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OBJECTIVES: To understand the status quo and related influencing factors of machine alarm fatigue of hemodialysis nurses in tertiary hospitals in Liaoning Province. METHODS: This cross-sectional study employed convenience sampling to select 460 nurses from 29 tertiary hospitals in Liaoning Province, who are involved in hemodialysis care. Surveys were conducted using the General Information Questionnaire, Alarm Fatigue Scale, National Aeronautics and Space Administration Task Load Index, and Maslach Burnout Inventory Scale. RESULTS: The overall machine alarm fatigue score for 460 hemodialysis nurses from 29 tertiary hospitals in Liaoning Province was 17.04 ± 3.21, indicating a moderate level. The multiple linear regression analysis shows that years of experience in hemodialysis nursing, the number of patients managed per shift, whether specialized nursing training has been received, self-reported health status, emotional exhaustion, and workload have statistically significant associations with alarm fatigue among hemodialysis nurses (p < 0.05). Among them, the years of experience in hemodialysis nursing are negatively correlated with alarm fatigue among hemodialysis nurses, whereas the number of patients managed per shift and workload are positively correlated with alarm fatigue among hemodialysis nurses. CONCLUSION: This study indicates that certain demographic factors, workload, and occupational burnout are associated with machine alarm fatigue among hemodialysis nurses. Therefore, hemodialysis-related managers should establish a Machine Alarm Management System, implement Personalized Thresholds and Delayed Alarms, ensure reasonable staffing arrangements, improve compassion fatigue, and enhance anticipatory care. Our findings have implications for improving the health and well-being of hemodialysis nurses, providing a conducive environment for professional training in hemodialysis, and ultimately addressing the current situation of machine alarm fatigue among hemodialysis nurses.
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Alarmas Clínicas , Enfermeras y Enfermeros , Diálisis Renal , Centros de Atención Terciaria , Humanos , Alarmas Clínicas/estadística & datos numéricos , Femenino , Adulto , Masculino , Enfermeras y Enfermeros/estadística & datos numéricos , Agotamiento Profesional , Estudios Transversales , Persona de Mediana Edad , Carga de TrabajoRESUMEN
Peritoneal fibrosis together with increased capillaries is the primary cause of peritoneal dialysis failure. Mesothelial cell loss is an initiating event for peritoneal fibrosis. We find that the elevated glucose concentrations in peritoneal dialysate drive mesothelial cell pyroptosis in a manner dependent on caspase-3 and Gasdermin E, driving downstream inflammatory responses, including the activation of macrophages. Moreover, pyroptosis is associated with elevated vascular endothelial growth factor A and C, two key factors in vascular angiogenesis and lymphatic vessel formation. GSDME deficiency mice are protected from high glucose induced peritoneal fibrosis and ultrafiltration failure. Application of melatonin abrogates mesothelial cell pyroptosis through a MT1R-mediated action, and successfully reduces peritoneal fibrosis and angiogenesis in an animal model while preserving dialysis efficacy. Mechanistically, melatonin treatment maintains mitochondrial integrity in mesothelial cells, meanwhile activating mTOR signaling through an increase in the glycolysis product dihydroxyacetone phosphate. These effects together with quenching free radicals by melatonin help mesothelial cells maintain a relatively stable internal environment in the face of high-glucose stress. Thus, Melatonin treatment holds some promise in preserving mesothelium integrity and in decreasing angiogenesis to protect peritoneum function in patients undergoing peritoneal dialysis.
