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INTRODUCTION AND OBJECTIVES: As a fatal clinical syndrome, acute liver failure (ALF) is characterized by overwhelming liver inflammation and hepatic cell death. Finding new therapeutic methods has been a challenge in ALF research. VX-765 is a known pyroptosis inhibitor and has been reported to prevent damage in a variety of diseases by reducing inflammation. However, the role of VX-765 in ALF is still unclear. MATERIALS AND METHODS: ALF model mice were treated with D-galactosamine (D-GalN) and lipopolysaccharide (LPS). LO2 cells were stimulated with LPS. Thirty subjects were enrolled in clinical experiments. The levels of inflammatory cytokines, pyroptosis-associated proteins and peroxisome proliferator-activated receptor α (PPARα) were detected using quantitative reverse transcription-polymerase chain reaction (qRTâPCR), western blotting and immunohistochemistry. An automatic biochemical analyzer was used to determine the serum aminotransferase enzyme levels. Hematoxylin and eosin (HE) staining was used to observe the pathological features of the liver. RESULTS: With the progression of ALF, the expression levels of interleukin (IL) -1ß, IL-18, caspase-1, and serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST) were increased. VX-765 could reduce the mortality rate of ALF mice, relieve liver pathological damage, and reduce inflammatory responses to protect against ALF. Further experiments showed that VX-765 could protect against ALF through PPARα, and this protective effect against ALF was reduced in the context of PPARα inhibition. CONCLUSIONS: As ALF progresses, inflammatory responses and pyroptosis deteriorate gradually. VX-765 can inhibit pyroptosis and reduce inflammatory responses to protect against ALF by upregulating PPARα expression, thus providing a possible therapeutic strategy for ALF.
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Fallo Hepático Agudo , PPAR alfa , Ratones , Animales , PPAR alfa/genética , PPAR alfa/metabolismo , Piroptosis , Lipopolisacáridos/metabolismo , Lipopolisacáridos/farmacología , Fallo Hepático Agudo/inducido químicamente , Fallo Hepático Agudo/prevención & control , Hígado/patología , Inflamación/prevención & control , Inflamación/metabolismo , Factor de Necrosis Tumoral alfa/metabolismo , Ratones Endogámicos C57BLRESUMEN
Newcastle disease virus (NDV) is one of the most important diseases in poultry. The present study generated recombinant surface-displayed Lactobacillus casei (L. casei) expressing the hemagglutinin-neuraminidase (HN) of NDV (Lc-pPG-HN) and a live pPG vector (Lc-pPG) and evaluated their immunogenicity. A 1670 bp HN gene fragment was successfully amplified and cloned into a prokaryotic protein expression system. Protein expression in the resulting recombinant Lc-pPG-HN (surface displayed) strain was verified using Western blotting and indirect immunofluorescence. A single band was observed on the Western blots, and the molecular weight of the corresponding protein was 63 kDa. A fluorescent signal for Lc-pPG-HN was observed using fluorescence microscopy. A total of 270 healthy chicks were divided into three treatment groups. Five replicates were used for each treatment, while six chicks were used per replicate. The following three treatment groups were used: physiological saline group (Control), Lc-pPG group and recombinant vaccine group (Lc-pPG-HN). The primary immunization and booster immunization of the chicks were performed via oral administration on 1 and 10 days old. Tissue and blood samples were collected from chickens that received oral recombinant L. casei strains on 1, 7, 14 and 21 days post-immunization for immune-related index analyses. Chickens orally immunized with Lc-pPG-HN showed significantly increased body weights and immune organ indices. Oral immunization with Lc-pPG-HN also enhanced the concentrations of serum interleukin-2 (IL-2), interferon-γ (IFN-γ), intestinal lavage fluid secretory immunoglobulin A (SIgA) and histomorphological development of the small intestine. Our results also indicated that recombinant L. casei significantly increased Lactobacillus and Bifidobacterium colonization and decreased the relative abundance of Escherichia coli (E. coli) in the chicken caecum. Similar enhancement effects from hemagglutination inhibition were also observed in the antibody titers. Oral administration of Lc-pPG-HN effectively protected against NDV and alleviated the symptoms of the NDV challenge. In summary, recombinant L. casei had positive impacts on the performance, immunological function, gut development, and microbiota of growing chicks and may be a potential therapeutic candidate against NDV.
