The study aimed to elucidate the mechanisms by which sulfur dioxide (SO2) alleviates organ damage during sepsis using RNA-Seq technology. A cecal ligation and puncture (CLP) sepsis model was established in rats, and the effects of SO2 treatment on organ damage were assessed through histopathological examinations. RNA-Seq was performed to analyze differentially expressed genes (DEGs), and subsequent functional annotations and enrichment analyses were conducted. The CLP model successfully induced sepsis symptoms in rats. Histopathological evaluation revealed that SO2 treatment considerably reduced tissue damage across the heart, kidney, liver, and lungs. RNA-Seq identified 950 DEGs between treated and untreated groups, with significant enrichment in genes associated with ribosomal and translational activities, amino acid metabolism, and PI3K-Akt signaling. Furthermore, gene set enrichment analysis (GSEA) showcased enrichments in pathways related to transcriptional regulation, cellular migration, proliferation, and calcium-ion binding. In conclusion, SO2 effectively mitigates multi-organ damage induced by CLP sepsis, potentially through modulating gene expression patterns related to critical biological processes and signaling pathways. These findings highlight the therapeutic promise of SO2 in managing sepsis-induced organ damage.

This investigation seeks to assess the impact of various temperature management approaches on the rates of death and organ failure among adult patients suffering from sepsis. A comprehensive search of PubMed, Embase, and CENTRAL was performed to identify randomized controlled trials (RCTs) published up to September 2024. These trials examined the impact of temperature management strategies on sepsis patients. Two independent investigators conducted literature screening, quality assessment, and data extraction. A meta-analysis was conducted using a fixed-effect model to evaluate outcome measures, including mortality and organ dysfunction. This study is registered with PROSPERO, CRD42024627677. The analysis incorporated eight RCTs, involving 1843 patients. The findings demonstrated that the management of hyperthermia markedly diminished the mortality risk among individuals suffering from sepsis (risk ratio = 0.47, 95% confidence interval [CI]: 0.37-0.59, p < 0.001), exhibiting low heterogeneity (I2 = 39%). However, the effects of hyperthermia on organ dysfunction remained unclear (Mean Difference [MD] = -0.92, 95% CI: -1.91 to 0.07, p = 0.07), exhibiting low heterogeneity (I2 = 0%). However, these effects on organ dysfunction were based on only two studies and 215 patients, which made them prone to a type II error. Hyperthermia management strategies are effective in reducing mortality among adults with sepsis. However, their impact on organ dysfunction requires further investigation through high-quality RCTs. Despite the limitations of this study, hyperthermia strategies offer a promising approach to multidimensional intervention in sepsis. Further studies should strengthen structured subgroup analyses and mechanistic studies based on RCTs to optimize treatment strategies under various clinical scenarios.

Recent advances in deep learning show significant potential in analyzing continuous monitoring electronic health records (EHR) data for clinical outcome prediction. We aim to develop a Transformer-based, Encounter-level Clinical Outcome (TECO) model to predict mortality in the intensive care unit (ICU) using inpatient EHR data.

The TECO model was developed using multiple baseline and time-dependent clinical variables from 2579 hospitalized COVID-19 patients to predict ICU mortality and was validated externally in an acute respiratory distress syndrome cohort (n = 2799) and a sepsis cohort (n = 6622) from the Medical Information Mart for Intensive Care IV (MIMIC-IV). Model performance was evaluated based on the area under the receiver operating characteristic (AUC) and compared with Epic Deterioration Index (EDI), random forest (RF), and extreme gradient boosting (XGBoost).

In the COVID-19 development dataset, TECO achieved higher AUC (0.89-0.97) across various time intervals compared to EDI (0.86-0.95), RF (0.87-0.96), and XGBoost (0.88-0.96). In the 2 MIMIC testing datasets (EDI not available), TECO yielded higher AUC (0.65-0.77) than RF (0.59-0.75) and XGBoost (0.59-0.74). In addition, TECO was able to identify clinically interpretable features that were correlated with the outcome.

The TECO model outperformed proprietary metrics and conventional machine learning models in predicting ICU mortality among patients with COVID-19, widespread inflammation, respiratory illness, and other organ failures.

The TECO model demonstrates a strong capability for predicting ICU mortality using continuous monitoring data. While further validation is needed, TECO has the potential to serve as a powerful early warning tool across various diseases in inpatient settings.

Sepsis is a life-threatening condition caused by a dysregulated response of the body in response to an infection that harms its tissues and organs. Interleukin-6 (IL-6) is a significant component of the inflammatory response as part of the pathogenesis of sepsis. It aids in the development of Acute lung injury and, subsequently, multiple organ dysfunction syndrome. This letter probes into the correlation between plasma IL-6 levels and the risk of developing acute lung injury and multiple organ dysfunction syndrome in critically ill patients with sepsis. While it shows promising results, limitations like its observational study design, a limited sample size, a single center involvement, single-time-point measurement, and a lack of a control group restrain its cogency. The study is a big step in identifying IL-6 as a biomarker to improve patient care.

Sepsis remains a leading cause of global morbidity and mortality, yet early diagnosis is hindered by the limited specificity and sensitivity of current biomarkers.

The aim of this study was to identify lncRNAs that play a key role in sepsis and provide potential biomarkers for the diagnosis and treatment of sepsis.

Transcriptomic data from sepsis patients were retrieved from the Chinese National Genebank (CNGBdb). Differential expression analysis identified 2,348 LncRNAs and 5,125 mRNAs (|FC|≥2, FDR < 0.05). Weighted gene co-expression network analysis (WGCNA) and meta-analysis were applied to screen core genes. Gene set enrichment analysis (GSEA) explored functional pathways, while single-cell sequencing and qPCR validated cellular localization and expression patterns.

WGCNA identified three key genes: LINC02363 (LncRNA), DYNLT1, and FCGR1B. Survival and meta-analyses revealed strong correlations between these genes and sepsis outcomes. GSEA highlighted LINC02363's involvement in "herpes simplex virus type 1 infection," "tuberculosis," and ribosome pathways. Single-cell sequencing showed FCGR1B's broad distribution across immune cells, while DYNLT1 localized predominantly in macrophages. qPCR confirmed significant upregulation of LINC02363 (p < 0.01), FCGR1B (p < 0.05), and DYNLT1 (p < 0.05) in sepsis patients compared to controls.

LINC02363 may serve as a new biomarker for the diagnosis and treatment of sepsis.

Septic older adults represent a vulnerable population with high mortality rates. Base excess (BE), an indicator of acid-base status, may serve as a prognostic marker in sepsis. This study aimed to investigate the association between BE and mortality in septic older adults.

A retrospective analysis included septic older adults (age ≥ 65 years) from the Medical Information Mart for Intensive Care (MIMIC)-IV database. The primary outcome was 30-day mortality. Multivariate Cox regression models and Kaplan-Meier analysis were used to assess the association between BE and 30-day mortality. A two-segment linear regression model with smooth curve fitting was employed to examine threshold effects of BE on clinical outcomes.

The study comprised 7379 participants, with a 21.8% 30-day mortality rate and an 18.6% in-hospital mortality rate. A nonlinear, U-shaped relationship (P < 0.001) was observed between BE and 30-day mortality in septic older adults, indicating increased risk with higher or lower BE levels. Various BE groups showed different hazard ratios for mortality: 2.7 (2.26-3.22), 1.86 (1.65-2.09), 1.41 (1.19-1.67), and 1.9 (1.4-2.58), respectively, compared with the reference group (-3 mEq/L ≤ BE < 3 mEq/L). The inflection point was calculated as 0.5 mEq/L.

