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1.
Mil Med Res ; 11(1): 62, 2024 Aug 26.
Artículo en Inglés | MEDLINE | ID: mdl-39183322

RESUMEN

BACKGROUND: The National Chest Pain Center Program (NCPCP) is a nationwide, quality enhancement program aimed at raising the standard of care for patients experiencing acute chest pain in China. The benefits of chest pain center (CPC) accreditation on acute coronary syndrome have been demonstrated. However, there is no evidence to indicate whether CPC accreditation improves outcomes for patients with acute aortic dissection (AAD). METHODS: We conducted a retrospective observational study of patients with AAD from 1671 hospitals in China, using data from the NCPCP spanning the period from January 1, 2016 to December 31, 2022. The patients were divided into 2 groups: pre-accreditation and post-accreditation admissions. The outcomes examined included in-hospital mortality, misdiagnosis, and Stanford type A AAD surgery. Multivariate logistic regression was employed to explore the relationship between CPC accreditation and in-hospital outcomes. Furthermore, we stratified the hospitals based on their geographical location (Eastern/Central/Western regions) or administrative status (provincial/non-provincial capital areas) to assess the impact of CPC accreditation on AAD patients across various regions. RESULTS: The analysis encompassed a total of 40,848 patients diagnosed with AAD. The post-accreditation group exhibited significantly lower rates of in-hospital mortality and misdiagnosis (12.1% vs. 16.3%, P < 0.001 and 2.9% vs. 5.4%, P < 0.001, respectively) as well as a notably higher rate of Stanford type A AAD surgery (61.1% vs. 42.1%, P < 0.001) compared with the pre-accreditation group. After adjusting for potential covariates, CPC accreditation was associated with substantially reduced risks of in-hospital mortality (adjusted OR 0.644, 95% CI 0.599-0.693) and misdiagnosis (adjusted OR 0.554, 95% CI 0.493-0.624), along with an increase in the proportion of patients undergoing Stanford type A AAD surgery (adjusted OR 1.973, 95% CI 1.797-2.165). Following CPC accreditation, there were significant reductions in in-hospital mortality across various regions, particularly in Western regions (from 21.5 to 14.1%). Moreover, CPC accreditation demonstrated a more pronounced impact on in-hospital mortality in non-provincial cities compared to provincial cities (adjusted OR 0.607 vs. 0.713). CONCLUSION: CPC accreditation is correlated with improved management and in-hospital outcomes for patients with AAD.


Asunto(s)
Acreditación , Disección Aórtica , Dolor en el Pecho , Mortalidad Hospitalaria , Humanos , China/epidemiología , Acreditación/estadística & datos numéricos , Acreditación/normas , Disección Aórtica/terapia , Disección Aórtica/mortalidad , Disección Aórtica/cirugía , Disección Aórtica/diagnóstico , Femenino , Estudios Retrospectivos , Masculino , Persona de Mediana Edad , Dolor en el Pecho/terapia , Dolor en el Pecho/diagnóstico , Anciano , Adulto , Modelos Logísticos
2.
Exp Cell Res ; 441(2): 114182, 2024 Aug 15.
Artículo en Inglés | MEDLINE | ID: mdl-39094903

RESUMEN

Kawasaki disease (KD) is a systemic vasculitis with an unknown cause that primarily affects children. The objective of this study was to explore the function and underlying mechanism of mitophagy in Mycoplasma pneumoniae (MP)-induced KD. To create MP-induced KD models, Human coronary endothelial cells (HCAECs) and DBA/2 mice were employed and treated with Mp-Lipid-associated membrane proteins (LAMPs). Lactate dehydrogenase (LDH) levels were tested to determine cellular damage or death. The inflammatory cytokines tumor necrosis factor (TNF)--α and interleukin (IL)-6 were measured using the Enzyme-Linked Immunosorbent Assay (ELISA) method. RT-qPCR and Western blotting were used to determine the expression of Intercellular Adhesion Molecule(ICAM)-1, vascular cell adhesion molecule (VCAM)-1, inducible nitric oxide synthase(iNOS), LC3, p62, PINK1(a mitochondrial serine/threonine-protein kinase), and PARKIN(a cytosolic E3-ubiquitin ligase). The adenosine triphosphate (ATP), reactive oxygen species (ROS), and mitochondrial membrane potential(MMP) levels were measured to determine mitochondrial function. Mitophagy was investigated using immunofluorescence and a mitophagy detection test. Autophagosome and mitochondrial morphology were examined using transmission electron microscopy. To identify inflammatory cell infiltration, hematoxylin and eosin staining was utilized. Mp-LAMPs increased the levels of TNF-α, IL-6, ICAM-1, VCAM-1, and iNOS in an HCAEC cell model, along with LDH release. After Mp-LAMPs exposure, there was a rise in LC3 and a reduction in p62. Meanwhile, the expression of PINK1 and Parkin was increased. Cyclosporin A dramatically increased ATP synthesis and MMP in HCAEC cells treated with Mp-LAMPs, while suppressing ROS generation, demonstrating excessive mitophagy-related mitochondrial dysfunction. Additionally, neither body weight nor artery tissue were affected due to PINK1 and Parkin suppression Cyclosporin A in Mp-LAMPs-treated mice. These findings indicated that PINK1/Parkin-mediated mitophagy inhibition may be a therapeutic target for MP-induced KD.


