Inhibition of the TCF12/VSIG4 axis by palbociclib diminishes the proliferation and migration of glioma cells and decreases the M2 polarization of glioma-associated microglia.

The CDK4/CDK6 inhibitor palbociclib has shown the encouraging promise in the treatment of glioma. Here, we elucidated how palbociclib exerts suppressive functions in the M2 polarization of glioma-related microglia and the progression of glioma. Xenograft experiments were used to evaluate the function in vivo. The mRNA levels of transcription factor 12 (TCF12) and VSIG4 were detected by RT-qPCR, and their protein levels were assessed by immunoblotting. Cell migration was tested by wound-healing assay. Cell cycle distribution and M1/M2 microglia phenotype analysis were performed by flow cytometry. The levels of IFN-γ, TNF-α, IL-6，and TGF-ß were measured by ELISA. The TCF12/VSIG4 association was verified by luciferase reporter and chromatin immunoprecipitation (ChIP) assays. In U251 and LN229 glioma cells, TCF12 and VSIG4 were overexpressed, and palbociclib reduced their expression levels. TCF12 upregulation enhanced the proliferation and migration of glioma cells and the M2 polarization of glioma-associated microglia in vitro as well as the tumorigenicity of U251 glioma cells in vivo, which could be reversed by palbociclib. Mechanistically, TCF12 could enhance VSIG4 transcription and expression by binding to the VSIG4 promoter. TCF12 deficiency led to repression in glioma cell proliferation and migration as well as microglia M2 polarization, which could be abolished by increased VSIG4 expression. Our study reveals the novel TCF12/VSIG4 axis responsible for the efficacy of palbociclib in combating glioma, offering a rationale for the application of palbociclib in glioma treatment.

Using Magnetic Molecularly Imprinted Polymer Technology for Determination of Fish Serum Glucose Levels.

In this study, a highly efficient magnetic molecularly imprinted polymer nanocomposite material was prepared using multi-walled carbon nanotubes as carriers. The characterization of the obtained nanocomposite material was conducted using Fourier transform infrared spectroscopy, a vibrating sample magnetometer, a thermogravimetric analyzer, a scanning electron microscope, and a transmission electron microscope. The adsorption properties of the nanocomposite material were evaluated through adsorption experiments, including static adsorption, dynamic adsorption, and selective recognition studies. The prepared nanocomposite material, serving as a selective adsorbent, was applied in magnetic solid-phase extraction. Subsequently, the derivatized samples were analyzed for glucose in fish serum using liquid chromatography-tandem mass spectrometry. Under optimal conditions, the detection limit was 0.30 ng/mL, the quantitation limit was 0.99 ng/mL, satisfactory spiked recovery rates were obtained, and the relative standard deviation was less than 1.1%. Using 2-deoxy-D-ribose as the template molecule and a structural analog of glucose allowed us to eliminate the potential template leakage in qualitative and quantitative analyses, effectively avoiding the issues of false positives and potential quantitative errors, compared to traditional methods. A method for detecting glucose levels in fish serum based on molecularly imprinted polymer technology has been successfully developed to determine the stress and health levels of fish.

Enhanced Aluminum-Ion Storage Properties of N-Doped Titanium Dioxide Electrode in Aqueous Aluminum-Ion Batteries.

Aqueous aluminum-ion batteries (AIBs) have great potential as devices for future large-scale energy storage systems due to the cost efficiency, environmentally friendly nature, and impressive theoretical energy density of Al. However, currently, available materials used as anodes for aqueous AIBs are scarce. In this study, a novel sol-gel method was used to synthesize nitrogen-doped titanium dioxide (N-TiO2) as a potential anode material for AIBs in water. The annealed N-TiO2 showed a high discharge capacity of 43.2 mAh g-1 at a current density of 3 A g-1. Analysis of the electrode kinetics revealed that the N-TiO2 anodes exhibited rapid diffusion of aluminum ions, low resistance to charge transfer, and high electronic conductivity, enabling good rate performance. The successful implementation of a nitrogen-doping strategy provides a promising approach to enhance the electrochemical characteristics of electrode materials for aqueous AIBs.

Ultrasensitive Electrochemical Platform for Dopamine Detection Based on CoNi-MOF@ERGO Composite.

An electrochemical sensor applied for dopamine (DA) detection was constructed. An easy static way was used to synthesize bimetallic CoNi-MOF. Next, it was mixed with graphene oxide (GO) under ultrasound to get a uniform suspension. Subsequently, the solution was coated on the glassy carbon electrode (GCE) to form CoNi-MOF@ERGO/GCE by the electrochemical reduction method. The interaction between CoNi-MOF and electrochemically reduced graphene oxide (ERGO) enhances the electrocatalytic performance for DA detection. CoNi-MOF@ERGO/GCE has a wider linear range (0.1-400 µM) and a lower detection limit (0.086 µM) under optimum conditions. Furthermore, it has been applied to test DA in human serum samples. The results reveal that the DA sensor shows excellent performance, which will provide a novel idea for more sensitive and quicker DA detection.

