Recalcitrant components accumulation in dissolved organic matter decreases microbial metabolic quotient of red soil under long-term manuring.

Microbial metabolism is closely related to soil carbon dioxide emissions, which in turn is related to environmental issues such as global warming. Dissolved organic matter (DOM) affects many fundamental biogeochemical processes such as microbial metabolism involved in soil carbon cycle, not only directly by its availability, but also indirectly by its chemodiversity. However, the association between the DOM chemodiversity and bioavailability remains unclear. To address this knowledge gap, soils from two agro-ecological experimental sites subjected to various long-term fertilizations in subtropical area was collected. The chemodiversity of DOM was detected by multi-spectroscopic techniques including ultraviolet-visible spectrophotometry, Fourier transform infrared spectroscopy and excitation emission matrices fluorescence spectroscopy. Results showed that long-term manure amendments significantly decreased microbial metabolic quotient (qCO2) by up to 57%. We also observed that long-term manure amendments significantly increased recalcitrant components of DOM (indicated by the aromaticity, humification index, the ratio of aromatic carbon to aliphatic carbon, and the relative abundances of humic-like components) and decreased labile components of DOM. Negatively correlation between the qCO2 and the proportion of recalcitrant components of DOM supported that accumulation in recalcitrant components of DOM increased microbial carbon utilization efficiency. Random forest models also showed the highest contribution of the relative abundances of humic-like components and the aromaticity of DOM in affecting qCO2. Both of the redundancy analysis and structural equation modeling further indicated the decisive role of soil pH in influencing the DOM chemodiversity. Soil pH explained 56.7% of the variation in the chemodiversity of DOM. The accumulation of recalcitrant components in DOM with increasing soil pH might be attributed to the accelerated microbial consumption of bioavailability components and/or to the negative impact on the solubility of bioavailability components. Overall, this research highlights the significance of long-term manure amendments in regulating qCO2 by altering the chemodiversity of soil DOM.

Evaluation of Haplo-Paraspinal-Muscle-Preserving Technique to Prevent Postoperative Axial Pain in Cervical Laminoplasty.

BACKGROUND: The present study aimed to assess the efficacy of a new haplo-paraspinal-muscle-preserving (HMP) laminoplasty technique in the treatment of cervical myelopathy. METHODS: The medical records of 68 patients diagnosed with multisegmental cervical myelopathy were retrospectively reviewed. Of these, 22 patients who underwent HMP laminoplasty were defined as the muscle-preserved group (MP), and 46 patients who underwent traditional open-door laminoplasty were enrolled and defined as the traditional open-door laminoplasty group (LP). Patient demographic data and surgical parameters like clinical and radiological parameters, operation duration, blood loss, and spinal canal expansion distance were compared. RESULTS: Average surgical time and blood loss were significantly reduced in the MP group when compared with the LP group (P < 0.05). Both groups demonstrated significant improvements in neurological function and spinal canal expansion (P > 0.05). However, the visual analog scale score in the MP group was significantly lower compared with the LP group at the 6-month follow-up (P < 0.05), but no differences were found at the 1-year follow-up. The loss of lordosis was more prominent in the LP group when compared with the MP group at 1-year follow-up (P < 0.05). Lower events of persistent axial pain were found in the MP group but with no statistical significance. More hinge side laminae fractures could be found in the MP group, but more hinge side displacements were found in the LP group. CONCLUSIONS: The HMP laminoplasty technique is relatively safe, effective, easier to perform, and better for lordosis maintenance and complication control compared with the traditional open-door technique. CLINICAL RELEVANCE: Although traditional open-door laminoplasty is an efficient approach in treating multisegmental cervical myelopathy, the complications could significantly affect the clinical outcome. Our new HMP laminoplasty technique has a lower complication rate and a better lordosis maintenance ability; therefore, it could be a better choice in treating multisegmental cervical myelopathy.

Cervical nerve root variant: report of two cases under the cervical endoscopy and review of clinical literature.

BACKGROUND: We know of five cases of cervical nerve root variants that have been reported, all of which were found during posterior cervical surgery. We reported two cases of cervical nerve root variants. One had two anomalous branches of the C7 root, is the other had a C5, C6 nerve root communication branch. CASE DESCRIPTION: A 62-year-old female presented with neck and right upper extremity pain, accompanied by hypaesthesia in her right forearm for 4 months. Preoperative X-ray film, magnetic resonance imaging (MRI) and computed tomography (CT) scan demonstrated C6-7 uncovertebral joint hyperplasia and foraminal stenosis. She underwent posterior cervical endoscopic foraminoplasty. The right C7 nerve root was observed to have two anomalous branches originated from a proximal trunk. After the surgery, the symptoms resolved. A 54-year-old female presented with radiating pain and numbness in her right arm and hand for 4 months. Preoperative MRI showed a C5/6 intervertebral disc herniation. She had hypaesthesia in radial side of her right arm and 1st-3rd fingers. Posterior cervical endoscopic foraminalplasty was performed for the patient. After decompression of the bony wall of the posterior nerve root canal, a 2-mm thick communicating nerve was observed emerging from the dura with the C6 nerve root and exiting to the caudal level. After the surgery, the symptoms resolved immediately. CONCLUSIONS: Cervical nerve root variant may be more apparent on edoscopic approaches to the cervical foraminae than at open surgery.