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Melatonina , Fibrosis Peritoneal , Humanos , Animales , Ratones , Fibrosis Peritoneal/etiología , Fibrosis Peritoneal/prevención & control , Fibrosis Peritoneal/patología , Melatonina/farmacología , Melatonina/uso terapéutico , Factor A de Crecimiento Endotelial Vascular , Piroptosis , Ultrafiltración , Células Epiteliales , Glucosa/farmacología , FibrosisRESUMEN
The construction of an in vitro differentiation system for human induced pluripotent stem cells (hiPSCs) has made exciting progress, but it is still of great significance to clarify the differentiation process. The use of conventional genetic and protein-labeled microscopes to observe or detect different stages of hiPSC differentiation is not specific enough and is cumbersome and time-consuming. In this study, in addition to analyzing the expression of gene/protein-related markers, we used a previously reported simple and excellent quantitative method of cellular telomerase activity based on a quartz crystal microbalance (TREAQ) device to monitor the dynamic changes in cellular telomerase activity in hiPSCs during myocardial differentiation under chemically defined conditions. Finally, by integrating these results, we analyzed the relationship between telomerase activity and the expression of marker genes/proteins as well as the cell type at each study time point. This dynamic quantitative measurement of cellular telomerase activity should be a promising indicator for monitoring dynamic changes in a stage of hiPSC differentiation and inducing cell types. This study provided a quantitative, dynamic and simple monitoring index for the in vitro differentiation process of hiPSC-CMs, which was a certain reference value for the optimization and improvement of the induction system.
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Células Madre Pluripotentes Inducidas , Telomerasa , Humanos , Telomerasa/genética , Telomerasa/metabolismo , Miocitos Cardíacos/metabolismo , Diferenciación Celular , Células CultivadasRESUMEN
Polyploidization is a major driver of genome diversification and environmental adaptation. However, the merger of different genomes may result in genomic conflicts, raising a major question regarding how genetic diversity is interpreted and regulated to enable environmental plasticity. By analyzing the genome-wide binding of 191 trans-factors in allopolyploid wheat, we identified like heterochromatin protein 1 (LHP1) as a master regulator of subgenome-diversified genes. Transcriptomic and epigenomic analyses of LHP1 mutants reveal its role in buffering the expression of subgenome-diversified defense genes by controlling H3K27me3 homeostasis. Stripe rust infection releases latent subgenomic variations by eliminating H3K27me3-related repression. The simultaneous inactivation of LHP1 homoeologs by CRISPR-Cas9 confers robust stripe rust resistance in wheat seedlings. The conditional repression of subgenome-diversified defenses ensures developmental plasticity to external changes, while also promoting neutral-to-non-neutral selection transitions and adaptive evolution. These findings establish an LHP1-mediated buffering system at the intersection of genotypes, environments, and phenotypes in polyploid wheat. Manipulating the epigenetic buffering capacity offers a tool to harness cryptic subgenomic variations for crop improvement.
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Epigenómica , Triticum , Triticum/genética , Triticum/metabolismo , Histonas/metabolismo , Epigénesis Genética , Genoma de Planta/genéticaRESUMEN
Ionic liquids (ILs) are thought to have negative effects on human health. Researchers have explored the effects of ILs on zebrafish development during the early stages, but the intergenerational toxicity of ILs on zebrafish development has rarely been reported. Herein, parental zebrafish were exposed to different concentrations (0, 12.5, 25, and 50 mg/L) of [Cn mim]NO3 (n = 2, 4, 6) for 1 week. Subsequently, the F1 offspring were cultured in clean water for 96 h. [Cn mim]NO3 (n = 2, 4, 6) exposure inhibited spermatogenesis and oogenesis in F0 adults, even causing obvious lacunae in the testis and atretic follicle oocytes in ovary. After parental exposure to [Cn mim]NO3 (n = 2, 4, 6), the body length and locomotor behavior were measured in F1 larvae at 96 hours post-fertilization (hpf). The results showed that the higher the concentration of [Cn mim]NO3 (n = 2, 4, 6), the shorter the body length and swimming distance, and the longer the immobility time. Besides, a longer alkyl chain length of [Cn mim]NO3 had a more negative effect on body length and locomotor behavior. RNA-seq analysis revealed several downregulated differentially expressed genes (DEGs)-grin1b, prss1, gria3a, and gria4a-enriched in neurodevelopment-related pathways, particularly the pathway for neuroactive ligand-receptor interaction. Moreover, several upregulated DEGs, namely col1a1a, col1a1b, and acta2, were mainly associated with skeletal development. Expression of DEGs was tested by RT-qPCR, and the outcomes were consistent with those obtained from RNA-Seq. We provide evidence showing the effects of parental exposure to ILs on the regulation of nervous and skeletal development in F1 offspring, demonstrating intergenerational effects.
