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To analyze the influence of diabetes mellitus on the clinical outcomes of moderately severe acute pancreatitis (MSAP) and severe acute pancreatitis (SAP). Methods: This retrospective study included patients diagnosed with MSAP and SAP at Shanxi Bethune Hospital from January 1, 2017, to December 31, 2021. Clinical data were collected, including patient demographics, 24-hour laboratory indicators, and inflammation indices. Propensity score matching (PSM) was used to compare outcomes before and after matching. Patients were randomized into training and validation sets (7:3) to develop and validate a clinical prediction model for infected pancreatic necrosis (IPN). Results: Among 421 patients, 79 had diabetes at admission. Before PSM, diabetic patients had higher incidences of peripancreatic fluid (71% vs 47%, p< 0.001) and IPN (48% vs 10%, p< 0.001), higher surgical intervention rates (24% vs 12%, p=0.008), and significant differences in abdominocentesis (22% vs 11%, p=0.014). After PSM, 174 patients were matched, and the diabetes group still showed higher incidences of peripancreatic fluid (69% vs 47%, p=0.008), IPN (48% vs 11%, p< 0.001), and surgical intervention rates (27% vs 13%, p=0.037). Diabetes, modified CT severity index (MCTSI), serum calcium, and HDL-c were identified as independent risk factors for IPN. The prediction model demonstrated good predictive value. Conclusion: In MSAP and SAP patients, diabetes mellitus can exert an influence on their clinical outcome and is an independent risk factor for IPN. The alignment diagram and web calculator constructed on the basis of diabetes mellitus, modified CT severity index (MCTSI), serum calcium and high-density lipoprotein cholesterol (HDL-c) have good predictive value and clinical guidance for the occurrence of IPN in MSAP and SAP. [ABSTRACT FROM AUTHOR]

Purpose: Acute pancreatitis is a common gastrointestinal emergency. Approximately 20% of patients with acute pancreatitis develop organ failure, which is significantly associated with adverse outcomes. This study aimed to establish an early prediction model for persistent organ failure in acute pancreatitis patients using 24-hour admission indicators. Patients and Methods: Clinical data and 24-h laboratory indicators of patients diagnosed with acute pancreatitis from January 1, 2017 to January 1, 2022 in Shanxi Bethune Hospital were collected. Patients from 2017 to 2021 were used as the training cohort to establish the prediction model, and patients from 2021 to 2022 were used as the validation cohort. Univariate logistic regression and LASSO regression were used to establish prediction models. The performance of the model was evaluated using area under the curve (AUC), calibration curves, and decision curve analysis (DCA), and subsequently validated in the validation group. Results: A total of 1166 patients with acute pancreatitis were included, a total of 145 patients suffered from persistent organ failure from 2017 to 2021. Data were initially selected for 100 variables, and after inclusion and exclusion, 46 variables were used for further analysis. Two prediction models were established and nomogram was drawn respectively. After comparison, the prediction values of the two models were similar (The univariate model AUC was 0.867, 95% CI (0.834– 0.9). The LASSO model AUC was 0.864, 95% CI (0.828– 0.895)), and the model established by LASSO regression was more parsimonious. A web calculator was developed using the model established by LASSO. Conclusion: Predictive model including 6 risk indicators can be used to predict the risk of persistent organ failure in patients with acute pancreatitis. [ABSTRACT FROM AUTHOR]

Background: Although observational studies have shown that physical activity is a protective factor for acute pancreatitis, the causal associations between PA/ sedentary behavior and acute pancreatitis (AP) and chronic pancreatitis (CP) remain unclear. Methods: We used Mendelian randomization as a strategy to assess the causalities between exposures and outcomes by simulating randomized experiments with genetic variation. The collected genetic variants data of physical activity were from UK Biobank, the data on sedentary behavior were also from UK Biobank, and both of them could be found in the GWAS catalog, and the data on AP and CP were from FinnGen. There were three physical activity related activity patterns (moderate to vigorous physical activity [MVPA], accelerometer-based physical activity with average acceleration, [AccAve] and accelerometer-based physical activity with accelerations >425 milli-gravities, [Acc425]) and three sedentary behavior-related lifestyle patterns (Leisure screen time [LST], Sedentary commuting, Sedentary behavior at work). We used inverse variance weighted (IVW), weighted median and MR-Egger for the analysis of Mendelian randomization, followed by sensitivity tests with the Cochran Q test, MR-Egger intercepts analysis and MR-PRESSO. Results: A causal relationship was found between LST and acute pancreatitis based on IVW analysis (odds ratios [OR] = 1.38, corresponding 95% confidence intervals [CI] = 1.16–1.64, p = 0.0002) and there were no causal relationships between physical activity/sedentary behavior and chronic pancreatitis. Sensitivity analysis showed no pleiotropy and heterogeneity of the results. Conclusions: Results show that reducing LST contributes to the prevention of acute pancreatitis, thereby reducing the health burden associated with it. [ABSTRACT FROM AUTHOR]

