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Background: Collateral formation from the extracranial carotid artery to ischemic brain tissue determines the clinical success of superficial temporal artery (STA) to middle cerebral artery (MCA) bypass surgery in adult patients with moyamoya disease, but postoperative collateral formation (PCF) after STA-MCA bypass surgery is unpredictable. Accurate preoperative prediction of acceptable PCF could improve patient selection. This study aims to develop a prediction nomogram model for PCF in this patient population. Methods: Adult patients with moyamoya disease undergoing the STA-MCA bypass surgery between January 2013 and December 2020 at a single institution were retrospectively or prospectively enrolled in this observational study. Data including potential clinical and radiological predictors were obtained from hospital records. A nomogram was generated based on a multivariate logistic regression analysis, to identify potential predictors associated with good PCF. The performance of the nomogram was evaluated for discrimination, calibration, and clinical utility. Results: Data from 243 patients with moyamoya disease who underwent the STA-MCA bypass surgery were analyzed to build the nomogram. After 1-year follow-up, 162 (66.7%) hemispheres had good PCF and 81 (33.3%) had poor PCF. Good PCF is associated with 3 preoperative factors: age at operation, a diameter of donor branch of STA, and the preinfarction period stage. Incorporating these 3 factors, the model achieved a concordance index of 0.88 (95% CI, 0.84–0.92) and had a well-fitted calibration curve and good clinical application value. A cutoff value of 100 was determined to predict good PCF via this nomogram. Conclusions: The nomogram exhibits high accuracy in predicting good PCF after the STA-MCA bypass surgery in adult patients with moyamoya disease and may allow surgeons to better evaluate preoperatively candidacy for successful bypass surgery.

Glioblastoma (GBM) constitutes the most lethal primary brain tumor for which immunotherapy has provided limited benefit. The unique brain immune landscape is reflected in a complex tumor immune microenvironment (TIME) in GBM. Here, single-cell sequencing of the GBM TIME revealed that microglia were under severe oxidative stress, which induced nuclear receptor subfamily 4 group A member 2 (NR4A2)–dependent transcriptional activity in microglia. Heterozygous Nr4a2 (Nr4a2+/−) or CX3CR1+ myeloid cell–specific Nr4a2 (Nr4a2fl/flCx3cr1Cre) genetic targeting reshaped microglia plasticity in vivo by reducing alternatively activated microglia and enhancing antigen presentation capacity for CD8+ T cells in GBM. In microglia, NR4A2 activated squalene monooxygenase (SQLE) to dysregulate cholesterol homeostasis. Pharmacologic NR4A2 inhibition attenuated the protumorigenic TIME, and targeting the NR4A2 or SQLE enhanced the therapeutic efficacy of immune-checkpoint blockade in vivo. Collectively, oxidative stress promotes tumor growth through NR4A2–SQLE activity in microglia, informing novel immune therapy paradigms in brain cancer. Significance: Metabolic reprogramming of microglia in GBM informs synergistic vulnerabilities for immune-checkpoint blockade therapy in this immunologically cold brain tumor. This article is highlighted in the In This Issue feature, p. 799

