MedNexus
Volume 42 · Issue 08 · 2026
MedNexus
Endovascular therapy is the main treatment strategy for ischemic cerebrovascular disease, covering three core areas: acute large vessel occlusion, intracranial atherosclerotic stenosis and carotid artery stenosis. The time window and indications of thrombectomy for acute large vessel occlusion are constantly expanding, but "ineffective recanalization" is still the bottleneck of treatment. Bridging therapy, anti-bridging strategy and individualized screening are currently hot spots. Endovascular treatment of intracranial atherosclerotic stenosis has experienced controversy, and new devices such as drug-eluting stents and drug-coated balloons are pushing it from anatomical repair to precise intervention. The efficacy of carotid stenting for carotid stenosis is no longer inferior to carotid endarterectomy. New evidence has been extended to people with asymptomatic severe carotid stenosis, and transcarotid revascularization has also shown unique advantages. This review combines recent research, guidelines and consensus to sort out the progress, controversy and direction in various fields, in order to provide reference for clinical decision-making and follow-up research.
There are about 11.9 million new strokes worldwide every year, of which cerebral hemorrhage accounts for about 28%[1,2]。 The onset of cerebral hemorrhage is acute, the condition is severe, the prognosis is poor, more than 1/3 of patients die within 1 month after the onset of cerebral hemorrhage[1]Its 30-day mortality rate is about 3 times that of ischemic stroke[3]。 For a long time, effective treatments for cerebral hemorrhage have been relatively limited, and most previous clinical trials have failed to demonstrate that interventions can stably improve patient functional outcomes. In recent years, some high-quality studies have obtained positive results in the fields of clustered management, intensive blood pressure reduction, anticoagulation reversal, and minimally invasive hematoma removal, suggesting that early and standardized active intervention may improve the clinical outcome of patients[4]。 This guide focuses on hypertensive intracerebral hemorrhage (HICH), the most common spontaneous cerebral hemorrhage in China and controversial in diagnosis and treatment. The prevention and treatment of HICH requires multi-disciplinary collaboration such as emergency department, neurosurgery, neurology, imaging, critical care and rehabilitation medicine. In 2020, multidisciplinary experts jointly formulated the "Chinese Multidisciplinary Diagnosis and Treatment Guidelines for Hypertensive Intracerebral Hemorrhage", which provides an important reference for standardizing the diagnosis and treatment of HICH[5]。 In view of recent research progress and the continuous accumulation of evidence-based evidence, it is necessary to integrate the latest results and transform them into more practical and actionable clinical practice recommendations. Therefore, it is of great significance to formulate the Guidelines for Multidisciplinary Diagnosis and Treatment of Hypertensive Intracerebral Hemorrhage (2026 Edition) based on the actual medical situation in China.
To investigate the safety and short-term efficacy of transcarotid artery revascularization (TCAR) in the treatment of patients with carotid artery stenosis.
The clinical data of 92 patients who underwent TCAR surgery in the Department of Interventional Radiology and Vascular Surgery of Peking University Third Hospital from June 2025 to January 2026 were retrospectively and consecutively included. The operation duration, common carotid artery occlusion time, postoperative lesion vessel stenosis rate, technical success rate (residual stenosis rate < 30%), perioperative complications were evaluated. Three months after operation, the clinical outcomes of patients were evaluated based on the modified Rankin Scale (mRS), and the occurrence of in-stent restenosis (stenosis rate > 50%) was assessed by carotid Doppler ultrasound.
The technical success rate of the 92 patients was 100%. The duration of common carotid artery occlusion was 7.8±2.8 minutes, 5 cases (5.4%) had obvious carotid sinus reflex during the operation. The operation duration was 85±23 minutes. Postoperative DSA showed that stenosis rate decreased from (83±9)% to (12±5)%. Two patients (2.2%) experienced complications including one patient with near-total occlusion who suffered hyperperfusion syndrome after the operation and one patient with a small amount of bleeding at the incision after the operation; no patient experienced cerebral ischemia or hemorrhage. Three months after operation, 69 patients were followed up and all had a good outcome (mRS ≤ 2 points), 58 patients underwent carotid Doppler ultrasound, and no in-stent restenosis occurred.
