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1.
N Engl J Med ; 388(14): 1272-1283, 2023 Apr 06.
Artículo en Inglés | MEDLINE | ID: mdl-36762852

RESUMEN

BACKGROUND: The role of endovascular therapy for acute stroke with a large infarction has not been extensively studied in differing populations. METHODS: We conducted a multicenter, prospective, open-label, randomized trial in China involving patients with acute large-vessel occlusion in the anterior circulation and an Alberta Stroke Program Early Computed Tomography Score of 3 to 5 (range, 0 to 10, with lower values indicating larger infarction) or an infarct-core volume of 70 to 100 ml. Patients were randomly assigned in a 1:1 ratio within 24 hours from the time they were last known to be well to undergo endovascular therapy and receive medical management or to receive medical management alone. The primary outcome was the score on the modified Rankin scale at 90 days (scores range from 0 to 6, with higher scores indicating greater disability), and the primary objective was to determine whether a shift in the distribution of the scores on the modified Rankin scale at 90 days had occurred between the two groups. Secondary outcomes included scores of 0 to 2 and 0 to 3 on the modified Rankin scale. The primary safety outcome was symptomatic intracranial hemorrhage within 48 hours after randomization. RESULTS: A total of 456 patients were enrolled; 231 were assigned to the endovascular-therapy group and 225 to the medical-management group. Approximately 28% of the patients in both groups received intravenous thrombolysis. The trial was stopped early owing to the efficacy of endovascular therapy after the second interim analysis. At 90 days, a shift in the distribution of scores on the modified Rankin scale toward better outcomes was observed in favor of endovascular therapy over medical management alone (generalized odds ratio, 1.37; 95% confidence interval, 1.11 to 1.69; P = 0.004). Symptomatic intracranial hemorrhage occurred in 14 of 230 patients (6.1%) in the endovascular-therapy group and in 6 of 225 patients (2.7%) in the medical-management group; any intracranial hemorrhage occurred in 113 (49.1%) and 39 (17.3%), respectively. Results for the secondary outcomes generally supported those of the primary analysis. CONCLUSIONS: In a trial conducted in China, patients with large cerebral infarctions had better outcomes with endovascular therapy administered within 24 hours than with medical management alone but had more intracranial hemorrhages. (Funded by Covidien Healthcare International Trading [Shanghai] and others; ANGEL-ASPECT ClinicalTrials.gov number, NCT04551664.).


Asunto(s)
Isquemia Encefálica , Infarto Cerebral , Procedimientos Endovasculares , Accidente Cerebrovascular Isquémico , Trombectomía , Humanos , Isquemia Encefálica/tratamiento farmacológico , Isquemia Encefálica/cirugía , Infarto Cerebral/tratamiento farmacológico , Infarto Cerebral/cirugía , China , Procedimientos Endovasculares/efectos adversos , Procedimientos Endovasculares/métodos , Fibrinolíticos/efectos adversos , Fibrinolíticos/uso terapéutico , Hemorragias Intracraneales/inducido químicamente , Hemorragias Intracraneales/etiología , Accidente Cerebrovascular Isquémico/tratamiento farmacológico , Accidente Cerebrovascular Isquémico/cirugía , Estudios Prospectivos , Accidente Cerebrovascular/tratamiento farmacológico , Accidente Cerebrovascular/cirugía , Trombectomía/efectos adversos , Trombectomía/métodos , Resultado del Tratamiento
2.
J Cell Mol Med ; 28(3): e18111, 2024 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-38235996

RESUMEN

Primary angle-closure glaucoma (PACG) is the leading cause of irreversible blindness in the world. Angle closure induced by pupil block and secondary iris synechia is the fundamental pathology of the PACG. The molecular mechanisms of angle closure have not yet been clearly illustrated. This study was designed to investigate the protein difference in the aqueous humour and explore new biomarker of the PACG. Aqueous humour (AH) was collected from patients with acute primary angle closure (APAC) and cataract (n = 10 in APAC group) and patients with cataract only (n = 10 in control group). Samples were pooled and measured using label-free proteome technology. Then, the differentially expressed proteins (DEPs) were verified by ELISA using independent AH samples (n = 20 each group). More than 400 proteins were revealed in both groups through proteomics. Comparing the two groups, there were 91DEPs. These proteins participate in biological activities such as inflammation, fibrosis, nerve growth and degeneration and metabolism. We found that the expression of transforming growth factor-ß2 and matrilin2 was downregulated in the APAC group. The two proteins are related to inflammation and extracellular matrix formation, which might be involved in angle closure. This study characterized DEPs in AH of the APAC and found a downregulated protein matrilin2.


