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With the global population continuously rising, efficient bioconversion of inedible agricultural by-products is crucial for human food and energy sustainability. We here propose solid-state fermentation approaches to efficiently convert biopolymers into oligomers/monomers by accelerating the natural degradation process of the versatile Streptomyces sp. strain SCUT-3. Using fish skin as a representative by-product, 54.3 g amino acids and 14.7 g peptides (91 % < 2500 Da) were recovered from 89.0 g protein in 100 g tilapia skin sample by collagenase-overexpressed SCUT-3 for seven days at a 1:4 substrate:liquid ratio. Fish skin collagen hydrolysates exhibited excellent anti-oxidation, anti-hypertension, scratch-repairing, anti-aging, anti-ultraviolet radiation, and anti-inflammation effects on human skin fibroblasts In vitro and zebrafish larvae in vivo, indicating their potential applications in healthcare/skincare and anti-atopic dermatitis. As Laozi said, the divine law follows nature. This study underscores the efficacy of genetically engineered SCUT-3 according to its natural biomass utilization laws in large-scale biopolymer conversion.

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Highly hydrophilic extracellular polymeric substance (EPS) with gel-like structure seriously plagues the development of sludge deep dewatering. Oxysulfur radicals-based oxidation driven by iron-bearing mineral proposes a promising strategy for effective EPS decomposition. However, the transformation and involved interaction mechanisms of aromatic proteins are still controversial due to the complex EPS structure. Herein, sulfite mediated siderite (denoted as Fe(II)/S(IV)) was developed for targeted transformation aromatic amino acids in EPS oxidation to strengthen sludge solid-liquid separation. The enhanced sludge dewaterability were benefited from the Fe(II)/S(IV) bonded interaction assisted by Fe3+/Fe2+ as redox interface that facilitating the release of intracellular bound water via diminish the hydrophily and bind strength with solid protons. The amide region nitrogen of aromatic amino acids (especially tyrosine and tryptophan) originating from EPS presented looser structure and lower spatial site resistance, which were attributed to the exposure of hydrophobic sites in amino groups after Fe(II)/S(IV) treatment. Furthermore, the effective decline of aromatic amino acids in inner layer-EPS (loosely bound EPS and tightly bound EPS) was directed from Fe-N targeted interaction by triggering a series of sulfate-based radical chain reactions. The good correlation between electron transfer amount (R2 = 0.926) and Fe-N (R2 = 0.925) with bonding interaction demonstrated that the complexation of aromatic amino acids with Fe sites on siderite/sulfite via Fe-N bonds, accounting for efficient sludge solid-liquid separation. This study deepens the understanding of sludge organic matter targeted transformation and provides a tactic for iron-based conditioning of sludge.

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Objective : To explore the roles of Neural precursor cell expressed developmentally down-regulated 1(NEDD1) in lung cancer tumorigenesis and the relationship between NEDD1 expression and clinicopathology of patients with lung adenocarcinoma (LUAD). Methods: Expression of NEDD1 or other proteins in tissues and cell lines were determined with immunohistochemistry or western blot, the data of patients with LUAD in The Cancer Genome Atlas (TCGA) datasets and LUAD tissue array were collected and analyzed, the effects of NEDD1 on proliferation, migration, cell cycle progression and apoptosis of cancer cells were detected with colony formation assay, transwell assay and Flow cytometry (FCM) analysis respectively. the impact of NEDD1 knockdown on DNA damage was analyzed using Immunofluorescence staining of H2AX and comet assay. Furthermore, the effect of NEDD1 on cancer cell proliferation in vivo was investigated in nude mice. Results : NEDD1 was upregulated in lung tissues and the NEDD1 immune score was an independent prognostic factor. Overexpression of NEDD1 promoted epithelial-mesenchymal transition, accelerated cell cycle progression, and enhanced the proliferation and migration of A549 and H1299 cells, while knockdown of NEDD1 resulted in the opposite phenotype and leaded to DNA damage. In addition, NEDD1 improved cell tumorigenicity in vivo. Conclusion : These findings suggest that NEDD1 plays important roles in lung cancer development and may therefore be a potential prognostic marker and promising therapeutic target for lung cancer therapy.

