Utilization of clinical and radiological parameters to predict cognitive prognosis in patients with mild-to-moderate traumatic brain injury.

Background: Cognitive impairment is a common sequela following traumatic brain injury (TBI). This study aimed to identify risk factors for cognitive impairment after 3 and 12 months of TBI and to create nomograms to predict them. Methods: A total of 305 mild-to-moderate TBI patients admitted to the First Affiliated Hospital with Nanjing Medical University from January 2018 to January 2022 were retrospectively recruited. Risk factors for cognitive impairment after 3 and 12 months of TBI were identified by univariable and multivariable logistic regression analyses. Based on these factors, we created two nomograms to predict cognitive impairment after 3 and 12 months of TBI, the discrimination and calibration of which were validated by plotting the receiver operating characteristic (ROC) curve and calibration curve, respectively. Results: Cognitive impairment was detected in 125/305 and 52/305 mild-to-moderate TBI patients after 3 and 12 months of injury, respectively. Age, the Glasgow Coma Scale (GCS) score, >12 years of education, hyperlipidemia, temporal lobe contusion, traumatic subarachnoid hemorrhage (tSAH), very early rehabilitation (VER), and intensive care unit (ICU) admission were independent risk factors for cognitive impairment after 3 months of mild-to-moderate TBI. Meanwhile, age, GCS score, diabetes mellitus, tSAH, and surgical treatment were independent risk factors for cognitive impairment after 12 months of mild-to-moderate TBI. Two nomograms were created based on the risk factors identified using logistic regression analyses. The areas under the curve (AUCs) of the two nomograms to predict cognitive impairment after 3 and 12 months of mild-to-moderate TBI were 0.852 (95% CI [0.810, 0.895]) and 0.817 (95% CI [0.762, 0.873]), respectively. Conclusion: Two nomograms are created to predict cognitive impairment after 3 and 12 months of TBI. Age, GCS score, >12 years of education, hyperlipidemia, temporal lobe contusion, tSAH, VER, and ICU admission are independent risk factors for cognitive impairment after 3 months of TBI; meanwhile, age, the GCS scores, diabetes mellitus, tSAH, and surgical treatment are independent risk factors of cognitive impairment after 12 months of TBI. Two nomograms, based on both groups of factors, respectively, show strong discriminative abilities.

Randomized controlled study on the curative effects of twist-drill craniotomy and burr-hole craniotomy in the treatment of chronic subdural hematoma.

The present randomized controlled study investigated the differences in the curative effects of twist-drill craniotomy (TDC) and burr-hole craniotomy (BHC) in the treatment of chronic subdural hematoma (CSDH). A total of 40 patients diagnosed with CSDH via head computed tomography (CT) who required surgical decompression from January 2016 to January 2017 were enrolled in the present study, and were randomly divided into a TDC group (n=20) and a BHC group (n=20). The modified Rankin scale (mRS) scores of patients were recorded prior to the operation, and at 48 h and 3 months after the operation. The differences in the mRS score (VmRS) among the groups were calculated using the Mann-Whitney U test. The 40 patients enrolled comprised 33 males and 7 females, and there were no significant differences in the general clinical characteristics between the two groups. In the BHC group, 3 patients had a pre-operative mRS score of 5 points, among which 2 cases died at 32 and 45 days after discharge. In the TDC group, 4 patients had a pre-operative mRS score of 5 points, among which 1 case died of epilepsy and pulmonary infection at 1 month after the operation. No difference in the mortality rate was present between the two groups. During the 3-month follow-up, head CT indicated that the intracranial hematoma in a total of 4 patients, including 3 cases in the TDC group and 1 case in the BHC group, completely disappeared. In the BHC group, 3 cases required a repeated incision and drainage after the first operation, while no secondary operation was required in any of the cases of the TDC group. The average length of stay at the hospital (LOS) after TDC was 9.00±2.91 days, which was significantly shorter than that after BHC (14.75±5.95 days). In the total sample of 40 patients, a longer LOS was associated with a higher risk of secondary operation due to recurrence after discharge. The variation value of the mRS score at 3 months after the operation and its ratio vs. the pre-operative score in the TDC group were significantly different from those in the BHC group, suggesting that the improvement of neurological function after TDC was significantly greater than that after BHC. Although 18 patients (90%) in the TDC group were cured, there was no significant difference from the cure rate in the BHC group [15 patients (75%)]. In conclusion, no significant differences were identified in the cure rate and the mortality rate of patients with CSDH after the two types of surgical treatment. However, the mRS score in the TDC group at 3 months after the operation exhibited a significantly greater improvement compared with that in the BHC group, and the overall LOS in the TDC group was significantly shorter than that in BHC group. Therefore, TDC is superior to BHC in the treatment of CSDH (trial registration no. ChiCTR-INR-16008368).

