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We present a rare case of low titre GAD65 antibody-associated autoimmune encephalitis and status epilepticus in a young woman. She initially presented with left arm dystonic movements, contractures and status epilepticus. Due to the concern of autoimmune encephalitis and seizures, the patient received intravenous immunoglobulin empirically. After the detection of low serum GAD65 antibodies, the patient underwent immunomodulation therapy with significant improvement. This case demonstrated that in autoimmune encephalitis, it is important to monitor serum GAD65 antibodies levels and consider immunotherapy, despite mildly elevated serum levels. The patient's history of left arm dystonic movements without impaired awareness may have been due to limb dystonia, a presenting symptom of stiff person syndrome (SPS), despite SPS more commonly affecting axial muscles. This case further demonstrates that GAD65 antibody-related syndromes can manifest with different neurological phenotypes including co-occurrence of epilepsy with possible focal SPS despite low GAD65 antibodies titres.
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Autoanticorpos , Glutamato Descarboxilase , Imunoglobulinas Intravenosas , Humanos , Feminino , Glutamato Descarboxilase/imunologia , Imunoglobulinas Intravenosas/uso terapêutico , Autoanticorpos/sangue , Adulto , Estado Epiléptico/tratamento farmacológico , Estado Epiléptico/imunologia , Encefalite/imunologia , Encefalite/diagnóstico , Imunoterapia/métodos , Doença de Hashimoto/imunologia , Doença de Hashimoto/diagnóstico , Doença de Hashimoto/tratamento farmacológico , Doença de Hashimoto/sangueRESUMO
BACKGROUND: Illness perceptions are an important factor affecting the prognosis of stroke patients. Evaluating the illness perceptions of stroke patients is of great importance for predicting their health behaviour and rehabilitation outcomes. However, there is no specific tool for assessing illness perceptions in stroke patients in China. OBJECTIVES: The objective of this study is to translate the Stroke Illness Perception Questionnaire-Revised (SIPQ-R) into Chinese and to psychometrically test the Chinese version of the scale in the population of Chinese stroke patients. METHODS: This was a methodological study. We investigated 593 stroke patients in the neurology department of a hospital in China from March to September 2021. We translated the SIPQ-R and adapted it to the cultural context, after which we evaluated the reliability and validity of the Chinese version of SIPQ-R. RESULTS: Exploratory factor analysis identified eight common factors that accounted for 71.74% of the total variance, and the factor loadings ranged from 0.530 to 0.933. Confirmatory factor analysis confirmed the eight-factor structure (χ2/df = 1.765, root mean square error of approximation = 0.053, incremental fit index = 0.906, comparative fit index = 0.905 and Tucker-Lewis index = 0.900). Internal consistency was confirmed by a Cronbach's alpha coefficient of 0.982. The test-retest reliability was 0.762. The results showed good content validity (the scale level content validity index was 0.940, and the item level content validity index values ranged from 0.860 to 0.960). There were no missing responses and floor or ceiling effects. The standard error of measurement and the smallest detectable change for the SIPQ-R were 45.49 and 126.10, respectively. CONCLUSIONS: The results of this study provide empirical evidence for the reliability and validity of the Chinese version of the SIPQ-R for stroke patients.
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Chemically modified superatoms have emerged as promising candidates in the new periodic table, in which Au13 and its doped M n Au13- n have been widely studied. However, their important counterpart, Ag13 artificial element, has not yet been synthesized. In this work, we report the synthesis of Ag13 nanoclusters using strong chelating ability and rigid ligands, that fills the gaps in the icosahedral superatomic metal clusters. After further doping Ag13 template with different degrees of Au atoms, we gained insight into the evolution of their optical properties. Theoretical calculations show that the kernel metal doping can modulate the transition of the excited-state electronic structure, and the electron transfer process changes from local excitation (LE) to charge transfer (CT) to LE. This study not only enriches the families of artificial superatoms, but also contributes to the understanding of the electronic states of superatomic clusters.
