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Abstract This study aims to explore the inhibitory effects of combined metformin and simvastatin therapy on the malignant progression of glioma. The research specifically examines how the maturation of SREBP2 as a transcription factor affects the expression of GLUT1 and GLUT6 in glioma cells. Additionally, it investigates the impact of this combination therapy on the biological functions and energy metabolism of glioma cells. To assess the functions of GLUT1/6, sh-GLUT1/6 plasmids were employed. The study determined the half-maximal inhibitory concentrations (IC50) of metformin and simvastatin using the CCK-8 assay. Subsequently, the effects of these drugs on glioma metabolism, proliferation, and apoptosis were explored in vitro and in vivo, using drug concentrations significantly lower than their respective IC50 values. The impact of drug treatment on GLUT1/6 and SREBP2 expression levels was also evaluated. The study elucidated the significant impact of GLUT1/6 on glioma cell functions, resulting in decreased glucose uptake. Moreover, it unveiled the regulatory role of SREBP2 in GLUT1 and GLUT6 transcription, alongside revealing differential expression of SREBP2 precursor and mature forms within gliomas. Following combined drug therapy, GLUT1/6 expression decreased, while the precursor form of SREBP2 increased, and mature SREBP2 reduced. This dual-drug treatment effectively modulated glioma cell energy metabolism. Subsequent in vivo experiments affirmed the augmented anti-tumor efficacy of combined drug therapy. Specifically, the synergistic action of metformin and simvastatin reshaped glioma metabolism, curbed malignant proliferation, promoted apoptosis, and demonstrated superior anti-tumor effects both in vitro and in vivo compared to individual administration of metformin or simvastatin. Importantly, the combination therapy achieved these effects at lower doses, rendering it a safer treatment option.

Abstract Glioblastoma (GBM) presents significant challenges due to its invasive nature and genetic heterogeneity. In this study, we investigated the impact of Small VCP/P97-Interacting Protein (SVIP) on GBM progression. Our results revealed elevated expression of Insulin-like Growth Factor Binding Protein 2 (IGFBP-2) and STIP1 homology and U-box containing protein 1 (STUB1), coupled with reduced SVIP levels in GBM samples. Notably, high IGFBP-2 expression correlated with poor prognosis. Mechanistically, SVIP competitively inhibited STUB1, selectively binding to VCP/p97, thereby reducing PTEN degradation. This SVIP-mediated regulation exerted influence on the PTEN/PI3K/AKT/mTOR pathway, leading to the suppression of GBM progression. Co-localization experiments demonstrated that SVIP hindered PTEN ubiquitination and degradation by outcompeting STUB1 for VCP/p97 binding. Moreover, SVIP overexpression resulted in reduced activation of AKT/mTOR signaling and facilitated autophagy. In vivo experiments using a GBM xenograft model substantiated the tumor-suppressive effects of SVIP, evident by suppressed tumor growth, decreased IGFBP-2 expression, and improved survival rates. Collectively, our findings underscore the functional significance of SVIP in GBM progression. By inhibiting STUB1 and stabilizing PTEN, SVIP modulates the expression of IGFBP-2 and attenuates the activation of the PI3K/AKT/mTOR pathway, thereby emerging as a promising therapeutic target for GBM treatment.

Abstract Photobiomodulation (PBM) has emerged as a rapidly growing and innovative therapeutic method for various illnesses in recent years. Due to the irreversible nature of Parkinson's disease (PD), it has proven challenging to impede or postpone the progression of the disease. Despite research on pharmacological approaches to halt neuronal degeneration, the viability of these techniques has been called into doubt due to apprehensions over potential side effects and the ethical implications associated with the utilization of embryonic cell transplantation. Hence, developing an innovative therapeutic approach to halting neuronal degeneration and safeguarding neurons from this neurodegenerative disorder is imperative. This review examines the pathogenesis, challenges, and limitations of conventional PD therapies, allowing a closer examination of PBM's distinctive approach within this medical context. Delving into PBM's therapeutic mechanisms in the cells, the effects of different wavelengths on cell therapies in PD patients, and considerations for patient care administration to overcome traditional challenges, this study offers insights into its potential as a promising avenue for PD management.