Asunto(s)
Mitofagia , Síndrome Mucocutáneo Linfonodular , Mycoplasma pneumoniae , Proteínas Quinasas , Ubiquitina-Proteína Ligasas , Animales , Síndrome Mucocutáneo Linfonodular/metabolismo , Síndrome Mucocutáneo Linfonodular/patología , Proteínas Quinasas/metabolismo , Humanos , Ratones , Ubiquitina-Proteína Ligasas/metabolismo , Ubiquitina-Proteína Ligasas/genética , Mycoplasma pneumoniae/patogenicidad , Ratones Endogámicos DBA , Células Endoteliales/metabolismo , Células Endoteliales/patología , Neumonía por Mycoplasma/metabolismo , Neumonía por Mycoplasma/patología , Neumonía por Mycoplasma/microbiología , Mitocondrias/metabolismo , Mitocondrias/patología , Especies Reactivas de Oxígeno/metabolismo , Potencial de la Membrana Mitocondrial
3.
Bioorg Med Chem ; 111: 117845, 2024 Sep 01.
Artículo en Inglés | MEDLINE | ID: mdl-39059249

RESUMEN

SR9009 is an activator of REV-ERBs with diverse biological activities, including improving exercise tolerance and controlling skeletal muscle mass. To optimise the carbamate motif of SR9009, analogues of SR9009 were synthesised and evaluated. All of them showed REV-ERB-α agonist activities. Among them, 5a, 5f, 5 g, 5m, and 5p showed potencies equivalent to or slightly higher than the potency of SR9009 in vitro. These data indicate that the halogenated benzyl group is an indispensable active group in these compounds. 5m, 5p and SR9009 improved exercise tolerance in normal mice in vivo. Additionally, in hyperlipidemic mice, 5m and 5p not only improved exercise tolerance but also lowered blood lipid levels. 5m and 5p displayed stronger hypoglycaemic activity than SR9009.


Asunto(s)
Glucolípidos , Miembro 1 del Grupo D de la Subfamilia 1 de Receptores Nucleares , Tiofenos , Animales , Ratones , Tiofenos/farmacología , Tiofenos/química , Tiofenos/síntesis química , Miembro 1 del Grupo D de la Subfamilia 1 de Receptores Nucleares/agonistas , Miembro 1 del Grupo D de la Subfamilia 1 de Receptores Nucleares/metabolismo , Glucolípidos/farmacología , Glucolípidos/química , Glucolípidos/síntesis química , Relación Estructura-Actividad , Masculino , Humanos , Estructura Molecular , Ratones Endogámicos C57BL , Pirrolidinas/farmacología , Pirrolidinas/química , Pirrolidinas/síntesis química , Hipoglucemiantes/farmacología , Hipoglucemiantes/síntesis química , Hipoglucemiantes/química , Relación Dosis-Respuesta a Droga , Tolerancia al Ejercicio/efectos de los fármacos
4.
Surg Endosc ; 38(9): 5178-5186, 2024 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-39043886

RESUMEN

BACKGROUND AND AIM: The incidence of rectal neuroendocrine tumors (R-NETs) has increased in recent years. However, the predictors of lymph node (LN) metastasis and clinical outcomes, particularly following endoscopic treatment, remain unclear. Our study aims to elucidate the potential risk factors for LN metastasis and the clinical outcomes of patients undergoing endoscopic resection in R-NETs. METHODS: A total of 128 patients with R-NETs were retrospectively identified from a single center between June 2012 and December 2021. Risk factors for LN metastasis in R-NETs were analyzed using multivariate analysis. Additionally, the clinical outcomes of endoscopic resections in patients with R-NETs were assessed. RESULTS: In our study, 128 patients with R-NETs were retrospectively analyzed. The risk factors for LN metastasis determined by multivariate analysis were tumor size and patient age at diagnosis. Among the 111 patients treated with endoscopic resection and with tumor margin records available, 92 underwent endoscopic submucosal dissection (ESD) and 19 underwent conventional endoscopic mucosal resection (EMR). There was no significant difference between the two groups regarding the positive rates of basal tumor margin and lateral tumor margin. Furthermore, 64 patients who underwent endoscopic resection for R-NETs were successfully followed up (range, 1.64-76.71 months), during which only one patient developed local recurrence. CONCLUSION: Tumor size and age at diagnosis were predictors for LN metastasis of R-NETs. Both ESD and EMR are alternative techniques with a favorable prognosis for R-NETs, even in cases with positive resection margins. However, due to the relatively small number of patients undergoing EMR and missing data in follow-up protocols, definitive conclusions require further large-scale studies.


