Integrative analysis of expression profile indicates the ECM receptor and LTP dysfunction in the glioma-related epilepsy.

BACKGROUND: Seizures are a common symptom in glioma patients, and they can cause brain dysfunction. However, the mechanism by which glioma-related epilepsy (GRE) causes alterations in brain networks remains elusive. OBJECTIVE: To investigate the potential pathogenic mechanism of GRE by analyzing the dynamic expression profiles of microRNA/ mRNA/ lncRNA in brain tissues of glioma patients. METHODS: Brain tissues of 16 patients with GRE and 9 patients with glioma without epilepsy (GNE) were collected. The total RNA was dephosphorylated, labeled, and hybridized to the Agilent Human miRNA Microarray, Release 19.0, 8 × 60 K. The cDNA was labeled and hybridized to the Agilent LncRNA + mRNA Human Gene Expression Microarray V3.0, 4 × 180 K. The raw data was extracted from hybridized images using Agilent Feature Extraction, and quantile normalization was performed using the Agilent GeneSpring. P-value < 0.05 and absolute fold change > 2 were considered the threshold of differential expression data. Data analyses were performed using R and Bioconductor. RESULTS: We found that 3 differentially expressed miRNAs (miR-10a-5p, miR-10b-5p, miR-629-3p), 6 differentially expressed lncRNAs (TTN-AS1, LINC00641, SNHG14, LINC00894, SNHG1, OIP5-AS1), and 49 differentially expressed mRNAs play a vitally critical role in developing GRE. The expression of GABARAPL1, GRAMD1B, and IQSEC3 were validated more than twofold higher in the GRE group than in the GNE group in the validation cohort. Pathways including ECM receptor interaction and long-term potentiation (LTP) may contribute to the disease's progression. Meanwhile, We built a lncRNA-microRNA-Gene regulatory network with structural and functional significance. CONCLUSION: These findings can offer a fresh perspective on GRE-induced brain network changes.

Mir-139-5p inhibits glioma cell proliferation and progression by targeting GABRA1.

Glioma is an extremely aggressive malignant neoplasm of the central nervous system. MicroRNA (miRNA) are known to bind to specific target mRNA to regulate post-transcriptional gene expression and are, therefore, currently regarded as promising biomarkers for glioma diagnosis and prognosis. The aim of the present study was to examine the pathogenesis and potential molecular markers of glioma by comparing the differential expression of miRNA and mRNA between glioma tissue and peritumor brain tissue. We explored the impact of screened core miRNA and mRNA on cell proliferation, invasion, and migration of glioma. An miRNA expression profile dataset (GSE90603) and a transcriptome profile dataset (GSE90598) were downloaded from combined miRNA-mRNA microarray chips in the Gene Expression Omnibus (GEO) database. Overall, 59 differentially expressed miRNAs (DEMs) and 419 differentially expressed genes (DEGs) were identified using the R limma software package. FunRich software was used to predict DEM target genes and miRNA-gene pairs, and Perl software was used to find overlapping genes between DEGs and DEM target genes. There were 129 overlapping genes regulated by nine miRNAs between target genes of the DEMs and DEGs. The Chinese Glioma Genome Atlas(CGGA) was analyzed in order to identify miRNAs with diagnostic and prognostic significance. MiR-139-5p, miR-137, and miR-338-3p were validated to be significantly linked to prognosis in glioma patients. Finally, we validated that miR-139-5p affected glioma malignant biological behavior via targeting gamma-aminobutyric acid A receptor alpha 1(GABRA1) through rescue experiments. Low miR-139-5p expression was correlated with survival probability and World Health Organization (WHO) grade. MiR-139-5p overexpression inhibited cell proliferation, migration, and invasion of glioma in vitro. GABRA1 was identified as a functional downstream target of miR-139-5p. Decreased GABRA1 expression was related to similar biological roles as miR-139-5p overexpression while upregulation of GABRA1 effectively reversed the inhibition effects of miR-139-5p. These results demonstrate a novel axis for miR-139-5p/GABRA1 in glioma progression and provide potential prognostic predictors and therapeutic target for glioma patients.

