DNAJC1 facilitates glioblastoma progression by promoting extracellular matrix reorganization and macrophage infiltration.

BACKGROUND: Glioblastoma (GBM) is a high-grade and heterogeneous subtype of glioma that presents a substantial challenge to human health, characterized by a poor prognosis and low survival rates. Despite its known involvement in regulating leukemia and melanoma, the function and mechanism of DNAJC1 in GBM remain poorly understood. METHODS: Utilizing data from the TCGA, CGGA, and GEO databases, we investigated the expression pattern of DNAJC1 and its correlation with clinical characteristics in GBM specimens. Loss-of-function experiments were conducted to explore the impact of DNAJC1 on GBM cell lines, with co-culture experiments assessing macrophage infiltration and functional marker expression. RESULTS: Our analysis demonstrated frequent overexpression of DNAJC1 in GBM, significantly associated with various clinical characteristics including WHO grade, IDH status, chromosome 1p/19q codeletion, and histological type. Moreover, Kaplan‒Meier and ROC analyses revealed DNAJC1 as a negative prognostic predictor and a promising diagnostic biomarker for GBM patients. Functional studies indicated that silencing DNAJC1 impeded cell proliferation and migration, induced cell cycle arrest, and enhanced apoptosis. Mechanistically, DNAJC1 was implicated in stimulating extracellular matrix reorganization, triggering the epithelial-mesenchymal transition (EMT) process, and initiating immunosuppressive macrophage infiltration. CONCLUSIONS: Our findings underscore the pivotal role of DNAJC1 in GBM pathogenesis, suggesting its potential as a diagnostic and therapeutic target for this challenging disease.

The role of ST3GAL4 in glioma malignancy, macrophage infiltration, and prognostic outcomes.

Background: Glioma, a prevalent malignancy of the brain and spinal cord, poses a considerable threat to human health. The association between aberrant sialic acid modification and glioma progression has been suggested, but the precise mechanism is still elusive. ST3GAL4, a sialoglycosyltransferase, is implicated in increased metastatic potential and poor prognosis in various cancers; however, its specific role in glioma requires further elucidation. Methods: We evaluated ST3GAL4 expression levels and their clinical relevance using the TCGA database, and we assessed immune infiltration via the Tumor Immune Evaluation Resource (TIMER) database. In vitro experiments were performed to determine the effects of ST3GAL4 knockdown on glioma cell malignancy, with additional co-culture assays to assess its impact on macrophage phenotype. Results: ST3GAL4 expression was markedly elevated in glioma tissues compared to normal brain tissues, with a strong correlation to glioma patient clinical characteristics. Survival analyses and receiver operating characteristic (ROC) curves suggested that ST3GAL4 is a feasible diagnostic and prognostic biomarker for glioma. Knockdown studies revealed that ST3GAL4 inhibition reduces glioma cell line proliferation, migration, and invasion, while causing G1 phase cell cycle arrest. ST3GAL4 appears to mediate glioma progression through extracellular matrix reorganization and EMT signaling pathway activation, further contributing to M2 macrophage polarization and infiltration within the tumor microenvironment. Conclusion: Our research highlights the critical role of ST3GAL4 in glioma development, positioning it as a promising candidate for diagnostic and therapeutic interventions.

Electric field induced the changes in structure and function of human transforming growth factor beta receptor type I: from molecular dynamics to docking.

The transforming growth factor beta (TGF-ß) signaling pathway is believed to play essential roles in several physiological activities, including cancer. TGF-ß receptor type I (TBR-I) is a key membrane receptor protein in the TGF-ß signaling pathway, which relates to many intracellular biological effects. In recent years, cold atmospheric plasma (CAP) has been found to have promising prospects in selective anticancer therapy and has confirmed its essential role in the TGF-ß signaling pathway. However, the ambiguous effect of CAP-induced electric field (EF) on TBR-I still limits the application of CAP in clinical therapy. Molecular dynamics is applied to assess the effect of EF on the structure of the extracellular domain of TBR-I using a series of indicators and methods, and then we discuss the ligand binding ability of TBR-I. Results show that moderate EF intensities' structural restraints may contribute to the structural stability and ligand-binding ability of TBR-I, but an EF higher than 0.1 V/nm will be harmful. What's more, EF induces a change in the docking interface of TBR-I, showing the conformation and position of special sequences of residues decide the ligand binding surface. The relevant results suggest that CAP-induced EF plays a crucial role in receptor-receptor interaction and provides significant guidelines for EF-related anticancer therapy.Communicated by Ramaswamy H. Sarma.

