Conocimiento en estudiantes de enfermería sobre sepsis quirúrgico / Knowledge in nursing students about surgical sepsis

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]

Association between the triglyceride glucose index and short-term mortality in septic patients with or without obesity: a retrospective cohort study.

BACKGROUND: Sepsis is a significant contributor to both intensive care unit (ICU) admissions and mortality among patients in ICU, with a rising prevalence of obesity. There is a lack of extensive research on the correlation between TyGI and findings in patients with sepsis, especially in obese patients. METHODS: This study used a retrospective cohort design and included patients with sepsis (≥18 years) from the Medical Information Mart for Intensive Care IV database. The association between TyGI and outcome was examined using multivariable logistic regression analysis. RESULTS: 8,840 patients with sepsis were included in the analysis. The in-ICU mortality rate was 9.7%. Non-survivors exhibited significantly greater TyGI levels than survivors [9.19(8.76-9.71) vs. 9.10(8.67-9.54), p < 0.001]. The adjusted multivariate regression model showed that elevated TyGI values were linked to a greater likelihood of death in ICU (odds ratio [OR] range 1.072-1.793, p < 0.001) and hospital (OR range 1.068-1.445, p = 0.005). Restricted Cubic Spline analysis revealed a nonlinear association between TyGI and in-ICU and in-hospital mortality risks within specified ranges. Subgroup analysis revealed interaction effects in the general obesity, abdominal obesity, and impaired fasting glucose subgroups (p = 0.014, 0.016, and < 0.001, respectively). CONCLUSION: TyGI was associated with an increased sepsis-related short-term mortality risk and adverse outcomes after ICU admission.

The association between blood urea nitrogen to albumin ratio and the 28 day mortality in tuberculosis patients complicated by sepsis.

The relationship between blood urea nitrogen to albumin ratio (BAR) and the prognosis of patients with tuberculosis (TB) complicated by sepsis remains unclear. This study aimed to explore the association between BAR and overall patient prognosis. This was a retrospective cohort study of patients with TB complicated by sepsis who were admitted to the intensive care unit (ICU) of the Public Health Clinical Center of Chengdu between January 2019 and February 2023. The relationship between BAR values and prognosis in these patients was investigated using multivariate Cox regression, stratified analysis with interaction, restricted cubic spline (RCS), and threshold effect analysis. Sensitivity analyses were conducted to assess the robustness of the results. Our study included 537 TB patients complicated by sepsis admitted in the ICU, with a median age of 63.0 (48.0, 72.0) years; 76.7% of whom were men. The multivariate-restricted cubic spline analysis showed a non-linear association between BAR and patient prognosis. In the threshold analysis, we found that TB patients complicated by sepsis and a BAR < 7.916 mg/g had an adjusted hazard ratio (HR) for prognosis of 1.163 (95% CI 1.038-1.303; P = 0.009). However, when the BAR was ≥ 7.916 mg/g, there was no significant increase in the risk of death. The results of the sensitivity analysis were stable.

Identification of organs of origin of macrophages that produce presepsin via neutrophil extracellular trap phagocytosis.

Presepsin (P-SEP) is a specific biomarker for sepsis. Monocytes produce P-SEP by phagocytosing neutrophil extracellular traps (NETs). Herein, we investigated whether M1 macrophages (M1 MΦs) are the primary producers of P-SEP after NET phagocytosis. We co-cultured M1 MΦs and NETs from healthy participants, measured P-SEP levels in the culture medium supernatant, and detected P-SEP using western blotting. When NETs were co-cultured with M1 MΦs, the P-SEP level of the culture supernatant was high. Notably, we demonstrated, for the first time, the intracellular kinetics of P-SEP production by M1 MΦs via NET phagocytosis: M1 MΦs produced P-SEP intracellularly 15 min after NET phagocytosis and then released it extracellularly. In a sepsis mouse model, the blood NET ratio and P-SEP levels, detected using ELISA, were significantly increased (p < 0.0001). Intracellular P-SEP analysis via flow cytometry demonstrated that lung, liver, and kidney MΦs produced large amounts of P-SEP. Therefore, we identified these organs as the origin of M1 MΦs that produce P-SEP during sepsis. Our data indicate that the P-SEP level reflects the trend of NETs, suggesting that monitoring P-SEP can be used to both assess NET-induced organ damage in the lungs, liver, and kidneys during sepsis and determine treatment efficacy.

