Acute respiratory distress syndrome (ARDS) is a clinical syndrome of acute hypoxic respiratory failure caused by diffuse lung inflammation and edema. ARDS can be precipitated by intrapulmonary factors or extrapulmonary factors, which can lead to severe hypoxemia. Patients suffering from ARDS have high mortality rates, including a 28‐day mortality rate of 34.8% and an overall in‐hospital mortality rate of 40.0%. The pathophysiology of ARDS is complex and involves the activation and dysregulation of multiple overlapping and interacting pathways of systemic inflammation and coagulation, including the respiratory system, circulatory system, and immune system. In general, the treatment of inflammatory injuries is a coordinated process that involves the downregulation of proinflammatory pathways and the upregulation of anti‐inflammatory pathways. Given the complexity of the underlying disease, treatment needs to be tailored to the problem. Hence, we discuss the pathogenesis and treatment methods of affected organs, including 2019 coronavirus disease (COVID‐19)‐related pneumonia, drowning, trauma, blood transfusion, severe acute pancreatitis, and sepsis. This review is intended to provide a new perspective concerning ARDS and offer novel insight into future therapeutic interventions.

Background/Objectives: Abnormal bile acid (BA) pool may play an important role in inducing liver damage in sepsis. Farnesoid X receptor (FXR) is a main negative feedback regulator of BA metabolism. This study aims to explore the protective effect and mechanism of the FXR agonist obeticholic acid (OCA) on liver dysfunction when sepsis occurs. Methods: A rat model of sepsis was induced by cecal ligation and puncture (CLP) for 24 h. Systematic inflammation, tissue injury, hepatic FXR, and BA transporter expression were investigated in the CLP rats and sham-operated control rats with and without OCA pre-treatment (10 mg/kg, gavage) at 2 h before operation. Liquid chromatography–tandem mass spectrometry (LC-MS/MS) assay was performed to access BA composition in the rats’ serum and livers. The injury and inflammatory effects of the elevated unconjugated BAs found in the CLP rats was further verified in a hepatic cell line BRL-3A in vitro. Results: Hepatic FXR was repressed in CLP rats, whereas OCA upregulated liver FXR and hepatic BA transporter expression, reduced total serum BA concentration, ameliorated the elevation of serum levels of IL-1β and IL-6, and improved liver and ileal tissue injuries. OCA administration reduced the elevated unconjugated BAs in both serum and liver, and effectively inhibited increases in cholic acid (CA), deoxycholic acid (DCA), and 7-ketoDCA concentrations in CLP rat livers. These BA fractions promoted the release of aspartate aminotransferase (AST) from BRL-3A cells and increased IL-6, CXCL2, and monocyte chemoattractant protein-1 (MCP-1) expression in the cells, along with enhanced transcription factor nuclear factor-κB activation. Conclusions: Liver inflammation and dysfunction during sepsis is attributable to significant changes in bile acid composition in the blood and liver. FXR activation reduces systemic inflammation and liver dysfunction by regulating bile acid homeostasis, especially inflammatory unconjugated bile acid components.

Over the years, pancreatic cancer has experienced a global surge in incidence and mortality rates, largely attributed to the influence of obesity and diabetes mellitus on disease initiation and progression. In this study, we investigated the pathogenesis of pancreatic cancer in mice subjected to a high‐fat diet (HFD) and observed an increase in citric acid expenditure. Notably, citrate treatment demonstrates significant efficacy in promoting tumor cell apoptosis, suppressing cell proliferation, and inhibiting tumor growth in vivo. Our investigations revealed that citrate achieved these effects by releasing secreted protein acidic and rich in cysteine (SPARC) proteins, repolarizing M2 macrophages into M1 macrophages, and facilitating tumor cell apoptosis. Overall, our research highlights the critical role of citric acid as a pivotal metabolite in the intricate relationship between obesity and pancreatic cancer. Furthermore, we uncovered the significant metabolic and immune checkpoint function of SPARC in pancreatic cancer, suggesting its potential as both a biomarker and therapeutic target in treating this patient population.

Background: Acute pancreatitis (AP) is a clinically common acute abdominal disease, whose pathogenesis remains unclear. The severe patients usually have multiple complications and lack specific drugs, leading to a high mortality and poor outcome. Acinar cells are recognized as the initial site of AP. However, there are no precise single-cell transcriptomic profiles to decipher the landscape of acinar cells during AP, which are the missing pieces of jigsaw we aimed to complete in this study. Methods: A single-cell sequencing dataset was used to identify the cell types in pancreas of AP mice and to depict the transcriptomic maps in acinar cells. The pathways’ activities were evaluated by gene sets enrichment analysis (GSEA) and single-cell gene sets variation analysis (GSVA). Pseudotime analysis was performed to describe the development trajectories of acinar cells. We also constructed the protein–protein interaction (PPI) network and identified the hub genes. Another independent single-cell sequencing dataset of pancreas samples from AP mice and a bulk RNA sequencing dataset of peripheral blood samples from AP patients were also analyzed. Results: In this study, we identified genetic markers of each cell type in the pancreas of AP mice based on single-cell sequencing datasets and analyzed the transcription changes in acinar cells. We found that acinar cells featured acinar-ductal metaplasia (ADM), as well as increased endocytosis and vesicle transport activity during AP. Notably, the endoplasmic reticulum stress (ERS) and ER-associated degradation (ERAD) pathways activated by accumulation of unfolded/misfolded proteins in acinar cells could be pivotal for the development of AP. Conclusion: We deciphered the distinct roadmap of acinar cells in the early stage of AP at single-cell level. ERS and ERAD pathways are crucially important for acinar homeostasis and the pathogenesis of AP.

Infectious complications (ICs) in acute pancreatitis (AP) are primarily driven by intestinal bacterial translocation, significantly increasing mortality and hospital stays. Despite this, the role of the gut microenvironment, particularly its metabolic aspects, in AP remains poorly understood. In this study, we investigated a cohort of patients with AP, and conducted supplemental murine studies, to explore the relationship between the gut metabolome and the development of ICs. Metabolomic analysis revealed that disruptions in gut tryptophan metabolism — especially reductions in serotonin and indole pathways — are key features associated with IC occurrence. Additionally, elevated plasma levels of tryptophan metabolites within the kynurenine pathway were identified as valuable predictive biomarkers for ICs. Mechanistic studies in murine models demonstrated that an impaired intestinal Th17 response, modulated by these tryptophan metabolites, plays a critical role in IC development. Serotonin supplementation enhanced Th17 responses, reducing IC incidence, while administration of kynurenic acid, a kynurenine metabolite, exacerbated pancreatic infections, potentially through immunosuppressive effects. These findings highlight the pivotal role of tryptophan metabolites in AP pathogenesis, emphasizing their potential as both predictive markers and therapeutic targets in IC management.

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.