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The exploitation of novel wound healing methods with real-time infection sensing and high spatiotemporal precision is highly important for human health. Pt-based metal-organic cycles/cages (MOCs) have been employed as multifunctional antibacterial agents due to their superior Pt-related therapeutic efficiency, various functional subunits and specific geometries. However, how to rationally apply these nanoscale MOCs on the macroscale with controllable therapeutic output is still challenging. Here, a centimeter-scale Pt MOC film was constructed via multistage assembly and subsequently coated on a N,N'-dimethylated dipyridinium thiazolo[5,4-d]thiazole (MPT)-stained silk fabric to form a smart wound dressing for bacterial sensing and wound healing. The MPT on silk fabric could be used to monitor wound infection in real-time through the bacteria-mediated reduction of MPT to its radical form via a color change. The MPT radical also exhibited an excellent photothermal effect under 660 nm light irradiation, which could not only be applied for photothermal therapy but also induce the disassembly of the Pt MOC film suprastructure. The highly ordered Pt MOC film suprastructure exhibited high biosafety, while it also showed improved antibacterial efficiency after thermally induced disassembly. In vitro and in vivo studies revealed that the combination of the Pt MOC film and MPT-stained silk can provide real-time information on wound infection for timely treatment through noninvasive techniques. This study paves the way for bacterial sensing and wound healing with centimeter-scale metal-organic materials.
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Platina , Infecção dos Ferimentos , Humanos , Platina/farmacologia , Cicatrização , Bandagens , Antibacterianos/farmacologia , Antibacterianos/química , Seda/química , Bactérias , Hidrogéis/farmacologiaRESUMO
Leptin receptor (LepR)-positive cells are key components of the bone marrow hematopoietic microenvironment, and highly enrich skeletal stem and progenitor cells that maintain homeostasis of the adult skeleton. However, the heterogeneity and lineage hierarchy within this population has been elusive. Using genetic lineage tracing and single-cell RNA sequencing, we found that Lepr-Cre labels most bone marrow stromal cells and osteogenic lineage cells in adult long bones. Integrated analysis of Lepr-Cre-traced cells under homeostatic and stress conditions revealed dynamic changes of the adipogenic, osteogenic, and periosteal lineages. Importantly, we discovered a Notch3+ bone marrow sub-population that is slow-cycling and closely associated with the vasculatures, as well as key transcriptional networks promoting osteo-chondrogenic differentiation. We also identified a Sca-1+ periosteal sub-population with high clonogenic activity but limited osteo-chondrogenic potential. Together, we mapped the transcriptomic landscape of adult LepR+ stem and progenitor cells and uncovered cellular and molecular mechanisms underlying their maintenance and lineage specification.
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Osso e Ossos/citologia , Receptores para Leptina/metabolismo , Análise de Célula Única/métodos , Células-Tronco/fisiologia , Envelhecimento/fisiologia , Animais , Antígenos Ly/metabolismo , Diferenciação Celular , Linhagem da Célula , Ensaio de Unidades Formadoras de Colônias , Feminino , Fraturas Ósseas , Perfilação da Expressão Gênica , Proteínas de Homeodomínio/metabolismo , Masculino , Proteínas de Membrana/metabolismo , Camundongos Endogâmicos C57BL , Camundongos Transgênicos , Rosiglitazona/farmacologia , Células-Tronco/citologia , Células-Tronco/efeitos dos fármacos , Estresse FisiológicoRESUMO
Ruthenium (Ru) complexes are developed as latent emissive photosensitizers for cancer and pathogen photodiagnosis and therapy. Nevertheless, most existing Ru complexes are limited as photosensitizers in terms of short excitation and emission wavelengths. Herein, we present an emissive Ru(II) metallacycle (herein referred to as 1) that is excited by 808-nm laser and emits at a wavelength of â¼1,000 nm via coordination-driven self-assembly. Metallacycle 1 exhibits good optical penetration (â¼7 mm) and satisfactory reactive oxygen species production properties. Furthermore, 1 shows broad-spectrum antibacterial activity (including against drug-resistant Escherichia coli) as well as low cytotoxicity to normal mammalian cells. In vivo studies reveal that 1 is employed in precise, second near-infrared biomedical window fluorescent imaging-guided, photo-triggered treatments in Staphylococcus aureus-infected mice models, with negligible side effects. This work thus broads the applications of supramolecular photosensitizers through the strategy of lengthening their wavelengths.
