Changes in Blood Pressure is Associated with Bone Loss in US Adults: A Cross-Sectional Study from NHANES 2005-2018.

Hypertension and osteoporosis are common geriatric diseases, sharing similar risk factors. This study aims to investigate this association and explore relatively mixed variables. Our study included 12,787 eligible participants from the National Health and Nutrition Examination Survey (NHANES) 2005-2018. Included participants had valid data on hypertension and osteoporosis, without tumors, liver diseases, gout or thyroid diseases. We explored the association between hypertension and osteoporosis by logistic regression and examined blood pressure and BMD/BMC by linear and non-linear regression. Moreover, we used machine learning models to predict the importance of various factors in the occurrence of osteoporosis and evaluated causality by mendelian randomization. Our study found that osteoporosis is significantly associated with hypertension [OR 2.072 (95% CI 2.067-2.077), p < 0.001]. After adjusting for co-variances, the association remained significant [OR 1.223 (95% CI 1.220-1.227), p < 0.001]. Our study showed that osteoporosis is positively associated with hypertension in the US population. A variety of factors influence this relationship. Specific regulatory mechanisms and confounding factors need to be further investigated.

Elucidating the role of RBM5 in osteoclastogenesis: a novel potential therapeutic target for osteoporosis.

Osteoporosis is a prevalent bone disease with multigene involved, and the molecular mechanisms of its pathogenesis are not entirely understood. This study aims to identify novel key genes involved in osteoporosis to discover potential pharmacological targets. We analyzed three microarray datasets and identified four differentially expressed genes. The LASSO model indicated that RNA-binding motif protein 5 (RBM5) is associated with osteoporosis and is a potential drug target. We conducted the Spearman correlation analysis and found 52 genes that were significantly related to RBM5. Enrichment analysis showed that these genes were primarily involved in RNA splicing and osteoclast differentiation pathways. By using lentivirus-based shRNA, we successfully knocked down RBM5 expression in RAW264.7 cell line, which showed that RBM5 knockdown significantly impaired their differentiation potential to mature osteoclasts and significantly inhibited bone-resorbing activity. RT-qPCR analyses revealed the expression of osteoclastogenesis marker genes was downregulated along with RBM5 expression. These findings suggest that RBM5 plays a crucial role in the pathogenesis of osteoporosis and provides a new potential pharmacological target.

Mediating oxidative stress through the Palbociclib/miR-141-3p/STAT4 axis in osteoporosis: a bioinformatics and experimental validation study.

Osteoporosis is a common bone disease characterized by loss of bone mass, reduced bone strength, and deterioration of bone microstructure. ROS-induced oxidative stress plays an important role in osteoporosis. However, the biomarkers and molecular mechanisms of oxidative stress are still unclear. We obtained the datasets from the Gene Expression Omnibus (GEO) database, and performed differential analysis, Venn analysis, and weighted correlation network analysis (WGCNA) analysis out the hub genes. Then, the correlation between inflammatory factors and hub genes was analyzed, and a Mendelian randomization (MR) analysis was performed on cytokines and osteoporosis outcomes. In addition, "CIBERSORT" was used to analyze the infiltration of immune cells and single-cell RNA-seq data was used to analyze the expression distribution of hub genes and cell-cell communications. Finally, we collected human blood samples for RT-qPCR and Elisa experiments, the miRNA-mRNA network was constructed using the miRBase database, the 3D structure was predicted using the RNAfold, Vfold3D database, and the drug sensitivity analysis was performed using the RNAactDrug database. We obtained three differentially expressed genes associated with oxidative stress: DBH, TAF15, and STAT4 by differential, WGCNA clustering, and Venn screening analyses, and further analyzed the correlation of these 3 genes with inflammatory factors and immune cell infiltration and found that STAT4 was significantly and positively correlated with IL-2. Single-cell data analysis showed that the STAT4 gene was highly expressed mainly in dendritic cells and monocytes. In addition, the results of RT-qPCR and Elisa experiments verified that the expression of STAT4 was consistent with the previous analysis, and a significant causal relationship between IL-2 and STAT4 SNPs and osteoporosis was found by Mendelian randomization. Finally, through miRNA-mRNA network and drug sensitivity analysis, we analyzed to get Palbociclib/miR-141-3p/STAT4 axis, which can be used for the prevention and treatment of osteoporosis. In this study, we proposed the Palbociclib/miR-141-3p/STAT4 axis for the first time and provided new insights into the mechanism of oxidative stress in osteoporosis.