TCAR surgery for carotid artery stenosis has a high technical success rate and could significantly reduce the incidence of cerebral embolism events. Its short-term follow-up shows a high patency rate.
To investigate the predictive value of DSA-derived distal intracranial flow fraction (iFF) in symptomatic non-acute intracranial atherosclerotic large vessel occlusion (NAICA-LVO) after successful endovascular recanalization treatment (ERT).
The discovery cohort consisted of symptomatic NAICA-LVO patients who underwent ERT at the Stroke Center, Affiliated Hospital of Nantong University from January 2023 to July 2024 and retrospectively enrolled; the validation cohort included prospectively enrolled symptomatic NAICA-LVO patients receiving ERT from August 2024 to March 2025. Patients were classified into two groups based on the 90-day modified Rankin scale (mRS) score: good prognosis (mRS≤2) and poor prognosis (mRS>2). Baseline and perioperative clinical characteristics were compared between groups. Multivariate stepwise logistic regression was used to identify independent factors associated with good prognosis. Receiver operating characteristic (ROC) curve analysis was performed to evaluate the predictive performance of distal iFF.
The discovery cohort included 84 patients and the validation cohort included 32 patients. There were no significant differences in baseline or perioperative characteristics between the two cohorts (all P>0.05). A total of 51 patients in the discovery cohort and 20 in the validation cohort achieved favorable outcomes, while 33 and 12 patients, respectively, had unfavorable outcomes at 90 days after successful ERT. In the discovery cohort, compared with the good prognosis group, the poor prognosis group had significantly higher preoperative National Institutes of Health Stroke Scale (NIHSS) scores and mRS scores, lower hemoglobin levels, smaller post-recanalization minimal luminal diameter, and lower iFF values (all P<0.05). ROC analysis showed that distal iFF predicted outcomes with an area under the curve of 0.80, with an optimal cutoff value of 0.84. Multivariate logistic regression identified higher preoperative NIHSS score as independently associated with poor prognosis (OR=0.84, 95%CI: 0.73-0.95, P=0.008), while higher hemoglobin (OR=1.05, 95%CI: 1.01-1.09, P=0.021) and distal iFF≥0.84 (OR=4.33, 95%CI: 1.41-14.49, P=0.012) were independently associated with good prognosis. In the discovery cohort, iFF≥0.84 yielded an accuracy of 71.4%, sensitivity of 68.6%, specificity of 75.8%, positive predictive value of 81.4%, and negative predictive value of 61.0%; corresponding values in the validation cohort were 75.0%, 70.0%, 83.3%, 87.5%, and 62.5%, respectively.
Distal iFF has predictive value for clinical outcomes after successful ERT in patients with symptomatic NAICA-LVO.
To explore the safety and efficacy of endovascular treatment (EVT) for acute anterior circulation medium-vessel occlusion (MeVO), and to analyze the influencing factors of patients′ prognosis.
A total of 285 patients with acute anterior circulation MeVO admitted to the Department of Neurology, Linyi People′s Hospital Affiliated to Shandong Second Medical University between January 2020 and June 2024 were retrospectively enrolled. The patients were divided into the EVT group (117 cases) and the medical treatment alone group (168 cases) according to treatment modalities. Propensity score matching (PSM) with a caliper value of 0.02 was performed in a 1 ∶1 ratio to balance baseline confounding factors. The 90-day modified Rankin Scale (mRS) score after treatment was used to evaluate clinical efficacy. Safety outcomes included the incidence of symptomatic intracranial hemorrhage within 48 hours, cerebral hernia within 7 days, and 90-day mortality. According to the 90-day mRS score, patients in the EVT group were further divided into the favorable prognosis subgroup (mRS score≤1) and the poor prognosis subgroup (mRS score>1). Multivariate logistic regression analysis was conducted to identify independent prognostic factors.