Aims: To explore angiopoietin-1 (Ang-1) involved in cerebral vasospasm (CVS) after aneurysmal subarachnoid hemorrhage (aSAH) through its effect on endoplasmic reticulum stress (ERS) and apoptosis of vascular endothelial cells (VECs). Background: CVS accounts for high morbidity and mortality of aSAH. Abnormal cellular physiological processes of VECs play a critical role in aSAH-induced CVS. In addition, Ang-1 is involved in regulating vascular structure and function. Objective: To study the role of Ang-1 played in CVS and the underlying mechanism. Methods: Blood samples of 130 aSAH patients were collected from 2016 to 2020 at West China Hospital of Sichuan University. A two-hemorrhage rodent model was employed to structure an aSAH-induced CVS rat model. Moreover, oxyHb was used to treat VECs to construct a CVS cell model in vitro. ELISA was used to measure the level of Ang-1 and HE staining to assess the rat's basilar arteries. Subsequently, CCK-8 was used to detect cell viability ability, and flow cytometry was used to test the cell apoptosis rate. Western blotting was used to determine the expression level of ERS marker and apoptosis-related proteins. Results: There was an abnormally low expression of Ang-1 in CVS patients and CVS rats; besides, oxyHb treatment decreased Ang-1 in VECs in a concentration-dependent manner. Ang-1 treatment led to the thinner basilar artery wall and lumen circumference in CVS rats; moreover, in oxyHbtreated VECs, Ang-1 treatment inhibited ERS and apoptosis. In addition, the expression of p-PI3K and p-Akt in the CVS group decreased, while the expression of p53 in the CVS group increased. The expression of p-PI3K and p-Akt in 8 CVS rats negatively correlates with the expression of Ang- 1, but the correlation between p53 and Ang-1 was positive. Furthermore, the results suggested that Ang-1 suppressed ERS and apoptosis of VECs through the regulated PI3K/Akt/p53 pathway. Conclusion: Elevated Ang-1 inhibited p53-mediated ERS and apoptosis of VECs through the activated PI3K/Akt pathway; Ang-1 might be an attractive treatment strategy for CVS.

Given the paucity of data on the subependymoma, we aimed to evaluate its risk factors from the Surveillance, Epidemiology, and End Results (SEER) database.We collected survival and clinical information on patients with subependymoma diagnosed between 1975 and 2016 from the SEER database and screened them according to inclusion and exclusion criteria. Then, univariate and multivariate Cox regression analyses were used to identify significant prognostic factors, and nomograms were constructed to visualize the results. The concordance index (C-index), receiver operating characteristic (ROC), and calibration curves were used to assess the predictive ability of the nomogram. We divided the patient scores into two groups according to the high- and low-risk groups and constructed a survival curve using Kaplan-Meier analysis.A total of 731 patients were initially enrolled, including 511 (69.9%) males and 220 (30.1%) females. After screening, a total of 581 patientswere further evaluated by statistical analysis. The 5- and 10-year survival estimates were 92.0% and 81.9%, respectively. Sex (male, p=0.018; HR=2.3547, 95% CI=1.158-4.788) and age (≥56 years, p0.001; HR=5.640, 95% CI= 3.139-10.133) were identified as independent prognostic factors for overall survival. The nomogram contained 4 prognostic factors. The C-index was 0.741, and the ROC and calibration curves also indicated the good predictability of the nomogram.In this large cohort, a significant association was noted between age/sex and outcome, which could serve an important role for patient education. Even though a significant association was not found between the extent of resection and outcome, the effect of surgery on prognosis should be further explored.

The third INTEnsive care bundle with blood pressure Reduction in Acute Cerebral hemorrhage Trial (INTERACT3) is an international, multicenter, stepped-wedge (4 phases/3 steps) cluster randomized trial involving 110 hospitals in mainly low- and middle-income countries during 2017–2022. The aim is to determine the effectiveness of a goal-directed care bundle of intensive blood pressure (BP) lowering, glycemic control, antipyrexia, and anticoagulation reversal treatment versus usual standard of care, in patients with acute intracerebral hemorrhage (ICH). After a “usual care” period, hospitals were randomly allocated to implementing care-bundle protocols for control targets (systolic BP

