ADAMTS8 inhibits glioma development in vitro and in vivo.

INTRODUCTION: In recent years, novel RNAs have been revealed to be regulators in glioma. ADAMTS8 has been reported to be reduced in brain tumours. In this study, we aimed to explore the role of ADAMTS8 in glioma. MATERIAL AND METHODS: Online bioinformatic tools, Gepia and Chinese Glioma Genome Atlas database (CGGA) were used to analyse the differential expression of ADAMTS8, overall survival and disease-free survival rates and the correlations between ADAMTS8 and matrix metallopeptidases (MMP2 and MMP9) in glioma. RT-qPCR and western blot experiments were performed to measure the mRNA and protein expression. ADAMTS8 expression was regulated in cells through transfection. Thereafter, the effect of ADAMTS8 on cells was investigated through the cell viability, apoptosis and transwell experiments. The epithelial-mesenchymal transition (EMT)-related proteins and also MMP2 and MMP9 were examined. The subcutaneous tumour model was established to validate the suppressive role of ADAMTS8 in tumour growth. RESULTS: ADAMTS8 expression was reduced in glioma tissues and cells. Higher expression of ADAMTS8 was correlated with higher survival rates. ADAMTS8 was correlated with MMP2 and MMP9 in glioma tissues. In glioma cells, overexpression of ADAMTS8 could inhibit the viability, invasion, migration and EMT, and MMP2 and MMP9, but promote the apoptosis of cells. The upregulation of ADAMTS8 could inhibit the tumour growth in vivo. CONCLUSIONS: ADAMTS8 was inhibited in glioma and the higher expression of ADAMTS8 might be related to better prognosis among glioma patients. Overexpression of ADAMTS8 inhibited the development of glioma in vitro and in vivo.

Comparison of Drug-Eluting Stent With Bare-Metal Stent in Patients With Symptomatic High-grade Intracranial Atherosclerotic Stenosis: A Randomized Clinical Trial.

Importance: In-stent restenosis (ISR) is the primary reason for stroke recurrence after intracranial stenting in patients who were treated with a standard bare-metal stent (BMS). Whether a drug-eluting stent (DES) could reduce the risk of ISR in intracranial atherosclerotic stenosis (ICAS) remains unclear. Objective: To investigate whether a DES can reduce the risk of ISR and stroke recurrence in patients with symptomatic high-grade ICAS. Design, Settings, and Participants: A prospective, multicenter, open-label randomized clinical trial with blinded outcome assessment was conducted from April 27, 2015, to November 16, 2018, at 16 medical centers in China with a high volume of intracranial stenting. Patients with symptomatic high-grade ICAS were enrolled, randomized, and followed up for 1 year. Intention-to-treat data analysis was performed from April 1 to May 22, 2021. Interventions: Patients were randomly assigned to receive DES (NOVA intracranial sirolimus-eluting stent system) or BMS (Apollo intracranial stent system) treatment in a 1:1 ratio. Main Outcomes and Measures: The primary efficacy end point was ISR within 1 year after the procedure, which was defined as stenosis that was greater than 50% of the luminal diameter within or immediately adjacent to (within 5 mm) the implanted stent. The primary safety end point was any stroke or death within 30 days after the procedure. Results: A total of 263 participants (194 men [73.8%]; median [IQR] age, 58 [52-65] years) were included in the analysis, with 132 participants randomly assigned to the DES group and 131 to the BMS group. The 1-year ISR rate was lower in the DES group than in the BMS group (10 [9.5%] vs 32 [30.2%]; odds ratio, 0.24; 95% CI, 0.11-0.52; P < .001). The DES group also had a significantly lower ischemic stroke recurrence rate from day 31 to 1 year (1 [0.8%] vs 9 [6.9%]; hazard ratio, 0.10; 95% CI, 0.01-0.80; P = .03). No significant difference in the rate of any stroke or death within 30 days was observed between the DES and BMS groups (10 [7.6%] vs 7 [5.3%]; odds ratio, 1.45; 95% CI, 0.54-3.94; P = .46). Conclusions and Relevance: This trial found that, compared with BMSs, DESs reduced the risks of ISR and ischemic stroke recurrence in patients with symptomatic high-grade ICAS. Further investigation into the safety and efficacy of DESs is warranted. Trial Registration: ClinicalTrials.gov Identifier: NCT02578069.