Ultrasound-guided versus fluoroscopy-guided lumbar selective nerve root block: a retrospective comparative study.

The purpose of this study is to compare the accuracy and effectiveness of ultrasound-guided and fluoroscopy-guided lumbar selective nerve root block (SNRB), and to explore the feasibility of ultrasound-guided methods. This retrospective study included patients with lumbar radicular pain who underwent ultrasound-guided and fluoroscopy-guided selective nerve root block at Honghui Hospital Affiliated to Xi'an Jiaotong University from August 2020 to August 2022. Patients were divided into U-SNRB group and F-SNRB group according to ultrasound-guided or fluoroscopy-guided selective nerve root block. There were 43 patients in U-SNRB group and 20 patients in F-SNRB group. The pain visual analogue scale (VAS) scores, Japanese Orthopaedic Association (JOA) scores, related indexes and complications were recorded and compared between the two groups before, 30 min, 1 month and 6 months after block. To evaluate the feasibility, accuracy and effectiveness of ultrasound-guided selective nerve root block. There were no complications in the process of selective nerve root block in both groups. The operating time and the times of closing needle angle adjustment in U-SNRB group were better than those in F-SNRB group, and the difference was statistically significant (P < 0.05). The VAS score and JOA score of patients in the two groups were significantly improved 30 min after block, 1 month and 6 months after block, and the difference was statistically significant (P < 0.05). There was no significant difference between the two groups (P > 0.05). The accuracy of ultrasound-guided selective nerve root block and the degree of pain relief of patients were similar to those of fluoroscopy guidance, but the operation time and needle angle adjustment times were significantly less than that of fluoroscopy, and could effectively reduce radiation exposure. Therefore, it can be used as a better way to guide for choice.

[Effectiveness of one-stage posterior eggshell osteotomy and long-segment pedicle screw fixation for ankylosing spondylitis kyphosis combined with acute thoracolumbar vertebral fracture].

Objective: To explore the safety and effectiveness of one-stage posterior eggshell osteotomy and long-segment pedicle screw fixation in the treatment of ankylosing spondylitis kyphosis combined with acute thoracolumbar vertebral fracture. Methods: A clinical data of 20 patients with ankylosing spondylitis kyphosis combined with acute thoracolumbar spine fracture, who were treated with one-stage posterior eggshell osteotomy and long-segment pedicle screw fixation between April 2016 and January 2022, was retrospectively analyzed. Among them, 16 cases were male and 4 cases were female; their ages ranged from 32 to 68 years, with an average of 45.9 years. The causes of injury included 10 cases of sprain, 8 cases of fall, and 2 cases of falling from height. The time from injury to operation ranged from 1 to 12 days, with an average of 7.1 days. The injured segment was T 11 in 2 cases, T 12 in 2 cases, L 1 in 6 cases, and L 2 in 10 cases. X-ray film and CT showed that the patients had characteristic imaging manifestations of ankylosing spondylitis, and the fracture lines were involved in the anterior, middle, and posterior columns and accompanied by different degrees of kyphosis and vertebral compression; and MRI showed that 12 patients had different degrees of nerve injuries. The operation time, intraoperative bleeding, intra- and post-operative complications were recorded. The visual analogue scale (VAS) score and Oswestry disability index (ODI) were used to evaluate the low back pain and quality of life, and the American spinal cord injury association (ASIA) classification was used to evaluate the neurological function. X-ray films were taken, and local Cobb angle (LCA) and sagittal vertical axis (SVA) were measured to evaluate the correction of the kyphosis. Results: All operations were successfully completed and the operation time ranged from 127 to 254 minutes (mean, 176.3 minutes). The amount of intraoperative bleeding ranged from 400 to 950 mL (mean, 722.5 mL). One case of dural sac tear occurred during operation, and no cerebrospinal fluid leakage occurred after repair, and the rest of the patients did not suffer from neurological and vascular injuries, cerebrospinal fluid leakage, and other related complications during operation. All incisions healed by first intention without infection or fat liquefaction. All patients were followed up 8-16 months (mean, 12.5 months). The VAS score, ODI, LCA, and SVA at 3 days after operation and last follow-up significantly improved when compared with those before operation ( P<0.05), and the difference between 3 days after operation and last follow-up was not significant ( P>0.05). The ASIA grading of neurological function at last follow-up also significantly improved when compared with that before operation ( P<0.05), including 17 cases of grade E and 3 cases of grade D. At last follow-up, all bone grafts achieved bone fusion, and no complications such as loosening, breaking of internal fixation, and pseudoarthrosis occurred. Conclusion: One-stage posterior eggshell osteotomy and long-segment pedicle screw fixation is an effective surgical procedure for ankylosing spondylitis kyphosis combined with acute thoracolumbar vertebral fracture. It can significantly relieve patients' clinical symptoms and to some extent, alleviate the local kyphotic deformity.

