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Hydrophobic bioactive compounds like astaxanthin (AST) exhibit poor water solubility and low bioavailability. Liposomes, which serve as nanocarriers, are known for their excellent biocompatibility and minimal immunogenicity. Traditionally, liposomes have been primarily constructed using phospholipids and cholesterol. However, the intake of cholesterol may pose a risk to human health. Phytosterol ester was reported to reduce level of cholesterol and improve properties of liposomes. In this study, phytosterol oleate was used to prepare liposomes instead of cholesterol to deliver AST (AST-P-Lip). The size range of AST-P-Lip was 100-220 nm, and the morphology was complete and uniform. In vitro studies showed that AST-P-Lip significantly enhanced the antioxidant activity and oral bioavailability of AST. During simulated digestion, AST-P-Lip protected AST from damage by gastric and intestinal digestive fluid. Additionally, AST-P-Lip had a good storage stability and safety. These results provide references for the preparation of novel liposomes and the delivery of bioactive compounds.

Asunto(s)

Colesterol , Liposomas , Fitosteroles , Xantófilas , Liposomas/química , Xantófilas/química , Xantófilas/farmacología , Xantófilas/administración & dosificación , Humanos , Fitosteroles/química , Fitosteroles/farmacología , Fitosteroles/administración & dosificación , Colesterol/química , Tamaño de la Partícula , Disponibilidad Biológica , Ácido Oléico/química , Composición de Medicamentos , Animales , Antioxidantes/química , Antioxidantes/farmacología

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Hyaluronic acid (HA) is an important component of extracellular matrices (ECM) and a linear polysaccharide involved in various physiological and pathological processes within the biological system. Several pathogens exploit HA degradation within the extracellular matrix to facilitate infection. While many intestinal microorganisms play significant roles in HA utilization in the human body, there remains a scarcity of related studies. This paper addressed this gap by screening intestinal microorganisms capable of degrading HA, resulting in the isolation of Clostridium perfringens G1121, which had been demonstrated the ability to degrade HA. Subsequent genome sequencing and analysis of C. perfringens G1121 revealed its utilization of the polysaccharide utilization loci of HA (PULHA), which was obtained by horizontal gene transfer. The PULHA contains a sequence encoding a hyaluronic acid-specific degradation enzyme designated CpHly8, belonging to polysaccharide lyase family 8. The specific activity of CpHly8 towards HA was 142.98 U/mg, with the optimum reaction temperature and pH observed at 50℃ and 6.0, respectively. The final product of HA degradation by CpHly8 was unsaturated hyaluronic acid disaccharide. Moreover, subcutaneous diffusion experiments with trypan blue in mice revealed that CpHly8 effectively promoted subcutaneous diffusion and sustained its effects long-term, suggesting its potential application as an adjunct in drug delivery. Overall, our study enriches our understanding of intestinal microbial degradation of HA, provides new evidence for horizontal gene transfer among intestinal microorganisms, and confirms that CpHly8 is a promising candidate for intestinal microbial hyaluronidase.

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Background: Several existing studies have shown a correlation between some of the blood and urine biomarkers and oral leukoplakia (OLK). However, the causality of this relationship remains uncertain. Thus, this study aimed to examine the causal association between 35 blood and urine biomarkers and OLK. Methods: Single nucleotide polymorphisms (SNPs) associated with 35 blood and urine biomarkers were selected as instrumental variables (IVs) using a two-sample Mendelian randomization(MR) study to assess the causal relationship between the biomarkers and the risk of oral leukoplakia. We used the inverse variance weighted (IVW) method as the main analysis. Furthermore, several sensitivity analyses were performed to assess heterogeneity, horizontal pleiotropy, and stability. Results: Based on the selection criteria of the Inverse Variance Weighted (IVW) method, the analysis found that 5 blood and urine biomarkers were significantly associated with the development of leukoplakia, of which the results of IVW showed that abnormalities of Apolipoprotein B (Apo B), Cholesterol, Low-density Lipoprotein (LDL), Triglycerides (TG) promoted the development of oral leukoplakia, and Non Albumin Protein (NAP) had a protective effect on the development of oral leukoplakia. We then performed a Bonferroni correction for these results, and after correction Apo B was still causally associated with the development of oral leukoplakia (IVW P<0.0007), whereas the other four biomarkers could only provide some evidence of predisposition. Conclusion: Our two-sample Mendelian randomization study supports the existence of a causal relationship between these five blood and urine biomarkers and the occurrence of oral leukoplakia, and provides evidence for a number of risk and protective factors for the development of oral leukoplakia; however, the definitive mechanisms for the occurrence and development of oral leukoplakia still remain to be elucidated, and further studies on these relevant mechanisms are still needed.

