Circ_0000006 and circ_0000160 regulate hsa-let-7e-5p/UBQLN4 axis in aortic dissection progression.

Aortic aneurysms (AA) and aorta dissection (AD) are life-threatening conditions with a rising incidence and high mortality rate. Recent research has linked non-coding RNAs to the regulation of AA and AD progression. In this study, we performed circRNA sequencing, microRNA (miRNA) sequencing, and messenger RNA (mRNA) sequencing on plasma samples from AA and AD patients to identify the key circRNA-miRNA-mRNA axis involved in the transition from AA to AD. Our results showed elevated levels of circ_0000006 and circ_0000160, along with decreased levels of hsa-let-7e-5p in AD samples compared to AA samples. Predictive analysis suggested that circ_0000006 and circ_0000160 potentially target hsa-let-7e-5p, which in turn may bind to the mRNA of Ubiquilin 4 (UBQLN4). In an AD cell model using vascular smooth muscle cells (VSMCs), silencing circ_0000006 and circ_0000160 attenuated the effects of platelet-derived growth factor (PDGF)-induced phenotypic changes, proliferation, and migration. This effect was partially reversed by inhibiting hsa-let-7e-5p. Furthermore, we found that overexpression of UBQLN4 counteracted the effects of hsa-let-7e-5p, suggesting UBQLN4 as a downstream mediator of hsa-let-7e-5p. In an animal model of AD, knockdown of circ_0000006 and circ_0000160 also showed protective effects against aortic septation. Overall, our findings indicate that the upregulation of circ_0000006 and circ_0000160 contributes to the progression from AA to AD by influencing abnormal phenotypic changes, migration, and proliferation of VSMCs. The Hsa-let-7e-5p/UBQLN4 axis may play a critical role in AD development. Targeting circ_0000006 and circ_0000160 could be a potential therapeutic strategy for preventing the progression of AD.

Spontaneous delayed migration or shortening after pipeline embolization device treatment of intracranial aneurysm: incidence, management, and risk factors.

BACKGROUND: Studies reporting spontaneous delayed migration or shortening (SDMS) after treatment with the Pipeline Embolization Device (PED) are limited. This study aimed to evaluate the incidence of SDMS after PED treatment, propose management strategies, and identify the risk factors contributing to its occurrence. METHODS: We retrospectively reviewed consecutive patients with an intracranial aneurysm (IA) treated with PEDs at three institutions. SDMS was classified as type I or II based on whether the PED covered the aneurysm neck. RESULTS: The total cohort comprised 790 patients. SDMS was identified in 24 (3.04%) patients. Eighteen of the 24 patients had type I SDMS and did not require retreatment, while the remaining six patients had type II SDMS and all received retreatment. Multivariate logistic regression showed that the difference between the proximal and distal parent artery diameters (DPAD) (adjusted OR 2.977; 95% CI 1.054 to 8.405; P=0.039) and device tortuosity index (DTI) (adjusted OR 8.059; 95% CI 2.867 to 23.428; P<0.001) were independent predictors of SDMS after PED treatment, while the difference in length (DL) (adjusted OR 0.841; 95% CI 0.738 to 0.958; P=0.009) and PED plus coiling (adjusted OR 0.288; 95% CI 0.106 to 0.785; P=0.015) were protective factors. CONCLUSION: The incidence of SDMS after PED treatment of IA was 3.04%. For patients with type I SDMS with incomplete aneurysm occlusion we recommend continuous imaging follow-up while, for patients with type II SDMS, we recommend aggressive retreatment. The DPAD and DTI were independent risk predictors of SDMS after PED treatment, while the DL and PED plus coiling were protective factors.

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.

Enhanced Sensitivity of A549 Cells to Doxorubicin with WS2 and WSe2 Nanosheets via the Induction of Autophagy.