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Líquidos Iónicos , Contaminantes Químicos del Agua , Animales , Masculino , Femenino , Humanos , Pez Cebra/metabolismo , Líquidos Iónicos/toxicidad , Testículo , Espermatogénesis , Contaminantes Químicos del Agua/toxicidad , Contaminantes Químicos del Agua/metabolismoRESUMEN
Background: After its approval by the European Union in 2011, CytoSorb therapy has been applied to control cytokine storm and lower the increased levels of cytokines and other inflammatory mediators in blood. However, the efficiency of this CytoSorb treatment in patients with coronavirus disease (COVID-19) still remains unclear. To elucidate the Cytosorb efficiency, we conducted a systematic review and single-arm proportion meta-analysis to combine all evidence available in the published literature to date, so that this comprehensive knowledge can guide clinical decision-making and future research. Methods: The literature published within the period 1 December 2019 to 31 December 2021 and stored in the Cochrane Library, Embase, PubMed, and International Clinical Trials Registry Platform (ICTRP) was searched for all relevant studies including the cases where COVID-19 patients were treated with CytoSorb. We performed random-effects meta-analyses by R software (3.6.1) and used the Joanna Briggs Institute checklist to assess the risk of bias. Both categorical and continuous variables were presented with 95% confidence intervals (CIs) as pooled proportions for categorical variables and pooled means for continuous outcomes. Results: We included 14 studies with 241 COVID-19 patients treated with CytoSorb hemadsorption. Our findings reveal that for COVID-19 patients receiving CytoSorb treatment, the combined in-hospital mortality was 42.1% (95% CI 29.5-54.6%, I2 = 74%). The pooled incidence of adjunctive extracorporeal membrane oxygenation (ECMO) support was 73.2%. Both the C-reactive protein (CRP) and interleukin-6 (IL-6) levels decreased after CytoSorb treatment. The pooled mean of the CRP level decreased from 147.55 (95% CI 91.14-203.96) to 92.36 mg/L (95% CI 46.74-137.98), while that of IL-6 decreased from 339.49 (95% CI 164.35-514.63) to 168.83 pg/mL (95% CI 82.22-255.45). Conclusions: The majority of the COVID-19 patients treated with CytoSorb received ECMO support. In-hospital mortality was 42.1% for the COVID-19 patients who had CytoSorb treatment. Both CRP and IL-6 levels decreased after Cytosorb treatment.
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COVID-19 , Humanos , COVID-19/terapia , Interleucina-6 , CitocinasRESUMEN
BACKGROUND: Gastric cancer (GC) is often diagnosed at an advanced stage and thus patients have a poor prognosis. This implies that early detection of this cancer will improve patient prognosis and survival. This systematic review explored the association of circulating protein and metabolite biomarkers with GC development. METHODS: A literature search was conducted until November 2021 on Medline, Embase, Cochrane library, and Web of Science databases. Studies were included if they assessed circulating proteins and metabolites in blood, urine, or saliva and determined their association with GC risk. Quality of identified studies was determined using the Newcastle-Ottawa scale for cohort studies. Random and fixed effects meta-analyses were performed to calculate pooled odds ratio. RESULTS: A total of 53 studies were included. High levels of anti-Helicobacter pylORi IgG levels, pepsinogen I (PGI) <30 µg/L and serum pepsinogen I/ pepsinogen II (PGI/II) ratio<3 were positively associated with risk of developing GC (pooled odds ratio (OR): 2.70; 95% CI: 1.44-5.04, 5.96, 95% CI: 2.65-13.42 and 4.43; 95% CI: 3.04-6.47). In addition, an inverse relationship was found between ferritin, iron and transferrin levels and risk of developing GC (OR: 0.62; 95% CI: 0.38-1,0.97; 95% CI: 0.94-1 and 0.85; 95% CI: 0.76-0.94). However, there was no association between levels of glucose, cholesterol, vitamin C, vitamin B12, vitamin A, α-Carotene, ß-Carotene, α-Tocopherol, γ-Tocopherol, and GC risk. CONCLUSION: The pooled analysis demonstrated that high levels of anti-Helicobacter pylORi IgG, PGI<30µg/L and serum PGI/II ratio <3 and low levels of ferritin, iron and transferrin were associated with risk of GC.
