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Alcoholic liver injury stands as a predominant pathogenic contributor to the global burden of liver diseases, with alcohol consumption serving as a significant determinant of worldwide morbidity and mortality. Given that liver-targeted therapy for mitigating alcoholic liver injury remains to be a major clinical challenge due to the poor specificity and instability associated with single targeting modification in actively targeted nanomedicine systems, bifunctional targeting modification may serve as a more promising strategy. Here, galactose-functionalized hyaluronic acid (Gal-HA) coated cationic solid lipid nanoparticles carrying silybin (Gal-HA/SIL-SLNPs) featuring dual-targeting hyaluronic acid (HA) and galactose (Gal) moieties, enabled specific liver surface targeting of asialoglycoprotein receptor (ASGPR) and cluster of differentiation 44 (CD44) proteins to enhance silybin uptake, while simultaneously ameliorating the deficiencies of positively charged lipid nanoparticles as drug carriers and preserving their stability in the bloodstream. Based on the findings, Gal-HA/SIL-SLNPs with excellent biocompatibility demonstrated improved cellular internalization and liver distribution, while also displaying ideal curative properties in a mouse model of alcohol-induced liver injury without causing damage to other organs. This work suggests that Gal-HA/SIL-SLNPs with dual modification may represent an encouraging approach for developing more effective liver targeted nano-drug delivery systems to achieve accurate medication for alcoholic liver injury.

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BACKGROUND: Despite the crucial role of mindfulness and self-care in nurses' physical and mental health, as well as their professional well-being, most nurses exhibit low levels of self-care. Moreover, there is a lack of understanding of the diverse subgroups of mindful self-care among nurses. OBJECTIVES: The present study delved into the diverse groups of mindful self-care among nurses and investigated the correlation between these groups and their mental health. METHODS: Convenience sampling was used to select nurses from Guizhou province, China, from August to September 2023. A total of 1020 nurses were investigated, and 1001 questionnaires were included, for an effective return rate of 98.1%. The demographic characteristics questionnaire, Chinese version of the Brief Mindful Self-Care Scale, Patient Health Questionnaire-9, Generalised Anxiety Disorder-7 and Perceived Stress Scale were used. Latent profile analysis was performed on the characteristics of nurses' mindful self-care, and the correlations between the latent profiles, demographic characteristics and mental well-being were identified using chi-square tests, Spearman correlation analyses and non-parametric tests. RESULTS: A total of 1001 nurses were included, and they were divided into four heterogeneous subgroups: the Inconsistent Mindful Self-Care Group (4.40%), Balanced Development Group (43.36%), Moderate Mindful Self-Care Group (39.36%), and High Mindful Self-Care Group (12.89%). Results of single factor analysis showed that the nurses' department and average monthly income were the factors influencing the potential profiles. Mindful self-care negatively correlated with anxiety and depression but was not correlated with perceived stress. There were significant differences in perceived stress, anxiety and depression between different mindful self-care groups. CONCLUSION: The present study used latent profile analysis to identify four distinct subgroups of hospital nurses based on their mindful self-care and revealed varying levels of anxiety, depression and perceived stress between groups. These results emphasise the need for tailored mindful self-care strategies to promote nurses' well-being.

Asunto(s)

Salud Mental , Atención Plena , Autocuidado , Humanos , China/epidemiología , Femenino , Adulto , Masculino , Encuestas y Cuestionarios , Enfermeras y Enfermeros/psicología , Persona de Mediana Edad , Adulto Joven

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The retreat of Himalayan glaciers and the expansion of glacial lakes due to global warming have increased the occurrence of glacial lake outburst debris flow (GLODF), posing a serious threat to downstream communities. However, there are gaps in understanding the changes in GLODF occurrence driven by climate change, which challenges disaster management and cross-border cooperation in the Himalayas. To consider this issue, our study presents a novel framework integrating environmental evolution, a process-driven indicator system, and a hybrid machine learning model to predict Himalayan GLODF occurrence in the 21st century. Our findings indicate ongoing temperature (0.27-0.60 °C/10a) and precipitation (1.30-5.00 %/10a) increases under both SSP245 and SSP585 scenarios. Meanwhile, Himalayan glaciers are projected to lose between 70 % and 86 % of their mass by 2100 compared to 2020. Additionally, 2722 ± 207 new glacial lakes are expected to emerge by 2100. GLODF occurrence probability index is anticipated to rise to 1.27-1.30 times the current levels, with the Western Himalayas and Indus basin as high-incidence areas. Currently and in the future, the China-Nepal border remains a hotspot for cross-border GLODF. Our framework offers valuable long-term insights into Himalayan GLODF occurrence trends in response to climate change.

