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This study aimed to determine the patterns of changes in structure, function, and cognitive ability in early-onset and late-onset older adults with focal epilepsy (OFE). This study first utilized the deformation-based morphometry analysis to identify structural abnormalities, which were used as the seed region to investigate the functional connectivity with the whole brain. Next, a correlation analysis was performed between the altered imaging findings and neuropsychiatry assessments. Finally, the potential role of structural-functional abnormalities in the diagnosis of epilepsy was further explored by using mediation analysis. Compared with healthy controls (n = 28), the area of reduced structural volume was concentrated in the bilateral cerebellum, right thalamus, and right middle cingulate cortex, with frontal, temporal, and occipital lobes also affected in early-onset focal epilepsy (n = 26), while late-onset patients (n = 31) displayed cerebellar, thalamic, and cingulate atrophy. Furthermore, correlation analyses suggest an association between structural abnormalities and cognitive assessments. Dysfunctional connectivity in the cerebellum, cingulate cortex, and frontal gyrus partially mediates the relationship between structural abnormalities and the diagnosis of early-onset focal epilepsy. This study identified structural and functional abnormalities in early-onset and late-onset focal epilepsy and explored characters in cognitive performance. Structural-functional coupling may play a potential role in the diagnosis of epilepsy.
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Idade de Início , Encéfalo , Epilepsias Parciais , Imageamento por Ressonância Magnética , Humanos , Masculino , Epilepsias Parciais/fisiopatologia , Epilepsias Parciais/diagnóstico por imagem , Epilepsias Parciais/patologia , Feminino , Pessoa de Meia-Idade , Idoso , Encéfalo/diagnóstico por imagem , Encéfalo/patologia , Encéfalo/fisiopatologia , Cognição/fisiologia , Testes Neuropsicológicos , AdultoRESUMO
Polymersomes, nanosized polymeric vesicles, have attracted significant interest in the areas of artificial cells and nanomedicine. Given their size, their visualization via confocal microscopy techniques is often achieved through the physical incorporation of fluorescent dyes, which however present challenges due to potential leaching. A promising alternative is the incorporation of molecules with aggregation-induced emission (AIE) behavior that are capable of fluorescing exclusively in their assembled state. Here, we report on the use of AIE polymersomes as artificial organelles, which are capable of undertaking enzymatic reactions in vitro. The ability of our polymersome-based artificial organelles to provide additional functionality to living cells was evaluated by encapsulating catalytic enzymes such as a combination of glucose oxidase/horseradish peroxidase (GOx/HRP) or ß-galactosidase (ß-gal). Via the additional incorporation of a pyridinium functionality, not only the cellular uptake is improved at low concentrations but also our platform's potential to specifically target mitochondria expands.
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Glucose Oxidase , Peroxidase do Rábano Silvestre , beta-Galactosidase , Glucose Oxidase/química , Humanos , beta-Galactosidase/química , beta-Galactosidase/metabolismo , Peroxidase do Rábano Silvestre/química , Peroxidase do Rábano Silvestre/metabolismo , Organelas/metabolismo , Corantes Fluorescentes/química , Polímeros/química , Fluorescência , Células HeLa , Mitocôndrias/metabolismoRESUMO
OBJECTIVE: Endovascular therapy (EVT) is the most successful treatment for patients with acute ischemic stroke (AIS) due to large vessel occlusion (LVO) in the anterior circulation. However, futile recanalization (FR) seriously affects the prognosis of these patients. The aim of this study was to investigate predictors of FR after EVT in patients with AIS. METHOD: Patients diagnosed with AIS due to anterior circulation LVO and receiving EVT between June 2020 and October 2022 were prospectively enrolled. FR after EVT was defined as a poor 90-day prognosis (modified Rankin Scale [mRS] score ≥ 3) despite achieving successful reperfusion (modified Thrombolysis in Cerebral Infarction [mTICI] classification of 2b-3). All included patients were categorized into control group (mRS score < 3) and FR group (mRS score ≥ 3). Demographic characteristics, comorbidities (hypertension, diabetes, atrial fibrillation, smoking, etc.), stroke-specific data (NIHSS score, ASPECT score and site of occlusion), procedure data (treatment type [direct thrombectomy vs. bridging thrombectomy], degree of vascular recanalization [mTICI], procedure duration time and onset-recanalization time), laboratory indicators (lymphocytes count, neutrophils count, monocytes count, C-reactive protein, neutrophil-to-lymphocyte ratio [NLR], monocyte-to-high-density lipoprotein ratio [MHR], lymphocyte-to-monocyte ratio [LMR], lymphocyte-to-C-reactive protein ratio [LCR], lymphocyte-to-high-density lipoprotein ratio[LHR], total cholesterol and triglycerides.) were compared between the two groups. Multivariate logistic regression analysis was performed to explore independent predictors of