Curcumin-activated Olfactory Ensheathing Cells Improve Functional Recovery After Spinal Cord Injury by Modulating Microglia Polarization Through APOE/TREM2/NF-κB Signaling Pathway.

Transplantation of curcumin-activated olfactory ensheathing cells (aOECs) improved functional recovery in spinal cord injury (SCI) rats. Nevertheless, little is known considering the underlying mechanisms. At the present study, we investigated the promotion of regeneration and functional recovery after transplantation of aOECs into rats with SCI and the possible underlying molecular mechanisms. Primary OECs were prepared from the olfactory bulb of rats, followed by treatment with 1µM CCM at 7-10 days of culture, resulting in cell activation. Concomitantly, rat SCI model was developed to evaluate the effects of transplantation of aOECs in vivo. Subsequently, microglia were isolated, stimulated with 100 ng/mL lipopolysaccharide (LPS) for 24 h to polarize to M1 phenotype and treated by aOECs conditional medium (aOECs-CM) and OECs conditional medium (OECs-CM), respectively. Changes in the expression of pro-inflammatory and anti-inflammatory phenotypic markers expression were detected using western blotting and immunofluorescence staining, respectively. Finally, a series of molecular biological experiments including knock-down of triggering receptor expressed on myeloid cells 2 (TREM2) and analysis of the level of apolipoprotein E (APOE) expression were performed to investigate the underlying mechanism of involvement of CCM-activated OECs in modulating microglia polarization, leading to neural regeneration and function recovery. CCM-activated OECs effectively attenuated deleterious inflammation by regulating microglia polarization from the pro-inflammatory (M1) to anti-inflammatory (M2) phenotype in SCI rats and facilitated functional recovery after SCI. In addition, microglial polarization to M2 elicited by aOECs-CM in LPS-induced microglia was effectively reversed when TREM2 expression was downregulated. More importantly, the in vitro findings indicated that aOECs-CM potentiating LPS-induced microglial polarization to M2 was partially mediated by the TREM2/nuclear factor kappa beta (NF-κB) signaling pathway. Besides, the expression of APOE significantly increased in CCM-treated OECs. CCM-activated OECs could alleviate inflammation after SCI by switching microglial polarization from M1 to M2, which was likely mediated by the APOE/TREM2/NF-κB pathway, and thus ameliorated neurological function. Therefore, the present finding is of paramount significance to enrich the understanding of underlying molecular mechanism of aOECs-based therapy and provide a novel therapeutic approach for treatment of SCI.

Identifying microbial signatures for patients with postmenopausal osteoporosis using gut microbiota analyses and feature selection approaches.

Osteoporosis (OP) is a metabolic bone disorder characterized by low bone mass and deterioration of micro-architectural bone tissue. The most common type of OP is postmenopausal osteoporosis (PMOP), with fragility fractures becoming a global burden for women. Recently, the gut microbiota has been connected to bone metabolism. The aim of this study was to characterize the gut microbiota signatures in PMOP patients and controls. Fecal samples from 21 PMOP patients and 37 controls were collected and analyzed using amplicon sequencing of the V3-V4 regions of the 16S rRNA gene. The bone mineral density (BMD) measurement and laboratory biochemical test were performed on all participants. Two feature selection algorithms, maximal information coefficient (MIC) and XGBoost, were employed to identify the PMOP-related microbial features. Results showed that the composition of gut microbiota changed in PMOP patients, and microbial abundances were more correlated with total hip BMD/T-score than lumbar spine BMD/T-score. Using the MIC and XGBoost methods, we identified a set of PMOP-related microbes; a logistic regression model revealed that two microbial markers (Fusobacteria and Lactobacillaceae) had significant abilities in disease classification between the PMOP and control groups. Taken together, the findings of this study provide new insights into the etiology of OP/PMOP, as well as modulating gut microbiota as a therapeutic target in the diseases. We also highlight the application of feature selection approaches in biological data mining and data analysis, which may improve the research in medical and life sciences.

Correlation of R2* with fat fraction and bone mineral density and its role in quantitative assessment of osteoporosis.

