Functional alterations of the brain default mode network and somatosensory system in trigeminal neuralgia.

Mapping the localization of the functional brain regions in trigeminal neuralgia (TN) patients is still lacking. The study aimed to explore the functional brain alterations and influencing factors in TN patients using functional brain imaging techniques. All participants underwent functional brain imaging to collect resting-state brain activity. The significant differences in regional homogeneity (ReHo) and amplitude of low frequency (ALFF) between the TN and control groups were calculated. After familywise error (FWE) correction, the differential brain regions in ReHo values between the two groups were mainly located in bilateral middle frontal gyrus, bilateral inferior cerebellum, right superior orbital frontal gyrus, right postcentral gyrus, left inferior temporal gyrus, left middle temporal gyrus, and left gyrus rectus. The differential brain regions in ALFF values between the two groups were mainly located in the left triangular inferior frontal gyrus, left supplementary motor area, right supramarginal gyrus, and right middle frontal gyrus. With the functional impairment of the central pain area, the active areas controlling memory and emotion also change during the progression of TN. There may be different central mechanisms in TN patients of different sexes, affected sides, and degrees of nerve damage. The exact central mechanisms remain to be elucidated.

PSMC2 promotes glioma progression by regulating immune microenvironment and PI3K/AKT/mTOR pathway.

BACKGROUND: Glioma, the most frequent and malignant central nervous system (CNS) cancer, has a bad outcome. Proteasome 26S subunit ATPase 2 (PSMC2) is an essential part of the 26S proteasome and promotes the development of several tumors. However, the pathway and function of PSMC2 in glioma have not been unelucidated. METHODS: This study analyzed PSMC2 expression in glioma tissues and its predictive significance for patients. We examined the link between PSMC2 and DNA methylation, immune cell infiltration, tumor immune cycle, immune cell homeostasis, and immune checkpoints. Subsequently, immunohistochemistry and in vitro trials were employed to validate the expression, prognostic potential, and function of PSMC2 in glioma. The mechanisms of PSMC2 in glioma were further explored. RESULTS: Our study revealed that PSMC2 expression increased in glioma tissues contrasted with healthy tissues, and patients with high PSMC2 glioma exhibited poor overall survival (OS) compared to the low-PSMC2 group. Immune profile analysis revealed that PSMC2 was positively related to immunosuppressive cell infiltration and immune checkpoints and adversely related to the cancer immune cycle and immune cell homeostasis. In cell-based investigations, the inhibition of PSMC2 was found to effectively suppress the aggressiveness and proliferation of glioma cell lines while also enhancing cell cycle arrest and promoting cell death. Gene Set Enrichment Analysis (GSEA), Gene Set Variation Analysis (GSVA), and in vitro experiments showed that PSMC2 promoted glioma development through the PI3K/AKT/mTOR pathway. CONCLUSIONS: PSMC2 was upregulated in glioma and promoted cancer progression by modulating the tumor immune microenvironment, cancer cell biological behavior, immune cell homeostasis, and the PI3K/AKT/mTOR pathway, providing a new option to treat glioma.

Tetracoordinate or tricoordinate? Planar tetracoordinate nitrogen in the NBe4H4- cluster stabilized by multicenter bonds.

Realization of planar tetracoordinate arrangements of nitrogen atoms is challenging because their preference for localized bonding (caused by its high electronegativity) makes them typically tricoordinate. This is especially true for the more electronegative oxygen atoms. Herein, we computationally designed two clusters NBe4H4- and OBe4H4; they contain a planar tetracoordinate nitrogen (ptN) and planar tetracoordinate oxygen (ptO) atom, respectively. Remarkably, the former is a dynamically stable global minimum, while the latter is not. The bonding analysis proves that planar tetracoordination in NBe4H4- favors over tricoordination because of the presence of multicenter delocalized bonds. In contrast, the planar tricoordination dominates due to its weak delocalized bonding ability of oxygen in the OBe4H4 cluster. Moreover, the 6σ/2π double aromaticity due to multicenter delocalized bonds allows the NBe4H4- cluster to obtain additional stability. This cluster is a promising synthetic due its dynamic and thermodynamic stability.

STEAP3 is a prognostic biomarker that promotes glioma progression by regulating immune microenvironment and PI3K-AKT pathway.

