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Smartphone distraction (SD) is closely related to depression, and the prevalence of SD among nursing students is gradually increasing. However, the potential mechanism of the effect of SD on nursing students' depression is unclear. A total of 574 nursing students were assessed using Smartphone Distraction Scale, Ruminative Response Scale, Hikikomori Questionnaire, and Patient Health Questionnaire-9. The results indicated that SD among nursing students had an impact on depression through four pathways: (1) SD was positively associated with depression (ß = 0.353, P < 0.001); (2) Rumination (ß = 0.199, 95% CI: 0.081 to 0.162) and social withdrawal (ß = 0.061, 95% CI: 0.034 to 0.091) mediated the effects of SD on depression, respectively; and (3) Rumination and social withdrawal played a chain mediating role in the effect of SD on nursing students' depression (ß = 0.027, 95% CI: 0.015 to 0.042). The negative impact of SD on nursing students' mental health should not be taken lightly. Schools and hospitals should guide nursing students to use smartphones correctly, including providing mental health education and professional psychological counselling; families could play a supervisory role and communicate regularly to understand the psychological state and learning of nursing students. These measures can help nursing students cope with stress and reduce the risk of depression.
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Depresión , Rumiación Cognitiva , Teléfono Inteligente , Aislamiento Social , Estudiantes de Enfermería , Femenino , Humanos , Masculino , Adulto Joven , China/epidemiología , Depresión/epidemiología , Depresión/psicología , Pueblos del Este de Asia , Aislamiento Social/psicología , Estudiantes de Enfermería/psicología , Encuestas y CuestionariosRESUMEN
BACKGROUND: Identifying high-risk populations and promoting stroke prevention measures can be achieved through studies on stroke and its risk factors. As a new alternative indicator of insulin resistance (IR), the triglyceride glucose (TyG) index may potentially increase stroke risk. However, the evidence confirming this association is inadequate and inconsistent, possibly due to variations in stroke assessment criteria or characteristics of the study populations. This study aims to evaluate the association between the TyG index and stroke risk level among individuals with normal-weight. METHODS: A total of 30,895 participants aged ≥ 40 years with normal-weight were enrolled in this study. The TyG index was calculated as Ln [fasting triglycerides (mg/dL) × fasting glucose (mg/dL)/2]. Normal-weight was described as a body mass index (BMI) of 18.5-<24.0 kg/m2. Stroke risk was assessed by the Stroke Risk Assessment Scale, developed by the China National Stroke Screening and Prevention Project. To evaluate the associations between the TyG index and stroke risk level, multivariate logistic regression models were employed. RESULTS: Results showed that when the TyG index was considered as a continuous variable, each one unit increase in the TyG index was associated with a significantly higher risk of stroke [Moderate-risk (OR, 2.15; 95% CI, 2.03-2.28; P<0.001); High-risk (OR, 3.83; 95% CI, 3.57-4.10; P<0.001)]. Compared with Q1 of the TyG index, Q4 was significantly associated with moderate stroke risk (OR, 2.73; 95% CI, 2.50-2.99; P<0.001) and high stroke risk (OR, 5.39; 95% CI, 4.83-6.01; P<0.001). The continuous TyG index was an important risk factor for high stroke risk in the metabolically obese, normal-weight (MONW) individuals (OR, 3.44;95% CI, 2.92-4.06; P < 0.001). In the MONW individuals, when Q1 was used as a reference, participants in Q4 (OR, 5.33; 95% CI, 4.19-6.78; P < 0.001) was significantly associated with high stroke risk. Subgroup analysis showed significant interaction in the age and sex subgroups in the overall population (Pinteraction <0.001). CONCLUSION: The risk of stroke is increased with the TyG index among Chinese adults of normal weight; hence, the index may be an important indicator for identifying high-risk stroke populations among individuals with normal body weight.
