Integrated analysis of single-cell sequencing and machine learning identifies a signature based on monocyte/macrophage hub genes to analyze the intracranial aneurysm associated immune microenvironment.

Monocytes are pivotal immune cells in eliciting specific immune responses and can exert a significant impact on the progression, prognosis, and immunotherapy of intracranial aneurysms (IAs). The objective of this study was to identify monocyte/macrophage (Mo/MΦ)-associated gene signatures to elucidate their correlation with the pathogenesis and immune microenvironment of IAs, thereby offering potential avenues for targeted therapy against IAs. Single-cell RNA-sequencing (scRNA-seq) data of IAs were acquired from the Gene Expression Synthesis (GEO) database. The significant infiltration of monocyte subsets in the parietal tissue of IAs was identified using single-cell RNA sequencing and high-dimensional weighted gene co-expression network analysis (hdWGCNA). The integration of six machine learning algorithms identified four crucial genes linked to these Mo/MΦ. Subsequently, we developed a multilayer perceptron (MLP) neural model for the diagnosis of IAs (independent external test AUC=1.0, sensitivity =100%, specificity =100%). Furthermore, we employed the CIBERSORT method and MCP counter to establish the correlation between monocyte characteristics and immune cell infiltration as well as patient heterogeneity. Our findings offer valuable insights into the molecular characterization of monocyte infiltration in IAs, which plays a pivotal role in shaping the immune microenvironment of IAs. Recognizing this characterization is crucial for comprehending the limitations associated with targeted therapies for IAs. Ultimately, the results were verified by real-time fluorescence quantitative PCR and Immunohistochemistry.

Role of inflammatory mediators in intracranial aneurysms: A review.

The formation, growth, and rupture of intracranial aneurysms (IAs) involve hemodynamics, blood pressure, external stimuli, and a series of hormonal changes. In addition, inflammatory response causes the release of a series of inflammatory mediators, such as IL, TNF-α, MCP-1, and MMPs, which directly or indirectly promote the development process of IA. However, the specific role of these inflammatory mediators in the pathophysiological process of IA remains unclear. Recently, several anti-inflammatory, lipid-lowering, hormone-regulating drugs have been found to have a potentially protective effect on reducing IA formation and rupture in the population. These therapeutic mechanisms have not been fully elucidated, but we can look for potential therapeutic targets that may interfere with the formation and breakdown of IA by studying the relevant inflammatory response and the mechanism of IA formation and rupture involved in inflammatory mediators.

Unveiling the intratumoral microbiota within cancer landscapes.

Recent advances in cancer research have unveiled a significant yet previously underappreciated aspect of oncology: the presence and role of intratumoral microbiota. These microbial residents, encompassing bacteria, fungi, and viruses within tumor tissues, have been found to exert considerable influence on tumor development, progression, and the efficacy of therapeutic interventions. This review aims to synthesize these groundbreaking discoveries, providing an integrated overview of the identification, characterization, and functional roles of intratumoral microbiota in cancer biology. We focus on elucidating the complex interactions between these microorganisms and the tumor microenvironment, highlighting their potential as novel biomarkers and therapeutic targets. The purpose of this review is to offer a comprehensive understanding of the microbial dimension in cancer, paving the way for innovative approaches in cancer diagnosis and treatment.

Intracranial aneurysm circulating exosome-derived LncRNA ATP1A1-AS1 promotes smooth muscle cells phenotype switching and apoptosis.

Exosomal long non-coding RNAs (LncRNAs) play a crucial role in the pathogenesis of cerebrovascular diseases. However, the expression profiles and functional significance of exosomal LncRNAs in intracranial aneurysms (IAs) remain poorly understood. Through high-throughput sequencing, we identified 1303 differentially expressed LncRNAs in the plasma exosomes of patients with IAs and healthy controls. Quantitative real-time polymerase chain reaction (qRT-PCR) verification confirmed the differential expression of LncRNAs, the majority of which aligned with the sequencing results. ATP1A1-AS1 showed the most significant upregulation in the disease group. Importantly, subsequent in vitro experiments validated that ATP1A1-AS1 overexpression induced a phenotype switching in vascular smooth muscle cells, along with promoting apoptosis and upregulating MMP-9 expression, potentially contributing to IAs formation. Furthermore, expanded-sample validation affirmed the high diagnostic value of ATP1A1-AS1. These findings suggest that ATP1A1-AS1 is a potential therapeutic target for inhibiting IAs progression and serves as a valuable clinical diagnostic marker.

