Clinical progression of ossification of the ligamentum flavum in thoracic spine: a 10- to 11-year follow-up study.

BACKGROUND: Thoracic ossification of ligamentum flavum (TOLF) can be asymptomatic and progress insidiously. But, long-term follow-up results of clinical progression of TOLF are still unknown. METHODS: The clinical progression of 81 patients with TOLF at our center, followed for 10 to 11 (mean, 10.3) years from May 2010 to November 2021, were analyzed. Among them, 51 patients with thoracic myelopathy were caused by single- or multi-segment TOLF, and received partial TOLF resection (30 patients) or total TOLF resection (21 patients). The remaining 30 patients showed TOLF on imaging examinations, but TOLF was not the responsible compressing factor causing myelopathy and with no TOLF resection. The mJOA score (total 11 scores) and spinal operation were used to evaluate the clinical progression at follow-up. RESULTS: During the 10- to 11-year follow-up of 81 TOLF patients, 71 (87.7%) had no deterioration of neurological function, and 10 (12.3%) patients had deterioration of neurological function and had another spinal operation, including only 4 (4.9%) suffered thoracic myelopathy caused by the progression of TOLF; 6 (7.4%) for other spinal diseases: 2 (2.5%) had fall damage and acute spinal cord injury at the TOLF level; 2 (2.5%) had thoracic myelopathy caused by ossification of posterior longitudinal ligament (OPLL); 2 (2.5%) had cervical spondylosis and received cervical operation. CONCLUSIONS: Most TOLF (87.7%) patients had no clinical progression and received no reoperations for TOLF in the ten-year dimension (mean, 10.3 years). Narrow spinal canal for TOLF increases the risk of traumatic paraplegia.

Dataglove for Sign Language Recognition of People with Hearing and Speech Impairment via Wearable Inertial Sensors.

Finding ways to enable seamless communication between deaf and able-bodied individuals has been a challenging and pressing issue. This paper proposes a solution to this problem by designing a low-cost data glove that utilizes multiple inertial sensors with the purpose of achieving efficient and accurate sign language recognition. In this study, four machine learning models-decision tree (DT), support vector machine (SVM), K-nearest neighbor method (KNN), and random forest (RF)-were employed to recognize 20 different types of dynamic sign language data used by deaf individuals. Additionally, a proposed attention-based mechanism of long and short-term memory neural networks (Attention-BiLSTM) was utilized in the process. Furthermore, this study verifies the impact of the number and position of data glove nodes on the accuracy of recognizing complex dynamic sign language. Finally, the proposed method is compared with existing state-of-the-art algorithms using nine public datasets. The results indicate that both the Attention-BiLSTM and RF algorithms have the highest performance in recognizing the twenty dynamic sign language gestures, with an accuracy of 98.85% and 97.58%, respectively. This provides evidence for the feasibility of our proposed data glove and recognition methods. This study may serve as a valuable reference for the development of wearable sign language recognition devices and promote easier communication between deaf and able-bodied individuals.

LGR5 regulates osteogenic differentiation of human thoracic ligamentum flavum cells by Wnt signalling pathway.

Thoracic ossification of the ligamentum flavum (TOLF) is ectopic ossification of the spinal ligaments. Histologically, the development of TOLF can be described as the process of endochondral ossification. However, the underlying aetiology has not been completely clarified. In this investigation, the gene expression profile associated with leucine-rich repeat-containing G-protein-coupled receptors (LGR) and Wnt signalling pathway in the thoracic ligamentum flavum cells (TLFCs) of different ossification stages was analysed via RNA sequencing. We further confirmed the significant differences in the related gene expression profile by Gene Ontology (GO) enrichment analysis. LGR5 was first identified in primary human TLFCs during osteogenic differentiation. To evaluate the effect of LGR5 on osteogenic differentiation, LGR5 has been knocked down and overexpressed in human TLFCs. We observed that the knockdown of LGR5 inhibited the activity of Wnt signalling and attenuated the potential osteogenic differentiation of TLFCs, while overexpression of LGR5 activated the Wnt signalling pathway and increased osteogenic differentiation. Our results provide important evidence for the potent positive mediatory effects of LGR5 on osteogenesis by enhancing the Wnt signalling pathway in TOLF.

Association analysis and functional study of COL6A1 single nucleotide polymorphisms in thoracic ossification of the ligamentum flavum in the Chinese Han population.