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OBJECTIVE: This study aims to explore the psychological distress course of Chinese amyotrophic lateral sclerosis (ALS) patients after the onset of the disease and to provide targeted nursing guidance. DESIGN: The interview content was analysed qualitatively. We used seven steps of Colaizzi's method to analyse the participants' data. SETTING: Wuhan, China, Traditional Chinese Medicine Hospital. PARTICIPANTS: A semistructured face-to-face interview were performed among 22 people with ALS from the motor neuron disease rehabilitation centre of a tertiary Chinese medicine hospital in China. RESULT: This study included a total of 22 participants, from whom three main themes regarding the psychological distress trajectory of ALS patients were extracted from the interview data: 'Time begins to run out' include tormented and restless waiting and shock and doubt in ALS disease confirmation, 'Family out of control' include the burden of stigma and function loss, the burden of missing family roles, the burden of marriage's emotional needs and the burden of offspring health, 'Way forward' include struggle between live and death and struggle between quality of life and the value of life. CONCLUSION: This study outlines the psychologically distressing journey of ALS patients. Studies have pointed out the need for targeted care to address patients' various sources of psychological distress to improve their quality of life and coping ability, increase their psychological resilience and reconstruct their life beliefs.
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Esclerosis Amiotrófica Lateral , Distrés Psicológico , Investigación Cualitativa , Calidad de Vida , Humanos , Esclerosis Amiotrófica Lateral/psicología , Femenino , Masculino , China , Persona de Mediana Edad , Adulto , Anciano , Estrés Psicológico/psicología , Entrevistas como Asunto , Estigma Social , Adaptación PsicológicaRESUMEN
OBJECTIVES: To examine clinically important adverse events (AEs) associated with methylphenidate (MPH) treatment of apathy in Alzheimer's Disease (AD) versus placebo, including weight loss, vital signs, falls, and insomnia. METHODS: The Apathy in Dementia Methylphenidate Trial 2 (ADMET2) trial was a multicenter randomized, placebo-controlled trial of MPH to treat apathy in individuals with apathy and AD. Participants in ADMET2 had vital signs and weight measured at monthly visits through 6 months. AEs, including insomnia, falls, and cardiovascular events, were reported at every visit by participants and families using a symptom checklist. RESULTS: The study included 98 participants in the MPH group and 101 in the placebo group. Participants in the MPH group experienced greater weight loss on average than the placebo through the 6-month follow-up, with a difference in change between MPH and placebo of 2.8 lb (95% confidence interval, CI: 0.7, 4.9 lb). No treatment group differences in change during the trial were found in systolic and diastolic blood pressure. More participants in the MPH group reported falls during the follow-up, 10 versus 6 in MPH and placebo groups, respectively. No differences in post-baseline insomnia were observed between the treatment groups. No participants reported instances of myocardial infarction, congestive heart failure, arrhythmia, stroke, or cardiomyopathy throughout the study period. CONCLUSIONS: MPH use in AD patients for treating apathy is relatively safe, particularly notable given the many medical comorbidities in this population. There was a statistically significant but modest weight loss associated with MPH use, and clinicians are thus advised to monitor weight during MPH treatment.
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Accidentes por Caídas , Enfermedad de Alzheimer , Apatía , Estimulantes del Sistema Nervioso Central , Metilfenidato , Pérdida de Peso , Humanos , Enfermedad de Alzheimer/tratamiento farmacológico , Metilfenidato/uso terapéutico , Metilfenidato/efectos adversos , Femenino , Masculino , Apatía/efectos de los fármacos , Anciano , Estimulantes del Sistema Nervioso Central/uso terapéutico , Estimulantes del Sistema Nervioso Central/efectos adversos , Anciano de 80 o más Años , Pérdida de Peso/efectos de los fármacos , Accidentes por Caídas/estadística & datos numéricos , Método Doble Ciego , Trastornos del Inicio y del Mantenimiento del Sueño/inducido químicamente , Trastornos del Inicio y del Mantenimiento del Sueño/tratamiento farmacológicoRESUMEN
Schwertmannite has attracted increasing interest for its excellent sorption of oxyanions such as AsO43-, CrO42-, and Sb(OH)6-. Controlling biomineralization by adjusting the Fe(II) oxidation rate and implementing alkali control can enhance the yield and adsorption performance of schwertmannite. However, the adsorption improvement mechanism is still unclear. The morphology, crystallinity, specific surface area (SSA) and oxyanion adsorption of schwertmannite synthesized with alkali control of solution pH and different Fe(II) oxidation rates were analyzed in this study. The differences in the adsorption mechanisms of As(V), Cr(VI) and Sb(V) on schwertmannite obtained under different synthesis conditions were also studied. Reducing the Fe(II) oxidation rate or maintaining the solution pH through alkali control significantly increased the SSA of schwertmannite and the proportion of outer-sphere sulfate. Alkali-controlled schwertmannite (Sch-C) exhibited superior As(V) and Sb(V) adsorption performance and slightly greater Cr(VI) adsorption than non-alkali-controlled schwertmannite. The As(V) and Sb(V) adsorption capacities of Sch-C greatly improved because the ultra-high SSA increased the surface hydroxyl content and reduced the passivation effect of amorphous precipitates on the mineral surface, allowing continuous sulfate exchange at inner mineral sites. An increased surface hydroxyl content had little effect on Cr(VI) adsorption, but an increased proportion of outer-sphere sulfate caused a slight increase in Cr(VI) adsorption. Sb(V) has a stronger hydroxyl exchange ability than As(V), but due to its octahedral structure, it exchanges only with outer-sphere sulfate on schwertmannite and hardly exchanges with inner-sphere sulfate.
