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Progress in understanding early human development has been impeded by the scarcity of reference datasets from natural embryos, particularly those with spatial information during crucial stages like gastrulation. We conducted high-resolution spatial transcriptomics profiling on 38,562 spots from 62 transverse sections of an intact Carnegie stage (CS) 8 human embryo. From this spatial transcriptomic dataset, we constructed a 3D model of the CS8 embryo, in which a range of cell subtypes are identified, based on gene expression patterns and positional register, along the anterior-posterior, medial-lateral, and dorsal-ventral axis in the embryo. We further characterized the lineage trajectories of embryonic and extra-embryonic tissues and associated regulons and the regionalization of signaling centers and signaling activities that underpin lineage progression and tissue patterning during gastrulation. Collectively, the findings of this study provide insights into gastrulation and post-gastrulation development of the human embryo.
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Embrión de Mamíferos , Gastrulación , Regulación del Desarrollo de la Expresión Génica , Imagenología Tridimensional , Humanos , Embrión de Mamíferos/metabolismo , Transcriptoma/genética , Gástrula/metabolismo , Gástrula/embriología , Transducción de Señal , Linaje de la Célula , Perfilación de la Expresión Génica , Tipificación del Cuerpo/genéticaRESUMEN
Pregnancy induces dramatic metabolic changes in females; yet, the intricacies of this metabolic reprogramming remain poorly understood, especially in primates. Using cynomolgus monkeys, we constructed a comprehensive multi-tissue metabolome atlas, analyzing 273 samples from 23 maternal tissues during pregnancy. We discovered a decline in metabolic coupling between tissues as pregnancy progressed. Core metabolic pathways that were rewired during primate pregnancy included steroidogenesis, fatty acid metabolism, and arachidonic acid metabolism. Our atlas revealed 91 pregnancy-adaptive metabolites changing consistently across 23 tissues, whose roles we verified in human cell models and patient samples. Corticosterone and palmitoyl-carnitine regulated placental maturation and maternal tissue progenitors, respectively, with implications for maternal preeclampsia, diabetes, cardiac hypertrophy, and muscle and liver regeneration. Moreover, we found that corticosterone deficiency induced preeclampsia-like inflammation, indicating the atlas's potential clinical value. Overall, our multi-tissue metabolome atlas serves as a framework for elucidating the role of metabolic regulation in female health during pregnancy.
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Metabolómica , Embarazo , Animales , Femenino , Humanos , Embarazo/metabolismo , Corticosterona/metabolismo , Metaboloma/fisiología , Placenta/metabolismo , Preeclampsia , Primates/metabolismoRESUMEN
The implication of 5-hydroxytryptamine 2C receptor (5-HT2CR) in depression is a topic of debate, and the underlying mechanisms remain largely unclear. We now elucidate hippocampal excitation-inhibition (E/I) balance underlies the regulatory effects of 5-HT2CR in depression. Molecular biological analyses showed that chronic mild stress (CMS) reduced the expression of 5-HT2CR in hippocampus. We revealed that inhibition of 5-HT2CR induced depressive-like behaviors, reduced GABA release and shifted the E/I balance towards excitation in CA3 pyramidal neurons by using behavioral analyses, microdialysis coupled with mass spectrum, and electrophysiological recording. Moreover, 5-HT2CR modulated neuronal nitric oxide synthase (nNOS)-carboxy-terminal PDZ ligand of nNOS (CAPON) interaction through influencing intracellular Ca2+ release, as determined by fiber photometry and coimmunoprecipitation. Notably, disruption of nNOS-CAPON by specific small molecule compound ZLc-002 or AAV-CMV-CAPON-125C-GFP, abolished 5-HT2CR inhibition-induced depressive-like behaviors, as well as the impairment in soluble N-ethylmaleimide-sensitive factor attachment protein receptor (SNARE) complex assembly-mediated GABA vesicle release and a consequent E/I imbalance. Importantly, optogenetic inhibition of CA3 GABAergic neurons prevented the effects of AAV-CMV-CAPON-125C-GFP on depressive behaviors in the presence of 5-HT2CR antagonist. Conclusively, our findings disclose the regulatory role of 5-HT2CR in depressive-like behaviors and highlight the hippocampal nNOS-CAPON coupling-triggered E/I imbalance as a pivotal cellular event underpinning the behavioral consequences of 5-HT2CR inhibition.
