Identification of core genes of craniopharyngioma angiogenesis based on single-cell nuclear transcriptome sequencing.

This study aimed to explore the core genes of craniopharyngioma angiogenesis for targeted vascular therapy based on single-cell nuclear transcriptome sequencing. For single-cell nuclear transcriptome sequencing, we collected six samples from the tumor center and adjacent hypothalamic tumor tissues from three patients with craniopharyngioma, as well as four normal brain tissues based on Gene Expression Omnibus. We screened genes with differential up-regulation between vascular endothelial cells of craniopharyngioma and those of normal brain tissues, performed GO and KEGG analysis, constructed the protein-protein interaction network, and selected key genes verified using immunofluorescence. After data cleaning and quality control, 623 craniopharyngioma endothelial cells and 439 healthy brain endothelial cells were obtained. Compared with normal brain endothelial cells, craniopharyngioma endothelial cells were screened for 394 differentially up-expressed genes (DEGs). GO and KEGG results showed that DEGs probably modulated endothelial cells, adherens junction, focal adhesion, migration, actin cytoskeleton, and invasion via the PI3K-AKT, Rap1, Ras, Wnt, and Hippo pathways. The core genes screened were CTNNB1, PTK2, ITGB1, STAT3, FYN, HIF1A, VCL, SMAD3, PECAM1, FOS, and CDH5. This study obtained possible anti-angiogenic genes in craniopharyngioma. Our results shed novel insights into molecular mechanisms and craniopharyngioma treatment.

Budding uninhibited by benzimidazoles 1 promotes cell proliferation, invasion, and epithelial-mesenchymal transition via the Wnt/ß-catenin signaling in glioblastoma.

The pathogenesis and progression of GBM (glioblastoma), as one of the most frequently occurring malignancies of the central nervous system, are regulated by several genes. BUB1 (budding uninhibited by benzimidazoles 1) is a mitotic checkpoint that plays an important role in chromosome segregation as well as in various tumors. However, its role in glioma is unknown. The current study discovered prominently elevated BUB1 in glioma and a significant relationship between BUB1 expression, a high World Health Organization grade, and a poor prognosis in glioma patients. Moreover, BUB1 triggered EMT (epithelial-mesenchymal transition) apart from promoting glioma cell proliferation, migration, and infiltration. Besides, BUB1 promoted EMT by activating the Wnt/ß-catenin axis. As implied by our study, BUB1 probably has the potential as a target for GBM management.

Sunitinib resistance in renal cell carcinoma: From molecular mechanisms to predictive biomarkers.

Currently, renal cell carcinoma (RCC) is the most prevalent type of kidney cancer. Targeted therapy has replaced radiation therapy and chemotherapy as the main treatment option for RCC due to the lack of significant efficacy with these conventional therapeutic regimens. Sunitinib, a drug used to treat gastrointestinal tumors and renal cell carcinoma, inhibits the tyrosine kinase activity of a number of receptor tyrosine kinases, including vascular endothelial growth factor receptor (VEGFR), platelet-derived growth factor receptor (PDGFR), c-Kit, rearranged during transfection (RET) and fms-related receptor tyrosine kinase 3 (Flt3). Although sunitinib has been shown to be efficacious in the treatment of patients with advanced RCC, a significant number of patients have primary resistance to sunitinib or acquired drug resistance within the 6-15 months of therapy. Thus, in order to develop more efficacious and long-lasting treatment strategies for patients with advanced RCC, it will be crucial to ascertain how to overcome sunitinib resistance that is produced by various drug resistance mechanisms. In this review, we discuss: 1) molecular mechanisms of sunitinib resistance; 2) strategies to overcome sunitinib resistance and 3) potential predictive biomarkers of sunitinib resistance.

Yi-Shen-Hua-Shi granules inhibit diabetic nephropathy by ameliorating podocyte injury induced by macrophage-derived exosomes.