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Infecções Bacterianas , Complexos de Coordenação , Fotoquimioterapia , Fármacos Fotossensibilizantes , Rutênio , Animais , Antibacterianos/farmacologia , Bactérias , Infecções Bacterianas/diagnóstico , Complexos de Coordenação/farmacologia , Escherichia coli/efeitos dos fármacos , Luz , Camundongos , Fármacos Fotossensibilizantes/farmacologia , Rutênio/farmacologia , Staphylococcus aureus/efeitos dos fármacosRESUMO
Though immunogenic cell death (ICD) has garnered significant attention in the realm of anticancer therapies, effectively stimulating strong immune responses with minimal side effects in deep-seated tumors remains challenging. Herein, we introduce a novel self-assembled near-infrared-light-activated ruthenium(II) metallacycle, Ru1105 (λem = 1105 nm), as a first example of a Ru(II) supramolecular ICD inducer. Ru1105 synergistically potentiates immunomodulatory responses and reduces adverse effects in deep-seated tumors through multiple regulated approaches, including NIR-light excitation, increased reactive oxygen species (ROS) generation, selective targeting of tumor cells, precision organelle localization, and improved tumor penetration/retention capabilities. Specifically, Ru1105 demonstrates excellent depth-activated ROS production (â¼1 cm), strong resistance to diffusion, and anti-ROS quenching. Moreover, Ru1105 exhibits promising results in cellular uptake and ROS generation in cancer cells and multicellular tumor spheroids. Importantly, Ru1105 induces more efficient ICD in an ultralow dose (10 µM) compared to the conventional anticancer agent, oxaliplatin (300 µM). In vivo experiments further confirm Ru1105's potency as an ICD inducer, eliciting CD8+ T cell responses and depleting Foxp3+ T cells with minimal adverse effects. Our research lays the foundation for the design of secure and exceptionally potent metal-based ICD agents in immunotherapy.
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Antineoplásicos , Neoplasias , Rutênio , Humanos , Rutênio/farmacologia , Espécies Reativas de Oxigênio , Morte Celular Imunogênica , Antineoplásicos/farmacologia , Antineoplásicos/uso terapêutico , Neoplasias/tratamento farmacológico , Lisossomos , Linhagem Celular TumoralRESUMO
Tricomponent cobalt(salen)-catalyzed carbofunctionalization of unsaturated substrates by radical-polar crossover has the potential to streamline access to broad classes of heteroatom-functionalized synthetic targets, yet the reaction platform has remained elusive, despite the well-developed analogous hydrofunctionalizations mediated by high-valent alkylcobalt intermediates. We report herein the development of a cobalt(salen) catalytic system that enables carbofunctionalization. The reaction entails a tricomponent decarboxylative 1,4-carboamination of dienes and provides a direct route to aromatic allylic amines by obviating preformed allylation reagents and protection of oxidation-sensitive aromatic amines. The catalytic system merges acridine photocatalysis with cobalt(salen)-catalyzed regioselective 1,4-carbofunctionalization that facilitates the crossover of the radical and polar phases of the tricomponent coupling process, revealing critical roles of the reactants, as well as ligand effects and the nature of the formal high-valent alkylcobalt species on the chemo- and regioselectivity.