Quantification of intracranial arterial stenotic degree evaluated by high-resolution vessel wall imaging and time-of-flight MR angiography: reproducibility, and diagnostic agreement with DSA.

OBJECTIVES: The purpose of this study was to compare the reproducibility and diagnostic agreement of high-resolution vessel wall imaging (HR-VWI) and time-of-flight magnetic resonance angiography (TOF-MRA) with digital subtraction angiography (DSA) to evaluate intracranial arterial stenosis. METHODS: We retrospectively enrolled patients who underwent HR-VWI and TOF-MRA with suspected intracranial artery disease and had DSA results from our institutional imaging database. Two neuroradiologists separately and independently evaluated anonymous image data for the stenotic lesions. DSA was analyzed by two neurointerventionalists and it served as a standard criterion. The reproducibility of these two MR techniques was determined by the intraclass correlation coefficients (ICCs). The diagnostic agreement to DSA was assessed by the concordance correlation coefficients (CCCs). RESULTS: A total of 246 lesions from 106 individuals were analyzed for stenotic degrees. The total intra-observer and inter-observer reproducibility of HR-VWI was excellent for identifying stenosis and better than of TOF-MRA. The overall concordance of HR-VWI with DSA was excellent with CCC = 0.932, whereas TOF-MRA was 0.694. In addition, HR-VWI could provide additional vessel wall information. CONCLUSIONS: HR-VWI has more advantages over TOF-MRA, such as better reproducibilities and diagnostic agreements with DSA to analyze intracranial arterial stenosis. It provides additional information that helps in clinical diagnosis and management. KEY POINTS: • High-resolution vessel wall imaging can assess intracranial arterial stenosis with a better reproducibility than TOF-MRA and has a higher diagnostic agreement with DSA. • High-resolution vessel wall imaging had a higher diagnostic agreement with DSA compared with TOF-MRA. • Apart from evaluating vascular stenosis, HR-VWI provided additional vessel wall information to help in clinical diagnosis.

Visualization of lenticulostriate artery by intracranial dark-blood vessel wall imaging and its relationships with lacunar infarction in basal ganglia: a retrospective study.

OBJECTIVES: There is close relationship between lenticulostriate arteries (LSAs) and lacunar infarctions (LIs) of the basal ganglia. The study aims to visualize the LSAs using high-resolution vessel wall imaging (VWI) on 3T system and explore the correlation between LSAs and LIs. METHODS: Fifty-six patients with LIs in basal ganglia, and 44 age-matched control patients were enrolled and analyzed retrospectively. The raw VWI images were reformatted into coronal slices in minimum intensity projection for further observation of LSAs. The risk factors of LIs in basal ganglia were analyzed by univariate and multivariate logistic regression. The correlation and linear regression analysis between the LSAs and LIs, ipsilateral MCA-M1 plaques were investigated. RESULTS: The total number (p < 0.01) and length (p < 0.01) of LSAs were statistically different between basal ganglias with and without LIs. The total number of LSAs and ipsilateral MCA-M1 plaques were independently related to LIs in basal ganglias. The mean length of LSAs were negatively correlated with number (r = - 0.33, p = 0.002) and volume (r = - 0.37, p = 0.001) of LIs. Age, drinking history, and mean length of LSAs were associated with LI occurrence in basal ganglia, and mean length of LSAs was correlated with larger volume of LIs. CONCLUSIONS: Number of LSA reduction and ipsilateral MCA-M1 plaques were associated with the presence of LIs in basal ganglias. Age increasing, drinking history, and shorter LSAs were correlated with the increasing of LIs. KEY POINTS: • Patients with LIs tend to have shorter LSAs. • The characteristics of LSAs and ipsilateral MCA-M1 plaques are associated with LIs in basal ganglias. • Age, drinking history, and mean length of LSAs are correlated with LI features in basal ganglias.

