Knockdown of trem2 promotes proinflammatory microglia and inhibits glioma progression via the JAK2/STAT3 and NF-κB pathways.

BACKGROUND: In the tumor immune microenvironment (TIME), triggering receptor expressed on myeloid cells 2 (trem2) is widely considered to be a crucial molecule on tumor-associated macrophages(TAMs). Multiple studies have shown that trem2 may function as an immune checkpoint in various malignant tumors, mediating tumor immune evasion. However, its specific molecular mechanisms, especially in glioma, remain elusive. METHODS: Lentivirus was transfected to establish cells with stable knockdown of trem2. A Transwell system was used for segregated coculture of glioma cells and microglia. Western blotting, quantitative real-time polymerase chain reaction (qRT‒PCR), and immunofluorescence (IF) were used to measure the expression levels of target proteins. The proliferation, invasion, and migration of cells were detected by colony formation, cell counting kit-8 (CCK8), 5-ethynyl-2'-deoxyuridine (EdU) and transwell assays. The cell cycle, apoptosis rate and reactive oxygen species (ROS) level of cells were assessed using flow cytometry assays. The comet assay and tube formation assay were used to detect DNA damage in glioma cells and angiogenesis activity, respectively. Gl261 cell lines and C57BL/6 mice were used to construct the glioma orthotopic transplantation tumor model. RESULTS: Trem2 was highly overexpressed in glioma TAMs. Knocking down trem2 in microglia suppressed the growth and angiogenesis activity of glioma cells in vivo and in vitro. Mechanistically, knockdown of trem2 in microglia promoted proinflammatory microglia and inhibited anti-inflammatory microglia by activating jak2/stat1 and inhibiting the NF-κB p50 signaling pathway. The proinflammatory microglia produced high concentrations of nitric oxide (NO) and high levels of the proinflammatory cytokines TNF-α, IL-6, and IL-1ß, and caused further DNA damage and promoted the apoptosis rate of tumor cells. CONCLUSIONS: Our findings revealed that trem2 in microglia plays a significant role in the TIME of gliomas. Knockdown of trem2 in microglia might help to improve the efficiency of inhibiting glioma growth and delaying tumor progression and provide new ideas for further treatment of glioma.

PKM2 interacts with and phosphorylates PHB2 to sustain mitochondrial quality control against septic cerebral-cardiac injury.

Sepsis induces profound disruptions in cellular homeostasis, particularly impacting mitochondrial function in cardiovascular and cerebrovascular systems. This study elucidates the regulatory role of the Pyruvate Kinase M2 (PKM2)- Prohibitin 2 (PHB2) axis in mitochondrial quality control during septic challenges and its protective effects against myocardial and cerebral injuries. Employing LPS-induced mouse models, we demonstrate a significant downregulation of PKM2 and PHB2 in both heart and brain tissues post-sepsis, with corresponding impairments in mitochondrial dynamics, including fission, fusion, and mitophagy. Overexpression of PKM2 and PHB2 not only restores mitochondrial function, as evidenced by normalized ATP production and membrane potential but also confers resistance to oxidative stress by mitigating reactive oxygen species generation. These cellular mechanisms translate into substantial in vivo benefits, with transgenic mice overexpressing PKM2 or PHB2 displaying remarkable resistance to sepsis-induced cardiomyocyte and neuronal apoptosis, and organ dysfunction. Our findings highlight the PKM2-PHB2 interaction as a novel therapeutic target for sepsis, providing a foundation for future research into mitochondrial-based interventions to treat this condition. The study's insights into the molecular underpinnings of sepsis-induced organ failure pave the way for potential clinical applications in the management of sepsis and related pathologies.

The value of whole tumor apparent diffusion coefficient histogram parameters in predicting meningiomas progesterone receptor expression.