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Tumor-associated myeloid cells (TAMCs) play a crucial role in orchestrating the dynamics of the tumor immune microenvironment. This heterogeneous population encompasses myeloid-derived suppressor cells, tumor-associated macrophages and dendritic cells, all of which contribute to the establishment of an immunosuppressive milieu that fosters tumor progression. Tumor-derived exosomes (TEXs), small extracellular vesicles secreted by tumor cells, have emerged as central mediators in intercellular communication within the tumor microenvironment. In this comprehensive review, we explore the intricate mechanisms through which TEXs modulate immune-suppressive effects on TAMCs and their profound implications in cancer progression. We delve into the multifaceted ways in which TEXs influence TAMC functions, subsequently affecting tumor immune evasion. Furthermore, we elucidate various therapeutic strategies aimed at targeting TEX-mediated immune suppression, with the ultimate goal of bolstering antitumor immunity.
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Exosomas , Células Supresoras de Origen Mieloide , Neoplasias , Humanos , Exosomas/patología , Neoplasias/patología , Terapia de Inmunosupresión , Células Mieloides , Microambiente TumoralRESUMEN
Nucleic acid detection of pathogens in a point-of-need (PON) manner is of great significance yet remains challenging for sensitive and accurate visual discrimination. Here, we report a CRISPR-Cas12a-mediated lateral flow assay for PON detection of Salmonella typhimurium (S.ty) that is a prevailing pathogen disseminated through tainted food. The variation of the fluorescence color of the test line is exploited to interpret the results, enabling the discrimination between positive and negative samples on the basis of a hue-recognition mechanism. By leveraging the cleavage activity of Cas12a and hue-recognition readout, the assay facilitated by recombinase polymerase amplification can yield a visual detection limit of 1 copy µL-1 for S.ty genomic DNA within 1 h. The assay also displays a high specificity toward S.ty in fresh chicken samples, as well as a sensitivity 10-fold better than that of the commercial test strip. Moreover, a semiquantitative detection of S.ty ranging from 0 to 4 × 103 CFU/mL by the naked eye is made possible, thanks to the easily discernible color change of the test line. This approach provides an easy, rapid, accurate, and user-friendly solution for the PON detection of Salmonella and other pathogens.
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Sistemas CRISPR-Cas , Salmonella typhimurium , Animales , Sistemas CRISPR-Cas/genética , Salmonella typhimurium/genética , Bioensayo , Pollos , Alimentos , Técnicas de Amplificación de Ácido NucleicoRESUMEN
BACKGROUND: Adhesion G protein-coupled receptors (aGPCRs), a distinctive subset of the G protein-coupled receptor (GPCR) superfamily, play crucial roles in various physiological and pathological processes, with implications in tumor development. Despite the global prevalence of breast cancer (BRCA), specific aGPCRs as potential drug targets or biomarkers remain underexplored. METHODS: UALCAN, GEPIA, Kaplan-Meier Plotter, MethSurv, cBiopportal, String, GeneMANIA, DAVID, Timer, Metascape, and qPCR were applied in this work. RESULTS: Our analysis revealed significantly increased transcriptional levels of ADGRB2, ADGRC1, ADGRC2, ADGRC3, ADGRE1, ADGRF2, ADGRF4, and ADGRL1 in BRCA primary tumors. Further analysis indicated a significant correlation between the expressions of certain aGPCRs and the pathological stage of BRCA. High expression of ADGRA1, ADGRF2, ADGRF4, ADGRG1, ADGRG2, ADGRG4, ADGRG6, and ADGRG7 was significantly correlated with poor overall survival (OS) in BRCA patients. Additionally, high expression of ADGRF2 and ADGRF4 indicated inferior recurrence-free survival (RFS) in BRCA patients. The RT-qPCR experiments also confirmed that the mRNA levels of ADGRF2 and ADGRF4 were higher in BRCA cells and tissues. Functional analysis highlighted the diverse roles of aGPCRs, encompassing GPCR signaling and metabolic energy reserves. Moreover, aGPCRs may exert influence or actively participate in the development of BRCA through their impact on immune status. CONCLUSION: aGPCRs, particularly ADGRF2 and ADGRF4, hold promise as immunotherapeutic targets and prognostic biomarkers in BRCA.
