Sepsis-associated liver injury is a severe complication of sepsis characterized by substantial metabolic alterations, yet longitudinal metabolomics resources for this condition remain limited. Here, we present an LC-MS-based longitudinal metabolomics dataset comprising 88 blood samples collected from healthy controls and sepsis patients with or without liver injury across multiple ICU-associated clinical time points. Comprehensive metabolomic profiling generated 18,247 high-quality metabolic features and 2,894 annotated metabolites, providing a resource for investigating temporal metabolite patterns with annotations related to nucleotide, lipid, and bile acid metabolism across clinical groups and sampling time points. Exploratory analytical approaches, including temporal clustering, weighted correlation network analysis, and regularized regression-based feature selection, were applied to facilitate characterization of longitudinal metabolic patterns within the dataset. This dataset provides a reusable resource for future studies on longitudinal metabolic dynamics, biomarker validation, integrative multi-omics analyses, and methodological development in sepsis and critical care research.

Mycophenolate mofetil (MMF) is a very powerful immunosuppressive drug used in preventing acute rejection in liver transplantation. However, MMF has some serious side effects, including hematologic and gastrointestinal disorders. This study was designed to investigate the relationship between the clinical events and the pharmacokinetics of mycophenolic acid (MPA) in Chinese liver transplant recipients. Sixty-three adult liver transplant recipients receiving 1.0 g of MMF twice daily in combination with tacrolimus were prospectively included. The MPA pharmacokinetic profiles (blood sampling time points: before the dose and 0.5, 1, 1.5, 2, 4, 6, 8, 10, and 12 hours after the dose) were monitored after transplantation. Every clinical event, including acute and MMF-related side effects, was monitored in all patients within 3 months. Two patients (3.2%) had an episode of acute rejection. Forty-two patients (66.7%) had 52 episodes of MMF-related side effects, including leukopenia, diarrhea, and infection. The 0-hour concentration (C(0h)), maximum (peak) concentration (C(max)), and area under the curve from 0 to 12 hours (AUC(0-12h)) in patients with side effects were significantly higher than those in patients without side effects (P < 0.05). The thresholds of side effects from receiver operating characteristic analysis were 2 mg/L (sensitivity, 52.4%; specificity, 90.5%) for C(0h), 10 mg/L (sensitivity, 45.2%; specificity, 85.7%) for C(max), and 40 mg h/L (sensitivity, 71.4%; specificity, 61.9%) for AUC(0-12h) (P < 0.05). Leukopenia was discriminated effectively in C(0h) and in C(max) (P < 0.05). These results demonstrate the close relationship between leukopenia and MPA pharmacokinetic parameters in the early period after liver transplantation. C(0h) and AUC(0-12h) of MPA could predict the subsequent occurrence of leukopenia. These values may be used in routine monitoring for MMF therapy.

BackgroundThe development of care-sensitive quality indicators represents an essential component of care management. Currently, there exists no objective, scientific, and sensitive assessment framework for evaluating sepsis care quality management in China.Methods and designThis mixed-methods investigation employed a three-phase design. Initially, a systematic literature review (2014–2024) across four databases identified evidence regarding sepsis care quality. Subsequently, semi-structured interviews were conducted with five clinical experts from emergency departments and intensive care units (ICUs) to examine their perspectives on nursing-sensitive quality indicators (NSQIs). Finally, a modified Delphi process engaged a multidisciplinary panel to refine and validate sepsis-specific NSQIs through systematic consensus-building.ResultsTwo rounds of expert consultation were completed with a questionnaire return rate of 100%. Sixteen experts, consisting of 10 nurses and 6 physicians, participated in the first and second rounds of the Delphi survey, respectively. The mean score of the expert authority coefficient Cr for the two rounds was 0.95 and 0.96 (Cr ≥ 0.7). The coordination coefficient (Kendall W) was 0.120-0.316 (p < 0.001) in the first round and 0.116–0.142 (p < 0.001) in the second round, both of which reached a significant consensus. A comprehensive list of sensitive indicators for sepsis care quality was established, encompassing three primary, nine secondary, and 30 tertiary indicators.ConclusionThe established NSQIs encompass three fundamental dimensions of sepsis care quality: importance, rationality, and feasibility.Clinical practice implicationsThis research provides a valuable framework for evaluating clinical care quality in sepsis management.

