SpliceTransformer predicts tissue-specific splicing linked to human diseases.

We present SpliceTransformer (SpTransformer), a deep-learning framework that predicts tissue-specific RNA splicing alterations linked to human diseases based on genomic sequence. SpTransformer outperforms all previous methods on splicing prediction. Application to approximately 1.3 million genetic variants in the ClinVar database reveals that splicing alterations account for 60% of intronic and synonymous pathogenic mutations, and occur at different frequencies across tissue types. Importantly, tissue-specific splicing alterations match their clinical manifestations independent of gene expression variation. We validate the enrichment in three brain disease datasets involving over 164,000 individuals. Additionally, we identify single nucleotide variations that cause brain-specific splicing alterations, and find disease-associated genes harboring these single nucleotide variations with distinct expression patterns involved in diverse biological processes. Finally, SpTransformer analysis of whole exon sequencing data from blood samples of patients with diabetic nephropathy predicts kidney-specific RNA splicing alterations with 83% accuracy, demonstrating the potential to infer disease-causing tissue-specific splicing events. SpTransformer provides a powerful tool to guide biological and clinical interpretations of human diseases.

Effects of adsorption of O2 and H2O molecules on the corrosion behavior of the NiTi alloy surface: a DFT investigation.

The influence of O2 and H2O adsorption significantly affects the electrochemical corrosion of the NiTi alloy, with unresolved corrosion disparities between the NiTi-B2 and NiTi-B19' phases. Density functional theory (DFT) calculations are utilized in this investigation to explore the adsorption of O atoms at varying coverages on the NiTi-B2(110) and NiTi-B19'(010) surfaces. The goal is to elucidate their oxidation behavior differences. Subsequently, the effect of O adsorption on the dissolution trends of these phases is assessed by inducing Ni/Ti vacancies to simulate alloy dissolution thermodynamically. Additionally, interactions between H2O molecules and O-pre-adsorbed NiTi alloy surfaces are examined to simulate the atomic evolution of the oxidized surface under exposure to humid air and corrosive solutions. The findings indicate a propensity of the NiTi-B19' phase to react with O, forming an oxide film more readily than the NiTi-B2 phase. O adsorption facilitates Ni dissolution and retards Ti dissolution on the alloy surface. Higher O coverage promotes easier dissolution of Ni and Ti atoms on the NiTi-B2(110) surface compared to the NiTi-B19'(010) surface, underscoring the greater corrosion resistance of the NiTi-B19' phase. Both clean and O-pre-adsorbed NiTi alloy surfaces physically adsorb H2O molecules. Notably, an O monolayer substantially mitigates the detrimental effects of H2O molecules on the corrosion resistance of alloy surfaces. This research contributes to a deeper comprehension of the corrosion mechanisms in NiTi alloys.

Mitochondrial tRNAGlu 14693A>G Mutation, an "Enhancer" to the Phenotypic Expression of Leber's Hereditary Optic Neuropathy.

Leber's hereditary optic neuropathy (LHON), a maternally inherited ocular disease, is predominantly caused by mitochondrial DNA (mtDNA) mutations. Mitochondrial tRNA variants are hypothesized to amplify the pathogenic impact of three primary mutations. However, the exact mechanisms remained unclear. In the present study, the synergistic effect of the tRNAGlu 14693A>G and ND6 14484T>C mutations in three Chinese families affected by LHON is investigated. The m.14693A>G mutation nearly abolishes the pseudouridinylation at position 55 of tRNAGlu, leading to structural abnormalities, decreased stability, aberrant mitochondrial protein synthesis, and increased autophagy. In contrast, the ND6 14484T>C mutation predominantly impairs complex I function, resulting in heightened apoptosis and virtually no induction of mitochondrial autophagy compared to control cell lines. The presence of dual mutations in the same cell lines exhibited a coexistence of both upregulated cellular stress responses to mitochondrial damage, indicating a scenario of autophagy and mutation dysregulation within these dual-mutant cell lines. The data proposes a novel hypothesis that mitochondrial tRNA gene mutations generally lead to increased mitochondrial autophagy, while mutations in genes encoding mitochondrial proteins typically induce apoptosis, shedding light on the intricate interplay between different genetic factors in the manifestation of LHON.