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Lacticaseibacillus casei , Enfermedad de Newcastle , Vacunas Virales , Animales , Anticuerpos Antivirales , Pollos/inmunología , Escherichia coli , Hemaglutininas/inmunología , Inmunidad , Lacticaseibacillus casei/genética , Neuraminidasa/inmunología , Enfermedad de Newcastle/prevención & control , Virus de la Enfermedad de Newcastle/genética , Vacunas Virales/genética , Vacunas Virales/inmunologíaRESUMEN
In this study, immunogenic efficacies of in ovo administration of Astragalus polysaccharide (APS) along with live Newcastle disease vaccine (live ND vaccine) (live VG/GA strain) were evaluated. Four hundred fertilized eggs were randomly divided into four groups (n = 100/group), and vaccinated in ovo, respectively, with solutions of APS, live ND vaccine, live ND vaccine combined with APS, and 0.9% physiological saline into their amniotic fluid on d 18.5 of incubation. Significant improvement of chicks' development was displayed in those vaccinated with live ND vaccine adjuvanted with APS in ovo, manifested as enhanced hatchability and gaining weight. Moreover, in ovo administration of live NDV vaccine plus APS could significantly enhance the serum anti-NDV antibody titres and interferon gamma (IFN-γ), interleukin (IL)-2, IL-4 and IL-6 concentrations, promote lymphocyte proliferative capability as well as improve the frequencies of CD4+ and CD8+ T cells in peripheral blood. Overall results indicated in ovo administration of live ND vaccine adjuvanted with APS could stimulate stronger humoral and cellular responses in newly hatched chicks.
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Enfermedad de Newcastle , Vacunas Virales , Animales , Anticuerpos Antivirales , Linfocitos T CD8-positivos , Pollos , Enfermedad de Newcastle/prevención & control , Virus de la Enfermedad de Newcastle , Polisacáridos/farmacologíaRESUMEN
The aims of the present study were to determine the role of miR-214 on left ventricular remodeling of rat heart with acute myocardial infarction (AMI) and to further investigate the underlying mechanism of miR-214-mediated myocardial protection. AMI was induced in which adenovirus-expressing miR-214 (Ad-miR-214), anti-miR-214, or Ad-GFP had been delivered into rats hearts 4 days prior, while a phosphatase and tensin homolog (PTEN) inhibitor was administered via intra-peritoneal injection 30 minutes prior to AMI. Changes in hemodynamic parameters were detected and recorded. Left ventricular (LV) dimensions and LV/BW were measured. Quantitative RT-PCR was used to determine the miR-214 expression levels of the myocytes in the infarcted, border, and non-infarcted areas of the LV. Myocardial infarct size was also measured. Flow cytometry analysis was performed to examine cellular apoptosis. Western blot analysis was performed to examine PTEN expression. The results showed that miR-214 was upregulated in both border and infarcted areas. Myocardial cell apoptosis was decreased in the Ad-miR-214 group, but was increased in the anti-miR-214 group, while there were no differences among the Ad-GFP-group, PTEN-ad-miR-214 group, or PTEN-anti-miR-214 group. Myocardial infarct size, LV dimensions, heart rate (HR), and LV end-diastolic pressure (LVEDP) were decreased while the maximal rates of rise or decline in blood pressure in the ventricular chamber (± dp/dt) and LV systolic pressure (LVSP) were increased in the Ad-miR-214 group, all of which exhibited opposite changes in the anti-miR-214 group. PTEN was downregulated in the Ad-miR-214 group and upregulated in the anti-miR-214 group. PTEN was decreased in both the border and infarcted areas compared with non-infarcted areas. The study results suggest that Ad-miR-214 improves LV remodeling and decreases the apoptosis of myocardial cells through PTEN, suggesting a possible mechanism by which Ad-miR-214 functions in protecting against AMI injury.
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Regulación de la Expresión Génica , Ventrículos Cardíacos/fisiopatología , MicroARNs/genética , Infarto del Miocardio/genética , Miocitos Cardíacos/patología , Fosfohidrolasa PTEN/genética , Monoéster Fosfórico Hidrolasas/genética , Animales , Apoptosis , Western Blotting , Modelos Animales de Enfermedad , MicroARNs/metabolismo , Infarto del Miocardio/patología , Infarto del Miocardio/fisiopatología , Miocitos Cardíacos/metabolismo , Fosfohidrolasa PTEN/biosíntesis , Monoéster Fosfórico Hidrolasas/biosíntesis , Reacción en Cadena de la Polimerasa , ARN/genética , Ratas , Ratas Sprague-Dawley , Regulación hacia Arriba , Remodelación Ventricular/genéticaRESUMEN
The electroencephalogram-based (EEG) brain-computer interface (BCI) has garnered significant attention in recent research. However, the practicality of EEG remains constrained by the lack of efficient EEG decoding technology. The challenge lies in effectively translating intricate EEG into meaningful, generalizable information. EEG signal decoding primarily relies on either time domain or frequency domain information. There lacks a method capable of simultaneously and effectively extracting both time and frequency domain features, as well as efficiently fuse these features. Addressing these limitations, a two-branch Manifold Domain enhanced transformer algorithm is designed to holistically capture EEG's spatio-temporal information. Our method projects the time-domain information of EEG signals into the Riemannian spaces to fully decode the time dependence of EEG signals. Using wavelet transform, the time domain information is converted into frequency domain information, and the spatial information contained in the frequency domain information of EEG signal is mined through the spectrogram. The effectiveness of the proposed TBEEG algorithm is validated on BCIC-IV-2a dataset and MAMEM-SSVEP-II datasets.