Network pharmacology -based study on the mechanism of traditional Chinese medicine in the treatment of glioblastoma multiforme.

BACKGROUND: Glioblastoma multiforme (GBM) is one of the most common primary malignant brain tumors. Yi Qi Qu Yu Jie Du Fang (YYQQJDF) is a traditional Chinese medicine (TCM) prescription for GBM. The present study aimed to use a network pharmacology method to analyze the underlying mechanism of YQQYJDF in treating GBM. METHODS: GBM sample data, active ingredients and potential targets of YQQYJDF were obtained from databases. R language was used to screen differentially expressed genes (DEGs) between GBM tissues and normal tissues, and to perform enrichment analysis and weighted gene coexpression network analysis (WGCNA). The Search Tool for the Retrieval of Interacting Genes/Proteins (STRING) database was used to perform a protein‒protein interaction (PPI) analysis. A Venn diagram was used to obtain the core target genes of YQQYJDF for GBM treatment. Molecular docking was used to verify the binding between the active ingredient molecules and the proteins corresponding to the core target genes. Cell proliferation assays and invasion assays were used to verify the effect of active ingredients on the proliferation and invasion of glioma cells. RESULTS: A total of 73 potential targets of YQQYJDF in the treatment of GBM were obtained. Enrichment analyses showed that the biological processes and molecular functions involved in these target genes were related to the activation of the G protein-coupled receptor (GPCR) signaling pathway and the regulation of hypoxia. The neuroactive ligand‒receptor pathway, the cellular senescence pathway, the calcium signaling pathway, the cell cycle pathway and the p53 signaling pathway might play important roles. Combining the results of WGCNA and PPI analysis, five core target genes and their corresponding four core active ingredients were screened. Molecular docking indicated that the core active ingredient molecules and the proteins corresponding to the core target genes had strong binding affinities. Cell proliferation and invasion assays showed that the core active ingredients of YQQYJDF significantly inhibited the proliferation and invasion of glioma cells (P < 0.01). CONCLUSIONS: The present study predicted the possible active ingredients and targets of YQQYJDF in treating GBM, and analyzed its possible mechanism. These results may provide a basis and ideas for further research.

Intracranial dissemination in a primary small cell carcinoma of the brain: a case report and literature review.

Primary intracranial small cell carcinoma (SCC) is extremely rare with only 8 previously reported cases. We describe a case of primary intracranial SCC with intracranial metastasis. A 46-year-old man presented with decreased vision and a red and swollen left eye. Brain magnetic resonance imaging (MRI) revealed a heterogeneously enhanced tumor on the left frontal lobe. Preoperative systemic computed tomography (CT), MRI, and positron emission tomography (PET)-CT revealed no extracranial tumors. The tumor on the left frontal lobe was excised. Immunohistochemical staining on the excision showed positivity for CD56, synaptophysin (Syn), cytokeratin (CK), and Ki-67 (30%), and negativity for thyroid transcriptional factor-1 (TTF-1), glial fibrillary acidic protein (GFAP), B-cell lymphoma 6 (Bcl-6), multiple myeloma oncogene 1 (MUM-1), C-Myc, Vimentin, P40, P53, CK7, CD3, CD5, CD20, CD79a, CD10, and CD23. The pathological examination strongly suggested that the tumor was a primary intracranial SCC. One year after the surgery, the patient was readmitted with slurred speech and slow movements. Three well-defined tumors were found in the left upper frontal lobe by brain MRI. Tumor resection was then performed. Further immunohistochemical examination of the excised tissue displayed the same pattern as previously, indicating the recurrence of intracranial SCC in the left frontal lobe. The patient received adjuvant chemotherapy and radiotherapy after the tumor resection. At the 2-year follow-up, he remained asymptomatic.

Clinical features and surgical outcomes of Rathke cleft cysts with suprasellar components: a single-center experience of 157 cases.

