Develop a Novel Nomogram to Predict Respiratory Failure in Acute Pancreatitis at Early Stage.

BACKGROUND: Respiratory failure is a common complication in patients suffering from moderately severe or severe acute pancreatitis (AP). The aim of this study was to develop a novel nomogram to predict respiratory failure in AP early. METHODS: Patients, who were hospitalized within 72 hours of AP onset from January 1, 2018, to April 31, 2021 were enrolled in the study. The patients were divided into two groups including respiratory failure group and no respiratory failure group. The demographic characteristics and laboratory parameters were compared between the two groups. A nomogram was established with stepwise logistic regression and "rms" packages of R software. RESULTS: A total of 190 patients were finally included. White blood count, hemoglobin, sodium and calcium were significantly different between the two groups (all p < 0.05). White blood count (odds ratio [OR] = 1.28, 95% confidence interval [CI]: 1.14 - 1.47, p < 0.001), lymphocyte count (OR = 2.92, 95% CI: 1.16 - 7.70, p = 0.023), albumin (OR = 1.15, 95% CI: 1.01 - 1.33, p = 0.045) and calcium (OR = 0.00, 95% CI: 0.00 - 0.01, p < 0.001) were independent risk factors for respiratory failure in AP patients. After stepwise logistic regression was applied, white blood count, albumin, and calcium were used for the construction of the nomogram. The area under the curve (AUC) of the nomogram for respiratory failure was 0.832, which was higher than the BISAP score, and the nomogram possessed high concordance as calibration curves showed. CONCLUSIONS: The nomogram could predict respiratory failure in AP at an early stage with high accuracy.

The relationships between emerging adults self-efficacy and motivation levels and physical activity: a cross-sectional study based on the self-determination theory.

Objectives: The study aims to examine the associations between exercise self-efficacy, motivation, physical activity, and body composition among emerging adults. Design: Cross-sectional. Methods: A convenience sample of 147 emerging adults participated in the Releasing Weight (RELEW) project. The InBody720 analyzer was used to measure body composition, and the International Physical Activity Questionnaire-Short, the Shortened Physical Activity Self-Efficacy Scale, and the Treatment Self-Regulation Questionnaire were used to measure self-reported physical activity, self-efficacy, and motivation. Structural Equation Modeling was used to exam the complex relationships among multiple variables. in this study. The Partial least squares structural equation modeling analysis with bootstrapping in Smart PLS 3 was employed to explore the path coefficients and t-values for the relationships that were thought to exist. Significance was determined using a threshold of p < 0.05. Results: The mean age of 147 participants was 18.5 ± 1.87, of whom 51.7% were female, recruited for this study. Exercise self-efficacy has a significant positive correlation with exercise motivation (r = 0.220, p = 0.008) and physical activity (r = 0.279, p < 0.001). Exercise motivation does not demonstrate significant associations with physical activity (r = 0.094, p = 0.298). Utilizing SEM, the model explained 9.2% of exercise self-efficacy, 11.8% of physical activity, and 68.3% of body composition variance. Mediation analysis revealed that exercise self-efficacy partially mediated the relationship between exercise motivation and physical activity (ß = 0.106, t = 2.538, p < 0.05), and physical activity partially mediated the relationship between exercise self-efficacy and body composition (ß = -0.296, t = 4.280, p < 0.001). Conclusion: This study sheds light on the complex relationships among motivation, self-efficacy, physical activity and body composition during emerging adulthood. Our results highlight the mediating role of self-efficacy and its impact on physical activity behaviors, offering valuable insights for targeted interventions and policy development to improve health outcomes in this demographic.

SPHK1 potentiates colorectal cancer progression and metastasis via regulating autophagy mediated by TRAF6-induced ULK1 ubiquitination.

