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ETHNOPHARMACOLOGICAL RELEVANCE: In accordance with the tenets of traditional Chinese medicine, sepsis is categorized into three distinct syndromes: heat syndrome, blood stasis syndrome, and deficiency syndrome. Xiaochaihu decoction (XCHD) has many functions, including the capacity to protect the liver, cholagogue, antipyretic, anti-inflammatory, and anti-pathogenic microorganisms. XCHD exerts the effect of clearing heat and reconciling Shaoyang. The XCHD contains many efficacious active ingredients, yet the mechanism of sepsis-induced cardiomyopathy (SIC) remains elusive. AIM OF THE STUDY: To investigate the molecular mechanisms underlying the protective effects of XCHD against SIC using an integrated approach combining network pharmacology and molecular biology techniques. MATERIALS AND METHODS: Network pharmacology methods identified the active ingredients, target proteins, and pathways affected by XCHD in the context of SIC. We conducted in vivo experiments using mice with lipopolysaccharide-induced SIC, evaluating cardiac function through echocardiography and histology. XCHD-containing serum was analyzed to determine its principal active components using ultra-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS). The effects of XCHD-containing serum on SIC were further tested in vitro in LPS-treated H9c2 cardiac cells. Protein expression levels were quantified via Western blotting and enzyme-linked immunosorbent assay (ELISA). Additionally, molecular docking was performed between the active components and ZBP1, a potential target protein. Overexpression of ZBP1 in H9c2 cells allowed for a deeper exploration of its role in modulating SIC-associated gene expression. RESULTS: UPLC-MS/MS identified 31 shared XCHD and XCHD-containing serum components. These included organic acids, terpenoids, and flavonoids, which have been identified as the active components of XCHD. Our findings revealed that XCHD alleviated LPS-induced myocardial injury, improved cardiac function, and preserved cardiomyocyte morphology in mice. In vitro studies, we demonstrated that XCHD-containing serum significantly suppressed the expression of inflammatory cytokines (IL-6, IL-1ß, and TNF-α) in LPS-induced H9c2 cells. Mechanistic investigations showed that XCHD downregulated genes associated with PANoptosis, a novel cell death pathway, suggesting its protective role in sepsis-damaged hearts. Conversely, overexpression of ZBP1 abolished the protective effects of XCHD and amplified PANoptosis-related gene expression. CONCLUSIONS: Our study provides the first evidence supporting the protective effects of XCHD against SIC, both in vitro and in vivo. The underlying mechanism involves the inhibition of ZBP1-initiated PANoptosis, offering new insights into treating SIC using XCHD.
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Cardiomiopatías , Medicamentos Herbarios Chinos , Sepsis , Animales , Medicamentos Herbarios Chinos/farmacología , Sepsis/tratamiento farmacológico , Sepsis/complicaciones , Cardiomiopatías/tratamiento farmacológico , Cardiomiopatías/metabolismo , Ratones , Masculino , Línea Celular , Ratones Endogámicos C57BL , Miocitos Cardíacos/efectos de los fármacos , Miocitos Cardíacos/metabolismo , Lipopolisacáridos/toxicidad , Farmacología en Red , Ratas , Modelos Animales de Enfermedad , Espectrometría de Masas en TándemRESUMEN
Objetivo: Determinar el nivel de conocimiento de los estudiantes de enfermería de la Universidad Técnica de Ambato sobre sepsis quirúrgica. Material y método: La presente investigación tiene un diseño de desarrollo observacional, de tipo descriptivo, cohorte transversal, con un enfoque cuantitativo, ya que el nivel de cono-cimiento se verá representado mediante tablas y gráficos para des-cribir la problemática del periodo octubre 2023 febrero 2024. Re-sultados: Se evidencia un alto porcentaje de respuestas incorrectas por cada ítem por parte de los estudiantes. La categoría Nivel de Conocimiento sobre Definición de Sepsis, fue respondida de ma-nera incorrecta con un porcentaje del 83,9%, la categoría Nivel de Conocimiento sobre Diagnóstico de Sepsis obtuvo 51,7% y, por úl-timo, la Nivel de Conocimiento sobre Tratamiento de Sepsis con el 29,2%. Conclusiones: El nivel de conocimiento de los estudiantes sobre Sepsis Quirúrgica es malo, debido a que existe una subesti-mación de la gravedad de la sepsis como afección potencialmente mortal, lo que puede traer un impacto negativo en los pacientes[AU]
Objective: Determine the level of knowledge of nursing students at the Technical University of Ambato about surgical sepsis. Mate-rials and methods: This research has an observational, descriptive, transversal development design, with a quantitative approach since the level of knowledge will be represented through tables and gra-phs to describe the problems of the period October 2023-February 2024. Results: A high percentage of incorrect answers for each item by the students is evident. The category Level of Knowledge about Definition of Sepsis was answered incorrectly with a percentage of 83.9%, the category Level of Knowledge about Diagnosis of Sepsis obtained 51.7% and, finally, the category Level of Knowledge about Treatment of Sepsis. Sepsis with 29.2%. Conclusions: The level of knowledge of students about Surgical Sepsis is poor because there is an underestimation of the severity of sepsis as a potentially fatal condition, which can have a negative impact on patients[AU]
