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Although anesthesia provides favorable conditions for surgical procedures, recent studies have revealed that the brain remains active in processing noxious signals even during anesthesia. However, whether and how these responses affect the anesthesia effect remains unclear. The ventrolateral periaqueductal gray (vlPAG), a crucial hub for pain regulation, also plays an essential role in controlling general anesthesia. Hence, it was hypothesized that the vlPAG may be involved in the regulation of general anesthesia by noxious stimuli. Here, we found that acute noxious stimuli, including capsaicin-induced inflammatory pain, acetic acid-induced visceral pain, and incision-induced surgical pain, significantly delayed recovery from sevoflurane anesthesia in male mice, whereas this effect was absent in the spared nerve injury-induced chronic pain. Pretreatment with peripheral analgesics could prevent the delayed recovery induced by acute nociception. Furthermore, we found that acute noxious stimuli, induced by the injection of capsaicin under sevoflurane anesthesia, increased c-Fos expression and activity in the GABAergic neurons of the ventrolateral periaqueductal gray. Specific reactivation of capsaicin-activated vlPAGGABA neurons mimicked the effect of capsaicin and its chemogenetic inhibition prevented the delayed recovery from anesthesia induced by capsaicin. Finally, we revealed that the vlPAGGABA neurons regulated the recovery from anesthesia through the inhibition of ventral tegmental area dopaminergic neuronal activity, thus decreasing dopamine (DA) release and activation of DA D1-like receptors in the brain. These findings reveal a novel, cell- and circuit-based mechanism for regulating anesthesia recovery by nociception, and it is important to provide new insights for guiding the management of the anesthesia recovery period.
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Anestésicos por Inhalación , Ratones Endogámicos C57BL , Nocicepción , Sustancia Gris Periacueductal , Sevoflurano , Sevoflurano/farmacología , Animales , Masculino , Ratones , Anestésicos por Inhalación/farmacología , Nocicepción/efectos de los fármacos , Nocicepción/fisiología , Sustancia Gris Periacueductal/efectos de los fármacos , Sustancia Gris Periacueductal/metabolismo , Mesencéfalo/efectos de los fármacos , Estado de Conciencia/efectos de los fármacos , Estado de Conciencia/fisiología , Periodo de Recuperación de la Anestesia , Capsaicina/farmacología , Neuronas GABAérgicas/efectos de los fármacos , Neuronas GABAérgicas/fisiologíaRESUMEN
Myelodysplastic neoplasms (MDSs) and chronic myelomonocytic leukemia (CMML) are clonal disorders driven by progressively acquired somatic mutations in hematopoietic stem cells (HSCs). Hypomethylating agents (HMAs) can modify the clinical course of MDS and CMML. Clinical improvement does not require eradication of mutated cells and may be related to improved differentiation capacity of mutated HSCs. However, in patients with established disease it is unclear whether (1) HSCs with multiple mutations progress through differentiation with comparable frequency to their less mutated counterparts or (2) improvements in peripheral blood counts following HMA therapy are driven by residual wild-type HSCs or by clones with particular combinations of mutations. To address these questions, the somatic mutations of individual stem cells, progenitors (common myeloid progenitors, granulocyte monocyte progenitors, and megakaryocyte erythroid progenitors), and matched circulating hematopoietic cells (monocytes, neutrophils, and naïve B cells) in MDS and CMML were characterized via high-throughput single-cell genotyping, followed by bulk analysis in immature and mature cells before and after AZA treatment. The mutational burden was similar throughout differentiation, with even the most mutated stem and progenitor clones maintaining their capacity to differentiate to mature cell types in vivo. Increased contributions from productive mutant progenitors appear to underlie improved hematopoiesis in MDS following HMA therapy.
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Leucemia Mielomonocítica Crónica , Síndromes Mielodisplásicos , Humanos , Leucemia Mielomonocítica Crónica/tratamiento farmacológico , Leucemia Mielomonocítica Crónica/genética , Leucemia Mielomonocítica Crónica/metabolismo , Síndromes Mielodisplásicos/tratamiento farmacológico , Síndromes Mielodisplásicos/genética , Células Madre Hematopoyéticas/metabolismo , Monocitos , Células ClonalesRESUMEN
Acute lung injury (ALI) is the pathophysiological precursor of acute respiratory distress syndrome. It is characterized by increased oxidative stress and exaggerated inflammatory response that disrupts redox reactions and immune homeostasis in the lungs, thereby posing significant clinical challenges. In this study, an internally functionalized thioether-enriched dendrimer Sr-G4-PEG is developed, to scavenge both proinflammatory cytokines and reactive oxygen species (ROS) and restore homeostasis during ALI treatment. The dendrimers are synthesized using an efficient and orthogonal thiol-ene "click" chemistry approach that involves incorporating thioether moieties within the dendritic architectures to neutralize the ROS. The ROS scavenging of Sr-G4-PEG manifests in its capacity to sequester proinflammatory cytokines. The synergistic effects of scavenging ROS and sequestering inflammatory cytokines by Sr-G4-PEG contribute to redox remodeling and immune homeostasis, along with the modulation of the NLRP3-pyroptosis pathway. Treatment with Sr-G4-PEG enhances the therapeutic efficacy of ALIs by alleviating alveolar bleeding, reducing inflammatory cell infiltration, and suppressing the release of inflammatory cytokines. These results suggest that Sr-G4-PEG is a potent nanotechnological candidate for remodeling redox and immune homeostasis in the treatment of ALIs, demonstrating the great potential of dendrimer-based nanomedicine for the treatment of respiratory pathologies.