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Interfaces Cerebro-Computador , Encéfalo , Humanos , Algoritmos , Análisis de Ondículas , Electroencefalografía , ImaginaciónRESUMEN
Purpose: The aim of this study was to investigate the relationship between ARF and coagulopathy in patients with sepsis and to explore the prognostic value of these conditions. Patients and Methods: The data of 271 patients with sepsis-associated coagulopathy admitted from June 2021 to June 2022 were reviewed. The patients were divided into a survival group and a nonsurviving group according to patient prognosis. Independent sample t tests were utilized to compare laboratory parameters within 24 hours of admission, as well as the APACHE II and SOFA scores, between the two patient groups. According to the sepsis-associated coagulation dysfunction (SAC) grading criteria for grading, Spearman correlation analysis was used to study the relationship between blood creatinine and SAC grading and assignment scores, and receiver operating characteristic (ROC) curves and Cox's proportional risk regression model were used to explore the factors affecting the prognosis of SAC patients. Results: Spearman correlation analysis revealed strong associations between serum creatinine (Scr) concentration, SAC classification, and SAC score, with coefficients above 0.7. SAC classification outcomes varied significantly with severity: mild severity had a 77.6% survival rate versus 22.4% mortality; moderate severity had 21.5% survival versus 78.5% mortality; and severe cases had a 0.7% survival rate versus 99.3% mortality (P<0.01 for all). Multivariate analysis revealed significant predictors of outcome, including multiple organ dysfunction syndrome (MODS), with an OR of 2.070 (P=0.019); the SOFA score (OR=1.200, P<0.01); the international normalized ratio (INR) (OR=0.72, P=0.013); and the Scr level (OR=0.995, P<0.01). The areas under the ROC curves for the SOFA score, APACHE II score, and SAC classification were >0.8, all P < 0.05. Conclusion: In patients with sepsis, SAC grade 3 or a SAC score of 4 or higher is associated with poorer prognosis, and the interaction of acute kidney injury exacerbates the degree of SAC, consequently affecting prognosis.
To investigate the relationship between acute renal dysfunction and coagulation dysfunction in patients with sepsis and to explore the prognostic value of these conditions. We collected information and laboratory indicators from 271 patients, classified these two groups of patients according to the grading criteria for sepsis-associated coagulation dysfunction (SAC), and compared the differences between them. We utilized Spearman correlation analysis to investigate the relationship between blood creatinine and the severity of sepsis-associated coagulation dysfunction (SAC). Additionally, we employed a Cox proportional hazards regression model to study the factors influencing the prognosis of SAC patients. This study revealed a significant positive correlation between blood creatinine levels and SAC grade. Furthermore, the presence of MODS, INR, blood creatinine, and SOFA score can serve as independent predictive factors for mortality. We can infer that there is a significant correlation between coagulation function parameters and blood creatinine levels, which play a crucial role in the diagnosis and prognostic analysis of sepsis. In patients with sepsis, a higher grade of SAC or an SAC score of 4 or higher indicates a poorer prognosis. Additionally, the interaction with acute kidney injury exacerbates the severity of SAC, thereby impacting patient prognosis.
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Signal transducer and activator of transcription 3 (STAT3) is essential for neural development and regeneration as a key transcription factor and mitochondrial activator. However, the mechanism of Stat3 in axon development and regeneration has not been fully understood. In this study, using zebrafish posterior lateral line (PLL) axons, we demonstrate that Stat3 plays distinct roles in PLL axon embryonic growth and regeneration. Our experiments indicate that stat3 is required for PLL axon extension. In stat3 mutant zebrafish, the PLL axon ends were stalled at the level of the cloaca, and expression of stat3 rescues the PLL axon growth in a cell-autonomous manner. Jak/Stat signaling inhibition did not affect PLL axon growth indicating Jak/Stat was dispensable for PLL axon growth. In addition, we found that Stat3 was co-localized with mitochondria in PLL axons and important for the mitochondrial membrane potential and ATPase activity. The PLL axon growth defect of stat3 mutants was mimicked and rescued by rotenone and DCHC treatment, respectively, which suggests that Stat3 regulates PLL axon growth through mitochondrial Stat3. By contrast, mutation of stat3 or Jak/Stat signaling inhibition retarded PLL axon regeneration. Meanwhile, we also found Schwann cell migration was also inhibited in stat3 mutants. Taken together, Stat3 is required for embryonic PLL axon growth by regulating the ATP synthesis efficiency of mitochondria, whereas Stat3 stimulates PLL axon regeneration by regulating Schwann cell migration via Jak/Stat signaling. Our findings show a new mechanism of Stat3 in axon growth and regeneration.