Assistive diagnostic indicators for infections related to lumbar posterior interbody fusion internal fixation: platelet count and mean platelet volume.

BACKGROUND: The most severe complication after posterior single-segment lumbar interbody fusion and internal fixation (PIFIF) surgery for degenerative lumbar diseases is deep surgical site infection (DSSI). Preoperatively diagnosing such complications proves to be challenging. Platelets, as acute-phase reactants, undergo changes in response to infections and inflammation. This study aims to assess whether platelet indices can further aid in the diagnosis of DSSI. METHODS: A single-center retrospective study was conducted from January 2016 to February 2021 at Xi'an Jiaotong University-Affiliated Honghui Hospital, involving 83 patients who underwent revision surgery after PIFIF due to lumbar degenerative diseases. Among them, 24 patients were diagnosed with DSSI based on combined bacterial culture and imaging data. Preoperative complete serological indicators including erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), and platelet count and mean platelet volume ratio (P/M ratio) were analyzed using receiver operating characteristic (ROC) curve analysis to determine cutoff values, sensitivity, and specificity. This was done to further assess the ability of these serological indicators to identify the occurrence of DSSI after PIFIF. RESULTS: There were no significant differences in baseline demographic characteristics between the two patient groups (P > 0.05). The P/M ratio was 13.54 ± 5.05 in the aseptic revision group, while it was 19.21 ± 6.30 in the DSSI revision patients, showing a significant difference (P < 0.001). ROC curve analysis revealed that the optimal cutoff value for the P/M ratio was 17.50, with a sensitivity of 58.3% and a specificity of 78.6%. The areas under the curve (AUC) for ESR, CRP, and P/M ratio were 0.797, 0.845, and 0.756, respectively. The negative predictive value (NPV) was 87.04%, 89.47%, and 82.45%, respectively; the positive predictive value (PPV) was 58.62%, 69.23%, and 53.84%, respectively, for ESR, CRP, and P/M ratio, respectively. When P/M ratio is used in combination with ESR and CRP, the AUC is 0.887, with a sensitivity of 95.4%, specificity of 67.8%, NPV of 97.56%, PPV of 54.76%. The diagnostic performance of the model for evaluating DSSI is significantly improved compared to using ESR and CRP alone (P < 0.05). CONCLUSION: Platelets and their related serum biomarkers are closely associated with DSSI. The P/M ratio can serve as a reliable test for screening DSSI and is worth considering for inclusion in the assessment of patients at risk of developing DSSI after potential PIFIF surgery.