Abstract The peptidyl-prolyl cis-trans isomerase Pin1 is a pivotal therapeutic target in cancers, but the regulation of Pin1 protein stability is largely unknown. High Pin1 expression is associated with SUMO1-modified protein hypersumoylation in glioma stem cells (GSCs), but the underlying mechanisms remain elusive. Here we demonstrate that Pin1 is deubiquitinated and stabilized by USP34, which promotes isomerization of the sole SUMO E2 enzyme Ubc9, leading to SUMO1-modified hypersumoylation to support GSC maintenance. Pin1 interacts with USP34, a deubiquitinase with preferential expression and oncogenic function in GSCs. Such interaction is facilitated by Plk1-mediated phosphorylation of Pin1. Disruption of USP34 or inhibition of Plk1 promotes poly-ubiquitination and degradation of Pin1. Furthermore, Pin1 isomerizes Ubc9 to upregulate Ubc9 thioester formation with SUMO1, which requires CDK1-mediated phosphorylation of Ubc9. Combined inhibition of Pin1 and CDK1 with sulfopin and RO3306 most effectively suppresses orthotopic tumor growth. Our findings provide multiple molecular targets to induce Pin1 degradation and suppress hypersumoylation for cancer treatment.

Radiometers and Wearable biosensors, as vital parts of the realm of quantum medicine, are becoming popular for their ability to continuously and immediately provide physiological data through single-cell spectroscopy, brain imaging, and noninvasive monitoring of biochemical markers in various neuroimaging and biofluids such as sweat, tears, and interstitial fluid. Various biosensing, microfluidic sampling, and transport technologies have been combined, made smaller, and incorporated with flexible materials to improve ease of use and comfort. Enhancing the understanding of the connections between noninvasive biofluids and blood analyte levels is crucial for improving the reliability of wearable biosensors. This review discusses the noninvasive monitoring of biomarkers such as hormones and metabolites utilizing electrochemical and optical biosensors, single-cell spectroscopy, and brain imaging. Increasing the number of biomarkers for monitoring will need further on-body bio affinity testing and various sensing devices. Large-scale validation studies with many participants are necessary to use wearable biosensors in therapeutic settings. Wearable biosensor technology's ability to quickly and accurately detect real-time physiological data in therapy might significantly impact our daily routines

Abstract Background Calcifying pseudoneoplasm of the neuraxis (CAPNON) is indeed a rare central nervous system lesion that can occur in central nervous system (CNS). Due to its infrequency and limited literature reports, it is challenging to diagnose and manage CAPNON. Case presentation In this intriguing study, we embarked on a quest to uncover the story of a 16-year-old girl who experienced bothersome headaches. Through advanced imaging techniques like computed tomography (CT) and magnetic resonance imaging (MRI), we glimpsed a delicate calcified growth within the lateral ventricles’ posterior horn. Motivated by our unwavering commitment to solving mysteries, we embarked on a surgical journey that not only freed the young patient from her ailment but also shed light on the true nature of her puzzling adversary—a remarkable CAPNON. Conclusions For patients with CAPNON who have multiple or non-respectable lesions, the primary goal is to alleviate symptoms. After alleviating the symptoms with partial resection, close monitoring of any residual lesions is essential. If there is no evidence for disease progression, a strategy of continued close observation is appropriate.

Abstract Glioblastoma (GBM) is the most common malignant primary brain cancer in adults and has constantly been a focus of research. Long noncoding RNAs (lncRNAs) play important roles in the development of cancers. To illustrate the role of lncRNAs in the development of glioblastoma, high-throughput RNA sequencing was performed to obtain the transcripts using three freshly isolated tumor tissue samples from GBM patients and three normal brain tissue samples from the traumatic brain of patients. Then, a lncRNA, MGCG (MGC70870 is expressed at a high level in glioblastoma), which has not been reported previously in GBM, was found to be associated with the prognosis of patients. The results of bioinformatic analysis showed that MGCG was correlated with autophagy and positively correlated with the expression of the autophagy-related gene ATG2A. The data of mass spectrometry demonstrated that the hnRNPK protein was a direct target interacting with MGCG, and MGCG/hnRNPK promoted the development of GBM by enhancing the translation of ATG2A and autophagy. In conclusion, the present study showed that MGCG has the potential to promote the development of GBM and may become a candidate for molecular diagnostics and treatment of tumors.

Summary: Amino acid formula (AAF) is increasingly consumed in infants with cow’s milk protein allergy; however, the long-term influences on health are less described. In this study, we established a mouse model by subjecting neonatal mice to an amino acid diet (AAD) to mimic the feeding regimen of infants on AAF. Surprisingly, AAD-fed mice exhibited dysbiotic microbiota and increased neuronal activity in both the intestine and brain, as well as gastrointestinal peristalsis disorders and depressive-like behavior. Furthermore, fecal microbiota transplantation from AAD-fed mice or AAF-fed infants to recipient mice led to elevated neuronal activations and exacerbated depressive-like behaviors compared to that from normal chow-fed mice or cow’s-milk-formula-fed infants, respectively. Our findings highlight the necessity to avoid the excessive use of AAF, which may influence the neuronal development and mental health of children.

