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Sepsis-induced cardiomyopathy (SIC) is characterized by high mortality and poor outcomes. This study aimed to explore the relationship between testosterone and soluble ST2 (sST2) and all-cause mortality in patients with SIC. Clinical data from SIC patients at Renmin Hospital of Wuhan University from January 2021 and March 2023 were reviewed. Serum testosterone and sST2 were measured at admission. Kaplan–Meier analysis and receiver operative characteristic curve (ROC) were used to estimate the predictive values of testosterone and sST2 on 28 days and 90 days mortality of SIC. A total of 327 male subjects with SIC were enrolled in this study. During the 28 days and 90 days follow-up, 87 (26.6%) and 103 deaths (31.5%) occurred, respectively. Kaplan–Meier analysis showed significantly higher 28 days and 90 days survival in patients with higher testosterone and decreased sST2 levels (p

Abstract Background Secondary nosocomial infections, which are commonly caused by carbapenem-resistant Klebsiella pneumoniae (CRKP) and vancomycin-resistant Enterococcus faecium (VRE), often develop in septic patients. This study aimed to identify the origin of secondary systemic pathogens and reveal the underlying mechanism of infection. Methods In this prospective, observational case–control study, a total of 34 septic patients, 33 non-septic intensive care unit (ICU) patients and 10 healthy individuals serving as controls were enrolled. Three hundred and twelve fecal samples were collected and subjected to 16S rRNA gene amplicon sequencing. Metagenome sequencing was performed to identify the homology between dominant CRKP or VRE in the intestine and pathogens isolated from secondary infectious sites. C57/BL mice were established as pseudo germ-free animal model by pretreatment with broad-spectrum antibiotics for two weeks. Results The abundance and diversity of the gut microbiota in septic patients was drastically decreased one week after ICU admission, potentially leading to the enrichment of antibiotic-resistant bacteria, such as CRKP. Furthermore, secondary bloodstream and abdominal infections caused by CRKP or VRE in septic patients occurred after intestinal colonization with the predominant bacterial species. Genomic analysis showed that bacteria isolated from secondary infection had high homology with the corresponding predominant intestinal opportunistic pathogens. In addition, animal model experiments validated the hypothesis that the administration of antibiotics caused the enrichment of CRKP and VRE among the intestinal microbiota, increasing the likelihood of permeation of other tissues and potentially causing subsequent systemic infection in pseudo germ-free mice. Conclusion Our study indicated that the pathogens causing secondary infection in septic patients might originate from the intestinal colonization of pathogens following broad-spectrum antibiotic treatment.

BackgroundDysfunction of the immune system would disturb the intestinal homeostasis and lead to inflammatory bowel disease (IBD). Dendritic cells (DCs) help maintain intestinal homeostasis and immediately respond to pathogens or injuries once the mucosa barriers are destroyed during IBD. G protein-coupled receptors(GPR)174 is an essential regulator of immunity that is widely expressed in most immune cells, including DCs. However, the role of GPR174 in regulating the immune function of DC in colitis has not been investigated.MethodsDextran sodium sulfate (DSS) was administered to establish the mice colitis model. Data of weight, length of colon, disease activity index (DAI), and macroscopic scores were collected. The flow cytometry was used to detect the infiltrations of T cells and DCs, the mean fluorescence intensity (MFI) of CD80, CD86, CD40, and major histocompatibility complex-II (MHC-II). And T cells proliferataion was measured by carboxyfluorescein diacetate succinimidyl ester (CFSE). The expression of cytokines (tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), interleukin-10 (IL-10), interferon-γ (IFN-γ), interleukin -4 (IL-4)) and GPR174 mRNA were measured by Elisa, quantitative polymerase chain reaction (qPCR), and immunofluorescence. RNA of bone-marrow-derived dendritic cells (BMDCs) was extracted for sequencing. Adoptive transfer of BMDCs was administrated intravenously.ResultsGpr174-/- mice exposed to 3% DSS showed significant alleviation characterized by reduced loss of weight, more minor colon damage, and better DAI and macroscopic scores. The expression of pro-inflammatory cytokines (TNF-α, IL-6) decreased, while anti-inflammatory cytokine (IL-10) increased compared with WT mice. In vitro, Gpr174-/- BMDCs showed less maturity, with a declined expression of MHC-II, CD80, CD86 and reduced TNF-α, higher IL-10 after LPS stimulation. Gpr174-/- BMDCs were less capable of activating OT-II naïve CD4+ T cells than WT BMDCs and induced more Th0 cells to differentiate into Treg while less into Th1. Furthermore, the transcriptome sequencing analysis exhibited that Gpr174 participated in TNF-α (NF-κB) signaling, leukocyte transendothelial migration, and Th1/Th2 cell differentiation pathways. Adoptive transfer of Gpr174-/- BMDCs to WT mice ameliorated DSS-induced colitis.ConclusionOur study indicated that GPR174 was involved in the pathogenesis of IBD by regulating the maturation of the dendritic cells to maintain immune homeostasis. TNF-α (NF-κB) signaling pathway, leukocyte transendothelial migration, and Th1/Th2 cell differentiation pathways may be the target pathway.

