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Multivariate Granger causality is a well-established approach for inferring information flow in complex systems, and it is being increasingly applied to map brain connectivity. Traditional Granger causality is based on vector autoregressive (AR) or mixed autoregressive moving average (ARMA) model, which are potentially affected by errors in parameter estimation and may be contaminated by zero-lag correlation, notably when modeling neuroimaging data. To overcome this issue, we present here an extended canonical correlation approach to measure multivariate Granger causal interactions among time series. The procedure includes a reduced rank step for calculating canonical correlation analysis (CCA), and extends the definition of causality including instantaneous effects, thus avoiding the potential estimation problems of AR (or ARMA) models. We tested this approach on simulated data and confirmed its practical utility by exploring local network connectivity at different scales in the epileptic brain analyzing scalp and depth-EEG data during an interictal period. [ABSTRACT FROM PUBLISHER]

Metabolic RNA labeling‐based time‐resolved single‐cell RNA sequencing (scRNA‐seq) has provided unprecedented tools to dissect the temporal dynamics and the complex gene regulatory networks of gene expression. However, this technology fails to reveal the spatial organization of cells in tissues, which also regulates the gene expression by intercellular communication. Herein, it is demonstrated that integrating time‐resolved scRNA‐seq with spatial transcriptomics is a new paradigm for spatiotemporal analysis. Metabolic RNA labeling‐based time‐resolved Well‐TEMP‐seq is first applied to profile the transcriptional dynamics of glioblastoma (GBM) cells and discover two potential pathways of EZH2‐mediated mesenchymal transition in GBM. With spatial transcriptomics, it is further revealed that the crosstalk between CCL2+ malignant cells and IL10+ tumor‐associated macrophages in the tumor microenvironment through an EZH2‐FOSL2‐CCL2 axis contributes to the mesenchymal transition in GBM. These discoveries show the power of integrative spatiotemporal scRNA‐seq to elucidate the complex gene regulatory mechanism and advance the understanding of cellular processes in disease. [ABSTRACT FROM AUTHOR]

Objective Methods Results Interpretation To explore the relationship between 35 trace metals in scalp hair and the glioma risk as well as the potential mediating roles of 27 plasma inflammatory cytokines.A case–control study involving 228 participants was performed in southeastern China. Trace metals in scalp hair were analyzed using inductively coupled plasma mass spectrometry, and multiplex cytokines were detected based on Luminex® technology. The least absolute shrinkage and selection operator (LASSO) regression in combination with four machine learning methods were used to select trace metals associated with gliomas. The joint exposure effect of trace metals was estimated using the generalized weighted quantile sum (gWQS) regression and quantile‐based g‐computation (qgcomp) algorithms.Both LASSO regression and random forest algorithms identified five trace metals (gadolinium [Gd], lithium [Li], thulium [Tm], thorium [Th], and molybdenum [Mo]) associated with gliomas. After adjustments for potential confounders, Gd (odds ratio [OR] = 2.84, 95% confidence interval [CI]: 1.89–4.43) and Li (OR = 1.77, 95% CI: 1.04–3.02) concentrations were positively associated with glioma risk, while Tm (OR = 0.36, 95% CI: 0.17–0.73) and Th (OR = 0.45, 95% CI: 0.28–0.71) exhibited inverse associations. Both gWQS and qgcomp algorithms showed Gd contributed most to the mixture effect. Moreover, there was a significant interaction between Gd and Tm or Th on glioma risk (p < 0.05). Notably, granulocyte–macrophage colony‐stimulating factor (GM‐CSF) mediated the association between Gd exposure and glioma risk by 25.75%.These findings suggest potential associations of certain trace metals, especially for Gd, with glioma risk, and may provide new insights into the mechanisms underlying from an inflammatory response perspective. [ABSTRACT FROM AUTHOR]

Cuproptosis is a newly discovered form of programmed cell death significantly depending on the transport efficacy of copper (Cu) ionophores. However, existing Cu ionophores, primarily small molecules with a short blood half‐life, face challenges in transporting enough amounts of Cu ions into tumor cells. This work describes the construction of carrier‐free nanoparticles (Ce6@Cu NPs), which self‐assembled by the coordination of Cu2+ with the sonosensitizer chlorin e6 (Ce6), facilitating sonodynamic‐triggered combination of cuproptosis and ferroptosis. Ce6@Cu NPs internalized by U87MG cells induce a sonodynamic effect and glutathione (GSH) depletion capability, promoting lipid peroxidation and eventually inducing ferroptosis. Furthermore, Cu+ concentration in tumor cells significantly increases as Cu2+ reacts with reductive GSH, resulting in the downregulation of ferredoxin‐1 and lipoyl synthase. This induces the oligomerization of lipoylated dihydrolipoamide S‐acetyltransferase, causing proteotoxic stress and irreversible cuproptosis. Ce6@Cu NPs possess a satisfactory ability to penetrate the blood‐brain barrier, resulting in significant accumulation in orthotopic U87MG‐Luc glioblastoma. The sonodynamic‐triggered combination of ferroptosis and cuproptosis in the tumor by Ce6@Cu NPs is evidenced both in vitro and in vivo with minimal side effects. This work represents a promising tumor therapeutic strategy combining ferroptosis and cuproptosis, potentially inspiring further research in developing logical and effective cancer therapies based on cuproptosis. [ABSTRACT FROM AUTHOR]

The occurrence of dural arteriovenous fistulas (DAVFs) at the craniocervical junction (CCJ) is an uncommon vascular malformation. The diagnosis and treatment of CCJ DAVFs present a formidable challenge. This study aims to investigate the effect of endovascular embolization and microsurgery on improving patient prognosis. This retrospective study included patients diagnosed with CCJ DAVFs who received treatment at the First Affiliated Hospital of Fujian Medical University between January 2000 and January 2023. The clinical records, imaging data, and treatment methods were obtained from the hospital's medical record system. The patients were classified into microsurgery and embolization groups based on the surgical technique employed for treatment. The primary outcome measures were surgical-associated neurological dysfunction (SAND) and long-term neurological outcomes. The Cox proportional hazard regression was utilized to determine hazard ratios and 95% confidence intervals (CI) to assess the relationship between treatment methods and prognosis. Kaplan-Meier survival analysis was employed to evaluate the incidence of SAND in both cohorts. This study recruited 46 patients with an average age of 53.72 ± 13.83 years. In the microsurgery group, there were 12 cases (26.1%) observed. While in the embolization group, there were 34 cases (73.9%). Of these patients, 16 (34.8%) experienced SAND after treatment. In the microsurgery group, there were 8 cases (75.0%), while in the embolization group, only 8 cases (23.5%) were reported. Specifically, the embolization group exhibited a significantly lower risk of SAND [adjusted hazard ratio = 0.259, 95% CI = 0.096–0.700; P = 0.008)] compared to the microsurgery group. Additionally, the combined Borden grade 2–3 was found to be significantly associated with SAND (adjusted hazard ratio = 3.150, 95% CI = 1.132–8.766; P = 0.028). The results of the Kaplan-Meier survival analysis indicated a statistically significant difference in the occurrence of favorable functional outcomes between the 2 groups (log-rank P = 0.0081). CCJ DAVFs are uncommon disorders characterized by a diverse range of clinical manifestations. The functional prognosis of endovascular treatment may be superior to microsurgery. [ABSTRACT FROM AUTHOR]

Background: Microsurgery alone often proves to be challenging in treating paraclinoid internal carotid artery (ICA) aneurysms, which are known for their complex anatomy. Method: A 53-year-old female with a large right ICA-superior hypophyseal artery (SHA) aneurysm underwent clipping repair. Mixed reality technology was utilized in the preoperative planning and anatomical study. During the surgery, the anterior clinoid process was removed intradurally to improve access to the aneurysm neck. The aneurysm was then secured with a long curved clip. The patient's recovery was successful without any complications. Conclusion: This report aims to shed light on the intricacies involved in clipping ICA-SHA aneurysms. [ABSTRACT FROM AUTHOR]