OBJECTIVES: To investigate the correlation of R2* with vertebral fat fraction (FF) and bone mineral density (BMD), and to explore its role in the quantitative assessment of osteoporosis (OP). METHODS: A total of 83 patients with low back pain (59.77 ± 7.46 years, 30 males) were enrolled, which underwent lumbar MRI in IDEAL-IQ sequences and quantitative computed tomography (QCT) scanning within 48h. The FF, R2*, and BMD of all 415 lumbar vertebrae were respectively measured. According to BMD, all vertebrae were divided into BMD normal, osteopenia, and OP groups, and the difference of FF and R2* among groups was analyzed by one-way ANOVA. The correlation between R2*, FF, and BMD was analyzed by Pearson's test. Taking BMD as the gold standard, the efficacies for FF and R2* in diagnosis of OP and osteopenia were assessed by receiver operating characteristic curve, and their area under the curve (AUC) was compared with DeLong's test. RESULTS: The FF and R2* were statistically different among groups (F values of 102.521 and 11.323, both p < 0.05), and R2* were significantly correlated with FF and BMD, respectively (r values of -0.219 and 0.290, both p < 0.05). In diagnosis of OP and osteopenia, the AUCs were 0.776 and 0.778 for FF and 0.638 and 0.560 for R2*, and the AUCs of R2* were lower than those of FF, with Z values of 4.030 and 4.087, both p < 0.001. CONCLUSION: R2* is significantly correlated with FF and BMD and can be used as a complement to FF and BMD for quantitative assessment of OP. KEY POINTS: • R2* based on IDEAL-IQ sequences has a definite but weak linear relationship with FF and BMD. • FF is significantly correlated with BMD and can effectively evaluate BMAT. • R2* can be used as a complement to FF and BMD for fine quantification of bone mineral loss and bone marrow fat conversion.

Supramolecular Hydrogel Microspheres of Platelet-Derived Growth Factor Mimetic Peptide Promote Recovery from Spinal Cord Injury.

Neural stem cells (NSCs) are considered to be prospective replacements for neuronal cell loss as a result of spinal cord injury (SCI). However, the survival and neuronal differentiation of NSCs are strongly affected by the unfavorable microenvironment induced by SCI, which critically impairs their therapeutic ability to treat SCI. Herein, a strategy to fabricate PDGF-MP hydrogel (PDGF-MPH) microspheres (PDGF-MPHM) instead of bulk hydrogels is proposed to dramatically enhance the efficiency of platelet-derived growth factor mimetic peptide (PDGF-MP) in activating its receptor. PDGF-MPHM were fabricated by a piezoelectric ceramic-driven thermal electrospray device, had an average size of 9 µm, and also had the ability to activate the PDGFRß of NSCs more effectively than PDGF-MPH. In vitro, PDGF-MPHM exerted strong neuroprotective effects by maintaining the proliferation and inhibiting the apoptosis of NSCs in the presence of myelin extracts. In vivo, PDGF-MPHM inhibited M1 macrophage infiltration and extrinsic or intrinsic cells apoptosis on the seventh day after SCI. Eight weeks after SCI, the T10 SCI treatment results showed that PDGF-MPHM + NSCs significantly promoted the survival of NSCs and neuronal differentiation, reduced lesion size, and considerably improved motor function recovery in SCI rats by stimulating axonal regeneration, synapse formation, and angiogenesis in comparison with the NSCs graft group. Therefore, our findings provide insights into the ability of PDGF-MPHM to be a promising therapeutic agent for SCI repair.

Quantitative Study of Vertebral Body and Paravertebral Muscle Degeneration Based on Dual-Energy Computed Tomography: Correlation With Bone Mineral Density.

OBJECTIVES: This study aimed to quantify the degeneration of the vertebral body and paravertebral muscles using dual-energy computed tomography (DECT) and study its relationship with osteoporosis. METHODS: A total of 130 patients with chronic low back pain were included in this study, and DECT scanning of the lumbar region was undertaken prospectively. By placing a standard quantitative computed tomography corrected phantom under the waist during the DECT procedure, bone mineral density (BMD) and the following quantitative parameters were obtained: calcium density (CaD), vertebral fat fraction (VFF), psoas major area, psoas major fat fraction, erector spinalis area, and erector spinalis fat fraction (ESFF). Independent sample t test and 1-way analysis of variance were used between different age-BMD groups. Pearson test was applied to determine correlations for all measurements, and a mathematical model of BMD was established through regression analysis. RESULTS: Calcium density, VFF, psoas major area, psoas major fat fraction, erector spinalis area, and ESFF were significantly different among the age-BMD groups (P < 0.05), and BMD was significantly correlated with these parameters (P < 0.05). Calcium density, VFF, and ESFF were included in the BMD regression equation: BMD = 69.062 + 11.637 × CaD - 1.018 × VFF - 0.726 × ESFF (R2 = 0.860, F = 125.979, P < 0.001). CONCLUSIONS: Degeneration of the vertebral body and paravertebral muscles can be quantitatively analyzed using DECT, and CaD, VFF, and ESFF were independent influencing factors of BMD.