Objetivo: Determinar o nível de conhecimento dos estudantes de enfermagem da Universidade Técnica de Ambato sobre sepse ci-rúrgica. Material e método: Esta pesquisa possui desenho de coor-te observacional, descritivo, transversal, com abordagem quantita-tiva, uma vez que o nível de conhecimento será representado por meio de tabelas e gráficos para descrever o problema no período de outubro de 2023 a fevereiro de 2024. Resultados: Uma parada. É evidente o percentual de respostas incorretas para cada item por parte dos alunos. A categoria Nível de Conhecimento sobre Defi-nição de Sepse foi respondida incorretamente com percentual de 83,9%, a categoria Nível de Conhecimento sobre Diagnóstico de Sepse obteve 51,7% e por fim, a categoria Nível de Conhecimen-to sobre Tratamento de Sepse com 29,2%. Conclusões: O nível de conhecimento dos estudantes sobre a Sepse Cirúrgica é baixo, pois há uma subestimação da gravidade da sepse como uma condição potencialmente fatal, que pode ter um impacto negativo nos pa-cientes[AU]
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Humanos , Masculino , Femenino , Conocimientos, Actitudes y Práctica en Salud , Sepsis/complicaciones , Sepsis/diagnóstico , EcuadorRESUMEN
OBJECTIVE: To construct and validate a nomogram model for predicting sepsis-associated acute kidney injury (SA-AKI) risk in intensive care unit (ICU) patients. METHODS: A retrospective cohort study was conducted. Adult sepsis patients admitted to the department of ICU of the 940th Hospital of Joint Logistic Support Force of PLA from January 2017 to December 2022 were enrolled. Demographic characteristics, clinical data within 24 hours after admission to ICU diagnosis, and clinical outcomes were collected. Patients were divided into training set and validation set according to a 7 : 3 ratio. According to the consensus report of the 28th Acute Disease Quality Initiative Working Group (ADQI 28), the data were analyzed with serum creatinine as the parameter and AKI occurrence 7 days after sepsis diagnosis as the outcome. Lasso regression analysis and univariate and multivariate Logistic regression analysis were performed to construct the nomogram prediction model for SA-AKI. The discrimination and accuracy of the model were evaluated by the Hosmer-Lemeshow test, receiver operator characteristic curve (ROC curve), decision curve analysis (DCA), and clinical impact curve (CIC). RESULTS: A total of 247 sepsis patients were enrolled, 184 patients developed SA-AKI (74.49%). The number of AKI patients in the training and validation sets were 130 (75.58%) and 54 (72.00%), respectively. After Lasso regression analysis and univariate and multivariate Logistic regression analysis, four independent predictive factors related to the occurrence of SA-AKI were selected, namely procalcitonin (PCT), prothrombin activity (PTA), platelet distribution width (PDW), and uric acid (UA) were significantly associated with the onset of SA-AKI, the odds ratio (OR) and 95% confidence interval (95%CI) was 1.03 (1.01-1.05), 0.97 (0.55-0.99), 2.68 (1.21-5.96), 1.01 (1.00-1.01), all P < 0.05, respectively. A nomogram model was constructed using the above four variables. ROC curve analysis showed that the area under the curve (AUC) was 0.869 (95%CI was 0.870-0.930) in the training set and 0.710 (95%CI was 0.588-0.832) in the validation set. The P-values of the Hosmer-Lemeshow test were 0.384 and 0.294, respectively. In the training set, with an optimal cut-off value of 0.760, a sensitivity of 77.5% and specificity of 88.1% were achieved. Both DCA and CIC plots demonstrated the model's good clinical utility. CONCLUSIONS: A nomogram model based on clinical indicators of sepsis patients admitted to the ICU within 24 hours could be used to predict the risk of SA-AKI, which would be beneficial for early identification and treatment on SA-AKI.
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Lesión Renal Aguda , Unidades de Cuidados Intensivos , Nomogramas , Curva ROC , Sepsis , Humanos , Lesión Renal Aguda/diagnóstico , Lesión Renal Aguda/etiología , Sepsis/diagnóstico , Sepsis/complicaciones , Estudios Retrospectivos , Factores de Riesgo , Modelos Logísticos , Femenino , Masculino , Creatinina/sangre , Persona de Mediana Edad , Estudios de CohortesRESUMEN
Sepsis-associated encephalopathy (SAE) is the most common neurological complication of sepsis, with an incidence of up to 70% in sepsis, and contributes to the increased mortality and disability in sepsis. To date, the exact pathogenesis of SAE is not clear. Most of current researches indicated that blood-brain barrier (BBB) dysfunction, active neuroinflammation, glial cell over activation as well as cerebral microcirculation dysfunction contributed to the pathophysiology of SAE. BBB, as a complex cellular structure between the central nervous system and the peripheral system, strictly controls the entrance and discharge of substances and plays an important role in maintaining the balance between biochemical system and immune system of central system. During the progress of sepsis, inflammatory cytokines and reactive oxygen species resulting from peripheral system directly or indirectly resulted in the damage to the integrity and structure of BBB, which helped above species easily enter into the central system. Above these damages caused glial cell activation (microglia and astrocyte), the imbalance of neurotransmitters, mitochondrial dysfunction and neural apoptosis, which also reversely contributed to the damage to the integrity and permeability of BBB via decreasing the expression of tight junctional protein between cells. Therefore, this review focuses on the structural and functional changes of BBB in SAE, and how these changes lead to the development of SAE, in order to seek a BBB-targeted therapy for SAE.