Objective: To observe the therapeutic effect of Yi-Shen-Hua-Shi (YSHS) granule in podocyte damage and diabetic nephropathy (DN) proteinuria and to explore the corresponding mechanism. Methods: The db/db mice were used to establish the DN model. Serum creatinine (SCr), blood urea nitrogen (BUN), and 24 h urinary proteinuria were detected with specific kits. Glomerular structural lesions and podocyte apoptosis were detected through HE staining, TUNEL assay, and immunofluorescence. The medicated serum of YSHS granule (YSHS-serum) or control serum was prepared. Macrophage-derived exosomes were extracted using an exosome extraction kit. Morphology and the protein concentration of exosomes were evaluated by a transmission electron microscope (TEM) and BCA kit. The activity and apoptosis of podocyte MPC5 cells, the M1 macrophage polarization, and the protein expression of an exosome marker and cleaved caspase were detected by the CCK8 experiment, flow cytometry, and Western blot, respectively. The miR-21a-5p expression in podocytes and the exosomes from macrophages were measured by qRT-PCR. The effect of YSHS granule on the infiltration of M1 macrophages in the kidney tissue in db/db mice was measured by immunofluorescence. Results: The YSHS granule could improve renal function, reduce proteinuria, and inhibit glomerular structural lesions and podocyte apoptosis in db/db mice. High-glucose (HG) stimulation and YSHS granule treatment did not affect the protein concentration in macrophage-derived exosomes. Macrophage-derived exosomes could inhibit the cell viability and increase apoptosis of podocytes, especially the exosomes from macrophages treated with HG and control serum. Compared with the exosomes secreted by macrophages after an HG treatment, the exosome from macrophages treated with HG and YSHS granule showed lower inhibitory effects on podocyte activity, accompanied by the decreased upregulating effects of macrophage-derived exosomes on the miR-21a-5p in podocytes. miR-21a-5p mimics could reduce podocyte activity and promote caspase-3 shearing. M1 polarization of macrophages could change the content of miR-21a-5p in macrophage-derived exosomes. In addition, YSHS granule could inhibit HG-induced M1 polarization of macrophages and M1 macrophage infiltration in renal tissues. Conclusion: The YSHS granule could improve the podocyte injury induced by macrophage-derived exosomes and alleviate the progression of DN. This regulation might be related to the inhibition of M1 macrophage polarization by YSHS granule and the reduction of the miR-21a-5p content in macrophage-derived exosomes.

Novel mutation in the SALL1 gene in a four-generation Chinese family with uraemia: A case report.

BACKGROUND: Approximately 10% of adults and nearly all children who receive renal replacement therapy have inherited risk factors or are related to genetic factors. In the past, due to the limitations of detection technology and the nonspecific manifestations of uraemia, the etiological diagnosis is unclear. In addition to common monogenic diseases and complex disorders, advanced testing techniques have led to the recognition of more hereditary renal diseases. Here, we report a four-generation Chinese family in which four individuals had a novel SALL1 mutation and presented with uraemia or abnormal urine tests. CASE SUMMARY: A 32-year-old man presented with end-stage renal disease with a 4-year history of dialysis. His father and paternal aunt both had a history of unexplained renal failure with haemodialysis, and his 10-year-old daughter presented with proteinuria. The patient had multiple congenital abnormalities, including bilateral overlapping toes, unilateral dysplastic external ears, and sensorineural hearing loss. His family members also presented with similar defects. Genetic testing revealed that the proband carried a novel heterozygous shift mutation in SALL1_exon 2 (c.3437delG), and Sanger sequencing confirmed the same mutation in all affected family members. CONCLUSION: We report a novel SALL1 exon 2 (c.3437delG) mutation and clinical syndrome with kidney disease, bilateral overlapping toes, unilateral dysplastic external ears, and sensorineural hearing loss in a four-generation Chinese family.

The Role of Ferroptosis in Acute Kidney Injury.

Ferroptosis is a novel cell death method discovered in recent years. It is usually accompanied by massive accumulations of iron and lipid peroxidation during cell death. Recent studies have shown that ferroptosis is closely associated with the pathophysiological processes of many diseases, such as tumors, neurological diseases, localized ischemia-reperfusion injury, kidney injury, and hematological diseases. How to intervene in the incidence and development of associated diseases by regulating the ferroptosis of cells has become a hot topic of research. This article provides a review of the role of ferroptosis in the pathogenesis and potential treatment of acute kidney injury.

[Corrigendum] Exosomal­miR­1184 derived from mesenchymal stem cells alleviates cisplatin­associated acute kidney injury.