Screw Pullout Strength After Pedicle Screw Reposition: A Finite Element Analysis.

RESEARCH DESIGN: Finite element analysis based on computed tomography images from the lumbar spine. OBJECTIVE: Determined the pullout strength of unsatisfactorily placed screws and repositioned screws after unsatisfactory place in lumbar spine surgery. BACKGROUND: Pedicle screws are widely used to stabilize the spinal vertebral body. Unsatisfactory screws could lead to surgical complications, and may need to be repositioned. Screw removal and reposition, however, may decrease pullout strength. METHODS: We conducted a three-dimensional finite element analysis based on high-resolution computed tomography images from a 39-year-old healthy woman. Pullout strength was determined with the screw placed in different orientations at the same entry point (as selected by the Magerl method), as well as after removal and reposition. The material properties of the vertebral body and the screw were simulated by using grayscale values and verified data, respectively. A load along the screw axis was applied to the end of the screw to simulate the pullout. RESULTS: The pullout strength was 1840.0 N with the Magerl method. For unsatisfactorily placed screws, the pullout strength was 1500.8 N at 20% overlap, 1609.6 N at 40% overlap, 1628.9 N at 60% overlap, and 1734.7 N at 80% overlap with the hypothetical screw path of the Magerl method. For repositioned screws, the pullout strength was 1763.6 N, with 20% overlap, 1728.3 N at 40% overlap, 1544.0 N at 60% overlap, and 1491.1 N at 80% overlap, with the original path. Comparison of repositioned screw with unsatisfactorily placed screw showed 14.04% decrease in pullout strength at 80% overlap, 5.21% decrease at 60% overlap, 7.37% increase at 40% overlap, and 17.51% increase at 20% overlap, with the screw path of the Magerl method. CONCLUSIONS: Removal and reposition increased the pullout strength at 20% and 40% overlap, but decreased the pullout strength at 60% and 80% overlap. For clinical translation, we recommend removal and reposition of the screw when the overlap is in the range of 20% to 40% or less. In vitro specimen studies are needed to verify these preliminary findings.

Thoracic Jia-Ji electro-acupuncture mitigates low skeletal muscle atrophy and improves motor function recovery following thoracic spinal cord injury in rats.

OBJECTIVES: The goal of this study was to determine whether electro-acupuncture (EA) stimulation might protect the motor endplate, minimize muscle atrophy in the hind limbs, and enhance functional recovery of rats with spinal cord injury (SCI). METHODS: Sprague-Dawley adult female rats (n = 30) were randomly assigned into Sham, SCI, and EA + SCI groups (n = 10 each). Rats in the Sham and SCI groups were bound in prone position only for 30 min, and rats in the EA + SCI group were treated with electro-acupuncture. The EA was conducted from the first day after surgery, lasted for 30 mins, once every day for 28 consecutive days. RESULTS: EA significantly prevented motor endplate degeneration, improved electrophysiological function, and ameliorated hindlimb muscle atrophy after SCI. Meanwhile, EA upregulated Tuj-1 expression, downregulated GFAP expression, and reduced glial scar formation. Additionally, after 4 weeks of EA treatment, the serum of SCI rats exhibited a reduced inflammatory response. CONCLUSION: These findings suggest that EA can preserve the motor endplate and reduce muscular atrophy. In addition, EA has been shown to improve the function of upper and lower neurons, reduce glial scar formation, suppress systemic inflammation, and improve axon regeneration.

A functionalized self-assembling peptide containing E7 and YIGSR sequences enhances neuronal differentiation of spermatogonial stem cells on aligned PCL fibers for spinal cord injury repair.