Asunto(s)
Resección Endoscópica de la Mucosa , Metástasis Linfática , Tumores Neuroendocrinos , Neoplasias del Recto , Humanos , Masculino , Neoplasias del Recto/patología , Neoplasias del Recto/cirugía , Estudios Retrospectivos , Femenino , Tumores Neuroendocrinos/cirugía , Tumores Neuroendocrinos/patología , Tumores Neuroendocrinos/secundario , Persona de Mediana Edad , Resección Endoscópica de la Mucosa/métodos , Anciano , Adulto , Factores de Riesgo , Resultado del Tratamiento , Recurrencia Local de Neoplasia/epidemiología , Recurrencia Local de Neoplasia/patología , Márgenes de Escisión
5.
Drug Dev Res ; 85(5): e22237, 2024 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-39032059

RESUMEN

The global prevalence of RNA virus infections has presented significant challenges to public health in recent years, necessitating the expansion of its alternative therapeutic library. Due to its evolutional conservation, RNA-dependent RNA polymerase (RdRp) has emerged as a potential target for broad-spectrum antiviral nucleoside analogues. However, after over half a century of structural modification, exploring unclaimed chemical space using frequently-used structural substitution methods to design new nucleoside analogues is challenging. In this study, we explore the use of the "ring-opening" strategy to design new base mimics, thereby using these base mimics to design new nucleoside analogues with broad-spectrum antiviral activities. A total of 29 compounds were synthesized. Their activity against viral RdRp was initially screened using an influenza A virus RdRp high-throughput screening model. Then, the antiviral activity of 38a was verified against influenza virus strain A/PR/8/34 (H1N1), demonstrating a 50% inhibitory concentration (IC50) value of 9.95 µM, which was superior to that of ribavirin (the positive control, IC50 = 11.43 µM). Moreover, 38a also has inhibitory activity against coronavirus 229E with an IC50 of 30.82 µM. In addition, compounds 42 and 46f exhibit an 82% inhibition rate against vesicular stomatitis virus at a concentration of 20 µM and hardly induce cytotoxicity in host cells. This work demonstrates the feasibility of designing nucleoside analogues with "ring-opening" bases and suggests the "ring-opening" nucleosides may have greater polarity, and designing prodrugs is an important aspect of optimizing their antiviral activity. Future research should focus on enhancing the conformational restriction of open-loop bases to mimic Watson-Crick base pairing better and improve antiviral activity.


Asunto(s)
Antivirales , Diseño de Fármacos , Nucleósidos , ARN Polimerasa Dependiente del ARN , Antivirales/farmacología , Antivirales/química , Antivirales/síntesis química , Nucleósidos/química , Nucleósidos/farmacología , ARN Polimerasa Dependiente del ARN/antagonistas & inhibidores , Subtipo H1N1 del Virus de la Influenza A/efectos de los fármacos , Humanos , Animales , Células de Riñón Canino Madin Darby , Perros , Relación Estructura-Actividad
6.
Mycopathologia ; 189(4): 59, 2024 Jun 18.
Artículo en Inglés | MEDLINE | ID: mdl-38890181

RESUMEN

Dermatophyte biofilms frequently count for inadequate responses and resistance to standard antifungal treatments, resulting in refractory chronic onychomycosis infection. Although antimicrobial photodynamic therapy (aPDT) has clinically proven to exert significant antifungal effects or even capable of eradicating dermatophyte biofilms, considerably less is known about the molecular mechanisms underlying aPDT and the potential dysregulation of signaling networks that could antagonize its action. The aim of this study is to elucidate the molecular mechanisms underlining aPDT combat against dermatophyte biofilm in recalcitrant onychomycosis and to decipher the potential detoxification processes elicited by aPDT, facilitating the development of more effective photodynamic interventions. We applied genome-wide comparative transcriptome analysis to investigate how aPDT disrupting onychomycosis biofilm formed by three distinct dermatophytes, including Trichophyton rubrum, Trichophyton mentagrophytes, and Microsporum gypseum, the most frequently occurring pathogenic species. In total, 352.13 Gb of clean data were obtained for the transcriptomes of dermatophyte biofilms with or without aPDT treatment, resulting in 2,422.42 million reads with GC content of 51.84%, covering 99.9%, 98.5% and 99.4% of annotated genes of T. rubrum, T. mentagrophytes, and M. gypseum, respectively. The genome-wide orthologous analysis identified 6624 transcribed single-copy orthologous genes in all three species, and 36.5%, 6.8% and 17.9% of which were differentially expressed following aPDT treatment. Integrative orthology analysis demonstrated the upregulation of oxidoreductase activities is a highly conserved detoxification signaling alteration in response to aPDT across all investigated dermatophyte biofilms. This study provided new insights into the molecular mechanisms underneath anti-dermatophyte biofilm effects of aPDT and successfully identified a conserved detoxification regulation upon the aPDT application.


