Lesion-Filling Index from Quantitative DSA Correlates with Hemorrhage of Cerebral AVM.

BACKGROUND AND PURPOSE: Rupture is the most life-threatening manifestation of cerebral AVMs. This study aimed to explore the hemodynamic mechanism of AVM rupture. We introduced a new quantitative DSA parameter that can reflect the degree of intranidal blood stasis, called the lesion-filling index. MATERIALS AND METHODS: This study examined patients with AVMs who had undergone both DSA and MR imaging between 2013 and 2014. Clinical presentations, angioarchitecture, and hemodynamic parameters generated from quantitative DSA were analyzed using univariate and multivariable logistic regression. The lesion-filling index was defined as the arterial diagnostic window divided by the volume of the AVM. To assess the correlation between the lesion-filling index and rupture, we incorporated the lesion-filling index into 2 published prediction models widely recognized for predicting AVM rupture risk, R2eD and VALE. The DeLong test was used to examine whether the addition of the lesion-filling index improved predictive efficacy. RESULTS: A total of 180 patients with AVMs were included. The mean lesion-filling index values in the ruptured group were higher compared with the unruptured group (390.27 [SD, 919.81] versus 49.40 [SD, 98.25]), P < .001). A higher lesion-filling index was significantly correlated with AVM rupture in 3 different multivariable logistic models, adjusting for angioarchitecture factors (OR = 1.004, P = .02); hemodynamic factors (OR = 1.005, P = .009); and combined factors (OR = 1.004, P = .03). Both R2eD (area under the curve, 0.601 versus 0.624; P = .15) and VALE (area under the curve, 0.603 versus 0.706; P < .001) predictive models showed improved predictive performance after incorporating the lesion-filling index and conducting 10-fold cross-validation. CONCLUSIONS: The lesion-filling index showed a strong correlation with AVM rupture, suggesting that overperfusion is the hemodynamic mechanism leading to AVM rupture.

Identification of potential hub genes and biological mechanism in rheumatoid arthritis and non-small cell lung cancer via integrated bioinformatics analysis.

BACKGROUND: Although there is evidence of the association between RA and NSCLC, little is known about their interaction mechanisms. The aim of this study is to identify potential hub genes and biological mechanism in RA and NSCLC via integrated bioinformatics analysis. METHODS: The gene expression datasets of RA and NSCLC were downloaded to discover and validate hub genes. After identifying DEGs, we performed enrichment analysis, PPI network construction and module analysis, selection and validation of hub genes. Moreover, we selected the hub gene PTPRC for expression and prognosis analysis, immune analysis, mutation and methylation analysis in NSCLC. Finally, we performed real-time PCR, colony formation assay, wound healing assay, transwell invasion assay, sphere formation assay and western blotting to validate the role of PTPRC in A549 cells. RESULTS: We obtained 320 DEGs for subsequent analysis. Enrichment results showed that the DEGs were mainly involved in Th1, Th2 and Th17 cell differentiation. In addition, four hub genes, BIRC5, PTPRC, PLEK, and FYN, were identified after selection and validation. These hub genes were subsequently shown to be closely associated with immune cells and related pathways. In NSCLC, PTPRC was downregulated, positively correlated with immune infiltration and immune cells. Experiments showed that PTPRC could promote the proliferation, migration and invasion, and the ability to form spheroids of A549 cells. In addition, PTPRC could regulate the increased expression of CD45, ß-catenin, c-Myc and LEF1 proteins. CONCLUSIONS: This study explored the hub genes and related mechanisms of RA and NSCLC, demonstrated the central role of the inflammatory response and the adaptive immune system, and identified PTPRC as an immune-related biomarker and potential therapeutic target for RA and NSCLC patients. In addition, PTPRC can significantly promote the proliferation, migration and invasion of A549 cells, and its mechanism may be to promote the EMT process by regulating the Wnt signaling pathway and promote cell stemness, which in turn has a promoting effect on A549 cells.

Overloaded transnidal pressure gradient as the hemodynamic mechanism leading to arteriovenous malformation rupture: a quantitative analysis using intravascular pressure monitoring and color-coded digital subtraction angiography.