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Lesión Pulmonar Aguda , Dendrímeros , Homeostasis , Oxidación-Reducción , Sulfuros , Dendrímeros/química , Lesión Pulmonar Aguda/tratamiento farmacológico , Lesión Pulmonar Aguda/metabolismo , Lesión Pulmonar Aguda/patología , Lesión Pulmonar Aguda/inmunología , Animales , Sulfuros/química , Especies Reactivas de Oxígeno/metabolismo , Ratones , Citocinas/metabolismo , Ratones Endogámicos C57BL , MasculinoRESUMEN
BACKGROUND: Gut microbiota (GM) have been implicated as important regulators of gastrointestinal symptom which is commonly occurred along with respiratory influenza A virus (IAV) infection, suggesting the involvement of the gut-to-lung axis in a host's response to IAV. IAV primarily destroys airway epithelium tight junctions (TJs) and consequently causes acute respiratory disease syndrome. It is known that GM and their metabolism produce an anti-influenza effect, but their role in IAV-induced airway epithelial integrity remains unknown. METHODS: A mouse model of IAV infection was established. GM were analyzed using 16S rRNA gene sequencing, and short-chain fatty acids (SCFAs) levels were measured. GM depletion and fecal microbiota transplantation (FMT) were conducted to validate the role of GM in IAV infection. A pair-feeding experiment was conducted to reveal whether IAV-induced GM dysbiosis is attributed to impaired food intake. Furthermore, human bronchial epithelial (HBE) cells were cocultured with IAV in the presence or absence of acetate. TJs function was analyzed by paracellular permeability and transepithelial electronic resistance (TEER). The mechanism of how acetate affects TJs integrity was evaluated in HBE cells transfected with G protein-coupled receptor 43 (GPR43) short hairpin RNA (shRNA). RESULTS: IAV-infected mice exhibited lower relative abundance of acetate-producing bacteria (Bacteroides, Bifidobacterium, and Akkermansia) and decreased acetate levels in gut and serum. These changes were partly caused by a decrease in food consumption (due to anorexia). GM depletion exacerbated and FMT restored IAV-induced lung inflammatory injury. IAV infection suppressed expressions of TJs (occludin, ZO-1) leading to disrupted airway epithelial barrier function as evidenced by decreased TEER and increased permeability. Acetate pretreatment activated GPR43, partially restored IAV-induced airway epithelial barrier function, and reduced inflammatory cytokines levels (TNF-α, IL-6, and IL-1ß). Such protective effects of acetate were absent in HBE cells transfected with GPR43 shRNA. Acetate and GPR43 improved TJs in an AMP-activated protein kinase (AMPK)-dependent manner. CONCLUSION: Collectively, our results demonstrated that GM protected airway TJs by modulating GPR43-AMPK signaling in IAV-induced lung injury. Therefore, improving GM dysbiosis may be a potential therapeutic target for patients with IAV infection.
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Acetatos , Microbioma Gastrointestinal , Lesión Pulmonar , Infecciones por Orthomyxoviridae , Uniones Estrechas , Animales , Uniones Estrechas/metabolismo , Microbioma Gastrointestinal/efectos de los fármacos , Acetatos/metabolismo , Humanos , Infecciones por Orthomyxoviridae/complicaciones , Ratones Endogámicos C57BL , Virus de la Influenza A , Trasplante de Microbiota Fecal , Receptores Acoplados a Proteínas G/metabolismo , Ratones , Células Epiteliales/metabolismo , Disbiosis , Ácidos Grasos Volátiles/metabolismoRESUMEN
PURPOSE: Well-differentiated papillary peritoneal mesothelial tumors (WDPMTs) are understudied and discrete from peritoneal mesotheliomas (PMs). We report clinicopathologic characteristics and outcomes of a large prospective WDPMT cohort. METHODS: Patients with WDPMT identified between August 2007 and December 2020 were followed through January 2023. Clinical characteristics and outcomes were annotated. Overall survival (OS) was assessed from pathologic diagnosis. Germline variants were analyzed, and targeted next-generation sequencing (NGS; MSK-IMPACT) data were compared to PMs and diffuse pleural mesotheliomas (DPMs). RESULTS: Among 54 patients, median age at diagnosis was 55 (range 20-76), 50% were female (n = 27), and 46% were smokers (n = 25; median 8 pack/years). Most (94%, n = 51) WDPMTs were found during surgical explorations for other indications, primarily other malignancies. Two patients underwent surgical resection for WDPMT; none received systemic therapy for WDPMT. Median OS was not reached (19/54; median follow up 4.5 years). Somatic NGS was available for 35% (19/54) of patients. TRAF7 alterations were enriched in WDPMT (89%; 17/19) compared with PM (0%; 0/50; p < 0.0001) and DPM (0%; 0/74; p < 0.0001). In WDPMT compared with PM and DPM, there were less BAP1 (0% [0/0] vs. 4% [8/50] vs. 46% [34/74]; p = 0.001 and p < 0.0001, respectively) and NF2 (0% [0/0] vs. 24% [12/50] vs. 31% [23/74]; p = 0.03 and p = 0.001 respectively) alterations. Pathogenic germline variants were present in 23% (4/17) of WDPMTs. CONCLUSIONS: Well-differentiated papillary peritoneal mesothelial tumors were primarily incidental findings. There was no WDPMT-related mortality, so there was no distinct role for routine cytoreductive surgery or systemic therapy. Genomic profiles can help to differentiate WDPMT from DPM and PM.