FR after EVT. RESULTS: A total of 196 patients were included in this study, among which 57 patients were included in the control group and 139 patients were included in the FR group. Age, proportion of patients with hypertension and diabetes mellitus, median NIHSS score, CRP level, procedure duration time, neutrophil count and NLR were higher in the FR group than in the control group. Lymphocyte count, LMR, and LCR were lower in the FR group than in the control group. There were no significant differences in platelet count, monocytes count, total cholesterol, triglycerides, HDL, LDL, gender, smoking, atrial fibrillation, percentage of occluded sites, onset-recanalization time, ASPECT score and type of treatment between the two groups. Multivariate logistic regression analysis demonstrated that NLR was independently associated with FR after EVT (OR = 1.37, 95%CI = 1.005-1.86, P = 0.046). CONCLUSION: This study demonstrated that high NLR was associated with a risk of FR in patients with AIS due to anterior circulation LVO. These findings may help clinicians determine which patients with AIS are at higher risk of FR after EVT. Our study can provide a theoretical basis for interventions in the aforementioned population.
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Procedimentos Endovasculares , AVC Isquêmico , Humanos , Masculino , Feminino , AVC Isquêmico/cirurgia , AVC Isquêmico/terapia , Idoso , Procedimentos Endovasculares/métodos , Pessoa de Meia-Idade , Idoso de 80 Anos ou mais , Futilidade Médica , Trombectomia/métodos , Estudos Prospectivos , PrognósticoRESUMO
Chronic hyperglycaemia is a chief feature of diabetes mellitus and complicates with many systematic anomalies. Non-human primates (NHPs) are excellent for studying hyperglycaemia or diabetes and associated comorbidities, but lack behavioural observation. In the study, behavioural, brain imaging and histological analysis were performed in a case of spontaneously hyperglycaemic (HGM) Macaca fascicularis. The results were shown that the HGM monkey had persistent body weight loss, long-term hyperglycaemia, insulin resistance, dyslipidemia, but normal concentrations of insulin, C-peptide, insulin autoantibody, islet cell antibody and glutamic acid decarboxylase antibody. Importantly, an impaired working memory in a delayed response task and neurological dysfunctions were found in the HGM monkey. The tendency for atrophy in hippocampus was observed by magnetic resonance imaging. Lenticular opacification, lens fibres disruptions and vacuole formation also occurred to the HGM monkey. The data suggested that the spontaneous HGM monkey might present diabetes-like characteristics and associated neurobehavioral anomalies in this case. This study first reported cognitive deficits in a spontaneous hyperglycaemia NHPs, which might provide evidence to use macaque as a promising model for translational research in diabetes and neurological complications.
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Catarata , Hiperglicemia , Macaca fascicularis , Animais , Hiperglicemia/metabolismo , Catarata/patologia , Masculino , Transtornos Cognitivos/etiologia , Transtornos Cognitivos/patologia , Doenças do Sistema Nervoso , Hipocampo/patologia , Hipocampo/metabolismoRESUMO
BACKGROUND: Single-nucleotide polymorphisms (SNPs) in the proprotein convertase subtilisin/kexin type 9 (PCSK9) gene are known to be associated with susceptibility to several cerebrovascular diseases, including ischemic stroke (IS). The aims of this study was to evaluate associations between PCSK9 gene polymorphisms and the risk of IS. Based on previous reports linking PCSK9 SNPs to plasma lipid levels and to atherosclerosis, and to inconsistencies in the reported associations between the SNPs, plasma lipid levels and IS risk, we choose the PCSK9 rs505151, rs529787, and rs17111503 to performe the association analysis. METHODS: Using multiple databases, all relevant case-control and cohort studies that matched our search criteria were collected. Quality assessment of included studies was performed using the Newcastle-Ottawa Scale. Demographic and genotype data were extracted from each study, and meta-analysis was performed using Stata/MP 17.0. Odds ratios (ORs) with 95% confidence intervals (CIs) were calculated using fixed and random effects models. RESULTS: A critical evaluation was conducted on ten case-control studies, involving a total of 2426 cases and 2424 controls. Pooled results from the allelic models indicated the PCSK9 rs505151 G allele (OR: 1.41, 95% CI: 1.06-1.87, p = 0.019, I2 = 53.9%) and the PCSK9 rs17111503 A allele (OR: 1.38, 95% CI: 1.22-1.55, p < 0.001, I2 = 43.5%) were significantly associated with IS. Study qualities ranged from moderate (n = 4) to good (n = 6). Begg's and Egger's tests results indicated there was no evidence of publication bias in the findings (p > 0.05). CONCLUSIONS: This meta-analysis demonstrated that G allele variant of PCSK9 rs505151 and A allele variant of PCSK9 rs17111503 were associated with an increased risk of IS. Based on our findings, these SNPs could serve as potential targets for the diagnosis and treatment of IS. The integration of information on genetic polymorphism into IS risk prediction model may be beneficial in routine clinical practice.