Our findings suggest a U-shaped relationship between BE and mortality in septic older adults, emphasizing the importance of monitoring acid-base status in sepsis management for this population. Geriatr Gerontol Int 2025; 25: 380-386.

This study analyzed potential key genes involved in the mechanism of acute liver injury induced by sepsis through bioinformatics techniques, aiming to provide novel insights for the identification of early-stage sepsis-induced acute liver injury and its diagnosis.

Gene chip data sets containing samples from acute liver injury induced by sepsis and control groups (GSE22009 and GSE60088) were selected from the Gene Expression Omnibus (GEO) database. Differentially expressed genes (DEGs) with |log fold change| >1 and p<0.05 were screened with the GEO2R tool, which was also used for the selection of upregulated DEGs in the chips with p<0.05. Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway, Gene Ontology, and protein-protein interaction (PPI) analyses were then conducted. Results were visualized using R language packages, including volcano plots, Venn diagrams, and boxplots. The intersection of candidate genes with relevant genes in the Comparative Toxicogenomics Database (CTD) was performed, and the clinical significance of these genes was explored through a literature review. A rat model of acute liver injury was developed by inducing sepsis with the cecum ligation and puncture method. Real-time PCR was performed to determine the gene expression in rat liver tissues.

A total of 646 upregulated DEGs were determined in GSE22009 and 146 in GSE60088. A Venn diagram was used to find the intersection of the upregulated DEGs between the two data sets, and 67 DEGs associated with sepsis-mediated acute liver damage were obtained. Enrichment analysis from the KEGG pathway showed that DEG upregulation was primarily associated with various pathways: TNF, NF-κB, IL-17, ferroptosis, mTOR, and JAK-STAT signaling pathways. DEGs resulted in three clusters and 15 candidate genes, as revealed by the PPI network and module analyses. Intersection with sepsis-induced acute liver injury-related genes in the CTD resulted in the identification of three significant differentially co-expressed genes: CXCL1, ICAM1, and TNFRSF1A. Sepsis-induced liver tissue indicated the overexpression of CXCL1, ICAM1, and TNFRSF1A mRNA, as compared with the control group (p<0.05).

The key genes identified and related signaling pathways provided insights into the molecular mechanisms of sepsis-induced acute liver injury. In vivo studies revealed the overexpression of CXCL1, ICAM1, and TNFRSF1A mRNA in sepsis-mediated injured liver tissues, providing a theoretical basis for early diagnosis and targeted treatment research.

Our study aim is to explore the mechanisms of short peptide passages on intestinal dysfunction in septic mice utilizing a metabolomics approach, which provides a new scientific basis for the clinical study of sepsis.

Mices were allocated at random into four groups: control (Con), cecal ligation and puncture followed by one, three or 7 day short-peptide-based enteral nutrition group (CLP + SPEN1), (CLP + SPEN3), and (CLP + SPEN7) groups. A liquid chromatography-mass spectrometry-based metabolomics method was used to analyze changes in serum metabolites in septic mice.

Short peptides showed effectiveness in reducing symptoms, mucosal inflammation, and intestinal function damage scores in septic mice. The 16sRNA analysis showcased significant variances in the distribution of bacterial communities between the CLP + SPEN1, CLP + SPEN3, and CLP + SPEN7 groups. At the phylum level, statistically significant variances in the relative abundance of Proteobacteria, Firmicutes, and Bacteroidetes were recognized. The metabolomics analysis results showed significant separation of metabolites between the CLP + SPEN1 and CLP + SPEN3 groups, as well as significant differences in metabolite profiles between the CLP + SPEN3 and CLP + SPEN7 groups. Utilizing a differential Venn diagram, four metabolites were commonly different; 10-heptadecanoic and dodecanoic acids had statistical significance. The abundance of both dodecanoic and lactic acid bacteria was negatively associated at the genus level.

Short peptides were found to promote the growth of beneficial bacteria, Lactobacillus and uncultured_bacterium_f_Muribaculaceae, while reducing intestinal metabolites such as Dodecanoic acid and 10-Heptadecenoic acid. Moreover the Lactobacillus may play a significant therapeutic role in the treatment of sepsis. However, due to the limited number of experimental samples, the exact mechanism of action of short peptides awaits further confirmation.

Background. Klebsiella pneumoniae is part of the ESKAPE (Enterococcus faecium, Staphylococcus aureus, K. pneumoniae, Acinetobacter baumannii, Pseudomonas aeruginosa and Enterobacter spp.) group of multidrug-resistant (MDR) pathogens. K. pneumoniae is the leading cause of antimicrobial resistance-associated mortality and the second leading cause of nosocomial bloodstream infections (BSIs), globally and in sub-Saharan Africa. Therefore, it was aimed to determine the antibiotic resistance patterns of K. pneumoniae isolated from blood cultures of patients with features of sepsis at Mulago National Referral Hospital, Uganda. Methods. The cross-sectional study on patients with features of sepsis utilized K. pneumoniae (n=30) isolated from positive blood culture specimens. The antibiotic resistance profile was determined by the Clinical and Laboratory Standards Institute's Kirby-Bauer disc diffusion method, which was used to classify the isolates as susceptible, intermediate and resistant. K. pneumoniae isolates that were resistant to third-generation cephalosporins were subjected to extended-spectrum β-lactamase (ESBL) screening and confirmation using the double-disc synergy test using cefotaxime, ceftazidime, ceftriaxone, cefotaxime-clavulanic acid and ceftazidime-clavulanic acid. The results were analysed for frequencies. Results. K. pneumoniae isolates showed emerging resistance to imipenem at 13% (4 out of 30) followed by amikacin at 17% (5 out of 30). There was intermediate resistance to gentamycin at 60% (18 out of 30). However, K. pneumoniae showed the highest resistance to piperacillin at 100% (30 out of 30) followed by sulphamethoxazole-trimethoprim and cefepime, both showing a percentage of 97% (29 out of 30). Up to 16 out of 30 (53.3%) of K. pneumoniae were positive for ESBL production, whilst 14 out of 30 (46.7%) were negative. Conclusion. There was a high prevalence of antibiotic-resistant ESBL-producing K. pneumoniae isolates from BSI of patients with features of sepsis in Uganda's Mulago National Referral Hospital.

Sepsis often led to multiple organ dysfunction (MODS) and even death. Although a variety of medicine were used to treat sepsis in clinic, there was still no specific and effective clinical medicine treatment. Exercise had been shown to work on MODS. However, in preclinical studies, there was no systematic evidence to summarize the effects of exercise training on sepsis.

To investigate the effects of exercise training on sepsis in preclinical studies and explore possible mechanisms to provide reliable preclinical evidence for the use of exercise training in sepsis.

Preclinical studies were retrieved from electronic databases (Pubmed, Embase, Cochrane Library, Scopus, Medline, Web of science) as of June 25, 2024. Our review included in vivo English studies evaluating the radioprotective effects of exercise training on sepsis. The quality of each study was assessed using the Center for Systematic Evaluation of Experimental Animal Studies (SYCLE) Animal Research Bias Risk Tool. All results were described comprehensively.

17 in vivo studies were included. Our comprehensive descriptive analysis showed that exercise could improve the general condition, lung injury, liver injury, kidney injury, heart and aortic injury, spleen and thymus injury, and other injuries in animals with sepsis. And its possible mechanisms were involved improving the general condition of sepsis animals, pathological and cell number of organs, anti-inflammation, anti-oxidative stress, anti-DNA damage, and so on.

