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1.
Front Endocrinol (Lausanne) ; 15: 1374245, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-39286273

RESUMO

Background: To identify the risk factors and construct a predictive model for early recurrence of hepatitis B virus(HBV-)- related hepatocellular carcinomas(HCCs) after radical resection. Data and methods: A total of 465 HBV-related HCC patients underwent radical resections between January 1, 2012 and August 31, 2018.Their data were collected through the inpatient information management system of the First Affiliated Hospital of University of Science and Technology of China. Survival and subgroup analyses of early recurrence among male and female patients were performed using Kaplan-Meier curves. The independent risk factors associated with early postoperative tumor recurrence were analyzed using multivariate Cox proportional hazards regression model. Based on these independent risk factors, a risk function model for early recurrence was fitted, and a column chart for the prediction model was drawn for internal and external validation. Results: A total of 181 patients developed early recurrences, including 156 males and 25 females. There was no difference in the early recurrence rates between males and females. Tumor diameters>5cm, microvascular invasion and albumin level<35 g/L were independent risk factors for early recurrence. A nomogram for the early recurrence prediction model was drawn; the areas under the curve for the model and for external verification were 0.638 and 0.655, respectively. Conclusion: Tumor diameter>5 cm, microvascular invasion, and albumin level<35 g/L were independent risk factors for early recurrence. The prediction model based on three clinical indicators could predict early recurrence, with good discrimination, calibration, and extrapolation.


Assuntos
Carcinoma Hepatocelular , Hepatectomia , Neoplasias Hepáticas , Recidiva Local de Neoplasia , Nomogramas , Humanos , Masculino , Feminino , Carcinoma Hepatocelular/cirurgia , Carcinoma Hepatocelular/virologia , Carcinoma Hepatocelular/patologia , Neoplasias Hepáticas/cirurgia , Neoplasias Hepáticas/virologia , Neoplasias Hepáticas/patologia , Recidiva Local de Neoplasia/patologia , Pessoa de Meia-Idade , Adulto , Fatores de Risco , Vírus da Hepatite B , Estudos Retrospectivos , Hepatite B/complicações , China/epidemiologia , Idoso , Prognóstico
2.
Pharm Dev Technol ; : 1-12, 2024 Sep 28.
Artigo em Inglês | MEDLINE | ID: mdl-39286881

RESUMO

Glioblastoma is a highly aggressive glioma with limited treatment options. Boron neutron capture therapy (BNCT) offers a promising approach for refractory cancers, utilizing boron-10 (10B) and thermal neutrons to generate cytotoxic particles. Effective BNCT depends on selective targeting and retention of 10B in tumors. Current BNCT drugs face issues with rapid clearance and poor tumor accumulation. To address this, we developed gold nanoparticles (AuNPs) functionalized with cyclic arginine-glycine-aspartic acid (cRGD) peptides as a nanocarrier for Sodium Mercaptododecaborate (BSH), resulting in AuNPs-BSH&PEG-cRGD. In vitro, AuNPs-BSH&PEG-cRGD increased 10B content in GL261 glioma cells by approximately 2.5-fold compared to unmodified AuNPs-BSH&PEG, indicating enhanced targeting due to cRGD's affinity for integrin receptor αvß3. In a subcutaneous glioma mouse model, 6 h post-intratumoral administration, the 10B concentration in tumors was 17.98 µg/g for AuNPs-BSH&PEG-cRGD, significantly higher than 0.45 µg/g for BSH. The tumor-to-blood (T/B) and tumor-to-normal tissue (T/N) ratios were also higher for AuNPs-BSH&PEG-cRGD, suggesting improved targeting and retention. This indicates that AuNPs-BSH&PEG-cRGD may enhance BNCT efficacy and minimize normal tissue toxicity. In summary, this study provides a novel strategy for BSH delivery and may broaden the design vision of BNCT nano-boron capture agents.

3.
Invest Ophthalmol Vis Sci ; 65(11): 43, 2024 Sep 03.
Artigo em Inglês | MEDLINE | ID: mdl-39330987

RESUMO

Purpose: Corneal wounding healing is critical for maintaining clear vision, however, a complete understanding of its dynamic regulatory mechanisms remains elusive. Here, we used single-cell RNA sequencing (scRNA-seq) to analyze the cellular activities and transcriptional changes of corneal limbal epithelial cells at different stages after wound healing in cynomolgus monkeys, which exhibit a closer transcriptomic similarity to humans. Methods: Corneal limbal tissues were collected during uninjured, 1-day and 3-day healing stages, dissociated into single cells, and subjected to scRNA-seq using the 10× Genomics platform. Cell types were clustered by graph-based visualization methods and unbiased computational analysis. Additionally, cell migration assays and immunofluorescent staining were performed on cultured human corneal epithelial cells. Results: We characterized nine cell clusters by scRNA-seq analysis of the cynomolgus monkey corneal epithelium. By comparing heterogeneous transcriptional changes in major cell types during corneal healing, we highlighted the importance of limbal epithelial cells (LEPCs) and basal epithelial cells (BEPCs) in extracellular matrix (ECM) formation and wound healing, as well as suprabasal epithelial cells (SEPCs) in epithelial differentiation during the healing processes. We further identified five different sub-clusters in LEPC, including the transit amplifying cell (TAC) sub-cluster that promotes early healing through the activation of thrombospondin-1 (THBS1) expression. Conclusions: Our study represents the first comprehensive exploration of the detailed transcriptome profile of individual corneal cells during the wound healing process in nonhuman primates. We demonstrate the intricate mechanisms involved in corneal healing and provide a promising avenue for potential therapies in corneal wound healing.