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Neoplasias Peritoneales , Humanos , Femenino , Persona de Mediana Edad , Neoplasias Peritoneales/terapia , Neoplasias Peritoneales/patología , Neoplasias Peritoneales/mortalidad , Masculino , Adulto , Anciano , Tasa de Supervivencia , Adulto Joven , Estudios de Seguimiento , Estudios Prospectivos , Pronóstico , Biomarcadores de Tumor/genética , Biomarcadores de Tumor/metabolismo , Mesotelioma/patología , Mesotelioma/mortalidad , Mesotelioma/terapia , Neoplasias Mesoteliales/patología , Neoplasias Mesoteliales/genéticaRESUMEN
In current optical systems, defocus blur is inevitable due to the constrained depth of field. However, it is difficult to accurately identify the defocus amount at each pixel position as the point spread function changes spatially. In this paper, we introduce a histogram-invariant spatial aliasing sampling method for reconstructing all-in-focus images, which addresses the challenge of insufficient pixel-level annotated samples, and subsequently introduces a high-resolution network for estimating spatially varying defocus maps from a single image. The accuracy of the proposed method is evaluated on various synthetic and real data. The experimental results demonstrate that our proposed model outperforms state-of-the-art methods for defocus map estimation significantly.
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BACKGROUND: Influenza A viruses (IAV) are extremely common respiratory viruses for the acute exacerbation of chronic obstructive pulmonary disease (AECOPD), in which IAV infection may further evoke abnormal macrophage polarization, amplify cytokine storms. Melatonin exerts potential effects of anti-inflammation and anti-IAV infection, while its effects on IAV infection-induced AECOPD are poorly understood. METHODS: COPD mice models were established through cigarette smoke exposure for consecutive 24 weeks, evaluated by the detection of lung function. AECOPD mice models were established through the intratracheal atomization of influenza A/H3N2 stocks in COPD mice, and were injected intraperitoneally with melatonin (Mel). Then, The polarization of alveolar macrophages (AMs) was assayed by flow cytometry of bronchoalveolar lavage (BAL) cells. In vitro, the effects of melatonin on macrophage polarization were analyzed in IAV-infected Cigarette smoking extract (CSE)-stimulated Raw264.7 macrophages. Moreover, the roles of the melatonin receptors (MTs) in regulating macrophage polarization and apoptosis were determined using MTs antagonist luzindole. RESULTS: The present results demonstrated that IAV/H3N2 infection deteriorated lung function (reduced FEV20,50/FVC), exacerbated lung damages in COPD mice with higher dual polarization of AMs. Melatonin therapy improved airflow limitation and lung damages of AECOPD mice by decreasing IAV nucleoprotein (IAV-NP) protein levels and the M1 polarization of pulmonary macrophages. Furthermore, in CSE-stimulated Raw264.7 cells, IAV infection further promoted the dual polarization of macrophages accompanied with decreased MT1 expression. Melatonin decreased STAT1 phosphorylation, the levels of M1 markers and IAV-NP via MTs reflected by the addition of luzindole. Recombinant IL-1ß attenuated the inhibitory effects of melatonin on IAV infection and STAT1-driven M1 polarization, while its converting enzyme inhibitor VX765 potentiated the inhibitory effects of melatonin on them. Moreover, melatonin inhibited IAV infection-induced apoptosis by suppressing IL-1ß/STAT1 signaling via MTs. CONCLUSIONS: These findings suggested that melatonin inhibited IAV infection, improved lung function and lung damages of AECOPD via suppressing IL-1ß/STAT1-driven macrophage M1 polarization and apoptosis in a MTs-dependent manner. Melatonin may be considered as a potential therapeutic agent for influenza virus infection-induced AECOPD.