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Infecciones por Helicobacter , Neoplasias Gástricas , Humanos , Pepsinógeno A , Biomarcadores , Pepsinógeno C , Inmunoglobulina G , Ferritinas , Hierro , TransferrinasRESUMEN
Phased, small interfering RNAs (phasiRNAs) are important for plant anther development, especially for male sterility. PhasiRNA biogenesis is dependent on genes like RNA polymerase 6 (RDR6), DICER-LIKE 4 (DCL4), or DCL5 to produce 21- or 24 nucleotide (nt) double-strand small RNAs. Here, we generated mutants of DCL4, DCL5 and RDR6 using CRISPR/Cas9 system and studied their effects on plant reproductive development and phasiRNA production in wheat. We found that RDR6 mutation caused sever consequence throughout plant development starting from seed germination and the dcl4 mutants grew weaker with thorough male sterility, while dcl5 plants developed normally but exhibited male sterility. Correspondingly, DCL4 and DCL5, respectively, specified 21- and 24-nt phasiRNA biogenesis, while RDR6 contributed to both. Also, the three key genes evolved differently in wheat, with TaDCL5-A/B becoming non-functioning and TaRDR6-A being lost after polyploidization. Furthermore, we found that PHAS genes (phasiRNA precursors) identified via phasiRNAs diverged rapidly among sub-genomes of polyploid wheat. Despite no similarity being found among phasiRNAs of grasses, their targets were enriched for similar biological functions. In light of the important roles of phasiRNA pathways in gametophyte development, genetic dissection of the function of key genes may help generate male sterile lines suitable for hybrid wheat breeding.
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Infertilidad Masculina , Triticum , Masculino , Humanos , Triticum/genética , Triticum/metabolismo , Sistemas CRISPR-Cas/genética , Fitomejoramiento , Proteínas de Plantas/genética , Proteínas de Plantas/metabolismo , ARN Interferente Pequeño/genética , Mutagénesis/genética , Plantas/genética , Infertilidad Masculina/genética , ARN de Planta/genética , Regulación de la Expresión Génica de las PlantasRESUMEN
INTRODUCTION: Venovenous extracorporeal membrane oxygenation (VV ECMO) is now considered a reasonable option to salvage acute respiratory distress syndrome (ARDS). However, we lack a rodent model for experimental studies. This study was undertaken to establish an animal model of VV ECMO in ARDS rats. METHODS: A total of 18 Sprague-Dawley (SD) rats (350 ± 50 g) were used in this study. Using a rat model of oleic acid (OA)-induced ARDS, VV ECMO was established through cavoatrial cannulation of the right jugular vein for venous drainage and venous reinfusion with a specially designed three-cavity catheter. Continuous arterial pressure monitoring was implemented by using a catheter through cannulation of the right femoral artery. The central temperature was monitored with a rectal probe. Arterial blood gas monitoring was implemented by a blood gas analyzer at three-time points: at baseline, 1-hour (after OA modeling), and 3.5-hour (after VV ECMO support). Lung tissue and bronchoalveolar lavage fluid were harvested respectively for protein concentration and pulmonary histologic evaluation to confirm the alleviation of lung injury during VV ECMO. RESULTS: Following ARDS induced by OA, ten rats were successfully established on VV ECMO without failure and survived the ECMO procedure. VV ECMO alleviated lung injury and restored adequate circulation for the return of lung function and oxygenation. VV ECMO was associated with decreased lung injury score, wet/dry weight ratio, and ï¬uid leakage into airspaces. CONCLUSION: We have established a reliable, economical, and functioning ARDS rat model of VV ECMO.