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Barrera Hematoencefálica , Encefalopatía Asociada a la Sepsis , Sepsis , Humanos , Encefalopatía Asociada a la Sepsis/fisiopatología , Sepsis/complicaciones , Sepsis/fisiopatología , Animales , Especies Reactivas de Oxígeno/metabolismo , Citocinas/metabolismo , Astrocitos/metabolismoRESUMEN
Sepsis associated Acute kidney injury (AKI) is a common clinical syndrome characterized by suddenly decreased in renal function and urinary volume. This study was designed to investigate the role of Aquaporin 1 (AQP1) and P53 in the development of sepsis-induced AKI and their potential regulatory mechanisms. Firstly, transcriptome sequencing analysis of mice kidney showed AQP1 expression was reduced and P53 expression was elevated in Cecal ligation and puncture (CLP)-induced AKI compared with controls. Bioinformatics confirmed that AQP1 expression was remarkably decreased and P53 expression was obviously elevated in renal tissues or peripheral blood of septic AKI patients. Moreover, we found in vivo experiments that AQP1 mRNA levels were dramatically decreased and P53 mRNA significantly increased following the increased expression of inflammation, apoptosis, fibrosis, NGAL and KIM-1 at various periods in septic AKI. Meanwhile, AQP1 and P53 protein levels increased significantly first and then decreased gradually in kidney tissue and serum of rats in different stages of septic AKI. Most importantly, in vivo and vitro experiments demonstrated that silencing of AQP1 greatly exacerbates renal or cellular injury by up-regulating P53 expression promoting inflammatory response, apoptosis and fibrosis. Overexpression of AQP1 prevented the elevation of inflammation, apoptosis and fibrosis by down-regulating P53 expression in Lipopolysaccharide (LPS)-induced AKI or HK-2 cells. Therefore, our results suggested that AQP1 plays a protective role in modulating AKI and can attenuate inflammatory response, apoptosis and fibrosis via downregulating P53 in septic AKI or LPS-induced HK-2cells. The pharmacological targeting of AQP1 mediated P53 expression might be identified as potential targets for the early treatment of septic AKI.
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Lesión Renal Aguda , Apoptosis , Acuaporina 1 , Fibrosis , Inflamación , Sepsis , Proteína p53 Supresora de Tumor , Lesión Renal Aguda/metabolismo , Lesión Renal Aguda/etiología , Proteína p53 Supresora de Tumor/metabolismo , Proteína p53 Supresora de Tumor/genética , Acuaporina 1/genética , Acuaporina 1/metabolismo , Animales , Sepsis/complicaciones , Sepsis/metabolismo , Ratones , Humanos , Masculino , Ratas , Modelos Animales de Enfermedad , Riñón/patología , Riñón/metabolismo , Ratones Endogámicos C57BL , Ratas Sprague-DawleyRESUMEN
OBJECTIVE: To establish a nomogram model for predicting the risk of sepsis in diabetic foot patients, and to provide reference for clinical prevention and treatment. METHODS: The clinical data of 430 patients with diabetic foot who were hospitalized in Chu Hsien-I Memorial Hospital of Tianjin Medical University from January 2022 to March 2023 were reviewed and collected, including age, gender, past medical history, smoking and drinking history, family history, diabetes course, Texas grade of diabetic foot and laboratory indicators within 24 hours after admission. Patients were divided into sepsis group and non-sepsis group according to the presence or absence of sepsis during hospitalization. The differences in clinical data between the two groups were compared. Multivariate Logistic regression analysis was used to screen the influencing factors of sepsis in patients with diabetic foot during hospitalization, and a nomogram predictive model was established. The performance of the prediction model was evaluated by receiver operator characteristic curve (ROC curve), calibration curve and decision curve analysis (DCA). Internal validation was performed by using Bootstrap method. RESULTS: A total of 430 patients were enrolled, among which 90 patients developed sepsis during hospitalization and 340 patients did not. There were statistically significant differences in diabetes course, Texas grade of diabetic foot, white blood cell count (WBC), neutrophil count (NEU), lymphocyte count (LYM), neutrophil to lymphocyte ratio (NLR), hemoglobin (Hb), albumin (Alb), glycosylated hemoglobin (HbA1c), C-reactive protein (CRP), and blood urea nitrogen (BUN) between the two groups. Multivariate Logistic regression analysis showed that diabetes course [odds ratio (OR) = 2.774, 95% confidence interval (95%CI) was 1.053-7.308, P = 0.039], Texas grade of diabetic foot (OR = 2.312, 95%CI was 1.014-5.273, P = 0.046), WBC (OR = 1.160, 95%CI was 1.042-1.291, P = 0.007), HbA1c (OR = 1.510, 95%CI was 1.278-1.784, P < 0.001), CRP (OR = 1.007, 95%CI was 1.000-1.014, P = 0.036) were independent risk factors for sepsis in patients with diabetic foot during hospitalization, while Alb was a protective factor (OR = 0.885, 95%CI was 0.805-0.972, P = 0.011). A nomogram predictive model was constructed based on the above 6 indicators. The ROC curve showed that the area under ROC curve (AUC) of the nomogram predictive model for identifying the sepsis patients was 0.919 (95%CI was 0.889-0.948). The AUC of the nomogram predictive model after internal verification was 0.918 (95%CI was 0.887-0.946). Hosmer-Lemeshow test showed χ 2 = 2.978, P = 0.936, indicating that the calibration degree of the predictive model was good. Calibration curve showed that the predicted probability of sepsis was in good agreement with the actual probability. DCA curve showed that the nomogram predictive model had good clinical usefulness. CONCLUSIONS: The nomogram predictive model based on the risk factors of diabetes course, Texas grade of diabetic foot, WBC, HbA1c, CRP and Alb has good predictive value for the occurrence of sepsis in patients with diabetic foot during hospitalization, which is helpful for clinical screening of the possibility of diabetic foot patients progressing to sepsis, and timely personalized intervention for different patients.