BACKGROUND: Both intrasuprasellar and suprasellar Rathke cleft cysts (RCCs) have suprasellar components, and we aimed to explore their clinical features and surgical outcomes. METHOD: Patients with surgically treated intrasuprasellar or suprasellar RCCs were retrospectively analyzed. All patients with intrasuprasellar RCCs were treated with the standard endoscopic endonasal approach (EEA, group I); the patients with suprasellar RCCs received the extended EEA (group II) or supraorbital keyhole approach (SKA, group III) according to the relevant indications. A surgical strategy of maximal safe resection aiming to protect neuroendocrine function was adopted. In addition, patients (distinguished from the above 3 groups) who had aggressive resection of suprasellar RCC were also enrolled for comparison of different surgical strategies. RESULTS: A total of 157 patients were eligible, including 121 patients with intrasuprasellar RCCs in group I, 19 patients with suprasellar RCCs in group II, and 17 patients with suprasellar RCCs in group III. Preoperatively, the patients with suprasellar RCC (groups II and III) more commonly presented with visual dysfunction, diabetes insipidus (DI), and hyperprolactinemia than the patients with intrasuprasellar RCCs (all p<0.05). A higher incidence of hypopituitarism and a larger diameter were observed for intrasuprasellar RCCs (both p<0.05). Postoperatively, group II had a higher rate of new-onset DI, hyponatremia, and recurrence than group I (all p<0.025) and similar outcomes to group III. For suprasellar RCCs, comparison of the maximal safe resection vs. aggressive resection (supplementary patients: 14 with extended EEA, 12 with SKA) showed similar improvement and recurrence, with higher rates of DI and hyponatremia with the latter strategy (all p<0.05). CONCLUSIONS: Suprasellar RCC is associated with more complicated preoperative presentations, intricate postoperative complications, and frequent recurrence compared with intrasuprasellar RCC. Under rational indications, both extended EEA and SKA achieve satisfactory outcomes. The strategy of maximal safe resection is recommended for greatest functional preservation.

Optimization of hydrolysis conditions of crop straw and its effect in Chlorella sorokiniana culture.

Taking straws of corn, wheat, and millet as raw materials, we pretreated them with alkaline hydrogen peroxide, and then hydrolyzed by cellulase and xylanase. We selected the total sugar content in the hydrolysate as the indicator to evaluate the hydrolysis of the straws from three crop species, and further optimized the conditions. Then, the hydrolysates of three types of crop straws were used as carbon source for Chlorella sorokiniana culture to assess their effects on microalgal cultivation. The results showed that the optimal hydrolysis conditions for the three crop straws were identified as solid-liquid ratio of 1:15, temperature of 30 ℃, and treatment time of 12 h. Under such optimal condition, the total sugar contents increased up to 1.677, 1.412, and 1.211 g·L-1 in the corn, millet and wheat straw hydrolysate, respectively. The hydrolysates from the three crop straw could significantly increase both algal biomass and lipid content of C. sorokiniana. Corn straw hydrolysate had the best effect, with high levels of algal biomass (1.801 g·L-1) and lipid content (30.1%). Therefore, we concluded that crop straw hydrolysates as carbon source could significantly promote microalgal biomass and lipid enrichment. The results could lay the foundation for the efficient conversion and utilization of straw lignocellulose raw materials, provide new knowledge for the resource utilization of agricultural wastes, as well as the theoretical basis for the efficient cultivation of microalgae using crop straw hydrolysates.

3D multimodal image fusion based on MRI in the preoperative evaluation of microvascular decompression: A meta­analysis.

Neurovascular compression (NVC) is the main cause of hemifacial spasm (HFS) or trigeminal neuralgia (TN), and frequently occurs at the root entry zone of cranial nerves. Microvascular decompression (MVD) is an effective surgical treatment for TN and HFS caused by NVC. The accurate preoperative diagnosis of NVC is crucial to the evaluation of MVD as an appropriate treatment for TN and HFS. Three-dimensional (3D) time-of-flight magnetic resonance angiography (3D TOF MRA) and high resolution T2-weighted imaging (HR T2WI) are used to detect NVC prior to MVD; however, this combination alone has certain disadvantages. Multimodal image fusion (MIF) may combine two or more images from the same or different modalities, allowing neurosurgeons to use the reconstructed 3D model to observe anatomical details more clearly from different perspectives. The aim of the present meta-analysis was to evaluate the effect of 3D MIF based on 3D TOF MRA combined with HR T2WI in the preoperative diagnosis of NVC, and thus to evaluate its clinical application value in the preoperative evaluation of MVD. Relevant studies available on PubMed, Embase, Web of Science, Scopus, China National Knowledge Infrastructure and the Cochrane Library, and published from the inception of each database to September 2022, were retrieved. Studies using 3D MIF based on 3D TOF MRA combined with HR T2WI to diagnose NVC in patients with TN or HFS were included. The Quality Assessment of Diagnostic Accuracy Studies checklist was used to evaluate the quality of the included studies. The statistical software Stata 16.0 was used to perform the meta-analysis. Data extraction was performed by two independent investigators and discrepancies were resolved by discussion. Pooled sensitivities, specificities, positive likelihood ratio (PLR), negative likelihood ratio (NLR), diagnostic odds ratio (DOR) and the area under the receiver operating characteristic curve (AUROC) were calculated as the main summary effect size. The I² and Q-test were used to assess heterogeneity. The present search identified 702 articles, of which 7 (comprising 390 patients) fulfilled the inclusion criteria. Bivariate analysis indicated that the pooled sensitivity and specificity of 3D MIF based on 3D TOF MRA combined with HR T2WI for detecting NVC were 0.97 (95% CI, 0.95-0.99) and 0.89 (95% CI, 0.77-0.95), respectively. The pooled PLR was 8.8 (95% CI, 4.1-18.6), the pooled NLR was 0.03 (95% CI, 0.02-0.06) and the pooled DOR was 291 (95% CI, 99-853). The AUROC was 0.98 (95% CI, 0.97-0.99). The studies had no substantial heterogeneity (I2=0; Q=0.000; P=0.50). The present results suggested that 3D MIF based on 3D TOF MRA combined with HR T2WI had excellent sensitivity and specificity for diagnosing NVC in patients with TN or HFS. Therefore, this method should serve a key role in MVD preoperative evaluation.

