patients in group B had a lower average visual analog scale score of back pain and Oswestry Disability Index score than patients in group A (P < 0.05). CONCLUSIONS: For aged patients with SST/LTB, ULL is a safer and more effective surgical treatment than BL.

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.

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.

Diagnostic efficiency of metagenomic next-generation sequencing on spinal infection and prognosis. / å®åŸºå› äºŒä»£æµ‹åºæŠ€æœ¯å¯¹è„ŠæŸ±æ„ŸæŸ“çš„è¯Šæ–­æ•ˆçŽ‡åŠé¢„åŽçš„å½±å“.

OBJECTIVES: Spinal infection is a rare infectious disease that is difficult to treat. The incidence of spinal infection is on the rise with the experiential use of antibiotics, the increasing incidence of drug-resistant bacteria, and the improvement of detection techniques. Traditional detection methods have limitations such as low sensitivity and long time-consuming in the diagnosis of spinal infection. In the clinical diagnosis and treatment of spinal infection, it has always been the focus and difficulty to determine the type of pathogens and to use antibiotics in a targeted manner. Many patients in the early stage of spinal infection due to the limitations of traditional detection methods cannot be quickly and accurately diagnosed, resulting in diagnosis delay, missed the best treatment time, bringing disastrous consequences to patients. There is an urgent need for a high-specificity, high-sensitivity, and time-saving test technique in clinical practice, which can simultaneously distinguish and identify the pathogen of spinal infection. Metagenomic next-generation sequencing (mNGS) is a new frontier technology emerging in recent years. It can detect all known pathogens in samples and has been used to diagnose clinically atypical and rare infectious diseases. This study aims to analyze the sensitivity of mNGS technique in diagnosing pathogens after spinal infection and its effect on prognosis. METHODS: Clinical data of 82 patients with spinal infection admitted to Xiangya Hospital of Central South University from January 2019 to December 2021 were retrospectively analyzed. Peripheral blood erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), and procalcitonin (PCT) were routinely performed before surgery, and focal tissue specimens were obtained during surgery. Microbial culture, histopathological examination, and mNGS detection were performed. All patients were assigned into a targeted medication group (n=71) and an experienced treatment group (n=1) based on the results of mNGS. After regular follow-up, the sensitivity of mNGS to detect pathogens of spinal infection and its effect on prognosis were evaluated. RESULTS: The positive rate of mNGS (86.59%, 71/82) was significantly higher than that of microbial culture (18.99%, 15/79) and PCT (30.23%, 13/43). There were no significant differences in preoperative temperature, white blood cell count, neutrophil ratio, and scores of Visual Analogue Scale between the targeted medication group and the experienced treatment group. Preoperative use of antibiotics had no significant effect on the positive rate of mNGS and microbial culture (P=0.681). According to the targeted medication group, postoperative CRP and ESR showed a decreasing trend, and the ESR was significantly lower than that of the experienced treatment group at 30 days follow-up (P=0.044). CONCLUSIONS: Compared with the microbial culture or PCT, mNGS has a higher sensitivity rate to detect pathogens of spinal infection. Patients receiving targeted antibiotics based on the results of mNGS have better outcomes than those receiving the experienced medicine.

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.

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.

Endoscopic L5/S1 discectomy through interlaminar approach for the patient with the high iliac crest and migrated disc herniation. / è„ŠæŸ±å† é•œæ¤Žæ¿é—´å ¥è·¯æ²»ç–—é«˜é«‚åµ´L5/S1è„±åž‚åž‹è °æ¤Žé—´ç›˜çªå‡ºç—‡.

