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Current therapeutic strategies for ischemic stroke fall short of the desired objective of neurological functional recovery. Therefore, there is an urgent need to develop new methods for the treatment of this condition. Exosomes are natural cell-derived vesicles that mediate signal transduction between cells under physiological and pathological conditions. They have low immunogenicity, good stability, high delivery efficiency, and the ability to cross the blood-brain barrier. These physiological properties of exosomes have the potential to lead to new breakthroughs in the treatment of ischemic stroke. The rapid development of nanotechnology has advanced the application of engineered exosomes, which can effectively improve targeting ability, enhance therapeutic efficacy, and minimize the dosages needed. Advances in technology have also driven clinical translational research on exosomes. In this review, we describe the therapeutic effects of exosomes and their positive roles in current treatment strategies for ischemic stroke, including their anti-inflammation, anti-apoptosis, autophagy-regulation, angiogenesis, neurogenesis, and glial scar formation reduction effects. However, it is worth noting that, despite their significant therapeutic potential, there remains a dearth of standardized characterization methods and efficient isolation techniques capable of producing highly purified exosomes. Future optimization strategies should prioritize the exploration of suitable isolation techniques and the establishment of unified workflows to effectively harness exosomes for diagnostic or therapeutic applications in ischemic stroke. Ultimately, our review aims to summarize our understanding of exosome-based treatment prospects in ischemic stroke and foster innovative ideas for the development of exosome-based therapies.
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D-mannitol is a six-carbon sugar alcohol and one of the most abundant polyols in the nature. With antioxidant and osmotic pressure-regulating effects and non-metabolism by the human body, D-mannitol has been widely used in functional food and pharmaceutical industries. At present, a major way for industrial production of D-mannitol is chemical hydrogenation. In addition, D-Mannitol can be produced by microbial metabolism or catalysis. Compared with the chemical hydrogenation, the microbial methods for synthesizing mannitol do not produce sorbitol as a by-product and have the advantages of mild reaction conditions, strong specificity, and high conversion rate. Microbial fermentation is praised for easy access of strains and raw materials and simple separation of the product. Microbial catalysis usually adopts a multi-enzyme coupling strategy, which uses enzymes produced by engineered bacteria for whole-cell catalysis, and the cofactor recycling pathway is introduced to replenish expensive cofactor. This method can achieve high yields with cheap substrates under mild conditions without the formation of by-products. However, the application of microbial methods in the industrial production of D-mannitol is limited by the high costs of fermentation media and substrates and the long reaction time. This article reviews the reported microbial methods for producing D-mannitol, including the use of high-yielding strains and their fermentation processes, the utilization of low-cost substrates, whole-cell catalytic strategies, and the process control for high productivity. The biosynthesis of mannitol is not only of great significance for promoting industrial upgrading and realizing green manufacturing, but also provides strong support for the development of new bio-based products to meet the growing market demand. With the continuous improvement of technological innovation and industrial chain, it is expected to become one of the main ways of mannitol production in the future.
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Fermentación , Microbiología Industrial , Manitol , Manitol/metabolismo , Microbiología Industrial/métodos , Bacterias/metabolismo , Bacterias/genética , Ingeniería Metabólica/métodosRESUMEN
The underlying mechanisms of diseases affecting the central nervous system (CNS) remain unclear, limiting the development of effective therapeutic strategies. Remarkably, cellular senescence, a biological phenomenon observed in cultured fibroblasts in vitro, is a crucial intrinsic mechanism that influences homeostasis of the brain microenvironment and contributes to the onset and progression of CNS diseases. Cellular senescence has been observed in disease models established in vitro and in vivo and in bodily fluids or tissue components from patients with CNS diseases. These findings highlight cellular senescence as a promising target for preventing and treating CNS diseases. Consequently, emerging novel therapies targeting senescent cells have exhibited promising therapeutic effects in preclinical and clinical studies on aging-related diseases. These innovative therapies can potentially delay brain cell loss and functional changes, improve the prognosis of CNS diseases, and provide alternative treatments for patients. In this study, we examined the relevant advancements in this field, particularly focusing on the targeting of senescent cells in the brain for the treatment of chronic neurodegenerative diseases (e.g., Alzheimer's disease, Parkinson's disease, and multiple sclerosis) and acute neurotraumatic insults (e.g., ischemic stroke, spinal cord injury, and traumatic brain injury).