Development of a novel angiogenesis-related lncRNA signature to predict the prognosis and immunotherapy of glioblastoma multiforme.

Background: Long noncoding RNA (lncRNA) can regulate tumorigenesis, angiogenesis, proliferation, and other tumor biological behaviors, and is closely related to the growth and progression of glioma. The purpose of this research was to investigate the role of angiogenesis-related lncRNA in the prognosis and immunotherapy of glioblastoma multiforme (GBM). Methods: Differential analysis was carried out to acquire angiogenesis-related differentially expressed lncRNAs (AR-DElncRNAs). The AR-DElncRNAs were then subjected to univariate Cox and least absolute shrinkage and selection operator (LASSO) analyses to construct a prognostic model. Based on the median risk score, patients were classified into high-risk and low-risk groups. Kaplan-Meier survival analysis was conducted to estimate the prognostic value of the prognostic model. In addition, a nomogram was built to predict individual survival probabilities by combining clinicopathological characteristics and a prognostic model. Furthermore, immune infiltration, immunotherapy, and drug sensitivity analyses were administered to investigate the differences between the high- and low-risk groups. Results: We identified 3 lncRNAs (DGCR5, PRKAG2-AS1, and ACAP2-IT1) that were significantly associated with the survival of GBM patients from the 255 AR-DElncRNAs based on univariate Cox and LASSO analyses. Then, a prognostic model was structured according to these 3 lncRNAs, from which we found that high-risk GBM patients had a worse prognosis than that of low-risk patients. Moreover, the risk score was determined to be an independent prognostic factor [hazard ratio (HR) =1.444; 95% confidence interval (CI): 1.014-2.057; P<0.05]. The immune microenvironment analysis revealed that the immune score, stromal score, and Estimation of STromal and Immune cells in MAlignant Tumor tissues using Expression data (ESTIMATE) score were significantly higher in the high-risk group than in the low-risk group. Neutrophils, macrophages, immature dendritic cells (iDCs), natural killer (NK) CD56dim cells, activated DCs (aDCs), and uncharacterized cells were different in the high- and low-risk groups. In addition, the high-risk group had a stronger sensitivity to immunotherapy. Furthermore, the sensitivity of 28 potential chemotherapeutic drugs differed significantly between the high- and low-risk groups. Conclusions: A novel angiogenesis-related lncRNA signature could be used to predict the prognosis and treatment of GBM.

Different MRI-based methods for the diagnosis of neurovascular compression in trigeminal neuralgia or hemifacial spasm: A network meta-analysis.

BACKGROUND: Accurate preoperative diagnosis of neurovascular compression (NVC) is crucial in the treatment of trigeminal neuralgia (TN) or hemifacial spasm (HFS). At present, there are many magnetic resonance imaging (MRI)-based methods for diagnosing NVC in clinical practice. This network meta-analysis (NMA) aimed to evaluate the diagnostic performance of different MRI-based imaging methods for NVC in patients with TN and HFS. MATERIALS AND METHODS: Related studies based on a search of PubMed, Embase, Web of Science and the Cochrane Library were retrieved. A two-way analysis of variance model was constructed for the Bayesian NMA to compare the performance of different diagnostic imaging methods. RESULTS: Our search identified 595 articles, of which 26 studies (including 2085 patients) related to 4 diagnostic imaging methods (3D time-of-flight magnetic resonance angiography (3D TOF MRA), high resolution T2-weighted imaging (HR T2WI), 3D TOF MRA combined with HR T2WI, and 3D multimodal image fusion (MIF) based on 3D TOF MRA combined with HR T2WI) were included in this NMA. The results showed that 3D MIF based on 3D TOF MRA combined with HR T2WI had the highest related sensitivity, the highest superiority index and the largest area under the receiver operating characteristic curve among all the methods. CONCLUSIONS: 3D MIF based on 3D TOF MRA combined with HR T2WI had better diagnostic performance for detecting NVC in patients with TN or HSF than other MRI-based imaging methods. This method can be used as an effective tool for preoperative evaluation of MVD.