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Circularly polarized light (CPL) detection is of great significance in various applications such as drug identification, sensing and imaging. Atomically precise chiral metal nanoclusters with intense circular dichroism (CD) signals are promising candidates for CPL detection, which can further facilitate device miniaturization and integration. Herein, we report the preparation of a pair of optically active chiral silver nanoclusters [Ag7(R/S-DMA)2(dpppy)3] (BF4)3 (R/S-Ag7) for direct CPL detection. The crystal structure and molecular formula of R/S-Ag7 clusters are confirmed by single-crystal X-ray diffraction and high-resolution mass spectrometry. R/S-Ag7 clusters exhibit strong CD spectra and CPL both in solution and solid states. When used as the photoactive materials in photodetectors, R/S-Ag7 enables effective discrimination between left-handed circularly polarized and right-handed circularly polarized light at 520â nm with short response time, high responsivity and considerable discrimination ratio. This study is the first report on using atomically precise chiral metal nanoclusters for CPL detection.
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AIMS: To identify factors associated with health behaviours among stroke survivors, through a multi-centre study. DESIGN: A sequential mixed methods design. METHODS: In the quantitative research phase, a total of 350 participants were recruited through multi-stage sampling from December 2022 to June 2023. General information questionnaires, The Stroke Prevention Knowledge Questionnaire (SPKQ), Short Form Health Belief Model Scale (SF-HBMS), Health Promoting Lifestyle Profile (HPLPII), and the WHOQOL-BREF (World Health Organization Quality of Life Questionnaire, Brief Version) were distributed across five tertiary hospitals in Henan province, China. For the qualitative research component, semi-structured interviews were conducted to explore the barriers and facilitators of health behaviour. This study adheres to the GRAMMS guidelines. RESULTS: A total of 315 participants (90.0%) completed the survey. Identified barriers to health behaviour included residing in rural areas, higher scores on the Charlson Comorbidity Index (CCI) and mRS, as well as lower scores on SPKQ, SF-HBMS and WHOQOL-BREF. Twenty-four individuals participated in qualitative interviews. Twenty-eight themes were identified and categorised by frequency, covering areas such as knowledge, skills, intentions, social influences, social/professional role and identity, environmental context and resources, beliefs about capabilities, beliefs about consequences and behavioural regulation. Both quantitative and qualitative data suggested that health behaviour among stroke survivors is at a moderate level, and the identified barrier factors can be mapped into the COM-B model (Capability, Opportunity, Motivation and Behaviour). CONCLUSION: The study indicates that key barriers to health behaviour among stroke survivors align with the COM-B model. These identified factors should be carefully considered in the planning of future systematic interventions aimed at improving health behaviours among stroke survivors. PATIENT OR PUBLIC CONTRIBUTION: Patients were invited to completed questionnaires in the study and semi-structured interviews. The investigators provided explanation of this study' content, purpose and addressed issues during the data collection.
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Comportamentos Relacionados com a Saúde , Acidente Vascular Cerebral , Sobreviventes , Humanos , Masculino , Feminino , Pessoa de Meia-Idade , Sobreviventes/psicologia , Sobreviventes/estatística & dados numéricos , Acidente Vascular Cerebral/psicologia , Inquéritos e Questionários , China , Idoso , Pesquisa Qualitativa , Adulto , Modelo de Crenças de Saúde , Conhecimentos, Atitudes e Prática em Saúde , Qualidade de Vida/psicologiaRESUMO
OBJECTIVE: This study was designed to estimate the effect of sticky bone combined with concentrated growth factor (CGF) on anterior alveolar horizontal augmentation during implantation. METHODS: Twenty-eight patients were randomly assigned to either the test group (Group 1, n = 14) or the control group (Group 2, n = 14). Patients in Group 1 and Group 2 underwent GBR using sticky bone combined with CGF and bone powders mixed with saline, respectively. On postoperative Day 7, the patients completed the visual analogue scale (VAS). Three-dimensional models of maxillary alveolar bone were reconstructed from CBCT data at different periods, and the bone volume conversion rate was calculated with the assistance of a measurement marker guide. Labial bone thickness before and after trauma closure and bone density at six months postoperatively were also measured. RESULTS: The mean bone volume conversion rate for Group 1 (72.09 ± 12.18%) was greater than that for Group 2 (57.47 ± 9.62%, P = 0.002). The VAS score was lower for Group 1 than for Group 2 (P = 0.032). At six months postoperatively, greater bone density was found in patients in Group 1 than in those in Group 2, although the difference was not statistically significant (P > 0.05). The change in the thickness of the labial bone graft material in Group 1 was smaller than that in Group 2 (P = 0.025). CONCLUSION: Sticky bone combined with CGF was able to achieve better bone augmentation than conventional GBR. With excellent mechanical properties and the capacity to release growth factors, sticky bone is an ideal material for bone grafting. TRIAL REGISTRATION: The study was registered at the Chinese Clinical Trial Registry on 10/04/2022 (Identification number: ChiCTR2200058500).
