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Endoscopic transmural drainage (TMD) has been accepted as the preferred therapy for symptomatic pancreatic fluid collections (PFCs). Recurrence of PFCs presents a unique challenge in patients with disrupted pancreatic duct (PD). We aimed to evaluate whether transpapillary drainage (TPD) provides additional benefits to TMD in patients with PD disruption. This was a multicenter retrospective study. Consecutive patients who underwent TMD, TPD, or combined drainage (CD) of PFCs were included. The primary outcome was to compare PFC recurrence among different groups. The secondary outcomes were the technical success rate, length of hospital stay, and procedure-related complications. A total of 153 patients, which consists of 57 patients with pancreatic pseudocysts and 96 patients with walled-off necrosis, were included. PFC recurrence was more common in patients with PD disruption than those with an intact main duct (19% vs 1.4%, P < 0.001). PD disruption was identified as a major risk factor of PFC recurrence by univariable and multivariable analyses. The recurrence rate of CD was significantly lower than TMD only or TPD only (6.5% vs 15.4% vs 22.7%, P < 0.01). The length of hospital stay of CD was significantly shorter than TMD only or TPD only (5 [3.0-9.0] vs 7.0 [5.0-12.0] vs 9 [7.0-16.0], P < 0.001). Dual-modality drainage did not increase procedure-related complications compared with TMD only (13.0% vs 12.8%, P > 0.05). Partial PD disruption was bridged in 87.3% cases while complete PD disruption was reconnected in 55.2% cases. Although statistically not significant, the clinical success rate in walled-off necrosis cases with actively bridged ducts was much higher than those with passively bridged ducts (76.9% vs 40%). Transpapillary pancreatic duct stenting seems to improve the efficacy of endoscopic TMD of pancreatic duct disruption-associated PFCs by reducing the recurrence rate and shortening the length of hospital stay.

Pancreatic ductal adenocarcinoma (PDAC) is a highly malignant cancer that lacks effective targets for therapy. Alteration of epidermal growth factor (EGF) expression has been recognized as an essential molecular event in pancreatic carcinogenesis. Accumulating studies have demonstrated that miRNAs play critical roles in EGF signaling regulation, tumor initiation, cell proliferation and apoptosis. Here, we demonstrated that miR-21 expression was induced by EGF in pancreatic cancer cells. miR-21 promoted EGF-induced proliferation, inhibited cell apoptosis and accelerated cell cycle progression. In vivo experiments confirmed the influence of miR-21 on tumor growth. Mechanistic studies revealed that miR-21 targeted MAPK/ERK and PI3K/AKT signaling pathways to modulate cell proliferation. In addition, Spry2 was proven to be a target of miR-21. Furthermore, miR-21 and Spry2 were significantly related to clinical features and may be valuable predictors of PDAC patient prognosis.

BackgroundEpidemiological studies assessing the relationship between dietary vitamin B2 and the risk of breast cancer have produced inconsistent results. Thus, we conducted this meta-analysis of epidemiologic studies to evaluate this association.MethodsWe searched English-language MEDLINE publications and conducted a manual search to screen eligible articles. A random-effect model was used to pool study-specific risk estimates. Egger’s linear regression test was also used to detect publication bias in meta-analysis.ResultsIn our meta-analysis, ten studies comprising totally 12,268 breast cancer patients were available in the analyses. Pooled relative risk (RR) comparing the highest to the lowest vitamin B2 intake and breast cancer incidence was 0.85 [95% confidence interval (CI) = 0.76–0.95]. No significant heterogeneity existed across the studies (P = 0.086, I2 = 40.7%). No publication bias was found. The results of dose–response analysis also showed that an increment of 1 mg/day was inversely related to the risk of breast cancer (RR = 0.94; 95% CI = 0.90–0.99).ConclusionsResults from our meta-analysis indicated that dietary vitamin B2 intake is weakly related to the reduced risk of breast cancer. Additional research is also necessary to further explore this association.

