BACKGROUND:Sepsis is a global health challenge associated with high morbidity and mortality rates. Early diagnosis and treatment are challenging because of the limited understanding of its underlying mechanisms. This study aimed to identify effective biomarkers for diagnosing and treating sepsis through an integrated multi-method approach. METHODS:Publicly available single-cell RNA sequencing (scRNA-seq) and bulk RNA-seq datasets were analyzed for naive CD4 + T cell-specific genes. Based on these hub genes, Mendelian randomization (MR) analysis, followed by the MR-Bayesian model averaging (MR-BMA) algorithm, was implemented to explore the causality between these genes and sepsis. In addition, single-cell-type expression analysis, cell-cell communication detection, metabonomic evaluation, clinical samples, and both in vivo and in vitro studies were conducted to unveil the underlying mechanisms of potential therapeutic targets. RESULTS:scRNA-seq revealed significant depletion of naive CD4 + T cells in sepsis, identifying 33 key genes. Both MR and MR-BMA analyses confirmed that elevated proportion of naive CD4 + T cell in total CD4 + T cells were related to sepsis occurrence (odds ratio [OR] = 0.90, 95% confidence interval [CI], 0.83-0.97, P = 0.007) and 28-day mortality associated with sepsis (OR = 0.75, 95% CI, 0.64-0.88, P <0.001). Notably, among the 33 hub genes, PC-esterase domain containing 1B ( PCED1B ) exhibited a strong causal association with 28-day mortality in patients with sepsis (OR = 0.64, 95% CI, 0.51-0.81, P <0.001), which was further validated by bulk RNA-seq analysis. PCED1B mediated the impact of proportion of naive CD4 + T cell in CD4 + T cell on sepsis-related mortality. In addition, clinical samples and both in vivo and in vitro experiments validated the elevated expression of PCED1B in naive CD4 + T cells derived from sepsis patients and mice. Mechanistic investigations revealed PCED1B+ CD4 + T cells may interact with monocytes/dendritic cells through the macrophage migration inhibitory factor (MIF)-(CD74 + CD44) axis, concurrently engaging with B cells/plasmablasts through the MIF-(CD74 + CXCR4) axis, thereby regulating multiple metabolic alterations in sepsis. CONCLUSION:The interplay between PCED1B and naive CD4 + T cells, as revealed by this study, is instrumental in developing immunotherapeutic strategies for sepsis.

Critical care medicine plays a pivotal role in addressing life-threatening conditions; however, its development in China is hindered by resource scarcity and inequitable distribution. Existing studies have mostly focused on ICU bed numbers or selected regions, and have rarely provided a comprehensive, nationwide assessment of ICU beds, staffing and equipment using standardized methods, nor have they systematically quantified population-based equity of ICU resources. To address this evidence gap and describe the current landscape of critical care capacity in China, we conducted a nationwide survey of critical care resources. The survey aimed to describe the current status of resources, quantify population-based equity, and explore regional and hierarchical disparities that may affect access to critical care. This cross-sectional survey was conducted from January 1, 2021, to December 31, 2023, encompassing public comprehensive hospitals, private hospitals, and specialty hospitals across 31 provinces (including municipalities) in China. A total of 4,744 hospitals with a comprehensive ICU provided valid responses and were included in the analysis; the overall response rate among eligible hospitals invited through provincial health authorities was approximately 89.80

Central line-associated bloodstream infection (CLABSI) represents a severe complication of indwelling intravascular catheters and is a leading cause of healthcare-associated infections in intensive care units (ICUs). CLABSI significantly increases mortality, prolongs hospital stays, and elevates healthcare costs. Recent large-scale clinical studies on the diagnosis, treatment, and prevention of CLABSI, alongside evolving patterns of antibiotic resistance and new antimicrobial developments, have necessitated updates to clinical management strategies. Hence, the Chinese Society of Critical Care Medicine (CSCCM) has updated the 2007 guideline on intravascular catheter-related infections. This guideline was developed using the GRADE (Grading of Recommendations Assessment, Development, and Evaluation) methodology for evidence assessment. The multidisciplinary working group formulated clinical questions, conducted systematic literature reviews, performed meta-analyses, and synthesized evidence to develop recommendations. These recommendations underwent iterative revisions through expert panel reviews, remote and in-person meetings, and two rounds of voting by the Society’s Standing Committee before finalization. The guideline comprises 52 recommendations, focusing on adult patients with central venous catheters in the ICU. Part 1 of this guideline focuses on the diagnosis and prevention of CLABSI. In Part 2, we will further analyze the management of catheters following infection and the appropriate use of antimicrobial agents. Practice Guideline Registration Practice Guideline Registration for Transparency, PREPARE-2024CN873.