Mild photothermal therapy (mPTT) has emerged as a highly promising approach for tumor ablation. However, the heat‐induced overexpression of heat shock proteins (HSPs) limits its efficacy by increasing cellular temperature tolerance. Herein, a self‐catalytically enhanced mild PTT strategy that directly disrupts the structure of HSPs to restore tumor cell sensitivity is proposed. In the proof‐of‐concept study, AgFeCu nanoparticles (AgFeCu NPs) with dual‐active catalytic centers (Fe‐Cu) and near‐infrared photothermal properties are developed. The AgFeCu NPs can efficiently catalyze the conversion of endogenous hydrogen peroxide into hydroxyl radicals in situ, leading to the degradation of HSPs and enhancing the therapeutic effects of mild PTT mediated by their Ag‐based substrates. Furthermore, AgFeCu NPs can also induce oxidative stress by depleting intracellular glutathione and promoting lipid peroxidation, thereby triggering tumor ferroptosis and resulting in significant tumor elimination in a U87MG murine tumor model. This self‐catalytically enhanced strategy maximizes the efficacy of mild PTT while minimizing damage to healthy tissues, which is expected to provide valuable insights for the development of next‐generation photothermal nanoagents for improved tumor therapeutics. [ABSTRACT FROM AUTHOR]

This article discusses a study that aimed to evaluate the effectiveness of the inactivated SARS-CoV-2 vaccine (CoronaVac) in patients with psoriasis and atopic dermatitis (AD). The study included 197 participants, including healthy controls, psoriasis patients, and AD patients. The results showed that all groups had enhanced antibody responses to the vaccine after the third dose. However, psoriasis patients who were not receiving treatment had lower antibody levels compared to those receiving anti-IL-17A treatment and healthy controls. The study suggests that correcting the Th1/Th17 imbalance in psoriasis patients may enhance the effectiveness of the COVID-19 vaccine. [Extracted from the article]

Background: Iron plays an important role in neuronal injury and edema formation after intracranial hemorrhage. However, the role of serum iron in aneurysmal subarachnoid hemorrhage (aSAH) is yet to be well-established. This study aims to identify whether serum iron could predict postoperative global cerebral edema (GCE) and poor outcome in aSAH. Methods: 847 patients' aSAH clinical data were retrospectively collected at the First Affiliated Hospital of Fujian Medical University. Data on demographics, clinical characteristics, and laboratory values were collected and analyzed through univariate and multivariate analyses. Propensity score matching (PSM) analysis was performed to balance the baseline differences between the groups. Results: The incidence of high-grade global cerebral edema (H-GCE) following aSAH was 12.99% (110/847). Serum iron levels [odds ratio (OR) = 1.143; 95% confidence interval (CI), (1.097–1.191); p < 0.001] were associated with the occurrence of H-GCE following aSAH in the univariate analysis. This association remained statistically significant even after adjusting for other variables in the multivariate model, with serum iron having an OR of 1.091 (95% CI, 1.043–1.141; p < 0.001) for GCE. After 1:1 PSM, serum iron levels ≤ 10.7 µmol/L remained a significant independent predictor of GCE (p = 0.002). The receiver operating characteristic (ROC) curve analysis determined that a serum iron cut-off value of ≤ 10.7 µmol/L was optimal for predicting H-GCE [Areas under the ROC curves (AUC) = 0.701, 95% CI, (0.669–0.732), p < 0.001; sensitivity, 67.27%; specificity, 63.77%] in patients with aSAH. Additionally, a trend was observed in which higher Hunt-Hess grades (HH grade) were associated with lower serum iron levels, and higher modified Fisher grades (mFisher grade) were associated with lower serum iron levels. In addition, the serum iron level was also associated with a 3-month functional neurological outcome (p < 0.001). Conclusions: The results of this study indicate that a decreased serum iron level serves as a clinically significant biomarker for the prediction of postoperative GCE and a poor outcome at 3-months in patients with aSAH. [ABSTRACT FROM AUTHOR]

Microglia-mediated neuroinflammatory responses play important roles in secondary neurological injury after traumatic brain injury (TBI). The TGF-β pathway participates in the regulation of M1/M2 phenotype transformation of microglia. TGF-β can activate the Smad pathway by binding to TGF-βRs, which is regulated by the cleavage function of A disintegrin and metalloproteinase 17 (ADAM17). However, the role of ADAM17 and the associated signaling pathways in the pathological process after TBI remain unclear. Herein, we assessed the transformation of microglia M1/M2 phenotype polarization and the neuroinflammatory response after the inhibition of ADAM17. The formation of TGF-βRs and TGF-β1/TGF-βRII complexes on microglia were detected to evaluate the effect of ADAM17 inhibition on the TGF-β1/Smad pathway. ADAM17 was highly expressed after TBI and mainly located in the microglia. the inhibition of ADAM17 improved neurological function after TBI. The neuroprotective effect of ADAM17 inhibition was related to a shift from the M1 microglial phenotype to the M2 microglial phenotype, thus reducing TBI-induced neuroinflammation. ADAM17 inhibition increased expression of TGF-βRs on the microglia membrane, promoted formation of TGF-β1/TGF-βRII complexes, and induced intranuclear translocation of Smads, which activated the TGF-β/Smad pathway. In conclusion, our study suggested that ADAM17 inhibition regulated microglia M1/M2 phenotype polarization through the TGF-β1/Smad pathway and influenced the neuroinflammatory response after TBI. [ABSTRACT FROM AUTHOR]

Stratification of spontaneous intracerebral hemorrhage (sICH) patients without cerebral herniation at admission, to determine the subgroups may be suffered from poor outcomes or benefit from surgery, is important for following treatment decision. The aim of this study was to establish and verify a de novo nomogram predictive model for long-term survival in sICH patients without cerebral herniation at admission. This study recruited sICH patients from our prospectively maintained ICH patient database (RIS-MIS-ICH, ClinicalTrials.gov Identifier: NCT03862729) between January 2015 and October 2019. All eligible patients were randomly classified into a training cohort and a validation cohort according to the ratio of 7:3. The baseline variables and long-term survival outcomes were collected. And the long-term survival information of all the enrolled sICH patients, including the occurrence of death and overall survival. Follow-up time was defined as the time from the onset to death of the patient or the last clinical visit. The nomogram predictive model was established based on the independent risk factors at admission for long-term survival after hemorrhage. The concordance index (C-index) and ROC curve were used to evaluate the accuracy of the predictive model. Discrimination and calibration were used to validate the nomogram in both the training cohort and the validation cohort. A total of 692 eligible sICH patients were enrolled. During the average follow-up time of 41.77 ± 0.85 months, a total of 178 (25.7%) patients died. The Cox Proportional Hazard Models showed that age (HR 1.055, 95% CI 1.038–1.071, P < 0.001), Glasgow Coma Scale (GCS) at admission (HR 2.496, 95% CI 2.014–3.093, P < 0.001) and hydrocephalus caused by intraventricular hemorrhage (IVH) (HR 1.955, 95% CI 1.362–2.806, P < 0.001) were independent risk factors. The C index of the admission model was 0.76 and 0.78 in the training cohort and validation cohort, respectively. In the ROC analysis, the AUC was 0.80 (95% CI 0.75–0.85) in the training cohort and was 0.80 (95% CI 0.72–0.88) in the validation cohort. SICH patients with admission nomogram scores greater than 87.75 were at high risk of short survival time. For sICH patients without cerebral herniation at admission, our de novo nomogram model based on age, GCS and hydrocephalus on CT may be useful to stratify the long-term survival outcomes and provide suggestions for treatment decision-making. [ABSTRACT FROM AUTHOR]