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BACKGROUND: Ovarian cancer (OvCa) is the most lethal of the gynecologic malignancies. Immune checkpoint inhibitors, which have revolutionized the treatment of multiple malignancies, have had limited efficacy in OvCa patients. This lack of effectiveness is partly due to the abnormal ovarian tumor microenvironment (TME), displaying a desmoplastic, highly fibrotic extracellular matrix. High extracellular matrix deposition leads to a buildup of compressive forces that cause tumor blood vessel collapse, reduced vessel perfusion, poor delivery of drugs, and compromised trafficking of cytotoxic T-cells to these tumors. METHODS: Using two syngeneic OvCa models, we tested the effect of losartan, a widely prescribed anti-hypertensive drug, on reprogramming the TME and chemosensitizing the cancer cells. RESULTS: Losartan treatment (i) reprograms the TME leading to increased vascular perfusion, and thus enhances drug delivery and immune effector cell intratumoral infiltration and function; and (ii) rewires the OvCa cells by suppressing the IGF-1 signaling, resulting in enhanced chemosensitivity. As a result of the combined tumor and stromal effects, losartan treatment enhances the efficacy of chemo-immunotherapy in OvCa models. CONCLUSION: The safety and low cost ( < $1-2/day) of losartan warrant rapid translation of our findings to patients with OvCa.
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Development of molecular diagnostics for lung cancer stratification and monitoring is crucial for the rational planning and timely adjustment of treatments to improve clinical outcomes. In this regard, we propose a nanocavity architecture to sensitively profile the protein signature on small extracellular vesicles (sEVs) to enable accurate, noninvasive staging and treatment monitoring of lung cancer. The nanocavity architecture is formed by molecular recognition through the binding of sEVs with the nanobox-based core-shell surface-enhanced Raman scattering (SERS) barcodes and mirrorlike, asymmetric gold microelectrodes. By imposing an alternating current on the gold microelectrodes, a nanofluidic shear force was stimulated that supported the binding of sEVs and the efficient assembly of the nanoboxes. The binding of sEVs further induced a nanocavity between the nanobox and the gold microelectrode that significantly amplified the electromagnetic field to enable the simultaneous enhancement of Raman signals from four SERS barcodes and generate patient-specific molecular sEV signatures. Importantly, evaluated on a cohort of clinical samples (n = 76) on the nanocavity architecture, the acquired patient-specific sEV molecular signatures achieved accurate identification, stratification, and treatment monitoring of lung cancer patients, highlighting its potential for transition to clinical utility.
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Vesículas Extracelulares , Ouro , Neoplasias Pulmonares , Análise Espectral Raman , Vesículas Extracelulares/química , Vesículas Extracelulares/metabolismo , Neoplasias Pulmonares/metabolismo , Humanos , Ouro/química , MicroeletrodosRESUMO
The molecular detection of multiple respiratory viruses provides evidence for the rational use of drugs and effective health management. Herein, we developed and tested the clinical performance of an electrohydrodynamic-driven nanobox-on-mirror platform (E-NoM) for the parallel, accurate, and sensitive detection of four respiratory viral antigens. The E-NoM platform uses gold-silver alloy nanoboxes as the core material with the deposition of a silver layer as a shell on the core surfaces to amplify and enable a reproducible Raman signal readout that facilitates accurate detection. Additionally, the E-NoM platform employs gold microelectrode arrays as the mirror with electrohydrodynamics to manipulate the fluid flow and enhance molecular interactions for an improved biosensing response. The presence of viral antigens binds the nanobox-based core-shell nanostructure on the gold microelectrode and creates the nanocavity with extremely strong "hot spots" to benefit sensitive analysis. Significantly, in a large clinical cohort with 227 patients, the designed E-NoM platform demonstrates the capability of screening respiratory infection with achieved clinical specificity, sensitivity, and accuracy of 100.0, 96.48, and 96.91%, respectively. It is anticipated that the E-NoM platform can find a position in clinical usage for respiratory disease diagnosis.