BACKGROUND: STEAP3 is a metal reductase located on the plasma membrane close to the nucleus and vesicles. Despite numerous studies indicating the involvement of STEAP3 in tumor advancement, the prognostic value of STEAP3 in glioma and the related mechanisms have not been fully investigated. METHODS: Initially, we examined the correlation between STEAP3 expression and the survival rate in various glioma datasets. To assess the prognostic capability of STEAP3 for one-year, three-year, and five-year survival, we created receiver operating characteristic (ROC) curves and nomograms. Additionally, an investigation was carried out to examine the mechanisms that contribute to the involvement of STEAP3 in gliomas, including immune and enrichment analysis. To confirm the expression of STEAP3 in LGG and GBM, tumor tissue samples were gathered, and cell experiments were conducted to explore the impacts of STEAP3. The function of STEAP3 in the tumor immune microenvironment was assessed using the M2 macrophage infiltration assay. RESULTS: We found that STEAP3 expressed differently in group with different age, tumor grade IDH and 1p19q status. The analysis of survival illustrated that glioma patients with high level of STEAP3 experienced shorter survival durations, especially for IDH-mutant astrocytoma. Cox analysis demonstrated that STEAP3 had potential to act as an independent prognostic factor for glioma. The predictive value of STEAP3 for glioma prognosis was demonstrated by ROC curves and nomogram. Immune analysis showed that STEAP3 may lead to a suppressive immune microenvironment through the control of immunosuppressive cell infiltration and Cancer-Immunity Cycle. Combining enrichment analysis and cell experiments, we discovered that STEAP3 can promote glioma progression through regulation of PI3K-AKT pathway and M2 macrophage infiltration. CONCLUSION: STEAP3 plays significant roles in the advancement of glioma by regulating immune microenvironment and PI3K-AKT pathway. It has the potential to serve as a therapy target for glioma.

Arylsulfatase D is a prognostic biomarker that promotes glioma cells progression through JAK2/STAT3 pathway and M2 macrophage infiltration.

Background: Arylsulfatase D (ARSD) belongs to the sulfatase family and plays a crucial role in maintaining the proper structure of bone and cartilage matrix. Although several researches have revealed the functions of ARSD in tumor progression, the prognostic value of ARSD in glioma and the related mechanisms have not been fully investigated. Methods: We performed a pan-cancer analysis of ARSD, and investigated the relationship between expression of ARSD and overall survival (OS) in multiple glioma datasets. ROC curves and nomograms were created to investigate the predictive capacity of ARSD. Immune and analysis were conducted to investigate the mechanisms underlying the roles of ARSD in glioma. Glioma tissue samples were collected to verify the expression of ARSD in glioma, while the functions of ARSD were explored using cell experiment. M2 macrophage infiltration assay was used to determine the relation between ARSD and tumor immune microenvironment. Results: Survival analysis indicated that individuals with high ARSD expression in glioma had a shorter survival time. Cox analysis showed that ARSD had a good ability for predicting prognosis in glioma. Immune analysis suggested that ARSD could regulate immune cell infiltration and affect the Cancer-Immunity Cycle to create an immunosuppressive environment. Combined with cell experiment and bioinformatic analysis, we found that ARSD can promote glioma progression through regulation of JAK2/STAT3 pathway and M2 macrophage infiltration. Conclusion: Our study found that ARSD can promote glioma development by regulating immune microenvironment and JAK2/STAT3 signaling pathway, which provided a potential therapy target for glioma treatment.

Advances in research on fat infiltration and lumbar intervertebral disc degeneration.

Low back pain (LBP) is a disabling condition with no available cure, severely affecting patients' quality of life. Intervertebral disc degeneration (IVDD) is the leading cause of chronic low back pain (CLBP). IVDD is a common and recurrent condition in spine surgery. Disc degeneration is closely associated with intervertebral disc inflammation. The intervertebral disc is an avascular tissue in the human body. Transitioning from hematopoietic bone marrow to bone marrow fat may initiate an inflammatory response as we age, resulting in bone marrow lesions in vertebrae. In addition, the development of LBP is closely associated with spinal stability imbalance. An excellent functional state of paraspinal muscles (PSMs) plays a vital role in maintaining spinal stability. Studies have shown that the diminished function of PSMs is mainly associated with increased fat content, but whether the fat content of PSMs is related to the degree of disc degeneration is still under study. Given the vital role of PSMs lesions in CLBP, it is crucial to elucidate the interaction between PSMs changes and CLBP. Therefore, this article reviews the advances in the relationship and the underlying mechanisms between IVDD and PSMs fatty infiltration in patients with CLBP.

