Haiyan Yin

Background: Hypomagnesemia is common in patients with cirrhosis. This study aimed to examine the association between serum magnesium levels and the risks of hospital-acquired spontaneous bacterial peritonitis (HA-SBP) and sepsis. Methods: This retrospective study included patients with cirrhosis who were hospitalized at the First People’s Hospital of Changde City, China, between May 2021 and June 2025. The exposure variable was the first serum magnesium measurement obtained within 48 hours of admission. The primary outcome was HA-SBP, and the secondary outcome was sepsis. Multivariable regression and restricted cubic spline (RCS) analyses were used to assess the associations. Results: A total of 1110 patients with cirrhosis were included. The incidences of HA-SBP and sepsis were 12.25% and 6.06%, respectively. Multivariable regression analysis showed that per 1-SD increase in serum magnesium, the risks of HA-SBP and sepsis decreased by 20.8% (odds ratio [OR] = 0.792, 95% confidence interval [CI]: 0.642–0.970, P = 0.026) and 35.5% (OR = 0.645, 95% CI: 0.464–0.883, P = 0.008), respectively. Compared with normomagnesemia, hypomagnesemia was associated with increased risks of HA-SBP (OR = 1.520, 95% CI: 1.009–2.286, P = 0.044) and sepsis (OR = 2.213, 95% CI: 1.189–4.177, P = 0.013). Sensitivity analyses yielded consistent results. RCS analysis showed a linear inverse association between serum magnesium levels and the risks of HA-SBP and sepsis (both P for nonlinearity > 0.05). In addition, the areas under the receiver operating characteristic curves for serum magnesium in predicting HA-SBP and sepsis were 0.635 (95% CI: 0.583–0.686) and 0.688 (95% CI: 0.617–0.758), respectively. Conclusions: Hypomagnesemia was associated with increased risks of HA-SBP and sepsis in patients with cirrhosis, and these findings should be further validated in prospective studies.

Sepsis is a life−threatening organ dysfunction caused by a dysregulated host response to infection and remains a leading cause of death worldwide. Hyperlactatemia, a hallmark metabolic disorder in sepsis, has recently been recognized as an epigenetic modulator via lysine lactylation. This Review synthesizes the evolving understanding of lactate—from a prognostic biomarker to a pathogenic mediator and, most recently, to an epigenetic modulator through lysine lactylation (Kla). Sepsis induces persistent Warburg−like glycolytic reprogramming in immune and parenchymal cells, generating lactate that not only serves as a metabolic fuel but also accumulates to drive covalent histone and non−histone Kla. Rather than merely indicating tissue hypoxia, this lactate surge directly remodels transcriptional and metabolic programs via both lactyl−CoA−dependent (p300/CBP, KAT2B) and lactyl−CoA−independent (AARS1/2) lactylation pathways. We dissect the emerging regulatory network of Kla in sepsis, including validated “writers” and “erasers”, as well as potential writers and erasers awaiting validation in sepsis models, and map their cell type–specific and substrate−specific effects on acute lung injury, cardiomyopathy, acute kidney injury, and vascular dysfunction. The identical lactylation mark—exemplified by H3K18la—exhibits a context−dependent duality, being protective in macrophages yet pathogenic in alveolar or tubular epithelia. This complexity underscores the urgent need for precision−oriented therapeutic strategies. We further explore how lactate and Kla shape the immunopathological landscape of sepsis by modulating macrophage polarization, trained immunity, neutrophil extracellular trap (NET) formation, and T−cell dysfunction, and we compare these effects with the relatively more uniform immunosuppressive role of lactylation in cancer. Finally, we map the currently known landscape of both histone and non−histone Kla across the various stages of sepsis, thereby providing new avenues for mechanism−based therapies in sepsis and other inflammation−associated disorders.

