Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 11.587
Filtrar
1.
JCI Insight ; 2024 Jul 02.
Artículo en Inglés | MEDLINE | ID: mdl-38954484

RESUMEN

Upon infection, naïve CD8+ T cells differentiate into cytotoxic effector cells to eliminate the pathogen-infected cells. Although many mechanisms underlying this process have been demonstrated, the regulatory role of chromatin remodel system in this process remains largely unknown. Here we showed that BRD7, a component of the polybromo-associated BRG1-associated factor complex (PBAF), was required for naïve CD8+ T cells to differentiate into functional short-lived effector cells (SLECs) in response to acute infections caused by influenza virus or lymphocytic choriomeningitis virus (LCMV). BRD7-deficiency in CD8+ T cells resulted in profound defects in effector population and functions, thereby impairing viral clearance and host recovery. Further mechanical studies indicated that the expression of BRD7 significantly turned to high from naïve CD8+ T cells to effector cells, bridged BRG1 and PBRM1 to the core module of PBAF complex, consequently facilitating the assembly of PBAF complex rather than BAF complex in the effector cells. The PBAF complex changed the chromatin accessibility at the loci of Tbx21 gene and up-regulated its expression, leading to the maturation of effector T cells. Our research confirms BRD7 and the PBAF complex are key in CD8+ T cell development and present a significant target for advancing immune therapies.

2.
Int J Gen Med ; 17: 2877-2886, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38947567

RESUMEN

Background: The aim of this study was to describe the demographic and clinical characteristics of hepatitis B virus (HBV) associated hepatocellular carcinoma (HCC), analyse the risk factors associated with HBV-associated HCC, and to provide some references to the diagnosis and treatment of HCC. Methods: This study retrospectively enrolled 730 patients, including 390 patients with chronic hepatitis B (CHB) as controls, and 340 patients with CHB complicated with HCC as patients. Relevant information and medical records of these participants were collected, including age, sex, cigarette smoking, alcoholism, diabetes mellitus (DM), hypertension, coronary heart disease (CHD), cirrhosis, occupation, ascites, HBV-DNA load, the qualitative analysis of HBsAg, HBsAb, HBeAg, HBeAb, and HBcAb serological markers, and levels of alanine transaminase (ALT), aspartate aminotransferase (AST), total bilirubin (TBIL), direct bilirubin (DBIL), gamma-glutamyltransferase (GGT), TNM stage, tumor size and tumor number. The T test, Chi-square test, non-parametric rank-sum test, logistic regression analyses were used to explore the influencing factors and their degree of association with HCC in patients with HBV. Results: The proportion of smoking, alcoholism, married status, DM, hypertension, and the rate of HBV-DNA with a viral load of ≥500 copies/mL were significantly higher in the HCC group than in the controls (all p<0.05). Cirrhosis was more common among patients with CHB+HCC than in controls (p=0.013). The proportion of patients with HBsAg, HBeAb, and HBcAb positive was greater in CHB+HCC group than that in CHB group. Logistic regression analysis indicated that age ≥60 years (OR: 1.835, 95% CI: 1.020-3.302, p=0.043), HBeAb positive (OR: 9.105, 95% CI: 4.796-17.288, p<0.001), antiviral treatment with entecavir (OR: 2.209, 95% CI: 1.106-4.409, p=0.025), and GGT (OR: 1.004, 95% CI: 1.001-1.007, p=0.002) were risk factors for HCC in patients with CHB. Conclusion: Advanced age, HBeAb positive, antiviral treatment with entecavir, and GGT were independent risk factors for HCC in HBV patients.