After PSM, there were 81 patients in each of the EVT group and the medication-only group. No significant differences were observed in baseline characteristics between the two groups after PSM (all P>0.05). The 90-day favorable prognosis rate was significantly higher in the EVT group than in the medical treatment alone group [58.0% (47/81) vs. 40.7% (33/81), P=0.023]. There were no significant between-group differences in the incidence of 48-hour symptomatic intracranial hemorrhage, 7-day cerebral hernia or 90-day mortality (all P>0.05). Univariate analysis revealed that compared with the poor prognosis subgroup, the favorable prognosis subgroup had a smaller volume of Tmax(time to maximum) >6 s [M(Q1, Q3): 92.09 (56.83, 136.75)ml vs. 122.00 (72.50, 185.00)ml], a higher proportion of lesions located in the right cerebral hemisphere [52.9%(36/68) vs. 28.6%(14/49)], and a higher rate of successful vascular recanalization (modified Thrombolysis in Cerebral Infarction grade 2b-3) [98.5% (67/68) vs. 85.7% (42/49)] (all P<0.05). Multivariate logistic regression analysis demonstrated that smaller ischemic penumbra volume (OR=0.072, 95%CI: 0.008-0.672, P=0.021), lesions in the right cerebral hemisphere (OR=2.639, 95%CI: 1.159-6.024, P=0.021) and successful vascular recanalization (OR=2.271, 95%CI: 1.110-4.643, P=0.025) were independent protective factors for favorable 90-day prognosis.
EVT is safe and effective for patients with acute anterior circulation MeVO. It can significantly improve the 90-day favorable functional outcome without increasing the risk of symptomatic intracranial hemorrhage. Patients with smaller ischemic penumbra volume, lesions in the right cerebral hemisphere and successful vascular recanalization tend to achieve better prognosis.
To investigate the factors that may affect the 2-year survival and the functional prognosis of survivors in elderly patients with aneurysmal subarachnoid hemorrhage (aSAH).
Retrospective analysis of clinical data from 193 elderly patients(aged ≥80 years) with aSAH included in the Chinese Multi-center Cerebral Aneurysm Database from January 2017 to December 2020. Baseline patient characteristics, treatment modalities, and 2-year follow-up information were collected. The primary outcome was all-cause mortality, and the secondary outcome was the modified Rankin Scale (mRS) score of 2-year survivors, where a score of 0-2 was defined as independent survival (favorable prognosis group) and a score of 3-5 as dependent survival (unfavorable prognosis group). Univariate and multivariate Cox regression models were used to identify risk factors for 2-year survival. The Kaplan-Meier curve was employed to compare the impact of different factors on survival rates. Univariate and multivariate logistic regression analyses were performed to identify risk factors influencing the functional prognosis of 2-year survivors of aSAH.
A total of 193 very elderly patients with aSAH were enrolled, of whom 33 were lost to follow-up. During the follow-up period, 95 patients died, and 65 survived for 2 years(44 cases in favorable prognosis group and 21 cases in unfavorable prognosis group). The cumulative mortality rate at 2 years post-onset was 53.4% (95%CI: 39.6%-54.9%), with primary aSAH being the leading cause of death (42.1%). Univariate and multivariate Cox regression analyses showed that a history of essential hypertension(HR=1.584, 95%CI: 1.002-2.505, P=0.049)and World Federation of Neurosurgical Societies (WFNS) grade Ⅳ-Ⅴ(HR=2.200, 95%CI: 1.285-3.766, P=0.004)were independent risk factors for 2-year mortality in very elderly patients with aSAH, whereas endovascular embolization of the aneurysm was an independent protective factor(HR=0.551, 95%CI: 0.359-0.844, P=0.006). Univariate analysis indicated that age, Hunt-Hess grade Ⅳ-Ⅴ, and WFNS grade Ⅳ-Ⅴ were factors associated with unfavorable prognosis in 2-year survivors of elderly patients with aSAH (both P<0.05). Multivariate logistic regression analysis revealed that WFNS grade Ⅳ- Ⅴ (OR=3.974, 95%CI: 1.014–15.568, P=0.048) was an independent risk factor for unfavorable prognosis in 2-year survivors of aSAH. Log-rank test results demonstrated that the 2-year survival rates of patients who underwent aneurysm surgical clipping (60.0%) and those who received endovascular embolization treatment (52.3%) were both higher than that of those who received conservative management (42.1%). Patients with a history of hypertension had a lower survival rate than those without (39.5% vs. 63.0%), and patients with WFNS grade Ⅳ-Ⅴhad a lower survival rate than those with grade Ⅰ-Ⅲ(27.4% vs.62.2%), Hunt-Hess grade Ⅳ-Ⅴ had a lower survival rate than those with grade Ⅰ-Ⅲ(23.6% vs.56.8%), with all differences being statistically significant (all P<0.05).