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Biomarcadores de Tumor , Neoplasias de la Mama , Regulación Neoplásica de la Expresión Génica , Receptores Acoplados a Proteínas G , Humanos , Femenino , Neoplasias de la Mama/genética , Neoplasias de la Mama/patología , Neoplasias de la Mama/metabolismo , Neoplasias de la Mama/mortalidad , Receptores Acoplados a Proteínas G/metabolismo , Receptores Acoplados a Proteínas G/genética , Biomarcadores de Tumor/metabolismo , Biomarcadores de Tumor/genética , Pronóstico , Terapia Molecular Dirigida , Línea Celular Tumoral , Perfilación de la Expresión Génica , Estimación de Kaplan-MeierRESUMEN
Hemorrhagic fever with renal syndrome (HFRS) and severe fever with thrombocytopenia syndrome (SFTS) are both endemic in rural areas and some characteristics are similar between HFRS and SFTS, which usually lead to misdiagnosis. In this study, we summarized and compared some characteristics of HFRS and SFTS which will provide scientific information for differential diagnosis. From 2011 to 2022, a total of 4336 HFRS cases and 737 SFTS cases were reported in Zhejiang Province. Compared to SFTS, there was a higher proportion of males among HFRS cases (72.46% [3142/4336] vs. 50.88% [375/737], p = 0.000). The median age of all 4336 HFRS cases was 49 (39, 59), while the median age of SFTS cases was 66 (57, 74). In addition, the involved counties of HFRS were more than SFTS, but the number of counties affected by SFTS increased from 2011 to 2022. The majority of SFTS cases occurred in summer (from May to July), but besides summer, HFRS cases also showed a peak in winter. Finally, our results showed that the case fatality rate of SFTS was significantly higher than that of HFRS. Although there were some similarities between HFRS and SFTS, our study found several differences between them, such as gender distribution, age distribution, and seasonal distribution, which will provide scientific information for differential diagnosis of HFRS and SFTS. Further studies should be carried out to explore the mechanism of these differences.
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Fiebre Hemorrágica con Síndrome Renal , Estaciones del Año , Síndrome de Trombocitopenia Febril Grave , Humanos , Fiebre Hemorrágica con Síndrome Renal/epidemiología , Fiebre Hemorrágica con Síndrome Renal/diagnóstico , Masculino , Persona de Mediana Edad , Femenino , Adulto , Anciano , Síndrome de Trombocitopenia Febril Grave/epidemiología , Síndrome de Trombocitopenia Febril Grave/virología , Síndrome de Trombocitopenia Febril Grave/diagnóstico , China/epidemiología , Diagnóstico DiferencialRESUMEN
Phosphorylation is indispensable in comprehending biological processes, while biological experimental methods for identifying phosphorylation sites are tedious and arduous. With the rapid growth of biotechnology, deep learning methods have made significant progress in site prediction tasks. Nevertheless, most existing predictors only consider protein sequence information, that limits the capture of protein spatial information. Building upon the latest advancement in protein structure prediction by AlphaFold2, a novel integrated deep learning architecture PhosAF is developed to predict phosphorylation sites in human proteins by integrating CMA-Net and MFC-Net, which considers sequence and structure information predicted by AlphaFold2. Here, CMA-Net module is composed of multiple convolutional neural network layers and multi-head attention is appended to obtaining the local and long-term dependencies of sequence features. Meanwhile, the MFC-Net module composed of deep neural network layers is used to capture the complex representations of evolutionary and structure features. Furthermore, different features are combined to predict the final phosphorylation sites. In addition, we put forward a new strategy to construct reliable negative samples via protein secondary structures. Experimental results on independent test data and case study indicate that our model PhosAF surpasses the current most advanced methods in phosphorylation site prediction.
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Apoptosis plays a pivotal role in pathogen elimination and maintaining homeostasis. However, viruses have evolved strategies to evade apoptosis, enabling their persistence within the host. Z-DNA binding protein 1 (ZBP1) is a potent innate immune sensor that detects cytoplasmic nucleic acids and activates the innate immune response to clear pathogens. When apoptosis is inhibited by viral invasion, ZBP1 can be activated to compensate for the effect of apoptosis by triggering an innate immune response. This review examined the mechanisms of apoptosis inhibition and ZBP1 activation during viral invasion. The authors outlined the mechanisms of ZBP1-induced type I interferon, pyroptosis and necroptosis, as well as the crosstalk between ZBP1 and the cGAS-STING signalling pathway. Furthermore, ZBP1 can reverse the suppression of apoptotic signals induced by viruses. Intriguingly, a positive feedback loop exists in the ZBP1 signalling pathway, which intensifies the innate immune response while triggering a cytokine storm, leading to tissue and organ damage. The prudent use of ZBP1, which is a double-edged sword, has significant clinical implications for treating infections and inflammation.
