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.

Phosphorylated heat shock protein 27 improves the bone formation ability of osteoblasts and bone marrow stem cells from patients with adolescent idiopathic scoliosis.

Background: Adolescent idiopathic scoliosis (AIS) is a scoliotic deformity of unknown etiology that occurs during adolescent development. Abnormal bone metabolism is closely related to AIS, but the cause is uncertain. Recent studies have shown that heat shock protein 27 (HSP27) and its phosphorylation (pHSP27) play important roles in bone metabolism. However, whether HSP27 and pHSP27 are involved in abnormal bone metabolism in AIS is unclear. Methods: Osteoblasts (OBs) and bone marrow stem cells (BMSCs) were extracted from the facet joints and bone marrow of AIS patients and controls who underwent posterior spinal fusion surgery. The expression levels of HSP27 and pHSP27, as well as the expression levels of bone formation markers in OBs from AIS patients and controls, were examined by quantitative real-time PCR (qRT-PCR) and Western blotting. The mineralization ability of OBs from AIS patients and controls was analyzed by alizarin red staining after osteogenic differentiation. Heat shock and thiolutin were used to increase the levels of pHSP27 in OBs, and the levels of bone formation markers were also investigated. In addition, the levels of pHSP27 and the bone formation ability of BMSCs from AIS patients and controls were investigated after heat shock treatment. Results: Lower pHSP27 levels and impaired osteogenic differentiation abilities were observed in the OBs of AIS patients than in those of controls. Thiolutin increased HSP27 phosphorylation and increased the mRNA levels of SPP1 and ALPL in OBs from AIS patients. Heat shock treatment increased SPP1 and HSP27 mRNA expression, pHSP27 levels, OCN expression, and mineralization ability of both OBs and BMSCs from AIS patients. Conclusion: Heat shock treatment and thiolutin can increase the levels of pHSP27 and further promote the bone formation of OBs and BMSCs from AIS patients. Therefore, decreased pHSP27 levels may be associated with abnormal bone metabolism in AIS patients.

Analysis of risk factors for deep vein thrombosis after spinal infection surgery and construction of a nomogram preoperative prediction model.

Objective: To investigate the differences in postoperative deep venous thrombosis (DVT) between patients with spinal infection and those with non-infected spinal disease; to construct a clinical prediction model using patients' preoperative clinical information and routine laboratory indicators to predict the likelihood of DVT after surgery. Method: According to the inclusion criteria, 314 cases of spinal infection (SINF) and 314 cases of non-infected spinal disease (NSINF) were collected from January 1, 2016 to December 31, 2021 at Xiangya Hospital, Central South University, and the differences between the two groups in terms of postoperative DVT were analyzed by chi-square test. The spinal infection cases were divided into a thrombotic group (DVT) and a non-thrombotic group (NDVT) according to whether they developed DVT after surgery. Pre-operative clinical information and routine laboratory indicators of patients in the DVT and NDVT groups were used to compare the differences between groups for each variable, and variables with predictive significance were screened out by least absolute shrinkage and operator selection (LASSO) regression analysis, and a predictive model and nomogram of postoperative DVT was established using multi-factor logistic regression, with a Hosmer- Lemeshow goodness-of-fit test was used to plot the calibration curve of the model, and the predictive effect of the model was evaluated by the area under the ROC curve (AUC). Result: The incidence of postoperative DVT in patients with spinal infection was 28%, significantly higher than 16% in the NSINF group, and statistically different from the NSINF group (P < 0.000). Five predictor variables for postoperative DVT in patients with spinal infection were screened by LASSO regression, and plotted as a nomogram. Calibration curves showed that the model was a good fit. The AUC of the predicted model was 0.8457 in the training cohort and 0.7917 in the validation cohort. Conclusion: In this study, a nomogram prediction model was developed for predicting postoperative DVT in patients with spinal infection. The nomogram included five preoperative predictor variables, which would effectively predict the likelihood of DVT after spinal infection and may have greater clinical value for the treatment and prevention of postoperative DVT.

Advances in the study of biomarkers related to bone metastasis in breast cancer.