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The objective of this study was to investigate the potential mechanisms by which (+)-catechin alleviates neuropathic pain. Thirty-two male Sprague-Dawley rats were divided into four groups: the sham group, the chronic constriction injury (CCI)group, the CCI+ ibuprofen group, and the CCI+ (+)-catechin group. CCI surgery induces thermal hyperalgesia in rats and (+)-catechin ameliorated CCI-induced thermal hyperalgesia and repaired damaged sciatic nerve in rats. CCI decreased SOD levels in male rat spinal cord dorsal horn and promoted MDA production, induced oxidative stress by increasing NOX4 levels and decreasing antioxidant enzyme HO-1 levels, and also increased protein levels of TLR4, p-NF-κB, NLRP3 inflammasome components, and IL-1ß. In contrast, (+)-catechin reversed the above results. In i vitro experiments, (+)-catechin reduced the generation of reactive oxygen species (ROS) in GMI-R1 cells after LPS stimulation and attenuated the co-expression of IBA-1 and NLRP3. It also showed significant inhibition of the NF-κB and NLRP3 inflammatory pathways and activation of the Nrf2-mediated antioxidant system. Overall, these findings suggest that (+)-catechin inhibits the activation of the NLRP3 inflammasome through the triggering of the Nrf2-induced antioxidant system, the inhibition of the TLR4/NF-κB pathway, and the production of ROS to alleviate CCI-induced neuropathic pain in male rats.
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Antioxidantes , Catequina , Inflamasomas , Proteína con Dominio Pirina 3 de la Familia NLR , Neuralgia , Transducción de Señal , Animales , Masculino , Ratas , Antioxidantes/farmacología , Catequina/farmacología , Hiperalgesia/metabolismo , Hiperalgesia/tratamiento farmacológico , Inflamasomas/metabolismo , Inflamasomas/efectos de los fármacos , Neuralgia/metabolismo , Neuralgia/tratamiento farmacológico , Factor 2 Relacionado con NF-E2/metabolismo , FN-kappa B/metabolismo , Proteína con Dominio Pirina 3 de la Familia NLR/metabolismo , Estrés Oxidativo/efectos de los fármacos , Ratas Sprague-Dawley , Especies Reactivas de Oxígeno/metabolismo , Transducción de Señal/efectos de los fármacos , Receptor Toll-Like 4/metabolismo , Receptor Toll-Like 4/efectos de los fármacosRESUMEN
Iron accumulation in tumors contributes to disease progression and chemoresistance. While targeting this process can influence various hallmarks of cancer, the immunomodulatory effects of iron chelation in the tumor microenvironment are unknown. Here, we report that treatment with deferiprone, an FDA-approved iron chelator, unleashes innate immune responses that restrain ovarian cancer. Deferiprone reprogrammed ovarian cancer cells towards an immunostimulatory state characterized by production of type I interferon (IFN) and overexpression of molecules that activate natural killer (NK) cells. Mechanistically, these effects were driven by innate sensing of mitochondrial DNA in the cytosol and concomitant activation of nuclear DNA damage responses triggered upon iron chelation. Deferiprone synergized with chemotherapy and prolonged the survival of mice with ovarian cancer by bolstering type I IFN responses that drove NK cell-dependent control of metastatic disease. Hence, iron chelation may represent an alternative immunotherapeutic strategy for malignancies that are refractory to current T cell-centric modalities.
