Intravenous administration of human chorionic membrane mesenchymal stem cells promotes functional recovery in a rat traumatic brain injury model.

Human chorionic membrane mesenchymal stem cells (hCM-MSCs) have increasingly emerged as an excellent source of transplanted cells for regenerative therapy as they can be isolated via a non-invasive and simple method with high proliferative capabilities. However, the roles and mechanisms of hCM-MSCs on traumatic brain injury (TBI) animal models have not been investigated yet. The aim of this study was to investigate the therapeutic potential and mechanism of hCM-MSCs transplantation in a rat model of TBI. Adult male Sprague-Dawley rats were subjected to moderate lateral fluid percussion-induced TBI. At 2 h after TBI, hCM-MSCs, or PBS were administered intravenously via the tail vein. Neurological function, brain water content, Evans blue dye extravasation, immunofluorescence staining, and enzyme-linked immunosorbent were evaluated. The results showed that transplanted hCM-MSCs were observed in the injured brain. Compared with the PBS group, hCM-MSCs treatment significantly decreased the numbers of M1 macrophages/microglia, MPO + neutrophils and caspase-3 + cells ( P  < 0.01). Meanwhile, hCM-MSCs treatment significantly reduced the expression levels of the pro-inflammatory cytokines (TNF-α, interleukin-(IL)6 and IL-1ß) while increasing the numbers of M2 macrophages/microglia and the expression of the anti-inflammatory cytokines IL-10 ( P  < 0.01). In addition, hCM-MSCs treatment significantly reduced brain water content and Evans blue extravasation. Lastly, hCM-MSCs treatment significantly promoted neurogenesis and angiogenesis, and attenuated neurological deficits. Collectively, these findings indicate that hCM-MSCs exhibited effective therapeutic efficacy in a rat TBI model, and its mechanism may be by reducing inflammation, apoptosis and the blood-brain barrier disruption, promoting angiogenesis and neurogenesis.

Experimental and numerical investigation on failure mechanism of expansive soil subgrade slope.

Shallow landslides of expensive soil slopes occur from time to time, and most engineering geological problems are directly or indirectly caused by soil structure cracks. The existence of tensile cracks can significantly affect the hydro-mechanical properties of soils. In this paper, the mechanism of expansive soil landslide formation is explored, and swelling pressures, and drying and wetting cycles are introduced into the discrete element method (DEM), and the landslide process of expansive soils is studied by the numerical simulation mothed. The relationship between the crack development and the instability of expansive soil slopes was investigated. The results show that under the condition of seasonal dry and wet alternation, the cracks of the expansive soil slope gradually develop, the rainwater infiltrates rapidly, the mechanical properties gradually deteriorate, and under the effect of such adverse cycle, the soil gradually softens and the stability decreases. Under the influence of human activities, vehicle loads and other factors, the slope body slides. These findings are helpful for the design and construction of expansive soil slopes and foundations.

Clinical relevance and outcome of familial papillary thyroid cancer: a single institution study of 626 familial cases.

Background: Whether familial thyroid cancer is more aggressive than sporadic thyroid cancer remains controversial. Additionally, whether the number of affected family members affects the prognosis is unknown. This study focused mainly on the comparison of the clinicopathological characteristics and prognoses between papillary thyroid cancer (PTC) patients with and without family history. Methods: A total of 626 familial papillary thyroid cancer (FPTC) and 1252 sporadic papillary thyroid cancer (SPTC) patients were included in our study. The clinical information associated with FPTC and SPTC was recorded and analyzed by univariate analysis. Results: Patients in the FPTC group had a higher rate of multifocality (p=0.001), bilaterality (p=0.000), extrathyroidal invasion (p=0.000), distant metastasis (p=0.012), lymph node metastasis (p=0.000), recurrence (p=0.000), a larger tumor size (p=0.000) and more malignant lymph nodes involved (central: p=0.000; lateral: p=0.000). In addition, our subgroup analysis showed no significant difference (p>0.05) between patients with only one affected family member and those with two of more group in all clinicopathological characteristics. In papillary thyroid microcarcinoma (PTMC) subgroup analysis, we found that FPTMC patients harbored significantly larger tumors (p=0.000), higher rates of multifocality (p=0.014), bilaterality (p=0.000), distant metastasis (p=0.038), lymph node metastasis (p=0.003), greater numbers of malignant lymph nodes (central: p=0.002; lateral: p=0.044), higher rates of I-131 treatment (p=0.000) and recurrence (p=0.000) than SPTMC patients. Conclusion: Our results indicated that PTC and PTMC patients with a positive family history had more aggressive clinicopathological behaviors, suggesting that more vigilant screening and management for FPTC may be helpful.