3.
Nutr Diabetes ; 14(1): 48, 2024 Jun 29.
Artículo en Inglés | MEDLINE | ID: mdl-38951151

RESUMEN

BACKGROUND: This study aimed to assess whether the Haptoglobin (Hp) genotype influences the relationship between hemoglobin (Hb) levels and the development of gestational diabetes mellitus (GDM). Additionally, it sought to evaluate the interaction and joint association of Hb levels and Hp genotype with GDM risk. METHODS: This retrospective study involved 358 women with GDM and 1324 women with normal glucose tolerance (NGT). Peripheral blood leukocytes were collected from 360 individuals at 14-16 weeks' gestation for Hp genotyping. GDM was diagnosed between 24-28 weeks' gestation. Interactive moderating effect, joint analysis, and mediation analysis were performed to evaluate the crosslink of Hb levels and Hp genotype with GDM risk. RESULTS: Women who developed GDM had significantly higher Hb levels throughout pregnancy compared to those with NGT. Increase first-trimester Hb concentration was associated with a progressive rise in GDM incidence, glucose levels, glycosylated hemoglobin levels, Homeostasis Model Assessment for Insulin Resistance (HOMA-IR) values, cesarean delivery rates, and composite neonatal outcomes. Spline regression showed a significant linear association of GDM incidence with continuous first-trimester Hb level when the latter exceeded 122 g/L. Increased first-trimester Hb concentration was an independent risk factor for GDM development after adjusting for potential confounding factors in both the overall population and a matched case-control group. The Hp2-2 genotype was more prevalent among pregnant women with GDM when first-trimester Hb exceeded 122 g/L. Significant multiplicative and additive interactions were identified between Hb levels and Hp genotype for GDM risk, adjusted for age and pre-pregnancy BMI. The odds ratio (OR) for GDM development increased incrementally when stratified by Hb levels and Hp genotype. Moreover, first-trimester Hb level partially mediated the association between Hp genotype and GDM risk. CONCLUSION: Increased first-trimester Hb levels were closely associated with the development of GDM and adverse pregnancy outcomes, with this association moderated by the Hp2-2 genotype.


Asunto(s)
Diabetes Gestacional , Genotipo , Haptoglobinas , Hemoglobinas , Primer Trimestre del Embarazo , Humanos , Femenino , Embarazo , Diabetes Gestacional/genética , Diabetes Gestacional/sangre , Diabetes Gestacional/epidemiología , Haptoglobinas/genética , Estudios Retrospectivos , Adulto , Hemoglobinas/análisis , China/epidemiología , Factores de Riesgo , Pueblo Asiatico/genética , Hemoglobina Glucada/análisis , Glucemia/análisis , Glucemia/metabolismo , Resistencia a la Insulina/genética , Pueblos del Este de Asia
4.
J Neuroinflammation ; 21(1): 167, 2024 Jul 02.
Artículo en Inglés | MEDLINE | ID: mdl-38956605

RESUMEN

BACKGROUND: Deposition of amyloid ß, which is produced by amyloidogenic cleavage of APP by ß- and γ-secretase, is one of the primary hallmarks of AD pathology. APP can also be processed by α- and γ-secretase sequentially, to generate sAPPα, which has been shown to be neuroprotective by promoting neurite outgrowth and neuronal survival, etc. METHODS: The global expression profiles of miRNA in blood plasma samples taken from 11 AD patients as well as from 14 age and sex matched cognitively normal volunteers were analyzed using miRNA-seq. Then, overexpressed miR-140 and miR-122 both in vivo and in vitro, and knock-down of the endogenous expression of miR-140 and miR-122 in vitro. Used a combination of techniques, including molecular biology, immunohistochemistry, to detect the impact of miRNAs on AD pathology. RESULTS: In this study, we identified that two miRNAs, miR-140-3p and miR-122-5p, both targeting ADAM10, the main α-secretase in CNS, were upregulated in the blood plasma of AD patients. Overexpression of these two miRNAs in mouse brains induced cognitive decline in wild type C57BL/6J mice as well as exacerbated dyscognition in APP/PS1 mice. Although significant changes in APP and total Aß were not detected, significantly downregulated ADAM10 and its non-amyloidogenic product, sAPPα, were observed in the mouse brains overexpressing miR-140/miR-122. Immunohistology analysis revealed increased neurite dystrophy that correlated with the reduced microglial chemotaxis in the hippocampi of these mice, independent of the other two ADAM10 substrates (neuronal CX3CL1 and microglial TREM2) that were involved in regulating the microglial immunoactivity. Further in vitro analysis demonstrated that both the reduced neuritic outgrowth of mouse embryonic neuronal cells overexpressing miR-140/miR-122 and the reduced Aß phagocytosis in microglia cells co-cultured with HT22 cells overexpressing miR-140/miR-122 could be rescued by overexpressing the specific inhibitory sequence of miR-140/miR-122 TuD as well as by addition of sAPPα, rendering these miRNAs as potential therapeutic targets. CONCLUSIONS: Our results suggested that neuroprotective sAPPα was a key player in the neuropathological progression induced by dysregulated expression of miR-140 and miR-122. Targeting these miRNAs might serve as a promising therapeutic strategy in AD treatment.