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Molecular materials possessing switchable magneto-optical properties are of great interest due to their potential applications in spintronics and molecular devices. However, switching their photoluminescence (PL) and single-molecule magnet (SMM) behavior via light-induced structural changes still constitutes a formidable challenge. Here, a series of cubane structures were synthesized via self-assembly of 9-anthracene carboxylic acid (HAC) and rare-earth ions. All complexes exhibited obvious photochromic phenomena and complete PL quenching upon Xe lamp irradiation, which were realized via the synergistic effect of photogenerated radicals and [4 + 4] photocycloaddition of the AC components. The quenched PL showed the largest fluorescence intensity change (99.72%) in electron-transfer photochromic materials. A reversible decoloration process was realized via mechanical grinding, which is unexpectedly in the electron-transfer photochromic materials. Importantly, an SMM behavior of the Dy analog was observed after room-temperature irradiation due to the photocycloaddition of AC ligands and the photogenerated stable radicals changed the electrostatic ligand field and magnetic coupling. Moreover, based on the remarkably photochromic and photoluminescent properties of these compounds, 2 demos were applied to support their application in information anti-counterfeiting and inkless printing. This work, for the first time utilizing the simultaneous modulation of photocycloaddition and photogenerated radicals in one system, realizes complete PL quenching and light-induced SMM behavior, providing a dynamical switch for the construction of multifunctional polymorphic materials with optical response and optical storage devices.
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COVID-19 , Modelo de Creencias sobre la Salud , Accidente Cerebrovascular Isquémico , Prevención Secundaria , Humanos , COVID-19/prevención & control , COVID-19/epidemiología , COVID-19/psicología , China/epidemiología , Accidente Cerebrovascular Isquémico/prevención & control , Prevención Secundaria/métodos , Intervención basada en la Internet , Masculino , Femenino , Cuarentena/psicología , Persona de Mediana Edad , Educación del Paciente como Asunto/métodosRESUMEN
In this experiment, the eutrophication system was established by adding sucrose and yeast powder, and the pH and dissolved oxygen were measured in a bioreactor in real time to study the effect of aerobic environment on the fermentation process of Polygonati Rhizoma extract by Lactiplantibacillus plantarum. To further analyze metabolic changes, UPLC-Q-Exactive MS was used for metabolomic analysis and metabolic profiling. Multivariate analysis was performed using principal component analysis and Orthogonal projections to latent structures discriminant analysis. Finally, 313 differential metabolites were selected, 196 of which were annotated through database matching. After fermentation, the content of short-chain fatty acids, lactic acid, and their derivatives increased significantly, and there were 13 kinds and 4 kinds, respectively. Both compounds and their derivatives are beneficial to the intestinal flora. Consequently, incorporating L. plantarum into the aerobic fermentation process of Polygonati Rhizoma extract within the eutrophic system is potentially advantageous in enhancing the impact of its fermentation solution on the gut microbiota and its effects on human health. Our findings for this kind of edible and medicinal material research and development offer useful insights.
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Fermentación , Lactobacillus plantarum , Polygonatum , Rizoma , Polygonatum/química , Polygonatum/metabolismo , Rizoma/química , Lactobacillus plantarum/metabolismo , Eutrofización , Extractos Vegetales/metabolismo , Extractos Vegetales/química , Ácido Láctico/metabolismo , Ácidos Grasos Volátiles/metabolismo , Reactores Biológicos/microbiología , Microbioma Gastrointestinal , MetabolómicaRESUMEN
BACKGROUND: Beat-to-beat blood pressure variability (BPV) is based on each heartbeat and represents a dynamic equilibrium process modulated by artery and cardiac involvement of pressure-receptive reflexes. To date, there remains a lack of prospective studies illustrating the clinical value of beat-to-beat BPV within 24 hours of acute ischemic stroke onset. METHODS AND RESULTS: This study prospectively monitored beat-to-beat blood pressure and heart rate in patients with acute ischemic stroke within 24 hours of onset using a noninvasive plethysmograph and calculated beat-to-beat BPV, heart rate variability, and the cross-correlation baroreflex sensitivity. A modified Rankin Scale score of ≥2 at 90 days was defined as an unfavorable prognosis. Multivariate logistic regression was performed, and the nomogram model was developed by adding the beat-to-beat BPV to the traditional model for predicting prognosis. Beat-to-beat BPV increased significantly in the unfavorable outcome group (P<0.05) compared with that in the favorable outcome group, whereas no difference was observed in beat-to-beat heart rate variability and cross-correlation baroreflex sensitivity between both groups (P>0.05). Furthermore, beat-to-beat BPV within 24 hours of acute ischemic stroke onset was independently associated with unfavorable outcome at 90 days (P<0.005). The addition of beat-to-beat BPV to the traditional model for predicting prognosis enhanced the area under the receiver operating characteristic curve from 0.816 to 0.830. CONCLUSIONS: Increased beat-to-beat BPV within 24 hours of acute ischemic stroke onset was independently associated with a poor prognosis at 90 days and may be a potential predictor for discriminating unfavorable prognosis.