Asunto(s)
Humor Acuoso , Catarata , Humanos , Enfermedad Aguda , Humor Acuoso/metabolismo , Catarata/metabolismo , Ensayo de Inmunoadsorción Enzimática , Inflamación/metabolismo , Factor de Crecimiento Transformador beta2/metabolismo , Proteínas Matrilinas/metabolismo
3.
Anal Chem ; 96(24): 10064-10073, 2024 Jun 18.
Artículo en Inglés | MEDLINE | ID: mdl-38842443

RESUMEN

The global spread of monkeypox has become a worldwide public healthcare issue. Therefore, there is an urgent need for accurate and sensitive detection methods to effectively control its spreading. Herein, we screened by phage display two peptides M4 (sequence: DPCGERICSIAL) and M6 (sequence: SCSSFLCSLKVG) with good affinity and specificity to monkeypox virus (MPXV) B21R protein. To simulate the state of the peptide in the phage and to avoid spatial obstacles of the peptide, GGGSK was added at the C terminus of M4 and named as M4a. Molecular docking shows that peptide M4a and peptide M6 are bound to different epitopes of B21R by hydrogen bonds and salt-bridge interactions, respectively. Then, peptide M4a was selected as the capture probe, phage M6 as the detection probe, and carbonized polymer dots (CPDs) as the fluorescent probe, and a colorimetric and fluorescent double-signal capture peptide/antigen/signal peptide-displayed phage sandwich ELISA triggered by horseradish peroxidase (HRP) through a simple internal filtration effect (IFE) was constructed. HRP catalyzes H2O2 to oxidize 3,3',5,5'-tetramethylbenzidine (TMB) to generate blue oxidized TMB, which can further quench the fluorescence of CPDs through IFE, enabling to detect MPXV B21R in colorimetric and fluorescent modes. The proposed simple immunoassay platform shows good sensitivity and reliability in MPXV B21R detection. The limit of detection for colorimetric and fluorescent modes was 27.8 and 9.14 pg/mL MPXV B21R, respectively. Thus, the established double-peptide sandwich-based dual-signal immunoassay provides guidance for the development of reliable and sensitive antigen detection capable of mutual confirmation, which also has great potential for exploring various analytical strategies for other respiratory virus surveillance.


Asunto(s)
Ensayo de Inmunoadsorción Enzimática , Péptidos , Ensayo de Inmunoadsorción Enzimática/métodos , Péptidos/química , Antígenos Virales/inmunología , Antígenos Virales/análisis , Antígenos Virales/química , Simulación del Acoplamiento Molecular , Peroxidasa de Rábano Silvestre/química , Peroxidasa de Rábano Silvestre/metabolismo , Límite de Detección , Colorantes Fluorescentes/química , Biblioteca de Péptidos , Bencidinas/química , Colorimetría/métodos
4.
Small ; 20(7): e2306221, 2024 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-37803408

RESUMEN

Direct ethanol fuel cells hold great promise as a power source. However, their commercialization is limited by anode catalysts with insufficient selectivity toward a complete oxidation of ethanol for a high energy density, as well as sluggish catalytic kinetics and low stability. To optimize the catalytic performance, rationally tuning surface structure or interface structure is highly desired. Herein, a facile route is reported to the synthesis of Rh nanosheets-supported tetrahedral Rh nanocrystals (Rh THs/NSs), which possess self-supporting homogeneous interface between Rh tetrahedrons and Rh nanosheets. Due to full leverage of the structural advantages within the given structure and construction of interfaces, the Rh THs/NSs can serve as highly active electro-catalysts with excellent mass activity and selectivity toward ethanol electro-oxidation. The in situ Fourier transform infrared reflection spectroscopy showed the Rh THs/NSs exhibit the highest C1 pathway selectivity of 23.2%, far exceeding that of Rh nanotetrahedra and Rh nanosheets. Density function theory calculations further demonstrated that self-interface between Rh nanosheets and tetrahedra is beneficial for C-C bond cleavage of ethanol. Meanwhile, the self-supporting of 2D nanosheets greatly enhance the stability of tetrahedra, which improves the catalytic stability.

5.
Opt Express ; 32(11): 19825-19836, 2024 May 20.
Artículo en Inglés | MEDLINE | ID: mdl-38859108

RESUMEN

Using the three-dimensional classical ensemble approach, we theoretically investigate the nonsequential double ionization of argon atoms in an intense laser field enhanced by bowtie-nanotip. We observe an anomalous decrease in the double ionization yield as the laser intensity increases, along with a significant gap in the low momentum of photoelectrons. According to our theoretical analysis, the finite range of the induced field by the nanostructure is the fundamental cause of the decline in double ionization yield. Driven by the enhanced inhomogeneous field, energetic electrons can escape from the finite range of nanotips without returning. This reduces the possibility of re-scattering on the nucleus and imprints the finite size effect into the double ionization yield and momentum distribution of photoelectrons in the form of yield decline and a gap in the photoelectron-momentum distribution.