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Aumento do Rebordo Alveolar , Implantação Dentária Endóssea , Humanos , Implantação Dentária Endóssea/métodos , Aumento do Rebordo Alveolar/métodos , Transplante Ósseo , Maxila/cirurgia , Peptídeos e Proteínas de Sinalização IntercelularRESUMO
The design and synthesis of stable porous materials capable of removing both hard and soft metal ions pose a significant challenge. In this study, a novel metal-organic framework (MOF) adsorbent named CdK-m-COTTTB was developed. This MOF material was constructed using sulfur-rich m-cyclooctatetrathiophene-tetrabenzoate (m-H4COTTTB) as the organic ligand and oxygen-rich bimetallic clusters as the inorganic nodes. The incorporation of both soft and hard base units within the MOF structure enables effective removal of various heavy metal ions, including both soft and hard acid species. In single-component experiments, the adsorption capacity of CdK-m-COTTTB for Pb2+, Tb3+, and Zr4+ ions reached levels of 636.94, 432.90, and 357.14 mg·g-1, respectively, which is comparable to specific MOF absorbents. The rapid adsorption process was found to be chemisorption. Furthermore, CdK-m-COTTTB exhibited the capability to remove at least 12 different metal ions in both separate and multicomponent solutions. The material demonstrated excellent acid-base stability and renewability, which are advantageous for practical applications. CdK-m-COTTTB represents the first reported pristine MOF material for the removal of both hard and soft acid metal ions. This work serves as inspiration for the design and synthesis of porous crystalline materials that can efficiently remove diverse heavy metal pollutants.
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Vaccination is the most effective means of preventing and controlling porcine epidemic diarrhea (PED). Conventional vaccines developed from porcine epidemic diarrhea virus (PEDV) GI-a subtypes (CV777 and SM98) have played a vital role in preventing classical PED. However, with the emergence of PEDV mutants in 2010, conventional PEDV GI-a subtype-targeting vaccines no longer provide adequate protection against PEDV GII mutants, thereby making novel-type PED vaccine development an urgent concern to be addressed. Novel vaccines, including nucleic acid vaccines, genetically engineered subunit vaccines, and live vector vaccines, are associated with several advantages, such as high safety and stability, clear targeting, high yield, low cost, and convenient usage. These vaccines can be combined with corresponding ELISA kits to differentiate infected from vaccinated animals, which is beneficial for disease confirmation. This review provides a detailed overview of the recent advancements in PED vaccines, emphasizing on the research and application evaluation of novel PED vaccines. It also considers the future directions and challenges in advancing these vaccines to widespread use in clinics.