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Barorreflejo , Presión Sanguínea , Frecuencia Cardíaca , Accidente Cerebrovascular Isquémico , Humanos , Masculino , Femenino , Presión Sanguínea/fisiología , Frecuencia Cardíaca/fisiología , Anciano , Accidente Cerebrovascular Isquémico/fisiopatología , Accidente Cerebrovascular Isquémico/diagnóstico , Pronóstico , Barorreflejo/fisiología , Estudios Prospectivos , Persona de Mediana Edad , Factores de Tiempo , Valor Predictivo de las Pruebas , Nomogramas , Pletismografía , Anciano de 80 o más Años , Estado FuncionalRESUMEN
RATIONALE: To date, the benefit of intravenous thrombolysis for acute ischemic stroke (AIS) patients without advanced neuroimaging selection is confined to within 4.5 h of onset. Our phase II EXIT-BT (Extending the tIme window of Thrombolysis by ButylphThalide up to 6 h after onset) trial suggested the safety, feasibility, and potential benefit of intravenous tenecteplase (TNK) in AIS between 4.5 and 6 h of onset. The EXIT-BT2 trial is a pivotal study undertaken to confirm or refute this signal. AIM: To investigate the efficacy and safety of TNK for AIS between 4.5 and 6 h of onset with or without endovascular treatment. SAMPLE SIZE ESTIMATES: A maximum of 1440 patients are required to test the superiority hypothesis with 80% power according to a two-sided 0.05 level of significance, stratified by age, sex, history of diabetes, location of vessel occlusion, baseline National Institute of Health stroke scale score, stroke etiology, and plan for endovascular treatment. DESIGN: EXIT-BT2 is a prospective, randomized, open-label, blinded assessment of endpoint (PROBE), and multi-center study. Eligible AIS patients between 4.5 and 6 h of onset are randomly assigned 1:1 into a TNK group or control group. The TNK group will receive TNK (0.25 mg/kg, a single bolus over 5-10 s, maximum 25 mg). The control group will receive standard medical care in compliance with national guidelines for acute ischemic stroke. Both groups will receive standard stroke care from randomization to 90 days after stroke onset according to national guidelines. OUTCOME: The primary efficacy endpoint is excellent functional outcome, defined as a modified Rankin Scale score 0-1 at 90 days after randomization, while the primary safety endpoint is symptomatic intracerebral hemorrhage, defined as National Institutes of Health Stroke Scale score increase ⩾4 caused by intracranial hemorrhage within 24 (-6/+12) h after randomization. CONCLUSIONS: The results of EXIT-BT2 may determine whether intravenous TNK has a favorable risk/benefit profile in AIS between 4.5 and 6 h of onset.