Gallic acid-selenium nanoparticles with dual anti-inflammatory and antioxidant functions for synergistic treatment of acute kidney injury.

The overexpression of inflammatory factors is closely related to the pathogenesis of acute kidney injury (AKI). Additionally, the overproduction of reactive oxygen species (ROS) further exacerbates the inflammatory response. In light of this, monotherapies focused solely on inflammation have proven to be suboptimal. Therefore, this study successfully developed a nanoparticle (SC@Se/GA) that possesses anti-inflammatory and antioxidant properties. The SC@Se/GA has a smaller size, better stability, and kidney-targeting. In vivo experiments showed that the GPx enzyme activity of SC@Se/GA increases by almost 50 % more than SC@Se alone, indicating its efficient ability to scavenge ROS. In the meantime, SC@Se/GA has a longer renal retention period (>24 h) than free drug GA, which can dramatically lower the levels of inflammatory factors TNF-α and IL-6. In summary, SC@Se/GA, through its synergistic anti-inflammatory and antioxidant effects, markedly alleviates CDDP-induced renal injury and restores renal function, providing a new effective strategy for treating AKI.

Common variants of vitamin D receptor gene polymorphisms and risk of gastric cancer: A meta-analysis.

BACKGROUND: While earlier studies have suggested that variations in the vitamin D receptor (VDR) gene could influence the susceptibility to gastric cancer (GC), the results have shown inconsistency. This meta-analysis aimed to examine the association of 5 common polymorphisms in VDR, including Taq1 rs731236 (T > C), FokI rs2228570 (C > T), Cdx2 rs11568820 (G > A), BsmI rs1544410 (G > A), and ApaI rs7975232 (G > T) with the risk of GC. METHODS: A comprehensive search was carried out in PubMed, Web of Science, and Scopus to identify relevant studies published until January 2024. Odds ratios (ORs) with 95% confidence intervals (CIs) were utilized to assess the magnitude of associations. RESULTS: Nine studies, with 2837 participants (1215 GC cases and 1622 healthy controls), were eligible. The FokI rs2228570 polymorphism showed a significant correlation with heightened susceptibility to GC under the recessive model (OR = 1.52; 95% CI: 1.06-2.19) and homozygote comparison (TT vs CC; OR = 1.59; 95% CI: 1.09-2.31). Taq1 rs731236 was also linked to an elevated risk of GC under the same models (recessive OR = 1.65; 95% CI: 1.14-2.39; homozygote OR = 1.68; 95% CI: 1.11-2.54). In the sensitivity analysis, when studies not adhering to Hardy-Weinberg equilibrium were excluded, the relationship between FokI rs2228570 polymorphism and GC disappeared, while the association for Taq1 rs731236 remained consistent. No significant association was identified for BsmI rs1544410, ApaI rs7975232, and Cdx2 rs11568820. CONCLUSION: This study revealed that FokI rs2228570 and Taq1 rs731236 polymorphisms of VDR might be linked to the odds of GC.

Small intestine submucosa decorated 3D printed scaffold accelerated diabetic bone regeneration by ameliorating the microenvironment.

The 3D printed scaffolds constructed from polymers have shown significant potential in the field of bone defect regeneration. However, the efficacy of these scaffolds can be markedly reduced in certain pathological conditions like diabetes, where an altered inflammatory microenvironment and diminished small blood vessels complicate the integration of these polymers with the host tissue. In this study, the bioactivity of a 3D-printed poly(lactide-co-glycolide) (PLGA) scaffold is enhanced through the integration of hydroxyapatite (HA), icariin (ICA), and small intestine submucosa (SIS), a form of decellularized extracellular matrix (dECM). The decoration of SIS on the 3D-printed PLGA/HA/ICA scaffold not only improves the mechanical and degradative performance, but also extends the release of ICA from the scaffold. Both in vitro and in vivo studies demonstrate that this functionalized scaffold mitigates the persistent inflammatory conditions characteristic of diabetic bone defects through inducing macrophages towards the M2 phenotype. Additionally, the scaffold promotes angiogenesis by enhancing the migration and tube formation of vascular cells. Furthermore, the synergistic effects of ICA and SIS with the HA scaffolds contribute to the superior osteogenic induction capabilities. This functionalization approach holds significant promise in advancing the treatment of bone defects within the diabetic population, paving a step forward in the application of polymer-based 3D printing technologies in regenerative medicine.

