RESUMEN
Developing anticancer drugs with low side effects is an ongoing challenge. Immunogenic cell death (ICD) has received extensive attention as a potential synergistic modality for cancer immunotherapy. However, only a limited set of drugs or treatment modalities can trigger an ICD response and none of them have cytotoxic selectivity. This provides an incentive to explore strategies that might provide more effective ICD inducers free of adverse side effects. Here, we report a metal-based complex (Cu-1) that disrupts cellular redox homeostasis and effectively stimulates an antitumor immune response with high cytotoxic specificity. Upon entering tumor cells, this Cu(II) complex enhances the production of intracellular radical oxidative species while concurrently depleting glutathione (GSH). As the result of heightening cellular oxidative stress, Cu-1 gives rise to a relatively high cytotoxicity to cancer cells, whereas normal cells with low levels of GSH are relatively unaffected. The present Cu(II) complex initiates a potent ferroptosis-dependent ICD response and effectively inhibits in vivo tumor growth in an animal model (c57BL/6 mice challenged with colorectal cancer). This study presents a strategy to develop metal-based drugs that could synergistically potentiate cytotoxic selectivity and promote apoptosis-independent ICD responses through perturbations in redox homeostasis.
Asunto(s)
Cobre , Glutatión , Homeostasis , Oxidación-Reducción , Animales , Ratones , Humanos , Glutatión/metabolismo , Ratones Endogámicos C57BL , Antineoplásicos/farmacología , Línea Celular Tumoral , Estrés Oxidativo/efectos de los fármacos , Sinergismo Farmacológico , Muerte Celular Inmunogénica/efectos de los fármacos , Complejos de Coordinación/farmacología , Complejos de Coordinación/química , Ferroptosis/efectos de los fármacos , Especies Reactivas de Oxígeno/metabolismo , Neoplasias Colorrectales/inmunología , Neoplasias Colorrectales/tratamiento farmacológico , Neoplasias Colorrectales/patología , Neoplasias Colorrectales/metabolismoRESUMEN
RATIONALE: Spirometry reference equations that are derived from a large, nationally representative, general population are warranted in China and the impact of using pre- and post-BD spirometry reference values has yet to be assessed in Chinese populations. OBJECTIVES: To present both the pre-BD and post-BD spirometry reference values for Chinese adults using the China Pulmonary Health (CPH) study. METHODS: A reference population of 17969 healthy, non-smoking participants in the CPH study was used to calculate the pre- and post-BD reference values for the forced expiratory volume in 1 s (FEV1), forced vital capacity (FVC) and FEV1/FVC. Both pre- and post-BD reference values were applied to the entire CPH population (50991 individuals) to illustrate the divergence between the use of references in determining the disease prevalence and severity grading. MEASUREMENTS AND MAIN RESULTS: The prevalence of airflow limitation was 5.36% using pre-BD reference and 8.02% using the post-BD reference. Individuals who had post-BD FEV1/FVC below post-BD but higher than pre-BD reference values were found to have significantly higher rates of self-reported respiratory symptoms, and significantly lower values in spirometry indicators than those above post-BD reference values. An additional 3.51% of participants were identified as grade II-IV COPD using the post-BD FEV1 predicted values. CONCLUSION: This study generated and applied pre- and post-bronchodilator spirometry reference values in a nationally representative Chinese adult population. Post-BD reference values may serve as an additional criterion in identifying individuals at risk for obstructive pulmonary diseases, its diagnostic and prognostic values should be further investigated.
RESUMEN
Glutathione (GSH) is the primary antioxidant in cells, and GSH consumption will break the redox balance in cells. Based on this, a method that uses high concentrations of GSH in the tumor microenvironment to trigger the redox reaction of Cu(II) to generate copper nanoprobes with fluorescence and tumor growth inhibition properties is proposed. The nanoprobe mainly exists in the form of Cu(I) and catalyzes the decomposition of hydrogen peroxide into hydroxyl radicals. At the same time, a simple and controllable carbon micro-nano electrode is used to construct a single-cell sensing platform, which enable the detection of glutathione content in single living cells after Cu(II) treatment, providing an excellent example for detecting single-cell biomolecules.