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ABSTRACT: Neurological diseases are a major health concern, and brain injury is a typical pathological process in various neurological disorders. Different biomarkers in the blood or the cerebrospinal fluid are associated with specific physiological and pathological processes. They are vital in identifying, diagnosing, and treating brain injuries. In this review, we described biomarkers for neuronal cell body injury (neuron-specific enolase, ubiquitin C-terminal hydrolase-L1, αII-spectrin), axonal injury (neurofilament proteins, tau), astrocyte injury (S100ß, glial fibrillary acidic protein), demyelination (myelin basic protein), autoantibodies, and other emerging biomarkers (extracellular vesicles, microRNAs). We aimed to summarize the applications of these biomarkers and their related interests and limits in the diagnosis and prognosis for neurological diseases, including traumatic brain injury, status epilepticus, stroke, Alzheimer's disease, and infection. In addition, a reasonable outlook for brain injury biomarkers as ideal detection tools for neurological diseases is presented.
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In order to guide the formulation of post-stroke treatment strategy in time, it is necessary to have real-time feedback on collateral circulation and revascularization. Currently used near-infrared II (NIR-II) probes have inherent binding with endogenous albumin, resulting in significant background signals and uncontrollable pharmacokinetics. Therefore, the albumin-escaping properties of the new probe, IR-808AC, was designed, which achieved timely excretion and low background signal, enabling the short-term repeatable injection for visualization of cerebral vessels and perfusion. We further achieved continuous observation of changes in collateral vessels and perfusion during the 7-d period in middle cerebral artery occlusion mice using IR-808AC in vivo. Furthermore, using IR-808AC, we confirmed that remote ischemic conditioning could promote collateral vessels and perfusion. Finally, we evaluated the revascularization after thrombolysis on time in embolic stroke mice using IR-808AC. Overall, our study introduces a novel methodology for safe, non-invasive, and repeatable assessment of collateral circulation and revascularization in real-time that is crucial for the optimization of treatment strategies.
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Modelos Animales de Enfermedad , Accidente Cerebrovascular , Animales , Accidente Cerebrovascular/diagnóstico por imagen , Ratones , Masculino , Imagen de Perfusión/métodos , Arterias Cerebrales/diagnóstico por imagen , Ratones Endogámicos C57BL , Albúminas/química , Infarto de la Arteria Cerebral Media/diagnóstico por imagen , Espectroscopía Infrarroja Corta/métodos , Circulación ColateralRESUMEN
AIMS: To investigate the characteristics of dynamic cerebral autoregulation (dCA) after intravenous thrombolysis (IVT) and assess the relationship between dCA and prognosis. METHODS: Patients with unilateral acute ischemic stroke receiving IVT were prospectively enrolled; those who did not were selected as controls. All patients underwent dCA measurements, by quantifying the phase difference (PD) and gain, at 1-3 and 7-10 days after stroke onset. Simultaneously, two dCA-based nomogram models were established to verify the predictive value of dCA for patients with mild-to-moderate stroke. RESULTS: Finally, 202 patients who received IVT and 238 who did not were included. IVT was positively correlated with higher PD on days 1-3 and 7-10 after stroke onset. PD values in both sides at 1-3 days after stroke onset and in the affected side at 7-10 days after onset were independent predictors of unfavorable outcomes in patients who received IVT. Additionally, in patients with mild-to-moderate stroke who received IVT, the dCA-based nomogram models significantly improved the risk predictive ability for 3-month unfavorable outcomes. CONCLUSION: IVT has a positive effect on dCA in patients with acute stroke; furthermore, dCA may be useful to predict the prognosis of patients with IVT.
