Netrin-1: A Serum Marker Predicting Cognitive Impairment after Spinal Cord Injury.

Objective: Although cognitive impairment has received more attention in recent years as a result of spinal cord injury (SCI), the pathogenic process that causes it is still unknown. The neuroprotective effects of Netrin as a family of laminin-related secreted proteins were discovered. The purpose of this study was to determine the changes of serum Netrin-1 after SCI and its relationship with cognitive impairment. Methods: 96 SCI patients and 60 controls were included in our study. We collected baseline data from all participants, measured their serum Netrin-1 levels, and followed up their cognitive levels 3 months later. Results: The clinical baseline values between the control and SCI groups were not significantly different (p > 0.05). However, the serum Netrin-1 level in the SCI group was significantly lower than that in the control group (528.4 ± 88.3 pg/ml vs. 673.5 ± 97.2 pg/ml, p < 0.05). According to the quartile level of serum Netrin-1 level in the SCI group, we found that with the increase of serum Netrin-1 level, the MoCA score also increased significantly (p < 0.001), indicating that the serum Netrin-1 level was positively correlated with the MoCA score after SCI. After controlling for baseline data, multiple regression analysis revealed that Netrin-1 remained an independent risk factor for cognitive impairment after SCI (=0.274, p = 0.036). Conclusions: Netrin-1 may be a neuroprotective factor for cognitive impairment, which may serve as a serum marker to predict cognitive impairment after SCI.

Elevated Serum Neuropeptide FF Levels Are Associated with Cognitive Decline in Patients with Spinal Cord Injury.

BACKGROUND: Spinal cord injury (SCI) has high incidence globally and is frequently accompanied by subsequent cognitive decline. Accurate early risk-categorization of SCI patients for cognitive decline using biomarkers can enable the timely application of appropriate neuroprotective measures and the development of new agents for the management of SCI-associated cognitive decline. Neuropeptide FF is an endogenous neuropeptide with a multitude of functions and is associated with neuroinflammatory processes. This prospective study investigated the predictive value of serum neuropeptide FF levels measured after acute SCI for subsequent cognitive decline. METHODS: 88 patients presenting with acute SCI without preexisting neurological injury, brain trauma, or severe systemic illness and 60 healthy controls were recruited. Serum neuropeptide FF levels, clinical, and routine laboratory variables including low-density lipoprotein, high-density lipoprotein, fasting blood glucose, total triiodothyronine (TT3), total thyroxine (TT4), and thyroid-stimulating hormone (TSH) levels collected from all subjects were assessed. Montreal cognitive assessment (MoCA) was performed 3 months after enrollment. SCI patients were grouped according to quartile of serum neuropeptide FF level and MoCA scores were compared using ANOVA. Additionally, multivariate linear regression with clinical and laboratory variables was performed to predict MoCA scores. RESULTS: SCI patients displayed significantly higher baseline serum neuropeptide FF levels than healthy controls (38.5 ± 4.1 versus 23.4 ± 2.0 pg/ml, p < 0.001∗∗). SCI patients in higher quartiles of baseline serum neuropeptide FF displayed significantly lower MoCA scores at 3 months. Linear regression analysis indicated serum neuropeptide FF levels as a significant independent predictor of worse MoCA scores after SCI (r = 0.331, p = 0.034∗). CONCLUSION: Early serum neuropeptide FF levels significantly and independently predicted cognitive decline after acute SCI among patients without preexisting neurological disorders.

Clinical Efficacy and Safety of "Three-Dimensional Balanced Manipulation" in the Treatment of Cervical Spondylotic Radiculopathy by Finite Element Analysis.

Cervical spondylotic radiculopathy (CSR) is the most commonly encountered cervical spine disorder. Cervical manipulation has been demonstrated as an effective therapy for patients. However, the mechanisms of manipulations have not been elucidated. A total of 120 cervical spondylotic radiculopathy patients were divided into the "three-dimensional balanced manipulation" treatment group (TBM group) and control group randomly. The control group was treated with traditional massage; the TBM treatment group was treated with "three-dimensional balanced manipulation" based on traditional massage. The symptoms and clinical efficacy of the patients were compared before and after treatment for one month. A three-dimensional finite element model was established. The mechanical parameters were imported to simulate TBM, and finite element analysis was performed. The results showed that the total effective rate was significantly higher in the TBM group compared with the control group. The biomechanical analysis showed the vertebral body stress was mainly distributed in the C3/4 spinous processes; the deformation mainly concentrated in the anterior processes of the C3 vertebral body. The intervertebral disc stress in the C3~C7 segment was mainly distributed in the anterior part of the C3/4 intervertebral disc, and the deformation extends to the posterior part of the C3/4 nucleus pulposus. In summary, these data are suggesting that TBM was effective in CSR treatment. The results of the finite element model and biomechanical analysis provide an important foundation for effectively avoiding iatrogenic injuries and improving the effect of TBM in the treatment of CSR patients.

The significance of ENAH in carcinogenesis and prognosis in gastric cancer.

The ENAH gene, which encodes a member of the enabled/vasodilator-stimulated phosphoprotein (Ena/VASP) family of proteins, is involved in the assembly of actin filaments required for cell adhesion and motility. Recent studies show overexpressed ENAH in several cancer types, and ENAH correlates with tumor invasiveness. This study aimed to investigate the expression and function of ENAH in primary gastric adenocarcinoma, and its prognostic significance. We found significantly increased mRNA (P = 0.0283) and protein (P = 0.0301) expression of ENAH in gastric cancer tissues. ENAH expression markedly associated with tumor size (P < 0.001), T stage (P < 0.001), N stage (P = 0.001), TNM stage (P < 0.001) and prognosis (P < 0.001). Cox regression analyses revealed ENAH expression as an independent predictor of overall survival (P = 0.019). We also analyzed data of 155 gastric cancer cases from The Cancer Genome Atlas (TCGA) and found that ENAH expression significantly correlated with age (P = 0.003), T stage (P = 0.023) and prognosis (P = 0.05). Furthermore, the function of ENAH in cell proliferation, colony formation, cell migration and invasion of gastric cancer cells was analyzed in vitro. Knockdown of ENAH expression suppressed cell proliferation, colony formation, cell migration and invasion in MKN45 cells. Conversely, overexpression of ENAH promoted cell proliferation, cell migration and invasion in MGC803 cells. Our research suggests that ENAH might play promoting functions in carcinogenesis and progression of gastric cancer, and may serve as a valuable prognostic marker for primary gastric adenocarcinoma patients.