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Sleep loss leads to significant pathophysiological consequences, including cognitive impairment. The neuroinflammation are pivotal factors in the pathogenesis of cognitive impairment induced by sleep loss. The phloretin (PHL), derived from peel of juicy fruits, has demonstrated potent anti-inflammatory properties. However, the precise influence of PHL on the cognitive impairment triggered by sleep loss and its underlying mechanism remain uncertain. In the present study, mice were subjected to sleep deprivation (SD) paradigm. Cognitive impairment induced by SD were significantly relieved by administration of PHL in a dose-dependent manner. Furthermore, PHL not only mitigated the synaptic losses but also enhanced dendritic spine density and neuronal activity within mice hippocampus following exposure to SD. Moreover, PHL treatment decreased the microglial numbers and altered microglial morphology in the hippocampus to restore the M1/M2 balances; these effects were accompanied by regulation of pro-/anti-inflammatory cytokine production and secretion in SD-exposed mice. Additionally, in vivo and in vitro studies showed PHL might attenuate the inflammation through the PPARγ/NF-κB pathway. Our findings suggest that PHL exerts inhibitory effects on microglia-mediated neuroinflammation, thereby providing protection against cognitive impairment induced by SD through a PPAR-γ dependent mechanism. The results indicate PHL is expected to provide a valuable candidate for new drug development for SD-induced cognitive impairment in the future.

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OBJECTIVE: This study aimed to investigate the impact of the donor-recipient BMI ratio on the survival outcomes of heart transplant recipients. METHODS: A retrospective analysis was conducted on 641 heart transplant patients who underwent surgery between September 2008 and June 2021. The BMI ratio (donor BMI divided by recipient BMI) was calculated for each patient. Kaplan-Meier survival analysis and Cox proportional hazards regression were performed to evaluate survival rates and determine the hazard ratio (HR) for mortality. RESULTS: Significant differences were found in donor age and donor-recipient height ratio between the BMI ratio groups. The BMI ratio ≥ 1 group had a higher mean donor age (37.27 ± 10.54 years) compared to the BMI ratio < 1 group (34.72 ± 11.82 years, p = 0.008), and a slightly higher mean donor-recipient height ratio (1.02 ± 0.06 vs. 1.00 ± 0.05, p = 0.002). The Kaplan-Meier survival analysis indicated that the survival rate in the BMI ratio ≥ 1 group was significantly lower than in the BMI ratio < 1 group. Cox multivariate analysis, adjusted for confounding factors, revealed a HR of 1.50 (95% CI: 1.08-2.09) for mortality in patients with a BMI ratio ≥ 1. No significant differences were observed in ICU stay, postoperative hospitalization days, or total mechanical ventilation time between the groups. CONCLUSION: A higher donor-recipient BMI ratio was associated with an increased risk of mortality in heart transplant recipients.

Asunto(s)

Índice de Masa Corporal , Trasplante de Corazón , Donantes de Tejidos , Humanos , Estudios Retrospectivos , Femenino , Masculino , Adulto , Donantes de Tejidos/estadística & datos numéricos , Tasa de Supervivencia/tendencias , Factores de Riesgo , Persona de Mediana Edad , Estudios de Seguimiento , Factores de Tiempo , Resultado del Tratamiento