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Axones , Pez Cebra , Animales , Axones/metabolismo , Regeneración Nerviosa/fisiología , Transducción de Señal/fisiología , Factor de Transcripción STAT3/metabolismo , Pez Cebra/metabolismoRESUMEN
Physiological signal monitoring and driver behavior analysis have gained increasing attention in both fundamental research and applied research. This study involved the analysis of driving behavior using multimodal physiological data collected from 35 participants. The data included 59-channel EEG, single-channel ECG, 4-channel EMG, single-channel GSR, and eye movement data obtained via a six-degree-of-freedom driving simulator. We categorized driving behavior into five groups: smooth driving, acceleration, deceleration, lane changing, and turning. Through extensive experiments, we confirmed that both physiological and vehicle data met the requirements. Subsequently, we developed classification models, including linear discriminant analysis (LDA), MMPNet, and EEGNet, to demonstrate the correlation between physiological data and driving behaviors. Notably, we propose a multimodal physiological dataset for analyzing driving behavior(MPDB). The MPDB dataset's scale, accuracy, and multimodality provide unprecedented opportunities for researchers in the autonomous driving field and beyond. With this dataset, we will contribute to the field of traffic psychology and behavior.
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Conducción de Automóvil , Movimientos Oculares , HumanosRESUMEN
Severe trauma could induce sepsis due to the loss of control of the infection, which may eventually lead to death. Accurate and timely diagnosis of sepsis with severe trauma remains challenging both for clinician and laboratory. Combinations of markers, as opposed to single ones, may improve diagnosis. We compared the diagnostic characteristics of routinely used biomarkers of sepsis alone and in combination, trying to define a biomarker panel to predict sepsis in severe patients. This prospective observational study included patients with severe trauma (Injury severity score, ISS = 16 or more) in the emergency intensive care unit (EICU) at a university hospital. Blood samples were collected and plasma levels of procalcitonin (PCT), C-reactive protein (CRP), interleukin-6 (IL-6) and serum amyloid A (SAA) were measured using commercial enzyme linked immunosorbent assay (ELISA) kits. A total of 100 patients were eligible for analysis. Of these, 52 were diagnosed with sepsis. CRP yielded the highest discriminative value followed by PCT. In multiple logistic regression, SAA, CRP, and PCT were found to be independent predictors of sepsis. Bioscore which was composed of SAA, CRP, and PCT was shown to be far superior to that of each individual biomarker taken individually. Therefore, compared with single markers, the biomarker panel of PCT, CRP, and SAA was more predictive of sepsis in severe polytrauma patients.
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Proteína C-Reactiva , Sepsis , Humanos , Polipéptido alfa Relacionado con Calcitonina , Proteína Amiloide A Sérica , Biomarcadores , Sepsis/diagnósticoRESUMEN
OBJECTIVE: To determine the role of microRNA 21(miR-21) on left ventricular remodeling of rat heart with ischemia-reperfusion (I/R) injury and to investigate the underlying mechanism of miR-21 mediated myocardium protection. METHODS: Rats were randomly divided into three groups: an I/R model group with Ad-GFP (Ad-GFP group), an I/R model group with Ad-miR-21 (Ad-miR-21 group) and a sham-surgery group. Changes in hemodynamic parameters were recorded at 1 week after I/R. Histological diagnosis was achieved by hematoxylin and eosin (H&E). Left ventricular (LV) dimensions, myocardial infarct size, LV/BW, collagen type â , type â ¢ and PCNA positive cells were measured. Primary cultures of neonatal rat cardiac ventricular myocytes were performed and cell ischemic injury was induced by hypoxia in a serum- and glucose-free medium, and reoxygenation (H/R). MiR-21 inhibitor and pre-miR-21 were respectively added to the culture medium for the miR-21 knockdown and for the miR-21 up-regulation. qRT-PCR was used to determine the miR-21 levels in cultured cells. Flow cytometry was performed to examine the cell apoptosis. RESULTS: In the Ad-miR-21 group, LV dimensions, myocardial infarct size, LV/BW, collagen type â , type â ¢ and PCNA positive cells all significantly decreased compared with the Ad-GFP group. At 1 week after I/R, the Ad-miR-21 significantly improved LVSP, LV +dp/dt(max), LV - dp/dt(min), and decreased heart rate (HR) and LVEDP compared with the Ad-GFP group. Compared with the Ad-GFP, the cell apoptotic rate significantly decreased in the Ad-miR-21 group. The miR-21 inhibitor exacerbated cardiac myocyte apoptosis and the pre-miR-21 decreased hypoxia/reoxygenation- induced cardiac myocyte apoptosis. CONCLUSIONS: Ad-miR-21 improves LV remodeling and decreases the apoptosis of myocardial cells, suggesting the possible mechanism by which Ad-miR-21 functions in protecting against I/R injury.