PURPOSE: This study investigated the value of whole tumor apparent diffusion coefficient (ADC) histogram parameters and magnetic resonance imaging (MRI) semantic features in predicting meningioma progesterone receptor (PR) expression. MATERIALS AND METHODS: The imaging, pathological, and clinical data of 53 patients with PR-negative meningiomas and 52 patients with PR-positive meningiomas were retrospectively reviewed. The whole tumor was outlined using Firevoxel software, and the ADC histogram parameters were calculated. The differences in ADC histogram parameters and MRI semantic features were compared between the two groups. The predictive values of parameters for PR expression were assessed using receiver operating characteristic curves. The correlation between whole-tumor ADC histogram parameters and PR expression in meningiomas was also analyzed. RESULTS: Grading was able to predict the PR expression in meningiomas (p = 0.012), though the semantic features of MRI were not (all p > 0.05). The mean, Perc.01, Perc.05, Perc.10, Perc.25, and Perc.50 histogram parameters were able to predict meningioma PR expression (all p < 0.05). The predictive performance of the combined histogram parameters improved, and the combination of grade and histogram parameters provided the optimal predictive value, with an area under the curve of 0.849 (95%CI: 0.766-0.911) and sensitivity, specificity, ACC, PPV, and NPV of 73.08%, 81.13%, 77.14%, 79.20%, and 75.40%, respectively. The mean, Perc.01, Perc.05, Perc.10, Perc.25, and Perc.50 histogram parameters were positively correlated with PR expression (all p < 0.05). CONCLUSION: Whole tumor ADC histogram parameters have additional clinical value in predicting PR expression in meningiomas.

Bisphenol A: Unveiling Its Role in Glioma Progression and Tumor Growth.

Gliomas represent the most common and lethal category of primary brain tumors. Bisphenol A (BPA), a widely recognized endocrine disruptor, has been implicated in the progression of cancer. Despite its established links to various cancers, the association between BPA and glioma progression remains to be clearly defined. This study aimed to shed light on the impact of BPA on glioma cell proliferation and overall tumor progression. Our results demonstrate that BPA significantly accelerates glioma cell proliferation in a time- and dose-dependent manner. Furthermore, BPA has been found to enhance the invasive and migratory capabilities of glioma cells, potentially promoting epithelial-mesenchymal transition (EMT) characteristics within these tumors. Employing bioinformatics approaches, we devised a risk assessment model to gauge the potential glioma hazards associated with BPA exposure. Our comprehensive analysis revealed that BPA not only facilitates glioma invasion and migration but also inhibits apoptotic processes. In summary, our study offers valuable insights into the mechanisms by which BPA may promote tumorigenesis in gliomas, contributing to the understanding of its broader implications in oncology.

EEF1E1 promotes glioma proliferation by regulating cell cycle through PTEN/AKT signaling pathway.

The cell cycle, a pivotal regulator of cell proliferation, can be significantly influenced by the phosphatase and tensin homolog (PTEN)/AKT signaling pathway's modulation of cyclin-related proteins. In our study, we discovered the crucial role of EEF1E1 in this process, as it appears to downregulate PTEN expression. Furthermore, our findings affirmed that EEF1E1 modulates downstream cell cycle-related proteins by suppressing the PTEN/AKT pathway. Cell cycle assay results revealed that EEF1E1 downregulation stunted the advancement of glioma cells in both the G1 and S phases. A suite of assays-Cell Counting Kit-8, colony formation, and ethyl-2'-deoxyuridine-substantiated that the EEF1E1 downregulation markedly curtailed glioma proliferation. We further validated this phenomenon through animal studies and coculture experiments on brain slices. Our comprehensive investigation indicates that EEF1E1 knockdown can effectively inhibit the glioma cell proliferation by regulating the cell cycle via the PTEN/AKT signaling pathway. Consequently, EEF1E1 emerges as a potential therapeutic target for glioma treatment, signifying critical clinical implications.

Mitochondrial subtype MB-G3 contains potential novel biomarkers and therapeutic targets associated with prognosis of medulloblastoma.