Assuntos
Epitélio Corneano , Macaca fascicularis , Análise de Célula Única , Transcriptoma , Cicatrização , Animais , Cicatrização/fisiologia , Cicatrização/genética , Epitélio Corneano/metabolismo , Lesões da Córnea/metabolismo , Lesões da Córnea/genética , Movimento Celular/fisiologia , Perfilação da Expressão Gênica , Células Cultivadas , Modelos Animais de Doenças , Humanos , Limbo da Córnea/citologia , Limbo da Córnea/metabolismo , Masculino
4.
J Affect Disord ; 365: 178-184, 2024 Nov 15.
Artigo em Inglês | MEDLINE | ID: mdl-39151760

RESUMO

BACKGROUND: Psychological resilience is defined as the process and outcome of individuals' successful adaptation to challenging life experiences. The Habenula (Hb) is known to be involved in the stress response; however, the relationship between Hb volume and resilience in humans remains unclear. This study investigated the correlation among resilience, Hb volume, and depressive tendencies in adults. METHODS: Hb volumes were assessed using deep learning techniques applied to 110 healthy participants. Resilience and depression were evaluated using the Connor-Davidson Resilience Scale and Beck Depression Inventory-II, respectively. We examined the relationship between Hb volume and resilience and assessed the mediating effects of resilience on the relationship between Hb volume and depressive tendencies. RESULTS: Correlation analysis revealed a positive correlation between resilience and Hb volume (partial r = 0.176, p = 0.001), which was more pronounced in women (partial r = 0.353, p = 0.003). Hb volumes on the left and right sides exhibited significant lateralization (LI = 0.031, 95 % CI = [0.016, 0.046]). Despite Hb asymmetry, lateralization was not significantly associated with resilience. The mediation analysis shows significant indirect effect of resilience on the relationship between Hb volume and depressive tendencies (ß = -0.093, 95%CI = [-0.189, -0.019]). CONCLUSION: This study found that populations with lower resilience have smaller Hb volume. Previous research has shown that Hb volume decreased with the increasing severity of depression symptoms in patients. Our findings support this view and extend it to a population that has not been clinically diagnosed with depression. Additionally, we found that psychological resilience can be predicted by Hb volume and may serve as a mediating factor indirectly affecting depressive tendencies, even in healthy individuals. LIMITATIONS: Due to its cross-sectional design, this study was unable to analyze dynamic changes in Hb volume during the process of resilience adaptation.


Assuntos
Depressão , Habenula , Resiliência Psicológica , Humanos , Feminino , Masculino , Habenula/fisiologia , Adulto , Depressão/psicologia , Imageamento por Ressonância Magnética , Adulto Jovem , Escalas de Graduação Psiquiátrica
5.
ACS Appl Mater Interfaces ; 16(35): 45969-45988, 2024 Sep 04.
Artigo em Inglês | MEDLINE | ID: mdl-39171973

RESUMO

Regional analgesia based on the local anesthetic ropivacaine plays a crucial role in postoperative pain management and recovery; however, the short duration of analgesia limits its clinical potential. Various drug delivery systems such as microparticles and lipid carriers have been used to prolong the analgesic effect, yet most of them are prone to abrupt release from the site of administration or have poor analgesic effects of less than 48 h, which fail to meet the needs of postoperative analgesia. In this study, a low-molecular-weight gelator sodium deoxycholate-based hydrogel loaded with ropivacaine (DC-ROP gel) was designed for long-acting analgesia. The noncovalent interaction between ropivacaine and sodium deoxycholate helps to improve the stability and sustained release performance of the gel. This internal drug-binding hydrogel also avoids experiencing the burst release effect commonly seen in polymer hydrogels previously reported for the slow release of local anesthetics. DC-ROP gel exhibited the dual advantages of self-healing after compression and long-term controlled release. In mice with inflammatory pain, DC-ROP gel achieved peripheral nerve block for more than 1 week after a single injection. Histological and blood biochemical analyses confirmed that the DC-ROP gel did not produce systemic toxicity, and cytotoxicity experiments demonstrated that the DC-ROP gel resulted in low irritation. These results suggest that DC-ROP gel provides a promising strategy for local anesthetics in long-term postoperative pain management, broadening the potential of bile salt-based low-molecular-weight hydrogels for drug delivery.