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Apoptosis , Inmunidad Innata , Humanos , Piroptosis , Inflamación , CitoplasmaRESUMEN
OBJECTIVE: Epstein-Barr virus (EBV)-associated gastric cancer (EBVaGC) is a distinct molecular subtype of gastric cancer (GC). At present, the clinical characteristics and prognostic implications of EBV infection and the potential clinical benefits of immune checkpoint blockade in GC remain to be clarified. Hence, this study was designed to analyze the clinical and pathological characteristics of GC patients with varying EBV infection states and compare their overall survival (OS). METHODS: A retrospective study was performed on 1031 consecutive GC patients who underwent gastrectomy at the Affiliated Hospital of Xuzhou Medical University from February 2018 to November 2022. EBV-encoded RNA (EBER) in situ hybridization (ISH) was used for EBV assessment, and immunohistochemical staining was used for evaluation of human epidermal growth factor receptor 2 (HER2), programmed death ligand 1 (PD-L1), and Ki67 expression. EBVaGC was defined as tumors with EBV positivity. In addition, EBV-negative GC (EBVnGC) patients were matched with EBVaGC patients based on seven clinicopathological parameters (age, gender, anatomic subsite, tumor size, Lauren classification, degree of differentiation, and tumor-node-metastasis [TNM] stage). The correlations of clinical features with HER2, PD-L1, and Ki67 expression were evaluated statistically. The survival of patients was assessed through medical records, telephone, or WeChat communication, and prognostic analysis was performed using the logrank test as well as univariable and multivariable regression analysis. RESULTS: Out of 1031 GC patients tested, 35 (3.4%) were diagnosed with EBVaGC. Notably, the EBVaGC group exhibited a distinct predominance of males and younger patients, significantly higher Ki67 and PD-L1 expression levels, and a lower prevalence of pericancerous nerve invasion than the EBVnGC group (P < 0.01). In the 35 EBVaGC cases, Ki67 expression was negatively correlated with age (P < 0.05), suggesting that a younger onset age was associated with higher Ki67 expression. In addition, PD-L1 expression was correlated with the degree of differentiation, T-stage, and clinical stage of the patient. Furthermore, PD-L1 expression was elevated in tumors with lower differentiation or at later stages (P < 0.05). Using univariate analysis, Ki67, PD-L1, and clinical stage were identified as significant factors influencing the overall survival (OS) of EBVaGC patients (P < 0.05). Moreover, multivariate survival analysis revealed that clinical stage and Ki67 expression were independent risk factors for the OS of the patients (P < 0.05), and the three-year OS rate of EBVaGC patients was 64.2%. CONCLUSION: EBV-ISH is a practical and valuable method to identify EBVaGC. Owing to its unique etiological, pathological, and clinical characteristics, patients with EBVaGC might benefit from immune checkpoint blockade therapy.
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Infecciones por Virus de Epstein-Barr , Herpesvirus Humano 4 , Neoplasias Gástricas , Humanos , Neoplasias Gástricas/virología , Neoplasias Gástricas/patología , Masculino , Femenino , Infecciones por Virus de Epstein-Barr/virología , Infecciones por Virus de Epstein-Barr/complicaciones , Infecciones por Virus de Epstein-Barr/mortalidad , Persona de Mediana Edad , Herpesvirus Humano 4/genética , Pronóstico , Estudios Retrospectivos , Anciano , Adulto , Antígeno B7-H1/metabolismo , Antígeno B7-H1/genética , Receptor ErbB-2/metabolismo , Receptor ErbB-2/genética , Antígeno Ki-67/metabolismo , ARN Viral/genética , GastrectomíaRESUMEN
Protein adducts are important biological targets for traceability of organophosphorus nerve agents (OPNAs). Currently, the recognized biomarkers that can be used in actual samples in the field of chemical forensics only include Y411 in albumin and the active nonapeptide in butyrylcholinesterase (BChE). To explore stable and reliable protein adducts and increase the accuracy of OPNAs traceability further, we gradually expanded OPNAs-albumin adducts based on single and group adduct collection. Several stable peptides were found via LC-MS/MS analysis in human serum albumin (HSA) exposed to OPNAs in a large exposure range. These adducts were present in HSA samples exposed to OPNAs of each concentration, which provided data support for the reliability