Superconductivity in Co-Layered LaCoSi.

It is known that few Co-based superconducting compounds have been found compared with their Fe- or Ni-based counterparts. In this study, we have found superconductivity of 4 K in the LaCoSi compound for the first time. The combined analysis of neutron and synchrotron X-ray powder diffractions reveals that LaCoSi exhibits an isostructure with the known Fe-based LiFeAs superconductor, which is the first "111" Co-based superconductor. First-principles calculation shows that LaCoSi presents a quasi-two-dimensional band structure that is also similar to that of LiFeAs. The small structural distortion may be more conducive to the emergence of superconductivity in the LaCoSi compound, which provides a direction for finding new Co-based superconducting compounds.

Correlation of Tunable CoSi4 Tetrahedron with the Superconducting Properties of LaCoSi.

It is known that as the FeAs4 tetrahedron in the Fe-based superconductor is close to the regular tetrahedron, critical temperature (Tc) can be greatly increased. Recently, a Co-based superconductor of LaCoSi (4 K) with "111" structure was found. In this work, we improve the Tc of LaCoSi through structural regulation. Tc can be increased by the chemical substitution of Co by Fe, while the superconductivity is suppressed by the Ni substitution. The combined analysis of neutron and synchrotron X-ray powder diffractions reveals that the change of the Si-Co-Si bond angles of the CoSi4 tetrahedron is possibly responsible for the determination of superconducting properties. The Fe chemical substitution is favorable for the formation of the regular tetrahedron of CoSi4. The present new Co-based superconductor of LaCoSi provides a possible method to enhance the superconductivity performance of the Co-based superconductors via controlling Co-based tetrahedra similar to those well established in the Fe-based superconductors.

Functional Roles of Long Non-Coding RNAs (LncRNAs) in Glioma Stem Cells.

Glioma, the most common and aggressive type of brain tumor, has a poor prognosis. Glioma stem cells (GSCs) are thought to be responsible for glioma genesis, proliferation, resistance to chemoradiotherapy, and recurrence. Long non-coding RNAs (lncRNAs) have been viewed as a prospective novel target in glioma therapy in recent years due to their functional roles in GSC biological processes. However, how lncRNAs interact with GSCs and the underlining mechanisms associated with these interactions are not yet clear. In this review, we briefly illustrate recent advancements in the functional roles of lncRNA and their potential mechanisms in GSCs.

[Survival analysis for high-grade glioma patients who received comprehensive treatment].

OBJECTIVE: To analyze the curative effect and prognostic factors for comprehensive therapy in patients with high-grade glioma.
 Methods: Patients with high-grade glioma (WHO grade III, grade IV) were chosen from July 2008 to May 2016 in the Hunan Cancer Hospital, and a retrospective analysis was performed in 64 patients with complete follow-up data.
 Results: The follow-up time was 3-111 (median 29.5) months, the median overall survival time was 36.00 (95% CI 22.85 to 49.16) months, the median progression-free survival time (PFS) was 21.00 (95% CI 9.72 to 32.28) months. The 1-year, 2-year, 3-year and 5-year survival rates of high-grade glioma patients were 87.50%, 56.25%, 40.63% and 17.19%, respectively. The univariate analysis of Log-Rank test and the Cox regression model analysis showed that the prognostic factors related to the prognosis of high-grade glioma patients were pathological grade, resection degree, and concurrent chemo-radiotherapy (P<0.05).
 Conclusion: The overall survival time, progression-free survival time and the 5-year survival rate of patients with high-grade glioma after comprehensive treatment is partially improved. The factors relevant to the prognosis of patients with high-grade glioma are pathological grade, resection degree, and concurrent chemo-radiotherapy, indicating that the glioma patients (WHO grade III) received total resection of the tumor and concurrent chemo-radiotherapy have better clinical effect.

The Autophagy Level Is Increased in the Synovial Tissues of Patients with Active Rheumatoid Arthritis and Is Correlated with Disease Severity.