Asunto(s)
Enfermedad de Alzheimer , Quimiotaxis , Ratones Endogámicos C57BL , MicroARNs , Microglía , MicroARNs/metabolismo , MicroARNs/genética , Animales , Enfermedad de Alzheimer/metabolismo , Enfermedad de Alzheimer/patología , Enfermedad de Alzheimer/genética , Ratones , Humanos , Microglía/metabolismo , Microglía/patología , Masculino , Quimiotaxis/fisiología , Femenino , Proteína ADAM10/metabolismo , Proteína ADAM10/genética , Secretasas de la Proteína Precursora del Amiloide/metabolismo , Secretasas de la Proteína Precursora del Amiloide/genética , Ratones Transgénicos , Anciano , Regulación de la Expresión Génica
5.
Accid Anal Prev ; 206: 107697, 2024 Jul 04.
Artículo en Inglés | MEDLINE | ID: mdl-38968864

RESUMEN

Speeding, a risky act of driving a vehicle at a speed exceeding the posted limit, has consistently emerged as a leading contributor to traffic fatalities. Identifying the risk factors associated with injury severity in speeding-related crashes is essential for implementing countermeasures aimed at preventing severe injury incidents and achieving Vision Zero goals. With the wealth of traffic crash data collected by various agencies, researchers have a valuable opportunity to conduct data-driven studies and employ various modeling methods to gain insights into the correlated factors affecting injury severity in traffic crashes. Machine learning models, owing to their superior predictive power compared to statistical models, are increasingly being adopted by researchers. These models, in conjunction with interpretation techniques, can reveal potential relationships between crash injury severity and contributing factors. Traffic crashes are inherently tied to geographic locations, distributed across road networks influenced by diverse socioeconomic and geographical factors. Recognizing spatial heterogeneity in traffic safety is crucial for tailored safety measures to address speeding-related crashes, as a one-size-fits-all approach may not work effectively everywhere. However, most existing machine learning models are unable to incorporate the spatial dependency among observations, such as traffic crashes, which hinders their ability to uncover spatial heterogeneity in traffic safety. To address this gap, this study introduces the Geographically Weighted Neural Network (GWNN) model, a spatial machine-learning model that integrates neural network (NN) and geographically weighted modeling approaches to investigate spatial heterogeneity in speeding-related crashes. Unlike the traditional NN model, which trains a single set of model parameters for all observations, the GWNN trains a local NN model for each crash location using a spatially weighted subsample of nearby crashes, allowing for the quantification of corresponding local effects of features through calculating local marginal effects. To understand the spatial heterogeneity in speeding-related crashes, this study extracted two years (2020 and 2021) of speeding-related crash data from Alabama for the development of the GWNN local models. The modeling results show significant spatial variability among several factors contributing to injury severity in speeding-related crashes. These factors include driver condition, vehicle type, crash type, speed limit, weather, crash time and location, roadway alignment, and traffic volume. Based on the GWNN modeling results, this study identified three types of spatial variations in relationships between contributing factors and crash injury severity: consistent positive associations, consistent negative associations, and inverse associations (i.e., marginal effects can vary between positive and negative depending on the location). This study contributes by integrating advanced machine learning and spatial modeling approaches to uncover intricate spatial patterns and factors influencing injury severity in speeding-related crashes, thereby facilitating the development of targeted policy implementations and safety interventions.

