Efficacy of computer-assisted robotic based clinical training program for spinal oncology education on pedicle screw placement.

Pedicle screw placement (PSP) is the fundamental surgical technique that requires high accuracy for novice orthopedists studying spinal oncology education. Therefore, we set forth to establish a computer-assisted robotic navigation training program for novice spinal oncology education. Novice orthopedists were involved in this study to evaluate the feasibility and safety of the computer-assisted robotic navigation (CARN) training program. In this research, trainees were randomly taught by the CARN training program and the traditional training program. We prospectively collected the clinical data of patients with spinal tumors from 1st May 2021 to 1st March 2022. The ability of PSP was evaluated by cumulative sum (CUSUM) analysis, learning curve, and accuracy of pedicle screws. The patients included in both groups had similar baseline characteristics. In the CUSUM analysis of the learning curve for accurate PSP, the turning point in the CARN group was lower than that in the traditional group (70th vs. 92nd pedicle screw). The LC-CUSUM test indicated competency for PSP at the 121st pedicle screw in the CARN group and the 138th pedicle screw in the traditional group. The accuracy of PSP was also significantly higher in the CARN group than in the traditional group (88.17% and 79.55%, P = 0.03 < 0.05). Furthermore, no major complications occurred in either group. We first described CARN in spinal oncology education and indicated the CARN training program as a novel, efficient and safe training program for surgeons.

Efficacy and safety of COVID-19 vaccines for patients with spinal tumors receiving denosumab treatment: An initial real-clinical experience study.

Background: Even if COVID-19 vaccine has gradually been adopted in the world, information of side effects and crosstalk in patients with spinal tumors is absent due to the exclusion from clinical research. In this research, we aimed to investigate the efficacy and safety for the patients with spinal tumors treated by denosumab. Methods: In this retrospective research, 400 patients under treatment of denosumab against spinal tumors in real-clinical experience were grouped into two cohorts according to the treatment of COVID-19 vaccine. And linked hospital data, serum samples and unsolicited related adverse events had been collected from January 22nd 2021 to June 1st 2021 respectively. Results: 233 patients of all participants who received regular treatment of denosumab were vaccinated by mRNA or inactivated vaccine. Patients of metastatic disease and primary osseous spinal tumor showed similar distribution in both two groups. Over the study period, within 176 patients tested the status of serologic response of vaccine, 88(81.48%) and 41(87.23%) individuals injected one or two inactivated vaccines had effective antibody against SARS-CoV-2 infections. As 21 patients (85.71%) treated by mRNA vaccine did. Considering of the safety of vaccine, most common systemic adverse events were nausea or vomiting (45 events vs 23events). Interestingly, fewer participants in the vaccine group were statistically recorded in local adverse events than in the placebo group (16 events vs 33 events). Conclusions: Our initial real-clinical experience suggests that COVID-19 vaccines are likely safe and effective in in patients with spinal tumors receiving denosumab treatment.

Robot and working tube-assisted invasion-controlled surgery for spinal metastases.

Objective: This study aims to highlight the use of robots in surgery and that of tube-assisted minimally invasive surgery for spinal metastases, as well as elaborate on the concept of invasion-controlled surgery (ICS). Summary of background: Many patients with spinal metastasis cancer cannot afford serious complications when undergoing traditional open surgery because of their poor physical condition. Robots and minimally invasive technology have been introduced into the field of spine surgery and they have shown significant advantages. Methods: Six patients who underwent robot and working tube-assisted ICS for spinal metastases. Relevant demographic, medical, surgical, and postoperative data were collected from medical records and analyzed. Results: Mean operative time was 3.8 h and the mean length of the surgical incision was 4.9 cm. The mean estimated blood loss was 400 ml. The mean bedtime and hospital length of stay were 3.2 days and 6.5 days, respectively. No obvious complications were reported during treatment. The mean accuracy of screw placement was 98%. The mean time for further system treatment after surgery was 5.8 days. All patients experienced significant pain relief. The mean preoperative visual analog scale (VAS) was 7.83 points. The mean VAS at 1 day, 1 week, and 1 month after surgery were 2.83, 1.83, and 1.17 points, respectively. Frankel grade was improved in five of six patients. One patient preoperatively with Frankel grade D was the same postoperatively. Conclusion: The concept of ICS is suitable for patients with spinal metastases. Robot and working tube-assisted ICS for spinal metastases is one of the safest and most effective treatment methods.