and stability of using adducts to trace OPNAs. Meanwhile, the formation mechanism of OPNAs-cysteine adduct was clarified via computer simulations. Then, these active sites found and modified peptides were used as raw materials for progressive expansion of albumin adducts. We constructed an OPNAs-HSA adducts group, in which a specific agent is the exposure source, and three or more active peptides constitute data sets for OPNAs traceability. Compared with single or scattered protein adducts, the OPNAs-HSA adduct group improves OPNAs identification by mutual verification using active peptides or by narrowing the identity range of the exposure source. We also determined the minimum detectable concentration of OPNAs for the adduct group. Two or more peptides can be detected when there is an exposure of 50 times the molar excess of OPNAs in relation to HSA. This improved the accuracy of OPNAs exposure and identity confirmation. A collection of OPNAs-albumin adducts was also examined. The collection was established by collecting, classifying, and integrating the existing albumin adducts according to the species to which each albumin belongs, the types of agents, and protease. This method can serve as a reference for discovering new albumin adducts, characteristic phosphonylated peptides, and potential biomarkers. In addition, to avoid a false negative for OPNAs traceability using albumin adducts, we explored OPNAs-cholinesterase adducts because cholinesterase is more reactive with OPNAs than albumin. Seven active peptides in red blood cell acetylcholinesterase (RBC AChE) and serum BChE can assist in OPNAs exposure and identity confirmation.
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Agentes Nerviosos , Compuestos Organofosforados , Albúmina Sérica Humana , Espectrometría de Masas en Tándem , Humanos , Agentes Nerviosos/química , Agentes Nerviosos/análisis , Compuestos Organofosforados/química , Espectrometría de Masas en Tándem/métodos , Albúmina Sérica Humana/química , Cromatografía Liquida/métodos , Biomarcadores/sangre , Péptidos/químicaRESUMEN
BACKGROUND: The involvement of quality of life as the UNAIDS fourth 90 target to monitor the global HIV response highlighted the development of patient-reported outcome (PRO) measures to help address the holistic needs of people living with HIV/AIDS (PLWHA) beyond viral suppression. This study developed and tested preliminary measurement properties of a new patient-reported outcome (PROHIV-OLD) measure designed specifically to capture influences of HIV on patients aged 50 and older in China. METHODS: Ninety-three older people living with HIV/AIDS (PLWHA) were interviewed to solicit items and two rounds of patient cognitive interviews were conducted to modify the content and wording of the initial items. A validation study was then conducted to refine the initial instrument and evaluate measurement properties. Patients were recruited between February 2021 and November 2021, and followed six months later after the first investigation. Classical test theory (CTT) and item response theory (IRT) were used to select items using the baseline data. The follow-up data were used to evaluate the measurement properties of the final instrument. RESULTS: A total of 600 patients were recruited at the baseline. Of the 485 patients who completed the follow-up investigation, 483 were included in the validation sample. The final scale of PROHIV-OLD contained 25 items describing five dimensions (physical symptoms, mental status, illness perception, family relationship, and treatment). All the PROHIV-OLD dimensions had satisfactory reliability with Cronbach's alpha coefficient, McDonald's ω, and composite reliability of each dimension being all higher than 0.85. Most dimensions met the test-retest reliability standard except for the physical symptoms dimension (ICC = 0.64). Confirmatory factor analysis supported the structural validity of the final scale, and the model fit index satisfied the criterion. The correlations between dimensions of PROHIV-OLD and MOS-HIV met hypotheses in general. Significant differences on scores of the PROHIV-OLD were found between demographic and clinical subgroups, supporting known-groups validity. CONCLUSIONS: The PROHIV-OLD was found to have good feasibility, reliability and validity for evaluating health outcome of Chinese older PLWHA. Other measurement properties such as responsiveness and interpretability will be further examined.