BACKGROUND: Medulloblastoma is the most common malignant brain tumor in children. There are four groups, each with different causal mutations, affected pathways and prognosis. Here, we investigated the role of mitochondria in medulloblastoma and whether there are differences between the different groups. METHODS: We compared the gene expression levels in the four different medulloblastoma groups (MB-WNT, MB-SHH, MB-G3 and MB-G4), with the focus on genes associated with mitochondria. We used several tools including Salmon, Tximeta, DESeq2, BiomaRt, STRING, Ggplot2, EnhancedVolcano, Venny 2.1 and Metscape. RESULTS: A total of 668 genes were differentially expressed and the most abundant genes were associated with cell division pathway followed by modulation of chemical synaptic transmission. We also identified several genes (ABAT, SOX9, ALDH5A, FOXM1, ABL1, NHLH1, NEUROD1 and NEUROD2) known to play vital role in medulloblastoma. Comparative expression analysis revealed OXPHOS complex-associated proteins of mitochondria. The most significantly expressed genes in the MB-SHH and MB-G4 groups were AHCYL1 and SFXN5 while PAICS was significantly upregulated in MB-WNT group. Notably, MB-G3 contained the most downregulated genes from the OXPHOS complexes, except COX6B2 which was strongly upregulated. CONCLUSIONS: We show the importance of mitochondria and compare their role in the four different medulloblastoma groups.

CircRNA-104718 promotes glioma malignancy through regulation of miR-218-5p/HMGB1 signalling pathway.

Increasing number of studies have proven that circular RNAs (circRNAs) play a major role in the biological processes of many different cancers, including glioma, especially as competitive molecular sponges of microRNAs (miRNAs). However, the clear molecular mechanism of the circRNA network in glioma is still not well understood. The expression level of circRNA-104718 and microRNA (miR)-218-5p in glioma tissues and cells were detected by quantitative real-time polymerase chain reaction (qRT-PCR). The target protein's expression level was assessed by western blotting. Bioinformatics systems were used to predict the possible microRNAs and target genes of circRNA-104718, after which dual-luciferase reporter assays were used to confirm the predicted interactions. The proliferation, invasion, migration and apoptosis of glioma cells were detected by CCK, EdU, transwell, wound-healing and flow cytometry assays. CircRNA-104718 was upregulated in human glioma tissues, and a higher level of circRNA-104718 indicated poorer outcomes in glioma patients. In contrast, in glioma tissues, miR-218-5p was downregulated. Knockdown of circRNA-104718 suppressed migration and invasion while boosting the apoptosis rate of glioma cells. In addition, the upregulation of miR-218-5p in glioma cells caused the same suppression. Mechanistically, circRNA-104718 inhibited the protein expression level of high mobility group box-1 (HMGB1) by acting as a molecular sponge for miR-218-5p. CircRNA-104718 is a suppressive factor in glioma cells and might represent a new target for the treatment of glioma patients. CircRNA-104718 modulates glioma cell proliferation through the miR-218-5p/HMGB1 signalling axis. CircRNA-104718 provides a possible mechanism for understanding the pathogenesis of glioma.

The effects of nurse driven mobility intervention (NDMI) on activities of daily living, mobility, fear of falling, and balance performance in hospitalized older patients: A pilot study.

A decrease in mobilization during hospitalization leads to a decline in physical function for older patients, and nurses play a critical role in mobility promotion. The purpose of this pilot study was to examine the feasibility of Nurse Driven Mobility Intervention (NDMI) in improving activities of daily living, mobility, fear of falling, balance performance, and maladaptive fall risk appraisal using a one-group pretest-posttest design. NDMI incorporates a multidisciplinary care team, early assessment, timely and frequent mobilization, and constant encouragement. A post-intervention interview was also conducted to explore the barriers and facilitators for mobilization during hospitalization. The result shows a significant improvement in balance performance.