Elevated blood glucose is frequently detected early after aneurysmal subarachnoid hemorrhage (aSAH). We aimed to investigate whether hyperglycemia at admission is associated with mortality in patients with aSAH.In a multicenter observational study of patients with aSAH, we defined normal glycemia, mild hyperglycemia, moderate hyperglycemia, and severe hyperglycemia as blood glucose of 4.00-6.09 mmol/L, 6.10-7.80 mmol/L, 7.81-10.00 mmol/L, and 10.00 mmol/L, respectively. We performed propensity score matching to obtain the adjusted odds ratios (OR) with 95 % confidence intervals (CI).Of 6771 patients with aSAH, 511(7.5 %) had died in hospital, and hyperglycemia at admission was observed in 4804 (70.9 %). Propensity scores matching analyses indicated that compared with normal glycemia, the odds of in-hospital mortality were slightly lower in patients with mild hyperglycemia (OR 0.89, 95 % CI 0.56-1.40), significantly higher in patients with moderate hyperglycemia (OR 1.90, 95 % CI 1.20-3.01), and in patients with severe hyperglycemia (OR 3.45, 95 % CI 2.15-5.53; P trend 0.001). Long-term survival was worse among patients with hyperglycemia and was proportional to its severity. Similar dose-response associations were evident for poor functional outcomes and major disability. Hyperglycemia was associated with an increased risk of hospital-acquired infections (OR 1.46, 95 % CI 1.29-1.66) and rebleeding (OR 1.58, 95 % CI 1.06-2.35).Among aSAH patients, hyperglycemia at admission was independently associated with increased mortality. Both moderate hyperglycemia and severe hyperglycemia were associated with an increased risk of mortality, but these associations were not seen in mild hyperglycemia (blood glucose 6.10-7.80 mmol/L).

As the second most common primary intracranial neoplasms, about 40% of pituitary adenomas (PAs) exhibit aggressive behaviors and resulting in poor patient prognosis. The molecular mechanisms underlying the aggressive behaviors of PAs are not yet fully understood. Biochemical studies have reported that programmed cell death 10 (PDCD10) is a component of the striatin-interacting phosphatase and kinase (STRIPAK) complex and plays a dual role in cancers in a tissue or disease-specific manner. In the present study, we report for the first time that the role of PDCD10 in PAs. Cell proliferation, migration and invasion were either enhanced by overexpressing or inhibited by silencing PDCD10 in PA cells. Moreover, PDCD10 significantly promoted epithelial–mesenchymal transition (EMT) of pituitary adenoma cells. Mechanistically, we showed that the expression of CXCR2, together with phosphorylation levels of AKT and ERK1/2 were regulated by PDCD10. Activation of CXCR2 inversed inactivation of AKT/ERK signal pathways and the tumor-suppressive effects induced by PDCD10 silencing. Finally, the pro-oncogenic effect of PDCD10 was confirmed by in vivo tumor grafting. Taken together, we demonstrate for the first time that PDCD10 can induce aggressive behaviors of PAs by promoting cellular proliferation, migration, invasion and EMT through CXCR2-AKT/ERK signaling axis CA extern

Background and Objective: The potential impact of rebleeding and delayed cerebral ischemia (DCI) on long-term survival in patients with aneurysmal subarachnoid hemorrhage (aSAH) remained unclear. This study aimed to investigate whether DCI and rebleeding increase the risk of long-term all-cause mortality in patients with aSAH who survived the follow-up period of one year. Methods: We retrospectively collected data on patients with atraumatic aSAH who were still alive 12 months after aSAH occurrence between December 2013 and June 2019 from the electronic health system. Patients were then classified by the occurrence of rebleeding or DCI during hospitalization. Death records were obtained from an administrative database, the Chinese Household Registration Administration System, until April 20, 2021. Multivariable Cox proportional hazards models were used to compare overall survival in different groups. Sensitivity analysis was performed with propensity-score matching (PSM). Results: A total of 2,607 patients were alive one year after aSAH. The crude annual death rate from any cause among patients who had rebleeding (7.2 per 100 person-years) and patients who had DCI (3.7 per 100 person-years) during hospitalization was higher than that of patients with neither event (2.1 per 100 person-years). Multivariate analysis showed that rebleeding is an independent risk factor for long-term mortality (adjusted hazard ratio (aHR), 2.37; 95% confidence interval (CI), 1.47- 3.81). DCI was an independent prognostic factor of poorer overall survival (aHR, 2.09; 95% CI, 1.54-2.84). Conclusions: Amongst patients alive one year after aSAH, rebleeding and DCI during hospitalization were independently associated with higher rates of long-term mortality.