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Apoptosis , Subtipo H3N2 del Virus de la Influenza A , Melatonina , Enfermedad Pulmonar Obstructiva Crónica , Animales , Melatonina/farmacología , Enfermedad Pulmonar Obstructiva Crónica/tratamiento farmacológico , Enfermedad Pulmonar Obstructiva Crónica/metabolismo , Enfermedad Pulmonar Obstructiva Crónica/virología , Enfermedad Pulmonar Obstructiva Crónica/fisiopatología , Ratones , Apoptosis/efectos de los fármacos , Células RAW 264.7 , Subtipo H3N2 del Virus de la Influenza A/efectos de los fármacos , Infecciones por Orthomyxoviridae/tratamiento farmacológico , Infecciones por Orthomyxoviridae/metabolismo , Infecciones por Orthomyxoviridae/inmunología , Ratones Endogámicos C57BL , Masculino , Macrófagos/efectos de los fármacos , Macrófagos/metabolismo , Progresión de la Enfermedad , Polaridad Celular/efectos de los fármacos , Modelos Animales de Enfermedad , Macrófagos Alveolares/efectos de los fármacos , Macrófagos Alveolares/metabolismo , Macrófagos Alveolares/virologíaRESUMEN
This investigation validated iodine binding in combination with lintnerization for studying the structural nature of the amorphous areas in starch granules. Lintners of four iodine vapor-stained and non-stained amylose-containing starches and their waxy counterparts were analyzed by high-performance anion-exchange chromatography (HPAEC). The composition of the lintners was strongly affected by the absence of amylose in barley and potato starch but not in maize and cassava starch. Iodine-stained waxy lintners possessed increased number of long B2 chains. ß-Limit dextrins of the lintners were very variable in composition. Iodine inclusion complexes washed out from the granular residues in the lintners (mostly from amylose-containing barley and maize starches) were also analyzed. Acid-soluble complexes from both amylose-containing and waxy starches possessed a lot of material with a degree of polymerization (DP) around 60 and a periodicity in size of DP 8-12. Such long chains were only minor components in water-soluble complexes of amylose-containing barley and maize starch lintners, and they lacked the size periodicity. Models of the principal structure of the acid and water-soluble complexes are suggested. It is concluded that acid hydrolysis of iodine-stained starch granules is a useful tool in structural analyses of the molecular composition of amorphous parts of starch granules.
RESUMEN
Structural nature of glucan chains in the amorphous part of granular starch was examined by iodine vapor treatment and lintnerization. Four iodine-stained amylose-containing normal starches and their waxy counterparts were examined under a microscope before, during, and after lintnerization. The presence of amylose retarded the lintnerization rate. The degree of retardation correlated with the structural type of the amylopectin component, suggesting that potato amylopectin (type 4 structure) interacts with amylose in the granules, whereas in barley granules (type 1 structure) the interaction is very weak. The inclusion complexes with iodine were not degraded by the acid treatment. Therefore, the iodine-glucan chain complex formation could be used to study the structural nature of the flexible, amorphous parts of the starch granules. Indeed, at the end of lintnerization, when 20%-30% of the granules remained, substantial amounts of blue-stained complexes were washed out from the granules especially from amylose-containing barley and maize starch, but also from both normal and waxy cassava and potato starch. The complexation with iodine did not affect the rate of lintnerization. This suggested that single helical structures were present during lintnerization also in the absence of iodine and this conformation was the reason for the acid resistance.
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BACKGROUND: A common complication of wounds is exuberant growth of fibrotic scar tissue, which can lead to hypertrophic scars or keloids. There are currently no treatments with good evidence for preventing excessive scar tissue formation. In this study, we explored the use of microneedle patches containing siRNA inhibiting SPARC mRNA in reducing the volume of post-surgical scars. OBJECTIVE: We aim to compare the differences in the volume of post-surgical scars between daily application of siRNA-embedded dissolving microneedle patches and silicone sheets. The primary study outcome measure was the 3D volume of scar elevation.Our hypothesis was that scar formation in the half of the wound treated with siRNA microneedle patches will be lesser, as reflected by a smaller 3D volume, as compared to the half treated with silicone sheets. METHODS: This was an 8-week, single-blinded intra-individually controlled randomised trial in a tertiary dermatological centre. Patients with two-week-old post-operative wounds were recruited. Each half of the scar was randomly assigned to the microneedle patch or silicone sheet. Three-dimensional (3D) volumes were obtained from the scars via a high-resolution scanner at day 0, 30 and 60. RESULTS: At day 30, scars treated with the microneedle patches had a lower geometric mean volume of 0.79mm3 when compared to scars treated with silicone sheets, with a difference in mean percentage volume reduction of 10.70%.At day 60, scars treated with the microneedle patches had a statistically significant lower volume (8.88mm3) when compared to the side treated with silicone sheets (12.77mm3, p=0.005), with a difference in mean percentage reduction of 9.66%. Additionally, there was also a statistically significant difference between the percentage reduction in scar volume, compared to baseline, on the side treated with microneedle patches (mean=83.78%) compared to the side treated with silicone sheets (mean=74.11%). CONCLUSIONS: There was a significantly greater reduction in the volume of post-surgical scars on the side treated with microneedle patches compared to the side treated with silicone sheets. This demonstrates the use of transdermal gene silencing technology for scar inhibition and that siRNA microneedle patches can be an effective and safe modality in the reduction of scar tissue formation. TRIAL REGISTRATION: Australian New Zealand Clinical Trials Registry (ANZCTR), ACTRN12622000558729, https://www.anzctr.org.au.
