The association between different physical activity (PA) patterns and cardiometabolic index (CMI) in US adult population from NHANES (2007-2016).

Background: Physical activity (PA) is widely recommended for preventing and combating obesity, but the most effective PA pattern for treating obesity remains unclear. Cardiometabolic index (CMI), derived from waist height ratio and triglycerides to high-density lipoprotein-cholesterol ratio, is a novel indicator for evaluating obesity. However, the relationship between different PA patterns and CMI remains unelucidated. Objective: This study aimed to explore the association between different PA patterns and CMI in U.S. adults. Methods: Participants with complete information in CMI, PA patterns, and other covariates in the National Health and Nutrition Examination Survey database (2007-2016) were included in this study. Multivariate linear regression models were utilized to explore the relationship between PA patterns and CMI. Moreover, stratified analyses, interaction tests and restricted cubic spline (RCS) regression analysis were used to investigate the stability and nonlinearity of the association, respectively. Results: A total of 16,442 adults were included in this study. After adjusting for all potential covariates, only the regularly active group was significantly associated with CMI reduction (ß = -0.13, 95% CI: 0.19 to -0.07, P < 0.0001), while the weekend warriors group did not achieve equivalent CMI reduction (ß = -0.09, 95% CI: 0.32 to 0.14, P = 0.4204). Subgroup analyses and interaction tests revealed that the CMI-PA association was more pronounced in the subgroup with age≤45 or >60, with higher education level, and who are current drinkers. Furthermore, RCS analysis indicated that total PA in a week was significantly, nonlinearly associated with CMI in non-inactive adults, and that a total of PA more than 330 min can reap favorable CMI reduction. Conclusion: Being regularly active is associated with significant CMI reduction, while being weekend warriors and insufficiently active do not achieve equivalent benefits. For non-inactive individuals, engaging in PA for more than 330 min weekly helps to reduce CMI effectively.

Relationship between paravertebral muscle function, pelvic incidence, and health-related quality of life in patients with degenerative spinal deformity.

BACKGROUND: Patients with degenerative spinal deformity often experience symptoms that seriously affect their quality of life, such as low back pain and dysfunction. This study aimed to investigate the relationship between paravertebral muscle function and pelvic incidence (PI) and their effect on health-related quality of life (HRQL) in patients with degenerative spinal deformity. METHODS: A total of 112 patients with degenerative spinal deformity in Southwest Hospital (Chongqing, China) were enrolled. They were divided into groups according to PI angle: high (PI > 60°, n = 37), normal (PI 50°-60°, n = 31), and low (PI < 50°, n = 44). Paravertebral muscle strength and endurance were assessed using the prone external fixation test frame. The sagittal vertical axis (SVA) was measured on X-rays of the spine in an anterolateral position, and all subjects were assessed with the Oswestry Disability Index (ODI), Roland-Morris questionnaire (RMQ), and 36-Item Short Form Health Survey (SF-36). Pearson or Spearman coefficients were used to assess the relationship of paravertebral muscle function with SVA, PI, and health-related quality of life. RESULTS: Maximal voluntary exercise (MVE) in the high-PI group was significantly lower than the MVE of both the normal- and low-PI groups (p < 0.05). There was no significant difference in MVE between the normal- and low-PI groups (p > 0.05). There was no significant difference in endurance time, SVA, ODI, RMQ, and SF-36 among the three groups. Paravertebral muscle MVE was negatively correlated with PI, SVA, ODI, and RMQ (r = - 0.193, - 0.210, - 0.283, - 0.277, p < 0.05). Endurance time of paravertebral muscle was also negatively correlated with SVA, ODI, and RMQ (r = - 0.200, - 0.420, - 0.348, p < 0.05) and positively correlated with SF-36 (r = 0.245, p < 0.05). In addition, paravertebral muscle MVE was positively correlated with the physical functioning score of the SF-36 (r = 0.251, p < 0.05), and the endurance time of paravertebral muscle was positively correlated with the physical functioning, physical role, bodily pain, and social function scores of the SF-36 (r = 0.342, 0.230, 0.209, 0.256, p < 0.05). CONCLUSIONS: High PI may serve as a risk factor for decreased paraspinal muscle strength in patients with degenerative spinal deformities. Early and targeted exercises focusing on paraspinal muscle strength and endurance could potentially be of positive significance in slowing down the progression of sagittal imbalance, alleviating functional disorders, and increasing health-related quality of life in patients with degenerative spinal deformity.