Rheumatoid arthritis (RA) is a complex and not fully understood autoimmune disease associated with multijoint damage. The main effector cells, the synovial fibroblasts, are apoptosis resistant and hyperplastic which indicate that autophagy level is high in synovial tissue. Real-time PCR, immunocytochemistry, and western blotting were used in this paper to study the autophagy status of the synovial tissues obtained from RA and OA patients at the time of joint replacement surgery. We further evaluated the correlation between autophagy levels with RA activity-associated serum markers with SPSS. The results showed that the expression levels (both in mRNA and in protein level) of autophagy-related proteins (belcin1, Atg5, and LC3) in the synovial tissue of patients with active rheumatoid arthritis (n = 20) were significantly higher than those in OA patients (n = 16). We further showed that the LC3-II/ß-actin relative gray value was strongly correlated with the serum levels of several RA activity-related markers: CRP, ESR, CCP, and RF. Our results indicate that evaluating the autophagy level of synovial biopsies might be a useful way to diagnose RA and to estimate the disease activity. Reducing the expression level of autophagy-related genes might become a new therapeutic target for active rheumatoid arthritis.

[The Molluscicidal Effect of Chlorosalicylicamide Sustained-release Granules on Oncomelania hupensis].

Objective: To evaluate the molluscicidal effect of the chlorosalicylicamide sustained-release granules (LDS-SRG) on Oncomelania hupensis. Methods: Seven effective concentrations or dosages of LDS-SRG, 0.1, 0.2, 0.4, 0.8, 1.6, 3.2 and 6.4 mg/L （for immersion test） or g/m2（for spraying test）, were prepared from the original 5% and 10% concentrations or dosages in the laboratory. In the immersion test, each concentration of LDS-SRG was incubated with 3 packs of snails（30 snails in each pack）, and each pack was taken for snail counting at 24, 48 and 72 h respectively. In the spraying test, each dosage of LDS-SRG was applied to 200 snails, and the snail mortality was calculated in 50 randmoly collected snails on days 3 and 7, and in the whole on day 14 after administration. In the field immersion test, LDS-SRG at concentrations of 0.4, 0.8 and 1.6 g/m3 was incubated with 6 packs of snails （30 snails in each pack）, and each 2 packs were taken at 24, 48, and 72 h to calculate the snail mortality. In the field spraying test, 0.8, 1.6 and 3.2 g/m2 LDS-SRG was sprayed in 3 snail-positive ditches （～100 m2）, and 10 boxes of snails were selected in each ditch on days 3, 7 and 14 to calculate the snail mortality. The 50% wettable powder of niclosamide ethanolamine salt （WPN） with effective concentrations or dosages of 1.0 mg/L （or g/m2 and g/m3） was used as the positive control. Fresh water served as the blank control. Results: In the labratory immersion test using the original concentration of 5%, both 0.1-6.4 mg/L LDS-SRG for 72 h and 1.6-6.4 mg/L LDS-SRG for 48 h caused 100% mortality; and the concentration lethal to 50% （LC50） at 24, 48 and 72 h was 0.70, 0.01 and 0.01 mg/L respectively. When using the original concentration of 10%, both 0.1-6.4 mg/L LDS-SRG for 72 h and 0.2-6.4 mg/L LDS-SRG for 48 h caused 100% mortality; and the LC50 at 24, 48 and 72 h was 0.15, 0.01 and 0.01 mg/L respectively. The labratory spraying test showed that 7-day administration of 1.6 and 6.4 g/m2 LDS-SRG as well as 14-day administration of 3.2 and 6.4 g/m2 LDS-SRG prepared from 5% dosage, resulted in a snail mortality>95%, with the LD50 on days 3, 7 and 14 being 0.06, 0.16, and 0.18 g/m2; 14-day administration of 1.6 g/m2 LDS-SRG as well as 7-day administration of 6.4 g/m2 LDS-SRG prepared from 10% dosage, resulted in a snail mortality>95%, with the LD50 on days 3, 7 and 14 being 3.29, 0.75, and 0.16 g/m2. The mortality by various dosages of LDS-SRG prepared from 5% dosage was significantly higher than that of the control group (P<0.05). In the field immersion test, the snail mortality by 1.6 g/m3 LDS-SRG prepared from 5% and 10% concentrations for 72 h was 96.43% and 98.21% respectively (P>0.05 versus the control group). In the field spraying test, the snail mortality by 3.2 g/m2 LDS-SRG prepared from 5% dosage for 3, 7 and 14 days was 93.99%, 91.18% and 86.48% respectively, and that from 10% dosage was 94.95%, 93.50% and 85.43%, all significantly higher than that of the control group （82.83%, 72.38% and 48.38%）（P<0.05）; the snail mortality by 0.8 g/m2 LDS-SRG prepared from 5% dosage for 14 days（66.51%） and that by 1.6 g/m2 LDS-SRG prepared from 5% dosage for 3 days（84.61%） were both significantly higher than that by 10% LDS-SRG（20.13% and 43.06%） （P<0.05）. Conclusion: The 5% and 10% LDS-SRG used separately in the immersion test and the spraying test both meet the requirements of the national standard of Efficacy Test Methods and Evaluation of Molluscicide for Pesticide Registration.

