The diagnostic and prognostic value of glial fibrillary acidic protein in traumatic brain injury: a systematic review and meta-analysis.

OBJECTIVES: Over the years, blood biomarkers have been extensively applied for diagnostic and prognostic assessment of traumatic brain injury (TBI). Herein, we conducted a meta-analysis to evaluate the diagnostic and prognostic value of glial fibrillary acidic protein (GFAP) for TBI patients. METHODS: The online databases, including PubMed, Embase, Cochrane Library, CNKI, and WFSD, were systematically retrieved from inception until May 2021. The RevMan 5.3 software and Stata 15 were used to conduct data analysis. RESULTS: A total of 22 eligible studies comprising 3709 patients were included in this meta-analysis. The pooled results indicated that serum GFAP had a diagnostic value in detecting traumatic intracranial lesions (AUC 0.81; 95% CI 0.77-0.84; p < 0.00001). The pooled sensitivity and specificity were 0.93 (95% CI 0.81-0.98), and 0.66 (95% 0.53-0.77; p < 0.00001), respectively. For assessment of unfavorable outcome, the pooled sensitivity, specificity and AUC value were 0.66 (95% CI 0.54-0.76; p < 0.00001), 0.82(95% CI 0.72-0.90; p < 0.00001), and 0.82 (95% CI 0.76-0.88; p < 0.00001), respectively. Besides, GFAP exhibited a significant value in predicting mortality (AUC 0.81; 95% CI 0.77-0.84; p < 0.00001), with high sensitivity and specificity (0.86, 95% CI 0.79-0.92, p < 0.00001, and 0.66, 95% CI 0.52-0.77, p < 0.00001). The subgroup analysis indicated that the type of TBI and cut-off value were potential sources of heterogeneity, which influenced the pooled AUC values for mortality prediction. CONCLUSIONS: Our meta-analysis indicated that GFAP had diagnostic and prognostic value for TBI patients, especially during the early TBI.

Aberrant brain functional hubs convergence in the acute severe traumatic brain injury patients with rapidly recovering.

PURPOSE: We aimed to identify the aberrant functional hubs in patients with acute severe traumatic brain injury (sTBI) and investigate whether they could help inform prognosis. METHODS: Twenty-eight sTBI patients and health controls underwent imaging scanning. The graph-theoretical measure of degree centrality (DC) was applied to identify the abnormal brain functional hubs and conjoined with regions of interest-based analysis to investigate their interaction and impact on whole-brain. We further split sTBI patients into two subgroups according to their recovery to explore whether the fractional amplitude of low-frequency fluctuation (fALFF) roles in functional connectivity (FC) differential areas to help inform the patients' long-term prognosis. RESULTS: We identified the part of prefrontal cortex (PFC), precentral and postcentral gyrus (Pre-/Post-CG), cingulate gyrus (CgG), posterior medial cortex (PMC), and brainstem that could be core hubs whose DC was significantly increased in patients with acute sTBI. The interaction strength of the paired hubs could be enhanced (CG-PFC, CgG-PFC, CG-brainstem, CgG-brainstem, PMC-brainstem, and PFC-brainstem) and weakened (CG-CgG, CG-PMC, CgG-PMC, and PMC-PFC), compared with healthy controls. We also found abnormal FC in 5 hubs to whole-brain. The spontaneous brain activities in the FC differential regions [e.g., the fALFF and mean fALFF value] were valid to predict outcome at 6-month in patients with sTBI. CONCLUSION: We demonstrated a compensatory mechanism that part of brain regions will converge into abnormal functional hubs in patients with acute sTBI, which provides a potential approach to objectively predicting patients' long-term outcome.

Investigating the mechanism and prognosis of patients with disorders of consciousness on the basis of brain networks between the thalamus and whole-brain.

Purpose: This study aimed to investigate the changes in the functional connectivity between the bilateral thalamus and the whole-brain in patients with severe traumatic brain injury (sTBI) patients suffering from disorders of consciousness (DOC) and to explore their potential prognostic representation capacity. Methods: The sTBI patients suffering from DOC and healthy controls underwent functional magnetic resonance imaging. We defined patients with the Extended Glasgow Outcome Score (GOS-E) ≥ 3 as the wake group and GOS-E = 2 as the coma group. The differences in functional connectivity between sTBI and healthy controls and between wake and coma groups were compared. Based on the brain regions with altered functional connectivity between wake and coma groups, they were divided into 26 regions of interest. Based on the Z-values of regions of interest, the receiver operating characteristic analysis was conducted to classify the prognosis of patients. Results: A total of 28 patients and 15 healthy controls were finally included. Patients who had DOC indicated a significant disruption of functional connectivity between the bilateral thalamus and the whole-brain (FDR corrected, P < 0.0007). The functional connectivity strength (bilateral thalamus to whole-brain) was significantly different between coma patients who went on to wake and those who were eventually non-awake at 6 months after sTBI (Alphasim corrected, P < 0.05). Furthermore, the 26 regions of interest had a similar or even better prognostic distinction ability than the admission Glasgow coma score. Conclusion: The thalamus-based system of consciousness of sTBI patients suffering from DOC is disrupted. There are differences in the thalamus-to-whole-brain network between wake and coma groups and these differences have potential prognostic characterization capability.