CircTCF25 serves as a sponge for miR-206 to support proliferation, migration, and invasion of glioma via the Jak2/p-Stat3/CypB axis.

Glioma is the most common primary malignant intracranial tumor in humans, and glioblastoma (GBM) has been associated with a more aggressive histology and poorer prognosis. There is growing evidence that circular RNAs (circRNAs) are involved in the progression of various malignancies; however, the role and molecular mechanism of circRNAs in glioma remain elusive. In the present study, we screened for differentially expressed circRNAs in gliomas by using a bioinformatics method. Significant upregulation in glioma tissues was verified by quantitative real-time polymerase chain reaction (qRT-PCR), and the prognostic value was evaluated. The potential oncogenic role of circular RNA TCF25 (circTCF25) in glioma was assessed both in vivo and in vitro. Bioinformatics analysis and luciferase reporter assays confirmed the interaction among circTCF25, microRNA-206 (miR-206), and its target gene Cyclophilin B (CypB). circTCF25 was predominantly located in the cytoplasm; the combination of mir-206 and circTCF25 reverses the effects of knockdown of circTCF25 on the proliferation, migration, invasion, and tumorigenesis of glioma cells. Competitive binding between circTCF25 and miR-206 mainly upregulates target gene CypB expression by preventing its inhibition of the Jak2/p-stat3 pathway. In addition, knockdown of circTCF25 reduced CypB expression by inhibiting JAK2/p-stat3, which was rescued by treatment with a miR-206 inhibitor. In summary, our findings demonstrate that the circTCF25/miR-206/CypB axis plays a vital role in glioma progression, migration, invasion, and tumorigenesis.

Modified Burr-Hole Craniostomy for the Treatment of Chronic Subdural Hematoma in Adults.

BACKGROUND: Burr-hole craniostomy (BHC) is considered to be the most effective method for the treatment of chronic subdural hematoma (CSDH), and middle meningeal artery embolization is a new therapy used in clinical practice in recent years to treat CSDH. However, the optimal therapeutic effect of these 2 procedures is still controversial. This study prospectively designed a modified burr-hole craniostomy (mBHC) with drainage to treat CSDH. METHODS: A total of 101 patients diagnosed with CSDH from January 2019 to April 2020 were prospectively included in this study. They were divided into BHC and mBHC groups. Among them, 40 selected CSDH patients received mBHC treatment. For comparison, 61 CSDH patients who received BHC treatment were used as the control group. Primary outcomes were hematoma recurrence and postoperative complications. Secondary outcomes included midline recovery, hematoma clearance, operation time, and hospital stay. The Chi-square test was used to compare the 6-month follow-up results between the 2 groups. RESULTS: Among patients treated with mBHC, 39 patients had a good prognosis, and one 87-year-old patient with bilateral hematoma died of postoperative heart failure. Of the patients treated with BHC, 52 patients had good prognoses, and one 53-year-old patient with unilateral hematoma died of postoperative acute intracranial bleeding. During the 6-month follow-up period, no relapse occurred in the patients treated with mBHC, whereas 8 (13%) of the patients treated with BHC relapsed. There was a significant difference in the recurrence rate between the 2 groups (P < 0.05). In addition, midline recovery, hematoma clearance rate, operation time, and complications were found to be significantly different statistically (P < 0.05), and other characteristics of operation and outcome were not significantly different (P > 0.05) between the 2 groups. CONCLUSIONS: Modified burr-hole craniostomy has a positive therapeutic effect on patients with CSDH and is more effective than conventional BHC therapy.

The Inhibitory Effect of miR-345 on Glioma Progression Is Closely Related to circRNA-hsa_circ_0073237 and HDGF.