6.
Exp Eye Res ; 243: 109903, 2024 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-38642601

RESUMEN

Pseudoexfoliation syndrome (PEX) is characterized by the deposition of fibrous pseudoexfoliation material (PEXM) in the eye, and secondary glaucoma associated with this syndrome has a faster and more severe clinical course. The incidence of PEX and pseudoexfoliative glaucoma (PEXG) exhibits ethnic clustering; however, few proteomic studies related to PEX and PEXG have been conducted in Asian populations. Therefore, we aimed to conduct proteomic analysis on the aqueous humor (AH) obtained from Uyghur patients with cataracts, those with PEX and cataracts, and those with PEXG and cataracts to better understand the molecular mechanisms of the disease and identify its potential biomarkers. To this end, AH was collected from patients with cataracts (n = 10, control group), PEX with cataracts (n = 10, PEX group), and PEXG with cataracts (n = 10, PEXG group) during phacoemulsification. Label-free quantitative proteomic techniques combined with bioinformatics were used to identify and analyze differentially expressed proteins (DEPs) in the AH of PEX and PEXG groups. Then, independent AH samples (n = 12, each group) were collected to validate DEPs by enzyme-linked immunosorbent assay (ELISA). The PEX group exhibited 25 DEPs, while the PEXG group showed 44 DEPs, both compared to the control group. Subsequently, we found three newly identified proteins in both PEX and PEXG groups, wherein FRAS1-related extracellular matrix protein 2 (FREM2) and osteoclast-associated receptor (OSCAR) exhibited downregulation, whereas coagulation Factor IX (F9) displayed upregulation. Bioinformatics analysis suggested that extracellular matrix interactions, abnormal blood-derived proteins, and lysosomes were mainly involved in the process of PEX and PEXG, and the PPI network further revealed F9 may serve as a potential biomarker for both PEX and PEXG. In conclusion, this study provides new information for understanding the proteomics of AH in PEX and PEXG.


Asunto(s)
Humor Acuoso , Síndrome de Exfoliación , Proteínas del Ojo , Proteómica , Humanos , Síndrome de Exfoliación/metabolismo , Humor Acuoso/metabolismo , Proteómica/métodos , Masculino , Femenino , Anciano , Proteínas del Ojo/metabolismo , China/epidemiología , Glaucoma de Ángulo Abierto/metabolismo , Persona de Mediana Edad , Biomarcadores/metabolismo , Ensayo de Inmunoadsorción Enzimática , Catarata/metabolismo , Presión Intraocular/fisiología
7.
Pharmacol Res ; : 107266, 2024 Jun 13.
Artículo en Inglés | MEDLINE | ID: mdl-38878918

RESUMEN

Cerebral ischemia-reperfusion injury (I/RI) is one of the principal pathogenic factors in the poor prognosis of ischemic stroke, for which current therapeutic options to enhance neurological recovery are notably insufficient. Dental pulp stem cell-derived extracellular vesicles (DPSC-EVs) have promising prospects in stroke treatment and the specific underlying mechanisms have yet to be fully elucidated. The present study observed that DPSC-EVs ameliorated the degree of cerebral edema and infarct volume by reducing the apoptosis of neurons. Furthermore, the miRNA sequencing and functional enrichment analysis identified that miR-877-3p as a key component in DPSC-EVs, contributing to neuroprotection and anti-apoptotic effects. Following target prediction and dual-luciferase assay indicated that miR-877-3p interacted with Bcl-2-associated transcription factor (Bclaf1) to play a function. The miR-877-3p inhibitor or Bclaf1 overexpression reversed the neuroprotective effects of DPSC-EVs. The findings reveal a novel therapeutic pathway where miR-877-3p, transferred via DPSC-EVs, confers neuroprotection against cerebral I/RI, highlighting its potential in promoting neuronal survival and recovery post-ischemia.

8.
J Endovasc Ther ; : 15266028241241193, 2024 Mar 27.
Artículo en Inglés | MEDLINE | ID: mdl-38533767

RESUMEN

PURPOSE: This study aimed to evaluate the impact of the diverse stent size selection on the clinical and angiographic outcomes of Willis covered stent (WCS) for the treatment of skull base cerebrovascular diseases. MATERIALS AND METHODS: A total of 147 patients with 151 skull base cerebrovascular diseases treated with WCS in 3 centers between January 2015 and July 2022 were included in this study. Several parameters depicting stent size and parent artery condition were incorporated into the analysis of the outcomes. RESULTS: Complete occlusion was found in 106 cases (68.2%) immediately after deployment and 126 cases (83.4%) after technical adjustment. In the multivariate logistics analysis, the difference between stent diameter and parent artery diameter (DD) was significantly associated with immediate endoleak without adjustment (odds ratio [OR]=0.410; p=0.005) and late endoleak (OR=0.275; p=0.028). In addition, differences between stent diameter and parent artery diameter at wide landing point (DSW) and differences between stent diameter and parent artery diameter at narrow landing point (DSN) was also was significant associated with immediate endoleak without adjustment and balloon re-dilation respectively. CONCLUSIONS: This study demonstrated that the diameter selection of the WCS was associated with the occurrence of endoleak during the treatment of skull base cerebrovascular diseases. Precise selection and evaluation of stent size and vessel condition were significant factors for skull base cerebrovascular diseases treated by WCS. CLINICAL IMPACT: This study demonstrates a significant association between the diameter selection of the Willis covered stent (WCS) and the occurrence of endoleak in the management of skull base cerebrovascular diseases. The results offer valuable medical evidence that can inform stent selection for WCS. The study emphasizes the significance of precise evaluation of stent size and vessel condition as crucial factors in WCS procedures. These findings underscore the importance of meticulous consideration and individualized approaches to stent selection, ultimately improving treatment outcomes in clinical practice.