RESUMEN

Background: GLP-1 receptor agonists (GLP-1 RA) have been proven to treat several metabolic diseases; however, the effects of GLP-1 RA on polycystic ovary syndrome (PCOS) remain unclear. Here, we aimed to investigate whether semaglutide, a novel GLP-1 RA, could alleviate ovarian inflammation in PCOS mice. Methods: Female C57BL/6J mice were subcutaneously injected with dehydroepiandrosterone for 21 days to establish the PCOS model. Then the mice were randomly divided into three groups: PCOS group (n = 6), S-0.42 group (semaglutide 0.42 mg/kg/w, n = 6), and S-0.84 group (semaglutide 0.84 mg/kg/w, n = 6). The remaining six mice were used as controls (NC). After 28 days of intervention, serum sex hormones and inflammatory cytokine levels were measured. Hematoxylin and eosin staining was used to observe the ovarian morphology. Immunohistochemical staining was used to detect the relative expression of CYP19A1, TNF-α, IL-6, IL-1ß, and NF-κB in ovaries. CYP17A1 and StAR were detected using immunofluorescence staining. Finally, the relative expressions of AMPK, pAMPK, SIRT1, NF-κB, IκBα, pIκBα, TNF-α, IL-6, and IL-1ß were measured using Western blotting. Results: First, after intervention with semaglutide, the weight of the mice decreased, insulin resistance improved, and the estrous cycle returned to normal. Serum testosterone and IL-1ß levels decreased significantly, whereas estradiol and progestin levels increased significantly. Follicular cystic dilation significantly improved. The expression of TNF-α, IL-6, IL-1ß, NF-κB, CYP17A1, and StAR in the ovary was significantly downregulated, whereas CYP19A1 expression was upregulated after the intervention. Finally, we confirmed that semaglutide alleviates ovarian tissue inflammation and improves PCOS through the AMPK/SIRT1/NF-κB signaling pathway. Conclusion: Semaglutide alleviates ovarian inflammation via the AMPK/SIRT1/NF­κB signaling pathway in PCOS mice.

Asunto(s)

Agonistas Receptor de Péptidos Similares al Glucagón , Péptidos Similares al Glucagón , Inflamación , Síndrome del Ovario Poliquístico , Transducción de Señal , Animales , Femenino , Ratones , Proteínas Quinasas Activadas por AMP/metabolismo , Modelos Animales de Enfermedad , Péptidos Similares al Glucagón/farmacología , Inflamación/tratamiento farmacológico , Inflamación/metabolismo , Ratones Endogámicos C57BL , FN-kappa B/metabolismo , Ovario/efectos de los fármacos , Ovario/patología , Ovario/metabolismo , Síndrome del Ovario Poliquístico/tratamiento farmacológico , Síndrome del Ovario Poliquístico/metabolismo , Síndrome del Ovario Poliquístico/patología , Transducción de Señal/efectos de los fármacos , Sirtuina 1/metabolismo , Agonistas Receptor de Péptidos Similares al Glucagón/farmacología

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To reveal the effect of wheat flour particle size on the quality deterioration of quick-frozen dumpling wrappers (QFDW) during freeze-thawed (F/T) cycles, the components and physicochemical properties of wheat flours with five different particle sizes were determined and compared, along with the changes in texture and sensory properties, water status, and microstructure of QFDW during F/T cycles. Results showed that as particle size decreased, the damaged starch content and B-type starch content increased, the water absorption increased, and the gluten strength decreased. Furthermore, F/T cycles negatively impacted the quality of QFDW, evidenced by decreased texture properties and sensory evaluation score, water redistribution, higher freezable water content, and disruption of gluten network. Notably, QFDW made from larger particle size wheat flours required the shortest duration when traversing the maximum ice crystal formation zone. The QFDW made from larger particle size wheat flours formed a more stable starch-gluten matrix, which resisted the damage caused by ice recrystallization, demonstrating better water binding capacity and F/T resistance. The results may provide theoretical guidance for the study of QFDW quality and the moderate processing of wheat flour in actual production.

Asunto(s)

Harina , Manipulación de Alimentos , Congelación , Glútenes , Tamaño de la Partícula , Almidón , Triticum , Agua , Harina/análisis , Triticum/química , Almidón/química , Almidón/análisis , Manipulación de Alimentos/métodos , Agua/química , Glútenes/análisis , Glútenes/química , Humanos

