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Abstract Background Due to the high mortality and disability rate of intracranial hemorrhage, headache is not the main focus of research on cerebral arteriovenous malformation (AVM), so research on headaches in AVM is still scarce, and the clinical understanding is shallow. This study aims to delineate the risk factors associated with headaches in AVM and to compare the effectiveness of various intervention treatments versus conservative treatment in alleviating headache symptoms. Methods This study conducted a retrospective analysis of AVMs who were treated in our institution from August 2011 to December 2021. Multivariable logistic regression analysis was employed to assess the risk factors for headaches in AVMs with unruptured, non-epileptic. Additionally, the effectiveness of different intervention treatments compared to conservative management in alleviating headaches was evaluated through propensity score matching (PSM). Results A total of 946 patients were included in the analysis of risk factors for headaches. Multivariate logistic regression analysis identified that female (OR 1.532, 95% CI 1.173–2.001, p = 0.002), supply artery dilatation (OR 1.423, 95% CI 1.082–1.872, p = 0.012), and occipital lobe (OR 1.785, 95% CI 1.307–2.439, p

Extracellular vesicles (EVs) mediate the intercellular crosstalk by transferring functional cargoes. Recently, we have discovered that BaP/BPDE exposure suppresses trophoblast cell migration/invasion and induces miscarriage, which are also regulate by lncRNAs at intracelluar levels. However, the EVs-mediated intercellular regulatory mechanisms are completely unexplored. Specifically, whether EVs might transfer BPDE-induced toxic lncRNA to fresh recipient trophoblast cells and suppress their migration/invasion to further induce miscarriage is completely unknown. In this study, we find that BPDE exposure up-regulates a novel lnc-HZ11, which suppresses EGR1/NF-κB/CXCL12 pathway and migration/invasion of trophoblast cells. Intercellular studies show that EV-HZ11 (lnc-HZ11 in EVs), which is highly expressed in BPDE-exposed donor cells, suppresses EGR1/NF-κB/CXCL12 pathway and migration/invasion in recipient cells by transferring lnc-HZ11 through EVs. Analysis of villous tissues collected from UM (unexplained miscarriage) patients and HC (healthy control) group shows that the levels of BPDE-DNA adducts, lnc-HZ11 or EV-lnc-HZ11, and EGR1/NF-κB/CXCL12 pathway are all associated with miscarriage. Mouse assays show that BaP exposure up-regulates the levels of lnc-Hz11 or EV-Hz11, suppresses Egr1/Nf-κb/Cxcl12 pathway, and eventually induces miscarriage. Knockdown of lnc-Hz11 by injecting EV-AS-Hz11 could effectively alleviate miscarriage in BaP-exposed mice. Furthermore, EV-HZ11 in serum samples could well predict the risk of miscarriage. Collectively, this study not only discovers EVs-HZ11-mediated intercellular mechanisms that BaP/BPDE suppresses trophoblast cell migration/invasion and induces miscarriage but also provides new approach for treatment against unexplained miscarriage through EV-HZ11.

Abstract Background Human Deltex 2 (DTX2) is a ubiquitin E3 ligase that functions as an oncogene and has been shown to participate in many human cancers. However, the role of DTX2 in glioma progression has remained obscure. In this study, we explore the mechanism underlying the function of DTX2 in glioma progression. Methods The associations between DTX2 expression and clinical characteristics of glioma were determined by bioinformatic analysis of data from The Cancer Genome Atlas and Human Protein Atlas. The expression of DTX2 in glioma tissues was detected using immunohistochemistry and western blotting. Lentivirus-mediated gene knockdown and overexpression were used to determine the effects of DTX2 and helicase-like transcription element (HLTF) on glioma cell proliferation and migration with CCK-8, cell colony formation, transwell, and wound healing assays; flow cytometry in vitro; and animal models in vivo. The interaction of the DTX2 and HLTF proteins was verified by immunoprecipitation assay and confocal microscopy. Results DTX2 was highly expressed in glioma samples, and this was correlated with worse overall survival. Silencing of DTX2 suppressed glioma cell viability, colony formation, and migration and induced cell apoptosis. In vitro ubiquitination assays confirmed that DTX2 could downregulate HLTF protein levels by increasing ubiquitination of the HLTF protein. We also observed that HLTF inhibited proliferation and migration of glioma cells. Subcutaneous xenografts with DTX2-overexpressing U87 cells showed significantly increased tumor volumes and weights. Conclusions We have identified DTX2/HLTF as a new axis in the development of glioma that could serve as a prognostic or therapeutic marker. Graphical abstract