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Síndrome de Inmunodeficiencia Adquirida , Calidad de Vida , Humanos , Persona de Mediana Edad , Anciano , Calidad de Vida/psicología , Encuestas y Cuestionarios , Reproducibilidad de los Resultados , Medición de Resultados Informados por el Paciente , China , Psicometría/métodosRESUMEN
AIMS: The intestinal biota, known for its colonization of the human intestine and its modulation of host pathophysiological responses through the immune and endocrine systems, has gained substantial interest in recent years due to its notable correlation with diabetes and stroke. METHODS: In order to examine this association, a comparative study was conducted on the intestinal biota and blood samples obtained from mouse models and type 2 diabetic patients with and without stroke complications. Advanced techniques, such as high-throughput sequencing and enzyme-linked immunosorbent assay were employed to identify the differences in the intestinal biota and blood indices of mouse models and patients. RESULTS: At the phylum level, the dominant gut bacteria identified in patients with diabetes mellitus and stroke were Firmicutes, Bacteroidetes, and Proteobacteria. It was noteworthy that the relative abundance of Bacteroides at the genus level was significantly diminished in the DB-PT group (photothrombotic diabetes mice) as compared to the DB group (diabetesmice). This result was consistent with observations in human samples. Additionally, significant variations were detected in lipid proteins, specifically APOA4, in diabetic patients with and without stroke. CONCLUSIONS: Stroke can diminish the abundance and diversity of intestinal biota, potentially correlating with lipid proteins in patients with diabetes.
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Microbes have been confirmed to play key role in biogeochemistry of antimony. However, the impact of indigenous bacteria (from active mines) on the behavior of dissolved antimony remained poorly understood. In current study, the hyper antimony-resistant strain, Achromobacter sp. 25-M, isolated from the world largest antimony deposit, Xikuangshan antimony deposit, was evaluated for its role in dissolved Sb(V) and Sb(III) precipitation and removal. Despite of the high resistance to Sb(III) (up to 50 mM), the facultative alkaliphile, 25-M was not capable of Sb(III) oxidation. Meanwhile 25-M can produce high amount of exopolymeric substance (EPS) with the presence of Sb, which prompted us to investigate the potential role of EPS in the precipitation and removal of Sb. To this end, 2 mM of Sb(III) and Sb(V) were added into the experimental systems with and without 25-M to discern the interaction mechanism between microbe and antimony. After 96 hrs' incubation, 88% [1.73 mM (210 mg/L)] of dissolved Sb(V) and 80% [1.57 mM (190 mg/L)] of dissolved Sb(III) were removed. X-ray diffraction and energy dispersive spectroscopy analysis confirmed the formation of valentinite (Sb2O3) in Sb(III) amended system and a solitary Sb(V) mineral mopungite [NaSb(OH)6] in Sb(V) amended group with microbes. Conversely, no precipitate was detected in abiotic systems. Morphologically valentinite was bowtie and mopungite was pseudo-cubic as indicated by scanning electronic microscopy. EPS was subjected to fourier transform infrared (FT-IR) analysis. FT-IR analysis suggested that -OH and -COO groups were responsible for the complexation and ligand exchange with Sb(III) and Sb(V), respectively. Additionally, the C-H group and N-H group could be involved in π-π interaction and chelation with Sb species. All these interactions between Sb and functional groups in EPS may subsequently favore the formation of valentinite and mopungite. Collectively, current results suggested that EPS play fundamental role in bioprecipitation of Sb, which offered a new strategy in Sb bioremediation.
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Antimonio , Minerales , Antimonio/química , Espectroscopía Infrarroja por Transformada de Fourier , Oxidación-Reducción , Difracción de Rayos X , AdsorciónRESUMEN
OBJECTIVE: Postoperative fasting following thoracoscopic surgery can cause intense thirst and oral discomfort. However, there is currently no research on ultraearly oral hydration (UEOH) in middle-aged or elderly patients after thoracoscopic surgery. The aim of this study was to investigate the effectiveness and safety of UEOH for improving oral discomfort after thoracoscopic surgery. METHODS: This single-center prospective double-blind randomized controlled trial was conducted from April 2022 to November 2023. A total of 64 middle-aged and elderly patients who underwent the first thoracoscopic surgery on the day were enrolled at our institution. Postoperatively, in the Postanesthesia Care Unit (PACU), patients were randomly assigned at a 1:1 ratio to either the UEOH group or the standard care (SC) group. The primary outcome was the patient's thirst score at 6 h after surgery. Secondary outcomes included the incidence of postoperative oral discomfort; pain scores; the occurrence of adverse reactions such as nausea, vomiting, regurgitation and aspiration; anxiety scores on the first postoperative day; the time to first flatus; and recovery satisfaction scores. RESULTS: The demographic and surgical characteristics were similar between the two groups. Patients in the UEOH group had lower thirst scores 6 h after surgery than did those in the SC group(16.1 ± 6.70 vs. 78.4 ± 8.42, P < 0.01). The incidence of postoperative oral discomfort (P < 0.01), anxiety scores on the first postoperative day (P<0.05), and time to first flatus (P<0.05) were better in the UEOH group. Additionally, the incidences of adverse reactions, such as postoperative nausea, vomiting, regurgitation and aspiration, were similar between the two groups (P>0.05). CONCLUSION: For middle-aged and elderly patients undergoing thoracoscopic surgery, the use of a modified UEOH protocol postoperatively can improve thirst and promote gastrointestinal recovery without increasing complications. TRIAL REGISTRATION: This single-center, prospective, RCT has completed the registration of the Chinese Clinical Trial Center at 07/12/2023 with the registration number ChiCTR2300078425.