Severe acute pancreatitis (SAP) is a complex inflammatory disorder with severe immune imbalance. This study investigates the therapeutic potential of extracellular vesicles derived from human adipose mesenchymal stem cells (hADSC-EVs) in modulating Treg differentiation and alleviating SAP. We conducted a phosphoproteomics analysis to evaluate phosphorylation levels, and administered hADSC-EVs in a mouse model of SAP and assessed their impact on Treg differentiation. Phosphoproteomics revealed a significant increase in p-STK3 following hADSC-EVs treatment, restoring Foxp3 level diminished by STK3 knockdown. HADSC-EVs promoted Treg differentiation in a concentration-dependent manner by targeting Foxp3 transcription. In the SAP mouse model, hADSC-EVs improved survival rates and mitigated histopathological alterations. In conclusion, our study revealed that STK3 effectively promotes Treg differentiation and enhances their immunosuppressive capabilities, thereby ameliorating inflammation and attenuating the pathological phenotypes associated with SAP. These findings provide valuable insights into the potential role of hADSC-EVs in regulating immune responses and promoting tissue repair.

Fluid balance in the early stages of severe acute pancreatitis (SAP) significantly impacts patient outcomes. This study aimed to identify the optimal fluid balance value affecting adverse outcomes in SAP patients to enhance fluid management. The study comprised two parts. Part 1 involved a retrospective review of 560 SAP patients at Ruijin Hospital (1996–2008) to determine the optimal fluid balance for in-hospital mortality using multivariable regression and ROC curve analysis. Part 2 prospectively examined 343 SAP patients in Emergency Intensive Care Unit at Ruijin Hospital (2020–2023) to validate findings regarding 30-day mortality and organ support. In Part 1, key independent risk factors for in-hospital mortality included age, weight, hypertension, APACHE II score, D0-D2/kg fluid balance, sugery and necrosis. The optimal predictive D0-D2/kg fluid balance value was found to be 48.4 ml/kg. In Part 2, exceeding this value indicated a higher risk for 30-day mortality (HR = 3.477) and increased need for mechanical ventilation (OR = 4.741) and blood purification (OR = 3.685). A D0-D2/kg fluid balance above 48.4 ml/kg correlates with poorer outcomes in SAP patients, providing guidance for clinicians in fluid management to improve prognosis.

Sepsis is a severe inflammatory condition often complicated by acute lung injury (ALI) with limited therapeutic options. S100 Calcium Binding Protein A9 (S100A9) as an alarmin is highly elevated in sepsis. We observed that S100A9 was lactylated in the lung tissues of septic mice, the role of which in regulating sepsis-related ALI remains unknown. S100A9 lactylation sites were identified in septic patients and CLP mice using immunoprecipitation and mass spectrometry. Mechanistic studies employed mutagenesis, co-immunoprecipitation, and luciferase assays. In this study, we confirmed that S100A9 was lactylated at K4 and K94 in septic patients. Lactylated S100A9 promoted its nuclear translocation, thereby enhancing its interaction with transcription factor CCAAT/enhancer-binding protein beta (Cebpb). The complex of S100A9 and Cebpb further promoted the transcriptional activation of downstream interleukin 1 beta (IL-1β), leading to sepsis-related ALI. Moreover, the knockout of S100A9 effectively alleviated sepsis-induced inflammatory response and lung injury. Our findings elucidated the importance of S100A9 lactylation in regulating inflammatory responses of macrophages in sepsis-induced ALI, providing novel insights into the pathophysiology of sepsis and potential therapeutic targets for sepsis-associated organ dysfunction.