Irisin reduces bone fracture by facilitating osteogenesis and antagonizing TGF-ß/Smad signaling in a growing mouse model of osteogenesis imperfecta.

Objective: Osteogenesis imperfecta (OI) is a congenital disorder characterized by muscle defect and skeletal fragility, and no cure is yet available. Crosstalk between bone and muscle has become a new coming focus of therapeutic strategy in OI. Irisin, a secreted myokine, was found to be involved in regulating bone metabolism, and may be beneficial for the treatment of OI. However, its effects in OI have yet to be determined. This study sought to determine whether Irisin therapy is capable of reducing fracture risk in OI and to investigate the potential mechanisms of action. Methods: Fibronectin type III domain containing 5 (FNDC5)/Irisin expression was assessed by enzyme-linked immunosorbent assay (ELISA) and immunohistochemical staining. In vivo, X-ray was used for fracture counting and micro-CT, dynamic histomorphometry analysis, immunohistochemistry, histomorphometry, and biomechanical test were used to evaluate the effects of Irisin on fracture frequency and bone quality in OI mouse model, oim/oim mouse. In vitro, osteogenesis-related gene expressions were determined by quantitative real-time PCR (qRT-PCR), western blot, and osteoblastogenesis assay were assessed by alkaline phosphatase (ALP) staining and alizarin red S (ARS) staining. Mechanistically, cell immunofluorescence staining, co-immunoprecipitation (co-IP) (Co-IP), molecular docking, western blot, luciferase reporter assay, and chromatin immunoprecipitation (ChIP) assay were used for elucidating the mechanisms of how Irisin antagonized transforming growth factor-ß (TGF-ß)/Smad signaling in oim/oim osteoblasts and further attenuated the inhibitory effect of TGF-ß1 on osteogenic differentiation. Results: Musculoskeletal system-related FNDC5/Irisin was decreased in the serum, muscle, and bone in oim/oim mice. Irisin administration reduced bone fracture and attenuated bone abnormalities by improving bone mass and strength and facilitating the expression of osteogenic differentiation markers. In vivo study and in vitro experiments showed that Irisin antagonized TGF-ß/Smad signaling by interfering with TGF-ß1-TGF-ß receptor II (TßRII) binding. In oim/oim osteoblasts, Irisin alleviated TGF-ß1-induced suppression of osteogenic differentiation through both integrin-dependent and integrin-independent mechanisms. Independent of integrin receptors, Irisin affected osteogenesis by activating ERK/p38 signaling and counteracting TGF-ß/Smad2/3 signaling. In particular, Irisin alleviated TGF-ß1-induced inhibition of Runx2 function at the osteocalcin promoter through decreasing Smad2/3 signaling and inducing HADC4/5 degeneration. Conclusions: Collectively, Irisin could effectively reduce bone fracture in oim/oim mice through promoting osteogenesis and counteracting TGF-ß/Smad signaling. Translational potential statement: Findings from this study provided evidence for using Irisin as a potential therapeutic reagent to prevent the progression of OI.

Dysfunction of Caveolae-Mediated Endocytic TßRI Degradation Results in Hypersensitivity of TGF-ß/Smad Signaling in Osteogenesis Imperfecta.

Osteogenesis imperfecta (OI) is a genetic disorder caused by mutations of type I collagen-related genes, and excessive transforming growth factor-beta (TGF-ß) signaling is a common mechanism. TGF-ß/Smad signaling has inhibitory effects on osteoblast differentiation and maturation and is mainly transduced and regulated by the internalization of a tetrameric receptor complex comprising types I and II TGF-ß receptors (TßRI and TßRII). During internalization, clathrin-mediated endocytosis enhances TGF-ß/Smad signaling via Smad2/3 phosphorylation and receptors recycling, while caveolae-mediated endocytosis turns off TGF-ß/Smad signaling by promoting receptor ubiquitination and degradation. In this study, using an animal model of OI (Colla2oim , osteogenesis imperfecta murine [oim]/oim mouse), we found that osteoblastic cells of oim/oim mice were more sensitive to the inhibitory effects of TGF-ß on osteoblast differentiation and maturation and had much higher cell membrane protein levels of TGF-ß receptors than those of wild-type (wt)/wt mice. Further results showed that clathrin-mediated endocytosis of TßRI was enhanced, whereas caveolae-mediated TßRI endocytic degradation was reduced in oim/oim mice, combined with reduced caveolin-1 (Cav-1) phosphorylation. In addition, type I collagen downregulated TßRI via focal adhesion kinase (FAK) and Src activation-dependent Cav-1 phosphorylation. To further examine this mechanism, 4-week-old oim/oim and wt/wt mice were treated with either TßRI kinase inhibitor (SD-208) or vehicle for 8 weeks. SD-208 treatment significantly reduced the fracture incidence in oim/oim mice. Micro-computed tomography and biomechanical testing showed that femoral bone mass and strength were significantly improved with SD-208 treatment in both genotypes. Additionally, SD-208 significantly promoted osteoblast differentiation and bone formation and inhibited bone resorption. In conclusion, dysfunction of caveolae-mediated endocytic TßRI degradation is a possible mechanism for the enhanced TGF-ß/Smad signaling in OI. Targeting this mechanism using a TßRI kinase inhibitor effectively reduced fractures and improved bone mass and strength in OI model and, thus, may offer a new strategy for the treatment of OI. © 2022 American Society for Bone and Mineral Research (ASBMR).