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BACKGROUND: Currently, tumor budding (TB) is defined as an important factor for a poor prognosis in various types of cancers. The authors identified a significant presence of TB-like structures at the tumor invasive front in giant cell tumor of bone (GCTB), which may have the same biologic function as TB. The objective of this report was to describe the distribution of TB in GCTB and investigate its correlation with clinicopathologic characteristics, the immune microenvironment, survival prognosis, and response to denosumab treatment. METHODS: This multicenter cohort study included 426 patients with GCTB who received treatment between 2012 and 2021 at four centers. Two independent pathologists performed visual assessments of TBL structures in hematoxylin-and-eosin-stained tumor sections. Immunohistochemistry was used to evaluate tumor-infiltrating lymphocyte subtypes (CD3-positive, CD4-positive, CD8-positive, CD20-positive, programmed cell death protein-1-positive, programmed cell death-ligand 1positive, and FoxP3-positive) as well as Ki-67 expression levels in 426 tissue samples. These parameters were then analyzed for associations with patient outcomes (local recurrence-free survival [LRFS] and overall survival [OS]), clinicopathologic characteristics, and response to denosumab treatment. RESULTS: High-grade TB was associated with poorer LRFS and OS in both patient groups. In addition, TB was correlated with various clinicopathologic features, tumor-infiltrating lymphocyte expression, and response to denosumab treatment. TB outperformed the traditional Enneking and Campanacci staging systems in predicting patient LRFS and OS. CONCLUSIONS: The current data support the assessment of TBL structures as a reliable prognostic tool in GCTB, potentially aiding in the development of personalized treatment strategies for patients.

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Tyrosine kinase inhibitors (TKIs) have revolutionized Philadelphia chromosome-positive (Ph+) acute lymphoblastic leukemia (ALL) treatment. The combination of blinatumomab and a TKI in the frontline setting has shown the safety and efficacy of the chemotherapy-free treatment approach in patients with Ph + ALL. This retrospective analysis included 19 patients with Ph + ALL and Ph-like ALL treated with the combination of blinatumomab and a TKI. Of the 14 newly diagnosed patients, the overall response, complete remission (CR), and molecular response (CMR) rates after one cycle of blinatumomab were 100% (10/10), 90% (9/10), and 57% (8/14), respectively. Of the five relapsed patients, the CR and CMR rates were 50% (2/4) and 40% (2/5). Blinatumomab in combination with TKIs is safe and effective and hence this combination therapy could be a viable therapeutic option in front-line treatment of patients with Ph + ALL.

Asunto(s)

Anticuerpos Biespecíficos , Protocolos de Quimioterapia Combinada Antineoplásica , Cromosoma Filadelfia , Leucemia-Linfoma Linfoblástico de Células Precursoras , Inhibidores de Proteínas Quinasas , Humanos , Anticuerpos Biespecíficos/uso terapéutico , Anticuerpos Biespecíficos/administración & dosificación , Anticuerpos Biespecíficos/efectos adversos , Femenino , Leucemia-Linfoma Linfoblástico de Células Precursoras/tratamiento farmacológico , Leucemia-Linfoma Linfoblástico de Células Precursoras/genética , Masculino , Inhibidores de Proteínas Quinasas/uso terapéutico , Inhibidores de Proteínas Quinasas/administración & dosificación , Adulto , Persona de Mediana Edad , Estudios Retrospectivos , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Anciano , Resultado del Tratamiento , Adulto Joven , Adolescente