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Apoptosis/fisiología , MicroARNs/metabolismo , Daño por Reperfusión/terapia , Remodelación Ventricular/fisiología , Animales , Apoptosis/genética , Células Cultivadas , Colágeno/metabolismo , Hemodinámica/genética , Hemodinámica/fisiología , Inmunohistoquímica , Masculino , MicroARNs/genética , Distribución Aleatoria , Ratas , Daño por Reperfusión/genética , Daño por Reperfusión/metabolismo , Remodelación Ventricular/genéticaRESUMEN
OBJECTIVE: To observe the influence of fluid resuscitation on patients suffered from myocardial injury with severe sepsis and septic shock, and to evaluate the markers of myocardial injury during fluid resuscitation. METHODS: Acute physiology and chronic health evaluation II (APACHE II) score of 78 patients with severe sepsis and septic shock induced by combined injuries was 18-35. Serum cardiac troponin I (cTnI), N-terminal-ventricular natriuretic peptide precursor (NT-proBNP) and the hemodynamic parameters were recorded before, 3 days, and 5 days after treatment, and correlative analysis was conducted. RESULTS: Serum cTnI was increased in 62.8% (49/78) patients with severe sepsis and septic shock, and in 73.5% of patients (36/49) the increase was greater than 2-fold of the borderline value, and in 30.6% of patients (15/49) was greater than 4-fold of the borderline value. The patients with elevated serum NT-proBNP at admission accounted for 46.2% (36/78), and after fluid resuscitation treatment, patients with continuously rising value accounted for 74.4% (58/78). The serum cTnI, NT-proBNP, pulmonary arterial wedge pressure (PAWP) and cardiac index (CI) after treatment in survival group (55 cases) were obviously improved, and changes in them in non-survival group (23 cases) was not obvious. The serum cTnI (µg/L) and NT-proBNP (ng/L) levels in the non-survival group were distinctly higher than those of the survival group (cTnI 3 days: 2.09 ± 1.00 vs. 1.57 ± 0.93, 5 days: 1.78 ± 0.67 vs. 0.72 ± 0.51; NT-proBNP 3 days: 3.52 ± 0.73 vs. 3.16 ± 0.65, 5 days: 3.21 ± 0.66 vs. 2.66 ± 0.58), and CI [ml·s(-1)·m(-2)] was obviously lower than that of the survival group (3 days: 57.6 ± 6.2 vs. 68.3 ± 5.6, 5 days: 40.5 ± 4.7 vs. 80.7 ± 6.8, all P < 0.05). The cTnI level (µg/L) of 46 patients whose fluid resuscitation achieved the target was lower than that of the 32 cases without achieving the target (1.16 ± 0.62 vs. 1.97 ± 0.76, P < 0.05), and the CI [ml·s(-1)·m(-2)] was obviously increased (61.2 ± 6.4 vs. 49.3 ± 6.1, P < 0.05). The results suggested that whether the fluid resuscitation achieved the target or not was not related to changes in serum NT-proBNP and PAWP. A positive correlation was found between serum cTnI and NT-proBNP (r = 0.865, Y = 2.069 + 0.695X, P < 0.01), also between NT-proBNP and PAWP (r = 0.762, Y = 1.125 + 4.929X, P < 0.01), and a negative correlation was found between cTnI and CI (r = -0.891, Y = 50.623 - 6.114X, P < 0.01). CONCLUSIONS: There is an obvious myocardial injury in the patient with severe sepsis and septic shock, and fluid resuscitation can improve the myocardial injury; the serum levels of cTnI and NT-proBNP are related to the prognosis of patients, but the significance of NT-proBNP guiding the fluid resuscitation can not be ascertained.
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Resucitación/métodos , Sepsis/terapia , Choque Séptico/terapia , APACHE , Adulto , Anciano , Femenino , Lesiones Cardíacas/prevención & control , Humanos , Masculino , Persona de Mediana Edad , Miocardio/metabolismo , Fragmentos de Péptidos/sangre , Pronóstico , Estudios Retrospectivos , Sepsis/etiología , Choque Séptico/sangre , Choque Séptico/etiología , Troponina I/sangreRESUMEN
Ototoxicity of drugs is an important inducement for hearing loss. Anisomycin is a candidate drug for parasite, cancer, immunosuppression, and mental disease. However, the ototoxicity of anisomycin has not been examined. In this study, the ototoxicity of anisomycin was evaluated using zebrafish lateral line. We found the zebrafish treated with anisomycin during lateral line development could inhibit hair cell formation in a time- and dose-dependent manner. After neuromasts are mature with differentiated hair cells by 5 day post-fertilization, anisomycin could induce hair cell loss effectively through chronic exposure rather than acute exposure. TUNEL assay and qPCR of apoptosis related genes tp53, casp8, casp3a, and casp3b indicated that cell apoptotic was induced by chronic anisomycin exposure. Furthermore, knocking down tp53 with antisense morpholino could attenuate the hair cell loss induced by anisomycin. In addition, we found that anisomycin chronic exposure also inhibited the proliferation of supporting cell. Together, these results indicate that chronic anisomycin exposure could induce hair cell death and block supporting cell proliferation, which causes hair cell loss in zebrafish neuromast. This study provides primary ototoxicity evaluation for anisomycin.