Non-neuronal and neuronal BACE1 elevation in association with angiopathic and leptomeningeal ß-amyloid deposition in the human brain.

BACKGROUND: Cerebral amyloid angiopathy (CAA) refers to the deposition of ß-amyloid (Aß) peptides in the wall of brain vasculature, commonly involving capillaries and arterioles. Also being considered a part of CAA is the Aß deposition in leptomeninge. The cellular origin of angiopathic Aß and the pathogenic course of CAA remain incompletely understood. METHODS: The present study was aimed to explore the pathogenic course of CAA in the human cerebrum via examination of changes in ß-secretase-1 (BACE1), the obligatory Aß producing enzyme, relative to Aß and other cellular markers, by neuroanatomical and biochemical characterizations with postmortem brain samples and primary cell cultures. RESULTS: Immunoreactivity (IR) for BACE1 was essentially not visible at vasculature in cases without cerebral amyloidosis (control group, n = 15, age = 86.1 ± 10.3 year). In cases with brain amyloid pathology (n = 15, age = 78.7 ± 12.7 year), increased BACE1 IR was identified locally at capillaries, arterioles and along the pia, localizing to endothelia, perivascular dystrophic neurites and meningeal cells, and often coexisting with vascular iron deposition. Double immunofluorescence with densitometric analysis confirmed a site-specific BACE1 elevation at cerebral arterioles in the development of vascular Aß deposition. Levels of BACE1 protein, activity and its immediate product (C99) were elevated in leptomeningeal lysates from cases with CAA relative to controls. The expression of BACE1 and other amyloidogenic proteins in the endothelial and meningeal cells was confirmed in primary cultures prepared from human leptomeningeal and arteriolar biopsies. CONCLUSION: These results suggest that BACE1 elevation in the endothelia and perivascular neurites may be involved in angiopathic Aß deposition, while BACE1 elevation in meningeal cells might contribute Aß to leptomeningeal amyloidosis.

PRRT2 mutations are related to febrile seizures in epileptic patients.

Previous studies reported that the proline-rich transmembrane protein 2 (PRRT2) gene was identified to be related to paroxysmal kinesigenic dyskinesia (PKD), infantile convulsions with PKD, PKD with migraine and benign familial infantile epilepsy (BFIE). The present study explores whether the PRRT2 mutation is a potential cause of febrile seizures, including febrile seizures plus (FS+), generalized epilepsy with febrile seizures plus (GEFS+) and Dravet syndrome (DS); thus, it may provide a new drug target for personalized medicine for febrile seizure patients. We screened PRRT2 exons in a cohort of 136 epileptic patients with febrile seizures, including FS+, GEFS+ and DS. PRRT2 genetic mutations were identified in 25 out of 136 (18.4%) febrile seizures in epileptic patients. Five loss-of-function and coding missense mutations were identified: c.649delC (p.R217Efs*12), c.649_650insC (p.R217Pfs*8), c.412C>G (p.Pro138Ala), c.439G>C (p.Asp147His) and c.623C>A (p.Ser208Tyr). PRRT2 variants were probably involved in the etiology of febrile seizures in epileptic patients.