The effects of back extensor strength in different body positions on health-related quality of life in patients with degenerative spinal deformity.

BACKGROUND: Degenerative spinal deformity (DSD) is believed to originate from degeneration of the discs and facet joints and vertebral wedging. Currently, the nosogeny of DSD is not yet fully clarified and there has been no systematic study on the impact of their lower back muscle strength on quality of life. OBJECTIVE: To determine the characteristics of back extensor strength (BES) in different body positions and examine their correlations with health-related quality of life (HQOL) in degenerative spinal deformity (DSD) patients. METHODS: Participants comprised 60 DSD patients and 40 healthy volunteers. Maximal isometric BES was evaluated by dynamometers with the subject in three different positions (standing, prone, sitting). The visual analogue scale (VAS) score, Oswestry Disability Index (ODI), Roland-Morris Disability Questionnaire (RMQ), and 36-item Short Form Health Survey (SF-36) score were used to evaluate patient HQOL. Correlations between the BES in different body positions and HQOL were analysed. RESULTS: The BES values in three body positions were significantly smaller in DSD patients than healthy subjects (P< 0.05). The standing BES was found to be negatively associated with ODI and RMQ (R= 0.313, p< 0.05 and R= 0.422, p< 0.01, respectively). A negative relationship between sitting BES and RMQ was also seen (R= 0.271, p< 0.05). In addition, the standing and prone BES were positively correlated with the physical functioning score of the SF-36 (R= 0.471, p< 0.01 and R= 0.289, p< 0.05, respectively), and the sitting BES was positively correlated with the role-physical score of the SF-36 (R= 0.436, p< 0.01). CONCLUSION: The results indicate that the back extensor muscle is compromised in DSD patients and there are differences in predicting the severity of disability and physical HQOL scores with BES in different positions. Standing BES was the most reliable contributor to HQOL among three body positions.

Correlation between strength/endurance of paraspinal muscles and sagittal parameters in patients with degenerative spinal deformity.

BACKGROUND: Sagittal imbalance is a common cause of low back pain and dysfunction in patients with degenerative spinal deformity (DSD), which greatly affects their quality of life. Strength and endurance are important functional physical indexes for assessing muscle condition. However, the correlation between sagittal parameters and paraspinal muscle strength/endurance is not yet clear. The purpose of this study was to analyze the correlation between strength/endurance of paraspinal muscles and sagittal parameters in patients with DSD. METHODS: There were 105 patients with DSD and 52 healthy volunteers (control group) enrolled. They were divided into the balance group [sagittal vertical axis (SVA) < 5 cm, n = 68] and imbalance group (SVA ≥ 5 cm, n = 37). The maximal voluntary exertion (MVE)/Endurance time (ET) of paravertebral muscles were assessed using the prone position test stand, and the sagittal parameters of the subjects were measured, namely, SVA, thoracic kyphosis (TK), lumbar lordosis (LL), pelvic incidence (PI), pelvic tilt (PT), and sacral slope (SS). Pearson coefficients were used to assess the correlation between paraspinal muscle MVE/ET and sagittal parameters. RESULTS: MVE and ET of paravertebral muscles in the control group were significantly higher than those in the balance and imbalance groups (P < 0.05), whereas MVE in the balance group was significantly higher than that in the imbalance group (P < 0.05). SVA in the imbalance group was significantly higher than those in the control and balance groups (P < 0.05). SS and TK in the control group were significantly higher than those in the imbalance group (P < 0.05), and PT and PI in the control group were significantly lower than those in the balance and imbalance groups (P < 0.05). LL in the imbalance group was significantly lower than that in the balance and control groups (P < 0.05). MVE, MVE/BH, and MVE/BW of paraspinal muscles in the imbalance group were negatively correlated with SVA and PT. Moreover, they were positively correlated with LL. CONCLUSIONS: Deformity may cause the decrease of MVE and ET of paraspinal muscles in the prone position in patients with DSD. Furthermore, the decline in MVE of paraspinal muscles may be a predisposing factor for the imbalance observed. The decrease of MVE/BW of paraspinal muscles may be involved in spinal compensation, and it is a sensitive indicator for sagittal imbalance and lumbar lordosis.