BackgroundIntracranial aneurysms (IA) is a common condition and may ultimately result in life-threatening hemorrhagic strokes. A precise understanding of the cellular and gene expression perturbations in human IA tissue may enlighten additional therapeutics for unruptured IA.MethodsA total of 21,332 qualified cells were obtained from four cell-sparse ruptured and unruptured human IA tissues. Detailed cell atlas and dynamics, gene expression perturbations, and inflammation features were thoroughly investigated using multiple machine learning-based algorithms.ResultsEndothelial cells, smooth muscle cells (SMCs), fibroblasts and, for the first time, pericytes have been identified in human IA tissue. A significant proportion of immune cells are also identified, with the number of monocyte/macrophages and neutrophils being notably higher in ruptured IA. By leveraging external datasets, macrophages characterized by transcriptional activation of NF-κB and HIVEP2 is most strongly associated with IA rupture. Interestingly, the recruitment and activation of macrophages and their functional characteristics in terms of TNFα and chemokine production remain consistent between unruptured and ruptured IA.ConclusionsThis study provides insights into the pathophysiology and molecular underpinnings of the IA wall and may motivate novel therapeutic options for unruptured IA.

Supplemental Figure S4 describes that NR4A2-knockdown affects lipid metabolism and promotes antigen presentation of microglia.

Glioblastoma (GBM) constitutes the most lethal primary brain tumor for which immunotherapy has provided limited benefit. The unique brain immune landscape is reflected in a complex tumor immune microenvironment (TIME) in GBM. Here, single-cell sequencing of the GBM TIME revealed that microglia were under severe oxidative stress, which induced nuclear receptor subfamily 4 group A member 2 (NR4A2)–dependent transcriptional activity in microglia. Heterozygous Nr4a2 (Nr4a2+/−) or CX3CR1+ myeloid cell–specific Nr4a2 (Nr4a2fl/flCx3cr1Cre) genetic targeting reshaped microglia plasticity in vivo by reducing alternatively activated microglia and enhancing antigen presentation capacity for CD8+ T cells in GBM. In microglia, NR4A2 activated squalene monooxygenase (SQLE) to dysregulate cholesterol homeostasis. Pharmacologic NR4A2 inhibition attenuated the protumorigenic TIME, and targeting the NR4A2 or SQLE enhanced the therapeutic efficacy of immune-checkpoint blockade in vivo. Collectively, oxidative stress promotes tumor growth through NR4A2–SQLE activity in microglia, informing novel immune therapy paradigms in brain cancer.Significance:Metabolic reprogramming of microglia in GBM informs synergistic vulnerabilities for immune-checkpoint blockade therapy in this immunologically cold brain tumor.This article is highlighted in the In This Issue feature, p. 799

Table S2 describes information of key research agents, data deposition and software versions.