Multienzyme Active Nanozyme for Efficient Sepsis Therapy through Modulating Immune and Inflammation Inhibition.

Sepsis, a life-threatening condition caused by a dysregulated immune response to infection, leads to systemic inflammation, immune dysfunction, and multiorgan damage. Various oxidoreductases play a very important role in balancing oxidative stress and modulating the immune response, but they are stored inconveniently, environmentally unstable, and expensive. Herein, we develop multifunctional artificial enzymes, CeO2 and Au/CeO2 nanozymes, exhibiting five distinct enzyme-like activities, namely, superoxide dismutase, catalase, glutathione peroxidase, peroxidase, and oxidase. These artificial enzymes have been used for the biocatalytic treatment of sepsis via inhibiting inflammation and modulating immune responses. These nanozymes significantly reduce reactive oxygen species and proinflammatory cytokines, achieving multiorgan protection. Notably, CeO2 and Au/CeO2 nanozymes with enzyme-mimicking activities can be particularly effective in restoring immunosuppression and maintaining homeostasis. The redox nanozyme offers a promising dual-protective strategy against sepsis-induced inflammation and organ dysfunction, paving the way for biocatalytic-based immunotherapies for sepsis and related inflammatory diseases.

Non-O1 and non-O139 Vibrio cholerae Septicemia and Cellulitis: a Case Report.

Non-O1 and non-O139 Vibrio cholerae (NOVC) are serogroups that do not produce cholera toxin and are not responsible for epidemics. Even though rarely encountered in clinical practice, they can cause a spectrum of different conditions ranging from mild gastrointestinal syndrome to extraintestinal diseases, of which bacteremia and wound infections are the most severe. Risk factors for severe disease are cirrhosis, neoplasms, and diabetes mellitus. The mortality rate of NOVC bacteremia in hospitalized patients ranges from 24 to 61.5%. Incidence of NOVC infections is still rare, and consensus recommendations on treatment are not available. We report a case of NOVC bacteremia associated with severe cellulitis in an immunocompetent 75-year-old man who had eaten raw seafood in a location by the northern Adriatic Sea (Italy). Twenty-four hours after intake, he developed a high fever and vomiting. Afterwards, he started noticing the appearance of cellulitis in his right leg, which worsened in a matter of hours. The patient had a history of compensated type 2 diabetes mellitus. NOVC was isolated from both blood cultures and the leg ulcer. The non-O1, non-O139 serogroup was confirmed, and the detection of the cholera toxin gene was negative. Both tests were performed by the Reference National Laboratory of Istituto Superiore di Sanità (ISS). Multiple antimicrobial regimens were administered, with complete recovery. In conclusion, considering the severity of NOVC-associated manifestations, it is of pivotal importance to reach etiological diagnosis for a target antimicrobial therapy and to consider V. cholerae infection in the differential diagnosis in the presence of risk factors and potential exposure.

Integrated clustering of multiple immune marker trajectories reveals different immunotypes in severely injured patients.