Roles of the Siglec family in bone and bone homeostasis.

Tremendous progress has been seen in the study of the role of sialic acid binding im-munoglobulin type lectins (Siglecs) in osteoimmunology in the past two decades. Interest in Siglecs as immune checkpoints has grown from the recognition that Siglecs have relevance to human disease. Siglecs play important roles in inflammation and cancer, and play key roles in immune cell signaling. By recognizing common sialic acid containing glycans on glycoproteins and glycolipids as regulatory receptors for immune cell signals, Siglecs are expressed on most immune cells and play important roles in normal homeostasis and self-tolerance. In this review, we describe the role that the siglec family plays in bone and bone homeostasis, including the regulation of osteoclast differentiation as well as recent advances in inflammation, cancer and osteoporosis. Particular emphasis is placed on the relevant functions of Siglecs in self-tolerance and as pattern recognition receptors in immune responses, thereby potentially providing emerging strategies for the treatment of bone related diseases.

Isokinetic strength assessment of trunk muscle and its relationship with spinal-pelvic parameters in patients with degenerative spinal deformity.

BACKGROUND: The incidence rate of degenerative spinal deformity (DSD) has gradually increased in the elderly. Currently, the relationship between the functional status of trunk muscle and the spinal-pelvic parameters of DSD patients remains unclear. OBJECTIVE: This paper aims to explore the relationship between the two factors and provide new clues for exploring the mechanism of the occurrence and development of DSD. METHODS: A total of 41 DSD patients treated in our hospital (DSD group) and 35 healthy volunteers (control group) were selected. Muscle strength was evaluated using an IsoMed-2000 isokinetic dynamometer, and the trunk flexor and extensor peak torque (PT) of subjects was measured at a low, medium, and high angular velocity of 30∘/s, 60∘/s, and 120∘/s, respectively. Hand grip strength (HGS) was assessed using an electronic grip dynamometer and Surgimap software was used to measure the spinal-pelvic parameters, including the sagittal vertical axis (SVA), thoracic kyphosis (TK), lumbar lordosis (LL), sacral slope (SS), pelvic tilt (PT), pelvic incidence rate (PI), and PI-LL, and the relationship between trunk muscle function and various parameters was analyzed. RESULTS: Under the three angular velocities, the flexor and extensor PT values in the DSD group were lower than those in the control group, and only the extensor PT showed a statistically significant difference (P< 0.05). There was no significant difference in HGS between the two groups (P> 0.05). In the DSD group, the extensor PT at 30∘/s was significantly negatively correlated with SVA (P< 0.05). At 60∘/s and 120∘/s, the extensor PT was significantly negatively correlated with SVA and PT (P< 0.05). CONCLUSION: Trunk extensor strength is significantly lower in DSD patients than in normal controls. The decline in trunk extensor strength in DSD patients is a type of local muscle dysfunction more closely related to the deformity, which is likely involved in the compensatory mechanism of DSD and may reflect the overall imbalance of the trunk.

Bioinformatics analysis of paravertebral muscles atrophy in adult degenerative scoliosis.