Preoperative Cervical Cobb Angle Is a Risk Factor for Postoperative Axial Neck Pain after Anterior Cervical Discectomy and Fusion with Zero-Profile Interbody.

OBJECTIVES: Anterior cervical discectomy and fusion (ACDF) with zero-profile interbody has a lower incidence of complications in treating cervical spondylotic myelopathy (CSM). However, postoperative axial neck pain is still commonly occurred, and the factors affecting which is not known. Here, we retrospectively analyze the risk factors for postoperative axial pain after performing ACDF with zero-profile implant in single-level CSM. METHODS: Patients who suffered from single-level CSM and who received ACDF with zero-profile implant between 2018 January to 2020 December were reviewed. Of 180 single-level CSM patients, 144 patients who passed the inclusion criteria were enrolled. Patients were divided into two groups according to the severity of postoperative axial pain as measured by postoperative neck visual analogue scale (nVAS). Clinical parameters including age, sex, smoking history, symptom duration, body mass index (BMI), the Japanese Orthopaedic Association (JOA) scores, as well as radiological parameters were obtained pre- and post-operatively, and the data were compared between two groups. Pearson's chi-square tests and Mann-Whitney U tests were implemented to identify statistically significant differences between subgroups for categorical and continuous data, respectively; otherwise, the data were tested with Student's t-test. Risk factors were identified using logistic regression. RESULTS: Of the patients (97.8%) achieved satisfied neurological recovery, and 88.2% of the patients achieved fusion at 1-year follow-up. 33% of the patients (48 patients out of 144) had sustained postoperative axial pain after the surgery. Comparison of different severity groups exhibited no significant differences in terms of the possible risk factors (P > 0.05) except for pre- and post-operative C2-C7 Cobb angles (6.33 ± 6.53 vs. 11.88 ± 7.41, P < 0.05; 13.49 ± 5.31 vs 16.64 ± 7.34, P < 0.05). Furthermore, correlation analysis showed that the preoperative C2-C7 Cobb angle is significantly correlated with the severity of the postoperative axial pain (R2  = 0.83, P < 0.01). In addition, logistic regression analysis demonstrated that the preoperative C2-C7 Cobb angle is an independent predictor of postoperative axial pain (P < 0.01, OR = 0.53). Further receiver operating characteristic (ROC) analysis displayed an area under the curve (AUC) of 0.78 (P < 0.01) for preoperative C2-C7 Cobb angle, and the optimal cutoff was 8.4° (sensitivity 0.77, specificity 0.65). CONCLUSION: The pre-operative C2-C7 Cobb angle is a risk factor for severe postoperative axial pain after anterior cervical discectomy and fusion with zero-profile interbody, and we should be cautious when poor preoperative C2-C7 Cobb angle is found in myelopathy patients planning to use zero-profile interbody to treat such patients.

A Novel Posterior Compression Score System for Outcome Prediction in Laminoplasty Treated OPLL Patients: A Propensity-Matched Analysis.

STUDY DESIGN: A retrospective observational study. OBJECTIVE: To describe a novel outcome indication system, the posterior compression score (PCS), and investigate its clinical value in cervical ossification of the posterior longitudinal ligament (OPLL) patients treated with laminoplasty. METHODS: A total of 282 OPLL patients who underwent laminoplasty from January 2013 to December 2018 were reviewed. The patients were divided into high-score (HS) or low-score (LS) groups based on whether the PCS was over 8. Propensity score matching analysis with a caliper of .1 was used to attenuate the potential selection bias. Clinical measurements, including the Japanese Orthopedic Association (JOA) score, visual analog scale (VAS), neck disability index (NDI), and radiological measurements, including C2-C7 lordotic angle and range of motion (ROM), were compared between the groups. RESULTS: The mean follow-up period was 29.87 ± 9.17 months. There were no significant differences between the two groups regarding patients' baseline demographical and clinical characteristics after propensity score matching. No significant differences were found in the operative time, blood loss, postoperative VAS score for neck and arm pain, postoperative C2-C7 lordotic angle, or postoperative ROM (P > .05). However, the postoperative JOA score and recovery rate were significantly higher in the HS group than in the LS group, while the postoperative NDI was significantly lower in the HS group (P < .05). CONCLUSION: OPLL patients with higher PCS scores displayed better clinical outcomes. The novel PCS system is suggested to be a reliable scoring system for surgical outcome evaluation in patients with cervical OPLL.