BACKGROUND: The immune response of critically ill patients, such as those with sepsis, severe trauma, or major surgery, is heterogeneous and dynamic, but its characterization and impact on outcomes are poorly understood. Until now, the primary challenge in advancing our understanding of the disease has been to concurrently address both multiparametric and temporal aspects. METHODS: We used a clustering method to identify distinct groups of patients, based on various immune marker trajectories during the first week after admission to ICU. In 339 severely injured patients, we initially longitudinally clustered common biomarkers (both soluble and cellular parameters), whose variations are well-established during the immunosuppressive phase of sepsis. We then applied this multi-trajectory clustering using markers composed of whole blood immune-related mRNA. RESULTS: We found that both sets of markers revealed two immunotypes, one of which was associated with worse outcomes, such as increased risk of hospital-acquired infection and mortality, and prolonged hospital stays. This immunotype showed signs of both hyperinflammation and immunosuppression, which persisted over time. CONCLUSION: Our study suggest that the immune system of critically ill patients can be characterized by two distinct longitudinal immunotypes, one of which included patients with a persistently dysregulated and impaired immune response. This work confirms the relevance of such methodology to stratify patients and pave the way for further studies using markers indicative of potential immunomodulatory drug targets.

Prognostication of the development of septic complications in children with burn injuries.

OBJECTIVE: Aim: To determine the prognostic criteria for the development of septic complications in children with thermal injury. PATIENTS AND METHODS: Materials and Methods: A single-center retrospective-prospective cohort study included a retrospective analysis of 98 medical histories of children of different ages with severe burns who were treated from 2007 to 2017. A prospective study was conducted among children (n=63) from 1 to 5 years old, who received various degrees severity burn injury, according to an open comparative method in the period from 2018 to 2021. RESULTS: Results: Indicators of a high risk of developing sepsis were burns by flames of any etiology, damage severity index ≥75 units, total burn surface ≥25 %, deep burn area ≥ 5%. The threshold value of procalcitonin (PCT) ≥ 0.86 ng/ml on the 1st-3rd day and PCT > 0.51 ng/ml on the 7th day of burn disease, had a prognostic value for assessing the probability of sepsis. On the 1st day of hospitalization, the development of sepsis was predicted if the C-reactive protein (CRP) value was higher than 6.98 ng/ml, on the 3rd - the CRP level was above 7.43 ng/ml, on the 7th day - above 7.28 ng/ml. CONCLUSION: Conclusions: Based on the obtained data, we selected the criteria with the best prognostic characteristics, which allows us to predict and prevent the development of sepsis in the early stages of burn disease in children.

Peripheral PD-1+NK cells could predict the 28-day mortality in sepsis patients.

Background: Unbalanced inflammatory response is a critical feature of sepsis, a life-threatening condition with significant global health burdens. Immune dysfunction, particularly that involving different immune cells in peripheral blood, plays a crucial pathophysiological role and shows early warning signs in sepsis. The objective is to explore the relationship between sepsis and immune subpopulations in peripheral blood, and to identify patients with a higher risk of 28-day mortality based on immunological subtypes with machine-learning (ML) model. Methods: Patients were enrolled according to the sepsis-3 criteria in this retrospective observational study, along with age- and sex-matched healthy controls (HCs). Data on clinical characteristics, laboratory tests, and lymphocyte immunophenotyping were collected. XGBoost and k-means clustering as ML approaches, were employed to analyze the immune profiles and stratify septic patients based on their immunological subtypes. Cox regression survival analysis was used to identify potential biomarkers and to assess their association with 28-day mortality. The accuracy of biomarkers for mortality was determined by the area under the receiver operating characteristic (ROC) curve (AUC) analysis. Results: The study enrolled 100 septic patients and 89 HCs, revealing distinct lymphocyte profiles between the two groups. The XGBoost model discriminated sepsis from HCs with an area under the receiver operating characteristic curve of 1.0 and 0.99 in the training and testing set, respectively. Within the model, the top three highest important contributions were the percentage of CD38+CD8+T cells, PD-1+NK cells, HLA-DR+CD8+T cells. Two clusters of peripheral immunophenotyping of septic patients by k-means clustering were conducted. Cluster 1 featured higher proportions of PD1+ NK cells, while cluster 2 featured higher proportions of naïve CD4+T cells. Furthermore, the level of PD-1+NK cells was significantly higher in the non-survivors than the survivors (15.1% vs 8.6%, P<0.01). Moreover, the levels of PD1+ NK cells combined with SOFA score showed good performance in predicting the 28-day mortality in sepsis (AUC=0.91,95%CI 0.82-0.99), which is superior to PD1+ NK cells only(AUC=0.69, sensitivity 0.74, specificity 0.64, cut-off value of 11.25%). In the multivariate Cox regression, high expression of PD1+ NK cells proportion was related to 28-day mortality (aHR=1.34, 95%CI 1.19 to 1.50; P<0.001). Conclusion: The study provides novel insights into the association between PD1+NK cell profiles and prognosis of sepsis. Peripheral immunophenotyping could potentially stratify the septic patients and identify those with a high risk of 28-day mortality.