Objective: This work focused on investigating if robot-assisted minimally invasive surgery improved middle term vital outcome for primary brainstem hemorrhage (PBSH). Methods: This work obtained clinical data from patients with PBSH admitted from July 2019 to August 2021. All cases were classified as surgical or conservative treatment group. The general information, Glasgow coma scale (GCS) score, Glasgow outcome score (GOS), along with survival time in patients 60 days after robot-assisted surgery were recorded and analyzed. Results: A prospective analysis was performed on 82 cases meeting eligibility criteria, including 36 from surgical group whereas 46 from the conservative group. Sixty days after onset, the death rate was found to be 19.44% and 50.00% of surgical and conservative groups, separately (cases versus controls, P

Abstract Introduction As a disorder of the brain in adults and children, traumatic brain injury (TBI) is considered the major cause of mortality and morbidity. As a serious complication of TBI, post-traumatic hydrocephalus (PTH) is commonly identified and significantly associated with neurocognitive impairment, motor dysfunction, and growth impairment. The long-term functional outcomes after shunt dependence are totally not clear. Methods This study included 6279 patients between 2012 and 2022. To identify the unfavorable functional outcomes and the PTH-related factors, we carried out univariable logistic regression analyses. To identify the occurrence time of PTH, we conducted the log-rank test and Kaplan–Meier analysis. Results Mean patient age was 51.03 ± 22.09 years. Of the 6279 patients with TBI, 327 developed PTH (5.2%). Several PTH development-associated factors, such as intracerebral hematoma, diabetes, longer initial hospital stay, craniotomy, low GCS (Glasgow Coma Scale), EVD (external ventricular drain), and DC (decompressive craniectomy) (p 80 years, repeated operations, hypertension, EVD, tracheotomy, and epilepsy (p

Abstract Understanding tumor heterogeneity and immune infiltrates within the tumor-immune microenvironment (TIME) is essential for the innovation of immunotherapies. Here, combining single-cell transcriptomics and chromatin accessibility sequencing, we profile the intratumor heterogeneity of malignant cells and immune properties of the TIME in primary central nervous system diffuse large B-cell lymphoma (PCNS DLBCL) patients. We demonstrate diverse malignant programs related to tumor-promoting pathways, cell cycle and B-cell immune response. By integrating data from independent systemic DLBCL and follicular lymphoma cohorts, we reveal a prosurvival program with aberrantly elevated RNA splicing activity that is uniquely associated with PCNS DLBCL. Moreover, a plasmablast-like program that recurs across PCNS/activated B-cell DLBCL predicts a worse prognosis. In addition, clonally expanded CD8 T cells in PCNS DLBCL undergo a transition from a pre-exhaustion-like state to exhaustion, and exhibit higher exhaustion signature scores than systemic DLBCL. Thus, our study sheds light on potential reasons for the poor prognosis of PCNS DLBCL patients, which will facilitate the development of targeted therapy.

Summary: Glioma, an aggressively growing and highly malignant brain tumor, poses substantial therapeutic challenges due to its resistance to radiotherapy and chemotherapy. Recent research has identified circRNAs as pivotal players in glioma formation and development. However, the roles of circRNA in the metabolic and immune regulation of glioma are unclear. In this study, circSOBP expression was significantly downregulated in glioma cells and specimens. Functionally, enhanced circSOBP expression mitigated cell proliferation, invasion, migration, and glycolysis in gliomas. Mechanistically, circSOBP inhibited glycolysis and activated the MDA5-mediated IKKε/TBK1/IRF3 signaling pathway by binding TKFC proteins. Furthermore, the elevated levels of IFN-I induced by the MDA5 pathway increased the number and activity of CD8+ T and NK cells in the immune response of the animal models. In summary, our findings have emphasized the critical role of circSOBP in binding and modulating TKFC protein, offering potential therapeutic avenue for targeting glioma metabolism and immunological reprogramming.

Abstract Tumor-associated exosomes play essential roles in intercellular communication and the foundation of cancer microenvironment in glioma. Many mRNAs, microRNAs (miRNAs) and proteins contained in tumor-associated exosomes can be transferred to recipient cells and contribute to the progression of tumor. Nevertheless, the cellular communication between malignant cells with different heterogeneities or characteristics and resultant tumor progression are still unclear in glioma. Here, we show that exosomes released from glioma stem-like cells (GSCs) contain a significant increasing level of miR-155-5p and could be horizontally transferred to surrounding glioma cells. High expression of miR-155-5p in plasma exosomes from patients was associated with glioma diagnosis and grading. Mechanically, we found that miR-155-5p markedly reduced the expression of acetyl-CoA thioesterase 12 (ACOT12), which played as a tumor suppressor in glioma. Furthermore, mesenchymal transition was significantly promoted in glioma cells treated with GSCs-derived exosomes. In conclusion, GSCs-derived exosomal miR-155-5p play a critical role in glioma progression and facilitating tumor aggressive growth by targeting ACOT12 and promoting mesenchymal transition. Exosomal miR-155-5p is also a potential predictive biomarker for glioma, which may provoke the development of novel diagnostic and therapeutic strategies against glioma.