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Infecções por Coronavirus , Vírus da Diarreia Epidêmica Suína , Doenças dos Suínos , Vacinas Virais , Suínos , Animais , Infecções por Coronavirus/prevenção & controle , Infecções por Coronavirus/veterinária , Vacinas Atenuadas , Diarreia/prevenção & controle , Diarreia/veterináriaRESUMO
Objective: To explore distinct longitudinal trajectories of resourcefulness among initial ischemic stroke patients from diagnosis to 12 months, and to identify whether sociodemographic factors, disease-related factors, self-efficacy, family function, and social support can predict patterns in the trajectories of resourcefulness. Methods: A prospective longitudinal study was conducted. Initial ischemic stroke patients who met inclusion and exclusion criteria were followed up when still in hospital (Preparing for discharge, Baseline, T1), at 1 month (T2), at 3 months (T3), at 6 months (T4), at 9 months (T5) and 12 months (T6) (±1 week) after discharge. General information, National Institute of Health Stroke Scale (NIHSS), Modified Rankin Scale (mRS), General Self-Efficacy Scale (GSES), General Family Functioning Subscale (FAD-GF), and Social Support Rate Scale (SSRS) were used in T1. The Resourcefulness Scale© was evaluated at 6 time points. Growth mixture modeling was used to identify trajectory patterns of resourcefulness. Logistic regression was used to identify predictors of resourcefulness trajectories. Results: Three longitudinal trajectories of resourcefulness were identified and named as the high-stable class (38.9%, n=71), fluctuation class (41.2%, n=75), and low-stable class (19.9%, n=36), respectively. Dwelling areas (x2=6.805, P=0.009), education (x2=44.865, P=0.000), monthly income (x2=13.063, P=0.001), NIHSS scores (x2=44.730, P=0.000), mRS scores (x2=51.788, P=0.000), Hcy (x2=9.345, P=0.002), GSES (x2=56.933, P=0.000), FAD-GF (x2=41.305, P=0.000) and SSRS (x2=52.373, P=0.000) were found to be statistically significant for distinguishing between different resourcefulness trajectory patterns. Lower education (OR=0.404), higher NIHSS(OR=6.672) scores, and higher mRS(OR=21.418) scores were found to be risk factors for lower resourcefulness, whereas higher education(OR=0.404), GSES(OR=0.276), FAD-GF(OR=0.344), and SSRS(OR=0.358) scores were identified as protective factors enhancing resourcefulness. Conclusion: This study obtained three patterns of trajectories and identified their predictive factors in initial ischemic stroke. The findings will assist health care professionals in identifying subgroups of patients and when they may be at risk of low resourcefulness and provide timely targeted intervention to promote resourcefulness.
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OBJECTIVE: Three-dimensional (3D) reconstructed models have been shown to improve visualization in complex female pelvic tumors. Cinematic rendering (CR) is a 3D imaging technique for computed tomography (CT) images, which creates more realistic images with the ability to enhance imaging of anatomical features for diagnosis. This study was set up to compare two types of 3D models and to validate the use of 3D anatomical techniques for the diagnosis of complex female pelvic tumors. METHODS: The preclinical, randomized, two-sequence crossover investigation was performed from December 2022 to January 2023 at First Affiliated Hospital of Chongqing Medical University. Sixteen residents and 10 attending surgeons assessed the cases of 23 patients with two types of 3D model images. The surgeons were randomly assigned to two assessment sequences (CR-3D model group and CT-3D model group). For each case, participants selected one question that probed fundamental questions about the tumor's genesis throughout each assessment period. Following a 4-week washout period, case assessments were transferred to the other image modality. RESULTS: The main result assessment was the accuracy of the answers. The time to answer the questions and the case assessment questionnaire was added as a secondary outcome. The mean scores in the CR-3D models (19.35 ± 1.87) varied significantly from those in the CT-CR group (16.77 ± 1.8) (P < 0.001), and solving the questions in the CT-3D model sequence (41.96 ± 6.31 s) varied significantly from that in the CR-3D model sequence (52.88 ± 5.95 s) (P < 0.001). Subgroup analysis revealed that there were statistically significant variations in the scores of female reproductive tumors, pelvic tumors other than the reproductive system, and retroperitoneal tumors (P = 0.005). Analysis of the assessment questionnaire showed that more surgeons choose CR 3D reconstruction (8.31 ± 0.76 vs 7.15 ± 1.19, P < 0.001). CONCLUSIONS: The results suggest that each 3D reconstruction method has its own advantages. Surgeons feel that CR reconstruction models are a useful technique that can improve their comprehension of complex pelvic tumors, while traditional 3D models have an advantage in terms of speed to diagnosis.