A Rare Instance of Spinal Cord Cavernous Malformation With Adjacent Intramedullary Microhemorrhage.

The natural history of spinal cord cavernous malformation (SCM) may be characterized by recurrent episodes of hemorrhage resulting in a range of neurologic deficits, most of which are microhemorrhage and subsequent gliosis that can lead to progressive myelopathy. Macrohemorrhage with acute onset of symptoms is extremely rare and leads to irreversible neurologic deficits. In this article, we present an unusual case of ruptured cavernous malformation (CM) in the cervical spinal cord with large extralesional hemorrhage. The patient underwent an operation of posterior longitudinal myelotomy and had a good neurologic recovery. A histologic examination revealed the typical features of cavernous angioma.

Identification of differentially expressed autophagy-related genes in cases of intracranial aneurysm: Bioinformatics analysis.

OBJECTIVE: Recent research indicates that autophagy is essential for the rupture of intracranial aneurysm (IA). This study aimed to examine and validate potential autophagy-related genes (ARGs) in cases of IA using bioinformatics analysis. METHODS: Two expression profiles (GSE54083 and GSE75436) were obtained from the Gene Expression Omnibus database. Differentially expressed ARGs (DEARGs) in cases of IA were screened using GSE75436, and enrichment analysis and Protein-Protein Interaction (PPI) networks were used to identify the hub genes and related pathways. Furthermore, a novel predictive diagnostic signature for IA based on the hub genes was constructed. The area under the Receiver Operating Characteristic curve (AUC) was used to evaluate the signature performance in GSE75436. RESULTS: In total, 75 co-expressed DEARGs were identified in the GSE75436 and GSE54083 dataset (28 upregulated and 47 downregulated genes). Enrichment analysis of DEARGs revealed several enriched terms associated with proteoglycans in cancer and human immunodeficiency virus 1 infection. PPI analysis revealed interactions between these genes. Hub DEARGs included insulin-like growth factor 1, clusters of differentiation 4, cysteine-aspartic acid protease 8, Bcl-2-like protein 11, mouse double mutant 2 homolog, toll-like receptor 4, growth factor receptor-bound protein 2, Jun proto-oncogene, AP-1 transcription factor subunit, hypoxia inducible factor 1 alpha, and erythroblastic oncogene B-2. Notably, the signature showed good performance in distinguishing IA (AUC = 0.87). The sig calibration curves showed good calibration. CONCLUSION: Bioinformatic analysis identified 75 potential DEARGs in cases of IA. This study revealed that IA is affected by autophagy, which could explain the pathogenesis of IA and aid in its diagnosis and treatment. However, future research with experimental validation is necessary to identify potential DEARGs in cases of IA.

Identification of diagnostic markers for moyamoya disease by combining bulk RNA-sequencing analysis and machine learning.