IntroductionParkinson’s disease (PD) is a neurodegenerative disorder characterized by dyskinesia and is closely related to oxidative stress. Uric acid (UA) is a natural antioxidant found in the body. Previous studies have shown that UA has played an important role in the development and development of PD and is an important biomarker. Subthalamic nucleus deep brain stimulation (STN-DBS) is a common treatment for PD.MethodsBased on resting state function MRI (rs-fMRI), the relationship between UA-related brain function connectivity (FC) and STN-DBS outcomes in PD patients was studied. We use UA and DC values from different brain regions to build the FC characteristics and then use the SVR model to predict the outcome of the operation.ResultsThe results show that PD patients with UA-related FCs are closely related to STN-DBS efficacy and can be used to predict prognosis. A machine learning model based on UA-related FC was successfully developed for PD patients.DiscussionThe two biomarkers, UA and rs-fMRI, were combined to predict the prognosis of STN-DBS in treating PD. Neurosurgeons are provided with effective tools to screen the best candidate and predict the prognosis of the patient.

In cancer, neutrophils are an important part of the tumour microenvironment (TME). Previous studies have shown that circulating and infiltrating neutrophils are associated with malignant progression and immunosuppression in gliomas. However, recent studies have shown that neutrophils have an antitumour effect. In this review, we focus on the functional roles of neutrophils in the circulation and tumour sites in patients with glioma. The mechanisms of neutrophil recruitment, immunosuppression and the differentiation of neutrophils are discussed. Finally, the potential of neutrophils as clinical biomarkers and therapeutic targets is highlighted. This review can help us gain a deeper and systematic understanding of the role of neutrophils, and provide new insights for treatment in gliomas.

Objective:Programming plays an important role in the outcome of deep brain stimulation (DBS) for Parkinson's disease (PD). This study introduced a new application for functional zonal image reconstruction in programming.MethodsFollow-up outcomes were retrospectively compared, including first programming time, number of discomfort episodes during programming, and total number of programming sessions between patients who underwent image-reconstruction-guided programming and those who underwent conventional programming. Data from 142 PD patients who underwent subthalamic nucleus (STN)-DBS between January 2017 and June 2019 were retrospectively analyzed. There were 75 conventional programs and 67 image reconstruction-guided programs.ResultsAt 1-year follow-up, there was no significant difference in the rate of stimulus improvement or superposition improvement between the two groups. However, patients who underwent image reconstruction-guided programming were significantly better at the first programming time, number of discomfort episodes during programming, and total number of programming sessions than those who underwent conventional programming.ConclusionImaging-guided programming of directional DBS leads was possible and led to reduced programming time and reduced patient side effects compared with conventional programming.

Abstract Background Glioblastoma is the most common primary malignant intracranial tumor with poor clinical prognosis in adults. Accumulating evidence indicates that long non-coding RNAs (lncRNAs) function as important regulators in cancer progression, including glioblastoma. Here, we identified a new lncRNA LPP antisense RNA-2 (LPP-AS2) and investigated its function and mechanism in the development of glioma. Methods High-throughput RNA sequencing was performed to discriminate differentially expressed lncRNAs and mRNAs between glioma tissues and normal brain tissues. Expression of LPP-AS2, epidermal growth factor receptor (EGFR) and miR-7-5p in glioma tissues and cell lines was detected by real-time quantitative PCR (RT-qPCR), and the functions of lncRNA LPP-AS2 in glioma were assessed by in vivo and in vitro assays. Insight into the underlying mechanism of competitive endogenous RNAs (ceRNAs) was obtained via bioinformatic analysis, dual luciferase reporter assays, RNA pulldown assays, RNA immunoprecipitation (RIP) and rescue experiments. Results The results of high-throughput RNA-seq indicated lncRNA LPP-AS2 was upregulated in glioma tissues and further confirmed by RT-qPCR. Higher LPP-AS2 expression was related to a poor prognosis in glioma patients. Based on functional studies, LPP-AS2 depletion inhibited glioma cell proliferation, invasion and promoted apoptosis in vitro and restrained tumor growth in vivo, overexpression of LPP-AS2 resulted in the opposite effects. In addition, LPP-AS2 and EGFR were observed in co-expression networks. LPP-AS2 was found to function as a ceRNA to regulate EGFR expression by sponging miR-7-5p in glioma cells. The result of chromatin immunoprecipitation (ChIP) assays validated that c-MYC binds directly to the promoter region of LPP-AS2. As a downstream protein of EGFR, c-MYC was modulated by LPP-AS2 and in turn enhanced LPP-AS2 expression. Thus, lncRNA LPP-AS2 promoted glioma tumorigenesis via a miR-7-5p/EGFR/PI3K/AKT/c-MYC feedback loop. Conclusions Our study elucidated that LPP-AS2 acted as an oncogene through a novel molecular pathway in glioma and might be a potential therapeutic approach for glioma diagnosis, therapy and prognosis.

