The integration of single-cell and bulk RNA-seq atlas reveals ERS-mediated acinar cell damage in acute pancreatitis.

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.

Pretreatment biomarkers as prognostic predictors of survival in patients with Pancreatic Cancer treated with Gemcitabine-based Therapy and 5-Fluorouracil: Neutrophil-to-lymphocyte ratio vs Platelet-to-lymphocyte ratio.

Although elevated neutrophil-to-lymphocyte ratio (NLR) and platelet-to-lymphocyte ratio (PLR) have been reported to be inverse prognostic predictors of survival in patients with pancreatic cancer (PC), the comparison of their prognostic roles in patients with PC undergoing gemcitabine-based chemotherapy and 5-fluorouracil (5-FU) remains unclear. This study was designed and performed to determine the predictive roles of NLR and PLR in patients diagnosed with PC who underwent one of these two regimens. We retrospectively enrolled 95 patients diagnosed with PC undergoing supportive care, gemcitabine-based chemotherapy or 5-FU therapy from January 2015 to October 2018. Univariate and multivariate Cox regression analyses were done to identify clinicopathological predictors of time to treatment failure (TTF) and overall survival (OS), including pretreatment NLR and PLR. The statistical data showed that pretreatment NLR was significantly associated with metastasis. Among all analyzed variables, pretreatment NLR was an independent prognostic predictor of both TTF and OS of patients with PC, with NLR>4.0 predicting worse survival. PLR, however, didn't independently predict TTF or OS. There were no significant difference in the OS of patients undergoing gemcitabine-based regimens and 5-FU regimens when divided into two subgroups: NLR ≤4.0 and >4.0. In conclusion, pretreatment NLR is a promising independent outcome predictor for patients with PC, while NLR might not be a suitable factor in the selection of regimens for patients with PC.

A lung cancer patient with deep vein thrombosis:a case report and literature review.

BACKGROUND: Venous thromboembolism (VTE) is a common problem in cancer patients and the incidence is increasing, especially for patients with lung cancer. Common features of these patients, like advanced stage, male gender, old age and chemotherapy, are risk factors of VTE. Here we reported a case in which the patient with lung cancer developed deep vein thrombosis (DVT) when receiving chemotherapy. CASE PRESENTATION: A 53-year-old male who was diagnosed with lung cancer with multiple metastasis developed severe DVT during chemotherapy. Despite the use of aspirin, warfarin and low molecular weight heparin (LMWH) for anticoagulant and thrombolytic therapy, the condition was still deteriorating, resulting in amputation finally. CONCLUSIONS: It's rare that the conditions of cancer patients who develop venous thromboembolism (VTE) keep deteriorating despite the administration of aspirin, warfarin and low weight molecular heparin. Both early diagnosis and prophylactic use of anticoagulants are suggested for cancer patients to improve the prognosis.