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Técnicas Biossensoriais , Nanopartículas Metálicas , Vírus , Humanos , Nanopartículas Metálicas/química , Prata/química , Ouro/química , Antígenos Virais , Análise Espectral RamanRESUMO
Cardiac remodeling (CR), characterized by cardiac hypertrophy and fibrosis, leads to the development and progression of heart failure (HF). Nowadays, emerging evidence implicated that inflammation plays a vital role in the pathogenesis of CR and HF. Astragaloside IV (AS-IV), an effective component of Astragalus membranaceus, exerts cardio-protective and anti-inflammatory effects, but the underlying mechanism remains not fully elucidated. This present study aimed to investigate the effects of AS-IV on cardiac hypertrophy and fibrosis in cultured H9C2 cells stimulated with LPS, as well as explore its underlying mechanisms. As a result, we found AS-IV could reduce the cell surface size, ameliorate cardiac hypertrophy and fibrosis in LPS-induced H9C2 cells. To specify which molecules or signaling pathways play key roles in the process, RNA-seq analysis was performed. After analyzing the transcriptome data, CCL2 has captured our attention, of which expression was sharply increased in model group and reversed by AS-IV treatment. The results also indicated that AS-IV could ameliorate the inflammatory response by down-regulating NF-κB signaling pathway. Additionally, a classical inhibitor of CCL2 (bindarit) were used to further explore whether the anti-inflammatory effect of AS-IV was dependent on this chemokine. Our results indicated that AS-IV could exert a potent inhibitory effect on CCL2 expression and down-regulated NF-κB signaling pathway in a CCL2-dependent manner. These findings provided a scientific basis for promoting the treatment of HF with AS-IV.
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Lipopolissacarídeos , NF-kappa B , Humanos , NF-kappa B/metabolismo , Lipopolissacarídeos/farmacologia , Miócitos Cardíacos/metabolismo , Transdução de Sinais , Cardiomegalia/induzido quimicamente , Cardiomegalia/tratamento farmacológico , Cardiomegalia/metabolismo , Anti-Inflamatórios/farmacologia , Colágeno/metabolismo , Fibrose , Quimiocina CCL2/metabolismoRESUMO
Cancer is a significant global health issue. Platinum-based chemotherapy drugs, including cisplatin, are crucial in clinical anti-cancer treatment. However, these drugs have limitations such as drug resistance, non-specific distribution, and irreversible toxic and side effects. In recent years, the development of metal-based agents has led to the discovery of other anti-cancer effects beyond chemotherapy. Precise spatiotemporal controlled external irradiation can activate metal-based agents at specific sites and play a different role from traditional chemotherapy. These strategies can not only enhance the anti-cancer efficiency, but also show fewer side effects and non-cross-drug resistance, which are ideal approaches to solve the problems caused by traditional platinum-based chemotherapy drugs. In this review, we focus on various metal-based agent-mediated cancer therapies that are activated by three types of external irradiation: near-infrared (NIR) light, ultrasound (US), and X-ray, and give some prospects. We hope that this review will promote the generation of new kinds of metal-based anti-cancer agents.
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Antineoplásicos , Neoplasias , Humanos , Antineoplásicos/química , Antineoplásicos/farmacologia , Antineoplásicos/uso terapêutico , Neoplasias/tratamento farmacológico , Neoplasias/radioterapia , Raios Infravermelhos , Complexos de Coordenação/química , Complexos de Coordenação/uso terapêutico , Complexos de Coordenação/farmacologia , Metais/química , Raios X , AnimaisRESUMO
BACKGROUND: Chimeric antigen receptor (CAR)-NK cell therapy has shown remarkable clinical efficacy and safety in the treatment of hematological malignancies. However, this efficacy was limited in solid tumors owing to hostile tumor microenvironment (TME). Radiotherapy is commonly used for solid tumors and proved to improve the TME. Therefore, the combination with radiotherapy would be a potential strategy to improve therapeutic efficacy of CAR-NK cells for solid tumors. METHODS: Glypican-3 (GPC3) was used as a target antigen of CAR-NK cell for hepatocellular carcinoma (HCC). To promote migration towards HCC, CXCR2-armed CAR-NK92 cells targeting GPC3 were first developed, and their cytotoxic and migration activities towards HCC cells were evaluated. Next, the effects of irradiation on the anti-tumor activity of CAR-NK92 cells were assessed in vitro and in HCC-bearing NCG mice. Lastly, to demonstrate the potential mechanism mediating the sensitized effect of irradiation on CAR-NK cells, the differential gene expression profiles induced by irradiation were analyzed and the expression of some important ligands for the NK-cell activating receptors were further determined by qRT-PCR and flow cytometry. RESULTS: In this study, we developed CXCR2-armed GPC3-targeting CAR-NK92 cells that exhibited specific and potent killing activity against HCC cells and the enhanced migration towards HCC cells. Pretreating HCC cells with irradiation enhanced in vitro anti-HCC effect and migration activity of CXCR2-armed CAR-NK92 cells. We further found that only high-dose (8 Gy) but not low-dose (2 Gy) irradiation in one fraction could significantly enhanced in vivo anti-HCC activity of CXCR2-armed CAR-NK92 cells. Irradiation with 8 Gy significantly up-regulated the expression of NK cell-activating ligands on HCC cells. CONCLUSIONS: Our results indicate the evidence that irradiation could efficiently enhance the anti-tumor effect of CAR-NK cells in solid tumor model. The combination with radiotherapy would be an attractive strategy to improve therapeutic efficacy of CAR-NK cells for solid tumors.