EFF_D_SVM: a robust multi-type brain tumor classification system.

Brain tumors are one of the most threatening diseases to human health. Accurate identification of the type of brain tumor is essential for patients and doctors. An automated brain tumor diagnosis system based on Magnetic Resonance Imaging (MRI) can help doctors to identify the type of tumor and reduce their workload, so it is vital to improve the performance of such systems. Due to the challenge of collecting sufficient data on brain tumors, utilizing pre-trained Convolutional Neural Network (CNN) models for brain tumors classification is a feasible approach. The study proposes a novel brain tumor classification system, called EFF_D_SVM, which is developed on the basic of pre-trained EfficientNetB0 model. Firstly, a new feature extraction module EFF_D was proposed, in which the classification layer of EfficientNetB0 was replaced with two dropout layers and two dense layers. Secondly, the EFF_D model was fine-tuned using Softmax, and then features of brain tumor images were extracted using the fine-tuned EFF_D. Finally, the features were classified using Support Vector Machine (SVM). In order to verify the effectiveness of the proposed brain tumor classification system, a series of comparative experiments were carried out. Moreover, to understand the extracted features of the brain tumor images, Grad-CAM technology was used to visualize the proposed model. Furthermore, cross-validation was conducted to verify the robustness of the proposed model. The evaluation metrics including accuracy, F1-score, recall, and precision were used to evaluate proposed system performance. The experimental results indicate that the proposed model is superior to other state-of-the-art models.

Comprehensive analysis of the prognostic and immunological signature of eight Tripartitemotif (TRIM) family molecules in human gliomas.

BACKGROUND: TRIM family molecules have been identified as being involved in the tumor progression of various cancer types. Increasingly, experimental evidence indicates that some of TRIM family molecules are implicated in glioma tumorigenesis. However, the diverse genomic changes, prognostic values and immunological landscapes of TRIM family of molecules have yet to be fully determined in glioma. METHODS: In our study, employing the comprehensive bioinformatics tools, we evaluated the unique functions of 8 TRIM members including TRIM5/17/21/22/24/28/34/47 in gliomas. RESULTS: The expression levels of 7 TRIM members (TRIM5/21/22/24/28/34/47) were higher in glioma as well as its diverse cancer subtypes than in normal tissues, whereas the expression level of TRIM17 was the opposite, lower in the former than in the latter. In addition, survival analysis revealed that the high expression profiles of TRIM5/21/22/24/28/34/47 were associated with poor overall survival (OS), disease-specific survival (DSS) and progress-free interval (PFI) in glioma patients, whereas TRIM17 displayed adverse outcomes. Moreover, the 8 TRIM molecules expression as well as methylation profiles remarkably correlated with different WHO grades. And genetic alterations, including mutations and copy number alterations (CNAs), in the TRIM family were correlated with longer OS, DSS and progress-free survival (PFS) in glioma patients. Furthermore, through Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis results of these 8 molecules and their related genes, we found that these molecules may change the immune infiltration of the tumor microenvironment and regulate the expression of immune checkpoint molecules (ICMs), affecting the occurrence and development of gliomas. The correlation analyses between the 8 TRIM molecules and TMB (tumor mutational burden)/MSI (microsatellite instability)/ICMs discovered that as the expression level of TRIM5/21/22/24/28/34/47 increased, the TMB score also increased significantly, while TRIM17 showed an opposite outcome. Further, a 6-gene signature (TRIM 5/17/21/28/34/47) for predicting overall survival (OS) in gliomas was built by using the least absolute shrinkage and selection operator (LASSO) regression, and the survival and time-dependent ROC analyses all were found to perform well in testing and validation cohorts. Results of multivariate COX regression analysis showed that TRIM5/28 are both expected to become independent risk predictors to guide clinical treatment. CONCLUSION: In general, the results indicate that TRIM5/17/21/22/24/28/34/47 might exert a crucial influence on gliomas tumorigenesis and might be putative prognostic markers and therapeutic targets for glioma patients.