Asunto(s)
Cobre , Glutatión , Glutatión/metabolismo , Cobre/química , Humanos , Neoplasias/metabolismo , Técnicas Biosensibles/métodos , Línea Celular Tumoral , Animales , Oxidación-Reducción , Espacio Intracelular/metabolismoRESUMEN
BACKGROUND: Chronic obstructive pulmonary disease (COPD) is a common respiratory disease and represents the third leading cause of death worldwide. This study aimed to investigate miRNA regulation of Receptor for Advanced Glycation End-products (RAGE), a causal receptor in the pathogenesis of cigarette smoke (CS)-related COPD, to guide development of therapeutic strategies. METHODS: RAGE expression was quantified in lung tissue of COPD patients and healthy controls, and in mice with CS-induced COPD. RNA-sequencing of peripheral blood from COPD patients with binding site prediction was used to screen differentially expressed miRNAs that may interact with RAGE. Investigation of miR-23a-5p as a potential regulator of COPD progression was conducted with miR-23a-5p agomir in COPD mice in vivo using histology and SCIREQ functional assays, while miR-23a-5p mimics or RAGE inhibitor were applied in 16-HBE human bronchial epithelial cells in vitro. RNA-sequencing, ELISA, and standard molecular techniques were used to characterize downstream signaling pathways in COPD mice and 16-HBE cells treated with cigarette smoke extract (CSE). RESULTS: RAGE expression is significantly increased in lung tissue of COPD patients, COPD model mice, and CSE-treated 16-HBE cells, while inhibiting RAGE expression significantly reduces COPD severity in mice. RNA-seq analysis of peripheral blood from COPD patients identified miR-23a-5p as the most significant candidate miRNA interaction partner of RAGE, and miR-23a-5p is significantly downregulated in mice and cells treated with CS or CSE, respectively. Injection of miR-23a-5p agomir leads to significantly reduced airway inflammation and alleviation of symptoms in COPD mice, while overexpressing miR-23a-5p leads to improved lung function. RNA-seq with validation confirmed that reactive oxygen species (ROS) signaling is increased under CSE-induced aberrant upregulation of RAGE, and suppressed in CSE-stimulated cells treated with miR-23a-5p mimics or overexpression. ERK phosphorylation and subsequent cytokine production was also increased under RAGE activation, but inhibited by increasing miR-23a-5p levels, implying that the miR-23a-5p/RAGE/ROS axis mediates COPD pathogenesis via ERK activation. CONCLUSIONS: This study identifies a miR-23a-5p/RAGE/ROS signaling axis required for pathogenesis of COPD. MiR-23a-5p functions as a negative regulator of RAGE and downstream activation of ROS signaling, and can inhibit COPD progression in vitro and in vivo, suggesting therapeutic targets to improve COPD treatment.
Asunto(s)
MicroARNs , Enfermedad Pulmonar Obstructiva Crónica , Animales , Humanos , Ratones , Pulmón/metabolismo , MicroARNs/metabolismo , Enfermedad Pulmonar Obstructiva Crónica/metabolismo , Especies Reactivas de Oxígeno/metabolismo , Receptor para Productos Finales de Glicación Avanzada/genética , Receptor para Productos Finales de Glicación Avanzada/metabolismoRESUMEN
BACKGROUND: The intestinal epithelium is one of the fastest self-renewal tissues in the body, and glutamine plays a crucial role in providing carbon and nitrogen for biosynthesis. In intestinal homeostasis, phosphorylation-mediated signaling networks that cause altered cell proliferation, differentiation, and metabolic regulation have been observed. However, our understanding of how glutamine affects protein phosphorylation in the intestinal epithelium is limited, and identifying the essential signaling pathways involved in regulating intestinal epithelial cell growth is particularly challenging. OBJECTIVES: This study aimed to identify the essential proteins and signaling pathways involved in glutamine's promotion of porcine intestinal epithelial cell proliferation. METHODS: Phosphoproteomics was applied to describe the protein phosphorylation landscape under glutamine treatment. Kinase-substrate enrichment analysis was subjected to predict kinase activity and validated by qRT-PCR and Western blotting. Cell Counting Kit-8, glutamine rescue experiment, chloroquine treatment, and 5-fluoro-2-indolyl deschlorohalopemide inhibition assay revealed the possible underlying mechanism of glutamine promoting porcine intestinal epithelial cell proliferation. RESULTS: In this study, glutamine starvation was found to significantly suppress the proliferation of intestinal epithelial cells and change phosphoproteomic profiles with 575 downregulated sites and 321 upregulated sites. Interestingly, phosphorylation of eukaryotic initiation factor 4E-binding protein 1 at position Threonine70 was decreased, which is a crucial downstream of the mechanistic target of rapamycin complex 1 (mTORC1) pathway. Further studies showed that glutamine supplementation rescued cell proliferation and mTORC1 activity, dependent on lysosomal function and phospholipase D activation. CONCLUSION: In conclusion, glutamine activates mTORC1 signaling dependent on phospholipase D and a functional lysosome to promote intestinal epithelial cell proliferation. This discovery provides new insight into regulating the homeostasis of the intestinal epithelium, particularly in pig production.