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Objective: Intellectual disability (ID) is a prevalent comorbidity in children with cerebral palsy (CP), presenting significant challenges to individuals, families and society. This study aims to develop a predictive model to assess the risk of ID in children with CP. Methods: We analyzed data from 885 children diagnosed with CP, among whom 377 had ID. Using least absolute shrinkage and selection operator regression, along with univariate and multivariate logistic regression, we identified key predictors for ID. Model performance was evaluated through receiver operating characteristic curves, calibration plots, and decision curve analysis (DCA). Bootstrapping validation was also employed. Results: The predictive nomogram included variables such as preterm birth, CP subtypes, Gross Motor Function Classification System level, MRI classification category, epilepsy status and hearing loss. The model demonstrated strong discrimination with an area under the receiver operating characteristic curve (AUC) of 0.781 (95% CI: 0.7504-0.8116) and a bootstrapped AUC of 0.7624 (95% CI: 0.7216-0.8032). Calibration plots and the Hosmer-Lemeshow test indicated a good fit (χ2= 7.9061, p = 0.4427). DCA confirmed the model's clinical utility. The cases were randomly divided into test group and validation group at a 7:3 ratio, demonstrating strong discrimination, good fit and clinical utility; similar results were found when stratified by sex. Conclusions: This predictive model effectively identifies children with CP at a high risk for ID, facilitating early intervention strategies. Stratified risk categories provide precise guidance for clinical management, aiming to optimize outcomes for children with CP by leveraging neuroplasticity during early childhood.

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BACKGROUND: The implementation and clinical impact of machine learning-based early warning systems for patient deterioration in hospitals have not been well described. We sought to describe the implementation and evaluation of a multifaceted, real-time, machine learning-based early warning system for patient deterioration used in the general internal medicine (GIM) unit of an academic medical centre. METHODS: In this nonrandomized, controlled study, we evaluated the association between the implementation of a machine learning-based early warning system and clinical outcomes. We used propensity score-based overlap weighting to compare patients in the GIM unit during the intervention period (Nov. 1, 2020, to June 1, 2022) to those admitted during the pre-intervention period (Nov. 1, 2016, to June 1, 2020). In a difference-indifferences analysis, we compared patients in the GIM unit with those in the cardiology, respirology, and nephrology units who did not receive the intervention. We retrospectively calculated system predictions for each patient in the control cohorts, although alerts were sent to clinicians only during the intervention period for patients in GIM. The primary outcome was non-palliative in-hospital death. RESULTS: The study included 13 649 patient admissions in GIM and 8470 patient admissions in subspecialty units. Non-palliative deaths were significantly lower in the intervention period than the pre-intervention period among patients in GIM (1.6% v. 2.1%; adjusted relative risk [RR] 0.74, 95% confidence interval [CI] 0.55-1.00) but not in the subspecialty cohorts (1.9% v. 2.1%; adjusted RR 0.89, 95% CI 0.63-1.28). Among high-risk patients in GIM for whom the system triggered at least 1 alert, the proportion of non-palliative deaths was 7.1% in the intervention period, compared with 10.3% in the pre-intervention period (adjusted RR 0.69, 95% CI 0.46-1.02), with no meaningful difference in subspecialty cohorts (10.4% v. 10.6%; adjusted RR 0.98, 95% CI 0.60-1.59). In the difference-indifferences analysis, the adjusted relative risk reduction for non-palliative death in GIM was 0.79 (95% CI 0.50-1.24). INTERPRETATION: Implementing a machine learning-based early warning system in the GIM unit was associated with lower risk of non-palliative death than in the pre-intervention period. Machine learning-based early warning systems are promising technologies for improving clinical outcomes.

Asunto(s)

Deterioro Clínico , Mortalidad Hospitalaria , Aprendizaje Automático , Humanos , Masculino , Femenino , Anciano , Estudios Retrospectivos , Puntuación de Alerta Temprana , Persona de Mediana Edad , Puntaje de Propensión , Medicina Interna