Paravertebral muscles (PVM) act as one of the major dynamic factors to maintain human upright activities and play a remarkable role in maintaining the balance of the trunk. Adult degenerative scoliosis (ADS) has become one of the important causes of disability in the elderly population owing to the changes in spinal biomechanics, atrophy and degeneration of PVM, and imbalance of the spine. Previously, many studies focused on the physical evaluation of PVM degeneration. However, the molecular biological changes are still not completely known. In this study, we established a rat model of scoliosis and performed the proteomic analysis of the PVM of ADS. The results showed that the degree of atrophy, muscle fat deposition, and fibrosis of the PVM of rats positively correlated with the angle of scoliosis. The proteomic results showed that 177 differentially expressed proteins were present in the ADS group, which included 105 upregulated proteins and 72 downregulated proteins compared with the PVM in individuals without spinal deformities. Through the construction of a protein-protein interaction network, 18 core differentially expressed proteins were obtained, which included fibrinogen beta chain, apolipoprotein E, fibrinogen gamma chain, thrombospondin-1, integrin alpha-6, fibronectin-1, platelet factor 4, coagulation factor XIII A chain, ras-related protein Rap-1b, platelet endothelial cell adhesion molecule 1, complement C1q subcomponent subunit A, cathepsin G, myeloperoxidase, von Willebrand factor, integrin beta-1, integrin alpha-1, leukocyte surface antigen CD47, and complement C1q subcomponent subunit B. Further analysis of the Kyoto Encyclopedia of Genes and Genomes pathway (KEGG) and immunofluorescence showed that the neutrophil extracellular traps (NETs) formation signaling pathway plays a major role in the pathogenesis of PVM degeneration in ADS. The results of the present study preliminarily laid the molecular biological foundation of PVM atrophy in ADS, which will provide a new therapeutic target for alleviating PVM atrophy and decreasing the occurrence of scoliosis.

Preoperative Magnetic Resonance Imaging Signal Intensity Classification Is Associated With Clinical Presentation and Surgical Outcomes in Myelopathy Caused by Thoracic Ossification of Ligamentum Flavum: A Multicenter Study.

STUDY DESIGN: Retrospective Cohort Study. OBJECTIVES: To explore whether classification of the increased signal intensity (ISI) on magnetic resonance imaging (MRI) correlates with clinical presentations and outcomes in symptomatic thoracic ossification of ligamentum flavum (T-OLF) patients. METHODS: All patients with symptomatic T-OLF who underwent laminectomy at four institutions were reviewed. The ISI on preoperative T2-weighted MRI was divided into 3 groups, Grade 0, none; Grade 1, light (obscure); and Grade 2, intense (bright). Neurological function before surgery and at follow-up was evaluated by the revised Japanese Orthopedic Association (JOA) score. Patients' demographics, clinical manifestations, and surgical outcomes were compared. RESULTS: A total of 94 patients were involved. Preoperative MRI showed 32 patients in Grade 0, 39 patients in Grade 1, and 23 patients in Grade 2. Low extremities numbness, weakness, and clinical signs were less frequent in Grade 0 patients. The grade of ISI was correlated with the duration of symptoms and cord compression. Grade 0 patients had a better preoperative JOA score than those with ISI changes, while Grade 2 patients showed worse neurological recovery, longer duration of operation, more intraoperative blood loss, and a higher incidence of perioperative complications. CONCLUSION: The classification of ISI is an effective parameter for preoperatively assessing cord compression, clinical severity, and surgical outcomes in T-OLF patients. Grade 0 patients have relatively mild neurological impairment but are more likely to be misdiagnosed. Grade 2 indicates the worst clinical impairment and neurological recovery, and implies a risky and challenging surgery.

Spatial Distribution, Antioxidant Capacity, and Spore Germination-Promoting Effect of Bibenzyls from Marchantia polymorpha.

Liverworts, considered to be the first plant type to successfully make the transition from water to land, can resist different oxidative stress. As characteristic constituents of liverworts, the bibenzyls are efficient antioxidants. In this study, spatial distributions of the bibenzyls within Marchantia polymorpha L., the model species of liverworts, were mapped using airflow-assisted desorption electrospray ionization imaging mass spectrometry. Bibenzyls were found to largely exist in the female receptacle of M. polymorpha, where lunularic acid was found to focus in the central region and bisbibenzyls were enriched in the periphery. The region-specific gene expression and antioxidant activities were characterized. In line with the spatial feature of bibenzyls, higher MpSTCS1A and Mp4CL expression levels and antioxidant ability were exhibited in the archegoniophore. The expression level of MpSTCS1A, and the content of total phenolic acid was increased after UV-B irradiation, suggesting bibenzyls play an important role in UV-B tolerance. Moreover, lunularic acid and extract of archegoniophore at a certain concentration can stimulate the spore germination under normal conditions and UV-B stress. These works broaden our understanding of the significance of bibenzyls in spore propagation and environmental adaptation.

Effects of combined adjustable Halo-pelvic fixation brace on cervical spine alignment in patients with severe rigid spinal deformity.