BACKGROUND:Previous research indicated that physicians possess limited knowledge of the diagnosis and treatment of invasive fungal disease (IFD). OBJECTIVE:This study aimed to assess the efficacy of training via video or PDF formats in increasing physicians' knowledge of IFD. METHODS:This was a multicentre, cluster-randomised controlled trial involving 18 tertiary hospitals in China. Physicians specialising in IFD clinical diagnosis and treatment from four departments were randomised 1:1 into a video training group or PDF training group, and questionnaires were completed before and after training. The primary outcome was the change in total questionnaire score before and after training. RESULTS:Of the 294 participants, 146 were assigned to the video group and 148 to the PDF group. Engagement with the training materials was observed among 127 participants from the video group and 135 from the PDF group. In the per-protocol set (PPS), post-training score improvements for total scores (p = 0.008), invasive candidiasis scores (p < 0.001), and invasive aspergillosis scores (p = 0.044) in the video group were significantly greater than those in the PDF group. Overall, 161 (61.5%) physicians in the PPS exhibited enhanced total scores post-training, with the video group outperforming the PDF group (70.9% vs. 52.6%, p = 0.002). The findings in the FAS were largely consistent with those observed in the PPS. CONCLUSION:Both video and PDF training modules are appealing to physicians. Further, the video training module displayed superior efficacy in improving physicians' knowledge of IFD.

Central line-associated bloodstream infection (CLABSI) is a severe complication of indwelling intravascular catheters and a leading cause of healthcare-associated infections in intensive care units (ICUs). CLABSI significantly increases mortality, prolongs hospital stays, and elevates healthcare costs. Recent large-scale clinical studies of CLABSI diagnosis, treatment, and prevention, alongside evolving antibiotic resistance patterns and new antimicrobial developments, have necessitated updates to clinical management strategies. Consequently, the Chinese Society of Critical Care Medicine (CSCCM) has updated the 2007 guideline on intravascular catheter-related infections. This guideline was developed using Grading of Recommendations Assessment, Development, and Evaluation (GRADE) methodology for evidence assessment. A multidisciplinary working group formulated clinical questions, conducted systematic literature reviews, performed meta-analyses, and synthesized evidence to draft recommendations. The recommendations underwent iterative revisions through expert panel reviews, remote and in-person meetings, and two rounds of voting by the Society’s Standing Committee before finalization. The guideline comprises 52 recommendations, focusing on adult patients in ICU with central venous catheters. This document, Part 1, addresses diagnosis and prevention, formulated using GRADE methodology. The aims of the guideline are to standardize best practices, reduce CLABSI incidence, and improve the outcomes of patients in ICUs.Practice Guideline Registration: Practice Guideline Registration for Transparency (PREPARE-2024CN873).