RESUMEN

Staphylococcus aureus is a notorious pathogen predominantly involved in skin and soft tissue infections, exhibiting a distinct innate sex bias. This study explores the influence of testosterone on the virulence of S. aureus and elucidates its underlying mechanisms. Utilizing a skin abscess model in intact and castrated male mice, we assessed the effects of testosterone on S. aureus pathogenicity. Compared to controls, castrated mice showed significantly reduced abscess sizes and decreased bacterial loads, highlighting the role of testosterone in modulating the severity of S. aureus infections. In vitro experiments revealed that testosterone enhances the hemolytic activity, cytotoxicity, and oxidative stress resistance of S. aureus. Real-time quantitative PCR analysis showed a significant upregulation of the genes encoding α-hemolysin (hla) and phenol-soluble modulin (psmα). Importantly, testosterone treatment significantly enhanced the expression of the accessory gene regulator (Agr) quorum-sensing system components (agrC, agrA, agrB, agrD), while the SaeRS system (saeR, saeS, and sbi) exhibited only slight changes. Gene knockout experiments revealed that deletion of agrC, rather than saeRS and agrBD, abolishes the testosterone-induced enhancement of hemolysis and gene expression, underscoring the key role of AgrC. Molecular docking simulations indicated a direct interaction between testosterone and AgrC protein, with a strong binding affinity at the active site residue SER201. This study provides new insights into the mechanistic basis of how testosterone enhances the pathogenicity of S. aureus, potentially contributing to increased male susceptibility to S. aureus infections and offering a targeted approach for therapeutic interventions.

Asunto(s)

Proteínas Bacterianas , Infecciones Estafilocócicas , Staphylococcus aureus , Testosterona , Masculino , Testosterona/farmacología , Testosterona/metabolismo , Animales , Staphylococcus aureus/genética , Staphylococcus aureus/patogenicidad , Staphylococcus aureus/efectos de los fármacos , Staphylococcus aureus/metabolismo , Ratones , Proteínas Bacterianas/genética , Proteínas Bacterianas/metabolismo , Virulencia , Infecciones Estafilocócicas/microbiología , Transactivadores/genética , Transactivadores/metabolismo , Regulación Bacteriana de la Expresión Génica , Percepción de Quorum , Simulación del Acoplamiento Molecular , Toxinas Bacterianas/metabolismo , Toxinas Bacterianas/genética , Absceso/microbiología , Hemólisis , Proteínas Hemolisinas/metabolismo , Proteínas Hemolisinas/genética

RESUMEN

ETHNOPHARMACOLOGICAL RELEVANCE: Traditional Chinese medicine (TCM) has shown notable effectiveness and safety in managing illnesses linked to cytokine storm(CS). Bailixiang tea (BLX), an herbal medicine formula, which is a compound Chinese medicine composed of Thymus mongolicus (Ronniger) Ronniger (Bailixiang), Glycyrrhiza uralensis Fisch. (Gancao), Citrus reticulata Blanco (Chenpi), Cyperus rotundus L. (Xiangfu), and Perilla frutescens (L.) Britton (Zisu). The objective of this study was to explore the capacity of BLX in improving LPS-induced CS. AIM OF THE STUDY: This study aimed to validate the mitigating effect of BLX on CS and to further investigate its mechanism. MATERIALS AND METHODS: mice were orally administered BLX for 24 h after being treated with 5 mg/kg lipopolysaccharide (LPS). Histopathological observations further confirmed the significant protective effect of BLX treatment against LPS-induced lung and spleen damage. Additionally, we aimed to explore the molecular mechanism underlying its effects through blood proteomics and transcriptomics analyses. Real-Time Quantitative PCR (RT-qPCR) was utilized to detect the levels of Toll-like receptor 2 (TLR2) , Matrix metalloproteinase 8 (MMP8) , Matrix metalloproteinase 9 (MMP9) , Integrin beta 2 (ITGB2) , Mitogen-activated protein kinase 8 (MAPK8) , Nuclear factor of kappa light polypeptide gene enhancer in B-cells inhibitor, epsilon (NFKBIE) , Nuclear factor of kappa light polypeptide gene enhancer in B-cells 2 (NFKB2) , and Glyceraldehyde-3-Phosphate Dehydrogenase (GAPDH)expressions in the lung tissue. RESULTS: The results demonstrated that BLX effectively down-regulated the overproduction of interleukin 6 (IL-6) and tumor necrosis factor-α (TNF-α) in both the serum and lung and spleen tissues. Furthermore, BLX effectively mitigated the overproduction of monocyte chemoattractant protein-1 (MCP-1) in the serum. Through comprehensive multi-omics analysis, it was revealed that BLX specifically targeted and regulated TLR2/MAPK8 and TLR2/NF-κB signaling pathways, which play a crucial role in the production of key cytokines. CONCLUSIONS: The findings of this study demonstrate that Bailixiang tea possesses the ability to alleviate lung tissue damage and inhibit the development of LPS-induced cytokine storm in mice. These effects are attributed to the tea's ability to suppress the TLR2/MAPK8 and TLR2/NF-κB pathways. Consequently, this research highlights the potential application of Bailixiang tea as a treatment option for cytokine storm.