Subsequently to the publication of this paper, the authors have noticed that Fig. 5 was published with inadvertent errors; essentially, the y­axis label in Fig. 5D should have read "TNF­α" instead of "IL­1ß" and conversely, in Fig. 5E, the y­axis label should have read "IL­1ß" instead of "TNF­α". The revised version of Fig. 5, with Figs. 5D and E now labelled correctly, is shown below. Note that these errors did not significantly affect either the results or the conclusions reported in this paper, and all the authors agree to this corrigendum. Furthermore, the authors thank the Editor of Molecular Medicine Reports for allowing them the opportunity to publish this corrigendum, and apologize to the readership for any inconvenience caused. [Molecular Medicine Reports 24: 795, 2021; DOI: 10.3892/mmr.2021.12435].

Association of central arterial blood pressure and left ventricular hypertrophy in patients with chronic kidney disease.

AIMS: In the general population, central arterial blood pressure has proved to be more closely related to left ventricular hypertrophy (LVH) than brachial arterial blood pressure. We aimed to investigate whether this relationship was true in patients with chronic kidney disease (CKD). METHODS: In this retrospective study, we reviewed the medical records of 289 adult patients with CKD from the Zhejiang Provincial People's Hospital in Zhejiang, China. Demographic, echocardiographic and brachial and central blood pressure parameters were retrieved from medical records. Central blood pressure was measured using the SphygmoCor® CvMS (AtCor, Australia) device and its corresponding software. Multivariate logistic regression analyses were performed to identify independent predictors of LVH. Receiver operating characteristic curves were used to determine the ability of central and brachial blood pressure to predict LVH. RESULTS: The left ventricular mass index was positively associated with both central and brachial blood pressures. However, multiple logistic regression analysis demonstrated that a central pulse pressure (CPP) ≥ 58 mm Hg was an independent risk factor for LVH (OR = 5.597, 95%CI 2.363-13.259, p < .001). Brachial pulse pressure is not superior to CPP in predicting LVH (area under the curve [AUC] = 0.695, 95%CI 0.634-0.756, p < .001 vs. AUC = 0.687, 95%CI: 0.626-0.748, p < .001, respectively; p = .4824). CONCLUSION: Our results suggested that, similarly to the general population, CPP is a better parameter for predicting the occurrence of LVH in patients with CKD.

Large mismatch profile predicts rapidly progressing brain edema in acute anterior circulation large vessel occlusion patients undergoing endovascular thrombectomy.

Background: Brain edema is a severe complication in patients with large vessel occlusion (LVO) that can reduce the effectiveness of endovascular therapy (EVT). This study aimed to investigate the association of the perfusion profile at baseline computed tomography (CT) perfusion with rapidly progressing brain edema (RPBE) after EVT in patients with acute anterior LVO. Methods: We retrospectively reviewed consecutive data collected from 149 patients with anterior LVO who underwent EVT at our center. Brain edema was measured by the swelling score (0-6 score), and RPBE was defined as the swelling score increased by more than 2 scores within 24 h after EVT. We investigated the effect of RPBE on poor outcomes [National Institute of Health Stroke Scale (NIHSS) score and modified Rankin scale (mRS) score at discharge, the occurrence of hemorrhagic transformation, and mortality rate in the hospital] using the Mann-Whitney U-test and chi-square test. A multivariate logistic regression model was used to assess the relationship between perfusion imaging parameters and RPBE occurrence. Results: Overall, 39 patients (26.2%) experienced RPBE after EVT. At discharge, RPBE was associated with higher NIHSS scores (Z = 3.52, 95% CI 2.0-12.0, P < 0.001) and higher mRS scores (Z = 3.67, 95% CI 0.0-1.0, P < 0.001) including the more frequent occurrence of hemorrhagic transformation (χ2 = 22.17, 95% CI 0.29-0.59, P < 0.001) and higher mortality rates in hospital (χ2 = 9.54, 95% CI 0.06-0.36, P = 0.002). Univariate analysis showed that intravenous thrombolysis, baseline ischemic core volume, and baseline mismatch ratio correlated with RPBE (all P < 0.05). After dividing the mismatch ratio into quartiles and performing a chi-square test between quartiles, we found that the occurrence of RPBE in Q4 (mismatch ratio > 11.3) was significantly lower than that in Q1 (mismatch ratio ≤ 3.0) (P < 0.05). The result of multivariate logistic regression analysis showed that compared with baseline mismatch ratio <5.1, baseline mismatch ratio between 5.1 and 11.3 (OR:3.85, 95% CI 1.06-14.29, P = 0.040), and mismatch ratio >11.3 (OR:5.26, 95% CI 1.28-20.00, P = 0.021) were independent protective factors for RPBE. Conclusion: In patients with anterior circulation LVO stroke undergoing successful EVT, a large mismatch ratio at baseline is a protective factor for RPBE, which is associated with poor outcomes.