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Mitochondrial genome (mtDNA) independent of nuclear gene is a set of double-stranded circular DNA that encodes 13 proteins, 2 ribosomal RNAs and 22 mitochondrial transfer RNAs, all of which play vital roles in functions as well as behaviors of mitochondria. Mutations in mtDNA result in various mitochondrial disorders without available cures. However, the manipulation of mtDNA via the mitochondria-targeted gene delivery faces formidable barriers, particularly owing to the mitochondrial double membrane. Given the fact that there are various transport channels on the mitochondrial membrane used to transfer a variety of endogenous substances to maintain the normal functions of mitochondria, mitochondrial endogenous substance transport-inspired nanomaterials have been proposed for mitochondria-targeted gene delivery. In this review, we summarize mitochondria-targeted gene delivery systems based on different mitochondrial endogenous substance transport pathways. These are categorized into mitochondrial steroid hormones import pathways-inspired nanomaterials, protein import pathways-inspired nanomaterials and other mitochondria-targeted gene delivery nanomaterials. We also review the applications and challenges involved in current mitochondrial gene editing systems. This review delves into the approaches of mitochondria-targeted gene delivery, providing details on the design of mitochondria-targeted delivery systems and the limitations regarding the various technologies. Despite the progress in this field is currently slow, the ongoing exploration of mitochondrial endogenous substance transport and mitochondrial biological phenomena may act as a crucial breakthrough in the targeted delivery of gene into mitochondria and even the manipulation of mtDNA.

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Técnicas de Transferencia de Gen , Mitocondrias , Nanoestructuras , Humanos , Mitocondrias/metabolismo , Nanoestructuras/química , Animales , Transporte Biológico , ADN Mitocondrial/genética , Edición Génica/métodos

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BACKGROUND: Stem cell therapy is a promising alternative for inflammatory diseases and tissue injury treatment. Exogenous delivery of mesenchymal stem cells is associated with instant blood-mediated inflammatory reactions, mechanical stress during administration, and replicative senescence or change in phenotype during long-term culture in vitro. In this study, we aimed to mobilize endogenous hematopoietic stem cells (HSCs) using AMD-3100 and provide local immune suppression using FK506, an immunosuppressive drug, for the treatment of inflammatory bowel diseases. METHODS: Reactive oxygen species (ROS)-responsive FK506-loaded thioketal microspheres were prepared by emulsification solvent-evaporation method. Thioketal vehicle based FK506 microspheres and AMD3100 were co-administered into male C57BL6/J mice with dextran sulfate sodium (DSS) induced colitis. The effect of FK506-loaded thioketal microspheres in colitis mice were evaluated using disease severity index, myeloperoxidase activity, histology, flow cytometry, and gene expression by qRT-PCR. RESULTS: The delivery of AMD-3100 enhanced mobilization of HSCs from the bone marrow into the inflamed colon of mice. Furthermore, targeted oral delivery of FK506 in an inflamed colon inhibited the immune activation in the colon. In the DSS-induced colitis mouse model, the combination of AMD-3100 and FK506-loaded thioketal microspheres ameliorated the disease, decreased immune cell infiltration and activation, and improved body weight, colon length, and epithelial healing process. CONCLUSION: This study shows that the significant increase in the percentage of mobilized hematopoietic stem cells in the combination therapy of AMD and oral FK506 microspheres may contribute to a synergistic therapeutic effect. Thus, low-dose local delivery of FK506 combined with AMD3100 could be a promising alternative treatment for inflammatory bowel diseases.