9.
Neurosurg Rev ; 47(1): 256, 2024 Jun 05.
Artículo en Inglés | MEDLINE | ID: mdl-38834876

RESUMEN

OBJECTIVE: White blood cells (WBC) play an important role in the inflammatory response of the body. Elevated WBC counts on admission in patients with subarachnoid hemorrhage (SAH) correlate with a poor prognosis. However, the role of longitudinal WBC trajectories based on repeated WBC measurements during hospitalization remains unclear. We explored the association between different WBC trajectory patterns and in-hospital mortality. METHODS: We analyzed a cohort of consecutive patients with SAH between 2012 and 2020. Group-based trajectory modeling (GBTM) was used to group the patients according to their white blood cell patterns over the first 4 days. Stabilized inverse probability treatment weighting (sIPTW) was used to balance baseline demographic and clinical characteristics. We analyzed the association between the WBC trajectory groups and in-hospital mortality using a Cox proportional hazards model. RESULTS: In total, 506 patients with SAH were included in this retrospective cohort. The final model identified two distinct longitudinal WBC trajectories. After adjusting for confounding factors, multivariate regression analysis suggested that an elevated longitudinal WBC trajectory increased the risk of in-hospital mortality (hazard ratio [HR], 2.476; 95% confidence interval [CI] 1.081-5.227; P = 0.024) before sIPTW, and (HR, 2.472; 95%CI 1.489-4.977; P = 0.018) after sIPTW. CONCLUSION: In patients with SAH, different clinically relevant groups could be identified using WBC trajectory analysis. The WBC count trajectory-initially elevated and then decreased- may lead to an increased risk of in-hospital mortality following SAH.


Asunto(s)
Mortalidad Hospitalaria , Hemorragia Subaracnoidea , Humanos , Hemorragia Subaracnoidea/mortalidad , Hemorragia Subaracnoidea/sangre , Masculino , Femenino , Persona de Mediana Edad , Anciano , Recuento de Leucocitos , Estudios Retrospectivos , Inflamación , Adulto , Pronóstico , Estudios de Cohortes
10.
Biochem Genet ; 2024 Jun 19.
Artículo en Inglés | MEDLINE | ID: mdl-38898268

RESUMEN

Osteoporosis, in which bones become fragile owing to low bone density and impaired bone mass, is a global public health concern. Bone mineral density (BMD) has been extensively evaluated for the diagnosis of low bone mass and osteoporosis. Circulating monocytes play an indispensable role in bone destruction and remodeling. This work proposed a machine learning-based framework to investigate the impact of circulating monocyte-associated genes on bone loss in osteoporosis patients. Females with discordant BMD levels were included in the GSE56815, GSE7158, GSE7429, and GSE62402 datasets. Circulating monocyte types were quantified via CIBERSORT, with subsequent selection of plasma cell-associated DEGs. Generalized linear models, random forests, extreme gradient boosting (XGB), and support vector machines were adopted for feature selection. Artificial neural networks and nomograms were subsequently constructed for osteoporosis diagnosis, and the molecular machinery underlying the identified genes was explored. SVM outperformed the other tuned models; thus, the expression of several genes (DEFA4, HLA-DPB1, LCN2, HP, and GAS7) associated with osteoporosis were determined. ANNs and nomograms were proposed to robustly distinguish low and high BMDs and estimate the risk of osteoporosis. Clozapine, aspirin, pyridoxine, etc. were identified as possible treatment agents. The expression of these genes is extensively posttranscriptionally regulated by miRNAs and m6A modifications. Additionally, they participate in modulating key signaling pathways, e.g., autophagy. The machine learning framework based on plasma cell-associated feature genes has the potential for estimating personalized risk stratification and treatment vulnerability in osteoporosis patients.

11.
J Stroke Cerebrovasc Dis ; 33(8): 107833, 2024 Jun 24.
Artículo en Inglés | MEDLINE | ID: mdl-38925449

RESUMEN

BACKGROUND AND PURPOSE: Flow-diversion treatment for intracranial aneurysms has been associated with the development of in-stent stenosis (ISS) for unclear reasons. We assess whether the size of the stent relative to that of the vessel (the stent-to-vessel diameter ratio, or SVR) may be predictive of the development of ISS after treatment with flow diverters. METHODS: We retrospectively reviewed patients with unruptured intracranial aneurysms who underwent flow-diversion treatment using either the Pipeline or Tubridge embolization device from September 2018 to September 2022. The relationship between SVR and ISS was analyzed. Multiple logistic regression models were used to determine the significant predictors. RESULTS: A total of 458 patients with 481 aneurysms were included. In a mean angiographic follow-up of 10.73 ± 3.97 months, ISS was detected in 68 cases (14.1 %). After adjusting for candidate variables, a higher distal SVR (DSVR) was associated with an increased risk of ISS (adjusted odds ratio [aOR] = 3.420, 95 % confidence interval [CI] = 1.182 - 9.889, p = 0.023). We conducted a subgroup analysis of the two different flow diverters to assess the effects of their individual characteristics. Our results showed a significant association between the DSVR and the incidence of ISS in both the Pipeline (aOR = 4.033, 95 % CI = 1.156-14.072, p = 0.029) and Tubridge groups (aOR = 11.981, 95 % CI=1.005-142.774, p = 0.049). CONCLUSION: A higher DSVR was associated with an increased risk of ISS. This may help neurointerventionalists select an appropriate stent size when conducting flow-diversion treatment for intracranial aneurysms.