PURPOSE: Genetic factors play a crucial role in thoracic ossification of the ligamentum flavum (TOLF). This study aimed to better understand the association between single nucleotide polymorphisms (SNP) in functional regions of the collagen VI, alpha 1 gene (COL6A1) and TOLF, and to confirm COL6A1 as a TOLF susceptibility gene. METHODS: Ten tag SNPs in COL6A1 were genotyped using the SNaPshot assay, and allele and genotype frequencies were compared between TOLF patients and control individuals. The function of SNPs associated with disease was studied. For COL6A1 promoter SNPs, the transcriptional activity of each haplotype was determined by luciferase reporter assays. For COL6A1 exonic SNPs, the effect of nucleotide substitutions on COL6A1 expression was determined by western blotting. COL6A1 mRNA expression in ligamentum flavum tissues from TOLF patients with different genotypes was examined using reverse transcription real-time PCR. RESULTS: Four SNPs were associated or possibly associated with TOLF, with higher pathogenic allele and genotype frequencies seen in TOLF patients compared with controls. The rs17551710/rs7671-GG/GG genotype appeared to be related to disease severity. Nucleotide substitutions at rs17551710 and rs7671 increased COL6A1 transcriptional activity and nucleotide substitutions at rs1053312 and rs13051496 increased COL6A1 protein expression. COL6A1 mRNA expression was significantly up-regulated in individuals with rs17551710/rs7671-GG/GG and rs1053312/rs13051496-AA+AG/CC genotypes compared with other genotypes. CONCLUSION: SNPs in the COL6A1 promoter and exonic regions are associated with TOLF in the Chinese Han population, and lead to up-regulated COL6A1 expression. We confirmed COL6A1 as a TOLF susceptibility gene that may be involved in TOLF pathology.

Genome-wide DNA methylation profile analysis in thoracic ossification of the ligamentum flavum.

Thoracic ossification of the ligamentum flavum (TOLF) causes serious spinal canal stenosis. The underlying aetiology may relate to genetic and inflammatory factors. DNA methylation plays a critical role in osteogenesis and inflammation, whereas there is no genome-wide DNA methylation analysis about TOLF. The two subtypes of TOLF (single-level and multiple-level) have distinct clinical features. Using micro-computed tomography (micro-CT), we showed the ossification arose from the joint between two vertebrae at one/both sides of ligament flavum. With Illumina Infinium Human Methylation 850 BeadChip arrays, genome-wide DNA methylation profile was measured in ligament flavum of eight healthy and eight TOLF samples. Only 65 of the differentially methylated cytosine-phosphate-guanine dinucleotides were found in both subtype groups. Principal component analysis and heat map analysis showed a different methylation pattern in TOLF samples, and methylation patterns of two subtypes are also distinct. The Gene Ontology enrichment analysis was significantly enriched in differentiation and inflammation. Pyrosequencing analysis and quantitative real-time polymerase chain reaction were performed to validate the arrays results and expression levels, to test six differentially methylated genes (SLC7A11, HOXA10, HOXA11AS, TNIK, homeobox transcript antisense RNA, IFITM1), using another independent samples (P < 0.05). Our findings first demonstrated an altered Genome-wide DNA methylation profile in TOLF, and implied distinct methylated features in two subtypes.

The prevalence and clinical characteristics of thoracic spinal stenosis: a systematic review.

PURPOSE: Thoracic spinal stenosis (TSS) is a rare disease secondary to multiple pathological changes that differ in prevalence and clinical characteristics. The epidemiological characteristics of these pathologies are largely unknown due to the limited case samples and regional differences. Therefore, a systematic review was conducted to elucidate the prevalence and clinical characteristics of TSS. METHODS: Case series and case reports on the ossification of the posterior longitudinal ligaments (OPLL), ossification of the ligamentum flavum (OLF) and thoracic disk herniation (TDH) were screened from PubMed, Embase and Web of Science databases and systematically reviewed. Epidemiological, demographic and segmental distribution data were extracted and analyzed. RESULTS: A total of 129 studies including 1935 subjects were selected, of which 361 (18.7%) were diagnosed with OPLL, 804 (41.5%) with OLF, 143 (7.4%) with OPLL + OLF and 627 (32.4%) with TDH. Most reports were from China, Japan and USA. Thoracic OPLL occurred mostly at the middle-thoracic spine (43.4%), while OLF predominately occurred at the lower-thoracic spine (63.1%). TDH was mainly localized in the middle (46.0%) and lower-thoracic (50.3%) spine. Thirty-two studies involving 524 patients described tandem spinal stenosis, of which 52.1% had accompanying cervical diseases and 35.9% lumbar diseases. CONCLUSIONS: There are significant differences in the age, sex and segment distribution characteristics of different pathologies leading to TSS. Tandem spinal stenosis is not uncommon and should be considered when diagnosing TSS. Our findings provide new insights into the prevalence and clinical characteristics of TSS and can help reduce misdiagnosis.