Assuntos
Anestésicos Locais , Ácido Desoxicólico , Hidrogéis , Ropivacaina , Ropivacaina/química , Ropivacaina/farmacologia , Hidrogéis/química , Hidrogéis/farmacologia , Animais , Ácido Desoxicólico/química , Camundongos , Anestésicos Locais/química , Anestésicos Locais/administração & dosagem , Anestésicos Locais/farmacologia , Analgesia/métodos , Masculino , Peso Molecular
6.
J Virol ; 98(9): e0063524, 2024 Sep 17.
Artigo em Inglês | MEDLINE | ID: mdl-39158346

RESUMO

Flavivirus infection capitalizes on cellular lipid metabolism to remodel the cellular intima, creating a specialized lipid environment conducive to viral replication, assembly, and release. The Japanese encephalitis virus (JEV), a member of the Flavivirus genus, is responsible for significant morbidity and mortality in both humans and animals. Currently, there are no effective antiviral drugs available to combat JEV infection. In this study, we embarked on a quest to identify anti-JEV compounds within a lipid compound library. Our research led to the discovery of two novel compounds, isobavachalcone (IBC) and corosolic acid (CA), which exhibit dose-dependent inhibition of JEV proliferation. Time-of-addition assays indicated that IBC and CA predominantly target the late stage of the viral replication cycle. Mechanistically, JEV nonstructural proteins 1 and 2A (NS1 and NS2A) impede 5'-adenosine monophosphate (AMP)-activated protein kinase (AMPK) activation by obstructing the liver kinase B1 (LKB1)-AMPK interaction, resulting in decreased p-AMPK expression and a consequent upsurge in lipid synthesis. In contrast, IBC and CA may stimulate AMPK by binding to its active allosteric site, thereby inhibiting lipid synthesis essential for JEV replication and ultimately curtailing viral infection. Most importantly, in vivo experiments demonstrated that IBC and CA protected mice from JEV-induced mortality, significantly reducing viral loads in the brain and mitigating histopathological alterations. Overall, IBC and CA demonstrate significant potential as effective anti-JEV agents by precisely targeting AMPK-associated signaling pathways. These findings open new therapeutic avenues for addressing infections caused by Flaviviruses. IMPORTANCE: This study is the inaugural utilization of a lipid compound library in antiviral drug screening. Two lipid compounds, isobavachalcone (IBC) and corosolic acid (CA), emerged from the screening, exhibiting substantial inhibitory effects on the Japanese encephalitis virus (JEV) proliferation in vitro. In vivo experiments underscored their efficacy, with IBC and CA reducing viral loads in the brain and mitigating JEV-induced histopathological changes, effectively shielding mice from fatal JEV infection. Intriguingly, IBC and CA may activate 5'-adenosine monophosphate (AMP)-activated protein kinase (AMPK) by binding to its active site, curtailing the synthesis of lipid substances, and thus suppressing JEV proliferation. This indicates AMPK as a potential antiviral target. Remarkably, IBC and CA demonstrated suppression of multiple viruses, including Flaviviruses (JEV and Zika virus), porcine herpesvirus (pseudorabies virus), and coronaviruses (porcine deltacoronavirus and porcine epidemic diarrhea virus), suggesting their potential as broad-spectrum antiviral agents. These findings shed new light on the potential applications of these compounds in antiviral research.


Assuntos
Proteínas Quinases Ativadas por AMP , Antivirais , Vírus da Encefalite Japonesa (Espécie) , Encefalite Japonesa , Metabolismo dos Lipídeos , Replicação Viral , Animais , Metabolismo dos Lipídeos/efeitos dos fármacos , Replicação Viral/efeitos dos fármacos , Vírus da Encefalite Japonesa (Espécie)/efeitos dos fármacos , Vírus da Encefalite Japonesa (Espécie)/fisiologia , Camundongos , Antivirais/farmacologia , Humanos , Encefalite Japonesa/tratamento farmacológico , Encefalite Japonesa/virologia , Proteínas Quinases Ativadas por AMP/metabolismo , Chalconas/farmacologia , Triterpenos/farmacologia , Proteínas não Estruturais Virais/metabolismo , Infecções por Flavivirus/tratamento farmacológico , Infecções por Flavivirus/virologia , Infecções por Flavivirus/metabolismo , Flavivirus/efeitos dos fármacos , Linhagem Celular
7.
Front Neurol ; 15: 1416557, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38994489

RESUMO

The abuse of nitrous oxide (N2O) poses a substantial public health challenge. In many countries, including China, regulations governing the utilization and accessibility to N2O remain ambiguous, particularly within the food industry. Here, we report a case of a 21-year-old female who presented with symptoms of subacute combined degeneration (SCD) of the spinal cord due to N2O abuse. The patient exhibited bilateral lower limb numbness and weakness, low serum vitamin B12 levels with elevated homocysteine levels, and lumbar spine magnetic resonance imaging (MRI) revealed abnormal signals of the spinal cord. Following cessation of N2O and comprehensive therapy including methylcobalamin and nerve growth factor, the symptoms significantly improved. A follow-up examination 3 months later showed good progress in gait stability. At a 5-year follow-up, the patient's previous clinical symptoms had completely disappeared, and her quality of life had returned to normal. This case underscores the urgency of raising awareness and prevention of N2O abuse, emphasizing the importance of timely diagnosis and comprehensive treatment for patient recovery. Clear formulation and enforcement of relevant regulatory measures are equally crucial in reducing instances of abuse.