Three-dimensional time-of-flight magnetic resonance angiography combined with high resolution T2-weighted imaging in preoperative evaluation of microvascular decompression.

BACKGROUND: Neurovascular compression (NVC) is the main cause of primary trigeminal neuralgia (TN) and hemifacial spasm (HFS). Microvascular decompression (MVD) is an effective surgical method for the treatment of TN and HFS caused by NVC. The judgement of NVC is a critical step in the preoperative evaluation of MVD, which is related to the effect of MVD treatment. Magnetic resonance imaging (MRI) technology has been used to detect NVC prior to MVD for several years. Among many MRI sequences, three-dimensional time-of-flight magnetic resonance angiography (3D TOF MRA) is the most widely used. However, 3D TOF MRA has some shortcomings in detecting NVC. Therefore, 3D TOF MRA combined with high resolution T2-weighted imaging (HR T2WI) is considered to be a more effective method to detect NVC. AIM: To determine the value of 3D TOF MRA combined with HR T2WI in the judgment of NVC, and thus to assess its value in the preoperative evaluation of MVD. METHODS: Related studies published from inception to September 2022 based on PubMed, Embase, Web of Science, and the Cochrane Library were retrieved. Studies that investigated 3D TOF MRA combined with HR T2WI to judge NVC in patients with TN or HFS were included according to the inclusion criteria. Studies without complete data or not relevant to the research topics were excluded. The Quality Assessment of Diagnostic Accuracy Studies checklist was used to assess the quality of included studies. The publication bias of the included literature was examined by Deeks' test. An exact binomial rendition of the bivariate mixed-effects regression model was used to synthesize data. Data analysis was performed using the MIDAS module of statistical software Stata 16.0. Two independent investigators extracted patient and study characteristics, and discrepancies were resolved by consensus. Individual and pooled sensitivities and specificities were calculated. The I² statistic and Q test were used to test heterogeneity. The study was registered on the website of PROSERO (registration No. CRD42022357158). RESULTS: Our search identified 595 articles, of which 12 (including 855 patients) fulfilled the inclusion criteria. Bivariate analysis showed that the pooled sensitivity and specificity of 3D TOF MRA combined with HR T2WI for detecting NVC were 0.96 [95% confidence interval (CI): 0.92-0.98] and 0.92 (95%CI: 0.74-0.98), respectively. The pooled positive likelihood ratio was 12.4 (95%CI: 3.2-47.8), pooled negative likelihood ratio was 0.04 (95%CI: 0.02-0.09), and pooled diagnostic odds ratio was 283 (95%CI: 50-1620). The area under the receiver operating characteristic curve was 0.98 (95%CI: 0.97-0.99). The studies showed no substantial heterogeneity (I2 = 0, Q = 0.001 P = 0.50). CONCLUSION: Our results suggest that 3D TOF MRA combined with HR T2WI has excellent sensitivity and specificity for judging NVC in patients with TN or HFS. This method can be used as an effective tool for preoperative evaluation of MVD.

A novel electrochemical sensor based on AuPd/UiO-66-NH2/GN composites for sensitive dopamine detection.

Metal-organic frameworks (MOFs) have emerged as interesting nanomaterials owing to their large surface area, high porosity, tunable pore architecture and easy functionalization. However, an inferior electrical conductivity hinders their application in electrochemical sensing. In this paper, gold-palladium alloy/UiO-66-NH2/graphene (AuPd/UiO-66-NH2/GN) composites were synthesized by loading alloys on the surfaces of MOFs and then attaching them to the graphene surface. The addition of metal nanoparticles and graphene enhanced the electron transfer ability of MOFs. Then, composites were used to modify a glassy carbon electrode (GCE) to construct a sensitive dopamine (DA) electrochemical sensor. The developed sensor manifested two linear relationships in lower concentration ranges and in higher concentration ranges with a 0.21 × 10-6 mol L-1 low detection limit (3σ/k) under optimal conditions. The results certified that the constructed sensor had high selectivity, excellent reproducibility and good stability, and had been used successfully for DA detection in actual human serum samples.

The MicroRNA-106a/20b Strongly Enhances the Antitumour Immune Responses of Dendritic Cells Pulsed with Glioma Stem Cells by Targeting STAT3.