OBJECTIVES: To explore the clinical efficacy of endoscopic L5/S1 discectomy through interlaminar approach for the patient with the high iliac crest and migrated disc herniation. METHODS: A retrospective study of 31 patients with the high iliac crest and migrated disc herniation at the L5/S1 level was conducted in our hospital. All of the consented patients accepted endoscopic L5/S1 discectomy through interlaminar approach from January 2016 to January 2019. Preoperative, postoperative, and follow-up Visual Analogue Scale (VAS) and Oswestry Disability Index (ODI) were used to assess the pain and waist function of patients. The clinical efficacy was evaluated according to Macnab criteria. RESULTS: All the patients were followed up for 12-48 (29.68±9.64) months. The operation time was (79.16±22.43) min. The times of fluoroscopy were 2.71±0.78. The VAS of low back and leg pain was 7.09±0.94 before the surgery, 1.45±1.23 at 3 months after the surgery, and 1.27±0.92 at the last follow-up. The VAS after the surgery and at the last follow-up was significantly lower than that before the operation (P<0.05). The ODI was 56.03±6.64 before the surgery, 16.45±6.83 at 3 months after the surgery, and 13.03±4.96 at the last follow-up. The ODI was significantly lower after the surgery and at the last follow-up compared with that before the surgery (P<0.05). The Macnab score at the last follow-up was graded as excellent in 26 cases, good in 3 cases, fair in 2 cases, and the percentage of excellent and good were 93.5%. Part of the nucleus pulposus remained in 2 cases after the operation, one case underwent endoscopic revision and one case received conservative treatment; postoperative pain due to nerve root irritation was in one case and relieved by conservative treatment. CONCLUSIONS: The endoscopic L5/S1 discectomy through interlaminar approach is a relatively safe and effective treatment for the patient with the high iliac crest and migrated disc herniation, which can reduce X-ray examinations and complications, and achieve satisfactory clinical outcomes.

Taxifolin Inhibits Receptor Activator of NF-κB Ligand-Induced Osteoclastogenesis of Human Bone Marrow-Derived Macrophages in vitro and Prevents Lipopolysaccharide-Induced Bone Loss in vivo.

It has been reported that taxifolin inhibit osteoclastogenesis in RAW264.7 cells. In our research, the inhibition effects of taxifolin on the osteoclastogenesis of human bone marrow-derived macrophages (BMMs) induced by receptor activator of NF-κB ligand (RANKL) as well as the protection effects in lipopolysaccharide-induced bone lysis mouse model have been demonstrated. In vitro, taxifolin inhibited RANKL-induced osteoclast differentiation of human BMMs without cytotoxicity. Moreover, taxifolin significantly suppressed RANKL-induced gene expression, including tartrate-resistant acid phosphatase, matrix metalloproteinase-9 nuclear factor of activated T cells 1 and cathepsin K, and F-actin ring formation. Further studies showed that taxifolin inhibit osteoclastogenesis via the suppression of the NF-κB signaling pathway. In vivo, taxifolin prevented bone loss in mouse calvarial osteolysis model. In conclusion, the results suggested that taxifolin has a therapeutic potential for osteoclastogenesis-related diseases such as osteoporosis, osteolysis, and rheumatoid arthritis.

Changes in circulating cell-free nuclear DNA and mitochondrial DNA of patients with adolescent idiopathic scoliosis.

BACKGROUND: Adolescent idiopathic scoliosis (AIS) which characterized by complex three-dimensional deformity of spine has been difficult to cure because of the unknown etiopathology and uncertainty of progression. Nowadays, circulating cell-free (ccf) DNA was found to be a potential biomarker for several benign and malignant diseases. However, whether ccf DNA can be a biomarker for AIS has not been reported yet. In this study, we investigate the circulating cell-free nuclear DNA (ccf n-DNA) and mitochondrial DNA (ccf mt-DNA) concentrations in the plasma of patients with AIS and controls (CT), and the changed plasma ccf n-DNA and ccf mt-DNA levels and their association with clinical parameters were assessed. METHODS: The plasma of peripheral blood from 69 AIS patients and 21 age-matched CT was collected for ccf DNA analysis. Quantitative PCR was used to detect ccf n-DNA and ccf mt-DNA levels, and correlation analyses between the ccf n-DNA and ccf mt-DNA levels and clinical characteristics were conducted. Receiver operator curves (ROC) were used to analyze the sensitivity and specificity of ccf n-DNA and ccf mt-DNA levels to different characteristics. RESULTS: The plasma ccf n-DNA levels of both GAPDH and ACTB were significantly decreased in AIS patients compared with those in controls, while the plasma ccf mt-DNA levels did not changed. According to sex-related analyses, the ccf n-DNA levels in male CT-M was higher than that in female CT and male AIS, but the ccf n-DNA levels in female AIS was not significantly changed when compared with male AIS or female CT. However, the concentration of ccf mt-DNA in female AIS increased significantly when compared with male AIS. Surprisingly, Lenke type-related analyses suggested that Lenke type 1 patients had lower ccf n-DNA levels, whereas Lenke type 5 patients had higher ccf mt-DNA levels compared with those of controls. However, a lower sensitivity and specificity of AIS predicted by ccf n-DNA or ccf mt-DNA levels was observed, whether in total, by sex, or by Lenke type. CONCLUSION: Although with no/little predictive accuracy of AIS/progressed AIS by ccf DNA levels, significantly changed plasma ccf DNA levels were observed in AIS patients compared with those in controls.