Integrative analysis of miRNA-mRNA network in idiopathic membranous nephropathy by bioinformatics analysis.

BACKGROUND: Currently, several specific antigens, M-type receptor for secretory phospholipase A2(PLA2R1), thrombospondin type-1 domain-containing 7A(THSD7A), and neural epidermal growth factor-like 1 protein (NELL-1), are discovered associated with the onset of idiopathic membranous nephropathy (IMN). But the pathomechanisms of IMN still need to be further claried. Understanding the mechanisms of IMN is required to improve its diagnosis and treatment. METHODS: In this study, we constructed miRNA regulatory networks to investigate IMN development. Moreover, miRNAs and mRNAs that were differentially expressed between Idiopathic Membranous Nephropathy (IMN) patients and normal controls were examined using the GSE115857 dataset and our previous sequence study. DE miRNA target genes were determined based on the FUNRICH software, starBase, miRDB, and miRWalk, and an miRNA-mRNA network was designed using DE-mRNAs that were negatively correlated with DE-miRNAs. The miRNA-mRNA network contained 228 miRNA-mRNA pairs. Thereafter, we conducted KEGG pathway, GO functional annotation, immune-related gene screening, protein interaction networks, and potential hub gene analyses. Furthermore, 10 miRNAs and 10 genes were determined and preliminarily validated using the validation dataset from GEO. Finally, we identified which pair may offer more accurate diagnosis and therapeutic targets for IMN. RESULTS: Two miRNA-mRNA pairs, miR-155-5p-FOS and miR-146a-5p-BTG2, were differentially expressed in IMN, indicating that these genes may affect IMN through immune processes. These findings may offer more accurate diagnoses and therapeutic targets for IMN.

Exosomal­miR­1184 derived from mesenchymal stem cells alleviates cisplatin­associated acute kidney injury.

Acute kidney injury (AKI) poses a severe threat to human health. MicroRNAs (miRNAs/miRs) are known to be involved in the progression of AKI; however, the function of miR­1184 in AKI remains unclear. Thus, the aim of the present study was to examine the role of this miRNA in kidney injury. In order to mimic AKI in vitro, HK­2 cells were treated with cisplatin. Bioinformatics analysis was performed to explore the differentially expressed miRNAs in AKI. A Cell Counting Kit­8 assay and flow cytometry were performed to examine cell viability and apoptosis, respectively. mRNA expression levels were detected via reverse transcription­quantitative PCR, and protein levels were investigated by western blot analysis. ELISA was performed to examine the levels of IL­1ß and TNF­α in the cell supernatants. The results revealed that miR­1184 expression was downregulated in AKI. Exosomes derived from miR­1184 agomir­treated mesenchymal stem cells (MSCs) significantly reversed cisplatin­induced cell growth inhibition by inhibiting apoptosis. Moreover, forkhead box O4 (FOXO4) was found to be the direct target of miR­1184, and exosomes expressing miR­1184 notably inhibited cisplatin­induced inflammatory responses in HK­2 cells via the mediation of IL­1ß and TNF­α. Furthermore, exosomes derived from miR­1184 agomir­treated MSCs significantly induced G1 phase arrest in HK­2 cells via the regulation of FOXO4, p27 Kip1 and CDK2. In conclusion, the present study demonstrated that exosomal­miR­1184 derived from MSCs alleviates cisplatin­associated AKI. Thus, the findings presented herein may shed new light onto the exploration of novel strategies for the treatment of AKI.

Outcomes of Traumatic Brain-Injured Patients With Glasgow Coma Scale < 5 and Bilateral Dilated Pupils Undergoing Decompressive Craniectomy.

