Background and Aims: Ambiguous understanding of tumors and the tumor microenvironments (TMEs) hinders accurate diagnosis and available treatment for multifocal hepatocellular carcinoma (HCC) covering intrahepatic metastasis (IM) and multicentric occurrence (MO). Here, we characterized the diverse TMEs of IM and MO identified by whole-exome sequencing (WES) at single-cell resolution. Approach and Results: We performed parallel WES and single-cell RNA sequencing (scRNA-seq) on twenty-three samples from seven patients to profile their TMEs when major results were validated by immunohistochemistry in the additional cohort. Integrative analysis of WES and scRNA-seq found that malignant cells in IM showed higher intra-tumor heterogeneity, stemness and more activated metabolism than those in MO. Tumors from IM shared similar TMEs while distinct TMEs were noticed in those from MO. Furthermore, CD20+ B cells, plasma cells and conventional type II dendritic cells (cDC2s) were decreased in IM relative to MO while T cells in IM exhibited a more terminally exhausted capacity with a higher proportion of proliferative/exhausted T cells than that in MO. Both CD20 and CD1C correlated with better prognosis in multifocal HCC. Additionally, MMP9+ tumor-associated macrophages were enriched across IM and MO which formed cellular niches with regulatory T cells (Tregs) and proliferative/exhausted T cells. Conclusions: Our findings deeply decipher the heterogeneous TMEs between IM and MO, which provide a comprehensive landscape of multifocal HCC. Export

Objective: To analyze clinical utility of pancreatitis activity scoring system (PASS) in prediction of persistent organ failure, poor prognosis, and in-hospital mortality in patients with moderately severe acute pancreatitis (MSAP) or severe acute pancreatitis (SAP) admitted to the intensive care unit (ICU).Methods: The study included a total of 140 patients with MSAP and SAP admitted to the ICU of Shandong Provincial Hospital from 2015 to 2021. The general information, biochemical indexes and PASS scores of patients at ICU admission time were collected. Independent risk factors of persistent organ failure, poor prognosis and in-hospital mortality were analyzed by binary logistic regression. Through receiver operating characteristic curve (ROC), the predictive ability of lactic acid, procalcitonin, urea nitrogen, PASS, and PASS in combination with urea nitrogen for the three outcomes was compared. The best cut-off value was determined.Results: Binary logistic regression showed that PASS might be an independent risk factor for patients with persistent organ failure (odds ratio [OR]: 1.027, 95% confidence interval [CI]: 1.014–1.039), poor prognosis (OR: 1.008, 95% CI: 1.001–1.014), and in-hospital mortality (OR: 1.009, 95% CI: 1.000–1.019). PASS also had a good predictive ability for persistent organ failure (area under the curve (AUC) = 0.839, 95% CI: 0.769–0.910) and in-hospital mortality (AUC = 0.780, 95% CI: 0.669–0.891), which was significantly superior to lactic acid, procalcitonin, urea nitrogen and Ranson score. PASS (AUC = 0.756, 95% CI: 0.675–0.837) was second only to urea nitrogen (AUC = 0.768, 95% CI: 0.686–0.850) in the prediction of poor prognosis. Furthermore, the predictive power of urea nitrogen in combination with PASS was better than that of each factor for persistent organ failure (AUC = 0.849, 95% CI: 0.779–0.920), poor prognosis (AUC = 0.801, 95% CI: 0.726–0.876), and in-hospital mortality (AUC = 0.796, 95% CI: 0.697–0.894).Conclusion: PASS was closely correlated with the prognosis of patients with MSAP and SAP. This scoring system may be used as a common clinical index to measure the activity of acute pancreatitis and evaluate disease prognosis.