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Phosphodiesterase 8 (PDE8), as a member of PDE superfamily, specifically promotes the hydrolysis and degradation of intracellular cyclic adenosine monophosphate (cAMP), which may be associated with pathogenesis of Alzheimer's disease (AD). However, little is currently known about potential role in the central nervous system (CNS). Here we investigated the distribution and expression of PDE8 in brain of mouse, which we believe can provide evidence for studying the role of PDE8 in CNS and the relationship between PDE8 and AD. Here, C57BL/6J mice were used to observe the distribution patterns of two subtypes of PDE8, PDE8A and PDE8B, in different sexes in vivo by western blot (WB). Meanwhile, C57BL/6J mice were also used to demonstrate the distribution pattern of PDE8 in selected brain regions and localization in neural cells by WB and multiplex immunofluorescence staining. Furthermore, the triple transgenic (3×Tg-AD) mice and wild type (WT) mice of different ages were used to investigate the changes of PDE8 expression in the hippocampus and cerebral cortex during the progression of AD. PDE8 was found to be widely expressed in multiple tissues and organs including heart, kidney, stomach, brain, and liver, spleen, intestines, and uterus, with differences in expression levels between the two subtypes of PDE8A and PDE8B, as well as two sexes. Meanwhile, PDE8 was widely distributed in the brain, especially in areas closely related to cognitive function such as cerebellum, striatum, amygdala, cerebral cortex, and hippocampus, without differences between sexes. Furthermore, PDE8A was found to be expressed in neuronal cells, microglia and astrocytes, while PDE8B is only expressed in neuronal cells and microglia. PDE8A expression in the hippocampus of both female and male 3×Tg-AD mice was gradually increased with ages and PDE8B expression was upregulated only in cerebral cortex of female 3×Tg-AD mice with ages. However, the expression of PDE8A and PDE8B was apparently increased in both cerebral cortex and hippocampus in both female and male 10-month-old 3×Tg-AD mice compared WT mice. These results suggest that PDE8 may be associated with the progression of AD and is a potential target for its prevention and treatment in the future.
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3',5'-AMP Cíclico Fosfodiesterasas , Enfermedad de Alzheimer , Ratones Endogámicos C57BL , Ratones Transgénicos , Animales , Femenino , Masculino , Ratones , 3',5'-AMP Cíclico Fosfodiesterasas/metabolismo , 3',5'-AMP Cíclico Fosfodiesterasas/genética , Enfermedad de Alzheimer/metabolismo , Encéfalo/metabolismo , Hipocampo/metabolismoRESUMEN
Although rapid progression and a poor prognosis in influenza A virus (IAV) infection-induced acute exacerbation of chronic obstructive pulmonary disease (AECOPD) are frequently associated with metabolic energy disorders, the underlying mechanisms and rescue strategies remain unknown. We herein demonstrated that the level of resting energy expenditure increased significantly in IAV-induced AECOPD patients and that cellular energy exhaustion emerged earlier and more significantly in IAV-infected primary COPD bronchial epithelial (pDHBE) cells. The differentially expressed genes were enriched in the oxidative phosphorylation (OXPHOS) pathway; additionally, we consistently uncovered much earlier ATP exhaustion, more severe mitochondrial structural destruction and dysfunction, and OXPHOS impairment in IAV-inoculated pDHBE cells, and these changes were rescued by melatonin. The level of OMA1-dependent cleavage of OPA1 in the mitochondrial inner membrane and the shift in energy metabolism from OXPHOS to glycolysis were significantly increased in IAV-infected pDHBE cells; however, these changes were rescued by OMA1-siRNA or melatonin further treatment. Collectively, our data revealed that melatonin rescued IAV-induced cellular energy exhaustion via OMA1-OPA1-S to improve the clinical prognosis in COPD. This treatment may serve as a potential therapeutic agent for patients in which AECOPD is induced by IAV.