Is Anterior Trans-Intervertebral Space Decompression Important in Treating Cervical Spondylosis with Severe Intervertebral Space Narrowing? A Retrospective Cohort Study.

OBJECTIVE: To evaluate the clinical efficacy and practicality of anterior trans-intervertebral space decompression and fusion (ATIDF) by comparing radiological and clinical outcomes between ATIDF and traditional anterior cervical corpectomy and fusion (ACCF) in cervical spondylosis patients with severe disc space narrowing. METHODS: Seventy-one cervical spondylosis patients with severe disc space narrowing underwent anterior cervical spine surgery were included in this retrospective study. Thirty-seven patients underwent ATIDF and 34 patients underwent ACCF. The neck disability index (NDI), Japan Orthopaedic Association (JOA) score and the Hirabayashi improvement rate were used to evaluate patient neurological status. Cervical sagittal alignment (C2-C7 Cobb angle), surgical segment sagittal alignment (Cobb angle of surgical segment) and disc space height were also compared between the two groups. RESULTS: There were 39 males and 32 females; mean age was 63.72 ± 6.36 years (range, 39-81 years). Mean follow-up was 22.4 months (range, 6-45 months). All patients achieved an adequate neurological improvement. There were no significant differences in NDI, JOA scores and Hirabayashi improvement rate between the two groups. The change of C2-7 Cobb angle and surgical segment Cobb angle were both greater in the ATIDF group. The average intervertebral height ratio of the patients in the ATIDF group increased significantly after surgery (0.38 ± 0.17 before surgery to 1.13 ± 0.32 after surgery, P < 0.01). The overall complication rate was lower in the ATIDF group than the ACCF group (35.14% and 44.12%). At 6 months follow-up, three patients in the ACCF group presented with subsidence of the titanium mesh cage. CONCLUSION: ATIDF is an effective technique for treating cervical spondylosis with severe disc space narrowing; it can achieve adequate decompression and improve sagittal alignment while avoiding and reducing the implant-related complications inherent to traditional ACCF.

Application of a new integrated low-profile anterior plate and cage system in single-level cervical spondylosis: a preliminary retrospective study.

BACKGROUND: Although ACDF has been widely used in treating cervical spondylosis and related diseases, the complications along with this anterior surgical technique have hindered its application and affected the postoperative outcome of the patients. Here, we investigated the clinical and radiological outcomes of a new integrated low-profile anterior plate and cage system for anterior cervical discectomy and fusion (ACDF) in treating cervical spondylosis. METHODS: A total of 96 cervical spondylosis patients who underwent single-level ACDF between 2018 to 2020 in our institute were enrolled. There were 28 patients using the new implants and 68 patients using the zero-profile (Zero-P) implants. The Japanese Orthopedic Association (JOA) score and the visual analog scale (VAS) were used to evaluate the clinical outcomes. The cervical and segmental Cobb angle and range of motion (ROM) were used to assessed the radiological outcomes. Incidence of complications were also recorded. All data were recorded at pre-operation, 6-month and 12-month post-operation. RESULTS: All patients were followed-up for at least 1-year, the mean follow-up time was over one year. The fusion rate was similar in the two groups. There was no significant difference in the postoperative JOA score recovery rate, postoperative VAS score of neck and arm pain, postoperative ROM, and incidence of complications between two groups (P > 0.05). However, postoperative cervical and segmental Cobb angle were better maintained in the new low-profile implant group compared to Zero-P group. CONCLUSIONS: The clinical outcomes of the new low-profile implant were satisfactory and comparable to that of zero-profile system. It may have advantages in improving and maintaining the cervical lordosis, and can be an alternative device for single-level cervical spondylosis treated with ACDF.

Anterior cervical discectomy and fusion, open-door laminoplasty, or laminectomy with fusion: Which is the better treatment for four-level cervical spondylotic myelopathy?

Four-level cervical spondylotic myelopathy (CSM) is a common disease affecting a large number of people, with the optimal surgical strategy remaining controversial. This study compared the clinical outcomes, radiological parameters, and postoperative complications of primarily performed surgical procedures such as anterior cervical discectomy and fusion (ACDF), open-door laminoplasty (LAMP), and laminectomy with fusion (LF) in treating four-level CSM. A total of 116 patients who received ACDF (38 cases), LAMP (45 cases), and LF (33 cases) were followed up for a minimum of 24 months were enrolled in this study and retrospectively analyzed. Clinical outcomes were evaluated using the Japanese Orthopedic Association (JOA) scoring system, the Neck Disability Index (NDI), and the Visual Analogue Scale (VAS). Changes in the curvature of the cervical spine were determined using the cervical curvature index (CCI) and the C2-C7 Cobb angle. Cervical mobility was evaluated using the C2-C7 range of motion (ROM) and active cervical ROM (aROM). Complications were recorded and compared among the three groups. All patients achieved significant improvement in JOA, NDI, and VAS scores at the final follow-up (P < 0.05), whereas no remarkable difference was found among the groups (P > 0.05). In addition, both C2-7 ROM and aROM were significantly reduced in the three groups and LAMP showed the least reduction relatively. As for complications, LAMP showed the lowest overall incidence of postoperative complications, and patients in the ACDF group were more susceptible to dysphagia, pseudoarthrosis than LAMP and LF. Considering improvements in clinical symptoms and neurological function, no remarkable difference was found among the groups. Nevertheless, LAMP had advantages over the other two surgical procedures in terms of preserving cervical mobility and reducing postoperative complications.