Exercise training could protect sepsis by anti-inflammatory, anti-oxidative stress, increased antibacterial ability, reduced cell death, improved metabolism, vital signs and MODS.

Although ketamine is an FDA-approved drug, its mechanism of action is not fully understood. Currently, there is an increase in its recreational use, causing irreparable social and physical damage. We report the case of a musician who developed sepsis due to gas necrosis in his arm after using veterinary ketamine purchased via the internet. Despite the amputation recommendation, it was possible to save the arm and preserve motor and sensory function. The scientific community, as well as the police and the government, must ponder the prescription, efficacy and safety of ketamine for medical treatments.

Atrial fibrillation (AF) is a common arrhythmia in critically ill patients. The objective of this narrative review is to evaluate the characteristics of patients who develop new-onset atrial fibrillation (NOAF) because of sepsis, current management of NOAF in sepsis patients, special consideration in different populations that developed NOAF, health economic and quality of life of patients. We conducted a literature search on PubMed to find research related to NOAF, sepsis and critical illness. Nineteen studies were analyzed for risk factors and outcomes. The incidence rate ranges from 0.53% to 43.9% among these studies. There were numerous risk factors that had been reported from these articles. The most reported risk factors included advanced age, male sex, White race, and cardiovascular comorbidities. The management of septic patients is significantly challenging because of the unfavorable cardiovascular consequences and thromboembolic hazards associated with NOAF. There are comprehensive guidelines available for managing AF, but the effectiveness and safety of therapies in patients with sepsis are still uncertain. Various approaches for managing newly diagnosed AF have been explored. Sinus rhythm can be restored through either pharmacological or non-pharmacological intervention or combination of both. In addition, thromboembolism is a complication that can occur in patients with AF and can have a negative impact on the prognosis of sepsis patients. The use of anticoagulation to prevent stroke after NOAF in sepsis patients is still controversial. Extensive prospective investigations are required to have a deeper understanding of the necessity for anticoagulation following NOAF in sepsis. Beside the treatment of NOAF, early detection of NOAF in sepsis plays a critical role. The prompt initiation of rhythm control medication following a clinical diagnosis of AF can enhance cardiovascular outcomes and reduce mortality in patients with AF and cardiovascular risk factors. Additionally, NOAF in the intensive care unit can prolong hospital stays, increasing hospitalization costs and burdening the hospital. Therefore, preventing and managing NOAF effectively not only benefit the patients but also the hospital in financial aspect. Lastly, to address the existing gaps in knowledge, future research should focus on developing machine learning models that can accurately anticipate risks, establish long-term follow-up protocols, and create complete monitoring systems. The focus is on early intervention and personalized approaches to improve outcomes and quality of life.

Sepsis in the neonatal period is a major health challenge in neonatal medicine because of its potential for rapid progression to multi-organ dysfunction, leading to higher morbidity and mortality. Although efforts have been made to advance the outcomes of neonates admitted to hospitals, there is a paucity of data regarding neonatal sepsis treatment outcomes in the study setting. Hence, the study aimed to assess outcomes and prognostic factors of sepsis among neonatal patients admitted to the neonatal intensive care unit in Hiwot Fana Comprehensive Specialized University Hospital in Ethiopia.

A facility-based cross-sectional study was conducted among 311 neonates with sepsis admitted from 1 January 2021 to 30 December 2023. Neonates were selected using systematic random sampling. Relevant data were extracted from medical records using a checklist. The data were entered into EpiData version 4.6 and analyzed using STATA version 17. Bivariable and multivariable logistic regression analyses were performed to identify factors associated with the outcome variable.

Eighty-four of 311 patients (27.8%) (95% CI: 22.7%-32.9%) died, while 218 (72.2%) were discharged after improvement. In the multivariable logistic regression analysis, low white blood cell (WBC) count [adjusted odds ratio (AOR) = 4.24, 95% CI: 1.5-12.5], desaturation (aOR = 3.00, 95% CI: 1.6-5.5), pre-term birth (aOR = 2.14, 95% CI: 1.1-4.0), lack of maternal antenatal care (ANC) follow-up (aOR = 2.4, 95% CI: 1.2-4.7), and chorioamnionitis (aOR = 2.8, 95% CI: 1.2-6.5) were significantly associated with neonatal sepsis mortality.

Approximately one-quarter of patients with neonatal sepsis died. The significant prognostic factors for sepsis were found to be low WBC count, desaturation, lack of ANC visits, and chorioamnionitis. Implementing targeted therapeutic interventions and addressing these prognostic factors could improve treatment outcomes.

The objective of this study was to investigate the biological activities and mechanisms of chlorogenic acid (CGA) in the treatment of septic acute liver injury (SALI) based on the network pharmacology, molecular docking, in vivo studies, and other techniques. Chlorogenic acid and potential related targets of septic acute liver injury were searched from the public databases. Then, the protein-protein interaction (PPI), Gene Ontology (GO), and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses were conducted. Subsequently, molecular docking was performed to predict the binding of the active compound to the core target. Finally, in vivo experiments were carried out for further validation. A total of 60 common targets were identified between acute septic liver injury and chlorogenic acid, among which 9 common core targets (EGFR, ESR1, GSK3B, PTGS2, TLR4, PPARA, HSP90AA1, ACE, and MMP9) were screened with Cytoscape. Molecular docking indicated that these core targets had good binding activity to chlorogenic acid (- 7.2, - 6.8, - 7.7, - 8.7, - 6.1, - 6.8, - 7.3, - 8.4, and - 8.6 kcal/mol respectively). In the SALI mouse model, chlorogenic acid can improve pathological damage to the liver and apoptosis of liver cells, and anti-inflammatory properties significantly by the TLR4/NF-κB pathway (all P < 0.05). The biological activity and regulatory network of CGA on SALI were revealed, and the anti-inflammatory effect of CGA was verified, which could be associated with the TLR4/NF-κB pathway.

Septic cardiomyopathy (SCM), as a complication of the septic process, severely affects the myocardial function of patients, but its pathogenesis remains unclear. The article aims to explore the mechanism of tripartite motif 10 (TRIM10) in rats with SCM and provide animal experimental basis for the treatment and prevention of SCM.

An SCM rat model was constructed by intraperitoneal injection of lipopolysaccharide (LPS). Sh-NC and sh-TRIM10 groups were injected with sh-NC and sh-TRIM10 in the tail vein for 3 consecutive days before SCM modeling. The expression of TRIM10 was detected by Western blot and reverse transcription-polymerase chain reaction analyses. Hematoxylin-eosin staining was performed to observe pathological changes in myocardium. Cardiomyocyte apoptosis was detected by flow cytometry. Serum levels of cardiac troponin I, myohemoglobin, creatine kinase-MB, interleukin-18 (IL-18), interleukin-1 β (IL-1β), tumor necrosis factor-α (TNF-α), superoxide dismutase, and glutathione peroxidase (GSH-Px) were detected by enzyme-linked immunosorbent assay. Apoptosis-related proteins and toll-like receptor 4 (TLR4)/nuclear transcription factor-κB (NF-κB) pathway-related proteins were explored by Western blot assay.

TRIM10 expression increased in the LPS group (P < 0.0001). Myocardial tissue injury in SCM rats was improved after TRIM10 reduction compared with that in the LPS group. Knockdown of TRIM10 decreased the levels of MDA (P < 0.01), IL-18 (P < 0.0001), IL-1β (P < 0.0001), and TNF-α (P < 0.0001) and increased the contents of SOD (P < 0.001) and GSH-Px (P < 0.001) compared with those in the LPS group. TRIM10 reduced the apoptosis of H9C2 cells (P < 0.0001). After TRIM10 interference, the expression of p-P65/P65 (P < 0.0001) and TLR4 (P < 0.0001) was decreased.