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Estudos Cross-Over , Imageamento Tridimensional , Neoplasias Pélvicas , Tomografia Computadorizada por Raios X , Humanos , Feminino , Neoplasias Pélvicas/diagnóstico por imagem , Adulto , Pessoa de Meia-Idade , Modelos AnatômicosRESUMO
Myosin light chain kinase (MLCK) is a dedicated kinase of myosin regulatory light chain (RLC), playing an essential role in the regulation of muscle contraction and cell motility. Much of the knowledge about MLCK comes from the study of vertebrate MLCK, and little is known about insect MLCK. Here, we identified the single MLCK gene in the locust Locusta migratoria, which spans over 1400 kb, includes 62 exons and accounts for at least five transcripts. We found that the five distinct transcripts of the locust MLCK gene are expressed in a tissue-specific manner, including three muscle-specific isoforms and two generic isoforms. To characterise the kinase activity of locust MLCK, we recombinantly expressed LmMLCK-G, the smallest locust MLCK isoform, in insect Sf9 cells. We demonstrated that LmMLCK-G is a Ca2+/calmodulin-dependent kinase that specifically phosphorylates serine 50 of locust muscle myosin RLC (LmRLC). Additionally, we found that almost all LmRLC molecules in the flight muscle and the hindleg muscles of adult locusts are phosphorylated.
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Proteínas de Insetos , Locusta migratoria , Quinase de Cadeia Leve de Miosina , Animais , Locusta migratoria/genética , Locusta migratoria/enzimologia , Quinase de Cadeia Leve de Miosina/genética , Quinase de Cadeia Leve de Miosina/metabolismo , Proteínas de Insetos/genética , Proteínas de Insetos/metabolismo , Sequência de Aminoácidos , Células Sf9 , Filogenia , Músculos/metabolismoRESUMO
Stroke is one of the top causes of death and disability worldwide. Cognitive impairments are found in more than 70% of individuals who have survived a stroke. Cognitive decline is a major contributor to disability, dependency, and morbidity. The prevalence and severity of dementia vary depending on different characteristics of the stroke and other clinical risk factors. Here we discuss the effects of stroke territory, patients' age, sex, cerebral blood flow, acute reperfusion therapy, and cognitive reserve of post-stroke cognitive decline. Potential predictive molecular and genetic biomarkers of post-stroke cognitive impairments are also discussed.
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To investigate the occurrence and 90-day mortality of cancer patients following unplanned admission to the intensive care unit (ICU), as well as to develop a risk prediction model for their 90-day prognosis. We prospectively analyzed data from cancer patients who were admitted to the ICU without prior planning within the past 7 days, specifically between May 12, 2021, and July 12, 2021. The patients were grouped based on their 90-day survival status, and the aim was to identify the risk factors influencing their survival status. A total of 1488 cases were included in the study, with an average age of 63.2 ± 12.4 years. The most common reason for ICU admission was sepsis (n = 940, 63.2%). During their ICU stay, 29.7% of patients required vasoactive drug support (n = 442), 39.8% needed invasive mechanical ventilation support (n = 592), and 82 patients (5.5%) received renal replacement therapy. We conducted a multivariate COX proportional hazards model analysis, which revealed that BMI and a history of hypertension were protective factors. On the other hand, antitumor treatment within the 3 months prior to admission, transfer from the emergency department, general ward, or external hospital, high APACHE score, diagnosis of shock and respiratory failure, receiving invasive ventilation, and experiencing acute kidney injury (AKI) were identified as risk factors for poor prognosis within 90 days after ICU admission. The average length of stay in the ICU was 4 days, while the hospital stay duration was 18 days. A total of 415 patients died within 90 days after ICU admission, resulting in a mortality rate of 27.9%. We selected 8 indicators to construct the predictive model, which demonstrated good discrimination and calibration. The prognosis of cancer patients who are unplanned transferred to the ICU is generally poor. Assessing the risk factors and developing a risk prediction model for these patients can play a significant role in evaluating their prognosis.