Refractive Error in Chinese Preschool Children: The Shanghai Study.

PURPOSE: To examine the prevalence of refractive error and some associated factors in Chinese preschool children. METHODS: The Jinshan District Eye Study was a school-based survey of eye health in a large sample of 4- to 6-year-olds attending kindergartens from May 2013 to December 2013 in Shanghai. Refractive error was measured using an autorefractor under noncycloplegic conditions. Axial length (AL) was measured with an ocular biometry system. In addition, body height and weight were also recorded. RESULTS: A total of 7,166 children successfully completed their refraction measurements. The median (interquartile range) of spherical equivalent (SE) for all the children was +0.25 D (-0.13 D to +0.62 D), and the range was -15.88 to +18.13 D. The mean AL for all the children was 22.35±0.70 mm, and the range was 18.20 to 27.71 mm. The overall prevalence of myopia (-1.00 D or less), hyperopia (+2.00 D or greater), and astigmatism (1.00 D or greater) were 5.9%, 1.0%, and 12.7%, respectively. After multivariate analysis, more myopic SE (or less hyperopic SE) was significantly associated with girls, longer AL, taller, and lighter. CONCLUSION: Shanghai has a high prevalence of refractive error in the world. However, longitudinal studies are needed to evaluate refractive changes over time in individual children and warranted to prevent the development of myopia.

Modulating calcium-mediated NFATc1 and mitogen-activated protein kinase deactivation underlies the inhibitory effects of kavain on osteoclastogenesis and bone resorption.

Osteoclasts are responsible for bone resorption during the process of bone remodeling. Increased osteoclast numbers and bone resorption activity are the main factors contributing to bone loss-related diseases such as osteoporosis. Therefore, modulating the formation and function of osteoclasts is critical for the effective treatment of osteolysis and osteoporosis. Kavain is the active ingredient extracted from the root of the kava plant, which possesses known anti-inflammatory properties. However, the effects of kavain on osteoclastogenesis and bone resorption remain unclear. In this study, we found that kavain inhibits receptor activator of nuclear factor-κB ligand (RANKL)-induced osteoclast differentiation and fusion using tartrate-resistant acid phosphatase staining and immunofluorescence. Furthermore, kavain inhibited bone resorption performed by osteoclasts. Using reverse transcription-polymerase chain reaction and western blot analysis, we found that kavain downregulates the expression of osteoclast marker genes, such as nuclear factor of activated T cells, cytoplasmic 1 (Nfatc1), v-atpase d2 (Atp6v0d2), dendrocyte expressed seven transmembrane protein (Dcstamp), matrix metallopeptidase 9 (Mmp9), cathepsin K (Ctsk), and Acp5. Additionally, kavain repressed RANKL-induced calcium oscillations, nuclear factor of activated T cells activation, and mitogen-activated protein kinase phosphorylation, while leaving NF-κB unaffected. We found no effects of kavain on either osteoblast proliferation or differentiation. Besides, kavain inhibited bone loss in ovariectomized mice by suppressing osteoclastogenesis. Collectively, these data suggest a potential use for kavain as a candidate drug for the treatment of osteolytic diseases.

Taxifolin enhances osteogenic differentiation of human bone marrow mesenchymal stem cells partially via NF-κB pathway.

Taxifolin, a flavonoid compound, has been reported to stimulate osteogenic differentiation in osteoblasts. The present study investigated whether taxifolin affects the osteogenic differentiation of human bone marrow mesenchymal stem cells (hBMSCs) and the molecular mechanisms involved. The proliferation and osteogenic differentiation of hBMSCs in the presence of taxifolin were examined by CCK-8 assay, alkaline phosphatase (ALP) activity, ALP staining and Alizarin red staining. The expression of osteogenic differentiation markers were detected by real-time quantitative PCR (RT-PCR) analysis and western blot assay. The activation of potential related pathways was examined by luciferase reporter assay, immunofluorescence and western blot analysis. Taxifolin treatment increased osteogenic differentiation of hBMSCs without cytotoxicity. Luciferase reporter assay showed that taxifolin could not activate estrogen receptor pathway, but inhibit TNF-α-induced NF-κB signaling pathway activation in osteogenic induction condition. Moreover, the nucleus translocation of NF-κB under TNF-α treatment was inhibited by taxifolin treatment. The taxifolin-induced osteogenic differentiation effects of hBMSCs were abolished by TNF-α treatment. In conclusion, our results suggested that taxifolin could promote osteogenesis of hBMSCs, partially through antagonism of NF-κB signaling pathway.

