Dysregulated lipid metabolism and intervertebral disc degeneration: the important role of ox-LDL/LOX-1 in endplate chondrocyte senescence and calcification.

BACKGROUND: Lipid metabolism disorders are associated with degeneration of multiple tissues and organs, but the mechanism of crosstalk between lipid metabolism disorder and intervertebral disc degeneration (IDD) has not been fully elucidated. In this study we aim to investigate the regulatory mechanism of abnormal signal of lipid metabolism disorder on intervertebral disc endplate chondrocyte (EPC) senescence and calcification. METHODS: Human intervertebral disc cartilage endplate tissue, cell model and rat hyperlipemia model were performed in this study. Histology and immunohistochemistry were used to human EPC tissue detection. TMT-labelled quantitative proteomics was used to detect differential proteins, and MRI, micro-CT, safranin green staining and immunofluorescence were performed to observe the morphology and degeneration of rat tail intervertebral discs. Flow cytometry, senescence-associated ß-galactosidase staining, alizarin red staining, alkaline phosphatase staining, DCFH-DA fluorescent probe, and western blot were performed to detect the expression of EPC cell senescence, senescence-associated secretory phenotype, calcification-related proteins and the activation of cell senescence-related signaling pathways. RESULTS: Our study found that the highly expressed oxidized low-density lipoprotein (ox-LDL) and Lectin-like oxidized low-density lipoprotein receptor 1 (LOX-1) in human degenerative EPC was associated with hyperlipidemia (HLP). TMT-labelled quantitative proteomics revealed enriched pathways such as cell cycle regulation, endochondral bone morphogenesis and inflammation. The rat model revealed that HLP could induce ox-LDL, LOX-1, senescence and calcification markers high expression in EPC. Moreover, we demonstrated that ox-LDL-induced EPCs senescence and calcification were dependent on the LOX-1 receptor, and the ROS/P38-MAPK/NF-κB signaling pathway was implicated in the regulation of senescence induced by ox-LDL/LOX-1 in cell model. CONCLUSIONS: So our study revealed that ox-LDL/LOX-1-induced EPCs senescence and calcification through ROS/P38-MAPK/NF-κB signaling pathway, providing information on understanding the link between lipid metabolism disorders and IDD.

Intraventricular ganglioglioma prognosis and hydrocephalus: the largest case series and systematic literature review.

BACKGROUND: Ganglioglioma is mostly found in cerebral parenchymal, and it is rarely located in the ventricular system. To date, ganglioglioma within the ventricular system has been reported in only 10 cases. Its prognosis and relationship with complicating hydrocephalus are unclear. METHODS: A total of 7 cases with intraventricular ganglioglioma diagnosed by the surgical pathology examination from June 2004 to April 2011 in our center were retrospectively analyzed. The clinical data were collected from the clinical medical records, and the tumor site, size and basement of tumor were analyzed. Follow up was performed to obtain the clinical outcomes. RESULTS: The 7 cases included 5 males and 2 females, with disease onset at 23.6 ± 14.9 years old. Epilepsy as the initial symptom was observed in 1 case. Reduced hearing, dizziness and weakness of both lower limbs were found in 1 case. Intracranial hypertension were detected in 5 cases, including 1 case complicating by decreased visual acuity. Tumors were located in the lateral ventricle in 5 cases, while 2 cases in the third ventricle. Hydrocephalus was observed in 5 cases, including 2 cases with severe hydrocephalus, and both underwent ventriculoperitoneal shunting. Total resection of tumors was performed in 5 cases, and 2 cases underwent gross total resection. The mean duration of follow-up was 28.7 months (8-90 months). Intracranial hypertension in all cases disappeared. Even radiotherapy post-surgery, one case with GTR relapsed 1 year later. However, the other 6 cases didn't relapse. CONCLUSIONS: Ganglioglioma in ventricular system is extremely rare, mainly with the symptoms of intracranial hypertension or seizure. The degree of hydrocephalus is closely related to the site of tumor's basement. The prognosis is good after total resection. The patients with GTR should be followed-up.

Meta-analysis of gemcitabine in brief versus prolonged low-dose infusion for advanced non-small cell lung cancer.

OBJECTIVE: To evaluate the efficacy and safety of gemcitabine (GEM) at 30 min standard-dose infusion (30 min-SDI) compared with prolonged low-dose infusion (P-LDI) in patients with advanced non-small-cell lung cancer (NSCLC). METHODS: Electronic databases including Pubmed, EMbase, Cochrane Library, CNKI, CBM, and VIP were searched using keywords "GEM", "P-LDI", and "NSCLC". Review Manager 5.3 was used to perform the meta-analysis. Primary endpoints were overall response rate (ORR) and 1-year survival rate (1-year SR). Secondary endpoints were grade 3/4 hematotoxicity and nausea/vomiting. In association. GRADE quality of evidence system was used to assess the results of meta-analysis. RESULTS: Six randomized controlled trials (RCTs) with a total of 637 patients were included and no statistical heterogeneity was found among the studies. The results showed that P-LDI was superior in ORR (RD = 0.09, 95% CI: 0.02 to 0.16, P = 0.02), but had a similar 1-year SR (RD = 0.05, 95% CI: -0.02 to 0.12, P = 0.18) as compared with 30 min-SDI. For grade 3/4 adverse events, there was no significant difference in anemia (RD = 0.02, 95% CI: -0.01 to 0.04, P = 0.27) and nausea/vomiting (RD = 0.01, 95% CI: -0.04 to 0.06, P = 0.64) between the two treatments. However, patients with P-LDI experienced less leukopenia (RD = -0.08, 95% CI: -0.15 to -0.01, P = 0.03) and thrombocytopenia ((RD = -0.05, 95% CI: -0.09 to -0.01, P = 0.006). The GRADE profile showed that the included RCTs had low quality of evidences. CONCLUSION: P-LDI was superior in terms of ORR, experienced less grade 3/4 thrombocytopenia and leukopenia compared with 30 min-SDI, and could be a viable treatment option for advanced NSCLC. However, the results need to be further verified by high quality trials and large samples owing to the low quality of evidences.