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Unidades de Terapia Intensiva , Neoplasias , Idoso , Humanos , Pessoa de Meia-Idade , Neoplasias/epidemiologia , Neoplasias/terapia , Prognóstico , Estudos Retrospectivos , Medição de Risco , Fatores de RiscoRESUMO
Background: Stroke is the second leading cause of death in adults worldwide. However, up to 80% of strokes can be prevented by modifying risk factors. Objective: The study aims to assess the effectiveness of the Health Ecology Model and Self-Determination Theory (HEM-SDT) based health management intervention among individuals at high risk of stroke. Methods: A randomized controlled trial was conducted in Zhengzhou from May 1st, 2020, to December 31st, 2020. A total of 229 participants were recruited for the study, with 116 individuals at high risk of stroke being randomly assigned to the HEM-SDT health management group, while 113 participants were enrolled in the control group, following their current routine practices. The Generalized Estimating Equation model (GEE) was used to analyze the differences in health knowledge, belief and, behavior between the two groups at the beginning of the intervention, and at 6-month intervals after the intervention. The chi-square test was utilized to assess the control rate of risk factors. Results: After 6 months of intervention, there were significant improvements in health knowledge, behavior, and belief among the participants. The study found significant differences in the interaction effects between time and group for health knowledge (Mean, SD = 25.62 ± 3.88, 95%CI: 7.944-9.604, Pï¼0.001), health belief (Mean, SD = 87.18 ± 14.21, 95%CI: 23.999-29.887, Pï¼0.001), and health behavior (Mean, SD = 173.28 ± 24.22, 95%CI: 22.332-36.904, Pï¼0.001). Additionally, the rates of hypertension, hyperglycemia, dyslipidemia, high or medium risk condition of stroke, obesity, hyperhomocysteinemia, smoking, alcohol consumption, and lack of exercise also showed statistical significance (Pï¼0.05) after the intervention. Conclusion: The HEM-SDT health management model improves the health knowledge, behavior, and beliefs in people at high risk of stroke and remarkably it shows improvement in modifiable risk factors. It can be recommended for systematic health management in people at high-risk of stroke.
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Purpose: To evaluate the role of interleukin-4 in influencing idiopathic epiretinal membrane (iERM) formation and early progression post cataract surgery (PCS) from clinical and experimental perspectives. Methods: We quantified levels of IL-4 in aqueous humor (AH) samples from 22 iERM patients and 31 control subjects collected before and 20 hours after cataract surgeries using ELISA. After a 3-month follow-up, the association between IL-4 levels and iERM progression measurements was identified. In addition, in vitro studies were conducted to investigate the effects of IL-4 on primary rat retinal Müller glia proliferation, migration, and glial-mesenchymal transition (GMT). Results: Concentrations of IL-4 were significantly higher in preoperative AH samples from iERM patients versus controls (P = 0.006). Postoperatively, although IL-4 levels were elevated in both groups compared to their respective preoperative levels, they were even more obviously so in the iERM group (P < 0.001). Multivariate linear regression analyses revealed that, postoperatively, IL-4 level elevation was positively associated with macular volume and thickness increase (both P < 0.05) in iERM patients. However, no correlations were observed between IL-4 level (changes) and clinical characters in the controls. In vitro studies demonstrated that IL-4 promoted Müller glia proliferation and migration and increased the expression of GMT-related markers in a manner independent of transforming growth factor-ß1 (TGF-ß1). Conclusions: IL-4 plays a crucial pro-fibrotic role in iERM formation and early progression 3 months PCS possibly by stimulating Müller glia proliferation, migration, and GMT in a TGF-ß1-independent manner. Translational Relevance: The current study suggests the potential of IL-4 as a novel therapeutic target for iERM.