Binary mono-anions with unprecedented anti-aromatic planar tetracoordinate carbon and nitrogen atoms.

Global minima (CBe4- and NBe4-) with planar tetracoordinate carbon and nitrogen atoms are stabilized by multicentric bonds. Their unusual anti-aromaticity is due to the strong localized Be-Be bonds preventing the full delocalization of the electrons in the CBe4/NBe4 skeleton. These binary mono-anions are expected to be experimentally realized in the gas phase.

The application of magnetic resonance imaging (MRI) for the prediction of surgical outcomes in trigeminal neuralgia.

Trigeminal neuralgia (TN) is a severe facial pain disorder that often requires surgical treatment. Neurovascular compression (NVC) has been widely accepted as the primary cause of classical TN (cTN). Vascular compression involving the near half of the cisternal segment of trigeminal nerve was the most likely cause of patient's symptoms. And severe NVC was a strong imaging predictor of an optimal surgical outcome. Operative treatments for cTN include microvascular decompression (MVD) and various ablative procedures. However, a significant proportion of cTN patients with significant NVC fail to achieve long-term pain relief after technically successful surgery. Neuroimaging using magnetic resonance imaging (MRI) provides a noninvasive method to generate objective biomarkers of eventual response to TN surgery. This paper reviewed the progress of research on the prediction of surgical outcomes in TN with MRI.

Procollagen C-protease enhancer protein is a prognostic factor for glioma and promotes glioma development by regulating multiple tumor-related pathways and immune microenvironment.

OBJECTIVES: Glioma is a common type of brain tumor with high incidence and mortality rates. Procollagen C-protease enhancer protein (PCOLCE) has been shown to regulate tumor growth and metastasis in several cancers. However, the role of PCOLCE in glioma is unknown. This study aims to assess the association between PCOLCE and prognosis of glioma, and investigated the potential mechanisms. METHODS: The prognostic value of PCOLCE was determined using data from nine publicly available glioma cohorts. We also investigated the relationship between PCOLCE and glioma immune microenvironment and predicted response to immunotherapy based on the expression levels of PCOLCE. The potential roles of PCOLCE in glioma were also explored and validated in cell experiment. RESULTS: Survival analysis suggested that high-PCOLCE expression was associated with poor prognosis in glioma. Upregulation of PCOLCE enhanced an immune suppressive microenvironment in glioma by regulating immunocyte infiltration and Cancer-Immunity Cycle. Cox and ROC analysis revealed that PCOLCE was a prognostic factor for glioma and could be used to predict survival of the patients. Patients with low-PCOLCE expression were more likely to respond to Immunotherapy with ICI (immune checkpoint inhibitor) and survive longer. Enrichment analysis showed that PCOLCE was associated with multiple tumor-related pathways. Finally, we demonstrated that the knockdown of PCOLCE inhibited glioma development by regulating cell cycle and promoting apoptosis in in vitro experiments. CONCLUSION: PCOLCE promotes glioma progression by regulating multiple tumor-related pathways and immune microenvironment and can be used as a prognostic factor for glioma.

Comprehensive analysis of TAMs marker genes in glioma for predicting prognosis and immunotherapy response.

Glioma is one of the most frequent types of primary tumors in central nervous system. Previous studies deomostrated that tumor-associated macrophages (TAMs) and their marker genes were significantly associated with immunologic suppression and immune escape of cancer. However, the molecular mechanism between glioma and TAM marker genes is still rarely reported. In this research, we performed a comprehensive analysis of the prognostic prediction value of TAM marker genes in multiple glioma cohorts. Further investigation indicated that the increased expression of TAM marker genes resulted in the immune suppressive microenvironment in glioma through regulating tumor-infiltrating immune cells and Cancer-Immunity Cycle. To better forecast the survival of glioma patients, we then developed gene risk models in four glioma datasets (CGGA, TCGA, Rembrandt and Gravendeel). Univariate and multivariate Cox analysis exhibited the good survival prediction ability and prognostic discrimination ability of our models. The results of immunotherapy prediction indicated that glioma patients with low risk were more likely to benefit from ICB (immune checkpoint blockade) treatment. Altogether, our research provided a comprehensive analysis of TAM marker genes and explored their value for predicting prognosis and immunotherapy response in glioma.