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Bencilaminas , Colitis , Ciclamas , Sulfato de Dextran , Ratones Endogámicos C57BL , Tacrolimus , Animales , Colitis/inducido químicamente , Colitis/terapia , Colitis/tratamiento farmacológico , Colitis/patología , Ratones , Masculino , Ciclamas/farmacología , Ciclamas/uso terapéutico , Tacrolimus/farmacología , Tacrolimus/uso terapéutico , Movilización de Célula Madre Hematopoyética/métodos , Compuestos Heterocíclicos/farmacología , Compuestos Heterocíclicos/uso terapéutico , Células Madre Hematopoyéticas/efectos de los fármacos , Células Madre Hematopoyéticas/metabolismo , Modelos Animales de Enfermedad , Terapia de Inmunosupresión , Inmunosupresores/farmacología , Inmunosupresores/uso terapéutico , Microesferas , Especies Reactivas de Oxígeno/metabolismo

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INTRODUCTION: Dementia is a growing public health concern, and providing long-term care for individuals affected by this condition is challenging for their family caregivers. While researchers have explored various intervention options to provide psychological support for dementia caregivers, mentalising imagery therapy (MIT) has gained significant recognition as an effective programme. Despite its significance and effectiveness, there is a lack of comprehensive scoping reviews of MIT in dementia caregiving. Thus, conducting such a review can provide valuable insights into the status and outcomes of MIT, identify gaps in existing research and provide recommendations for a more effective clinical practice. METHODS AND ANALYSIS: This study proposes a scoping review conducted according to the Joanna Briggs Institute, Arksey and O'Malley's methodological framework, as well as the Preferred Reporting Items for Systematic Reviews and Meta-Analyses-Scoping Review Extension. PubMed, Web of Science, Embase, Scopus, CINAHL and PsycINFO databases will be searched while grey literature will be retrieved via Google Scholar. Covidence will be used to manage the literature selection process and remove duplicate publications. Two researchers will independently screen the literature according to the inclusion criteria, with any discrepancies resolved through discussions with a third researcher. Data will be presented in a structured tabular format, with a narrative synthesis providing an overview of the findings on the identified research gaps and the effectiveness of MIT in the field of dementia caregiving. ETHICS AND DISSEMINATION: In a scoping review, no ethical approval is necessary. The results will be published in a peer-reviewed journal. TRIAL REGISTRATION NUMBER: The scoping review protocol has been registered with Open Science Framework (https://doi.org/10.17605/OSF.IO/FHRG8).

Asunto(s)

Cuidadores , Demencia , Imágenes en Psicoterapia , Proyectos de Investigación , Humanos , Cuidadores/psicología , Demencia/terapia , Imágenes en Psicoterapia/métodos , Literatura de Revisión como Asunto , Revisiones Sistemáticas como Asunto

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Substrate integrated waveguides (SIWs) components play a crucial role in microwave devices fabricated by printed circuit board (PCB) technology. Bound states in the continuum (BICs) have high-quality factors that approach infinity. So far, there is little research on BICs in SIWs. Therefore, we studied a symmetry-protected BIC generated by the coupling between SIW and SIW resonators to fill this gap. Using the revised coupled mode theory (CMT), we explored the mechanism of resonance generation in this system. In addition, the effect of the geometrical parameters on the resonance is also investigated and higher Q3dB factors are obtained. The findings offer new insights into the design of BIC devices by traditional PCB technology, thus contributing to future applications in the integrated circuits field.