Asunto(s)
Glutamina , Fosfolipasa D , Animales , Porcinos , Diana Mecanicista del Complejo 1 de la Rapamicina/metabolismo , Glutamina/farmacología , Glutamina/metabolismo , Fosfolipasa D/metabolismo , Intestinos , Proteínas/metabolismo , Mucosa Intestinal/metabolismo , Proliferación CelularRESUMEN
The E3 ubiquitin ligase Tripartite-motif 3 (TRIM3) is known to play a crucial role in tumor suppression in various tumors through different mechanisms. However, its function and mechanism in ovarian cancer have yet to be elucidated. Our study aims to investigate the expression of TRIM3 in ovarian cancer and evaluate its role in the development of the disease. Our findings revealed a significant decrease in TRIM3 mRNA and protein levels in ovarian cancer tissues and cells when compared to normal ovarian epithelial tissues and cells. Furthermore, we observed a negative correlation between the protein level of TRIM3 and the FIGO stage, as well as a positive correlation with the survival of ovarian cancer patients. Using gain and loss of function experiments, we demonstrated that TRIM3 can inhibit cell proliferation, migration and invasion of the ovarian cancer cells in vitro, as well as suppress tumor growth in vivo. Mechanistic studies showed that TRIM3 interacts with lactate dehydrogenase A, a key enzyme in the glycolytic pathway, through its B-box and coiled-coil domains and induces its ubiquitination and proteasomal degradation, leading to the inhibition of glycolytic ability in ovarian cancer cells. RNA-sequencing analysis revealed significant alterations in the phosphatidylinositol signaling pathways upon TRIM3 overexpression. Additionally, overexpression of TRIM3 inhibited the phosphorylation of AKT. In conclusion, our study demonstrated that TRIM3 exerts a tumor-suppressive effect in ovarian cancer, at least partially, by downregulating LDHA and inhibiting the AKT signaling pathway, and thus leading to the inhibition of glycolysis and limiting the growth of ovarian cancer cells.
RESUMEN
Gastric cancer (GC) is the leading cause of cancer-related death worldwide, and it is associated with a combination of genetic, environmental, and microbial risk factors. Helicobacter pylori (H. pylori) is classified as a type I carcinogen, however, the exact regulatory mechanisms underlying H. pylori-induced GC are incompletely defined. MicroRNAs (miRNAs), one of small non-coding RNAs, negatively regulate gene expression through binding to their target genes. Dysregulation of miRNAs is crucial in human cancer. A noteworthy quantity of aberrant miRNAs induced by H. pylori through complex regulatory networks have been identified. These miRNAs substantially affect genetic instability, cell proliferation, apoptosis, invasion, metastasis, autophagy, chemoresistance, and the tumor microenvironment, leading to GC development and progression. Importantly, some H. pylori-associated miRNAs hold promise as therapeutic tools and biomarkers for GC prevention, diagnosis, and prognosis. Nonetheless, clinical application of miRNAs remains in its infancy with multiple issues, including sensitivity and specificity, stability, reliable delivery systems, and off-target effects. Additional research on the specific molecular mechanisms and more clinical data are still required. This review investigated the biogenesis, regulatory mechanisms, and functions of miRNAs in H. pylori-induced GC, offering novel insights into the potential clinical applications of miRNA-based therapeutics and biomarkers.
Asunto(s)
Infecciones por Helicobacter , Helicobacter pylori , MicroARNs , Neoplasias Gástricas , Humanos , Neoplasias Gástricas/microbiología , Neoplasias Gástricas/genética , MicroARNs/genética , MicroARNs/metabolismo , Helicobacter pylori/genética , Infecciones por Helicobacter/microbiología , Infecciones por Helicobacter/genética , Infecciones por Helicobacter/complicaciones , Animales , Biomarcadores de Tumor/genética , Biomarcadores de Tumor/metabolismo , Regulación Neoplásica de la Expresión GénicaRESUMEN
BACKGROUND: Treatment for parameningeal rhabdomyosarcoma (PM-RMS) has been a challenge since local control is difficult. The goal of this study was to analyse the impact of different local treatment approaches on childhood PM-RMS patients and help dispel the doubt that whether secondary radical surgery (SRS) should be encouraged in the management of PM-RMS. METHODS: A total of 17 children with PM-RMS who received unified systemic chemotherapy and individualized local therapy such as radiotherapy (RT) and/or SRS were included in this retrospective study. The overall survival (OS) and event free survival (EFS) were compared between groups adopting different local strategies. RESULTS: The 3-year OS and EFS of our PM-RMS patients was 75.5% and 56.5% respectively. The OS and EFS of patients who received SRS were both significantly lower than that of the non-SRS group (3-year OS: 50.0% vs 90.0%, P = .031; 3-year EFS: 33.3% vs 60.6%, P = .020). The OS and EFS of the patients who received RT was higher than that of the patients of the non-RT group (3-year OS: 85.6% vs 0%, P = .001; 3-year EFS: 64.0% vs 0%, P = .011). CONCLUSION: This study illustrates that SRS was associated with poor prognosis of PM-RMS and should not be routinely performed. Optimized RT strategies along with more intensive chemotherapy may be alternative options to improve the survival of patients with PM-RMS. Multi-center, large sample and prospective studies are needed to further validate these findings.