BACKGROUND: The hemodynamics of brain arteriovenous malformations (AVMs) may have implications for hemorrhage. This study aimed to explore the hemodynamics of ruptured AVMs by direct microcatheter intravascular pressure monitoring (MIPM) and indirect quantitative digital subtraction angiography (QDSA). METHODS: We recruited patients with AVMs at a tertiary neurosurgery center from October 2020 to March 2023. In terms of MIPM, we preoperatively super-selected a predominant feeding artery and main draining vein through angiography to measure intravascular pressure before embolization. In processing of QDSA, we adopted previously standardized procedure for quantitative hemodynamics analysis of pre-embolization digital subtraction angiography (DSA), encompassing main feeding artery, nidus, and the main draining vein. Subsequently, we investigated the correlation between AVM rupture and intravascular pressure from MIPM, as well as hemodynamic parameters derived from QDSA. Additionally, we explored the interrelationships between hemodynamic indicators in both dimensions. RESULTS: After strict screening of patients, our study included 10 AVMs (six ruptured and four unruptured). We found that higher transnidal pressure gradient (TPG) (53.00±6.36 vs 39.25±8.96 mmHg, p=0.042), higher feeding artery pressure (FAP) (72.83±5.46 vs 65.00±6.48 mmHg, p=0.031) and higher stasis index of nidus (3.54±0.73 vs 2.43±0.70, p=0.043) were significantly correlated with AVM rupture. In analysis of interrelationships between hemodynamic indicators in both dimensions, a strongly positive correlation (r=0.681, p=0.030) existed between TPG and stasis index of nidus. CONCLUSIONS: TPG and FAP from MIPM platform and nidus stasis index from QDSA platform were correlated with AVM rupture, and both were positively correlated, suggesting that higher pressure load within nidus may be the central mechanism leading to AVM rupture.

Association of nidus size and rupture in brain arteriovenous malformations: Insight from angioarchitecture and hemodynamics.

This study aims to investigate the correlation between AVM size and rupture by examining natural history, angioarchitecture characteristics, and quantitative hemodynamics. A retrospective review of 90 consecutive AVMs from the MATCH registry was conducted. Patients were categorized into small nidus (< 3 cm) and large nidus (≥ 3 cm) groups based on the Spetzler-Martin grading system. Natural history analysis used prospective cohort survival data, while imaging analysis examined angioarchitecture characteristics and quantitative hemodynamic parameters measured with QDSA. The small-nidus group had a significantly higher annualized rupture risk (2.3% vs. 1.0%; p = 0.011). Cross-sectional imaging revealed independent hemorrhagic risk factors, including small nidus (OR, 4.801; 95%CI, 1.280-18.008; p = 0.020) and draining vein stenosis (OR, 6.773; 95%CI, 1.179-38.911; p = 0.032). Hemodynamic analysis identified higher stasis index in the feeding artery (OR, 2.442; 95%CI, 1.074-5.550; p = 0.033), higher stasis index in the draining vein (OR, 11.812; 95%CI, 1.907-73.170; p = 0.008), and lower outflow gradient in the draining vein (OR, 1.658; 95%CI, 1.068-2.574; p = 0.024) as independent predictors of AVM rupture. The small nidus group also showed a higher likelihood of being associated with hemorrhagic risk factors. Small AVM nidus has a higher risk of rupture based on natural history, angioarchitecture, and hemodynamics. Clinical Trial Registration-URL: http://www.clinicaltrials.gov . Unique identifier: NCT04572568.

Rupture-related quantitative hemodynamics of the supratentorial arteriovenous malformation nidus.

OBJECTIVE: The hemodynamics of a brain arteriovenous malformation (AVM) nidus may be closely related to clinical presentation. The authors of this study aimed to explore the hemorrhagic quantitative hemodynamic indicators of the nidus through quantitative digital subtraction angiography (QDSA). METHODS: The quantitative hemodynamic parameters were generated from QDSA. Three data sets were used to explore independent quantitative hemodynamic indicators associated with AVM rupture. The training data set was exploited to discover independent quantitative hemodynamic indicators of AVM rupture by performing univariate and multivariate logistic regression analyses. The authors plotted receiver operating characteristic curves to validate the diagnostic performance of the hemorrhagic hemodynamic indicators using the training and two external validation data sets. Kaplan-Meier survival analysis was adopted to verify the predictive power of these risk indicators of future hemorrhage in the external prospective validation data set. RESULTS: A total of 151 patients were included in this study, 91 in the training set and 30 in each of the two validation sets. A higher stasis index and slower transnidal relative velocity (TRV) of the nidus were significantly correlated with AVM rupture. The areas under the curve (AUCs) of the stasis index (nidus) were 0.765 and 0.815 and those of the TRV (nidus) were 0.735 and 0.796, respectively, in the training and retrospective external validation sets. Kaplan-Meier survival analysis confirmed the validity of the stasis index and TRV in predicting future rupture risk in the prospective validation data set (p = 0.008 and 0.041, respectively, log-rank test). CONCLUSIONS: A higher stasis index (nidus) and slower TRV (nidus) in QDSA were associated with AVM rupture and were effective indicators of future hemorrhage, suggesting that the core mechanisms underlying AVM rupture could be intravascular blood stasis and occlusive hyperemia of the nidus.