Association between dietary magnesium intake and liver fibrosis among type 2 diabetes mellitus patients: a cross-sectional study from the NHANES database.

Liver fibrosis (LF) is a common complication of type 2 diabetes mellitus (T2DM). Studies have found that dietary magnesium (Mg), as an antioxidant nutrient, may be related to the occurrence and development of liver diseases. The aim of the present study was to evaluate the association between dietary Mg and the risk of LF in T2DM patients. In this cross-sectional study, data of T2DM patients, aged ≥18 years, were extracted from the National Health and Nutrition Examination Survey (NHANES 2017-2018). Dietary Mg intake information was obtained by 24-hour dietary recall review. Covariates included sociodemographic information, lifestyle, laboratory data, disease history and medication history, extracted from the database. Weighted univariable and multivariable logistic regression models were used to assess the association between dietary Mg intake and LF among T2DM patients, with odds ratio (OR) and 95% confidence interval (CI). Subgroup analyses based on patients with or without a history of hepatic steatosis were further assessed. A total of 945 participants were finally included, of whom 219 (23.17%) had LF. After adjusting for covariates, a high level of dietary Mg intake (OR=0.40, 95% CI: 0.17-0.93) was associated with lower odds of LF in T2DM patients, especially in patients with a history of hepatic steatosis (OR=0.39, 95% CI: 0.17-0.87). High dietary Mg intake has potential benefits in maintaining a healthy liver in T2DM patients. Sufficient Mg-rich foods and Mg supplementation may be beneficial for liver health management among T2DM patients. Further cohort studies are needed to confirm these findings.

TGF-ß1 mediates hypoxia-preconditioned olfactory mucosa mesenchymal stem cells improved neural functional recovery in Parkinson's disease models and patients.

BACKGROUND: Parkinson's disease (PD) is a neurodegenerative disorder characterized by the degeneration of dopaminergic neurons in the substantia nigra (SN). Activation of the neuroinflammatory response has a pivotal role in PD. Mesenchymal stem cells (MSCs) have emerged as a promising therapeutic approach for various nerve injuries, but there are limited reports on their use in PD and the underlying mechanisms remain unclear. METHODS: We investigated the effects of clinical-grade hypoxia-preconditioned olfactory mucosa (hOM)-MSCs on neural functional recovery in both PD models and patients, as well as the preventive effects on mouse models of PD. To assess improvement in neuroinflammatory response and neural functional recovery induced by hOM-MSCs exposure, we employed single-cell RNA sequencing (scRNA-seq), assay for transposase accessible chromatin with high-throughput sequencing (ATAC-seq) combined with full-length transcriptome isoform-sequencing (ISO-seq), and functional assay. Furthermore, we present the findings from an initial cohort of patients enrolled in a phase I first-in-human clinical trial evaluating the safety and efficacy of intraspinal transplantation of hOM-MSC transplantation into severe PD patients. RESULTS: A functional assay identified that transforming growth factor-ß1 (TGF-ß1), secreted from hOM-MSCs, played a critical role in modulating mitochondrial function recovery in dopaminergic neurons. This effect was achieved through improving microglia immune regulation and autophagy homeostasis in the SN, which are closely associated with neuroinflammatory responses. Mechanistically, exposure to hOM-MSCs led to an improvement in neuroinflammation and neural function recovery partially mediated by TGF-ß1 via activation of the anaplastic lymphoma kinase/phosphatidylinositol-3-kinase/protein kinase B (ALK/PI3K/Akt) signaling pathway in microglia located in the SN of PD patients. Furthermore, intraspinal transplantation of hOM-MSCs improved the recovery of neurologic function and regulated the neuroinflammatory response without any adverse reactions observed in patients with PD. CONCLUSIONS: These findings provide compelling evidence for the involvement of TGF-ß1 in mediating the beneficial effects of hOM-MSCs on neural functional recovery in PD. Treatment and prevention of hOM-MSCs could be a promising and effective neuroprotective strategy for PD. Additionally, TGF-ß1 may be used alone or combined with hOM-MSCs therapy for treating PD.