Abstract The roles of some long non-coding RNAs (lncRNAs) in intracranial aneurysm (IA) have been investigated in many studies. The aim of this study is to elucidate the mechanism of lncRNA metastasis-associated lung adenocarcinoma transcript 1 (MALAT1)/microRNA-143 (miR-143)/vascular endothelial growth factor-A (VEGFA) signal axis in vascular endothelial injury-induced IA. MALAT1, miR-143, and VEGFA expression in IA tissues and normal arterial tissues were detected. Matrix metalloproteinase 9 (MMP-9) in tissues, von Willebrand factor (vWF) in serum and tissues, and endothelin-1 (ET-1) in serum were detected. The modeled IA rats were injected with silenced or overexpressed MALAT1 for detecting vascular endothelial injury. Vascular endothelial cells from patients with IA were abstracted and transfected with silenced or overexpressed MALAT1 to verify the impacts of MALAT1 on cell viability and apoptosis. The connections among MALAT1, miR-143, and VEGFA were verified by online prediction, luciferase activity, and RNA-pull down assays. Overexpression of MALAT1 and VEGFA and poor expression of miR-143 were found in IA tissues. Downregulation of MALAT1 inhibited blood pressure, the expression of ET-1, vWF, and MMP-9, as well as the apoptotic index of vascular endothelial cells of rats with IA. Downregulated MALAT1 inhibited apoptosis and promoted viability of vascular endothelial cells in IA. MALAT1 bound to miR-143 and miR-143 targeted VEGFA. This study suggests that MALAT1 elevates VEGFA expression through competitive binding to miR-143, thereby boosting apoptosis and attenuating viability of vascular endothelial cells in IA.

ObjectivePolymorphous low-grade neuroepithelial tumor of the young (PLNTY) is a novel distinct epileptogenic neoplasm, and its clinical, imaging, histopathological, and molecular features were already known in the existing literature. We aimed to analyze the surgical management of PLNTY combined with these known characteristics.MethodsEight patients underwent surgical treatment in our center between December 2017 and December 2020, and the postoperative pathology was diagnosed as PLNTY. Their clinical data, imaging, pathological, molecular characteristics, and seizure outcome were retrospectively analyzed. Follow-up evaluations and a literature review were performed.ResultsThe 8 patients included 1 woman and 7 men, aged between 5 and 51 years old (mean = 31.6, median = 29). The preoperative symptoms of all 8 cases were seizures. Four tumors were situated in the temporal lobes, and one of the four extratemporal tumors was in the occipital lobe and three were in the frontal lobe. Enlarged and gross total resections were performed in 2 cases and the other 6 cases, respectively. All cases exhibited intense labeling of CD34, and absence of 1p/19q codeletion and IDH1 or IDH2 mutation. B-Raf proto-oncogene (BRAF) V600E mutation was presented in 4 (66.7%) of 6 detected cases. The postoperative seizure outcome of Engel class I was achieved in 6 cases (75%).ConclusionPLNTY represents distinctive histologic, immunophenotypic and biomolecular features, and has high epileptogenicity. Early surgical intervention and enlarged resection of PLNTY associated with epilepsy will help to improve the postoperative seizure-free rate.