NEAT1 regulates MPP+-induced neuronal injury by targeting miR-124 in neuroblastoma cells.

Long non-coding RNAs (lncRNAs) have been reported to play important roles in Parkinson's disease (PD) pathogenesis. It was indicated that lncRNA nuclear enriched abundant transcript 1 (NEAT1) is involved in PD. However, the underlying mechanism of NEAT1 is still not fully explored. Human neuroblastoma cell line SH-SY5Y was treated with 1-Methyl-4-phenylpyridinium (MPP+) to mimic PD model in vitro. qRT-PCR was employed to detect the expression of NEAT1, IL-1ß, IL-6 and TNF-α. Starbase database, RNA pull-down assay and RNA immunoprecipitation (RIP) assay were performed to verify the relationship between NEAT1 and miR-124. MTT assay and flow cytometry assay were used to detect cell viability and apoptosis. Elisa was introduced to measure the levels of IL-1ß, IL6 and TNF-α in culture media. We found that NEAT1 expression was significantly increased in SH-SY5Y cells after MPP+ treatment in dose- and time- dependent manners. MPP+ induced the expression and secretion of IL-1ß, IL-6 and TNF-α, inhibited cell viability and induced apoptosis while these effects could be rescued by NEAT1 silencing. miR-124 was a target of NEAT1. Anti-miR-124 could reverse the effects caused by NEAT1 knockdown in MPP+ treated SH-SY5Y cells. Therefore, we speculated that NEAT1 may regulate MPP+ induced neuronal injury by targeting miR-124 in SH-SY5Y cells.

Retracted Article: Long noncoding RNA HOTAIR promotes cell apoptosis by sponging miR-221 in Parkinson's disease.

Parkinson's disease (PD) is a common neurological disorder that is detrimental to the health of older people worldwide. Long noncoding RNAs (lncRNAs) have been reported to play essential roles in the pathogenesis and therapeutics of PD. LncRNA homeobox transcript antisense intergenic RNA (HOTAIR) is expressed in PD samples; however, the exact roles of HOTAIR and its mechanism remain largely unclear. Herein, the neurotoxins 1-methyl-4-phenylpyridine (MPP+) and 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) were used to establish PD models in vitro and in vivo. The expressions of HOTAIR and microRNA-221 (miR-221) were measured by the quantitative real-time polymerase chain reaction (qRT-PCR). Cell viability and apoptosis were detected by the 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2-H-tetrazolium bromide (MTT) assay and western blot or flow cytometry, respectively. The interaction between HOTAIR and miR-221 was explored by luciferase activity and RNA immunoprecipitation (RIP). The tyrosine hydroxylase (TH)-positive cells in MPTP-treated-mouse midbrains were analyzed by immunohistochemistry. The HOTAIR expression was up-regulated and that of miR-221 was down-regulated in the serum of PD patients and MPP+-treated SH-SY5Y cells. Overexpression of HOTAIR inhibited cell viability and promoted apoptosis in MPP+-treated SH-SY5Y cells. However, the down-regulation of HOTAIR showed an opposite effect. Moreover, miR-221 was validated to be bound to HOTAIR, and its addition reversed the regulatory effect of HOTAIR on cell viability and apoptosis in MPP+-treated SH-SY5Y cells. Moreover, the knockdown of HOTAIR attenuated the degree of PD and cell apoptosis by regulating miR-221 in MPTP-treated mice. In conclusion, HOTAIR contributed to cell apoptosis by sponging miR-221 in PD. This study elucidates a new mechanism for understanding the pathogenesis of PD and provides a promising target for the treatment of PD.

Silencing the autophagy-specific gene Beclin-1 contributes to attenuated hypoxia-induced vasculogenic mimicry formation in glioma.