Treatment and outcomes of 28 patients with spinal metastasis from gynecological cancer.

The aim of this study was to provide some useful information concerning clinical characteristics, surgical treatment, potential contributing factor and prognostic factors for patients with gynecological cancer (GC) spinal metastasis. We reviewed 28 patients with GC spinal metastasis in our spine tumor center between July 2008 and July 2015. Surgeries were performed on 22 of them. Univariate and multivariate analyses were conducted to identify potential prognostic factors affecting spinal metastasis-free survival (SMFS) and overall survival. The operative patients responded favorably according to decrease of VAS score and increase of Frankel grade after surgery. The 1- and 2-year survival rates in all patients were 60.7 and 41.0%, respectively. Univariate analysis suggested that age at diagnosis with GC was the potential contributing factor for spinal metastasis, while Frankel grade, ECOG-PS, visceral metastasis and chemotherapy were the potential prognostic factors affecting survival. Multivariate analysis indicated that the independent prognostic factors came from visceral metastasis and chemotherapy. Surgery played an important role in improving patients' quality of life. Patients over 50 years old had a shorter SMFS after diagnosed with GC. Visceral metastasis was an adverse prognostic factor for patients with GC spinal metastasis, while chemotherapy was a favorable one.

Surgical management of spinal liposarcoma: a case series of 7 patients and literature review.

PURPOSE: Liposarcoma, one of the most common soft tissue sarcomas originates from primitive mesenchymal cells. But spinal involvement of either primary or metastatic liposarcoma is rare. Here we present our experience of seven consecutive patients with spinal liposarcoma. METHOD: We retrospectively reviewed our patients who have spinal liposarcoma from January 2009 to December 2013. All patients were surgically treated at least once at our spine tumor center and be confirmed as liposarcoma after surgery. All patients' information and follow-up data were collected afterwards. RESULTS: A total of six male and one female patients have been included. Five of them had mobile spinal involvement while the others had sacral involvement. Six piecemeal and one en-bloc resections were successfully performed. Patients' Frankel scores were upgraded with one level or at least preserved postoperatively. The average time of follow-up was 24.6 ± 13.9 months. Three patients died 13, 15 and 24 months after surgical treatment, respectively while the other four patients were still alive and one of them alive with disease at the end of follow-up. CONCLUSION: The outcome and prognosis of spinal liposarcoma is poor, and surgical resections should be considered when diagnosis is confirmed. For those whose tumors were too large to resect and/or with multiple metastases, effective treatment options are currently limited. Therefore, multidisciplinary treatment should be adopted, intraoperative chemotherapy, systemic chemotherapy and radiotherapy for instance.

Factors associated with improved survival following surgical treatment for metastatic prostate cancer in the spine: retrospective analysis of 29 patients in a single center.

BACKGROUND: Prostate cancer (PCa) is very common and frequently metastasizes to the spine. However, PCa spinal metastases were rarely reported in the literature. In this study, the outcome of therapies and prognostic factors affecting surgical outcomes for patients with PCa spinal metastases are discussed to select the best candidates for aggressive surgical resection. METHODS: All patients affected by the spinal metastatic PCa surgically treated at our spine tumor center were reviewed. Overall survival was analyzed from the time of spinal surgery. A univariate survival analysis and a multivariate Cox proportional hazard analysis to identify independent prognostic factors were carried out. The survival rate was estimated by the Kaplan-Meier method, and differences were analyzed by the log-rank test. Factors with P values of 0.1 or less were subjected to multivariate analysis for survival rate by multivariate Cox proportional hazard analysis. RESULTS: A total of 31 consecutive patients were identified. Of these, 29 underwent surgical resection. The median survival time of all patients after their spinal surgery was 44.0 months. Visceral metastases, revised Tokuhashi scores (0-8/9-11/12-15), Tomita scores (7-10/2-6), hormone status, and bisphosphonate treatment were suggested as the potential prognostic factors through univariate analysis. As they were submitted to the multivariate Cox regression model, visceral metastases and Tomita score were found as independent prognostic factors. CONCLUSIONS: Patients without visceral metastases and a Tomita score no more than 6 are favorable prognostic factors for PCa metastases in the mobile spine.