Elderly patients with aSAH have a high 2-year mortality rate. A history of essential hypertension and a high WFNS grade are important risk factors for long-term mortality, while active endovascular embolization can improve patient survival. Furthermore, a high WFNS grade on admission may indicate an increased risk of unfavorable prognosis in surviving patients.
To quantitatively analyze the intraoperative blood pressure characteristics at the distal segment of the superficial temporal artery(STA) beyond the anastomotic site during side-to-side STA-middle cerebral artery(MCA) anastomosis.
A total of 16 patients with moyamoya disease who underwent combined revascularization at Department of Neurosurgery, Huashan Hospital, Fudan University, between June 2024 and July 2025 were retrospectively enrolled. According to the intraoperatively assessed diameter ratio between the STA and the M4 segment of the MCA, patients were classified into Group A(ratio>2.0), Group B(ratio 1.5-2.0), and Group C(ratio<1.5). After completion of the anastomosis, a pressure-sensing device was introduced into the STA distal to the anastomosis. The measured parameters included donor artery pressure(PSTA), pressure at the anastomotic site after the donor and recipient blood flows reached dynamic equilibrium(PO), and mean recipient artery pressure(PMCA). The STA pressure reduction index was calculated to evaluate the differences in distal STA blood flow pressure at the anastomotic site among the three groups.
Among the 16 patients, 5 were in Group A, 5 in Group B, and 6 in Group C. Intraoperative pressure measurements were successfully completed in all patients, and no measurement-related complications occurred. There were no significant differences in systemic invasive arterial pressure, PMCA and PSTA among groups A, B, and C (all P>0.05). The median PO values [M(Q1, Q3)] were 69.0(64.0, 70.0), 50.0(45.0, 59.0), and 43.5 (36.5, 50.5) mmHg (1 mmHg=0.133 kPa) in groups A, B, and C, respectively. The corresponding STA pressure reduction indices [M(Q1, Q3)] were 0.13(0.12, 0.18), 0.38(0.32, 0.40), and 0.50(0.39, 0.60), respectively. Both PO and the STA pressure reduction index differed significantly among the three groups (both P<0.01).
The donor-to-recipient vessel diameter ratio may be an important determinant of distal donor hemodynamic pressure. A larger ratio is associated with higher distal STA pressure.
To analyze the imaging characteristics of optical coherence tomography (OCT) in radiation-induced carotid artery disease and to investigate its value in guiding endovascular treatment.
Patients with radiation-induced carotid artery lesions following radiotherapy for head and neck tumors who underwent endovascular treatment at Department of Interventional Radiology, the First Affiliated Hospital of Zhengzhou University between February 2023 and January 2025 were retrospectively enrolled. Clinical and imaging data were collected and analyzed. Preoperative OCT and two-dimensional digital subtraction angiography (DSA) images were reviewed to characterize the intraluminal imaging features of the lesions. Procedure-related complications were documented to evaluate the safety of the intervention. After treatment, clinical follow-up was conducted every 2 months through outpatient visits or telephone interviews. Neurological outcomes were assessed using the modified Rankin Scale(mRS). Treatment efficacy was evaluated by computed tomography angiography (CTA) or DSA during follow-up.