Asunto(s)
Arthrodermataceae , Biopelículas , Perfilación de la Expresión Génica , Fotoquimioterapia , Biopelículas/efectos de los fármacos , Arthrodermataceae/efectos de los fármacos , Arthrodermataceae/genética , Microsporum/efectos de los fármacos , Microsporum/genética , Humanos , Antifúngicos/farmacología , Onicomicosis/microbiología , Onicomicosis/tratamiento farmacológico , Transcriptoma
7.
EBioMedicine ; 105: 105203, 2024 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-38896919

RESUMEN

BACKGROUND: Hybrid immunity to SARS-CoV-2, resulting from both vaccination and natural infection, remains insufficiently understood in paediatric populations, despite increasing rates of breakthrough infections among vaccinated children. METHODS: We conducted a prospective longitudinal study to investigate the magnitude, specificity, and cytokine profile of antigen-specific T cell responses elicited by breakthrough SARS-CoV-2 infection in a cohort of mRNA-vaccinated children (n = 29) aged 5-11. This longitudinal analysis involved six distinct time points spanning a 16-month period post-vaccination, during which we analysed a total of 159 blood samples. All children who were followed for at least 12 months (n = 26) experienced a breakthrough infection. We conducted cytokine release assays using minimal blood samples, and we verified the cellular origin of these responses through intracellular cytokine staining. FINDINGS: After breakthrough infection, children who had received mRNA vaccines showed enhanced Th1 responses specific to Spike peptides. Additionally, their Spike-specific T cells exhibited a distinctive enrichment of CD4+ IFN-γ+IL10+ cells, a characteristic akin to adults with hybrid immunity. Importantly, vaccination did not impede the development of multi-specific T cell responses targeting Membrane, Nucleoprotein, and ORF3a/7/8 antigens. INTERPRETATION: Children, previously primed with a Spike-based mRNA vaccine and experiencing either symptomatic or asymptomatic breakthrough infection, retained the ability to enhance and diversify Th1/IL-10 antigen-specific T cell responses against multiple SARS-CoV-2 proteins. These findings mirror characteristics associated with hybrid cellular immunity in adults, known to confer resistance against severe COVID-19. FUNDING: This study was funded by the National Medical Research Council (NMRC) Singapore (COVID19RF-0019, MOH-000019, MOH-000535, OFLCG19May-0034 and MOH-OFYIRG19nov-0002).


Asunto(s)
COVID-19 , SARS-CoV-2 , Humanos , COVID-19/inmunología , COVID-19/prevención & control , COVID-19/virología , SARS-CoV-2/inmunología , Niño , Estudios Longitudinales , Masculino , Femenino , Preescolar , Citocinas/metabolismo , Glicoproteína de la Espiga del Coronavirus/inmunología , Vacunas contra la COVID-19/inmunología , Vacunas contra la COVID-19/administración & dosificación , Estudios Prospectivos , Vacunación , Vacunas de ARNm/inmunología , Linfocitos T/inmunología , Células TH1/inmunología
8.
Adv Mater ; 36(35): e2404010, 2024 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-38935245

RESUMEN

The imperfect charge behavior at the interfaces of perovskite/electron-transport layer (ETL)/transparent conducting oxide (TCO) limits the further performance improvement of perovskite/silicon tandem solar cells. Herein, an indium tin oxide interlayer is deposited between ETL and TCO to address this issue. Specifically, the interlayer is prepared using an all-physical and H2O-free method, electron-beam evaporation, which can avoid any potential damage to the underlying perovskite and ETL layers. Moreover, the interlayer's composition can be readily tuned by changing the evaporator component, enabling authors to regulate the contact resistance and energy-level alignment of the ETL/TCO interface. Consequently, the resultant perovskite/silicon tandem solar cells exhibit an impressive power conversion efficiency (PCE) of 30.8% (certified 30.3%). Moreover, the device retains 98% of its initial PCE after continuous operation under ambient conditions for 1078 h, representing one of the most stable and efficient perovskite/silicon tandem solar cells.

9.
Small ; : e2401447, 2024 May 01.
Artículo en Inglés | MEDLINE | ID: mdl-38693087

RESUMEN

Topological defects are widely recognized as effective active sites toward a variety of electrochemical reactions. However, the role of defect curvature is still not fully understood. Herein, carbon nanomaterials with rich topological defect sites of tunable curvature is reported. The curved defective surface is realized by controlling the high-temperature pyrolytic shrinkage process of precursors. Theoretical calculations demonstrate bending the defect sites can change the local electronic structure, promote the charge transfer to key intermediates, and lower the energy barrier for oxygen reduction reaction (ORR). Experimental results convince structural superiority of highly-curved defective sites, with a high kinetic current density of 22.5 mA cm-2 at 0.8 V versus RHE for high-curvature defective carbon (HCDC), ≈18 times that of low-curvature defective carbon (LCDC). Further raising the defect densities in HCDC leads to the dual-regulated products (HCHDC), which exhibit exceptionally outstanding ORR activity in both alkaline and acidic media (half-wave potentials: 0.88 and 0.74 V), outperforming most of the reported metal-free carbon catalysts. This work uncovers the curvature-activity relationship in carbon defect for ORR and provides new guidance to design advanced catalysts via curvature-engineering.