Glioma is the most common primary malignant tumor of the central nervous system and has a poor prognosis. Therefore, exploring the key molecular targets is a new opportunity for basic research and clinical treatment of glioma. Previous studies found that circRNA-hsa_circ_0073237 was upregulated in gliomas. Our further analyses of the biological function and molecular mechanism of hsa_circ_0073237 showed that hsa_circ_0073237 was also upregulated in glioma cell lines and could combine with miR-345 to inhibit its expression. miR-345 was downregulated in glioma tissues and cells, and targeted to regulate the expression of hepatoma-derived growth factor (HDGF), while HDGF expression was enhanced in glioma. Hsa_circ_0073237 promoted the expression of HDGF in glioma cells by adsorbing miR-345. Hsa_circ_0073237 siRNA, miR-345, and HDGF siRNA effectively inhibited cell viability and invasion and promoted cell apoptosis. When expression of hsa_circ_0073237 and miR-345 was inhibited simultaneously, cell viability, apoptosis, and invasion did not change significantly; however, after transfection with HDGF overexpression vector, the effects of hsa_circ_0073237 siRNA and miR-345 on glioma cell viability, apoptosis, and invasion were obviously reversed. Further construction of glioma xenograft models in nude mice confirmed that the introduction of miR-345 in vivo effectively inhibited tumor growth, significantly reduced tumor diameter and weight, and obviously decreased the expression of HDGF. Therefore, hsa_circ_0073237 can regulate the biological functions of glioma cells through miR-345/HDGF, thereby affecting the progression of tumors, indicating that the hsa_circ_0073237/miR-345/HDGF pathway may be a key target for the treatment of glioma.

Inhibition of fruit softening by cold plasma treatments: affecting factors and applications.

Softening is a common phenomenon of texture changes associated with plant cell walls, inducing a decrease in the quality of fruit. Inhibiting the softening is effective to extend the shelf life of fruit. Cold plasma (CP), as a novel nonthermal technology, has been applied to keep the freshness of the fruit. This review centers on applying cold plasma treatments to the inhibition of fruit softening. Different pathways for inhibiting fruit softening by CP treatments, including maintenance of fruit firmness, reduction in the activities of enzymes, inactivation of fungal pathogens and lowering of respiration rates, are discussed. The biochemistry of fruit softening and the fundamental of cold plasma are also presented. In general, among all postharvest technologies, cold plasma is a promising method with many advantages, showing great potential in maintaining the quality and inhibiting the softening of the fruit. Future work should focus on process optimization to achieve better results in maintaining fruit freshness, and commercial applications of cold plasma technology should also be explored.

SLC1A2 mediates refractory temporal lobe epilepsy with an initial precipitating injury by targeting the glutamatergic synapse pathway.

This study aimed to identify the genes related to epilepsy and their effects on epilepsy, as well as the underlying mechanism. Using microarray analysis, differentially expressed genes (DEGs) were screened out and then used to build weighted gene coexpression networks using WGCNA. Module membership and evaluation of gene significance (GS) were adopted to detect hub genes. The DAVID online tool was used to understand the function of modules and target genes. The Licl-pilocarpine chronic rat epilepsy model was used to simulate mesial temporal lobe epilepsy with an initial precipitating injury. Hippocampal expression of the proteins solute carrier family 1 member 2 (SLC1A2), glial fibrillary acidic protein, interleukin-1ß (IL-1ß), tumor necrosis factor α (TNF-α), and N-methyl-d-aspartic acid receptor (NMDAR) was determined by ELISA and Western blot. Nissl staining was used to measure neuronal loss. Immunohistochemistry was performed to assess the percentage of positive cells to reflect the distribution of NMDAR1. Here, 3232 potential genes highly correlated with epilepsy were selected from the screened DEGs, among which SLC1A2 was related to brain development and its expression was significantly decreased in epilepsy patients. According to Gene Ontology and KEGG analysis, SLC1A2 mediates epilepsy through the glutamatergic synapse pathway. Tissue experiments suggested that Slc1a2 could genuinely ameliorate epilepsy through the glutamatergic synapse pathway, mitigate neuronal loss, and suppress astrocytosis and inflammatory responses. Our study suggested that low hippocampal content of SLC1A2 is a potential biomarker of epilepsy and may affect the function of neurons through the glutamatergic synapse pathway. © 2018 IUBMB Life, 71(1):213-222, 2019.