BACKGROUND: The molecular subtype of breast cancer is one of the most important factors affecting patient prognosis. The study aimed to analyze the association between quantitative and qualitative features of contrast-enhanced mammography (CEM) images and breast cancer molecular subtypes. METHODS: This retrospective double-center study included women who underwent CEM between November 2017 and April 2020. Each patient had at least 1 malignant lesion confirmed by pathology. The CEM images were evaluated by 2 radiologists to obtain quantitative and qualitative image features. The molecular subtypes were studied as dichotomous outcomes, including luminal versus non-luminal, human epidermal growth factor receptor (HER2)-enriched versus non-HER2-enriched, and triple-negative breast cancer (TNBC) versus non-TNBC subtypes. The association between the image features and molecular subtypes was analyzed by multivariate logistic regression, with odds ratios (ORs) and 95% confidence intervals (CIs) provided. RESULTS: A total of 151 patients with 160 malignant lesions were included in the study. For quantitative features, a higher standard deviation of lesion density was associated with non-luminal (OR =0.88, 95% CI: 0.81 to 0.96, P=0.004) and HER2-enriched breast cancers (OR =1.16, 95% CI: 1.04 to 1.28, P=0.006). The relative degree of enhancement (RDE) and contrast-to-noise ratio (CNR) were not associated with molecular subtypes. However, a higher CNR/lesion size (OR =1.06, 95% CI: 1.01 to 1.12, P=0.012) was associated with luminal subtype cancers, and a higher RDE/lesion size (OR =0.94, 95% CI: 0.88 to 1.00, P=0.035) or a higher CNR/lesion size (OR =0.94, 95% CI: 0.88–1.00, P=0.038) was associated with non-TNBCs. For qualitative features, the presence of calcification was associated with HER2-enriched breast cancers (OR =2.91, 95% CI: 1.10 to 7.67, P=0.031). The presence of architectural distortion was associated with luminal cancer (OR =14.50, 95% CI: 1.91 to 110.14, P=0.010) and non-TNBC (OR =0.05, 95% CI: 0.00 to 0.43, P=0.022). Non-mass enhancement (OR =2.78, 95% CI: 1.08 to 7.14, P=0.033) was associated with HER2-enriched breast cancers. An association remained after adjustments for age, breast thickness, and breast density (all adjusted P

Human activity has fundamentally altered wildfire on Earth, creating serious consequences for human health, global biodiversity, and climate change. However, it remains difficult to predict fire interactions with land use, management, and climate change, representing a serious knowledge gap and vulnerability. We used expert assessment to combine opinions about past and future fire regimes from 98 wildfire researchers. We asked for quantitative and qualitative assessments of the frequency, type, and implications of fire regime change from the beginning of the Holocene through the year 2300. Respondents indicated that direct human activity was already influencing wildfires locally since at least ~12,000 years BP, though natural climate variability remained the dominant driver of fire regime until around 5000 years BP. Responses showed a ten-fold increase in the rate of wildfire regime change during the last 250 years compared with the rest of the Holocene, corresponding first with the intensification and extensification of land use and later with anthropogenic climate change. Looking to the future, fire regimes were predicted to intensify, with increases in fire frequency, severity, and/or size in all biomes except grassland ecosystems. Fire regime showed quite different climate sensitivities across biomes, but the likelihood of fire regime change increased with higher greenhouse gas emission scenarios for all biomes. Biodiversity, carbon storage, and other ecosystem services were predicted to decrease for most biomes under higher emission scenarios. We present recommendations for adaptation and mitigation under emerging fire regimes, concluding that management options are seriously constrained under higher emission scenarios.Competing Interest StatementThe authors have declared no competing interest. Introduction Methods and materials Results and discussion Timing and type of future fire regime change Consequences of fire regime change Our capacity to prevent, control, or adapt to future fire regimes Charting a course in a world of uncertainty Expert assessment application in fire management

Low serum albumin levels have been identified as a predictor of infectious complications in critically ill patients. However, the association in patients with aneurysmal subarachnoid hemorrhage (aSAH) remains unclear. We aimed to evaluate the prognostic value of hypoalbuminemia using blood samples at admission in patients with aSAH.In a multicenter observational study of patients with aSAH, serum albumin counts were collected on admission. Hypoalbuminemia was defined as a total albumin level 35 g/L. Multivariable logistic regression analyses and propensity score matching were performed to obtain the adjusted odds ratios (ORs) with 95% confidence intervals (CI) for the primary outcome of hospital-acquired infections.A total of 5448 patients were included in the observational cohort study. The odds of hospital-acquired infections were significantly higher in patients with albumin levels 30-34.9 g/L (OR 1.62, 95% CI 1.38-1.90), 25-29.9 g/L (OR 1.97, 95% CI 1.54-2.51), and 24.9 g/L (OR 2.43, 95% CI 1.53-3.86) compared with patients with albumin level ≥ 35 g/L. The odds of hospital-acquired infections with a change in albumin levels from admission to 48-72 h later of lower than - 10 g/L and - 10 to - 5 g/L were 1.67 (95% CI 1.41-1.86) and 1.24 (95% CI 1.05-1.46), respectively, compared with a change in albumin levels of - 5 to 5 g/L.In this large study of matched patients with aSAH, hypoalbuminemia at admission was associated with hospital-acquired infections. A decrease in serum albumin levels within 72 h of admission was associated with higher hospital-acquired infections.