8.
Sheng Wu Gong Cheng Xue Bao ; 40(7): 2070-2086, 2024 Jul 25.
Artigo em Chinês | MEDLINE | ID: mdl-39044576

RESUMO

The binding of proteins and ligands is a crucial aspect of life processes. The calculation of the protein-ligand binding affinity (PLBA) offers valuable insights into protein function, drug screening targets protein receptors, and enzyme modifications. In recent years, artificial intelligence (AI) has experienced rapid advancements, becoming widely used in PLBA prediction. This is attributed to its robust feature extraction ability, superior algorithm accuracy, and speedy calculations. Our paper aims to provide a comprehensive overview of AI predication process, associated resources, application scenarios, challenges, and potential solutions, serving as a valuable reference for the relevant research endeavors.


Assuntos
Algoritmos , Inteligência Artificial , Ligação Proteica , Proteínas , Ligantes , Proteínas/metabolismo , Proteínas/química
9.
Cancer Epidemiol Biomarkers Prev ; 33(10): 1368-1374, 2024 Oct 02.
Artigo em Inglês | MEDLINE | ID: mdl-39037332

RESUMO

BACKGROUND: Higher magnesium intake was linked to a lower risk of hepatocellular carcinoma (HCC). However, the relationship between blood magnesium level and HCC has not been fully characterized, especially among patients with liver cirrhosis who are at a higher risk for HCC. METHODS: In the Mass General Brigham Biobank, we developed a new prospective cohort of 1,430 patients with liver cirrhosis without liver cancer history using the validated International Classification of Diseases codes. We used Cox proportional hazards models to generate hazard ratios (HRs) with 95% confidence intervals (CI) for incident HCC and used generalized estimating equations to compare changes in liver biomarkers according to baseline blood magnesium, adjusting for age, sex, race, lifestyles, body mass index, type 2 diabetes, model for end-stage liver disease score, and hepatitis infection. RESULTS: During a median follow-up period of 4.26 years, 109 patients developed HCC. Magnesium deficiency (<1.70 mg/dL; N = 158) was associated with a higher risk of HCC (HR = 1.93; 95% CI, 1.12-3.30) compared with magnesium sufficiency (≥1.70 mg/dL; N = 1282). This association remained robust in the 1-year lag analysis (HR = 2.18; 95% CI, 1.11-4.28) and in sensitivity analysis excluding patients with alcoholic liver disease (HR = 2.41; 95% CI, 1.23-4.74). Magnesium in the lowest quartile was associated with a faster increase in alanine transaminase (ß = 4.35; 95% CI, 1.06-7.63), aspartate aminotransferase (ß = 6.46; 95% CI, 0.28-12.6), direct bilirubin (ß = 0.18; 95% CI, 0.01-0.35), and total bilirubin (ß = 0.21; 95% CI, 0.03-0.39), compared with the highest quartile. CONCLUSIONS: Lower blood magnesium level is associated with higher HCC risk and unfavorable liver biomarker changes. IMPACT: If confirmed, our findings may potentially enable better identification of high-risk patients for HCC and inform better management strategies for liver cirrhosis.


Assuntos
Carcinoma Hepatocelular , Cirrose Hepática , Neoplasias Hepáticas , Magnésio , Humanos , Carcinoma Hepatocelular/sangue , Carcinoma Hepatocelular/epidemiologia , Feminino , Neoplasias Hepáticas/sangue , Neoplasias Hepáticas/epidemiologia , Neoplasias Hepáticas/etiologia , Masculino , Magnésio/sangue , Estudos Prospectivos , Pessoa de Meia-Idade , Cirrose Hepática/sangue , Cirrose Hepática/complicações , Cirrose Hepática/epidemiologia , Fatores de Risco , Idoso , Adulto
10.
Small ; : e2402177, 2024 Jul 30.
Artigo em Inglês | MEDLINE | ID: mdl-39077951

RESUMO

Accurate assessment of phenotypic and genotypic characteristics of bacteria can facilitate comprehensive cataloguing of all the resistance factors for better understanding of antibiotic resistance. However, current methods primarily focus on individual phenotypic or genotypic profiles across different colonies. Here, a Digital microfluidic-based automated assay for whole-genome sequencing of single-antibiotic-resistant bacteria is reported, enabling Genotypic and Phenotypic Analysis of antibiotic-resistant strains (Digital-GPA). Digital-GPA can efficiently isolate and sequence antibiotic-resistant bacteria illuminated by fluorescent D-amino acid (FDAA)-labeling, producing high-quality single-cell amplified genomes (SAGs). This enables identifications of both minor and major mutations, pinpointing substrains with distinctive resistance mechanisms. Digital-GPA can directly process clinical samples to detect and sequence resistant pathogens without bacterial culture, subsequently provide genetic profiles of antibiotic susceptibility, promising to expedite the analysis of hard-to-culture or slow-growing bacteria. Overall, Digital-GPA opens a new avenue for antibiotic resistance analysis by providing accurate and comprehensive molecular profiles of antibiotic resistance at single-cell resolution.