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Carcinoma Hepatocelular , Movimento Celular , Células Matadoras Naturais , Neoplasias Hepáticas , Receptores de Antígenos Quiméricos , Carcinoma Hepatocelular/radioterapia , Carcinoma Hepatocelular/patologia , Carcinoma Hepatocelular/terapia , Carcinoma Hepatocelular/imunologia , Células Matadoras Naturais/imunologia , Células Matadoras Naturais/efeitos da radiação , Neoplasias Hepáticas/radioterapia , Neoplasias Hepáticas/patologia , Neoplasias Hepáticas/terapia , Neoplasias Hepáticas/imunologia , Animais , Humanos , Linhagem Celular Tumoral , Receptores de Antígenos Quiméricos/metabolismo , Movimento Celular/efeitos da radiação , Glipicanas/metabolismo , Receptores de Interleucina-8B/metabolismo , Ensaios Antitumorais Modelo de Xenoenxerto , Camundongos , Regulação Neoplásica da Expressão Gênica/efeitos da radiação , Imunoterapia Adotiva/métodos , Microambiente Tumoral/efeitos da radiação , Citotoxicidade Imunológica/efeitos da radiaçãoRESUMO
The initiation and progression of atherosclerotic plaque caused by abnormal lipid metabolism is one of the main causes of atherosclerosis (AS). Lipid droplet accumulation has become a novel research pointcut for AS treatment in recent years. In AS patients, miR-135b level was up-regulated relative to the normal cases, which showed negative correlations with the levels of Semaphorin 3A (SEMA3A) and circZNF609, separately. The U937-derived macrophages were cultured with ox-LDL to establish AS models in vitro. After that, the lipid accumulation, inflammation, mitochondrial dysfunction and cell death were evaluated by ORO, ELISA, RT-qPCR, western blot, JC-1 and FCM assays respectively. Transfection of the circZNF609 expression vector notably declined lipid accumulation, attenuated inflammation, reduced mitochondrial dysfunction and inhibited cell death in ox-LDL-stimulated cells. The direct binding of miR-135b to circZNF609 in vitro was confirmed using RIP assay, and SEMA3A expression was up-regulated by circZNF609 overexpression. After manipulating the endogenous expressions of circZNF609, miR-135b and SEMA3A, the above damages in ox-LDL-stimulated cells were rescued by inhibition of miR-135b expression and overexpression of circZNF609 or SEMA3A. Besides, the AS mice model was built to demonstrate the excessive lipid accumulation, increasing inflammation and cell death in AS pathogenesis according to the results of HE staining, ELISA and IHC assays, while these damages were reversed after overexpression of circZNF609 or SEMA3A. In AS models, overexpressed circZNF609 prevents the AS progression through depleting miR-135b expression and subsequent up-regulation of SEMA3A expression to overwhelm lipid accumulation, mitochondrial dysfunction and cell death.