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Anisomicina/toxicidad , Muerte Celular/efectos de los fármacos , Células Ciliadas Auditivas/efectos de los fármacos , Sistema de la Línea Lateral/efectos de los fármacos , Pez Cebra/crecimiento & desarrollo , Animales , Apoptosis/efectos de los fármacos , Proliferación Celular/efectos de los fármacosRESUMEN
Objective: To explore the effect of high-flow humidified oxygen therapy (HFNC) on patients with respiratory failure after general anesthesia extubation for multiple injuries. Methods: 214 patients with multiple injuries in our hospital who underwent general anesthesia and suffered respiratory failure after weaning extubation and received sequential treatment were included. And, they were divided into control group (HFNC group) and observation group (NIMV group) according to the random number table method. Patients in the control group (125 cases) used high-flow nasal cannula (HFNC) after general anesthesia extubation, while patients in the observation group (89 cases) used NIMV. The respiratory rate, heart rate, finger pulse oxygen, oxygenation index (PaO2/FiO2), and re-tracheal intubation rate in the two groups were compared at 2, 8, and 24 hours after sequential treatment, and the mortality rate and hospital stay of ICU time were whole-course observation. And, the effect of conventional oxygen inhalation or HFNC on oxygenation and prognosis was analyzed. Then, SPSS21.0 software was applied for statistical analysis. To analyze the effect of conventional oxygen inhalation or HFNC on the improvement of oxygenation and prognosis, the receiver operating characteristic (ROC) curve can be used to evaluate the feasibility and treatment effect of high-flow nasal oxygen therapy (HFNC) for patients with respiratory failure after general anesthesia extubation for multiple injuries. Results: Compared with the NIMV group, the respiratory frequency and heart rate of the HFNC group were significantly improved after 2 h, 8 h, and 24 h. At the same time, the finger pulse oxygen and oxygenation index increased significantly and returned to normal levels. HFNC can significantly reduce the reintubation rate, ICU hospital stay, and mortality rate. The area under the ROC curve was 0.9102, with 95% CI (0.8256, 0.9949) and P < 0.0001. Conclusion: For patients with multiple injuries undergoing general anesthesia and respiratory failure after weaning and extubation, the application of HFNC can moderate patients' heart rate and respiratory rate faster, increase oxygenation index and finger pulse oxygen, and reduce the reintubation rate, mortality rate, and ICU stay. At the same time, it can effectively improve the respiratory failure of patients after extubation and reduce the occurrence of complications.
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Traumatismo Múltiple , Insuficiencia Respiratoria , Extubación Traqueal , Anestesia General , Humanos , Oxígeno , Terapia por Inhalación de Oxígeno , Insuficiencia Respiratoria/etiología , Insuficiencia Respiratoria/terapiaRESUMEN
BACKGROUND: This study set out to determine key lncRNAs correlated with sepsis via constructing competing endogenous RNA (ceRNA) network. METHODS: Three septic patients and three healthy controls were recruited to obtain lncRNA profiles in this current study. Combined with the mRNA profiles by RNA-sequencing, an integrated analysis of mRNA expression profiles downloaded from GEO was performed to obtain the differentially expressed mRNAs (DEmRNAs). Based on differentially expressed lncRNAs (DElncRNAs) and DEmRNAs acquired in this present study and differentially expressed miRNAs (DEmiRNAs) acquired in previous study, a ceRNA network was constructed. Furthermore, LINC00963 was validated in THP-1 cells by performing loss of function assays. RESULTS: In this analysis, a total of 290 DEmRNAs and 46 DElncRNAs were detected in sepsis. Parkinson's disease, Oxidative phosphorylation and Cardiac muscle contraction were significantly enriched KEGG pathways in sepsis. XPO1, CUL4A, and NEDD8 were three hub proteins of sepsis-specific PPI network. A ceRNA network, which contained 16 DElncRNA-DEmiRNA pairs and 82 DEmiRNA-DEmRNA pairs, involving 5 lncRNAs, 10 miRNAs, and 60 mRNAs, was obtained. The function experiments indicated that knockdown of LINC00963 could promote cell proliferation, reduce cytokine expression, and suppress inflammasome activation and phagocytosis in LPS-induced THP-1 cells. CONCLUSION: This study determined key lncRNAs involved in sepsis, which may contribute to the development for novel treatment strategy of sepsis.