10.
Vaccine ; 42(12): 2951-2954, 2024 Apr 30.
Artículo en Inglés | MEDLINE | ID: mdl-38584057

RESUMEN

Heterologous Sinovac-CoronaVac booster(s) in 12-17-year-olds who had a moderate/severe reaction to Pfizer-BNT162b2 mRNA vaccine was found to safe with no serious adverse events reported. In those primed with 1 dose of Pfizer-BNT162b2 vaccine, subsequent boosters with 2 doses of Sinovac-CoronaVac vaccines achieved neutralizing antibody levels which were comparable to those who had received 2 doses of Pfizer-BNT162b2 vaccines followed by 1 dose of Sinovac-CoronaVac vaccination. Adolescents with 1 Pfizer-BNT162b2 followed by 2 Sinovac-CoronaVac vaccines developed T-cell responses against broad peptides including membrane, nucleoprotein 1 and 2 but levels were highest for Spike protein and lasted until day 150 post-vaccination.


Asunto(s)
Vacuna BNT162 , Vacunación , Vacunas de Productos Inactivados , Adolescente , Humanos , Anticuerpos Neutralizantes , Anticuerpos Antivirales , Vacuna BNT162/efectos adversos , Vacunación/efectos adversos , Vacunas de Productos Inactivados/efectos adversos , Niño
11.
Biosens Bioelectron ; 255: 116271, 2024 Jul 01.
Artículo en Inglés | MEDLINE | ID: mdl-38583355

RESUMEN

The metal-organic frameworks (MOFs) nanozyme-mediated paper-based analytical devices (PADs) have shown great potential in portable visual determination of phenolic compounds in the environment. However, most MOF nanozymes suffer from poor dispersibility and block-like structure, which often prompts deposition and results in diminished enzymatic activity, severely hindering their environmental applications. Here, we proposed colorimetric PADs for the visual detection of dichlorophen (Dcp) based on its significant inhibitory effect on the two-dimensional (2D) MOF nanozyme activity. Specifically, we synthesized a 2D Cu TCPP (Fe) (defined as 2D-CTF) MOF nanozyme exhibiting excellent dispersibility and remarkable peroxidase-like (POD-like) activity, which could catalyze the oxidation and subsequent color change of 3,3',5,5'-tetramethylbenzidine even under neutral conditions. Notably, the POD-like activity of 2D-CTF demonstrated a unique response to Dcp because of the occupation of Fe-N4 active sites on the 2D-CTF. This property enables the use of 2D-CTF as a highly efficient catalyst to develop colorimetric PADs for naked-eye and portable detection of Dcp. We believe that the proposed colorimetric PADs offer an efficient method for Dcp assay and open fresh avenues for the advancement of colorimetric sensors for analyzing of phenolic toxic substances in real samples.


Asunto(s)
Técnicas Biosensibles , Diclorofeno , Estructuras Metalorgánicas , Estructuras Metalorgánicas/química , Técnicas Biosensibles/métodos , Peroxidasas/química , Peroxidasa , Colorimetría/métodos , Fenoles , Peróxido de Hidrógeno/química
12.
Dig Dis Sci ; 69(6): 2184-2192, 2024 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-38653945

RESUMEN

BACKGROUND: The role of endoscopic resection (ER) in gastric gastrointestinal stromal tumors (GISTs) has not been fully elucidated. AIMS: The purpose of this work was to evaluate the clinical effectiveness and safety of ER in patients with GISTs originating from the muscularis propria (MP). METHODS: A total of 233 consecutive patients with gastric GISTs originating from the MP layer, who underwent ER between February 2012 and May 2023, were included in this study. Clinical characteristics, tumor features, and outcomes were recorded and compared between patients who underwent en bloc resection and piecemeal resection. RESULTS: Among the 233 patients, the median size of GISTs was 12 mm (range 5-60 mm). Risk assessment categorized 190 patients as very low risk, 26 as low risk, 10 as moderate risk, and 7 as high risk. The procedures performed included endoscopic submucosal excavation (127 cases), endoscopic full-thickness resection (103 cases), and submucosal tunneling endoscopic resection (3 cases). The complete and R0 resection rate was 93.1%. Complications occurred in 4.7% of cases (perioperative perforations 1.7%, perioperative bleeding 1.3%, both 0.9%), resulting in conversion to surgery in 1.3% of cases. Risk factors associated with piecemeal resection were tumor size [odds ratio (OR) 0.402, 95% confidence interval (CI) 0.207-0.783; P = 0.007] and shape (OR 0.045, 95% CI 0.009-0.235; P < 0.001). CONCLUSIONS: ER is proven to be an effective and reasonably safe approach for gastric GISTs originating from the MP. Notably, larger tumor size and irregular shape are identified as risk factors for piecemeal resection during ER procedures.