RESUMEN

Plastids are essential, semi-autonomous organelles in plants that carry out a multitude of functions during development. Plastids existing in different subtypes are derived from proplastids progenitors and interconvert in response to environmental and growth cues. Most efforts focus on the differentiation from proplastid to other forms. However, the studies of proplastid development are insufficient and whether proplastid biogenesis affects plant growth is yet to be determined. Arabidopsis TIC236, a translocon component at the inner membrane of the chloroplast envelope, is critical for importing chloroplast-targeted preproteins and chloroplast division. In this study, we uncovered the fundamental influence of proplastid biogenesis on embryo development by exploring the function of TIC236 during embryogenesis. Widespread and strong expression of TIC236 was observed in leaves and embryos. The null mutant tic236 had an embryo-lethal phenotype, with cell division in the mutant embryos delayed starting at the octant stage and arrested at the globular stage. Transmission electron microscopy revealed enlarged proplastids with an aberrant inner structure at the dermatogen and globular stages that ultimately did not differentiate into chloroplasts. Additionally, the fluorescence signal distribution patterns of tic236 embryos carrying the pDR5rev::3xVENUS-N7, pPIN1::PIN1-GFP, pWOX5::GFP, and pSCR::H2B-YFP reporter systems were altered. Together, we provide genetic evidence supporting proplastid biogenesis plays a vital role in embryo development and TIC236 is identified as an indispensable player, ensuring normal proplastid development.

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With the progress of aging, the incidence of vascular calcification (VC) gradually increases, which is correlated with cardiovascular events and all-cause death, aggravating global clinical burden. Over the past several decades, accumulating approaches targeting the underlying pathogenesis of VC have provided some possibilities for the treatment of VC. Unfortunately, none of the current interventions have achieved clinical effectiveness on reversing or curing VC. The purpose of this review is to make a summary of novel perspectives on the interventions of VC and provide reference for clinical decision-making.

RESUMEN

A colorimetric aptasensor based on the dual recognition of magnetic carbon dots (M-CDs) and copper-based metal-organic frameworks (Cu-MOFs) was constructed for the visual detection of Staphylococcus aureus (S. aureus). Aptamer-modified Cu-MOFs could specifically identify target bacteria and exhibited peroxidase-like activity by catalyzing the colorimetric reaction of the 3,3',5,5'-tetramethylbenzidine-H2O2 (TMB-H2O2) system. M-CDs electrostatically attracted bacteria because of their strong positive electrical properties and offered better capturing performance compared with magnetic beads owing to their smaller size. Visual detection of the target was achieved using the color change of the reaction catalyzed by the resuspension of the sandwich-structured complex. The bacteria were sensitively detected with a limit of detection (LOD) of 1 CFU mL-1 using the peroxidase catalytic activity of Cu-MOFs. Non-target bacteria produced negative results, demonstrating the excellent selectivity of the proposed aptasensor. The strategy showed good recovery in real sample detection, showing great potential for visual monitoring of pathogenic bacteria, and could provide a reference for further development of novel sensing platforms for bacterial detection.