12.
J Perianesth Nurs ; 2024 Feb 26.
Artículo en Inglés | MEDLINE | ID: mdl-38416105

RESUMEN

PURPOSE: The postanesthesia care unit (PACU) is an indispensable part of modern medicine which provides critical care to patients to ensure safe and smooth emergence from anesthesia. The adverse events in the PACU have been widely investigated in adults. However, little is known about the adverse events in pediatric populations. This study was designed to investigate adverse events, including the incidence, disease spectrum, and possible risk factors, in pediatric patients in the PACU at a tertiary pediatric hospital. DESIGN: This is a retrospective observational study. METHODS: Children admitted to the PACU at the Children's Hospital of Fudan University from September 2021 to August 2022 were included in the study. The following adverse events were recorded: hypothermia, fever, adverse airway events, hypotension, hypertension, prolonged length of stay in PACU, pain, reintubation, neurological events, unplanned admission to the intensive care unit, arrhythmia, water-electrolyte imbalance, and bleeding requiring medical intervention. Descriptive analyses, t tests, and χ2 tests were performed. FINDINGS: A total of 16,012 children were included in the study, and 305 adverse events occurred in 237 (1.48%) children. The three most frequently occurring adverse events were prolonged stay in the PACU (8.4%), adverse airway events (5.6%), and abnormal temperature (2.7%). Age, American Society of Anesthesiologists' grade, and general surgery were independent risk factors of both overall adverse events and prolonged stay in the PACU in multivariate logistic regression analysis. Children with adverse events stayed in the PACU significantly longer than those without adverse events (60.04 ± 1.01 vs 95.8 ± 47.25 minutes, P < .05). Compared with the other surgeries, a significantly higher proportion of severe pain (37.5% vs 0%) after thoracic surgery, prolonged stay in the PACU (52.9% vs 36.4%) after general surgery, and neurological events (14.7% vs 0%) after neurological surgery was detected, while a significantly lower proportion of adverse airway events after general surgery (21.1% vs 43%) and neurological surgery (8.8% vs 43%) was detected, respectively. CONCLUSIONS: Our study reports the current incidence and spectrum of adverse events in the PACU at a tertiary pediatric hospital. Patients with young age, high American Society of Anesthesiologists' grade, and those from the general surgery department are at a significantly increased risk of adverse events in the PACU. Significant differences were detected in the proportion of specific adverse events after specific surgeries.

13.
Anal Chem ; 95(30): 11359-11364, 2023 08 01.
Artículo en Inglés | MEDLINE | ID: mdl-37464726

RESUMEN

Signal amplification techniques are highly desirable for the analysis of low-level targets that are closely related with diseases and the monitoring of important biological processes. However, it is still challenging to achieve this goal in a facile and economical way. Herein, we developed a novel dual signal amplification strategy by combining urease catalysis with the release of Ag+ from silver nanoparticles (AgNPs). This strategy was used for quantifying a DNA sequence (HIV-1) related with human immunodeficiency virus (HIV). DNA target HIV-1 hybridizes with the capture DNA probe on magnetic beads and the reporter DNA probe on AgNPs, forming a sandwich complex. The captured AgNPs are then transformed into numerous Ag+ ions that inactivate numerous ureases. Without catalytic production of ammonia from urea, the substrate solution shows a low pH 5.8 that will increase otherwise. The pH change is monitored by a pH indicator (phenol red), which allows for colorimetric detection. The proposed approach is sensitive, easy to use, economic, and universal, exhibiting a low detection limit of 9.7 fM (i.e., 1.94 attomoles) and a dynamic linear range of 4 orders for HIV-1 sequence detection.


Asunto(s)
Técnicas Biosensibles , Nanopartículas del Metal , Ácidos Nucleicos , Humanos , Plata , Ureasa , Colorimetría , Sondas de ADN , Catálisis , Técnicas Biosensibles/métodos , Técnicas de Amplificación de Ácido Nucleico
14.
Anal Chem ; 95(33): 12532-12540, 2023 08 22.
Artículo en Inglés | MEDLINE | ID: mdl-37553756