11.
Front Neurol ; 15: 1365445, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38919968

RESUMO

Purpose: This systematic review and meta-analysis aimed to evaluate the efficacy of repetitive transcranial magnetic stimulation (rTMS) in postherpetic neuralgia (PHN). Methods: Through an extensive search in four databases until October 2023, we selected five randomized controlled trials adhering to our specific criteria, involving 257 patients in total. For continuous outcomes, the standardized mean difference (SMD) was calculated. Heterogeneity among the studies was assessed using Cochran's I 2 and Q statistics, adopting a random-effects model for I 2 values over 50%. For assessing potential publication bias, we utilized both funnel plot and Egger's test. Results: Our analysis found that rTMS reduced the overall visual analogue scale (VAS) (SMD: -1.52, 95% CI: -2.81 to -0.23, p = 0.02), VAS at 1 month post-treatment (SMD: -2.21, 95% CI: -4.31 to -0.10, p = 0.04), VAS at 3 months post-treatment (SMD: -1.51, 95% CI: -2.81 to -0.22, p = 0.02), as well as patients' global impression of change scale (PGIC) (SMD: -1.48, 95% CI: -2.87 to -0.09, p = 0.04) and short-form McGill pain questionnaire (SF-MPQ) (SMD: -1.25, 95% CI: -2.41 to -0.09, p = 0.03) compared to the sham-rTMS group. Conclusion: Our study suggests that rTMS might have a potential alleviating effect on PHN symptoms. However, due to the limited number of studies and variations in rTMS parameters, larger sample studies involving more diverse populations, as well as further clarification of the most appropriate stimulation protocol, are still needed. Systematic review registration: https://www.crd.york.ac.uk/prospero/, Identifier ID: CRD42023488420.

12.
Transl Vis Sci Technol ; 13(6): 6, 2024 Jun 03.
Artigo em Inglês | MEDLINE | ID: mdl-38874976

RESUMO

Purpose: To evaluate the ability of swept-source optical coherence tomography angiography (SS-OCTA) to assess lid margin vascularity. Methods: This prospective, cross-sectional trial enrolled 125 participants, including 15 control subjects and 110 meibomian gland dysfunction (MGD) patients. Lid margin blood flow density (LMBFD) was obtained using SS-OCTA. LMBFD was assessed for repeatability in 54 of 125 participants and for reproducibility in 23 of 125 participants. The efficacy of LMBFD was validated in the 125 participants, who were divided into mild (n = 46), moderate (n = 42), and severe groups (n = 37) according to the lid margin vascularity severity shown in the slit-lamp photographs. Correlations between LMBFD and MG-related parameters, such as ocular surface disease index (OSDI), fluorescein tear break-up time (FTBUT), cornea fluorescein staining (CFS), lid margin score (LMS), and meibomian gland expressibility (ME), were analyzed in all 125 participants. Results: Repeatability and reproducibility coefficients were satisfactorily high in the scan mode with a scan area of 6 mm × 6 mm (intraclass correlation coefficient [ICC] repeatability = 0.905; ICC reproducibility = 0.986) and a scan area of 9 mm × 9 mm (ICC repeatability = 0.888; ICC reproducibility = 0.988). The LMBFD gradually increased in the mild, moderate, and severe groups (P < 0.001). LMBFD was significant correlated with OSDI (r = 0.290, P = 0.001), FTBUT (r = -0.195, P = 0.030), CFS (r = 0.352, P < 0.001), ME (r = 0.191, P = 0.033), and LMS (r = 0.370, P < 0.001). Conclusions: LMBFD may be a noninvasive, repeatable, reproducible, and efficient index for the quantitative evaluation of eyelid margin vascularity in the future. Translational Relevance: We demonstrated that SS-OCTA has the potential to evaluate the eyelid margin vascularity in MGD patients and guide future treatment strategies in clinics.


Assuntos
Pálpebras , Tomografia de Coerência Óptica , Humanos , Tomografia de Coerência Óptica/métodos , Masculino , Feminino , Estudos Prospectivos , Estudos Transversais , Pessoa de Meia-Idade , Reprodutibilidade dos Testes , Adulto , Pálpebras/irrigação sanguínea , Pálpebras/diagnóstico por imagem , Idoso , Disfunção da Glândula Tarsal/diagnóstico por imagem , Fluxo Sanguíneo Regional , Angiografia/métodos , Glândulas Tarsais/diagnóstico por imagem
13.
Neurosci Bull ; 40(9): 1261-1273, 2024 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-38937384

RESUMO

The activity of occipitotemporal regions involved in linguistic reading processes, such as the ventral occipitotemporal cortex (vOT), is believed to exhibit strong interactions during higher-order language processing, specifically in the connectivity between the occipital gyrus and the temporal gyrus. In this study, we utilized functional magnetic resonance imaging (fMRI) with psychophysiological interaction (PPI) and dynamic causal modeling (DCM) to investigate the functional and effective connectivity in the occipitotemporal network during speed reading. We conducted the experiment with native Japanese speakers who underwent and without speed-reading training and subsequently performed established reading tasks at different speeds (slow, medium, and fast) while undergoing 3-Tesla Siemens fMRI. Our activation analyses revealed significant changes in occipital and temporal regions as reading speed increased, indicating functional connectivity within the occipitotemporal network. DCM results further demonstrated more intricate effective connections and high involvement within the occipitotemporal pathway: (1) reading signals originated from the inferior occipital gyrus (iO), distributed to the vOT and the posterior superior temporal sulcus (pSTS), and then gathered in the anterior superior temporal sulcus (aSTS); (2) reading speed loads had modulation effects on the pathways from the aSTS to vOT and from the iO to vOT. These findings highlight the complex connectivity and dynamic interactions within the occipitotemporal network during speed-reading processes.