HMGB1 acts in synergy with lipopolysaccharide in activating rheumatoid synovial fibroblasts via p38 MAPK and NF-κB signaling pathways.

Synovial fibroblasts (SF) play a central role in the inflammatory and destructive process in rheumatoid arthritis (RA). High-mobility group box chromosomal protein 1 (HMGB1) or lipopolysaccharide (LPS) alone failed to induce significant changes in proliferation of cultured SF from RA patients, but premixed HMGB1 with LPS (HMGB1-LPS) significantly facilitated SF proliferation. HMGB1 alone failed to induce IL-6, MMP-3, and MMP-13 production in cultured SF but greatly enhanced LPS-induced expression of IL-6, MMP-3, and MMP-13 at both mRNA and protein levels. HMGB1-LPS synergistically upregulated TLR4 and receptor for advanced glycation endproducts (RAGE) expression on the surface of SF. Both blockers of TLR4 and RAGE significantly inhibited the synergistic effects of HMGB1-LPS on the production of IL-6 and MMPs, but blocking antibodies to TLR2 failed. HMGB1-LPS synergistically increased intracellular levels of phosphorylated p38 and phosphorylated I κ B. Furthermore, both NF- κ B inhibitor Bay11-7085 and p38 inhibitor SB203580 significantly suppressed the enhanced production of IL-6 and MMPs induced by HMGB1-LPS. In conclusion, HMGB1 acts in synergy with LPS to upregulate TLR4 and RAGE expression on the surface of SF in RA and then to augment IL-6, MMP-3, and MMP-13 production, which depends on p38 MAPK and NF-κB activation.

Pathological mechanisms of neuroimmune response and multitarget disease-modifying therapies of mesenchymal stem cells in Parkinson's disease.

Parkinson's disease (PD) is a neurodegenerative disease characterized by the degeneration of dopaminergic neurons in the substantia nigra (SN); the etiology and pathological mechanism of the disease are still unclear. Recent studies have shown that the activation of a neuroimmune response plays a key role in the development of PD. Alpha-synuclein (α-Syn), the primary pathological marker of PD, can gather in the SN and trigger a neuroinflammatory response by activating microglia which can further activate the dopaminergic neuron's neuroimmune response mediated by reactive T cells through antigen presentation. It has been shown that adaptive immunity and antigen presentation processes are involved in the process of PD and further research on the neuroimmune response mechanism may open new methods for its prevention and therapy. While current therapeutic regimens are still focused on controlling clinical symptoms, applications such as immunoregulatory strategies can delay the symptoms and the process of neurodegeneration. In this review, we summarized the progression of the neuroimmune response in PD based on recent studies and focused on the use of mesenchymal stem cell (MSC) therapy and challenges as a strategy of disease-modifying therapy with multiple targets.

Treatment of hard-to-heal wound after huge scalp tumor resection and reconstruction: a case report.

Introduction and importance: Free skin flap transplantation and titanium mesh reconstruction can effectively repair the scalp and skull defects caused by massive scalp tumour resection. Postoperative flap infection is a common complication. Due to the presence of titanium mesh, once infection occurs, a second operation is required to remove the titanium mesh, which brings a great physical and economic burden to the patient. Case presentation: In this case of postoperative infection, the authors used a conservative treatment based on dressing change, preserved the titanium mesh and flap, avoided secondary surgery, and successfully controlled the infection. Clinical discussion: The treatment strategy is mainly divided into three steps: the first stage is to control infection, the authors use complexed iodine to repeatedly disinfect wounds, subcutaneous dead space, exposed titanium mesh, and antibiotic treatment for bacterial culture results; the second stage is to promote granulation growth, After infection control, the authors remove old granulation after each wound disinfection, and then instill fibroblast growth factor to promote subcutaneous granulation growth to fill dead space, and also provide a base platform for epidermal growth; the third stage is mainly epidermal healing, Change the dressing every day to observe the growth of the epidermis. Conclusion: This case suggests that conservative treatment strategy based on dressing change is also a potential treatment option for postoperative infection of the flap with exposure of the titanium plate.