BackgroundCurrently, there is a lack of intuitive analysis regarding the development trend, main authors, and research hotspots in the field of cerebral arteriovenous malformation treatment, as well as a detailed elaboration of possible research hotspots.MethodsA bibliometric analysis was conducted on data retrieved from the Web of Science core collection database between 2000 and 2022. The analysis was performed using R, VOSviewer, CiteSpace software, and an online bibliometric platform.ResultsA total of 1,356 articles were collected, and the number of publications has increased over time. The United States and the University of Pittsburgh are the most prolific countries and institutions in the field. The top three cited authors are Kondziolka D, Sheehan JP, and Lunsford LD. The Journal of Neurosurgery and Neurosurgery are two of the most influential journals in the field of brain arteriovenous malformation treatment research, with higher H-index, total citations, and number of publications. Furthermore, the analysis of keywords indicates that “aruba trial,” “randomised trial,” “microsurgery,” “onyx embolization,” and “Spetzler-Martin grade” may become research focal points. Additionally, this paper discusses the current research status, existing issues, and potential future research directions for the treatment of brain arteriovenous malformations.ConclusionThis bibliometric study comprehensively analyses the publication trend of cerebral arteriovenous malformation treatment in the past 20 years. It covers the trend of international cooperation, publications, and research hotspots. This information provides an important reference for scholars to further study cerebral arteriovenous malformation.

The cell division cycle associated (CDCA) genes regulate the cell cycle; however, their relationship with prognosis in glioma has been poorly reported in the literature. The Cancer Genome Atlas (TCGA) was utilized to probe the CDCA family in relation to the adverse clinical features of glioma. Glioma single-cell atlas reveals specific expression of CDCA3, 4, 5, 8 in malignant cells and CDCA7 in neural progenitor cells (NPC)-like malignant cells. Glioma data from TCGA, the China Glioma Genome Atlas Project (CGGA) and the gene expression omnibus (GEO) database all demonstrated that CDCA2, 3, 4, 5, 7 and 8 are prognostic markers for glioma. Further analysis identified CDCA2, 5 and 8 as independent prognostic factors for glioma. Lasso regression-based risk models for CDCA families demonstrated that high-risk patients were characterized by high tumor mutational burden (TMB), low levels of microsatellite instability (MSI), and low tumor immune dysfunction and rejection (TIDE) scores. These pointed to immunotherapy for glioma as a potentially viable treatment option Further CDCA clustering suggested that the high CDCA subtype exhibited a high macrophage phenotype and was associated with a higher antigen presentation capacity and high levels of immune escape. In addition, hsa-mir-15b-5p was predicted to be common regulator of CDCA3 and CDCA4, which was validated in U87 and U251 cells. Importantly, we found that CDCAs may indicate response to drug treatment, especially rapamycin, in glioma. In summary, our results suggest that CDCAs have potential applications in clinical diagnosis and as drug sensitivity markers in glioma.