Moyamoya disease (MMD) remains a chronic progressive cerebrovascular disease with unknown etiology. A growing number of reports describe the development of MMD relevant to infection or autoimmune diseases. Identifying biomarkers of MMD is to understand the pathogenesis and development of novel targeted therapy and may be the key to improving the patient's outcome. Here, we analyzed gene expression from two GEO databases. To identify the MMD biomarkers, the weighted gene co-expression network analysis (WGCNA) and the differential expression analyses were conducted to identify 266 key genes. The KEGG and GO analyses were then performed to construct the protein interaction (PPI) network. The three machine-learning algorithms of support vector machine-recursive feature elimination (SVM-RFE), random forest and least absolute shrinkage and selection operator (LASSO) were used to analyze the key genes and take intersection to construct MMD diagnosis based on the four core genes found (ACAN, FREM1, TOP2A and UCHL1), with highly accurate AUCs of 0.805, 0.903, 0.815, 0.826. Gene enrichment analysis illustrated that the MMD samples revealed quite a few differences in pathways like one carbon pool by folate, aminoacyl-tRNA biosynthesis, fat digestion and absorption and fructose and mannose metabolism. In addition, the immune infiltration profile demonstrated that ACAN expression was associated with mast cells resting, FREM1 expression was associated with T cells CD4 naive, TOP2A expression was associated with B cells memory, UCHL1 expression was associated with mast cells activated. Ultimately, the four key genes were verified by qPCR. Taken together, our study analyzed the diagnostic biomarkers and immune infiltration characteristics of MMD, which may shed light on the potential intervention targets of moyamoya disease patients.

Role of succinylation modification in central nervous system diseases.

Diseases of the central nervous system (CNS), including stroke, brain tumors, and neurodegenerative diseases, have a serious impact on human health worldwide, especially in elderly patients. The brain, which is one of the body's most metabolically dynamic organs, lacks fuel stores and therefore requires a continuous supply of energy substrates. Metabolic abnormalities are closely associated with the pathogenesis of CNS disorders. Post-translational modifications (PTMs) are essential regulatory mechanisms that affect the functions of almost all proteins. Succinylation, a broad-spectrum dynamic PTM, primarily occurs in mitochondria and plays a crucial regulatory role in various diseases. In addition to directly affecting various metabolic cycle pathways, succinylation serves as an efficient and rapid biological regulatory mechanism that establishes a connection between metabolism and proteins, thereby influencing cellular functions in CNS diseases. This review offers a comprehensive analysis of succinylation and its implications in the pathological mechanisms of CNS diseases. The objective is to outline novel strategies and targets for the prevention and treatment of CNS conditions.

Effectiveness of MEP and SSEP Monitoring in the Diagnosis of Neurological Dysfunction Immediately After Craniotomy Aneurysm Clipping.

OBJECTIVE: To explore the diagnostic accuracy of motor-evoked potential (MEP) and somatosensory-evoked potential (SSEP) monitoring in predicting immediate neurological dysfunction after craniotomy aneurysm clipping. METHODS: A total of 184 patients with neurosurgery aneurysms in the Affiliated Hospital of Qingdao University from April 2019 to December 2021 were retrospectively included. All patients underwent craniotomy aneurysm clipping, and MEP and SSEP were used to monitor during the operation. Receiver operating characteristic (ROC) curve analysis was used to determine the optimal cutoff value for early warning of MEP and SSEP amplitude decline and to evaluate the effectiveness of MEP and SSEP changes in predicting immediate postoperative neurological dysfunction. RESULTS: Among the 184 patients with intracranial aneurysms, the incidences of immediate postoperative neurological dysfunction were 44.4% (12/27) and 3.2% (5/157) in patients with intraoperative MEP changes and without changes, respectively. For SSEP, The incidence rates were 52.6% (10/19) and 4.2% (7/165), respectively, and the differences were statistically significant ( P <0.001). Significant changes in intraoperative MEP and SSEP were significantly associated with the development of immediate postoperative neurological deficits ( P <0.05). The critical values for early warning of MEP and SSEP amplitude decrease were: 61.6% ( P < 0.001, area under the curve 0.803) for MEP amplitude decrease and 54.6% ( P <0.001, area under the curve 0.770) for SSEP amplitude decrease. The sensitivity and specificity of MEP amplitude change in predicting immediate postoperative neurological dysfunction were 70.6% and 91.0%, respectively. For SSEP amplitude changes, the sensitivity and specificity were 58.8% and 95.8%, respectively. CONCLUSIONS: Motor-evoked potential and SSEP monitoring have moderate sensitivity and high specificity for immediate postoperative neurological dysfunction after craniotomy aneurysm clipping. Motor-evoked potential is more accurate than SSEP. Patients with changes in MEP and SSEP are at greatly increased risk of immediate postoperative neurologic deficits.

