Neuroprotective effects of rapamycin on spinal cord injury in rats by increasing autophagy and Akt signaling

Rapamycin treatment has been shown to increase autophagy activity and activate Akt phosphorylation, suppressing apoptosis in several models of ischemia reperfusion injury. However, little has been studied on the neuroprotective effects on spinal cord injury by activating Akt phosphorylation. We hypothesized that both effects of rapamycin, the increased autophagy activity and Akt signaling, would contribute to its neuroprotective properties. In this study, a compressive spinal cord injury model of rat was created by an aneurysm clip with a 30 g closing force. Rat models were intraperitoneally injected with rapamycin 1 mg/kg, followed by autophagy inhibitor 3-methyladenine 2.5 mg/kg and Akt inhibitor IV 1 μg/kg. Western blot assay, immunofluorescence staining and terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling assay were used to observe the expression of neuronal autophagy molecule Beclin 1, apoptosis-related molecules Bcl-2, Bax, cytochrome c, casp ase-3 and Akt signaling. Our results demonstrated that rapamycin inhibited the expression of mTOR in injured spinal cord tissue and up-regulated the expression of Beclin 1 and phosphorylated-Akt. Rapamycin prevented the decrease of bcl-2 expression in injured spinal cord tissue, reduced Bax, cytochrome c and caspase-3 expression levels and reduced the number of apoptotic neurons in injured spinal cord tissue 24 hours after spinal cord injury. 3-Methyladenine and Akt inhibitor IV intervention suppressed the expression of Beclin-1 and phosphorylated-Akt in injured spinal cord tissue and reduced the protective effect of rapamycin on apoptotic neurons. The above results indicate that the neuroprotective effect of rapamycin on spinal cord injury rats can be achieved by activating autophagy and the Akt signaling pathway.

Bone metastases from hepatocellular carcinoma:clinical features and prognostic factors

BACKGROUND: Bone metastases (BMs) from hepatocellular carcinoma (HCC) is an increasingly common disease in Asia. We assessed the clinical features, prognostic factors, and differences in outcomes related to BMs among patients with different treatments for HCC. METHODS: Forty-three consecutive patients who were diagnosed with BMs from HCC between January 2010 and December 2014 were retrospectively enrolled. The clinical features were identified, the impacts of prognostic factors on survival were statistically analyzed, and clinical data were compared. RESULTS: The median patient age was 54 years; 38 patients were male and 5 female. The most common site for BMs was the trunk (69.3%). BMs with extension to the soft tissue were found in 14 patients (32.5%). Most (90.7%) of the lesions were mixed osteolytic and osteoblastic, and most (69.8%) patients presented with multiple BMs. The median survival after BMs diagnosis was 11 months. In multivariate analyses, survival after BM diagnosis was correlated with Karnofsky performance status (P=0.008) and the Child-Pugh classification (P<0.001); BM-free survival was correlated with progression beyond the University of California San Francisco criteria (P<0.001) and treatment of primary tumors (P<0.001). BMs with extension to soft tissue were less common in liver transplantation patients. During metastasis, the control of intrahepatic tumors was improved in liver transplantation and hepatectomy patients, compared to conservatively treated patients. CONCLUSIONS: The independent prognostic factors of survival after diagnosis of BMs were the Karnofsky performance status and Child-Pugh classification. HCC patients developed BMs may also benefit from liver transplantation or hepatectomy.

Clinical significance of microRNA-130b in osteosarcoma and its role in cell growth and invasion

Objective: To investigate clinical signii cance of microRNA-130b(mi R-130b) in osteosarcoma and its role in cell growth and invasion. Methods: miR-130b expression was detected in 68 samples of surgically resected osteosarcoma and matched normal tumor-adjacent tissues by q RT-PCR. The expression of miR-130b was altered by corresponding vectors in osteosarcoma cells, and then Western blot was used to detect the expression of PPAR毭. Brd U cell proliferation and Transwell assays were performed to determine cell proliferation and invasion. Results: The expression of miR-130b in osteosarcoma tissues was signii cantly higher than that in normal tumor-adjacent tissues. Its expression in patients with metastasis was signii cantly higher than that in those without metastases. miR-130b expression in tumor tissues was signii cantly associated with tumor size, clinical stage and distant metastasis. And its expression was signii cantly correlated with overall survival and disease free survival. miR-130b overexpression obviously repressed the expression of PPAR毭, and resulted in signii cant increase of Saos-2 cell proliferation and invasion. On the contrast, repressing miR-130b expression with its inhibitor signii cantly increased PPAR毭 expression, and inhibited MG-63 cell proliferation and invasion. Conclusions: The high-expression of miR-130b is correlated with the adverse clinicopathological features and poor prognosis in osteosarcoma. miR-130b may regulate proliferation and invasion of osteosarcoma cells by targeting PPAR毭, suggesting miR-130b may play a key role in the progression of osteosarcoma.