Association of IFNG gene polymorphisms with pulmonary tuberculosis but not with spinal tuberculosis in a Chinese Han population.

Spinal tuberculosis (STB) is an extrapulmonary form of tuberculosis (TB) caused by Mycobacterium tuberculosis (Mtb), which accounts for around 2% of all TB cases and can lead to spine degeneration. It is widely accepted that host genetic factors participate in the pathogenesis of active TB, but the factors controlling which TB form will manifest after Mtb infection remain unknown. We hypothesized that a genetic difference may exist between the development of STB and pulmonary tuberculosis (PTB). Here, three single nucleotide polymorphisms (SNPs) in the IFNG gene (rs2069718), IRGM gene (rs10065172), and MBL2 gene (rs11003125) were genotyped among 183 PTB patients, 177 STB patients, and 360 healthy controls from the Chinese Han population. We found that rs2069718 genotypes were significantly associated with PTB (TT, p = 0.007; CT, p = 0.008) but not STB, and the TT genotype (p = 0.046) of rs2069718 were less common in PTB than in STB. In contrast, neither PTB nor STB were found to be associated with rs10065172 and rs11003125. Overall, we found a difference in the rs2069718 genetic distribution between the STB and PTB patients in a Chinese Han population. The rs2069718 TT genotype was associated with a protective role in PTB but not STB development during active Mtb infection.

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.

Estradiol via estrogen receptor beta inhibits chondrogenesis of mouse vertebral growth plate in vitro.

PURPOSE: Abnormal growth of vertebral growth plate (VGP) was considered as one of the etiologic factors in adolescent idiopathic scoliosis (AIS). Previous studies described that estrogen played an important role in the pathogenesis of AIS. The present study was aimed to investigate the effect of estrogen/estrogen receptor axis on mouse VGP chondrocytes in vitro. METHODS: Chondrocytes were isolated from mouse VGP and treated with or without 17ß-estradiol (E2). Cell proliferation was measured by the cell growth rate assay. Gene expression of collagen type II and aggrecan were evaluated by real-time PCR. Expression of the proliferating cell nuclear antigen (PCNA), Sox9, and Smad4 were detected by Western blotting. RESULTS: Estradiol inhibited the proliferation of VGP chondrocytes and the gene expression of collagen type II and aggrecan and downregulated the protein expression of PCNA, Sox9, and Smad4. In addition, the inhibitory effect of estradiol was reversed by ERß small interfering RNA (siRNA) or PHTPP, an ERß antagonist. CONCLUSIONS: Estradiol via estrogen/estrogen receptor ß axis inhibits the proliferation and differentiation of VGP chondrocytes, which might give some new insight into the regulatory mechanism of bone development.

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.

Identification of pathogen composition in a Chinese population with iatrogenic and native vertebral osteomyelitis by using mNGS.

BACKGROUND: Early antimicrobial therapy is crucial regarding the prognosis of vertebral osteomyelitis, but early pathogen diagnosis remains challenging. OBJECTIVE: In this study, we aimed to differentiate the types of pathogens in iatrogenic vertebral osteomyelitis (IVO) and native vertebral osteomyelitis (NVO) to guide early antibiotic treatment. METHODS: A total of 145 patients, who had confirmed spinal infection and underwent metagenomic next-generation sequencing (mNGS) testing, were included, with 114 in the NVO group and 31 in the IVO group. Using mNGS, we detected and classified 53 pathogens in the 31 patients in the IVO group and 169 pathogens in the 114 patients in the NVO group. To further distinguish IVO from NVO, we employed machine learning algorithms to select serum biomarkers and developed a nomogram model. RESULTS: The results revealed that the proportion of the Actinobacteria phylum in the NVO group was approximately 28.40%, which was significantly higher than the 15.09% in the IVO group. Conversely, the proportion of the Firmicutes phylum (39.62%) in the IVO group was markedly increased compared to the 21.30% in the NVO group. Further genus-level classification demonstrated that Staphylococcus was the most common pathogen in the IVO group, whereas Mycobacterium was predominant in the NVO group. Through LASSO regression and random forest algorithms, we identified 5 serum biomarkers including percentage of basophils (BASO%), percentage of monocytes (Mono%), platelet volume (PCT), globulin (G), activated partial thromboplastin time (APTT) for distinguishing IVO from NVO. Based on these biomarkers, we established a nomogram model capable of accurately discriminating between the two conditions. CONCLUSION: The results of this study hold promise in providing valuable guidance to clinical practitioners for the differential diagnosis and early antimicrobial treatment of vertebral osteomyelitis.