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Pie Diabético , Nomogramas , Sepsis , Humanos , Sepsis/diagnóstico , Sepsis/complicaciones , Sepsis/sangre , Pie Diabético/diagnóstico , Pie Diabético/sangre , Pie Diabético/epidemiología , Factores de Riesgo , Modelos Logísticos , Curva ROC , Femenino , Masculino , Persona de Mediana EdadRESUMEN
OBJECTIVE: To investigate the protective effects of an anti-inflammatory mixture on acute lung injury (ALI) induced by sepsis in rats, as well as its possible mechanisms. METHODS: A total of 40 Sprague-Dawley (SD) rats were randomly divided into the sham group, septic ALI model group (model group), 3-methyladenine (3-MA) control group, and anti-inflammatory mixture pretreatment group, with 10 rats in each group. Cecal ligation and perforation (CLP) was performed to reproduce a septic ALI model. The rats in the sham group only underwent opening and closing the abdomen without perforation and ligation. Both groups were given saline gavage and intraperitoneal injection for 3 consecutive days before surgery. The 3-MA control group was given intraperitoneal injection of saline and autophagy inhibitor 3-MA 15 mg/kg for 3 consecutive days before modeling. The anti-inflammatory mixture pretreatment group was given 8.8 mL/kg of anti-inflammatory mixture by gavage [the composition of anti-inflammatory mixture: rhubarb 15 g (after the next), coptis chinensis 15 g, baical skullcap root 12 g, magnoliae cortex 12 g, dahurian patrinia herb 30 g] and saline intraperitoneal injection for 3 consecutive days before modeling. The rats in each group were anesthetized 24 hours after surgery and died due to abdominal aortic blood collection. Enzyme-linked immunosorbent assay (ELISA) was used to detect the levels of serum inflammatory cytokines interleukins (IL-1ß and IL-6). Lung tissue was taken and then the bronchoalveolar lavage fluid (BALF) was collected, and the levels of IL-1ß and IL-6 were detected by ELISA. Lung wet/dry weight (W/D) ratio was measured. After hematoxylin-eosin (HE) staining, the histopathological changes of the lungs were observed under light microscopy. Western blotting was used to detect the expression of autophagy markers microtubule-associated protein 1 light chain 3- II/I (LC3- II/I) and Beclin-1 protein in lung tissue. Autophagosomes in lung tissue were observed with transmission electron microscopy. RESULTS: Compared with the sham group, the rats in the model group exhibited severe destruction of lung tissue structure, with significant infiltration of inflammatory cells, the lung W/D ratio and the levels of IL-1ß and IL-6 in serum and BALF were significantly increased, the expressions of LC3- II/I and Beclin-1 protein were down-regulated, the autophagosomes were more. The rats in the 3-MA control group exhibited more severe lung tissue injury as compared with the model group, the lung W/D ratio and the levels of inflammatory cytokines in serum and BALF were further increased, the expressions of LC3- II/I and Beclin-1 protein still showed a decrease tendency as compared with the sham group, and the autophagosomes were less than that in the model group. Compared with the model group, the anti-inflammatory mixture pretreatment group showed milder lung tissue injury with a minimal amount of inflammatory cell infiltration, the lung W/D ratio was significantly reduced (7.07±1.02 vs. 11.33±1.85, P < 0.05), the levels of IL-1ß and IL-6 in both serum and BALF were significantly decreased [IL-1ß (ng/L): 26.04±3.86 vs. 40.83±5.46 in serum, 17.75±2.02 vs. 26.86±4.32 in BALF; IL-6 (ng/L): 91.28±10.15 vs. 129.44±13.05 in serum, 76.06±7.51 vs. 120.91±7.47 in BALF, all P < 0.05], and the ratio of LC3- II/I and Beclin-1 protein expression were significantly increased [LC3- II/I ratio: 1.23±0.02 vs. 0.60±0.02, Beclin-1 protein (Beclin-1/GAPDH): 2.37±0.33 vs. 0.62±0.05, both P < 0.05]. Furthermore, an increase in the number of autophagosomes was observed. CONCLUSIONS: The anti-inflammatory mixture improves lung injury in rats with sepsis induced by CLP and reduce inflammation levels, potentially through upregulation of Beclin-1-mediated autophagy.
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Lesión Pulmonar Aguda , Autofagia , Beclina-1 , Ratas Sprague-Dawley , Sepsis , Animales , Lesión Pulmonar Aguda/etiología , Lesión Pulmonar Aguda/metabolismo , Ratas , Sepsis/complicaciones , Sepsis/metabolismo , Sepsis/tratamiento farmacológico , Autofagia/efectos de los fármacos , Masculino , Beclina-1/metabolismo , Antiinflamatorios/farmacología , Proteínas Reguladoras de la Apoptosis/metabolismo , Interleucina-1beta/metabolismo , Pulmón/patología , Pulmón/metabolismo , Interleucina-6/metabolismo , Modelos Animales de EnfermedadRESUMEN
OBJECTIVE: To explore the causal relationship between thyroid dysfunction and sepsis based on the bidirectional two-sample Mendelian randomization (MR) method. METHODS: The genome-wide association study (GWAS) dataset were selected to screen single nucleotide polymorphisms (SNP) associated with thyroid dysfunction as instrumental variable (IV) for genetic variation, using hypothyroidism and hyperthyroidism as exposure factor and sepsis as outcome factor. Potential causal relationship between thyroid dysfunction and sepsis was analyzed using a bidirectional two-sample MR method primary analysis method of inverse-variance weighted (IVW). Potential pleiotropic analysis of SNP was performed using the MR Egger regression intercept test. Sensitivity analysis was performed using the "leave one out" test. Reverse MR method was used to prove the causal relationship. RESULTS: The GWAS data were screened based on the three main assumptions of MR, resulting in 101 SNP strongly associated with hypothyroidism and 10 SNP strongly associated with hyperthyroidism entering the MR analysis. The results of the MR using the IVW method showed that the risk of sepsis in individuals with hypothyroidism was 2.293 times higher than those without hypothyroidism [odds ratio (OR) = 2.293, 95% confidence interval (95%CI) was 1.199-4.382, P = 0.012]. There was no significant difference in the risk of sepsis between hyperthyroid and non-hyperthyroid populations (OR = 1.049, 95%CI was 0.999-1.100, P = 0.560). MR Egger regression intercept test showed that the included SNP did not have pleiotropy, and the MR-PRESSO test did not find outliers. Sensitivity analysis suggested that the results of MR were stable. The results of the reverse MR analysis showed that the reverse causal relationship between hyperthyroidism and sepsis was not proved (OR = 0.996, 95%CI was 0.988-1.004, P = 0.338), which further confirmed the robust MR analysis result. CONCLUSIONS: The results of the bidirectional two-sample MR analysis show that hypothyroidism can increase the risk of sepsis onset, while there is no causal relationship between hyperthyroidism and sepsis.