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Redes Reguladoras de Genes , Mapas de Interacción de Proteínas , ARN Largo no Codificante/genética , Sepsis/genética , Proteínas Cullin/genética , Proteínas Cullin/metabolismo , Humanos , Carioferinas/genética , Carioferinas/metabolismo , Proteína NEDD8/genética , Proteína NEDD8/metabolismo , ARN Largo no Codificante/metabolismo , Receptores Citoplasmáticos y Nucleares/genética , Receptores Citoplasmáticos y Nucleares/metabolismo , Sepsis/metabolismo , Células THP-1 , Proteína Exportina 1RESUMEN
The immunomodulatory effect of Acanthopanax senticosus polysaccharide (ASPS) on immunosuppressed chickens induced by cyclophosphamide (Cy) was observed in this study. Four hundred 7-day-old chickens were randomly divided into 4 groups: vaccinated control group (VC group), Cy-challenged control group (Cy group), Cy-challenged + low-dose ASPS group (ASPSL + Cy group), and Cy-challenged + high-dose ASPS group (ASPSH + Cy group). All groups except the VC group were injected with Cy at a dose of 80 mg/kg/day of BW for 3 successive days to induce immunosuppression. At the age of 10 d, the ASPSL + Cy group and ASPSH + Cy group were intramuscularly injected with 0.2 mL of ASPS at the dose of 100 and 200 mg/mL/day, respectively, once a day for 3 successive days. The Cy group was injected with saline solution in the same way as the 2 ASPS groups. At the age of 14 d, the chickens were vaccinated with Newcastle disease (ND) vaccine in all groups. On day 7, 14, 21, and 28 after the vaccination, BW, lymphocyte proliferation, the serum antibody titers of the ND vaccine, the proportion of CD4+ and CD8+ T lymphocytes, and the concentrations of interferon gamma and IL-2 were determined. The results showed that chickens were injected with Cy at a dose of 80 mg/kg of BW for 3 d displayed lower immune responses than the control group, indicating that the immunosuppressive model was successfully established. At most time points, both high and low doses of ASPS could significantly promote lymphocyte proliferation; enhance BW, antibody titers, and the proportion of CD4+ and CD8+ T lymphocytes; and raised the concentrations of interferon gamma and IL-2 in Cy-treated chickens compared with those in the Cy control group (P < 0.05). These results indicated that ASPS could resist immunosuppression induced by Cy and may be a new-type immune adjuvant to improve vaccination in normal and immunosuppressed chickens.
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Pollos/inmunología , Eleutherococcus/inmunología , Terapia de Inmunosupresión/veterinaria , Enfermedad de Newcastle , Vacunas Virales , Adyuvantes Inmunológicos , Animales , Anticuerpos/sangre , Recuento de Linfocito CD4/métodos , Recuento de Linfocito CD4/veterinaria , Linfocitos T CD8-positivos/citología , Proliferación Celular , Ciclofosfamida/administración & dosificación , Inmunosupresores/administración & dosificación , Interferón gamma/sangre , Interleucina-2/sangre , Enfermedad de Newcastle/prevención & control , Virus de la Enfermedad de Newcastle/inmunología , Polisacáridos/inmunología , Distribución AleatoriaRESUMEN
In this study, the effects of synbiotic inclusion at the intra-amniotic stage in layer chicks were evaluated with different parameters, such as performance, immunological function, intestinal development, and cecal microflora content. A total of 1,200 eggs with fertile embryos were allocated into four treatment groups. For every treatment, five replicates were used, and 60 eggs were included in each replicate. The following four treatment groups were established: the non-injected group, 0.9% physiological saline injection (saline) group, 1 × 106 CFU/egg Lactobacillus plantarum injection (probiotic) group, and 1 × 106 CFU/egg L. plantarum + 2 mg/egg Astragalus polysaccharide injection (synbiotic) group. In ovo injection was carried out at 18.5 days of incubation. The results showed that in ovo injection of probiotics or synbiotics did not affect the hatching or growth performance of the chicks but significantly increased their feed intake (FI), body weight (BW), and the feed conversion ratio (FCR). Additionally, in ovo injection of synbiotics enhanced the levels of serum interleukin-2 (IL-2), interferon-γ (IFN-γ), and secretory immunoglobulin A (SIgA) in intestinal lavage fluid and the histomorphological development of the small intestine. Our results also indicated that intra-amniotic synbiotic injection significantly increased Lactobacillus and Bifidobacterium colonization while decreasing the relative abundance of Escherichia coli in the chicken cecum (P < 0.05). In summary, in ovo injection of synbiotics had positive impacts on the performance, immunological function, gut development, and microbiota of growing chicks.
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The purpose of this study was to examine the effects of in ovo injection of Astragalus polysaccharide (APS) on hatchability, body weight (BW), intestinal histomorphology, the number of IgA+ cells and sIgA content in intestine, and the expression of intestinal immune-related genes in broiler chickens. On day 18 of the incubation, a total of 960 live embryo eggs were weighed and randomly divided into 4 treatment groups: a control group and three APS groups. The eggs in the control group were injected with 0.5 mL physiological saline. The eggs in the APS groups were injected with 3 different amounts of APS in 0.5 mL physiological saline: 1 mg (APSL), 2 mg (APSM) and 4 mg (APSH). The solution was injected into the amnion of each egg. The results showed that in ovo injection of APS did not affect the hatchability but increased the body weight of the 14 d and 21 d chickens, with a significant increase observed in the APSM group (P < 0.05). At most time points, the villus height (VH) was increased (P < 0.05) and the crypt depth (CD) was decreased (P < 0.05) in the small intestine of the broilers, with higher VH/CD ratios in the APSL and APSM groups compared with the control group. The number of IgA+ cells in the mucosa and the secretory immunoglobulin A (sIgA) levels in the intestinal washings were higher in the APSM and APSH groups than in the APSL and control groups. The gene expression levels of interleukin (IL)-2, interleukin (IL)-4, interferon gamma (IFN-γ), and Toll-like receptor (TLR)-4 were significantly enhanced by APS stimulation at most time points (P < 0.05). These results indicated that in ovo injection of APS has the potential of promoting intestinal development and enhancing intestinal mucosal immunity of broiler chickens in the early stage after hatching.