M1 macrophage-derived oncostatin M induces osteogenic differentiation of ligamentum flavum cells through the JAK2/STAT3 pathway.

Background: M1 macrophages (Mφs) are involved in osteogenic differentiation of ligamentum flavum (LF) cells and play an important role in heterotopic ossification. However, the mechanism by which M1 Mφs influence osteogenic differentiation of LF cells has not been studied. Methods: The effect of conditioned medium including secretions of M1 Mφs (CM-M1) on LF cells was analyzed by GeneChip profiling and ingenuity pathway analysis (IPA). THP-1 cells were polarized into M1 Mφs and CM-M1 was used to induce LF cells. In addition, LF cells were induced by CM-M1 in the presence of cyclooxygenase 2 (COX-2) inhibitors or oncostatin M (OSM)-neutralizing antibodies. Based on the presence of OSM, knockout of OSMR or GP130 receptors, or addition of the Janus kinase 2 (JAK2) inhibitor AZD1480 or signal transducer and activator of transcription 3 (STAT3) inhibitor Stattic were examined for effects on osteogenic differentiation of LF cells. OSM secretion was quantified by ELISA, while qPCR and western blot were used to evaluate expression of osteogenic genes and receptor and signaling pathway-related proteins, respectively. Results: GeneChip and IPA results indicate that the OSM signaling pathway and its downstream signaling molecules JAK2 and STAT3 are significantly activated. ELISA results indicate that OSM is highly expressed in cells treated with CM-M1 and lowly expressed in cells treated with CM-M1 and a COX-2 inhibitor. Besides, CM-M1 induces osteogenic differentiation of LF cells, which is weakened when COX-2 inhibitors or OSM-neutralizing antibody are added to it. Recombinant OSM could induce osteogenic differentiation of LF cells and upregulate expression of OSMR, GP130, phosphorylated (P)-JAK2, and P-STAT3. Upon knockdown of OSMR or GP130, or the addition of AZD1480 or Stattic, P-JAK2 and P-STAT3 expression were decreased and osteogenic differentiation was reduced. Conclusion: M1 Mφ-derived OSM induces osteogenic differentiation of LF cells and the JAK2/STAT3 signaling pathway plays an important role.

Imaging signs for preoperative diagnosis of dural ossification in patients with thoracic ossification of the ligamentum flavum: a blind, randomized diagnostic accuracy study.

Background: Dural ossification (DO) is the leading cause of surgery-related dural tear in patients with ossification of the ligamentum flavum (OLF). An accurate preoperative diagnosis of DO is conducive to the selection of appropriate surgical methods. Although several imaging signs, such as Banner cloud sign (BCs), tram-track sign (TTs), and comma sign (Cs) have been proposed for the preoperative diagnosis of DO, their diagnostic value has not been well studied. The aim of this study was to explore the diagnostic value of BCs, TTs, and Cs, and provide evidence-based data for their clinical application. Methods: This is a blind, randomized diagnostic study using retrospectively collected data from 102 consecutive patients who were diagnosed with OLF and underwent decompression surgery between January 2018 and June 2019. A total of 8 surgeons with different qualifications were recruited to read these imaging signs to identify the presence of DO. Surgical records were used as the reference standard. Sensitivity, specificity, and the area under the receiver operating characteristic (ROC) curve (AUC) were used to evaluate the diagnostic accuracy of each imaging sign and their different combinations. Results: Of the 102 patients, 21 were diagnosed with DO. BCs had a significantly higher diagnostic accuracy than TTs and Cs, with the AUC of 0.704, 0.607, and 0.593, respectively. The specificity of BCs, Cs, TTs, and their combination in diagnosing DO was 91.5%, 92.1%, 68.3%, and 62.2%, respectively. In the combined diagnostic test, the results showed that the combined diagnosis accuracy of BCs and Cs was the highest, and the AUC was 0.738. The combination of BCs, Cs, and TTs increased the sensitivity of diagnosing DO (77.5%), but did not improve the diagnostic accuracy, and the AUC was 0.699. Conclusions: BCs had higher diagnostic accuracy than TTs and Cs. BCs and Cs were highly specific for DO, whereas TTs could be confusing due to their non-specific presentations. The combination of BCs, TTs, and Cs improved the sensitivity of DO diagnosis, but not the specificity and accuracy.