6.
Medicine (Baltimore) ; 103(27): e38750, 2024 Jul 05.
Artículo en Inglés | MEDLINE | ID: mdl-38968515

RESUMEN

BACKGROUND: Bladder cancer (BLCA) is a prevalent and aggressive cancer associated with high mortality and poor prognosis. Currently, studies on the role of disulfidptosis-related long non-coding RNAs (DRLs) in BLCA are limited. This study aims to construct a prognostic model based on DRLs to improve the accuracy of survival predictions for patients and identify novel targets for therapeutic intervention in BLCA management. METHODS: Transcriptomic and clinical datasets for patients with BLCA were obtained from The Cancer Genome Atlas. Using multivariate Cox regression and least absolute shrinkage and selection operator techniques, a risk prognostic signature defined by DRLs was developed. The model's accuracy and prognostic relevance were assessed through Kaplan-Meier survival plots, receiver operating characteristic curves, concordance index, and principal component analysis. Functional and pathway enrichment analyses, including Gene Ontology, Kyoto Encyclopedia of Genes and Genomes, and Gene Set Enrichment Analysis, were conducted to elucidate the underlying biological processes. Immune cell infiltration was quantified using the CIBERSORT algorithm. Differences and functions of immune cells in different risk groups were evaluated through single-sample Gene Set Enrichment Analysis. The Tumor Immune Dysfunction and Exclusion predictor and tumor mutational burden (TMB) assessments were utilized to gauge the likelihood of response to immunotherapy. Drug sensitivity predictions were made using the Genomics of Drug Sensitivity in Cancer database. RESULTS: A robust 8-DRL risk prognostic model, comprising LINC00513, SMARCA5-AS1, MIR4435-2HG, MIR4713HG, AL122035.1, AL359762.3, AC006160.1, and AL590428.1, was identified as an independent prognostic indicator. This model demonstrated strong predictive power for overall survival in patients with BLCA, revealing significant disparities between high- and low-risk groups regarding tumor microenvironment, immune infiltration, immune functions, TMB, Tumor Immune Dysfunction and Exclusion scores, and drug susceptibility. CONCLUSION: This study introduces an innovative prognostic signature of 8 DRLs, offering a valuable prognostic tool and potential therapeutic targets for bladder carcinoma. The findings have significant implications for TMB, the immune landscape, and patient responsiveness to immunotherapy and targeted treatments.


Asunto(s)
ARN Largo no Codificante , Neoplasias de la Vejiga Urinaria , Neoplasias de la Vejiga Urinaria/genética , Neoplasias de la Vejiga Urinaria/mortalidad , Neoplasias de la Vejiga Urinaria/patología , Neoplasias de la Vejiga Urinaria/tratamiento farmacológico , Humanos , ARN Largo no Codificante/genética , Pronóstico , Biomarcadores de Tumor/genética , Masculino , Estimación de Kaplan-Meier , Femenino , Transcriptoma , Curva ROC
9.
Urolithiasis ; 52(1): 103, 2024 Jul 03.
Artículo en Inglés | MEDLINE | ID: mdl-38960942

RESUMEN

Kidney stones and infections significantly affect patients' health-related quality of life (HRQOL); however, the relationship between urinary tract infections (UTIs) and HRQOL in patients with kidney stones remains unclear. This study aimed to investigate the relationship using the validated Chinese version of the Wisconsin Stone Quality of Life questionnaire (C-WISQOL). We prospectively recruited 307 patients with kidney stones to complete the C-WISQOL before and after stone removal. The participants were diagnosed with UTI based on the presence of pyuria or bacteriuria with or without clinical symptoms. The psychometric properties of the C-WISQOL were statistically analyzed. Multivariate linear regression was used to predict the risk factors for impaired HRQOL in patients with stones and UTIs. The questionnaire is a reliable and robust tool for evaluating HRQOL in Chinese-speaking patients with urolithiasis. The UTI and kidney stone co-occurrence was significantly associated with female sex, diabetes mellitus, more previous stone events, higher antibiotic usage, positive stone- or UTI-related symptoms, and postoperative residual stones. The preoperative C-WISQOL scores and improvement in the HRQOL after stone removal in patients clinically diagnosed with UTI were significantly inferior to those in patients without UTI. The regression analyses showed that worse HRQOL was predicted by more previous stone events and positive stone- or UTI-related symptoms. In contrast, the presence of diabetes mellitus and postoperative residual stone fragments predicted a lower improvement in the HRQOL. These findings underscore UTI's harmful impact on perioperative HRQOL in patients with kidney stones and could help strategies benefit those patients.