Objective: Decompressive craniectomy (DC) plays an important role in the treatment of patients with severe traumatic brain injury (sTBI) with mass lesions and intractably elevated intracranial hypertension (ICP). However, whether DC should be performed in patients with bilateral dilated pupils and a low Glasgow Coma Scale (GCS) score is still controversial. This retrospective study explored the clinical outcomes and risk factors for an unfavorable prognosis in sTBI patients undergoing emergency DC with bilateral dilated pupils and a GCS score <5. Methods: The authors reviewed the data from patients who underwent emergency DC from January 2012 to March 2019 in a medical center in China. All data, such as patient demographics, radiological findings, clinical parameters, and preoperative laboratory variables, were extracted. Multivariate logistic regression analysis was performed to determine the factors associated with 30-day mortality and 6-month negative neurological outcome {defined as death or vegetative state [Glasgow Outcome Scale (GOS) score 1-2]}. Results: A total of 94 sTBI patients with bilateral dilated pupils and a GCS score lower than five who underwent emergency DC were enrolled. In total, 74 patients (78.7%) died within 30 days, and 84 (89.4%) had a poor 6-month outcome (GOS 1-2). In multivariate analysis, advanced age (OR: 7.741, CI: 2.288-26.189), prolonged preoperative activated partial thromboplastin time (aPTT) (OR: 7.263, CI: 1.323-39.890), and low GCS (OR: 6.162, CI: 1.478-25.684) were associated with a higher risk of 30-day mortality, while advanced age (OR: 8.812, CI: 1.817-42.729) was the only independent predictor of a poor 6-month prognosis in patients undergoing DC with preoperative bilateral dilated pupils and a GCS score <5. Conclusions: The mortality and disability rates are extremely high in severe TBI patients undergoing emergency DC with bilateral fixed pupils and a GCS score <5. DC is more valuable for younger patients.

Mortality in chronic kidney disease patients with COVID-19: a systematic review and meta-analysis.

At the beginning of 2020, the outbreak of coronavirus disease 2019 (COVID-19) led to a worldwide pandemic and mass panic. The number of infected people has been increasing exponentially since, and the mortality rate has also been concomitantly increasing. At present, no study has summarized the mortality risk of COVID-19 in patients with chronic kidney disease (CKD). Therefore, the aim of the present study was to conduct a literature review and meta-analysis to understand the frequency of mortality among CKD patients infected with COVID-19. A comprehensive systematic search was conducted on the PubMed, Embase, and Cochrane databases to find articles published until May 15, 2020. Study quality was assessed using a modified version of the Newcastle-Ottawa Scale. After careful screening based on the inclusion and exclusion criteria, 3,867,367 patients from 12 studies were included. The mortality rate was significantly higher among CKD patients with COVID-19 infection than among CKD patients without COVID-19 infection, as indicated by a pooled OR of 5.81 (95% CI 3.78-8.94, P < 0.00001, I2 = 30%). The patients were then stratified into ≥ 70 and < 70 years, and subgroup analysis revealed that among CKD patients with COVID-19 infection, the mortality rate was higher in the < 70 years group (OR 8.69, 95% CI 7.56-9.97, P < 0.0001) than in the ≥ 70 years group (OR 2.44, 95% CI 0.75-6.63, P = 0.15). Thus, COVID-19 patients with CKD have a high mortality risk and require a comprehensive multidisciplinary management strategy.

Differential Expression of Urinary Exosomal Small RNAs in Idiopathic Membranous Nephropathy.

BACKGROUND: Idiopathic membranous nephropathy (IMN) is a major cause of adult nephrotic syndromes, and reliable noninvasive biomarkers for diagnosis and monitoring are urgently needed. In this study, we performed small RNA (sRNA) sequencing to explore sRNA profiles of urinary exosomes derived from IMN patients and healthy controls (CON) to provide clues for identifying novel noninvasive sRNA biomarkers for IMN. METHODS: Urine samples were collected from five healthy controls and six patients with IMN. High-throughput sequencing was used to screen sRNA expression profiles of urinary exosomes from patients with IMN in two independent cohorts. RESULTS: Urinary exosomes were successfully isolated and used to obtain exosomal sRNAs. We screened 131 differentially expressed miRNAs, including 28 specifically expressed miRNAs, then explored the top 10 specifically expressed miRNAs in all IMN individuals. The specifically expressed miRNAs and differentially expressed miRNAs provide potential biomarkers for IMN. Additionally, we discovered numerous sRNAs derived from genomic repetitive sequences, which could represent an exciting new area of research. CONCLUSION: Herein, we revealed significant differences in expression profiles of urinary exosomal miRNAs and repetitive region-derived sRNAs between patients with IMN and healthy controls. The findings could facilitate the development of potential molecular targets for membranous nephropathy.

Predictors of 30-Day Mortality in Traumatic Brain-Injured Patients after Primary Decompressive Craniectomy.