One-stage surgical treatment for upper thoracic spinal tuberculosis by internal fixation, debridement, and combined interbody and posterior fusion via posterior-only approach.

PURPOSE: To investigate the clinical efficacy and feasibility of one-stage surgical treatment for upper thoracic spinal tuberculosis by internal fixation, debridement, and combined interbody and posterior fusion via a posterior-only approach. METHODS: Fourteen patients (eight males, six females) with upper thoracic tuberculosis whose lesions were confined to two adjacent segments were admitted to our hospital. Their ages ranged from 23 to 72 years (average, 50 years). The American Spinal Injury Association (ASIA) impairment scale was used to assess neurological function. ASIA classification showed that preoperatively, one patient was grade A, two patients were grade B, eight patients were grade C, and three patients were grade D. All patients were treated with one-stage surgical treatment by internal fixation, debridement, and combined interbody and posterior fusion via a posterior-only approach. Patients were evaluated preoperatively and postoperatively by measurement of thoracic kyphotic angles using Cobb angle evaluation, determination of erythrocyte sedimentation rate (ESR), evaluation of ASIA impairment scale, and radiological examination. RESULTS: Operation time ranged from 70 to 135 min, (average, 110 min). Intraoperative blood loss ranged from 200 to 950 mL (average, 450 mL). All patients were followed up for 22 to 48 months postoperatively (average, 31.5 months). No sinus tract formation, cerebrospinal meningitis, or recurrence of tuberculosis occurred. All patients had significant postoperative improvement in ASIA classification scores. The thoracic kyphotic angles were significantly decreased to 12°-26° postoperatively, and at final follow-up were 13°-28°. The ESR recovered to normal within 6 months postoperatively in all patients. Bone fusion was achieved within 3-8 months (average, 5.5 months). CONCLUSIONS: One-stage surgical treatment for upper thoracic spinal tuberculosis by internal fixation, debridement, and combined interbody and posterior fusion via a posterior-only approach can be an effective and feasible treatment method.

Clinical application value of metagenomic next-generation sequencing in the diagnosis of spinal infections and its impact on clinical outcomes.

This study aimed to evaluate the impact of precise treatment administered according to the results of metagenomic next-generation sequencing (mNGS) on the clinical outcomes of patients with spinal infections. In this multicenter retrospective study, the clinical data of 158 patients with spinal infections who were admitted to Xiangya Hospital Central South University, Xiangya Boai Rehabilitation Hospital, The First Hospital of Changsha, and Hunan Chest Hospital from 2017 to 2022 were reviewed. Among these 158 patients, 80 patients were treated with targeted antibiotics according to the mNGS results and were assigned to the targeted medicine (TM) group. The remaining 78 patients with negative mNGS results and those without mNGS and negative microbial culture results were treated with empirical antibiotics and assigned to the empirical drug (EM) group. The impact of targeted antibiotics based on the mNGS results on the clinical outcomes of patients with spinal infections in the two groups was analyzed. The positive rate of mNGS for diagnosing spinal infections was significantly higher than that of microbiological culture (X 2=83.92, P<0.001), procalcitonin (X 2=44.34, P<0.001), white blood cells (X 2=89.21, P < 0.001), and IGRAs (Interferon-gamma Release Tests) (X 2 = 41.50, P < 0.001). After surgery, C-reactive protein (CRP) and erythrocyte sedimentation rate (ESR) showed a decreasing trend in the patients with spinal infections in both the TM and EM groups. The decrease in CRP was more obvious in the TM group than in the EM group at 7, 14 days, 3, and 6 months after surgery (P<0.05). The decrease in ESR was also significantly obvious in the TM group compared with the EM group at 1 and 6 months after surgery (P<0.05). The time taken for CRP and ESR to return to normal in the TM group was significantly shorter than that in the EM group (P<0.05). There was no significant difference in the incidence of poor postoperative outcomes between the two groups. The positive rate of mNGS for the diagnosis of spinal infection is significantly higher than that of traditional detection methods. The use of targeted antibiotics based on mNGS results could enable patients with spinal infections to achieve a faster clinical cure.