TRIM10 knockdown can reduce inflammation, oxidative stress, and apoptosis in SCM rats and has a protective effect on cardiomyocytes, which may be attributed to the regulation of the TLR4/NF-κB pathway.

Septic shock is a life-threatening condition characterized by a failure of organ systems and a high mortality rate. Cuproptosis is a new form of cell death that is triggered by copper overload. However, the relationship between cuproptosis-related genes and septic shock remains unclear.

The GSE26440 dataset from the GEO database was used to screen differentially expressed genes (DEGs) between control and septic shock samples. Additionally, hub genes related to the progression of septic shock and cuproptosis were screened by Venn analysis. RT-qPCR was utilized to validate the expression of hub genes in peripheral blood lymphocytes from septic shock patients and healthy controls. Next, functional analysis and immune cells infiltration were performed.

SLC31A1 and MTF1 levels were obviously elevated and LIAS and LIPT1 levels were downregulated in septic shock samples, compared to normal controls. The diagnostic values of the four genes were confirmed with receiver operating characteristic (ROC) curves. Additionally, SLC31A1 and MTF1 showed a positive correlation with natural killer cells and LIAS and LIPT1 exhibited a positive correlation with CD8+ T cells. Furthermore, compared to low-level groups, MAPK signaling was activated in the high-SLC31A1 level group, VEGF signaling was activated in the high-MTF1 level group and lipoic acid metabolism was activated in high-LIAS and high-LIPT1 level groups.

This study demonstrates that SLC31A1, MTF1, LIAS, and LIPT1 are dysregulated in septic shock samples, and these genes exhibit potential diagnostic efficacy in septic shock, suggesting that these genes may be potential biomarkers for the diagnosis of septic shock.

HY209 is a synthesized sodium taurodeoxycholate (TDCA) that is expected to serve as a novel treatment for sepsis by inhibiting the inflammasomal activation that suppresses the production of pro-inflammatory cytokines. This study aimed to assess the safety, tolerability and pharmacokinetics (PKs) of HY209 after intravenous administration in healthy subjects.

A dose-block randomized, double-blind, placebo-controlled, single ascending dose study was conducted. Eight subjects in each dose group were randomized to receive an intravenous administration of HY209 (0.1, 0.2, 0.4, 0.8 and 1.6 mg/kg) or a placebo at a 3:1 ratio. Safety and tolerability variables including adverse events (AEs) and vital signs were monitored. For the PK analysis, serial blood samples were collected for 72 hours at baseline and up to 24 hours post-dose. A power model was used to evaluate the dose-proportionality of HY209. Given that TDCA is an endogenous compound, time-matched baseline differences in plasma concentrations were analyzed.

A total of 39 subjects completed the study. All AEs were mild, and no serious AEs were observed. There was no significant correlation between the frequency of AEs and the administered dose. A circadian pattern was observed in the plasma TDCA concentration at baseline. After infusion, the plasma TDCA was rapidly eliminated; the plasma TDCA concentration at one hour after the end of infusion showed no significant differences from the baseline. The baseline-adjusted maximum plasma concentration of TDCA demonstrated dose-proportionality in a HY209 range of 0.1-1.6 mg/kg.

A single intravenous administration of HY209 was well tolerated and its systemic exposure showed dose-proportionality in a dose range between 0.1 and 1.6 mg/kg.

Sepsis is a systemic inflammatory response syndrome of multiorgan failure caused by dysregulation of the host response to infection and is a major cause of death in critically ill patients. In recent years, with the continuous development of sequencing technology, the intestinal microecology of this disease has been increasingly studied. The gut microbiota plays a host-protective role mainly through the maintenance of normal immune function and the intestinal barrier. Recent evidence suggests that intestinal flora dysbiosis plays a crucial role in sepsis. Clostridium butyricum (C. butyricum), which has been used as a probiotic in poultry feed since its discovery, has been found to play a potential protective role in intestinal infections, inflammatory bowel disease (IBD), colorectal cancer, and other diseases in recent studies. In this review, we continue to focus on the important role and mechanism of C. butyricum as a probiotic in human diseases, especially intestinal diseases. Additionally, we evaluate the research progress of C. butyricum in treatment of sepsis to identify more therapeutic targets for the clinical treatment of sepsis.

Sepsis-associated acute kidney injury (S-AKI) is a critical complication that significantly contributes to the morbidity and mortality of sepsis patients. This narrative review explores the complex and multifactorial pathophysiology of S-AKI, which involves hemodynamic alterations, microcirculatory dysfunction, endothelial damage, inflammatory responses, oxidative stress, and direct tubular injury. Conventional perspectives linking S-AKI primarily to reduced renal blood flow are now being reconsidered, with growing insights highlighting the significance of microcirculatory dysfunction and endothelial activation as key contributors. The review also discusses the current diagnostic approaches for S-AKI, emphasizing the limitations of existing biomarkers and the need for earlier and more accurate detection methods. Standard treatment strategies focus on supportive care, including fluid management, vasopressor therapy, and renal replacement therapy. However, these approaches often fail to address the underlying mechanisms of S-AKI, resulting in persistently high mortality rates. Emerging therapies, including the use of antioxidants, anti-inflammatory agents, and stem cell-based treatments, offer the potential for improved outcomes. These innovative approaches aim to target the pathophysiological processes at the molecular level, offering hope for better management of S-AKI. The review highlights the need for ongoing research to further understand the mechanisms driving S-AKI and to develop more effective therapeutic strategies.

Acute kidney injury (AKI) frequently occurs as a complication of sepsis. PANoptosis refers to a type of inflammatory programmed cell death that exhibits key characteristics of apoptosis, necroptosis, and pyroptosis. Here, we evaluated the role of absent in melanoma 2 (AIM2) and eukaryotic translation initiation factor 2 alpha kinase 2 (EIF2AK2) in septic AKI.

A septic AKI model was created through cecal ligation and puncture (CLP), while an in vitro model was developed using lipopolysaccharide (LPS)-stimulated HK2 cells. Hematoxylin and eosin (HE), Periodic acid-Schiff (PAS), and TUNEL staining were conducted to assess kidney injury in mice. Levels of serum creatinine (Scr) and blood urea nitrogen (BUN) were detected by kits. Gene expression was detected utilizing RT-qPCR, and Western blot was used to test protein levels. Immunofluorescence was employed to measure EIF2AK2 and AIM2 expression in mouse kidney tissue. Lactate dehydrogenase (LDH) activity assay was conducted to evaluate cytotoxicity. Co-immunoprecipitation (Co-IP) was performed to verify the binding relationship between EIF2AK2 and AIM2.

AIM2 expression was increased in the renal tissue of mice subjected to CLP. Activation of the inflammasome and PANoptosis were observed in the renal tissue of CLP mice. AIM2 depletion attenuated PANoptosis in LPS-treated HK-2 cells. Additionally, EIF2AK2 could directly target AIM2, leading to a positive regulation of AIM2 expression. Notably, EIF2AK2 induced PANoptosis through upregulating AIM2 in HK-2 cells stimulated by LPS.

Our results revealed the important role of EIF2AK2-induced AIM2 upregulation in the activation of PANoptosis during septic AKI.