Plaque characteristics and hemodynamics contribute to neurological impairment in patients with ischemic stroke and transient ischemic attack.

OBJECTIVES: We aimed to investigate differential characteristics of plaque in the middle cerebral artery (MCA) and hemodynamics in patients with ischemic stroke and transient ischemic attack (TIA), and to develop a predictive model for the presence of ischemic stroke and neurological impairment. METHODS: Sixty-seven patients with acute ischemic events in MCA territory who underwent high-resolution vessel wall imaging between September 2016 and August 2018 were reviewed retrospectively. Patients were assigned to either the stroke group or TIA group, according to diffusion-weighted imaging and neurological examination. Plaque characteristics and anterograde score (AnS) were calculated. Tmax > 6.0-s volume was acquired by RApid Processing of perfusIon and Diffusion software. Multivariate logistic regression analysis and multiple linear regression analysis were performed to establish a predictive model for irreversible infarction occurrence and clinical severity. RESULTS: Forty-five patients were assigned to the stroke group, and 22 were assigned to the TIA group. Plaque length, intraplaque hemorrhage (IPH), enhancement, AnS, and Tmax > 6.0-s volumes were significantly different between the two groups (p < 0.05). IPH and AnS were independent predictors for patients with stroke (p = 0.020 and 0.034, respectively). Tmax > 6.0-s volume, IPH, hypertension, and AnS were associated with high National Institutes of Health Stroke Scale (NIHSS) scores (all p < 0.05, R = 0.725, and adjusted R2 = 0.494). CONCLUSIONS: IPH and AnS are useful in predicting stroke occurrence. Tmax > 6.0-s volume, IPH, hypertension, and AnS are associated with neurological impairment of the patients. KEY POINTS: • Ischemic stroke and TIA patients have different plaque characteristics and hemodynamics. • Intraplaque hemorrhage and anterograde score have high diagnostic efficiency for ischemic stroke. • The combination of Tmax > 6.0-s volume, intraplaque hemorrhage, hypertension, and anterograde score can predict the National Institutes of Health Stroke Scale scores of patients.

Strategically acquired gradient echo (STAGE)-derived MR angiography might be a superior alternative method to time-of-flight MR angiography in visualization of leptomeningeal collaterals.

OBJECTIVES: This study aimed to compare the performance of strategically acquired gradient echo (STAGE)-derived MR angiography and time-of-flight MR angiography (TOF-MRA) in visualization of leptomeningeal collaterals (LMCs). METHODS: Between May 2018 and January 2020, 75 participants (47 healthy volunteers and 28 intracranial atherosclerotic disease [ICAD] patients) undergoing TOF-MRA and STAGE-MRA were prospectively included. Image quality was scored at the internal carotid artery (ICA) terminus, proximal middle cerebral artery (MCA), and LMCs. Quantitative analysis included calculation of contrast-to-noise ratios (CNRs) in the M1-4 segments and number of LMCs counted in the line signal intensity profiles. Comparisons of image qualitative scores, CNRs, and number of LMCs were calculated using the Wilcoxon rank-sum test. RESULTS: Image qualitative scores were significantly higher in STAGE-MRA than in TOF-MRA for the ICA terminus, proximal MCA, and LMCs (ps < 0.05) in 75 participants. When referred to digital subtraction angiography (DSA) in 25 ICAD patients, STAGE-MRA showed higher qualitative scores only at LMCs. CNRs in the M1-4 segments were significantly higher in STAGE-MRA than in TOF-MRA (218.7 ± 90.7 vs 176.2 ± 72.6, 195.7 ± 86.0 vs 146.6 ± 71.7, 176.4 ± 71.6 vs 125.8 ± 61.1, 126.2 ± 62.9 vs 78.8 ± 43.6; all ps < 0.001). STAGE-MRA showed more LMCs (11.4 ± 3.4) than TOF-MRA (8.4 ± 3.3) with p < 0.05. CONCLUSIONS: STAGE-MRA might be superior to TOF-MRA in qualitative and quantitative assessment of LMCs in both healthy volunteers and ICAD patients; thus, it may serve as an alternative method in evaluating LMC. KEY POINTS: • Strategically acquired gradient echo (STAGE)-derived magnetic resonance angiography is a newly developed sequence with a pair of rephasing/dephasing gradient echoes. • STAGE-MRA enables higher image qualitative score, improves contrast-to-noise ratio, and shows greater number of leptomeningeal collaterals (LMCs) in healthy volunteers and patients with intracranial atherosclerotic disease. • LMC visualization by STAGE-MRA shows good to excellent inter-observer agreement.