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The present study aimed to investigate outcomes following open surgery for extensive skull base ORN. Open surgery through a personalized sequential approach was employed to deal with five cases of extensive skull base ORN. Two patients with mild cases underwent regional debridement and sequestrectomy, and three patients with severe cases underwent extensive resection with reconstruction using free anterolateral thigh (ALT) flap. Biological glues and vascularized flaps were used for obturation of the skull base bony defect to prevent postoperative cerebrospinal fluid (CSF) leakage. The infections were controlled by antibiotic administrations which strictly followed the principles of antimicrobial stewardship (AMS). As results, both regional debridement plus sequestrectomy and extensive resection achieved satisfied outcomes in all patients. No severe complications and delayed hospitalization occurred. During the follow-up period (8-19 months), all patients were alive, pain free, without crusting or purulent discharge, and no sequestration or CSF leakage occurred. In conclusion, a personalized sequential approach including open surgery, pedicled/vascularized free flap reconstruction and AMS was advocated for patients with extensive skull base ORN.
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Colgajos Tisulares Libres , Osteorradionecrosis , Procedimientos de Cirugía Plástica , Neoplasias de la Base del Cráneo , Humanos , Osteorradionecrosis/cirugía , Osteorradionecrosis/complicaciones , Base del Cráneo/cirugía , Neoplasias de la Base del Cráneo/cirugía , Colgajos Tisulares Libres/cirugía , Pérdida de Líquido Cefalorraquídeo/cirugía , Estudios Retrospectivos , Complicaciones Posoperatorias/cirugíaRESUMEN
cGAS-STING signaling plays a critical role in radiotherapy (RT)-mediated immunomodulation. However, RT alone is insufficient to sustain STING activation in tumors under a safe X-ray dose. Here, we propose a radiosensitization cooperated with cGAS stimulation strategy by engineering a core-shell structured nanosized radiosensitizer-based cGAS-STING agonist, which is constituted with the hafnium oxide (HfO2) core and the manganese oxide (MnO2) shell. HfO2-mediated radiosensitization enhances immunogenic cell death to afford tumor associated antigens and adequate cytosolic dsDNA, while the GSH-degradable MnO2 sustainably releases Mn2+ in tumors to improve the recognition sensitization of cGAS. The synchronization of sustained Mn2+ supply with cumulative cytosolic dsDNA damage synergistically augments the cGAS-STING activation in irradiated tumors, thereby enhancing RT-triggered local and system effects when combined with an immune checkpoint inhibitor. Therefore, the synchronous radiosensitization with sustained STING activation is demonstrated as a potent immunostimulation strategy to optimize cancer radio-immuotherapy.