Asunto(s)
Cálculos Renales , Calidad de Vida , Infecciones Urinarias , Humanos , Femenino , Masculino , Persona de Mediana Edad , Cálculos Renales/complicaciones , Cálculos Renales/cirugía , Infecciones Urinarias/psicología , Infecciones Urinarias/complicaciones , Infecciones Urinarias/epidemiología , Infecciones Urinarias/etiología , Estudios Prospectivos , Adulto , Encuestas y Cuestionarios/estadística & datos numéricos , Factores de Riesgo , Anciano , Psicometría
10.
J Vis Exp ; (208)2024 Jun 14.
Artículo en Inglés | MEDLINE | ID: mdl-38949305

RESUMEN

Conventional static cold storage (SCS) exacerbates ischemic injury in the DCD liver, leading to severe complications for transplant recipients. To address this issue, clinical application of MP technology for donor liver preservation is underway. Simultaneously, efforts are focused on the development of various MP instruments, validated through relevant animal model experiments. Effective large animal trials play a pivotal role in clinical applications. However, challenges persist in the ex vivo preservation of DCD livers and the transplantation procedure in pigs. These hurdles encompass addressing the prolonged preservation of donor livers, conducting viability tests, alleviating ischemic injuries, and shortening the anhepatic phase. The use of a variable temperature-controlled MP device facilitates the prolonged preservation of DCD livers through sequential Dual Hypothermic Oxygenated Machine Perfusion (DHOPE) and Normothermic Machine Perfusion (NMP) modes. This protocol enhances the porcine OLTx model by improving the quality of DCD livers, optimizing the anastomosis technique, and reducing the duration of the anhepatic phase.


Asunto(s)
Trasplante de Hígado , Hígado , Preservación de Órganos , Perfusión , Animales , Trasplante de Hígado/métodos , Preservación de Órganos/métodos , Porcinos , Perfusión/métodos , Hígado/cirugía
11.
Antonie Van Leeuwenhoek ; 117(1): 98, 2024 Jul 09.
Artículo en Inglés | MEDLINE | ID: mdl-38981868

RESUMEN

An aerobic, Gram-stain-negative bacterium, designated as SYSU D00382T, was sourced from soil of Gurbantunggut Desert, PR China. The strain was short-rod-shaped, oxidase-positive and catalase-negative, with yellow-colored, convex, round, and smooth colonies on TSA plate. Growth and proliferation occurred at 4-37 °C (optimal: 28-30 °C), pH 5.0-8.0 (optimal: pH 6.0-7.0) and NaCl concentration of 0-2.5% (optimal: 0-0.5%). The 16S rRNA gene based phylogenetic assessment showed that SYSU D00382T belonged to the genus Pedobacter, and was most closely related to Pedobacter ginsengisoli Gsoil 104T with similarity of 97.7%. The genomic DNA G+C content of SYSU D00382T was 46.4%. The average nucleotide identity (ANI) and digital DNA-DNA hybridization (dDDH) values between SYSU D00382T and P. ginsengisoli Gsoil 104T were 75.7% and 17.5%, respectively. The main polar lipid was phosphatidylethanolamine. The major fatty acids (> 5%) were iso-C15:0, iso-C17:0 3-OH, summed features 3 and 9. The sole respiratory quinone identified was MK-7. The phylogeny based on 16S rRNA gene and whole-genome sequences revealed that SYSU D00382T formed a robust lineage with P. ginsengisoli Gsoil 104T. Based on phenotypic, phylogenetic and genotypic data, a novel specie named Pedobacter deserti sp. nov. is proposed. The type strain is SYSU D00382T (= CGMCC 1.18627T = MCCC 1K04972T = KCTC 82279T).


Asunto(s)
Técnicas de Tipificación Bacteriana , Composición de Base , ADN Bacteriano , Clima Desértico , Ácidos Grasos , Pedobacter , Filogenia , ARN Ribosómico 16S , Microbiología del Suelo , Pedobacter/genética , Pedobacter/clasificación , Pedobacter/aislamiento & purificación , Pedobacter/fisiología , ARN Ribosómico 16S/genética , ADN Bacteriano/genética , Ácidos Grasos/análisis , China , Hibridación de Ácido Nucleico , Análisis de Secuencia de ADN
12.
Ann Med Surg (Lond) ; 86(7): 3880-3886, 2024 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-38989172