Establishment and validation of five autophagy-related signatures for predicting survival and immune microenvironment in glioma.

BACKGROUND: Gliomas, especially Glioblastoma multiforme, are the most frequent type of primary tumors in central nervous system. Increasing researches have revealed the relationship between autophagy and tumor, while the molecular mechanism of autophagy in glioma is still rarely reported. OBJECTIVE: Our research aims to conform the autophagy-related genes (ARGs) implicated in the development and progression of glioma and improve our understanding of autophagy in glioma. METHODS: 20 candidate ARGs were screened through the protein-protein interaction network. We also downloaded the publicly accessible glioma data for 665 individuals from TCGA and 970 individuals from CGGA with RNA sequences and clinicopathological information. Subsequently, univariate and multivariate Cox regression analysis identified 5 key ARGs among the 20 candidate genes as key prognostic genes for survival, GSEA and immune response analysis. RESULTS: ATG5, BCL2L1, CASP3, CASP8, GAPDH were identified as key ARGs in our research. Further studies showed that the high-risk population was linked to a dismal prognosis and suggested an immune-inhibitory microenvironment. GSEA results demonstrated that high risk population was closely related to DNA repair, hypoxia pathways, implicated in immunosuppression and carcinogenesis. Through CMap, we finally identified 14 candidate drugs for the ARG high risk population. CONCLUSIONS: This study established and verified an ARG risk model, which can serve as an independent predictor for prognosis, reflect on the strength of the immune response and predict the potential drugs in glioma. Our findings offer new understandings of ARG molecular mechanism and promising therapeutic targets for glioma treatment.

Predictive potential of STEAP family for survival, immune microenvironment and therapy response in glioma.

Glioma is the most commonly diagnosed primary tumor of central nervous system. Previous studies found that the six-transmembrane epithelial antigen of prostate (STEAP) family can regulate the biological behaviors of several cancers. However, the role of STEAP family in glioma remains unclear. Here, we systematically evaluated the relationship between STEAP family and prognosis of glioma patients in multiple cohorts. The analysis showed that dysregulation of STEAP family may affect cancer-immunity cycle, immune infiltration and phenotypes resulting in an immunosuppressive microenvironment in glioma. To accurately predict the prognosis of glioma patients, gene-based risk models were established based on the expression of STEAP1, 2 and 3. Multivariate and univariate Cox analyses demonstrated that the risk models could independently predict the prognosis of glioma. Finally, chemotherapy and immune therapy responses for high- and low-risk patients were predicted. In conclusion, this study systematically analyzed the role of STEAP family in glioma and established a model for predicting therapy response in patients with glioma.

Modulation of vascular integrity and neuroinflammation by peroxiredoxin 4 following cerebral ischemia-reperfusion injury.

Ischemic stroke is a leading cause of morbidity and mortality worldwide, with oxidative stress playing a key role in the injury mechanism of thrombolytic therapy. There is increasing evidence that oxidative stress damages endothelial cells (ECs), degrades tight junction proteins (TJs), and contributes to increased blood-brain barrier (BBB) permeability. It has been demonstrated that the breakdown of BBB could increase the risk of intracerebral hemorrhagic transformation in ischemic stroke. And an episode of cerebral ischemia/reperfusion (I/R) also initiates oxidative stress-mediated inflammatory processes in ECs, which further promotes BBB disruption and the progression of brain injury. Previous studies have revealed that antioxidants could inhibit ROS generation and attenuate BBB disruption after cerebral I/R. Peroxiredoxin 4 (Prx4) is a member of the antioxidant enzymes family (Prx1-6) and has been characterized to be an efficient H2O2 scavenger. It should be noted that Prx4 may be directly involved in the protection of ECs from the effects of ROS and function in ECs as a membrane-associated peroxidase. This paper reviewed the implication of Prx4 on vascular integrity and neuroinflammation following a cerebral I/R injury.

Activation of NADPH/ROS pathway contributes to angiogenesis through JNK signaling in brain endothelial cells.