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Homeostasis , Accidente Cerebrovascular Isquémico , Terapia Trombolítica , Humanos , Masculino , Femenino , Anciano , Persona de Mediana Edad , Pronóstico , Terapia Trombolítica/métodos , Homeostasis/fisiología , Homeostasis/efectos de los fármacos , Accidente Cerebrovascular Isquémico/tratamiento farmacológico , Accidente Cerebrovascular Isquémico/fisiopatología , Fibrinolíticos/administración & dosificación , Fibrinolíticos/uso terapéutico , Circulación Cerebrovascular/fisiología , Circulación Cerebrovascular/efectos de los fármacos , Estudios Prospectivos , Activador de Tejido Plasminógeno/administración & dosificación , Activador de Tejido Plasminógeno/uso terapéutico , Administración Intravenosa , Valor Predictivo de las Pruebas , Anciano de 80 o más Años , Nomogramas , Accidente Cerebrovascular/tratamiento farmacológico , Accidente Cerebrovascular/fisiopatologíaRESUMEN
Considering the high probability of recurrence or metastasis after thyroidectomy, it is meaningful to develop a rapid, sensitive and specific method for monitoring thyrophyma-related biomarkers. In this study, a homogeneous electrochemiluminescence immunoassay (HO-ECLIA) coupled with magnetic beads (MBs)-based enrichment tactic was established for the determination of thyrophyma-related thyroglobulin (Tg). Importantly, owing to the abundant surface groups and good biocompatibility of carbon quantum dots (CQDs), the incorporation of CQDs onto the Tg antigen surface was achieved, resulting in the formation of Tg-encapsulated CQDs (CQDs-Tg), which served not only as an ECL probe but as a biorecognition element. Under optimal experimental conditions, the proposed platform demonstrated a wide linear range from 0.01 to 100 ng·mL-1 with a detection limit of 6.9 pg·mL-1 (S/N = 3), and performed well in real serum sample analysis against interference. Collectively, the proposed platform exhibited the rapid response, satisfactory sensitivity and specificity toward Tg in complex serum milieu, and held a considerable potential for clinical prognosis monitoring of thyrophyma.
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Técnicas Electroquímicas , Inmunoensayo , Tiroglobulina , Humanos , Carbono/química , Técnicas Electroquímicas/métodos , Inmunoensayo/métodos , Límite de Detección , Mediciones Luminiscentes/métodos , Puntos Cuánticos/química , Tiroglobulina/sangreRESUMEN
Strain S30A2T, isolated from the acid mine drainage sediment of Mengzi Copper Mine, Yunnan, is proposed to represent a novel species of the sulphur-oxidizing genus Acidithiobacillus. Cells were Gram-stain-negative, non-endospore forming, highly motile with one or two monopolar flagella and rod-shaped. The strain was mesophilic, growing at 30-50 °C (optimum, 38 °C), acidophilic, growing at pH 2.0-4.5 (optimum, pH 2.5), and tolerant of 0-4â% (w/v; 684 mol l-1) NaCl. The 16S rRNA gene-based sequence analysis showed that strain S30A2T belongs to the genus Acidithiobacillus and shows the largest similarity of 96.6â% to the type strain Acidithiobacillus caldus KUT. The genomic DNA G+C content of strain S30A2T was 59.25 mol%. The average nucleotide identity ANIb and ANIm values between strain S30A2T and A. caldus KUT were 70.95 and 89.78â%, respectively and the digital DNA-DNA hybridization value was 24.9â%. Strain S30A2T was strictly aerobic and could utilize elementary sulphur and tetrathionate to support chemolithotrophic growth. The major cellular fatty acid of S30A2T was C19â:â1ω7c. The respiratory quinones were ubiquinone-8 and ubiquinone-7. Based upon its phylogenetic, genetic, phenotypic, physiologic and chemotaxonomic characteristics, strain S30A2T is considered to represent a novel species of the genus Acidithiobacillus, for which the name Acidithiobacillus acidisediminis sp. nov. is proposed. The type strain is S30A2T (=CGMCC 1.17059T=KCTC 72580T).