Combination of Plaque Characteristics, Pial Collaterals, and Hypertension Contributes to Misery Perfusion in Patients With Symptomatic Middle Cerebral Artery Stenosis.

BACKGROUND: Atherosclerotic plaque in the middle cerebral artery (MCA) is linked to ischemic stroke events, but the relationship between plaque characteristics and cerebral perfusion is unclear. PURPOSE: To investigate MCA plaque characteristics between intracranial atherosclerotic patients with and without hypoperfusion area, and to identify the variables affecting hypoperfusion volume. STUDY TYPE: Retrospective. POPULATION: Seventy-one patients with MCA stenosis (>50%), and all with ischemic onset in recent 2 weeks. FIELD STRENGTH/SEQUENCE: 3.0T MRI / diffusion-weighted imaging (DWI), time-of-flight magnetic resonance angiography (TOF-MRA), inversion-recovery prepared sampling perfection with application-optimized contrast using different flip angle evolutions (IR-SPACE), dynamic susceptibility contrast perfusion-weighted imaging (DSC-PWI). ASSESSMENT: Plaque characteristics including eccentric index (EI), eccentricity, plaque length, and enhancement on MCA were measured on IR-SPACE. Pial collaterals (PCs) were evaluated on axial TOF-MRA source images. Time-to-maximum (Tmax) maps with a threshold more than 6 seconds were assessed by rapid processing of perfusion and diffusion (RAPID) software. STATISTICAL TESTS: Two independent-samples t-tests, Mann-Whitney U-test, chi-square test, Z test, univariate and multivariate logistic analysis, and receiver operating characteristic (ROC) curve were used. RESULTS: Patients with hypoperfusion had fewer eccentric plaque, lower EI, longer plaque length, and poor PCs compared with those without (P = 0.002, 0.016, 0.003, and 0.001). Eccentricity, plaque length, PCs, and hypertension were the factors independently associated with the occurrence of hypoperfusion after adjustment for risk factors of cerebrovascular disease (P = 0.014, 0.017, 0.035, and 0.018). The area under the curve (AUC) (95% confidence interval) was 0.865 (0.763-0.934) for a combination of the above four variables, which was significantly higher than any variable alone (P < 0.001, 0.016, < 0.001, and < 0.001). Patients with lower EI, concentric morphology, and grade 2 enhancement trended to have larger hypoperfusion volume (P = 0.028, 0.037, and 0.009). DATA CONCLUSION: Plaque eccentricity, plaque length, PCs, and hypertension showed an association with the occurrence of hypoperfusion. LEVEL OF EVIDENCE: 4 Technical Efficacy Stage: 2 J. Magn. Reson. Imaging 2020;51:195-204.

Middle cerebral artery thrombus susceptibility-weighted imaging mapping predicts prognosis.