Breast cancer is by far the most common malignancy in females. And bone is the most common site of distant metastasis in breast cancer, accounting for about 65 to 75% of all metastatic breast cancer patients.1,2Bone metastasis is an important factor affecting the prognosis of breast cancer. When patients have early-stage breast cancer without metastasis, their 5-year survival rate is as high as 90%, and once metastasis occurs, their 5-year survival rate will drop to 10%.3 Bone radionuclide imaging (ECT), X-ray, CT scan, MRI and other imaging tests to diagnose breast cancer bone metastasis are commonly used in clinical, It is currently believed that breast cancer bone metastasis is a multistep process: first, breast cancer cells need to acquire invasive and metastatic properties; breast cancer cells enter the blood circulation and migrate from blood breast cancer cells enter the blood circulation and migrate from blood vessels to bone tissue in a targeted manner; breast cancer cells adhere and remain in bone tissue and colonise it; and finally, it leads to bone destruction.4 Several key molecules are involved in breast cancer bone metastasis, and serum biomarkers are generally able to detect pathological changes earlier Several key molecules are involved in breast cancer bone metastasis, and serum biomarkers are generally able to detect pathological changes earlier than imaging.5 This review describes the progress of serum biomarkers for breast cancer bone metastasis.

A predictive model for early clinical diagnosis of spinal tuberculosis based on conventional laboratory indices: A multicenter real-world study.

Background: Early diagnosis of spinal tuberculosis (STB) remains challenging. The aim of this study was to develop a predictive model for the early diagnosis of STB based on conventional laboratory indicators. Method: The clinical data of patients with suspected STB in four hospitals were included, and variables were screened by Lasso regression. Eighty-five percent of the cases in the dataset were randomly selected as the training set, and the other 15% were selected as the validation set. The diagnostic prediction model was established by logistic regression in the training set, and the nomogram was drawn. The diagnostic performance of the model was verified in the validation set. Result: A total of 206 patients were included in the study, including 105 patients with STB and 101 patients with NSTB. Twelve variables were screened by Lasso regression and modeled by logistic regression, and seven variables (TB.antibody, IGRAs, RBC, Mono%, RDW, AST, BUN) were finally included in the model. AUC of 0.9468 and 0.9188 in the training and validation cohort, respectively. Conclusion: In this study, we developed a prediction model for the early diagnosis of STB which consisted of seven routine laboratory indicators.

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.

Upregulated estrogen receptors impairs myogenesis and elevates adipogenesis related factor levels in the paravertebral muscles of patients with idiopathic scoliosis.

The prevalence of idiopathic scoliosis (IS) is 2-3% worldwide and is more common in girls. Estrogen receptors (ERs) is supposed to be related to sex differences and development of IS. Meanwhile, paravertebral muscle (PVM) abnormalities play important roles in the pathogenesis of IS. But the changes of ERs between the PVMs from IS patients and controls, and the mechanism by which ERs may affect IS patients remain unclear. Thus, the expression levels of ERs, myogenesis regulator (MYOG) and adipogenesis related factors (CEBPA, PPARγ, FABP4), as well as morphological changes in the PVMs and primary skeletal muscle mesenchymal progenitor cells (hSM-MPCs) of IS patients and controls were investigated. Increased expression levels of ERs and CEBPA, PPARγ, FABP4, together with severe myofiber necrosis and fat infiltration, were found in the PVMs of IS patients. Meanwhile, upregulated ERs, FABP4 and CEBPA, downregulated MYOG and impaired myogenesis were also revealed in the hSM-MPCs of IS patients compared with those of controls. Upregulation of ERs inhibited myogenesis but increased expression of CEBPA and FABP4 in C2C12 myoblasts. Nevertheless, treatment of ER antagonist increased expression of MYOG, enhanced myogenesis and decreased expression of CEBPA and FABP4 in skeletal muscle cells of IS patients. Therefore, our study suggested that PVMs specific upregulation of ERs could impair myogenesis and increase the expression of adipogenesis related factors, further leading to PVMs abnormalities in IS patients.

The pre-surgical role of halo-traction in patients with cervical infection associated with refractory kyphosis: a retrospective study.