The excellent physicochemical properties of two-dimensional transition-metal dichalcogenides (2D TMDCs) such as WS2 and WSe2 provide potential benefits for biomedical applications, such as drug delivery, photothermal therapy, and bioimaging. WS2 and WSe2 have recently been used as chemosensitizers; however, the detailed molecular basis underlying WS2- and WSe2-induced sensitization remains elusive. Our recent findings showed that 2D TMDCs with different thicknesses and different element compositions induced autophagy in normal human bronchial epithelial cells and mouse alveolar macrophages at sublethal concentrations. Here, we explored the mechanism by which WS2 and WSe2 act as sensitizers to increase lung cancer cell susceptibility to chemotherapeutic agents. The results showed that WS2 and WSe2 enhanced autophagy flux in A549 lung cancer cells at sublethal concentrations without causing significant cell death. Through the autophagy-specific RT2 Profiler PCR Array, we identified the genes significantly affected by WS2 and WSe2 treatment. Furthermore, the key genes that play central roles in regulating autophagy were identified by constructing a molecular interaction network. A mechanism investigation uncovered that WS2 and WSe2 activated autophagy-related signaling pathways by interacting with different cell surface proteins or cytoplasmic proteins. By utilizing this mechanism, the efficacy of the chemotherapeutic agent doxorubicin was enhanced by WS2 and WSe2 pre-treatment in A549 lung cancer cells. This study revealed a feature of WS2 and WSe2 in cancer therapy, in which they eliminate the resistance of A549 lung cancer cells against doxorubicin, at least partially, by inducing autophagy.

Comparison of conservative management, microsurgery only, and microsurgery with preoperative embolization for unruptured arteriovenous malformations: A propensity score weighted prospective cohort study.

AIMS: To compare the efficacy and deficiency of conservative management (CM), microsurgery (MS) only, and microsurgery with preoperative embolization (E + MS) for unruptured arteriovenous malformations (AVMs). METHODS: We prospectively included unruptured AVMs undergoing CM, MS, and E + MS from our institution between August 2011 and August 2021. The primary outcomes were long-term neurofunctional outcomes and hemorrhagic stroke and death. In addition to the comparisons among CM, MS, and E + MS, E + MS was divided into single-staged hybrid and multi-staged E + MS for further analysis. Stabilized inverse probability of treatment weighting using propensity scores was applied to control for confounders by treatment indication across the three groups. RESULTS: Of 3758 consecutive AVMs admitted, 718 patients were included finally (266 CM, 364 MS, and 88 E + MS). The median follow-up duration was 5.4 years. Compared with CM, interventions (MS and E + MS) were associated with neurological deterioration. MS could lower the risk of hemorrhagic stroke and death. Multi-staged E + MS was associated with neurological deterioration and higher hemorrhagic risks compared with MS, but the hybrid E + MS operation significantly reduced the hemorrhage risk. CONCLUSION: In this study, unruptured AVMs receiving CM would expect better neurofunctional outcomes but bear higher risks of hemorrhage than MS or E + MS. The single-staged hybrid E + MS might be promising in reducing inter-procedural and subsequent hemorrhage.

Timing of microsurgical resection for ruptured brain arteriovenous malformations: a propensity score-matched analysis using prospective single-center registry data.