Emergence of a Complete Heavy-Quark Spin Symmetry Multiplet: Seven Molecular Pentaquarks in Light of the Latest LHCb Analysis.

A recent analysis by the LHCb Collaboration suggests the existence of three narrow pentaquarklike states-the P_{c}(4312), P_{c}(4440), and P_{c}(4457)-instead of just one in the previous analysis [the P_{c}(4450)]. The closeness of the P_{c}(4312) to the D[over ¯]Σ_{c} threshold and the P_{c}(4440) and P_{c}(4457) to the D[over ¯]^{*}Σ_{c} threshold suggests a molecular interpretation of these resonances. We show that these three pentaquarklike resonances can be naturally accommodated in a contact-range effective field theory description that incorporates heavy-quark spin symmetry. This description leads to the prediction of all the seven possible S-wave heavy antimeson-baryon molecules [that is, there should be four additional molecular pentaquarks in addition to the P_{c}(4312), P_{c}(4440), and P_{c}(4457)], providing the first example of a heavy-quark spin symmetry molecular multiplet that is complete. If this is confirmed, it will not only give us an impressive example of the application of heavy-quark symmetries and effective field theories in hadron physics, it will also uncover a clear and powerful ordering principle for the molecular spectrum, reminiscent of the SU(3)-flavor multiplets to which the light hadron spectrum conforms.

The quality assessment of clinical practice guidelines for intracranial aneurysms: a systematic appraisal.

Intracranial aneurysms are common in adults. The relevant guidelines for patients with intracranial aneurysms aim to standardize the clinical practice and decision making for these patients. However, their management is controversial, and the quality of the guidelines has not been assessed. We aim to evaluate the quality of the guidelines for intracranial aneurysms as well as to compare and analyze the recommendations between different guidelines. Systematic searches were conducted to identify the guidelines for intracranial aneurysms from general electronic and guideline databases. Two independent reviewers identified the guidelines and extracted the data, and four reviewers independently evaluated the eligible guidelines through the AGREE II tool. Agreement among reviewers was measured using the intraclass correlation coefficient. A total of 12 guidelines, which were published from 1997 to 2016, were included. The agreement among reviewers was high (intraclass correlation coefficient, 0.85 (95% CI: 0.8-0.89)). The mean scores of six domains ranged from 16.5 to 57.5% (scope and purpose 57.5% (39-68%); stakeholder 30.8% (19-46%); rigor 31.9% (19-52%); clarity 57.2% (42-79%); applicability 24.9% (16-42%); and editorial independence: 16.5% (0-58%)). Furthermore, 202 recommendations related to intracranial aneurysms were collected from the included guidelines. Of these, 143 reported the quality of evidence and/or strength, and 119 reported both the quality of evidence and the strength. Of the 119 recommendations, there were six class A and 20 class B recommendations based on level III evidence. There were 12 recommendations in which the contents were similar between different guidelines and two recommendations with the opposite contents. The AGREE II scores of the guidelines for intracranial aneurysms were relatively low. The majority of recommendations were rated as classes A and B and based on levels II and III evidence. Approximately a fifth of strong recommendations was based on a low quality of evidence without interpretation or explanation.

Defining optimal cutoff value of MGMT promoter methylation by ROC analysis for clinical setting in glioblastoma patients.