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Estudio de Asociación del Genoma Completo , Hipertiroidismo , Análisis de la Aleatorización Mendeliana , Polimorfismo de Nucleótido Simple , Sepsis , Humanos , Sepsis/genética , Sepsis/complicaciones , Hipertiroidismo/genética , Hipertiroidismo/complicaciones , Hipotiroidismo/genética , Factores de Riesgo , Enfermedades de la Tiroides/genéticaRESUMEN
Sepsis is a common and severe infectious disease, and its associated coagulation dysfunction can cause disseminated intravascular coagulation (DIC) and organ failure, leading to a significant increase in mortality. Pyroptosis is a form of programmed cell death mediated by caspase-1 in the classical pathway and caspase-4/caspase-5/caspase-11 in the non-classical pathway, along with the effector molecule gasdermin (GSDM) family. Recent studies have shown that pyroptosis plays an important role in the development of coagulation disorders in sepsis. Pyroptosis leads to the formation of cytoplasmic membrane pores, cell swelling and membrane rupture, as well as the release and enhanced activity of procoagulant contents, strongly promoting the development of systemic coagulation activation and DIC in sepsis. Therefore, exploring the role and molecular mechanisms of pyroptosis in sepsis-related coagulation disorders is of great significance for the prevention and treatment of sepsis. This article provides a review of the mechanisms involved in pyroptosis and coagulation disorders in sepsis, as well as the role and mechanisms of pyroptosis in sepsis-associated coagulation disorders to provide new ideas for sepsis related research.
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Trastornos de la Coagulación Sanguínea , Coagulación Intravascular Diseminada , Piroptosis , Sepsis , Sepsis/metabolismo , Sepsis/complicaciones , Sepsis/fisiopatología , Humanos , Trastornos de la Coagulación Sanguínea/etiología , Coagulación Intravascular Diseminada/etiología , Caspasas/metabolismo , Caspasa 1/metabolismo , AnimalesRESUMEN
Sepsis is a life-threatening organ dysfunction caused by the host's dysfunctional response to infection. Sepsis-induced cardiomyopathy (SICM), as a serious complication of sepsis, is an acute reversible cardiac dysfunction syndrome unrelated to myocardial ischemia, which affects the outcome and prognosis of sepsis. As a complex microbial system, gut microbiota has been confirmed to be involved in the development of coronary heart disease, hypertension, heart failure and other cardiovascular diseases, and is also related to the occurrence and development of sepsis. However, there are few studies on the relationship between gut microbiota and SICM. This paper reviews the current research progress on gut microbiota and SICM, aiming at provide a new idea for clinical treatment of SICM.
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Cardiomiopatías , Disbiosis , Microbioma Gastrointestinal , Sepsis , Sepsis/complicaciones , Sepsis/microbiología , Humanos , Cardiomiopatías/etiología , Cardiomiopatías/microbiologíaRESUMEN
Sepsis is a systemic inflammatory reaction syndrome caused by infections. Acute lung injury (ALI) occurs first and most frequently in patients with sepsis. Gentiopicroside (GPS), which originates mostly from Gentiana, is classified as a secoiridoid glycosides. Terpenoid glycosides have various biological effects, including liver protection, blood glucose and cholesterol level management, and anti-inflammatory and antitumor effects. However, presently, the biochemical foundation and mechanism of the anti-inflammatory effects of GPS in sepsis-induced ALI have not been explained. In the present study, we established a rat model of sepsis ALI induced by cecal ligation and puncture. This enables us to observe the effects of GPS therapy, which significantly reduced the inflammatory response (TNF-α, IL-1ß, and IL-6), nitrogen stress, oxidative stress, and severity of ALI at both the whole animal and molecular levels. In addition, GPS ameliorates LPS-induced ALI via regulation of inflammatory response and cell proptosis in BEAS-2B. This study provides a theoretical basis for treating sepsis-induced ALI with GPS.
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Lesión Pulmonar Aguda , Glucósidos Iridoides , Sepsis , Animales , Sepsis/complicaciones , Sepsis/tratamiento farmacológico , Glucósidos Iridoides/farmacología , Glucósidos Iridoides/uso terapéutico , Lesión Pulmonar Aguda/etiología , Lesión Pulmonar Aguda/tratamiento farmacológico , Ratas , Masculino , Ratas Sprague-Dawley , Modelos Animales de Enfermedad , Estrés Oxidativo/efectos de los fármacos , Inflamación/tratamiento farmacológicoRESUMEN
The prognosis of septic patients with cirrhosis is worse compared to septic patients without cirrhosis. Early and accurate prognosis determination in patients with cirrhosis and sepsis is pivotal for guiding treatment decisions. The aim of this study was to investigate the association between albumin-corrected anion gap (ACAG) and clinical prognosis of patients with sepsis and cirrhosis. This study extracted data of patients with sepsis and cirrhosis from the Medical Information Mart for Intensive Care (MIMIC-IV) database. A total of 1340 patients (64.6% male) were enrolled. After confounders adjusting, elevated ACAG had a significant association with 28-day mortality (HR1.604; 95% CI 1.258-2.048; P < 0.001). Restricted cubic spline revealed that a linear relationship between ACAG and 28-day mortality (P-nonlinear = 0.089, P-overall = 0.001). According to the ROC curve analysis, the ACAG demonstrated a higher area under the curve (AUC) of 0.703 compared to AG (0.675). Kaplan-Meier analysis revealed higher 28-day mortality in high ACAG group (log-rank test, χ^2 = 175.638, P < 0.001). Furthermore, subgroup analysis showed a significant interaction between ACAG and etiology of cirrhosis (P for interaction = 0.014). Therefore, ACAG could provide clinicians with valuable insights for guiding interventions in this high-risk population.