To minimize surgical complications and staged procedures halo-traction is often used during deformity corrections. But the use of halo-traction in the treatment of refractory cervical kyphosis secondary to infections has never been reported. This study investigated the role of halo-traction in the treatment of cervical infection patients associated with refractory kyphosis. We retrospectively reviewed 48 patients with cervical infection associated with refractory kyphosis who were treated in our spine department. Patients were divided into two groups, the traction group (A) and the non-traction group (B). Group A underwent preoperative halo-traction followed by surgery, while group B underwent surgery alone. Between the two groups, we analyzed the kyphosis deformity correction, level of fusions, erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), functional improvement by Neck disability index (NDI) score, and complications. Group A had a better correction of kyphosis deformity compared to group B (27.01 ± 11.54)0 versus (18.08 ± 10.04)0 (P = 0.01, Z = - 2.44). No statistically significant differences between the two groups in terms of functional improvement, level of fusions, ESR and CRP. Group B had 3 revision surgery cases. Preoperative halo-traction followed by surgery is superior in kyphosis correction in the treatment of patients with cervical infections with refractory kyphosis.

Analysis of the diagnostic efficacy of the QuantiFERON-TB Gold In-Tube assay for preoperative differential diagnosis of spinal tuberculosis.

Background: Differential diagnosis of spinal tuberculosis is important for the clinical management of patients, especially in populations with spinal bone destruction. There are few effective tools for preoperative differential diagnosis in these populations. The QuantiFERON-TB Gold In-Tube (QFT-GIT) test has good sensitivity and specificity for the diagnosis of tuberculosis, but its efficacy in preoperative diagnosis of spinal tuberculosis has rarely been investigated. Method: A total of 123 consecutive patients with suspected spinal tuberculosis hospitalized from March 20, 2020, to April 10, 2022, were included, and the QFT-GIT test was performed on each patient. We retrospectively collected clinical data from these patients. A receiver operating characteristic (ROC) curve was plotted with the TB Ag-Nil values. The cutoff point was calculated from the ROC curve of 61 patients in the study cohort, and the diagnostic validity of the cutoff point was verified in a new cohort of 62 patients. The correlations between TB Ag-Nil values and other clinical characteristics of the patients were analyzed. Results: Of the 123 patients included in the study, 51 had confirmed tuberculosis, and 72 had non-tuberculosis disease (AUC=0.866, 95% CI: 0.798-0.933, P<0.0001). In patients with spinal tuberculosis, the QFT-GIT test sensitivity was 92.16% (95% CI: 80.25%-97.46%), and the specificity was 67.14% (95% CI: 54.77%-77.62%). The accuracy of diagnostic tests in the validation cohort increased from 77.42% to 80.65% when a new cutoff point was selected (1.58 IU/mL) from the ROC curve of the study cohort. The TB Ag-Nil values in tuberculosis patients were correlated with the duration of the patients' disease (r=0.4148, P=0.0025). Conclusion: The QFT-GIT test is an important test for preoperative differential diagnosis of spinal tuberculosis with high sensitivity but low specificity. The diagnostic efficacy of the QFT-GIT test can be significantly improved via application of a new threshold (1.58 IU/mL), and the intensity of the QFT-GIT test findings in spinal tuberculosis may be related to the duration of a patient's disease.

Evaluating Bacterial Pathogenesis Using a Model of Human Airway Organoids Infected with Pseudomonas aeruginosa Biofilms.