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Oxigenación por Membrana Extracorpórea , Lesión Pulmonar , Síndrome de Dificultad Respiratoria , Ratas , Animales , Oxigenación por Membrana Extracorpórea/métodos , Ratas Sprague-Dawley , Arteria Femoral , Síndrome de Dificultad Respiratoria/terapiaRESUMEN
The destruction of the pulmonary epithelial barrier in acute respiratory distress syndrome is caused by the damage of the alveolar epithelial cells. Oroxin A is an effective flavonoid component derived from the medicinal plant Oroxylum indicum (L.) Kurz. In this study, the oleic acid (OA)-induced A549 cell injury model was established in vitro to explore the protective mechanism of Oroxin A. The experiment was divided into the following groups: control, OA and OA + Oroxin A group. The OA-induced A549 cell injury was dose (time)-dependent and was detected by the CCK-8 assay. The protein and mRNA expression levels associated with pyroptosis are detected by Western blotting and RT-qPCR. After Oroxin A treatment, the levels of IL-1ß, IL-18 and LDH released were significantly lower than the OA group. In terms of pyroptosis, Oroxin A can inhibit the expression of pyroptosis-related protein and mRNA. Significantly, the surfactant protein C (SPC) level in the OA + Oroxin A group was significantly higher than that in the OA group. The treatment with Oroxin A alleviates the OA-induced injury in the A549 cells, and its mechanism may be related to the inhibition of A549 cells pyroptosis and prevention of the degradation of the SPC.
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Ácido Oléico , Tensoactivos , Humanos , Células A549 , Ácido Oléico/farmacologíaRESUMEN
INTRODUCTION: Although venovenous extracorporeal membrane oxygenation (VV ECMO) is a reasonable salvage treatment for acute respiratory distress syndrome (ARDS), it requires sedating the patient. Sevoflurane and propofol have pulmonary protective and immunomodulatory properties. This study aimed to compare the effectiveness of sevoflurane and propofol on rats with induced ARDS undergoing VV ECMO. METHODS: Fifteen sprague-dawley (SD) rats were randomly divided into three groups: Con group, sevoflurane (Sevo) group and propofol (Pro) group. Arterial blood gas tests were performed at time pointsT0 (baseline), T1 (the time to ARDS), and T2 (weaning from ECMO). Oxygenation index (PaO2/FiO2) was calculated, and lung edema assessed by determining the lung wet:dry ratio. The protein concentration in bronchial alveolar lavage fluid (BALF) was determined by using bicinchoninic acid assay. Haematoxylin and eosin staining was used to evaluate the lung pathological scores in each group. IL-1ß and TNF-α were also measured in the BALF, serum and lung. RESULTS: Oxygenation index showed improvement in the Sevo group versus Pro group. The wet:dry ratio was reduced in the Sevo group compared with propofol-treated rats. Lung pathological scores were substantially lower in the Sevo group versus the Pro group. Protein concentrations in the BALF and levels of IL-1ß and TNF-α in the Sevo group were substantially lower versus Pro group. CONCLUSION: This study demonstrates that compared with propofol, sevoflurane was more efficacious in improving oxygenation and decreasing inflammatory response in rat models with ARDS subject to VV ECMO treatment.