KDELR2 as a diagnostic and prognostic biomarker of bladder urothelial carcinoma and its correlation with immune infiltration.

KDELR2 has been reported as a promotive factor for the genesis and progression of several malignancies. However, it is uncertain how it affects bladder urothelial carcinoma (BLCA). Using data extracted from online databases, an enhanced expression of KDELR2 in BLCA tissues was verified. Overexpression of KDELR2 was correlated with advanced clinicopathologic characteristics and unfavourable prognosis of BLCA. Receiver operating characteristic analysis highlighted the potential diagnostic value of KDELR2. Univariate and multivariate logistic regression analyses further revealed the predictive effect of KDELR2 for the prognosis of BLCA. KDELR2 was primarily enriched in biological functions related to organization of the extracellular matrix. TIMER, ssGSEA and GEPIA analyses suggested that KDELR2 expression is positively related to the infiltration of macrophages, Th2 cells and neutrophils. Finally, knocking-down of KDELR2 in T24 cells resulted in reduced proliferation, migration and macrophages recruitment. These results suggest that KDELR2 overexpression is an indicator for poor prognosis of BLCA and it has the potential to be employed as an immunotherapy target for BLCA.

A Novel Technology for 3D-Printing Artificial Vertebral Bodies for Treating Lumbar Spine Adrenal Pheochromocytoma Metastases: A Case Report and Review of the Literature.

BACKGROUND: Pheochromocytoma is an adrenal medullary neuroendocrine tumor that rarely metastasizes to the spine. Currently, its specific treatment methods still present challenges. CASE DESCRIPTION: A 41-year-old male patient who underwent left total adrenalectomy due to pheochromocytoma 3 years ago presented with lower back pain, accompanied by numbness and decreased muscle strength in both legs, as well as decreased sensation. Abnormal transmittance of the L3 vertebral body could be seen on anterior-posterior and lateral lumbar X-rays, irregular bone destruction of the L3 vertebral body was found on CT, and an MRI scan showed that the tumor was located within the L3 vertebral body, protruding into the spinal canal and compressing the epidural sac. No recurrence was found in the abdomen. Preoperatively, perform local embolization of the blood vessels supplying the tumor. First, the L2-3 intervertebral disc, L3-4 intervertebral disc and L3 vertebral body were removed using an anterior approach, the whole tumor was removed, and some of the vertebrae were taken for pathological examination and replaced with a 3D-printed prosthesis. Then, four pedicle screws were placed in the bilateral pedicles of L2 and L4 using the posterior approach, pre-bent connecting rods were installed to replace the bone cortex of the lamina and articular process followed by bone graft fusion of the interlaminar and facet joints. The postoperative results were satisfactory, and there were no perioperative complications. CONCLUSION: Lumbar pheochromocytoma metastasis is rare, difficult to treat, and should be considered in spinal metastases' differential diagnoses so early diagnosis can be made based on medical history and imaging. Preoperative local vascular imaging and embolization of the blood supply vessels were performed. After total en-bloc spondylectomy of the tumor during surgery, a prosthesis was implanted and combined with pedicle screw fixation to reconstruct spinal biomechanical stability, achieving satisfactory results. Therefore, 3D printed artificial vertebral bodies are a good choice for treating adrenal pheochromocytoma lumbar metastasis. The key to successful treatment is close interdisciplinary collaboration in formulating rigorous comprehensive perioperative plans.

M1 polarization enhances the antitumor activity of chimeric antigen receptor macrophages in solid tumors.