Because cancer may affect sepsis prognosis, yet its association as a comorbidity remains unclear, this study aimed to evaluate the association between pre-existing cancer and mortality in critically ill septic patients. This retrospective cohort study utilized the Medical Information Mart for Intensive Care IV version 3.0 database (2008-2022), focusing on adult ICU patients with sepsis and underlying cancer as the exposure variable. The primary outcome was 28-day all-cause mortality, analyzed using 1:1 propensity score matching (PSM). We acknowledge that detailed oncological information (cancer type, stage, treatment) was unavailable from the database, which may introduce heterogeneity and affect result interpretation. The original cohort included 16,057 patients with sepsis but not cancer and 2,674 with sepsis and cancer. After PSM, both groups were balanced with 2,673 patients. The cancer group had a greater 28-day all-cause mortality rate as compared to the non-cancer group (35.84% vs. 18.97%, respectively), with a hazard ratio (HR) of 2.09 (95% confidence interval [CI]: 1.878~ 2.33, p < 0.001). Sensitivity analysis showed a consistently elevated risk (HR = 1.39, 95% CI: 1.211 ~ 1.586, p < 0.001). Furthermore, cancer was associated with increased in-hospital and 90-day mortality rates among sepsis patients. Subgroup analyses showed elevated mortality risk for sepsis patients with pre-existing cancer relative to non-cancer patients regardless of stratification by age, sex, Charlson Comorbidity Index score (CCI), Sequential Organ Failure Assessment score(SOFA), lymphocyte count, mechanical ventilation requirement,norepinephrine status or acute kidney injury within 48 h of ICU admission. Among critically ill patients with sepsis, underlying cancer is associated with a higher 28-day all-cause mortality. This association does not imply causation. Further prospective studies are warranted to validate these findings.Clinical trial number: This study was registered with the Chinese Clinical Trial Registry on April 22, 2025 (registration number: ChiCTR-PID-270259).

Sepsis is a life-threatening syndrome associated with high morbidity and mortality, underscoring the urgent need for early diagnostic biomarkers and therapeutic targets. However, current diagnostic strategies remain insufficiently precise because of the complex immune dysregulation and immune microenvironment heterogeneity that characterize sepsis. This study aimed to identify reliable diagnostic biomarkers for sepsis and explore their immune regulatory mechanisms together with potential therapeutic relevance using multidimensional bioinformatic analyses.

This study aimed to investigate the heterogeneity of treatment effect for intra‐aortic balloon pump (IABP) across various lactate trajectories in patients with acute myocardial infarction‐related cardiogenic shock (AMICS) supported by veno‐arterial extracorporeal membrane oxygenation (VA‐ECMO). Retrospective data from the China Extracorporeal Life Support Registry included AMICS patients who received VA‐ECMO. The latent class growth model was used to identify distinct lactate trajectories. The primary outcome was in‐hospital mortality. Baseline characteristics and outcomes were compared across trajectory classes, and the heterogeneity of treatment effect for IABP was assessed. Among 1264 patients, three lactate trajectories were identified. Compared with Class 1, both Class 2 (odds ratio [OR] 2.03, 95% confidence interval [CI] 1.54–2.67) and Class 3 (OR 3.99, 95% CI 2.77–5.78) had significantly higher in‐hospital mortality. Moreover, heterogeneity of treatment effect across the classes was found. IABP use was associated with increased risks of in‐hospital mortality and multiple complications (bleeding, renal, metabolic, and infection) in Class 1, whereas no associations were observed in Class 2 or Class 3, except for a higher risk of infection in Class 2. In summary, lactate trajectories can stratify mortality risk in AMICS patients receiving VA‐ECMO support and reflect heterogeneous responses to IABP treatment.

Objective: Clinical reasoning is a fundamental and critical competency for physicians. However, how to effectively help resident trainees to develop and enhance this ability remains a challenge for medical instructors. In this study, a teaching approach that combines simulation-based “Debriefing with Good Judgment” (DwGJ) with Case-Based Learning (CBL) was employed to improve the clinical reasoning among standardized training residents. The effectiveness of teaching strategy was evaluated. Methods: This study was designed and conducted as a randomized controlled educational trial. A total of 70 residents at the Clinical Skills Training Center of the First Affiliated Hospital of Jinan University, Guangzhou, China, were recruited in the 2023–2024 academic year. These residents from Internal Medicine, Surgery, Obstetrics and Gynecology, Pediatrics, Emergency Medicine, and Intensive Care Medicine, were randomly assigned to either a control group or a DwGJ group. There were 35 participants in each group. The control group received conventional CBL instruction, practicing skills within a clinical scenario, while the DwGJ group incorporated a DwGJ session following hands-on practice session. Upon course completion, participants evaluated the instructor and course, their clinical reasoning competencies (including clinical thinking, and systematic thinking, and evidence-based thinking) were surveyed, and theoretical and practical examination scores were compared. Results: There was no significant difference between two groups in instructor evaluation. However, the DwGJ group reported significantly higher satisfaction with the course. Moreover, the DwGJ group outperformed the control group in all subcomponents of clinical reasoning, including critical thinking, systematic thinking, and evidence-based thinking. Both the theoretical test scores and skill scores were significantly higher in the DwGJ group (64.40 ± 13.22 and 80.54 ± 7.4, respectively) compared to the control group (52.34 ± 18.42, p = 0.02 and 72.32 ± 7.6, p < 0.01, respectively). Conclusion: The integration of simulation-based DwGJ with CBL demonstrates more efficacy in enhancing resident trainees’ clinical reasoning abilities, through fostering their critical, systematic, and evidence-based thinking.