To verify whether mesenchymal stem cells cocultured with tanshinone IIA may ameliorate Alzheimer's disease by inhibiting oxidative stress.Sixty male Sprague-Dawley rats were randomly divided into 4 groups named Sham, Aβ25-35, mesenchymal stem cells, and mesenchymal stem cells (tanshinone IIA). The rats were treated according to different groups. The neurobehavioral performance of Sprague-Dawley rats was evaluated via Morris water maze test. Histological changes were checked via hematoxylin-eosin staining. The levels of total antioxidant activity (T-AOC), superoxide dismutase (SOD), glutathione peroxidase (GSH-PX) and malondialdehyde in hippocampus were assayed by ELISA kit. The levels of Aβ, p-tau/tau, and p-AMP-activated protein kinase/AMP-activated protein kinase in hippocampus were checked by Western blot.Our research showed that the injection of mesenchymal stem cells (tanshinone IIA) into the hippocampus alleviated learning and memory deficits and reduced hippocampal neuronal injury in the Alzheimer's disease rats. Moreover, mesenchymal stem cells (tanshinone IIA) treatment suppressed oxidative stress, attenuated Aβ accumulation reduced Tau hyperphosphorylation, and enhanced the activity of AMP-activated protein kinase in the hippocampus of the Alzheimer's disease rats. However, there were almost no significant difference between the mesenchymal stem cells and Aβ25-35 groups.Mesenchymal stem cells (tanshinone IIA) transplantation may be a potential treatment for curing Alzheimer's disease, which may be related to the inhibition of oxidative stress.

Background: The third INTEnsive care bundle with blood pressure Reduction in Acute Cerebral Haemorrhage Trial is an ongoing international, multicentre, stepped wedge, cluster-randomized trial to determine the effectiveness of a goal-directed care bundle (early intensive blood pressure [BP] lowering, glycaemic control, treatment of pyrexia, and reversal of anticoagulation), as compared to standard of care, on patient-centred outcomes after acute intracerebral haemorrhage (ICH). An embedded process evaluation aims to identify factors related to the uptake and implementation of the intervention. Herein, we present the process evaluation results for hospital sites in China. Methods/Design: A mixed methods approach, including surveys, focused group discussions and interviews with clinicians, routine monitoring, and recruitment logs were used to collect data across purposively sampled hospitals. Medical Research Council guidance and normalization process theory were used as theoretical frameworks for design, data analysis, and synthesis. Results: Twenty quantitative surveys were completed with clinicians, and 26 interviews and 2 focus group discussions were conducted during 2019–2020. The care bundle was generally delivered as planned and acceptable by doctors and nurses, but difficulties were reported in achieving the protocol-defined target levels of BP and glycaemic control. Resistance to implementing the care bundle occurred for patients perceived to be at high risk of adverse effects. Common organizational contextual factors that impeded implementation included delayed processes and limited medication supply, while established background care procedures, expertise, and capacity influenced its integration into routine practice. Areas to facilitate implementation included optimizing workflow within available resources, having a dedicated team, and recognizing the potential benefits of the intervention. Conclusions: Varied established care protocols across sites, different levels of background expertise, and lack of staff capacity impeded the integration of goal-directed care bundle into routine practice for ICH patients in China. Ready identification, and efforts to address, these barriers could facilitate uptake of future guideline-recommended interventions for the management of patients with ICH.