Resistance to temozolomide (TMZ) chemotherapy poses a significant challenge in the treatment of glioblastoma (GBM). Hypermethylation in O6-methylguanine-DNA methyltransferase (MGMT) promoter is thought to play a critical role in this resistance. Pyrosequencing (PSQ) has been shown to be accurate and robust for MGMT promoter methylation testing. The unresolved issue is the determination of a cut-off value for dichotomization of quantitative MGMT PSQ results into "MGMT methylated" and "MGMT unmethylated" patient subgroups as a basis for further treatment decisions. In this study, receiver operating characteristic (ROC) curve analysis was used to identify an optimal cutoff of MGMT promoter methylation by testing mean percentage of methylation of 4 CpG islands (76-79) within MGMT exon 1. The area under the ROC (AUC) as well as the best cutoff to classify the methylation were calculated. Positive likelihood ratio (LR+) was chosen as a diagnostic parameter for defining an optimal cut-off. Meanwhile, we also analyzed whether mean percentage of methylation at the investigated CpG islands could be regarded as a marker for evaluating prognostication. ROC analysis showed that the optimal threshold was 12.5% (sensitivity: 60.87%; specificity: 76%) in response to the largest LR+ 2.54. 12.5% was established to distinguish MGMT promoter methylation, which was confirmed using validation set. According to the cutoff value, the MGMT promoter methylation was found in 58.3% of GBM. Mean methylation level of the investigated CpG sites strong correlated with overall survival (OS), which means GBM patients with a high level of methylation survived longer than those with low level of methylation(log-rank test, P = 0.017). In conclusion, ROC curve analysis enables the best cutoff for discriminating MGMT promoter methylation status. LR+ can be used as a key factor that evaluates cutoff. The promoter methylation level of MGMT by PSQ in GBM patients had prognostic value.

Myeloperoxidase Nuclear Imaging for Epileptogenesis.

PURPOSE: To determine if myeloperoxidase (MPO) is involved in epileptogenesis and if molecular nuclear imaging can be used to noninvasively map inflammatory changes in epileptogenesis. MATERIALS AND METHODS: The animal and human studies were approved by the institutional review boards. Pilocarpine-induced epileptic mice were treated with 4-aminobenzoic acid hydrazide (n = 46), a specific irreversible MPO inhibitor, or saline (n = 42). Indium-111-bis-5-hydroxytryptamide-diethylenetriaminepentaacetate was used to image brain MPO activity (n = 6 in the 4-aminobenzoic acid hydrazide and saline groups; n = 5 in the sham group) by using single photon emission computed tomography/computed tomography. The role of MPO in the development of spontaneous recurrent seizures was assessed by means of clinical symptoms and biochemical and histopathologic data. Human brain specimens from a patient with epilepsy and a patient without epilepsy were stained for MPO. The Student t test, one-way analysis of variance, and Mann-Whitney and Kruskal-Wallis tests were used. Differences were regarded as significant if P was less than .05. RESULTS: MPO and leukocytes increased in the brain during epileptogenesis (P < .05). Blocking MPO delayed spontaneous recurrent seizures (99.6 vs 142 hours, P = .016), ameliorated the severity of spontaneous recurrent seizures (P < .05), and inhibited mossy fiber sprouting (Timm index, 0.31 vs 0.03; P = .003). Matrix metalloproteinase activity was upregulated during epileptogenesis in an MPO-dependent manner (1.44 vs 0.94 U/mg, P = .049), suggesting that MPO acts upstream of matrix metalloproteinases. MPO activity was mapped during epileptogenesis in vivo in the hippocampal regions. Resected temporal lobe tissue from a human patient with refractory epilepsy but not the temporal lobe tissue from a patient without seizures demonstrated positive MPO immunostaining, suggesting high translational potential for this imaging technology. CONCLUSION: The findings of this study highlight an important role for MPO in epileptogenesis and show MPO to be a potential therapeutic target and imaging biomarker for epilepsy.

Endoscopic decompression of the optic canal for traumatic optic neuropathy.