Asunto(s)
Rabdomiosarcoma , Niño , Humanos , Lactante , Estudios Retrospectivos , Rabdomiosarcoma/tratamiento farmacológico , Rabdomiosarcoma/radioterapia , Terapia Combinada , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , China/epidemiologíaRESUMEN
Ichthyophthirius multifiliis is a parasite that poses a considerable threat to aquaculture and the ornamental fish industry, but with limited effective treatment options available. This study employed RT-qPCR to detect and analyze the expression changes of partial toll-like receptor (TLR) genes (TLR1 and TLR21), adapter protein and signal transduction molecule genes (MyD88, TRIF, NF-κB, IRAK4, and IRF3), and cytokines (IL-6, IL-8, IL-13, CXC-α and CXCR1), as well as complement C3, in the skin, gill, fin, liver, head kidney and spleen of Rhinogobio ventralis under different infection conditions. Additionally, tissue sections and scanning electron microscopy were utilized to observe the pathological changes in the gills and fins of R. ventralis after infection with I. multifiliis. The expression patterns of TLR-related DEGs (differentially expressed genes) in diseased wild fish were analyzed, revealing upregulation of TLR1, TLR21, MyD88, NF-κB, IRAK4, TRIF, IRF3, IL-6, IL-8, IL-13, CXC-α, CXCR1, and C3 genes in various tissues, indicating that these genes may be involved in the immune response of R. ventralis to I. multifiliis infection. To further analyze the gene expression of sampled from the field, an artificial infection model of R. ventralis was established under laboratory conditions, with additional sampling from the skin and fins. These genes continued to show varying degrees of upregulation, but the results were not entirely consistent with those from Wudongde samples, which may be due to the more complex environment in the wild or differences in the degree of I. multifiliis infection in wild fish. The infection of I. multifiliis caused severe damage to the gills and fins of R. ventralis, characterized by extensive secretions on the gill and fin surfaces, with the presence of attached I. multifiliis trophonts, including damage and loss of gill filaments, swollen gill lamellae, and deformed gill plates, as well as cell proliferation and necrosis of gill epithelial cells. This study sheds light on the role of the TLR signaling pathway in resisting I. multifiliis infection and its associated histopathological changes in R. ventralis, providing valuable insights for the prevention and treatment of I. multifiliis infection in R. ventralis.
RESUMEN
Trivalent arsenicals such as arsenite (AsIII) and methylarsenite (MAsIII) are thought to be ubiquitous in flooded paddy soils and have higher toxicity than pentavalent forms. Fungi are widely prevalent in the rice rhizosphere, and the latter is considered a hotspot for As uptake. However, few studies have focused on alleviating As toxicity in paddy soils using fungi. In this study, we investigated the mechanism by which the protein TaGlo1, derived from the As-resistant fungal strain Trichoderma asperellum SM-12F1, mitigates AsIII and MAsIII toxicity in paddy soils. Taglo1 gene expression in Escherichia coli BL21 conferred strong resistance to AsIII and MAsIII, while purified TaGlo1 showed a high affinity for AsIII and MAsIII. Three cysteine residues (Cys13, Cys18, and Cys71) play crucial roles in binding with AsIII, while only two (Cys13 and Cys18) play crucial roles for MAsIII binding. TaGlo1 had a stronger binding strength for MAsIII than AsIII. Importantly, up to 90.2% of the homologous TaGlo1 proteins originate from fungi by GenBank searching. In the rhizospheres of 14 Chinese paddy soils, Taglo1 was widely distributed and its gene abundance increased with porewater As. This study highlights the potential of fungi to mitigate As toxicity and availability in the soil-rice continuum and suggests future microbial strategies for bioremediation.