Intervertebral Foramen Width Is an Important Factor in Deciding Additional Uncinate Process Resection in ACDF-a Retrospective Study.

Background: Anterior cervical discectomy and fusion (ACDF) has been established as a classic procedure for the management of cervical radiculopathy. However, it is unclear whether combined uncinate process resection (UPR) is necessary for treating cervical radiculopathy. Here, we investigated the clinical outcome of ACDF combined with UPR compared to ACDF alone to determine the necessity of UPR in treating cervical radiculopathy. Hypothesis: Uncinate process resection may be necessary in certain patients along with ACDF to achieve better clinical outcomes of cervical radiculopathy. Patients and Methods: Fifty-five patients underwent ACDF with UPR, and 126 patients without UPR were reviewed. The width and height of the intervertebral foramen were measured by 45° oblique X-rays. We also measured the Japanese Orthopedic Association (JOA) score and visual analog scale (VAS) score. C2-C7 Cobb angles were obtained from all patients pre- and post-operatively. Meanwhile, linear regression analysis was used to evaluate the relationship between the clinical outcomes and the intervertebral foramen width before surgery. Results: Linear regression analysis indicated that the improvement in the JOA and VAS scores was irrelevant to both the pre-operative width of the intervertebral foramen (wIVF) and the height of the intervertebral foramen (hIVF) in the ACDF+UPR group. However, pre-operative wIVF was associated with post-operative JOA and VAS scores in the ACDF alone group. Those with pre-operative wIVF <3 mm in the ACDF group had the least improvement in post-operative clinical symptoms due to the change in wIVF (P > 0.05). The ACDF group whose wIVF was over 3 mm showed similar clinical outcomes to the ACDF + UPR group, and wIVF significantly increased post-operatively (P < 0.05). The fusion rate and C2-C7 Cobb angles did not show significant differences between the two groups (P > 0.05). Discussion: Our current findings suggest that UPR should be considered when wIVF is <3 mm pre-operatively. However, there is no need to sacrifice the uncovertebral joint in ACDF when the pre-operative wIVF is over 3 mm. Level of Evidence: Level III.

Increased Expression of Integrin Alpha 6 in Nucleus Pulposus Cells in Response to High Oxygen Tension Protects against Intervertebral Disc Degeneration.

The destruction of the low oxygen microenvironment in nucleus pulposus (NP) cells played a critical role in the pathogenesis of intervertebral disc degeneration (IVDD). The purpose of this study was to determine the potential role of integrin alpha 6 (ITG α6) in NP cells in response to high oxygen tension (HOT) in IVDD. Immunofluorescence staining and western blot analysis showed that the levels of ITG α6 expression were increased in the NP tissue from IVDD patients and the IVDD rat model with mild degeneration, which were reduced as the degree of degeneration increases in severity. In NP cells, the treatment of HOT resulted in upregulation of ITG α6 expression, which could be alleviated by blocking the PI3K/AKT signaling pathway. Further studies found that ITG α6 could protect NP cells against HOT-induced apoptosis and oxidative stress and protect NP cells from HOT-inhibited ECM protein synthesis. Upregulation of ITG α6 expression by HOT contributed to maintaining NP tissue homeostasis through the interaction with hypoxia-inducible factor-1α (HIF-1α). Furthermore, silencing of ITG α6 in vivo could obviously accelerate puncture-induced IVDD. Taken together, these results revealed that the increase of ITG α6 expression by HOT in NP cells might be a protective factor in IVD degeneration as well as restore NP cell function.

The Heterogeneity of Infiltrating Macrophages in Metastatic Osteosarcoma and Its Correlation with Immunotherapy.