Pseudomonas aeruginosa is one of the leading invasive agents of human pulmonary infection, especially in patients with compromised immunity. Prior studies have used various in vitro models to establish P. aeruginosa infection and to analyze transcriptomic profiles of either the host or pathogen, and yet how much those works are relevant to the genuine human airway still raises doubts. In this study, we cultured and differentiated human airway organoids (HAOs) that recapitulate, to a large extent, the histological and physiological features of the native human mucociliary epithelium. HAOs were then employed as a host model to monitor P. aeruginosa biofilm development. Through dual-species transcriptome sequencing (RNA-seq) analyses, we found that quorum sensing (QS) and several associated protein secretion systems were significantly upregulated in HAO-associated bacteria. Cocultures of HAOs and QS-defective mutants further validated the role of QS in the maintenance of a robust biofilm and disruption of host tissue. Simultaneously, the expression magnitude of multiple inflammation-associated signaling pathways was higher in the QS mutant-infected HAOs, suggesting that QS promotes immune evasion at the transcriptional level. Altogether, modeling infection of HAOs by P. aeruginosa captured several crucial facets in host responses and bacterial pathogenesis, with QS being the most dominant virulence pathway showing profound effects on both bacterial biofilm and host immune responses. Our results revealed that HAOs are an optimal model for studying the interaction between the airway epithelium and bacterial pathogens. IMPORTANCE Human airway organoids (HAOs) are an organotypic model of human airway mucociliary epithelium. The HAOs can closely resemble their origin organ in terms of epithelium architecture and physiological function. Accumulating studies have revealed the great values of the HAO cultures in host-pathogen interaction research. In this study, HAOs were used as a host model to grow Pseudomonas aeruginosa biofilm, which is one of the most common pathogens found in pulmonary infection cases. Dual transcriptome sequencing (RNA-seq) analyses showed that the cocultures have changed the gene expression pattern of both sides significantly and simultaneously. Bacterial quorum sensing (QS), the most upregulated pathway, contributed greatly to biofilm formation, disruption of barrier function, and subversion of host immune responses. Our study therefore provides a global insight into the transcriptomic responses of both P. aeruginosa and human airway epithelium.

A Tibetan ice core covering the past 1,300 years radiometrically dated with 39Ar.

Ice cores from alpine glaciers are unique archives of past global and regional climate conditions. However, recovering climate records from these ice cores is often hindered by the lack of a reliable chronology, especially in the age range of 100 to 500 anni (a) for which radiometric dating has not been available so far. We report on radiometric 39Ar dating of an ice core from the Tibetan Plateau and the construction of a chronology covering the past 1,300 a using the obtained 39Ar ages. This is made possible by advances in the analysis of 39Ar using the laser-based detection method atom trap trace analysis, resulting in a twofold increase in the upper age limit of 39Ar dating. By measuring the anthropogenic 85Kr along with 39Ar we quantify and correct modern air contamination, thus removing a major systematic uncertainty of 39Ar dating. Moreover, the 85Kr data for the top part of the ice core provide information on firn processes, including the age difference between the ice and its enclosed gas. This first application of 39Ar and 85Kr to an ice core facilitates further ice cores from nonpolar glaciers to be used for recovering climate records of the Common Era, a period including pronounced anomalies such as the Little Ice Age and the Medieval Warm Period.

Cervical Staphylococcus aureus Infection after Receiving the Third Dose of COVID-19 Vaccination: A Case Report.

INTRODUCTION: Vaccination is one of the most effective ways to control the COVID-19 pandemic. However, as the number of people vaccinated against COVID-19 continues to increase, there are more reports on the safety of vaccines. So far, there have been no reported cases of spinal infection associated with COVID-19 vaccination. Recently, we admitted a patient who developed cervical Staphylococcus aureus infection resulting in high paraplegia after receiving the third dose of COVID-19 vaccine when the symptoms of cold did not completely disappear. CASE PRESENTATION: The patient was a 70-year-old man who received the third injection of COVID-19 vaccine when the cold symptoms were not completely gone. On the day after the injection, the patient developed severe neck and shoulder pain, accompanied by numbness and fatigue in the limbs. MRI examination of the cervical spine on day 6 after vaccination showed no obvious signs of infection. The patient had progressive weakness in the extremities. On the ninth day after vaccination, the patient developed paralysis of both lower limbs and significant sensory loss. Cervical abscess and cervical spinal cord injury were considered for cervical CT and MRI examination on the 15th day after vaccination. We used an anterior approach to remove as much of the lesion as possible. Staphylococcus aureus was detected and antibiotic treatment was continued after surgery. The patient's pain symptoms were significantly relieved, which prevented the abscess from further pressing the spinal cord and provided possible conditions for the recovery of neurological function in the later stage. CONCLUSION: This case is the first reported cervical Staphylococcus aureus infection resulting in high paraplegia after receiving the third dose of COVID-19 vaccine with low immunity. This case raises awareness of this rare but potentially life-threatening adverse reaction, and reminds people to hold off when their immune system is weakened.