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Hafnio , Compuestos de Manganeso , Neoplasias , Humanos , Compuestos de Manganeso/farmacología , Óxidos/farmacología , Óxidos/uso terapéutico , Inmunoterapia , Neoplasias/tratamiento farmacológico , Neoplasias/radioterapia , NucleotidiltransferasasRESUMEN
Infiltration and activation of intratumoral T lymphocytes are critical for immune checkpoint blockade (ICB) therapy. Unfortunately, the low tumor immunogenicity and immunosuppressive tumor microenvironment (TME) induced by tumor metabolic reprogramming cooperatively hinder the ICB efficacy. Herein, we engineered a lactate-depleting MOF-based catalytic nanoplatform (LOX@ZIF-8@MPN), encapsulating lactate oxidase (LOX) within zeolitic imidazolate framework-8 (ZIF-8) coupled with a coating of metal polyphenol network (MPN) to reinforce T cell response based on a "two birds with one stone" strategy. LOX could catalyze the degradation of the immunosuppressive lactate to promote vascular normalization, facilitating T cell infiltration. On the other hand, hydrogen peroxide (H2O2) produced during lactate depletion can be transformed into anti-tumor hydroxyl radical (â¢OH) by the autocatalytic MPN-based Fenton nanosystem to trigger immunogenic cell death (ICD), which largely improved the tumor immunogenicity. The combination of ICD and vascular normalization presents a better synergistic immunopotentiation with anti-PD1, inducing robust anti-tumor immunity in primary tumors and recurrent malignancies. Collectively, our results demonstrate that the concurrent depletion of lactate to reverse the immunosuppressive TME and utilization of the by-product from lactate degradation via cascade catalysis promotes T cell response and thus improves the effectiveness of ICB therapy.
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Estructuras Metalorgánicas , Neoplasias , Humanos , Ácido Láctico/farmacología , Estructuras Metalorgánicas/farmacología , Peróxido de Hidrógeno/farmacología , Linfocitos T , Inmunoterapia , Línea Celular Tumoral , Microambiente TumoralRESUMEN
AIM: The objective of this study was to evaluate the efficacy of Tai Chi, a mind-body movement therapy originating from China, on depression in middle-aged and older adults. METHODS: A systematic search was conducted in seven databases (Embase, Cochrane, Medline, Wanfang, SinoMed, Weipu date, CNKI) for Randomized Controlled Trials (RCTs) published until Apr 16, 2023. The quality assessment, heterogeneity analysis, subgroup analysis, and sensitivity analysis of 12 RCTs selected from the literature were performed. Meta-analyses were conducted using RevMan 5.4 software. RESULTS: The study included 12 trials comprising 731 participants that met the inclusion criteria. The findings revealed that Tai Chi significantly improved depression in middle-aged and older adults [SMD = -1.21, 95% CI (-1.59, -0.83), I2 = 87.6%, P < 0.001]. Subgroup analysis revealed that the number of exercise weeks within the specified range, the total duration of exercise, and Tai Chi maneuvers had the greatest benefits on depression in middle-aged and elderly people. The results demonstrated that interventions lasting more than 24 weeks were more effective [SMD = -1.66, 95% CI (-2.28, -1.04), P < 0.05] than those lasting only 12 weeks [SMD = -0.73, 95% CI (-1.08, -0.38), P < 0.05]. The effect size was more significant when the total duration of the intervention was more than 2400 min [SMD = -1.31, 95% CI (-1.71, -0.92), P < 0.001], and when the 24-style Tai Chi exercise was selected [SMD = -1.06, 95% CI (-1.37, -0.75), P < 0.001], the difference was also statistically significant. Funnel plots combined with sensitivity analyses, Begg's and Egger's tests indicated no publication bias. CONCLUSION: The study suggests that Tai Chi can be an alternative therapy for reducing depression in middle-aged and older adults. It is recommended to prolong the Tai Chi exercise period to more than 24 weeks, with a total exercise duration of more than 2400 min, and 24-style Tai Chi should be selected to achieve the best therapeutic effect in middle-aged and older adults with depression. It should be noted that there may be lower-quality studies in the RCT literature analyzed, which may limit the general applicability and credibility of the conclusions.