BACKGROUND: Chimeric antigen receptor macrophage (CAR-M) therapy is a novel cancer immunotherapy approach that integrates CAR structure and macrophage functions. CAR-M therapy has shown unique and impressive antitumor effects in immunotherapy for solid tumors. However, the polarization state of macrophages can affect the antitumor effect of CAR-M. We hypothesized that the antitumor activity of CAR-Ms may be further improved after inducing M1-type polarization. METHODS: In this report, we constructed a novel HER2-targeting CAR-M, which was composed of humanized anti-HER2 scFv, CD28 hinge region and FcγRI transmembrane domain and intracellular domain. Phagocytosis, tumor-killing capacities, and cytokine release of CAR-Ms were detected with or without M1-polarization pretreatment. Several syngeneic tumor models were used to monitor the in vivo antitumor activity of M1-polarized CAR-Ms. RESULTS: After polarization with LPS combined with interferon-γ in vitro, we found that the phagocytic and tumor-killing capacities of CAR-Ms against target cells were significantly enhanced. The expression of costimulatory molecules and proinflammatory cytokines was also significantly increased after polarization. By establishing several syngeneic tumor models in vivo, we also demonstrated that infusing polarized M1-type CAR-Ms could effectively suppress tumor progression and prolong the survival of tumor-bearing mice with enhanced cytotoxicity. CONCLUSIONS: We demonstrated that our novel CAR-M can effectively eliminate HER2-positive tumor cells both in vitro and in vivo, and M1 polarization significantly enhanced the antitumor ability of CAR-M, resulting in a stronger therapeutic effect in solid cancer immunotherapy.

Necroptosis of nucleus pulposus cells involved in intervertebral disc degeneration through MyD88 signaling.

Background context: Low back pain, affecting nearly 40% of adults, mainly results from intervertebral disc degeneration (IVDD), while the pathogenesis of IVDD is still not fully elucidated. Recently, some researches have revealed that necroptosis, a programmed necrosis, participated in the progression of IVDD, nevertheless, the underlying mechanism remains unclear. Purpose: To study the mechanism of necroptosis of Nucleus Pulposus (NP) cells in IVDD, focusing on the role of MyD88 signaling. Study design: The expression and co-localization of necroptotic indicators and MyD88 were examined in vivo, and MyD88 inhibitor was applied to determine the role of MyD88 signaling in necroptosis of NP cells in vitro. Methods: Human disc specimens were collected from patients receiving diskectomy for lumbar disc herniation (LDH) or traumatic lumbar fractures after MRI scanning. According to the Pfirrmann grades, they were divided into normal (Grades 1, 2) and degenerated groups (4, 5). Tissue slides were prepared for immunofluorescence to assess the co-localization of necroptotic indicators (RIP3, MLKL, p-MLKL) and MyD88 histologically. The combination of TNFα, LPS and Z-VAD-FMK was applied to induce necroptosis of NP cells. Level of ATP, reactive oxygen species (ROS), live-cell staining and electron microscope study were employed to study the role of MyD88 signaling in necroptosis of NP cells. Results: In vivo, the increased expression and co-localization of necroptotic indicators (RIP3, MLKL, p-MLKL) and MyD88 were found in NP cells of degenerated disc, while very l low fluorescence intensity in tissue of traumatic lumbar fractures. In vitro, the MyD88 inhibitor effectively rescued the necroptosis of NP cells, accompanied by increased viability, ATP level, and decreased ROS level. The effect of MyD88 inhibition on necroptosis of NP cells was further confirmed by ultrastructure of mitochondria shown by Transmission Electron Microscope (TEM). Conclusion: Our results indicated that the involvement of MyD88 signaling in the necroptosis of NP cells in IVDD, which will replenish the pathogenesis of IVDD and provide a novel potential therapeutic target for IVDD.

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.

MYC inhibition reprograms tumor immune microenvironment by recruiting T lymphocytes and activating the CD40/CD40L system in osteosarcoma.