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BACKGROUND: Risk factors like female sex, fistula location, hypertension, albumin, diabetes, arteriovenous graft (AVG), age, and other factors are related to arteriovenous fistula thrombus (AVFT), but the consistency and magnitude of their associations have not been confirmed by meta-analysis. OBJECTIVES: The purpose of this study was to provide a comprehensive and up-to-date synthesis of evidence on the association between potential risk factors and AVFT. METHODS: In this systematic review and meta-analysis, PubMed, Embase, Cochrane Library, and Web of Science databases were searched for articles published up to April 20th, 2022, and cohort, cross-sectional, and case-control studies examining the association (odds ratio [OR]) between potential risk factors and AVFT were identified. The other inclusion criteria were sufficient data for analysis and nonoverlapping datasets, excluding reviews, meta-analyses, and articles with overlapping datasets. Extracted variables included first author, publication year, study type, sample size, percentage of women, vascular access type, risk or protective factors, and measure of association (adjusted estimates of effect of all risk factors). The study protocol is registered at PROSPERO (CRD42020201884) and followed Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. RESULTS: Among the 27 identified studies, data from 24 cohort, 2 case-control, and 1 cross-sectional study were included in this review. When compared to non-AVFT, our data showed that the significant risk factors were AVG (pooled OR = 6.28, 95% CI = 1.79-22.02, p = 0.004, I2 = 87%), age (pooled OR = 1.06, 95% CI = 1.00-1.13, p = 0.05, I2 = 98%), female sex (pooled OR = 2.62, 95% CI = 2.56-2.69, p < 0.00001, I2 = 0%), C-reactive protein (pooled OR = 1.18, 95% CI = 1.08-1.30, p = 0.0005, I2 = 90%), fistula site (distal) (pooled OR = 3.64, 95% CI = 1.74-7.62, p = 0.0006, I2 = 47%), hypertension (pooled OR = 1.21, 95% CI = 1.00-1.47, p = 0.05, I2 = 46%), CD34+KDR+ cell (pooled OR = 1.85, 95% CI = 1.33-2.57, p = 0.0002, I2 = 0%), and eprex use (pooled OR = 5.36, 95% CI = 1.82-15.77, p = 0.002, I2 = 0%). CONCLUSIONS: The meta-analysis suggests that AVG, age, female sex, CRP level, fistula site (distal), hypertension, CD34+KDR+ cell, and the use of eprex are independent risk factors for AVFT. Therefore, clinical medical staff should treat these risk factors carefully, identify them early, and prevent them early to reduce the occurrence of AVFT.
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Fístula Arteriovenosa , Hipertensión , Trombosis , Femenino , Humanos , Estudios Transversales , Epoetina alfa , Factores de Riesgo , Trombosis/etiología , MasculinoRESUMEN
Liver injury is an important complication that may arise in patients suffering from coronavirus disease 2019 (COVID-19) and is accompanied by a transient increase of transaminases and/or other liver enzymes. Liver function test (LFT) abnormalities generally disappear when the COVID-19 resolves or hepatotoxic drugs are discontinued. The LFT abnormalities are associated with drug-induced liver injury (DILI), due to the overuse of antimalarials, antivirals, and antimicrobials. Studies have reported varying levels of these liver injuries in COVID-19 patients; however, most involve elevated serum aminotransferases. Hepatic dysfunction is significantly high in patients with severe illness and has poor outcome. Normally, the liver is involved in the metabolism of many drugs, including nucleoside analogs and protease inhibitors, which are currently repurposed to treat COVID-19. In addition to the manifestation of COVID-19, drugs implemented in its treatment may aggravate liver injuries. Thus, DILI should be considered especially in those COVID-19 patients with underlying liver disease. It was unclear whether the elevated liver enzymes have originated from the underlying disease or DILI in this population. Furthermore, it is difficult to establish a direct relationship between a specific drug and liver injury. Another possible effect of liver damage may due to inflammatory cytokine storm in severe COVID-19. Liver injury can change metabolism, excretion, dosing, and expected concentrations of the drugs, which may make it difficult to achieve a therapeutic dose of the drug or increase the risk of adverse effects. These repurposed drugs have shown limited efficacy against the virus and the disease itself; however, they still pose risk of adverse effects. Careful and close monitoring of LFTs in COVID-19 patients can provide early diagnosis of liver injury, and the risk of DILI could be reduced. Also, drug interactions in liver-transplanted patients should always be kept in mind for certain immunosuppressive therapies and their known signs of DILI. Altogether, abnormal LFTs should not be regarded as a contraindication to use COVID-19 experimental therapies if needed under emergent status.