NM@Fe-DMY exhibits catalase (CAT) and superoxide dismutase (SOD)-like activities, effectively converting superoxide anion to harmless oxygen and thereby reducing reactive oxygen species (ROS) levels. Additionally, it activates SLC7A11, facilitating the transport of cysteine/glutathione into cells while suppressing the SPHK1/p-mTOR pathway activity. Ultimately, this promotes increased expression of glutathione peroxidase 4 (GPX4) and inhibits lipid peroxidation (LPO), consequently inhibiting ferroptosis. [Display omitted] • NM@Fe-DMY improves the prognosis of early brain injury after subarachnoid hemorrhage. • NM@Fe-DMY reverses ferroptosis and alters microglial polarization. • Neutrophil membranes cross blood–brain barrier and target area of inflammation. Early brain injury (EBI) refers to the immediate injury and neuroinflammation in the brain after subarachnoid hemorrhage (SAH). The current drugs used to treat SAH are inadequate due to their disappointing ability to penetrate the blood–brain barrier (BBB) and their limited anti-inflammatory effects, leading to unsatisfactory therapeutic outcomes for EBI. Herein, we developed a biomimetic nanozyme (Fe-DMY) using a metal-polyphenol self-assembly method, involving the coordination of ferric ion (Fe3+) and dihydromyricetin (DMY), then encapsulated Fe-DMY in neutrophil membranes (NM) to form NM@Fe-DMY, which targets to neuroinflammatory regions. NM@Fe-DMY exhibits strong catalase- and superoxide dismutase-like catalytic activities, suggesting its potential to reduce oxidative stress in SAH. This leads to reduced lipid peroxidation, increased expression of glutathione peroxidase 4 and prevented ferroptosis. Furthermore, The NM@Fe-DMY has demonstrated effective penetration of the BBB in vivo, accumulating in SAH injury region and exhibiting significant therapeutic efficacy including neural function recovery and improvement of spatial memory. Importantly, NM@Fe-DMY also induces the polarization of microglia from M1-like to M2-like subtypes, interrupting the detrimental cycle of neuroinflammation in EBI. This study introduces a new NM-wrapped biomimetic nanozyme strategy for effectively targeting neuroinflammatory regions and enhancing the treatment of EBI following SAH. [ABSTRACT FROM AUTHOR]

Xingfen Su and Ke Jin contributed equally to this work.Correction to: Acta Neurochirurgicahttps://doi.org/10.1007/s00701-024-05939-wThe correct name of the first author is "Xingfen Su", not "Xinfeng Su".The original article has been corrected.Publisher's NoteSpringer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.By Xingfen Su; Ke Jin; Jianping Song and Dezhi KangReported by Author; Author; Author; Author [Extracted from the article]

The Fe@MT nanocatalyst not only effectively converts overproduced hydrogen peroxide into highly active hydroxyl radical but also depletes endogenous glutathione, releasing mitoxantrone, which promotes irreversible ferroptosis via elevating the intracellular production of sensitive polyunsaturated fatty acids and inducing lethal lipid peroxidation. Additionally, Fe@MT nanocatalyst demonstrates significant photothermal capacity, triggering catalytic and metabolic vulnerability-amplified ferroptosis. [Display omitted] • Amplify ferroptotic vulnerability by enriching ROS-sensitive PUFAs production. • A simple self-assembly strategy is used to synthesize nanomedicine. • Synergistic therapy of catalytic therapy and photothermal therapy. • Fe@MT as an effective ferroptosis inducer. Ferroptosis is associated with excessive lipid peroxidation (LPO) accumulation, followed by membrane fragmentation. Although lipid metabolism is essential for regulating ferroptosis execution in tumors, there has been no use of nanomedicine to modulate the effect of metabolic vulnerability on ferroptosis. This study presents a metal-phenolic nanocatalyst (Fe@MT nanocatalyst), self-assembled using ferric ions (Fe3+) and coordinating with mitoxantrone (MT). This nanocatalyst accumulates lipid peroxides to strengthen ferroptotic vulnerability by initiating reactive oxygen species (ROS) storm and remodeling polyunsaturated fatty acids (PUFAs)-containing lipid metabolism. Fe@MT nanocatalyst catalytically converts endogenous hydrogen peroxide into highly active hydroxyl radical and depletes high intracellular levels of glutathione upon its internalization by U87MG cells, resulting in the release of MT, which in return promotes irreversible ferroptosis by elevating the intracellular production of ROS-sensitive PUFAs and inducing lethal LPO. Fe@MT nanocatalyst exhibits near-infrared photothermal property because of Fe3+ and MT self-assembly, causing photothermal-amplified catalytic ferroptosis therapy. This study sheds new light on promoting the sensitivity and execution of ferroptosis by reinforcing lethal lipid metabolism and accumulating excessive LPO and will establish an exploitable interaction between ferroptosis and lipid metabolic vulnerability in cancer. [ABSTRACT FROM AUTHOR]

Background: Temozolomide (TMZ) resistance limits its application in glioma. Exosome can carry circular RNAs (circRNAs) to regulate drug resistance via sponging microRNAs (miRNAs). miRNAs can control mRNA expression by regulate the interaction with 3'UTR and methylation. Nanog homeobox (NANOG) is an important biomarker for TMZ resistance. Hitherto, it is unknown about the role of exosomal hsa_circ_0072083 (circ_0072083) in TMZ resistance in glioma, and whether it is associated with NANOG via regulating miRNA sponge and methylation. Methods: TMZ-resistant (n = 36) and sensitive (n = 33) patients were recruited. The sensitive cells and constructed resistant cells were cultured and exposed to TMZ. circ_0072083, miR-1252-5p, AlkB homolog H5 (ALKBH5) and NANOG levels were examined via quantitative reverse transcription polymerase chain reaction and western blot. The half maximal inhibitory concentration (IC50) of TMZ, cell proliferation, apoptosis, migration and invasion were analyzed via Cell Counting Kit-8, colony formation, flow cytometry, wound healing and transwell assays. The in vivo function was assessed using xenograft model. The N6-methyladenosine (m6A) level was analyzed via methylated RNA immunoprecipitation (MeRIP). Target relationship was investigated via dual-luciferase reporter assay and RNA immunoprecipitation. Warburg effect was investigated via lactate production, glucose uptake and key enzymes expression. Exosome was isolated and confirmed via transmission electron microscopy and specific protein expression. Results: circ_0072083 expression was increased in TMZ-resistant glioma tissues and cells. circ_0072083 knockdown restrained the resistance of resistant cells via decreasing IC50 of TMZ, proliferation, migration, invasion and xenograft tumor growth and increasing apoptosis. circ_0072083 silence reduced NANOG expression via blocking ALKBH5-mediated demethylation. circ_0072083 could regulate NANOG and ALKBH5 via targeting miR-1252-5p to control TMZ resistance. Warburg effect promoted the release of exosomal circ_0072083 in resistant cells. Exosomal circ_0072083 from resistant cells increased the resistance of sensitive cells to TMZ in vitro and xenograft model. Exosomal circ_0072083 level was enhanced in resistant patients, and it had a diagnostic value and indicated a lower overall survival in glioma. Conclusion: Exosomal circ_0072083 promoted TMZ resistance via increasing NANOG via regulating miR-1252-5p-mediated degradation and demethylation in glioma. [ABSTRACT FROM AUTHOR]

Keywords: Keyhole approach; Neurosurgery; Brain tumor; Aneurysm; Expert consensus EN Keyhole approach Neurosurgery Brain tumor Aneurysm Expert consensus 1 17 17 02/03/21 20210201 NES 210201 Qin Lan and Michael Sughrue contributed equally to this work. For anterior communicating artery aneurysms, the sylvian fissure is usually located at the lateral third of the bone window; two-thirds of the brain tissue exposed under the bone window is the frontal lobe, and the remaining third is the temporal lobe. For middle cerebral artery aneurysms or lateral posterior communicating artery aneurysms, the sylvian fissure is usually placed in the center of the bone window so that the temporal lobe can be slightly retracted after opening the sylvian fissure. It is extremely difficult to modify the surgical corridor during an operation [[62]]; for most aneurysm cases with intraoperative bleeding, the surgeon will control the bleeding and clip the aneurysm on his own, as space for the assistant to operate is limited [[38], [62]]. Technique for intraoperative aneurysm rupture The surgical procedures for aneurysm clipping using the keyhole approach are the same as those for the conventional microsurgical technique, even in the case of treating ruptured aneurysms. [Extracted from the article]

An amendment to this paper has been published and can be accessed via a link at the top of the paper. [ABSTRACT FROM AUTHOR]