Elevated LILRB1 expression predicts poor prognosis and is associated with tumor immune infiltration in patients with glioma.

BACKGROUND: Leukocyte immunoglobulin-like receptor subfamily B1 (LILRB1) is regarded as an inhibitory molecule. However, the importance of LILRB1 expression in glioma has not yet been determined. This investigation examined the immunological signature, clinicopathological importance and prognostic value of LILRB1 expression in glioma. METHODS: We used data from the UCSC XENA database, the Cancer Genome Atlas (TCGA) database, the Chinese Glioma Genome Atlas (CGGA) database, the STRING database, the MEXPRESS database and our clinical glioma samples to perform bioinformatic analysis and used vitro experiments to examine the predictive value and potential biological roles of LILRB1 in glioma. RESULTS: Higher LILRB1 expression was considerably present in the higher WHO grade glioma group and was linked to a poorer prognosis in patients with glioma. Gene set enrichment analysis (GSEA) revealed that LILRB1 was positively correlated with the JAK/STAT signaling pathway. LILRB1 combined with tumor mutational burden (TMB) and microsatellite instability (MSI) may be a promising indicator for the effectiveness of immunotherapy in patients with glioma. Increased LILRB1 expression was positively linked with the hypomethylation, M2 macrophage infiltration, immune checkpoints (ICPs) and M2 macrophage makers. Univariate and multivariate Cox regression analyses determined that increased LILRB1 expression was a standalone causal factor for glioma. Vitro experiments determined that LILRB1 positively enhanced the proliferation, migration and invasion in glioma cells. MRI images demonstrated that higher LILRB1 expression was related with larger tumor volume in patients with glioma. CONCLUSION: Dysregulation of LILRB1 in glioma is correlated with immune infiltration and is a standalone causal factor for glioma.

Influence of the area of the aqueduct and region of interest on quantification of stroke volume in healthy volunteers using phase-contrast cine magnetic resonance imaging.

BACKGROUND: Phase-contrast cine magnetic resonance imaging (PC-MRI) has been used to measure cerebrospinal fluid (CSF) flow dynamics, but the influence of the area of the aqueduct and region of interest (ROI) on quantification of stroke volume (SV) has not been assessed. PURPOSE: To assess the influence of the area of the ROI in quantifying the aqueductal SV measured with PC-MRI within the cerebral aqueduct. MATERIAL AND METHODS: Nine healthy volunteers (mean age = 29.6 years) were enrolled in the study, and brain MRI examinations were performed on a 3.0-T system. Quantitative analysis of the aqueductal CSF flow was performed using manual ROI placement. ROIs were separately drawn for each of the 12 phases of the cardiac cycle, and changes in aqueduct size during the cardiac cycle were determined. The SV was calculated using 12 different aqueductal ROIs and compared with the SV calculated using a fixed ROI size. RESULTS: There was variation in the size of the aqueduct during the cardiac cycle. In addition, the measured SV increased with a greater area of the ROI. A significant difference in the calculated SVs with the 12 variable ROIs was observed compared with that using a fixed ROI throughout the cardiac cycle. CONCLUSION: To establish reliable reference values for the SV in future studies, a variable ROI should be considered.

Ventriculoperitoneal shunt malfunction diagnosis based on substance dilution.