OBJECTIVE: The optimal microsurgical timing in ruptured brain arteriovenous malformations (AVMs) is not well understood and is surrounded by controversy. This study aimed to elucidate the impacts of microsurgical resection timing on clinical outcomes. METHODS: The authors retrieved and reviewed the records on all ruptured AVMs treated at their institution and registered in a nationwide multicenter prospective collaboration registry between August 2011 and August 2021. Patients were dichotomized into an early resection group (≤ 30 days from the last hemorrhagic stroke) and a delayed resection group (> 30 days after the last hemorrhagic stroke). Propensity score-matched analysis was used to compare long-term outcomes. The primary outcome was neurological status as assessed using the modified Rankin Scale (mRS). The secondary outcomes were complete obliteration rate, postoperative seizure, and postoperative hemorrhage. RESULTS: Of the 3649 consecutive AVMs treated at the authors' institution, a total of 558 ruptured AVMs were microsurgically resected and had long-term follow-up. After propensity score matching, 390 ruptured AVMs (195 pairs) were included in the comparison of outcomes. The mean (± standard deviation) clinical follow-up duration was 4.93 ± 2.94 years in the early resection group and 5.61 ± 2.56 years in the delayed resection group. Finally, as regards the distribution of mRS scores, short-term neurological outcomes were better in the delayed resection group (risk difference [RD] 0.3%, 95% CI -0.1% to 0.6%, p = 0.010), whereas long-term neurological outcomes were similar between the two groups (RD 0.0%, 95% CI -0.2% to 0.2%, p = 0.906). Long-term favorable neurological outcomes (early vs delayed: 90.8% vs 90.3%, p > 0.999; RD 0.5%, 95% CI -5.8% to 6.9%; RR 1.01, 95% CI 0.94-1.07) and long-term disability (9.2% vs 9.7%, p > 0.999; RD -0.5%, 95% CI -6.9% to 5.8%; RR 0.95, 95% CI 0.51-1.75) were also similar between these groups. In terms of secondary outcomes, postoperative seizure (early vs delayed: 8.7% vs 5.6%, p = 0.239; RD 3.1%, 95% CI -2.6% to 8.8%; RR 1.55, 95% CI 0.74-3.22), postoperative hemorrhage (1.0% vs 1.0%, p > 0.999; RD 0.0%, 95% CI -3.1% to 3.1%; RR 1.00, 95% CI 0.14-7.04), and hospitalization time (16.4 ± 8.5 vs 19.1 ± 7.9 days, p = 0.793) were similar between the two groups, whereas early resection had a lower complete obliteration rate (91.3% vs 99.0%, p = 0.001; RD -7.7%, 95% CI -12.9% to 3.1%; RR 0.92, 95% CI 0.88-0.97). CONCLUSIONS: Early and delayed resection of ruptured AVMs had similar long-term neurological outcomes. Delayed resection can lead to a higher complete obliteration rate, although the risk of rerupture during the resection waiting period should be vigilantly monitored.

Predicting Persistent Aneurysm Filling After Pipeline Embolization Device Treatment in Patients with Intracranial Aneurysm: Development and External Validation of a Nomogram Model.

The pipeline embolization device (PED) is an effective endovascular treatment modality for intracranial aneurysm (IA), but nearly one-fifth of IAs treated with a PED remain persistently filling at 1-year angiography follow-up. Developing a nomogram to predict persistent aneurysm filling after PED treatment can help neurointerventionalists identify aneurysms with incomplete occlusion and change their treatment strategies. This retrospective study included patients with IA treated with a PED from three institutions between April 2016 and April 2022, assigned to a derivation or validation cohort. Multivariate logistic regression analysis was used to identify predictors and develop a nomogram to predict persistent aneurysm filling after PED treatment in the derivation cohort. Predictive accuracy and clinical benefits of the nomogram were assessed using area under the receiver operating characteristic curve (AUC), calibration curves, and decision curve analysis (DCA). In total, 1006 patients with IA were included, 786 in the derivation cohort and 220 in the validation cohort. Over mean follow-up time 18.36 ± 8.58 months, 142 (14.1%) patients developed persistent aneurysm filling after PED treatment, 110 (14.0%) in the derivation cohort and 32 (14.5%) in the validation cohort. In multivariate logistic regression analysis, we developed a nomogram incorporating five predictors: aneurysms located in the basilar artery, dissecting aneurysms, maximum diameter, aneurysms with incorporated branches, and PED plus coiling. AUCs of the nomogram were 0.810 (95% confidence interval [CI], 0.765-0.856) in the derivation cohort and 0.840 (95% CI, 0.754-0.925) in the validation cohort. Calibration curve and DCA analysis demonstrated the utility and clinical application value of this nomogram. This nomogram provides individualized prediction of persistent aneurysm filling after PED treatment for patients with IA, representing a practical approach to effectiveness evaluation. This tool can help neurointerventionalists to identify aneurysms with incomplete occlusion and change their treatment strategy.

Recurrence of Cerebral Arteriovenous Malformation Following Complete Obliteration Through Endovascular Embolization.