Development of chemotherapy resistance remains a major obstacle for glioma management. Exosome-mediated transfer of circular RNAs (circRNAs) are being found to have relevance to many human cancers, including glioma. The purpose of this study is to explore the effect and underlying mechanism of exosomal circRNA nuclear factor I X (CircNFIX) on temozolomide (TMZ) chemoresistance in glioma. Our results indicated that exosomal CircNFIX was up-regulated in the serum of TMZ-resistant patients and predicted poor prognosis. Exosomal CircNFIX from TMZ-resistant cells conferred TMZ resistance to recipient sensitive cells through the enhancement of cell migration and invasion and the repression of cell apoptosis under TMZ exposure. CircNFIX directly interacted with miR-132 by binding to miR-132. CircNFIX knockdown enhanced TMZ sensitivity in resistant glioma cells by up-regulating miR-132. Additionally, exosomal CircNFIX promoted tumor growth and its depletion enhanced TMZ sensitivity in glioma cells in vivo. Taken together, our study suggests that exosome-mediated transfer of CircNFIX enhances TMZ resistance in glioma at least partially through sponging miR-132, highlighting a potentially prognostic biomarker and therapeutic target for improving the clinical benefits of TMZ treatment in patients with glioma. [ABSTRACT FROM AUTHOR]

To retrospectively analyze the relationship between fibrinogen levels and outcomes in poor-grade aneurysmal subarachnoid hemorrhage (aSAH). We recruited 66 patients with poor-grade aSAH who were treated by neurosurgical clipping between January 2010 and December 2015. Serum samples were taken immediately on admission. Baseline information, complications, and outcomes at 6 months were recorded. Univariate and multivariate logistic regression analyses were used to explore the relationship between fibrinogen levels and clinical outcomes. Nineteen men and 47 women were included; the average age was 57.2 years. The median of the admission serum fibrinogen level was 3.3 g/L. Of the 66 patients, 18 had died by 6 months after initial hemorrhage, whereas 48 patients survived. Multivariate analyses showed that Hunt and Hess grade V (odds ratio [OR], 3.89; 95% confidence interval [CI], 1.06–14.20; P = 0.04) and admission serum fibrinogen level <2.5 g/L (OR, 6.15; 95% CI, 1.67–22.67; P = 0.006) were significantly associated with 6-month mortality. In addition, admission serum fibrinogen level was negatively correlated with delayed cerebral ischemia, and admission serum fibrinogen level <2.5 g/L (OR, 3.86; 95% CI, 0.99–15.09; P = 0.05) was also significantly associated with delayed cerebral ischemia. Patients with poor-grade aSAH with reduced admission fibrinogen level have a higher risk of delayed cerebral ischemia and 6-month mortality compared with those without. The admission serum fibrinogen level might be useful as a predictor and treatment target in patients with poor-grade sSAH who have undergone surgical treatment. [ABSTRACT FROM AUTHOR]

Background: Circular RNA nuclear factor I X (circNFIX) has been reported to play an important role in glioma progression. However, the mechanism by which circNFIX participates in glioma progression remains poorly understood. Methods: GERIA online were used to analyze the abnormally expressed genes in glioma tissues. The expression levels of circNFIX, microRNA (miR)-378e and Ribophorin-II (RPN2) were measured by quantitative real-time polymerase chain reaction or western blot. Cell cycle distribution, apoptosis, glycolysis, migration and invasion were determined by flow cytometry, special kit and trans-well assays, respectively. The target association between miR-378e and circNFIX or RPN2 was confirmed by luciferase reporter assay, RNA immunoprecipitation and pull-down. Xenograft model was established to investigate the role of circNFIX in vivo. Results: The expression of circNFIX was enhanced in glioma tissues and cells compared with matched controls and high expression of circNFIX indicated poor outcomes of patients. Knockdown of circNFIX led to arrest of cell cycle, inhibition of glycolysis, migration and invasion and promotion of apoptosis in glioma cells. circNFIX was a sponge of miR-378e. miR-378e overexpression suppressed cell cycle process, glycolysis, migration and invasion but promoted apoptosis. miR-378e silence abated the suppressive role of circNFIX knockdown in glioma progression. RPN2 as a target of miR-378e was positively regulated via circNFIX by competitively sponging miR-378e. Silencing circNFIX decreased glioma xenograft tumor growth by regulating miR-378e/RPN2 axis. Conclusion: Knockdown of circNFIX inhibits progression of glioma in vitro and in vivo by increasing miR-378e and decreasing RPN2, providing a novel mechanism for understanding the pathogenesis of glioma. [ABSTRACT FROM AUTHOR]

Neuroglobin (Ngb) overexpression is considered as an intrinsic neuroprotective response. Therefore, exogenous Ngb increased in brain tissues has become a promising therapeutic strategy for neurological diseases. Previous studies demonstrated that transactivator of transcription (TAT) protein transduction domain was able to mediate synthetic Ngb entrance into neurons, and then protected brain from hypoxia-ischemic injury. However, the role of recombinant Ngb on early brain injury following subarachnoid hemorrhage (SAH) has not been elucidated. The objectives of this study were to investigate the expression of endogenous Ngb in brain using a rabbit model of SAH, and to verify whether TAT-Ngb fusion protein could be delivered into brain parenchyma, as well as to explore the neuroprotective effect of Ngb and its possible mechanisms. We found that Ngb expressions were up regulated in the transcript and protein levels in a similar time dependent manner after SAH as compared to the sham group. Moreover, TAT-Ngb fusion protein was successfully generated and transferred into brain neurons. Compared with the saline- and Ngb-treated group, neuronal viabilities and neurological outcomes were significantly improved 72 h post-SAH in the TAT-Ngb-treated group. Likewise, anti-apoptotic Bcl-2 protein was also elevated obviously. Conversely, pro-apoptotic factors including caspase 3, caspase 9 and Bax were greatly decreased after TAT-Ngb treatment. Our results suggest that Ngb plays a neuroprotective effect in rabbits suffering from SAH possibly through inhibiting the SAH-induced activation of mitochondria apoptotic pathway. Furthermore, TAT-mediated Ngb delivery into brain may be a promising therapeutic approach. [ABSTRACT FROM AUTHOR]

Glioblastoma (GBM) is a highly heterogeneous disease with poor clinical outcome. To comprehensively dissect molecular landscape of GBM and heterogeneous distribution and potential role of Enhancer of zeste homolog 2 (EZH2) in tumor microenvironment (TME). Single-cell RNA sequencing (scRNA-seq) analysis was performed in GBM samples from 8 patients. Deconvolution analysis, immunofluorescence (IF) microscopy, reverse-transcription quantitative polymerase chain reaction (RT-qPCR), colony formation experiments, and Cell Counting Kit-8 (CCK-8) assays were performed to confirmed the potential role of EZH2 in TME cells. Malignant cells exhibited remarkable heterogeneity in abnormal metabolic patterns. A mesenchymal-2-like (MES2-like) GBM subcluster with glial-immune dual feature was firstly discovered, which were associated with highly activated hallmark pathways, immune evasion associated transcription factor (IRF8), and poor survival. The oncogene, EZH2 , was heterogeneously expressed in malignant cells and immune cells consistent with proliferative genes, cell-cycle transcription factors, and similar activated hallmark pathways. In a tumor-associated macrophages (TAMs) subset (macrophage.3), EZH2 was highly expressed with similar changes of transcriptomic dynamics with cell-cycle genes and macrophages M2-phetotype genes. In addition, the subset tightly interacted with malignant cells. Deconvolution analysis showed increased abundance of the subset in GBM compared to low-grade glioma (LGG) and significant association with worse prognosis. Functional verification experiments confirmed the pro-tumor role of TAMs with EZH2 overexpression in GBM. Our study illustrated a MES2-like GBM subcluster characterized by glial-immune dual feature and highlighted the pro-tumor role of a TAMs subset characterized by EZH2 overexpression. • ScRNA-seq is a valuable resource to depict cellular heterogeneity and intercellular crosstalk of GBM. • MES2-like malignant subcluster with glial-immune dual feature was firstly discovered. • A macrophage cluster characterized by EZH2 has tight interactions with malignant cells and other TME cells. • Functional verification experiments confirmed the pro-tumor role of EZH2 in tumor-associated macrophages. [ABSTRACT FROM AUTHOR]

Gliosarcoma, a variant of glioblastoma multiforme (GBM), is a highly invasive malignant tumor. Unfortunately, this disease still marked by poor prognosis regardless of modern treatments. It is of great significance to discover specific molecular probes targeting gliosarcoma for early cancer diagnosis and therapy. Herein, we have selected a group of DNA aptamers with high affinity and selectivity against gliosarcoma cells K308 using cell-SELEX. All the dissociation constants of these aptamers against gliosarcoma cells were in the nanomolar range and aptamer WQY-9 has the highest affinity and good selectivity among them. Furthermore, truncated aptamer sequence, WQY-9-B, shows similar recognition ability to aptamer WQY-9. In addition, WQY-9-B was found to be able to bind selectively and internalize into cytoplasm of target cancer cell at 37 °C. More importantly, compared to a random sequence, aptamer WQY-9-B showed excellent recognition rate (73.3%) for tissue sections of clinical gliosarcoma samples. These data suggests that aptamer WQY-9-B has excellent potential as an effective molecular probe for gliosarcoma diagnosis. [ABSTRACT FROM AUTHOR]