Backgrounds: Previous studies reported inconsistent results regarding associations between apolipoprotein E (APOE) polymorphism and clinical outcomes after ischemic stroke (IS), intracerebral hemorrhage (ICH), or subarachnoid hemorrhage (SAH). Thus, the study was designed to make a systematic review and meta-analysis regarding the association between APOE polymorphism and clinical outcome after IS, ICH, and SAH. Methods: To identify studies eligible for this meta-analysis, we searched for articles published before August 2021 in the databases (PubMed, Web of Science, and Google Scholar). We used STATA 12.0 software to compute hazard ratios (HRs) and their 95% confidence intervals (CIs) regarding APOE polymorphism and clinical outcome after IS, ICH, and SAH. Results: Meta-analysis showed no significant association between APOE polymorphism and functional outcome after IS with fixed effects models (ε4 carrier vs. non-ε4 carrier: HR, 1.00; 95% CI: 0.83–1.21, I2 = 29.4%, p = 0.183; ε2 carrier vs. non-ε2 carrier: HR, 0.92; 95% CI: 0.72–1.16, I2 = 15.6%, p = 0.307). Meta-analysis showed that ICH patients carrying ε4 allele have increased risk of poor outcome in Caucasian population with fixed effects models (ε4 carrier vs. non-ε4 carrier: HR, 1.75; 95% CI: 1.19–2.57, I2 = 0.0%, p = 0.543). Meta-analysis showed no significant association between APOE polymorphism and functional outcomes after SAH with random effects models (ε4 carrier vs. non-ε4 carrier: HR, 1.51; 95% CI: 0.80–2.84, I2 = 57.1%, p = 0.022). Conclusions: In conclusion, the present study demonstrated APOE ε4 carriers show worse functional outcomes after ICH, but not after IS or SAH. More large-scale studies were critical to explore the association between APOE polymorphism and clinical outcome after IS, ICH, and SAH.

Aneurysmal subarachnoid haemorrhage (aSAH), resulting from the rupture of intracranial aneurysms, can yield high mortality and disability. This study aimed to explore the immune infiltration of aneurysmal tissues and investigate a novel mechanism underlying aSAH. We downloaded datasets containing expression profiles of aneurysmal and normal arterial tissues from the online database. Then a comprehensive bioinformatic strategy was conducted to select the biomarkers of aneurysmal tissues. Two calculation algorithms were performed to identify the unique immune characteristics between aneurysmal tissues and normal arteries. Double immunofluorescence staining was used to investigate the role of pathway-related proteins in the inflammatory process after aSAH. Six microarray datasets were integrated, and another RNA-sequencing dataset was used as the validation dataset. Functional enrichment analysis of the differentially expressed genes indicated that immune-related processes were closely related to the progression of aSAH. We then performed immune microenvironment infiltration analysis, and the results suggested macrophages were abnormally enriched in aneurysmal tissues. Core gene MSR1 was filtered through a comprehensive bioinformatic strategy. Our analysis suggested that MSR1 might be associated with macrophage activation and migration. Our study elucidated the impact of macrophage and MSR1 on aSAH progression. These findings were helpful in gaining insight into the immune heterogeneity of aneurysmal tissues and normal arteries, and in identifying patients who might benefit from immunotherapy.