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AVC Isquêmico , Pró-Proteína Convertase 9 , Humanos , AVC Isquêmico/genética , Lipídeos , Polimorfismo de Nucleotídeo Único , Pró-Proteína Convertase 9/genéticaRESUMO
Depression is a major psychological disorder with a growing impact worldwide. Traditional methods for detecting the risk of depression, predominantly reliant on psychiatric evaluations and self-assessment questionnaires, are often criticized for their inefficiency and lack of objectivity. Advancements in deep learning have paved the way for innovations in depression risk detection methods that fuse multimodal data. This paper introduces a novel framework, the Audio, Video, and Text Fusion-Three Branch Network (AVTF-TBN), designed to amalgamate auditory, visual, and textual cues for a comprehensive analysis of depression risk. Our approach encompasses three dedicated branches-Audio Branch, Video Branch, and Text Branch-each responsible for extracting salient features from the corresponding modality. These features are subsequently fused through a multimodal fusion (MMF) module, yielding a robust feature vector that feeds into a predictive modeling layer. To further our research, we devised an emotion elicitation paradigm based on two distinct tasks-reading and interviewing-implemented to gather a rich, sensor-based depression risk detection dataset. The sensory equipment, such as cameras, captures subtle facial expressions and vocal characteristics essential for our analysis. The research thoroughly investigates the data generated by varying emotional stimuli and evaluates the contribution of different tasks to emotion evocation. During the experiment, the AVTF-TBN model has the best performance when the data from the two tasks are simultaneously used for detection, where the F1 Score is 0.78, Precision is 0.76, and Recall is 0.81. Our experimental results confirm the validity of the paradigm and demonstrate the efficacy of the AVTF-TBN model in detecting depression risk, showcasing the crucial role of sensor-based data in mental health detection.
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Depressão , Humanos , Depressão/diagnóstico , Gravação em Vídeo , Emoções/fisiologia , Aprendizado Profundo , Expressão Facial , Feminino , Masculino , Adulto , Redes Neurais de ComputaçãoRESUMO
In recent years, embedded system technologies and products for sensor networks and wearable devices used for monitoring people's activities and health have become the focus of the global IT industry. In order to enhance the speech recognition capabilities of wearable devices, this article discusses the implementation of audio positioning and enhancement in embedded systems using embedded algorithms for direction detection and mixed source separation. The two algorithms are implemented using different embedded systems: direction detection developed using TI TMS320C6713 DSK and mixed source separation developed using Raspberry Pi 2. For mixed source separation, in the first experiment, the average signal-to-interference ratio (SIR) at 1 m and 2 m distances was 16.72 and 15.76, respectively. In the second experiment, when evaluated using speech recognition, the algorithm improved speech recognition accuracy to 95%.