3D Bioprinting of Artificial Skin Substitute with Improved Mechanical Property and Regulated Cell Behavior through Integrating Patterned Nanofibrous Films.

Three-dimensional (3D) bioprinting has advantages for constructing artificial skin tissues in replicating the structures and functions of native skin. Although many studies have presented improved effect of printing skin substitutes in wound healing, using hydrogel inks to fabricate 3D bioprinting architectures with complicated structures, mimicking mechanical properties, and appropriate cellular environments is still challenging. Inspired by collagen nanofibers withstanding stress and regulating cell behavior, a patterned nanofibrous film was introduced to the printed hydrogel scaffold to fabricate a composite artificial skin substitute (CASS). The artificial dermis was printed using gelatin-hyaluronan hybrid hydrogels containing human dermal fibroblasts with gradient porosity and integrated with patterned nanofibrous films simultaneously, while the artificial epidermis was formed by seeding human keratinocytes upon the dermis. The collagen-mimicking nanofibrous film effectively improved the tensile strength and fracture resistance of the CASS, making it sewable for firm implantation into skin defects. Meanwhile, the patterned nanofibrous film also provided the biological cues to guide cell behavior. Consequently, CASS could effectively accelerate the regeneration of large-area skin defects in mouse and pig models by promoting re-epithelialization and collagen deposition. This research developed an effective strategy to prepare composite bioprinting architectures for enhancing mechanical property and regulating cell behavior, and CASS could be a promising skin substitute for treating large-area skin defects.

Targeting adipocyte ESRRA promotes osteogenesis and vascular formation in adipocyte-rich bone marrow.

Excessive bone marrow adipocytes (BMAds) accumulation often occurs under diverse pathophysiological conditions associated with bone deterioration. Estrogen-related receptor α (ESRRA) is a key regulator responding to metabolic stress. Here, we show that adipocyte-specific ESRRA deficiency preserves osteogenesis and vascular formation in adipocyte-rich bone marrow upon estrogen deficiency or obesity. Mechanistically, adipocyte ESRRA interferes with E2/ESR1 signaling resulting in transcriptional repression of secreted phosphoprotein 1 (Spp1); yet positively modulates leptin expression by binding to its promoter. ESRRA abrogation results in enhanced SPP1 and decreased leptin secretion from both visceral adipocytes and BMAds, concertedly dictating bone marrow stromal stem cell fate commitment and restoring type H vessel formation, constituting a feed-forward loop for bone formation. Pharmacological inhibition of ESRRA protects obese mice against bone loss and high marrow adiposity. Thus, our findings highlight a therapeutic approach via targeting adipocyte ESRRA to preserve bone formation especially in detrimental adipocyte-rich bone milieu.

Anti-inflammatory Fucoidan-ConA oral insulin nanosystems for smart blood glucose regulation.

The smart oral administration Insulin device has the potential to improve glycemic management. It can reduce the risk of hypoglycemia associated with exogenous Insulin (INS) therapy while also avoiding many of the disadvantages associated with subcutaneous injections. Furthermore, diabetes mellitus (DM) is an endocrine illness characterized by inflammation, and it is critical to minimize the amount of inflammatory markers in diabetic patients while maintaining average blood glucose. In this study, a responsive nanosystem vitamin B12-Fucoidan-Concanavalin A (VB12-FU-ConA NPs) with anti-inflammatory action was developed for smart oral delivery of Insulin. Con A has high sensitivity and strong specificity as a glucose-responsive material. Fucoidan has anti-inflammatory, immunomodulatory, and hypoglycemic functions, and it can bind to Con A to form a reversible complex. Under high glucose conditions, free glucose competitively binds to Con A, which swells the nanocarrier and promotes Insulin release. Furthermore, in the low pH environment of the gastrointestinal tract, positively charged VB12 and anionic fucoidan bind tightly to protect the Insulin wrapped in the carrier, and VB12 can also bind to intestinal epithelial factors to improve transit rate, thereby promoting INS absorption. In vitro tests showed that the release of nanoparticles in hyperglycemic solutions was significantly higher than the drug release in normoglycemic conditions. Oral delivery of the nanosystems dramatically lowered blood glucose levels in type I diabetic mice (T1DM) during in vivo pharmacodynamics, minimizing the risk of hypoglycemia. Blood glucose levels reached a minimum of 8.1 ± 0.4 mmol/L after 8 h. Administering the nanosystem orally notably decreased the serum levels of tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6) in diabetic mice. The nano delivery system can be degraded and metabolized in the intestinal tract after being taken orally, demonstrating good biodegradability and biosafety. In conclusion, the present study showed that VB12-FU-ConA nanocarriers are expected to be a novel system for rationalizing blood glucose.