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Depresión , Taichi Chuan , Anciano , Humanos , Persona de Mediana Edad , China , Ejercicio Físico , Taichi Chuan/métodos , Depresión/terapia , Ensayos Clínicos Controlados Aleatorios como AsuntoRESUMEN
Objective: The popularization of the internet provides the possibility to improve the depressive symptoms (DS) and social isolation of middle-aged and older adults with functional disability. There was a significant correlation between internet use and DS in middle-aged and older adults with functional disability, but the relationship between internet use, social isolation, and DS remains to be confirmed. Methods: Data were obtained from 7,955 middle-aged and older adults aged 45 years and older from the 2018 China Health and Retirement Longitudinal Study (CHARLS). Multiple linear regression models were used to analyze the association between internet use and DS, and the Sobel test was used to explore mediating models. Results: Results showed that internet use was negatively associated with DS among Chinese middle-aged and older adults. Among them, social needs (B = -0.770, p = 0.041), and information reception (B = -1.067, p = 0.007) were significantly related to DS in middle-aged and older adults. Only information reception (B = -3.161, p = 0.031) was significantly related to DS among middle-aged and older adults with functional disability. Social isolation partially mediated the association between internet use and DS in middle-aged and older adults without functional disability, whereas it was fully mediated in middle-aged and older adults with functional disability. Conclusion: This study indicates that when formulating health policies to promote the mental health of Chinese middle-aged and older adults, the use of the internet should not be overlooked.
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Depresión , Uso de Internet , Estudios Longitudinales , Depresión/psicología , Aislamiento Social , JubilaciónRESUMEN
Radiotherapy (RT) is one of the important clinical treatments for local control of triple-negative breast cancer (TNBC), but radioresistance still exists. Ferroptosis has been recognized as a natural barrier for cancer progression and represents a significant role of RT-mediated anticancer effects, while the simultaneous activation of ferroptosis defensive system during RT limits the synergistic effect between RT and ferroptosis. Herein, we engineered a tumor microenvironment (TME) degradable nanohybrid with a dual radiosensitization manner to combine ferroptosis induction and high-Z effect based on metal-organic frameworks for ferroptosis-augmented RT of TNBC. The encapsulated l-buthionine-sulfoximine (BSO) could inhibit glutathione (GSH) biosynthesis for glutathione peroxidase 4 (GPX4) inactivation to break down the ferroptosis defensive system, and the delivered ferrous ions could act as a powerful ferroptosis executor via triggering the Fenton reaction; the combination of them induces potent ferroptosis, which could synergize with the surface decorated Gold (Au) NPs-mediated radiosensitization to improve RT efficacy. In vivo antitumor results revealed that the nanohybrid could significantly improve the therapeutic efficacy and antimetastasis efficiency based on the combinational mechanism between ferroptosis and RT. This work thus demonstrated that combining RT with efficient ferroptosis induction through nanotechnology was a feasible and promising strategy for TNBC treatment.
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Ferroptosis , Neoplasias de la Mama Triple Negativas , Humanos , Anestésicos Locales , Butionina Sulfoximina , Fibrinolíticos , Glutatión , Línea Celular Tumoral , Microambiente TumoralRESUMEN
Objectives: Some ceRNA associated with lncRNA have been considered as possible diagnostic and therapeutic biomarkers for obstructive sleep apnea (OSA). We intend to identify the potential hub genes for the development of OSA, which will provide a foundation for the study of the molecular mechanism underlying OSA and for the diagnosis and treatment of OSA. Methods: We collected plasma samples from OSA patients and healthy controls for the detection of ceRNA using a chip. Based on the differential expression of lncRNA, we identified the target genes of miRNA that bind to lncRNAs. We then constructed lncRNA-related ceRNA networks, performed functional enrichment analysis and protein-protein interaction analysis, and performed internal and external validation of the expression levels of stable hub genes. Then, we conducted LASSO regression analysis on the stable hub genes, selected relatively significant genes to construct a simple and easy-to-use nomogram, validated the nomogram, and constructed the core ceRNA sub-network of key genes. Results: We successfully identified 282 DElncRNAs and 380 DEmRNAs through differential analysis, and we constructed an OSA-related ceRNA network consisting of 292 miRNA-lncRNAs and 41 miRNA-mRNAs. Through PPI and hub gene selection, we obtained 7 additional robust hub genes, CCND2, WT1, E2F2, IRF1, BAZ2A, LAMC1, and DAB2. Using LASSO regression analysis, we created a nomogram with four predictors (CCND2, WT1, E2F2, and IRF1), and its area under the curve (AUC) is 1. Finally, we constructed a core ceRNA sub-network composed of 74 miRNA-lncRNA and 7 miRNA-mRNA nodes. Conclusion: Our study provides a new foundation for elucidating the molecular mechanism of lncRNA in OSA and for diagnosing and treating OSA.