National Brain Tumour Registry of China (NBTRC) statistical report of primary brain tumours diagnosed in China in years 2019-2020.

Background: The lack of a well-designed brain tumour registry with standardized pathological diagnoses in underdeveloped countries hinders the ability to compare epidemiologic data across the globe. The National Brain Tumour Registry of China (NBTRC), created in January 2018, is the first multi-hospital-based brain tumour registry in China. Patient data reported to the NBTRC in years 2019-2020 were assessed. Methods: Tumour pathology was based on the 2016 World Health Organization (WHO) classification of tumours of the central nervous system and ICD-O-3. The anatomical site was coded per the Surveillance, Epidemiology, and End Results (SEER) solid tumour module (version of July 2019). The cases were tabulated by histology and anatomical site. Categorical variables were reported as numbers (percentages). The distribution of tumours by age (0-14, 15-19, 20-39, 40-64, and 65+ years) was analysed. Findings: There were a total of 25,537 brain tumours, foremost among them meningioma (23.63%), followed by tumours of the pituitary (23.42%), and nerve sheath tumours (9.09%). Glioblastoma, the most common and lethal form of primary brain cancer in adults, represented 8.56% of all cases. Of note, 6.48% of the malignant tumours were located in the brain stem. The percentage of malignant brain tumours decreased with increasing age, 24.08% in adults (40+ years), 30.25% in young adults (20-39 years), 35.27% in adolescents (15-19 years), and 49.83% in children (0-14 years). Among the 2107 paediatric patients, the most common sites were ventricle (17.19%), brainstem (14.03%), pituitary and craniopharyngeal duct (13.4%), and cerebellum (12.3%), a distribution that differed from that of the entire cohort. The histology distribution was also unique in children, with glioblastoma much less incident compared to the whole cohort (3% vs. 8.47%, p < 0.01). 58.80% of all patients chose higher-level neurosurgical hospitals outside of their province of residence. The median in-hospital length of stay (LOS) for the various pathologies ranged from 11 to 19 days. Interpretation: The histological and anatomical site distribution of brain tumours in the NBTRC was statistically different in the subgroup of children (0-14 years). Patient choice of pursuing trans-provincial treatment was common and the in-hospital LOS was longer compared to that reported in similar European and American patient populations, which merits further attention. Funding: The National Key Research and Development Program of China (2015BAI12B04, 2013BAI09B03, 2014BAI04B01, and 2021YFF1201104) and Chinese National Natural Science Foundation of China (81971668).

Notoginsenoside R1 alleviates spinal cord injury through the miR-301a/KLF7 axis to activate Wnt/ß-catenin pathway.

Spinal cord injury (SCI) is a devastating incident that induces neuronal loss and dysfunction. Notoginsenoside R1 (NGR1) has been reported to exhibit a neuroprotective role after SCI. In this study, the effect and molecular mechanisms of NGR1 in models of SCI were further investigated. Rat adrenal pheochromocytoma cell line (PC-12) were stimulated with lipopolysaccharide (LPS) to establish a cell model of SCI-like condition. The changes of proinflammatory cytokines and associated proteins were analyzed using enzyme linked immunosorbent assay (ELISA) and western blotting. A rat model of SCI was established. Nissl staining were used to observe the morphological characteristics of spinal cord tissues. reverse transcription-quantitative PCR (RT-qPCR) was used to measure the expression of miR-301a andKrüppel-like factor 7 (KLF7). Our results showed that NGR1 alleviated LPS-triggered apoptosis and inflammation in PC-12 cells. MiR-301a was upregulated in LPS-stimulated PC-12 cells and was downregulated by NGR1 treatment. MiR-301a overexpression reversed the effect of NGR1 in LPS-treated PC-12 cells. KLF7 was verified to be targeted by miR-301a. NGR1 activated Wnt/ß-catenin signaling in LPS-treated PC-12 cells by inhibiting miR-301a and upregulating KLF7. Moreover, blocking wingless/integrated (Wnt)/ß-catenin signaling eliminated the protective effect of NGR1 against SCI in vitro and in vivo. Overall, NGR1 could reduce inflammation and apoptosis and promote functional recovery of SCI rats by activating Wnt/ß-catenin pathway.

miR-138-5p Inhibits the Growth and Invasion of Glioma Cells by Regulating WEE1.