The efficacy of immune checkpoint blockade (ICB) therapy depends on sufficient infiltration and activation of primed tumor-specific cytotoxic T lymphocytes (CTLs) in the tumor microenvironment. However, many tumor types, including osteosarcoma, mainly display immune-desert or immune-excluded phenotypes, which are characterized by a lack of tumor-infiltrating lymphocytes and a poor response to ICB monotherapy. Thus, novel therapeutic strategies are urgently needed to surmount these obstacles. In this study, we found that the expression of the c-Myc oncogene is negatively correlated with the T cell infiltration rate in osteosarcoma. Pharmacological inhibition of c-Myc with JQ-1 significantly reduced tumor burden and improved overall survival in an immunocompetent syngeneic murine model of osteosarcoma (K7M2). A mechanistic study revealed that JQ-1 administration dramatically reprogrammed the tumor immune microenvironment (TIME) within K7M2 tumors. On the one hand, JQ-1 can promote T cell trafficking into tumors by increasing the expression and secretion of T cell-recruiting chemokines. On the other hand, JQ-1 is capable of facilitating crosstalk between antigen-presenting dendritic cells and T cells through the CD40/CD40L costimulatory pathway, leading to activation of tumor-specific CTLs. Combined treatment with anti-PD-1 antibody and JQ-1 resulted in more pronounced tumor regression than either monotherapy, showing an obvious synergistic effect. These findings uncover for the first time that c-Myc inhibition can promote T cell infiltration and activation in osteosarcoma in multiple ways, delivering a one-two punch for modulating TIME. The present work also provides the basis for establishing c-Myc inhibitor and ICB coadministration as a novel therapeutic regimen for patients with osteosarcoma.

Safety and Efficacy of Minimally Invasive Transforaminal Lumbar Interbody Fusion Combined with Gelatin Sponge Impregnated with Dexamethasone and No Drainage Tube after Surgery in the Treatment of Lumbar Degenerative Disease.

OBJECTIVE: The aim of the present study was to use a gelatin sponge impregnated with dexamethasone, combined with minimally invasive transforaminal lumbar interbody fusion (MIS-TLIF) and no drainage tube after the operation for early postoperative recurrence of root pain caused by edema. METHODS: A prospective case series study was designed. From September 2015 to January 2018, eligible patients diagnosed with lumbar degenerative disease underwent MIS-TLIF combined with a gelatin sponge impregnated with dexamethasone and no drainage tube after surgery. The short-term clinical data were collected, such as visual analog scale (VAS) scores for low back pain and leg pain preoperatively and on postoperative days (POD) 1-10, time bedridden postoperatively, and length of hospital stay postoperatively. Long-term indicators include the Japanese Orthopaedic Association (JOA) score, the Oswestry Disability Index (ODI) score, and the 36-Item Short-Form Health Survey (SF-36) score, evaluated preoperatively and 1 week, 3 months, and more than 1 year postoperatively. RESULTS: Complete clinical data was obtained for 139 patients. All patients were followed up for more than 12 months (13.7 ± 3.3 months). The average bedridden period was 1.5 ± 0.4 days and hospital stays were 2.7 ± 0.9 days. The VAS score of leg and back pain on POD 1-10 were all decreased compared with preoperation (all P < 0.0001). At the last follow up, the VAS scores for back pain and leg pain (0.69 ± 0.47; 1.02 ± 0.55) and the ODI score (11.1 ± 3.5) decreased (all P < 0.0001), and the JOA score (27.1 ± 3.2) and the SF-36 (physical component summary, 50.5 ± 7.3; mental component summary, 49.4 ± 8.9) increased (all P < 0.0001) compared with preoperative values. Patients' early and long-term levels of satisfaction postoperatively were 92.8% and 97.8%, respectively. At POD 7 and the last follow-up, the improvement rate of the JOA score, respectively, was 41.8% ± 10.6% and 87.7% ± 8.2%, and clinical effects assessed as significantly effective according to the improvement rate of the JOA score was 16.5% and 66.9%, respectively. There were 2 (1.4%) cases with complications, including 1 (0.7%) case of wound infection and 1 (0.7%) case of deep vein thrombosis. There were no device-related complications or neurological injuries. CONCLUSION: Use of a gelatin sponge impregnated with dexamethasone combined with MIS-TLIF and no drainage tube after the operation, compared with previous studies, appears to be safe and feasible to reduce recurrent back pain and leg pain after decompression in the treatment of lumbar degenerative disease.

The role of Notch ligand Jagged1 in osteosarcoma proliferation, metastasis, and recurrence.