A total of 9 patients were included, comprising 1 patient with common carotid artery stenosis, 2 with stenosis of the C1 segment of the internal carotid artery (ICA), 1 with stenosis of the C2-C3 ICA segments, and 5 with dissection or pseudoaneurysm involving the C2 ICA segments. OCT examination and endovascular treatment were successfully completed in all patients. Treatment strategies included covered stent implantation in 5 patients and parent artery occlusion with coils in 4 patients. OCT findings were as follows: stenotic lesions demonstrated indistinct intima-media boundaries and multiple high-backscattering, low-attenuation regions with blurred margins within the vessel wall. In addition to these features, dissection/pseudoaneurysm lesions showed intimal flaps, vessel wall defects, and abnormal extraluminal cavities protruding beyond the vascular lumen. Postoperative imaging demonstrated complete resolution of stenosis and disappearance of the aneurysm with satisfactory stent apposition in all 5 patients treated with covered stents (4 stenotic lesions and 1 pseudoaneurysm). In the 4 patients treated with parent artery occlusion, complete occlusion of the parent artery was achieved with no residual aneurysm visualization. One patient with a C2 segment pseudoaneurysm treated with a covered stent died from massive oral and nasal hemorrhage 5 days after the procedure. The remaining 8 patients experienced complete resolution or marked improvement of clinical symptoms, and all had a mRS score≤2 at discharge. Clinical follow-up was obtained in 8 patients for a mean duration of 12.2±2.9 months (4~16 months). During follow-up, 2 patients died due to tumor progression. The remaining 6 patients had the mRS scores≤2 at the last follow-up, with no newly developed neurological deficits. Excluding the 3 deceased patients, all remaining 6 patients underwent imaging follow-up (CTA in 4 patients and DSA in 2 patients) for a mean duration of 7.7±3.2 months (3~12 months). At the last imaging follow-up, mild in-stent stenosis was observed in 1 patient, whereas the remaining patients demonstrated patent stent flow (2 cases) or complete parent artery occlusion without recurrence (3 cases).
Blurring of the intima-media boundary accompanied by multiple high-backscattering, low-attenuation regions, with or without intimal disruption of the vessel wall, represents the characteristic OCT imaging features of radiation-induced carotid artery lesions. OCT may provide valuable information for the diagnosis of these lesions and for planning individualized endovascular treatment strategies.
To investigate the expression characteristics, immune relevance, and prognostic value of nicotinamide phosphoribosyltransferase (NAMPT) in glioma.
Sequencing data and clinical information from mRNA-seq Dataset 1 (n=325) and Dataset 2 (n=693) of the Chinese Glioma Genome Atlas (CGGA) were used to compare NAMPT expression across different clinical and pathological subgroups. Over-representation analysis was performed using Gene Ontology (GO) biological processes, Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways, and Hallmark gene sets, followed by gene set enrichment analysis (GSEA). Subsequently, enrichment curves were plotted for the significantly enriched pathways to characterize the transcriptional features and biological functions associated with NAMPT expression. The CIBERSORT algorithm was used to estimate immune cell infiltration in tumor tissues and to assess the association between NAMPT expression and the tumor immune infiltration pattern. Patients were stratified into high- and low-expression groups according to the median relative expression level of NAMPT, and overall survival (OS) was used as the survival endpoint. The log-rank test was used to compare OS between the high- and low-expression groups in the overall cohort and in patients with isocitrate dehydrogenase(IDH)-mutant or IDH-wild-type gliomas. Multivariable Cox proportional hazards regression analysis was performed to determine whether NAMPT expression was an independent prognostic factor in patients with glioma.
In both datasets, NAMPT was highly expressed in World Health Organization grade Ⅳ and IDH wild type gliomas (both P<0.001). Functional enrichment analysis in Dataset 1 showed that NAMPT-related genes were mainly enriched in inflammation and immune regulation-related pathways, including TNFA/NF-κB signaling and inflammatory response. In addition, these genes were enriched in pathways associated with malignant tumor phenotypes, such as hypoxia and epithelial-mesenchymal transition. GSEA further indicated that high NAMPT expression was positively associated with the enrichment of gene sets related to TNFA/NF-κB signaling, inflammatory response, hypoxia, and epithelial-mesenchymal transition. Immune infiltration analysis indicated that NAMPT expression was associated with a myeloid cell-enriched immune microenvironment, particularly neutrophils and M0 macrophages. Survival analysis showed that, in both Dataset 1 and Dataset 2, patients with high NAMPT expression had significantly shorter OS than those with low NAMPT expression in the overall glioma cohort (both P<0.001). Stratified analysis further demonstrated that high NAMPT expression was associated with shorter OS in both IDH-mutant and IDH-wild-type gliomas (all P<0.05). Multivariable Cox proportional hazards regression analysis identified high NAMPT expression as an independent predictor of poor prognosis in patients with glioma (Dataset 1: HR=2.127, 95%CI: 1.511-2.992, P<0.001; Dataset 2: HR=1.415, 95%CI: 1.080-1.856, P=0.012).