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Myocardial ischemia causes myocardial inflammation. Research indicates that the venoarterial extracorporeal membrane oxygenation (VA ECMO) provides cardiac support; however, the inflammatory response caused by myocardial ischemia remains unresolved. Dexamethasone (Dex), a broad anti-inflammatory agent, exhibits a cardioprotective effect. This study aims to investigate the effect of Dex on a rat model of acute myocardial infarction (AMI) supported by VA ECMO. Male Sprague-Dawley rats (300-350 g) were randomly divided into three groups: Sham group (n = 5), ECMO group (n = 6), and ECMO + Dex group (n = 6). AMI was induced by ligating the left anterior descending (LAD) coronary artery. Sham group only thoracotomy was performed but LAD was not ligated. The ECMO and ECMO + Dex groups were subjected to 1 h of AMI and 2 h of VA ECMO. In the ECMO + Dex group, Dex (0.2 mg/kg) was intravenously injected into the rats after 1 h of AMI. Lastly, myocardial tissue and blood samples were harvested for further evaluation. The ECMO + Dex group significantly reduced infarct size and levels of cTnI, cTnT, and CK-MB. Apoptotic cells and the expression levels of Bax, Caspase3, and Cle-Caspase3 proteins were markedly lower in the ECMO + Dex group than that in the ECMO group. Neutrophil and macrophage infiltration was lower in the ECMO + Dex group than in the ECMO group. A significant reduction was noted in ICAM-1, C5a, MMP-9, IL-1ß, IL-6, and TNF-α. In summary, our findings revealed that Dex alleviates myocardial injury in a rat model of AMI supported by VA ECMO.
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Dexametasona , Oxigenación por Membrana Extracorpórea , Infarto del Miocardio , Isquemia Miocárdica , Animales , Dexametasona/uso terapéutico , Masculino , Infarto del Miocardio/metabolismo , Infarto del Miocardio/terapia , Isquemia Miocárdica/metabolismo , Ratas , Ratas Sprague-DawleyRESUMEN
BACKGROUND: The preferred configuration for bridging patients with respiratory failure while awaiting lung transplantation is venovenous extracorporeal membrane oxygenation (VV ECMO). However, the protective effect of VV ECMO on the lung, as well as the underlying mechanisms, are still unknown. METHODS: We investigated the role of VV ECMO in preventing lung injury in vivo using a rat model. Additionally, the effects of Hippo/YAP signaling on alveolar epithelial type II cells (AT2)-mediated alveolar epithelial recovery in VV ECMO rats were also investigated. In the bronchoalveolar lavage fluid (BALF) and lung tissue, RNA sequencing, lung injury, edema, and cytokine expression were evaluated. RESULTS: VV ECMO significantly improved severe hypoxemia, reduced lung edema, and inflammatory response, and altered alveolar epithelial function, as indicated by reduced protein concentrations in BALF. This was associated with Hippo/YAP signaling activation, according to RNA sequencing analysis. Furthermore, we discovered that after VV ECMO, AT2 cells proliferated and differentiated, and this increase in AT2 cell activity was correlated to the increased nuclear expression of YAP, which is critical for alveolar epithelial recovery from lung injury. During VV ECMO, verteporfin-induced YAP inhibition and the loss of the oxygenator delayed lung alveolar epithelial recovery and led to a prolonged inflammatory response. CONCLUSIONS: These findings suggest that VV ECMO protects against lung injury by activating the Hippo/YAP signaling pathway. Strategies aimed at increasing YAP activity in AT2 cells could thus aid alveolar epithelial recovery, making VV ECMO easier for lung transplantation.
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Oxigenación por Membrana Extracorpórea , Lesión Pulmonar , Animales , Citocinas , Edema , Lesión Pulmonar/terapia , Ratas , VerteporfinaRESUMEN
BACKGROUND: Currently, the interaction between proton pump inhibitors (PPIs) and their effects on hemodialysis (HD) patients has not been clarified. OBJECTIVES: Here, we aimed to explore the association between PPIs and adverse outcomes in HD patients. METHODS: A search was performed on the PubMed, Embase, Cochrane Library, and Web of Science databases for relevant articles published up to April 10, 2022. Studies examining the association (odds ratio [OR]) between PPIs and side effects were identified. The study followed guidelines prescribed in the Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA), and was registered with PROSPERO (CRD42021291177). RESULTS: A total of 12 studies comprising 4,227,497 HD patients with PPIs were identified. Results showed that PPI use was associated with an increased risk of bone fracture and hip fracture in the HD patients (pooled OR = 1.29, 95% CI = 1.21-1.37, p < 0.00001, I2 = 0%; pooled OR = 1.37, 95% CI = 1.12-1.67, p = 0.002, I2 = 82%). Besides, HD patients who received PPIs were more likely to develop hypomagnesemia compared with those who did not receive PPIs (pooled OR = 2.79, 95% CI = 1.95-4.00, p < 0.00001, I2 = 0%). In addition, PPIs use was linked to abdominal aortic calcification and all-cause mortality (pooled OR = 2.03, 95% CI = 1.28-3.24, p = 0.003, I2 = 0%) (pooled OR = 1.44, 95% CI = 1.17-1.78, p = 0.0006, I2 = 0%). CONCLUSIONS: Taken together, the present results demonstrate that PPIs use in HD patients is independently associated with adverse reactions such as hip fracture, hypomagnesemia, abdominal aortic calcification, and all-cause mortality. Thus, the use of PPIs in HD patients should be carefully evaluated and optimized.