Effect of down-regulation of voltage-gated sodium channel Nav1.7 on activation of astrocytes and microglia in DRG in rats with cancer pain

Objective:To evaluate the effect of down-regulation of Nav1.7 on the activation of astrocytes and microglia in DRG of rats with cancer pain,and explore the transmission of the nociceptive information.Methods:Lentiviral vector harboring RNAi sequence targeting the Navl.7 gene was constructed,and Walker 256 breast cancer cell and morphine was injected to build the bone cancer pain model and morphine tolerance model in rats.Lentiviral vector was injected.Rats in each model were divided into 4 groups:model group,PBS group,vehicle group and LV-Nav1.7 group.The expression levels of GFAP and OX42 in dorsal root ganglia(DRG) were measured.Results:After the animal model was built,the level of Navl.7,GFAP and OX42 was improved obviously with the time prolonged,which was statistically significant(P<0.05).The expression level of GFAP and OX42 in the DRG in the LV-Navl.7 group declined obviously compared to the model group,PBS group and vehicle group(P<0.05).Conclusions:Intrathecal injection of Navl.7 shRNA lentiviral vector can reduce the expression of Nav1.7and inhibit the activation of astrocytes and microglia in DRG.The effort is also effective in morphine tolerance bone cancer pain model rats.

Combination of methylprednisolone and rosiglitazone promotes recovery of neurological function after spinal cord injury

Methylprednisolone exhibits anti-inflammatory antioxidant properties, and rosiglitazone acts as an anti-inflammatory and antioxidant by activating peroxisome proliferator-activated receptor-y in the spinal cord. Methylprednisolone and rosiglitazone have been clinically used during the early stages of secondary spinal cord injury. Because of the complexity and diversity of the inflammatory process after spinal cord injury, a single drug cannot completely inhibit inflammation. Therefore, we assumed that a combination of methylprednisolone and rosiglitazone might promote recovery of neurological function after secondary spinal cord injury. In this study, rats were intraperitoneally rejected with methylprednisolone （30 mg/kg） and rosiglitazone （2 mg/kg） at 1 hour after injury, and methylprednisolone （15 mg/kg） at 24 and 48 hours after injury. Rosiglitazone was then administered once every 12 hours for 7 consecutive days. Our results demonstrated that a combined treatment with methylprednisolone and rosiglitazone had a more pronounced effect on attenuation of inflammation and cell apoptosis, as well as increased functional recovery, compared with either single treatment alone, indicating that a combination better pro- moted recovery of neurological function after injury.

念珠菌脊柱感染发生在H7N9治愈的患者一例报道及文献分析念珠菌脊柱感染和曲霉菌脊柱感染的临床区别（英文）

目的:报道在H7N9治愈患者中发现念珠菌脊柱感染病例,并总结念珠菌和曲霉菌脊柱感染的临床表现,处理方法和预后等不同点。创新点:首次报道在H7N9禽流感治愈患者中出现念珠菌脊柱感染,经过彻底的清创融合内固定和唑类抗真菌药治疗取得良好疗效。文献研究发现了念珠菌和曲霉菌这两大主要真菌在脊柱感染中的临床表现、处理方法和临床结局均有不同。念珠菌脊柱感染治愈率为92.3%,而曲霉菌为70.2%。其可能的原因有以下四点,念珠菌血培养结果阳性率更高(41.0%vs.24.5%),神经损害发生概率更低(25.6%vs.43.6%),手术方式更多地选用彻底病灶清除加融合内固定(60.5%vs.39.6%),术后多选用唑类抗真菌药。方法:在Pub Med和Google Scholar搜集念珠菌和曲霉菌脊柱感染的病例,提取患者一般信息、临床症状、感染部位、病原学结果、治疗方法、治疗结局和复发等情况进行总结分析。结论:念珠菌脊柱感染的治愈率相对曲霉菌脊柱感染更高,这可能与念珠菌可以早期发现,神经损害较少,更多地选用彻底病灶清除和唑类抗真菌药有关。真菌脊柱感染可以通过合适的手术和抗真菌药取得良好临床疗效。