Mir-758-5p Suppresses Glioblastoma Proliferation, Migration and Invasion by Targeting ZBTB20.

BACKGROUND/AIMS: To determine the cellular functions and clinical significance of micro-758-5p (miR-758-5p) in glioblastoma (GBM) by targeting zinc finger and BTB domain-containing protein 20 (ZBTB20). METHODS: Fifty-five paired GBM tissues and adjacent normal tissues, GBM cell lines (U118, LN-299, H4, A172, U87-MG, and U251), and normal human astrocyte cell line (HEB) were used. miR-758-5p mimics, ZBTB20 siRNA, and pcDNA3.1-ZBTB20 were transiently transduced into cancer cells independently or together. qRT-PCR was conducted to analyze the expression of miR-758-5p and ZBTB20. Luciferase reporter assays were performed to determine the effect of miR-758-5p on ZBTB20. Western blot was applied to measure the expression of ZBTB20, PCNA, and cleaved caspase3. Cell Counting Kit-8 (CCK8), colony formation, FACS, and Transwell assays were carried out to detect cellular proliferation, apoptosis, migration, and invasion. Xenograft experiments were implemented to evaluate tumor growth and metastasis in vivo. RESULTS: miR-758-5p was significantly downregulated in GBM tissues and cell lines compared with that in adjacent normal tissues and HEB cells. miR-758-5p overexpression inhibited the proliferation, migration, and invasion of GBM cells and induced apoptosis by regulating the ZBTB20 expression. Pearson correlation analysis also confirmed that miR-758-5p was inversely correlated with ZBTB20 in GBM tissues. miR-758-5p suppressed tumor growth and metastasis in vivo. The restored ZBTB20 expression partially rescued the miR-758-5p-induced inhibition of GBM cell proliferation, migration, and invasion. Kaplan-Meier curve analysis revealed that a high miR-758-5p expression indicated an enhanced prognosis of patients with GBM. CONCLUSION: miR-758-5p suppressed GBM progression by targeting ZBTB20. The miR-758-5p/ZBTB20 axis might be a promising therapeutic target for GBM treatment.

Circular RNA Complement Factor H (CFH) Promotes Glioma Progression by Sponging miR-149 and Regulating AKT1.

BACKGROUND Circular RNAs (circRNAs) are widely expressed in mammals and can regulate the development and progression of human tumors. has_circ_0015758 (circ-CFH) is an exon circRNA transcript from the GRCh37/hg19 fragment of chromosome 1 and is homologous to the protein-coding gene complement factor H (CFH). Currently, the function of circ-CFH in glioma remains unclear. MATERIAL AND METHODS In our study, circ-CFH, miR-149, and Akt1 mRNA expression levels were analyzed by qRT-PCR assays. To investigate the function of circ-CFH in cell proliferation, circ-CFH knockdown models were established by using circ-CFH siRNAs. Cell proliferation abilities were measured by CCK-8 and colony formation assays and in vivo experiments. In addition, the interaction between circ-CFH and miR-149 was assessed by luciferase reporter assays. RESULTS Circ-CFH expression was significantly upregulated in glioma tissue and was correlated with tumor grade. Circ-CFH expression levels were also markedly higher in U251 and U373 glioma cell lines. Circ-CFH knockdown inhibited cell proliferation and colony formation abilities. Luciferase assays indicated that circ-CFH functions as a miR-149 sponge and inhibits its function in U251 and U373 cells. Subsequently, AKT1 was identified as a direct target of the circ-CFH/miR-149 axis. CONCLUSIONS Circ-CFH promotes glioma progression by sponging miR-149 and regulating the AKT1 signaling pathway. The circ-CFH/miR-149/AKT1 regulation axis may be a potential target for glioma therapy.