RESUMEN

Background: Syncope is a serious consequence in patients with hypertrophic obstructive cardiomyopathy (HOCM). Percutaneous endocardial septal radiofrequency ablation (PESA) has emerged as a promising intervention to alleviate symptoms and enhance the quality of life for HOCM patients. However, little is known about the effects of PESA on syncope in HOCM. The authors aimed to study the effects of PESA on syncope in patients with HOCM. Materials and methods: Nineteen patients with HOCM and syncope were enrolled. The left ventricular outflow tract gradient (LVOTG) of the patients was more than 50 mmHg despite medication. The participants underwent PESA under the guidance of intracardiac echocardiography (ICE) combined with a three-dimensional electrophysiological mapping system. The patients were followed for 3 (3-5.5) months. Results: The mean age of the patients was 54.8±13.7 years. Out of the 19 participants, 7 (37%) were females. During the follow-up, the syncope was completely alleviated in 14 patients (73.7%) or the syncope episodes were reduced greater than or equal to 80% in 16 patients (84.2%). The mean NYHA functional class significantly improved from 2.2±0.7 at baseline to 1.7±0.6 during follow-up (P=0.002). The LVOTG and septal thickness showed a decreasing trend from baseline to follow-up (LVOTG: P=0.083, septal thickness: P=0.086). Conclusion: The authors' investigation provides evidence supporting the effectiveness of PESA in reducing syncope episodes in patients with HOCM.

13.
Nucleic Acids Res ; 2024 Jul 12.
Artículo en Inglés | MEDLINE | ID: mdl-38994558

RESUMEN

CasX (also known as Cas12e), a Class 2 CRISPR-Cas system, shows promise in genome editing due to its smaller size compared to the widely used Cas9 and Cas12a. Although the structures of CasX-sgRNA-DNA ternary complexes have been resolved and uncover a distinctive NTSB domain, the dynamic behaviors of CasX are not well characterized. In this study, we employed single-molecule and biochemical assays to investigate the conformational dynamics of two CasX homologs, DpbCasX and PlmCasX, from DNA binding to target cleavage and fragment release. Our results indicate that CasX cleaves the non-target strand and the target strand sequentially with relative irreversible dynamics. The two CasX homologs exhibited different cleavage patterns and specificities. The dynamic characterization of CasX also reveals a PAM-proximal seed region, providing guidance for CasX-based effector design. Further studies elucidate the mechanistic basis for why modification of sgRNA and the NTSB domain can affect its activity. Interestingly, CasX has less effective target search efficiency than Cas9 and Cas12a, potentially accounting for its lower genome editing efficiency. This observation opens a new avenue for future protein engineering.

14.
Commun Biol ; 7(1): 824, 2024 Jul 06.
Artículo en Inglés | MEDLINE | ID: mdl-38971948

RESUMEN

The expression dysregulation of microRNAs (miRNA) has been widely reported during cancer development, however, the underling mechanism remains largely unanswered. In the present work, we performed a systematic integrative study for genome-wide DNA methylation, copy number variation and miRNA expression data to identify mechanisms underlying miRNA dysregulation in lower grade glioma. We identify 719 miRNAs whose expression was associated with alterations of copy number variation or promoter methylation. Integrative multi-omics analysis revealed four subtypes with differing prognoses. These glioma subtypes exhibited distinct immune-related characteristics as well as clinical and genetic features. By construction of a miRNA regulatory network, we identified candidate miRNAs associated with immune evasion and response to immunotherapy. Finally, eight prognosis related miRNAs were validated to promote cell migration, invasion and proliferation through in vitro experiments. Our study reveals the crosstalk among DNA methylation, copy number variation and miRNA expression for immune regulation in glioma, and could have important implications for patient stratification and development of biomarkers for immunotherapy approaches.


Asunto(s)
Neoplasias Encefálicas , Variaciones en el Número de Copia de ADN , Metilación de ADN , Regulación Neoplásica de la Expresión Génica , Glioma , MicroARNs , Humanos , Glioma/genética , Glioma/inmunología , Glioma/patología , MicroARNs/genética , MicroARNs/metabolismo , Neoplasias Encefálicas/genética , Neoplasias Encefálicas/inmunología , Neoplasias Encefálicas/patología , Epigenómica , Genómica , Redes Reguladoras de Genes , Línea Celular Tumoral , Evasión Inmune/genética , Epigénesis Genética , Femenino , Masculino , Pronóstico , Clasificación del Tumor
16.
Heliyon ; 10(12): e32289, 2024 Jun 30.
Artículo en Inglés | MEDLINE | ID: mdl-38975141