UXT is widely expressed in human and mouse tissues and aberrantly expressed in various tumor tissues. UXT may play a pro-cancer or tumor suppressor role in different tumor types and microenvironments with different mechanisms of action. Studies have shown that UXT can interact with related receptors to exert its functions and affect tumor proliferation and metastasis, leading to a poor prognosis when the biological functions of these tumors are changed. Interestingly, the signaling pathways and mechanism-related molecules that interact with UXT are closely related to the occurrence of hepatocellular carcinoma (HCC) during disease progression. This article reviews the research progress of UXT and prospects for its application in HCC, with the aim of providing possible scientific suggestions for the basic research, diagnosis and treatment of HCC. [ABSTRACT FROM AUTHOR]

Background: Pancreatic cancer is a common malignant tumor. Multiple studies have shown that procollagen lysyl-hydroxylase (PLOD) family genes were closely related to tumor progression and metastasis in a variety of human cancers. This study aimed to explore the prognosis and biological role of PLOD family genes in pancreatic adenocarcinoma (PAAD). Methods: GEPIA, GEO, HPA, CCLE, Kaplan–Meier plotter, cBioPortal, LinkedOmics, DAVID6.8, STRING, and TIMER were employed to determine the prognostic values and biological function of PLOD family members in PAAD. Results: The mRNA and protein expression patterns of PLOD family members were noticeably up-regulated in PAAD compared with normal tissues. PLOD family gene expression was also up-regulated in pancreatic cancer cell lines. PLOD1 was correlated with histological and pathological grades of pancreatic cancer. PLOD2 was related to histological grade. The high expression of PLOD1-2 was correlated with the poor overall survival rate and relapse-free survival rate in patients with PAAD. Additionally, PLODs showed high sensitivity and specificity in distinguishing pancreatic cancer from normal tissues. Through the functional enrichment analysis of PLOD-related genes in PAAD, we found that PLODs were enriched in collagen fiber tissue structure, lysine degradation, and collagen biosynthesis. Pathway analysis confirmed that PLODs regulated the proliferation, migration, and metastasis of pancreatic cancer through the RalGEF-Ral signaling pathway. Furthermore, the level of expression of PLOD1-2 was positively correlated with the activity of tumor-infiltrating immune cells, including CD8+T cells, neutrophils, macrophages, and dendritic cells. The level of expression of PLOD3 was inversely correlated with the level of infiltration of CD8+T cells. PLOD1 and PLOD2 were highly expressed in pancreatic cancer tissues with TP53 and KRAS mutations, respectively. However, the level of expression of PLOD3 in SMAD4 wild-type pancreatic cancer was increased. Conclusion: The findings showed that individual PLOD genes or PLOD family genes could be potential prognostic biomarkers for PAAD. [ABSTRACT FROM AUTHOR]

Prefoldin complex subunits (PFDNs) and prefoldin-like complex subunits (PFDLNs) collaborate in protein folding, modulate endoplasmic reticulum stress. The association between PFDN/PFDLN and the immune microenvironment of HCC remains unclear. We investigated the biological significance of PFDNs and PFDLNs in HCC using bioinformatics. The relationship between PFDNs/PFDLNs and HCC was analysed using TCGA, and Human Protein Atlas. The protein–protein interaction (PPI) network was performed through String and Cytoscape. In addition, mutations in PFDNs and PFDLNs were analysed using cBioPortal. Clinical correlation analysis, survival analysis was conducted by using UALCAN and Kaplan–Meier analysis. The protein-protein interaction (PPI) network was performed through String and Cytoscape. The GO and KEGG enrichment analyses were also carried out. CCK-8 and Flow cytometry analysis were used to detect the proliferation and apoptosis of PFDN1 and UXT knockdown HCC cells. Immune infiltrates analyses was were conducted using the TIMER and TISIDB to determine whether PFDNs/PFDLNs are predictive biomarkers of immune cell infiltration. We observed that PFDNs and PFDLNs were significantly overexpressed in HCC tissues compared to normal liver tissues. This abnormal expression was associated with worse clinicopathological features and negatively affected patient survival. PFDNs and PFDLNs have varying degrees of mutations in HCC, which may be related to their abnormal expression. In addition, up-regulated PFDN1 and UXT were found to promote HCC proliferation and inhibit apoptosis in vitro. Finally, the expression of certain PFDNs and PFDLNs in the tumour microenvironment was positively correlated with the level of tumour-infiltrating immune cells and significantly enhanced the infiltration of immune cells in the microenvironment. PFDNs and PFDLNs are valuable predictive biomarkers for immune infiltration in HCC and may assist in tumour immunotherapy research and prognosis prediction in the future. [ABSTRACT FROM AUTHOR]

The ubiquitous expressed transcript (UXT) , a member of the prefoldin-like protein family, modulates regulated cell death (RCD) such as apoptosis and autophagy-mediated cell death through nuclear factor-κB (NF-κB), tumor necrosis factor-α (TNF-α), P53, P62, and methylation, and is involved in the regulation of cell metabolism, thereby affecting tumor progression. UXT also maintains immune homeostasis and reduces proteotoxicity in neuro-degenerative diseases through selective autophagy and molecular chaperones. Herein, we review and further elucidate the mechanisms by which UXT affects the regulation of cell death, maintenance of immune homeostasis, and neurodegenerative diseases and discuss the possible UXT involvement in the regulation of ferroptosis and immunogenic cell death, and targeting it to improve cancer treatment outcomes by regulating cell death and immune surveillance., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Han, Mo, Wang, Xu, Fu and Tian.)