Abnormal default mode network could be a potential prognostic marker in patients with disorders of consciousness.

OBJECTIVES: The study aimed to investigate disorders of consciousness (DOC) mechanisms of patients with severe traumatic brain injury (sTBI) related to default mode network (DMN) and to introduce a machine learning model that predicts the prognosis of these patients for 6 months. METHODS: The sTBI patients suffering from DOC and healthy controls underwent functional magnetic resonance imaging. We defined patients with Extended Glasgow Outcome Score ≥ 5 as good outcome group, otherwise they were poor outcome group. The differences of DMN between sTBI and healthy controls and between good and poor outcome groups were compared. Based on the brain regions with altered functional connectivity between good and poor outcome groups, they were divided into 8 regions of interests according to side. The Z values of the regions of interests were extracted by Rest 1.8. Based on Z values, the Subspace K-Nearest Neighbor (Subspace KNN) was conducted to classify prognosis of sTBI patients suffering from DOC. RESULTS: A total of 84 DMNs derived from patients and 45 DMNs from healthy controls were finally analyzed. The connectivity of the DMN was significantly decreased in sTBI patients suffering from DOC (Alphasim corrected, P < 0.05). In addition, compared with the poor outcome group (DMN samples = 60), the brain regions of DMN with decreased functional connectivity in the good outcome group (DMN samples = 24) the following bilateral areas: brodman Area 11, anterior cingulate and paracingulate gyri, brodman Area 25, olfactory cortex (Alphasim corrected, P < 0.05). The ability of Subspace KNN machine learning to distinguish the prognosis of patients (area under curve) was 0.97. CONCLUSIONS: The interruption of DMN may be one of the reasons for DOC in patients with sTBI. Furthermore, based on early DMN (1-4 weeks), Subspace KNN machine learning has the potential value to distinguish the prognosis (6 months after brain trauma) of sTBI patients suffering from DOC.

Circular RNA circRNA_0067934 promotes glioma development by modulating the microRNA miR-7/ Wnt/ß-catenin axis.

Glioma, one of the most prevalent malignant tumors, is well-known for its poor prognosis and low survival rate among patients. As a type of non-coding RNA, circular RNAs (circRNAs) play a significant role in tumor progression. However, the function and role of circRNAs in glioma development remain unclarified. In our experiments, the relative expression level of circRNA_0067934 and miR-7 in glioma tissue was detected by qRT-PCR, and specific gene knockdown was mediated by siRNA and miRNA-inhibitor. Dual-luciferase reporter assay was carried out to determine whether miR-7 successfully targeted circRNA_0067934. Also, CCK-8 and Transwell were performed to evaluate the malignant behaviors of glioma tissues. Western blotting and immunofluorescence were used to evaluate relative protein expression levels. The results of qRT-PCR indicated that circRNA_0067934 was over-expressed in glioma tissues, and down regulation of circRNA_0067934 reduced the tumor progression by inhibiting cell proliferation, invasion, and migration. The relative expression level of miR-7 was significantly reduced in glioma tissues, which showed a negative association with the expression of circRNA_0067934. CircRNA_0067934 could tagete the miR-7 to regulate progression of glioma cell. In addition, the Wnt/ß-catenin signaling pathway might involve in down stream regulation of circRNA_0067934 and miR-7. In conclusion, our results revealed that circRNA_0067934 regulates glioma cells progression by targeting miR-7/ Wnt/ß-catenin axis.

Design of bovine lactoferricin-derived peptide and its expression and activity in Pichia pastoris.

Bovine lactoferrin peptide has been shown to be a broad-spectrum antimicrobial peptide. Based on the relationship between the structure and function of antimicrobial peptides, the antimicrobial peptide databases and protein analysis software were used to optimize the design of bovine lactoferricin peptide (LfcinB). The designed bovine lactoferricin-derived peptide (LfcinBD) gene fragment was inserted into a pPIC9K-His plasmid to construct a recombinant expression vector. After linearization of the Recombinant plasmid, Pichia pastoris GS115 cells were transfected with linearized recombinant plasmid by using electroporation and LfcinBD gene expression was induced with methanol. After the fermentation, supernatant was separated by low-temperature high-speed centrifugation. Ultrafiltration and freeze drying of the fermentation supernatant were performed, purified. Experimental results showed that the LfcinBD had stronger bacteriostatic activity against Staphylococcus aureus than the natural bovine lactoferrin peptide (LfcinB) produced under the same fermentation conditions. The effective expression of the optimized bovine lactoferricin-derived peptide was detected using SDS-PAGE electrophoresis. This study lays the foundation for further exploration to improve the biological activities of antimicrobial peptides.