Identification and experimental validation of cuproptosis regulatory program in a sepsis immune microenvironment through a combination of single-cell and bulk RNA sequencing.

Background: In spite of its high mortality rate and poor prognosis, the pathogenesis of sepsis is still incompletely understood. This study established a cuproptosis-based risk model to diagnose and predict the risk of sepsis. In addition, the cuproptosis-related genes were identified for targeted therapy. Methods: Single-cell sequencing analyses were used to characterize the cuproptosis activity score (CuAS) and intercellular communications in sepsis. Differential cuproptosis-related genes (CRGs) were identified in conjunction with single-cell and bulk RNA sequencing. LASSO and Cox regression analyses were employed to develop a risk model. Three external cohorts were conducted to assess the model's accuracy. Differences in immune infiltration, immune cell subtypes, pathway enrichment, and the expression of immunomodulators were further evaluated in distinct groups. Finally, various in-vitro experiments, such as flow cytometry, Western blot, and ELISA, were used to explore the role of LST1 in sepsis. Results: ScRNA-seq analysis demonstrated that CuAS was highly enriched in monocytes and was closely related to the poor prognosis of sepsis patients. Patients with higher CuAS exhibited prominent strength and numbers of cell-cell interactions. A total of five CRGs were identified based on the LASSO and Cox regression analyses, and a CRG-based risk model was established. The lower riskScore cohort exhibited enhanced immune cell infiltration, elevated immune scores, and increased expression of immune modulators, indicating the activation of an antibacterial response. Ultimately, in-vitro experiments demonstrated that LST1, a key gene in the risk model, was enhanced in the macrophage in response to LPS, which was closely related to the decrease of macrophage survival rate, the enhancement of apoptosis and oxidative stress injury, and the imbalance of the M1/M2 phenotype. Conclusions: This study constructed a cuproptosis-related risk model to accurately predict the prognosis of sepsis. We further characterized the cuproptosis-related gene LST1 to provide a theoretical framework for sepsis therapy.

Exploring the relationship between life course adiposity and sepsis: insights from a two-sample Mendelian randomization analysis.

Objectives: The relationship between adiposity and sepsis has received increasing attention. This study aims to explore the causal relationship between life course adiposity and the sepsis incidence. Methods: Mendelian randomization (MR) method was employed in this study. Instrumental variants were obtained from genome-wide association studies for life course adiposity, including birth weight, childhood body mass index (BMI), childhood obesity, adult BMI, waist circumference, visceral adiposity, and body fat percentage. A meta-analysis of genome-wide association studies for sepsis including 10,154 cases and 454,764 controls was used in this study. MR analyses were performed using inverse variance weighted, MR Egger regression, weighted median, weighted mode, and simple mode. Instrumental variables were identified as significant single nucleotide polymorphisms at the genome-wide significance level (P < 5×10-8). The sensitivity analysis was conducted to assess the reliability of the MR estimates. Results: Analysis using the MR analysis of inverse variance weighted method revealed that genetic predisposition to increased childhood BMI (OR = 1.29, P = 0.003), childhood obesity (OR = 1.07, P = 0.034), adult BMI (OR = 1.38, P < 0.001), adult waist circumference (OR = 1.01, P = 0.028), and adult visceral adiposity (OR = 1.53, P < 0.001) predicted a higher risk of sepsis. Sensitivity analysis did not identify any bias in the MR results. Conclusion: The results demonstrated that adiposity in childhood and adults had causal effects on sepsis incidence. However, more well-designed studies are still needed to validate their association.