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Acidithiobacillus , Técnicas de Tipificación Bacteriana , Composición de Base , ADN Bacteriano , Ácidos Grasos , Sedimentos Geológicos , Minería , Hibridación de Ácido Nucleico , Filogenia , ARN Ribosómico 16S , Análisis de Secuencia de ADN , Azufre , ARN Ribosómico 16S/genética , Azufre/metabolismo , ADN Bacteriano/genética , Ácidos Grasos/análisis , Sedimentos Geológicos/microbiología , Acidithiobacillus/clasificación , Acidithiobacillus/genética , Acidithiobacillus/aislamiento & purificación , China , Oxidación-Reducción , Crecimiento Quimioautotrófico , Ubiquinona , Cobre/metabolismoRESUMEN
Background: Restless legs syndrome (RLS) is a prevalent sensorimotor nervous system disorder in patients accompanied with insomnia, blood pressure fluctuation, and sympathetic dysfunction. These symptoms may disrupt cerebral hemodynamics. Dynamic cerebral autoregulation (dCA) describes the temporary response of cerebrovascular system to abrupt fluctuations in blood pressure, which keep cerebral blood flow stable and serve as a marker of cerebrovascular system ability. Objective: This research aimed to assess dCA in RLS patients. Methods: In this study, RLS patients were recruited and subsequently classified into four groups (mild, moderate, severe, and very severe) based on the International RLS Rating Scale (IRLS). Healthy controls matched for age and sex were enrolled. All participants were evaluated dCA by assessing phase difference (PD). A portion of patients with RLS was reassessed for dCA after one month of medication therapy (pramipexole [0.125 mg/day] and gabapentin [300 mg/day]). Results: There were altogether 120 patients with RLS and 30 controls completed the polysomnography and dCA assessment. PD was lower in the moderate, severe, and very severe RLS groups than that in the controls and mild RLS groups. Periodic limb movement index (PLMI), arousal index, and IRLS all showed a linear correlation with PD in RLS patients. Additionally, PD increased in RLS patients after therapy. Conclusion: The dCA was compromised in moderate, severe, and very severe RLS patients and was negatively correlated with the IRLS, arousal index, and PLMI. After 1 month of therapy, dCA improved in RLS patients.
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BACKGROUND: Recent research suggests that periodontitis can increase the risk of chronic obstructive pulmonary disease (COPD). In this study, we performed two-sample Mendelian randomization (MR) and investigated the causal effect of periodontitis (PD) on the genetic prediction of COPD. The study aimed to estimate how exposures affected outcomes. METHODS: Published data from the Gene-Lifestyle Interaction in the Dental Endpoints (GLIDE) Consortium's genome-wide association studies (GWAS) for periodontitis (17,353 cases and 28,210 controls) and COPD (16,488 cases and 169,688 controls) from European ancestry were utilized. This study employed a two-sample MR analysis approach and applied several complementary methods, including weighted median, inverse variance weighted (IVW), and MR-Egger regression. Multivariable Mendelian randomization (MVMR) analysis was further conducted to mitigate the influence of smoking on COPD. RESULTS: We chose five single-nucleotide polymorphisms (SNPs) as instrumental variables for periodontitis. A strong genetically predicted causal link between periodontitis and COPD, that is, periodontitis as an independent risk factor for COPD was detected. PD (OR = 1.102951, 95% CI: 1.005-1.211, p = 0.039) MR-Egger regression and weighted median analysis results were coincident with those of the IVW method. According to the sensitivity analysis, horizontal pleiotropy's effect on causal estimations seemed unlikely. However, reverse MR analysis revealed no significant genetic causal association between COPD and periodontitis. IVW (OR = 1.048 > 1, 95%CI: 0.973-1.128, p = 0.2082) MR Egger (OR = 0.826, 95%CI:0.658-1.037, p = 0.1104) and weighted median (OR = 1.043, 95%CI: 0.941-1.156, p = 0.4239). The results of multivariable Mendelian randomization (MVMR) analysis, after adjusting for the confounding effect of smoking, suggest a potential causal relationship between periodontitis and COPD (P = 0.035). CONCLUSION: In this study, periodontitis was found to be independent of COPD and a significant risk factor, providing new insights into periodontitis-mediated mechanisms underlying COPD development.