BackgroundThe safety of extracranial–intracranial (EC–IC) bypass in the management of anterior circulation intracranial aneurysms (IAs) remains to be determined. This systematic review aims to summarize the existing evidence and provide guidance for the precise management of IAs.Data sourceWe constructed search strategies and comprehensively searched Pubmed, Medline, Embase, Web of science, and Cochrane library.MethodsThis systematic review was actualized according to the PRISMA statement. We evaluated study quality using the methodological index for non-randomized study (MINORS). Effect sizes were pooled using a random-effects model. Heterogeneity between studies was assessed using the I2 test. Publication bias was assessed using the Egger's test. The registration number for this systematic review is CRD42023396730.ResultThis systematic review included a total of 21 articles, involving 915 patients. Postoperative bypass patency rate was 99% (95% CI 0.98–1.00); short-term follow-up was 98% (95% CI 0.94–1.00); long-term follow-up was 95% (95% CI 0.93–0.97). The long-term follow-up occlusion rate of saphenous vein was higher than that of radial artery (OR 6.10 95% CI 1.04–35.59). Short-term surgery-related mortality was 0.3% (95% CI 0.000–0.012); long-term follow-up was 0.4% (95% CI 0.000–0.013); The proportion of patients with a score of 0–2 on the modified Rankin Scale (mRS) during long-term follow-up was 92% (95% CI 0.86–0.98). The incidence rates of long-term follow-up complications were: ischemic 3% (95% CI 0.01–0.06); hemorrhagic 1% (95% CI 0.00–0.03); neurological deficit 1% (95% CI 0.00–0.03); other 3% (95% CI 0.01–0.06).LimitationMost of the included studies were retrospective studies. Studies reporting preoperative status were not sufficient to demonstrate postoperative improvement. Lack of sufficient subgroup information such as aneurysm rupture status.ConclusionEC–IC therapy for anterior circulation IAs has a high safety profile. Higher level of evidence is still needed to support clinical decision.Systematic review registrationhttps://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42023396730, identifier: CRD42023396730.

Abstract Identifying the mechanism of glioma progression is critical for diagnosis and treatment. Although studies have shown that guanylate-binding protein 2(GBP2) has critical roles in various cancers, its function in glioma is unclear. In this work, we demonstrate that GBP2 has high expression levels in glioma tissues. In glioma cells, depletion of GBP2 impairs proliferation and migration, whereas overexpression of GBP2 enhances proliferation and migration. Regarding the mechanism, we clarify that epidermal growth factor receptor (EGFR) signaling is regulated by GBP2, and also demonstrate that GBP2 interacts directly with kinesin family member 22(KIF22) and regulates glioma progression through KIF22/EGFR signaling in vitro and in vivo. Therefore, our study provides new insight into glioma progression and paves the way for advances in glioma treatment.

Beijing, the capital of China, with a population of more than 21 million, is a mega city that is located on the migration route between East Asia and Australia. Owing to the process of urbanization, more urban spaces have been occupied by artificial buildings and facilities in the past. Since the implementation of the Measures of the National Voluntary Tree Planting Movement by the State Council in Beijing in 1982, urban green spaces (especially urban parks) have been greatly increased, promoting the restoration of ecosystem in Beijing. Interestingly, bird biodiversity greatly increased with the expanding of urban green spaces, and more new records of birds were found by the booming development of bird watching activities in Beijing. A total of 503 bird species have been found in Beijing to date, including 27 Class I species (Aythya baeri, Grus japonensis, Emberiza jankowskii, etc.) and 89 Class II species (Grus grus, Paradoxornis heudei, etc.) in the List of Key Protected Wildlife in China, most of which are the flagship species of the wetland ecosystem and forest ecosystem. This suggests that Beijing has become one of the richest mega cities in the world in terms of bird biodiversity. Therefore, the long-term conservation of urban biodiversity should be considered during the process of urbanization construction.

Dural arteriovenous fistulas of the hypoglossal canal (HCDAVFs) involving the anterior condylar confluence (ACC) and anterior condylar vein (ACV) are infrequent. Although transvenous embolization through the internal jugular vein (IJV) is the preferred treatment option for type I and II fistulas, it can be difficult if the IJV is unavailable. Here we report a rare case of HCDAVF in which the most common transvenous embolization access via IJV was not available. The patient underwent transarterial and transvenous onyx embolization. Transarterial embolization (TAE) aimed at controlling the arterial inflow and subsequently TVE was performed via the external jugular vein (EJV), the facial vein, the ophthalmic vein, the cavernous sinus, ACC, and ultimately to the fistula pouch. Complete obliteration of the HCDAVF was achieved without complications. We suggest that transvenous embolization (TVE) via the EJV and the facial vein can be effective in cases where trans-IJV is not possible.