Asunto(s)
Contaminantes del Suelo , Suelo , Suelo/química , Arsenitos , Microbiología del Suelo , OryzaRESUMEN
OBJECTIVE: To investigate the association between circulating secretoneurin (SN) and angiographic coronary collateralization in stable angina patients with chronic coronary total occlusion (CTO). METHODS: SN concentrations in serum were measured in 641 stable angina patients with CTO by radioimmunoassay. The status of coronary collaterals from the contra-lateral vessel was visually estimated using the Rentrop grading system, and was categorized into poor (grade 0 or 1) or good (grade 2 or 3) collateralization. RESULTS: Serum SN levels were significantly higher in patients with good coronary collaterals compared to those with poor collaterals (175.23 ± 52.09 pmol/L vs. 143.29 ± 42.01 pmol/L, P < 0.001). Serum SN increased stepwise across Rentrop score 0 to 3 (P < 0.001), and increasing SN tertiles were associated with higher proportion of good coronary collateralization (OR, 1.907; 95% CI, 1.558 ~ 2.335, P < 0.001). After adjustment for confounding variables, serum SN (per tertile) remained an independent factor for predicting good coronary collaterals (OR, 1.870; 95% CI, 1.515 ~ 2.309; P < 0.001). Moreover, the diagnostic value of serum SN (per tertile) was consistent after stratifying patients based on gender, age, body mass index, hypertension, diabetes, history of smoking, severity of coronary artery disease and kidney function (OR: 1.511 ~ 2.680, P interaction ≥ 0.327). CONCLUSION: Elevated circulating SN reflects good angiographic coronary collaterals in stable angina patients with CTO. The findings may provide insight into decision-making for these patients.
Asunto(s)
Angina Estable , Hipertensión , Neuropéptidos , Humanos , Angina Estable/diagnóstico por imagen , CorazónRESUMEN
BACKGROUND: Impaired collateral formation is a major factor contributing to poor prognosis in type 2 diabetes mellitus (T2DM) patients with atherosclerotic cardiovascular disease. However, the current pharmacological treatments for improving collateral formation remain unsatisfactory. The induction of endothelial autophagy and the elimination of reactive oxygen species (ROS) represent potential therapeutic targets for enhancing endothelial angiogenesis and facilitating collateral formation. This study investigates the potential of molybdenum disulfide nanodots (MoS2 NDs) for enhancing collateral formation and improving prognosis. RESULTS: Our study shows that MoS2 NDs significantly enhance collateral formation in ischemic tissues of diabetic mice, improving effective blood resupply. Additionally, MoS2 NDs boost the proliferation, migration, and tube formation of endothelial cells under high glucose/hypoxia conditions in vitro. Mechanistically, the beneficial effects of MoS2 NDs on collateral formation not only depend on their known scavenging properties of ROS (H2O2, â¢O2-, and â¢OH) but also primarily involve a molecular pathway, cAMP/PKA-NR4A2, which promotes autophagy and contributes to mitigating damage in diabetic endothelial cells. CONCLUSIONS: Overall, this study investigated the specific mechanism by which MoS2 NDs mediated autophagy activation and highlighted the synergy between autophagy activation and antioxidation, thus suggesting that an economic and biocompatible nano-agent with dual therapeutic functions is highly preferable for promoting collateral formation in a diabetic context, thus, highlighting their therapeutic potential.
Asunto(s)
Diabetes Mellitus Experimental , Diabetes Mellitus Tipo 2 , Humanos , Ratones , Animales , Diabetes Mellitus Tipo 2/tratamiento farmacológico , Especies Reactivas de Oxígeno/metabolismo , Células Endoteliales/metabolismo , Molibdeno/farmacología , Molibdeno/uso terapéutico , Diabetes Mellitus Experimental/tratamiento farmacológico , Diabetes Mellitus Experimental/metabolismo , Peróxido de Hidrógeno/metabolismo , AutofagiaRESUMEN
BACKGROUND: Erectile dysfunction (ED) is closely associated with dyslipidemia; however, it is yet unknown how ED and remnant cholesterol (RC) are related. As such, this research sought to explore the correlation between RC and ED among individuals with diagnosed with diabetes. METHODS: This cross-sectional study used information from 215 males from National Health and Nutrition Examination Survey (NHANES) from 2001 to 2004. RC was calculated as follows: the values of high-density lipoprotein cholesterol (HDL-c) and low-density lipoprotein cholesterol (LDL-c) were subtracted from the total cholesterol (TC) value, while ED diagnoses were based on self-reports. Weighted logistic regression analyses using both univariate and multivariate approaches were conducted to assess the correlation between RC and ED. RESULTS: After comprehensive adjustment, multivariable logistic regression models revealed a strong correlation between RC and ED in subjects with diabetes (with an odds ratio (OR) of 7.49 and a 95% confidence interval (CI) of 1.98-28.37; P = 0.004). On categorizing RC into 3 grades (T1-T3), the OR corresponding to higher RC grade increased. Despite the results not reaching statistical significance upon categorization, a consistent and statistically significant trend (P for trend < 0.05) was observed. CONCLUSION: This study indicated a correlation between increased RC levels and a higher prevalence of ED in diabetic males. RC may serve as a promising predictor of ED in individuals with diabetes. However, additional studies are required to confirm these findings.