Clipping and coiling of intracranial aneurysms in the elderly patients: clinical features and treatment outcomes.

Objective: In recent years, more and more cases of intracranial aneurysms (IAs) have been found in elderly patients, and neurosurgical interventions have increased, but there is still no consensus on the best treatment strategy for elderly patients. In elderly patients, endovascular coiling (EC) is more popular than surgical clipping (SC) due to its advantages of less trauma and faster recovery. However, SC has made great progress in recent years, significantly improving the prognosis of elderly patients. Therefore, it is necessary to further explore the effects of different treatment modalities on clinical prognosis, hospital stay, and hospital cost of elderly IA patients, and select the most appropriate treatment modalities. Methods: The authors retrospectively analyzed 767 patients with intracranial aneurysms admitted to the facility between August 2017 and December 2022. Prognostic risk factors and multivariate logistic regression were analyzed for elderly patients treated with EC or SC. The area under the receiver operating characteristic (ROC) curve was used to calculate the predictive power of each independent predictor between the treatment groups. Results: Our study included 767 patients with aneurysms, of whom 348 (45.4%) were elderly, 176 (22.9%) underwent endovascular coiling, and 172 (22.4%) underwent microsurgical clipping. A comparison of elderly patients treated with EC and SC showed a higher prevalence of hypertension in the EC group (P = 0.011) and a higher Hunt-Hess score on admission in the SC group (P = 0.010). Patients in the EC group had shorter hospital stays but higher costs (P = 0.000 and P = 0.000, respectively). Patients treated with SC had a higher incidence of postoperative cerebral infarction and poor prognosis (P = 0.002 and P = 0.008, respectively). Through multi-factor logistic analysis, it was found that age (OR 1.209, 95% CI 1.047-1.397, P = 0.010), length of stay (LOS) (OR 1.160, 95 CI% 1.041-1.289, P = 0.007), and complications (OR 31.873, 95 CI% 11.677-320.701, P = 0.000) was an independent risk factor for poor prognosis in elderly patients with EC. In elderly patients treated with SC, age (OR 1.105, 95% CI 1.010-1.209, P = 0.029) was an independent risk factor for poor prognosis. Conclusion: EC and SC interventions in elderly adults carry higher risks compared to non-older adults, and people should consider these risks and costs when making a decision between intervention and conservative treatment. In elderly patients who received EC or SC treatments, EC showed an advantage in improving outcomes in elderly patients although it increased the economic cost of the patient's hospitalization.

The value of indocyanine green-FLOW800 in microvasculature for predicting cerebral hyperperfusion syndrome in moyamoya disease patients.

Among the notable complications of direct hemodynamic reconstruction for moyamoya disease (MMD) is cerebral hyperperfusion syndrome (CHS). In this study, we evaluated hemodynamic changes in small regional microvasculature (SRMV) around the anastomosis site by using indocyanine green (ICG)-FLOW800 video angiography and verified that it better predicted the onset of CHS. Intraoperative ICG-FLOW800 analysis was performed on 31 patients (36 cerebral hemispheres) with MMD who underwent superficial temporal artery-middle cerebral artery (MCA) bypass grafting at our institution. The regions of interest were established in the SRMV and thicker MCA around the anastomosis. Calculations were made for half-peak to time (TTP1/2), cerebral blood volume (CBV), and cerebral blood flow (CBF). According to the presence or absence of CHS after surgery, CHS and non-CHS groups of patients were separated. The results showed that ΔCBV and ΔCBF were substantially greater in SRMV than in MCA (p < 0.001). Compared with the non-CHS group, ΔCBF and ΔCBV of SRMV and MCA were considerably greater in the CHS group (p < 0.001). ΔCBF and ΔCBV on the ROC curve for both SRMV and MCA had high sensitivity and specificity (SRMV: ΔCBF, AUC = 0.8586; ΔCBV, AUC = 0.8158. MCA: ΔCBF, AUC = 0.7993; ΔCBV, AUC = 0.8684). ICG-FLOW800 video angiography verified the differential hemodynamic changes in the peri-anastomotic MCA and SRMV before and after bypass surgery in patients with MMD.