A new deep convolutional neural network incorporating attentional mechanisms for ECG emotion recognition.

Using ECG signals captured by wearable devices for emotion recognition is a feasible solution. We propose a deep convolutional neural network incorporating attentional mechanisms for ECG emotion recognition. In order to address the problem of individuality differences in emotion recognition tasks, we incorporate an improved Convolutional Block Attention Module (CBAM) into the proposed deep convolutional neural network. The deep convolutional neural network is responsible for capturing ECG features. Channel attention in CBAM is responsible for adding weight information to ECG features of different channels and spatial attention is responsible for the weighted representation of ECG features of different regions inside the channel. We used three publicly available datasets, WESAD, DREAMER, and ASCERTAIN, for the ECG emotion recognition task. The new state-of-the-art results are set in three datasets for multi-class classification results, WESAD for tri-class results, and ASCERTAIN for two-category results, respectively. A large number of experiments are performed, providing an interesting analysis of the design of the convolutional structure parameters and the role of the attention mechanism used. We propose to use large convolutional kernels to improve the effective perceptual field of the model and thus fully capture the ECG signal features, which achieves better performance compared to the commonly used small kernels. In addition, channel attention and spatial attention were added to the deep convolutional model separately to explore their contribution levels. We found that in most cases, channel attention contributed to the model at a higher level than spatial attention.

Factors Affecting the Surgical Outcomes of Patients Treated With "de-tension" Surgical Strategy for Multilevel Ossification of the Posterior Longitudinal Ligament in the Thoracic Spine: A Minimum 2-year Follow-Up Study of 83 Patients in a Single Center.

STUDY DESIGN: Retrospective cohort study. OBJECTIVES: To describe the clinical characteristics and surgical outcomes of patients with multilevel-ossification of the posterior longitudinal ligament (mT-OPLL), and to identify risk factors for unfavorable outcomes. METHODS: Patients who were diagnosed with mT-OPLL and underwent one-stage thoracic posterior laminectomy combined with selective OPLL resection, spinal cord de-tension, and fusion surgery between August 2012 and October 2020 were recruited. Patients' demographic-, surgical- and radiological-related parameters were collected and analyzed. Neurological status was evaluated with mJOA score, and recovery rate (RR) was calculated using the Hirabayashi formula. According to RR, patients were divided into a favorable outcome group (FOG, RR ≥50%) and an unfavorable outcome group (UOG, RR <50%). Univariate and multivariate analyses were used to compare the difference between the 2 groups and to identify risk factors for unfavorable outcomes. RESULTS: A total of 83 patients were included, with an average age of 50.6 ± 8.3 years. Cerebrospinal fluid leakage (60.2%) and transient neurological deterioration (9.6%) were the most common complications. The average mJOA score improved from preoperative 4.3 ± 2.2 to 9.0 ± 2.4 at the last follow-up, and the mean RR was 74.9 ± 26.3%. Disease duration, preoperative nonambulatory status, and the number of decompressed levels were identified as potential risk factors by Univariate analysis (all P < .05). Multivariate analysis showed that the preoperative disease duration and nonambulatory status were independent risk factors for unfavorable outcomes. CONCLUSIONS: Long disease duration and nonambulatory status before surgery were independent risk factors for unfavorable outcomes.

Percutaneous Kyphoplasty Versus Percutaneous Vertebroplasty for Neurologically Intact Osteoporotic Kümmell's Disease: A Systematic Review and Meta-Analysis.

STUDY DESIGN: Systematic review and meta-analysis. OBJECTIVE: Percutaneous vertebroplasty (PVP) and percutaneous kyphoplasty (PKP) are minimally invasive techniques widely used for the treatment of neurologically intact osteoporotic Kümmell's disease (KD), but which treatment is preferable remains controversial. Therefore, this study aimed to shed light on this issue. METHODS: Six databases were searched for all relevant studies based on the PRISMA guidelines. Two investigators independently conducted a quality assessment, extracted the data and performed all statistical analyses. RESULTS: Eight studies encompassing 438 neurologically intact osteoporotic KD patients met the inclusion criteria. Compared to PVP, PKP was associated with greater improvement in the short- and long-term Cobb angle [SMD = -0.37, P = 0.007; SMD = -0.34, P = 0.012], short-term anterior vertebral height [SMD = 0.43, P = 0.003] and long-term middle vertebral height [SMD = 0.57, P = 0.012] and a lower cement leakage rate [SMD = 0.50, P = 0.003] but produced more consumption (cement injection volume, operative time, fluoroscopy times, intraoperative blood loss and operation cost). However, there were no differences between the 2 procedures in the short- and long-term VAS and ODI scores, long-term anterior vertebral height, overall complications or new vertebral fractures. CONCLUSIONS: Both procedures are equally effective for neurologically intact KD in terms of the clinical outcomes, with the exception of a lower cement leakage risk and better radiographic improvement for PKP but greater resource consumption. Based on the evidence available, good clinical judgment should be exercised in the selection of patients for these procedures.