Asunto(s)
Diabetes Mellitus , Disfunción Eréctil , Hiperlipidemias , Masculino , Humanos , Disfunción Eréctil/epidemiología , Disfunción Eréctil/etiología , Disfunción Eréctil/diagnóstico , Encuestas Nutricionales , Factores de Riesgo , Estudios Transversales , ColesterolRESUMEN
OBJECTIVE: To explore the association between cardiovascular health (CVH) measured by Life's Essential 8 (LE8) and the prevalence of urinary incontinence (UI). METHOD: A cross-section study was conducted using data from the National Health and Nutrition Examination Survey 2007-2012. 22,609 people aged ≥ 20 years with complete information on LE8 metrics and UI questionnaires were enrolled. Participants were divided into three groups (low: < 50, moderate: ≥ 50 and < 80, high: ≥ 80) based on the cut-off of LE8. Weighted proportions, multivariable logistic regression analysis and stratified logistic regression were performed to examine the association between LE8 and the prevalence of three types of UI separately (stress UI (SUI), urge UI (UUI), mixed UI (MUI)) by confounding factors adjusted. Spline smooth was conducted to find whether a linear relationship existed. In addition, sensitive analyses were also conducted to observe the stability. RESULT: A total of 22,609 adults were involved in the study, and participants were divided into three groups (low 42.2 ± 6.3, moderate 66.1 ± 8.1, high 86.8 ± 5.1) according to the cut-off points of LE8. The multivariable logistic regression suggested that LE8 is inversely associated with the prevalence of SUI (OR = 0.98, 95%CI 0.98 to 0.99), UUI (OR = 0.98, 95%CI 0.98 to 0.99), and MUI (OR = 0.98, 95%CI 0.97 to 0.98) in the fully-adjusted model. Compared with the low group, people with high scores of LE8 had a lower prevalence of SUI (OR = 0.45, 95%CI 0.37 to 0.55), UUI (OR = 0.49, 95%CI 0.40 to 0.60), and MUI (OR = 0.41, 95%CI 0.30 to 0.55). The result of the sensitive analysis showed the robustness of the main analysis. CONCLUSION: The prevalence of UI (SUI, UUI, or MUI) is inversely associated with the LE8 score, which suggests that maintaining a good CVH with a higher LE8 score is accompanied by lower prevalence rates of UUI, SUI, and MUI.
Asunto(s)
Enfermedades Cardiovasculares , Encuestas Nutricionales , Incontinencia Urinaria , Humanos , Femenino , Masculino , Prevalencia , Persona de Mediana Edad , Adulto , Estudios Transversales , Incontinencia Urinaria/epidemiología , Enfermedades Cardiovasculares/epidemiología , Anciano , Adulto Joven , Encuestas y CuestionariosRESUMEN
BACKGROUND: Despite being a prognostic predictor, cardiac autonomic dysfunction (AD) has not been well investigated in chronic obstructive pulmonary disease (COPD). We aimed to characterise computed tomography (CT), spirometry, and cardiopulmonary exercise test (CPET) features of COPD patients with cardiac AD and the association of AD with CT-derived vascular and CPET-derived ventilatory efficiency metrics. METHODS: This observational cohort study included stable, non-severe COPD patients. They underwent clinical evaluation, spirometry, CPET, and CT. Cardiac AD was determined based on abnormal heart rate responses to exercise, including chronotropic incompetence (CI) or delayed heart rate recovery (HRR) during CPET. RESULTS: We included 49 patients with FEV1 of 1.2-5.0 L (51.1-129.7%), 24 (49%) had CI, and 15 (31%) had delayed HRR. According to multivariate analyses, CI was independently related to reduced vascular volume (VV; VV ≤ median; OR [95% CI], 7.26 [1.56-33.91]) and low ventilatory efficiency (nadir VE/VCO2 ≥ median; OR [95% CI], 10.67 [2.23-51.05]). Similar results were observed for delayed HRR (VV ≤ median; OR [95% CI], 11.46 [2.03-64.89], nadir VE/VCO2 ≥ median; OR [95% CI], 6.36 [1.18-34.42]). CONCLUSIONS: Cardiac AD is associated with impaired pulmonary vascular volume and ventilatory efficiency. This suggests that lung blood perfusion abnormalities may occur in these patients. Further confirmation is required in a large population-based cohort.