OBJECTIVE: To explore the influence of Beclin-1 on vasculogenic mimicry (VM) induced by hypoxia in glioma. METHODS: CD34-PAS staining was carried out to observe VM formation, and immunohistochemistry was used to determine the expression levels of Beclin-1, HIF-1α, VEGF and MMP2 in 105 patients with primary glioma. Human glioma U87MG cells were divided into Normoxia, Hypoxia, Hypoxia + NC siRNA and Hypoxia + Beclin-1 siRNA groups. Cobalt chloride (CoCl2) was used to stimulate hypoxic conditions, and a VM tube formation assay was used to detect VM formation. Wound healing and Transwell invasion assays were used to detect the invasive and migratory abilities of U87MG cells, respectively. Fluorescent LC3 puncta analysis was performed to examine the status of autophagic flux. Expression levels of Beclin-1 and VM-related molecules were determined using real-time quantitative-polymerase chain reaction (RT-qPCR) and western blotting. RESULTS: There were 34 VM-positive cases and 71 VM-negative cases among 105 glioma patients, and VM formation was correlated with pathological grade and the expression of Beclin-1, HIF-1α, VEGF and MMP2. Positive relations were found between Beclin-1 and the expression of HIF-1α, VEGF and MMP2. Under hypoxic conditions, significant increases in the total length of tubes, migration rate, invasion cell number and expression of VM-related molecules were found in U87MG cells. Silencing Beclin-1 markedly decreased hypoxia-induced VM formation and the invasive and migratory abilities, together with the expression of VM-related molecules, in U87MG cells and significantly inhibited the autophagic flux. CONCLUSION: Silencing Beclin-1 can attenuate hypoxia-induced VM formation and the metastatic ability of U87MG cells and is a potential target for VM inhibition in glioma.

Activation of sonic hedgehog signaling pathway in olfactory neuroblastoma.

OBJECTIVES: Sonic hedgehog (Shh) signaling pathway is associated with tumor development; however, the role of Shh signaling in the development of olfactory neuroblastoma (ONB) is unknown. This study aimed to investigate the relationship between the regulation of Shh signaling and the pathogenesis of ONB. METHODS: The expression of Shh signaling components was characterized by immunohistochemistry in human non-tumor olfactory epithelium and ONB specimens, and by RT-PCR and immunoblotting in human ONB cell lines. The impact of the treatment with cyclopamine (a selective inhibitor of the Shh pathway) and/or exogenous Shh on ONB cell proliferation, cycle and apoptosis was examined by MTT, soft agar colony formation and flow cytometry assays, respectively. The influence of Shh signaling on the expression of Shh signaling components and cell cycle-related regulators was determined by immunoblotting and quantitative RT-PCR, respectively. RESULTS: The expression of Pacthed1, Gli1 and Gli2 was detected in 70, 70, and 65% of human ONB specimens, respectively, and in proportion of ONB cell lines, but not in non-tumor olfactory epithelium. Treatment with cyclopamine inhibited the proliferation and colony formation of ONB cells, induced ONB cell cycle arrest and apoptosis, and down-regulated the expression of Pacthed1, Gli1 and cyclin D1, but up-regulated p21 expression in vitro. These regulatory effects of cyclopamine were partially or completely erased by exogenous Shh. CONCLUSION: These data suggest that the Shh signaling pathway is crucial for the growth of ONB.

A critical role of Sonic Hedgehog signaling in maintaining the tumorigenicity of neuroblastoma cells.

Accumulated evidence suggests a major role for the activation of the Sonic Hedgehog (SHH) signaling pathway in the development of neural crest stem cells that give rise to the sympathetic nervous system. We therefore investigated the involvement of SHH signaling in the pathogenesis of neuroblastoma, a common childhood malignant tumor of the sympathetic nervous system. Human neuroblastoma cell lines and a majority of primary neuroblastoma specimens showed high-level expression of the pathway targets and components, indicating persistent activation of the SHH pathway. All of the neuroblastoma cell lines we examined expressed significant levels of SHH ligand, suggesting an autocrine, ligand-dependent activation of the SHH pathway in neuroblastoma cells. Inhibition of SHH signaling by cyclopamine induced apoptosis and blocked proliferation in all major types of neuroblastoma cells, and abrogated the tumorigenicity of neuroblastoma cells. Moreover, the knockdown of GLI2 in neuroblastoma BE (2)-C and SK-N-DZ cell lines resulted in the inhibition of colony formation. Our study has revealed a molecular mechanism for the persistent activation of the SHH pathway which promotes the development of neuroblastoma, and suggests a new approach for the treatment of this childhood malignant tumor. (Cancer Sci 2009; 100: 1848-1855).