RESUMEN

Chloroplast (cp) genome sequences have been extensively used for phylogenetic and evolutionary analyses, as many have been sequenced in recent years. Identification of Quercus is challenging because many species overlap phenotypically owing to interspecific hybridization, introgression, and incomplete lineage sorting. Therefore, we wanted to gain a better understanding of this genus at the level of the maternally inherited chloroplast genome. Here, we sequenced, assembled, and annotated the cp genomes of the threatened Quercus marlipoensis (160,995 bp) and Q. kingiana (161,167 bp), and mined these genomes for repeat sequences and codon usage bias. Comparative genomic analyses, phylogenomics, and selection pressure analysis were also performed in these two threatened species along with other species of Quercus. We found that the guanine and cytosine content of the two cp genomes were similar. All 131 annotated genes, including 86 protein-coding genes, 37 transfer RNA genes, and 8 ribosomal RNA genes, had the same order in the two species. A strong A/T bias was detected in the base composition of simple sequence repeats. Among the 59 synonymous codons, the codon usage pattern of the cp genomes in these two species was more inclined toward the A/U ending. Comparative genomic analyses indicated that the cp genomes of Quercus section Ilex are highly conserved. We detected eight highly variable regions that could be used as molecular markers for species identification. The cp genome structure was consistent and different within and among the sections of Quercus. The phylogenetic analysis showed that section Ilex was not monophyletic and was divided into two groups, which were respectively nested with section Cerris and section Cyclobalanopsis. The two threatened species sequenced in this study were grouped into the section Cyclobalanopsis. In conclusion, the analyses of cp genomes of Q. marlipoensis and Q. kingiana promote further study of the taxonomy, phylogeny and evolution of these two threatened species and Quercus.

Asunto(s)

Especies en Peligro de Extinción , Evolución Molecular , Genoma del Cloroplasto , Filogenia , Quercus , Quercus/genética , Genoma del Cloroplasto/genética , Uso de Codones , Cloroplastos/genética

RESUMEN

BACKGROUND: This study assessed the effect of hydrocortisone-fludrocortisone combination therapy on the mortality of patients with septic shock. METHODS: A literature search was conducted using Medline, Embase, the Cochrane Library, ClinicalTrials.gov, and other databases for articles published until October 1, 2023. Only clinical studies that assessed the clinical efficacy and safety of hydrocortisone-fludrocortisone therapy for the treatment of septic shock were included. The primary outcome was the in-hospital mortality rate. RESULTS: Seven studies with a total of 90, 756 patients were included. The study group exhibited lower in-hospital mortality rates (40.8% vs. 42.8%; OR, 0.86; 95% CI, 0.80-0.92). Compared to the control group, the study group also had lower intensive care unit (ICU) mortality (OR, 0.77; 95% CI, 0.63-0.95), 28-day mortality (OR, 0.85; 95% CI, 0.72-1.00), 90-day mortality (OR, 0.85; 95% CI, 0.71-1.01), 180-day mortality (OR, 0.82; 95% CI, 0.68-0.90), and one-year mortality (OR, 0.70; 95% CI, 0.42-1.16). Subgroup analyses showed a similar trend, particularly prominent in the pooled analysis of randomized clinical trials, multicenter studies, and ICU patients, the study drug regimen involved hydrocortisone at a dose of 50 mg every 6 h in combination with fludrocortisone at 50 µg daily, with the control group receiving either placebo or standard care. Hydrocortisone-fludrocortisone also increased vasopressor-free days and reduced vasopressor duration, without elevating the risk of adverse events. CONCLUSIONS: This study emphasizes the potential survival benefits of hydrocortisone-fludrocortisone combination therapy for patients with septic shock and its additional advantages, including reduced vasopressor use.

RESUMEN

BACKGROUND: In recent years, there has been a growing trend in the utilization of observational studies that make use of routinely collected healthcare data (RCD). These studies rely on algorithms to identify specific health conditions (e.g. diabetes or sepsis) for statistical analyses. However, there has been substantial variation in the algorithm development and validation, leading to frequently suboptimal performance and posing a significant threat to the validity of study findings. Unfortunately, these issues are often overlooked. METHODS: We systematically developed guidance for the development, validation, and evaluation of algorithms designed to identify health status (DEVELOP-RCD). Our initial efforts involved conducting both a narrative review and a systematic review of published studies on the concepts and methodological issues related to algorithm development, validation, and evaluation. Subsequently, we conducted an empirical study on an algorithm for identifying sepsis. Based on these findings, we formulated specific workflow and recommendations for algorithm development, validation, and evaluation within the guidance. Finally, the guidance underwent independent review by a panel of 20 external experts who then convened a consensus meeting to finalize it. RESULTS: A standardized workflow for algorithm development, validation, and evaluation was established. Guided by specific health status considerations, the workflow comprises four integrated steps: assessing an existing algorithm's suitability for the target health status; developing a new algorithm using recommended methods; validating the algorithm using prescribed performance measures; and evaluating the impact of the algorithm on study results. Additionally, 13 good practice recommendations were formulated with detailed explanations. Furthermore, a practical study on sepsis identification was included to demonstrate the application of this guidance. CONCLUSIONS: The establishment of guidance is intended to aid researchers and clinicians in the appropriate and accurate development and application of algorithms for identifying health status from RCD. This guidance has the potential to enhance the credibility of findings from observational studies involving RCD.