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Acute viral myocarditis (AVMC) is a common acute myocardial inflammation caused by viral infections, which can lead to severe cardiac dysfunction. Several long noncoding RNAs (lncRNAs) with aberrant expression have been identified in the pathogenesis of AVMC. However, the expression profiles and functions of lncRNAs in AVMC have not been fully elucidated. In the present study, we constructed AVMC mouse models by intraperitoneal injection of coxsackievirus B3 (CVB3) and performed RNA sequencing (RNA-seq) on heart tissues to investigate the differences in lncRNAs and messenger RNAs (mRNAs) expression profiles. Based on the cutoff criteria of adjusted p-values (padj) <0.05 and |log2FoldChange| >1, a total of 1122 differentially expressed lncRNAs (DElncRNAs) and 3186 differentially expressed mRNAs (DEmRNAs) were screened, including 734 upregulated and 388 downregulated lncRNAs, 1821 upregulated and 1365 downregulated mRNAs. RT-qPCR analysis validated that the expression patterns of 12 randomly selected genes (6 DElncRNAs and 6 DEmRNAs) were highly consistent with those in RNA-seq, proving the reliability of the RNA-seq data. Then, Gene Ontology and Kyoto Encyclopedia of Genes and Genomes enrichment analyses revealed that differentially expressed genes were mainly involved in metabolic and immune-related processes. Furthermore, co-expression networks between DElncRNAs and DEmRNAs in cytokine-cytokine receptor interaction, MAPK signaling pathway, and PI3K-Akt signaling pathway were constructed to study the molecular interactions of these molecules. Our study, for the first time, reveals the expression profiles of lncRNAs and mRNAs associated with AVMC, which may shed light on the roles of lncRNAs in disease pathogenesis and aid in discovering new therapeutic targets.
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Miocarditis , ARN Largo no Codificante , Ratones , Animales , Perfilación de la Expresión Génica , ARN Largo no Codificante/genética , Fosfatidilinositol 3-Quinasas , Reproducibilidad de los Resultados , ARN Mensajero/genéticaRESUMEN
OBJECTIVES: The semiburied design of the traditional internal distractor has a relatively high risk of infection and aesthetic problems. To reduce these potential risks, a modified internal distractor with design of pre-embedding curvilinear rail, drive screw, and universal joint was invented. Its stress distribution characteristics and the effect on curvilinear distraction osteogenesis (DO) in vivo were further tested. MATERIALS AND METHODS: Finite element analysis (FEA) was performed on a model of the human mandible and distraction device to measure the stress distribution during curvilinear DO. Six beagles underwent curvilinear DO and consolidation using the new device. Radiological and histological examinations were performed on the new bone. RESULTS: On FEA, the stress was concentrated in the condyle (128.6 MPa) and curved guide rails (324.8 MPa). Four of the six animals completed the DO period and were consolidated for 12 weeks. Secondary infections were not observed. Radiography showed that a new fan-shaped bone-15.5 ± 5.5 mm in length and 4.6 ± 1.6 mm in height-was formed in the bone gap. Micro-computed tomography and histological examinations of specimens indicated that the structure of the new bone was similar to that of the normal bone. CONCLUSIONS: The modified internal curvilinear distraction device meets the mechanical strength requirement and achieve curvilinear DO in animal experiments.
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Experimentación Animal , Osteogénesis por Distracción , Perros , Humanos , Animales , Análisis de Elementos Finitos , Microtomografía por Rayos X , Mandíbula/cirugía , Mandíbula/patología , Osteogénesis por Distracción/métodos , Tornillos ÓseosRESUMEN
The DSMB: The Toughest Job in Clinical TrialsIn this review article, the authors discuss methods that DSMBs can use to compare the absolute and relative risks of benefits and adverse effects between trial interventions and illustrate how the DSMB can use this approach to evaluate the balance of these competing risks. Two approaches are discussed - the win ratio and the DOOR probability on one treatment relative to another.