The purpose of this study was to determine whether intraoperative electrocorticography (ECoG) results and postoperative pathological findings are associated with long-term epileptic outcomes in patients with cerebral cavernous malformations (CCMs). To identify all consecutive patients with surgically treated CCM-related epilepsy (CRE) referred to our hospital, our prospectively maintained database of patients with CCM was reviewed (NCT03467295). For these patients, an ECoG-guided extended lesionectomy was performed, in which the CCM, surrounding hemosiderin, and detected epileptic foci were removed. Intraoperative ECoG results and postoperative pathological findings were documented in detail. Engel Class I was defined as a favorable outcome, while Engel Class II-IV was considered an unfavorable outcome. The patients were followed up for at least 2 years. The relationship between ECoG results, postoperative pathological findings, and epileptic outcomes was analyzed. A total of 522 patients with CCM were reviewed, and 85 patients with epileptic CCM were enrolled in this study. At the last clinical visit, 83.5 % of the patients experienced favorable postoperative outcomes. Multivariate analysis revealed that residual epileptic waves detected by intraoperative ECoG (OR 13.64; Cl 2.13–87.11; p = 0.006) and concomitant focal cortical dysplasia (FCD) (OR 11.37; Cl 1.63–79.27; p = 0.014) were independent factors significantly correlated with long-term epileptic outcomes. Most (61; 93.8 %) of the 65 patients with CRE without FCD achieved favorable outcomes. Residual epileptiform discharges after excision and concomitant FCD may be associated with poorer long-term epileptic outcomes in patients with CRE. Close follow-up and strict administration of oral antiepileptic drugs may be needed for these patients. [ABSTRACT FROM AUTHOR]

Objective Neuroglobin (Ngb) has a high affinity for oxygen and helps prevent hypoxic-ischemic brain damage. In this study we analyzed the relationship between Ngb levels and clinical outcomes of aneurysmal subarachnoid hemorrhage (aSAH). Methods Serum Ngb levels were measured in 58 patients with aSAH and 27 control individuals using the enzyme-linked immunosorbent assay. To continuously assess aSAH, we measured serum Ngb levels on days 1, 2, 3, 5, and 7 after aSAH. Clinical data were collected using the Hunt and Hess Scale, the Glasgow Coma Scale (GCS), the World Federation of Neurological Surgeons (WFNS) Scale, and the modified Fisher Scale. Clinical outcomes included 6-month mortality and 6-month unfavorable outcomes (modified Rankin Scale (mRS) score of 3–6). Results Serum Ngb levels increased after aSAH, peaked on day 2, and then gradually decreased. Serum Ngb levels on admission were higher in the patient group than in the control group (7.67 ± 2.56 ng/mL vs. 6.45 ± 0.88 ng/mL, P < 0.05). Multivariate logistic regression analysis indicated that serum Ngb levels on day 2 after aSAH were independently related to 6-month mortality (odds ratio [OR] = 0.265, 95% confidence interval [CI] = 0.094–0.747, P < 0.05) and 6-month unfavorable outcomes (OR = 1.919, 95% CI = 1.158–3.180, P < 0.05), and receiver operating characteristic curve analysis showed that serum Ngb levels on day 2 predicted 6-month mortality and 6-month unfavorable outcomes, with areas under the curve of 0.893 ( P < 0.05; 95% CI, 0.812–0.974) and 0.818 ( P < 0.05; 95% CI, 0.691–0.954), respectively, based on the best thresholds. Conclusions Serum Ngb levels on day 2 after aSAH were strongly associated with poor outcomes in aSAH, suggesting that Ngb may be a novel biomarker for predicting poor outcomes in aSAH. [ABSTRACT FROM AUTHOR]

Intracerebral hemorrhage is a lethal cerebrovascular disease, and the inevitable secondary brain injury (SBI) is responsible for serious disability and death. Perfect therapeutic goal is to minimize SBI and restore neurobehavioral functions. Recently, neuroprotection is highlighted to reduce SBI, but it still faces "Neuronal survival but impaired functions" dilemma. Herein, this work further proposes a novel combinational therapeutic strategy of neuroprotection and neurogenesis toward this goal. However, appropriate therapeutic agents are rarely reported, and their discovery and development are urgently needed. Selenium participates in various physiological/pathological processes, which is hypothesized as a potential targeting molecule. To explore this effect, this work formulates an ultra-small selenium nanodot with a seleno-amino acid derived carbon dot domain and a hydrophilic PEG layer, surprisingly finding that it increases various selenoproteins levels at perihematomal region, to not only exert multiple neuroprotective roles at acute phase but promote neurogenesis and inhibit glial scar formation at recovery phase. At a safe dose, this combinational strategy effectively prevents SBI and recovers neurobehavioral functions to a normal level. Furthermore, its molecular mechanisms are revealed to broaden application scopes in other complex diseases., (© 2024. The Author(s).)

Objective: To investigate the surgical management and outcomes of trapped temporal horn (TTH) following resection of lateral ventricle trigonal or peritrigonal tumors., Methods: Patients who underwent surgical treatment for TTH in three different tertiary centers between 2012 and 2022 were retrospectively studied. The primary outcome was reoperation rate., Results: Thirty-one patients were included for analysis. The underlying pathology was meningioma in 17 patients, central neurocytoma in 7, glioma in 4, ependymoma in 2, and cavernous malformation in 1. The median KPS score was 50 (range 10-90) and the mean volume of TTH was 53.1 ± 29.9 cm³ (range 14.8-118.6). Six patients (19.3 %) required multiple operations. A total of 39 procedures were performed, including 28 CSF shunting, 2 endoscopic septostomy, 3 microsurgical fenestration or temporal tip lobectomy via craniotomy, 2 decompressive craniectomy (DC), and 4 shunt revisions. Reoperation rates according to procedure were as follows: 10.7 % (3/28) for CSF shunting, 50 % (1/2) for endoscopic septostomy, 100 % (2/2) for DC, and 0 (0/3) for microsurgical fenestration or temporal tip lobectomy. CSF shunting tended to have a lower reoperation rate compared to other surgical approaches (p = 0.079). The reoperation rate was significantly higher for DC than for other surgical techniques (p = 0.025)., Conclusion: CSF shunting was the most frequently used technique with a relatively low revision rate. Long-term patency can be achieved through endoscopic septostomy in selected patients. Microsurgical fenestration or temporal tip lobectomy should be reserved for refractory cases. DC has limited effectiveness and should not be recommended., Competing Interests: Declaration of competing interest The authors indicated no potential conflicts of interest., (Copyright © 2024 Elsevier Ltd, BASO ~ The Association for Cancer Surgery, and the European Society of Surgical Oncology. All rights reserved.)

The mechanisms underlying lipid metabolic disorders in Parkinson's diseases (PD) remain unclear. Weighted Gene Co-Expression Network Analysis (WGCNA) was conducted to identify PD-related modular genes and differentially expressed genes (DEGs). Lipid metabolism-related genes (LMRGs) were extracted from Molecular Signatures Database. Candidate genes were assessed with overlapping modular genes, DEGs, and LMRGs for the purpose of building protein-protein interaction (PPI) networks. Then, biomarkers were generated by machine learning and Backpropagation Neural Network development according to candidate genes. Biomarker-based enrichment and network modulation analyses were executed to investigate related signaling pathways. Following dimensionality reduction clustering and annotation, scRNA-seq was submitted to cellular interactions and trajectory analysis to analyze regulatory mechanisms of critical cells. Finally, qRT-PCR was conducted to confirm the expression of biomarkers in PD patients. Four biomarkers (MSMO1, ELOVL6, AACS, and CERS2) were obtained and highly predictive after analysis mentioned above. Then, OPC, Oli, and Neu cells were the primary expression sites for biomarkers according to scRNA-seq studies. Finally, we confirmed mRNA of MSMO1, ELOVL6 and AACS were downregulated in PD patients comparing with control, while CERS2 was upregulated. In conclusion, MSMO1, ELOVL6, AACS, and CERS2 related to LMRGs could be new biomarkers for diagnosing and treating PD., (© 2024. The Author(s).)