Arteriovenous malformation (AVM) recurrence after embolization was rarely reported. This study aimed to explore the potential risk factors of recurrence in angiographically obliterated AVMs treated with endovascular embolization. This study reviewed AVMs treated with embolization only in a prospective multicenter registry from August 2011 to December 2021, and ultimately included 92 AVMs who had achieved angiographic obliteration. Recurrence was assessed by follow-up digital subtraction angiography (DSA) or magnetic resonance imaging (MRI). Hazard ratios (HRs) with 95% confidence intervals were calculated using Cox proportional hazards regression models. Nineteen AVMs exhibited recurrence on follow-up imaging. The recurrence rates after complete obliteration at 6 months, 1 year, and 2 years were 4.35%, 9.78%, and 13.0%, respectively. Multivariate Cox regression analysis identified diffuse nidus (HR 3.208, 95% CI 1.030-9.997, p=0.044) as an independent risk factor for recurrence. Kaplan-Meier analysis confirmed a higher cumulative risk of recurrence with diffuse nidus (log-rank, p=0.016). Further, in the exploratory analysis of the effect of embolization timing after AVM rupture on recurrence after the complete obliteration, embolization within 7 days of the hemorrhage was found as an independent risk factor (HR 4.797, 95% CI 1.379-16.689, p=0.014). Kaplan-Meier analysis confirmed that embolization within 7 days of the hemorrhage was associated with a higher cumulative risk of recurrence in ruptured AVMs (log-rank, p<0.0001). This study highlights the significance of diffuse nidus as an independent risk factor for recurrence after complete embolization of AVMs. In addition, we identified a potential recurrent risk associated with early embolization in ruptured AVMs.

Long-term outcomes of microsurgery and stereotactic radiosurgery as the first-line treatment for arteriovenous malformations: a propensity score-matched analysis using nationwide multicenter prospective registry data.

BACKGROUND: This study aimed to compare the risk and benefit profile of microsurgery (MS) and stereotactic radiosurgery (SRS) as the first-line treatment for unruptured and ruptured arteriovenous malformations (AVMs). MATERIALS AND METHODS: The authors included AVMs underwent MS or SRS as the first-line treatment from a nationwide prospective multicenter registry in mainland China. The authors used propensity score-matched methods to balance baseline characteristics between the MS and SRS groups. The primary outcomes were long-term hemorrhagic stroke or death, and the secondary outcomes were long-term obliteration and neurological outcomes. Subgroup analyses and sensitivity analyses with different study designs were performed to confirm the stability of our findings. RESULTS: Of the 4286 consecutive AVMs in the registry from August 2011 to December 2021; 1604 patients were eligible. After matching, 244 unruptured and 442 ruptured AVMs remained for the final analysis. The mean follow-up duration was 7.0 years in the unruptured group and 6.1 years in the ruptured group. In the comparison of primary outcomes, SRS was associated with a higher risk of hemorrhagic stroke or death both in the unruptured and ruptured AVMs (unruptured: hazard ratio 4.06, 95% CI: 1.15-14.41; ruptured: hazard ratio 4.19, 95% CI: 1.58-11.15). In terms of the secondary outcomes, SRS was also observed to have a significant disadvantage in long-term obliteration [unruptured: odds ratio (OR) 0.01, 95% CI: 0.00-0.04; ruptured: OR 0.09, 95% CI: 0.05-0.15]. However, it should be noted that SRS may have advantages in preventing neurofunctional decline (unruptured: OR 0.56, 95% CI: 0.27-1.14; ruptured: OR 0.41, 95% CI: 0.23-0.76). The results of subgroup analyses and sensitivity analyses were consistent in trend but with slightly varied powers. CONCLUSIONS: This clinical practice-based real-world study comprehensively compared MS and SRS for AVMs with long-term outcomes. MS is more effective in preventing future hemorrhage or death and achieving obliteration, while the risk of neurofunctional decline should not be ignored.

Comparison of Long-Term Outcomes in Ruptured Diffuse Brain Arteriovenous Malformations Between Interventional Therapy and Conservative Management.