Background: Evaluate the effect of the miRNA-106a/20b on the efficacy of DCs pulsed with GSCs in activating GSC-specific T cell responses. Methods: We cultured GSCs and prepared GSC antigen lysates by apoptosis. Then, immature DCs were pulsed with GSC antigen lysates in vitro. STAT3 levels in DCs were assessed by Western blotting, and the expression of CD80, CD86, and MHC-II was tested by fluorescence-activated cell sorting. The production and secretion of the cytokines IL-6, IL-12, TNF-α, and IL-10 in DCs induced by GSCs were determined by enzyme-linked immunosorbent assay. Finally, the cytotoxic functions of T cells stimulated by GSC-DC fusion cells transfected with a miR-106a/20b mimic in vitro and the antitumour activity in vivo were detected. Results: We found that the levels of miR-106a/20b were downregulated, but the expression of STAT3 was significantly upregulated. Simultaneously, the inhibition of STAT3 in the fusion cells by STAT3-specific siRNA caused significant upregulation of the expression of CD80, CD86, and MHC-II, and the secretion of the cytokines IL-6 and IL-12 was substantially increased, IL-10 was markedly decreased. These findings revealed that STAT3 is an important regulator of DC maturation. Furthermore, the interactional binding sites between the 3'-untranslated region (3'-UTR) of STAT3 mRNA and miR-106a/20b were predicted by bioinformatics and verified by a dual-luciferase assay. Moreover, the reduction in STAT3 levels in GSC-DCs enhanced the generation of CD8+ T cells and reduced the generation of Foxp3+ regulatory T cells. Meanwhile, the secretion of the T cell cytokine IFN-γ was significantly increased. Further research showed that DCs after miR-106a/20b-mimics transfection could promote the inhibition of GSC proliferation by T cells in vitro and suppress tumour growth in vivo. Conclusions: This study indicted that the miR-106a/20b activation could be one of the important molecular mechanisms leading to enhance antitumour immune responses of GSC-mediated DCs, which downregulated the expression of STAT3 to alleviate its the inhibitory effect.

Effects of cruciate embedding fascia-bone flap technique on grade II-III cerebral spinal fluid leak in endoscopic endonasal surgery.

BACKGROUND: Cerebral spinal fluid (CSF) leak remains an important issue in endoscopic endonasal surgery (EES). A standard protocol for skull base closure has not yet been established, and the application of rigid buttress has not been given sufficient attention. To emphasize the functions of support and fixation from rigid buttress in reconstruction, we introduced the cruciate embedding fascia-bone flap (CEFB) technique using autologous bone graft to buttress the fascia lata attachment to the partially sutured skull base dural defect and evaluated its efficacy in a consecutive case series of grade II-III CSF leaks in EES. METHODS: Data from consecutive patients diagnosed with sellar region lesions with grade II-III CSF leaks during EES were collected from May 2015 to May 2020. Skull base reconstructions were performed with the CEFB or the conventional pedicle vascularized nasoseptal flap (PNSF). Related clinical data were analysed. The combined use of the CEFB and PNSF was applied to an additional supplemental case series of patients with grade III leak and multiple high-risk factors. RESULTS: There were 110 and 65 patients included in the CEFB and PNSF groups, respectively. The CEFB demonstrated similar effects on the incidence of postoperative CSF leak (2.7%), intracranial infection (4.5%), and lumbar drainage (LD) placement (5.5%) as PNSF (3.1%, 3.1%, and 6.2%), but with less epistaxis (CEFB: 0%, PNSF: 6.2%) and nasal discomforts (CEFB: 0%, PNSF: 7.7%). The LD duration (CEFB: 6.67 ± 2.16 days, PNSF: 10.50 ± 2.38 days), bed-stay time (CEFB: 5.74 ± 1.58 days, PNSF: 8.83 ± 3.78 days) and hospitalization time (CEFB: 10.49 ± 5.51 days, PNSF: 13.58 ± 5.50 days) were shortened in the CEFB group. The combined use of CEFB and PNSF resulted in 0 postoperative CSF leaks in the supplemental case series of 23 highly susceptible patients. CONCLUSION: This study suggested that the new CEFB technique has the potential to prevent postoperative CSF leak in EES. The results indicated that it can be used effectively without PNSF in suitable cases or applied in addition to a PNSF with high compatibility when necessary. Its effectiveness should be further verified with a larger cohort and better design in the next step. Trial Registration Current Controlled Trials ChiCTR2100044764 (Chinese Clinical Trial Registry); date of registration: 27 March 2020. Retrospectively registered.

Circ_RPPH1 regulates glioma cell malignancy by binding to miR-627-5p/miR-663a to induce SDC1 expression.