M1 Macrophage-Derived Interleukin-6 Promotes the Osteogenic Differentiation of Ligamentum Flavum Cells.

STUDY DESIGN: Basic experimental study. OBJECTIVE: The aim of this study was to clarify the role of macrophages (Mφs) in the osteogenic differentiation of ligamentum flavum (LF) cells. SUMMARY OF BACKGROUND DATA: Mφs and secreted factors are involved in the regulation of cell osteogenic differentiation, and play an important role in the process of heterotopic ossification. Whether Mφs are involved in the development of ossification of the ligamentum flavum (OLF) have not been reported. METHODS: The expression of CD68+ Mφs in ossified LF tissue was identified by immunohistochemical staining. THP-1 cells were polarized to M1 and M2, and identified by flow cytometry and immunofluorescence. The alkaline phosphatase activity and osteogenic differentiation-related gene expression in LF cells were evaluated following incubation with each Mφs conditioned medium (CM). Enzyme-linked immunosorbent assay was used to detect the pro-inflammatory cytokines in the supernatants, and qPCR was used to detect the expression of the corresponding receptors in the LF cells after incubation with the CM. LF cells were induced with CM-M1 in the presence of neutralizing antibodies to further test whether cytokines secreted by M1 Mφs impacted their osteogenic differentiation. RESULTS: CD68+ Mφs were found on the OLF samples. THP-1 cells were polarized into M1 and M2, and both M1 and M2 Mφs promoted the osteogenic differentiation of LF cells. The concentrations of tumor necrosis factor (TNF)-α, interleukin (IL)-1 ß, and IL-6 in M1 Mφ supernatants were greater than those in M2, and greater levels of these cytokine receptors were observed in LF cells induced with CM-M1 than those with CM-M2. Osteogenic differentiation of LF cells induced by CM-M1 decreased after IL-6 was neutralized; however, not after IL-1ß and TNF-α were neutralized. CONCLUSION: M1 Mφ-derived IL-6 promotes the osteogenic differentiation of LF cells, which may be a pathway in which Mφs regulate the osteogenic differentiation of LF cells.

Deciphering Obesity-Related Gene Clusters Unearths SOCS3 Immune Infiltrates and 5mC/m6A Modifiers in Ossification of Ligamentum Flavum Pathogenesis.

Background: Ossification of ligamentum flavum (OLF) is an insidious and debilitating heterotopic ossifying disease with etiological heterogeneity and undefined pathogenesis. Obese individuals predispose to OLF, whereas the underlying connections between obesity phenotype and OLF pathomechanism are not fully understood. Therefore, this study aims to explore distinct obesity-related genes and their functional signatures in OLF. Methods: The transcriptome sequencing data related to OLF were downloaded from the GSE106253 in the Gene Expression Omnibus (GEO) database. The obesity-related differentially expressed genes (ORDEGs) in OLF were screened, and functional and pathway enrichment analysis were applied for these genes. Furthermore, protein-protein interactions (PPI), module analysis, transcription factor enrichment analysis (TFEA), and experiment validation were used to identify hub ORDEGs. The immune infiltration landscape in OLF was depicted, and correlation analysis between core gene SOCS3 and OLF-related infiltrating immune cells (OIICs) as well as 5mC/m6A modifiers in OLF was constructed. Results: Ninety-nine ORDEGs were preliminarily identified, and functional annotations showed these genes were mainly involved in metabolism, inflammation, and immune-related biological functions and pathways. Integrative bioinformatic algorithms determined a crucial gene cluster associated with inflammatory/immune responses, such as TNF signaling pathway, JAK-STAT signaling pathway, and regulation of interferon-gamma-mediated signaling. Eight hub ORDEGs were validated, including 6 down-regulated genes (SOCS3, PPARG, ICAM-1, CCL2, MYC, and NT5E) and 2 up-regulated genes (PTGS2 and VEGFA). Furthermore, 14 differential OIICs were identified by ssGSEA and xCell, and SOCS3 was overlapped to be the core gene, which was associated with multiple immune infiltrates (dendritic cells, macrophage, and T cells) and six m6A modifiers as well as four 5mC regulators in OLF. Reduced SOCS3 and FTO expression and up-regulated DNMT1 level in OLF were validated by Western blotting. Conclusion: This study deciphered immune/inflammatory signatures of obesity-related gene clusters for the first time, and defined SOCS3 as one core gene. The crosstalk between 5mC/m6A methylation may be a key mediator of SOCS3 expression and immune infiltration. These findings will provide more insights into molecular mechanisms and therapeutic targets of obesity-related OLF.