Brain arteriovenous malformations (AVMs) with a diffuse nidus structure present a therapeutic challenge due to their complexity and elevated risk of hemorrhagic events. This study examines the long-term effectiveness of interventional therapy versus conservative management in reducing hemorrhagic stroke or death in patients with ruptured diffuse AVMs. The analysis was conducted based on a multi-institutional database in China. Patients were divided into two groups: conservative management and interventional therapy. Using propensity score matching, patients were compared for the primary outcome of hemorrhagic stroke or death and the secondary outcomes of disability and neurofunctional decline. Out of 4286 consecutive AVMs in the registry, 901 patients were eligible. After matching, 70 pairs of patients remained with a median follow-up of 4.0 years. The conservative management group showed a trend toward higher rates of the primary outcome compared to the interventional group (4.15 vs. 1.87 per 100 patient-years, P = 0.090). While not statistically significant, intervention reduced the risk of hemorrhagic stroke or death by 55% (HR, 0.45 [95% CI 0.18-1.14], P = 0.094). No significant differences were observed in secondary outcomes of disability (OR, 0.89 [95% CI 0.35-2.26], P = 0.813) and neurofunctional decline (OR, 0.65 [95% CI 0.26 -1.63], P = 0.355). Subgroup analysis revealed particular benefits in interventional therapy for AVMs with a supplemented S-M grade of II-VI (HR, 0.10 [95% CI 0.01-0.79], P = 0.029). This study suggests a trend toward lower long-term hemorrhagic risks with intervention when compared to conservative management in ruptured diffuse AVMs, especially within supplemented S-M grade II-VI subgroups. No evidence indicated that interventional approaches worsen neurofunctional outcomes.

Lung inflammation perturbation by engineered nanoparticles.

In recent years, the unique and diverse physicochemical properties of nanoparticles have brought about their wide use in many fields; however, it is necessary to better understand the possible human health risks caused by their release in the environment. Although the adverse health effects of nanoparticles have been proposed and are still being clarified, their effects on lung health have not been fully studied. In this review, we focus on the latest research progress on the pulmonary toxic effects of nanoparticles, and we summarized their disturbance of the pulmonary inflammatory response. First, the activation of lung inflammation by nanoparticles was reviewed. Second, we discussed how further exposure to nanoparticles aggravated the ongoing lung inflammation. Third, we summarized the inhibition of the ongoing lung inflammation by nanoparticles loaded with anti-inflammatory drugs. Forth, we introduced how the physicochemical properties of nanoparticles affect the related pulmonary inflammatory disturbance. Finally, we discussed the main gaps in current research and the challenges and countermeasures in future research.

Association of embolization with long-term outcomes in brain arteriovenous malformations: a propensity score-matched analysis using nationwide multicenter prospective registry data.

BACKGROUND: Brain arteriovenous malformations (AVMs) account for 25% of hemorrhagic strokes in young adults. Although embolization has been widely performed as a stand-alone procedure to cure brain AVM, it is undermined whether patients benefit from this treatment. This study aimed to compare the long-term outcome of hemorrhagic stroke or death in patients with either conservative management or stand-alone embolization for AVM. METHODS: The study population was derived from a nationwide multicenter prospective collaboration registry (the MATCH registry) between August 2011 and August 2021. The propensity score-matched survival analysis was performed in the overall and stratified AVM cases (unruptured and ruptured), respectively, to compare the long-term outcome of hemorrhagic stroke or death, and neurological status. The efficacy of distinct embolization strategies was also evaluated. Hazard ratios (HRs) with 95% CI were calculated using Fine-Gray competing risk models. RESULTS: Of the 3682 consecutive AVMs, 906 underwent either conservative management or embolization as the stand-alone management strategy. After propensity score matching, a total of 622 (311 pairs) patients constituted an overall cohort. The unruptured and ruptured subgroups were composed of 288 cases (144 pairs) and 252 cases (126 pairs), respectively. In the overall cohort, embolization did not prevent long-term hemorrhagic stroke or death compared with conservative management [2.07 vs. 1.57 per 100 patient-years; HR, 1.28 (95% CI, 0.81-2.04)]. Similar results were maintained in both unruptured AVMs [1.97 vs. 0.93 per 100 patient-years; HR, 2.09 (95% CI, 0.99-4.41)] and ruptured AVMs [2.36 vs. 2.57 per 100 patient-years; HR, 0.76 (95% CI, 0.39-1.48)]. Stratified analysis showed that the target embolization might be beneficial for unruptured AVMs [HR, 0.42 (95% CI, 0.08-2.29)], while the curative embolization improved the outcome of ruptured AVMs [HR, 0.29 (95% CI, 0.10-0.87)]. The long-term neurological status was similar between these two strategies. CONCLUSIONS: This prospective cohort study did not support a substantial superiority of embolization over conservative management for AVMs in preventing long-term hemorrhagic stroke or death.