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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.

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.

Abnormal TNS3 gene methylation in patients with congenital scoliosis.

BACKGROUND: Congenital scoliosis (CS) is a congenital deformity of the spine resulting from abnormal and asymmetrical development of vertebral bodies during pregnancy. However, the etiology and mechanism of CS remain unclear. Epigenetics is the study of heritable variations in gene expression outside of changes in nucleotide sequence. Among these, DNA methylation was described first and is the most characteristic and most stable epigenetic mechanism. Therefore, in this study, we aim to explore the association between genome methylation and CS which are not been studied before. METHODS: Two pairs of monozygotic twins were included, with each pair involving one individual with and one without CS. Agilent SureSelect XT Human Methyl-Sequencing was used for genome methylation sequencing. MethylTarget was used to detect methylation levels in target regions. Immunohistochemistry was performed to visualize expression of associated genes in candidate regions. RESULTS: A total of 75 differentially methylated regions were identified, including 24 with an increased methylation level and 51 with a decreased methylation level in the CS group. Nine of the differentially methylated regions were selected (TNS3, SEMAC3, GPR124, MEST, DLK1, SNTG1, PPIB, DEF8, and GRHL2). The results showed that the methylation level of the promoter region of TNS3 was 0.72 ± 0.08 in the CS group and 0.43 ± 0.06 in the control group (p = 0.00070 < 0.01). There was no significant difference in the degree of methylation of SEMAC3, GPR124, MEST, DLK1, SNTG1, PPIB, DEF8, or GRHL2 between the two groups. Immunohistochemistry showed significantly decreased TNS3 expression in the cartilage of the articular process in CS (CS: 0.011 ± 0.002; control: 0.018 ± 0.006, P = 0.003 < 0.01). CONCLUSION: Compared with the control group, high-level methylation of the TNS3 promoter region and low TNS3 expression in the cartilage layer of the articular process characterize CS. Thus, DNA methylation and TNS3 may play important roles in the pathogenesis of CS.

Posterior-only debridement, bone fusion, single-segment versus short-segment instrumentation for mono-segmental lumbar or lumbosacral pyogenic vertebral osteomyelitis: minimum five year follow-up outcomes.

BACKGROUND: Pyogenic vertebral osteomyelitis (PVO), which is a potentially life-threatening condition and is associated with significant morbidity and mortality, is a cause of back pain that can lead to neurologic deficits if not diagnosed in time and effectively treated. The objective of this study is to compare the efficacy of posterior single-segment and short-segment fixation combined with one-stage posterior debridement and fusion for the treatment of mono-segmental lumbar or lumbosacral PVO. METHODS: Charts of all patients with mono-segmental lumbar or lumbosacral PVO were treated by single-stage posterior debridement, bone graft fusion, and pedicle screw fixation from April 2012 to January 2016. All patients were divided into two groups: sinlge-segment fixation (Group A, n = 31) and short-segment fixation (Group B, n = 36). These patients were followed up for a minimum of five years. The clinical efficacy was evaluated and compared on average operation time, blood loss, visual analog scale (VAS), erythrocyte sedimentation rate (ESR), C-Reactive protein (CRP), neurological function recovery and local lordotic angle. RESULTS: All 67 patients were completely cured during the follow-up. All patients had significant improvement of neurological condition and pain relief at the final follow-up. The VAS was 7.1 ± 0.7 in group A and 7.2 ± 0.6 in group B pre-operatively, which decreased to 2.1 ± 0.6 and 2.0 ± 0.7, respectively, at three months after surgery, then reduced to 0.4 ± 0.5 and 0.5 ± 0.5, respectively, at the final follow-up. ESR, CRP returned to normal limits in all patients 3 months after surgery. The mean blood loss and operation time in group A were less than that in group B (P < 0.05). The local lordotic angle in group A was increased from preoperative - 1.7 ± 7.9° to postoperative 5.8 ± 7.1°, with angle loss of 1.5 ± 0.8° at the final follow-up, respectively (P < 0.05). The local lordotic angle in group B was increased from preoperative - 1.6 ± 7.8° to postoperative 13.5 ± 6.2°, with angle loss of 1.3 ± 0.8° at the final follow-up, respectively (P < 0.05). In the mean postoperative local lordotic angle, there was significant difference between the two groups at the time of immediate postoperative period or the final follow-up (P < 0.05). CONCLUSION: Posterior-only debridement, interbody graft using titanium mesh cage, posterior single-segment instrumentation and fusion represent a safe and effective treatment option for selected patients with mono-segmental lumbar and lumbosacral PVO. This approach may preserve more lumbar normal motor units with less blood loss and operation time when compared with that of short-segment fixation. But short-segment fixation was superior to the single-segment fixation in the correction of kyphosis.