BACKGROUND: Metastatic osteosarcoma is a common and fatal bone tumor. Several studies have found that tumor-infiltrating immune cells play pivotal roles in the progression of metastatic osteosarcoma. However, the heterogeneity of infiltrating immune cells across metastatic and primary osteosarcoma remains unclear. METHODS: Immune infiltration analysis was carried out via the "ESTIMATE" and "xCell" algorithms in primary and metastatic osteosarcoma. Then, we evaluated the prognostic value of infiltrating immune cells in 85 osteosarcomas through the Kaplan-Meier (K-M) and receiver operating characteristic (ROC) curve. Infiltrations of macrophage M1 and M2 were evaluated in metastatic osteosarcoma, as well as their correlation with immune checkpoints. Macrophage-related prognostic genes were identified through Weighted Gene Coexpression Network Analysis (WGCNA), Lasso analysis, and Random Forest algorithm. Finally, a macrophage-related risk model had been constructed and validated. RESULTS: Macrophages, especially the macrophage M1, sparingly infiltrated in metastatic compared with the primary osteosarcoma and predicted the worse overall survival (OS) and disease-free survival (DFS). Macrophage M1 was positively correlated with immune checkpoints PDCD1, CD274 (PD-L1), PDCD1LG2, CTLA4, and TIGIT. In addition, four macrophage-related prognostic genes (IL10, VAV1, CD14, and CCL2) had been identified, and the macrophage-related risk model had been validated to be reliable for evaluating prognosis in osteosarcoma. Simultaneously, the risk score showed a strong correlation with several immune checkpoints. CONCLUSION: Macrophages potentially contribute to the regulation of osteosarcoma metastasis. It can be used as a candidate marker for metastatic osteosarcoma' prognosis and immune checkpoints blockades (ICBs) therapy. We constructed a macrophage-related risk model through machine-learning, which might help us evaluate patients' prognosis and response to ICBs therapy.

Lactobacillus paracasei S16 Alleviates Lumbar Disc Herniation by Modulating Inflammation Response and Gut Microbiota.

Lumbar disc herniation (LDH) is a common cause for low back pain. In this study, we aimed to explore the effects of a specific Lactobacillus paracasei (L. paracasei), L. paracasei S16, on the symptoms of LDH using a mouse model of LDH. The results showed that L. paracasei S16 treatment improved the behavior, increased the cell proliferation, and decreased the apoptosis in LDH mice. Moreover, L. paracasei S16 treatment alleviated the aberrant inflammation response in the LDH mice, which is characterized by the decreased anti-inflammatory cytokines, increased pro-inflammatory cytokines, and decreased percentage of Th1 and Th2 cells and Th17/Treg ratio. 16S rRNA sequencing results showed that the LDH mice treated with L. paracasei S16 have higher relative abundance of Lachnospiraceae and Ruminococcaceae and lower abundance of Lactobacillaceae than mice in the LDH group. Additionally, the serum metabolites involved in the linoleic acid metabolism, alanine. aspartate, and glutamate, glycerophospholipid, and TCA cycle were significantly decreased and the metabolite involved in purine metabolism was significantly increased after the L. paracasei S16 treatment in the LDH mice. These results showed that administration of L. paracasei S16 can improve inflammation response, alter gut microbiota, and modulate serum metabolomics in a mouse model of LDH.

Integrated transcriptome and proteome analyses identify novel regulatory network of nucleus pulposus cells in intervertebral disc degeneration.

BACKGROUND: Degeneration of intervertebral disc is a major cause of lower back pain and neck pain. Studies have tried to unveil the regulatory network using either transcriptomic or proteomic analysis. However, neither have fully elucidated the exact mechanism of degeneration process. Since post-transcriptional regulation may affect gene expression by modulating the translational process of mRNA to protein product, a combined transcriptomic and proteomic study may provide more insight into the key regulatory network of Intervertebral disc degeneration. METHODS: In order to obtain the proteomic and transcriptomic data, we performed label-free proteome analysis on freshly isolated nucleus pulposus cells and obtained transcriptome profiling data from the Gene Expression Omnibus repository. To identify the key regulatory network of intervertebral disc degeneration in nucleus pulposus cells, we performed bioinformatic analyses and established a protein-RNA interacting network. To validate the candidate genes, we performed in vitro experimentation and immunochemistry labeling to identify their potential function during nucleus pulposus degeneration. RESULTS: The label-free proteome analysis identified altogether 656 proteins, and 503 of which were differentially expressed between nucleus pulposus cells from degenerated or normal disc cells. Using the existing nucleus pulposus transcriptomic profiling data, we integrated the proteomic and transcriptomic data of nucleus pulposus cells, and established a protein-RNA interacting network to show the combined regulatory network of intervertebral disc degeneration. In the network, we found 9 genes showed significant changes, and 6 of which (CHI3L1, KRT19, COL6A2, DPT, TNFAIP6 and COL11A2) showed concordant changes in both protein and mRNA level. Further functional analysis showed these candidates can significantly affect the degeneration of the nucleus pulposus cell when altering their expression. CONCLUSIONS: This study is the first to use combined analysis of proteomic and transcriptomic profiling data to identify novel regulatory network of nucleus pulposus cells in intervertebral disc degeneration. Our established protein-RNA interacting network demonstrated novel regulatory mechanisms and key genes that may play vital roles in the pathogenesis of intervertebral disc degeneration.

Comparable Effects of Strontium Ranelate and Alendronate Treatment on Fracture Reduction in a Mouse Model of Osteogenesis Imperfecta.