RESUMEN

Pancreatic fibrosis (PF) is primarily characterized by aberrant production and degradation modes of extracellular matrix (ECM) components, resulting from the activation of pancreatic stellate cells (PSCs) and the pathological cross-linking of ECM mediated by lysyl oxidase (LOX) family members. The excessively deposited ECM increases matrix stiffness, and the over-accumulated reactive oxygen species (ROS) induces oxidative stress, which further stimulates the continuous activation of PSCs and advancing PF; challenging the strategy toward normalizing ECM homeostasis for the regression of PF. Herein, ROS-responsive and Vitamin A (VA) decorated micelles (named LR-SSVA) to reverse the imbalanced ECM homeostasis for ameliorating PF are designed and synthesized. Specifically, LR-SSVA selectively targets PSCs via VA, thereby effectively delivering siLOXL1 and resveratrol (RES) into the pancreas. The ROS-responsive released RES inhibits the overproduction of ECM by eliminating ROS and inactivating PSCs, meanwhile, the decreased expression of LOXL1 ameliorates the cross-linked collagen for easier degradation by collagenase which jointly normalizes ECM homeostasis and alleviates PF. This research shows that LR-SSVA is a safe and efficient ROS-response and PSC-targeted drug-delivery system for ECM normalization, which will propose an innovative and ideal platform for the reversal of PF.

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Matriz Extracelular , Fibrosis , Nanopartículas , Especies Reactivas de Oxígeno , Especies Reactivas de Oxígeno/metabolismo , Matriz Extracelular/metabolismo , Animales , Fibrosis/metabolismo , Resveratrol/farmacología , Humanos , Células Estrelladas Pancreáticas/metabolismo , Células Estrelladas Pancreáticas/efectos de los fármacos , Páncreas/metabolismo , Páncreas/patología , Enfermedades Pancreáticas/metabolismo , Modelos Animales de Enfermedad , Estrés Oxidativo/efectos de los fármacos , Vitamina A/metabolismo , Ratones , Ratas , Sistemas de Liberación de Medicamentos/métodos

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Herein we developed a multicolor lateral flow immunoassay (LFIA) test strip for rapid and simultaneous quantitative detection of aflatoxin B1 (AFB1) and zearalenone (ZEN). Three differently colored aggregation-induced emission nanoparticles (AIENPs) were designed as LFIA signal tags, with red and green AIENPs for targeting AFB1 and ZEN at the test line, and yellow AIENPs for indicating the validity of the test strip at the control (C) line. After surface functionalization with antibodies, the developed AIENP-based multicolor LFIA allows simultaneous and accurate quantification of AFB1 and ZEN using an independent C-line assisted ratiometric signal output strategy. The detection limits of AFB1 and ZEN were 6.12 and 26 pg/mL, respectively. The potential of this method for real-world applications was well demonstrated in corn and wheat. Overall, this multicolor LFIA shows great potential for field screening of multiple mycotoxins and can be extended to rapid and simultaneous monitoring of other small molecule targets.

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Nanopartículas del Metal , Micotoxinas , Zearalenona , Zearalenona/análisis , Aflatoxina B1/análisis , Anticuerpos Monoclonales , Micotoxinas/análisis , Inmunoensayo/métodos , Límite de Detección , Contaminación de Alimentos/análisis

RESUMEN

Non-small cell lung cancer (NSCLC) shows high drug resistance and leads to low survival due to the high level of mutated Tumor Protein p53 (TP53). Cisplatin is a first-line treatment option for NSCLC, and the p53 mutation is a major factor in chemoresistance. We demonstrate that cisplatin chemotherapy increases the risk of TP53 mutations, further contributing to cisplatin resistance. Encouragingly, we find that the combination of cisplatin and fluvastatin can alleviate this problem. Therefore, we synthesize Fluplatin, a prodrug consisting of cisplatin and fluvastatin. Then, Fluplatin self-assembles and is further encapsulated with poly-(ethylene glycol)-phosphoethanolamine (PEG-PE), we obtain Fluplatin@PEG-PE nanoparticles (FP NPs). FP NPs can degrade mutant p53 (mutp53) and efficiently trigger endoplasmic reticulum stress (ERS). In this study, we show that FP NPs relieve the inhibition of cisplatin chemotherapy caused by mutp53, exhibiting highly effective tumor suppression and improving the poor NSCLC prognosis.