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Metabolismo Energético , GTP Fosfohidrolasas , Virus de la Influenza A , Melatonina , Enfermedad Pulmonar Obstructiva Crónica , Humanos , Metabolismo Energético/efectos de los fármacos , GTP Fosfohidrolasas/metabolismo , GTP Fosfohidrolasas/genética , Virus de la Influenza A/efectos de los fármacos , Gripe Humana/metabolismo , Gripe Humana/tratamiento farmacológico , Melatonina/farmacología , Metaloendopeptidasas , Fosforilación Oxidativa/efectos de los fármacos , Enfermedad Pulmonar Obstructiva Crónica/metabolismo , Enfermedad Pulmonar Obstructiva Crónica/tratamiento farmacológicoRESUMEN
This study examines the impact of Notoginsenoside R1 (NGR1), a compound from Panax notoginseng, on the maturation of porcine oocytes and their embryonic development, focusing on its effects on antioxidant levels and mitochondrial function. This study demonstrates that supplementing in vitro maturation (IVM) medium with NGR1 significantly enhances several biochemical parameters. These include elevated levels of glutathione (GSH), nuclear factor erythrocyte 2-related factor 2 (NRF2) and mRNA expression of catalase (CAT) and GPX. Concurrently, we observed a decrease in reactive oxygen species (ROS) levels and an increase in JC-1 immunofluorescence, mitochondrial distribution, peroxisome proliferator-activated receptor-γ coactivator-1α (PGC1α) and nuclear NRF2 mRNA levels. Additionally, there was an increase in ATP production and lipid droplets (LDs) immunofluorescence. These biochemical improvements correlate with enhanced embryonic outcomes, including a higher blastocyst rate, increased total cell count, enhanced proliferative capacity and elevated octamer-binding transcription factor 4 (Oct4) and superoxide dismutase 2 (Sod2) gene expression. Furthermore, NGR1 supplementation resulted in decreased apoptosis, reduced caspase 3 (Cas3) and BCL2-Associated X (Bax) mRNA levels and decreased glucose-regulated protein 78 kD (GRP78) immunofluorescence in porcine oocytes undergoing in vitro maturation. These findings suggest that NGR1 plays a crucial role in promoting porcine oocyte maturation and subsequent embryonic development by providing antioxidant levels and mitochondrial protection.
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Antioxidantes , Desarrollo Embrionario , Ginsenósidos , Técnicas de Maduración In Vitro de los Oocitos , Mitocondrias , Oocitos , Animales , Antioxidantes/farmacología , Ginsenósidos/farmacología , Técnicas de Maduración In Vitro de los Oocitos/veterinaria , Mitocondrias/efectos de los fármacos , Desarrollo Embrionario/efectos de los fármacos , Oocitos/efectos de los fármacos , Femenino , Porcinos , Especies Reactivas de Oxígeno/metabolismo , Técnicas de Cultivo de Embriones/veterinariaRESUMEN
PURPOSE: To compare the outcomes of type II pediatric phalangeal neck fractures (PPNFs) treated with closed reduction and cast immobilization (CRCI) versus closed reduction percutaneous pinning (CRPP), and evaluated the clinical efficacy of conservative versus surgical treatment of type II PPNFs via meta-analysis. METHODS: Patients aged ≤ 14 years with type II PPNFs were divided into conservative (CRCI) and operative (CRPP) groups. Radiographs measured angulation and translation; hand function was assessed with total active range of motion (TAM) and Quick-DASH. Complication rates were also compared between the groups. A meta-analysis of conservative versus operative treatment confirmed the clinical results. Statistical analysis was performed using SPSS 26.0 and R studio 3.0 with two-tailed, chi-squared, and Mann-Whitney U or t-tests, P < 0.05. Meta-analysis used fixed or random effects models, calculating mean differences and odds ratios for outcomes, and assessing heterogeneity with I2 and Q tests. RESULTS: Final angulation (3.4° ± 3.7° and 4.9° ± 5.4° vs. 3.6° ± 3.7° and 4.2° ± 4.3°) and displacement (6.3% ± 5.8% and 5.7% ± 4.7% vs. 5.8% ± 5.5% and 3.2% ± 4.2%) in the coronal and sagittal planes were not different statistically between the conservative and surgical groups (P > 0.05), but improved significantly compared to preoperative values (P < 0.05). Although Quick-DASH scores were comparable in both groups (P = 0.105), conservatively treated patients had a significantly better TAM at the last follow-up visit (P = 0.005). The complication rates were 24.2% and 41.7% in the surgical and conservatively treated groups respectively (P = 0.162). However, the latter primarily experienced imaging-related complications, whereas the former experienced functional complications (P = 0.046). Our meta-analysis (n = 181 patients) also showed comparable functional (P = 0.49) and radiographic (P = 0.59) outcomes and complication rates (P = 0.21) between the surgical (94 patients) and conservative (87 patients) groups. CONCLUSIONS: Conservative and surgical treatments are both reliable and safe approaches for managing type II PPNF in children. However, conservatively treated patients generally experience similar radiographic outcomes, lower complication rates, and better functional outcomes than surgically treated ones.