Background: Spinal cord injury (SCI) induces neuronal death and disrupts the nerve fiber bundles, which leads to partial or complete sensorimotor function loss of the limbs. Transplantation of exogenous neurons derived from stem cells to the lesion site becomes a new neurorestorative strategy for SCI treatment. Spermatogonial stem cells (SSCs) can attain pluripotency features by converting to embryonic stem-like cells in vitro. However, differentiating SSCs into lineage-specific neurons is quite difficult and low efficiency. Methods: Immunofluorescence, immunohistochemistry, Western blotting, whole-cell patch clamp, and behavioral tests were performed to verify that self-assembled hydrogels could improve the directional differentiation efficiency of SSCs and the feasibility of SSC-derived neurons in the treatment of spinal cord injury. Results: We developed a novel self-assembled peptide Nap-FFGEPLQLKMCDPGYIGSR (Nap-E7-YIGSR) coated with aligned electrospun PCL fibers to enhance neuronal differentiation of SSCs. The Nap-E7-YIGSR peptide could evenly self-assemble on the surface of PCL fibers, enhanced the materials's hydrophilicity, and improved the SSC affinity of PCL fibers through the stem cell adhesion peptide sequence EPLQLKM domain. In addition, Nap-E7-YIGSR could effectively induce SSC neuron differentiation by activating the integrin ß1/GSK3ß/ß-catenin signaling pathway. Moreover, implanting the induced neurons derived from SSCs into SCI lesion sites in rats resulted in the formation of new relay circuits, myelination, and synapse formation. Furthermore, SSC-derived neurons could survive and function in the spinal cord injury microenvironment, boosting the recovery of locomotion. Conclusion: The combination of the multifunctional peptide and aligned fibers can potentially trigger SSC differentiation to neurons, facilitating neuronal replacement therapy and promoting functional recovery after SCI.

Feature selection approaches identify potential plasma metabolites in postmenopausal osteoporosis patients.

INTRODUCTION: Postmenopausal women with osteoporosis (PMOP) are prone to fragility fractures. Osteoporosis is associated with alterations in the levels of specific circulating metabolites. OBJECTIVES: To analyze the metabolic profile of individuals with PMOP and identify novel metabolites associated with bone mineral density (BMD). METHODS: We performed an unsupervised metabolomics analysis of plasma samples from participants with PMOP and of normal controls (NC) with normal bone mass. BMD values for the lumber spine and the proximal femur were determined using dual-energy X-ray absorptiometry. Principal component analysis (PCA) and supervised partial least squares discriminant analysis (PLS-DA) were performed for metabolomic profile analyses. Metabolites with P < 0.05 in the t-test, VIP > 1 in the PLS-DA model, and SNR > 0.3 between the PMOP and NC groups were defined as differential abundant metabolites (DAMs). The SHapley additive explanations (SHAP) method was utilized to determine the importance of permutation of each DAM in the predictive model between the two groups. ROC analysis and correlation analysis of metabolite relative abundance and BMD/T-scores were conducted. KEGG pathway analysis was used for functional annotation of the candidate metabolites. RESULTS: Overall, 527 annotated molecular markers were extracted in the positive and negative total ion chromatogram (TIC) of each sample. The PMOP and NC groups could be differentiated using the PLS-DA model. Sixty-eight DAMs were identified, with most relative abundances decreasing in the PMOP samples. SHAP was used to identify 9 DAM metabolites as factors distinguishing PMOP from NC. The logistic regression model including Triethanolamine, Linoleic acid, and PC(18:1(9Z)/18:1(9Z)) metabolites demonstrated excellent discrimination performance (sensitivity = 97.0, specificity = 96.6, AUC = 0.993). The correlation analysis revealed that the abundances of Triethanolamine, PC(18:1(9Z)/18:1(9Z)), 16-Hydroxypalmitic acid, and Palmitic acid were significantly positively correlated with the BMD/T score (Pearson correlation coefficients > 0.5, P < 0.05). Most candidate metabolites were involved in lipid metabolism based on KEGG functional annotations. CONCLUSION: The plasma metabolomic signature of PMOP patients differed from that of healthy controls. Marker metabolites may help provide information for the diagnosis, therapy, and prevention of PMOP. We highlight the application of feature selection approaches in the analysis of high-dimensional biological data.

Accuracy and applicability of dual-energy computed tomography in quantifying vertebral bone marrow adipose tissue compared with magnetic resonance imaging.

OBJECTIVES: To evaluate the accuracy of dual-energy computed tomography (DECT) in quantifying bone marrow adipose tissue (BMAT) and its applicability in the study of osteoporosis (OP). METHODS: A total of 83 patients with low back pain (59.77 ± 7.46 years, 30 males) were enrolled. All patients underwent lumbar DECT and magnetic resonance imaging (MRI) scanning within 48 h, and the vertebral fat fraction (FF) was quantitatively measured, recorded as DECT-FF and MRI-FF. A standard quantitative computed tomography (QCT) phantom was positioned under the waist during DECT procedure to realize the quantization of bone mineral density (BMD). The intraclass correlation coefficient (ICC) and Bland-Altman method was used to evaluate the agreement between DECT-FF and MRI-FF. The Pearson test was used to study the correlation between DECT-FF, MRI-FF, and BMD. With BMD as a gold standard, the diagnostic efficacy of DECT-FF and MRI-FF in different OP degrees was compared by receiver operating characteristic (ROC) curve and DeLong test. RESULTS: The values of DECT-FF and MRI-FF agreed well (ICC = 0.918). DECT-FF and MRI-FF correlated with BMD, with r values of -0.660 and -0.669, respectively (p < 0.05). In the diagnosis of OP and osteopenia, the areas under curve (AUC) of DECT-FF was, respectively, 0.791 and 0.710, and that of MRI-FF was 0.807 and 0.708, and there was no significant difference between AUCs of two FF values (with Z values of 0.503 and 0.066, all p > 0.05). CONCLUSION: DECT can accurately quantify the BMAT of vertebrae and has the same applicability as MRI in the study of OP.

