Objective: Oxytocin (OT) is synthesized within the paraventricular nucleus and supraoptic nucleus of the hypothalamus. In addition to its role in uterine contraction, OT plays an important antinociceptive role; however, the underlying molecular mechanisms of antinociceptive role of OT remain elusive. We hypothesized that the antinociceptive effect of OT on neuropathic pain may occur via inhibition of TRPV1 activation in the spinal cord. The present study explores the antinociceptive role of OT and its mechanisms in neuropathic pain. Methods: Partial sciatic nerve ligation (pSNL) was performed to induce neuropathic pain. Animal behaviors were measured using a set of electronic von Frey apparatus and hot plate. Electrophysiological recordings and molecular biological experiments were performed. Results: Intrathecal administration of OT alleviated both mechanical allodynia and thermal hyperalgesia in pSNL rats (n = 6, per group, P < 0.0001, saline vs. OT group). Electrophysiological data revealed that OT significantly inhibited the enhancement of frequency and amplitude of spontaneous excitatory post-synaptic currents induced presynaptically by TRPV1 activation in the spinal cord. Moreover, the inhibitory effect of OT on capsaicin-induced facilitation of excitatory transmission was blocked by co-treatment with saclofen, while intrathecal administration of OT dramatically inhibited capsaicin-induced ongoing pain in rats, (n = 6, per group, P < 0.0001, saline vs. OT group). The paw withdrawal latency in response to heat stimulation was significantly impaired in TRPV1KO mice 3 days after pSNL upon OT (i.t.) treatment, compared with wild type mice (n = 6, P < 0.05). Finally, OT prevented TRPV1 up-regulation in spinal cords of pSNL model rats. Conclusion: OT relieves neuropathic pain through GABA release and presynaptic TRPV1 inhibition in the spinal cord. OT and its receptor system might be an intriguing target for the treatment and prevention of neuropathic pain.

Spinal cord injury (SCI) is one common neurological condition which involves primary injury and secondary injury. Neuron inflammation and apoptosis after SCI is the most important pathological process of this disease. Here, we tried to explore the influence and mechanism of miRNAs on the neuron inflammatory response and apoptosis after SCI. First, by re-analysis of Gene Expression Omnibus dataset (accession GSE19890), miR-182 was selected for further study because of its suppressive effects on the inflammatory response in the various types of injuries. Functional experiments demonstrated that miR-182 overexpression promoted functional recovery, reduced histopathological changes, and alleviated spinal cord edema in mice. It was also observed that miR-182 overexpression reduced apoptosis and attenuated the inflammatory response in spinal cord tissue, as evidenced by the reduction of tumor necrosis factor (TNF)-α, interleukin (IL)-6, and IL-1β, and the induction of IL-10. Using a lipopolysaccharide (LPS)-induced SCI model in BV-2 cells, we found that miR-182 was downregulated in the BV-2 cells following LPS stimulation, and upregulation of miR-182 improved LPS-induced cell damage, as reflected by the inhibition of apoptosis and the inflammatory response. IκB kinase β (IKKβ), an upstream target of the NF-κB pathway, was directly targeted by miR-182 and miR-182 suppressed its translation. Further experiments revealed that overexpression of IKKβ reversed the anti-apoptosis and anti-inflammatory effects of miR-182 in LPS stimulated BV-2 cells. Finally, we found that miR-182 overexpression blocked the activation of the NF-κB signaling pathway in vitro and in vivo, as demonstrated by the downregulation of phosphorylated (p‑) IκB-α and nuclear p-p65. Taken together, these data indicate that miR-182 improved SCI-induced secondary injury through inhibiting apoptosis and the inflammatory response by blocking the IKKβ/NF-κB pathway. Our findings suggest that upregulation of miR-182 may be a novel therapeutic target for SCI.