Prognostic Risk Factors of One-stage Surgical Clipping in aSAH Elderly Patients with MIAs.

OBJECTIVE: To discuss the prognostic factors affecting the prognosis of 1-stage surgical clipping in aneurysmal subarachnoid hemorrhage (aSAH) elderly patients with multiple intracranial aneurysms (MIAs). MATERIALS AND METHODS: A total of 84 elderly patients with aSAH who had MIAs and underwent 1-stage surgical clipping were retrospectively analyzed. Follow-up was conducted with patients 30 days after discharge using the Glasgow Outcome Scale (GOS). A GOS score of 1 to 3 was defined as a poor outcome, and a GOS score of 4 to 5 was defined as a good outcome. General information (gender, age, size of aneurysm, location of rupture of the responsible aneurysm, H-H grade, CT characteristics of aSAH, number of subarachnoid hemorrhages, operation opportunity, postoperative complications, and intraoperative rupture) and complications（cerebral infarction, hydrocephalus, electrolyte disturbance, and encephaledema）were recorded. Univariate analysis and multivariate regression analysis were used to analyze factors that may affect outcomes. RESULTS: Univariate analysis showed that the number of SAH events ( P =0.005), intraoperative rupture ( P =0.048) and postoperative complications ( P =0.002) were associated with the prognosis of aSAH elderly patients with MIAs undergoing 1-stage surgery. Multivariate analysis showed that the number of SAH events (odds ratio [OR] 4.740, 95% confidence interval [CI] 1.056 to 21.282, P =0.042) and postoperative complications (OR 4.531, 95% CI 1.266 to 16.220, P =0.020) were independently associated with the prognosis of aSAH elderly patients with MIAs undergoing 1-stage surgery. CONCLUSIONS: The number of SAH events and postoperative complications are independent risk factors for the prognosis of aSAH elderly patients with MIAs undergoing 1-stage surgery. These factors contribute to the timely treatment of potentially related patients.

Preoperative prognostic nutrition index can independently predict the 6-month prognosis of elderly patients undergoing neurosurgical clipping for aneurysmal subarachnoid hemorrhage.

The number of elderly patients with aneurysmal subarachnoid hemorrhage (aSAH) is increasing annually. The prognostic nutritional index (PNI) is used as a novel and valuable prognostic marker for various neoplastic diseases and other critical illnesses. This study aimed to identify the short-term prognostic value of preoperative PNI in elderly patients who underwent neurosurgical clipping for aSAH. This retrospective study included elderly patients with aSAH who underwent neurosurgical clipping from January 2018 to December 2020. Clinical variables and 6-month outcomes were collected and compared. Epidemiological data and effect factors of prognosis were evaluated. Multivariate logistic regression and receiver operating characteristics (ROC) curve analyses were used to evaluate the predictive value of preoperative PNI. Multiple logistic regression was performed to establish a nomogram. A total of 124 elderly patients were enrolled. Multivariate logistic regression analysis showed that preoperative PNI (odds ratio (OR), 0.779; 95% confidence interval (CI), 0.689-0.881; P < 0.001), Hunt-Hess grade (OR, 3.291; 95%CI, 1.816-5.966; P < 0.001), and hydrocephalus (OR, 9.423; 95%CI, 2.696-32.935; P < 0.001) were significant predictors. The area under the ROC curve of PNI was 0.829 (95% CI, 0.755-0.903; P < 0.001) with a sensitivity and specificity of 68.4% and 83.3%, respectively, and the cutoff value was 46.36. Patients with preoperative PNI of < 46.36 had a significantly unfavorable 6-months prognosis (F = 40.768, P < 0.001). Preoperative PNI is independently correlated with the 6-month prognosis in elderly patients who undergo neurosurgical clipping for aSAH.