Asunto(s)
Enfermedades Pulmonares , Enfermedad Pulmonar Obstructiva Crónica , Humanos , Frecuencia Cardíaca/fisiología , Enfermedades Pulmonares/complicaciones , Prueba de Esfuerzo/métodos , Espirometría , Tolerancia al Ejercicio/fisiologíaRESUMEN
This study aims to explore the pharmacological substance basis of Qi Ge Decoction (QG) in antihyperlipidemia through a combination of metabolomics and serum pharmacochemistry. We used ultra-performance liquid chromatography quadrupole-time-of-flight/MS (UPLC Q-TOF/MS) to analyze and identify the chemical constituents of QG in vitro and in blood chemical components. The metabolomics technology was used to analyze serum biomarkers of QG in preventing and treating hyperlipidemia. We constructed a mathematical model of the relationship between constituents absorbed into the blood and endogenous biomarkers and explored the potential therapeutic application of QG for the prevention and treatment of hyperlipidemia. Compared with the model group, the levels of total cholesterol and triglyceride in the QG group were significantly decreased (P < 0.01). A total of 12 chemical components absorbed into the blood were identified, and 48 biomarkers of the hyperlipidemia model were obtained from serum metabolomic analysis, of which 15 metabolites were backregulated after QG intervention. Puerarin, hesperetin, puerarin xyloside, calycosin, and monohydroxy-tetramethoxyflavone had a high correlation with the biomarkers regulated by QG. This study elucidated the material basis of QG in the intervention of hyperlipidemia, thereby facilitating future research aimed at further revealing the pharmacodynamic material basis of QG's antihyperlipidemic effects.
Asunto(s)
Medicamentos Herbarios Chinos , Hiperlipidemias , Hipolipemiantes , Metabolómica , Metabolómica/métodos , Hipolipemiantes/sangre , Hipolipemiantes/farmacocinética , Hipolipemiantes/química , Cromatografía Líquida de Alta Presión/métodos , Animales , Hiperlipidemias/tratamiento farmacológico , Hiperlipidemias/sangre , Masculino , Biomarcadores/sangre , Ratas , Metaboloma/efectos de los fármacos , Ratas Sprague-Dawley , Espectrometría de Masas/métodosRESUMEN
The aim of this work was to explore the differences between various pharmaceutical processes in combined solutions of a single decoction (QGHBY) and a combined decoction (QGHJY) of Qi-Ge decoction from the perspective of chemical composition changes, so as to further guide the clinical application of drugs. A combined solution of a single decoction and a combined decoction of Astragali Radix, Puerariae Lobatae Radix and Citri Reticulatae Chachiensis Pericarpium was prepared with the same technological parameters. The chemical components of the two were detected and identified based on UPLC-Q-TOF/MS, and the different components were determined by principal component analysis. Eighty-eight compounds were identified in the pharmaceutical solution of Qi-Ge decoction. Principal component analysis revealed 11 different components of QGHBY and QGHJY with the conditions of Variable Importance in Projection (VIP) ≥ 1, fold change ≥ 2 and p < 0.05, among which hesperidin, hesperitin, isosinensetin, sinensetin and 5-demethylnobiletin were the components of Citri Reticulatae Chachiensis Pericarpium. The levels of these 11 different components in QGHJY were higher than those of QGHBY. The combined decoction is beneficial for the dissolution of flavonoids and other chemical components, and there is a significant difference in the content of chemical components between modern herbal concentrate granules and traditional decoctions.