A Preclinical Model of Sepsis-Induced Myopathy with Disuse in Mice.

Sepsis is a major cause of in-hospital deaths. Improvements in treatment result in a greater number of sepsis survivors. Approximately 75% of the survivors develop muscle weakness and atrophy, increasing the incidence of hospital readmissions and mortality. However, the available preclinical models of sepsis do not address skeletal muscle disuse, a key component for the development of sepsis-induced myopathy. Our objective in this protocol is to provide a step-by-step guideline for a mouse model that reproduces the clinical setting experienced by a bedridden septic patient. Male C57Bl/6 mice were used to develop this model. Mice underwent cecal ligation and puncture (CLP) to induce sepsis. Four days post-CLP, mice were subjected to hindlimb suspension (HLS) for seven days. Results were compared with sham-matched surgeries and/or animals with normal ambulation (NA). Muscles were dissected for in vitro muscle mechanics and morphological assessments. The model results in marked muscle atrophy and weakness, a similar phenotype observed in septic patients. The model represents a platform for testing potential therapeutic strategies for the mitigation of sepsis-induced myopathy.

Ribonuclease inhibitor 1 emerges as a potential biomarker and modulates inflammation and iron homeostasis in sepsis.

Sepsis, marked by organ dysfunction, necessitates reliable biomarkers. Ribonuclease inhibitor 1 (RNH1), a ribonuclease (RNase) inhibitor, emerged as a potential biomarker for acute kidney injury and mortality in thoracoabdominal aortic aneurysm patients. Our study investigates RNH1 dynamics in sepsis, its links to mortality and organ dysfunction, and the interplay with RNase 1 and RNase 5. Furthermore, we explore RNH1 as a therapeutic target in sepsis-related processes like inflammation, non-canonical inflammasome activation, and iron homeostasis. We showed that RNH1 levels are significantly higher in deceased patients compared to sepsis survivors and correlate with creatine kinase, aspartate and alanine transaminase, bilirubin, serum creatinine and RNase 5, but not RNase 1. RNH1 mitigated LPS-induced TNFα and RNase 5 secretion, and relative mRNA expression of ferroptosis-associated genes HMOX1, FTH1 and HAMP in PBMCs. Monocytes were identified as the predominant type of LPS-positive PBMCs. Exogenous RNH1 attenuated LPS-induced CASP5 expression, while increasing IL-1ß secretion in PBMCs and THP-1 macrophages. As RNH1 has contradictory effects on inflammation and non-canonical inflammasome activation, its use as a therapeutic agent is limited. However, RNH1 levels may play a central role in iron homeostasis during sepsis, supporting our clinical observations. Hence, RNH1 shows promise as biomarkers for renal and hepatic dysfunction and hepatocyte injury, and may be useful in predicting the outcome of septic patients.

Abdominal wound closure in the presence of sepsis: our experience with the use of subcutaneous drain.