Exosomes derived from olfactory ensheathing cells provided neuroprotection for spinal cord injury by switching the phenotype of macrophages/microglia.

Transplantation of olfactory ensheathing cells (OECs) has been demonstrated to be beneficial for spinal cord injury (SCI) by modulating neuroinflammation, supporting neuronal survival and promoting angiogenesis. Besides OECs, the conditioned medium (CM) from OECs has also been proved to have therapeutic effects for SCI, indicating that the bioactive substances secreted by OECs are essential for its protective effects. Nevertheless, there is still little information regarding the underlying mechanisms. Considering that exosomes are crucial for intercellular communication and could be secreted by different types of cells, we speculated that the therapeutic potential of OECs for SCI might be partially based on their exosomes. To examine whether OECs could secret exosomes, we isolated exosomes by polyethylene glycol-based method, and identified them by electron microscopy study, nanoparticle tracking analysis (NTA) and western blotting. In view of phagocytic ability of microglia and its distinct roles in microenvironment regulation after SCI, we then focused the effects of OECs-derived exosomes (OECs-Exo) on microglial phenotypic regulation. We found that the extracted OECs-Exo could be engulfed by microglia and partially reverse the LPS-induced pro-inflammatory polarization through inhibiting NF-κB and c-Jun signaling pathways in vitro. Furthermore, OECs-Exo were found to inhibit the polarization of pro-inflammatory macrophages/microglia while increased the numbers of anti-inflammatory cells after SCI. Considering that the neuronal injury is closely related to the activation state of macrophages/microglia, co-culture of microglia and neurons were performed. Neuronal death induced by LPS-treated microglia could be significantly alleviated when microglia treated by LPS plus OECs-Exo in vitro. After SCI, NeuN-immunostaining and axonal tract-tracing were performed to assess neuronal survival and axon preservation. Our data showed that the OECs-Exo promoted the neuronal survival and axon preservation, and facilitated functional recovery after SCI. Our findings provide a promising therapeutic strategy for SCI based on exosome-immunomodulation.

Surgical treatment of the lower cervical brucellosis with osteoporosis in the northwest region of China: review of 22 cases.

OBJECTIVE: To analyze the surgical treatment of patients with cervical brucellosis with osteoporosis over a 4-year period in Northwest China. METHODS: From 2013 to 2018, 22 patients (12 males and 10 females) with lower cervical spine brucellosis (C3-C7) underwent anterior lesion debridement, decompression, bone grafting and internal fixation combined with posterior bone graft fusion and internal fixation (ADDF+PIF). The follow-up period averaged 37.4 months (ranging from 24 to 57 months). RESULTS: Involvement of 1 vertebra was observed in 3 patients, involvement of 3 vertebrae was observed in 9 patients, and involvement of 3 vertebrae was observed in 10 patients. Before surgery, 1 patient had Frankel grade B, 2 had grade C, 9 had grade D, and 10 had grade E. In the final follow-up, 12 patients had neurological deficits, 10 patients improved by one grade, 6 patients improved by two grades, and the neurological status of 6 patients remained unchanged. In all cases, it was observed that bone fusion required 6.8 months on average. The kyphosis Cobb angle was enhanced from an average of 11.5° preoperatively (range 0°-24°) to 0.13° postoperatively (range 1°-5°), and there was no vital loss of correction in the follow-up. CONCLUSIONS: ADDF+PIF is an effective and safe treatment for patients with lower cervical brucellosis with osteoporosis.

Plasma lipidomics analysis reveals altered lipids signature in patients with osteonecrosis of the femoral head.