High NAMPT expression is associated with higher histological grade, activation of inflammatory signaling pathways, myeloid immune cell infiltration and poor prognosis in gliomas.
To investigate the potential causal relationship between genetically predicted Parkinson disease and the risk of epilepsy using a two-sample Mendelian randomization (MR) approach.
Publicly available genome-wide association study (GWAS) summary statistics were used. GWAS data for Parkinson disease were obtained from the IEU Open GWAS database (ieu-b-7; European population; including 33 674 cases and 449 056 controls; 17 891 936 single nucleotide polymorphism (SNP), and GWAS data for epilepsy were obtained from the GWAS catalog database (ebi-a-GCST90018840; European population; including 4 382 cases and 453 928 controls; 24 186 492 SNP). Genetically predicted Parkinson disease was considered the exposure, and epilepsy was considered the outcome. A unidirectional two-sample MR analysis was performed to evaluate the potential causal relationship between Parkinson disease and epilepsy. SNP loci significantly associated with Parkinson disease were selected as instrumental variables and harmonized with epilepsy GWAS data. The inverse variance weighted (IVW) method was used as the primary method for causal effect estimation. MR-Egger regression, weighted median, simple mode, and weighted mode methods were used as supplementary analyses to assess the consistency and robustness of the results. Cochran Q test and the MR-Egger intercept test were used to evaluate heterogeneity and horizontal pleiotropy, respectively. Leave-one-out analysis was performed as a sensitivity analysis.
A total of 22 independent SNPs were included as instrumental variables. IVW analysis showed a negative association between genetically predicted Parkinson disease and the risk of epilepsy (fixed-effect model: OR=0.93, 95%CI: 0.88-0.99, P=0.02; random-effect model: OR=0.93, 95%CI: 0.88-0.98, P=0.01). The weighted median and weighted mode methods also supported a negative association between Parkinson disease and epilepsy risk(both P<0.05). MR-Egger regression did not show a statistically significant association (P=0.12). Cochran Q test and the MR-Egger intercept test suggested no significant heterogeneity or horizontal pleiotropy among the instrumental variables (both P>0.05). Leave-one-out analysis showed that the overall results were not driven by any single SNP.
This unidirectional two-sample MR study suggests a stable negative causal association between genetically predicted Parkinson disease and the risk of epilepsy.
To establish patient-derived cell line, patient-derived xenograft (PDX), and patient-derived tumor-like cell cluster (PTC) models for Group 4 medulloblastoma (MB).
Transcriptome sequencing was performed on 81 fresh pediatric MB samples obtained during surgeries at the Neurosurgery Center, Beijing Tiantan Hospital, Capital Medical University from June 2020 to May 2022, to determine their molecular subgroup. Fresh Group 4 MB samples were subjected to primary cell culture in vitro to establish stable MB cell lines. The cell lines were implanted intracranially into 6 to 8 weekold male nonobese diabetic/severe combined immunodeficient (NOD/SCID) mice to assess tumorigenicity in vivo. Primary tumor cells were implanted intracranially into NOD/SCID mice to establish PDX models. Additionally, primary tumor cells were seeded in lowattachment culture plates to establish PTC models. Immunofluorescence staining using MB molecular subtype-specific marker antibodies was performed on both patient tumor tissues and PDX tissues to confirm the molecular subgroup. Immunofluorescence staining with anti-5hydroxymethylcytosine (5hmC) antibody was used to verify aberrant epigenetic features. In vitro drug sensitivity testing was conducted on the cell lines and PTCs using arsenic trioxide (As2O3), and the inhibitory effects on cell lines and PTCs were determined by the CCK-8 assay and the CellTiter-Lumi™ chemiluminescent assay, respectively.