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Dolor Postoperatorio , Sed , Persona de Mediana Edad , Anciano , Humanos , Estudios Prospectivos , Flatulencia , Náusea y Vómito Posoperatorios/epidemiología , Náusea y Vómito Posoperatorios/prevención & control , Toracoscopía , Método Doble CiegoRESUMEN
BACKGROUND: Healthcare accessibility and utilization are important social determinants of health. Lack of access to healthcare, including missed or no-show appointments, can have negative health effects and be costly to patients and providers. Various office-based approaches and community partnerships can address patient access barriers. OBJECTIVES: (1) To understand provider perceptions of patient barriers; (2) to describe the policies and practices used to address late or missed appointments, and (3) to evaluate access to patient support services, both in-clinic and with community partners. METHODS: Mailed cross-sectional survey with online response option, sent to all Nebraska primary care clinics (n = 577) conducted April 2020 and January through April 2021. Chi-square tests compared rural-urban differences; logistic regression of clinical factors associated with policies and support services computed odds ratios (OR) and 95% confidence intervals (CI). RESULTS: Response rate was 20.3% (n = 117), with 49 returns in 2020. Perceived patient barriers included finances, higher among rural versus urban clinics (81.6% vs. 56.1%, p =.009), and time (overall 52.3%). Welcoming environment (95.5%), telephone appointment reminders (74.8%) and streamlined admissions (69.4%) were the top three clinic practices to reduce missed appointments. Telehealth was the most commonly available patient support service in rural (79.6%) and urban (81.8%, p =.90) clinics. Number of providers was positively associated with having a patient navigator/care coordinator (OR = 1.20, CI = 1.02-1.40). For each percent increase in the number of privately insured patients, the odds of providing legal aid decreased by 4% (OR = 0.96, CI = 0.92-1.00). Urban clinics were less likely than rural clinics to provide social work services (OR = 0.16, CI = 0.04-0.67) or assist with applications for government aid (OR = 0.22, CI = 0.06-0.90). CONCLUSIONS: Practices to reduce missed appointments included a variety of reminders. Although finances and inability to take time off work were the most frequently reported perceived barriers for patients' access to timely healthcare, most clinics did not directly address them. Rural clinics appeared to have more community partnerships to address underlying social determinants of health, such as transportation and assistance applying for government aid. Taking such a wholistic partnership approach is an area for future study to improve patient access.
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COVID-19 , Humanos , COVID-19/epidemiología , Estudios Transversales , Pandemias , Instituciones de Atención Ambulatoria , Políticas , Atención Primaria de SaludRESUMEN
TP53, functioning as the keeper of the genome, assumes a pivotal function in the inhibition of tumorigenesis. Recent studies have revealed that p53 regulates ferroptosis pathways within tumor cells and is closely related to tumorigenesis. Therefore, we summarize the pathways and mechanisms by which p53 regulates ferroptosis and identify a series of upstream and downstream molecules involved in this process. Furthermore, we construct a p53-ferroptosis network centered on p53. Finally, we present the progress of drugs to prevent wild-type p53 (wtp53) degeneration and restore wtp53, highlighting the deficiencies of drug development and the prospects for p53 in cancer treatment. These findings provide novel strategies and directions for future cancer therapy.