A sphingolipid metabolite regulator, sphingosine kinase 1 (SPHK1), plays a critical role in the development of colorectal cancer (CRC). Studies have demonstrated that invasion and metastasis of CRC are promoted by SPHK1-driven autophagy. However, the exact mechanism of SPHK1 drives autophagy to promote tumor progression remains unclear. Here, immunohistochemical detection showed the expression of SPHK1 and tumor necrosis factor receptor-associated factor-6 (TRAF6) in human CRC tissues was stronger than in adjacent normal tissues, they were both associated with distance metastasis. It was discovered that knockdown of SPHK1 reduced the expression of TRAF6, inhibited autophagy, and inhibited the growth and metastasis of CRC cells in vitro. Moreover, the effects of SPHK1-downregulating were reversed by overexpression of TRAF6 in CRC cells transfected by double-gene. Overexpression of SPHK1 and TRAF6 promoted the expression of autophagy protein LC3 and Vimentin, while downregulated the expression of autophagy protein P62 and E-cadherin. The expression of autophagy-related ubiquitination protein ULK1 and Ubiquitin protein were significantly upregulated in TRAF6-overexpressed CRC cells. In addition, autophagy inhibitor 3-methyladenine (3MA) significantly inhibited the metastasis-promoting effect of SPHK1 and TRAF6, suppressed the expression of LC3 and Vimentin, and promoted the expression of P62 and E-cadherin, in CRC cells. Immunofluorescence staining showed SPHK1 and TRAF6 were co-localized in HT29 CRC cell membrane and cytoplasm. Immunoprecipitation detection showed SPHK1 was efficiently combined with the endogenous TRAF6, and the interaction was also detected reciprocally. Additionally, proteasome inhibitor MG132 treatment upregulated the expression of TRAF6 and the level of Ubiquitin protein, in SPHK1-downregulating CRC cells. These results reveal that SPHK1 potentiates CRC progression and metastasis via regulating autophagy mediated by TRAF6-induced ULK1 ubiquitination. SPHK1-TRAF6-ULK1 signaling axis is critical to the progression of CRC and provides a new strategy for the therapeutic control of CRC.

Effects of late evening snacks on glucose homeostasis in cirrhotic patients: A meta-analysis.

BACKGROUND: Insulin resistance and hepatogenic diabetes are common complications in patients with liver cirrhosis. Previous studies have shown that reducing the fasting phase by supplying a late evening snack (LES) is a potential intervention to improve substrate utilization and liver function. However, the underlying mechanisms need to be further elucidated. The purpose of current meta-analysis is to evaluate effects of LES on glucose homeostasis in cirrhotic patients. METHODS: Electronic databases including PubMed, Web of Science, and major scientific conference sessions were searched without language restriction and carried out on March 1, 2022 with an additional manual search of bibliographies of relevant articles. A total of 4145 studies were identified, and 10 studies were eligible for the meta-analysis, comprising 631 patients (319 in the LES group and 312 in the non-LES group). Subgroup analyses were performed to investigate the effect of LES on cirrhotic patients with or without diabetes. RESULTS: Analysis showed that LES intervention had significant effects in cirrhotic patients for glycemic parameters on fasting plasma glucose, fasting insulin, and glycosylated hemoglobin respective effect sizes of -8.7, -0.86, and -0.76. Subgroup result revealed that the effect of LES on fasting plasma glucose is higher in cirrhotic patients with diabetes group than cirrhotic patients without diabetes group, and long-term LES supplementation (>2 months) was more beneficial to maintain glucose homeostasis in cirrhotic patients than that of short-term supplementation (<2 months). LES also had significant effect on nutritional metabolic parameters like including albumin and non-protein respiratory quotient. CONCLUSION: Meta-analysis indicated that LES not only improved malnutrition in cirrhotic patients with or without diabetes but also maintain glucose homeostasis in cirrhotic patients with diabetes. LES is a promising and simple intervention that beneficial to maintain glucose homeostasis in cirrhotic patients.

Interaction mechanisms between autophagy and ferroptosis: Potential role in colorectal cancer.

Colorectal cancer (CRC) is a common malignancy that has the second highest incidence and mortality rate. Although there are many personalized treatment options for CRC, the therapeutic effects are ultimately limited by drug resistance. Studies have aimed to block the initiation and progression of CRC by inducing cell death to overcome this obstacle. Substantial evidence has indicated that both autophagy and ferroptosis play important regulatory roles in CRC. Autophagy, a lysosome-dependent process by which cellular proteins and organelles are degraded, is the basic mechanism for maintaining cell homeostasis. The duality and complexity of autophagy in cancer therapy is a hot topic of discussion. Ferroptosis, a regulated cell death pathway, is associated with iron accumulation-induced lipid peroxidation. The activation of ferroptosis can suppress CRC proliferation, invasion and drug resistance. Furthermore, recent studies have suggested an interaction between autophagy and ferroptosis. Autophagy can selectively degrade certain cellular contents to provide raw materials for ferroptosis, ultimately achieving antitumor and anti-drug resistance. Therefore, exploring the interaction between autophagy and ferroptosis could reveal novel ideas for the treatment of CRC. In this review, we describe the mechanisms of autophagy and ferroptosis, focusing on their roles in CRC and the crosstalk between them.