Asunto(s)
Tumores del Estroma Gastrointestinal , Neoplasias Gástricas , Humanos , Tumores del Estroma Gastrointestinal/cirugía , Tumores del Estroma Gastrointestinal/patología , Masculino , Femenino , Persona de Mediana Edad , Neoplasias Gástricas/cirugía , Neoplasias Gástricas/patología , Anciano , Adulto , Anciano de 80 o más Años , Resección Endoscópica de la Mucosa/métodos , Resección Endoscópica de la Mucosa/efectos adversos , Mucosa Gástrica/cirugía , Mucosa Gástrica/patología , Resultado del Tratamiento , Estudios Retrospectivos , Gastroscopía/métodos , Gastroscopía/efectos adversos , Factores de Riesgo , Complicaciones Posoperatorias/epidemiología , Complicaciones Posoperatorias/etiología
13.
Acta Biomater ; 180: 407-422, 2024 05.
Artículo en Inglés | MEDLINE | ID: mdl-38614414

RESUMEN

Facile construction of a fully biodegradable spherical nucleic acid (SNA) nanoplatform is highly desirable for clinical translations but remains rarely explored. We developed herein the first polycarbonate-based biodegradable SNA nanoplatform for self-codelivery of a chemotherapeutic drug, doxorubicin (DOX), and a human liver-specific miR122 for synergistic chemo-gene therapy of hepatocellular carcinoma (HCC). Ring-opening polymerization (ROP) of a carbonate monomer leads to a well-defined polycarbonate backbone for subsequent DOX conjugation to the pendant side chains via acidic pH-cleavage Schiff base links and miR122 incorporation to the chain termini via click coupling, affording an amphiphilic polycarbonate-DOX-miR122 conjugate, PBis-Mpa30-DOX-miR122 that can self-assemble into stabilized SNA. Besides the desired biodegradability, another notable merit of this nanoplatform is the use of miR122 not only for gene therapy but also for enhanced innate immune response. Together with the ICD-triggering effect of DOX, PBis-Mpa30-DOX-miR122 SNA-mediated DOX and miR122 codelivery leads to synergistic immunogenicity enhancement, resulting in tumor growth inhibition value (TGI) of 98.1 % significantly higher than those of the groups treated with only drug or gene in a Hepa1-6-tumor-bearing mice model. Overall, this study develops a useful strategy toward biodegradable SNA construction, and presents a drug and gene-based self-codelivery SNA with synergistic immunogenicity enhancement for efficient HCC therapy. STATEMENT OF SIGNIFICANCE: Facile construction of a fully biodegradable SNA nanoplatform is useful for in vivo applications but remains relatively unexplored likely due to the synthetic challenge. We report herein construction of a polycarbonate-based SNA nanoplatform for co-delivering a chemotherapeutic drug, DOX, and a human liver-specific miR-122 for synergistic HCC treatment. In addition to the desired biodegradability properties, this SNA nanoplatform integrates DOX-triggered ICD and miR-122-enhanced innate immunity for simultaneously activating adaptive and innate immunities, which leads to potent antitumor efficiency with a TGI value of 98.1 % in a Hepa1-6-tumor-bearing mice model.


Asunto(s)
Inmunidad Adaptativa , Doxorrubicina , Inmunidad Innata , MicroARNs , Doxorrubicina/farmacología , Doxorrubicina/química , MicroARNs/genética , Animales , Inmunidad Innata/efectos de los fármacos , Humanos , Inmunidad Adaptativa/efectos de los fármacos , Ratones , Carcinoma Hepatocelular/tratamiento farmacológico , Carcinoma Hepatocelular/patología , Carcinoma Hepatocelular/inmunología , Nanopartículas/química , Neoplasias Hepáticas/tratamiento farmacológico , Neoplasias Hepáticas/inmunología , Neoplasias Hepáticas/patología , Ratones Desnudos , Ratones Endogámicos BALB C
14.
Biosens Bioelectron ; 257: 116295, 2024 Aug 01.
Artículo en Inglés | MEDLINE | ID: mdl-38653013

RESUMEN

Hyperbolic metamaterial (HMM) biosensors based on metals have superior performance in comparison with conventional plasmonic biosensors in the detection of low concentrations of molecules. In this study, a nanorod HMM (NHMM) biosensor based on refractive index changes for carcinoembryonic antigen (CEA) detection is developed using secondary antibody modified gold nanoparticle (AuNP-Ab2) nanocomposites as signal amplification element for the first time. Numerical analysis based on finite element method is conducted to simulate the perturbation of the electric field of bulk plasmon polariton (BPP) supported by a NHMM in the presence of a AuNP. The simulation reveals an enhancement of the localized electric field, which arises from the resonant coupling of BPP to the localized surface plasmon resonance supported by AuNPs and is beneficial for the detection of changes of the refractive index. Furthermore, the AuNP-Ab2 nanocomposites-based NHMM (AuNP/Ab2-NHMM) biosensor enables CEA detection in the visible and near-infrared regions simultaneously. The highly sensitive detection of CEA with a wide linear range of 1-500 ng/mL is achieved in the near-infrared region. The detectable concentration of the AuNP/Ab2-NHMM biosensor has a 50-fold decrease in comparison with a NHMM biosensor. A low detection limit of 0.25 ng/mL (1.25 pM) is estimated when considering a noise level of 0.05 nm as the minimum detectable wavelength shift. The proposed method achieves high sensitivity and good reproducibility for CEA detection, which makes it a novel and viable approach for biomedical research and early clinical diagnostics.