Alendronate (Aln) has been the first-line drug for osteogenesis imperfecta (OI), while the comparable efficacy of Aln and strontium ranelate (SrR) remains unclear. This study is aimed at comparing the effects of SrR and Aln treatment in a mouse model of OI. Three-week-old oim/oim and wt/wt female mice were treated with SrR (1800 mg/kg/day), Aln (0.21 mg/kg/week), or vehicle (Veh) for 11 weeks. After the treatment, the average number of fractures sustained per mouse was significantly reduced in both SrR- and Aln-treated oim/oim mice. The effect was comparable between these two agents. Both SrR and Aln significantly increased trabecular bone mineral density, bone histomorphometric parameters (bone volume, trabecular number, and cortical thickness and area), and biomechanical parameters (maximum load and stiffness) as compared with the Veh group. Both treatments reduced bone resorption parameters, with Aln demonstrating a stronger inhibitory effect than SrR. In contrast to its inhibitory effect on bone resorption, SrR maintained bone formation. Aln, however, also suppressed bone formation coupled with an inhibitory effect on bone resorption. The results of this study indicate that SrR has comparable effects with Aln on reducing fractures and improving bone mass and strength. In clinical practice, SrR may be considered an option for patients with OI when other medications are not suitable or have evident contraindications.

Efficacy and Safety of Ultrasonic Bone Curette-assisted Dome-like Laminoplasty in the Treatment of Cervical Ossification of Longitudinal Ligament.

OBJECTIVE: To assess the efficacy and safety of ultrasonic bone curette-assisted dome-like laminoplasty in the treatment of ossification of longitudinal ligament (OPLL) involving C2 . METHODS: A total of 64 patients with OPLL involving C2 level were enrolled. Thirty-eight patients who underwent ultrasonic bone curette-assisted dome-like laminoplasty were defined as ultrasonic bone curette group (UBC), and 28 patients who underwent traditional high-speed drill-assisted dome-like laminoplasty were defined as high-speed drill group (HSD). Patient characteristics such as age, sex, body mass index (BMI), symptomatic duration, and other information like the type of OPLL, the time of surgery, blood loss, C2 -C7 Cobb angle change and complications were all recorded and compared. The Japanese Orthopaedic Association (JOA) score, the nerve root functional improvement rate (IR), and the visual analogue scale (VAS) were used to assess neurological recovery and pain relief. The change of the distance between the apex of ossification and a continuous line connecting the anterior edges of the lamina was measured to assess the spinal expansion extent. The measured data were statistically processed and analyzed using SPSS 21.0 software, and the measurement data were expressed as mean ± SD. RESULTS: In ultrasonic bone curette (UBC) group and high-speed drill group (HSD) group, the average time for laminoplasty was 52.3 ± 18.2 min and 76.0 ± 21.8 min and the mean bleeding loss volume was 155.5 ± 41.3 mL and 177.4 ± 54.7 mL, respectively, with a statistically significant difference between the groups. Both groups demonstrated a significant improvement in neurological function. However, the VAS score in UBC group was lower than in HSD group at the 6-month follow-up (P < 0.05), but there was no significant difference at 1-year follow-up. We found that the loss of lordosis was 1.5° ± 1.0° in UBC group, which is significantly lower than that of HSD group at 1-year follow-up (3.8° ± 1.2°, P < 0.05). According to the change of canal dimension, we found that the expansion extent of the spinal canal in UBC group was similar to that of HSD group (P > 0.05). Only one patient in the UBC group and five patients in the HSD group displayed cerebrospinal fluid (CSF) leakag. CONCLUSIONS: With the use of ultrasonic bone curette in OPLL dome-like decompression, the decompression surgery could be completed relatively safely and quickly. It effectively reduced the amount of intraoperative blood loss and complications, and had better initial recovery of neck pain.

Thoracic de-kyphosis for revision surgery of a failure case of endoscopic discectomy: a case report and literature review.

BACKGROUND: Indications and clinical outcomes of percutaneous endoscopic thoracic discectomy(PETD) in treating thoracic disc herniation is rarely reported and still controversial. We reported an unsatisfied recovery of thoracic disc herniation with PETD, treated by a second posterior thoracic laminectomy and Ponte osteotomy. CASE DESCRIPTION: A male presented with lower extremity weakness and stagger caused by T3/4 intervertebral disc herniation. The upper thoracic curve was in excessive kyphosis with T2-5 Cobb angle of 34.3 degrees. The preoperative ODI score was 34 and Roelzs's JOA score was 14. Percutaneous transforaminal endoscopic thoracic discectomy (PETD) from a posterior lateral approach was performed. At five-month follow-up, his thoracic back pain and staggering gait did not improve. The postoperative T2-5 Cobb angle was 32.1 degrees, the ODI score was 24 and Roelzs's JOA score was 14. A second posterior thoracic decompression this time with fixation was performed, but no disc herniation was detected. A Ponte osteotomy was performed to correct the kyphosis. One month after the second surgery, muscle strength of the lower limbs was improving with the T2-5 Cobb angle decreased to 19.4 degrees, the ODI score decreased to 10 and Roelzs's JOA score increase to 16. Six month later, the ODI score decreased to 0 and Roelzs's JOA score improved to 18. In review of the literature, PETD doesn't guarantee the patient a satisfactory neurological recovery for kyphotic thoracic disc herniation. Posterior decompression with Ponte osteotomy may be beneficial to release the tension and decompression of the spinal cord tension. CONCLUSIONS: Thoracic disc herniation with kyphosis angle >20 degrees (T2-5), percutaneous endoscopic thoracic discectomy is not likely to get good neurologic results. Posterior laminectomy with ponte osteotomy might be beneficial for these patients to induce dorsal drifting of the spinal cord from anterior herniation.