Hypertriglyceridemia-induced acute pancreatitis (HTG-AP) is a common cause of acute pancreatitis and is associated with worse clinical outcomes. Early prediction of prolonged hospitalization may facilitate clinical management and resource allocation. We aimed to develop and validate a web-based dynamic nomogram to predict prolonged length of stay (LOS) in patients with HTG-AP. We retrospectively analyzed 608 patients with HTG-AP admitted between 2014 and 2024. Patients were randomly divided into a training cohort (n = 487) and an internal validation cohort (n = 121). An independent external cohort of 39 patients (2021–2023) was used for external validation, and temporal validation was performed using a time-based split within the development cohort. Predictor variables were selected using LASSO regression and SHAP analysis. Independent predictors were identified by multivariate logistic regression and incorporated into a web-based nomogram. Model performance was assessed by discrimination, calibration, and decision curve analysis. Five independent predictors—systemic inflammatory response syndrome (SIRS), blood glucose, serum calcium, D-dimer, and APACHE II score—were included. Using LOS > 14 days as the endpoint, prolonged hospitalization occurred in 60.6

BACKGROUND:Hypertriglyceridemia-induced acute pancreatitis (HTG-AP) has become the second leading cause of acute pancreatitis in China, accounting for approximately 20% of cases. Although lipid apheresis (LA) reduces triglyceride (TG) levels, its clinical utility and patient selection criteria remain unclear. OBJECTIVE:This study aimed to evaluate LA outcomes in patients with HTG-AP, comparing outcomes between those with baseline TG levels of 22.4 to 56.5 mmol/L and >56.5 mmol/L. METHODS:This was a single-center retrospective cohort study utilizing data from the electronic medical records of Ruijin Hospital, Shanghai Jiao Tong University School of Medicine (from January 2014 to August 2024). RESULTS:A total of 608 patients with HTG-AP were included, of whom 123 underwent LA. After propensity score matching, 65 matched pairs were included. Generalized linear model analysis showed that LA was significantly associated with higher odds of intensive care unit (ICU) admission (β = 2.49, P < .01). The LA group had higher TG levels (β = 0.48, P < .01) and higher Acute Physiology and Chronic Health Evaluation II scores on day 3 (β = 0.16, P = .047). No significant differences were observed in C-reactive protein, systemic inflammatory response syndrome, computed tomography severity index, or sequential organ failure assessment scores. Among LA-treated patients, those with baseline TG >56.5 mmol/L had a significantly higher likelihood of prolonged hospitalization (length of stay >14 days) compared with the 22.4 to 56.5 mmol/L group (β = 1.43, P < .01). Sensitivity analyses supported the robustness of the primary results. CONCLUSION:LA therapy was associated with higher odds of ICU admission in patients with HTG-AP. Among LA-treated patients, baseline TG >56.5 mmol/L predicted prolonged hospitalization, which was supported by sensitivity analysis.

Background Currently, there are no objective, scientific, and sensitive assessment frameworks for evaluating sepsis care quality management in China. This study aimed to address this gap by developing and validating nursing-sensitive quality indicators (NSQIs) tailored to sepsis management in Chinese clinical settings. Methods This mixed-methods investigation involved three phases. A systematic literature review (2014–2024) across four databases identified evidence regarding sepsis care quality. Subsequently, semi-structured interviews were conducted with 16 clinical experts from emergency departments (EDs) and intensive care units (ICUs) to examine their perspectives on NSQIs. Finally, a modified Delphi process engaged a multidisciplinary panel to refine and validate sepsis-specific NSQIs through a systematic consensus-building process. Result Two rounds of expert consultation were completed, with a 100% questionnaire return rate. Sixteen experts (10 nurses and six physicians) participated in the first and second rounds of the Delphi survey. The mean score of the expert authority coefficient for the two rounds was 0.96. The range of Kendall W values was 0.120–0.316 (P < 0.001). A comprehensive list of sensitive indicators for sepsis care quality was established, encompassing three primary, nine secondary, and 30 tertiary indicators. Conclusion The established NSQIs encompass three fundamental dimensions of sepsis care quality: importance, rationality, and operational feasibility. This two-round Delphi process achieved expert consensus, confirming the system’s alignment with clinical guidelines and feasibility. Clinical practice implications: This research provides a valuable framework for evaluating clinical care quality in sepsis management.