OBJECTIVE: To evaluate the effect of continuous traction with a combined adjustable Halo-pelvic fixation brace on the cervical spine alignment in patients with severe rigid spinal deformity and analyze its related factors. METHODS: We conducted a retrospective cohort study of 21 patients with severe rigid spinal deformity treated in our department between 2015 and 2019. All subjects received combined adjustable Halo-pelvic fixation brace traction before secondary orthopedic surgery. The influence of the Halo-pelvic fixation brace on the cervical spine alignment was evaluated by measuring the parameters of lateral cervical X-ray at three time points: before traction, at the end of traction, and 6 months after orthopedic surgery. The correlation between parameter changes and total traction duration was analyzed to explore factors influencing cervical alignment. RESULTS: The C2L-C7L angle was 22.40 ± 15.91° before traction, which decreased to 5.91 ± 6.78° at the end of traction but increased to 14.51 ± 10.07° after orthopedic surgery (BT vs ET p < 0.005, ET vs AOS p < 0.005, BT vs AOS p < 0.005). Accordingly, C2L-C7U angle, C2L-C6L angle, C2L-C6U angle, C2L-C5L angle, C7 or T1 slope, C2-C7 SVA, SCA, C2-T1 Ha, C0 slope, and C0-C2 angle also changed similarly to C2L-C7L angle. Furthermore, moderate correlation was observed between C2L-C7L angle and total traction volume (r = 0.563, p = 0.008) and SCA and traction duration (r = 0.525, p = 0.015). However, no significant correlation was found between other cervical alignment parameters and total traction volume and traction duration. CONCLUSIONS: The continuous traction of a combined adjustable Halo-pelvic fixation brace can affect the cervical spine alignment of patients with severe rigid spinal deformity and straighten the physiological curvature of the cervical spine. However, the sagittal alignment gradually recovers after the traction, without any adverse effects on the orthopedic surgery and global balance after the operation; therefore, this apparatus is worthy of wide application.

Prognosticators and Prognostic Nomograms for Leiomyosarcoma Patients With Metastasis.

Individual survival prediction and risk stratification are of vital importance to optimize the individualized treatment of metastatic leiomyosarcoma (LMS) patients. This study aimed to identify the prognostic factors for metastatic LMS patients and establish prognostic models for overall survival (OS) and cancer-specific survival (CSS). The data of LMS patients with metastasis between 2010 and 2015 were extracted from the Surveillance, Epidemiology, and End Results (SEER) database. The entire cohort was randomly divided into a training cohort and a validation cohort. The influences of primary tumor site, localized and distant metastases, and sites and number of metastases on the prognosis of metastatic LMS patients were firstly explored by Kaplan-Meier curves and log-rank tests. Furthermore, the effective therapeutic regimens and prognosticators for metastatic LMS patients were also analyzed by Cox analysis. In addition, two prognostic nomograms for OS and CSS were established, and their predictive performances were evaluated by the methods of receiver operating characteristic (ROC) curves, time-dependent ROC curves, calibration curves, and decision curve analysis (DCA). A total of 498 patients were finally collected from the SEER database and were randomly assigned to the training set (N = 332) and validation set (N = 166). No significant differences in OS were observed in patients with distant organ metastasis and localized metastasis. For patients who have already developed distant organ metastasis, the sites and number of metastases seemed to be not closely associated with survival. Patients who received chemotherapy got significantly longer survival than that of their counterparts. In univariate and multivariate Cox analyses, variables of surgery, chemotherapy, age, and tumor size were identified as independent predictors for OS and CSS, and distant metastasis was also independently associated with CSS. The areas under the curve (AUCs) of ROC curves of the nomogram for predicting 1-, 3-, and 5-year OS were 0.770, 0.800, and 0.843, respectively, and those for CSS were 0.777, 0.758, and 0.761, respectively. The AUCs of time-dependent AUCs were all over 0.750. The calibration curves and DCA curves also showed excellent performance of the prognostic nomograms. Metastasis is associated with reduced survival, while the sites and the number of metastases are not significantly associated with survival. The established nomogram is a useful tool that can help to perform survival stratification and to optimize prognosis-based decision-making in clinical practice.