OBJECTIVE: Primary decompressive craniectomy (DC) is an important therapeutic technique for severe head-injured patients with space-occupying lesions in emergency situations, but these patients are still at high risk for unfavorable outcomes. This study aimed to investigate the predictors of 30-day mortality in adult patients undergoing primary DC after traumatic brain injury (TBI). METHODS: All adult patients (≥18 years of age) who underwent primary DC from January 2012 to March 2019 were included. Demographic, clinical, surgical, and laboratory variables were collected for analysis. Early mortality was defined as 30-day mortality after DC. First, a univariate analysis (P < 0.05) was used to compare survivors and nonsurvivors. Multivariate logistic regression analysis was used to identify the predictors of 30-day mortality for patients who underwent primary DC. RESULTS: A total of 387 patients were enrolled in the study. The 30-day mortality was 31.52% (122/387). The median age at presentation was 49 years (interquartile range, 38-60), and 316 (81.65%) patients were male. In the multivariate logistic regression analysis, the factors associated with 30-day mortality included age (odds ratio [OR], 1.068; 95% confidence interval [CI], 1.040-1.096; P < 0.001), bilateral unreactive pupils (OR, 12.734; 95% CI, 4.129-39.270; P < 0.001), subdural hemorrhage (OR, 3.468; 95% CI, 1.305-9.218; P < 0.013), completely effaced basal cistern (OR, 3.52; 95% CI, 1.568-7.901; P = 0.002), intraoperative hypotension (OR, 11.532; 95% CI, 4.222-31.499; P < 0.001), preoperative activated partial thromboplastin time (OR, 6.905; 95% CI, 2.055-23.202; P = 0.002), and Injury Severity Score (OR, 1.081; 95% CI, 1.031-1.133; P = 0.002). CONCLUSIONS: In patients undergoing primary DC after traumatic brain injury, the predictors of 30-day mortality include age, bilateral unreactive pupils, subdural hemorrhage, completely effaced basal cistern, intraoperative hypotension, preoperative activated partial thromboplastin time, and Injury Severity Score.

Position-deviation-compensation demodulation method for multi-channel polarized low-coherence interferometry.

A position-deviation-compensation demodulation method is proposed to improve the channel adaptability of Fabry-Perot (F-P) sensor in a multi-channel optical fiber F-P sensing system. By combining the envelope peak position (EPP) retrieval process and the position compensation process, the proposed method enables the accurate demodulation of F-P sensors in all channels. Thereinto, the EPP retrieval process uses the phase information to recover the EPP with high precision; the position compensation process compensates the position deviation by an optical-path-based model, which is established to illustrate the principle of the position deviation between different channels. We carried out the pressure experiment to verify the effectiveness of the proposed method. The experiment results showed that the demodulation errors of all channels are no more than 0.13 kPa, which demonstrated that our approach is reliable for improving the channel adaptability of F-P sensors.

Fourteen-Day Mortality in Pediatric Patients with Traumatic Brain Injury After Early Decompressive Craniectomy: A Single-Center Retrospective Study.

OBJECTIVE: The purpose of this study was to analyze the risk factors for 14-day mortality in pediatric patients undergoing early decompressive craniectomy (DC) after traumatic brain injury (TBI). METHODS: This retrospective analysis included all pediatric patients (≤16 years of age) undergoing DC within 12 hours of TBI between August 2011 and July 2017 at the authors' institute. Demographic information, clinical characteristics, surgical information, and laboratory parameters were retrieved from medical records. Risk factors for 14-day mortality were analyzed using multivariate logistic regression models. First, potentially relevant variables were compared between those who died within 14 days versus those who did not. Variables with P < 0.10 were entered into the final multivariate regression analysis. RESULTS: A total of 36 patients (23 boys and 13 girls; median age, 7 years) were included in the analysis. Fall (n = 19, 52.8%) was the leading cause of injury. The 14-day mortality was 38.9% (14/36). At the time of admission, the median Glasgow Score Scale (GCS) was 6 (IQR 4-8), and the mean Injury Severity Score (ISS) (± standard deviation) was 29.03 ± 8.54. Preoperative hypoxia, defined as oxyhemoglobin arterial saturation <90% or apnea >20 seconds, was observed in 6 patients (16.7%). Coagulopathy was present in 14 patients (38.9%). Multivariate logistic regression analysis suggested an association between 14-day mortality and younger age (odds ratio [OR] = 0.708, 95% confidence interval [CI]: 0.513-0.978; P = 0.036) and higher ISS (OR = 1.399; 95% CI: 1.023-1.914; P = 0.035). CONCLUSIONS: In children undergoing early DC after TBI, risk factors for 14-day mortality include younger age and higher ISS.