In clinical work, the magnetic resonance imaging markers of cerebral small vessel disease (CSVD) are frequently observed in moyamoya disease (MMD), but the clinical significance of these markers in MMD remains unclear. This study aimed to fill this gap and systematically investigate its clinical significance. In this retrospective cohort study, we screened all adult patients with MMD hospitalized from January 2016 to January 2020 and collected their baseline clinical and imaging information. Univariate and multivariate logistic regression analyses were then performed to determine which imaging markers were independently associated with MMD characteristics, including cerebrovascular morphology, cerebral hemodynamics, cerebrovascular events, and postoperative collateral formation (PCF). A total of 312 cerebral hemispheres images were collected from the 156 patients with MMD. Using multivariate logistic regression analysis, the following results were generated: (1) The presence of lacunes (OR, 2.094; 95% CI, 1.109-3.955; p = 0.023) and severe white matter hyperintensities (WMH) (OR, 3.204; 95% CI, 1.742-5.892; p < 0.001) were associated with a Suzuki stage ≥ IV; (2) the presence of lacunes (OR, 6.939; 95% CI, 3.384-14.230; p < 0.001), higher numbers of enlarged perivascular spaces in centrum semiovale (CSO-EPVS) (OR, 1.046; 95% CI, 1.024-1.067; p < 0.001), and severe WMH (OR, 2.764; 95% CI, 1.463-5.223; p = 0.002) were associated with the reduced regional cerebral blood flow; (3) the presence of lacunes (OR, 12.570; 95% CI, 2.893-54.624; p = 0.001), higher numbers of CSO-EPVS (OR, 1.103; 95% CI, 1.058-1.150; p < 0.001), and severe WMH (OR, 5.982; 95% CI, 1.727-20.716; p = 0.005) were associated with ischemic cerebrovascular events; (4) the higher number of CSO-EPVS (OR, 1.077; 95% CI, 1.026-1.131; p = 0.003) was associated with good PCF. The lacunes, WMH, and CSO-EPVS were independently associated with these MMD characteristics. In conclusion, this study provided a novel and potential framework for the practical assessment of MMD by magnetic resonance imaging.

BACKGROUND AND PURPOSE We aimed to build a nomogram, based on patients with spontaneous intracerebral hemorrhage (SICH), to predict the probability of mortality and morbidity at 7 days and 90 days, respectively. METHODS We performed a retrospective study, with patients at less than 6 h from ictus admitted to the department of neurosurgery in a single institute, from January 2011 to December 2018. A total of 1036 patients with SICH were included, 486 patients (46.9%) were 47-66 years old at diagnosis, and 711 patients (68.6%) were male. The least absolute shrinkage and section operator method was performed to identify the key adverse factors predicting the outcomes in patients with SICH, and multivariate logistic regression analysis was built on these variables, and then the results were visualized by a nomogram. The discrimination of the prognostic models was measured and compared by means of Harrell's concordance index (C-index), calibration curve, area under the curve (AUC), and decision curve analysis (DCA). RESULTS Multivariate logistic regression analysis revealed that factors affecting 7-day mortality, including the following: age, therapy, Glasgow Coma Scale (GCS) admission, location, ventricle involved, hematoma volume, white blood cell (WBC), uric acid (UA), and L-lactic dehydrogenase (LDH); and factors affecting 90-day mortality, including temperature, therapy, GCS admission, ventricle involved, WBC, international normalized ratio, UA, LDH, and systolic blood pressure. The C-index for the 7-day mortality and 90-day mortality prediction nomogram was 0.9239 (95% CI = 0.9061-0.9416) and 0.9241 (95% CI = 0.9064-0.9418), respectively. The AUC of 7-day mortality was 92.4, as is true of 90-day mortality. The calibration curve and DCA indicated that nomograms in our study had a good prediction ability. For 90-day morbidity, age, marital status, and GCS at 7-day remained statistically significant in multivariate analysis. The C-index for the prediction nomogram was 0.6898 (95% CI = 0.6511-0.7285), and the calibration curve, AUC as well as DCA curve indicated that the nomogram for the prediction of good outcome demonstrated good agreement in this cohort. CONCLUSIONS Nomograms in this study revealed many novel prognostic demographic and laboratory factors, and the individualized quantitative risk estimation by this model would be more practical for treatment management and patient counseling.