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BACKGROUND AND AIM: Population-based studies comparing clinical characteristics and survival disparities between patients with small bowel adenocarcinoma (SBA) and small bowel neuroendocrine tumors (SBNETs) in the United States are limited. METHODS: Data for patients with SBA or SBNETs, obtained from the Surveillance, Epidemiology, and End Results database for the years between 2000 and 2018 were analyzed. RESULTS: Between 2000 and 2018, the age-adjusted incidence of SBA experienced a marginal increase whereas SBNETs demonstrated a significant increase, emerging as the predominant subtype of small bowel cancer (SBC). Diagnoses peaked at ages 65-69 years for SBA and 60-64 years for SBNETs, with the latter exhibiting a heightened age-specific incidence and maintaining equilibrium in gender distribution. Clinicopathologic disparities revealed SBA's duodenal predilection, larger tumor size, and advanced stages, contrasting with SBNETs' ileal predilection, early-stage presentation, and superior outcomes. SBNETs patients underwent surgery more frequently but received less chemotherapy and radiation than SBA patients. Factors intricately correlated with a diagnosis of SBNETs included female gender, White race, advanced age, marital status, recent diagnoses, superior tumor differentiation, smaller size, distal location, and early-stage presentation. Survival analysis unveiled a remarkable 79% reduction in the mortality risk for SBNETs compared with SBA. Subgroup analysis further confirmed the consistently favorable survival advantages of SBNETs, highlighting the clinical relevance of histological classification in prognostication. CONCLUSION: Compared with SBA, SBNETs exhibited distinctive clinicopathological features characterized by a higher inclination toward low-grade and early-stage manifestations, thereby contributing to superior survival outcomes.

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Alzheimer's disease (AD) is a neurological disease with memory loss and cognitive decline, which affects a large proportion of the aging population. Regrettably, there are no drug to reverse or cure AD and drug development for the primary theory of amyloid beta deposition has mostly failed. Therefore, there is an urgent need to investigate novel strategies for preventing AD. Recent studies demonstrate that imbalance of mitochondrial homeostasis is a driver in Aß accumulation, which can lead to the occurrence and deterioration of cognitive impairment in AD patients. This suggests that regulating neuronal mitochondrial homeostasis may be a new strategy for AD. We summarize the importance of mitochondrial homeostasis in AD neuron and its regulatory mechanisms in this review. In addition, we summarize the results of studies indicating mitochondrial dysfunction in AD subjects, including impaired mitochondrial energy production, oxidative stress, imbalance of mitochondrial protein homeostasis, imbalance of fusion and fission, imbalance of neuronal mitochondrial biogenesis and autophagy, and altered mitochondrial motility, in hope of providing possible therapeutic approaches for AD.

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Background: Angioimmunoblastic T-cell lymphoma (AITL) is known for its unfavorable survival prognosis. Chidamide has shown efficacy in relapsed/refractory AITL, but its efficacy in newly diagnosed AITL is uncertain. Objective: This retrospective research aimed to evaluate the effectiveness and safety of chidamide when used with doxorubicin, cyclophosphamide, prednisone, and vincristine (CHOP) in comparison to CHOP by itself for individuals newly diagnosed with AITL, and to examine the impact of transplantation. Method: This was an analysis that compared outcomes among patients who received chidamide + CHOP on a clinical trial vs. historical controls who received CHOP alone, enrolling a total of sixty-six treatment-naive AITL patients between April 2014 and November 2022. Among them, thirty-three received chidamide in addition to CHOP (chidamide group), while thirty-three received CHOP alone (control group). The clinical characteristics were balanced between the two groups. All patients were scheduled to undergo up to six courses of treatment before transplantation. Results: The chidamide group had a significantly longer median overall survival (OS) compared to the control group, with a median OS that was not reached, as opposed to 20 months in the control group (p = 0.002). In the control group, the median progression-free survival (PFS) was 11 months, while in the chidamide group, it was 22 months (p = 0.080). In the high-risk group (IPI ≥ 3), the chidamide group demonstrated notably superior complete response (CR) and overall response rate (ORR) compared to the control cohort (p = 0.002, p = 0.034). The PFS and OS in the chidamide group were not reached, and there were significant differences compared to the control group (p = 0.007, p = 0.003). The median OS of the transplanted group was longer than the non-transplanted group (p = 0.004). On multivariate analysis, chidamide group reduced the hazards of death in the total cohort. Conclusion: As the study was non-random and retrospective, Chidamide combined with chemotherapy should be tested in randomized trials given its potential to improve prognosis in treatment-naive AITL patients. Furthermore, autologous hematopoietic stem cell transplantation (auto-HSCT) has demonstrated enhanced overall survival in individuals with AITL. Clinical trial registration: https://clinicaltrials.gov/, NCT03268889.