A score system used to screen the suitability for recanalization in carotid artery occlusions.

Recanalization of chronic occluded internal carotid arteries has the potential to provide significant benefits for patients in the future, but the procedure is technically challenging. Therefore, this study aimed to identify a better method to predict the success of recanalization for patients with chronic internal carotid artery occlusion. The study's overall success rate was 73.77%. The multivariate logistic regression analysis revealed that two factors were independent predictors of successful recanalization: the continuous low signal lumen in the occluded segment of the internal carotid artery on the MRI image without contrast (OR: 15.9; 95% CI: 2.67-94.63) and the architecture of the clinoid segment of the internal carotid artery on the MRI image with contrast (OR: 11.97; 95% CI: 2.44-58.79). Based on the model coefficient, the researchers established an MRI score system. The MRI score system's area under the curve (AUC) in predicting successful recanalization was 0.916 (95% CI: 0.815 to 0.972; p < 0.001) with a sensitivity of 83.33% and a specificity of 72.22%. Compared to the previous score system based on the DSA morphology, the MRI system had a similar sensitivity and a better specificity. Therefore, the continuous low signal lumen in the occluded segment of the internal carotid artery on the MRI image without contrast and the architecture of the clinoid segment of the internal carotid artery on the MRI image with contrast were identified as independent predictors for successful recanalization in patients with chronic internal carotid artery occlusion (CICAO).

Asymmetric migration dynamics of the tropical Asian and Australasian floras.

The tropical Asian and Australasian floras have a close relationship, and is a vital distribution pattern of seed plants worldwide. As estimated, more than 81 families and 225 genera of seed plants distributed between tropical Asia and Australasia. However, the evolutionary dynamics of two floras were still vague. Here, a total of 29 plant lineages, represented the main clades of seed plants and different habits, were selected to investigate the biotic interchange between tropical Asia and Australasia by integrated dated phylogenies, biogeography, and ancestral state reconstructions. Our statistics indicated that 68 migrations have occurred between tropical Asia and Australasia since the middle Eocene except terminal migrations, and the migration events from tropical Asia to Australasia is more than 2 times of the reverse. Only 12 migrations occurred before 15 Ma, whereas the remaining 56 migrations occurred after 15 Ma. Maximal number of potential dispersal events (MDE) analysis also shows obvious asymmetry, with southward migration as the main feature, and indicates the climax of bi-directional migrations occurred after 15 Ma. We speculate that the formation of island chains after the Australian-Sundaland collision and climate changes have driven seed plant migrations since the middle Miocene. Furthermore, biotic dispersal and stable habitat may be crucial for floristic interchange between tropical Asia and Australasia.

Development and Validation of a Scoring System for Hemorrhage Risk in Brain Arteriovenous Malformations.