BACKGROUND: Accumulating evidence has demonstrated the role of differentially expressed miRNAs in glioma progression. Our previous bioinformatics analyses revealed a role of miR-138-5p in glioma. miR-138-5p was decreased in various tumors, and He et al. found that miR-138-5p had an inhibitory effect on glioma cells in 2021. However, the role of miR-138-5p in the development of glioma and the underlying mechanism is unknown. In this study, we explored whether miR-138-5p affects the biology of glioma by regulating WEE1 expression. METHODS: miR-138-5p and WEE1 G2 checkpoint kinase (WEE1) RNA and protein expression levels in glioma tissues were detected with qRT-PCR and western blotting, respectively. The effects of miR-138-5p and WEE1 on glioma cell migration and invasion were investigated using Transwell assays. CCK-8 assay was used to measure the effects of miR-138-5p and WEE1 on glioma cell proliferation. The mortality of glioma cells transfected with miR-138-5p and WEE1 was measured with flow cytometry. The relationship between miR-138-5p and WEE1 was explored using a luciferase reporter analysis. RESULTS: Functional studies indicated that overexpression of miR-138-5p suppressed cell proliferation, migration, and invasion and promoted death in glioma cell lines. WEE1 was identified as a target of miR-138-5p, and overexpression of miR-138-5p significantly suppressed the levels of WEE1. Moreover, reintroduction of WEE1 partially abrogated miR-138-5p-induced suppression of motility and invasion in glioma cells. CONCLUSION: The low expression of miR-138-5p in glioma suggests a tumor suppressor role for this miRNA. miR-138-5p suppresses glioma progression by regulating WEE1. These data provide new insights into the molecular mechanism of glioma.

Erratum: The expression of Wnt-1 inducible signaling pathway protein-2 in astrocytoma: Correlation between pathological grade and clinical outcome.

[This corrects the article DOI: 10.3892/ol.2014.2663.].

Genomic comparison between cerebrospinal fluid and primary tumor revealed the genetic events associated with brain metastasis in lung adenocarcinoma.

Lung adenocarcinoma (LUAD) is most common pathological type of lung cancer. LUAD with brain metastases (BMs) usually have poor prognosis. To identify the potential genetic factors associated with BM, a genomic comparison for BM cerebrospinal fluid (CSF) and primary lung tumor samples obtained from 1082 early- and late-stage LUAD patients was performed. We found that single nucleotide variation (SNV) of EGFR was highly enriched in CSF (87% of samples). Compared with the other primary lung tissues, copy number gain of EGFR (27%), CDK4 (11%), PMS2 (11%), MET (10%), IL7R (8%), RICTOR (7%), FLT4 (5%), and FGFR4 (4%), and copy number loss of CDKN2A (28%) and CDKN2B (18%) were remarkably more frequent in CSF samples. CSF had significantly lower tumor mutation burden (TMB) level but more abundant copy number variant. It was also found that the relationships among co-occurrent and mutually exclusive genes were dynamically changing with LUAD development. Additionally, CSF (97% of samples) harbored more abundant targeted drugs related driver and fusion genes. The signature 15 associated with defective DNA mismatch repair (dMMR) was only identified in the CSF group. Cancer associated pathway analysis further revealed that ErbB (95%) and cell cycle (84%) were unique pathways in CSF samples. The tumor evolution analysis showed that CSF carried significantly fewer clusters, but subclonal proportion of EGFR was remarkably increased with tumor progression. Collectively, CSF sequencing showed unique genomic characteristics and the intense copy number instability associated with cell cycle disorder and dMMR might be the crucial genetic factors in BM of LUAD.