Identification of microRNAs associated with glioma diagnosis and prognosis.

The sensitivity and specificity of microRNAs (miRNAs) for diagnosing glioma are controversial. We therefore performed a meta-analysis to systematically identify glioma-associated miRNAs. We initially screened five miRNA microarray datasets to evaluate the differential expression of miRNAs between glioma and normal tissues. We next compared the expression of the miRNAs in different organs and tissues to assess the sensitivity and specificity of the differentially expressed miRNAs in the diagnosis of glioma. Finally, pathway analysis was performed using GeneGO. We identified 27 candidate miRNAs associated with glioma initiation, progression, and patient prognosis. Sensitivity and specificity analysis indicated miR-15a, miR-16, miR-21, miR-23a, and miR-9 were up-regulated, while miR-124 was down-regulated in glioma. Ten signaling pathways showed the strongest association with glioma development and progression: the p53 pathway feedback loops 2, Interleukin signaling pathway, Toll receptor signaling pathway, Parkinson's disease, Notch signaling pathway, Cadherin signaling pathway, Apoptosis signaling pathway, VEGF signaling pathway, Alzheimer disease-amyloid secretase pathway, and the FGF signaling pathway. Our results indicate that the integration of miRNA, gene, and protein expression data can yield valuable biomarkers for glioma diagnosis and treatment. Indeed, six of the miRNAs identified in this study may be useful diagnostic and prognostic biomarkers in glioma.

Advantages of a dual-color fluorescence-tracing glioma orthotopic implantation model: Detecting tumor location, angiogenesis, cellular fusion and the tumor microenvironment.

Various organs of the body have distinct microenvironments with diverse biological characteristics that can influence the growth of tumors within them. However, the mechanisms underlying the interactions between tumor and host cells are currently not well understood. In the present study, a dual-color fluorescence-tracing glioma orthotopic implantation model was developed, in which C6 rat glioma cells labeled with the red fluorescent dye CM-Dil, and SU3 human glioma cells stably expressing red fluorescence protein, were inoculated into the right caudate nucleus of transgenic female C57BL/6 nude mice expressing enhanced green fluorescent protein. The dual-color tracing with whole-body in vivo fluorescence imaging of xenografts was performed using a live imaging system. Frozen sections of the transplanted tumor were prepared for histological analyses, in order to detect the presence of invading tumor cells, blood vessels and cellular fusion. Dual-color images were able to distinguish between red tumor cells and green host cells. The results of the present study suggested that a dual-color fluorescence-tracing glioma orthotopic implantation model may be convenient for detecting tumor location, angiogenesis, cellular fusion, and the tumor microenvironment.

Alteration of DNA damage signaling pathway profile in radiation-treated glioblastoma stem-like cells.

The present study aimed to investigate the alteration of the DNA damage signaling pathway profile in radiation-treated glioblastoma stem-like cells (GSLCs), and also aimed to explore potential targets for overcoming glioblastoma radioresistance. Serum-free medium was used to isolate and culture GSLCs. Cell growth was detected using a cell counting kit-8 assay and cell sorting analysis was performed by flow cytometry. X-ray irradiation was produced by a Siemens-Primus linear accelerator. Reverse transcription-quantitative polymerase chain reaction (qPCR)was performed to investigate target genes. SPSS 15.0 was used for all statistical analyses. Human glioblastoma U251 and U87 cells were cultured in serum-free medium supplemented with epidermal growth factor and fibroblast growth factor 2, which constitutes tumor sphere medium, and demonstrated sphere formation, with significantly increased the proportion of CD133+ and Nestin+ cells, which are referred to as GSLCs. The present data revealed that treatment with 10 Gy X-ray radiation alters the expression profile of DNA damage-associated genes in GSLCs. The expression levels of 12 genes demonstrated a ≥2-fold increase in the irradiated U87 GSLCs compared with the untreated U87 GSLCs. Three genes, consisting of XPA, RAD50 and PPP1R15A, were selected from the 12 genes by gene functional searching and qPCR confirmatory studies, as these genes were considered to be potential targets for overcoming radioresistance. The expression of XPA, RAD50 and PPP1R15A is significantly increased in U87 and U251 radiation resistant GSLCs, indicating three potential targets for overcoming the radioresistance of GSLCs.