RESUMEN

Background: Cuproptosis, a type of regulated cell death that was recently identified, has been linked to the development of a variety of diseases, among them being cancers. Nevertheless, the prognostic significance and therapeutic implications of the cuproptosis potential index in hepatocellular carcinoma (HCC) remain uncertain. Methods: Single-sample gene set enrichment analysis (ssGSEA) and Weighted Gene Co-expression Network Analysis (WGCNA) methodology was conducted to ascertain the identification of modular genes that are closely linked to cuproptosis. In addition, the gene signature indicative of prognosis was formulated by employing univariate Cox regression analysis in conjunction with a random forest algorithm. The efficacy of this gene signature in predicting outcomes was confirmed through validation in both The Cancer Genome Atlas (TCGA) and International Cancer Genome Consortium (ICGC) datasets. Furthermore, a study was undertaken to evaluate the association between the risk score and various clinical-pathological characteristics, explore the biological processes linked to the gene signature, and analyze tumor mutational burden and somatic mutations. Lastly, potential drugs targeting the identified gene signature were identified through screening. Results: The results of our comprehensive analysis across multiple cancer types demonstrated a positive correlation between an elevated cuproptosis potential index (CPI) and an accelerated rate of tumor progression. Furthermore, employing the WGCNA technique, we successfully identified 640 genes associated with cuproptosis. Among these genes, we meticulously screened and validated a seven-gene signature (TCOF1, NOP58, TMEM69, FARSB, DHX37, SLC16A3, and CBX2) that exhibited substantial prognostic significance. Using the median risk score, the division of HCC patients into cohorts with high- and low-risk highlighted significant disparities in survival results, wherein the group with higher risk exhibited a less favorable overall survival. The risk score exhibited commendable predictive efficacy. Moreover, the in vitro knockdown of FARSB significantly hindered cell viability, induced G1 phase arrest, increased apoptosis, and impaired migration in HepG2 and Huh7 cells. Conclusion: Our research has successfully identified a strong seven-gene signature linked to cuproptosis, which could be utilized for prognostic evaluation and risk stratification in patients with HCC. Furthermore, the discovered gene signature, coupled with the functional analysis of FARSB, presents promising prospects as potential targets for therapeutic interventions in HCC.

17.
Aging Med (Milton) ; 7(3): 258-268, 2024 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-38975298

RESUMEN

This practice guideline focuses on the cognitive assessment for mild cognitive impairment in the Guangdong-Hong Kong-Macao Greater Bay Area. To achieve the standardization and normalization of its clinical practice and generate individualized intervention, the National Core Cognitive Center of the Second Affiliated Hospital of Guangzhou Medical University, the Cognitive Disorders Branch of Chinese Geriatic Society, the Dementia Group of Neurology Branch of Guangdong Medical Association and specialists from Hong Kong and Macao developed guidelines based on China's actual conditions and efficiency, economic cost and accuracy. The article addresses the significance, background, and the process of the assessment and follow-up to realize the promotion and dissemination of cognitive assessment.