BACKGROUND: Osteosarcoma is the most common primary bone cancer occurring in young adults and the 5-year survival rate of patients with metastatic osteosarcoma is less than 30% due to high metastatic recurrence and drug resistance. Notch is a highly conserved cell to cell signaling pathway in evolution, and Jagged1 is an important ligand of Notch. Although some studies have found that Notch receptors and ligands including Jagged1 were highly expressed in osteosarcoma tissues and osteosarcoma cells, the role of Jagged1 in osteosarcoma progression and metastasis are still not clear. METHODS: Tumor tissues were collected from 68 patients and immunohistochemical staining was employed to group these patients by expression of Jagged1. Real-time quantitative PCR and Western blotting were used to detect the expression of Jagged1. We used siRNA to knockdown the expression of Jagged1 in F5M2 cells. Colony formation assay and MTT were employed to detect and analyze the proliferation of F5M2 cells with or without knockdown of Jagged1. Transwell assay were used to detect the migration and invasion of F5M2 cells. RESULTS: In this study, we found that the high expression of Jagged1 is closely related to the metastasis and recurrence of osteosarcoma in 68 clinical specimens. The expression of Jagged1 in F5M2 cells with high metastasis was significantly higher than that in F4 cells with low metastasis. Knockdown of Jagged1 led to lower ability of proliferation, migration, and invasion in F5M2 cells. CONCLUSION: The high expression of Jagged1 is closely related to the metastasis and recurrence of osteosarcoma. Knockdown of Jagged1 significantly reduced the proliferation, migration, and invasion of osteosarcoma cells. Our results suggested that knockdown of Jagged1 may be a potentially effective treatment for metastatic osteosarcoma.

Intraoperative anti-inflammatory drugs combined with no drainage after MIS-TLIF in the treatment of recurrent lumbar disc herniation: an RCT.

BACKGROUND: Minimally invasive-transforaminal lumbar interbody fusions (MIS-TLIF), in which the nerve root pain is caused by early postoperative edema reaction, is a common clinical complication. However, there is no effective method to solve this problem. We aimed to use gelatin sponge impregnated with mixed anti-inflammatory drugs combined with no drainage after MIS-TLIF to optimize postoperative effect in the treatment of recurrent lumbar disc herniation (LDH). METHODS: From June 2018, the middle-aged patients (45-60 years old) with recurrent LDH were recruited. Included patients were treated with MIS-TLIF surgery, and no drainage tube was placed after surgery. All patients were randomly divided into intervention group (gelatin sponge impregnated with mixed anti-inflammatory drugs) and control group (saline was immersed in gelatin sponge as a control). RESULTS: The intervention group included 63 cases, and the control group included 65 cases. The length of hospital stays and bedridden period in the intervention group were significantly lower than those in the control group (P < 0.05). The VAS score of low back pain in the intervention group was significantly lower than that of the control group at postoperative days 1-6 (P < 0.05, for all). The VAS scores of leg pain in the intervention group at postoperative days 1-9 were statistically lower than the control group (P < 0.05, for all). CONCLUSIONS: Application of gelatin sponge impregnated with mixed anti-inflammatory drugs combined with no drainage after MIS-TLIF can significantly further optimize the surgical effect of recurrent LDH and shorten the bedridden period and hospital stays, to achieve the purpose of early rehabilitation. TRIAL REGISTRATION: China Clinical Trial Registration Center, ChiCTR1800016236. Registered on May 21, 2018, http://www.chictr.org.cn/listbycreater.aspx.

Radiological and clinical differences between robotic-assisted pedicle screw fixation with and without real-time optical tracking.