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Hilos Ortopédicos , Moldes Quirúrgicos , Falanges de los Dedos de la Mano , Humanos , Niño , Falanges de los Dedos de la Mano/lesiones , Falanges de los Dedos de la Mano/cirugía , Masculino , Femenino , Adolescente , Fijación Interna de Fracturas/métodos , Fijación Interna de Fracturas/instrumentación , Fijación Interna de Fracturas/efectos adversos , Resultado del Tratamiento , Fracturas Óseas/cirugía , Rango del Movimiento Articular , PreescolarRESUMEN
BACKGROUND: Prior studies have indicated team members' interaction behaviors may predict creativity among nursing students. METHODS: This study investigated the correlation between interaction behaviors and creativity, both individual- and team-level, among nursing students. In this cross-sectional quantitative study, data were obtained from self-reported questionnaires. Individual creativity was assessed using the Torrance Tests of Creative Thinking scale; the perceived team interaction behavior and team creativity were assessed using validated instruments. Canonical correlation analysis was conducted to determine the overall correlation between interaction behaviors, and creativity, and the moderating effect of female proportion dominance was also examined. RESULTS: A total of 164 nursing students (84.1% female) arranged into 14 teams were included in this study. Canonical correlation analysis showed a positive correlation between interaction behaviors and creativity (correlation = 0.88). All dimensions of interactive behaviors were positively related to creativity dimensions. A stronger correlation to team creativity (correlation = 1) was found compared to individual creativity (correlation = 0.07). This study demonstrated that individual interactive behaviors including spontaneous communication and helping behavior predicted high team creativity. CONCLUSIONS: This insight may be valuable for nursing education programs seeking to foster creativity and effective teamwork. The potential moderating effect of female proportions on team interaction behaviors and creativity should be investigated further.
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This study aims to investigate whether the current wound classifications were valid for the treatment prognosis of subjects treated for limb-threatening diabetic foot ulcers (LTDFU). A total of 1548 patients with LTDFU and infection were studied, with wounds recorded using the Wagner, Texas, PEDIS and WIfI classifications while major lower extremity amputations (LEAs) or in-hospital mortality incidences were defined as poor outcomes. Among them, 153 (9.9%) patients received major LEAs and 38 (2.5%) patients died. After adjustments, the Wagner classification and Texas stage as well as clinical factors such as comorbidity with major adverse cardiac events (MACE), being under dialysis and having serum levels of C-reactive protein (CRP) and albumin were independent factors for prognosis. For patients without dialysis, Wagner and Texas stage stood out independently for prognosis. For patients on dialysis, only levels of CRP (odds ratio [OR] = 2.2 in Wagner, OR = 2.0 in WIfI, OR = 2.2 in Texas, OR = 2.3 in PEDIS) and albumin (OR = 0.4 in four classifications) were valid predictors. The Wagner system and Texas stage were valid for predicting prognosis in treatment for LTDFUs, suggesting a role of vascular perfusion. MACE history, levels of CRP and albumin level should assist in prediction; more significantly, only levels of CRP and albumin appeared valid for those subjects undergoing dialysis.
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Diabetes Mellitus , Pie Diabético , Humanos , Pie Diabético/cirugía , Factores de Riesgo , Cicatrización de Heridas , Pronóstico , Extremidad Inferior , Recuperación del Miembro/efectos adversos , Albúminas , Estudios Retrospectivos , Isquemia/terapia , Resultado del TratamientoRESUMEN
BACKGROUND & PROBLEMS: Urinary tract infection (UTI), one of the most common types of healthcare-associated infections, is associated with increased hospital stay durations and healthcare costs. Our unit is located in the internal medicine ward of a medical center. In 2020, infection control data revealed a rise in the UTI rate to 2.03‱, which was higher than the hospital-wide average of 1.52‱. This prompted the initiation of this improvement project. PURPOSE: The aim of this study was to develop effective solutions to address UTI-related issues, improve the knowledge and skills of nurses and caregivers involved in UTI care, reduce indwelling catheter duration and environmental sources of infection, and, ultimately, decrease the incidence of UTIs in our ward. RESOLUTIONS: Through problem analysis, nurses and caregivers were found to lack sufficient UTI-care-related knowledge and skills, leading to an increase in infection cases. A UTI assessment and standardized workflow were developed. Self-learning materials were provided, and regular assessments were conducted. Urine bag labels and bilingual perineal hygiene videos were designed. In addition, an antimicrobial bed scale was developed to reduce the potential sources of infection. RESULTS: Six months after project implementation, a significant improvement was found in the accuracy of UTI care among nurses and caregivers. The average indwelling catheter duration decreased to 4.7 days and the UTI rate dropped to 1.48‱, successfully achieving the project goals. CONCLUSIONS: The authors recommend incorporating UTI-prevention knowledge and skills into pre-employment training and promoting the use of antimicrobial bed scales to significantly reduce the incidence of UTIs.