Objectives To evaluate the efficacy and safety of Ilaprazole in preventing stress ulcer-associated upper gastrointestinal bleeding in critically ill patients. Design A Randomized, Double-Blind, non-inferiority Phase 3 Trial. Setting 70 hospitals across China from July 16, 2021, to April 28, 2022. Patients 441 Patients (mean age 59 years; 150 female) at high risk for stress ulcer bleeding requiring invasive mechanical ventilation were enrolled. Interventions Patients were randomly assigned to receive either Ilaprazole (10 mg once daily, first dose doubled; 220 patients) or esomeprazole (40 mg twice daily; 221 patients). Measurements and main results 441 patients (mean age 59 years; 150 female) were enrolled: 220 received Ilaprazole and 221 received esomeprazole. In FAS set, the primary endpoint occurred in 213 (96.80%) patients in the Ilaprazole and 215 (97.30%) in esomeprazole arms (Absolute Risk Difference: -0.47, 95% CI: -4.02, 3.03, p = 0.772). Secondary outcomes showed comparable incidences of clinically insignificant UGI bleeding, any gastrointestinal bleeding, 28-day mortality, ICU mortality, and pneumonitis. Adverse events were similar between groups, but Ilaprazole had a significantly lower incidence of hepatobiliary disorders (0.9% vs. 5%, p = 0.012). Conclusions Ilaprazole demonstrated non-inferiority to esomeprazole in preventing UGI bleeding in critically ill patients at high risk of stress ulcer.

[This corrects the article DOI: 10.1016/j.jointm.2025.08.011.].

Background::Previous studies have highlighted the importance of intensive care units (ICUs) in providing specialized care for critically ill patients. However, little is known about the current distribution of ICU resources, medical personnel, and available technologies across hospitals of different levels in Chinese mainland. In response, this study evaluated the distribution of ICU resources, personnel, major diseases, medical techniques, and the relationship between ICU bed availability and economic development to provide an overview of the current state of ICU services in Chinese mainland.Methods::A comprehensive questionnaire was distributed to intensivists at all levels of hospitals in Chinese mainland via the Questionnaire Starmini-program, a commonly used web-based survey platform in China. The questionnaire covered a wide range of items, including the demographic characteristics of intensivists, ICU type and capacity, composition of medical teams, disease classification, and available medical techniques.Results::Data were analyzed from 3637 intensivists working in 2005 hospitals throughout Chinese mainland, representing approximately half of all hospitals with ICU settings nationwide. The median number of hospital beds was 1000 (interquartile range [IQR], 547-1800), and the median number of ICU beds was 17 (IQR: 11-25). Overall, 600 (IQR: 300-1091) patients were admitted to the ICU annually at each hospital. The mean number of ICU beds per 100,000 people was 5.31 in 2022. The majority of the surveyed medical groups (ranging from 97.7% to 98.8%) led by chief physicians have experience in treating the eight most common conditions managed in the ICU, including severe pneumonia, cardiogenic shock, hypovolemic shock, sepsis, septic shock, cardiopulmonary resuscitation, acute respiratory distress syndrome, and acute renal injury. Regarding essential medical techniques in the ICU, 98.2%, 86.5%, 71.2%, and 24.1% of surveyed hospitals have implemented invasive mechanical ventilation, continuous blood purification, bedside ultrasound, and extracorporeal membrane oxygenation, respectively.Conclusions::This survey indicates that, although ICUs in Chinese mainland have advanced significantly to some extent, there are still challenges to address, such as regional disparities and hospital grade differences.

Biomarkers have been identified to predict, diagnose and prognosticate acute kidney injury (AKI) but existing studies are heterogenous and contradictory. To compare diagnostic performance of AKI biomarkers, evaluate the quality of AKI biomarker studies and to develop standards for reporting studies of diagnostic test accuracy (DTA) of AKI biomarkers. A systematic literature review was conducted to identify studies focusing on the diagnostic performance of AKI biomarkers published before February 2025. Retrieved DTA studies were assessed for methodological quality and completeness using the QUADAS-2 and Standards for Reporting Diagnostic Accuracy (STARD) 2015 checklists. An international 17 member expert panel was convened to agree consensus standards for AKI biomarker studies (STARDaki) via a modified Delphi process. 122 DTA studies for AKI biomarkers were identified, but 15 were insufficiently reported. Of the remaining 107 studies, only 19 reported on diagnosis of AKI within 48 h of sampling. Of these studies, only 16 were considered high-quality based on the QUADAS-2 criteria. The compliance level with the STARD checklist was too low to permit meta-analysis. The expert panel agreed criteria for patient selection, reference standards, and reporting of test–retest reliability to supplement the STARD guidance for AKI biomarker studies. Most studies examining AKI biomarker performance fail to conform to the STARD standards for reporting, leading to poor diagnostic accuracy estimates and reduced clinical applicability and generalizability. An expert panel proposed STARDaki criteria to advance the development and clinical use of AKI biomarkers ( www.stardaki.icu ).