Comparison of Outcomes between Stent Retriever Combined with Contact Aspiration and Contact Aspiration Alone in Patients without Hyperdense Artery Sign/Susceptibility Vessel Sign.

PURPOSE: To examine the relationship between hyperdense artery sign (HAS)/susceptibility vessel sign (SVS) and thrombus composition and evaluate the effect of HAS/SVS status on the association between first-line thrombectomy techniques and outcomes in patients with acute anterior circulation large vessel occlusion (LVO). MATERIALS AND METHODS: From January 2018 to June 2021, 103 consecutive patients with acute anterior circulation LVO (75 [63.1%] men; median age, 66 years) who underwent thrombectomy and for whom the removed clot was available for histological analyses were retrospectively reviewed. The presence of HAS and SVS was assessed on unenhanced computed tomography (CT) and susceptibility-weighted imaging, respectively. Association of first-line thrombectomy techniques (stent retriever [SR] combined with contact aspiration [CA] vs CA alone) with outcomes was assessed according to HAS/SVS status. RESULTS: Among the included patients, 55 (53.4%) were HAS/SVS-negative, and 69 (67.0%) underwent first-line SR + CA. Higher relative densities of fibrin/platelets (0.56 vs 0.51; P < .001) and lower relative densities of erythrocytes (0.32 vs 0.42; P < .001) were observed in HAS/SVS-negative patients compared with HAS/SVS-positive patients. First-line SR + CA was associated with reduced odds of distal embolization (adjusted odds ratio, 0.18; 95% CI, 0.04-0.83; P = .027) and a more favorable 90-day functional outcome (adjusted odds ratio, 5.29; 95% CI, 1.06-26.34; P = .042) in HAS/SVS-negative patients and a longer recanalization time (53 vs 25 minutes; P = .025) and higher risk of subarachnoid hemorrhage (24.2% vs 0%; P = .044) in HAS/SVS-positive patients. CONCLUSIONS: Absence of HAS/SVS may indicate a higher density of fibrin/platelets in the thrombus, and first-line SR + CA yielded superior functional outcomes than CA alone in patients with acute LVO without HAS/SVS.

Deafness-associated tRNAPhe mutation impaired mitochondrial and cellular integrity.

Defects in mitochondrial RNA metabolism have been linked to sensorineural deafness that often occurs as a consequence of damaged or deficient inner ear hair cells. In this report, we investigated the molecular mechanism underlying a deafness-associated tRNAPhe 593T > C mutation that changed a highly conserved uracil to cytosine at position 17 of the DHU-loop. The m.593T > C mutation altered tRNAPhe structure and function, including increased melting temperature, resistance to S1 nuclease-mediated digestion, and conformational changes. The aberrant tRNA metabolism impaired mitochondrial translation, which was especially pronounced by decreases in levels of ND1, ND5, CYTB, CO1, and CO3 harboring higher numbers of phenylalanine. These alterations resulted in aberrant assembly, instability, and reduced activities of respiratory chain enzyme complexes I, III, IV, and intact supercomplexes overall. Furthermore, we found that the m.593T > C mutation caused markedly diminished membrane potential, and increased the production of reactive oxygen species in the mutant cell lines carrying the m.593T > C mutation. These mitochondrial dysfunctions led to the mitochondrial dynamic imbalance via increasing fission with abnormal mitochondrial morphology. Excessive fission impaired the process of autophagy including the initiation phase, formation, and maturation of the autophagosome. In particular, the m.593T > C mutation upregulated the PARKIN-dependent mitophagy pathway. These alterations promoted an intrinsic apoptotic process for the removal of damaged cells. Our findings provide critical insights into the pathophysiology of maternally inherited deafness arising from tRNA mutation-induced defects in mitochondrial and cellular integrity.