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Antiinfecciosos , Infección Hospitalaria , Humanos , Hospitales , Control de Infecciones , Medicina InternaRESUMEN
Numerous insects including pests and beneficial species undertake windborne migrations over hundreds of kilometers. In East Asia, climate-induced changes in large-scale atmospheric circulation systems are affecting wind-fields and precipitation zones and these, in turn, are changing migration patterns. We examined the consequences in a serious rice pest, the brown planthopper (BPH, Nilaparvata lugens) in East China. BPH cannot overwinter in temperate East Asia, and infestations there are initiated by several waves of windborne spring or summer migrants originating from tropical areas in Indochina. The East Asian summer monsoon, characterized by abundant rainfall and southerly winds, is of critical importance for these northward movements. We analyzed a 42-year dataset of meteorological parameters and catches of BPH from a standardized network of 341 light-traps in South and East China. We show that south of the Yangtze River during summer, southwesterly winds have weakened and rainfall increased, while the summer precipitation has decreased further north on the Jianghuai Plain. Together, these changes have resulted in shorter migratory journeys for BPH leaving South China. As a result, pest outbreaks of BPH in the key rice-growing area of the Lower Yangtze River Valley (LYRV) have declined since 2001. We show that these changes to the East Asian summer monsoon weather parameters are driven by shifts in the position and intensity of the Western Pacific subtropical high (WPSH) system that have occurred during the last 20 years. As a result, the relationship between WPSH intensity and BPH immigration that was previously used to predict the size of the immigration to the LYRV has now broken down. Our results demonstrate that migration patterns of a serious rice pest have shifted in response to the climate-induced changes in precipitation and wind pattern, with significant consequences for the population management of migratory pests.
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Hemípteros , Oryza , Tiempo (Meteorología) , China , AnimalesRESUMEN
OBJECTIVES: Neisseria meningitidis is one of the major pathogens of meningitis in children worldwide and causes invasive meningococcal disease (IMD), which is a critical illness that mainly presents as meningitis and/or septicemia in children. Identification of N. meningitidis in cerebrospinal fluid (CSF) is the gold standard for the diagnosis of meningococcal meningitis, but antigen tests have advantages such as timely results, relatively low cost, and convenience. Yet, the diagnostic accuracy of antigen tests remains uncertain. Therefore, the aim of this meta-analysis was to evaluate the diagnostic accuracy of antigen tests for N. meningitidis in CSF. METHODS: We searched the PubMed, Embase, and Cochrane Library databases for studies evaluating the diagnostic accuracy of antigen tests for N. meningitidis in CSF. We included studies that provided sufficient data to construct a 2 × 2 table on a per-sample basis. To determine the overall sensitivity and specificity of the antigen tests, we used polymerase chain reaction (PCR) as the reference standard and employed the hierarchical summary receiver operating characteristic model. RESULTS: Nine studies with 4533 CSF samples were included. The meta-analysis yielded a pooled sensitivity of 91.2% (95% confidence interval [CI]: 80.0%-100.0%) and a pooled specificity of 93.8% (95% CI: 83.9%-100.0%). A subgroup analysis of 2 studies that reported the outcomes of MeningoSpeed yielded a pooled sensitivity of 93.4% (95% CI: 90.0%-95.8%) and a pooled specificity of 91.9% (95% CI: 88.6%-94.4%). Antigen testing for the N. meningitidis serogroup X had a pooled sensitivity of 92.4% (95% CI: 85.2%-96.2%) and a pooled specificity of 99.2% (95% CI: 78.7%-100.0%). CONCLUSIONS: The studied antigen tests had high sensitivity and specificity for the diagnosis of meningococcal meningitis in CSF specimens. Antigen testing could serve as an accurate diagnostic method for assessing patients who have a suspected N. meningitidis infection.
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AIMS: We aimed to assess the eradication efficacy and factors that influencing it of high-dose dual therapy (HDDT) in Gansu region, Northwest China. METHODS: A total of 216 treatment-naive patients with Helicobacter pylori infection were randomly assigned to two groups for the 14-day eradication treatment: the HDDT group (amoxicillin 750 mg q.i.d. and esomeprazole 40 mg t.i.d.) and the amoxicillin and clarithromycin-containing bismuth quadruple therapy group (ACBQT: esomeprazole 20 mg, bismuth potassium citrate 2 g, amoxicillin 1 g, and clarithromycin 500 mg; b.i.d.). The eradication rates, adverse effects and patient compliance of these two groups were compared. Eradication efficacy was determined by 13 C urea breath test (13 C UBT) 4-8 weeks after finishing treatment. Antibiotic resistance was determined by the Epsilometer testing (E-test) method. RESULTS: The eradication rates for the HDDT and ACBQT groups were 71.0% and 74.7% (P = .552) by per-protocol analysis, and 65.7% and 68.5% (P = .664) by intention-to-treat analysis. The overall adverse event rates in the HDDT and ACBQT groups were 2.0% and 43.4% (P < .001), respectively. The resistance rates to amoxicillin, clarithromycin, tetracycline, levofloxacin and metronidazole were 15.2%, 42.0%, 5.4%, 35.7% and 83.0%, respectively. Amoxicillin resistance and delta over baseline (DOB) of 13 C UBT ≥ 20 before treatment significantly reduced the eradication rate in 112 participants with H. pylori cultured. CONCLUSION: The HDDT as first-line treatment for H. pylori was unsatisfactory in Gansu. Amoxicillin resistance and DOB of 13 C UBT ≥ 20 before treatment were significantly correlated with H. pylori eradication failure.