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Cirrosis Hepática , Sepsis , Humanos , Cirrosis Hepática/mortalidad , Cirrosis Hepática/complicaciones , Masculino , Femenino , Sepsis/mortalidad , Sepsis/complicaciones , Pronóstico , Persona de Mediana Edad , Anciano , Equilibrio Ácido-Base , Albúmina Sérica/análisis , Albúmina Sérica/metabolismo , Curva ROC , Estimación de Kaplan-Meier , BiomarcadoresRESUMEN
The study aims to evaluate the prognosis and risk factors of sepsis-associated thrombocytopenia (SAT) among patients with coagulopathy, and to provide evidence of the relationship between adverse outcomes and potential risks. Patients with sepsis-associated coagulopathy were included in the study from January 2014 to December 2022. The primary outcome was sepsis-associated thrombocytopenia (platelet count less than 100 *109/L), which was evaluated by logistic regression models adjusted for demographic characteristics and comorbidities. Among patients in the SAT group, 54% developed severe SAT, while 16% of these patients recovered from thrombocytopenia. The in-hospital mortality rate was significantly higher in the SAT group compared to the non-SAT group (31% in SAT group vs 23.9% in non-SAT group, p = 0.029). Even after adjusting for age, gender, Charlson comorbidity, white blood cell, and Sequential Organ Failure Assessment score, the differences in mortality rate persisted (Odds Ratio 0.72, [95% Confidence Interval 0.52-0.92]). Correlation analyses revealed that prothrombin time (r = 0.08, p = 0.50), international normalized ratio (r = 0.08, p = 0.42), prothrombin activity (r = -0.06, p > 0.999), D-dimer (r = -0.02, p > 0.999), and inflammatory parameters such as C-reactive protein (r = -0.11, p = 0.37) were not significantly correlated with platelet counts. According to subgroup analyses, patients with lung infection complicated by SAT had slightly higher mortality (OR 0.66, [95% CI, 0.46 to 0.94]). Sepsis-associated coagulopathy indicates a subset of critical ill patients, with those experiencing thrombocytopenia at greater risk for in-hospital death compared to those without it.
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Trastornos de la Coagulación Sanguínea , Sepsis , Trombocitopenia , Humanos , Sepsis/complicaciones , Sepsis/mortalidad , Sepsis/sangre , Masculino , Femenino , Factores de Riesgo , Trombocitopenia/sangre , Anciano , Persona de Mediana Edad , Trastornos de la Coagulación Sanguínea/etiología , Trastornos de la Coagulación Sanguínea/sangre , Trastornos de la Coagulación Sanguínea/mortalidad , Mortalidad HospitalariaRESUMEN
BACKGROUND: Sepsis-induced cardiomyopathy (SICM) is a common and life-threatening complication of sepsis, significantly contributing to elevated mortality. This study aimed to identify crucial indicators for the prompt and early assessment of SICM. METHODS: Patients diagnosed with sepsis or SICM within 24 h of intensive care unit (ICU) admission were enrolled in this prospective observational study. Patients were assigned to the training set, validation set and external test set. The primary endpoint was 7-day ICU mortality, and the secondary endpoint was 28-day ICU mortality. Three machine learning algorithms were utilized to identify relevant indicators for diagnosing SICM, incorporating 64 indicators including serum biomarkers associated with cardiac, renal, and liver function, lipid metabolism, coagulation, and inflammation. Internal and external validations were performed on the screening results. Patients were then stratified based on the cut-off value of the most diagnostically effective biomarker identified, and their prognostic outcomes were observed and analyzed. RESULTS: A total of 270 patients were included in the training and validation set, and 52 patients were included in the external test set. Age, sex, and comorbidities did not significantly differ between the sepsis and SICM groups (P > 0.05). The support vector machine (SVM) algorithm identified six indicators with an accuracy of 84.5%, the random forest (RF) algorithm identified six indicators with an accuracy of 81.9%, and the logistic regression (LR) algorithm screened out seven indicators. Following rigorous selection, a diagnostic model for sepsis-induced cardiomyopathy was established based on heart-type fatty acid binding protein (H-FABP) (OR 1.308, 95% CI 1.170-1.462, P < 0.001) and retinol-binding protein (RBP) (OR 1.020, 95% CI 1.006-1.034, P < 0.05). H-FABP alone exhibited the highest diagnostic performance in both the internal (AUROC 0.689, P < 0.05) and external sets (AUROC 0.845, P < 0.05). Patients with SICM were further stratified based on an H-FABP diagnostic cut-off value of 8.335 ng/mL. Kaplan-Meier curve analysis demonstrated that elevated H-FABP levels at admission were associated with higher 7-day ICU mortality in patients with SICM (P < 0.05). CONCLUSIONS: This study revealed that H-FABP concentrations measured within 24 h of patient admission could serve as a crucial biomarker for the early and rapid diagnosis and short-term prognostic evaluation of SICM.