Knowledge Mapping of Intracranial Aneurysm Clipping: A Bibliometric and Visualized Study (2001-2021).

BACKGROUND: Intracranial aneurysms (IAs) are common cerebrovascular diseases with high rates of mortality and disability. With the development of endovascular treatment technologies, the treatment of IAs has gradually turned to endovascular methods. However, because of the complex disease characteristics and technical challenges of IA treatment, surgical clipping still plays an important role. However, no summary has been performed of the research status and future trends in IA clipping. METHODS: Publications related to IA clipping from 2001 to 2021 were retrieved from the Web of Science Core Collection database. We conducted a bibliometric analysis and visualization study with the help of VOSviewer software and R program. RESULTS: We included 4104 articles from 90 countries. The volume of publications on IA clipping, in general, has increased. The United States, Japan, and China were the countries with the most contributions. The University of California, San Francisco, Mayo Clinic, and the Barrow Neurological Institute are the main research institutions. World Neurosurgery and the Journal of Neurosurgery were the most popular journal and most co-cited journal, respectively. These publications came from 12,506 authors, of whom Lawton, Spetzler, and Hernesniemi had reported the most studies. The reports from the past 21 years on IA clipping can generally be divided into 5 parts: (1) characteristics and technical difficulties of IA clipping; (2) perioperative management and imaging evaluation of IA clipping; (3) risk factors for subarachnoid hemorrhage caused by rupture after IA clipping; (4) outcomes, prognosis, and related clinical trials of IA clipping; and (5) endovascular management for IA clipping. "Occlusion," "experience," "internal carotid artery," "intracranial aneurysms," "management," and "subarachnoid hemorrhage" were the major keywords for future research hotspots. CONCLUSIONS: The results from our bibliometric study have clarified the global research status of IA clipping between 2001 and 2021. The United States contributed the most publications and citations, and World Neurosurgery and Journal of Neurosurgery can be considered landmark journals in this field. Studies regarding occlusion, experience, management, and subarachnoid hemorrhage will be the research hotspots related to IA clipping in the future.

Microsurgical treatment of blood blister-like aneurysms: efficacy of clip-on-wrapping with autologous dura mater.

OBJECTIVE: To present a consecutive 20-year series of blood blister-like aneurysms (BBAs) to show that clip-on-wrapping with a Y-shaped autologous dura mater enables treatment of BBAs with a low complication rate and a satisfactory curative result. METHODS: A retrospective review was performed from patients with BBAs of the internal carotid artery (ICA) at the Affiliated Hospital of Qingdao University from 1999 to 2019. Diagnosis and treatment options were analyzed. Outcome was assessed using the modified Rankin scale (mRS). RESULTS: A total of 30 patients with BBAs of the ICA were included. Among these patients, 20 patients underwent microsurgical treatment (15 patients were treated by clip-on-wrapping with a Y-shaped autologous dura mater), the other 10 patients underwent endovascular treatment. All patients presented with subarachnoid hemorrhage (SAH). Four angiograms were initially negative. For all patients, intraoperative rupture occurred in five cases, but no postoperative aneurysm rupture occurred in this series. Three cases with clinical or radiologic cerebral infarctions were observed. The outcome was favorable in 26 patients. CONCLUSIONS: Clip-reinforced wrapping technique using a Y-shaped autologous dura mater may be an effective method for treating BBAs.

Prognosis and immune response of a cuproptosis-related lncRNA signature in low grade glioma.