Asunto(s)

Algoritmos , Estado de Salud , Estudios Observacionales como Asunto , Humanos , Estudios Observacionales como Asunto/métodos , Estudios Observacionales como Asunto/normas , Reproducibilidad de los Resultados , Recolección de Datos/métodos , Recolección de Datos/normas , Recolección de Datos/estadística & datos numéricos

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This study aimed to investigate the association between glucocorticoid administration and outcomes in critically ill patients with ARDS using the Medical Information Mart for Intensive Care (MIMIC)-III database. Data were collected from the MIMIC-III database, which consists of critically ill participants between 2001 and 2012 in the USA. A total of 1831 adult critically ill patients with ARDS were enrolled from the MIMIC-III database. The 60-day and in-hospital mortality, were the primary endpoints. Secondary outcomes included length of stay (LOS) in the hospital and intensive care unit (ICU), 28-day ventilator-free days, ICU mortality, and 28-day mortality. A total of 1831 patients were included in the data analysis. After propensity score (PS) matching, 464 patients diagnosed with ARDS were matched between the glucocorticoid treatment and control groups. Glucocorticoids were associated with increased in-hospital mortality [hazard ratio (HR) 1.32; 95% CI 1.01-1.71; P = .039], longer ICU stay [HR 2.25; 95% CI 0.84-3.65; P = .002], and shorter ventilation-free days at 28 days in all ARDS patients [HR -2.70; 95% CI -4.28--1.13; P = .001]. The 60-day mortality was higher in the glucocorticoid group (44.83% vs 35.34%; P = .154; HR 1.24; 95% CI 0.93-1.66). Excluding the impact of the glucocorticoid initiation time, from day 15 to day 60, mortality was significantly higher in the glucocorticoid group compared to the non-glucocorticoid group (27.16% vs 12.70%; P < .001; HR 1.75; 95% CI 1.32-2.32). Glucocorticoid administration was associated with worse 60-day and in-hospital survival, longer ICU stay, and shorter ventilator-free days on day 28 in patients with ARDS. Our findings suggest careful consideration of glucocorticoids for ARDS.

Asunto(s)

Glucocorticoides , Mortalidad Hospitalaria , Unidades de Cuidados Intensivos , Tiempo de Internación , Puntaje de Propensión , Síndrome de Dificultad Respiratoria , Humanos , Glucocorticoides/administración & dosificación , Glucocorticoides/uso terapéutico , Masculino , Femenino , Síndrome de Dificultad Respiratoria/mortalidad , Síndrome de Dificultad Respiratoria/tratamiento farmacológico , Persona de Mediana Edad , Tiempo de Internación/estadística & datos numéricos , Unidades de Cuidados Intensivos/estadística & datos numéricos , Anciano , Bases de Datos Factuales , Enfermedad Crítica/mortalidad , Adulto , Respiración Artificial/estadística & datos numéricos , Estados Unidos/epidemiología