Assuntos
Mapeamento Encefálico , Imageamento por Ressonância Magnética , Lobo Occipital , Leitura , Lobo Temporal , Humanos , Masculino , Lobo Occipital/fisiologia , Lobo Occipital/diagnóstico por imagem , Feminino , Adulto Jovem , Lobo Temporal/fisiologia , Lobo Temporal/diagnóstico por imagem , Adulto , Vias Neurais/fisiologia , Vias Neurais/diagnóstico por imagem , Rede Nervosa/fisiologia , Rede Nervosa/diagnóstico por imagem
14.
Curr Med Sci ; 44(3): 648-656, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38748371

RESUMO

OBJECTIVE: Sepsis is considered a major cause of health loss in children and had high mortality and morbidity. Currently, there is no reliable model for predicting the prognosis of pediatric patients with sepsis. This study aimed to analyze the clinical characteristics of sepsis in children and assess the risk factors associated with poor prognosis in pediatric sepsis patients to identify timely interventions and improve their outcomes. METHODS: This study analyzed the clinical indicators and laboratory results of septic patients hospitalized in the Pediatric Intensive Care Unit of Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, China, from January 1, 2019, to December 31, 2021. Risk factors for sepsis were identified by logistic regression analyses. RESULTS: A total of 355 children with sepsis were enrolled, with 333 children (93.8%) in the good prognosis group, and 22 children (6.2%) in the poor prognosis group. Among them, there were 255 patients (71.8%) in the sepsis group, and 100 patients (28.2%) in the severe sepsis group. The length of hospital stay in the poor prognosis group was longer than that in the good prognosis group (P<0.01). The levels of interleukin 1ß (IL-1ß) in the poor prognosis group were higher than those in the good prognosis group (P>0.05), and the platelet (PLT), albumin (ALB), and hemoglobin (Hb) levels were lower in the poor prognosis group (P<0.01). The IL-8 levels in the severe sepsis group were higher than those in the sepsis group (P<0.05). Multiple logistic regression analysis suggested that lower Hb levels, ALB levels, peak PLT counts, and higher IL-1ß levels were independent risk factors for poor prognosis in children with sepsis. CONCLUSION: Lower Hb, ALB, and PLT counts and elevated IL-1ß are independent risk factors for poor prognosis in children with sepsis.


Assuntos
Unidades de Terapia Intensiva Pediátrica , Sepse , Humanos , Masculino , Recém-Nascido , Pré-Escolar , Sepse/sangue , Sepse/mortalidade , Tempo de Internação , Prognóstico , China/epidemiologia , Fatores de Risco , Interleucina-1beta/sangue , Interleucina-8/sangue , Hemoglobinas/metabolismo , Contagem de Plaquetas , Albuminas/metabolismo
15.
Cytokine ; 180: 156663, 2024 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-38815522

RESUMO

BACKGROUND: Glioma represents the predominant malignant brain tumor. This investigation endeavors to elucidate the impact and prospective mechanisms of glycolysis-related lncARSR on glioma. METHODS: LncARSR level was assessed in normal glial cells and glioma cells. Cell proliferation, migration, and invasion measurements were conducted through CCK-8, wound healing, and transwell assay. Flow cytometry was utilized to measure cell apoptosis and cell cycle. Biochemical assay kits and immunoblotting were employed to measure the content of glycolysis-related indicators and protein expression, respectively. We analyzed the impact of both lncARSR knockdown and overexpression of the Signal Transducer and Activator of Transcription 3 (STAT3) on Hexokinase 2 (HK2) using dual luciferase reporter assays and Chromatin Immunoprecipitation (ChIP) experiments. Further assessment of the impact of lncARSR on glioma progression was conducted through animal experiments. RESULTS: LncARSR was expressed at elevated levels in glioma cells compared to normal glial cells. Overexpressing lncARSR enhanced proliferation, migration, invasion, and G2/M phase arrest in glioma cells and also increased glucose, lactate, ATP production, as well as the expression of HK2, PFK1, PKM2, GLUT1, and LDHA. STAT3 binding to the HK2 gene promoter was weakened following the knockdown of lncARSR. Upregulation of STAT3 reversed the suppressed functions of knocking down lncARSR on cell proliferation, migration, invasion, G2/M phase arrest, and glycolysis and counteracted its promotional effect on cell apoptosis. In vivo, knocking down lncARSR inhibits glioma growth and ki67 and PCNA expression. CONCLUSION: LncARSR promotes the development of glioma by enhancing glycolysis through the STAT3-HK2 axis.