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Aminopiridinas , Protocolos de Quimioterapia Combinada Antineoplásica , Benzamidas , Adulto , Anciano , Femenino , Humanos , Masculino , Persona de Mediana Edad , Aminopiridinas/uso terapéutico , Aminopiridinas/administración & dosificación , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Benzamidas/uso terapéutico , Benzamidas/administración & dosificación , Benzamidas/efectos adversos , Ciclofosfamida/uso terapéutico , Ciclofosfamida/administración & dosificación , Doxorrubicina/uso terapéutico , Doxorrubicina/administración & dosificación , Doxorrubicina/efectos adversos , Linfoma de Células T/mortalidad , Linfoma de Células T/terapia , Linfoma de Células T/tratamiento farmacológico , Linfoma de Células T/diagnóstico , Prednisona/uso terapéutico , Prednisona/administración & dosificación , Estudios Retrospectivos , Resultado del Tratamiento , Vincristina/uso terapéutico , Vincristina/administración & dosificación

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Boron Neutron Capture Therapy is being promoted with the development of accelerator neutron sources, and many new accelerator-based BNCT facilities are being built. In Particle Accelerator Facility project of Sun Yat-sen University, we plan to build a terminal for BNCT research based on an 8 MeV, CW 3 mA proton accelerator. In this paper, we present a beam-shaping assembly for this proton accelerator with such low 24 kW beam power, using composite moderator materials composed of five elements: Mg, Al, F, O, and Li. The calculation result of FLUKA with ENDF/B and JENDL libraries shows that the epithermal neutron beam flux is 1.57×109n/cm2/s with the CW 3 mA proton beam. The fast neutron component and the gamma ray component under free-air condition are 1.49×10-13Gy∙cm2 and 8.12×10-14Gy∙cm2 respectively, in line with IAEA-TECDOC-1223 design recommendations. The thermal analysis shows that the maximum temperature of beryllium target is 706.5 K, and the structure materials of BSA do not melt.

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In this study, novel chitosan/polyethylene oxide/Ti3C2Tx 2D MXene nanosheets (CS/PEO/Ti3C2Tx) nanofibers were successfully prepared by a continuous electrospinning process. During the electrospinning process, induced by the syringe tip capillary effects and electric field force, the Ti3C2Tx nanosheets were aligned along the direction of the nanofiber formation to occur a highly oriented structure. This well-ordered arrangement of the inorganic Ti3C2Tx nanosheets within the organic polymer matrix nanofiber was similar with nacre-like 'brick-and-motar' structure to some extent, resulting in a marked increase in thermal stability and mechanical properties of the resultant CS/PEO/Ti3C2Tx nanofiber. As 4 wt% of Ti3C2Tx nanosheets loaded, the highest tensile strength of the CS/PEO/Ti3C2Tx nanofiber mats was achieved as 31.7 MPa, about two times that of neat CS/PEO nanofibers. Uniformly dispersed Pd nanoparticles in size of about 1.6 nm have been successfully immobilized on the composite nanofiber with a solution impregnation process. With a loading as low as 0.2 mol% of Pd, the resultant Pd@CS/PEO/Ti3C2Tx composite nanofiber catalysts were highly active for both Heck and Sonogashira coupling reactions with broad reactants application scope, and could be recycled 15 runs without significant loss of activities.

