Epidural electrical stimulation effectively restores locomotion function in rats with complete spinal cord injury.

Epidural electrical stimulation can restore limb motor function after spinal cord injury by reactivating the surviving neural circuits. In previous epidural electrical stimulation studies, single electrode sites and continuous tetanic stimulation have often been used. With this stimulation, the body is prone to declines in tolerance and locomotion coordination. In the present study, rat models of complete spinal cord injury were established by vertically cutting the spinal cord at the T8 level to eliminate disturbance from residual nerve fibers, and were then subjected to epidural electrical stimulation. The flexible extradural electrode had good anatomical topology and matched the shape of the spinal canal of the implanted segment. Simultaneously, the electrode stimulation site was able to be accurately applied to the L2-3 and S1 segments of the spinal cord. To evaluate the biocompatibility of the implanted epidural electrical stimulation electrodes, GFAP/Iba-1 double-labeled immunofluorescence staining was performed on the spinal cord below the electrodes at 7 days after the electrode implantation. Immunofluorescence results revealed no significant differences in the numbers or morphologies of microglia and astrocytes in the spinal cord after electrode implantation, and there was no activated Iba-1+ cell aggregation, indicating that the implant did not cause an inflammatory response in the spinal cord. Rat gait analysis showed that, at 3 days after surgery, gait became coordinated in rats with spinal cord injury under burst stimulation. The regained locomotion could clearly distinguish the support phase and the swing phase and dynamically adjust with the frequency of stimulus distribution. To evaluate the matching degree between the flexible epidural electrode (including three stimulation contacts), vertebral morphology, and the level of the epidural site of the stimulation electrode, micro-CT was used to scan the thoracolumbar vertebrae of rats before and after electrode implantation. Based on the experimental results of gait recovery using three-site stimulation electrodes at L2-3 and S1 combined with burst stimulation in a rat model of spinal cord injury, epidural electrical stimulation is a promising protocol that needs to be further explored. This study was approved by the Animal Ethics Committee of Chinese PLA General Hospital (approval No. 2019-X15-39) on April 19, 2019.

Neuroprotective effect of lignans extracted from Eucommia ulmoides Oliv. on glaucoma-related neurodegeneration.

Glaucoma is a progressive neurodegenerative disease, characterized by retinal ganglion cells (RGCs) and axon degeneration. The development of neuroprotective drug is required for improving the efficiency of glaucoma treatment. Eucommia ulmoides Oliv. has been used as a source of traditional medicine and as a beneficial health food. Lignans is one of the main bioactive components of Eucommia ulmoides. Here, we show that lignans protects RGCs against oxidative stress-induced injury in vitro. Moreover, lignans exerts neuroprotective effect on glaucoma-associated optic neuropathy in glaucomatous rats. Lignans treatment could improve oxidative stress response in RGCs and retinas of glaucomatous rats. Lignans plays an anti-oxidative stress role via the activation of AMPK signaling. This study provides evidence that lignans possesses protective effect on glaucoma-associated optic neuropathy. Lignans might be an alternative for the prevention and treatment of glaucomatous neurodegeneration.

Long noncoding RNA-MEG3 is involved in diabetes mellitus-related microvascular dysfunction.

Microvascular dysfunction is an important characteristic of diabetic retinopathy. Long non-coding RNAs (lncRNAs) play important roles in diverse biological processes. In this study, we investigated the role of lncRNA-MEG3 in diabetes-related microvascular dysfunction. We show that MEG3 expression level is significantly down-regulated in the retinas of STZ-induced diabetic mice, and endothelial cells upon high glucose and oxidative stress. MEG3 knockdown aggravates retinal vessel dysfunction in vivo, as shown by serious capillary degeneration, and increased microvascular leakage and inflammation. MEG3 knockdown also regulates retinal endothelial cell proliferation, migration, and tube formation in vitro. The role of MEG3 in endothelial cell function is mainly mediated by the activation of PI3k/Akt signaling. MEG3 up-regulation may serve as a therapeutic strategy for treating diabetes-related microvascular complications.

Diagnostic value of osteopontin in ovarian cancer: a meta-analysis and systematic review.

AIMS: Osteopontin (OPN) plays an important role in many physiological and pathological processes (wound healing, inflammation, immune response, and tumorigenesis). This meta-analysis assessed the diagnostic value of osteopontin in ovarian cancer. METHODS AND RESULTS: Searches in Embase and PubMed were conducted, in order to identify eligible studies on osteopontin expression and its diagnostic value in ovarian cancer. The revised Quality Assessment for Studies of Diagnostic Accuracy (QUADAS-2) tool was applied to examine the quality of these studies and the overall osteopontin diagnostic accuracy in ovarian cancer was pooled using the bivariate model. The publication bias was assessed using funnel plots and Deek's test. This search methodology resulted in 13 studies with a total of 839 ovarian cancer patients and 1439 controls in this meta-analysis. The overall osteopontin diagnostic sensitivity and specificity of ovarian cancer were 0.66 (95% CI, 0.51-0.78) and 0.88 (95% CI, 0.78-0.93), respectively. The area under summary receiver operating characteristic (sROC) curves (AUC) was 0.85 (95%CI, 0.81-0.88). There was no significant publication bias observed across the eligible studies. However, a major design deficiency of the eligible studies is the issue of subject selection bias. CONCLUSIONS: Osteopontin could be a useful biomarker in diagnosis of ovarian cancer. Due to the design deficits of the eligible studies, a future study with a larger sample size and better design is needed to rigorously confirm the diagnostic potential of osteopontin in ovarian cancer.

Prognostic value of neutrophil to lymphocyte ratio for gastric cancer.

BACKGROUND: Although the prognostic value of the neutrophil to lymphocyte ratio (NLR) in gastric cancer (GC) patients has been investigated by many studies, the results are heterogeneous. The objective of this systematic review is to ascertain the prognostic value of NLR in GC patients. METHODS: PubMed and Embase were retrieved to identify potential studies published before 8 June, 2014. Newcastle-Ottawa Scale (NOS) for cohort study was used to assess the quality of all eligible studies. RESULTS: Of the 20 studies included in this systematic review, 17 studies investigated the effect of NLR on overall survival (OS), 11 studies reported that NLR negatively affected OS in their multivariante analysis, and 16 studies reported that NLR negatively affected OS in univariate analysis. Three studies investigated the effect of NLR on progression-free survival (PFS), reporting that increased NLR was associated with worse PFS. Four studies investigated the effect of NLR on disease-free survival (DFS), two of which reported that increased NLR was associated with worse DFS. Two studies investigated the effect of NLR on disease special survival (DSS), but neither observed any significant association between NLR and DSS. The major design deficiencies of the studies available were retrospective data collection, inadequacy of follow-up cohorts, and unavailability of the method used for outcome assessment. CONCLUSIONS: Based on the above findings, we conclude that NLR may be a useful prognostic index (PI) for GC. In addition, future studies with prospective design, long-term follow-up and fully adjusted confounding factors are needed to rigorously assess the prognostic value of NLR for GC.