Background: We aimed to explore the differences in plasma biomarker levels between patients with familial cerebral cavernous malformations (FCCM) and their healthy first-degree relatives (FDRs) and between FCCM patients with and without severe chronic disease aggressiveness (CDA)., Methods: Magnetic resonance imaging (MRI) scanning and genetic testing was performed in patients with multiple CCMs and their FDRs. Sixty-seven plasma biomarkers were tested using a customised multiplex bead immunoassay kit. Univariate and multivariate unconditional logistic regression analyses were conducted to determine the associations between plasma factors and the risk of developing FCCM and severe CDA. Receiver operating characteristic (ROC) curves were generated for each independent risk factor., Results: Plasma factors of 37 patients with FCCM and 37 FDRs were examined. Low CD31 ( P < 0.001) and BDNF levels ( P = 0.013) were independent risk factors for FCCM. The best model was achieved by combining the results of CD31 and BDNF (AUC = 0.845, sensitivity 0.838, specificity 0.784, cutoff score - 4.295) to distinguish patients with FCCM from healthy FDRs. Low serpin E1/PAI-1 ( P = 0.011) and high ROBO4 levels ( P = 0.013) were independent risk factors for severe CDA in patients with FCCM. The best model was achieved by combining the results of E1/PAI-1 and ROBO4 levels (AUC = 0.913, sensitivity 1.000, specificity 0.760, cutoff score - 0.525) to identify patients with FCCM and severe CDA., Conclusions: The plasma concentrations of CD31 and BDNF seem to be lower in patients with FCCM than in their healthy FDRs. Low serpin E1/PAI-1 and high ROBO4 concentrations may be correlated with high lesion burden and risk of recurrent bleeding., Competing Interests: Competing interests The authors declare no competing interests.

Objective: This study aims to investigate the prevalence of familial cerebral cavernous malformations (FCCMs) in first-degree relatives (FDRs) using familial screening, to describe the distribution of initial symptoms, lesion count on cranial MRI and pathogenic gene in patients., Methods: Patients with multiple CCMs who enrolled from the Treatments and Outcomes of Untreated Cerebral Cavernous Malformations in China database were considered as probands and FDRs were recruited. Cranial MRI was performed to screen the CCMs lesions, and whole-exome sequencing was performed to identify CCM mutations. MRI and genetic screening were combined to diagnose FCCM in FDRs, and the results were presented as prevalence and 95% CIs. The Kaplan-Meier (KM) method was used to calculate the cumulative incidence of FCCM., Results: 33 (76.74%) of the 43 families (110 FDRs) were identified as FCCM (85 FDRs). Receiver operating characteristic analysis revealed three lesions on T2-weighted imaging (T2WI) were the strong indicator for distinguishing probands with FCCM (sensitivity, 87.10%; specificity, 87.50%). Of the 85 FDRs, 31 were diagnosed with FCCM, resulting in a prevalence of 36.5% (26.2%-46.7%). In families with FCCMs, the mutation rates for CCM1 , CCM2 and CCM3 were 45.45%, 21.21% and 9.09%, respectively. Furthermore, 53.13% of patients were asymptomatic, 17.19% were intracranial haemorrhage and 9.38% were epilepsy. The mean age of symptom onset analysed by KM was 46.67 (40.56-52.78) years., Conclusion: Based on MRI and genetic analysis, the prevalence of CCMs in the FDRs of families with FCCMs in China was 36.5%. Genetic counselling and MRI screening are recommended for FDRs in patients with more than three CCM lesions on T2WI., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Meningiomas rank among the most common intracranial tumors, and surgery stands as the primary treatment modality for meningiomas. The precise subtyping and diagnosis of meningiomas, both before and during surgery, play a pivotal role in enabling neurosurgeons choose the optimal surgical program. In this study, we utilized multiphoton microscopy (MPM) based on 2-photon excited fluorescence and second-harmonic generation to identify 5 common meningioma subtypes. The morphological features of these subtypes were depicted using the MPM multichannel mode. Additionally, we developed 2 distinct programs to quantify collagen content and blood vessel density. Furthermore, the lambda mode of the MPM characterized architectural and spectral features, from which 3 quantitative indicators were extracted. Moreover, we employed machine learning to differentiate meningioma subtypes automatically, achieving high classification accuracy. These findings demonstrate the potential of MPM as a noninvasive diagnostic tool for meningioma subtyping and diagnosis, offering improved accuracy and resolution compared with traditional methods., (Copyright © 2024 United States & Canadian Academy of Pathology. Published by Elsevier Inc. All rights reserved.)

Purpose: Our aims were to investigate the presence of choroid plexus (CP) inflammation in chronic-phase intracerebral hemorrhage (ICH) patients and to characterize any inflammatory cells in the CP., Patients and Methods: An in vivo 18 F-DPA714 PET study was undertaken in 22 chronic-phase ICH patients who were admitted to the First Affiliated Hospital of Fujian Medical University or Tianjin Medical University General Hospital from April 2017 to June 2020. Ten control participants with nonhemorrhagic central nervous system diseases were included. Choroid plexus 18 F-DPA714 uptake was calculated as the average SUVR. To aid the interpretation of the 18 F-DPA714 uptake results at the CP level, Cy5-DPA714 in vivo imaging and immunofluorescence staining were used to show the presence of CP inflammation in an ICH mouse model during the chronic phase (14 weeks after ICH). Then immunofluorescence staining against translocator protein and other specific biomarkers was used to characterize the cells present in the inflamed CP of ICH mice in the chronic phase., Results: PET imaging showed that CP DPA714 SUVRs in chronic-phase ICH patients were higher than in controls (mean CP SUVR ± SD; ICH group: 1.05 ± 0.35; control group: 0.81 ± 0.21; P = 0.006). Immunofluorescence staining of the CP in ICH model mice identified a population of CD45 + immune cells, peripheral monocyte-derived CD14 + cells, CD68 + phagocytes, and CD11b + resident microglia/macrophages expressing translocator protein, possibly contributing to the increased 18 F-DPA714 uptake., Conclusions: Our study shows that CP DPA714 uptake in chronic-phase ICH patients was higher than that of participants with nonhemorrhagic central nervous system diseases, which means that CP inflammation is still active in chronic-phase ICH patients., Competing Interests: Conflicts of interest and sources of funding: The authors declared no conflicts of interest. The study was supported by the National Natural Science Foundation of China (grant no. 82171327, 82171982, and 82371466), the Stroke Prevention and Treatment Project of the National Health Commission–Research and Popularization of Appropriate Intervention Technology for the Stroke High Risk Group in China (GN2018R002), the Fujian Science and Technology Innovation Joint Fund Project (2019Y9118), the Technology Platform Construction Project of Fujian Province (2020Y2003 and 2021Y2001), the Major Scientific Research Specialty Project of Fujian Province (2022ZD01003), and the Natural Science Foundation of Fujian Province (2023J01590 and 2023J06031). The funders had no role in the design and conduct of the study; collection, management, analysis, and interpretation of the data; preparation, review, or approval of the article; and decision to submit the article for publication., (Copyright © 2023 The Author(s). Published by Wolters Kluwer Health, Inc.)