Guanylate binding protein 2 (GBP2) is a member of the guanine binding protein family, and its relationship with prognostic outcomes and tumor immune microenvironments in glioma remains elusive. We found GBP2 were increased in glioma tissues at both mRNA and protein levels. Kaplan-Meier curves revealed that high GBP2 expression was linked with worse survival of glioma patients, and multivariate Cox regression analysis indicated that high GBP2 expression was an independent prognostic factor for glioma. Combined analysis in immune database revealed that the expression of GBP2 was significantly related to the level of immune infiltration and immunomodulators. Single-cell analysis illustrated the high expression of GBP2 in malignant glioma cells showed the high antigen presentation capability, which were confirmed by real-time polymerase chain reaction (qRT-PCR) data. Additionally, the hsa-mir-26b-5p and hsa-mir-335-5p were predicted as GBP2 regulators and were validated in U87 and U251 cells. Our results first decipher immune-related characteristics and noncoding regulators of GBP2 in glioma, which may provide insights into associated immunotherapies and prognostic predictor.

Intracranial aneurysm is a severe cerebral disorder involving complicated risk factors and endovascular coiling is a common therapeutic selection for intracranial aneurysm. The recurrence is a clinical challenge in intracranial aneurysms after coil embolization. With this study, we provided a meta-analysis of the risk factors for the recurrence of intracranial aneurysm after coil embolization. Nine studies were included with a total of 1,270 studies that were retrieved from the database. The sample size of patients with intracranial aneurysms ranged from 241 to 3,530, and a total of 9,532 patients were included in the present meta-analysis. The intracranial aneurysms that occurred in middle cerebral artery (MCA) (OR = 1.09, 95% CI: 1.03–1.16, P = 0.0045) and posterior circulation (OR = 2.01, 95% CI: 1.55–2.60, P = 0.000) presented the significantly higher risk of recurrence after coil embolization. Meanwhile, intracranial aneurysms of size > 7 mm (OR = 5.38, 95%CI: 3.76–7.70, P = 0.000) had a significantly higher risk of recurrence after coil embolization. Moreover, ruptured aneurysm (OR = 2.86, 95% CI: 2.02–4.04, P = 0.000) and subarachnoid hemorrhage (SAH) (OR = 1.57, 95% CI: 1.20–2.06, P = 0.001) was positively correlated with the risk of recurrence after coil embolization. In conclusion, this meta-analysis identified the characteristics of intracranial aneurysms with MCA, posterior circulation, size > 7 mm, ruptured aneurysm, and SAH as the risk factors of recurrence after coil embolization for intracranial aneurysms.

BackgroundTimely and accurate prediction of delayed cerebral ischemia is critical for improving the prognosis of patients with aneurysmal subarachnoid hemorrhage. Machine learning (ML) algorithms are increasingly regarded as having a higher prediction power than conventional logistic regression (LR). This study aims to construct LR and ML models and compare their prediction power on delayed cerebral ischemia (DCI) after aneurysmal subarachnoid hemorrhage (aSAH).MethodsThis was a multicenter, retrospective, observational cohort study that enrolled patients with aneurysmal subarachnoid hemorrhage from five hospitals in China. A total of 404 aSAH patients were prospectively enrolled. We randomly divided the patients into training (N = 303) and validation cohorts (N = 101) according to a ratio of 75–25%. One LR and six popular ML algorithms were used to construct models. The area under the receiver operating characteristic curve (AUC), accuracy, balanced accuracy, confusion matrix, sensitivity, specificity, calibration curve, and Hosmer–Lemeshow test were used to assess and compare the model performance. Finally, we calculated each feature of importance.ResultsA total of 112 (27.7%) patients developed DCI. Our results showed that conventional LR with an AUC value of 0.824 (95%CI: 0.73–0.91) in the validation cohort outperformed k-nearest neighbor, decision tree, support vector machine, and extreme gradient boosting model with the AUCs of 0.792 (95%CI: 0.68–0.9, P = 0.46), 0.675 (95%CI: 0.56–0.79, P < 0.01), 0.677 (95%CI: 0.57–0.77, P < 0.01), and 0.78 (95%CI: 0.68–0.87, P = 0.50). However, random forest (RF) and artificial neural network model with the same AUC (0.858, 95%CI: 0.78–0.93, P = 0.26) were better than the LR. The accuracy and the balanced accuracy of the RF were 20.8% and 11% higher than the latter, and the RF also showed good calibration in the validation cohort (Hosmer-Lemeshow: P = 0.203). We found that the CT value of subarachnoid hemorrhage, WBC count, neutrophil count, CT value of cerebral edema, and monocyte count were the five most important features for DCI prediction in the RF model. We then developed an online prediction tool (https://dynamic-nomogram.shinyapps.io/DynNomapp-DCI/) based on important features to calculate DCI risk precisely.ConclusionsIn this multicenter study, we found that several ML methods, particularly RF, outperformed conventional LR. Furthermore, an online prediction tool based on the RF model was developed to identify patients at high risk for DCI after SAH and facilitate timely interventions.Clinical Trial Registrationhttp://www.chictr.org.cn, Unique identifier: ChiCTR2100044448.