Previous studies indicated that G-protein coupled receptor 174 (GPR174) is involved in the dysregulated immune response of sepsis, however, the clinical value and effects of GPR174 in septic patients are still unknown. This study is aimed to evaluate the potential value of GPR174 as a prognostic biomarker for sepsis and explore the pathological function of GPR174 in cecal ligation and puncture (CLP)-induced septic mice. In this prospective longitudinal study, the expressions of peripheral GPR174 mRNA were measured in 101 septic patients, 104 non-septic ICU controls, and 46 healthy volunteers at Day 1, 7 after ICU (Intensive Care Unit) admission, respectively. Then, the clinical values of GPR174 for the diagnosis, severity assessment, and prognosis of sepsis were analyzed. Moreover, the expressions of GPR174 mRNA in CLP-induced septic mice were detected, and Gpr174-knockout (KO) mice were used to explore its effects on inflammation. The results showed that the levels of GPR174 mRNA were significantly decreased in septic patients compared with non-septic ICU and healthy controls. In addition, the expressions of GPR174 mRNA were correlated with the lymphocyte (Lym) counts, C-reactive protein (CRP), and APACHE II and SOFA scores. The levels of GPR174 mRNA at Day 7 had a high AUC in predicting the death of sepsis (0.83). Further, we divided the septic patients into the higher and lower GPR174 mRNA expression groups by the ROC cut-off point, and the lower group was significantly associated with poor survival rate (P = 0.00139). Similarly, the expressions of peripheral Gpr174 mRNA in CLP-induced septic mice were also significantly decreased, and recovered after 72 h. Intriguingly, Gpr174-deficient could successfully improve the outcome with less multi-organ damage, which was mainly due to an increased level of IL-10, and decreased levels of IL-1β and TNF-α. Further, RNA-seq showed that Gpr174 deficiency significantly induced a phenotypic shift toward multiple immune response pathways in septic mice. In summary, our results indicated that the expressions of GPR174 mRNA were associated with the severity of sepsis, suggesting that GPR174 could be a potential prognosis biomarker for sepsis. In addition, GPR174 plays an important role in the development of sepsis by regulating the inflammatory response.

Background. The prognostic nutritional index (PNI) has been reported to significantly correlate with poor survival and postoperative complications in patients with various diseases, but its relationship with mortality in COVID-19 patients has not been addressed. Method. A multicenter retrospective study involving patients with severe COVID-19 was conducted to investigate whether malnutrition and other clinical characteristics could be used to stratify the patients based on risk. Results. A total of 395 patients were included in our study, with 236 patients in the training cohort, 59 patients in the internal validation cohort, and 100 patients in the external validation cohort. During hospitalization, 63/236 (26.69%) and 14/59 (23.73%) patients died in the training and validation cohorts, respectively. PNI had the strongest relationships with the neutrophil-lymphocyte ratio (NLR) and lactate dehydrogenase (LDH) level but was less strongly correlated with the CURB65, APACHE II, and SOFA scores. The baseline PNI score, platelet (PLT) count, LDH level, and PaO2/FiO2 (P/F) ratio were independent predictors of mortality in COVID-19 patients. A nomogram incorporating these four predictors showed good calibration and discrimination in the derivation and validation cohorts. A PNI score less than 33.405 was associated with a higher risk of mortality in severe COVID-19 patients in the Cox regression analysis. Conclusion. These findings have implications for predicting the risk of mortality in COVID-19 patients at the time of admission and provide the first direct evidence that a lower PNI is related to a worse prognosis in severe COVID-19 patients.