PURPOSE: Traumatic optic neuropathy (TON) is a serious complication of head trauma with the incidence rate of 0.5%-5%. The aim of this study was to investigate the therapeutic efficacy of endoscopic decompression of the optic canal for optic nerve injuries. METHODS: In this study, 11 patients treated in our hospital from January 2009 to January 2015 with the visual loss resulting from TON were retrospectively reviewed for preoperative vision, visual evoked potential (VEP) scan, surgical approach, postoperative visual acuity, complications, and follow-up results. RESULTS: All these patients received endoscopic decompression of the optic canal. At the 3-month follow- up, the visual acuity improvement rate of the 11 patients was 45.5%. The vision acuity of 2 cases improved from hand movement to 0.08 and 0.3 after operation. Another patient's vision acuity returned to 0.05 compared to light sensation preoperatively. Two cases had finger counting before surgery but they had a vision acuity of 0.4 and light sensation respectively after surgery. However, the other 6 cases' vision did not improve after surgery. CONCLUSION: Endoscopic decompression of the optic canal is an effective way to cure TON. VEP could be used as an important reference for preoperative and prognosis evaluation. Operative time after trauma is only a relative condition that may affect the therapeutic effect of optic canal decompression. Poor results of this procedure may be related to the severity of the optic nerve injury.

Quality appraisal of clinical practice guidelines on glioma.

Clinical practice guidelines (CPGs) play an important role in healthcare. The guideline development process should be precise and rigorous to ensure that the results are reproducible and not vague. To determine the quality of guidelines, the Appraisal of Guidelines and Research and Evaluation (AGREE) instrument was developed and introduced. The aim of the present study was to assess the methodological quality of clinical practice guidelines on glioma. Eight databases (including MEDLINE and Embase) were searched till to August, 2013. The methodological quality of the guidelines was assessed by four authors independently using the AGREE II instrument. Fifteen relevant guidelines were included from 940 citations. The overall agreement among reviewers was moderate (intra-class correlation coefficient = 0.83; 95% confidence interval [CI], 0.66-0.92). The mean scores were moderate for the domains "scope and purpose" (59.54) and "clarity of presentation" (65.46); however, there were low scores for the domains "stakeholder involvement" (43.80), "rigor of development" (39.01), "applicability" (31.89), and "editorial independence" (30.83). Only one third of the guidelines described the systematic methods for searching, and nearly half of the (47%) guidelines did not give a specific recommendation. Only four of 15 described a procedure for updating the guideline; meanwhile, just six guidelines in this field can be considered to be evidence-based. The quality and transparency of the development process and the consistency in the reporting of glioma guidelines need to be improved. And the quality of reporting of guidelines was disappointing. Many other methodological disadvantages were identified. In the future, glioma CPGs should be based on the best available evidence and rigorously developed and reported. Greater efforts are needed to provide high-quality guidelines that serve as a useful and reliable tool for clinical decision-making in this field.

Extracellular vesicles: Mediators of microenvironment in hypoxia-associated neurological diseases.

Hypoxia is a prevalent characteristic of numerous neurological disorders including stroke, Alzheimer's disease, and Parkinson's disease. Extracellular vesicles (EVs) are minute particles released by cells that contain diverse biological materials, including proteins, lipids, and nucleic acids. They have been implicated in a range of physiological and pathological processes including intercellular communication, immune responses, and disease progression. EVs are believed to play a pivotal role in modulating the microenvironment of hypoxia-associated neurological diseases. These EVs are capable of transporting hypoxia-inducible factors such as proteins and microRNAs to neighboring or remote cells, thereby influencing their behavior. Furthermore, EVs can traverse the blood-brain barrier, shielding the brain from detrimental substances in the bloodstream. This enables them to deliver their payload directly to the brain cells, potentially intensifying the effects of hypoxia. Nonetheless, the capacity of EVs to breach the blood-brain barrier presents new opportunities for drug delivery. The objective of this study was to elucidate the role of EVs as mediators of information exchange during tissue hypoxia, a pathophysiological process in ischemic stroke and malignant gliomas. We also investigated their involvement in the progression and regression of major diseases of the central nervous system, which are pertinent to the development of therapeutic interventions for neurological disorders.