An AIE Controlled "Off-On" Cu2+-Sensitive Probe for Early Detection of Renal Fibrosis.

Early detection of renal fibrosis (RF) is very important given that it is irreversible when it progresses to the terminal stage. A key marker of RF pathogenesis is activation of myomyofibroblasts, and its targeted imaging may be a promising approach for early detection of RF, but no study has directly imaged activation of renal myomyofibroblasts. Cu2+ plays a major role in the fibrotic activity of myofibroblasts. Herein, inspired by that Cu2+ can complex with bovine serum albumin (BSA), BSA-Ag2S quantum dots (QDs) with aggregation-induced emission (AIE) property are synthesized. Then BSA-Ag2S QDs are modified by chitosan (CS) with renal targeting and hyaluronic acid (HA) with myofibroblast targeting to obtain the AIE assay system (QDs@CS@HA). The system is simple to synthesize, and produces a rapid NIR fluorescence signal turn-on response and a low detection limit of 75 × 10-9 m to Cu2+. In addition, cellular and animal experiments have shown that QDs@CS@HA has good biosafety and cell-targeted imaging capability for RF. Based on the successful application of QDs@CS@HA and the mechanism of RF progression in early RF detection, it is expected that QDs@CS@HA may detect RF before the appearance of clinical symptoms.

RNA modifications in cellular metabolism: implications for metabolism-targeted therapy and immunotherapy.

Cellular metabolism is an intricate network satisfying bioenergetic and biosynthesis requirements of cells. Relevant studies have been constantly making inroads in our understanding of pathophysiology, and inspiring development of therapeutics. As a crucial component of epigenetics at post-transcription level, RNA modification significantly determines RNA fates, further affecting various biological processes and cellular phenotypes. To be noted, immunometabolism defines the metabolic alterations occur on immune cells in different stages and immunological contexts. In this review, we characterize the distribution features, modifying mechanisms and biological functions of 8 RNA modifications, including N6-methyladenosine (m6A), N6,2'-O-dimethyladenosine (m6Am), N1-methyladenosine (m1A), 5-methylcytosine (m5C), N4-acetylcytosine (ac4C), N7-methylguanosine (m7G), Pseudouridine (Ψ), adenosine-to-inosine (A-to-I) editing, which are relatively the most studied types. Then regulatory roles of these RNA modification on metabolism in diverse health and disease contexts are comprehensively described, categorized as glucose, lipid, amino acid, and mitochondrial metabolism. And we highlight the regulation of RNA modifications on immunometabolism, further influencing immune responses. Above all, we provide a thorough discussion about clinical implications of RNA modification in metabolism-targeted therapy and immunotherapy, progression of RNA modification-targeted agents, and its potential in RNA-targeted therapeutics. Eventually, we give legitimate perspectives for future researches in this field from methodological requirements, mechanistic insights, to therapeutic applications.

Deficient tRNA posttranscription modification dysregulated the mitochondrial quality controls and apoptosis.

Mitochondria are dynamic organelles in cellular metabolism and physiology. Mitochondrial DNA (mtDNA) mutations are associated with a broad spectrum of clinical abnormalities. However, mechanisms underlying mtDNA mutations regulate intracellular signaling related to the mitochondrial and cellular integrity are less explored. Here, we demonstrated that mt-tRNAMet 4435A>G mutation-induced nucleotide modification deficiency dysregulated the expression of nuclear genes involved in cytosolic proteins involved in oxidative phosphorylation system (OXPHOS) and impaired the assemble and integrity of OXPHOS complexes. These dysfunctions caused mitochondrial dynamic imbalance, thereby increasing fission and decreasing fusion. Excessive fission impaired the process of autophagy including initiation phase, formation, and maturation of autophagosome. Strikingly, the m.4435A>G mutation upregulated the PARKIN dependent mitophagy pathways but downregulated the ubiquitination-independent mitophagy. These alterations promoted intrinsic apoptotic process for the removal of damaged cells. Our findings provide new insights into mechanism underlying deficient tRNA posttranscription modification regulated intracellular signaling related to the mitochondrial and cellular integrity.