Assuntos
Movimento Celular , Proliferação de Células , Glioma , Glicólise , Hexoquinase , RNA Longo não Codificante , Fator de Transcrição STAT3 , Fator de Transcrição STAT3/metabolismo , Glioma/metabolismo , Glioma/patologia , Glioma/genética , Hexoquinase/metabolismo , Hexoquinase/genética , Humanos , RNA Longo não Codificante/genética , RNA Longo não Codificante/metabolismo , Linhagem Celular Tumoral , Animais , Movimento Celular/genética , Camundongos , Neoplasias Encefálicas/metabolismo , Neoplasias Encefálicas/patologia , Neoplasias Encefálicas/genética , Regulação Neoplásica da Expressão Gênica , Camundongos Nus , Apoptose , Transdução de Sinais
16.
BMC Genomics ; 25(1): 423, 2024 Apr 29.
Artigo em Inglês | MEDLINE | ID: mdl-38684946

RESUMO

BACKGROUND: Single-cell clustering has played an important role in exploring the molecular mechanisms about cell differentiation and human diseases. Due to highly-stochastic transcriptomics data, accurate detection of cell types is still challenged, especially for RNA-sequencing data from human beings. In this case, deep neural networks have been increasingly employed to mine cell type specific patterns and have outperformed statistic approaches in cell clustering. RESULTS: Using cross-correlation to capture gene-gene interactions, this study proposes the scCompressSA method to integrate topological patterns from scRNA-seq data, with support of self-attention (SA) based coefficient compression (CC) block. This SA-based CC block is able to extract and employ static gene-gene interactions from scRNA-seq data. This proposed scCompressSA method has enhanced clustering accuracy in multiple benchmark scRNA-seq datasets by integrating topological and temporal features. CONCLUSION: Static gene-gene interactions have been extracted as temporal features to boost clustering performance in single-cell clustering For the scCompressSA method, dual-channel SA based CC block is able to integrate topological features and has exhibited extraordinary detection accuracy compared with previous clustering approaches that only employ temporal patterns.


Assuntos
Análise de Célula Única , Análise de Célula Única/métodos , Análise por Conglomerados , Humanos , Epistasia Genética , Análise de Sequência de RNA/métodos , Redes Reguladoras de Genes , Biologia Computacional/métodos , Perfilação da Expressão Gênica/métodos , Algoritmos , Aprendizado Profundo , Redes Neurais de Computação
17.
J Cardiovasc Electrophysiol ; 35(5): 1007-1016, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38468346

RESUMO

INTRODUCTION: Cather ablation (CA) is a well-recognized treatment alternative for atrial fibrillation (AF) patients despite more than 20% ablation-treated patients suffering from AF recurrence. The underlying mechanism of AF recurrence postablation is probably associated with high cardiac parasympathetic activity, which can be assessed with deceleration capacity (DC) of heart rate. Given that the relationship between DC and AF recurrence is still controversial, this systematic review and meta-analysis was performed to investigate the characteristics of DC in patients with and without AF recurrence, evaluating the prognostic value of DC in AF patients after CA. METHODS: A literature search was systematically performed in the Embase, PubMed, Web of Science, China National Knowledge Infrastructure (CNKI), and Wanfang databases until October 01, 2023. The observational studies reporting either the pre- and postablation DC in both recurrence and non-recurrence groups or the ratios based on DC for predicting AF recurrence were mainly included. Weighted mean differences (WMD) or odds ratios (OR) based on DC would be calculated with a random-effect model, if heterogeneity estimated with the I2 index and Q statistic was significant (I2 > 50% or p < .05); otherwise, a fixed-effect model would be utilized. RESULTS: A total of eight observational studies involving 914 AF patients treated with radiofrequency or cryoballoon ablation were included in this study. Ablation-treated patients with AF recurrence had the higher DC postablation in relation to those without recurrence (WMD, 1.00; 95% confidence interval [CI], 0.33-1.67; p < .01), which was present up to 3 months of follow-up (WMD, 1.54; 95% CI, 1.11-1.96; p < .01), whereas there was no statistical significance in DC before ablation between recurrence and non-recurrence groups (WMD, 0.34; 95% CI, -0.12 to 0.79; p = .15). The high DC postablation was a risk factor for AF recurrence in ablation-treated patients (OR, 2.17; 95% CI, 1.44-3.25; p < .01). CONCLUSION: The high DC postablation was associated with the risk of AF recurrence, suggesting that DC may act as a prognostic indicator in AF patients treated with CA.


Assuntos
Fibrilação Atrial , Ablação por Cateter , Desaceleração , Frequência Cardíaca , Valor Preditivo dos Testes , Recidiva , Adulto , Idoso , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Potenciais de Ação , Fibrilação Atrial/fisiopatologia , Fibrilação Atrial/cirurgia , Fibrilação Atrial/diagnóstico , Ablação por Cateter/efeitos adversos , Medição de Risco , Fatores de Risco , Fatores de Tempo , Resultado do Tratamento
18.
BMJ Open ; 14(3): e077859, 2024 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-38431298