Objectives: Patients requiring surgery for secondary peritonitis demonstrate a significantly increased risk for incisional surgical site infection. This study aimed to evaluate the efficacy of subcutaneous wound drain post-laparotomy for contaminated surgical wounds. Design: This was a prospective comparative hospital-based study. Setting: Patients who had surgery for secondary peritonitis in Irrua Specialist Teaching Hospital were studied. Participants: Fifty patients aged 16 years and above who presented with secondary peritonitis. Intervention: Patients who met the inclusion criteria were randomized into two equal groups. Group A had a suction drain placed in the subcutaneous space after laparotomy while Group B did not. Main outcome measures: Development of incisional surgical site infection, wound dehiscence, and duration of post-operative hospital stay. Results: The incidence of incisional surgical site infection was significantly less in Group A (20%) than in Group B (68%). There was no case of wound dehiscence in Group A as against 3 (12%) in Group B. The difference was not statistically significant. The mean duration of hospital stay was significantly less with subcutaneous suction drain (8.96+2.81 Vs 14.04+8.05; p = 0.005). Conclusion: Subcutaneous suction drainage is beneficial in abdominal wall closure in cases of peritonitis as it significantly reduces the incidence of incisional surgical site infection and the duration of postoperative hospital stay. The reduction in surgical wound dehiscence observed in this study was, however, not statistically significant. Funding: None declared.

Exosome-shuttled miR-150-5p from LPS-preconditioned mesenchymal stem cells down-regulate PI3K/Akt/mTOR pathway via Irs1 to enhance M2 macrophage polarization and confer protection against sepsis.

Rationale: Sepsis is a life-threatening organ dysfunction and lack of effective measures in the current. Exosomes from mesenchymal stem cells (MSCs) reported to alleviate inflammation during sepsis, and the preconditioning of MSCs could enhance their paracrine potential. Therefore, this study investigated whether exosomes secreted by lipopolysaccharide (LPS)-pretreated MSCs exert superior antiseptic effects, and explored the underlying molecular mechanisms. Methods: Exosomes were isolated and characterized from the supernatants of MSCs. The therapeutic efficacy of normal exosomes (Exo) and LPS-pretreated exosomes (LPS-Exo) were evaluated in terms of survival rates, inflammatory response, and organ damage in an LPS-induced sepsis model. Macrophages were stimulated with LPS and treated with Exo or LPS-Exo to confirm the results of the in vivo studies, and to explain the potential mechanisms. Results: LPS-Exo were shown to inhibit aberrant pro-inflammatory cytokines, prevent organ damages, and improve survival rates of the septic mice to a greater extent than Exo. In vitro, LPS-Exo significantly promoted the M2 polarization of macrophages exposed to inflammation. miRNA sequencing and qRT-PCR analysis identified the remarkable expression of miR-150-5p in LPS-Exo compared to that in Exo, and exosomal miR-150-5p was transferred into recipient macrophages and mediated macrophage polarization. Further investigation demonstrated that miR-150-5p targets Irs1 in recipient macrophages and subsequently modulates macrophage plasticity by down-regulating the PI3K/Akt/mTOR pathway. Conclusion: The current findings highly suggest that exosomes derived from LPS pre-conditioned MSCs represent a promising cell-free therapeutic method and highlight miR-150-5p as a novel molecular target for regulating immune hyperactivation during sepsis.

Mecp2 promotes the anti-inflammatory effect of alpinetin via epigenetic modification crosstalk.

In recent years, inflammatory disorders have emerged as a significant concern for human health. Through ongoing research on anti-inflammatory agents, alpinetin has shown promising anti-inflammatory properties, including involvement in epigenetic modification pathways. As a crucial regulator of epigenetic modifications, Mecp2 may play a role in modulating the epigenetic effects of alpinetin, potentially impacting its anti-inflammatory properties. To test this hypothesis, two key components, p65 (a member of NF-KB family) and p300 (a type of co-activator), were screened by the expression profiling microarray, which exhibited a strong correlation with the intensity of LPS stimulation in mouse macrophages. Meanwhile, alpinetin demonstrates the anti-inflammatory properties through its ability to disrupt the synthesis of p65 and its interaction with promoters of inflammatory genes, yet it did not exhibit similar effects on p300. Additionally, Mecp2 can inhibit the binding of p300 by attaching to the methylated inflammatory gene promoter induced by alpinetin, leading to obstacles in promoter acetylation and subsequently impacting the binding of p65, ultimately enhancing the anti-inflammatory capabilities of alpinetin. Similarly, in a sepsis mouse model, it was observed that homozygotes overexpressing Mecp2 showed a greater reduction in organ damage and improved survival rates compared to heterozygotes when administered by alpinetin. However, blocking the expression of DNA methyltransferase 3A (DNMT3A) resulted in the loss of Mecp2's anti-inflammatory assistance. In conclusion, Mecp2 may augment the anti-inflammatory effects of alpinetin through epigenetic 'crosstalk', highlighting the potential efficacy of a combined therapeutic strategy involving Mecp2 and alpinetin for anti-inflammatory intervention.