Sepsis frequently induces intestinal barrier injury, which exacerbates systemic inflammation, and contributes to high mortality. Group 3 innate lymphoid cells (ILC3s) are key regulators of mucosal immunity, yet their role in sepsis-associated intestinal injury remains incompletely understood. We found circulating ILCPs were reduced in patients with sepsis. In an LPS-induced murine sepsis model, colonic ILC3 numbers declined whereas the residual population showed increased frequencies of IL-22- and GM-CSF-producing cells. RORγt-deficient mice exhibited impaired induction of colonic IL-22 and GM-CSF, increased intestinal permeability, and aggravated histopathological injury. Adoptive transfer of purified wild-type ILC3s restored colonic IL-22 and GM-CSF levels and partially improved barrier integrity. Mechanistically, septic ILC3s showed hypoxia-associated mitochondrial impairment and accumulation of mitochondrial ROS. increased mtROS contributed to enhanced NF-κB p65 phosphorylation and selectively supported IL-22 and GM-CSF production. Recombinant IL-22 or GM-CSF ameliorated intestinal injury. However, ROS scavenging or NF-κB inhibition increased ILC3 apoptosis, indicating that ROS-NF-κB axis also supports residual ILC3 survival. Together, these findings identify a mitochondria-associated ROS-NF-κB program that sustains protective cytokine production and survival in residual intestinal ILC3s during sepsis, although it is insufficient to prevent ongoing ILC3 loss and intestinal injury.

Abstract Introduction Intra‐abdominal pressure (IAP) and gut microbiota have been associated with the prognosis of patients with sepsis receiving early enteral nutrition (EEN). In this study, we investigated this association and its prognostic value. Methods In this prospective observational study, we enrolled patients with sepsis receiving EEN. Firth's penalized logistic regression and restricted cubic spline (RCS) analyses were used to assess the association between IAP, Chao1 index, and prognosis. The gut microbiota composition and functional potential were analyzed using 16S ribosomal RNA gene sequencing and phylogenetic investigation of communities by reconstruction of unobserved states 2. Results Among the 52 patients, exploratory regression analyses showed that elevated IAP and a decreased Chao1 index were associated with a higher intensive care unit and 28‐d mortality, with no significant interaction ( p > 0.05). RCS analysis revealed an “L‐shaped” nonlinear relationship between the Chao1 index and mortality. RNA sequencing confirmed significant differences in the community structure between the high‐ and low‐IAP groups (analysis of similarity R = 0.197, p = 0.001; Adonis R 2 = 0.042, p = 0.005). Taxonomically, the low‐IAP group was significantly enriched with obligate anaerobic commensals (e.g., Blautia and Faecalibacterium), whereas the high‐IAP group was enriched with the absolute dominance of facultative pathogens, notably Enterococcus. Functional prediction showed significant upregulation of membrane transport and carbohydrate metabolism pathways in the high‐IAP group. Conclusion Elevated IAP and reduced microbiota diversity were associated with poor outcomes in patients with sepsis receiving EEN. A high‐IAP phenotype was also associated with significant taxonomic dysbiosis and predicted metabolic functional alterations.

[This corrects the article DOI: 10.1016/j.jointm.2025.05.002.].