Sepsis-induced acute lung injury (SI-ALI) leads to significant deaths in critically ill patients worldwide. This study explores the mechanism of EZH2 regulating ferroptosis of alveolar epithelial cells (AECs) in SI-ALI. In vitro cell model and in vivo mouse lung injury model of sepsis were established. EZH2 expression in lung tissues was intervened by sh-EZH2, followed by H&E staining observation of lung tissue pathological changes. EZH2, H3K27me3, USP10, GPX4, and ACSL4 expressions were determined by qRT-PCR or Western blot. ROS, GSH, and iron ion levels were detected using fluorescent labeling and reagent kits, respectively. ChIP analyzed the enrichment of EZH2 and H3K27me3 on USP10 promoter. The binding between USP10 and GPX4, and the ubiquitination level of GPX4 were detected using Co-IP. EZH2 was highly expressed in lung tissues of SI-ALI mice. EZH2 silencing alleviated ALI and ferroptosis of AECs; EZH2 increased the H3K27me3 level on USP10 promoter through histone methylation. USP10 stabilized GPX4 protein expression through ubiquitination; inhibition of USP10 partially reversed the inhibitory effect of EZH2 silencing on ferroptosis of AECs. In conclusion, EZH2 depresses USP10 expression by promoting histone H3K27me3 modification on USP10 promoter, thereby enhancing ubiquitination degradation of GPX4 and ultimately facilitating ferroptosis of AECs in sepsis.

Sepsis is a complex clinical syndrome characterized by a heterogenous host immune response. Historically, static protein and transcriptomic metrics have been employed to describe the underlying biology. Here, we tested the hypothesis that ex vivo functional TNF expression as well as an immunologic endotype based on both IFNγ and TNF expression could be used to model clinical outcomes in sepsis patients.

This prospective, observational study of patient samples collected from the SPIES consortium included patients at five health systems enrolled over 17 months, with 46 healthy control patients, 68 ICU patients without sepsis, and 107 ICU patients with sepsis. Whole blood was collected on day 1, 4, and 7 of ICU admission. Outcomes included in-hospital and 180-day mortality and non-favorable discharge disposition defined by skilled nursing facility, long-term acute care facility, or hospice. Whole blood ELISpot assays were conducted to quantify TNF expression [stimulated by lipopolysaccharide (LPS)] and IFNγ expression (stimulated by anti-CD3/CD28 mAb), which were then used for assignment to one of four subgroups including an 'immunocompetent', 'immunosuppressed endotype', and two 'mixed' endotypes.

Whole blood TNF spot-forming units were significantly increased in septic and CINS patients on days 4 and 7 compared to healthy subjects. In contrast, TNF expression per cell on days 1, 4, and 7 was significantly lower in both septic and critically ill non-septic (CINS) patients compared to healthy subjects. Early increases in total TNF expression were associated with favorable discharge disposition and lower in-hospital mortality. 'Immunocompetent' endotype patients on day 1 had a higher proportion of favorable to non-favorable discharges compared to the 'immunosuppressed' endotype. Similarly, 'immunocompetent' endotype patients on day 4 had a higher in-hospital survival compared to the 'immunosuppressed' endotype patients. Finally, among septic patients, decreased total TNF and IFNγ expression were associated with 180-day mortality.

Increased ex vivo whole blood TNF expression is associated with improved clinical outcomes. Further, the early 'immunocompetent' endotype is associated with favorable discharge and improved in-hospital and 180-day survival. The ability to functionally stratify septic patients based on blood cell function ex vivo may allow for identification of future immune modulating therapies.

Sepsis is an inevitable stage of bacterial invasion characterized by an uncontrolled inflammatory response resulting in a syndrome of multiorgan dysfunction. Most conventional antibiotics used to treat sepsis are efficacious, but they have undesirable side effects. The green synthesised Ag NPs were synthesized by 5 g of the earthworm extract dissolved in a volume of 500mL of distilled water and then added to 2,500 mL aqueous solution of 1mM silver nitrate at 40 °C. After 4 h, the mixture was then allowed to dry overnight at 60 °C. Later, Ag NPs were washed and collected. They were characterized by X-ray diffraction, ultraviolet-visible spectroscopy, and transmission electron microscopy. Sepsis model as induced by feces-intraperitoneal injection method. Eighteen male mice were assigned into three main groups: the control group, the sepsis-model group, and the Ag NPs-treated group. The control group received a single oral dose of distilled water and, after two days, intraperitoneally injected with 30% glycerol in phosphate buffer saline. The Sepsis-model group received a single oral dose of distilled water. Ag NPs - The treated group received a single oral dose of 5.5 mg/kg of Ag NPs. After two days, the sepsis-model group and Ag NPs-treated group were intraperitoneally injected with 200 µL of faecal slurry. Ag NPs treatment in septic mice significantly decreased liver enzyme activities, total protein, and serum albumin. Moreover, Ag NPs significantly enhanced kidney function, as indicated by a significant decrease in the levels of creatinine, urea, and uric acid. In addition, Ag NPs showed a powerful antioxidant effect via the considerable reduction of malondialdehyde and nitric oxide levels and the increase in antioxidant content. The histopathological investigation showed clear improvement in hepatic and kidney architecture. Our findings demonstrate the protective efficacy of biogenic Ag NPs against sepsis-induced liver and kidney damage.

Asparaginase-associated pancreatitis (AAP) is a major challenge for continuing asparaginase therapy. We aimed to investigate the acute and long-term complications and survival rates related to first and second AAP episodes in Chinese children with haematological malignancies.

We retrospectively analysed clinical data of children with pancreatitis who received asparaginase chemotherapy for acute lymphoblastic leukaemia (ALL), acute mixed cell leukaemia, and non-Hodgkin's lymphoma at Shanghai Children's Medical Center from November 2013 to November 2023.

Of the 76 children included in the study, 12 had local complications (15.79%), with no deaths recorded. Systemic complications manifested in 28 patients (36.84%), resulting in 3 deaths (3.95%). Four patients (5.26%) developed long-term complications (chronic pancreatitis or insulin-dependent diabetes mellitus). No significant differences in local or long-term complications were recorded between children in the asparaginase re-exposed (n=39) and non-re-exposed (n=45) groups. Among the re-exposed patients, eight (25.81%) experienced a second attack without fatalities or complications. Survival analysis of intermediate- to high-risk patients revealed a significantly higher event-free survival (EFS) rate for the re-exposed group than for the non-re-exposed group. The second AAP episode's occurrence and severity had no relation to the first AAP episode's severity, and the second AAP episode was significantly less severe than the first (p<0.001).

The second AAP episode's occurrence is unrelated to the first AAP episode's severity, and the second AAP episode's severity is significantly lower than that of the first. Further, asparaginase therapy could improve EFS in children with intermediate and high-risk ALL.

A Two-sample Mendelian randomization (MR) Analysis was used to assess the causal relationship between non-small cell lung cancer (NSCLC) and sepsis.

Single nucleotide polymorphisms (SNPs) closely associated with NSCLC were utilized as instrumental variables (IVs) in this study. The Inverse Variance Weighted (IVW) method was used as the primary method for MR analysis, supplemented by the Weighted median, Weighted model, and MR-Egger regression method. Sensitivity analysis was conducted to improve result robustness, and data from various sources were validated and integrated. Bonferroni tests were applied to adjust for multiple comparisons.