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Antineoplásicos , Carcinoma de Pulmón de Células no Pequeñas , Neoplasias Pulmonares , Nanopartículas , Fosfatidiletanolaminas , Polietilenglicoles , Humanos , Carcinoma de Pulmón de Células no Pequeñas/tratamiento farmacológico , Carcinoma de Pulmón de Células no Pequeñas/genética , Carcinoma de Pulmón de Células no Pequeñas/patología , Cisplatino/farmacología , Cisplatino/uso terapéutico , Proteína p53 Supresora de Tumor/genética , Proteína p53 Supresora de Tumor/metabolismo , Neoplasias Pulmonares/tratamiento farmacológico , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/patología , Resistencia a Antineoplásicos/genética , Fluvastatina/uso terapéutico , Recurrencia Local de Neoplasia/tratamiento farmacológico , Recurrencia Local de Neoplasia/genética , Línea Celular Tumoral , Antineoplásicos/farmacología , Antineoplásicos/uso terapéutico , Mutación

RESUMEN

BACKGROUND/AIM: This study examined the clinical significance of very high preoperative carbohydrate antigen 19-9 (CA19-9) levels in patients with early-stage colorectal cancer (CRC). PATIENTS AND METHODS: We retrospectively analyzed the clinicopathological data of patients who underwent curative resection for primary CRC (c-Stage I-III) between 2004 and 2022 in our facility. The patients were classified into three groups according to the preoperative CA19-9 level: normal (≤37.0 U/ml), high (>37.0 to ≤100.0 U/ml), and very high (>100.0 U/ml). RESULTS: Of 971 patients, 885 (91.1%), 67 (6.9%), and 19 (2.0%) had normal, high, and very high CA19-9 levels, respectively. Overall survival (very high vs. normal: p<0.0001, very high vs. high: p=0.01) and recurrence-free survival (very high vs. normal: p<0.0001, very high vs. high: p=0.18) were significantly worse in the very high group. On multivariate analysis including TNM stage, very high preoperative CA19-9 levels were independently associated with worse overall (odds ratio=4.54; 95% confidence interval=2.03-10.16; p=0.0002) and recurrence-free survival (odds ratio=3.49; 95% confidence interval=1.82-6.69; p=0.0002). CONCLUSION: High preoperative CA19-9 levels were associated with poor survival in early-stage CRC. Careful intraoperative observation and close follow-up might be necessary.

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Antígeno CA-19-9 , Neoplasias Colorrectales , Humanos , Biomarcadores de Tumor , Estudios Retrospectivos , Antígeno Carcinoembrionario , Pronóstico , Estadificación de Neoplasias , Neoplasias Colorrectales/patología

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OBJECTIVES: To examine whether patients who had a stroke with high recurrence risk perception would have healthier behaviour and to explore whether perceived social support would function as a mediator. DESIGN: A cross-sectional study. SETTING: The study was conducted in a public tertiary hospital in China. PARTICIPANTS: A total of 254 patients with stroke were invited to participate, and 250 patients with stroke completed questionnaires validly. PRIMARY AND SECONDARY OUTCOME MEASURES: Questionnaires were administered offline to collect data, consisting of four parts: general demographics and scales related to recurrence risk perception, perceived social support, and health behaviour. A path analysis and correlation analysis were used to analyse the data. RESULTS: Out of 250 patients with stroke, 78.4% had moderately low health behaviour. The majority (70.8%) of these patients were elderly. High recurrence risk perception and high perceived social support were significantly associated with better health behaviour (all p<0.001). Perceived social support mediated the relationship between recurrence risk perception and health behaviour after controlling for age, gender, education and monthly income in the regression model (95% CI 0.263 to 0.460) and the effect value was 0.360. It was also confirmed that perceived social support had the highest mediation effect with a proportion of mediation up to 59.31%. CONCLUSIONS: Recurrence risk perception and perceived social support were influential factors in promoting health behaviour. Moreover, the impact of recurrence risk perception on health behaviour was partially mediated by perceived social support. Therefore, to enhance the sustainability of health behaviour, it is crucial to inform patients with stroke about the risk of recurrence. Patients with more perception of recurrence risk can improve their recovery confidence and thus perceive more social support.