Cuproptosis is a newly discovered new mechanism of programmed cell death, and its unique pathway to regulate cell death is thought to have a unique role in understanding cancer progression and guiding cancer therapy. However, this regulation has not been studied in low grade glioma (LGG) at present. In this study, data on low grade glioma patients were downloaded from the TCGA database. We screened the genes related to cuproptosis from the published papers and confirmed the lncRNAs related to them. We applied univariate/multivariate, and LASSO regression algorithms, finally identified 11 lncRNAs for constructing prognosis prediction models, and constructed a risk scoring model. The reliability and validity test of the model indicated that the model could well distinguish the prognosis and survival of LGG patients. Furthermore, the analyses of immunotherapy, immune microenvironment, as well as functional enrichment were also performed. Finally, we verified the expression of these six prognostic key lncRNAs using real-time polymerase chain reaction (RT-PCR). In conclusion, this study is the first analysis based on cuproptosis-related lncRNAs in LGG and aims to open up new directions for LGG therapy.

Foreboding lncRNA markers of low-grade gliomas dependent on metabolism.

At present, there is no systematic study on the signature of long-chain noncoding RNAs (lncRNAs) involved in metabolism that can fully predict the prognosis in patients with low-grade gliomas (LGGs). Therefore, consistent metabolic-related lncRNA signatures need to be established. The Cancer Genome Atlas (TCGA) was used to identify the expression profile of lncRNAs containing 529 LGGs samples. LncRNAs and genes related to metabolism are used to establish a network in the form of coexpression to screen lncRNAs related to metabolism. LncRNA was more clearly described by univariate Cox regression. Moreover, lncRNA signatures were explored by multivariate Cox regression and lasso regression. The risk score was established according to the signature and it was an unattached prognostic marker according to Cox regression analysis. Functional enrichment of lncRNAs was shown by employing Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG). Univariate Cox retrospective analysis showed that 543 metabolism-related lncRNAs were independent prognostic factors of LGG, and multivariate Cox regression analysis confirmed that 19 metabolism-related lncRNAs were prognostic genes of LGG. In the risk model, the low-risk group had a higher Overall survival (OS) than the high-risk group (P < .001). Univariate Cox regression analysis of risk score and clinical factors showed that risk score was an independent prognostic factor (P < .001, HR = 1.047, 95% CI: 1.038-1.056). Multivariate Cox results showed that risk score could predict the prognosis of LGG (P < .001, HR = 1.036, 95% CI: 1.026-1.045). ROC curve analysis showed that risk score could predict the prognosis of LGG. The areas of 1-year, 3-years, and 5 years are 0.891, 0.904 and 0.832. GO and KEGG analysis showed that metabolism-related lncRNAs was mainly concentrated in the pathways related to tumor metabolism. In order to find a more stable and reliable target for the treatment of LGG, we established 19 metabolic-related lncRNAs prognostic model, and determined that it can predict the prognosis of LGG patients. This provides a new solution approach to the poor prognosis of patients with LGG and may reverse the trend of LGG's transformation to high-grade gliomas.

A Novel-Defined Necroptosis-Related miRNA Signature for Forecasting the Prognosis of Low-Grade Glioma.

Background: Increasing evidence has shown that necroptosis has enormous significance in the generation and deterioration of cancer, and miRNA molecular markers involved in necroptosis in low-grade gliomas (LGGs) have not been thoroughly reported. Methods: Using the miRNA data of 512 samples from The Cancer Genome Atlas (TCGA), 689 miRNAs from LGG samples were split into high immunity score and low immunity score groups for analysis. The differential miRNAs related to necroptosis were analyzed by univariate Cox regression analysis. On the basis of the outcome of univariate Cox regression analysis, miRNAs with significant differences were selected to construct a multivariate Cox regression model and calculate the risk score. Then, we evaluated whether the risk score could be used as an unaided prognostic factor. Results: Overall, six differential miRNAs were identified (hsa-miR-148a-3p, hsa-miR-141-3p, hsa-miR-223-3p, hsa-miR-7-5p, hsa-miR-500a-3p, and hsa-miR-200a-5p). Univariate and multivariate Cox regression analyses were performed, and the c index was 0.71. Then, by mixing the risk score with clinicopathological factors, univariate Cox regression (HR: 2.7146, 95% CI: 1.8402-4.0044, P < 0.0001) and multivariate Cox regression analyses (HR: 2.3280, 95% CI: 1.5692-3.4536, P < 0.001) were performed. The data suggested that the risk score is an unaided prognostic indicator, which is markedly related with the overall survival time of LGG sufferers. Thus, a lower risk score is correlated with better prediction of LGG. Conclusion: In order to achieve the ultimate goal of improving the living conditions of patients, we established prognostic risk model using 6 miRNAs related to necroptosis, which has the ability to predict the prognosis of LGG. It is possible to further enrich the therapeutic targets for LGG and provide clinical guidance for the treatment of LGG in the future.