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Biomarcadores , Cardiomiopatías , Proteínas de Unión a Ácidos Grasos , Sepsis , Humanos , Masculino , Femenino , Biomarcadores/sangre , Cardiomiopatías/sangre , Cardiomiopatías/diagnóstico , Cardiomiopatías/etiología , Sepsis/sangre , Sepsis/complicaciones , Sepsis/diagnóstico , Persona de Mediana Edad , Estudios Prospectivos , Proteínas de Unión a Ácidos Grasos/sangre , Anciano , Proteína 3 de Unión a Ácidos Grasos/sangre , Unidades de Cuidados Intensivos , Pronóstico , Curva ROC , Máquina de Vectores de SoporteRESUMEN
OBJECTIVE: Environmental factors such as noise and music can significantly impact physiological responses, including inflammation. This study explored how environmental factors like noise and music affect lipopolysaccharide (LPS)-induced inflammation, with a focus on systemic and organ-specific responses. MATERIALS AND METHODS: 24 Wistar rats were divided into four groups (n = 6 per group): Control group, LPS group, noise-exposed group, and music-exposed group. All rats, except for the Control group, received 10 mg/kg LPS intraperitoneally. The rats in the noise-exposed group were exposed to 95 dB noise, and the music-exposed group listened to Mozart's K. 448 music (65-75 dB) for 1 h daily over 7 days. An enzyme-linked immunosorbent assay was utilized to detect the levels of inflammatory cytokines, including tumor necrosis factor-α (TNF-α) and interleukin-1ß (IL-1ß), in serum and tissues (lung, liver, and kidney). Western blot examined the phosphorylation levels of nuclear factor-κB (NF-κB) p65 in organ tissues. RESULTS: Compared with the Control group, LPS-induced sepsis rats displayed a significant increase in the levels of TNF-α and IL-1ß in serum, lung, liver, and kidney tissues, as well as a remarkable elevation in the p-NF-κB p65 protein expression in lung, liver, and kidney tissues. Noise exposure further amplified these inflammatory markers, while music exposure reduced them in LPS-induced sepsis rats. CONCLUSION: Noise exposure exacerbates inflammation by activating the NF-κB pathway, leading to the up-regulation of inflammatory markers during sepsis. On the contrary, music exposure inhibits NF-κB signaling, indicating a potential therapeutic effect in reducing inflammation.
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Lipopolisacáridos , Música , Ruido , Ratas Wistar , Sepsis , Animales , Lipopolisacáridos/toxicidad , Sepsis/inmunología , Sepsis/complicaciones , Ruido/efectos adversos , Masculino , Interleucina-1beta/sangre , Factor de Necrosis Tumoral alfa/sangre , Factor de Necrosis Tumoral alfa/metabolismo , Pulmón/inmunología , Pulmón/metabolismo , Inflamación , Hígado/metabolismo , Ratas , Riñón/metabolismo , FN-kappa B/metabolismo , Citocinas/sangre , Citocinas/metabolismoRESUMEN
OBJECTIVE: Aim: To study xylate effect on the renal toxin-excreting function with diabetes mellitus (DM) complicated by endogenous intoxication syndrome of purulentseptic genesis. PATIENTS AND METHODS: Materials and Methods: The effect of infusions with sorbilact or Ringer's solution in the regimen 3 ml/kg/hour during 3 hours on toxin-excreting function of the kidneys in patients with type 2 DM complicated by EIS is studied. RESULTS: Results: In the period of the research, xylate increased cleaning blood plasma (extracellular water space) from the total toxicity by 6,0±1,9 ml/min (230±72,3%, Δ Ñ<0,05). Ringer's solution infusion in the fragment of intensive care of the same group of patients (n=53) was determined by increase of clearance of toxic substances by 4,3±1,2 ml/min (165±46,0%, Δ ÑÑ<0,05). At the same time, xylate infusion decreased the total blood plasma toxicity by 22±4,6 IU/ml (14±2,9%, Δ ÑÑ<0,05), and Ringer's solution - by 12±3,9 IU/ml (7±2,2%, Δ Ñ Ringer's solution) in patients with Type 2 DM complicated by endogenous intoxication syndrome of purulent-septic genesis. At the same time, xylate infusion reduced the total plasma toxicity by 22±4.6 IU/ml (14±2.9%, Δ pÑ<0.05), Ringer's solution - by 12±3.9 IU/ml (7±2.2%, Δ pÑ<0.05). CONCLUSION: Conclusions: Infusion therapy solutions (xylate, Ringer's solution) within the study regimen (3 ml/kg/h for three hours) activate the renal excreting function and reduce the level of toxemia (xylate > Ringer's solution) in patients with Type 2 DM complicated by endogenous intoxication syndrome of purulent-septic genesis. At the same time, xylate infusion reduced the total plasma toxicity by 22±4.6 IU/ml (14±2.9%, Δ pÑ<0.05), Ringer's solution - by 12±3.9 IU/ml (7±2.2%, Δ pÑ<0.05).
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Diabetes Mellitus Tipo 2 , Humanos , Masculino , Femenino , Persona de Mediana Edad , Diabetes Mellitus Tipo 2/complicaciones , Solución de Ringer , Riñón , Sepsis/complicaciones , Adulto , Soluciones Isotónicas/administración & dosificación , AncianoRESUMEN
BACKGROUND: Sepsis-associated encephalopathy (SAE) is a neuronal injury with poor prognosis. Mitochondrial dysfunction is critical in SAE development, and hydrogen gas (H2) has a protective effect on septic mice. This study aimed to investigate the effect of high concentration (67%) of H2 on SAE and whether it is related to mitochondrial biogenesis and mitochondrial dynamics. METHODS: A mouse sepsis model was induced by cecal ligation and puncture. The mice inhalated 67% H2 for 1 h at 1 and 6 h post-surgery, respectively. The 7-day survival rate was recorded. Cognitive function was assessed using the Y-maze test and Morris water maze test. Serum inflammatory factors, antioxidant enzymes, as well as mitochondrial function indexes including mitochondrial membrane potential (MMP) and ATP in the hippocampal tissue were evaluated 24 h after surgery. Mitochondrial dynamic proteins (DRP1 and MFN2) and biosynthetic proteins (PGC-1α, NRF2, and TFAM) in the hippocampal tissue were detected. Moreover, the morphology of mitochondria was observed by transmission electron microscopy. RESULTS: Inhalation of 67% H2 improved the 7-day survival rates and recognition memory function of septic mice, alleviated brain antioxidant enzyme activity (SOD and CAT), and reduced serum proinflammatory cytokine levels. H2 inhalation also enhanced the expression of MFN2 and mitochondrial biogenesis-related factors (PGC-1α, NRF2, and TFAM) and decreased the expression of fission protein (DRP1), leading to improvement in mitochondrial function, as evidenced by MMP and ATP levels. CONCLUSIONS: Inhalation of high concentration (67%) of H2 in septic mice improved the survival rate and reduced neuronal injury. Its mechanism might be mediated by enhancing mitochondrial biogenesis and mitochondrial dynamics.