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Comités de Monitoreo de Datos de Ensayos ClínicosRESUMEN
Using the melamine borate and crosslinked ß-cyclodextrin as shell materials, the double-shell microcapsules (Mic-DP) of red phosphorus (RP) was prepared, and its flame-retardant effect on polyamide 6 (PA6) was investigated. Compared with RP, Mic-DP showed lower hygroscopic and better inoxidizability. The limiting oxygen index (LOI) of PA6/13%Mic-DP was 27.8%, and PA6/13%Mic-DP reached V-0 rating. After the addition of 13% Mic-DP, the total exothermic (THR), peak exothermic (PK-HRR), and average effective thermal combustion (AV-EHC) rates of PA6 decreased. In addition, in order to investigate its flame-retardant mechanism, the pyrolysis gas chromatography-mass spectrometry (Py-GC-MS), scanning electron microscopy (SEM), and Fourier transform infrared (FT-IR) methods were used, and the results showed that mic DP acted as a flame retardant in the gas and condensed phases. The Mic-DP exhibited good compatibility and dispersibility in PA6.
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BACKGROUND: Myocardial inflammation and apoptosis are key processes in coxsackievirus B3 (CVB3)-induced acute viral myocarditis (AVMC). Accumulating evidence reveals the essential roles of long noncoding RNAs (lncRNAs) in the pathogenesis of AVMC. Here, we aimed to evaluate the biological functions of a novel lncRNA guanylate-binding protein 9 (lncGBP9) in AVMC progression and further explore its underlying mechanisms. METHODS: Initially, mouse models of AVMC were constructed by CVB3 infection. The expression and localization of lncGBP9 in heart tissues were analyzed using RT-qPCR and FISH. Adeno-associated virus serotype 9 (AAV9)-mediated lncGBP9 knockdown was then employed to clarify its roles in survival, cardiac function, and myocardial inflammation and apoptosis. Moreover, the mRNA and protein levels of pro-inflammatory cytokines (TNF-α, IL-6, and IL-1ß) were detected by RT-qPCR and ELISA, and the regulation of lncGBP9 knockdown on the NF-κB signaling pathway was investigated by Western blotting. Using an in vitro model of HL-1 cardiomyocytes exposed to CVB3 infection, the effects of lncGBP9 knockdown on cell viability, inflammation, and apoptosis were further evaluated in vitro. RESULTS: Increased lncGBP9 expression was detected in the heart tissues of AVMC mice and CVB3-infected HL-1 cells, and was mainly located in the cytoplasm. Knockdown of lncGBP9 remarkably alleviated the severity of AVMC in CVB3-infected mice, as verified by improved cardiac function, and reduced myocardial inflammation and apoptosis. Additionally, lncGBP9 knockdown suppressed the NF-κB signaling pathway and consequently reduced productions of pro-inflammatory cytokines in vivo. In vitro functional assays further confirmed that lncGBP9 knockdown promoted cell viability, inhibited cell apoptosis, and reduced pro-inflammatory cytokines release in CVB3-infected HL-1 cells through suppressing NF-κB activation. CONCLUSIONS: Collectively, lncGBP9 knockdown exerts anti-inflammatory and anti-apoptotic effects in CVB3-induced AVMC, which may be mediated in part via NF-κB signaling pathway. These findings highlight lncGBP9 as an attractive target for therapeutic interventions.
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Infecciones por Coxsackievirus , Miocarditis , Ratones , Animales , Miocarditis/genética , FN-kappa B/metabolismo , Enterovirus Humano B/metabolismo , Infecciones por Coxsackievirus/genética , Infecciones por Coxsackievirus/metabolismo , Infecciones por Coxsackievirus/patología , Transducción de Señal , Inflamación/metabolismo , Apoptosis , Citocinas/metabolismo , Ratones Endogámicos BALB CRESUMEN
PURPOSE: The purpose of this trial was to evaluate the safety and efficacy of OC-01 (varenicline solution), a nicotinic acetylcholine receptor agonist nasal spray, on signs and symptoms of dry eye disease. METHODS: A phase 2b, multicenter, randomized, double-masked, vehicle-controlled trial (ONSET-1; NCT03636061) was performed. Patients were aged 22 years or older with a physician's diagnosis of dry eye disease and previous use of artificial tears were randomized 1:1:1:1 to control (vehicle nasal spray twice daily [BID]), OC-01 0.006 mg BID, OC-01 0.03 mg BID, and OC-01 0.06 mg BID. The primary end point was the change in the anesthetized Schirmer test score from baseline to day 28 in the study eye. The secondary end points included the change in the eye dryness score from baseline to day 28. RESULTS: One hundred eighty-two patients were randomized. After 28 days, patients who received OC-01 0.03 or 0.06 mg showed a statistically significant improvement in tear film production relative to vehicle, with least squares mean differences from vehicle of 7.7 mm [95% confidence interval, 3.8-11.7; P < 0.001] with OC-01 0.03 mg and 7.5 mm (95% confidence interval, 3.4-11.6; P < 0.001) with OC-01 0.06 mg. Patients receiving OC-01 0.03 mg showed a significant reduction in the eye dryness score by day 28 versus vehicle (P = 0.021); those receiving the OC-01 0.06 mg dose showed a nonsignificant reduction versus vehicle. OC-01 administration was associated with sneezing (62%-84%) and cough (9%-25%); these were transient and predominantly mild in severity. CONCLUSIONS: OC-01 nasal spray administered BID at 0.03 and 0.06 mg resulted in significant improvements in signs and symptoms of dry eye disease, was well tolerated, and warrants further clinical investigation.