Stress hyperglycemia increases short-term mortality in acute ischemic stroke patients after mechanical thrombectomy.

BACKGROUND AND PURPOSE: Glucose-to-glycated hemoglobin ratio (GAR) is considered a more reliable marker of stress hyperglycemia by correcting for basal blood glucose levels. This study aimed to investigate the extent to which GAR is associated with 3 month and 1 year all-cause mortalities in patients with acute ischemic stroke (AIS) undergoing mechanical thrombectomy (MT). METHODS: We retrospectively followed 553 AIS patients who underwent MT. The degree of stress hyperglycemia was quantified as the GAR, defined as fasting plasma glucose (mmol/L)/hemoglobin A1c (HbA1c) (%) on the second day after admission. According to the GAR quartiles, the patients were further categorized into four groups (group 1-group 4). We assessed the association between GAR and all-cause mortalities, clinical outcomes during hospitalization and function outcomes at 3 months. The associations between stress hyperglycemia and all-cause mortalities were analyzed using a Cox proportional-hazards model, while other outcomes were analyzed using multiple logistic regression analysis. RESULTS: The follow-up lasted a median of 18 months (range 0-66 months). The 3 month mortality rate was 9.58% (n = 53) and the 1 year mortality rate was 18.62% (n = 103). The Kaplan-Meier analysis revealed a significant inverse relationship between GAR and mortality (P < 0.001). In the Cox proportional-hazards model at 3 months, compared with group1, group 4 of GAR was associated with a significant increase in the risk of 3 month mortality (hazard ratio [HR] = 4.11, 95% confidence interval [CI] 1.41-12.0, P = 0.01) after adjusting for potential covariates. On multivariate logistic regression analysis, GAR was strongly associated with an increased risk of 3 month poor function outcome. CONCLUSIONS: Stress hyperglycemia, quantified by a higher GAR, is associated with all-cause mortality and poor functional outcomes in patients with AIS who undergo MT. Furthermore, GAR may contribute to improving the predictive efficiency of all-cause mortality in patients with AIS after MT, especially short-term all-cause mortality.

Long-term voice outcomes of medialization thyroplasty with adjustable implant for unilateral vocal fold paralysis.

OBJECTIVES: Medialization thyroplasty (MT) using various implants has been employed as a corrective procedure for unilateral vocal fold paralysis (UVFP). A newly developed APrevent® vocal implant system (VOIS) offers an innovative solution with a finely adjustable design. This study aimed to investigate the long-term functional voice outcomes and benefits of postoperative adjustments in patients receiving MT using the VOIS-implant. METHODS: This is a prospective case series study at single tertiary medical center. Fourteen adult patients diagnosed with UVFP received MT with the VOIS implant and were followed up for more than 1 year. Implant adjustment procedure by injecting 0.9% physiological saline solution was performed both during and after the surgery to optimize glottal closure and voice quality. Objective voice outcomes and acoustic parameters were assessed preoperatively and postoperatively at various timepoints. RESULTS: Thirteen patients (93%) received intraoperative balloon adjustment, ranging from 0.05to 0.12 ml. Four patients underwent adjustments postoperatively and exhibited a positive trend towards immediately improving acoustic voice quality. Our long-term results demonstrated a notable improvement after the surgery in voice quality, with significant decreases in VHI-30 and improvements in perceptual parameters of GRBAS scale, acoustic measures such as jitter and signal-to-noise ratio (p < 0.001) and cepstral peak prominence smoothed in sustained vowel and short sentences. The voice outcomes remained stable more than 1 year follow-up. CONCLUSIONS: Overall, MT with VOIS implantation provides a favorable long-term outcomes and stability in voice quality for patients with UVFP and also an effective tool for postoperative adjustment without major revision surgeries.