Unsupervised clustering analysis classified the 81 MB samples into four major molecular subgroups: 4 WNT MBs, 4 SHH MBs, 14 Group 3 MBs, and 59 Group 4 MBs. Among the 12 cultured Group 4 MB samples, one large cell/anaplastic MB (LC/AMB) subtype achieved continuous and stable propagation for over 20 passages, and was designated as BNI-G4MB-001 cell line. Immunofluorescence staining of this cell line demonstrated high expression of integrase interactor 1 (INI1), synaptophysin (Syn), and neuronal nuclei antigen (NeuN). Intracranial injection of different doses of the cell line into NOD/SCID mice resulted in tumor formation in all cases; notably, the high-dose cell group with the frontal lobe injection (1×106 cells/mouse, n=4) exhibited significantly shortened survival compared with the low-dose cell grour with the frontal lobe injection (2×105 cells/mouse, n=3) and the cerebellum group (2×105 cells/mouse, n=3)[survival times: 15.50±2.29 days, 23.00±4.08 days, and 21.33±1.70 days, respectively; P=0.037]. After intracranial implantation of primary tumor cells, mouse deaths were observed gradually between 4 and 6 weeks; necropsy confirmed tumor formation with a maximum diameter of 0.5 to 1.0 cm. RNA sequencing analysis revealed a high similarity in gene expression profiles between the PDX tumors and the patient tumor (r=0.948, P<0.001). Hematoxylin and eosin (HE) staining showed that both patient tumor and PDX tumors displayed LC/AMB characteristics. Immunofluorescence staining demonstrated strong positivity for KCNA1 antibody in both patient tumor and PDX tumors. Immunofluorescence staining with 5hmC antibody revealed markedly reduced 5hmC levels in patient tumor and PDX tumors compared with normal tissues (26.3% vs. 88.4%; 27.9% vs. 89.7%). Primary tumor cells were cultured in low-adhesion cell culture plate PTCs at day 21 (diameter approximately 200 μm). In vitro drug sensitivity assays showed that As2O3 inhibited the proliferation of BNI-G4MB-001 cells. The PTC model treated with 100 μmol/ml As2O3 exhibited cell death.
The established patient derived in vitro and in vivo models of Group 4 MB recapitulated the histopathological and molecular biological features of the patient tumor, and thus represent favorable preclinical research subjects.
To investigate the role of senescence-related genes in prognostic evaluation of glioblastomas (GBMs), to construct a prognostic risk score model, and to verify the biological function of the key gene CDGSH iron sulfur domain2 (CISD2) using in vitro cell experiments.
The GSE83300 dataset (training set, 49 cases) was obtained from the Gene Expression Omnibus database, and the Cancer Genome Atlas (TCGA)-GBM dataset (validation set, 131 cases) from TCGA. A total of 307 senescence-related genes were retrieved from the Human Ageing Genomic Resources database. In the training set, the median age was used as the cutoff value, and the Kaplan-Meier method was applied to evaluate the effect of age on survival. Univariate Cox regression, least absolute shrinkage and selection operator (LASSO) regression, and multivariate Cox regression were performed to screen key senescence-related genes and construct a risk score model. Patients were divided into high and low-risk groups based on the median risk score. The predictive performance of the model was assessed using receiver operating characteristic (ROC) curves and validated in the independent cohort. Risk score was further included in training set to identify independent prognostic factors, and a Nomogram model was established. Its predictive efficiency was evaluated using ROC curves and calibration curves. Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment, "estimate", and CIBERSORT analyses were used to explore differences in signaling pathways and immune infiltration between high and low-risk groups. The Tumor Immune Dysfunction and Exclusion (TIDE) score and Genomics of Drug Sensitivity in Cancer (GDSC) database were applied to predict immunotherapeutic responses and potential sensitive drugs. The key gene with the highest hazard ratio-CISD2 was selected for in vitro functional validation. CISD2 was knocked down in U87 glioma cells, which were divided into a control group and a CISD2-small interfering RNA knockdown group (siCISD2 group). Knockdown efficiency was verified by western blot (WB). Colony formation, wound-healing, and transwell invasion assays were performed to assess cell proliferation, migration, and invasion, respectively.