18.
Postgrad Med ; : 1-12, 2024 Jul 09.
Artículo en Inglés | MEDLINE | ID: mdl-38975648

RESUMEN

BACKGROUND: Whether to perform acromioplasty in arthroscopic rotator cuff repair (ARCR) is controversial, and the optimal surgical approach for rotator cuff tear repair is unknown. The purpose of this study was to compare the reoperation rate, retear rate and patient-reported outcomes (PROs) of ARCR with those of ARCR combined with acromioplasty (ARCR-A). METHODS: PubMed, Embase and Cochrane Library were searched for relevant literature dated between database inception and 4 December 2023. The primary outcomes of this study were the reoperation rate and the retear rate. The secondary outcomes were PROs, including the visual analogue scale (VAS) pain score, the American Shoulder and Elbow Surgeons (ASES) score, the University of California-Los Angeles (UCLA) score, the Constant score and the Western Ontario Rotator Cuff (WORC) score. The quality of the included studies was evaluated by using the risk of bias assessment tool. RevMan 5.3 software was used for meta-analysis. Fixed (I2 <50%) or random (I2 ≥50%) effects models were applied to calculate the effect size. RESULTS: Meta-analysis revealed that ARCR-A had a lower reoperation rate (OR = 0.35, 95%CI: 0.15-0.85, p = 0.02), but the difference in the retear rate between ARCR-A and ARCR was not significant (p = 0.25). In type 2 acromion patients, the reoperation rate was not significantly different between ARCR and ARCR-A (p = 0.12), but, for type 3 acromion patients, the retear rate was lower for ARCR-A than for ARCR (OR = 0.12, 95%CI: 0.01-0.94, p = 0.04). There were statistically significant differences in the 6-month postoperative Constant scores (p < 0.001), VAS pain scores (p = 0.003) 12-month postoperative ASES scores (p = 0.02) and 24-month postoperative WORC scores (p = 0.04), but these differences were not clinically significant. CONCLUSIONS: Combining ARCR with acromioplasty can reduce the rate of reoperation, especially in patients with type 3 acromion, but it provides no clinically important change in the retear rate and postoperative PRO compared with ARCR.

19.
World J Oncol ; 15(4): 598-611, 2024 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-38993244

RESUMEN

Background: Impact of radiotherapy (RT) for esophageal cancer (EC) patients on the development of secondary head and neck cancer (SHNC) remains equivocal. The objective of this study was to investigate the link between definitive RT used for EC treatment and subsequent SHNC. Methods: This study was conducted using the Surveillance, Epidemiology, and End Results (SEER) database to collect the data of primary EC patients. Fine-Gray competing risk regression and standardized incidence ratio (SIR) and propensity score matching (PSM) method were used to match SHNC patients with only primary head and neck cancer (HNC) patients. Overall survival (OS) rates were applied by Kaplan-Meier analysis. Results: In total, 14,158 EC patients from the SEER database were included, of which 9,239 patients (65.3%) received RT and 4,919 patients (34.7%) received no radiation therapy (NRT). After a 12-month latency period, 110 patients (1.2%) in the RT group and 36 patients (0.7%) in the NRT group experienced the development of SHNC. In individuals with primary EC, there was an increased incidence of SHNC compared to the general US population (SIR = 5.95, 95% confidence interval (CI): 5.15 - 6.84). Specifically, the SIR for SHNC was 8.04 (95% CI: 6.78 - 9.47) in the RT group and 3.51 (95% CI: 2.64 - 4.58) in the NRT group. Patients who developed SHNC after RT exhibited significantly lower OS compared to those after NRT. Following PSM, the OS of patients who developed SHNC after RT remained significantly lower than that of matched patients with only primary HNC. Conclusion: An association was discovered between RT for EC and increased long-term risk of SHNC. This work enables radiation oncologists to implement mitigation strategies to reduce the long-term risk of SHNC in patients who have received RT following primary EC.

20.
J Colloid Interface Sci ; 675: 488-495, 2024 Jul 08.
Artículo en Inglés | MEDLINE | ID: mdl-38986322

RESUMEN

As a promising sustainable power source in intelligent electronics, Triboelectric Nanogenerators (TENGs) have garnered widespread interest, with various strategies explored to enhance their output performance. However, most optimization methods for triboelectric materials have focused solely on tuning chemical compositions or fabricating surface microstructures. Here, we have prepared amino-functionalized reduced graphene oxide (FRGO)/polyimide (PI) composite films (PI-FRGO) via in-situ polymerization, aimed at enhancing PI materials' nanotribological power generation performance. By varying the doping levels of amino groups and controlling the FRGO proportion during synthesis, we can explore the optimal FRGO/PI composite film ratio. At a p-Phenylenediamine: reduced Graphene Oxide (PPDA: RGO) ratio of 1:1 and an FRGO addition of 0.1 %, the output electrical performance peaks with a voltage of 58 V, a charge of 33 nC and a current of 12 µA, nearly 2 times that of a pure PI film. We have fabricated a TENG with an optimally formulated PI-FRGO composite to explore its application potential. Under a 10 MΩ external load resistance, the TENG can deliver a power density of 3.5 mW/m2 and can be powering small devices. This work presents new effective strategies to significantly enhance TENG output performance and promote their widespread application.

SELECCIÓN DE REFERENCIAS
DETALLE DE LA BÚSQUEDA
...