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Neurodiversity is a perspective on cognition which suggests a non-pathological view of individual cognitive differences. Aesthetics research on neurodivergent brains has generally been limited to neuropsychological cases. Although this research has been integral to establishing the neurological correlates of aesthetic experience, it is crucial to expand this paradigm to more psychologically complex disorders. We offer a review of research on aesthetic preference in neurodivergent brains beyond neuropsychological cases: across populations with psychotic disorder, anhedonia and depression, anxiety disorder, and autism. We identify stable patterns of aesthetic bias in these populations, relate these biases to symptoms at perceptual, emotional, and evaluative levels of cognition, review relevant neurological correlates, and connect this evidence to current neuroaesthetics theory. Critically, we synthesize the reviewed evidence and discuss its relevance for three brain networks regularly implicated in aesthetic processing: the mesocorticolimbic reward circuit, frontolimbic connections, and the default mode network. Finally, we propose that broadening the subject populations for neuroaesthetics research to include neurodiverse populations is instrumental for yielding new insights into aesthetic processing in the brain.

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Encéfalo , Estética , Humanos , Encéfalo/fisiología , Trastornos Mentales/fisiopatología

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BACKGROUND: Scoliosis secondary to cerebral palsy is one of the common complications of cerebral palsy in children with cerebral palsy. OBJECTIVE: This study aimed to explore the efficacy of rehabilitation combined with brace correction in patients with scoliosis secondary to cerebral palsy. METHODS: A total of 52 patients with scoliosis secondary to cerebral palsy were selected from our hospital from April 2019 to April 2022 and divided into the control group and experimental group according to the statistical randomization method (n= 26 in each group). Control group: mean age (14.28 ± 2.31) years; 16 males and 10 females. Experimental group: average age (14.24 ± 2.35) years; 15 males and 11 females. The control group wore scoliosis orthopedic brace, while the experimental group was treated with rehabilitation manipulation and rehabilitation training (including gymnastic training and weight training) on the basis of the control group for 1 year. The clinical efficacy of the two groups was compared and observed; the number of degrees of scoliosis (Cobb angle), the angle of vertebral rotation (AVR) and the distance of the parietal vertebrae from the sacral midline (AVT) were compared before and after treatment; the incidence of adverse events during treatment was observed in the two groups. RESULTS: After treatment, both groups showed significant improvement in the overall effectiveness of treatment, Cobb's angle, AVR and AVT compared with those before treatment (P< 0.05). The experimental group had a significantly higher overall effective rate of treatment than the control group (P< 0.05), a significantly smaller Cobb's angle and AVR than the control group (P< 0.05) and a significantly shorter AVT than the control group (P< 0.05). The incidence of adverse events during treatment was lower in both groups and was not significantly different (P> 0.05). CONCLUSION: The combination of rehabilitation physiotherapy and bracing is effective in optimizing the clinical outcome of patients with scoliosis secondary to cerebral palsy, improving their scoliosis dysfunction and providing a high level of safety in treatment.

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Dose prediction is a crucial step in automated radiotherapy planning for liver cancer. Several deep learning-based approaches for dose prediction have been proposed to enhance the design efficiency and quality of radiotherapy plan. However, these approaches usually take CT images and contours of organs at risk (OARs) and planning target volume (PTV) as a multi-channel input and is thus difficult to extract sufficient feature information from each input, which results in unsatisfactory dose distribution. In this paper, we propose a novel dose prediction network for liver cancer based on hierarchical feature fusion and interactive attention. A feature extraction module is first constructed to extract multi-scale features from different inputs, and a hierarchical feature fusion module is then built to fuse these multi-scale features hierarchically. A decoder based on attention mechanism is designed to gradually reconstruct the fused features into dose distribution. Additionally, we design an autoencoder network to generate a perceptual loss during training stage, which is used to improve the accuracy of dose prediction. The proposed method is tested on private clinical dataset and obtains HI and CI of 0.31 and 0.87, respectively. The experimental results are better than those by several existing methods, indicating that the dose distribution generated by the proposed method is close to that approved in clinics. The codes are available at https://github.com/hired-ld/FA-Net.