OBJECTIVE: To study radiological and clinical differences between robotic-assisted pedicle screw fixation with and without real-time optical tracking. METHODS: Patients who underwent lumbar internal fixation in our hospital from June 2017 to February 2020 were divided into Tinavi group (with optical tracking) and Renaissance group (without optical tracking) according to assisted technology. The imaging data of the patients were collected, and the accuracy of screw implantation was measured according to Rampersaud A-D grade. Clinical outcomes such as operative time, fluoroscopic time and radiations dose were also collected. RESULTS: A total of 376 patients were included, including 201 patients in the Tinavi group with 968 screws implanted and 175 patients in the Renaissance group with 822 screws implanted. The accuracy of "perfect" and "clinically acceptable" pedicle screw implantation in the Tinavi group was 94.9%-98.7%, respectively, while in the Renaissance group was 91.2%-94.5%, respectively. There was significant difference between the two groups (P < 0.05). The operative time and operative time per screw in the Tinavi group were lower than those in the Renaissance group. However, fluoroscopic time per screw and radiations dose of the Tinavi group were significantly higher than those of the Renaissance group. CONCLUSION: Optical tracking in robotic system appears to increase accuracy because of the ability to detect the real-time position of the patient. Although there are still many problems to be solved, robot with optical tracking system shows its great potential in clinical application.

Radiological and Clinical Differences between Tinavi Orthopedic Robot and O-Arm Navigation System in Thoracolumbar Screw Implantation for Reconstruction of Spinal Stability.

BACKGROUND Pedicle screw fixation is one of the most commonly used methods in spine surgery. We introduce a surgical robot system from China based on 3-dimensional fluoroscopy imaging and compare it with the commonly used O-arm navigation system. We study the differences in accuracy, safety, and clinical effect in auxiliary pedicle screw fixation. MATERIAL AND METHODS Patients who underwent thoracolumbar internal fixation in our hospital from 2017 to 2019 were divided into a robot and navigation group according to whether surgery was assisted by the Tinavi orthopedic robot or O-arm navigation system. Imaging data of patients were searched from the image system and accuracy of screw implantation was measured by Rampersaud A to D grade classification. Deviation sagittal, deviation transversal, and facet joint violation were also measured and calculated. RESULTS In total, 306 patients were included: 136 patients in the robot group with 760 screws implanted; 166 patients in the navigation group with 908 screws implanted. The accuracy of "perfect" and "clinically acceptable" pedicle screw implantation was 96.2% and 99.6%, respectively, in the robot group and 90.5% and 96.7%, respectively, in the navigation group, with a significant difference between the 2 groups (P<0.05). The sagittal and transversal deviations in the robot group were significantly less than those in the navigation group (P<0.05). CONCLUSIONS The Tinavi orthopedic robot can significantly improve surgical accuracy and safety of pedicle screw fixation, as compared with that of O-arm navigation technology, without increasing complications. It shows great potential in clinical application.

miR­193b exhibits mutual interaction with MYC, and suppresses growth and metastasis of osteosarcoma.

Emerging evidence has indicated that microRNAs (miRs) are involved in the malignant behavior of cancer. The present study explored the role of miR­193b in the development and metastasis of osteosarcoma. Compared with F4 osteosarcoma cells, which have a relatively low metastatic potential, highly metastatic F5M2 cells exhibited a lower expression of miR­193b. Furthermore, miR­193b exerted negative effects on cell proliferation, colony formation, cell cycle progression, migration and invasion, and induced apoptosis. In vivo studies revealed negative influences of miR­193b on tumorigenesis and metastasis. The tumor­suppressive role of miR­193b was achieved by targeting KRAS and stathmin 1 (STMN1). Notably, overexpression of KRAS and STMN1 attenuated the miR­193b­induced inhibition of malignant behaviors. There was a double­negative regulatory loop between MYC and miR­193b, with MYC inhibiting miR­193b expression by directly binding to its promoter region and miR­193b negatively influencing MYC expression indirectly through some unknown mechanism. Collectively, these findings indicated that miR­193b may serve a tumor suppressive role in osteosarcoma by targeting KRAS and STMN1. The double­negative regulatory loop between MYC and miR­193b may contribute to the sustained upregulation of MYC, the downregulation of miR­193b, and to the subsequently enhanced expression of KRAS and STMN1, which may eventually lead to the development and metastasis of osteosarcoma.