Sub-satisfactory stenting recanalization of severe vascular stenosis of the posterior circulation can significantly improve cerebral hemodynamic perfusion.

PURPOSE: To investigate the effect of sub-satisfactory stenting recanalization of severe vascular stenosis of the posterior circulation on cerebral hemodynamic perfusion. MATERIALS AND METHODS: Patients with severe vascular stenosis of the posterior circulation who had undergone three-dimensional cerebral angiography before and after stenting were retrospectively enrolled. Computational fluid dynamic (CFD) analysis of hemodynamic parameters at the stenosis, perforating branch, and normal arterial segments proximal and distal to the stenosis were performed. RESULTS: Sixty-two patients with basilar artery stenosis aged 60.9 ±â€¯9.6 years were enrolled, and stent angioplasty resulted in the reduction of stenosis degree from 85.3 ±â€¯7.2% before to 18.6 ±â€¯6.4% after stenting. After stenting, at the proximal normal artery, the total pressures had significantly (P < 0.05) decreased, whereas all the other parameters (WSS, cell Reynolds number, velocity, vorticity, turbulence intensity, turbulence kinetic energy and dissipation rate) had significantly (P < 0.05) increased. At the stenosis, all hemodynamic parameters had significantly decreased. At the stenosis perforating branch, the WSS, cell Reynolds number, velocity, and vorticity were all significantly decreased, and the total pressure, turbulence intensity, kinetic energy, and dissipation rate were all significantly increased. At the distal normal artery, the total flow pressure (perfusion pressure) and velocity were both significantly (P < 0.05) increased, and the total pressure, WSS, cell Reynolds number, vorticity, turbulence intensity, kinetic energy, and dissipation rate were all significantly (P < 0.05) decreased. The hemodynamic parameters after stenting were closer to those after virtual stenosis repair at all measurements. CONCLUSION: Sub-satisfactory recanalization has significantly restored the stenosis and improved the hemodynamic parameters near the stenosis and at the root of the perforating branch, thus significantly improving the cerebral perfusion, similar to the changes of hemodynamic status and cerebral perfusion after virtual removal of the vascular stenosis. This may indicate the good effect of sub-satisfactory stenting recanalization of the vascular stenosis at the posterior circulation.

Comparison of clinical outcomes in patients with acute ischemic stroke who underwent endovascular treatment using different perfusion modalities: a real-world multicenter study.

Background: Advanced perfusion modalities are increasingly popular for various diseases. However, few studies have focused on contrasting perfusion patterns. Objective: This study aimed to compare the time efficiency and clinical outcomes of patients with acute ischemic stroke (AIS) who underwent endovascular treatment (EVT) before one-stop arterial spin labeling (ASL) and computed tomography perfusion (CTP) protocols. Methods: This study retrospectively included 326 patients with AIS who had accepted EVT within 24 h of onset from four comprehensive stroke centers between October 2017 and September 2022. After 1:1 matching of the propensity scores, 202 patients were separated into two groups: the ASL group (n = 101) and the CTP group (n = 101). Results: Functional independence at 90 days (modified Rankin Scale [mRS] 0-2; p = 0.574), onset-to-puncture time (p = 0.231), door-to-puncture time (p = 0.136), and door-to-perfusion time (p = 0.646) were not significantly different between the two groups. The proportion of EVT complications (31.7% in the ASL group vs. 14.9% in the CTP group, p = 0.005) and symptomatic intracranial hemorrhage (sICH) at 24 h (23.8% in the ASL group vs. 9.9% in the CTP group, p = 0.008) in the CTP group were lower than the ASL group. The ischemic core volume was a common predictor of favorable outcomes in both ASL (p < 0.001) and CTP (p < 0.001) groups. Conclusion: There were no significant differences in time efficiency and efficacy outcomes between the two groups of patients receiving one-stop ASL and CTP. The proportion of sICH at 24 h and EVT complications of patients in the CTP group was lower than the ASL group. The ischemic core volume was an independent predictor for favorable outcomes.