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Conductas Relacionadas con la Salud , Accidente Cerebrovascular , Humanos , Anciano , Estudios Transversales , Apoyo Social , Percepción , China , Encuestas y Cuestionarios

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Mesenchymal stem cell (MSC)-based therapies show great potential in treating various diseases. However, control of the fate of injected cells needs to be improved. In this work, we developed an efficient methodology for modulating chondrogenic differentiation of MSCs. We fabricated heterospheroids with two sustained-release depots, a quaternized chitosan microsphere (QCS-MP) and a poly (lactic-co-glycolic acid) microsphere (PLGA-MP). The results show that heterospheroids composed of 1 × 104 to 5 × 104 MSCs formed rapidly during incubation in methylcellulose medium and maintained high cell viability in long-term culture. The MPs were uniformly distributed in the heterospheroids, as shown by confocal laser scanning microscopy. Incorporation of transforming growth factor beta 3 into QCS-MPs and of dexamethasone into PLGA-MPs significantly promoted the expression of chondrogenic genes and high accumulation of glycosaminoglycan in heterospheroids. Changes in crucial metabolites in the dual drug depot-engineered heterospheroids were also evaluated using 1H NMR-based metabolomics analysis to verify their successful chondrogenic differentiation. Our heterospheroid fabrication platform could be used in tissue engineering to study the effects of various therapeutic agents on stem cell fate.

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Quitosano , Células Madre Mesenquimatosas , Copolímero de Ácido Poliláctico-Ácido Poliglicólico/farmacología , Microesferas , Quitosano/farmacología , Ácido Poliglicólico/farmacología , Ácido Láctico/farmacología , Glicoles , Preparaciones de Acción Retardada/farmacología , Células Cultivadas , Diferenciación Celular , Condrogénesis

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Idiopathic pulmonary fibrosis (IPF) is a progressive lung disease with high mortality. The Food and Drug Administration-approved drugs, nintedanib and pirfenidone, could delay progressive fibrosis by inhibiting the overactivation of fibroblast, however, there was no significant improvement in patient survival due to low levels of drug accumulation and remodeling of honeycomb cyst and interstitium surrounding the alveoli. Herein, we constructed a dual drug (verteporfin and pirfenidone)-loaded nanoparticle (Lip@VP) with the function of inhibiting airway epithelium fluidization and fibroblast overactivation to prevent honeycomb cyst and interstitium remodeling. Specifically, Lip@VP extensively accumulated in lung tissues via atomized inhalation. Released verteporfin inhibited the fluidization of airway epithelium and the formation of honeycomb cyst, and pirfenidone inhibited fibroblast overactivation and reduced cytokine secretion that promoted the fluidization of airway epithelium. Our results indicated that Lip@VP successfully rescued lung function through inhibiting honeycomb cyst and interstitium remodeling. This study provided a promising strategy to improve the therapeutic efficacy for IPF.

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Quistes , Fibrosis Pulmonar Idiopática , Nanopartículas , Humanos , Verteporfina , Fibrosis Pulmonar Idiopática/tratamiento farmacológico , Pulmón

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During liver fibrogenesis, the reciprocal crosstalk among capillarized liver sinusoidal endothelial cells (LSECs), activated hepatic stellate cells (HSCs), and dysfunctional hepatocytes constructs a self-amplifying vicious cycle, greatly exacerbating the disease condition and weakening therapeutic effect. Limited by the malignant cellular interactions, the previous single-cell centric treatment approaches show unsatisfactory efficacy and fail to meet clinical demand. Herein, a vicious cycle-breaking strategy is proposed to target and repair pathological cells separately to terminate the malignant progression of liver fibrosis. Chondroitin sulfate-modified and vismodegib-loaded nanoparticles (CS-NPs/VDG) are designed to efficiently normalize the fenestrae phenotype of LSECs and restore HSCs to quiescent state by inhibiting Hedgehog signaling pathway. In addition, glycyrrhetinic acid-modified and silybin-loaded nanoparticles (GA-NPs/SIB) are prepared to restore hepatocytes function by relieving oxidative stress. The results show successful interruption of vicious cycle as well as distinct fibrosis resolution in two animal models through multiregulation of the pathological cells. This work not only highlights the significance of modulating cellular crosstalk but also provides a promising avenue for developing antifibrotic regimens.