BackgroundAlthough the RNA-dependent RNA polymerase (RdRp) complex is a therapeutic target for influenza, evidence on the pharmacology, resistance, and clinical impact of RdRp-targeting inhibitors in high-risk populations remains fragmented. This scoping review on RdRp-targeting inhibitors identifies the research gaps and characterizes their mechanisms of action, pharmacokinetics, efficacy, safety, and resistance patterns.MethodsFollowing the “Preferred Reporting Items for Systematic Reviews and Meta-Analyses extension for Scoping Reviews” guidelines, a comprehensive search for studies was conducted across PubMed, Embase, the Cochrane Library, China National Knowledge Infrastructure, Wanfang, and ClinicalTrials.gov from inception to October 2025. Preclinical and clinical studies on influenza RdRp-targeting inhibitors were included, with data charted across eight domains.ResultsFrom 1,282 identified records (English: 1197; Chinese: 85), 156 articles were included. PA inhibitors emerged as the most extensively documented class. Preclinical findings demonstrated potent antiviral activity of PA inhibitors and emerging PB1/PB2 analogs, with variability in pharmacokinetic profiles. Clinical evidence showed PA inhibitors consistently shorten the time to symptom relief and accelerate viral RNA clearance compared with standard therapy. RdRp-targeting inhibitors showed an acceptable tolerability profile. Resistance was a notable challenge, primarily involving PA-I38 substitutions. Evidence on drug–drug interactions was limited to early-phase trials. A significant evidence gap remains for high-risk populations; baloxavir being the only agent widely studied in high-risk adults.ConclusionRdRp-targeting antivirals represent a promising frontier for influenza treatment, with PA inhibitors being the most extensively validated class. While PB1 and PB2 inhibitors diversify the therapeutic pipeline, their development is hindered by the need for multiple-dose regimens and the emergence of drug resistance. Future research should prioritize inhibitor designs that minimize resistance, as well as combination regimens, to accelerate clinical translation.

Major adverse kidney events within 30 days (MAKE30) are associated with poor outcomes in patients with sepsis-associated acute kidney injury (SA-AKI). This study aimed to develop and validate a nomogram-based prediction model for MAKE30 in SA-AKI patients. Clinical and laboratory data were collected from SA-AKI patients admitted to eight tertiary Grade-A hospitals in Shanghai between January 2021 and October 2022, forming the development cohort. External validation was performed using data from SA-AKI patients treated at Ruijin Hospital between January 2017 and December 2019. A predictive nomogram was constructed using LASSO regression followed by multivariate logistic regression. Model performance was assessed using area under the curve (AUC), calibration plots, decision curve analysis (DCA), and clinical impact curves (CIC). The model was subsequently validated in the external validation cohort. A total of 531 SA-AKI patients were included, with 372 in the development cohort and 159 in the validation cohort. The incidence of MAKE30 was 55.6

In acute pancreatitis (AP), the release of mitochondrial DNA (mtDNA) from pancreatic acinar cells (PACs) plays a pivotal role in triggering a lethal systemic inflammatory response. Despite the importance of mtDNA release, the regulatory mechanisms upstream of this event remain poorly understood, hindering the development of targeted therapeutic strategies. To address this, we utilized single-cell RNA sequencing, CUT Tag, luciferase reporter assays, and experiments in a PAC-specific knockout mouse model to investigate the transcriptional program governing vesicle transport and mtDNA release in the context of AP. Our analysis revealed that vesicle transport pathways were activated in AP PACs and identified Runx1 as a core transcriptional regulator. We discovered that Runx1 directly binds and activates the Snx9 promoter. This interaction initiates a pathological cascade wherein Runx1-Snx9 signaling drives mitochondrial fragmentation and the biogenesis of intracellular mitochondrial-derived vesicles (MDVs). Under AP conditions, these MDVs are diverted from degradative pathways and routed to the secretory machinery to be released as pathogenic, extracellular mitochondrial-derived vesicles (Ex-MDVs). These Ex-MDVs were confirmed to be highly pathogenic, strongly activating the cGAS-STING pathway in macrophages. Notably, PAC-specific deletion of Runx1 in a mouse model significantly mitigated pancreatic injury and suppressed the systemic inflammatory storm associated with AP. This study is the first to elucidate the Runx1-Snx9 transcriptional axis as the core upstream mechanism responsible for the anomalous generation and secretion of Ex-MDVs from PACs during AP, providing novel insights into AP pathogenesis and identifying this axis as a potential therapeutic target.