OBJECTIVE: Current methods for the diagnosis of ventriculoperitoneal (VP) shunt malfunction lack specific standards; therefore, it may be missed or misdiagnosed. Hence, providing a reliable diagnostic method will help improve the accuracy of preoperative decision-making. Therefore, the aim of the study was to provide a new method for the diagnosis of VP shunt malfunction. METHODS: After in vitro testing, we enrolled a total of 12 patients with VP shunt malfunction. Before revision surgery, 0.1 mL of a 5% sodium valproate (SV) solution was injected into the reservoir; 0.1 mL of the cerebrospinal fluid (CSF) was withdrawn 20 minutes later from the reservoir to measure the SV concentration. The process was repeated on the seventh day after surgery and compared with the preoperative results. RESULTS: The mean ±â€Šstandard deviation preoperative SV concentration in the cerebrospinal fluid was greater than the postoperative concentration (5967.8 ±â€Š1281.3 vs 391.1 ±â€Š184.6 µg/mL, P = .001). CONCLUSION: The proposed method is a reliable, safe, and relatively simple alternative for the diagnosis of VP shunt malfunction and further provides a reference for treatment.

LINC00662 sponges miR-107 accelerating the invasiveness and proliferation of glioma cells.

Increasing evidence revealed that the aberrant expression of long non-coding RNAs (lncRNAs) has been implicated in tumorigenesis. However, the role and mechanisms of LINC00662 in glioma have not been elucidated. Here, we show that upregulation of LINC00662 expression in glioma is associated with advanced clinical features and poor prognosis. Our results from loss-of-function assays suggest that LINC00662 silencing suppresses the proliferative and invasive abilities of glioma cells. In vivo, glioma growth was inhibited by depletion of LINC00662 in nude mice. Mechanistically, LINC00662 directly interacts with miR-107. The High-mobility group box 1 protein (HMGB1) is a known target of miR-107. Moreover, rescue assays reveal that HMGB1 overexpression (or miR-107 inhibition) reverses the glioma growth inhibition caused by LINC00662 knockdown. In conclusion, our results indicate that LINC00662 acts as an oncogene in glioma by modulating the miR-107/HMGB1 axis, suggesting that LINC00662 could be a novel therapeutic target for glioma treatment.

Evaluation of an artificial intelligent hydrocephalus diagnosis model based on transfer learning.

To design and develop artificial intelligence (AI) hydrocephalus (HYC) imaging diagnostic model using a transfer learning algorithm and evaluate its application in the diagnosis of HYC by non-contrast material-enhanced head computed tomographic (CT) images.A training and validation dataset of non-contrast material-enhanced head CT examinations that comprised of 1000 patients with HYC and 1000 normal people with no HYC accumulating to 28,500 images. Images were pre-processed, and the feature variables were labeled. The feature variables were extracted by the neural network for transfer learning. AI algorithm performance was tested on a separate dataset containing 250 examinations of HYC and 250 of normal. Resident, attending and consultant in the department of radiology were also tested with the test sets, their results were compared with the AI model.Final model performance for HYC showed 93.6% sensitivity (95% confidence interval: 77%, 97%) and 94.4% specificity (95% confidence interval: 79%, 98%), with area under the characteristic curve of 0.93. Accuracy rate of model, resident, attending, and consultant were 94.0%, 93.4%, 95.6%, and 97.0%.AI can effectively identify the characteristics of HYC from CT images of the brain and automatically analyze the images. In the future, AI can provide auxiliary diagnosis of image results and reduce the burden on junior doctors.

The diagnosis of ventriculoperitoneal shunt malfunction by using phase-contrast cine magnetic resonance imaging.

The ventriculoperitoneal (VP) shunt is a gold standard procedure to treat hydrocephalus. However, shunt malfunction is the common complications after surgery. In this study, we utilize phase-contrast cine magnetic resonance imaging (PC cine MRI) to improve the diagnosis of VP shunt malfunction. In in vitro and in vivo experiment results demonstrate the cerebrospinal fluid (CSF) flow velocities in the shunt tube are significantly decreased in the shunt malfunction group, which indicated PC cine MRI could evaluate the CSF flow dynamics of VP shunt effectively. This method is noninvasive and simple, also can improve the diagnosis of shunt malfunction.