After Bonferroni tests correcting the combined results, MR analysis revealed a significant association between genetically predicted NSCLC and an increased susceptibility to sepsis (odds ratios [OR]: 1.140, 95% confidence interval [CI]: 1.085-1.199, P = 2.61 × 10- 7). The combined results demonstrated that NSCLC is associated with a heightened risk of sepsis in patients under 75 years of age (OR: 1.085, 95%CI: 1.037-1.353, P = 3.84 × 10- 4). Furthermore, lung adenocarcinoma (LUAD) was found to be potentially associated with an increased susceptibility to sepsis (OR: 1.040, 95% CI: 1.009-1.073, P = 1.16 × 10- 2). These results withstood multiple sensitivity analyses, demonstrating their robustness.

This study confirms that NSCLC can significantly increase susceptibility to sepsis at the genetic level, providing valuable insights for the early identification of individuals at risk for sepsis.

Background Sepsis is a potentially fatal condition that necessitates prompt identification and assessment of its severity for effective management. However, evaluating sepsis severity using the Sequential Organ Failure Assessment (SOFA) and Acute Physiology and Chronic Health Evaluation (APACHE II) scores can be complex and costly. This study aimed to assess the association between neutrophil-to-lymphocyte ratio (NLR) and sepsis severity, as well as the role of NLR as a predictive indicator of sepsis severity in ICU patients. Methods This cross-sectional study was conducted among 180 ICU-admitted patients at Benazir Bhutto Hospital (BBH) in Rawalpindi, Pakistan, from January 2022 to January 2023. Participants were enrolled using defined inclusion and exclusion criteria along with consecutive sampling. Following ethical approval and informed consent, data were collected using a self-structured form. The study population was divided into three groups based on sepsis severity, which was assessed via the SOFA score. Data analysis was performed using IBM SPSS Statistics for Windows, Version 25.0 (Released 2017; IBM Corp., Armonk, NY, USA) through chi-squared tests, one-way ANOVA, Pearson's correlation, and a simple linear regression model, with a significance threshold set at p < 0.05. Results In the study population of 180 patients, the frequencies of sepsis, severe sepsis, and septic shock were 69 (38.34%), 86 (47.78%), and 25 (13.88%), respectively. Significant variations were observed among the three study groups in the means of the PaO2/FiO2 ratio, mean arterial pressure, Glasgow Coma Scale score, total bilirubin level, serum creatinine level, platelet count, SOFA score, neutrophil count, lymphocyte count, and NLR (p < 0.05). Pearson's correlation analysis indicated a strong positive correlation between the NLR and SOFA score, with a correlation coefficient (r) of 0.80 and significance at p < 0.001. Furthermore, linear regression analysis identified NLR as a significant predictor of sepsis severity, with a beta coefficient (β) of 3.55 and a 95% CI of 1.92-5.60 (p < 0.001). Conclusions In the current study, a positive and significant correlation was found between the NLR and the severity of sepsis. Higher NLR values were associated with increased SOFA scores, indicating a greater severity of sepsis. This study supports the use of NLR as a complementary and cost-effective tool for the early detection of high-risk patients with sepsis, facilitating timely interventions and improving outcomes, particularly in under-resourced healthcare settings.

Background Sepsis is a critical and potentially fatal medical condition characterized by significant illness and death rates. Early recognition and assessment of sepsis severity are vital for its optimal management. Determination of its severity by Sequential Organ Failure Assessment (SOFA) and Acute Physiology and Chronic Health Evaluation (APACHE) II, is quite a complex process as these score systems require complex and costly investigations. Therefore, this study was designed to determine the predictive capacity of serum albumin levels for the severity of sepsis in intensive care unit (ICU) patients. Methods This cross-sectional study was carried out on 201 ICU-admitted patients with diagnosed sepsis at Benazir Bhutto Hospital (BBH), Rawalpindi, Pakistan from March 2022 to April 2023. Recruitment of patients was performed through consecutive sampling and predefined inclusion and exclusion criteria. Prior to the data collection, ethical approval and informed consent were obtained. Data was gathered via a self-designed proforma. SOFA score was applied for the determination of the severity of sepsis. Patients were categorized into three groups based on sepsis severity (SOFA score). Data analysis was done in the Statistical Package for the Social Sciences (SPSS) version 25. Descriptive and inferential statistics compared study variables. Pearson's correlation and a simple linear regression model were used to assess the relationship between serum albumin levels and sepsis severity and the predictive capacity of serum albumin levels for sepsis severity respectively. The statistical significance of the p-value was set at less than 0.05. Results Among the 201 patients, 64 (31.84%) had sepsis, 98 (48.75%) had severe sepsis, and 39 (19.41%) had septic shock. Hypoalbuminemia was present among 119 (59.20%) patients while 82 (40.80%) patients had normal albumin levels. Significant differences were found in the total bilirubin, serum creatinine, platelet count, PaO2/FiO2 ratio, mean arterial pressure, Glasgow Coma Scale score, SOFA score, serum albumin level, and the prevalence of normal and low albumin levels across three study groups (p < 0.05). Pearson's correlation analysis showed a strong negative correlation between serum albumin level and SOFA score (correlation coefficient (r) = -0.78, p = 0.001). Linear regression analysis confirmed an inverse relationship between serum albumin levels and SOFA scores (beta coefficient = -2.70, p = 0.002). Conclusions In the present study, serum albumin level was noted as a reliable predictor of sepsis severity in ICU patients. Lower serum albumin levels were associated with higher SOFA scores, indicating more severe sepsis. This study supports the use of serum albumin as a simple and cost-effective biomarker for early identification of sepsis severity, particularly in resource-limited settings.

Quercetin (QUE) has been found to inhibit the progression of sepsis-related diseases, including sepsis-induced cardiomyopathy (SIC). More information about the role and mechanism of QUE in SIC progression deserves further exploration. Human cardiomyocytes (AC16) were induced with LPS to mimic SIC cell models. Cell proliferation and apoptosis were determined using CCK8 assay, EdU assay, and flow cytometry. Cell inflammation and ferroptosis were evaluated by detecting IL-1β, TNF-α, Fe2+, ROS, GSH, and GPX4 levels. 5-lipoxygenase (ALOX5) expression was examined by quantitative real-time PCR and western blot. LPS treatment reduced AC16 cell proliferation, while enhanced apoptosis, inflammation, and ferroptosis. QUE repressed LPS-induced AC16 cell apoptosis, inflammation, and ferroptosis. ALOX5 was upregulated in SIC patients, and its expression was reduced by QUE. ALOX5 knockdown restrained LPS-induced apoptosis, inflammation, and ferroptosis in AC16 cells. The inhibitory effect of QUE on LPS-induced myocardial injury could be reversed by ALOX5 overexpression. QUE promoted the activity of PI3K/AKT pathway by reducing ALOX5 expression. QUE could alleviate LPS-induced myocardial injury by regulating ALOX5/PI3K/AKT pathway, suggesting that QUE might be used for treating SIC.

Septic shock, a severe manifestation of infection-induced systemic immune response, poses a critical threat resulting in life-threatening multi-organ failure. Early diagnosis and intervention are imperative due to the potential for irreversible organ damage. However, specific and sensitive detection tools for the diagnosis of septic shock are still lacking.

Gene expression files of early septic shock were obtained from the Gene Expression Omnibus (GEO) database. CIBERSORT analysis was used to evaluate immune cell infiltration. Genes related to immunity and disease progression were identified using weighted gene co-expression network analysis (WGCNA), followed by enrichment analysis. CytoHubba was then employed to identify hub genes, and their relationships with immune cells were explored through correlation analysis. Blood samples from healthy controls and patients with early septic shock were collected to validate the expression of hub genes, and an external dataset was used to validate their diagnostic efficacy.