BACKGROUND:Sepsis, a life-threatening condition marked by organ dysfunction due to a dysregulated host response to infection, involves complex physiological and biochemical abnormalities. AIM:To develop a multivariate model to predict 4-, 6-, and 8-week mortality risks in intensive care units (ICUs). STUDY DESIGN:A retrospective cohort of 2389 sepsis patients was analysed using data captured by a clinical decision support system. Patients were randomly allocated into training (n = 1673) and validation (n = 716) sets at a 7:3 ratio. Least Absolute Shrinkage and Selection Operator (LASSO) regression identified variables incorporated into a multivariate Cox proportional hazards regression model to construct a prognostic nomogram. The area under the receiver operating characteristic curve (AUROC) assessed model accuracy, while performance was evaluated for discrimination, calibration and clinical utility. RESULTS:A risk score was developed based on 11 independent predictors from 35 initial factors. Key predictors included minimum Acute Physiology and Chronic Health Evaluation II (APACHE II) score as having the greatest impact on prognosis, followed by days of mechanical ventilation, number of vasopressors, maximum and minimum Sequential Organ Failure Assessment (SOFA) scores, infection sources, Gram-positive or Gram-negative bacteria and malignancy. The nomogram demonstrated superior discriminative ability, with AUROC values of 0.882 (95% confidence interval [CI], 0.855-0.909) and 0.851 (95% CI, 0.804-0.899) at 4 weeks; 0.836 (95% CI, 0.798-0.874) and 0.820 (95% CI, 0.761-0.878) at 6 weeks; and 0.843 (95% CI, 0.800-0.887) and 0.794 (95% CI, 0.720-0.867) at 8 weeks for training and validation sets, respectively. CONCLUSION:A validated nomogram and web-based calculator were developed to predict in-hospital mortality in ICU sepsis patients. Targeting identified risk factors may improve outcomes for critically ill patients. RELEVANCE TO CLINICAL PRACTICE:The developed prediction model and nomogram offer a tool for assessing in-hospital mortality risk in ICU patients with sepsis, potentially aiding in nursing decisions and resource allocation.

Effective early prediction of acute pancreatitis (AP) severity remains an unmet clinical need due to limited molecular characterization of systemic immune responses. We performed integrated single-cell RNA sequencing with T- and B-cell receptor profiling on peripheral blood mononuclear cells from AP patients (n = 7) at days 1, 3, and 7 after admission. Immune landscape analysis revealed marked inter-patient heterogeneity, with a distinct expansion of MZB1-expressing plasma cells that were strongly associated with complicated AP and recovery. Functional validation in an independent cohort (n = 14) confirmed disease-associated plasma cell markers, alongside altered serum immunoglobulin and cytokine profiles (n = 32). From these findings, we established a nine-gene B-cell-derived transcriptomic signature (S100A8, DUSP1, JUN, HBA2, FOS, CYBA, JUNB, S100A9, and WDR83OS) predictive of AP severity. This model demonstrated high discriminative performance in internal validation (n = 114; AUROC > 0.95, superior to standard clinical scoring systems), and sustained accuracy in external validation cohorts of AP (n = 87) and AP combined with non-AP sepsis (n = 174) for predicting persistent organ failure. Our study identifies a mechanistic and predictive role for MZB1⁺ plasma cells in AP pathogenesis, offering a novel immune-based stratification strategy with potential for precision clinical management.

Primary cardiac angiosarcoma is a relatively rare tumor that frequently metastasizes by the time of diagnosis, with a poor prognosis. Currently, there is no uniform treatment, with surgical resection, radiotherapy, and chemotherapy being the mainstays of treatment. We report the case of a man in his early 30s who presented to the emergency department with hemoptysis and was found to have massive pericardial effusion and right atrial occupancy upon investigation. Subsequent examination revealed hypermetabolic foci in the lungs and femur, and a final biopsy confirmed the presence of a primary cardiac angiosarcoma. The patient died 3 days after diagnosis due to cardiopulmonary failure, with a survival period of 4 months from symptom onset to death. This report describes one of the few cases of cardiac tumor with respiratory symptoms.

