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Overt hepatic encephalopathy (OHE), a serious complication of liver cirrhosis, is associated with alterations in lipid and lipoprotein metabolism. We evaluated the correlation between high-density lipoprotein cholesterol (HDL-C) levels and transplant-free (TF) mortality in patients with OHE. Patients with OHE admitted to Beijing Ditan Hospital between January 2010 and August 2016 (n = 821) and between September 2016 and December 2020 (n = 480) were included in the training and validation sets, respectively. Independent predictors were explored by a multivariate Cox regression analysis, and the area under the receiver operating characteristic curve (AUC) was used to assess the prognostic value of these factors. The prognostic value of HDL-C was good (AUC at 1 year: 0.745) and was equivalent to that of the Model for End-Stage Liver Disease (MELD) score (AUC at 1 year: 0.788). The optimal threshold values for HDL-C and MELD were 0.5 mmol/L and 17, respectively. The 1-year TF mortality rates in the low-risk (HDL-C ≥ 0.5 mmol/L and MELD < 17) and high-risk (HDL-C < 0.5 mmol/L and MELD ≥ 17) groups were 7.5% and 51.5% in the training set and 10.1% and 48.2% in the validation set, respectively. HDL-C level < 0.5 mmol/L and MELD score > 17 can facilitate the identification of high-risk patients and provide a basis for timely treatment. [ABSTRACT FROM AUTHOR]

Enteral nutrition (EN) represents a fundamental and efficacious therapeutic approach in acute pancreatitis (AP). Our objective is to investigate the modulation of gut microbiota through enteral nutrition. This prospective observational study enrolled 35 AP patients and implemented timely enteral nutrition intervention. Inflammatory markers, including C-reactive protein (CRP), were assessed before and after EN, while the dynamic alterations in gut microbiota were analyzed using 16S rDNA sequencing technology. Following EN, CRP significantly decreased, effectively mitigating the inflammatory response. Due to inter-individual variations in post-enteral nutrition inflammatory status, patients were further stratified into H group (CRP≥50 mg/L) and L group (CRP<50 mg/L) for subsequent analysis. Comparative evaluation of clinical characteristics between the two groups revealed that the H group exhibited a significantly higher risk of adverse prognosis including respiratory dysfunction and infectious complications. Dynamic monitoring of gut microbiota demonstrated a substantial increase in microbial diversity after EN accompanied by a decrease in opportunistic pathogens such as Enterococcus , Escherella-Shigella , and Klebsiella , along with an augmentation of beneficial bacteria including Bacteroides and Fusobacterium. The composition of gut microbiota varied according to the levels of inflammation among AP patients: Shigella predominated within Group H, while Actinomyces and Enterococcus constituted the dominant bacterial population within Group L. Furthermore, Spearman correlation analysis revealed significant associations between specific microbial communities within the gut and inflammatory markers such as neutrophil to albumin ratio (NAR) and lymphocyte to C-reactive protein ratio (LCR). EN can modify gut microbiota and alleviate inflammation, thereby affecting the severity and prognosis of AP patients. [Display omitted] • Enteral nutrition provides essential nutrients and energy to gut microbiome. • Enteral nutrition enhances the intestinal microecology and alleviates inflammation. • Dynamic alterations in the composition of gut microbiota during acute pancreatitis. • A significant correlation exists between gut microbiota and inflammation. [ABSTRACT FROM AUTHOR]

PLAU is known as a selected serine protease converting plasminogen to plasmin. The role of PLAU in the development of pan-cancer, especially bladder urothelial carcinoma (BLCA) remains unclear. A variety of online tools and cancer databases, including TCGA, GETx, HPA database, GSCALite, UALCAN, ESTIMATE, CIBERSORT, ssGSEA algorithms and SangerBox website, were applied to investigate the associations between PLAU expression and prognosis, genetic alterations, pathway activation, and tumor immunity in pan-cancer. Through cBioPortal and STITCH platforms, the oncogenic role of PLAU and related targeting medicines in BLCA were also explored. We verified the expression of PLAU in pan-cancer cells and its function in bladder cancer cell lines using wet-lab experiments. PLAU expression levels were significantly higher in most cancer tissues. PLAU had a certain accuracy in the diagnosis of various types of cancers (90 % AUC > 0.700). In BLCA, PLAU has abundant methylated sites and showed statistical differences in clinical features. PLAU was involved in tumor immune infiltration, and especially positively correlated with neutrophil infiltration. High-expressed PLAU indicated poorer prognosis in the BLCA patients receiving Atezolizumab. A high mRNA and protein expression levels of PLAU were observed in pan-cancer cell lines, especially BLCA cells. Knockdown of PLAU inhibited the invasive, proliferative, and aggressive phenotypes of bladder cancer cells. Immunohistochemical staining validated PLAU's higher expression in BLCA tissues than in adjacent non-cancerous tissues. And overexpression of PLAU was associated with more advanced TNM stage, and high infiltrating depth. Our study revealed that PLAU can serve as a potential therapeutic target and prognostic marker for various malignancies, especially BLCA. • Integrated analyses on multi-omics characteristics of PLAU on tumor microenvironment, immunotherapy, and prognosis. • A high expression level of Plasminogen Activator was related to a short Overall Survival in most cancer types. • PLAU expression is positively correlated with neutrophils infiltration in cancers. • High-expressed PLAU indicated poorer prognosis in the bladder cancer patients receiving Atezolizumab. [ABSTRACT FROM AUTHOR]