Asunto(s)
Técnicas Biosensibles , Antígeno Carcinoembrionario , Oro , Límite de Detección , Nanopartículas del Metal , Nanotubos , Resonancia por Plasmón de Superficie , Oro/química , Antígeno Carcinoembrionario/sangre , Antígeno Carcinoembrionario/análisis , Nanopartículas del Metal/química , Nanotubos/química , Humanos , Resonancia por Plasmón de Superficie/métodos , Técnicas Biosensibles/métodos , Anticuerpos Inmovilizados/química
15.
Asian Nurs Res (Korean Soc Nurs Sci) ; 18(2): 89-96, 2024 May.
Artículo en Inglés | MEDLINE | ID: mdl-38583799

RESUMEN

PURPOSE: This study aims to investigate the current status of affiliate stigma among parents of autistic children, analyze the influencing factors, explore the relationship among mindfulness, coping styles, and affiliate stigma, and verify the mediating role of coping styles between mindfulness and affiliate stigma in parents of children with autism in China. METHOD: Between February and April 2023, the Child Development Behaviour Centre of a public hospital in China recruited 345 parents of children with autism. These parents completed the general information questionnaire, the Mindful Attention Awareness Scale, the Affiliate Stigma Scale, and the Simple Coping Style Questionnaire. We then adapted the Hayes Process Macro and Bootstrap methods to examine the mediating effects of coping styles between mindfulness and affiliate stigma. RESULTS: (1) The total affiliate stigma score of parents of children with autism was 48.53 (standard deviation:: 10.74). Parents' age, monthly family income, duration of care, mindfulness, and coping styles were the influencing factors of parental affiliate stigma. (2) Mindfulness was positively correlated with positive coping style (r = 0.33, p < .01) and negatively correlated with negative coping style, affiliate stigma (r = -0.38, -0.39, p < .01), whereas affiliate stigma was negatively correlated with positive coping style (r = -0.34, p < .01) and positively correlated with negative coping style (r = 0.41, p < .01). (3) Positive coping style and negative coping style play a parallel mediating role between mindfulness and affiliate stigma of parents of autistic children. CONCLUSIONS: Parents of children with autism experience significant levels of affiliate stigma. Mindfulness has a direct impact on associated stigma in parents of children with autism and also indirectly predicts associated stigma through the intermediary influence of positive and negative coping styles. Healthcare professionals could perform mindfulness interventions from an optimistic psychology viewpoint to boost parents' mindfulness and coping abilities, thereby accomplishing the objective of mitigating affiliate stigma.


Asunto(s)
Adaptación Psicológica , Trastorno del Espectro Autista , Atención Plena , Padres , Estigma Social , Humanos , Masculino , Femenino , Trastorno del Espectro Autista/psicología , Trastorno del Espectro Autista/enfermería , China , Padres/psicología , Adulto , Niño , Persona de Mediana Edad , Encuestas y Cuestionarios , Preescolar
16.
Heliyon ; 10(5): e27181, 2024 Mar 15.
Artículo en Inglés | MEDLINE | ID: mdl-38449603

RESUMEN

Nowadays, the ongoing electrical vehicles and energy storage devices give a great demand of high-energy-density lithium battery. The commercial graphite anode has been reached the limit of the theoretical capacity. Herein, we introduce lithium metal anode to demonstrate the promising anode which can replace graphite. Lithium metal has a high theoretical capacity and the lowest electrochemical potential. Hence, using lithium metal as the anode material of lithium batteries can reach the limit of energy and power density of lithium batteries. However, lithium metal has huge flaw such as unstable SEI layer, volume change and dendrites formation. Therefore, we give a review of the lithium metal anode on its issues and introduce the existing research to overcome these. Besides, we give the perspective that the engineering problems also restrict the commercial use of lithium metal. This review provides the reasonable method to enhance the lithium metal performance and give the development direction for the subsequent research.

17.
Biomark Med ; 18(2): 69-77, 2024 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-38440878

RESUMEN

Background: This study aimed to investigate the clinical value of the red blood cell distribution width (RDW) in severe Mycoplasma pneumoniae pneumonia (MPP). Methods: A total of 185 children with diagnosed severe MPP were included. The patients' case records and laboratory examination data were analyzed retrospectively. The children were grouped into quartiles based on RDW. Results: Univariate analysis revealed that RDW was significantly correlated with the Pediatric Risk of Mortality (PRISM) III score, Sepsis-Related Organ Failure Assessment score, incidence of invasive intubation and 30-day in-hospital mortality. After adjustment for the severity of illness, multivariate analysis revealed that the PRISM III score and RDW were factors independently associated with 30-day in-hospital mortality. Conclusion: This study revealed that RDW could be correlated with the long-term prognosis and severity of severe MPP.