Asunto(s)
Medicamentos Herbarios Chinos , Espectrometría de Masas , Medicamentos Herbarios Chinos/química , Medicamentos Herbarios Chinos/análisis , Cromatografía Líquida de Alta Presión/métodos , Espectrometría de Masas/métodos , Análisis de Componente Principal , Flavonoides/análisis , Flavonoides/químicaRESUMEN
Objective: The objective of this study was to evaluate the efficacy of hysteroscopic electroresection in the treatment of atypical endometrial hyperplasia and to determine the prognostic factors. Methods: 226 patients with endometrial dysplasia treated in hospital from January 2021 to August 2022 were selected and divided into control group (113 cases) and study group (113 cases) according to different treatment methods selected by the patients themselves. The control group received curettage plus conventional progesterone treatment, while the study group received hysteroscopic electroresection plus conventional progesterone treatment. After 6 months of treatment, the clinical efficacy (complete response, partial response and progress) of the two groups were evaluated, complications and adverse drug reactions of the two groups were analyzed, and estrogen levels before and after treatment were compared between the two groups. After 1 year follow-up, patients were divided into relapse group and non-recurrence group according to whether they had relapse or not. Clinical data of the two groups were compared to analyze the related factors affecting the prognosis of patients. Results: (1) Chi-square test results showed that the total effective rate of the study group was higher (96.46% VS 77.88%) than that of the control group (P < .05). The complication rate and recurrence rate of the study group were lower than those of the control group (1.77% VS 7.96%, 4.42% VS 21.24%) (P < .05). (2) t test results of independent samples showed that after 6 months of treatment, the levels of luteinizing hormone (LH) and follicle-stimulating hormone (FSH) in the study group were lower than those in the control group (P < .05); (3) The t test results of independent samples indicated that the age and body mass index of the relapsed group were higher than those of the non-relapsed group (P < .05); Chi-square test results showed that the proportion of diabetes was higher than that of the group without recurrence, and the proportion of hysteroscopic electroresection was lower than that of the group without recurrence (P < .05). (4) Logistic regression model was established, and the results showed that age (OR=1.159), body mass index (OR=1.529) and diabetes (OR=3.861) were the risk factors for prognosis of patients with endometrial dysplasia (P < .05), and hysteroscopic electroresection was the protective factor (OR < 1, P < .05). Conclusion: Hysteroscopic electroresection shows significant potential in the treatment of atypical hyperplasia of endometrial, and can improve clinical efficacy and reduce complications by effectively regulating estrogen secretion. In addition, studies have shown that the prognosis of endometrial dysplasia may be related to the age of patients, body mass index and diabetes mellitus. Therefore, for patients with the above risk factors, early consideration of hysteroscopic electrotomy therapy is recommended to reduce recurrence rates and provide important informational support for treatment protocols and clinical guidelines.
RESUMEN
BACKGROUND: Advanced nursing practice and education with a Master's degree as the necessary preparation, is viewed as a major strategy to cultivate senior nursing talents. Competencies are central to advanced nursing practice and education, but how can competencies be measured? Entrustable professional activities (EPAs) have been used widely in medicine as a practical approach for bridging the gaps between competency and clinical practice. Considering the paucity of research in EPAs for nursing graduates in China, it is needed to develop EPAs specifically for Chinese Master of Nursing Specialist (MNS) graduates to improve patient safety and quality patient care. OBJECTIVES: To develop and evaluate a core competency-based EPAs framework for Chinese MNS graduates. METHODS: A four-stage approach was adopted for the EPAs development, including: (1) forming a research team, (2) drafting an initial EPAs framework, (3) reviewing EPAs framework, and (4) conducting EPAs consensus assessment. RESULTS: A framework containing twelve EPAs was developed, including: 1) perform health assessments, 2) identify and prioritize nursing diagnoses, 3) formulate and implement care plan, 4) perform basic and specialized care operations, 5) recognize and manage medication needs of patients, 6) assess and manage patients with mental health problems, 7) recognize and assist in rescuing critically ill patients, 8) perform transition and handover, 9) participate in multidisciplinary team collaborative care, 10) provide health education and nursing consultation, 11) formulate and implement discharge plans, and 12) instruct nursing students in a clinical setting. The I-CVI score for the two rounds of Delphi ranged from 0.92 â¼ 1.00 and 0.96 â¼ 1.00, respectively. The mean of Equal's score for the three domains ranged from 4.20 â¼ 4.47, 4.25 â¼ 4.51, and 4.23 â¼ 4.37, respectively. CONCLUSION: The developed EPAs framework in this study is a reliable tool to assess the core competencies of Chinese MNS graduates in clinical practice and assist with their curricula design.
RESUMEN
In response to the issues of low model recognition accuracy and weak generalization in mechanical equipment fault diagnosis due to scarce data, this paper proposes an innovative solution, a cross-device secondary transfer-learning method based on EGRUN (efficient gated recurrent unit network). This method utilizes continuous wavelet transform (CWT) to transform source domain data into images. The EGRUN model is initially trained, and shallow layer weights are frozen. Subsequently, random overlapping sampling is applied to the target domain data to enhance data and perform secondary transfer learning. The experimental results demonstrate that this method not only significantly improves the model's ability to learn fault features but also enhances its classification accuracy and generalization performance. Compared to current state-of-the-art algorithms, the model proposed in this study shows faster convergence speed, higher diagnostic accuracy, and superior robustness and generalization, providing an effective approach to address the challenges arising from scarce data and varying operating conditions in practical engineering scenarios.