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Estudio de Asociación del Genoma Completo , Análisis de la Aleatorización Mendeliana , Polimorfismo de Nucleótido Simple , Enfermedad Pulmonar Obstructiva Crónica , Fumar , Humanos , Enfermedad Pulmonar Obstructiva Crónica/genética , Enfermedad Pulmonar Obstructiva Crónica/epidemiología , Factores de Riesgo , Fumar/epidemiología , Fumar/efectos adversos , Periodontitis/genética , Periodontitis/epidemiología , Índice de Severidad de la Enfermedad , Predisposición Genética a la Enfermedad , Enfermedades Periodontales/genética , Enfermedades Periodontales/epidemiologíaRESUMEN
Background and purpose: Early blood-brain barrier (BBB) disruption in patients with acute ischemic stroke (AIS) can be detected on perfusion computed tomography (PCT) images before undergoing reperfusion therapy. In this study, we aimed to determine whether early disruption of the BBB predicts intracranial hemorrhage transformation (HT) in patients with AIS undergoing endovascular therapy and further identify factors influencing BBB disruption. Methods: We retrospectively analyzed general clinical and imaging data derived from 159 consecutive patients with acute anterior circulation stroke who were admitted to the Department of Neurology of the First Hospital of Jilin University, and who underwent endovascular treatment between January 1, 2021, and March 31, 2023. We evaluated the relationship between BBB destruction and intracranial HT before endovascular reperfusion therapy and examined the risk factors for early BBB destruction. Results: A total of 159 patients with assessable BBB leakage were included. The median (interquartile range, IQR) age was 63 (54-70) years, 108 (67.9%) patients were male, and the median baseline National Institutes of Health Stroke Scale (NHISS) score was 12 (10-15). Follow-up non-contrast computed tomography (NCCT) detected HT in 63 patients. After logistic regression modeling adjustment, we found that BBB leakage in the true leakage area was slightly more than 2-fold risk of HT (odds ratio [OR], 2.01; 95% confidence interval [CI] 1.02-3.92). Heart rate was also associated with HT (OR, 1.03, 95% CI, 1.00-1.05). High Blood-brain barrier permeability (BBBP) in the true leakage area was positively correlated with infarct core volume (OR, 1.03; 95% CI, 1.01-1.05). Conclusion: Early BBB destruction before endovascular reperfusion therapy was associated with HT, whereas high BBBP correlated positively with infarct core volume.
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Background: Some common modified vascular risk factors remain poorly controlled among stroke survivors, and educational programs may help improve these conditions. Objective: This study aimed to evaluate the effect of a planned web-based educational intervention based on the health belief model (HBM) in promoting secondary prevention among patients with ischemic stroke. Methods: An evaluation-blinded quasi-experimental trial with a historical control group was conducted. Patients admitted from March to June 2020 were assigned to the historical control group, and patients admitted from July to October 2020 were assigned to the intervention group. The control group received routine health management. The intervention group received 6 additional sessions based on the HBM via Tencent Meeting, an audio and video conferencing application, within 3 months after discharge. Sessions were held every 2 weeks, with each session lasting approximately 40 minutes. These sessions were conducted in small groups, with about 8 to 10 people in each group. The primary outcomes were changes in blood pressure (BP), low-density lipoprotein cholesterol (LDL-C), hemoglobin A1c (HbA1c), and the proportion of patients achieving the treatment target. The secondary outcomes were medication adherence, assessed with the Morisky Medicine Adherence Scale (MMAS), and disability, assessed with the modified Rankin scale. Results: In total, 315 patients experiencing their first-ever stroke were analyzed. More patients in the intervention group had controlled BP (41.9% vs 28.4%; adjusted odds ratio [aOR] 1.93; P=.01), LDL-C (83.1% vs 67.7%; aOR 2.66; P=.001), and HbA1c (91.9% vs 83.9%; aOR: 3.37; P=.04) levels as well as a significant postintervention decrease in the systolic BP (adjusted ß -3.94; P=.02), LDL-C (adjusted ß -0.21; P=.008), and HbA1c (adjusted ß -0.27; P<.001), compared with control groups. Significant between-group differences were observed in medication adherence (79.4% vs 63.2%; aOR 2.31; P=.002) but not in favorable functional outcomes. Conclusions: A web-based education program based on the HBM may be more effective than current methods used to educate patients having strokes on optimal vascular risk factors and medication adherence.