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Hidrógeno , Dinámicas Mitocondriales , Encefalopatía Asociada a la Sepsis , Animales , Encefalopatía Asociada a la Sepsis/tratamiento farmacológico , Ratones , Hidrógeno/farmacología , Hidrógeno/administración & dosificación , Hidrógeno/uso terapéutico , Dinámicas Mitocondriales/efectos de los fármacos , Masculino , Administración por Inhalación , Hipocampo/efectos de los fármacos , Hipocampo/metabolismo , Mitocondrias/efectos de los fármacos , Mitocondrias/metabolismo , Sepsis/complicaciones , Sepsis/tratamiento farmacológico , Sepsis/metabolismo , Ratones Endogámicos C57BL , Potencial de la Membrana Mitocondrial/efectos de los fármacos , Aprendizaje por Laberinto/efectos de los fármacosRESUMEN
BACKGROUND: Sepsis-induced pulmonary injury (SPI) is a common complication of sepsis with a high rate of mortality. N4-acetylcytidine (ac4C) is mediated by the ac4C "writer", N-acetyltransferase (NAT)10, to regulate the stabilization of mRNA. This study aimed to investigate the role of NAT10 in SPI and the underlying mechanism. METHODS: Twenty-three acute respiratory distress syndrome (ARDS) patients and 27 non-ARDS volunteers were recruited. A sepsis rat model was established. Reverse transcription-quantitative polymerase chain reaction was used to detect the expression of NAT10 and transferrin receptor (TFRC). Cell viability was detected by cell counting kit-8. The levels of Fe2+, glutathione, and malondialdehyde were assessed by commercial kits. Lipid reactive oxygen species production was measured by flow cytometric analysis. Western blot was used to detect ferroptosis-related protein levels. Haematoxylin & eosin staining was performed to observe the pulmonary pathological symptoms. RESULTS: The results showed that NAT10 was increased in ARDS patients and lipopolysaccharide-treated human lung microvascular endothelial cell line-5a (HULEC-5a) cells. NAT10 inhibition increased cell viability and decreased ferroptosis in HULEC-5a cells. TFRC was a downstream regulatory target of NAT10-mediated ac4C acetylation. Overexpression of TFRC decreased cell viability and promoted ferroptosis. In in vivo study, NAT10 inhibition alleviated SPI. CONCLUSION: NAT10-mediated ac4C acetylation of TFRC aggravated SPI through promoting ferroptosis.
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Ferroptosis , Receptores de Transferrina , Sepsis , Sepsis/metabolismo , Sepsis/complicaciones , Sepsis/etiología , Acetilación , Animales , Humanos , Ratas , Masculino , Receptores de Transferrina/metabolismo , Receptores de Transferrina/genética , Femenino , Lesión Pulmonar/metabolismo , Lesión Pulmonar/etiología , Lesión Pulmonar/patología , Modelos Animales de Enfermedad , Acetiltransferasas/metabolismo , Acetiltransferasas/genética , Persona de Mediana Edad , Antígenos CD/metabolismo , Antígenos CD/genética , Citidina/análogos & derivados , Citidina/farmacología , Línea Celular , Síndrome de Dificultad Respiratoria/metabolismo , Síndrome de Dificultad Respiratoria/etiología , Síndrome de Dificultad Respiratoria/patología , Ratas Sprague-Dawley , Supervivencia CelularRESUMEN
Sepsis is generally triggered by a dysfunctional host response to infection, and it can result in life-threatening organ dysfunction. Alpinia officinarum Hance (AO) exhibits regulatory functions in some diseases. However, whether AO extract (AOE) plays a promoting role in sepsis--triggered myocardial injury is unclear. This study was aimed at investigating the regulatory effects of AOE on myocardial ferroptosis and inflammation in sepsis, and the regulation effects on the lncRNA MIAT/TRAF6/NF-κB axis. Lipopolysaccharide (LPS) was used to treat mice for establishing an in vivo sepsis model. The pathological changes in heart tissues were observed through hematoxylin-eosin (HE) staining. The levels of CK-MB, cTnl, MDA, SOD, IL-1ß, IL-18, IL-6, and TNF-α in serum were detected through enzyme-linked immunosorbent assay (ELISA). The level of Fe2+ was assessed, and the protein expressions (ACSL4, GPX4, TRAF6, p-P65, and P65) were examined through western blot. The expressions of lncRNA MIAT and TRAF6 were measured through real-time quantitative polymerase chain reaction (RT-qPCR). Our results demonstrated that AOE treatment ameliorated sepsis-triggered myocardial damage by reducing the disordered cardiomyocytes, the destroyed sarcolemma, and the CK-MB and cTnl levels. In addition, AOE treatment inhibited sepsis-induced myocardial ferroptosis and inflammation by regulating Fe2+, ACSL4, GPX4, IL-1ß, IL-18, IL-6, and TNF-α levels. Moreover, the improvement effect of AOE was strengthened with the increase in the dose of AOE (25, 50, 100 mg/kg). It was also revealed that AOE treatment retarded the lncRNA MIAT/TRAF6/NF-κB axis. Rescue assays manifested that overexpression of MIAT reduced the cardioprotective effect of AOE. In conclusion, AOE relieved sepsis-induced myocardial ferroptosis and inflammation by inhibiting lncRNA MIAT/TRAF6/NF-κB axis. These findings may provide a potential therapeutic drug for the treatment of sepsis.