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Algoritmos , Dispositivos Eletrônicos Vestíveis , Humanos , Processamento de Sinais Assistido por Computador , Localização de SomRESUMO
AIM: Compared to the conventional cardiopulmonary resuscitation (CCPR), potential benefits of extracorporeal cardiopulmonary resuscitation (ECPR) for patients with cardiac arrest (CA) are still controversial. We aimed to determine whether ECPR can improve the prognosis of CA patients compared with CCPR. METHODS: We systematically searched PubMed, EMBASE, and Cochrane Library from database's inception to July 2023 to identify randomized controlled trials (RCTs) or cohort studies that compared ECPR with CCPR in adults (aged ≥ 16 years) with out-of-hospital cardiac arrest (OHCA) and in-hospital cardiac arrest (IHCA). This meta-analysis was performed using a random-effects model. Two researchers independently reviewed the relevance of the study, extracted data, and evaluated the quality of the included literature. The primary outcome was short-term (from hospital discharge to one month after cardiac arrest) and long-term (≥ 90 days after cardiac arrest) survival with favorable neurological status (defined as cerebral performance category scores 1 or 2). Secondary outcomes included survival at 1 months, 3-6 months, and 1 year after cardiac arrest. RESULTS: The meta-analysis included 3 RCTs and 14 cohort studies involving 167,728 patients. We found that ECPR can significantly improve good neurological prognosis (RR 1.82, 95%CI 1.42-2.34, I2 = 41%) and survival rate (RR 1.51, 95%CI 1.20-1.89, I2 = 62%). In addition, the results showed that ECPR had different effects on favorable neurological status in patients with OHCA (short-term: RR 1.50, 95%CI 0.98- 2.29, I2 = 55%; long-term: RR 1.95, 95% CI 1.06-3.59, I2 = 11%). However, ECPR had significantly better effects on neurological status than CCPR in patients with IHCA (short-term: RR 2.18, 95%CI 1.24- 3.81, I2 = 9%; long-term: RR 2.17, 95% CI 1.19-3.94, I2 = 0%). CONCLUSIONS: This meta-analysis indicated that ECPR had significantly better effects on good neurological prognosis and survival rate than CCPR, especially in patients with IHCA. However, more high-quality studies are needed to explore the role of ECPR in patients with OHCA.
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Reanimação Cardiopulmonar , Humanos , Reanimação Cardiopulmonar/métodos , Prognóstico , Parada Cardíaca/terapia , Parada Cardíaca/mortalidade , Oxigenação por Membrana Extracorpórea/métodos , Parada Cardíaca Extra-Hospitalar/terapia , Parada Cardíaca Extra-Hospitalar/mortalidadeRESUMO
OBJECTIVE: To explore the cause of inconsistency between the results of trisomy 7 by expanded non-invasive prenatal testing (NIPT-PLUS) and trisomy 18 by prenatal diagnosis. METHODS: A pregnant woman who received genetic counseling at Jiaozuo Maternal and Child Health Care Hospital on July 5, 2020 was selected as the study subject. NIPT-PLUS, systematic ultrasound and interventional prenatal testing were carried out. The middle segment and root of umbilical cord, center and edge of the maternal and fatal surface of the placenta were sampled for the validation by copy number variation sequencing (CNV-seq). RESULTS: The result of NIPT-PLUS indicated that the fetus has trisomy 7. Systematic ultrasound has shown multiple malformations including atrioventricular septal defect, horseshoe kidney, and rocker-bottom feet. However, QF-PCR, chromosomal karyotyping analysis, and CNV-seq of amniotic fluid samples all showed that the fetus was trisomy 18. Validation using multiple placental samples confirmed that the middle segment of the umbilical cord contains trisomy 18, the center of the placenta contained trisomy 7, and other placental sites were mosaicism for trisomy 7 and trisomy 18. Notably, the ratio of trisomy 18 became lower further away from the umbilical cord. CONCLUSION: The false positive results of trisomy 7 and false negative trisomy 18 by NIPT-PLUS was probably due to the existence of placental mosaicism. Strict prenatal diagnosis is required needed aneuploidy is detected by NIPT-PLUS to exclude the influence of placental mosaicisms.
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Transtornos Cromossômicos , Trissomia , Criança , Gravidez , Feminino , Humanos , Trissomia/diagnóstico , Trissomia/genética , Síndrome da Trissomía do Cromossomo 18/diagnóstico , Síndrome da Trissomía do Cromossomo 18/genética , Placenta , Variações do Número de Cópias de DNA , Diagnóstico Pré-Natal/métodos , Transtornos Cromossômicos/genética , AneuploidiaRESUMO
Cell division in eukaryotes is a highly regulated process that is critical to the life of a cell. Dysregulated cell proliferation, often driven by anomalies in cell Cyclin-dependent kinase (CDK) activation, is a key pathological mechanism in cancer. Recently, selective CDK4/6 inhibitors have shown clinical success, particularly in treating advanced-stage estrogen receptor (ER)-positive and human epidermal growth factor receptor 2 (HER2)-negative breast cancer. This review provides an in-depth analysis of the action mechanism and recent advancements in CDK4/6 inhibitors, categorizing them based on their structural characteristics and origins. Furthermore, it explores proteolysis targeting chimers (PROTACs) targeting CDK4/6. We hope that this review could be of benefit for further research on CDK4/6 inhibitors and PROTACs.