TP53INP2 (tumor protein p53-inducible nuclear protein 2), known as an autophagy protein, is essential for regulating transcription and starvation-induced autophagy, which plays a crucial role in the oncogenesis and progression of various cancers. The present study aims to investigate the expression pattern, function and prognostic value of TP53INP2 in colorectal cancer (CRC). Here, we report that low expression of TP53INP2 correlates with poor survival in CRC patients. TP53INP2 was significantly downregulated in CRC tissues compared with adjacent tissues. As the malignancy of CRC progresses, the expression level of TP53INP2 gradually decreased. Knockdown of TP53INP2 promoted CRC cell proliferation and tumor growth in mice. Mechanistically, TP53INP2 deficiency decreased phosphorylation of β-catenin on S33, S37, and T41, resulting in increased accumulation of β-catenin and enhanced nuclear translocation and transcriptional activity. Moreover, we further demonstrated that TP53INP2 sequestered TIM50, thereby inhibiting its activation of β-catenin. Taken together, our findings indicate that the downregulation of TP53INP2 promotes CRC progression by activating β-catenin and suggest that TP53INP2 may be a candidate therapeutic target for CRC. • Low TP53INP2 expression is associated with poor prognosis in colorectal cancer. • Loss of TP53INP2 function decreases phospho-S33/S37/T41 β-catenin, leading to CRC proliferation and tumor progression. • TP53INP2 sequesters TIM50 to inhibit its activation of β-catenin. • TP53INP2 could be used as a marker for diagnosis and treatment of highly malignant colorectal cancer. [ABSTRACT FROM AUTHOR]

• We developed a prognostic nomogram for 30-day mortality in patients with OHE. • MELD and NLR provided risk stratification for patient outcomes. • Patients with MELD ≥ 23 and NLR ≥ 4 have a high mortality rate. Overt hepatic encephalopathy (OHE) is a serious complication of liver disease. We aimed to develop a dynamic nomogram for estimating the probability of 30-day transplant-free mortality in patients with OHE and hepatitis B-related cirrhosis (HBC). We identified 402 patients with OHE and HBC at the Beijing Ditan Hospital between January 2011 and July 2016. Independent risk factors were determined using multivariate Cox proportional hazards regression analysis. A dynamic nomogram was established to predict the probability of 30-day transplant-free mortality. The discrimination and clinical usefulness of the nomogram were estimated using the area under the receiver operating characteristic (AUC) and calibration curves, and decision curve analysis. A prospective cohort of 208 patients was enrolled for validation. The model for end-stage liver disease (MELD) score and neutrophil-to-lymphocyte ratio (NLR) were independently associated with the 30-day transplant-free mortality. The AUC values of the nomogram were 0.881 and 0.879 in the derivation and validation cohorts, respectively, and the discrimination ability was superior to that of the established models. The calibration plot fitted the predicted survival and observed probabilities well. The incidence of mortality was 2.0% (3/151) in patients with MELD scores < 23 and NLR < 4, and 55.4% (41/92) in those with MELD scores ≥ 23 and NLR ≥ 4. The dynamic nomogram can predict the risk of 30-day transplant-free mortality in patients with OHE and HBC. Patients with MELD scores ≥ 23 and NLR ≥ 4 have a high mortality rate and should be admitted to intensive care. [ABSTRACT FROM AUTHOR]

CRKL (CRK Like Proto-Oncogene) belongs to the Crk family and is a 39-kDa adapter protein that encodes SH2 and SH3 (src homologs) domains. To identify its oncogenic role in malignant melanoma, we investigated the association between CRKL and mutation, prognosis, tumor mutation burden, immune cell infiltration of melanoma, and explored the associations between CRKL and immunotherapy response. Our results showed that abnormal CRKL expression is associated with poor prognosis in melanoma and is significantly correlated with immune-activated pathways and processes, immune cell infiltrations, and expression of immunoregulators. Importantly, we found that CRKL expression is a predictive biomarker for anti-PD1 therapy response in melanoma patients. Furthermore, inhibiting CRKL expression in melanoma cell lines suppressed their proliferation and metastasis, as well as activated the pyroptosis-related pathway. Our study provides potential mechanisms of melanoma pathogenesis, which may suggest new avenues for targeted therapy in this disease. • This study comprehensively analyzed the role of CRKL in malignant melanoma, including its relationship with prognosis, epigenetic modifications, cancer stemness, immune regulation, and inflammatory pathways. • In addition to inhibiting proliferation and metastasis, our findings reveal a close association between CRKL and the NLRP3-GSDMD-caspase-1 dependent pyroptosis pathway. • CRKL expression accurately predicts the immune response of melanoma, and patients with low expression levels exhibit greater responsiveness to anti-PD1 therapy. [ABSTRACT FROM AUTHOR]