Quantitative evaluation of hemodynamics after partial embolization of brain arteriovenous malformations.

BACKGROUND: To explore the hemodynamic changes after embolization of arteriovenous malformations (AVMs) using quantitative digital subtraction angiography (QDSA). METHODS: We reviewed 74 supratentorial AVMs that underwent endovascular embolization and performed a quantitative hemodynamic analysis comparing parameters in pre- and post-operative DSA in correlation with rupture. The AVMs were further divided into two subgroups based on the embolization degree: Group I: 0%-50%, Group II: 51%-100%. In the intergroup analysis, we examined the correlations between embolization degree and hemodynamic parameter changes. RESULTS: A longer time to peak (TTP) of the main feeding artery (OR 11.836; 95% CI 1.388 to 100.948; P=0.024) and shorter mean transit time (MTT) of the nidus (OR 0.174; 95% CI 0.039 to 0.766; P=0.021) were associated with AVM rupture. After embolization, all MTTs were significantly prolonged (P<0.05). The full width at half maximum (FWHM) duration of the main feeding artery was significantly shortened (P<0.001), and several hemodynamic parameters of the main draining vein changed significantly (TTP: prolonged, P=0.005; FWHM: prolonged, P=0.014; inflow gradient: decreased, P=0.004; outflow gradient: decreased, P=0.042). In the subgroup analysis, several MTT parameters were significantly prolonged in both groups (P<0.05), and the MTT increase rate in Group II was greater than in Group I (P<0.05). CONCLUSIONS: Embolization can significantly change the hemodynamics of AVMs, especially when an embolization degree >50% is obtained. Partial embolization may reduce the AVM rupture risk in hemodynamics perspective.

Alpha-fetoprotein/endoplasmic reticulum stress signaling mitigates injury in hepatoma cells.

Alpha-fetoprotein (AFP) and endoplasmic reticulum (ER) stress play multiple roles in hepatocellular carcinoma. Here, we analyzed the crosstalk between AFP and ER stress in human hepatoma cells. We induced ER stress in human hepatoma cell lines (HepG2 and SK-Hep1 cells) with thapsigargin (TG, an ER stress inducer), and mitigated ER stress with 4-phenylbutyrate acid (4-PBA, an ER stress inhibitor). AFP expression was knocked down by AFP short hairpin RNA and rescued by the pCI-AFP vector. AFP expression and ER stress were examined, and their roles in apoptosis, necroptosis, and proliferation were analyzed. TG significantly induced ER stress, apoptosis, necroptosis, and intracellular AFP protein levels, and reduced proliferation and AFP mRNA expression as well as supernatant AFP protein levels in HepG2 and SK-Hep1 cells. 4-PBA pretreatment partially reversed those changes in HepG2 cells. By contrast to AFP overexpression, knockdown of AFP significantly exacerbated TG-induced ER stress, apoptosis, and necroptosis, and decreased proliferation and the expression of activating transcription factor 6 alpha. In conclusion, ER stress causes the accumulation of AFP protein, which may be related to the reduction of AFP secretion. Accumulated AFP mitigates apoptosis and necroptosis and restores the proliferation of hepatoma cells by reducing ER stress.

Failure analysis: enamel fracture after debonding orthodontic brackets.

OBJECTIVE: To determine the location and size of enamel fracture (EF) when debonding a bracket. MATERIALS AND METHODS: Tests on actual EF situations were conducted in different debonding load modes (tension, shear, and torsion) via mechanical testing, finite element model (FEM) analysis, and scanning electronic microscopy (SEM). Through these simultaneous analyses of the relationships among debonding load modes, value/distribution of stress, and actual enamel fracture location/size, an investigation was undertaken to explore the complex failure mode during enamel fracture after debonding of an orthodontic bracket. RESULTS: The EF usually was located in the area where the force was exerted during various loading modes. The tensile, shear, and torsion debonding modes produce EF sizes and incidences with no significant differences. Findings on FEM matched the mechanical testing and SEM results. CONCLUSIONS: The EF locations coincided with the areas where the tensile, shear, or torsion force was exerted. Therefore, the dentist should give extra care and attention to these specific areas of enamel after debonding. The sizes and incidences of EF produced by these three debonding modes showed no significant difference. Thus, clinically, when the sizes and incidences of produced EF are considered, it should not matter which of these three exerting forces is used to debond a bracket.