miR­454­3p suppresses cell migration and invasion by targeting CPEB1 in human glioblastoma.

MicroRNAs (miRNA/miRs) serve crucial roles in the progression of human glioblastoma (GBM); however, the exact regulatory mechanisms of miRNAs in human GBM remain unclear. The present study aimed to investigate the roles of miR­454­3p in human GBM. Reverse transcription­quantitative polymerase chain reaction (RT­qPCR) analysis was performed to examine the expression of miR­454­3p in glioma tissues and adjacent tissues. Human GBM cell lines (LN­229, A172 and GL15) and a normal human astrocyte cells (HA1800) were used for analysis. In addition, RT­qPCR and western blotting were applied for mRNA and protein expression analysis, respectively. The cell proliferation was measured using a Cell Counting kit­8 assay. Furthermore, scratch and Transwell assays were employed for the analysis of cell migration and invasion. A luciferase reporter assay was used to verify the target of miR­454­3p. The results revealed that miR­454­3p was downregulated in the glioma tissues and GBM cell lines, including LN­229, A172 and GL15. Additionally, the overexpression of miR­454­3p significantly suppressed the proliferation, migration and invasion of LN­229 cells. Furthermore, cytoplasmic polyadenylation element­binding protein 1 (CPEB1) was confirmed as a direct target of miR­454­3p. These findings indicated that the overexpression of miR­454­3p inhibited cell proliferation, migration and invasion by downregulating CPEB1. Therefore, miR­454­3p may act as a tumor suppressor and represent an effective therapeutic strategy in GBM.

Fms related tyrosine kinase 1 (Flt1) functions as an oncogene and regulates glioblastoma cell metastasis by regulating sonic hedgehog signaling.

Studies have shown that the abnormal expression of Fms related tyrosine kinase 1 (Flt1) is associated with multiple malignancies, yet its role in glioblastoma pathology remains to be elucidated. In this study, we investigated the role of Flt1 in regulating proliferation, migration and invasion of glioblastoma cells by establishing glioblastoma cell strains with constitutively silenced or elevated Flt1 expression. We demonstrate that ectopic expression of Flt1 promotes glioblastoma cells migration, invasion through cell scratching and Transwell assays. Further study has indicated that Flt1 knockdown prevents the spread of glioblastoma cells in vivo. Conversely, we also show that suppression of Flt1 expression inhibits migration and invasion of glioblastoma cells. Finally, our findings demonstrate that Flt1 promotes invasion and migration of glioblastoma cells through sonic hedgehog (SHH) signaling pathway. Our study suggests that galectin-1 represents a crucial regulator of glioblastoma cells metastasis. Thus, the detection and targeted treatment of Flt1-expressing cancer serves as a new therapeutic target for glioblastoma.

TGF-ß1/Smad3 Signaling Pathway Suppresses Cell Apoptosis in Cerebral Ischemic Stroke Rats.