INTRODUCTION: Although studies have established a link between lipid metabolism disorder and osteonecrosis of the femoral head (ONFH), the characteristics of the circulating lipidome signature of ONFH have not yet been investigated and need to be explored. OBJECTIVES: We aimed to explore the plasma lipidome signatures in patients with ONFH, and to identify specific lipid biomarkers of ONFH. METHODS: In this study, a comprehensive detection and analysis of plasma lipidomics was conducted in clinical human cohort, including 32 healthy normal control (NC) subjects and 91 ONFH patients in different subgroups [alcohol-induced ONFH (AONFH), steroid-induced ONFH (SONFH), and traumatic-induced ONFH (TONFH)] or at different disease stages (stage I, II, III and IV of ONFH) using ultra-high performance liquid chromatography-tandem mass spectrometry (UHPLC-MS/MS). RESULTS: Overall, the plasma lipidome profile differs between ONFH and NC samples. Lipidome signature including 22 common differentially expressed lipids (DELs) in all three subgroups (variable importance in projection > 1, P < 0.05, fold change > 1.5 or < 0.67, compared to the NC group) was identified. Besides, the subtype-specific lipidome profiles for each ONFH subgroup were also analyzed. Generally, the AONFH subgroup has the largest number of DELs, and the plasma levels of triacylglycerol lipid compounds increased obviously in the AONFH samples. In the subgroup of SONFH, the relative abundance of lipid 4-Aminobenzoic acid increased significantly with changes in the expression of several of its interactive genes. We have identified that 9 stage-positive and 2 stage-negative lipids may function as novel biomarkers predicting the progression of ONFH. CONCLUSION: Our study presents an overview of the phenotype-related plasma lipidome signature of patients with ONFH. The results will provide insight into the mechanisms underlying the metabolism of lipids in the pathogenesis and progression of ONFH and help identify novel lipids biomarkers or disease diagnosis and treatment targets.

Transcriptome-wide association study identifies multiple genes and pathways associated with thyroid function.

Thyroid dysfunction is a common endocrine disease measured by thyroid-stimulating hormone (TSH) level. Although >70 genetic loci associated with TSH have been reported through genome-wide association studies (GWASs), the variants can only explain a small fraction of the thyroid function heritability. To identify novel candidate genes for thyroid function, we conducted the first large-scale transcriptome-wide association study (TWAS) for thyroid function using GWAS-summary data for TSH levels in up to 119 715 individuals combined with precomputed gene expression weights of six panels from four tissue types. The candidate genes identified by TWAS were further validated by TWAS replication and gene expression profiles. We identified 74 conditionally independent genes significantly associated with thyroid function, such as PDE8B (P = 1.67 × 10-282), PDE10A (P = 7.61 × 10-119), NR3C2 (P = 1.50 × 10-92) and CAPZB (P = 3.13 × 10-79). After TWAS replication using UKBB datasets, 26 genes were replicated for significant associations with thyroid-relevant diseases/traits. Among them, 16 genes were causal for their associations to thyroid-relevant diseases/traits and further validated in differential expression analyses, including two novel genes (MFSD6 and RBM47) that did not implicate in previous GWASs. Enrichment analyses detected several pathways associated with thyroid function, such as the cAMP signaling pathway (P = 7.27 × 10-4), hemostasis (P = 3.74 × 10-4), and platelet activation, signaling and aggregation (P = 9.98 × 10-4). Our study identified multiple candidate genes and pathways associated with thyroid function, providing novel clues for revealing the genetic mechanisms of thyroid function and disease.

Global Analysis of Microbiota Signatures in Four Major Types of Gastrointestinal Cancer.

The gut microbiota has been previously linked with tumorigenesis and gastrointestinal cancer progression; however, intra-tumor microbiota analysis has just emerged and deserves increasing attention. Based on the public databases of The Cancer Microbiome Atlas (TCMA) and The Cancer Genome Atlas (TCGA), this study identified the tissue/organ microbial signatures generated from 443 biosamples of four major gastrointestinal cancer types, including esophageal carcinoma (ESCA), which further includes esophageal adenocarcinoma (EAD) and esophageal squamous cell carcinoma (ESCC), stomach adenocarcinoma (STAD), colon adenocarcinoma (COAD), and rectum adenocarcinoma (READ). According to partial least squares discrimination analysis (PLS-DA), the profile differences in microbial communities between the tumor and normal samples were not particularly noticeable across the four cancer cohorts, whereas paired comparison analyses revealed several specific differences in bacteria between tumor and normal samples in the EAD, STAD, and COAD samples. The taxa classified from the phylum to genus level revealed a trend of distinguishable microbial profiles between upper and lower gastrointestinal tumors. The Bacteroidetes/Firmicutes ratio in lower gastrointestinal tract tumors was nearly three times that in upper gastrointestinal tract tumors. We also determined the relative tissue/organ-prevalent microbes for each of the four cohorts at the order and genus levels. Microbe Alistipes, Blautia, Pasteurellales, and Porphyromonas compositions were correlated with the clinical characteristics of patients with gastrointestinal cancer, particularly colorectal cancer. Taken together, our findings indicate that microbial profiles shift across different gastrointestinal cancer types and that microbial colonization is highly site-specific. Composition of specific microbes can be indicative of cancer stage or disease progression. Overall, this study indicates that the microbial community and abundance in human tissues can be determined using publicly available data, and provides a new perspective for intra-tissue/organ microbiota research.