Pathophysiological role of ion channels and transporters in HER2-positive breast cancer.

The incidence of breast cancer (BC) has been increasing each year, and BC is now the most common malignant tumor in women. Among the numerous BC subtypes, HER2-positive BC can be treated with a variety of strategies based on targeting HER2. Although there has been great progress in the treatment of HER2-positive BC, recurrence, metastasis and drug resistance remain considerable challenges. The dysfunction of ion channels and transporters can affect the development and progression of HER2-positive BC, so these entities are expected to be new therapeutic targets. This review summarizes various ion channels and transporters associated with HER2-positive BC and suggests potential targets for the development of new and effective therapies.

Light rare earth elements hinder bone development via inhibiting type H vessels formation in mice.

Light rare earth elements (LREEs) are widely used in medical, industrial, and agricultural fields. Wide application of light rare earth and exposure to these elements in human society leads to increasing accumulation of LREE in human skeletal system. However, the effects of LREEs on human bone health is not clear. In this study, we found that LREE reduced CD31highEmcnhigh endothelial cell mediated type H vessels formation at the metaphyseal sites, resulting in reduced bone mass and low bone quality in mouse bone development. To explore the underlying mechanism, we induced bone marrow macrophages (BMMs) to preosteoclasts (pOCs) with exposure of LREE (Pr3+, Nd3+, Sm3+). The cytotoxicity of LREE was evaluated by CCK-8. Platelet-derived growth factor (PDGF-BB) is the cytokine secreted by pOCs that most responsible for inducing Type H vessel formation. We used ELISA kit to determine the PDGF-BB level in pOC supernatant, and mouse serum finding that the PDGF-BB level was reduced by LREEs treatment. Then we tested the ability of migration and tube formation of HUVECs using condition medium from pOCs. The migration and tube formation ability of HUVECs were both suppressed with LREEs pretreatment. We concluded that LREEs hinder mouse bone development by suppressing type H vessels associated bone formation. DATA AND MATERIALS AVAILABILITY: All data generated or analyzed during this study are included in this article. Please contact the corresponding author for unique material requests. Some material used in the reported research may require requests to collaborators and agreements with both commercial and non-profit institutions, as specified in the paper. Requests are reviewed by Third Military Medical University to verify whether the request is subject to any intellectual property or confidentiality obligations. Any material that can be shared will be released via a Material Transfer Agreement.

Corrigendum to 'Phosphorylation inhibition of protein-tyrosine phosphatase 1B tyrosine-152 induces bone regeneration coupled with angiogenesis for bone tissue engineering' [Bioactive Mater. Vol. 6, Issue 7, Pages 2039-2057].

[This corrects the article DOI: 10.1016/j.bioactmat.2020.12.025.].

Laminin alpha 4 promotes bone regeneration by facilitating cell adhesion and vascularization.

Selective cell retention (SCR) has been widely used as a bone tissue engineering technique for the real-time fabrication of bone grafts. The greater the number of mesenchymal stem cells (MSCs) and endothelial progenitor cells (EPCs) retained in the scaffold, the better the osteoinductive and angiogenic properties of the scaffold's microenvironment. Improved bioscaffold properties in turn lead to improved bone graft survival, bone regeneration, and angiogenesis. Laminin plays a key role in cell-matrix adhesion, cell proliferation, and differentiation. We designed a collagen-binding domain (CBD) containing the core functional amino acid sequences of laminin α4 (CBD-LN peptide) to supplement the functional surface of a collagen-based decalcified bone matrix (DBM) scaffold. This scaffold promoted MSCs and EPCs early cell adhesion through up-regulating the expression of integrin α5ß1 and integrin αvß3 respectively, thus accelerated the following cell spreading, proliferation, and differentiation. Interestingly, it promoted the retention of MSCs (CD90+/CD105+ cells) and EPCs (CD31+ cells) in the scaffold following the use of clinical SCR technology. Furthermore, the DBM/CBD-LN scaffold induced the formation of type H vessels through the activation of the HIF-1α signaling pathway. The DBM/CBD-LN scaffold displayed rapid bone formation and angiogenesis in vivo, suggesting that it might be used as a new biomaterial in bone tissue engineering. STATEMENT OF SIGNIFICANCE: Selective cell retention technology (SCR) has been utilized in clinical settings to manufacture bioactive bone grafts. Specifically, demineralized bone matrix (DBM) is a widely-used SCR clinical biomaterial but it displays poor adhesion performance and angiogenic activity. In this work, we designed a collagen-binding domain (CBD) containing the core functional amino acid sequences of laminin α4 to supplement the functional surface of a collagen-based DBM scaffold. This bioscaffold promoted SCR-mediated MSCs and EPCs early cell adhesion, thus accelerated the following cell spreading, proliferation, and differentiation. Our results indicate this bioscaffold greatly induced osteogenesis and angiogenesis in vivo. In general, this bioscaffold has a good prospect for SCR application and may provide highly bioactive bone implant in clinical environment.