Background:The CD4+T-cell count is a key indicator for evaluating immunosuppression. Infections significantly influence the survival and prognosis of critically ill patients. This study aims to systematically evaluate the association between reduced CD4+ T-cell counts and lung infections in immunosuppressed ICU patients, offering clinical evidence to guide the management of lung infections in this population. Methods:This retrospective, single-center study included 40 immunocompromised patients admitted to the ICU from January 1, 2021, to June 30, 2023. All participants underwent metagenomic next-generation sequencing. Patients with suspected lung infections based on their CD4+T-cell counts were divided into mild (350/µL<CD4+T-cell count<500/µL), moderate (200 /µL<CD4+T-cell count ≤ 350/µL), and severe (CD4+T-cell count ≤200/µL) groups. Microecological analysis was performed on each group. Intergroup comparisons were conducted for 28-day mortality, hospital length of stay, and ICU length of stay. Results:Amang these forty immunosuppressed patients, 8 were assigned to the mild group, 16 to the moderate group, and 16 to the severe group. Streptococcus pneumoniae was almost all distributed in moderate patients (75.0%), while severe patients had a higher proportion of fungi detected (25.7%). Respiratory microbiome analysis identified Acinetobacter baumannii, Human alphaherpesvirus 1, and Klebsiella pneumoniae as the most abundant species. Although no significant difference in the alpha diversity index was found among the groups, index values were lower in the severe group than in the moderate group. Beta diversity analysis showed that the microbial community structure did not significantly differ among the three groups. A total of 27 microbial markers were obtained, with multiple streptococcal species showing enrichment in moderate group and Candida tropicalis in severe group. By day 28, four patients (50.0%) in the mild group had died compared with six (37.5%) in the moderate group and nine (56.3%) in the severe group. There were no significant difference in the duration of ICU or hospital stays. Conclusions:This study on ICU-admitted immunocompromised patients identified the prevalent pathogens and microbiome features associated with pulmonary infections, as well as their relationship with CD4+T-cell depletion. These findings are valuable for optimizing clinical diagnosis and treatment strategies and may contribute to improving patient outcomes.

Background:Molecular point-of-care testing (mPOCT) offers rapid identification of respiratory pathogens, but its impact on antibiotic use and patient outcomes remains uncertain. We aimed to comprehensively evaluate the effects of mPOCT on antibiotic use and major clinical outcomes in patients presenting with acute respiratory tract infections (ARTIs). Methods:We searched MEDLINE, Embase, Web of Science, CENTRAL, CNKI, and Wanfang Data from inception to July 1, 2025, for randomised controlled trials (RCTs) evaluating mPOCT for patients presenting with ARTIs (PROSPERO CRD420251069333). The primary outcome was antibiotic use, assessed using pooled risk ratio (RR) with random-effects models. Risk of bias and certainty of evidence were assessed using the Risk Of Bias instrument for Use in SysTematic reviews-for Randomised Controlled Trials (ROBUST-RCT) and core Grading of Recommendations, Assessment, Development and Evaluation (GRADE), respectively. Findings:We included 25 RCTs involving 12,638 patients, of whom 61.0% were adults. Overall, mPOCT probably had little to no important effect on antibiotic use (RR 0.95, 95% CI 0.90-1.00; moderate certainty) or treatment duration (mean difference -0.44 days, 95% CI -0.98 to 0.09; moderate certainty). In adults, high-certainty evidence showed no effect on antibiotic use (RR 1.00, 95% CI 0.98-1.02), whereas in children, low-certainty evidence suggested a potential reduction (RR 0.79, 95% CI 0.65-0.97). Although mPOCT increased appropriate antibiotic prescribing (RR 2.07, 95% CI 1.55-2.77; moderate certainty), it did not affect 30-day mortality (RR 0.97, 95% CI 0.82-1.15; high certainty) and intensive care unit admission (RR 0.90, 95% CI 0.65-1.25; high certainty). Interpretation:Moderate to high certainty evidence suggests that mPOCT does not meaningfully reduce overall antibiotic use or improve patient outcomes, particularly in adults, despite enhancing prescribing appropriateness. Routine use of mPOCT for adults with ARTIs is therefore not supported. Funding:National Natural Science Foundation of China, the Postdoctoral Science Foundation, the Chongqing Municipality Joint Science and Health Major Medical Research Project, Outstanding Youth in Science and Technology, the Chongqing Youth Talent Fund, and the Research Foundation Flanders.