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Martial arts training focuses on whole-body movement patterning, philosophy, interpersonal interactions, and functional self-defense. Such training has positive impacts on physical, psychological, and cognitive well-being in older adults and children with and without clinical conditions. We hypothesize that martial arts training can be delivered as a form of exercise therapy for people at all ages to enhance overall health.
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Terapia por Exercício , Artes Marciais , Criança , Humanos , Idoso , Artes Marciais/psicologiaRESUMO
Type I photosensitizers offer an advantage in photodynamic therapy (PDT) due to their diminished reliance on oxygen levels, thus circumventing the challenge of hypoxia commonly encountered in PDT. In this study, we present the synthesis and comprehensive characterization of a novel type I photosensitizer derived from a cyclometalated Ir(III)-rhodamine complex. Remarkably, the complex exhibits a shift in absorption and fluorescence, transitioning from "off" to "on" states in aprotic and protic solvents, respectively, contrary to initial expectations. Upon exposure to light, the complex demonstrates the effective generation of O2- and ·OH radicals via the type I mechanism. Additionally, it exhibits notable photodynamic antibacterial activity against both Gram-positive and Gram-negative bacteria, demonstrated through in vitro and in vivo experiments. This research offers valuable insights for the development of novel type I photosensitizers.
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Antibacterianos , Bactérias Gram-Negativas , Bactérias Gram-Positivas , Irídio , Testes de Sensibilidade Microbiana , Fotoquimioterapia , Fármacos Fotossensibilizantes , Rodaminas , Fármacos Fotossensibilizantes/farmacologia , Fármacos Fotossensibilizantes/química , Fármacos Fotossensibilizantes/síntese química , Antibacterianos/farmacologia , Antibacterianos/química , Antibacterianos/síntese química , Bactérias Gram-Negativas/efeitos dos fármacos , Rodaminas/química , Rodaminas/farmacologia , Irídio/química , Irídio/farmacologia , Bactérias Gram-Positivas/efeitos dos fármacos , Complexos de Coordenação/farmacologia , Complexos de Coordenação/química , Complexos de Coordenação/síntese química , Animais , Raios Infravermelhos , Estrutura Molecular , CamundongosRESUMO
In vivo imaging in the second near-infrared window (NIR-II, 1000-1700 nm), which enables us to look deeply into living subjects, is producing marvelous opportunities for biomedical research and clinical applications. Very recently, there has been an upsurge of interdisciplinary studies focusing on developing versatile types of inorganic/organic fluorophores that can be used for noninvasive NIR-IIa/IIb imaging (NIR-IIa, 1300-1400 nm; NIR-IIb, 1500-1700 nm) with near-zero tissue autofluorescence and deeper tissue penetration. This review provides an overview of the reports published to date on the design, properties, molecular imaging, and theranostics of inorganic/organic NIR-IIa/IIb fluorophores. First, we summarize the design concepts of the up-to-date functional NIR-IIa/IIb biomaterials, in the order of single-walled carbon nanotubes (SWCNTs), quantum dots (QDs), rare-earth-doped nanoparticles (RENPs), and organic fluorophores (OFs). Then, these novel imaging modalities and versatile biomedical applications brought by these superior fluorescent properties are reviewed. Finally, challenges and perspectives for future clinical translation, aiming at boosting the clinical application progress of NIR-IIa and NIR-IIb imaging technology are highlighted.