LncRNA OIP5-AS1 Knockdown Targets miR-183-5p/GLUL Axis and Inhibits Cell Proliferation, Migration and Metastasis in Nasopharyngeal Carcinoma.

Nasopharyngeal carcinoma (NPC) is often associated with the infection of Epstein-Barr virus in nasopharynx and is mainly happened in South China and Southeast Asia. Recently, noncoding RNAs have been reported to regulate NPC carcinogenesis. LncRNA OIP5-AS1 participates in tumorigenesis and progression; however, the inherent mechanism of OIP5-AS1-mediated progression of NPC is unclear. In the current study, we aimed to explore the role of OIP5-AS1 in NPC progression. We measured the cell viability, apoptosis, migration, and invasion in NPC cells after OIP5-AS1 modulation. Moreover, we determined whether OIP5-AS1 exerts its oncogenic functions via sponging miR-183-5p in NPC. Furthermore, we determined whether glutamate ammonia ligase (GLUL) was a downstream target of miR-183-5p. We found that OIP5-AS1 downregulation inhibited the viability, migration and invasion of NPC via targeting miR-183-5p. We also identified that GLUL might be a potential downstream target of miR-183-5p in NPC cells. Mechanistically, OIP5-AS1 promotes cell motility via regulating miR-183-5p and GLUL in NPC cells. We concluded that OIP5-AS1 performed its biological functions via targeting miR-183-5p and GLUL in NPC cells.

Spinous Process Combined With a Titanium Mesh Cage as a Bone Graft in the Stability Reconstruction of Lumbar or Lumbosacral Spinal Tuberculosis.

Background: Autogenous bone grafts, such as iliac bone or rib struts, have been used in the anterior reconstruction of spinal tuberculosis (STB) and have their own benefits and limitations. Here, we introduced a new method, the spinous process (SP), combined with a titanium mesh cage (TMC) as a bone graft in the stability reconstruction of lumbar or lumbosacral STBs. By retrospectively comparing patients who received SP+TMC to traditional TMC bone grafts or allogeneic bone grafts in terms of safety, efficacy and cost-effectiveness, we aimed to evaluate whether SP+TMC could be a possible alternative method. Methods: From 2010 to 2018, 69 patients who underwent one-stage posterior debridement with grafts and internal fixation within a single lumbar or lumbosacral segment were included in this study. Twelve patients who received SP combined with a TMC (SP+TMC, group A), 30 patients who received a TMC only (group B), and 27 patients who received allografts (group C) were included. Measurements including operative time, blood loss, length of hospital stay, visual analog scale (VAS) score, Oswestry Disability Index (ODI), erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), American Spinal Injury Association Impairment (ASIA) grade, final follow-up (FFU) duration and postoperative complications were recorded. Radiological measurements, including the number of segments fixated, the number of pedicle screws used, the Cobb angle, pelvic parameters, and the bony fusion time, were reviewed. All outcomes were analyzed using SPSS 25. Results: We found that the SP+TMC group had fewer fixation segments, fewer pedicle screws implanted, a shorter operative time, reduced blood loss, and a considerably lower hospital cost than allografts. In addition, the TMC group had a comparable clinical outcome with the TMC group regarding lower economic cost. Conclusion: Our study demonstrates that compared to a TMC or allograft, the use of SP combined with a TMC as a bone graft is an effective and reliable approach for the surgical management of one-level lumbar or lumbosacral spinal tuberculosis, leading to effective restoration of spinal stability. Furthermore, this approach is a cost-effective structural bone grafting method, especially for patients in developing countries.

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.