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Catarata , Membrana Epirretiniana , Animais , Humanos , Ratos , Membrana Epirretiniana/cirurgia , Membrana Epirretiniana/metabolismo , Interleucina-4 , Retina/metabolismo , Fator de Crescimento Transformador beta1RESUMO
Rice (Oryza sativa L.) is an important food crop in Taiwan, among which fragrant rice is highly regarded for its special aroma when cooked. During the storage of fragrant rice, the aroma components will change, which will affect the aroma quality of fragrant rice. Therefore, headspace solid-phase microextraction (HS-SPME) was used in this study, combined with gas chromatography and gas chromatography-mass spectrometry, to analyze the difference in the aroma components of Taikeng No. 4 (TK4), Tainung No. 71 (TN71), Kaohsiung No. 147 (KH147), and Taichung No. 194 (TC194) fragrant rice. A total of 28 aroma components were identified in the four varieties of fragrant rice, and the main components were all Nonanal. Among them, TK4 contains a very high content of hydrocarbons, including Tridecane and Dodecane; TN71, KH147, and TC194 contain mainly aldehydes such as Nonanal and Hexanal. During different storage times, the contents of alcohols, monoterpenes, aromatic aldehydes, and furans increased with storage time, while the content of aliphatic aldehydes decreased with storage time. After storage, the fragrant rice samples showed a tendency for the total volatile component content to decrease, with the most pronounced reduction observed in Nonanal content.
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Objective: To explore the relationships among self-perceived burden, resourcefulness and depression, and to study further whether resourcefulness mediates the effects of self-perceived burden on depression in young and middle-aged stroke patients. Methods: A cross-sectional survey was conducted with 1050 young and middle-aged stroke patients. We used a general demographic questionnaire, Self-Perceived Burden Scale (SPBS), Resourcefulness Scale© (RS) and Hamilton Depression Scale (HAMD) to assess self-perceived burden, resourcefulness, and depression. Statistical methods included correlation analysis, multiple linear regression, and structural equation model. Results: 1018 valid questionnaires were collected with a response rate of 96.95%. Resourcefulness was inversely correlated with self-perceived burden (r = -0.367, p < 0.01) and depression (r = -0.625, p < 0.01); Self-perceived burden was positively associated with depression (r = 0.698, p < 0.01). Multiple linear regression analyses showed that resourcefulness mediated the effects of self-perceived burden on depression; The structural equation model demonstrated that the resourcefulness mediated the relationship between self-perceived burden and depression. Conclusion: Resourcefulness is a mediator between self-perceived burden and depression. Medical staff adjust the psychological state of stroke patients based on the theory of resourcefulness, thereby improving their problem-solving ability, actively encouraging patients to establish problem-solving strategies, providing disease rehabilitation knowledge and skills, and promoting the improvement of resourcefulness level.
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BACKGROUND: Dysfunction of microglia during aging affects normal neuronal function and results in the occurrence of neurodegenerative diseases. Retinal microglial senescence attributes to retinal ganglion cell (RGC) death in glaucoma. This study aims to examine the role of ATP-P2X7R in the mediation of microglia senescence and glaucoma progression. METHODS: Forty-eight participants were enrolled, including 24 patients with primary open-angle glaucoma (POAG) and age-related cataract (ARC) and 24 patients with ARC only. We used ARC as the inclusion criteria because of the availability of aqueous humor (AH) before phacoemulsification. AH was collected and the adenosine triphosphate (ATP) concentration was measured by ATP Assay Kit. The chronic ocular hypertension (COH) mouse model was established by microbead occlusion. Microglia were ablated by feeding PLX5622 orally. Mouse bone marrow cells (BMCs) were prepared and infused into mice through the tail vein for the restoration of microglia function. Western blotting, qPCR and ELISA were performed to analyze protein and mRNA expression in the ocular tissue, respectively. Microglial phenotype and RGC survival were assessed by immunofluorescence. The mitochondrial membrane potential was measured using a JC-1 assay kit by flow cytometry. RESULTS: ATP concentrations in the AH were increased in older adults and patients with POAG. The expression of P2X7R was upregulated in the retinal tissues of mice with glaucoma, and functional enrichment analysis showed that P2X7R was closely related to cell aging. Through in vivo and in vitro approaches, we showed that pathological activation of ATP-P2X7R induced accelerated microglial senescence through impairing PTEN-induced kinase 1 (PINK1)-mediated mitophagy, which led to RGC damage. Additionally, we found that replacement of senescent microglia in COH model of old mice with BMCs from young mice reversed RGC damage. CONCLUSION: ATP-P2X7R induces microglia senescence by inhibiting PINK1-mediated mitophagy pathway. Specific inhibition of ATP-P2X7R may be a fundamental approach for targeted therapy of RGC injury in microglial aging-related glaucoma.