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Síndromes de Ojo Seco , Receptores Nicotínicos , Síndromes de Ojo Seco/diagnóstico , Síndromes de Ojo Seco/tratamiento farmacológico , Humanos , Gotas Lubricantes para Ojos/uso terapéutico , Rociadores Nasales , Receptores Nicotínicos/uso terapéutico , Resultado del Tratamiento , Vareniclina/uso terapéuticoRESUMEN
Background: This paper aimed to summarize our experience in the nursing of acute graft-versus-host disease (aGVHD) after simultaneous pancreas-kidney transplantation (SPK). Methods: We retrospectively collected and analyzed the demographic characteristics, preoperative evaluation, donor evaluation, screening, and surgical methods of patients with aGVHD after SPK in our center from September 2016 to September 2019. Results: One patient developed intractable diarrhea with decline in platelet (PLT), white blood cell (WBC), and red blood cell (RBC) counts. Meanwhile, the other two patients experienced facial and trunk rashes, hepatic impairment, as well as decreased PLT, WBC, and RBC counts. We took the following nursing interventions: establishing an intensive care team and close monitoring of changes in the condition; protective isolation to minimize exogenous infections; nursing of pulmonary infections; and nutritional support. However, despite careful treatment and nursing, the conditions of the three patients subsequently worsened rapidly and became uncontrollable, and all died. Conclusions: aGVHD is extremely rare after SPK, and no literature exists concerning nursing care or management related to this condition. Clinical manifestations and histopathology are helpful for diagnosis; however, treatment outcomes might be unsatisfactory and the prognosis is poor. Early detection, diagnosis, and intervention have a positive impact on the prognosis of aGVHD, and proper nursing can benefit patients.
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With the successful marriage between nanotechnology and oncology, various high-Z element containing nanoparticles (NPs) are approved as radiosensitizers to overcome radiation resistance for enhanced radiotherapy (RT). Unfortunately, NPs themselves lack specificity to tumors. Due to the inherent tropism nature of malignant cells, mesenchymal stem cells (MSCs) emerge as cell-mediated delivery vehicles for functional NPs to improve their therapeutic index. Herein, radiosensitive bismuth selenide (Bi2 Se3 ) NPs-laden adipose-derived mesenchymal stromal cells (AD-MSCs/Bi2 Se3 ) are engineered for targeted RT of non-small cell lung cancer (NSCLC). The results reveal that the optimized intracellular loading strategy hardly affects cell viability, specific surface markers, or migration capability of AD-MSCs, and Bi2 Se3 NPs can be efficiently transported from AD-MSCs to tumor cells. In vivo biodistribution test shows that the Bi2 Se3 NPs accumulation in tumor is increased 20 times via AD-MSCs-mediated delivery. Therefore, AD-MSCs/Bi2 Se3 administration synchronized with X-ray irradiation controls the tumor progress well in orthotopic A549 tumor bearing mice. Considering that MSCs migrate better to irradiated tumor cells in comparison to nonirradiated ones and MSCs preferentially accumulate within lung tissues after systemic administration into accounts, the tumor-tropic MSCs/NPs system is feasible and promising for targeted RT treatment of NSCLC.