BackgroundsAs a most widely used machine learning method, tree-based algorithms have not been applied to predict delayed cerebral ischemia (DCI) in elderly patients with aneurysmal subarachnoid hemorrhage (aSAH). Hence, this study aims to develop the conventional regression and tree-based models and determine which model has better prediction performance for DCI development in hospitalized elderly patients after aSAH.MethodsThis was a multicenter, retrospective, observational cohort study analyzing elderly patients with aSAH aged 60 years and older. We randomly divided the multicentral data into model training and validation cohort in a ratio of 70–30%. One conventional regression and tree-based model, such as least absolute shrinkage and selection operator (LASSO), decision tree (DT), random forest (RF), and eXtreme Gradient Boosting (XGBoost), was developed. Accuracy, sensitivity, specificity, area under the precision-recall curve (AUC-PR), and area under the receiver operating characteristic curve (AUC-ROC) with 95% CI were employed to evaluate the model prediction performance. A DeLong test was conducted to calculate the statistical differences among models. Finally, we figured the importance weight of each feature to visualize the contribution on DCI.ResultsThere were 111 and 42 patients in the model training and validation cohorts, and 53 cases developed DCI. According to AUC-ROC value in the model internal validation, DT of 0.836 (95% CI: 0.747–0.926, p = 0.15), RF of 1 (95% CI: 1–1, p < 0.05), and XGBoost of 0.931 (95% CI: 0.885–0.978, p = 0.01) outperformed LASSO of 0.793 (95% CI: 0.692–0.893). However, the LASSO scored a highest AUC-ROC value of 0.894 (95% CI: 0.8–0.989) than DT of 0.764 (95% CI: 0.6–0.928, p = 0.05), RF of 0.821 (95% CI: 0.683–0.959, p = 0.27), and XGBoost of 0.865 (95% CI: 0.751–0.979, p = 0.69) in independent external validation. Moreover, the LASSO had a highest AUC-PR value of 0.681 than DT of 0.615, RF of 0.667, and XGBoost of 0.622 in external validation. In addition, we found that CT values of subarachnoid clots, aneurysm therapy, and white blood cell counts were the most important features for DCI in elderly patients with aSAH.ConclusionsThe LASSO had a superior prediction power than tree-based models in external validation. As a result, we recommend the conventional LASSO regression model to predict DCI in elderly patients with aSAH.

PurposeEndovascular coil occlusion is a successful and rapidly evolving strategy used to treat patients who present with intracranial aneurysms. This study aimed to compare the safety and efficacy of the Avenir® and AxiumTM passive mechanically detachable coil systems.MethodsA prospective, multicenter, randomized controlled study was carried out at ten medical centers from March 2018 to December 2019. A series of consecutive patients diagnosed with intracranial aneurysms were randomly assigned to undergo endovascular treatment with either the Avenir® or the AxiumTM mechanically detachable coil systems. The short-term outcomes from the two groups were compared with a focus on treatment efficacy and safety.ResultsA total of 162 and 161 patients were enrolled in the Avenir and Axium groups, respectively. The rate of successful coil detachment was 100% for the Avenir group and 99.38% for the Axium group. At the six-month follow-up visit, the overall aneurysm occlusion rate was 94.66% for the Avenir group and 96.95% for the Axium group (p > 0.05). We observed no statistically significant differences in clinical condition (as per the modified Rankin Scale) or the degree of aneurysm occlusion (as determined by digital subtraction angiography [DSA] and Raymond-Roy Occlusion Classification). Surgical complications were reported in 27 subjects in the Avenir group and 22 in the Axium group (p > 0.05). DSA performed at 6 months revealed complete aneurysm occlusion in 84 and 86% of patients in the Avenir and Axium groups, respectively.ConclusionWe observed no significant short-term differences with respect to efficacy or safety when using either Avenir® or AxiumTM coils for the treatment of intracranial aneurysms.