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Ferroptosis , Proteína p53 Supresora de Tumor , Humanos , Proteína p53 Supresora de Tumor/genética , Proteína p53 Supresora de Tumor/metabolismo , Ferroptosis/genética , CarcinogénesisRESUMEN
Polyhexamethylene guanidine (PHMG) is manufactured and applied extensively due to its superior disinfectant capabilities. However, the inhalatory exposure to PHMG aerosols is increasingly recognized as a potential instigator of pulmonary fibrosis, prompting an urgent call for elucidation of the underlying pathophysiological mechanisms. Within this context, alveolar macrophages play a pivotal role in the primary immune defense in the respiratory tract. Dysregulated lipid metabolism within alveolar macrophages leads to the accumulation of foam cells, a process that is intimately linked with the pathogenesis of pulmonary fibrosis. Therefore, this study examines PHMG's effects on alveolar macrophage foaminess and its underlying mechanisms. We conducted a 3-week inhalation exposure followed by a 3-week recovery period in C57BL/6 J mice using a whole-body exposure system equipped with a disinfection aerosol generator (WESDAG). The presence of lipid-laden alveolar macrophages and downregulation of pulmonary tissue lipid transport proteins ABCA1 and ABCG1 were observed in mice. In cell culture models involving lipid-loaded macrophages, we demonstrated that PHMG promotes foam cell formation by inhibiting lipid efflux in mouse alveolar macrophages. Furthermore, PHMG-induced foam cells were found to promote an increase in the release of TGF-ß1, fibronectin deposition, and collagen remodeling. In vivo interventions were subsequently implemented on mice exposed to PHMG aerosols, aiming to restore macrophage lipid efflux function. Remarkably, this intervention demonstrated the potential to retard the progression of pulmonary fibrosis. In conclusion, this study underscores the pivotal role of macrophage foaming in the pathogenesis of PHMG disinfectants-induced pulmonary fibrosis. Moreover, it provides compelling evidence to suggest that the regulation of macrophage efflux function holds promise for mitigating the progression of pulmonary fibrosis, thereby offering novel insights into the mechanisms underlying inhaled PHMG disinfectants-induced pulmonary fibrosis.
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Desinfectantes , Fibrosis Pulmonar , Ratones , Animales , Fibrosis Pulmonar/metabolismo , Guanidina/toxicidad , Guanidina/metabolismo , Ratones Endogámicos C57BL , Aerosoles y Gotitas Respiratorias , Pulmón , Guanidinas/metabolismo , Macrófagos , Desinfectantes/farmacología , LípidosRESUMEN
Psoriasis is an immune-mediated chronic inflammatory skin disease that affects 2% to 3% of the world's population. It is widely assumed that immune cells and cytokines acting together play a crucial part in the pathophysiology of psoriasis by promoting the excessive proliferation of skin keratinocytes and inflammatory infiltration. Interleukins (ILs), as a critical component of cytokines, have been closely associated with the pathogenesis and progression of psoriasis. This review summarizes the current contribution of ILs to psoriasis and describes the role each IL performs in psoriasis. Furthermore, the paper presents the therapeutic effects and application prospects of biologics developed for ILs in clinical treatment and experiments. The study aims to further the research on ILs in the treatment of psoriasis.
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Interleucinas , Psoriasis , Humanos , Psoriasis/tratamiento farmacológico , Psoriasis/patología , Piel/patología , Queratinocitos/patología , CitocinasRESUMEN
'Lantian 26', a leading elite winter wheat cultivar in Gansu Province since its release in 2010, exhibits high resistance or immunization to stripe rust in the adult-plant stage under a high disease pressure in Longnan (southeastern Gansu). Identifying the resistance genes in 'Lantian 26' could provide a basis for enhanced durability and high levels of resistance in wheat cultivars. Here, a segregating population was developed from a cross between a highly susceptible wheat cultivar Mingxian 169 and the highly stripe rust-resistant 'Lantian 26'. The F2 and F2:3 progenies of the cross were inoculated with multiple prevalent virulent races of stripe rust for adult-plant-stage-resistance evaluation in two different environments. Exon sequence alignment analysis revealed that a stripe rust resistance gene on the 718.4- to 721.2-Mb region of chromosome 7BL, tentatively named as YrLT26, and a cosegregation sequence-tagged site (STS) marker GY17 was developed and validated using the F2:3 population and 103 wheat cultivars. The other two resistance genes, Yr9 and Yr30, were also identified in 'Lantian 26' using molecular markers. Therefore, the key to high and durable resistance to stripe rust at the adult stage is the combination of Yr9, Yr30, and YrLT26 genes in 'Lantian 26'. This could be a considerable strategy for improving the wheat cultivars with effective and durable resistance in the high-pressure region for stripe rust.