Background: Parkinson’s disease (PD) represents one of the most frequently seen neurodegenerative disorders, while anxiety accounts for its non-motor symptom (NMS), and it has greatly affected the life quality of PD cases. Bilateral subthalamic nucleus deep brain stimulation (STN-DBS) can effectively treat PD. This study aimed to develop a clinical prediction model for the anxiety improvement rate achieved in PD patients receiving STN-DBS. Methods: The present work retrospectively enrolled 103 PD cases undergoing STN-DBS. Patients were followed up for 1 year after surgery to analyze the improvement in HAMA scores. Univariate and multivariate logistic regression were conducted to select factors affecting the Hamilton Anxiety Scale (HAMA) improvement. A nomogram was established to predict the likelihood of achieving anxiety improvement. Receiver operating characteristic (ROC) curve analysis, decision curve analysis (DCA), and calibration curve analysis were conducted to verify nomogram performance. Results: The mean improvement in HAMA score was 23.9% in 103 patients; among them, 68.9% had improved anxiety, 25.2% had worsened (Preop) anxiety, and 5.8% had no significant change in anxiety. Education years, UPDRS-III preoperative score, and HAMA preoperative score were independent risk factors for anxiety improvement. The nomogram-predicted values were consistent with real probabilities. Conclusions: Collectively, a nomogram is built in the present work for predicting anxiety improvement probability in PD patients 1 year after STN-DBS. The model is valuable for determining expected anxiety improvement in PD patients undergoing STN-DBS.

Prolactinomas have been reported to impair cognition in broad aspects. However, few studies investigated the influence of prolactinomas on cognitive flexibility never mentioning the underlying neural and electrophysiological mechanism. We recorded scalp electroencephalography (EEG) in a colour-shape switching task. Patients with prolactinomas showed longer reaction time in switch trials and larger switch costs relative to healthy controls (HCs). Compared to HCs who showed stronger frontal theta activity in switch trials, the generally weak frontal theta activity in patients implied that they could not afford the executive control to configure task sets. Meanwhile, machine-learning based classification revealed that patients manifested non-selective brain patterns in response to different task types (colour vs. shape task) and different task states (switch vs. repeat state), which collectively suggested the cognitive dysfunction in preparation for a changing environment. Compared to HCs who showed stronger frontoparietal synchronization in switch trials, this enhanced frontoparietal connectivity was disrupted among patients with severe prolactinomas. This finding implicated greater hyperprolactinemia was linked to a larger decrease in cognitive performance. Taken together, the present study highlighted frontal theta power, and frontoparietal connectivity at theta band as the electrophysiological markers of the impaired cognitive flexibility and task control in patients with prolactinomas.

Glioma, especially glioblastoma, is the most common and lethal brain tumor. In line with the complicated vascularization processes and the strong intratumoral heterogeneity, tumor-associated blood vessels in glioma are regulated by multiple types of cells through a variety of molecular mechanisms. Components of the tumor microenvironment, including tumor cells and tumor-associated stromata, produce various types of molecular mediators to regulate glioma angiogenesis. As critical regulatory molecules, non-coding RNAs (ncRNAs) inside cells or secreted to the tumor microenvironment play essential roles in glioma angiogenesis. In this review, we briefly summarize recent studies about the production, delivery, and functions of ncRNAs in the tumor microenvironment, as well as the molecular mechanisms underlying the regulation of angiogenesis by ncRNAs. We also discuss the ncRNA-based therapeutic strategies in the anti-angiogenic therapy for glioma treatment.

Background: Main motor characteristics in Parkinson's disease (PD) include bradykinesia, rigidity, and tremors. With the development of neuromodulation techniques, it has become possible to use deep brain stimulation (DBS) to control the symptoms of PD. However, since the subthalamic nucleus(STN) and globus pallidus interna (GPi) DBS have their own advantages and disadvantages, it is difficult to control symptoms of the patients. It is essential to find new stimulation methods.Case Presentation: A 33-year-old male PD patient with onset at the age of 12 years. The onset of the disease is presented with bradykinesia and progressively developed severe choreic dyskinesia with the use of medications. We then performed a thorough evaluation of the patient and decided to perform bilateral globus pallidus interna combined with subthalamic nucleus variable frequency DBS (bSGC-DBS) implantation, and after 2 years of follow-up the patient's bradykinesia and dyskinesia symptoms and quality of life improved significantly.Conclusions: This is the first case of bSCG-DBS in a PD patient with refractory dyskinesia, and the first report of encouraging results from this clinical condition. This important finding explores multi-electrode and multi-target stimulation for the treatment of dystonia disorders.