BACKGROUND: Susceptibility weighted imaging and mapping (SWIM) of magnetic resonance imaging (MRI) is used to evaluate cerebral arterial thrombosis. The aim of this research was to assess susceptibility, length, and clot burden score (CBS) of thrombus in the middle cerebral artery (MCA) and their relationship with cerebral infarction and early clinical prognosis in patients with acute or subacute cerebral infarction. METHODS: In total, 56 patients with acute or subacute cerebral infarction (with the time from onset to admission less than 72 h) and only unilateral MCA occlusion were included in the current study. All the patients had the corresponding susceptibility vessel sign (SVS) on susceptibility-weighted imaging (SWI). Parameters including susceptibility, length, and CBS of thrombus were obtained from SWI and SWIM. The differences in susceptibility of different portions of the thrombus were compared with each other by one-way ANOVA test. The relationship between susceptibility and stroke onset time was further analyzed by Spearman correlation analysis, in addition to the relationships between susceptibility, length, CBS, diffusion-weighted imaging-Alberta stroke program early CT score (DWI-ASPECTS), and admission and discharge National Institutes of Health Stroke Scale (NIHSS). RESULTS: The susceptibility among different portions and different segments of thrombus showed no statistical difference. The susceptibility and length were weakly yet negatively correlated with DWI-ASPECTS (rs=-0.382, -0.457; P=0.004, 0.000). The susceptibility was weakly yet positively correlated with admission NIHSS and discharged NIHSS (rs=0.403, 0.430; P=0.002, 0.001). CBS was weakly yet positively correlated with DWI-ASPECTS (rs=0.349; P=0.008) and weakly yet negatively correlated with admission and discharged NIHSS (rs=-0.375, -0.335; P=0.004, 0.012). CONCLUSIONS: The susceptibility remained consistent regardless of location, length, and onset time, which indicates that the thrombus composition was similar when detected on SWI less than 72 h from the onset. Susceptibility and CBS may help to predict clinical severity and short-term clinical prognosis to some extent.

Assembly of pi-functionalized quaternary ammonium compounds with graphene hydrogel for efficient water disinfection.

Graphene hydrogels hold great potential for the disinfection of bacteria-contaminated water. However, the intrinsic antibacterial activity of graphene hydrogels is not satisfactory, and the incorporation of other antibacterial agents often results in their unwanted releases. Here, we present a new strategy to improve the antibacterial activities of graphene hydrogels. We first synthesized a new pi-conjugated molecule containing five aromatic rings and two side-linked quaternary ammonium (QA) groups, denoted as piQA. Next, we fabricated composite gravity filters by assembling piQA with reduced graphene oxide (rGO) hydrogel. The rGO hydrogel helps to form a sponge-like physical sieve, contributes to the overall antibacterial activity, and provides abundant pi-rich surfaces. The large aromatic cores of piQA allow the formation of collectively strong pi-pi interactions with rGO, resulting in a high piQA mass loading of ∼31 wt%. Due to the sieving effect of rGO hydrogel and the synergistic antibacterial activity of rGO and piQA, the filters prepared based on piQA-rGO assemblies can remove over 99.5% of Gram-negative Escherichia coli (E. coli) and Gram-positive Staphylococcus aureus (S. aureus) cells with a high-water treatment capacity of 10 L g-1. Furthermore, the piQA-rGO assemblies show low toxicity towards two different mammalian cell lines (L929 and macrophages), and the release of piQA is also negligible. Overall, the new piQA-rGO assembly demonstrates high potential for water disinfection applications.

Increased susceptibility of asymmetrically prominent cortical veins correlates with misery perfusion in patients with occlusion of the middle cerebral artery.