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NLRC5, the largest member of the nucleotide-binding and oligomerization domain (NOD)-like receptor (NLR) family, has been reported to participate in the regulation of immune function and is associated with chronic inflammatory diseases. However, the biological function of NLRC5 in hepatocellular carcinoma (HCC) has not been fully demonstrated. The aim of this study is to evaluate NLRC5 expression in the tumor tissues of HCC patients undergoing surgical treatment, assess its prognostic value, and explore its relationship with critical immune-related molecules within the tumor microenvironment. A total of 100 patients with hepatitis B virus-associated HCC receiving surgical treatment were enrolled in the study. Immunohistochemical results were obtained by scoring the intensity of cellular staining and the percentage of positive cells in the tissue sections. The association between NLRC5 expression levels and the main clinicopathological factors was analyzed by Chi-square test method. The prognostic values were analyzed by COX regression model and the Kaplan-Meier survival curve. Receiver operating characteristic (ROC) curve analysis was performed to assess the predictive performance of NLRC5 in postoperative patients with HCC. IHC showed that high expression of NLRC5 was observed in 67% of HCC tissue samples. Chi-square test showed that NLRC5 was a risk factor associated with tumor number, satellite nodule, and envelope invasion. Kaplan-Meier survival curves and COX survival analysis showed that high expression of NLRC5 was significantly associated with decreased overall survival (OS) in HCC patients (HR = 1.79, 95% CI 1.03-3.12, p = .041). However, univariate logistic regression analysis revealed that NLRC5 showed positive relationship with GZMB and CD8α suggesting its role in immune escape of HCC. ROC curve analysis showed that the combination of tumor number, envelope invasion, and NLRC5 expression (area under the curve = 0.824, sensitivity = 77.30%, specificity = 82.4%) can more accurately evaluate the prognosis of HCC patients compared to the combination of only tumor number and envelope invasion (area under the curve = 0.690, sensitivity = 43.9%, specificity = 94.1%).NLRC5 plays a crucial role in progression of HCC and can be considered as a potential prognostic and predictive biomarker. Targeting NLRC5 may provide an attractive therapeutic approach for HCC.

Asunto(s)

Biomarcadores de Tumor , Carcinoma Hepatocelular , Péptidos y Proteínas de Señalización Intracelular , Neoplasias Hepáticas , Humanos , Carcinoma Hepatocelular/patología , Carcinoma Hepatocelular/genética , Carcinoma Hepatocelular/metabolismo , Carcinoma Hepatocelular/mortalidad , Neoplasias Hepáticas/patología , Neoplasias Hepáticas/genética , Neoplasias Hepáticas/metabolismo , Neoplasias Hepáticas/mortalidad , Masculino , Femenino , Péptidos y Proteínas de Señalización Intracelular/metabolismo , Péptidos y Proteínas de Señalización Intracelular/genética , Persona de Mediana Edad , Pronóstico , Biomarcadores de Tumor/metabolismo , Biomarcadores de Tumor/genética , Adulto , Anciano , Estimación de Kaplan-Meier , Curva ROC , Microambiente Tumoral , Inmunohistoquímica , Relevancia Clínica

RESUMEN

OBJECTIVE: Accurate diagnoses and personalized treatments in medicine rely on identifying causality. However, existing causal discovery algorithms often yield inconsistent results due to distinct learning mechanisms. To address this challenge, we introduce MINDMerge, a multi-causal investigation and discovery framework designed to synthesize causal graphs from various algorithms. METHODS: MINDMerge integrates five causal models to reconcile inconsistencies arising from different algorithms. Employing credibility weighting and a novel cycle-breaking mechanism in causal networks, we initially developed and tested MINDMerge using three synthetic networks. Subsequently, we validated its effectiveness in discovering risk factors and predicting acute kidney injury (AKI) using two electronic medical records (EMR) datasets, eICU Collaborative Research Database and MIMIC-III Database. Causal reasoning was employed to analyze the relationships between risk factors and AKI. The identified causal risk factors of AKI were used in building a prediction model, and the prediction model was evaluated using the area under the receiver operating characteristics curve (AUC) and recall. RESULTS: Synthetic data experiments demonstrated that our model outperformed significantly in capturing ground-truth network structure compared to other causal models. Application of MINDMerge on real-world data revealed direct connections of pulmonary disease, hypertension, diabetes, x-ray assessment, and BUN with AKI. With the identified variables, AKI risk can be inferred at the individual level based on established BNs and prior information. Compared against existing benchmark models, MINDMerge maintained a higher AUC for AKI prediction in both internal (AUC: 0.832) and external network validations (AUC: 0.861). CONCLUSION: MINDMerge can identify causal risk factors of AKI, serving as a valuable diagnostic tool for clinical decision-making and facilitating effective intervention.

Asunto(s)

Lesión Renal Aguda , Algoritmos , Registros Electrónicos de Salud , Humanos , Lesión Renal Aguda/diagnóstico , Factores de Riesgo , Causalidad , Masculino , Femenino , Curva ROC