Glioblastomas are the most frequently diagnosed and one of the most lethal primary brain tumors, and one of their key features is a dysplastic vascular network. However, because the origin of the tumor blood vessels remains controversial, an optimal preclinical tumor model must be established to elucidate the tumor angiogenesis mechanism, especially the role of tumor cells themselves in angiogenesis. Therefore, shell-glioma cell (U118)-red fluorescent protein (RFP)/core-human umbilical vein endothelial cell (HUVEC)-green fluorescent protein (GFP) hydrogel microfibers were coaxially bioprinted. U118–RFP and HUVEC–GFP cells both exhibited good proliferation in a three-dimensional (3D) microenvironment. The secretability of both vascular endothelial growth factor A and basic fibroblast growth factor was remarkably enhanced when both types of cells were cocultured in 3D models. Moreover, U118 cells promoted the vascularization of the surrounding HUVECs by secreting vascular growth factors. More importantly, U118–HUVEC-fused cells were found in U118–RFP/HUVEC–GFP hydrogel microfibers. Most importantly, our results indicated that U118 cells can not only recruit the blood vessels of the surrounding host but also directly transdifferentiate into or fuse with endothelial cells to participate in tumor angiogenesis in vivo. The coaxially bioprinted U118–RFP/HUVEC–GFP hydrogel microfiber is a model suitable for mimicking the glioma microenvironment and for investigating tumor angiogenesis.

Background: The diagnosis of hydrocephalus is mainly based on imaging findings. However, the significance of many imaging indicators may change, especially in some degenerative diseases, and even lead to misdiagnosis. Methods: This study explored the effectiveness of commonly used morphological parameters and typical radiographic findings in hydrocephalus diagnosis. The patients’ imaging data were divided into three groups, including the hydrocephalus group, the symptomatic group, and the normal control group. The diagnostic validity and weight of various parameters were compared between groups by multiple machine learning methods. Results: Our results demonstrated that Evans’ ratio is the most valuable diagnostic indicator compared to the hydrocephalus group and the normal control group. But frontal horns’ ratio is more useful in diagnosing patients with symptoms. Meanwhile, the sign of disproportionately enlarged subarachnoid space and third ventricle enlargement could be effective diagnostic indicators in all situations. Conclusion: Both morphometric parameters and radiological features were essential in diagnosing hydrocephalus, but the weights are different in different situations. The machine learning approaches can be applied to optimize the diagnosis of other diseases and consistently update the clinical diagnostic criteria.

Objective: The Ki-67 index is an indicator of the active proliferation and aggressive behavior of pituitary adenomas (PAs). Appropriate pre- and intra-operatives of the Ki-67 index can help surgeons develop better and more personalized treatment strategies for patients with PAs. This study aimed to investigate the influence factors for predicting the Ki-67 index in PAs. Methods: Data of 178 patients with PAs confirmed by pathology were retrospectively analyzed. According to the Ki-67 index, the patients were divided into the Ki-67 < 3% and Ki-67 ≥ 3% cohorts. Patient data, including age, sex, postoperative immunohistochemical pituitary hormone positive index, Knosp grade, tumor breaking through the sellar floor, rich blood supply to the tumor, tumor located inside the sella, erosion of the dorsum sellae bone, and pituitary-specific transcription factor, were collected. A univariate logistic analysis was used to evaluate the influence factors for a high Ki-67 index. Multiple regression and receiver operating characteristic (ROC) curve were used to analyze the factors with p < 0.05. The mutant status of Ki-67 index was predicted by nomogram. Results: Multivariate regression analysis showed that rich blood supply to the tumor and erosion of the dorsum sellae bone were independent risk factors for the Ki-67 proliferation index. The ROC curves demonstrated that age, rich blood supply to the tumor, and erosion of the dorsum sellae bone can predict the occurrence of a high Ki-67 index. Together, the three risk factors provide a stronger ability to predict the Ki-67 index. The nomogram was developed and validated. Conclusion: Age, rich blood supply to the tumor, and erosion of the dorsum sellae bone are influencing factors for predicting the Ki-67 index. Suitable nomogram prediction models were developed and validated, and there is potential for personalized treatment for PA patients.

Neuroblastoma is the most common extracranial neuroendocrine tumor in childhood. Although many studies have tried to find effective treatments, there are still numerous limitations in current clinical targeted therapy. So, it is important to find new therapeutic targets and strategies from a new perspective. Our previous study reported that the androgen receptor (AR) promotes the growth of neuroblastoma in vitro and in vivo. Based on documentary investigation, we postulated that the AR–SCAP–SREBPs-CYP17/HMGCR axis may regulate cholesterol and androgens synthesis and form a positive enhancement loop promoting NB progression. Clinical samples and Oncomine database analysis proved the activation of AR–SCAP–SREBPs-CYP17/HMGCR axis in neuroblastoma. The combination of inhibitors of HMGCR (statins) and CYP17A1 (abiraterone acetate) showed synergistic effect that significantly inhibited the proliferation and migration with decreased expression of related genes detected in vitro and in vivo suggesting the dual-targeted therapy had the potential to inhibit the progression of neuroblastoma in spite of its MYCN status. This study provides new ideas for clinical treatment of neuroblastoma with efficacy and reduced toxicity.