BACKGROUND: Recent studies revealed the key role of circular RNA (circRNA) in glioma progression. However, the effect of circ_0000520, also named as circRNA ribonuclease P RNA component H1 (circ_RPPH1), in glioma development was unknown. The study aimed to reveal the role of circ_RPPH1 in glioma cell malignancy. METHODS: Human astrocytes (NHA) and glioma cell lines (A172 and U251) were employed in this study. Quantitative real-time polymerase chain reaction and western blot were used to check the expression of circ_RPPH1, microRNA-627-5p (miR-627-5p), miR-663a and syndecan 1 (SDC1). Immunohistochemistry assay was conducted to assess the protein expression of nuclear proliferation marker ki67 and matrix metalloprotein 9 (MMP9). Cell viability was assessed by 3-(4,5-Dimethylthazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. Cell proliferation and apoptosis were investigated by flow cytometry analysis, 5-Ethynyl-29-deoxyuridine, or cell colony formation assay. Cell migration and invasion were evaluated by transwell assays. The interaction between miRNAs (miR-627-5p and miR-663a) and circ_RPPH1 or SDC1 was identified by a dual-luciferase reporter assay. A mouse model assay was performed to reveal the impact of circ_RPPH1 knockdown on glioma cell malignancy in vivo by analyzing neoplasm volume and weight. RESULTS: Circ_RPPH1 and SDC1 expression were significantly increased, whereas miR-627-5p and miR-663a expression were decreased in glioma tissues and cells in comparison with healthy brain tissues or human astrocytes. Circ_RPPH1 depletion led to the decreased cell proliferation, migration and invasion, and the increased cell apoptosis. Additionally, circ_RPPH1 bound to miR-627-5p/miR-663a and mediated glioma cell processes by interacting with them. SDC1 overexpression attenuated miR-627-5p/miR-663a-mediated actions. Moreover, circ_RPPH1 regulated SDC1 expression through interaction with miR-627-5p and/or miR-663a. Furthermore, circ_RPPH1 knockdown inhibited glioma cell malignancy in vivo, accompanied by the decreases of ki67 and MMP9 expression. CONCLUSION: Circ_RPPH1 knockdown inhibited glioma tumorigenesis by downregulating SDC1 by binding to miR-627-5p/miR-663a, showing that circ_RPPH1 might be an effective therapeutic target for glioma.

Downregulation of Astrocyte Elevated Gene-1 Expression Combined with All-Trans Retinoic Acid Inhibits Development of Vasculogenic Mimicry and Angiogenesis in Glioma.

OBJECTIVE: This study aimed to investigate the effects of downregulating astrocyte elevated gene-1 (AEG-1) expression combined with all-trans retinoic acid (ATRA) on vasculogenic mimicry (VM) formation and angiogenesis in glioma. METHODS: U87 glioma cells were transfected with AEG-1 shRNA lentiviral vectors (U87-siAEG-1) and incubated in a medium containing 20 µmol/L ATRA. Matrigel-based tube formation assay was performed to evaluate VM formation, and the cell counting kit-8 (CCK-8) assay was used to analyze the proliferation of glioma cells in vitro. Reverse transcription-quantitative polymerase chain reaction and Western blot analysis were used to investigate the mRNA and protein expression of related genes, respectively. Glioma xenograft models were generated via subcutaneous implantation of glioma cells in nude mice. Tumor-bearing mice received an intraperitoneal injection of ATRA (10 mg/kg per day). Immunohistochemistry was used to evaluate the expression of related genes and the microvessel density (MVD) in glioma xenograft models. CD34/periodic acid-Schiff double staining was performed to detect VM channels in vivo. The volume and weight of tumors were measured, and a tumor growth curve was drawn to evaluate tumor growth. RESULTS: A combination of ATRA intervention and downregulation of AEG-1 expression significantly inhibited the proliferation of glioma cells in vitro and glioma VM formation in vitro and in vivo. It also significantly decreased MVD and inhibited tumor growth. Further, the expression levels of matrix metalloproteinase (MMP)-2, MMP-9, vascular endothelial-cadherin (VE-cadherin), and vascular endothelial growth factor (VEGF) in glioma significantly decreased in vivo and in vivo. CONCLUSION: Hence, a combinatorial approach might be effective in treating glioma through regulating MMP-2, MMP-9, VEGF, and VE-cadherin expression.

Modified surgical method of supra- and infratentorial epidural hematoma and the related anatomical study of the squamous part of the occipital bone.