Acute pancreatitis (AP) is a severe inflammatory disorder associated with metabolic reprogramming and mitochondrial dysfunction. This study investigated central carbon metabolism alterations in pancreatic acinar cells during AP, elucidated the molecular mechanisms of tricarboxylic acid (TCA) cycle disorders, and explored the role of protein hypersuccinylation in AP pathogenesis. Using in vitro and in vivo AP models, targeted metabolomics and bioinformatics analyses revealed TCA cycle dysregulation characterized by elevated succinyl-CoA and decreased succinate levels. Colorimetric assays, mass spectrometry, and site-directed mutagenesis demonstrated that SIRT5 downregulation led to SUCLA2 hypersuccinylation at K118, inhibiting succinyl-CoA synthetase activity and triggering a vicious cycle of succinyl-CoA accumulation and SUCLA2 succinylation. Adenovirus-mediated SIRT5 overexpression and SUCLA2 knockdown clarified the SIRT5-SUCLA2 pathway's role in regulating TCA cycle disorders. Protein succinylation levels positively correlated with pancreatic tissue damage and mitochondrial injury severity. Succinylome analysis identified cytochrome c1 (CYC1) as a key hypersuccinylated protein, and the SIRT5-SUCLA2 pathway regulated its succinylation level and electron transport chain complex III activity. Hypersuccinylation induced mitochondrial DNA release, activating the cGAS-STING pathway, contributing to multiple organ dysfunction syndrome. Modulating the SIRT5-SUCLA2 axis attenuated TCA cycle dysregulation, protein hypersuccinylation, mitochondrial damage, and inflammatory responses in AP. These findings reveal novel mechanisms linking the SIRT5-SUCLA2 axis, TCA cycle dysfunction, and protein hypersuccinylation in AP pathogenesis, providing potential therapeutic targets for AP treatment.

Objective·To investigate the role and mechanism of sirtuin 5(SIRT5)in pulmonary microvascular endothelial cell injury in sepsis.Methods·Wild-type(WT)and Sirt5 gene knockout C57BL/6 male mice underwent cecal ligation and puncture(CLP)surgery.Following euthanasia,lung tissues were collected.Pulmonary inflammation was assessed using hematoxylin and eosin(H-E)staining;vascular leakage was evaluated by Evans blue(EB)staining;coagulation function in mice was analyzed via immunofluorescence staining of lung tissues.Immunohistochemical staining was employed to detect vascular cell adhesion molecule-1(VCAM-1)protein expression,thereby assessing endothelial inflammation in CLP-treated mice.By using gene editing technology,SIRT5 was knocked down or overexpressed in human umbilical vein endothelial cells(HUVECs),and the cells were subsequently stimulated with lipopolysaccharide(LPS)to induce endothelial inflammation.Protein expression levels of VCAM-1,tissue factor(TF),and other endothelial injury markers were detected by Western blotting,and inflammatory cytokines such as interleukin-6(IL-6)and IL-1β,were detected by quantitative real-time PCR(qPCR).In addition,transcriptomic sequencing was performed on HUVECs overexpressing SIRT5,and key genes including F2R-like thrombin or trypsin receptor 3(F2RL3),serpin family A member 3(SERPINA3),and transforming growth factor β2/β3(TGF-β2/3)were validated by qPCR.Results·Sirt5 knockout significantly aggravated lung injury in CLP mice,reducing their survival rates(P<0.001).H-E staining showed increased inflammatory infiltration in the lung tissue of the mice,while EB staining indicated increased vascular leakage(P<0.001).Immunofluorescence revealed elevated fibrinogen deposition.In HUVECs with SIRT5 knockdown,the protein levels of VCAM-1 and TF,as well as the mRNA levels of inflammatory factors including IL-6,IL-1β,VCAM-1,and E-selectin,were significantly upregulated(all P<0.001),whereas overexpression of SIRT5 reversed these effects.Transcriptome sequencing analysis indicated that SIRT5 regulated endothelial inflammation and coagulation responses by inhibiting the F2RL3/SERPINA3/TGF-β pathway.Conclusion·SIRT5 negatively regulates the F2RL3/SERPINA3/TGF-β signaling axis,thereby alleviating endothelial inflammation and promoting coagulation responses,suggesting its potential protective role in sepsis-induced lung injury.