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Neoplasias da Mama , Quinase 6 Dependente de Ciclina , Humanos , Feminino , Quinase 4 Dependente de Ciclina , Proteólise , Inibidores de Proteínas Quinases/farmacologia , Inibidores de Proteínas Quinases/uso terapêutico , Neoplasias da Mama/tratamento farmacológicoRESUMO
We describe the presentation and treatment of the first reported case of a nasopharyngeal pleomorphic lipoma. The mass was successfully treated with a combined endoscopic trans-oral surgical excision approach by using low temperature-controlled plasma technology, resulting in optimal patient outcomes. Laryngoscope, 134:2710-2712, 2024.
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Lipoma , Neoplasias Nasofaríngeas , Humanos , Neoplasias Nasofaríngeas/cirurgia , Neoplasias Nasofaríngeas/diagnóstico , Neoplasias Nasofaríngeas/patologia , Lipoma/cirurgia , Lipoma/patologia , Lipoma/diagnóstico , Masculino , Feminino , Pessoa de Meia-Idade , Nasofaringe/patologia , Nasofaringe/cirurgia , Nasofaringe/diagnóstico por imagemRESUMO
Objective: To investigate the safety of continuing aspirin use in patients with coronary heart disease undergoing thyroid surgery during the perioperative period. Methods: Forty-four patients with coronary heart disease who underwent thyroid surgery in our department from July 2019 to June 2023 were selected as the observation group, and the observation group continued to use aspirin during the perioperative period. Forty-four patients who underwent the same surgery during the same period without coronary heart disease and without anticoagulant or antiplatelet therapy were selected as control group 1. Another 44 patients with coronary heart disease who underwent the same surgery from August 2015 to June 2019 and used low molecular weight heparin bridging during the perioperative period were selected as control group 2. Clinical data from the 3 groups of patients were collected for retrospective analysis. Results: The age and proportion of male patients in the observation group and control group 2 were higher than those in control group 1, and the total hospital stay in control group 2 was longer than in the observation group and control group 1, with statistically significant differences (all P < .05). There were no statistically significant differences in surgical time, intraoperative blood loss, postoperative drainage volume, duration of drainage tube retention, postoperative hospital stay, and perioperative hemoglobin, platelet, and international normalized ratio between the 3 groups of patients (all P > .05). All patients in the 3 groups successfully completed surgery without serious complications or death during the perioperative period. Conclusion: Continuing to use aspirin in patients with coronary heart disease who undergo thyroid surgery during the perioperative period can safely complete surgery without increasing the risk of intraoperative and postoperative bleeding.
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Colchicine binding site inhibitors (CBSIs) have attracted much attention due to their antitumor efficacies and the advantages of inhibiting angiogenesis and overcoming multidrug resistance. However, no CBSI has been currently approved for cancer treatment due to the insufficient efficacies, serious toxicities and poor pharmacokinetic properties. Design of dual-target inhibitors is becoming a potential strategy for cancer treatment to improve anticancer efficacy, decrease adverse events and overcome drug resistance. Therefore, we reviewed dual-target inhibitors of colchicine binding site (CBS), summarized the design strategies and the biological activities of these dual-target inhibitors, expecting to provide inspiration for developing novel dual inhibitors based on CBS.
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Antineoplásicos , Colchicina , Neoplasias , Humanos , Colchicina/metabolismo , Colchicina/química , Antineoplásicos/farmacologia , Antineoplásicos/química , Antineoplásicos/síntese química , Sítios de Ligação/efeitos dos fármacos , Neoplasias/tratamento farmacológico , Neoplasias/metabolismo , Moduladores de Tubulina/química , Moduladores de Tubulina/farmacologia , Moduladores de Tubulina/uso terapêutico , Estrutura Molecular , AnimaisRESUMO
OBJECTIVES: To investigate the prevalence of depression and anxiety symptoms among older adults in an urban district in China, as well as their associated factors. DESIGN: Cross-sectional study. SETTING: General communities in Shenzhen, Guangdong, China. PARTICIPANTS: A total of 5372 community-dwelling older adults aged 65 years or older were initially recruited. Ultimately, 5331 participants met the inclusion criteria and were included in this study. METHODS: Participants completed a sociodemographic questionnaire, along with assessments including the Patient Health Questionnaire-9, Generalised Anxiety Scale-7, UCLA Loneliness Simplification Scale, Insomnia Severity Index Scale (ISI), Community Dementia Brief Screening Scale and the 8-item Dementia Screening Questionnaire. Statistical analyses included the Shapiro-Wilk test, independent t-test, Wilcoxon rank test, χ2 test and univariate and multivariate linear regression analysis. RESULTS: The prevalence of depression and anxiety symptoms among older adults in Shenzhen communities was 10.4% and 11.3%, respectively. In multivariate analysis, age (B=-0.01, p<0.05), relatively poor health status in the past year (B=1.00, p<0.01), poor health status in the past year (B=2.40, p<0.01), ISI score (B=0.21, p<0.01), -item Ascertain Dementia Questionnaire (AD8) score (B=0.22, p<0.01), UCLA Loneliness Scale (ULS) score (B=0.24, p<0.01) were significantly associated with the severity of depression symptom, Compared with their respective reference categories, relatively poor health status in the past year (B=0.50, p<0.01), poor health status in the past year (B=1.32, p<0.01), ISI score (B=0.23, p<0.01), sleep duration (B=0.05, p<0.01), AD8 score (B=0.21, p<0.01), Community Screening Instrument for Dementia score (B=0.13, p<0.01), ULS score (B=0.22, p<0.01) were significantly associated with the severity of anxiety symptom. CONCLUSIONS: We observed a high prevalence of depression and anxiety symptoms among older adults in this study. The existing welfare system and infrastructure should remain and targeted mental health programmes addressing the identified risk factors should be proposed.