Importance: The dilemma between natural rupture risk and adverse outcomes of intervention is of major concern for patients with unruptured arteriovenous malformations (AVMs). The existing risk score for AVM rupture includes factors that are controversial and lacks prospective validation. Objective: To develop and robustly validate a reliable scoring system to predict the rupture risk of AVMs. Design, Setting, and Participants: This prognostic study developed a prediction model derived from a single-center cohort (derivation cohort) and validated in a multicenter external cohort (multicenter external validation cohort) and a cohort of patients receiving conservative treatment management (conservative treatment validation cohort). Patients were recruited from a nationwide multicenter prospective collaboration registry in China. A total of 4135 patients were enrolled in the registry between August 1, 2011, and September 1, 2021. Of those, 3962 patients were included in the study (3585 in the derivation cohort and 377 in the multicenter external validation cohort); 1028 patients from the derivation cohort who had time-to-event data and prerupture imaging results were included in the conservative treatment validation cohort. Data were analyzed from March 10 to June 21, 2022. Main Outcomes and Measures: A scoring system was developed based on risk factors identified from a literature review and a robust selection process. Patients were stratified into different risk groups based on scores to calculate hemorrhage-free probability in future years, and Kaplan-Meier curves were plotted to visualize risk stratification. Receiver operating characteristic curves were used to assess the discrimination of models. Univariable analyses (logistic regression analysis for descriptive data and Cox regression analysis for survival data) were used to compare baseline information and assess bias. Results: Among 3962 patients (2311 men [58.3%]; median [IQR] age, 26.1 [14.6-35.5] years), 3585 patients (2100 men [58.6%]; median [IQR] age, 25.9 [14.6-35.0] years) were included in the derivation cohort, and 377 patients (211 men [56.0%]; median [IQR] age, 26.4 [14.5-39.2] years) were included in the multicenter external validation cohort. Thirty-six hemorrhages occurred over a median (IQR) follow-up of 4.2 (0.3-6.0) years among 1028 patients in the conservative treatment validation cohort. Four risk factors were used to develop the scoring system: ventricular system involvement, venous aneurysm, deep location, and exclusively deep drainage (VALE). The VALE scoring system performed well in all 3 cohorts, with areas under the receiver operating characteristic curve of 0.77 (95% CI, 0.75-0.78) in the derivation cohort, 0.85 (95% CI, 0.81-0.89) in the multicenter external validation cohort, and 0.73 (95% CI, 0.65-0.81) in the conservative treatment validation cohort. The 10-year hemorrhage-free rate was 95.5% (95% CI, 87.1%-100%) in the low-risk group, 92.8% (95% CI, 88.8%-97.0%) in the moderate-risk group, and 75.8% (95% CI, 65.1%-88.3%) in the high-risk group; the model discrimination was significant when comparing these rates between the high-risk group and the low- and moderate-risk groups (P < .001 for both comparisons). Conclusions and Relevance: In this prognostic study, the VALE scoring system was developed to distinguish rupture risk among patients with AVMs. The stratification of unruptured AVMs may enable patients with low risk of rupture to avoid unnecessary interventions. These findings suggest that the scoring system is a reliable and applicable tool that can be used to facilitate patient and physician decision-making and reduce unnecessary interventions or unexpected AVM ruptures.

Multimodality treatment for brain arteriovenous malformation in Mainland China: design, rationale, and baseline patient characteristics of a nationwide multicenter prospective registry.

BACKGROUND: Brain arteriovenous malformation (AVM) is an important cause of hemorrhagic stroke in young adults, which can lead to severe neurological impairment. The registry of Multimodality treatment for brain ArTeriovenous malformation in mainland CHina (MATCH) is a national prospective registry to identify the natural history of AVMs in Asian population; to investigate traditional and emerging hemorrhagic predictors; and to explore the superiority of the multidisciplinary assessment in improving the long-term outcomes.  METHODS: Consecutive AVM patients will be enrolled from 52 participating hospitals in mainland China. Baseline demographic, clinical and imaging data will be collected prospectively. Conservation, microsurgery, embolization, stereotactic radiosurgery (SRS), and multimodal strategies are all included in this study. Patients will be divided into experimental and control group according to whether the treatment protocols are formulated by multidisciplinary team. Neurofunctional status, subsequent hemorrhage, seizure, and novel neurofunctional deficit will be queried at 3 months, annually (1 and 2 years), 3 years, and 10 years follow-up. RESULTS: Between August 2011 and April 2021, 3241 AVMs were enrolled in 11 participating sites. Among them, 59.0% were male with an average age of 28.4 ± 14.6 years, 61.2% had rupture history and 2268 hemorrhagic events occurred before admission. The median Spetzler-Martin grade and Lawton-Young grade was 3 and 5, respectively. Microsurgery is the dominant strategy (35.7%), with a similar proportion of embolization, SRS, and a combination of both (12.7%; 14.8%; 11.8%; respectively). Among them, 15.43% underwent multidisciplinary assessment and received standardized treatment. At the most recent follow-up, 7.8% were lost and the median follow-up duration was 5.6 years. CONCLUSIONS: The MATCH study is a large-sample nationwide prospective registry to investigate multimodality management strategy for AVMs. Data from this registry may also provide the opportunity for individualized risk assessment and the development of optimal individual management strategies. TRIAL REGISTRATION: ClinicalTrials.gov Registry ( NCT04572568 ).