RESUMEN

Rapid and sensitive antigen detection using a lateral flow immunoassay (LFIA) is crucial for diagnosing infectious diseases due to its simplicity, speed, and user-friendly features. However, it remains a critical issue to explore specific biorecognition elements and powerful signal amplification. In this study, taking SARS-CoV-2 as a proof of concept, a specific peptide, WFLNDSELIML, binding to the SARS-CoV-2 spike (S) antigen was identified by a nonamplified biopanning method, which exhibited high affinity to the target, with a dissociation constant of 9.29 ± 1.55 nM. Molecular docking analysis reveals that this peptide binds to the N-terminal domain of the SARS-CoV-2 S antigen. Then, using this peptide as a capture probe and angiotensin-converting enzyme 2 as a detection probe, a peptide-based lateral flow immunoassay (pLFIA) for the sensitive detection of the SARS-CoV-2 S antigen without any antibody was developed, for which a polydopamine nanosphere (PDA)@MnO2 nanocomposite with excellent oxidase-like activity was used as a colorimetric label, exhibiting dual-mode remarkable signal amplification of natural melanin and on-demand nanozyme catalytic enhancement. The PDA@MnO2-based pLFIA is capable of detecting the SARS-CoV-2 S antigen with a limit of detection of 8.01 pg/mL, which is 18.7 times lower than that of a conventional pLFIA tagged with gold nanoparticles. Additionally, the as-proposed PDA@MnO2-based pLFIA can detect up to 150 transduction units/mL SARS-CoV-2 pseudoviruses spiked in saliva samples. Given the outstanding analytical performance, the proposed PDA@MnO2-based pLFIA may offer a reliable option for the rapid diagnosis of SARS-CoV-2.


Asunto(s)
Antígenos de Grupos Sanguíneos , COVID-19 , Nanopartículas del Metal , Humanos , COVID-19/diagnóstico , Oro , Compuestos de Manganeso , Simulación del Acoplamiento Molecular , Óxidos , SARS-CoV-2 , Inmunoensayo
15.
J Transl Med ; 21(1): 106, 2023 02 10.
Artículo en Inglés | MEDLINE | ID: mdl-36765373

RESUMEN

The Bacillus Calmette-Guérin (BCG) vaccine was discovered a century ago and has since been clinically applicable. BCG can not only be used for the prevention of tuberculosis, but also has a non-specific protective effect on the human body called trained immunity that is mediated by innate immune cells such as monocytes, macrophages, and natural killer cells. Mechanisms of trained immunity include epigenetic reprogramming, metabolic reprogramming, and long-term protection mediated by hematopoietic stem cells. Trained immunity has so far shown beneficial effects on cancer, viral-infections, autoimmune diseases, and a variety of other diseases, especially bladder cancer, respiratory viruses, and type 1 diabetes. The modulation of the immune response by BCG has led to the development of a variety of recombinant vaccines. Although the specific mechanism of BCG prevention on diseases has not been fully clarified, the potential role of BCG deserves further exploration, which is of great significance for prevention and treatment of diseases.


Asunto(s)
Mycobacterium bovis , Tuberculosis , Humanos , Vacuna BCG/uso terapéutico , Inmunidad Entrenada , Tuberculosis/prevención & control , Macrófagos , Inmunidad Innata
16.
J Magn Reson Imaging ; 57(1): 113-123, 2023 01.
Artículo en Inglés | MEDLINE | ID: mdl-35652452

RESUMEN

BACKGROUND: Aneurysm inflow angle has been shown to be associated with hemodynamic changes by computational fluid dynamics. However, these studies were based on single aneurysm model and were limited to side-wall aneurysms. PURPOSE: To investigate the association between inflow angle and morphology, hemodynamic, and inflammation of intracranial side-wall and bifurcation aneurysms. STUDY TYPE: Prospective. POPULATION: A total of 62 patients (aged 58.34 ± 12.39, 44 female) with 59 unruptured side-wall aneurysms and 17 unruptured bifurcation aneurysms were included. FIELD STRENGTH/SEQUENCE: A 3.0 T; 3D fast field echo sequence (TOF-MRA); free-breathing, 3D radio-frequency-spoiled, multi-shot turbo field echo sequence (4D-flow MRI); 3D black-blood T1-weighted volumetric turbo spin echo acquisition sequence (T1 -VISTA) ASSESSMENT: Two neuroradiologists assessed the inflow angle and size for intracranial aneurysms in 3D space with TOF-MRA images. The average and maximum inflow velocity (Vavg-IA , Vmax-IA ), blood flow (Flowavg-IA , Flowmax-IA ), and average wall shear stress (WSSavg-IA ) for aneurysms were assessed from 4D-flow MRI in regions of interest drawn by two neuroradiologists. The aneurysmal wall enhancement (AWE) grades between precontrast and postcontrast T1 -VISTA images were evaluated by three neuroradiologists. STATISTICAL TESTS: Kruskal-Wallis H test, χ2 test, Pearson's correlation coefficient, scatter plots and regression lines, multivariate logistic regression analysis (partial correlation r) were performed. A P < 0.05 was considered statistically significant. RESULTS: The WSSavg-IA (0.52 ± 0.34 vs. 0.27 ± 0.22) and AWE grades (1.38 ± 1.04 vs. 2.02 ± 0.68) between the two inflow angle subgroups of side-wall aneurysms were significantly different. The aneurysm size (rs  = 0.31), WSSavg-IA (rs  = -0.45), and AWE grades (rs  = 0.45) were significantly correlated with inflow angle in side-wall aneurysms. While in bifurcation aneurysms, there were no significant associations between inflow angle and size (P = 0.901), Vavg-IA (P = 0.699), Vmax-IA (P = 0.482), Flowavg-IA (P = 0.550), Flowmax-IA (P = 0.689), WSSavg-IA (P = 0.573), and AWE grades (P = 0.872). DATA CONCLUSION: A larger aneurysm size, a lower WSS and a higher AWE grade were correlated with a larger inflow angle in side-wall aneurysms. EVIDENCE LEVEL: 3 TECHNICAL EFFICACY: Stage 2.