Asunto(s)
Mycoplasma pneumoniae , Neumonía , Niño , Humanos , Estudios Retrospectivos , Factores de Riesgo , Índices de Eritrocitos , Pronóstico , Eritrocitos , Neumonía/diagnóstico
18.
Innovation (Camb) ; 5(3): 100599, 2024 May 06.
Artículo en Inglés | MEDLINE | ID: mdl-38510071

RESUMEN

Elucidating the temporal process of immune remodeling under immunosuppressive treatment after liver transplantation (LT) is critical for precise clinical management strategies. Here, we performed a single-cell multi-omics analysis of peripheral blood mononuclear cells (PBMCs) collected from LT patients (with and without acute cellular rejection [ACR]) at 13 time points. Validation was performed in two independent cohorts with additional LT patients and healthy controls. Our study revealed a four-phase recovery process after LT and delineated changes in immune cell composition, expression programs, and interactions along this process. The intensity of the immune response differs between the ACR and non-ACR patients. Notably, the newly identified inflamed NK cells, CD14+RNASE2+ monocytes, and FOS-expressing monocytes emerged as predictive indicators of ACR. This study illuminates the longitudinal evolution of the immune cell landscape under tacrolimus-based immunosuppressive treatment during LT recovery, providing a four-phase framework that aids the clinical management of LT patients.

19.
Adv Sci (Weinh) ; 11(24): e2306388, 2024 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-38477522

RESUMEN

CD47-SIRPα axis is an immunotherapeutic target in tumor therapy. However, current monoclonal antibody targeting CD47-SIRPα axis is associated with on-target off-tumor and antigen sink effects, which significantly limit its potential clinical application. Herein, a biomimetic nano-degrader is developed to inhibit CD47-SIRPα axis in a site-specific manner through SIRPα degradation, and its efficacy in acute myocardial infarction (AMI) is evaluated. The nano-degrader is constructed by hybridizing liposome with red blood cell (RBC) membrane (RLP), which mimics the CD47 density of senescent RBCs and possesses a natural high-affinity binding capability to SIRPα on macrophages without signaling capacity. RLP would bind with SIRPα and induce its lysosomal degradation through receptor-mediated endocytosis. To enhance its tissue specificity, Ly6G antibody conjugation (aRLP) is applied, enabling its attachment to neutrophils and accumulation within inflammatory sites. In the myocardial infarction model, aRLP accumulated in the infarcted myocardium blocks CD47-SIRPα axis and subsequently promoted the efferocytosis of apoptotic cardiomyocytes by macrophage, improved heart repair. This nano-degrader efficiently degraded SIRPα in lysosomes, providing a new strategy for immunotherapy with great clinical transformation potential.


Asunto(s)
Antígeno CD47 , Macrófagos , Receptores Inmunológicos , Antígeno CD47/inmunología , Antígeno CD47/metabolismo , Animales , Receptores Inmunológicos/metabolismo , Ratones , Macrófagos/inmunología , Macrófagos/efectos de los fármacos , Macrófagos/metabolismo , Modelos Animales de Enfermedad , Infarto del Miocardio/inmunología , Inhibidores de Puntos de Control Inmunológico/farmacología , Antígenos de Diferenciación/inmunología , Fagocitosis/efectos de los fármacos , Biomimética/métodos , Humanos , Eferocitosis
20.
J Adv Nurs ; 80(7): 2813-2821, 2024 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-38482900

RESUMEN

AIM: To measure the association of leader-member exchange and team-member exchange with nurses' innovative behaviours through social exchange theory. BACKGROUND: The field of nursing is actively advocating innovation. Other fields have proven that leader-member exchange and team-member exchange can promote innovative behaviour, but such an association is not clear in nursing. DESIGN: A cross-sectional study. METHODS: A total of 560 nurses were selected from five tertiary hospitals in Henan Province (China) by multistage sampling. Data were collected from a self-report questionnaire. Thirty nurses in the pre-survey were used to verify the validity of the questionnaire. SPSS PROCESS macro was used to verify the association of leader-member exchange and team-member exchange with nurses' innovative behaviours. RESULTS: Leader-member exchange and team-member exchange were significantly associated with nurses' innovative behaviours, and team-member exchange had a mediating effect on the relationship between leader-member exchange and innovative behaviour. CONCLUSIONS: Leader-member exchange and team-member exchange positively affect nurses' innovative behaviours. Leader-member exchange can promote nurses' innovative behaviours through the mediating role of team-member exchange. IMPACT: This study indicated that leader-member exchange and team-member exchange should be given more attention in promoting nurses' innovative behaviours. This finding has implications for the promotion of innovative behaviours in nurses. Leaders need to focus on the innovative needs of nurses and offer support. Meanwhile, leadership training programs are necessary for managers to create positive team relationships. PATIENT OR PUBLIC CONTRIBUTION: No patient or public involvement.


Asunto(s)
Liderazgo , Personal de Enfermería en Hospital , Humanos , Estudios Transversales , Adulto , Femenino , Masculino , China , Encuestas y Cuestionarios , Personal de Enfermería en Hospital/psicología , Relaciones Interprofesionales , Persona de Mediana Edad , Actitud del Personal de Salud
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