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Glaucoma de Ângulo Aberto , Glaucoma , Hipertensão Ocular , Camundongos , Animais , Células Ganglionares da Retina/patologia , Microglia/metabolismo , Trifosfato de Adenosina/farmacologia , Glaucoma de Ângulo Aberto/complicações , Glaucoma de Ângulo Aberto/metabolismo , Glaucoma de Ângulo Aberto/patologia , Hipertensão Ocular/patologia , Glaucoma/metabolismo , Modelos Animais de Doenças , Proteínas Quinases/metabolismoRESUMO
KATP channels are metabolic sensors for intracellular ATP/ADP ratios, play essential roles in many physiological processes, and are implicated in a spectrum of pathological conditions. SUR2A-containing KATP channels differ from other subtypes in their sensitivity to Mg-ADP activation. However, the underlying structural mechanism remains poorly understood. Here we present a series of cryo-EM structures of SUR2A in the presence of different combinations of Mg-nucleotides and the allosteric inhibitor repaglinide. These structures uncover regulatory helix (R helix) on the NBD1-TMD2 linker, which wedges between NBD1 and NBD2. R helix stabilizes SUR2A in the NBD-separated conformation to inhibit channel activation. The competitive binding of Mg-ADP with Mg-ATP to NBD2 mobilizes the R helix to relieve such inhibition, allowing channel activation. The structures of SUR2B in similar conditions suggest that the C-terminal 42 residues of SUR2B enhance the structural dynamics of NBD2 and facilitate the dissociation of the R helix and the binding of Mg-ADP to NBD2, promoting NBD dimerization and subsequent channel activation.
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Canais de Potássio Corretores do Fluxo de Internalização , Receptores de Sulfonilureias/metabolismo , Canais de Potássio Corretores do Fluxo de Internalização/metabolismo , Trifosfato de Adenosina/metabolismo , Difosfato de Adenosina/metabolismo , Dimerização , Canais KATP/metabolismoRESUMO
BACKGROUND: Elevated intraocular pressure (IOP) and optic nerve edema occurring during prone surgeries may cause ocular and optic nerve ischaemia injury. We hypothesized that a liberal fluid protocol might further increase IOP and optic nerve sheath diameter (ONSD) than a restrictive fluid protocol for patients in the prone position. METHODS: A single-centre, prospective and randomized trial was conducted. Patients were randomly allocated into 2 groups: the liberal fluid infusion group, in which repeated bolus doses of Ringer's lactate solution were given to maintain pulse pressure variation (PPV) within 6~9%, and the restrictive fluid infusion group, where PPV was maintained within 13-16%. IOP and ONSD were measured in both eyes at 10min after the anaesthesia induction in the supine position, 10min after the prone position placement, and 1h and 2h since the prone position was placed, at the conclusion of surgery, and returned to the supine position. RESULTS: A total of 97 patients were recruited and completed the study. IOP increased significantly from 12±3mmHg in the supine position to 31±5 mmHg (p<0.001) at the end of surgery in the liberal fluid infusion group and from 12±2 to 28±4 mmHg (p<0.001) in the restrictive fluid infusion group. There was a statistically significant difference in the change of IOP over time between the two groups (p=0.019). ONSD increased significantly from 5.3±0.3mm in the supine position to 5.5±0.3mm (p<0.001) at the end of surgery in both groups (both p<0.001). There was no statistically significant difference in the change of ONSD over time between the two groups (p>0.05). CONCLUSIONS: Compared to the restrictive fluid protocol, the liberal fluid protocol increased IOP but not ONSD in patients undergoing prone spine surgery. TRIAL REGISTRATION: The study was registered in ClinicalTrials.gov ( https://clinicaltrials.gov ) prior to patient enrollment, ID: NCT03890510, on March 26, 2019. The principal investigator was Xiao-Yu Yang.