Asunto(s)
Aneurisma Intracraneal , Humanos , Femenino , Aneurisma Intracraneal/diagnóstico por imagen , Estudios Prospectivos , Imagenología Tridimensional , Hemodinámica/fisiología , Imagen por Resonancia Magnética , Inflamación/diagnóstico por imagen
17.
Eur Radiol ; 33(11): 7967-7977, 2023 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-37314476

RESUMEN

OBJECTIVES: We aim to investigate associations between different coil strategies and outcomes in the aneurysms treated by a pipeline embolization device (PED). METHODS: Patients with medium-to-giant-sized aneurysms treated by PED were included. The total cohort was divided into PED-alone and PED-coiling groups, and the PED-coiling group was further divided into loose and dense packing subgroups. Multivariate logistic analyses and stabilized inverse probability of treatment weighting (sIPTW) were performed to investigate the relationships between coiling strategies and outcomes. Restricted cubic spline (RCS) curves were used to describe the coiling degree and angiographic outcome relationship. RESULTS: A total of 398 patients with 410 aneurysms were included. Aneurysms treated with PED coiling had a lower incomplete occlusion rate (15.3% vs. 30.3%, p = 0.002), higher total perioperative complication rate (14.2% vs. 3.5%, p = 0.001), longer production time (142.14 min vs. 101.26 min, p < 0.001), and higher total cost ($45,158.63 vs. $34,680.91, p < 0.001) than those treated with PED alone. There were no differences in outcomes between the loose and dense packing subgroups. However, the total cost was higher in the dense packing group ($43,787.46 vs. $47,288.32, p = 0.001) than in the loose packing group. The result was still robust in the multivariate and sIPTW analyses. The RCS curves showed "L-shape" relationships between the coil degree and angiographic outcomes. CONCLUSION: Compared with PED alone, PED coiling could improve aneurysm occlusion. However, it could also increase the total complication risk, prolong procedure time, and increase the total cost. Compared with loose packing, dense packing did not enhance the treatment effectiveness but increased the treatment cost. CLINICAL RELEVANCE STATEMENT: The additional treatment effect from coiling embolization declines sharply after a certain point. Specifically, the aneurysm occlusion rate is roughly stable when the coil number is greater than 3 or the total coil length is longer than 150 cm. KEY POINTS: • Compared with pipeline embolization device (PED) alone, PED combined with coiling can improve aneurysm occlusion. • Compared with PED alone, PED combined with coiling increases the total complication risk, cost, and prolongs procedure time. • Compared with loose packing, dense packing did not increase the treatment effectiveness but increased the cost.


Asunto(s)
Embolización Terapéutica , Aneurisma Intracraneal , Humanos , Aneurisma Intracraneal/terapia , Aneurisma Intracraneal/cirugía , Puntaje de Propensión , Embolización Terapéutica/métodos , Prótesis Vascular , Resultado del Tratamiento , Angiografía de Substracción Digital , Estudios Retrospectivos
18.
Eur Radiol ; 2023 Oct 16.
Artículo en Inglés | MEDLINE | ID: mdl-37843574

RESUMEN

OBJECTIVES: To design a deep learning-based framework for automatic segmentation and detection of intracranial aneurysms (IAs) on magnetic resonance T1 images and test the robustness and performance of framework. METHODS: A retrospective diagnostic study was conducted based on 159 IAs from 136 patients who underwent the T1 images. Among them, 127 cases were randomly selected for training and validation, and 32 cases were used to assess the accuracy and consistency of our algorithm. We developed and assembled three convolutional neural networks for the segmentation and detection of IAs. The segmentation and detection performance of the model were compared with the ground truth, and various metrics were calculated at the voxel level, IAs level, and patient level to show the performance of our framework. RESULTS: Our assembled model achieved overall Dice, voxel-level sensitivity, specificity, balanced accuracy, and F1 score of 0.802, 0.874, 0.9998, 0.937, and 0.802, respectively. A coincidence greater than 0.7 between the aneurysms predicted by the model and the ground truth was considered as a true positive. For IAs detection, the sensitivity reached 90.63% with 0.58 false positives per case. The volume of IAs segmented by our model showed a high agreement and consistency with the volume of IAs labeled by experts. CONCLUSION: The deep learning framework is achievable and robust for IAs segmentation and detection. Our model offers more clinical application opportunities compared to digital subtraction angiography (DSA)-based, CTA-based, and MRA-based methods. CLINICAL RELEVANCE STATEMENT: Our deep learning framework effectively detects and segments intracranial aneurysms using clinical routine T1 sequences, showing remarkable effectiveness and offering great potential for improving the detection of latent intracranial aneurysms and enabling early identification. KEY POINTS: •There is no segmentation method based on clinical routine T1 images. Our study shows that the proper deep learning framework can effectively localize the intracranial aneurysms. •The T1-based segmentation and detection method is more universal than other angiography-based detection methods, which can potentially reduce missed diagnoses caused by the absence of angiography images. •The deep learning framework is robust and has the potential to be applied in a clinical setting.