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Nanotubos de Carbono , Medicina de Precisão , Corantes Fluorescentes , Humanos , Imagem Molecular , Imagem Óptica/métodosRESUMO
BACKGROUND: Giant ovarian cysts (GOCs)complicated with progressive bulbar paralysis (PBP) are very rare, and no such literature about these cases have been reported. Through the diagnosis and treatment of this case, the perioperative related treatment of such patients was analyzed in detail, and early-stage ovarian mucinous carcinoma was unexpectedly found during the treatment, which provided reference for clinical diagnosis and treatment of this kind of diseases. CASE PRESENTATION: In this article, we reported a 38-year-old female patient. The patient was diagnosed with PBP 2 years ago. Examination revealed a large fluid-dominated cystic solid mass in the pelvis measuring approximately 28.6×14.2×8.0 cm. Carbohydrate antigen19-9(CA19-9) 29.20 IU/mL and no other significant abnormalities were observed. The patient eventually underwent transabdominal right adnexal resection under regional anesthesia, epidural block. Postoperative pathology showed mucinous carcinoma in some areas of the right ovary. The patient was staged as stage IA, and surveillance was chosen. With postoperative follow-up 1 month later, her CA19-9 decreased to 14.50 IU/ml. CONCLUSIONS: GOCs combined with PBP patients require a multi-disciplinary treatment. Preoperative evaluation of the patient's PBP progression, selection of the surgical approach in relation to the patient's fertility requirements, the nature of the ovarian cyst and systemic condition are required. Early mucinous ovarian cancer accidentally discovered after operation and needs individualized treatment according to the guidelines and the patient's situation. The patient's dysphagia and respiratory function should be closely monitored during the perioperative period. In addition, moral support from the family is also very important.
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Adenocarcinoma Mucinoso , Neoplasias Ovarianas , Humanos , Feminino , Adulto , Neoplasias Ovarianas/complicações , Neoplasias Ovarianas/cirurgia , Neoplasias Ovarianas/diagnóstico , Adenocarcinoma Mucinoso/complicações , Adenocarcinoma Mucinoso/cirurgia , Adenocarcinoma Mucinoso/diagnóstico , Assistência Perioperatória/métodos , Cistos Ovarianos/cirurgia , Cistos Ovarianos/complicações , Cistos Ovarianos/diagnóstico , Estadiamento de NeoplasiasRESUMO
Background: Bloodstream infection is amongst the leading causes of mortality for critical postoperative patients. However, data, especially from developing countries, are scary. Clinical decision-making tools for predicting postoperative bloodstream infection-related mortality are important but still lacking. Objective: To analyze the distribution of pathogens and develop a nomogram for predicting mortality in patients with postoperative bloodstream infection in the surgical intensive care unit. Methods: The clinical data, infection and pathogen-related data, and prognosis of patients with PBSI in the SICU from January 2017 to January 2022 were retrospectively collected. The distribution of pathogens and clinical characteristics of patients with PBSI were analyzed. The patients were assigned to a died group and a survived group according to their survival status. Independent predictors for mortality were identified by univariate and multivariate analyses. A nomogram for predicting PBSI-related death was developed based on these independent predictors. Calibration and decision-curve analysis were established to evaluate the nomogram. We collected postoperative patients admitted to our center from February 2022 to June 2023 as external validation sets to verify the nomogram. We also add the Brier score to further validate the model. Results: In the training set, 7128 patients admitted to the SICU after different types of surgery were collected. A total of 198 patients and 308 pathogens were finally enrolled. The mean age of patients with PBSI was 64.38 ± 16.22 (range 18-90) years, and 56.1% were male. Forty-five patients (22.7%) died in the hospital. Five independent predictors including BMI, APACHE II score, estimated glomerular filtration rate (eGFR), urine volume in the first 24 hours after surgery, and peak temperature before positive blood cultures were selected to establish the nomogram. The area under the receiver operating characteristic curve for the prediction model was 0.922. Calibration curve and decision curve analysis showed good performance of the nomogram. Seventy patients with PBSI were collected as an external validation set, and thirteen patients died in this set. The external validation set was used to validate the nomogram, and the results showed that the AUC was 0.930 which was higher than that in the training set indicating that the nomogram had a good discrimination. The brier score was 0.087 for training set and 0.050 for validation set. Conclusions: PBSI was one of the key issues that clinicians were concerned and could be assessed with a good predictive model using simple clinical factors.