Log-rank test showed that older GBM patients had significantly shorter survival than younger patients (P=0.043). Univariate Cox regression identified 51 senescence-related prognostic genes. After LASSO and multivariate Cox regression, VEGFA, NFKBIA, and CISD2 were identified as key prognostic genes in GBM. A risk score model was constructed accordingly. The high-risk group showed a significantly higher mortality rate (P=0.015) and shorter median survival time (P<0.001) than the low-risk group. The areas under the ROC curve (AUC) for 1, 2, and 3-year survival in the training set were 0.72, 0.85, and 0.85, respectively, with consistent results in the validation set. For the Nomogram model, AUC for 1, 2, and 3-year survival prediction were 0.70, 0.82, and 0.81, respectively, and calibration curves indicated good agreement. KEGG analysis revealed abnormal activation of chemokine and cytokine signaling pathways in the high-risk group. Immune infiltration analysis showed that the low-risk group had higher immune cell scores. The high-risk group exhibited increased M2 macrophage infiltration but decreased infiltration of naive B cells, CD8+ T cells, resting memory CD4+ T cells, and Tregs (all P<0.05). All three key genes were positively correlated with M2 macrophage infiltration and negatively correlated with other immune cell subsets (all P<0.05). TIDE scores were significantly higher in the high-risk group (P=0.045), which also showed a lower proportion of immunotherapy-sensitive patients (28% vs. 60%). GDSC analysis indicated that the half-maximal inhibitory concentrations of sapanisertib, staurosporine, and dasatinib were significantly lower in the high-risk group than in the low-risk group(all P<0.05). WB confirmed that CISD2 protein expression was significantly lower in the siCISD2 group than in the control group (0.47±0.06 vs. 1.01±0.12, P=0.002). Colony formation, wound-healing and transwell assays demonstrated that proliferation (59.3±4.7 vs.112.0±7.6), migration (66.6%±1.8% vs. 78.1%±1.4%), and invasion (148.3±18.1 vs. 297.3±22.1) of U87 cells were significantly reduced in the siCISD2 group compared with the control group (all P< 0.05).
The prognostic risk score model based on VEGFA, NFKBIA and CISD2 effectively predicts survival in patients with GBM. CISD2 functions as a potential oncogene and therapeutic target, providing a basis for prognostic evaluation and precision therapy of GBM.
Intracranial growing teratoma is a rare intracranial germ cell tumor, which refers to intracranial germ cell tumors containing teratoma components. After chemotherapy or radiotherapy, the malignant cellular components in the tumor can be effectively eliminated, but the benign teratoma components increase instead. This article retrospectively reports the clinical data of three children with intracranial growth teratoma syndrome diagnosed and treated in the Department of Neurosurgery, Children's Hospital affiliated to Nanjing Medical University from November 2023 to March 2024. After diagnostic radiotherapy or chemotherapy, serum tumor markers decreased to varying degrees in 3 children, but the tumor progressed significantly or the curative effect was not good, and all of them underwent further surgical resection. Three children recovered well after operation and continued to improve radiotherapy and chemotherapy; No tumor recurrence was observed during the follow-up period from 20 to 24 months postoperatively.
The incidence of intracranial aneurysm in children is low, the anatomical position is special, and the clinical treatment is difficult. At present, there is no unified consensus on the clinical diagnosis and treatment plan and the selection of surgical procedures for this disease. This article retrospectively reports an 8-year-old male child with ruptured vertebral artery V4 dissection aneurysm admitted to the Department of Neurosurgery of the Affiliated Hospital of Jining Medical College in May 2023. He was treated with bilateral external ventricular drainage, endovascular embolization combined with tumor-bearing artery occlusion, posterior fossa craniectomy and decompression, ventricular puncture and drainage, and ventriculo-peritoneal shunt. After operation, he was given standardized rehabilitation intervention and long-term follow-up. Cerebral angiography 2 years after operation showed no recurrence of the aneurysm, and the collateral branches of the occlusive section of the tumor-bearing artery were established to compensate the blood supply. The neurological function of the children continued to improve.
In the past 30 years, many breakthroughs have been made in the basic research of glioma, but a large number of research results have not been effectively translated into clinical practice. Preclinical research model is a key carrier to connect basic research and clinical application, and its selection and optimization directly relate to the efficiency and reliability of clinical translation of research results. This paper systematically sorts out the current commonly used preclinical research models of in vivo and in vitro glioma, focusing on incorporating emerging technology models such as organoid and three-dimensional bioprinting, and compares and analyzes the characteristics, advantages and disadvantages of each model in combination with different research scenarios and research purposes, in order to provide reference for researchers in model selection and mechanism research.
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