Background: Abnormalities in regulated cell death (RCD) are involved in multiple diseases. However, the role of RCD in intracranial aneurysms (IA) remains unknown. The aim of this study was to explore different RCD processes in the pathogenesis of IA., Methods: Four microarray datasets (GSE75436, GSE54083, GSE13353, GSE15629) and one RNA sequencing (RNA-seq) dataset (GSE122897) were extracted from the Gene Expression Omnibus (GEO) database. The microarray datasets were merged to form the training set, while the RNA-seq dataset was used as the validation set. Differentially expressed genes (DEGs), gene set enrichment analysis (GSEA), and gene set variation analysis (GSVA) were used to investigate the role of different types of RCD, including apoptosis, necroptosis, autophagy, ferroptosis and pyroptosis in the formation of IA. A novel cell death classification system for IA was established using an unsupervised consensus clustering algorithm based on cell death signature genes. Differences in functional enrichment, cell death-related regulators, and immune infiltration between two cell death clusters were evaluated. Finally, predictive genes were identified using the least absolute shrinkage and selection operator (LASSO) regression, random forest and logistic regression, allowing a prediction model to be constructed for IA rupture., Results: Multiple RCD processes were significantly activated in IAs compared to controls. A total of 33 signature genes related to cell death were identified. The IA samples were divided into two clusters based on the cell death signature. The cell death-high subtype had a relatively higher rate of rupture, and higher enrichment levels for multiple cell death processes and several signal transduction and immune-related pathways. Immune infiltration analysis showed that cell death scores were correlated with multiple immune cell types, including macrophages, mast cells, T cells and B cells. A six-gene prediction model was constructed to predict rupture. The area under curves (AUCs) for predicting rupture in the training and validation cohorts were 0.924 and 0.855, respectively., Conclusions: Comprehensively analysis of RCD in IA and found that multiple RCD types are likely to be involved in IA formation and rupture. These cell death processes were correlated with inflammation and immunity. We present novel insights into the mechanism of IA pathogenesis that should help to guide further research., Competing Interests: The authors declare no conflict of interest., (© 2023 The Author(s). Published by IMR Press.)

Background: Systemic atherosclerosis and carotid intima-media thickness (IMT) have been widely used in clinical practice for ischemic stroke; however, little is known about the risk factors for unruptured intracranial aneurysms (UIAs) in patients with ischemic stroke (IS). Therefore, we performed this study to identify the risk factors and construct a prediction model for UIA in patients with IS., Methods: Data were retrospectively collected from patients with IS from 2015 to 2022 at the First Hospital of Quanzhou City, Quanzhou, Fujian, China. Risk factors for UIA in patients with IS were identified using a multivariate logistic regression model, and a receiver operating characteristic (ROC) curve was applied to construct the prediction model., Results: Out of the 122 patients with IS, 52 who presented with UIA (ISUIA) were categorized into the study group and the remaining 70 IS patients without UIA into the control group. Patients in the ISUIA group had lower carotid IMT and carotid artery plaque scores than those in the IS group ( P < 0.05). Multivariate analyses found that aspirin use (OR: 12.987; P = 0.031), elevated C-reactive protein (CRP) level (OR: 1.019; P = 0.004), and carotid IMT > 0.09 mm (OR: 0.218; P < 0.001) were significantly associated with the risk of UIA in patients with IS. However, UIA in patients with IS was unaffected by the carotid artery plaque score ( P = 0.114). The constricted prediction model based on the abovementioned factors for UIA in IS patients was 0.79 (95% CI: 0.71-0.87)., Conclusion: The findings revealed that the risk factors for UIA in patients with IS included aspirin use, elevated CRP level, and smaller carotid IMT, and the predictive value of the prediction model was relatively better., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Gao, Kang, Zhang, Jiang, He and Wu.)

Subarachnoid hemorrhage (SAH) is an acute catastrophic neurological disorder with high morbidity and mortality. Ferroptosis is one of the pathophysiological processes during secondary brain injury of SAH, which could be inhibited by ferrostatin-1 (Fer-1) effectively. Peroxiredoxin6 (PRDX6) is an antioxidant protein and is currently proven to be associated with lipid peroxidation in ferroptosis except in GSH/GPX4 and FSP1/CoQ10 antioxidant systems. However, the alteration and function of PRDX6 in SAH are still unknown. In addition, whether PRDX6 is involved in the neuroprotection of Fer-1 in SAH is yet to be investigated. Endovascular perforation was employed to induce the SAH model. Fer-1 and in vivo siRNA aiming to knockdown PRDX6 were administrated intracerebroventricularly to investigate relevant regulation and mechanism. We confirmed the inhibition of ferroptosis and neuroprotection from brain injury by Fer-1 in SAH. The induction of SAH reduced the expression of PRDX6, which could be alleviated by Fer-1. Accordingly, dysregulated lipid peroxidation indicated by GSH and MDA was improved by Fer-1, which was counteracted by si-PRDX6. Similarly, the neuroprotection of Fer-1 in SAH was diminished by the knockdown of PRDX6 and the administration of a calcium-independent phospholipase A2 (iPLA2) inhibitor. PRDX6 is involved in ferroptosis induced by SAH and is associated with Fer-1 neuroprotection from brain injury via its iPLA2 activity., (Copyright © 2023 The Author(s). Published by Wolters Kluwer Health, Inc.)

Family cerebral cavernous malformations (FCCMs) are mainly inherited through the mutation of classical CCM genes, including CCM1/KRIT1, CCM2/MGC4607, and CCM3/PDCD10. FCCMs can cause severe clinical symptoms, including epileptic seizures, intracranial hemorrhage (ICH), or functional neurological deficits (FNDs). In this study, we reported a novel mutation in KRIT1 accompanied by a NOTCH3 mutation in a Chinese family. This family consists of 8 members, 4 of whom had been diagnosed with CCMs using cerebral MRI (T1WI, T2WI, SWI). The proband (II-2) and her daughter (III-4) had intracerebral hemorrhage and refractory epilepsy, respectively. Based on whole-exome sequencing (WES) data and bioinformatics analysis from 4 patients with multiple CCMs and 2 normal first-degree relatives, a novel KRIT1 mutation, NG&#95;012964.1 (NM&#95;194456.1): c.1255-1G > T (splice-3), in intron 13 was considered a pathogenic gene in this family. Furthermore, based on 2 severe and 2 mild CCM patients, we found an SNV missense mutation, NG&#95;009819.1 (NM&#95;000435.2): c.1630C > T (p.R544C), in NOTCH3. Finally, the KRIT1 and NOTCH3 mutations were validated in 8 members using Sanger sequencing. This study revealed a novel KRIT1 mutation, NG&#95;012964.1 (NM&#95;194456.1): c.1255-1G > T (splice-3), in a Chinese CCM family, which had not been reported previously. Moreover, the NOTCH3 mutation NG&#95;009819.1 (NM&#95;000435.2): c.1630C > T (p.R544C) might be a second hit and associated with the progression of CCM lesions and severe clinical symptoms., (© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Importance: Stroke is the leading cause of death in China. However, recent data about the up-to-date stroke burden in China are limited., Objective: To investigate the urban-rural disparity of stroke burden in the Chinese adult population, including prevalence, incidence, and mortality rate, and disparities between urban and rural populations., Design, Setting, and Participants: This cross-sectional study was based on a nationally representative survey that included 676 394 participants aged 40 years and older. It was conducted from July 2020 to December 2020 in 31 provinces in mainland China., Main Outcomes and Measures: Primary outcome was self-reported stroke verified by trained neurologists during a face-to-face interviews using a standardized protocol. Stroke incidence were assessed by defining first-ever strokes that occurred during 1 year preceding the survey. Strokes causing death that occurred during the 1 year preceding the survey were considered as death cases., Results: The study included 676 394 Chinese adults (395 122 [58.4%] females; mean [SD] age, 59.7 [11.0] years). In 2020, the weighted prevalence, incidence, and mortality rates of stroke in China were 2.6% (95% CI, 2.6%-2.6%), 505.2 (95% CI, 488.5-522.0) per 100 000 person-years, and 343.4 (95% CI, 329.6-357.2) per 100 000 person-years, respectively. It was estimated that among the Chinese population aged 40 years and older in 2020, there were 3.4 (95% CI, 3.3-3.6) million incident cases of stroke, 17.8 (95% CI, 17.5-18.0) million prevalent cases of stroke, and 2.3 (95% CI, 2.2-2.4) million deaths from stroke. Ischemic stroke constituted 15.5 (95% CI, 15.2-15.6) million (86.8%) of all incident strokes in 2020, while intracerebral hemorrhage constituted 2.1 (95% CI, 2.1-2.1) million (11.9%) and subarachnoid hemorrhage constituted 0.2 (95% CI, 0.2-0.2) million (1.3%). The prevalence of stroke was higher in urban than in rural areas (2.7% [95% CI, 2.6%-2.7%] vs 2.5% [95% CI, 2.5%-2.6%]; P = .02), but the incidence rate (485.5 [95% CI, 462.8-508.3] vs 520.8 [95% CI, 496.3-545.2] per 100 000 person-years; P < .001) and mortality rate (309.9 [95% CI, 291.7-328.1] vs 369.7 [95% CI, 349.1-390.3] per 100 000 person-years; P < .001) were lower in urban areas than in rural areas. In 2020, the leading risk factor for stroke was hypertension (OR, 3.20 [95% CI, 3.09-3.32])., Conclusions and Relevance: In a large, nationally representative sample of adults aged 40 years or older, the estimated prevalence, incidence, and mortality rate of stroke in China in 2020 were 2.6%, 505.2 per 100 000 person-years, and 343.4 per 100 000 person-years, respectively, indicating the need for an improved stroke prevention strategy in the general Chinese population.