Burr hole drainage and burr hole drainage with irrigation to treat chronic subdural hematoma: A systematic review and meta-analysis.

OBJECTIVE: Numerous studies have investigated different operative procedures for treating chronic subdural hematoma (CSDH); however, the results are controversial. This meta-analysis was performed to evaluate the efficacy of burr hole drainage without irrigation (BHD) and burr hole drainage with irrigation (BHDI) for CSDH. METHODS: We searched the following electronic databases to identify all studies from their inception to September 2017: Cochrane Library, Science Direct, MEDLINE, EMBASE, Scopus, Google Scholar, the China Biomedical Database (CBM), and the Chinese National Knowledge Infrastructure (CNKI). Randomized clinical trials (RCTs), prospective cohort studies, retrospective observational cohort studies, and case-control studies investigating BHD and BHDI for the treatment of CSDH were included. The Cochrane Collaboration's RevMan 5.3 software was used for meta-analysis. RESULTS: In total, 7 retrospective cohort studies and 2 RCTs involving 993 participants were included. Comprehensive analysis results of 9 studies indicated that the recurrence of the BHDI was similar to that in BHD (odds ratio [OR] = 1.27, 95% confidence interval [CI] = .61-2.63, P = .53). Moreover, analysis for comparing recurrence in the 2 RCTs was not significantly different (OR = 1.14, 95% CI = .16-8.24, P = .95).In addition, meta-analysis of pneumocephalus (OR = 5.91, 95% CI = .61-56.86, P = .12) and mortality (OR = 0.94, 95% CI 0.14-6.16, P = .95) was not significantly different. CONCLUSIONS: The results of this meta-analysis demonstrated that procedures with or without irrigation in the treatment of CSDH might have similar effect regarding recurrence and complications; therefore, irrigation might not be necessary. However, well-conducted RCTs and high-quality observational studies are still required to corroborate this issue.

A Simple and Reliable Method for the Diagnosis of Ventriculoperitoneal Shunt Malfunction.

OBJECTIVE: To provide a simple and reliable method for the diagnosis of ventriculoperitoneal shunt malfunction. METHODS: A total of 14 participants were enrolled in this study, consisting of 7 patients with suspected shunt malfunction and 7 control cases with apparent normal drainage. In all cases, 0.1 mL of 5% glucose solution was injected into the reservoir and 0.1 mL of cerebrospinal fluid was withdrawn from the reservoir 20 minutes later to measure glucose concentration. RESULTS: The glucose concentration in cerebrospinal fluid of the shunt malfunction group was greater than that of the control group (P < 0.05). CONCLUSIONS: The proposed method is reliable, safe, and relatively simple for the diagnosis of ventriculoperitoneal shunt malfunction and provides a reference for treatment.

Transplantation of human amniotic mesenchymal stem cells promotes neurological recovery in an intracerebral hemorrhage rat model.

Human amniotic membrane mesenchymal stem cells (hAMSCs) have recently been suggested as ideal candidate stem cells for cell-based therapy. Many studies have reported the therapeutic effects of hAMSCs in numerous disease models. However, no studies have used hAMSCs to treat intracerebral hemorrhage (ICH). In the present study, we examined the therapeutic potential of hAMSCs in a rat model of ICH, and characterized the possible mechanisms of action. Adult male Wistar rats were subjected to ICH by intrastriatal injection of VII collagenase, and then were intracerebrally administered hAMSCs, fibroblasts, or phosphate-buffered saline (PBS) at 24 h after ICH. Compared with the fibroblasts and the PBS control, hAMSCs treatment significantly promoted neurological recovery, and reduced the numbers of ED1(+) activated microglia, as well as myeloperoxidase (MPO(+)), and caspase-3(+) cells in the brain injury model. In addition, hAMSCs treatment significantly increased the expression of brain-derived neurotrophic factor (BDNF) and vascular endothelial growth factor (VEGF) in the injured brain, and promoted neurogenesis and angiogenesis, compared with the fibroblasts and the PBS control. The transplanted hAMSCs survived for at least 27 days and were negative for ß-tubulin III and glial fibrillary acidic protein (GFAP). Taken together, the results suggest that hAMSCs treatment significantly promotes neurological recovery in rats after ICH. The mechanism of action could be mediated by inhibition of inflammation and apoptosis, increasing neurotrophic factor expression, and promotion of neurogenesis and angiogenesis. Thus, hAMSCs are candidate stem cells for the treatment of ICH.