RESUMO

INTRODUCTION: Early eye screening and treatment can reduce the incidence of blindness by detecting and addressing eye diseases at an early stage. The Ophthalmologist Robot is an automated device that can simultaneously capture ocular surface and fundus images without the need for ophthalmologists, making it highly suitable for primary application. However, the accuracy of the device's screening capabilities requires further validation. This study aims to evaluate and compare the screening accuracies of ophthalmologists and deep learning models using images captured by the Ophthalmologist Robot, in order to identify a screening method that is both highly accurate and cost-effective. Our findings may provide valuable insights into the potential applications of remote eye screening. METHODS AND ANALYSIS: This is a multicentre, prospective study that will recruit approximately 1578 participants from 3 hospitals. All participants will undergo ocular surface and fundus images taken by the Ophthalmologist Robot. Additionally, 695 participants will have their ocular surface imaged with a slit lamp. Relevant information from outpatient medical records will be collected. The primary objective is to evaluate the accuracy of ophthalmologists' screening for multiple blindness-causing eye diseases using device images through receiver operating characteristic curve analysis. The targeted diseases include keratitis, corneal scar, cataract, diabetic retinopathy, age-related macular degeneration, glaucomatous optic neuropathy and pathological myopia. The secondary objective is to assess the accuracy of deep learning models in disease screening. Furthermore, the study aims to compare the consistency between the Ophthalmologist Robot and the slit lamp in screening for keratitis and corneal scar using the Kappa test. Additionally, the cost-effectiveness of three eye screening methods, based on non-telemedicine screening, ophthalmologist-telemedicine screening and artificial intelligence-telemedicine screening, will be assessed by constructing Markov models. ETHICS AND DISSEMINATION: The study has obtained approval from the ethics committee of the Ophthalmology and Optometry Hospital of Wenzhou Medical University (reference: 2023-026 K-21-01). This work will be disseminated by peer-review publications, abstract presentations at national and international conferences and data sharing with other researchers. TRIAL REGISTRATION NUMBER: ChiCTR2300070082.


Assuntos
Lesões da Córnea , Retinopatia Diabética , Ceratite , Oftalmologistas , Robótica , Humanos , Estudos Prospectivos , Inteligência Artificial , Cegueira/diagnóstico , Cegueira/etiologia , Retinopatia Diabética/diagnóstico , Estudos Multicêntricos como Assunto
19.
J Refract Surg ; 40(3): e126-e132, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38466764

RESUMO

PURPOSE: To use artificial intelligence (AI) technology to accurately predict vault and Implantable Collamer Lens (ICL) size. METHODS: The methodology focused on enhancing predictive capabilities through the fusion of machine-learning algorithms. Specifically, AdaBoost, Random Forest, Decision Tree, Support Vector Regression, LightGBM, and XGBoost were integrated into a majority-vote model. The performance of each model was evaluated using appropriate metrics such as accuracy, precision, F1-score, and area under the curve (AUC). RESULTS: The majority-vote model exhibited the highest performance among the classification models, with an accuracy of 81.9% area under the curve (AUC) of 0.807. Notably, LightGBM (accuracy = 0.788, AUC = 0.803) and XGBoost (ACC = 0.790, AUC = 0.801) demonstrated competitive results. For the ICL size prediction, the Random Forest model achieved an impressive accuracy of 85.3% (AUC = 0.973), whereas XG-Boost (accuracy = 0.834, AUC = 0.961) and LightGBM (accuracy = 0.816, AUC = 0.961) maintained their compatibility. CONCLUSIONS: This study highlights the potential of diverse machine learning algorithms to enhance postoperative vault and ICL size prediction, ultimately contributing to the safety of ICL implantation procedures. Furthermore, the introduction of the novel majority-vote model demonstrates its capability to combine the advantages of multiple models, yielding superior accuracy. Importantly, this study will empower ophthalmologists to use a precise tool for vault prediction, facilitating informed ICL size selection in clinical practice. [J Refract Surg. 2024;40(3):e126-e132.].


Assuntos
Lentes Intraoculares , Lentes Intraoculares Fácicas , Humanos , Inteligência Artificial , Aprendizado de Máquina , Algoritmos , Área Sob a Curva , Estudos Retrospectivos
20.
Huan Jing Ke Xue ; 45(3): 1328-1336, 2024 Mar 08.
Artigo em Chinês | MEDLINE | ID: mdl-38471849

RESUMO

The contents of eight carbonaceous subfractions were determined by simultaneously collecting PM2.5 samples from four sites in different functional areas of Tianjin in 2021. The results showed that the organic carbon (OC) concentration was 3.7 µg·m-3 to 4.4 µg·m-3, and the elemental carbon (EC) concentration was 1.6 µg·m-3 to 1.7 µg·m-3, with the highest OC concentration in the central urban area. There was no significant difference in EC concentration. The concentration of PM2.5 showed the distribution characteristics of the surrounding city>central city>peripheral area. The OC/EC minimum ratio method was used to estimate the concentrations of secondary organic carbon (SOC) in PM2.5, and the results showed that the secondary pollution was more prominent in the surrounding city, with SOC accounting for 48.8%. The correlation between carbon subcomponents in each functional area showed the characteristics of the peripheral area>central area>surrounding area, all showing the strongest correlation between EC1 and OC2 and EC1 and OC4. By including the carbon component concentration into the positive definite matrix factorization (PMF) model for source apportionment, the results showed that road dust sources(9.7%-23.5%), coal-combustion sources (10.2%-13.3%), diesel vehicle exhaust (12.6%-20.2%)and gasoline vehicle exhaust (18.9%-38.8%)were the main sources of carbon components in PM2.5 in Tianjin. The pollution sources of carbon components were different in different functional areas, with the central city and peripheral areas mainly affected by gasoline vehicle exhaust; the surrounding city was more prominently affected by the secondary pollution and diesel vehicle exhaust.

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