This study used a clinical dataset to investigate the proportion of the newly found bone lesions in malignant patients diagnosed by biopsy as being benign, malignant but unrelated to the primary malignancy, or bone metastases of the primary malignancy. The clinical factors that might affect the correlation between bone lesions and the primary malignancy were also analyzed. It is expected to obtain some information contributing to the clinical decision-making regarding the need for biopsy of these lesions from the research results. Data from patients with a single known malignant tumor who had undergone biopsy of newly found bone lesions at our research institution between January 2012 and December 2017 were reviewed. Based on the pathology results, included cases were divided into a bone-metastasis-of-primary-tumor group (Group 1) and a non-bone-metastasis-of-primary-tumor group (Group 2). The sex, age, diagnostic interval time between the primary malignancy and bone lesions, clinical symptoms, number of involved bones, sites of bone biopsy, and 18F-FDG PET/CT results were compared between groups. A total of 117 patients (92 in Group 1 and 25 in Group 2) were included in the study. There was no significant difference in the sex, age or diagnostic interval time between patient groups. Of all the cases, 17.9% (21/117) were identified to be benign lesions such as fibrous dysplasia (n = 2), bone tuberculosis (n = 1), simple bone cyst (n = 1), aneurysmal bone cyst (n = 1), or solitary fibrous tumor (n = 1). Meanwhile, 3.4% (4/117) were new malignancies including chondrosarcoma (n = 1), plasmacytoma (n = 1) and bone metastases unrelated to the primary malignancy (n = 2). Bone metastases pertinent to the primary tumor accounted for 78.6% (92/117) of cases. Liver (n = 18), kidney (n = 14), breast (n = 13) and lung (n = 12) were the most common cancers among cases. Cases with clinical symptoms exhibited a higher likelihood of their bone lesions being diagnosed as bone metastases of their primary malignancy than those without clinical symptoms (81.3% (87/107) vs. 50.0% (5/10)) (P = 0.021). Neither the number of bone lesions nor the biopsy sites appeared to influence whether the bone lesions were metastases of the primary malignancy or not. In PET/CT examination, the mean maximum standardized uptake values of the two groups were similar. This study indicated that more than 1/5 of newly identified bone lesions in patients with a single known malignancy were not clinically associated with their primary tumors. Furthermore, 3.4% of these were newly discovered malignant bone tumors. The presence of clinical symptoms may be a significant factor affecting whether a new bone lesion is clinically linked to a patient's primary malignancy. Based on the experience from these patients, as for the newly found bone lesions, it is worthy to perform an active biopsy on those asymptomatic ones to avoid misdiagnosis and less biopsy on symptomatic ones for the sake of less cost and risks.

A secondary injury induced by a spinal cord injury (SCI) remains the main cause of devastating neural dysfunction; therefore, it has been the subject of focused research for many years. Long noncoding RNA (lncRNA) has been found to participate in the SCI process, and this finding presents a high potential for diagnosis and treatment; however, the role of lncRNA in a secondary injury induced by SCI remains unclear. The aim of this study was to investigate the regulatory effect of lncRNA growth arrest–specific transcript 5 (GAS5) in secondary injury during SCI. The SCI mice model and hypoxic cellular model were established to research the roles of lncRNA GAS5 during SCI. Reverse transcription quantitative polymerase chain reaction (qRT-PCR) was conducted to determine the expression levels of microR-93 (miR-93) and lncRNA GAS5. Western blot analysis of the apoptosis regulator protein and terminal deoxynucleotidyl transferase dUTP nick end labeling assay was conducted to evaluate neuron cell apoptosis. Basso, Beattie, and Bresnahan (BBB) scores were calculated to assess neurological function. Flow cytometry was used to determine neuron cell apoptosis. The associations among GAS5, miR-93, and the phosphatase and tensin homolog (PTEN) were disclosed using RNA immunoprecipitation (RIP) assay, RNA pulldown assay, and dual-luciferase reporter assay. QRT-PCR demonstrated that GAS5 was significantly upregulated in both the SCI mice and hypoxic cellular models. GAS5 knockdown suppressed neuron cell apoptosis and inflammatory response in the SCI mice model. Further studies have indicated that GAS5 functions as a competing endogenous RNA (ceRNA) by sponging miR-93 in neuronal cells. In addition, PTEN was a target of miR-93, and GAS5 knockdown exhibited its anti-apoptotic and anti-inflammatory effects through the miR-93/PTEN axis. These findings suggest that the GAS5/miR-93/PTEN axis may be a promising therapeutic target for SCI.

Objective: To compare the spinal stability with different fixation methods after thoracic TES using finite element analysis Methods: The spinal finite element model was established from a healthy volunteer, and the validity was verified. The models of T8 thoracic total en bloc spondylectomy (TES) with and without artificial vertebral body were established combination with different fixation methods: the first was long segment fixation with fixed segments T5–7, T9–11; the second was short segment fixation with fixed segments T6–7, T9–10; the third was modified short segment with a pair of vertebral body screws on T7 and T9 added on the basis of short segment fixation. The motions of each model in standing state were simulated in software. The range of motion (ROM) and internal fixation stress changes were analyzed. Results: When anterior support was effective, the three fixation methods could effectively maintain the stability of the spine. However, when anterior support failed, the ROM of the long segment fixation group and the short segment fixation group in the flexion-extension directions was significantly higher than that of when the anterior support existed, while the modified short segment fixation group had no significant changes. Meanwhile, the stress of internal fixation in the long segment fixation group and the short segment fixation group were greatly increased. However, there were no significant changes in modified short segment fixation group. Conclusion: After TES, the presence of the thoracic cage gives partial anterior stabilization. When the anterior support failed, the modified short segment fixation method can provide better stability.