Phosphorylation inhibition of protein-tyrosine phosphatase 1B tyrosine-152 induces bone regeneration coupled with angiogenesis for bone tissue engineering.

A close relationship has been reported to exist between cadherin-mediated cell-cell adhesion and integrin-mediated cell mobility, and protein tyrosine phosphatase 1B (PTP1B) may be involved in maintaining this homeostasis. The stable residence of mesenchymal stem cells (MSCs) and endothelial cells (ECs) in their niches is closely related to the regulation of PTP1B. However, the exact role of the departure of MSCs and ECs from their niches during bone regeneration is largely unknown. Here, we show that the phosphorylation state of PTP1B tyrosine-152 (Y152) plays a central role in initiating the departure of these cells from their niches and their subsequent recruitment to bone defects. Based on our previous design of a PTP1B Y152 region-mimicking peptide (152RM) that significantly inhibits the phosphorylation of PTP1B Y152, further investigations revealed that 152RM enhanced cell migration partly via integrin αvß3 and promoted MSCs osteogenic differentiation partly by inhibiting ATF3. Moreover, 152RM induced type H vessels formation by activating Notch signaling. Demineralized bone matrix (DBM) scaffolds were fabricated with mesoporous silica nanoparticles (MSNs), and 152RM was then loaded onto them by electrostatic adsorption. The DBM-MSN/152RM scaffolds were demonstrated to induce bone formation and type H vessels expansion in vivo. In conclusion, our data reveal that 152RM contributes to bone formation by coupling osteogenesis with angiogenesis, which may offer a potential therapeutic strategy for bone defects.

Assessment of isokinetic trunk muscle strength and its association with health-related quality of life in patients with degenerative spinal deformity.

BACKGROUND: A considerable portion of the elderly population are increasingly afflicted by degenerative spinal deformity (DSD), which seriously affects patient health-related quality of life (HRQoL). HRQoL index is used across many studies to show correlations between radio-graphical alignment, disability, and pain in patients with DSD. However, imaged structural deformity represents only one aspect for consideration, namely, the disability effect of DSD. We assessed the isokinetic strength of trunk muscle in patients with degenerative spinal deformity (DSD), and investigated its relationship with HRQoL. METHODS: In total, 38 patients with DSD (DSD group) and 32 healthy individuals (control group) were recruited. Both groups were homogeneous for age, weight, height and body mass index (BMI). Assessments were performed using the isokinetic dynamometer IsoMed-2000; trunk extensor, flexor strength and flexion/extension (F/E) ratios were explored concentrically at speeds of 30°, 60° and 120° per second. The grip strength of both hands was measured using a hand-held dynamometer. Visual analogue scale (VAS) scores, the Oswestry Disability Index (ODI), a Roland-Morris disability questionnaire (RDQ), and a 36-item Short Form Health Survey (SF-36) evaluated patient HRQoL. Correlations between trunk strength and HRQoL were analyzed. RESULTS: When compared with the control group, the DSD group showed lower trunk extensor strength at three velocity movements, and higher F/E ratios at 60° and 120°/s (p < 0.05). Both groups exhibited similar trunk flexor strength and grip strength (p > 0.05). In DSD group, trunk extensor strength at 60°/s was negatively associated with ODI and RDQ (p < 0.05). A negative relationship between trunk flexor strength at 120°/s and ODI was also recorded (p < 0.05). In addition, trunk extensor strength at 60°/s and trunk flexor strength at 120°/s were positively correlated with physical functioning and role-physical scores according to the SF-36 (p < 0.05). CONCLUSIONS: We identified isolated trunk extensor myopathy in DSD, which causes an imbalance in trunk muscle strength. Isokinetic trunk extensor strength at 60°/s and trunk flexor strength at 120°/s can predict disability, and decrease physical HRQoL in DSD patients.