Ethnopharmacological relevance Yi-Shen-Hua-Shi granules (YSHSG) have been shown to improve kidney function in various renal disorders, which are characterized by the sudden decline and impairment of kidney function. Aim of the study : To investigate the precise mechanisms and targets of YSHSG in combating sepsis-induced AKI. Materials and methods Through network pharmacology, the active ingredients, main target proteins, and related signaling pathways of YSHSG in the treatment of sepsis-induced AKI were predicted. The AKI model was induced by sepsis using the cecal ligation and puncture (CLP) technique. Prior to the operation, YSHSG was administered intragastrically once daily for 1 week. Blood and kidney tissues were collected 48 h post-CLP to verify the network pharmacology analysis. Results The core target proteins of YSHSG in the treatment of sepsis-induced AKI include AKT1, JUN, IL6, PTGS2, NFKBIA, MAPK3, Caspase-3 and MMP9, which were further confirmed by molecular docking. Pathway analyses such as Gene Ontology (GO) and the Kyoto Encyclopedia of Genes and Genomes (KEGG) show that YSHSG plays a role in protecting the kidneys from sepsis-induced AKI through the PI3K/AKT, TNF, and IL17 signaling pathways. These findings were validated using qPCR and western blotting. In vivo experiments demonstrated that YSHSG inhibits the activation of TNF and IL17 signaling pathways while protecting against deactivation of the PI3K/AKT signaling pathway in sepsis-induced AKI. YSHSG also exhibits an effect on attenuating inflammation response and pyroptosis processes associated with the PI3K/AKT, TNF, and IL17 signaling pathways. Conclusion YSHSG mitigated sepsis-induced AKI by influencing the PI3K/AKT, TNF, and IL17 signaling pathways associated with inflammation and pyroptosis.

Septic shock, the most severe manifestation of sepsis, is characterized by profound circulatory failure and carries the highest mortality risk among sepsis-related conditions. Current therapeutic strategies remain primarily supportive, emphasizing empirical antimicrobial therapy and advanced organ system support. The immunomodulatory properties of corticosteroids in sepsis pathophysiology have been extensively investigated since the 1970s, though current guidelines recommend corticosteroid therapy for sepsis patients, albeit with a weak evidence base. In this review, we explore the molecular underpinnings of corticosteroid activity in septic shock and clinical evidence from randomized controlled trials, with a special emphasis on the stabilization of hemodynamics and the impact on mortality outcomes. Furthermore, we analyze recent advances in pharmacodynamic understanding that may inform more targeted corticosteroid administration in septic shock.

Critical care medicine is a clinical medical discipline that studies the pathogenesis, progression, diagnosis, and management of life-threatening diseases caused by various etiological factors. The Intensive Care Unit (ICU), as the core clinical setting of critical care medicine, is responsible for the full-cycle management of critically ill patients, covering a series of comprehensive measures from early warning to rehabilitation. In 2024, the National Health Commission and seven other ministries jointly issued the “Opinions on Strengthening the Capacity Building of Critical Care Medical Services”, promoting the discipline into a new stage of high‑quality development. Based on this, the Chinese Society of Critical Care Medicine (CSCCM) organized domestic experts to discuss and formulate the “Guidelines for the Construction and Management of Critical Care Medicine in China (2025 Edition).” The guidelines focus on core elements of discipline organization and development, covering nine areas: ICU ward construction, ICU admission criteria, staffing and technical requirements for professionals, equipment configuration, quality management, professional training and continuing education, scientific research, response to public health emergencies, and improved service models. The working group initially formed recommended entries through initiation, literature search and screening, and synthesis of medical evidence. The preliminary recommendations were then revised through expert panel reviews, remote and face-to-face meetings, revisions, and finally finalized by voting at the Standing Committee of CSCCM, resulting in the establishment of foundational and developmental discipline construction guidelines. The guidelines apply to ICUs in secondary and above healthcare institutions, providing a scientific framework for discipline planning, construction, and management to enhance the quality of critical care services.Practice guideline registration: Practice Guideline Registration for Transparency (PREPARE-2025CN972).

This document specifies the definitions, diagnostic criteria, and treatment requirements for sepsis. It aims to provide a standardized approach for the diagnosis and treatment of sepsis in medical institutions at all levels. The content is based on the latest research and clinical practices, with the goal of improving the management and outcomes of sepsis patients.