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Células Endoteliales , Liposomas , Nanopartículas , Animales , Células Endoteliales/metabolismo , Proteínas Hedgehog/metabolismo , Proteínas Hedgehog/uso terapéutico , Cirrosis Hepática , Hígado/metabolismo

RESUMEN

In advanced liver fibrosis (LF), macrophages maintain the inflammatory environment in the liver and accelerate LF deterioration by secreting proinflammatory cytokines. However, there is still no effective strategy to regulate macrophages because of the difficulty and complexity of macrophage inflammatory phenotypic modulation and the insufficient therapeutic efficacy caused by the extracellular matrix (ECM) barrier. Here, AC73 and siUSP1 dual drug-loaded lipid nanoparticle is designed to carry milk fat globule epidermal growth factor 8 (MFG-E8) (named MUA/Y) to effectively inhibit macrophage proinflammatory signals and degrade the ECM barrier. MFG-E8 is released in response to the high reactive oxygen species (ROS) environment in LF, transforming macrophages from a proinflammatory (M1) to an anti-inflammatory (M2) phenotype and inducing macrophages to phagocytose collagen. Collagen ablation increases AC73 and siUSP1 accumulation in hepatic stellate cells (HSCs) and inhibits HSCs overactivation. Interestingly, complete resolution of liver inflammation, significant collagen degradation, and HSCs deactivation are observed in methionine choline deficiency (MCD) and CCl4 models after tail vein injection of MUA/Y. Overall, this work reveals a macrophage-focused regulatory treatment strategy to eliminate LF progression at the source, providing a new perspective for the clinical treatment of advanced LF.

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Cirrosis Hepática , Macrófagos , Humanos , Cirrosis Hepática/terapia , Macrófagos/metabolismo , Colágeno , Fenotipo

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BACKGROUND:Minimally invasive surgery is developing rapidly.Robot-assisted minimally invasive transforaminal lumbar interbody fusion and robot-assisted unilateral biportal endoscopic transforaminal/posterior lumbar interbody fusion are important posterior minimally invasive surgical approaches to treat lumbar degenerative diseases.However,it is worth discussing which operation method is more advantageous. OBJECTIVE:To compare the clinical efficacy and imaging examination between different operation groups,and discuss the clinical application value of robot-assisted minimally invasive lumbar posterior fusion technology to treat lumbar degenerative diseases. METHODS:Clinical data of 83 patients with lumbar degenerative diseases from January 2018 to June 2022 at the Department of Orthopedics,Sichuan Academy of Medical Sciences&Sichuan Provincial People's Hospital were retrospectively analyzed.Of them,27 patients received robot-assisted minimally invasive transforaminal lumbar interbody fusion treatment(group A);30 patients received robot-assisted unilateral biportal endoscopic transforaminal/posterior lumbar interbody fusion treatment(group B),and 26 traditional minimally invasive transforaminal lumbar interbody fusion patients were selected as the control group(group C).There were no significant differences in gender,age,body mass index,surgical segment,preoperative visual analog scale score and Oswestry Disability Index among the three groups(P＞0.05).The operation time,intraoperative blood loss,complications,fluoroscopic dose,fluoroscopic time,and fluoroscopic frequency were compared among the three groups.Gertzbein-Robbins'classification was used to evaluate the accuracy of percutaneous pedicle screw.Visual analog scale and Oswestry Disability Index scores were evaluated after surgery.The excellent and good rate of the three surgical options was evaluated using Macnab's criteria. RESULTS AND CONCLUSION:(1)The operation time of group A was significantly shorter than that of groups B and C(P＜0.05),but there was no significant difference between group B and group C(P＞0.05).The intraoperative blood loss in group B was significantly less than that in group A,and that in group A was significantly less than that in group C(P＜0.05).(2)The fluoroscopic dose,fluoroscopic time,and fluoroscopic frequency of group C were significantly higher than those of groups A and B(P＜0.05).(3)Visual analog scale score and Oswestry Disability Index in the three groups significantly improved after operation when compared with that before operation(P＜0.05),but there was no significant difference among the three groups 1 day and 6 months after surgery(P＞0.05).(4)Postoperative imaging showed that the accuracy of percutaneous pedicle screw placement in groups A and B was better than that in group C(P＜0.05).(5)There was no significant difference in the excellent and good rate of MacNab criteria among the three groups(P＞0.05).(6)There was no significant difference in complications among the three groups(P＞0.05).(7)The results indicated that robot-assisted minimally invasive transforaminal lumbar interbody fusion and robot-assisted unilateral biportal endoscopic transforaminal/posterior lumbar interbody fusion are effective surgery methods for lumbar degenerative diseases.Compared with traditional minimally invasive transforaminal lumbar interbody fusion,robot-assisted minimally invasive transforaminal lumbar interbody fusion surgery has higher efficiency,less intraoperative radiation and higher internal fixation accuracy,which has a good clinical application value.