Trends of epidemiological characteristics of traumatic spinal cord injury in China, 2009-2018.

OBJECTIVE: We focus on providing the first comprehensive national dataset on the incidence, injury aetiology and mortality of TSCI in China. METHODS: A multi-stage stratified cluster sampling method was used. We included TSCI cases from all hospitals in three regions, nine provinces and 27 cities in China via search of electronic medical records and retrospectively analysed the characteristics of TSCI in China from 2009 to 2018. We estimated the incidence of TSCI in the total population and subgroups. RESULTS: There were 5954 actual cases in 2009, corresponding to a total estimated TSCI incidence of 45.1 cases per million population (95% CI, 44.0-46.3). There were 10,074 actual cases in 2018, corresponding to a total estimated TSCI incidence of 66.5 cases per million population (95% CI, 65.2-67.8) (P < 0.001; annual average percentage change (AAPC), 4.4%). From 2009 to 2018, the incidence of almost all sex/age groups showed an increasing trend over time (P < 0.001; AAPC, 0.7-8.8%). The elderly population (aged 65-74) displayed the highest incidence of TSCI (with an average annual incidence of 127.1 cases per million [95% CI, 119.8-134.3]). CONCLUSIONS: The TSCI incidence increased significantly from 2009 to 2018. The incidence in the elderly populations was consistently high and continues to increase over time. The mortality of TSCI patients in hospitals is relatively low and continues to decrease each year, but elderly individuals remain at a high risk of hospital death.

Dual-Energy Computed Tomography Virtual Noncalcium Technique in Diagnosing Osteoporosis: Correlation With Quantitative Computed Tomography.

OBJECTIVE: The aim of this study was to evaluate dual-energy computed tomography (CT) virtual noncalcium (VNCa) technique as a means of quantifying osteoporosis. METHODS: Dual-energy CT scans were obtained prospectively, targeting lumbar regions of 55 patients with chronic low back pain. A standard quantitative CT (QCT) phantom was positioned at the waist during each procedure, using proprietary software (QCT Pro; Mindways, Tex) to measure bone mineral density (BMD) in each vertebral body. Vendor dual-energy analytic software was altered with a specially modified configuration file to produce a "Virtual Non Calcium" or "VNCa" output, as such output variables were remapped to produce the following calcium values rather than iodine, yielding the following QCT parameters: CT value of calcium (originally "contrast media" [CM]), CT value of mixed energy imaging (regular CT value [rCT]), calcium density (originally "contrast agent density" [CaD]), and fat fraction (FF). Pearson test served to assess correlations between BMD and these parameters. Multiple linear regression analysis was applied to construct an equation for generating regressive BMD (rBMD) values. In gauging diagnostic accuracies, the criterion-standard BMD cutoff point (<80 mg/cm3) was adopted for QCT, whereas the rBMD threshold was defined by receiver operating characteristic curve. RESULTS: Contrast media, rCT, CaD, and FF values (reflecting CT value of calcium, regular CT value, calcium density, and fat fraction, respectively) significantly correlated with BMD (r values: 0.885, 0.947, 0.877, and 0.492, respectively; all P < 0.01). Contrast media, CaD, and FF showed independent associations with BMD; the regressive equation was formulated as follows: rBMD = 54.82 - 0.19 × CM + 20.03 × CaD - 1.24 × FF. The area under the curve of rBMD in diagnosing osteoporosis was 0.966 ± 0.009 (P < 0.01). At an rBMD threshold of less than 81.94 mg/cm3, sensitivity and specificity were 90.0% and 92.0%, respectively. CONCLUSIONS: Dual-energy CT VNCa technique may constitute a valid alternative method for quantifying the mineral content and marrow fat composition of bone in diagnostic assessments of osteoporosis.