Dysregulation of MicroRNAs in Hypertrophy and Ossification of Ligamentum Flavum: New Advances, Challenges, and Potential Directions.

Pathological changes in the ligamentum flavum (LF) can be defined as a process of chronic progressive aberrations in the nature and structure of ligamentous tissues characterized by increased thickness, reduced elasticity, local calcification, or aggravated ossification, which may cause severe myelopathy, radiculopathy, or both. Hypertrophy of ligamentum flavum (HLF) and ossification of ligamentum flavum (OLF) are clinically common entities. Though accumulated evidence has indicated both genetic and environmental factors could contribute to the initiation and progression of HLF/OLF, the definite pathogenesis remains fully unclear. MicroRNAs (miRNAs), one of the important epigenetic modifications, are short single-stranded RNA molecules that regulate protein-coding gene expression at posttranscriptional level, which can disclose the mechanism underlying diseases, identify valuable biomarkers, and explore potential therapeutic targets. Considering that miRNAs play a central role in regulating gene expression, we summarized current studies from the point of view of miRNA-related molecular regulation networks in HLF/OLF. Exploratory studies revealed a variety of miRNA expression profiles and identified a battery of upregulated and downregulated miRNAs in OLF/HLF patients through microarray datasets or transcriptome sequencing. Experimental studies validated the roles of specific miRNAs (e.g., miR-132-3p, miR-199b-5p in OLF, miR-155, and miR-21 in HLF) in regulating fibrosis or osteogenesis differentiation of LF cells and related target genes or molecular signaling pathways. Finally, we discussed the perspectives and challenges of miRNA-based molecular mechanism, diagnostic biomarkers, and therapeutic targets of HLF/OLF.

Integrating Bioinformatic Strategies with Real-World Data to Infer Distinctive Immunocyte Infiltration Landscape and Immunologically Relevant Transcriptome Fingerprints in Ossification of Ligamentum Flavum.

PURPOSE: Ossification of the ligamentum flavum (OLF) is a multifactorial disease characterized by an insidious and debilitating process of abnormal bone formation in ligamentum tissues. However, its definite pathogenesis has not been fully elucidated. Potential links between the immune system and various forms of heterotopic ossification have been discussed for many years, whereas no research investigated the immune effects on the initiation and development of OLF. Therefore, we attempt to shed light on this issue. METHODS: A series of bioinformatic algorithms were integrated to evaluate the immune score and the immunocyte infiltration patterns between OLF and normal samples, screen OLF-related and immune-related differentially expressed genes (OIDEGs), and analyze their biological functions. Correlation analysis inferred OIDEGs-related differentially expressed lncRNAs (OIDELs) and infiltrating immune cells (OIICs) to construct an immunoregulatory network. RESULTS: Differential immune score and immune cell infiltration were determined between two groups, and 10 OIDEGs with diverse biological function annotations were identified and verified. A lncRNA-gene-immunocyte regulatory network further revealed 10 OIDEGs, 41 OIDELs and 7 OIICs that were highly correlated. Among them, CD1E and STAT3 were predicted as hub genes whether at the expression level or interaction level. cDCs emerged as having the most prominent differences and the highest degree of connectivity. FO393414.3, AC096734.1, LINC01137 and DLX6-AS1 with the greatest number of OIDEGs were thought to be more likely to participate in immunoregulation of OLF. CONCLUSION: This is the first research to preliminarily elucidate OLF-related immunocyte infiltration landscape and immune-associated transcriptome signatures based on bioinformatic strategies and real-world data, which may provide compelling insights into the pathogenesis and therapeutic targets of OLF.

Resurfacing hemiarthroplasty versus stemmed hemiarthroplasty for glenohumeral osteoarthritis: a meta-analysis.