Asunto(s)

Aprendizaje Profundo , Neoplasias Hepáticas , Dosificación Radioterapéutica , Planificación de la Radioterapia Asistida por Computador , Humanos , Neoplasias Hepáticas/diagnóstico por imagen , Planificación de la Radioterapia Asistida por Computador/métodos , Redes Neurales de la Computación , Tomografía Computarizada por Rayos X/métodos , Órganos en Riesgo

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BACKGROUND: The prognostic value of the pretreatment prognostic nutritional index (PNI) for gynaecological malignancies remain unclear. This meta-analysis aimed to explore the predictive significance of the PNI for gynaecological tumours. METHODS: The PubMed, Embase, Web of Science, and Cochrane Library databases were searched up to January 30, 2024, to identify relevant studies. Hazard ratios (HRs) and 95% confidence intervals (CIs) were calculated to assess the associations of the PNI with overall survival (OS), progression-free survival (PFS), and disease-free survival (DFS) in patients with gynaecological tumours. We examined the correlation of the PNI with clinicopathological parameters of patients with gynaecological carcinoma by utilizing pooled odds ratios (ORs) and 95% CIs. RESULTS: A total of 28 articles involving 9,428 patients were included in the meta-analysis. The results revealed that a low PNI significantly predicted worse OS (HR = 1.60, 95% CI: 1.39-1.84, P < 0.001), PFS (HR = 1.63, 95% CI: 1.20-2.23, P = 0.002), and DFS (HR = 1.73, 95% CI: 1.19-2.52, P = 0.004). In addition, the subgroup analysis confirmed that the PNI had a prognostic effect on OS for all cancer types, but a significant association with PFS was not observed in patients with cervical cancer. A low PNI was significantly associated with FIGO stages III‒IV (OR = 2.30, 95% CI: 1.89‒2.80, P < 0.001) and LN metastasis (OR = 2.76, 95% CI: 2. 05‒3.73, P < 0.001). CONCLUSION: The PNI may be noninvasive and promising biomarker for predicting the prognosis of patients with gynaecological tumours.

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Neoplasias Endometriales , Evaluación Nutricional , Neoplasias Ováricas , Neoplasias del Cuello Uterino , Humanos , Femenino , Pronóstico , Neoplasias Endometriales/mortalidad , Neoplasias Endometriales/patología , Neoplasias Endometriales/diagnóstico , Neoplasias Ováricas/mortalidad , Neoplasias Ováricas/patología , Neoplasias del Cuello Uterino/patología , Neoplasias del Cuello Uterino/mortalidad , Neoplasias del Cuello Uterino/diagnóstico , Supervivencia sin Enfermedad

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Endothelial dysfunction may contribute to pathogenesis of Takotsubo cardiomyopathy, but mechanism underlying endothelial dysfunction in the setting of catecholamine excess has not been clarified. The study reports that D1/D5 dopamine receptor signaling and small conductance calcium-activated potassium channels contribute to high concentration catecholamine induced endothelial cell dysfunction. For mimicking catecholamine excess, 100 µM epinephrine (Epi) was used to treat human cardiac microvascular endothelial cells. Patch clamp, FACS, ELISA, PCR, western blot and immunostaining analyses were performed in the study. Epi enhanced small conductance calcium-activated potassium channel current (ISK1-3) without influencing the channel expression and the effect was attenuated by D1/D5 receptor blocker. D1/D5 agonists mimicked the Epi effect, suggesting involvement of D1/D5 receptors in Epi effects. The enhancement of ISK1-3 caused by D1/D5 activation involved roles of PKA, ROS and NADPH oxidases. Activation of D1/D5 and SK1-3 channels caused a hyperpolarization, reduced NO production and increased ROS production. The NO reduction was membrane potential independent, while ROS production was increased by the hyperpolarization. ROS (H2O2) suppressed NO production. The study demonstrates that high concentration catecholamine can activate D1/D5 and SK1-3 channels through NADPH-ROS and PKA signaling and reduce NO production, which may facilitate vasoconstriction in the setting of catecholamine excess.