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Liposomas

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Objective To explore the efficacy of T-cell spot test of tuberculosis infection(T-SPOT.TB)in the differential diagnosis of spinal tuberculosis(STB),and optimize diagnostic efficacy through the optimal cut-off value of receiver operating characteristic(ROC)curve.Methods Clinical data of patients with spinal infection in a hospi-tal from January 2010 to May 2019 were collected,including preoperative T-SPOT.TB test results,white blood cell count,C-reactive protein,erythrocyte sedimentation rate,procalcitonin,and tuberculosis antibodies,etal.Clinical diagnosis was conducted based on diagnostic criteria.The sensitivity and specificity of T-SPOT.TB in preoperative diagnosis of STB and other spinal infection was analyzed,and the diagnostic efficacy of the optimized T-SPOT.TB indicators was evaluated.Results A total of 132 patients were included in this study,out of whom 78 patients(59.09％)were diagnosed with STB,and 54(40.91％)were diagnosed with non-tuberculosis(non-TB)spinal in-fection.The sensitivity and specificity of T-SPOT.TB in differential diagnosis of STB were 67.68％and 66.67％,respectively.Univariate logistic regression analysis showed that compared with non-TB spinal infection,the OR va-lue of T-SPOT.TB test in diagnosing STB was 4.188(95％CI:1.847-9.974,P＜0.001).The optimized T-SPOT.TB evaluation index through ROC curve to determine the optimal cut-off values of ESAT-6,CFP-10,and CFP-10+ESAT-6 for differential diagnosis of STB and non-TB spinal infection were 12.5,19.5,and 36,respec-tively,and area under curve(AUC)values were 0.765 6,0.741 5,and 0.778 6,respectively,all with good diag-nostic efficacy.CFP-10+ESAT-6 had the highest AUC.CFP-10+ESAT-6 specific spot count had higher efficacy in the diagnosis of STB,with a diagnostic accuracy of 75.56％,higher than 67.42％of pre-optimized T-SPOT.TB.Conclusion T-SPOT.TB test has high diagnostic efficacy in differentiating STB from non-TB spinal infection.Posi-tivity in T-SPOT.TB test,especially with spot count of CFP-10+ESAT-6 over 36,indicates a higher likelihood of STB.

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Stem cells have garnered significant attention in regenerative medicine owing to their abilities of multi-directional differentiation and self-renewal. Despite these encouraging results, the market for stem cell products yields limited, which is largely due to the challenges faced to the safety and viability of stem cells in vivo. Besides, the fate of cells re-infusion into the body unknown is also a major obstacle to stem cell therapy. Actually, both the functional protection and the fate tracking of stem cells are essential in tissue homeostasis, repair, and regeneration. Recent studies have utilized cell engineering techniques to modify stem cells for enhancing their treatment efficiency or imparting them with novel biological capabilities, in which advances demonstrate the immense potential of engineered cell therapy. In this review, we proposed that the "engineered stem cells" are expected to represent the next generation of stem cell therapies and reviewed recent progress in this area. We also discussed potential applications of engineered stem cells and highlighted the most common challenges that must be addressed. Overall, this review has important guiding significance for the future design of new paradigms of stem cell products to improve their therapeutic efficacy.

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Ingeniería Celular , Medicina Regenerativa , Medicina Regenerativa/métodos , Trasplante de Células Madre , Diferenciación Celular