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Demência , Depressão , Humanos , Idoso , Estudos Transversais , Prevalência , Depressão/psicologia , Ansiedade/psicologia , China/epidemiologia , Demência/epidemiologiaRESUMO
Objective: To investigate the incidence of ischemic stroke complications after endovascular treatment for basilar artery stenosis used preoperative high-resolution magnetic resonance vascular wall imaging (HRMR/VWI) and diffusion-weighted imaging (DWI). Methods: The clinical data of 47 patients with severe symptomatic basilar artery stenosis (stenosis rate ≥70 %) treated with endovascular therapy at the Neuro-interventional Center from December 2017 to December 2021 were retrospectively analyzed. High-resolution magnetic resonance angiography (HRMR VWI) and DWI were used to evaluate the location of atherosclerotic plaque at basilar artery stenosis and the distribution of cerebral infarction lesions in all patients before surgery.According to the CISS classification system for ischemic stroke, patients were divided into a perforation group and a hypoperfusion group, and the general situation, plaque distribution, and incidence of ischemic stroke complications 7 days after endovascular treatment in the two groups were analyzed. Results: There was no significant difference in baseline data between the two groups. After 7 days of intravascular treatment, the incidence of ischemic stroke was higher in the perforation group (20.0 %) than in the hypoperfusion group (0.0 %), and the difference was statistically significant (P = 0.027). A significant association was found between the perforation group and the hypoperfusion group for the incidence of ischemic stroke at 7 days (P = 0.003, OR = 2.347; 95 % CI = 2.056-4.268). There were a higher proportion of ventral plaques (74.1 %) and a lower proportion of dorsal plaques (33.3 %) in the hypoperfusion group, which were 15.0 % and 90.0 % in the perforation group, respectively (χ2 = 16.045, P < 0.001; χ2 = 15.092, P < 0.001). There was no significant difference in the proportion of left and right plaques between the two groups. Conclusions: The risk of ischemic stroke is greater in patients with perforator artery obstruction undergoing endovascular therapy, and lower in patients with hypoperfusion/embolus removal.
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Objective: Depression is a common mental illness with a high prevalence rate and is a significant contributor to the global burden of diseases. Various factors are associated with depression, and its etiology is complex. Instead of focusing on single-factor effects, this study aimed to explore a combination of high-risk factor sets for depression among adult community residents. Methods: We conducted a cross-sectional survey in Shenzhen, China, from January 2021 to March 2021. A simple sampling method was used to enroll participants. A total of 1,965 adult residents completed the survey and were assessed using the Patient Health Questionnaire-9 (PHQ-9), the Eysenck Personality Questionnaire-Revised Short Scale for Chinese (EPQ-RSC), and the Psychosocial Stress Survey for Groups (PSSG). The fuzzy-set qualitative comparative analysis method was used to explore the high-risk factor sets for depression among adult community residents. Results: The prevalence of depression among the surveyed adult residents in Shenzhen was 6.36%. The mean scores of PHQ-9 were higher among women and unmarried residents. The combination of low extroversion (e) and high neuroticism (N) in personality traits, along with high scores for life events (V), negative emotional responses to events (G), positive emotional responses to events (O), and positive coping styles to events (I) (denoted as e*N*V*G*O*I) constituted a high-risk factor set for depression. The overall consistency was 0.843, and the overall coverage was 0.330. Conclusion: Our study suggested that stressful life events together with personality traits including neuroticism and introversion serve as crucial factors for depression among adult community residents, regardless of the coping strategies they adopt. This study provides data for developing comprehensive interventions such as regulating neuroticism and introversion levels and reducing stressors to prevent the occurrence of depression among adult community residents.