Although forest conversions have long been a focus in carbon (C) research, the relationship between soil erosion and the dynamic change of soil organic carbon (SOC) has not been well-quantified. The objective of this study was to investigate the effects of converting CBF (coniferous and broad-leaved mixed forests) to economic forests, including CF (chestnut forest), HF (hawthorn forest), and AF (apple forest), on the soil structure and nutrient loss in the Huaibei Rocky Mountain Areas, China. A 137Cs tracer method was used to provide soil erosion data in order to quantify the loss of aggregate-associated SOC. The results showed that forest management operations caused macro-aggregates to decrease by 1.69% in CF, 4.52% in AF, and 3.87% in HF. Therefore, the stability of aggregates was reduced. The SOC contents in each aggregate size decreased significantly after forest conversion, with the largest decreases occurring in AF. We quantified the loss of 0.15, 0.38, and 0.31 Mg hm−2 of aggregate-associated SOC after conversion from CBF to CF, AF, and HF, respectively. These results suggest that forest management operations have a negative impact on soil quality and fertility. CF has better vegetation coverage and less human interference, making it more prominent among the three economic forests species. Therefore, when developing forest management operations, judicious selection of tree varieties and appropriate management practices are extremely critical. In addition, measures should be taken to increase surface cover to reduce soil erosion and achieve sustainable development of economic forests.

The progressive injury of retinal ganglion cells(RGCs)is a common occurrence in several eye diseases, which ultimately may lead to irreversible blindness. Currently, there are still no effective or ideal treatments for it in practice, however some recent studies show that stem cell transplantation may provide a promising new idea for neuroprotection and replacement of retinal ganglion cells. This paper will review the research progress of stem cell transplantation-based treatment.

The study of emergency decision making (EDM) is helpful to reduce the difficulty of decision making and improve the efficiency of decision makers (DMs). The purpose of this paper is to propose an innovative genetic algorithm for emergency decision making under resource constraints. Firstly, this paper analyzes the emergency situation under resource constraints, and then, according to the prospect theory (PT), we further propose an improved value measurement function and an emergency loss levels weighting algorithm. Secondly, we assign weights for all emergency locations using the best⁻worst method (BWM). Then, an improved genetic algorithm (GA) based on prospect theory (PT) is established to solve the problem of emergency resource allocation between multiple emergency locations under resource constraints. Finally, the analyses of example show that the algorithm can shorten the decision-making time and provide a better decision scheme, which has certain practical significance.

BACKGROUND: FRAT1 positively regulates the Wnt/β-catenin signaling pathway by inhibiting GSK-3-mediated phosphorylation of β-catenin. It was originally characterized as a protein frequently rearranged in advanced T cell lymphoma, but has recently also been identified as a proto-oncogene involved in tumorigenesis. Our previous studies showed that FRAT1 was dramatically overexpressed in gliomas and its expression level was significantly increased along with clinicopathological grades. METHODS: In the current study, we used RT-PCR and Western blotting to assess the mRNA and protein levels of FRAT1 in three glioma cell lines. In addition, to evaluate its functional role in gliomas, we examined the effects of FRAT1 knockdown on proliferation, migration and invasion in vitro and tumor growth in vivo using glioblastoma U251 cells and RNAi. RESULTS: FRAT1 was highly expressed in all three glioma cell lines. RNAi-mediated down-regulation of endogenous FRAT1 in human glioblastoma U251 cells resulted in suppression of cell proliferation, arrest of cell cycle, inhibition of cell migration and invasion in vitro. Moreover, FRAT1 depletion significantly impaired tumor xenograft growth in nude mice. CONCLUSIONS: Our results highlight the potential role of FRAT1 in tumorigenesis and progression of glioblastoma. These findings provide a biological basis for FRAT1 as a potential molecular marker for improved pathological grading and as a novel candidate therapeutic target for glioblastoma management.