OBJECTIVES: To evaluate tissue perfusion and venous susceptibility in ischaemic stroke patients as a means to predict clinical status and early prognosis. METHODS: A retrospective study of 51 ischaemic stroke patients were enrolled in this study. Susceptibility, perfusion and National Institute of Health stroke scale (NIHSS) were compared between patients with and without asymmetrically prominent cortical veins (APCVs). The correlation between susceptibility, perfusion and NIHSS was performed. RESULTS: Compared to patients without APCVs, the age of patients with APCVs was statistically older (p = 0.017). Patients with APCVs at discharge showed clinical deterioration in their NIHSS. Mean transit time (MTT), time to peak (TTP) and cerebral blood flow (CBF) in the stroke hemisphere were statistically delayed/decreased in patients with and without APCVs (all p < 0.05). In patients with APCVs, the changes in susceptibility positively correlated with increases in MTT and TTP (p < 0.05). Susceptibility and TTP positively correlated and CBF negatively correlated with NIHSS both at admission and discharge (p < 0.05). CONCLUSIONS: Patients with APCVs have a tendency of deterioration. The presence of APCVs indicates the tissue has increased oxygen extraction fraction. Increased susceptibility from APCVs positively correlated with the delayed MTT and TTP, which reflects the clinical status at admission and predicts an early prognosis. KEY POINTS: • Patients with and without APCVs have similar misery perfusion. • Patients with APCVs have a tendency of deterioration compared to those without. • The presence of APCVs indicated the tissue has increased oxygen extraction fraction. • Increased susceptibility from APCVs positively correlated with the MTT and TTP. • Increased susceptibility from APCVs reflected the clinical status at admission.

Expression of Neuropeptide Y and Its Relationship with Molecular and Morphological Changes in Human Pituitary Adenomas.

The purpose of this study was to explore the role of neuropeptide Y (NPY) on molecular and histological changes in human pituitary adenomas. The localization of NPY and its expression at the protein, messenger RNA (mRNA), and receptor levels were investigated here in different subcategories of pituitary adenomas. Immunohistochemical staining was performed in all cases to assess expression of NPY. Reverse transcription-polymerase chain reaction (RT-PCR) was used to study the mRNA expression of NPY. NPY subcellular localization was observed using immunoelectron microscopy in cytoplasm, rough endoplasmic reticulum, and cell matrix in four of the six cases of pituitary adenoma. NPY protein expression was observed in 59.6% of 57 cases of pituitary adenoma and in 2 cases of pituitary hyperplasia. mRNA expression of NPY was observed in all 57 cases of pituitary adenoma and in 2 cases of pituitary hyperplasia. Significantly different levels of expression were observed across different subcategories of pituitary adenoma. mRNA expression of Y1R and Y2R was observed across all subcategories of pituitary adenomas, and a positive correlation was observed between NPY and Y2R. In conclusion, evidence is provided here for the expression of NPY and its receptors, Y1R and Y2R, in human pituitary adenoma, and the levels of expression were found to differ across different subcategories. Differences in expression of Y2R in human pituitary adenomas were found to have remarkable statistical significance.

Tagging SNPs in the MTHFR gene and risk of ischemic stroke in a Chinese population.

Stroke is currently the leading cause of functional impairments worldwide. Folate supplementation is inversely associated with risk of ischemic stroke. Methylenetetrahydrofolate reductase (MTHFR) is an important enzyme involved in folate metabolism. The aim of this study is to examine whether genetic variants in MTHFR gene are associated with the risk of ischemic stroke and fasting total serum homocysteine (tHcy) level. We genotyped nine tag SNPs in the MTHFR gene in a case-control study, including 543 ischemic stroke cases and 655 healthy controls in China. We found that subjects with the rs1801133 TT genotype and rs1801131 CC genotype had significant increased risks of ischemic stroke (adjusted odds ratio (OR)=1.82, 95% confidence interval (CI): 1.27-2.61, p=0.004; adjusted OR=1.99, 95% CI: 1.12-3.56, p=0.01) compared with subjects with the major alleles. Haplotype analysis also found that carriers of the MTHFR CTTCGA haplotype (rs12121543-rs13306553-rs9651118-rs1801133-rs2274976-rs1801131) had a significant reduced risk of ischemic stroke (adjusted OR=0.53, 95% CI: 0.35-0.82) compared with those with the CTTTGA haplotype. Besides, the MTHFR rs1801133 and rs9651118 were significantly associated with serum levels of tHcy in healthy controls (p<0.0001 and p=0.02). These findings suggest that variants in the MTHFR gene may influence the risk of ischemic stroke and serum tHcy.