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OBJECTIVE: To investigate the protective effect of quercetin (QR) on acute liver injury induced by diquat (DQ) poisoning in mice and its mechanism. METHODS: Eighty healthy male C57BL/6 mice with SPF grade were randomly divided into control group, DQ model group, QR treatment group, and QR control group, with 20 mice in each group. The DQ poisoning model was established by a one-time intraperitoneal injection of DQ solution (40 mg/kg); the control and QR control groups received equivalent amounts of distilled water through intraperitoneal injection. Four hours after modeling, the QR treatment group and the QR control group received 0.5 mL QR solution (50 mg/kg) through gavage. Meanwhile, an equivalent amount of distilled water was given orally to the control group and the DQ model group. The treatments above were administered once daily for seven consecutive days. Afterwards, the mice were anesthetized, blood and liver tissues were collected for following tests: changes in the structure of mice liver tissue were observed using transmission electron microscopy; the levels of serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST) were detected using enzyme linked immunosorbent assay (ELISA); the levels of glutathione (GSH), superoxide dismutase (SOD), and malondialdehyde (MDA) in liver tissues were measured using the water-soluble tetrazolium-1 (WST-1) method, the thiobarbituric acid (TBA) method, and enzymatic methods, respectively; the protein expressions of nuclear factor erythroid 2-related factor 2 (Nrf2), heme oxygenase-1 (HO-1), Kelch-like ECH-associated protein 1 (Keap1), and activated caspase-9 in liver tissues were detected using Western blotting. RESULTS: Severe mitochondrial damage was observed in the liver tissues of mice in the DQ model group using transmission electron microscopy, yet mitochondrial damage in the QR treatment group showed significant alleviation. Compared to the control group, the DQ model group had significantly increased levels of MDA in liver tissue, serum AST, and ALT, yet had significantly decreased levels of GSH and SOD in liver tissue. In comparison to the DQ model group, the QR treatment group exhibited significant reductions in serum levels of ALT and AST, as well as MDA levels in liver tissue [ALT (U/L): 52.60±6.44 vs. 95.70±8.00, AST (U/L): 170.45±19.33 vs. 251.10±13.09, MDA (nmol/mg): 12.63±3.41 vs. 18.04±3.72], and notable increases in GSH and SOD levels in liver tissue [GSH (µmol/mg): 39.49±6.33 vs. 20.26±3.96, SOD (U/mg): 121.40±11.75 vs. 81.67±10.01], all the differences were statistically significant (all P < 0.01). Western blotting results indicated that the protein expressions of Nrf2 and HO-1 in liver tissues of the DQ model group were significantly decreased compared to the control group. On the other hand, the protein expressions of Keap1 and activated caspase-9 were conspicuously higher when compared to the control group. In comparison to the DQ model group, the QR treatment group showed a significant increase in the protein expressions of Nrf2 and HO-1 in liver tissues (Nrf2/ß-actin: 1.17±0.08 vs. 0.92±0.45, HO-1/ß-actin: 1.53±0.17 vs. 0.84±0.09). By contrast, there was a notable decrease in the protein expressions of Keap1 and activated caspase-9 (Keap1/ß-actin: 0.48±0.06 vs. 1.22±0.09, activated caspase-9/ß-actin: 1.17±0.12 vs. 1.59±0.30), the differences were statistically significant (all P < 0.01). CONCLUSIONS: QR may reduce acute liver injury induced by DQ poisoning in mice via activating Keap1/Nrf2 signaling pathway.