BACKGROUND: Though total shoulder arthroplasty (TSA) has been an acknowledged treatment option for glenohumeral osteoarthritis, resurfacing hemiarthroplasty (RHA) and stemmed hemiarthroplasty (SHA) may be preferred in some circumstances by surgeons, especially for treating young or active patients. However, decision-making between the RHA and SHA is controversial. Therefore, we conducted a meta-analysis to systematically compare two surgical procedures in terms of postoperative functional outcomes, range of motion (ROM), pain relief, complication rates, risk of revision. METHODS: The PubMed, Embase, Web of Science and Cochrane Library were searched from inception to January 1, 2020, for all articles that compared the clinical effectiveness and safety of RHA with SHA. All eligible studies were selected based on certain screening criteria. Two investigators independently conducted the quality assessment and extracted the data. Fixed-effect and random-effect models were used for pooled results according to the degree of heterogeneity. All statistical analyses were performed by employing Stata software 14.0. RESULTS: A total of six comparative studies involving 2568 shoulders (1356 RHA and 1212 SHA) were included in the final analysis. Patients were followed up for at least 1 year in each study. Pooled results showed that RHA was associated with a better visual analog scale (SMD 0.61, p = 0.001) but higher revision rates (OR 1.50, p = 0.016) when compared to SHA. There were no significant differences in functional outcomes, such as Constant-Murley score (SMD 0.06, P = 0.878), American Shoulder and Elbow Surgeons score (SMD 0.05, P = 0.880), Western Ontario Osteoarthritis of the Shoulder index (SMD 0.43, p = 0.258) and quick-Disabilities of the Arm, Shoulder and Hand score (SMD 0.06, p = 0.669). In addition, no differences were observed in forward flexion (SMD 0.16, p = 0.622), external rotation (SMD -0.17, P = 0.741) and overall complication rates (OR 1.42, p = 0.198). CONCLUSION: This is the first meta-analysis to investigate the clinical efficacy and safety of RHA in comparison with SHA for the treatment of glenohumeral osteoarthritis. The results demonstrated that the two surgical techniques were equivalent in terms of postoperative functional outcomes and complication rate. However, RHA provided greater pain relief but posed a higher risk for revision than SHA. More high-quality studies with long-term follow up are warranted to give more convincing evidence.

Ultrasonic bone scalpel for thoracic spinal decompression: case series and technical note.

BACKGROUND: Thoracic spinal stenosis (TSS) is a rare but intractable disease that fails to respond to conservative treatment. Thoracic spinal decompression, which is traditionally performed using high-speed drills and Kerrison rongeurs, is a time-consuming and technically challenging task. Unfavorable outcomes and high incidence of complications are the major concerns. The development and adaptation of ultrasonic bone scalpel (UBS) have promoted its application in various spinal operations, but its application and standard operating procedure in thoracic decompression have not been fully clarified. Therefore, the purpose of this study is to describe our experience and technique note of using UBS and come up with a standard surgical procedure for thoracic spinal decompression. METHODS: A consecutive of 28 patients with TSS who underwent posterior thoracic spinal decompression surgery with UBS between December 2014 and May 2015 was enrolled in this study. The demographic data, perioperative complications, operation time, estimated blood loss, and pre- and postoperative neurological statuses were recorded and analyzed. Neurological status was evaluated with a modified Japanese Orthopaedic Association (JOA) scale, and the neurological recovery rate was calculated using the Hirabayashi's Method. RESULTS: Thoracic spinal decompression surgery was successfully carried out in all cases via a single posterior approach. The average age at surgery was 49.7 ± 8.5 years. The mean operative time of single-segment laminectomy was 3.0 ± 1.4 min, and the blood loss was 108.3 ± 47.3 ml. In circumferential decompression, the average blood loss was 513.8 ± 217.0 ml. Two cases of instrument-related nerve root injury occurred during operation and were cured by conservative treatment. Six patients experienced cerebrospinal fluid (CSF) leakage postoperatively, but no related complications were observed. The mean follow-up period was 39.7 ± 8.9 months, the average JOA score increased from 4.7 before surgery to 10.1 postoperatively, and the average recovery rate was 85.8%. CONCLUSIONS: The UBS is an optimal instrument for thoracic spinal decompression, and its application enables surgeons to decompress the thoracic spinal cord safely and effectively. This standard operating procedure is expected to help achieve favorable outcomes and can be used to treat various pathologies leading to TSS.