Twelve immune cells showed significant infiltration differences in early septic shock compared to control, such as neutrophils, M0 macrophages, and natural killer cells. The identified immune and disease-related genes were mainly enriched in immune, cell signaling, and metabolism pathways. In addition, six hub genes were identified (PECAM1, F11R, ITGAL, ICAM3, HK3, and MCEMP1), all significantly associated with M0 macrophages and exhibiting an area under curve of over 0.7. These genes exhibited abnormal expression in patients with early septic shock. External datasets and real-time qPCR validation supported the robustness of these findings.

Six immune-related hub genes may be potential biomarkers for early septic shock.

Septic shock, a severe manifestation of infection-induced systemic immune response, poses a critical threat resulting in life-threatening multi-organ failure. Early diagnosis and intervention are imperative due to the potential for irreversible organ damage. However, specific and sensitive detection tools for the diagnosis of septic shock are still lacking.

Gene expression files of early septic shock were obtained from the Gene Expression Omnibus (GEO) database. CIBERSORT analysis was used to evaluate immune cell infiltration. Genes related to immunity and disease progression were identified using weighted gene co-expression network analysis (WGCNA), followed by enrichment analysis. CytoHubba was then employed to identify hub genes, and their relationships with immune cells were explored through correlation analysis. Blood samples from healthy controls and patients with early septic shock were collected to validate the expression of hub genes, and an external dataset was used to validate their diagnostic efficacy.

Twelve immune cells showed significant infiltration differences in early septic shock compared to control, such as neutrophils, M0 macrophages, and natural killer cells. The identified immune and disease-related genes were mainly enriched in immune, cell signaling, and metabolism pathways. In addition, six hub genes were identified (PECAM1, F11R, ITGAL, ICAM3, HK3, and MCEMP1), all significantly associated with M0 macrophages and exhibiting an area under curve of over 0.7. These genes exhibited abnormal expression in patients with early septic shock. External datasets and real-time qPCR validation supported the robustness of these findings.

Six immune-related hub genes may be potential biomarkers for early septic shock.

To construct and validate a nomogram model for predicting sepsis complicated by acute lung injury (ALI).

The healthcare records of 193 sepsis patients hospitalized at The Affiliated Tai'an City Central Hospital of Qingdao University from January 2022 to December 2023 were retrospectively reviewed. Among these patients, 69 were in the ALI group and 124 in the non-ALI group. A nomogram prediction model was constructed using logistic regression analysis. Its predictive performance was evaluated through various measures, including the area under the curve (AUC), calibration curve, decision curve, sensitivity, specificity, accuracy, recall rate, and precision rate.

The predictive factors included the neutrophil/lymphocyte ratio (NLR), oxygenation index (PaO2/FiO2), tumor necrosis factor-α (TNF-α), and acute physiology and chronic health evaluation II (APACHE II). The nomogram training set achieved an AUC of 0.959 (95% CI: 0.924-0.995), an accuracy of 92.59%, a recall of 96.70%, and a precision of 92.63%. In the validation set, the AUC was 0.938 (95% CI: 0.880-0.996), with an accuracy of 89.66%, a recall of 93.94%, and a precision of 88.57%. The calibration curve demonstrated that the prediction results were consistent with the actual findings. The decision curve indicated that the model has clinical applicability.

NLR, PaO2/FiO2, TNF-α, and APACHE II are closely associated with ALI in sepsis patients. A nomogram model based on these four variables shows strong predictive performance and may be used as a clinical decision-support tool to help physicians better identify high-risk groups.

Sepsis is a severe medical condition characterized by a systemic inflammatory response, often culminating in multiple organ dysfunction and high mortality rates. In recent years, there has been a growing recognition of the pivotal role played by mitochondrial damage in driving the progression of sepsis. Various factors contribute to mitochondrial impairment during sepsis, encompassing mechanisms such as reactive nitrogen/oxygen species generation, mitophagy inhibition, mitochondrial dynamics change, and mitochondrial membrane permeabilization. Damaged mitochondria actively participate in shaping the inflammatory milieu by triggering key signaling pathways, including those mediated by Toll-like receptors, NOD-like receptors, and cyclic GMP-AMP synthase. Consequently, there has been a surge of interest in developing therapeutic strategies targeting mitochondria to mitigate septic pathogenesis. This review aims to delve into the intricate mechanisms underpinning mitochondrial dysfunction during sepsis and its significant impact on immune dysregulation. Moreover, we spotlight promising mitochondria-targeted interventions that have demonstrated therapeutic efficacy in preclinical sepsis models.

The present study utilized network pharmacology to identify therapeutic targets and mechanisms of Rehmannia glutinosa in sepsis treatment. RNA-sequencing was conducted on peripheral blood samples collected from 23 sepsis patients and 10 healthy individuals. Subsequently, the RNA sequence data were analyzed for differential expression. Identification of active components and their putative targets was achieved through the HERB and SwissTarget Prediction databases, respectively. Functional enrichment analysis was performed using GO and KEGG pathways. Additionally, protein-protein interaction networks were constructed and survival analysis of key targets was conducted. Single-cell RNA sequencing provided cellular localization data, while molecular docking explored interactions with central targets. Results indicated significant involvement of identified targets in inflammation and Th17 cell differentiation. Survival analysis linked several targets with mortality rates, while molecular docking highlighted potential interactions between active components and specific targets, such as rehmaionoside a with ADAM17 and rehmapicrogenin with CD81. Molecular dynamics simulations confirmed the stability of these interactions, suggesting Rehmannia glutinosa's role in modulating immune functions in sepsis.

Sepsis is a syndrome precipitated by immune dysregulation in response to infection, and represents a pivotal factor in global mortality attributed to diseases. The recent consensus delineates sepsis as a perilous state of organ dysfunction arising from the host's maladaptive reaction to infection. It masks the complexity and breadth of the immune mechanisms involved in sepsis, which is characterized by simultaneous hyperinflammation and immunosuppression. Sepsis is highly correlated with the dysregulation of immune response, which is mainly mediated by various immune cells and their interactions. This syndrome can lead to a plethora of complications, encompassing systemic inflammatory response, metabolic disturbances, infectious shock, MODS, and DIC. Furthermore, more research studies have been conducted on sepsis in the past few years. The pathological characteristics of sepsis have been improved or treated by targeting signaling pathways like NF-B, JAK-STAT, PI3K-Akt, and p38-MAPK. Combined drug therapy is better than single drug therapy for sepsis. This article will review the latest progress in the pathogenesis and treatment of sepsis.

As a grave and highly lethal clinical challenge, sepsis, along with its consequent multiorgan dysfunction, affects millions of people worldwide. Sepsis is a complex syndrome caused by a dysregulated host response to infection, leading to fatal organ dysfunction. An increasing body of evidence suggests that the pathogenesis of sepsis is both intricate and rapid and involves various cellular responses and signal transductions mediated by post-translational modifications (PTMs). Hence, a comprehensive understanding of the mechanisms and functions of PTMs within regulatory networks is imperative for understanding the pathological processes, diagnosis, progression, and treatment of sepsis. In this review, we provide an exhaustive and comprehensive summary of the relationship between PTMs and sepsis-induced organ dysfunction. Furthermore, we explored the potential applications of PTMs in the treatment of sepsis, offering a forward-looking perspective on the understanding of infectious diseases.