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Nomogramas , Sepse , Humanos , Masculino , Adolescente , Adulto Jovem , Adulto , Pessoa de Meia-Idade , Idoso , Idoso de 80 Anos ou mais , Feminino , Estudos Retrospectivos , Unidades de Terapia Intensiva , Complicações Pós-Operatórias , Cuidados CríticosRESUMO
Correction for 'Near-infrared metal agents assisting precision medicine: from strategic design to bioimaging and therapeutic applications' by Chonglu Li et al., Chem. Soc. Rev., 2023, 52, 4392-4442, https://doi.org/10.1039/D3CS00227F.
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Metal agents have made incredible strides in preclinical research and clinical applications in recent years, but their short emission/absorption wavelengths continue to be a barrier to their distribution, therapeutic action, visual tracking, and efficacy evaluation. Nowadays, the near-infrared window (NIR, 650-1700 nm) provides a more accurate imaging and treatment option. Thus, there has been ongoing research focusing on developing multifunctional NIR metal agents for imaging and therapy that have deeper tissue penetration. The design, characteristics, bioimaging, and therapy of NIR metal agents are covered in this overview of papers and reports published to date. To start with, we focus on describing the structure, design strategies, and photophysical properties of metal agents from the NIR-I (650-1000 nm) to NIR-II (1000-1700 nm) region, in order of molecular metal complexes (MMCs), metal-organic complexes (MOCs), and metal-organic frameworks (MOFs). Next, the biomedical applications brought by these superior photophysical and chemical properties for more accurate imaging and therapy are discussed. Finally, we explore the challenges and prospects of each type of NIR metal agent for future biomedical research and clinical translation.
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Diagnóstico por Imagem , Medicina de Precisão , Metais , Corantes Fluorescentes/química , Imagem Óptica/métodosRESUMO
Background: The aim of this study was to investigate the effects of different pressurization modes during high-load bench press training on muscle activation and subjective fatigue in bodybuilders. Methods: Ten bodybuilders participated in a randomized, self-controlled crossover experimental design, performing bench press training under three different pressurization modes: T1 (low pressure, high resistance), T2 (high pressure, high resistance), and C (non-pressurized conventional). Surface EMG signals were recorded from the pectoralis major, deltoid, and triceps muscles using a Delsys Trigno wireless surface EMG during bench presses. Subjective fatigue was assessed immediately after the training session. Results: (1) Pectoralis major muscle: The muscle activation degree of the T1 group was significantly higher than that of the blank control group during the bench press (p < 0.05). The muscle activation degree of the T2 group was significantly higher than that of the C group during the bench press (p < 0.05). In addition, the muscle activation degree of the T2 group was significantly higher than that of the T1 group during the first group bench press (p < 0.05). (2) Deltoid muscle: The muscle activation degree of the T2 group during the third group bench press was significantly lower than the index values of the first two groups (p < 0.05). The muscle activation degree in the experimental group was significantly higher than that in the C group (p < 0.05). The degree of muscle activation in the T2 group was significantly higher than that in the T1 group during the first bench press (p < 0.05). (3) Triceps: The muscle activation degree of the T1 group was significantly higher than the index value of the third group during the second group bench press (p < 0.05), while the muscle activation degree of the T2 group was significantly lower than the index value of the first two groups during the third group bench press (p < 0.05). The degree of muscle activation in all experimental groups was significantly higher than that in group C (p < 0.05). (5) RPE index values in all groups were significantly increased (p < 0.05). The RPE value of the T1 group was significantly higher than that of the C group after bench press (p < 0.05). The RPE value of the T1 group was significantly higher than that of the C group after bench press (p < 0.05). In the third group, the RPE value of the T1 group was significantly higher than that of the C and T2 groups (p = 0.002) (p < 0.05). Conclusions: The activation of the pectoralis major, triceps brachii, and deltoid muscles is significantly increased by high-intensity bench press training with either continuous or intermittent pressurization. However, continuous pressurization results in a higher level of perceived fatigue. The training mode involving high pressure and high resistance without pressurization during sets but with 180 mmHg occlusion pressure and pressurization during rest intervals yields the most pronounced overall effect on muscle activation.