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Células Endoteliales , Epinefrina , Especies Reactivas de Oxígeno , Transducción de Señal , Humanos , Transducción de Señal/efectos de los fármacos , Células Endoteliales/metabolismo , Células Endoteliales/efectos de los fármacos , Especies Reactivas de Oxígeno/metabolismo , Óxido Nítrico/metabolismo , Catecolaminas/metabolismo , Canales de Potasio de Pequeña Conductancia Activados por el Calcio/metabolismo , Endotelio Vascular/metabolismo , Endotelio Vascular/patología , Endotelio Vascular/efectos de los fármacos , Proteínas Quinasas Dependientes de AMP Cíclico/metabolismo , NADPH Oxidasas/metabolismo , Receptores de Dopamina D5/metabolismo , Receptores de Dopamina D1/metabolismo , Receptores Dopaminérgicos/metabolismo

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Background: Erythrocyte dysfunction is a characteristic of diabetes mellitus (DM). However, erythrocyte-associated biomarkers do not adequately explain the high prevalence of DM. Here, we describe red blood cell distribution width to albumin ratio (RAR) as a novel inflammatory biomarker for evaluating an association with DM prevalence and prognosis of all-cause mortality. Methods: Data analyzed in this study were extracted from the National Health and Nutrition Examination Survey (NHANES) 1999-2020. A total of 40,558 participants (non-DM and DM) were enrolled in the study; RAR quartiles were calibrated at Q1 [2.02,2.82] mL/g, Q2 (2.82,3.05] mL/g, Q3 (3.05,3.38] mL/g, and Q4 (3.38,12.08] mL/g. A total of 8,482 DM patients were followed (for a median of 84 months), of whom 2,411 died and 6,071 survived. The prevalence and prognosis associated with RAR and DM were analyzed; age and sex were stratified to analyze the prevalence of RAR in DM and the sensitivity of long-term prognosis. Results: Among non-DM (n=30,404) and DM (n=10,154) volunteers, DM prevalence in RAR quartiles was 8.23%, 15.20%, 23.92%, and 36.39%. The multivariable odds ratio (OR) was significant for RAR regarding DM, at 1.68 (95% CI 1.42, 1.98). Considering Q1 as a foundation, the Q4 OR was 2.57 (95% CI 2.11, 3.13). The percentages of DM morbidity varied across RAR quartiles for dead (n=2,411) and surviving (n=6,071) DM patients. Specifically, RAR quartile mortality ratios were 20.31%, 24.24%, 22.65%, and 29.99% (P<0.0001). The multivariable hazard ratio (HR) for RAR was 1.80 (95% CI 1.57, 2.05). Considering Q1 as a foundation, the Q4 HR was 2.59 (95% CI 2.18, 3.09) after adjusting for confounding factors. Sensitivity analysis revealed the HR of male DM patients to be 2.27 (95% CI 1.95, 2.64), higher than females 1.56 (95% CI 1.31, 1.85). DM patients who were 60 years of age or younger had a higher HR of 2.08 (95% CI1.61, 2.70) as compared to those older than 60 years, who had an HR of 1.69 (95% CI 1.47, 1.94). The HR of RAR in DM patients was optimized by a restricted cubic spline (RCS) model; 3.22 was determined to be the inflection point of an inverse L-curve. DM patients with a RAR >3.22 mL/g suffered shorter survival and higher mortality as compared to those with RAR ≤3.22 mL/g. OR and HR RAR values were much higher than those of regular red blood cell distribution width. Conclusions: The predictive value of RAR is more accurate than that of RDW for projecting DM prevalence, while RAR, a DM risk factor, has long-term prognostic power for the condition. Survival time was found to be reduced as RAR increased for those aged ≤60 years among female DM patients.

Asunto(s)

Diabetes Mellitus , Índices de Eritrocitos , Encuestas Nutricionales , Humanos , Masculino , Femenino , Pronóstico , Persona de Mediana Edad , Prevalencia , Diabetes Mellitus/epidemiología , Diabetes Mellitus/sangre , Adulto , Anciano , Biomarcadores/sangre , Eritrocitos/metabolismo , Albúmina Sérica/análisis , Albúmina Sérica/metabolismo