Recent evidences have shown that reactive oxygen species (ROS) are involved in regulating angiogenesis and preventing tissue injury. However, the precise molecular mechanisms behind ROS-induced angiogenesis are still unknown. The aim of the present study was to investigate the effects of ROS-induced angiogenesis in rat brain microvessel endothelial cells (rBMECs) and identify involving the signal pathways. For initial experiments, the rBMECs were incubated with different concentrations of hydrogen peroxide (H2O2). For the second experiments, the rBMECs were respectively treated with ROS scavenger dimethylthiourea (DMTU), NADPH oxidase (Nox) inhibitor apocynin, small interfering RNAs-mediated knock down Nox2 or Nox4, or pretreated with c-Jun N-terminal kinase (JNK) inhibitor SP600125. The cell proliferation, migration, tube formation, and the expressions of several important neuroangiogenic factors including vascular endothelial growth factor (VEGF), brain derived neurotrophic factor (BDNF), matrix metalloproteinase (MMP) -9 and phos-JNK were measured. Low level of H2O2 significantly promoted endothelial cell (EC) proliferation, migration and tube formation and upregulated levels of VEGF, BDNF, MMP-9 and phos-JNK. DMTU and apocynin significantly inhibited endothelial angiogenesis and downregulated these protein levels. As expected, knockdown of Nox2 or Nox4 expression blocked endothelial angiogenesis and downregulated the expressions of pro-neuroangiogenic factors. Furthermore, H2O2-induced endothelial angiogenesis and high expressions of pro-neuroangiogenic factors were decreased by SP600125. In conclusion, Nox-derived ROS were required for endothelial angiogenesis. Low level of ROS may activate JNK signaling pathway and upregulate pro-neuroangiogenic factors, ultimately mediating endothelial angiogenesis.

Primary retroperitoneal paraganglioma mimicking a ureteral tumor: a case report and literature review.

Paragangliomas (PGLs) arise from chromaffin cells of the extra-adrenal sites along the sympathetic and/or the parasympathetic chain. Majority of the PGLs occur in the abdomen. When retroperitoneal PGLs produce symptoms of compression or invasion of adjacent organs, they could be misdiagnosed as a tumor of adjacent organs. Here, we report a rare case of ureteral obstruction caused by an extra-adrenal retroperitoneal PGL that mimicked a ureteral tumor. A 46-year-old female presented with a 2-year history of hypertension. Routine laboratory tests were unremarkable. The computed tomography (CT) scan showed a hypervascular mass located in the left mid-ureteral section. Ureteropyelography revealed left ureteral obstruction at the level of L4 to L5 vertebrae and hydroureteronephrosis. Cystoscopy confirmed left ureteral obstruction. Based on the clinical and imaging findings, a left ureteral tumor was suspected preoperatively. The tumor was completely resected, and the involved segment of the ureter was removed. No significant enlarged lymph nodes were seen in the pelvic cavity and retroperitoneum. A histopathological examination of the tumor confirmed retroperitoneal PGL partly infiltrating the ureter. The patient's blood pressure returned to the normal range postoperatively. Our case demonstrates the importance of considering extra-adrenal PGL in the differential diagnosis of retroperitoneal tumors.

A Systematic Meta-Analysis of the Effect of Interprofessional Education on Health Professions Students' Attitudes.

Interprofessional education (IPE) is based on collaborative practices that increase the occasions for communication among those in various health professions. However, there is a paucity of literature about the effectiveness of IPE programs in health professions education. The aim of this systematic review and meta-analysis was to objectively assess the literature on the effectiveness of IPE in improving health professions students' attitudes after training. The major scholarly databases were searched for relevant IPE studies involving predoctoral health professions students. Two independent researchers selected the studies, extracted the data, and assessed the quality of the studies. Meta-analyses of the outcomes were performed using random effects models. Sixteen articles were ultimately selected for detailed review and meta-analysis. The meta-analysis showed that IPE training had a significant influence on students' understanding of collaboration and resulted in better attitudes about interprofessional teamwork. Subscale analysis showed that one subscale score (roles and responsibilities) did not statistically significantly improve after IPE training (p=0.06), whereas the other four subscale items showed statistically significant improvements (p<0.01). The test for overall effects showed that IPE training had a significantly positive influence on students' attitudes about IPE (Z=6.85, p<0.01). Subgroup results showed that medical students had more positive attitudes about IPE than did dental students. Regardless of profession, women students responded with significantly more positive feedback than did men students (p=0.02). These results suggest that intervention through IPE training has had positive effects in health professions education. Gender was an important factor impacting the outcomes of IPE. However, further clinical practice interventions may be helpful to enhance the IPE competence of health professions students.