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BACKGROUND: Sepsis is a life-threatening organ dysfunction, initiated by a dysregulated host response to infection. This study aimed to determine key genes and microRNAs (miRNAs) correlated with sepsis. METHODS: Three patients with sepsis and three healthy individuals treated as controls were recruited in the current study. To identify differentially expressed mRNAs (DEmRNAs) and differentially expressed miRNAs (DEmiRNAs) between patients with sepsis and controls, RNA-sequencing and bioinformatics analysis were conducted. DEmiRNA-target DEmRNAs analysis and functional annotation of DEmiRNA-target DEmRNAs were performed. Dataset GSE46955, used to validate the expression of selected DEmRNAs, was downloaded from the Gene Expression Omnibus database. RESULTS: Compared with septic patients, a total of 1199 DEmRNAs and 23 DEmiRNAs were identified. Based on DEmiRNA-target DEmRNAs analysis, hsa-miR-106b-5p (degree = 155), hsa-miR-128-3p (degree = 128), and hsa-miR-144-3p (degree = 79) were the top 3 DEmiRNAs that covered most DEmRNAs. The T cell receptor signaling pathway, pathways in cancer, FoxO signaling pathway, and influenza A were the significantly enriched Kyoto Encyclopedia of Genes and Genomes pathways of DEmiRNA-target DEmRNAs in sepsis. CONCLUSION: We identified key genes and miRNAs related to sepsis. Our findings will provide new insights into understanding sepsis pathogenesis.
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MicroARNs/análisis , ARN Mensajero/análisis , Sepsis/genética , Análisis de Secuencia de ARN/métodos , Adolescente , Adulto , Biología Computacional , Humanos , Masculino , Transducción de SeñalRESUMEN
OBJECTIVE: To elucidate effects of intensive insulin therapy and target glucose control on hemodynamics and cardiac function in patients with septic shock. METHODS: Twenty-seven patients of septic shock with myocardial depression were divided into routine group (14 cases, level of blood glucose was 4.1 to 6.1 mmol/L) and target group (13 cases, level of blood glucose was 6.2 to 8.3 mmol/L). Hemodynamics and cardiac function parameters were obtained via pulmonary artery catheter after 48 hours. RESULTS: Mean blood glucose level in target group was lower than that in routine group [(6.0+/-1.5) mmol/L vs. (8.2+/-1.9) mmol/L, P<0.05], with dosage of insulin infusion in target group increased as compared with that of routine group [(10.3+/-3.7) U/h vs. (7.5+/-3.0) U/h, P<0.05]. Furthermore, oxygenation index (PaO(2)/FiO(2)), stroke volume index (SVI), cardiac index (CI) and oxygen delivery index (DO(2)I) were increased 20.2%, 23.3%, 15.1% and 11.7%, respectively (all P<0.05). On the other hands, there was no significant difference between target and routine group in mean artery pressure, acute physiology and chronic health evaluation II (APACHEII) score, blood lactic acid (all P>0.05), although the incidence of severe hypoglycemia was higher in target group than the routine group (38.5% vs. 28.6%, P>0.05). CONCLUSION: Intensive insulin therapy and blood glucose control may improve hemodynamic status and enhance cardiac function in patients with septic shock and myocardial depression.
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Hemodinámica/efectos de los fármacos , Insulina/administración & dosificación , Choque Séptico/fisiopatología , Adulto , Femenino , Corazón/efectos de los fármacos , Corazón/fisiopatología , Humanos , Insulina/uso terapéutico , Masculino , Persona de Mediana Edad , Choque Séptico/tratamiento farmacológicoRESUMEN
The aim of this study was to investigate the protective effect of erythropoietin (EPO) against acute myocardial injury and its underlying mechanisms. Mice (n=146) were randomly divided in a doubleblind manner into four groups, sham, Rocephin, EPO and sepsis, and mortality was observed on the seventh day after cecal ligation and puncture. In addition, a total of 252 rats were randomly divided into three groups, sham, EPO and sepsis, and indicators of cardiac function, inflammatory mediators and serum creatine kinase levels were assessed. Mitochondrial membrane potential, cell apoptosis and nuclear factor κlightchainenhancer of activated B cells (NFκB) p65 expression levels were detected using flow cytometry. Following intervention with EPO, the mortality rate in mice with sepsis was significantly reduced and the cardiac function of septic rats was significantly improved. In addition, the levels of inflammatory mediators, serum creatine kinase and apoptosis and the myocardial mitochondrial membrane potential and expression of NFκB p65 in cardiac tissue were all improved following EPO treatment, and the differences between the results for the sepsis and EPO groups were statistically significant (P<0.05). These findings suggest that EPO reduces the myocardial inflammatory response in septic rats, attenuates the reduction in mitochondrial membrane potential and inhibits myocardial cell apoptosis by reducing NFκB p65 expression, and therefore exerts a protective effect in the myocardium.