Paeoniflorin Atttenuates Amyloidogenesis and the Inflammatory Responses in a Transgenic Mouse Model of Alzheimer's Disease.

Alzheimer's disease (AD) is associated with the inflammatory response in response to amyloid ß-peptide (Aß). Previous studies have suggested that paeoniflorin (PF) shows anti-inflammatory and neuroprotective effects in inflammation-related diseases. However, the impacts of PF on AD have not been investigated. In the present study, we showed that a 4-week treatment with PF could significantly inhibit Aß burden, Aß-induced over activation of astrocytes and microglia, downregulation of proinflammatory cytokines, and upregulation of anti-inflammatory cytokines in the brain. In addition, we demonstrated that chronic treatment with PF inhibited the activation of glycogen synthase kinase 3ß (GSK-3ß) and reversed neuroinflammtory-induced activation of nuclear factor-kappa B (NF-κB) signaling pathways. Moreover, PF exerted inhibitory effects on NALP3 inflammasome, caspase-1, and IL-1ß. Collectively, in the present study, we demonstrated that PF exhibits neuroprotective effects in amyloid precursor protein (APP) and presenilin 1 (PS1) double-transgenic (APP/PS1) mice via inhibiting neuroinflammation mediated by the GSK-3ß and NF-κB signaling pathways and nucleotide-binding domain-like receptor protein 3 inflammasome. Thus, these results suggest that PF might be useful to intervene in development or progression of neurodegeneration in AD through its anti-inflammatory and anti-amyloidogenic effects.

Effect of erythrocytes on brain water content and haem oxygenase-1 expression in rats with traumatic intracerebral haemorrhage.

BACKGROUND: Studies have demonstrated that brain oedema formation following spontaneous intracerebral haemorrhage is associated with substances derived from blood clots or blood components. However, these studies did not completely reveal the role of blood components in brain oedema formation following traumatic intracerebral haemorrhage (TICH). Here, we explore the role of erythrocytes in brain oedema development by studying the effect of erythrocytes on brain water content (BWC) and expression of haem oxygenase-1 (HO-1) in rats with TICH. METHODS: A total of 120 Sprague-Dawley rats were randomly divided into four experimental treatment groups: traumatic brain injury (TBI), TBI plus whole blood (WB), TBI plus lysed red blood cells (RBCs; LRBC) and TBI plus packed RBCs (PRBC). Following TBI, which was established by applying a free-falling device, WB, LRBC or PRBC were infused with stereotactic guidance into the injured cortex to produce a model of TICH. All rats were killed at 1, 3 or 5 days after TBI or TICH. BWC was measured, and immunohistochemistry for HO-1 was performed. RESULTS: In the WB, PRBC and TBI groups, BWC at 3 days post-TBI or post-TICH was the greatest. However, BWC in the LRBC group at 1 day was markedly higher than that at 3 and 5 days. Comparisons among the four groups showed that BWC in the LRBC group was the highest at 1 day, and the highest at 3 days in the WB and PRBC groups; there was no significant difference at 5 days. Positive expression of HO-1 in the WB, PRBC and LRBC groups coincided with changes in BWC. CONCLUSIONS: Our results indicate that erythrocytes play an important role in delayed brain oedema formation (3 days post-injury) following TICH, but have no significant influence on brain oedema at early stages (1 day post-injury), and that the mechanisms of delayed brain oedema involve RBC breakdown products.