The serum levels of presepsin correlate with parameters indicating cholestasis in sepsis; however, the probability and significance of this association remain uncertain. We aimed to ascertain whether infection, as signaled by presepsin levels, is the primary determinant of elevated biliary parameters in sepsis.

A unicenter, retrospective study included 396 COVID-free emergency-admitted patients, in which presepsin level was determined. Presepsin, neutrophil count, leukocyte count, C reactive protein, and fibrinogen evaluated the septic/inflammatory state. The statistically significant factors associated with cholestasis, ALT, and AST were analyzed by Fisher's exact test and Spearman regression with Bonferroni's correction.

Presepsin emerged as the most likely variable correlated with all cholestasis markers: alkaline phosphatase (p = 7 × 10-8), gamma-glutamyl transferase (p = 5 × 10-10), and conjugated bilirubin (p = 4 × 10-15). Thrombocyte count, C reactive protein, age, creatinine, urea, lactate, and blood pressure, were associated with only one or two of these markers.

In a sepsis setting, the increase in cholestasis-related parameters is associated with presepsin with a higher probability than hemodynamic, inflammatory, or coagulation-related variables. Determining this robust link between sepsis and cholestasis could eliminate unnecessary imaging procedures in critically ill patients, enabling clinicians to focus efforts on addressing the primary infectious cause.

The abnormality of the immune system caused by infection is a contributor to the organ dysfunctions associated with sepsis. The balance between Th17/Treg cells is essential for maintaining immune homeostasis. Bergapten is a natural furocoumarin and has been reported to alleviate the Th17/Treg imbalance. Here, we explored the effects of bergapten on the inflammation and immune state in mouse models of sepsis.

The model was established using the cecal ligation and puncture method. Mice were administered 30 mg/kg bergapten. Histological examination, RT-qPCR, enzyme-linked immunosorbent assay, immunoblotting, immunofluorescence, immunohistochemistry, and flow cytometry were used to evaluate the effects of bergapten in vivo.

Bergapten ameliorated lung damage, reduced lung wet/dry weight ratio, inhibited myeloperoxidase activity, and reduced inflammatory cell infiltration. Bergapten also restrained sepsis-induced inflammation via inhibition of inflammatory cytokines and NF-κB signaling. These effects were accompanied by the restored Th17/Treg balance induced by bergapten. Bergapten decreased the number of Th17 cells and elevated the number of Tregs, and this effect was mediated by the signal transducer and activator of transcription 5 (STAT5)/Forkhead box P3 (Foxp3) and STAT3/retinoid-related orphan receptor-γt (RORγt) pathways.

Bergapten exerted anti-inflammatory effects in acute lung injury by improving the Th17/Treg balance, which suggested a potential of bergapten as an immunomodulatory drug treating sepsis-associated diseases.

The objective of this study was to explore the correlation between statin administration in the intensive care unit (ICU) setting and the in-hospital mortality risk of patients suffering from sepsis-induced coagulopathy (SIC).

Utilizing a retrospective cohort study design, this investigation collected data from the Medical Information Mart for Intensive Care (MIMIC)-IV spanning 2008 to 2019. The diagnosis of SIC was established based on a SIC score of 4 or above. Statin usage during the ICU period was extracted from the prescription records based on the keywords of statin medications. The primary endpoint analyzed was the in-hospital mortality within the ICU, characterized by any death occurring during the ICU admission.

During the follow-up, which had a median duration of approximately 7.28 days, 18.19% of the 4,777 SIC patients died in the ICU. Statin was linked with a decrease in the risk of in-hospital mortality for SIC patients in the ICU [hazard ratio (HR): 0.73, 95% confidence interval (CI): 0.60-0.89, P = 0.002]. Relative to rosuvastatin, the use of atorvastatin (HR: 0.54, 95% CI: 0.34-0.85, P = 0.008) or simvastatin (HR: 0.55, 95% CI: 0.33-0.92, P = 0.024), as well as combinations of multiple statins (HR: 0.36, 95% CI: 0.15-0.86, P = 0.022), was associated with a reduction in ICU in-hospital mortality risk. Subgroup analysis also suggested that the use of atorvastatin, simvastatin, or a combination of statins had an advantage over rosuvastatin in reducing ICU in-hospital mortality in SIC patients older than 65 years of age or SIC patients with respiratory failure or cardiogenic shock (all P < 0.05).

The present study supports the potential benefits of statin use in mortality in SIC patients during ICU stays. The study encourages clinicians to consider the benefits of statins and supports the ongoing exploration of statins for enhanced outcomes in critical care settings.

Sepsis is a frequent cause of admission to intensive care units (ICUs). High mortality rates are estimated globally, and in our country, few studies have reported one-year survival. The objective of this study is to determine one-year survival in patients with sepsis admitted to the ICU in Colombia, compared with the survival of patients admitted for other conditions.

Retrospective cohort study using administrative databases from the Ministry of Health of Colombia. One-year survival and the adjusted hazard ratio for survival, adjusted for comorbidities included in the Charlson Index, were determined using a Cox proportional hazards model for patients admitted for other causes as well as for those admitted for sepsis. This was then compared with an inverse propensity score weighting model.

A total of 116.407 patients were initially admitted to the ICUs, with 12.056 (10.36%) diagnosed with sepsis. Within the first year, 4.428 (36.73%) patients died due to sepsis. Age and male gender were associated with an increased risk of death from sepsis, and the covariates associated with one-year mortality were as follows: age over 80 years with HR 9.91 (95% CI: 9.22-10.65), renal disease with HR 3.16 (95% CI: 3.03-3.29), primary tumoral disease with HR 2.07 (95% CI: 1.92-2.23), liver disease with HR 2.27 (95% CI: 2.07-2.50), and metastatic solid tumor with HR 2.03 (95% CI: 1.92-2.15).

This study revealed a high one-year sepsis mortality rate in the population, associated with variables such as age over 80 years, the presence of renal disease, liver disease, connective tissue diseases, and cancer. Men exhibited higher mortality compared to women.

This study aimed to discover diagnostic and prognostic biomarkers for sepsis immunotherapy through analyzing the novel cellular death process, cuproptosis.

We used transcriptome data from sepsis patients to identify key cuproptosis-related genes (CuRGs). We created a predictive model and used the CIBERSORT algorithm to observe the link between these genes and the septic immune microenvironment. We segregated sepsis patients into three subgroups, comparing immune function, immune cell infiltration, and differential analysis. Single-cell sequencing and real-time quantitative PCR were used to view the regulatory effect of CuRGs on the immune microenvironment and compare the mRNA levels of these genes in sepsis patients and healthy controls. We established a sepsis forecast model adapted to heart rate, body temperature, white blood cell count, and cuproptosis key genes. This was followed by a drug sensitivity analysis of cuproptosis key genes.

Our results filtered three key genes (LIAS, PDHB, PDHA1) that impact sepsis prognosis. We noticed that the high-risk group had poorer immune cell function and lesser immune cell infiltration. We also discovered a significant connection between CuRGs and immune cell infiltration in sepsis. Through consensus clustering, sepsis patients were classified into three subgroups. The best immune functionality and prognosis was observed in subgroup B. Single-cell sequencing exposed that the key genes manage the immune microenvironment by affecting T cell activation. The qPCR results highlighted substantial mRNA level reduction of the three key genes in the SP compared to the HC. The prediction model, which combines CuRGs and traditional diagnostic indicators, performed better in accuracy than the other markers. The drug sensitivity analysis listed bisphenol A as highly sensitive to all the key genes.

Our study suggests these CuRGs may offer substantial potential for sepsis prognosis prediction and personalized immunotherapy.