Bi-needle technique versus transforaminal endoscopic spine system technique for percutaneous endoscopic lumbar discectomy in treating intervertebral disc calcification: a propensity score matched cohort analysis.

OBJECTIVE: The aim of this study was to evaluate the clinical results of a Bi-needle technique and conventional transforaminal endoscopic spine system (TESSYS) technique for percutaneous endoscopic lumbar discectomy (PELD) in treating patients with intervertebral disc calcification (IDC). BACKGROUND: PELD has gained acceptance for treating patients with IDC. The Bi-needle technique was designed to improve the efficiency and safety of PELD. METHOD: Bi-needle and TESSYS group within each cohort were balanced using 1:1 propensity score matching. Finally, 32 patients with IDC treated by Bi-needle technique from December 2015 to September 2017 were enrolled and 25 patients treated by TESSYS technique from the same spine surgery center between January 2013 and October 2017 were enrolled as controls. RESULTS: Propensity score matching generated 22 Bi-needle and 22 TESSYS patients. There were no significant differences in visual analog scale and lumbar Japanese Orthopaedic Association scores between Bi-needle and TESSYS group. Operative time and rate of complications in the Bi-needle was significantly better than the TESSYS group (p < 0.01). CONCLUSIONS: Both surgical methods achieved good clinical outcomes. However, compared with the TESSSY technique, operative time of the Bi-needle technique is shorter, and rate of complications is lower.

The relationship between preoperative cervical sagittal balance and clinical outcome of laminoplasty treated cervical ossification of the posterior longitudinal ligament patients.

BACKGROUND CONTEXT: Laminoplasty is a common surgical method used to treat patients with cervical ossification of the posterior longitudinal ligament (OPLL). Although laminoplasty is preferred over traditional laminectomy, the factors affecting the complications and outcomes are unclear. Recently, sagittal balance indexes have been revealed to be predictors of clinical outcomes in patients with cervical degenerative diseases, but their relationships with laminoplasty-treated OPLL outcomes remains unknown. PURPOSE: The purpose of this study is to evaluate the relationship of preoperative cervical sagittal balance indexes and clinical outcome in laminoplasty treated OPLL patients. STUDY DESIGN: This is a retrospective case study. PATIENT POPULATION: Between January 2015 and January 2017, 181 consecutively included patients who underwent cervical laminoplasty for OPLL were enrolled (male:female ratio=126:75; mean age=60.2 years). Cervical spine lateral radiographs in neutral, flexion, and extension positions were taken before and 2 years after the surgery. OUTCOME MEASURES: The C2-C7 Cobb angle, T1 slope, C1-C7 sagittal vertical axis (SVA), C2-C7 SVA, CGH (center of gravity of the head)-C7 SVA, cervical JOA (Japanese Orthopedic Association) score, and neck VAS (visual analogue scale) score were measured preoperatively and postoperatively at the 2-year follow-up. METHODS: The patients were divided into two groups according to changes in the lordotic angle or the recovery rate of the JOA score. The relationships between the postoperative lordosis loss or the clinical outcome and the preoperative variables, including the patient's age, JOA score, C2-C7 Cobb angle, T1 slope, C1-C7 SVA, C2-C7 SVA, and CGH-C7 SVA, were investigated. RESULTS: The patients were divided into two groups according to the postoperative change in the C2-C7 Cobb angle. There were no differences in the age, preoperative C2-C7 Cobb angle, C1-C7 SVA, or C2-C7 SVA; there was only a difference in the preoperative CGH-C7 SVA and T1 slope level (p=.038, p=.042). The postoperative JOA and JOA recovery rate were related to the postoperative lordosis loss in cervical alignment (p=.048, p=.031). We again divided the patients into two groups according to the JOA recovery rate and found that only the preoperative CGH-C7 SVA and C1-C7 SVA were related to the neurological outcome (p=.011, p=.047). According to the multivariate logistic regression analysis, higher preoperative CGH-C7 SVA levels were significantly associated with decreases in the lordosis angle postoperatively and the clinical outcome (p=.018, OR=1.225; p=.034, OR=1.654). The ROC (receiver operating characteristic) analysis revealed that the proper cutoff value of preoperative CGH-C7 SVA for predicting the postoperative loss of lordosis and clinical outcomes is 3.8 cm. CONCLUSION: Preoperative cervical sagittal balance indexes are related to the outcomes of OPLL patients after laminoplasty. Patients with high preoperative CGH-C7 SVA levels have a high probability of developing sagittal imbalances and neurological symptoms of the cervical spine, and this measurement can be used as a predictor of outcomes in laminoplasty-treated cervical OPLL patients.