BACKGROUND We desired to observe the changes of transforming growth factor-ß1/drosophila mothers against decapentaplegic protein (TGF-ß1/Smad3) signaling pathway in the hippocampus region of cerebral ischemic stroke rats so that the effects of this pathway on nerve cells can be investigated. MATERIAL AND METHODS The ischemic stroke models were built by middle cerebral artery occlusion (MCAO) in vivo and oxygen-glucose deprivation (OGD) in vitro. TGF-ß1 and TGF-ß1 inhibitors were injected into rat models while TGF-ß1, TGF-ß1 siRNA, Smad3, and Smad3 siRNA were transfected into cells. Infarct sizes were measured using triphenyltetrazolium chloride (TTC) staining, while the apoptosis rate of cells were calculated by Annexin V-fluorescein isothiocyanate/propidium iodide (Annexin V-FITC/PI) staining. Levels of TGF-ß1, Smad3, and Bcl-2 were examined by real-time polymerase chain reaction (RT-PCR), immunohistochemical, and Western blot analysis. RESULTS The expressions of TGF-ß1/Smad3 signal pathway were significantly increased in both model rats and BV2 cells, whereas the expression of Bcl-2 was down-regulated (P<0.05). The TGF-ß1/Smad3 signal pathway exhibited protective effects, including the down-regulation of infarction size in cerebral tissues and the down-regulation of apoptosis rate of BV2 cells by increasing the expression of Bcl-2 (P<0.05). In addition, these effects could be antagonized by the corresponding inhibitors and siRNA (P<0.05). CONCLUSIONS The TGF-ß1/Smad3 signaling pathway was up-regulated once cerebral ischemic stroke was simulated. TGF-ß1 may activate the expression of Bcl-2 via Smad3 to suppress the apoptosis of neurons.

Overexpression of Protease Serine 8 Inhibits Glioma Cell Proliferation, Migration, and Invasion via Suppressing the Akt/mTOR Signaling Pathway.

Protease serine 8 (PRSS8), a serine peptidase, has a widespread expression in normal epidermal cells. Recently, many researchers demonstrated downregulation of PRSS8 in cancer tissues as well as its tumor suppressor role in cancer development. However, the biological functions of PRSS8 in glioma remain unclear. In the current study, we demonstrated a decreased expression of PRSS8 in glioma tissues and cell lines. PRSS8 upregulation inhibited glioma cell proliferation, migration, and invasion. In addition, xenograft experiments showed that PRSS8 overexpression suppressed glioma cell growth in vivo. We also found that upregulated PRSS8 reduced the protein expression levels of p-Akt and p-mTOR in glioma cells. Taken together, our study demonstrated that overexpression of PRSS8 inhibited glioma cell proliferation, migration, and invasion via suppressing the Akt/mTOR signaling pathway. Therefore, PRSS8 may act as a novel therapeutic target for glioma.

Tumor microRNA-335 expression is associated with poor prognosis in human glioma.

MicroRNA-335 (miR-335), as a transcript of genomic region chromosome 7q32.2, acts as a tumor suppressor or tumor promoter in various human malignancies. Especially, it has been reportedly shown to be an oncogene in human glioma cell line in vitro, but its expression in human glioma tissues is not yet determined. The aim of this study was to investigate the clinical significance of miR-335 expression in glioma. MiR-335 expression in human gliomas and nonneoplastic brain tissues was measured by real-time quantitative RT-PCR assay. The association of miR-335 expression with clinicopathological factors and prognosis of glioma patients was statistically analyzed. The expression level of miR-335 in glioma tissues was significantly higher than that in corresponding nonneoplastic brain tissues (P < 0.001). In addition, high miR-335 expression was significantly associated with a higher WHO grade (P = 0.001). Survival analysis demonstrated that patients with high miR-335 expression tumors had significantly shorter survival times than those with low miR-335 expression tumors (P = 0.01) and that miR-335 was an independent prognostic factor (P = 0.02). Especially, subgroup analyses according to tumor histologic grade revealed that the mean survival time of patients with high grade (III-IV) was significantly worse for high miR-335 expression group than for low miR-335 expression group (P = 0.002), but no significant difference was found for patients with WHO grade I-II (P = 0.16). These results indicated that miR-335 expression was increased in human gliomas and was associated with advanced tumor progression. Furthermore, miR-335 expression was demonstrated for the first time to be an independent marker for predicting the clinical outcome of patients with gliomas.