19.
Eur Radiol ; 33(7): 4918-4926, 2023 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-36840766

RESUMEN

OBJECTIVE: This cross-sectional study aimed to investigate the associations between aneurysm wall enhancement (AWE), atherosclerotic protein levels, and aneurysm size in unruptured intracranial fusiform aneurysms (IFAs). METHODS: Patients with IFAs underwent high-resolution magnetic resonance imaging (HR-MRI) and atherosclerotic protein examinations from May 2015 to December 2021 were collected. A CRstalk (signal intensity [SI] of IFA wall/SI of pituitary stalk) > 0.60 was considered to indicate AWE. Atherosclerotic protein data was obtained from the peripheral blood. Aneurysmal characteristics included the maximal diameter of the cross-section (Dmax), location, type of IFA, presence of mural thrombus, and mural clots. Statistical analyses were performed with univariate analysis, logistic regression analysis, and Spearman's correlation coefficient. RESULTS: Seventy-one IFAs from 71 patients were included in the study. Multivariate analysis revealed statin use (OR = 0.189, p = 0.026) and apolipoprotein B (Apo-B) level (OR = 6.019, p = 0.026) were the independent predictors of AWE in IFAs. In addition, statin use (OR = 0.813, p = 0.036) and Apo-B level (OR = 1.610, p = 0.003) were also the independent predictors of CRstalk. Additionally, we found that CRstalk and AWE were significantly positively associated with Dmax (rs = 0.409 and 0.349, respectively; p < 0.001 and p = 0.003, respectively). CONCLUSIONS: There may be correlations between AWE, atherosclerotic protein levels, and aneurysm size in patients with IFAs. Apo-B and statin use were independent predictors of AWE in IFAs, which have the potential to be new therapeutic targets for IFAs. KEY POINTS: • There may be correlations between aneurysm wall enhancement, atherosclerotic protein levels in the peripheral blood, and aneurysm size in patients with intracranial fusiform aneurysms. • Apolipoprotein B and statin use were independent predictors of aneurysm wall enhancement in intracranial fusiform aneurysms.


Asunto(s)
Inhibidores de Hidroximetilglutaril-CoA Reductasas , Aneurisma Intracraneal , Trombosis , Humanos , Estudios Transversales , Inhibidores de Hidroximetilglutaril-CoA Reductasas/uso terapéutico , Aneurisma Intracraneal/diagnóstico por imagen , Aneurisma Intracraneal/patología , Imagen por Resonancia Magnética/métodos , Apolipoproteínas
20.
BMC Neurol ; 23(1): 45, 2023 Jan 28.
Artículo en Inglés | MEDLINE | ID: mdl-36709247

RESUMEN

BACKGROUND: Small multiple intracranial aneurysms (SMIAs) are known to be more prone to rupture than are single aneurysms. However, specific recommendations for patients with small MIAs are not included in the guidelines of the American Heart Association and American Stroke Association. In this study, we aimed to evaluate the feasibility of machine learning-based cluster analysis for discriminating the risk of rupture of SMIAs. METHODS: This multi-institutional cross-sectional study included 1,427 SMIAs from 660 patients. Hierarchical cluster analysis guided patient classification based on patient-level characteristics. Based on the clusters and morphological features, machine learning models were constructed and compared to screen the optimal model for discriminating aneurysm rupture. RESULTS: Three clusters with markedly different features were identified. Cluster 1 (n = 45) had the highest risk of subarachnoid hemorrhage (SAH) (75.6%) and was characterized by a higher prevalence of familiar IAs. Cluster 2 (n = 110) had a moderate risk of SAH (38.2%) and was characterized by the highest rate of SAH history and highest number of vascular risk factors. Cluster 3 (n = 505) had a relatively mild risk of SAH (17.6%) and was characterized by a lower prevalence of SAH history and lower number of vascular risk factors. Lasso regression analysis showed that compared with cluster 3, clusters 1 (odds ratio [OR], 7.391; 95% confidence interval [CI], 4.074-13.150) and 2 (OR, 3.014; 95% CI, 1.827-4.970) were at a higher risk of aneurysm rupture. In terms of performance, the area under the curve of the model was 0.828 (95% CI, 0.770-0.833). CONCLUSIONS: An unsupervised machine learning-based algorithm successfully identified three distinct clusters with different SAH risk in patients with SMIAs. Based on the morphological factors and identified clusters, our proposed model has good discrimination ability for SMIA ruptures.


Asunto(s)
Aneurisma Roto , Aneurisma Intracraneal , Hemorragia Subaracnoidea , Humanos , Aneurisma Intracraneal/epidemiología , Aneurisma Intracraneal/complicaciones , Estudios Transversales , Hemorragia Subaracnoidea/epidemiología , Hemorragia Subaracnoidea/etiología , Análisis por Conglomerados , Factores de Riesgo , Aneurisma Roto/epidemiología , Aneurisma Roto/complicaciones , Aprendizaje Automático
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