CCL14 exacerbates intraplaque vulnerability by promoting neovascularization in the human carotid plaque.

OBJECTIVE: To examine the role of CCL14 in the neovascularization process and vulnerability progression within carotid plaques by investigating the mechanism of CCL14 regulation of VEGF-A. METHODS: We first performed histological analysis and immunohistochemical staining of human carotid plaque tissue to detect the expression of CCL14, JAK2, STAT3 and VEGF-A. We next examined the protein expression of CCL14, VEGF-A, JAK2, STAT3, and phosphorylation of JAK2 and STAT3 in human carotid atherosclerotic plaques by Western blotting. Finally, we performed in vitro culture of human umbilical vein endothelial cells (HUVEC). In the tube formation assay of HUVEC, we added CCL14 siRNA or VEGF-A siRNA to the culture medium using lentiviral transfection to knock down CCL14 or VEGF-A and grouped them for control assays, and detected the changes in the expression of the above proteins using Western blotting. RESULTS: Histological and Western blotting analysis of human carotid plaque samples showed that the expression of CCL14 and VEGF-A was higher in the vulnerable plaques than in stable plaques. In the in vitro cultures of HUVEC, CCL14 was found to increase the number and length of intercellularly generated tubular structures. CCL14 increases VEGF-A expression via activating JAK2/STAT3 signaling. CONCLUSION: In the human carotid plaques, CCL14 promotes angiogenesis by upregulation of VEGF-A via JAK2/STAT3 pathway and thus drives the progression of carotid plaques vulnerability.

Predictors of Oculomotor Nerve Palsy with Posterior Communicating Aneurysm Clipping in a Surgically Treated Series of 585 Patients: A Single-Center Study.

BACKGROUND: Oculomotor nerve palsy (OMNP) is a known risk in surgical management of intracranial aneurysms. The aim of this study was to determine the risk factors for surgery-induced OMNP. METHODS: This retrospective study examined 585 patients with posterior communicating artery aneurysms treated surgically between January 2000 and July 2019. The patients were categorized into 2 groups according to whether they experienced OMNP. Multiple factors, including sex, age, history of subarachnoid hemorrhage, Hunt and Hess grade, Fisher grade, preoperative time, sizes, sides, number, orientation, intraoperative rupture, and morphology, were analyzed to identify factors associated with surgery-induced OMNP. RESULTS: The overall OMNP rate was 4.4%. In univariate analysis, large size (P < 0.001), posterior infratentorial projection (P = 0.003), number of subarachnoid hemorrhages (P = 0.005), and late preoperative time (P < 0.001) were associated with increased risk of OMNP. Overall, multivariate logistic regression analysis showed that size (10.1-25 mm: odds ratio [OR] 30.083, P = 0.001, 95% confidence interval [CI], 3.703-244.419; >25 mm: OR 62.179, P = 0.012, 95% CI, 2.402-1609.418), intraoperative rupture (OR 3.018, P = 0.035, 95% CI, 1.083-8.412), and preoperative time (>14 days: OR 10.985, P < 0.001, 95% CI, 3.840-31.428) were independent risk factors of surgery-induced OMNP. CONCLUSIONS: This study showed that size, intraoperative rupture, and preoperative time were independent predictors of surgery-induced OMNP. Use of advanced technologies during the operation can assist in avoiding this complication.