The interleukins (ILs) are a pluripotent cytokine family that have been reported to regulate ischemic stroke and cerebral ischemia/reperfusion (I/R) injury. IL-22 is a member of the IL-10 superfamily and plays important roles in tissue injury and repair. However, the effects of IL-22 on ischemic stroke and cerebral I/R injury remain unclear. In the current study, we provided direct evidence that IL-22 treatment decreased infarct size, neurological deficits, and brain water content in mice subjected to cerebral I/R injury. IL-22 treatment remarkably reduced the expression of inflammatory cytokines, including IL-1β, monocyte chemotactic protein- (MCP-) 1, and tumor necrosis factor- (TNF-) α, both in serum and the ischemic cerebral cortex. In addition, IL-22 treatment also decreased oxidative stress and neuronal apoptosis in mice after cerebral I/R injury. Moreover, IL-22 treatment significantly increased Janus tyrosine kinase (JAK) 2 and signal transducer and activator of transcription (STAT) 3 phosphorylation levels in mice and PC12 cells, and STAT3 knockdown abolished the IL-22-mediated neuroprotective function. These findings suggest that IL-22 might be exploited as a potential therapeutic agent for ischemic stroke and cerebral I/R injury.

Background: Parkinson’s disease is a common neurodegenerative disease, with depression being a common non-motor symptom. Bilateral subthalamic nucleus deep brain stimulation is an effective method for the treatment of Parkinson’s disease. Thus, this study aimed to establish a nomogram of the possibility of achieving a better depression improvement rate after subthalamic nucleus deep brain stimulation in patients with Parkinson’s disease. Methods: We retrospectively analyzed 103 patients with Parkinson’s disease who underwent subthalamic nucleus deep brain stimulation and were followed up for the improvement of their Hamilton Depression scale scores 1 year postoperatively. Univariate and multivariate logistic regression analyses were used to select factors affecting the improvement rate of depression. A nomogram was then developed to predict the possibility of achieving better depression improvement. Furthermore, the discrimination and fitting performance was evaluated using a calibration diagram, receiver operating characteristics, and decision curve analysis. Results: The mean and median improvement rates of Hamilton Depression scores were 13.1 and 33.3%, respectively. Among the 103 patients, 70.8% had an improved depression, 23.3% had a worsened depression, and 5.8% remained unchanged. Logistic multivariate regression analysis showed that age, preoperative Parkinson’s Disease Questionnaire, Hamilton Anxiety, and Hamilton Depression scores were independent factors for the possibility of achieving a better depression improvement rate. Based on these results, a nomogram model was developed. The nomogram had a C-index of 0.78 (95% confidence interval: 0.69–0.87) and an area under the receiver operating characteristics of 0.78 (95% confidence interval: 0.69–0.87). The calibration plot and decision curve analysis further demonstrated goodness-of-fit between the nomogram predictions and actual observations. Conclusion: We developed a nomogram to predict the possibility of achieving good depression improvement 1 year after subthalamic nucleus deep brain stimulation in patients with Parkinson’s disease, which showed a certain value in judging the expected depression improvement of these patients.

Purpose: Parkinson’s disease (PD) is a common neurodegenerative disease, for which cognitive impairment is a non-motor symptom (NMS). Bilateral subthalamic nucleus deep brain stimulation (STN-DBS) is an effective treatment for PD. This study established a nomogram to predict cognitive improvement rate after STN-DBS in PD patients. Methods: We retrospectively analyzed 103 PD patients who underwent STN-DBS. Patients were followed up to measure improvement in MoCA scores one year after surgery. Univariate and multivariate logistic regression analyses were used to identify factors affecting improvement in cognitive status. A nomogram was developed to predict this factor. The discrimination and fitting performance were evaluated by receiver operating characteristics (ROC) analysis, calibration diagram, and decision curve analysis (DCA). Results: Among 103 patients, the mean improvement rate of the MoCA score was 37.3% and the median improvement rate was 27.3%, of which 64% improved cognition, 27% worsened cognition, and 8.7% remained unchanged. Logistic multivariate regression analysis showed that years of education, UPDRSIII drug use, MoCA Preop, and MMSE Preop scores were independent factors affecting the cognitive improvement rate. A nomogram model was subsequently developed. The C-index of the nomogram was 0.98 (95%CI, 0.97–1.00), and the area under the ROC was 0.98 (95%CI 0.97–1.00). The calibration plot and DCA demonstrated the goodness-of-fit between nomogram predictions and actual observations. Conclusion: Our nomogram could effectively predict the possibility of achieving good cognitive improvement one year after STN-DBS in patients with PD. This model has value in judging the expected cognitive improvement of patients with PD undergoing STN-DBS.