Dendritic cells-derived interferon-λ1 ameliorated inflammatory bone destruction through inhibiting osteoclastogenesis.

Bone infection contributing to inflammatory osteolysis is common in orthopedic surgery. The dynamic balance between bone formation and bone resorption is destroyed due to excessive osteoclast fusion and differentiation, which results in severe bone matrix loss. Many therapeutic approaches that restrain osteoclast formation and function act as efficient ways to prevent inflammatory bone erosion. We have demonstrated for the first time that dendritic cells-derived interferon-λ1 (IFN-λ1) inhibited inflammatory bone destruction in vivo and explored its underlying mechanisms on osteoclast formation in vitro. We found that IFN-λ1 was highly expressed in infectious bone tissue compared with that of non-infectious bone tissue. Additionally, dendritic cells marker genes such as CD80, CD86, and CD1a were higher expressed in infectious bone tissue than that of non-infectious bone tissue. Dendritic cells that were pretreated with LPS showed high expression of IFN-λ1. Moreover, conditioned medium of LPS-pretreated dendritic cells significantly inhibited osteoclast differentiation, as determined by TRAP staining assay. This suppressive effect was reversed by adding an IFN-λ1 monoclonal antibody. It was also investigated whether exogenous IFN-λ1 restrained osteoclastogenesis, bone resorption, F-actin ring formation, osteoclast-specific gene expression, release of pro-inflammatory cytokines, and translocation of p65 and NFATc1 by preventing the NF-κB signaling pathway and NLRP3 inflammasome formation, as well as by inducing the JAK-STAT signaling pathways in vitro. In vivo study indicated that IFN-λ1 prevents lipopolysaccharide (LPS)-induced inflammatory bone destruction by inhibiting excessive osteoclast fusion and bone resorption activity. In conclusion, our findings confirmed that dendritic cells-derived IFN-λ1 could attenuate osteoclast formation and bone resorptive activity in vitro and in vivo. These novel findings pave the way for the use of exogenous IFN-λ1 as a potential therapeutic treatment for excessive osteoclast-related diseases, such as inflammatory osteolysis, by regulating osteoclastogenesis to maintain the dynamic balance between bone formation and bone resorption.

Assessment of the association between paraspinal muscle degeneration and quality of life in patients with degenerative lumbar scoliosis.

The present study aimed to determine the characteristics of multifidus, erector spinae and psoas major degeneration in elderly patients with degenerative lumbar scoliosis (DLS) and the correlation between asymmetric changes and patient quality of life. A total of 49 patients with lumbar scoliosis (DLS group) and 38 healthy individuals (control group) were prospectively examined. The functional cross-sectional area, cross-sectional area difference index (CDI) and fat infiltration rate (FIR) of the multifidus, erector spinae and psoas major at the apical vertebral level were measured using MRI. The visual analogue scale (VAS) score, Oswestry Disability Index (ODI) and 36-item Short Form Health Survey (SF-36) score were used to evaluate patient quality of life. Correlations between the degree of asymmetric muscular degeneration and quality of life were analysed. The CDI of the multifidus, erector spinal and psoas major was higher in the DLS group compared with that in the control group. The CDI of the multifidus was found to be positively associated with the Cobb angle of lumbar scoliosis. Similar results were obtained for fat infiltration between the two groups. In addition, the CDI and FIR difference index of the multifidus was positively correlated with the VAS score and ODI but negatively correlated with the SF-36 score. The quality of life significantly decreased with increasing asymmetric atrophy and fat infiltration in the multifidus. Thus, strategies to enhance the function of the multifidus may have a positive impact on quality of life (Chinese Clinical Trial Registry, registration date, 2018.11.12; registration no. ChiCTR1800019459.).