Identification and verification of m6A-related miRNAs correlated with prognosis and immune microenvironment in colorectal cancer.

It's well known that N6-methyladenosine (m6A) modification is the most abundant modification in multiple RNA species. miRNAs play important roles in m6A modification and are closely related with occurrence and development of colorectal cancer (CRC). Thus, the aim of this study was to identify the prognostic value of m6A-related miRNAs and explore the correlation between the miRNAs and immune microenvironment in CRC. The differentially expressed m6A regulators and differentially expressed miRNAs between CRC tissues and adjacent normal tissues were identified based on TCGA dataset, and the m6A-related miRNAs were screened. The CRC patients from TCGA were randomized (1:1) into training set and validation set, and the risk score was established in the training set. Next, risk score was verified in the validation set and GSE92928 from GEO datasets. Besides, the relationship among tumor mutational burden, immune microenvironment and risk score were analyzed. What's more, RT-qPCR were used to explore the expression levels of the miRNAs in risk score between SW480 and SW620. A total of 29 m6A-related miRNAs were screened out, and a 5-differentially expressed miRNAs risk score was established. Kaplan-Meier analysis and ROC curves revealed the risk score could predict the prognosis of CRC, accurately. Similarly, the patients in the high-risk group had shorter overall survival in GSE92928. The risk score was relevant with the tumor mutational burden and immune infiltration, and the expression of HAVCR2 was significant difference between 2 risk groups. The expression levels of miR-328-3p, miR-3934-5p, miR-664b-5p and miR-3677-3p were down-regulated in SW620 compared with SW480, only the expression level of miR-200c-5p was up-regulated in SW620. The findings provided the new insights into the correlation between miRNAs and m6A regulators. The m6A-related miRNAs could predict the prognosis of CRC and provide the valuable information of immunotherapy in CRC patients.

SphK1-driven autophagy potentiates focal adhesion paxillin-mediated metastasis in colorectal cancer.

Invasion and metastasis are the main causes of colorectal cancer (CRC)-related death. Accumulating evidence suggested that sphingosine kinase 1 (SphK1) promoted the metastasis of CRC and autophagy played an important role in SphK1 promoting the metastasis of malignancy. However, the mechanism by which SphK1-driven autophagy promotes invasion and metastasis in CRC remains to be clarified. In the present study, immunohistochemical detection showed the expression of SphK1 and paxillin was higher in human CRC tissues than those of normal colorectal mucosal tissues, they were both associated with TNM staging, lymphatic, and distance metastasis. In addition, study of in situ tumor transplantation model in nude mice showed that the suppression of SphK1 inhibited the growth of colonic orthotopic implantation tumors and the expression of paxillin, p-paxillin, LC3 in the tumor. So, SphK1 may promote CRC metastasis via inducing the expression of paxillin expression and its phosphorylation, in vivo. Furthermore, results of CCK8 assay, transwell and wound healing assays showed that SphK1 promoted the viability, invasion, and metastasis of CRC cells. Transmission electron microscopy detection showed that SphK1 is the key factor in autophagy induction in CRC cells. Moreover, western blot examination indicated that the expression of LC3Ⅱ/Ⅰ, paxillin, p-paxillin, MMP-2, and vimentin was enhanced in SphK1-overexpressed CRC cells and suppressed in SphK1 knockdown CRC cells, meanwhile, the expression of E-cadherin was suppressed in SphK1-overexpressed CRC cells and enhanced in SphK1 knockdown CRC cells. Suppression of autophagy by 3MA reversed the expression of paxillin and its phosphorylation in SphK1-overexpressed CRC cells, indicated that SphK1-driven autophagy induced the expression of paxillin and its phosphorylation in CRC cells. Together, these findings reveal that SphK1-driven autophagy may promote the invasion and metastasis of CRC via promoting the expression of focal adhesion paxillin and its phosphorylation.