Assuntos
Doença Hepática Induzida por Substâncias e Drogas , Diquat , Fígado , Camundongos Endogâmicos C57BL , Quercetina , Animais , Masculino , Camundongos , Quercetina/farmacologia , Fígado/efeitos dos fármacos , Fígado/metabolismo , Doença Hepática Induzida por Substâncias e Drogas/metabolismo , Doença Hepática Induzida por Substâncias e Drogas/tratamento farmacológico , Caspase 9/metabolismo , Proteína 1 Associada a ECH Semelhante a Kelch/metabolismo , Estresse Oxidativo/efeitos dos fármacos , Fator 2 Relacionado a NF-E2/metabolismo , Alanina Transaminase/sangue , Proteínas de Membrana , Heme Oxigenase-1RESUMO
OBJECTIVES: Multiple myeloma (MM) is a class of malignant plasma cell diseases. An increasing application of autologous stem cell transplantation (ASCT) and anti-myeloma agents represented by proteasome inhibitors (PIs) has improved the response rates and survival of MM patients. Patients progressing within 12 months were recently categorized with functional high-risk (FHR), which could not be clarified by existing genetic risk factors, with poor outcomes. Our study aimed to investigate clinical indices related to FHR and seek prognostic roles in transplant-eligible MM patients. METHODS: Demographic and individual baseline clinical characteristics were compared by using the Pearson's chi-square and Mann-Whitney U test. Progression-free survival (PFS) and overall survival (OS) were described by Kaplan-Meier estimates and compared using the log-rank test. Logistic regression analysis was used to assess the association of baseline characteristics at MM diagnosis with FHR status. RESULTS: From 18th January 2010 to 1st December 2022, 216 patients were included and divided into two groups according to the FHR status. There was no difference in baseline data between the two groups. Renal impairment (RI, Scr > 2 mg/dL) was common in MM patients and made sense in FHR status. AST levels were validated as independent predictors for FHR status (p = 0.019). DISCUSSION: Patients with RI or higher AST levels (AST > 40 U/L) tended to have worse outcomes. However, transplants had apparently improved prognoses. CONCLUSION: Therefore, in the PIs era, transplantations are still effective therapies for transplant-eligible MM patients.
Assuntos
Transplante de Células-Tronco Hematopoéticas , Mieloma Múltiplo , Humanos , Mieloma Múltiplo/tratamento farmacológico , Estudos Retrospectivos , Inibidores de Proteassoma/uso terapêutico , Transplante AutólogoRESUMO
In this study, to address the defects of sodium alginate (SA), such as its susceptibility to disintegration, silica was coated on the outer layer of sodium alginate hydrogel beads in order to improve its swelling and slow-release properties. Tetraethyl orthosilicate (TEOS) was used as the hydrolyzed precursor, and the solution of silica precursor was prepared by sol-gel reaction under acidic conditions. Then SA-silica hydrogel beads prepared by ionic crosslinking method were immersed into the SiO2 precursor solution to prepare SA-silica hydrogel beads. The chemical structure and morphology of the hydrogel beads were characterized by XRD, FTIR, and SEM, and the results showed that the surface of SA-silica beads was successfully encapsulated with the outer layer of SiO2, and the surface was smooth and dense. The swelling experiments showed that the swelling performance effectively decreased with the increase of TEOS molar concentration, and the maximum swelling ratio of the hydrogel beads decreased from 41.07 to 14.3, and the time to reach the maximum swelling ratio was prolonged from 4 h to 8 h. The sustained-release experiments showed that the SA-silica hydrogel beads possessed a good pH sensitivity, and the time of sustained-release was significantly prolonged in vitro. Hemolysis and cytotoxicity experiments showed that the SA-silica hydrogel beads were biocompatible when the TEOS molar concentration was lower than 0.375 M. The SA-silica-2 hydrogel beads had good biocompatibility, swelling properties, and slow-release properties at the same time.
RESUMO
Antitumor agents often lack effective penetration and accumulation to achieve high therapeutic efficacy in treating solid tumors. Nanomotor-based nanomaterials offer a potential solution to address this obstacle. Among them, nitric oxide (NO) based nanomotors have garnered attention for their potential applications in nanomedicine. However, there widespread clinical adoption has been hindered by their complex preparation processes. To address this limitation, we have developed a NO-driven nanomotor utilizing a convenient and scalable nanogel preparation procedure. These nanomotors, loaded with the fluorescent probe / sonosensitizer chlorin e6 (Ce6), were specifically engineered for sonodynamic therapy. Through comprehensive in vitro investigations using both 2D and 3D cell models, as well as in vivo analysis of Ce6 fluorescent signal distribution in solid tumor models, we observed that the self-propulsion of these nanomotors significantly enhances cellular uptake and tumor penetration, particularly in solid tumors. This phenomenon enables efficient access to challenging tumor regions and, in some cases, results in complete tumor coverage. Notably, our nanomotors have demonstrated long-term in vivo biosafety. This study presents an effective approach to enhancing drug penetration and improving therapeutic efficacy in tumor treatment, with potential clinical relevance for future applications.