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Inhibidores de la Bomba de Protones , Diálisis Renal , Humanos , Enfermedad Iatrogénica , Magnesio , Oportunidad Relativa , Inhibidores de la Bomba de Protones/efectos adversos , Diálisis Renal/efectos adversosRESUMEN
ABSTRACT: Coronavirus disease 2019, caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has spread worldwide, resulting in over 250 million infections and >5 million deaths. Most antiviral drugs and vaccines have shown limited efficacy against SARS-CoV-2. Clinical data revealed that except for the large number of self-healing mild cases, moderate and severe cases mostly survived after supportive treatment but not specific drug administration or vaccination. The endothelial system is the first physiological barrier, and its structural stability is of critical importance in conferring disease resistance. Membrane lipid components, particularly sphingosine-1-phosphate (S1P), play a central role in stabilizing the cell membrane.Here, we used "Boolean Operators" such as AND, OR, and NOT, to search for relevant research articles in PubMed, then reviewed the potential of S1P in inhibiting SARS-CoV-2 infection by stabilizing the endothelial system, this is the major aim of this review work.Reportedly, vasculitis and systemic inflammatory vascular diseases are caused by endothelial damage resulting from SARS-CoV-2 infection. S1P, S1P receptor (SIPR), and signaling were involved in the process of SARS-CoV-2 infection, and S1P potentially regulated the function of EC barrier, in turn, inhibited the SARS-CoV-2 to infect the endothelial cells, and ultimately has the promising therapeutic value to coronavirus disease 2019.Taken together, we conclude that maintaining or administering a high level of S1P will preserve the integrity of the EC structure and function, in turn, lowering the risk of SARS-CoV-2 infection and reducing complications and mortality.
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COVID-19 , Células Endoteliales , Humanos , Lisofosfolípidos , SARS-CoV-2 , Esfingosina/análogos & derivadosRESUMEN
BACKGROUND: Managing the burden of care for patients with chronic debilitating diseases is an important issue. Herein, we assessed the burden in primary family members caring for uremic patients on maintenance peritoneal dialysis. METHODS: One hundred seventy caregivers and 170 patients were recruited. Self-perceived scoring along the Zarit Caregiver Burden Scale (ZCBS), World Health Organization Five-item Well-Being Index (WHO-5), and Warwick-Edinburgh Mental Well-being Scale (WEMWBS) were determined for caregivers. RESULTS: There was an inverse relationship between ZCBS and WHO-5 or WEMWBS scores in caregivers, suggesting that the higher the burden, the lesser the self-perceived well-being. One hundred two of 170 caregivers (60%) reported mild to moderate burden, indicating a common presence of mild to moderate caring-related mental and physical stress. Moreover, 31 caregivers (18.2%) reported moderate to severe burden. Several patient disease factors, including diabetes and frailty, increased caregiver burden, while insurance coverage and out-of-pocket medical costs were also positively correlated. Caregivers who lived with patients and spent longer hours in caring-related activities had higher burden scores, while regular exercise seemed to partially alleviate the burden. CONCLUSION: Our study clearly showed that caring for patients with maintenance peritoneal dialysis caused physical, mental, and social burden in family caregivers, with the extent of the stress being influenced by patients' disease severity and other demographic factors in both patients and caregivers.