Berberine protects against sepsis-related acute lung injury in rats via PPAR-γ signaling pathway upregulation and improvement at the cellular level: Functional, biochemical, and immunohistochemistry study.

This study aimed to assess the prophylactic effects of Berberine on experimentally induced lung sepsis and examine its effects on selected cytokines, genes, and protein expression besides the histopathological evaluation. Berberine significantly reduced the wet/dry lung ratio, the broncho-alveolar lavage fluid (BALF) protein, cells, neutrophils percentage, and cytokines levels. In addition, pretreatment with Berberine decreased the myeloperoxidase (MPO) and malondialdehyde (MDA) levels and decreased gene expression of nuclear factor kappa B (NF-κB), monocyte chemoattractant protein-1 (MCP-1), and the intracellular adhesion molecule 1 (ICAM-1) by RT-qPCR analysis, revealing Berberine's antioxidant and anti-inflammatory mode of action. Western blot analysis revealed increased peroxisome proliferator-activated receptor gamma (PPAR-γ) expression in the Berberine pretreated group compared to the cecal ligation and puncture (CLP) group, in which the histopathological examination evidenced this improvement. In conclusion, Berberine improved lung sepsis via its PPAR-γ mediated antioxidant and anti-inflammatory effects.

Analysis and Modelling of the Predictive Value of PCT, PLR and NLR for Ureteric Sepsis after Ureteral Stone Surgery: A Retrospective Cohort Study.

OBJECTIVE: This study aimed to analyse the value of procalcitonin (PCT), neutrophil-to-lymphocyte ratio (NLR) and platelet-to-lymphocyte ratio (PLR) in predicting postoperative ureteral stone complications of urogenic sepsis. The production of a clinical prediction model could provide additional direction to reduce the likelihood of postoperative urogenital sepsis. METHODS: The clinical data of 520 patients with ureteral stones who underwent surgical treatment from January 2022, to September 2023, in the hospital were retrospectively analysed. The patients were divided into urogenic sepsis group (n = 42) and non-urogenic sepsis group (n = 478) in accordance with the occurrence of urogenic sepsis in the postoperative period. The peripheral blood PCT, PLR and NLR levels were collected within 24 h postoperatively in the two groups. The receiver operating characteristic (ROC) curve was employed to evaluate the predictive value of PCT, PLR and NLR levels for postoperative urogenital sepsis in patients with ureteral stones. RESULTS: Logistic regression analysis showed that PCT (odds ratio (OR) = 4.25, 95% CI: 1.85-9.78), PLR (OR = 4.00, 95% CI: 1.78-9.05) and NLR (OR = 2.29, 95% CI: 1.05-5.01) were risk factors for postoperative complication sepsis in patients with ureteral stones (p < 0.05). The ROC curves showed that the areas under the curve of PCT, PLR and NLR levels alone and in combination for predicting urogenic sepsis complications after emergency ureteral stone surgery were 0.683, 0.692, 0.611 and 0.799, respectively. CONCLUSIONS: Urogenic sepsis leads to increased serum PCT, NLR and PLR levels in patients undergoing surgical treatment for ureteral stones. Physicians should pay close attention to these indices to provide further theoretical support for reducing postoperative urogenic sepsis.