In China, the improvement in amenities has been often criticized for not addressing the priorities of residents' demand due to over-standardised, top-down practices and the misallocation of resources. Previous studies have investigated how people's wellbeing or quality of life is associated with neighbourhood attributes. However, very few have researched how identifying and prioritizing the improvement in neighbourhood amenities could significantly enhance neighbourhood satisfaction. Therefore, this paper investigated the residents' perception on the neighbourhood amenities in Wuhan, China, and explored the application of the Kano-IPA model for prioritizing the improvement in amenities in both commodity-housing and traditional danwei neighbourhoods. Firstly, total 5100 valid questionnaires were distributed through street face-to-face surveying to solicit the residents' perceptions of the usage and satisfaction of amenities in different neighbourhoods. Then, various statistical techniques, including descriptive, logistical regression modelling were adopted to analyse the general characteristics and significant associations of amenities' usage and demand. Lastly, an age-friendly strategy for the improvement in amenities in old neighbourhoods was proposed by referring to the widely applied Kano-IPA marketing model. The results showed that there is no significant difference in the usage frequency of amenities among different neighbourhoods. However, significant differences of associations between residents' perception on amenities and neighbourhood satisfaction were identified among different groups of residents. To demonstrate prioritizing neighbourhood amenities in double-aging neighbourhoods, basic, excitement, and performance factors fitting age-friendly scenarios were determined and categorized. This research can provide a reference for allocating financial budgets and determining schedules to improve neighbourhood amenities. It also showcased the variances of residents' demands and the provision of public goods among different neighbourhoods in urban China. Similar studies can be expected in addressing different scenarios that challenges emerged, such as suburban or resettled neighbourhoods where low-income residents generally live.

Background: The stroke burden in China has increased during the past 40 years. The present study aimed to determine the recent trends in the prevalence of stroke from 2013 to 2019 stratified by sociodemographic characteristics, including sex, age, residence, ethnicity, and province within a population-based screening project in China., Methods: We made use of data generated from 2013 to 2019 in the China Stroke High-risk Population Screening Program. All living subjects with confirmed stroke at interview were considered to have prevalent stroke. All analyses of prevalence of stroke were weighted and results were presented as percentage and 95% confidence interval (CI)., Findings: A total of 4229,616 Chinese adults aged ≥40 years from 227 cities in the 31 provinces were finally included. The enrollment rate ranged from 58.8% (2017) to 67.8% (2013). The weighted prevalence of stroke increased annually from 2013 to 2019, being 2.28% (95% CI: 2.28-2.28%) in 2013, 2.34% (2.34-2.35%) in 2014, 2.43% (2.43-2.43%) in 2015, 2.48% (2.48-2.48%) in 2016, 2.52% (2.52-2.52%) in 2017, 2.55% (2.55-2.55%) in 2018, and 2.58% (2.58-2.58%) in 2019 ( p for trend <0.001). The weighted prevalence of stroke was higher for male sex, older age, and residence in rural and northeast areas., Interpretation: The prevalence of stroke in China and most provinces has continued to increase in the past 7 years (2013-2019). These findings, especially in provinces with high stroke prevalence, can help public health officials to increase province capacity for stroke and related risk factors prevention., Fundings: This study was supported by grants from the National Major Public Health Service Projects., Competing Interests: None., (© 2022 The Authors.)

Glioblastoma (GBM) is the most common primary malignancy of the central nervous system in adults. The prognosis for late-stage glioblastoma (World Health Organization grade IV astrocytic glioma) is very poor. Novel treatment options are sought after and evaluated by clinicians and researchers, and remarkable advances have been made in surgical techniques, radiotherapy, and chemotherapy. However, the treatment of glioblastoma remains extremely difficult and it can extend the lives of patients by only a few months. There has been notable progress in the field of immunotherapy, particularly with the use of tumor vaccines, for treating glioblastoma; especially peptide vaccines and cell-based vaccines such as dendritic cell vaccines and tumor cell vaccines. However, the results of the current clinical trials for vaccination are not satisfactory. This article reviews the progress in the development of vaccines for glioblastoma., (© 2022. The Author(s).)

Background: Calcification of adamantinomatous craniopharyngioma (ACP) often causes problems with tumor resection, leading to a high incidence of deadly complications and tumor recurrence. Histone acetyltransferase (HAT) and histone deacetylase (HDAC) are 2 key enzymes that regulate histone acetylation and play important roles in tumor development. However, the roles of HAT and HDAC in the calcification and osteoblastic differentiation of ACP are not known., Methods: In this study, primary cells were isolated from ACP tissues, and calcification was induced with bone morphogenetic protein 2 (Bmp2). HDAC3 expression was assessed in 12 tissue samples by Western blotting and immunohistochemistry. ACP calcification was assessed by Alizarin red staining. A luciferase reporter assay was performed to examine the interaction between miR-181b and the 3'-untranslated region of the polycomb chromobox 4 (CBX4) gene., Results: Our results showed that the expression of HDAC3 was increased in the calcified ACP samples, but inhibition of HDAC3 promoted ACP cell calcification and osteoblastic differentiation. Mechanistically, HDAC3 nuclear translocation was suppressed by Bmp2, leading to Runx2 protein expression and Osterix, osteocalcin (OCN), osteopontin (OPN), and alkaline phosphatase (ALP) mRNA expression. In addition, this process was suppressed by CBX4, which stabilized the nuclear localization of HDAC3. miR-181b, the expression of which was increased in Bmp2-induced ACP cells, directly targeted and decreased CBX4 expression and inhibited the nuclear localization of HDAC3., Conclusions: Our results demonstrate that Bmp2 increases miR-181b levels to directly target and inhibit CBX4 expression, leading to a reduction in the CBX4-dependent regulation of HDAC3 nuclear translocation, which results in Runx2 activation/osteoblastic differentiation and calcium deposition in ACP. Further studies targeting these cascades may contribute to therapeutic interventions used for recurrent ACP. Video Abstract., (© 2021. The Author(s).)

Background: COVID-19 pandemic has forced physicians to quickly determine the patient's condition and choose treatment strategies. This study aimed to build and validate a simple tool that can quickly predict the deterioration and survival of COVID-19 patients., Methods: A total of 351 COVID-19 patients admitted to the Third People's Hospital of Yichang between 9 January to 25 March 2020 were retrospectively analyzed. Patients were randomly grouped into training (n = 246) or a validation (n = 105) dataset. Risk factors associated with deterioration were identified using univariate logistic regression and least absolute shrinkage and selection operator (LASSO) regression. The factors were then incorporated into the nomogram. Kaplan-Meier analysis was used to compare the survival of patients between the low- and high-risk groups divided by the cut-off point., Results: The least absolute shrinkage and selection operator (LASSO) regression was used to construct the nomogram via four parameters (white blood cells, C-reactive protein, lymphocyte≥0.8 × 10 9 /L, and lactate dehydrogenase ≥400 U/L). The nomogram showed good discriminative performance with the area under the receiver operating characteristic (AUROC) of 0.945 (95% confidence interval: 0.91-0.98), and good calibration (P = 0.539). Besides, the nomogram showed good discrimination performance and good calibration in the validation and total cohorts (AUROC = 0.979 and AUROC = 0.954, respectively). Decision curve analysis demonstrated that the model had clinical application value. Kaplan-Meier analysis illustrated that low-risk patients had a significantly higher 8-week survival rate than those in the high-risk group (100% vs 71.41% and P < 0.0001)., Conclusion: A simple-to-use nomogram with excellent performance in predicting deterioration risk and survival of COVID-19 patients was developed and validated. However, it is necessary to verify this nomogram using a large-scale multicenter study.