Papaverine Infusion Through Aortic Root before Cardiac Self-recovery in Heart Valve Replacement with TiO2 Nanocrystalline Film Material.

This work was to investigate TiO2 nanocrystalline film material in heart valve replacement (HVR) and the effect of papaverine infusion through the aortic root before cardiac self-recovery during the HVR. TiO2 nanocrystalline films were prepared by radio frequency (RF) reactive sputtering. The crystallization characteristics and surface morphology of TiO2 nanocrystalline films were observed by X-ray diffraction and scanning electron microscopy, and the anti-platelet adhesion and anti-coagulation properties of the films were analyzed. 86 patients with heart valve disease were selected and all underwent HVR. They were randomly divided into a control group (routine treatment) and an experimental group (papaverine perfusion through aortic root), with 43 cases in each group. The rate of cardiac self-recovery and the dosage of dopamine were observed. The results showed that the TiO2 nanocrystalline film was composed of a large number of uniform particles, and the average particle size was about 18.97 ± 7.28 nm. The rate of cardiac self-recovery in the experimental group was 97.67%, which was significantly higher than that in the control group (67.44%) (P< 0.05). The dosage of epinephrine, dopamine, and duration of cardiopulmonary bypass (CPB) assistance in the observation group were less than those in the control group (P < 0.05). These results indicated that TiO2 nanocrystalline film could be used in HVR, and papaverine infusion through aortic root before HVR and myocardial protection measures can significantly improve the rate of cardiac self-recovery and promote postoperative recovery.

Basic Psychological Needs Satisfaction Mediates the Link between Strengths Use and Teachers' Work Engagement.

Work engagement is a core indicator that reflects the quality of teachers' occupational lives and the development of students, but few studies have explored the connection between strengths use and work engagement of teachers and the mechanisms underlying this relationship. This paper aimed to investigate how the relation of strengths use with work engagement is affected by a teacher's satisfaction of basic psychological needs. For this purpose, 648 teachers in China completed questionnaires. The results revealed that strengths use exhibited a positive correlation with work engagement and needs satisfaction. Furthermore, autonomy, competence, and relatedness satisfaction mediated the effect of strengths use on work engagement for teachers. The results suggest that autonomy, competence, and relatedness satisfaction serve as factors that mediate the effect of strengths use on work engagement. The significance and limitations of the study are discussed.

Perturbation of autophagy: An intrinsic toxicity mechanism of nanoparticles.

Nanoparticles (NPs) have been widely used for various purposes due to their unique physicochemical properties. Such widespread applications greatly increase the possibility of human exposure to NPs in various ways. Once entering the human body, NPs may interfere with cellular homeostasis and thus affect the physiological system. As a result, it is necessary to evaluate the potential disturbance of NPs to multiple cell functions, including autophagy. Autophagy is an important cell function to maintain cellular homeostasis, and minimizing the disturbance caused by NP exposures to autophagy is critical to nanosafety. Herein, we summarized the recent research progress in nanotoxicity with particular focuses on the perturbation of NPs to cell autophagy. The basic processes of autophagy and complex relationships between autophagy and major human diseases were further discussed to emphasize the importance of keeping autophagy under control. Moreover, the most recent advances on perturbation of different types of NPs to autophagy were also reviewed. Last but not least, we also discussed major research challenges and potential coping strategies and proposed a safe-by-design strategy towards safer applications of NPs.