BACKGROUND: Supra- and infratentorial acute epidural hematoma (SIEDH) is a common posterior cranial fossa epidural hematoma located at the inner surface of the squamous part of the occipital bone (SOB). Traditionally, surgical treatment of the SIEDH requires a combined supra-infratentorial craniotomy. AIM: To analyze the morphological characteristics of the SOB and introduce a single supratentorial craniotomy for SIEDH. METHODS: Skull computed tomography (CT) scan data from 32 adult patients were collected from January 1, 2019 to January 31, 2020. On the median sagittal plane of the CT scan, the angle of the SOB (ASOB) was defined by two lines: Line A was defined from the lambdoid suture (LambS) to the external occipital protuberance (EOP), while line B was defined from the EOP to the posterior edge of the foramen magnum (poFM). The operative angle for the SIEDH (OAS) from the supra- to infratentorial epidural space was determined by two lines: The first line passes from the midpoint between the EOP and the LambS to the poFM, while the second line passes from the EOP to the poFM. The ASOB and OAS were measured and analyzed. RESULTS: Based on the anatomical study, a single supratentorial craniotomy was performed in 8 patients with SIEDH. The procedure and the results of the modified surgical method were demonstrated in detail. For males, the ASOB was 118.4 ± 4.7 and the OAS was 15.1 ± 1.8; for females, the ASOB was 130.4 ± 5.1 and the OAS was 12.8 ± 2.0. There were significant differences between males and females both in ASOB and OAS. The smaller the ASOB was, the larger the OAS was. The bone flaps in 8 patients were designed above the transverse sinus intraoperatively, and the SIEDH was completely removed without suboccipital craniotomy. The SOB does not present as a single straight plane but bends at an angle around the EOP and the superior nuchal lines. The OAS was negatively correlated with the ASOB. CONCLUSION: The single supratentorial craniotomy for SIEDH is reliable and effective.

Effect of Respiratory Training Combined with Core Muscle Training on the Overall Motor Function and Activities of Daily Living of Patients with Early and Midterm Stroke.

Stroke is a cerebral ischemic or hemorrhagic disease with sudden onset and rapid progress. To analyze the effect of respiratory training combined with core muscle training on the overall motor function and activities of daily living of patients with early and midterm stroke, 90 cases with early and midterm stroke admitted to the neurological department of our hospital from April 2018 to April 2019 were chosen as the research objects. According to the odd or even hospitalization numbers, they were equally divided into the study group and the reference group. Both groups received basic drug treatment. On this basis, the reference group was given routine rehabilitation training, while the study group was given respiratory training combined with core muscle training. The clinical indexes of both groups before and after intervention were evaluated to analyze the effect of different training methods on the rehabilitation of patients with early and midterm stroke. There was no significant difference in gender ratio, average age, average BMI, average course of disease, stroke types, MAS grading, location of limb dysfunction, and combined disease between the two groups (P < 0.05). The total clinical effective rate of the study group after intervention was obviously higher than that of the reference group (P < 0.05). The MoCA scores of both groups after intervention were obviously higher than those before intervention, and the score of the study group after intervention was obviously higher than that of the reference group. The scores of limb motor function, activities of daily living, and balance function at T 2, T 3, and T 4 in the study group were obviously higher than those in the reference group (P < 0.001). At 4 and 8 weeks after intervention, the 10 m MWS of the study group was obviously higher than that of the reference group (P < 0.001), while the TUGT was obviously lower (P < 0.001). Respiratory training combined with core muscle training can obviously improve the activities of daily living, cognitive function, and limb motor function of patients with early and midterm stroke, which is worth popularizing and using.

NEK2 enhances malignancies of glioblastoma via NIK/NF-κB pathway.

Glioblastoma (GBM) is one of the most lethal primary brain tumor with a poor median survival less than 15 months. Despite the development of the clinical strategies over the decades, the outcomes for GBM patients remain dismal due to the strong proliferation and invasion ability and the acquired resistance to radiotherapy and chemotherapy. Therefore, developing new biomarkers and therapeutic strategies targeting GBM is in urgent need. In this study, gene expression datasets and relevant clinical information were extracted from public cancers/glioma datasets, including TCGA, GRAVENDEEL, REMBRANDT, and GILL datasets. Differentially expressed genes were analyzed and NEK2 was picked as a candidate gene for subsequent validation. Human tissue samples and corresponding data were collected from our center and detected by immunohistochemistry analysis. Molecular biological assays and in vivo xenograft transplantation were performed to confirm the bioinformatic findings. High-throughput RNA sequencing, followed by KEGG analysis, GSEA analysis and GO analysis were conducted to identify potential signaling pathways related to NEK2 expression. Subsequent mechanism assays were used to verify the relationship between NEK2 and NF-κB signaling. Overall, we identified that NEK2 is significantly upregulated in GBM and the higher expression of NEK2 exhibited a poorer prognosis. Functionally, NEK2 knockdown attenuated cell proliferation, migration, invasion, and tumorigenesis of GBM while NEK2 overexpression promoted the GBM progression. Furthermore, High-throughput RNA sequencing and bioinformatics analysis indicated that NEK2 was positively related to the NF-κB signaling pathway in GBM. Mechanically, NEK2 activated the noncanonical NF-κB signaling pathway by phosphorylating NIK and increasing the activity and stability of NIK. In conclusion, NEK2 promoted the progression of GBM through activation of noncanonical NF-κB signaling, indicating that NEK2- NF-κB axis could be a potential drug target for GBM.