Breast cancer bone metastases may block normal bone remodeling and promote bone degradation, during which several signaling pathways and small non-coding miRNAs might all play a role. miRNAs and target mRNAs that might be associated with breast cancer bone metastasis were analyzed and selected using bioinformatics analyses based on online data. The 3′ untranslated region of key factors associated with breast cancer metastasis were examined for candidate miRNA binding site using Targetscan. The predicted binding was validated. The specific effects of single miRNA and dynamic effects of the miRNA-mRNA axis on breast cancer cell metastasis were investigated. miR-556-5p was downregulated in breast cancer samples according to online datasets and experimental analyses. In breast cancer cells, miR-556-5p overexpression inhibited, whereas miR-556-5p inhibition promoted cancer cell invasion and migration. Among key factors associated with breast cancer bone metastasis, parathyroid hormone related protein (PTHrP) 3′UTR possessed miR-556-5p binding site. Through direct binding, miR-556-5p negatively regulated PTHrP expression. In breast cancer cell lines, miR-556-5p inhibition promoted, whereas PTHrP silencing suppressed cancer cell migration, invasion, and epithelial-mesenchymal transition; the effects of miR-556-5p inhibition were partially reversed by PTHrP silencing. In summary, miR-556-5p targets PTHrP to modulate the cell migration and invasion of breast cancer.

Pancreatic adenocarcinoma (PC), one of the most fatal diseases, usually generates a poor prognosis in advanced stages. N6-methyladenosine modification has emerged as a crucial participant in tumor development and recurrence. Methyltransferase-like 14 (METTL14), as a core member of methyltransferases, is involved in tumor progression and metastasis. However, the potential mechanism by which METTL14 regulates long noncoding RNAs (lncRNAs) in PC remains unclear. RNA immunoprecipitation (RIP), methylated RNA immunoprecipitation quantitative PCR (MeRIP-qPCR), and fluorescence in situ hybridization (FISH) were used to explore the underlying mechanisms. In our study, we found that METTL14 expression was upregulated in PC patients, and was associated with poor prognosis. In vitro and in vivo experiments, knocking down METTL14 suppressed tumor metastasis. RNA-seq and bioinformatics analyses were used to identify LINC00941 as the downstream target of METTL14. Mechanistically, LINC00941 was upregulated by METTL14 in an m6A-dependent way. LINC00941 was recruited and recognized by IGF2BP2. METTL14 enhanced the affinity of IGF2BP2 for LINC00941, while IGF2BP2 promoted the stabilization of LINC00941, which contributed to the migration and invasion of PC cells. Overall, our research revealed that METTL14 promoted the metastasis of PC through m6A modification of LINC00941. Targeting the METTL14-LINC00941-IGF2BP2 axis may provide promising therapeutic approaches for PC.

Mahalanobis-Taguchi System (MTS) is an effective algorithm for dimensionality reduction, feature extraction and classification of data in a multidimensional system. However, when applied to the field of high-dimensional small sample data, MTS has challenges in calculating the Mahalanobis distance due to the singularity of the covariance matrix. To this end, we construct a modified Mahalanobis-Taguchi System (MMTS) by introducing the idea of proper orthogonal decomposition (POD). The constructed MMTS expands the application scope of MTS, taking into account correlations between variables and the influence of dimensionality. It can not only retain most of the original sample information features, but also achieve a substantial reduction in dimensionality, showing excellent classification performance. The results show that, compared with expert classification, individual classifiers such as NB, RF, k-NN, SVM and superimposed classifiers such as Wrapper + RF, MRMR + SVM, Chi-square + BP, SMOTE + Wrapper + RF and SMOTE + MRMR + SVM, MMTS has a better classification performance when extracting orthogonal decomposition vectors with eigenvalues greater than 0.001.

In dynamic parameter design, there is often a different functional relationship between response variables and signal factors. SNR is an important tool for the parameter design of dynamic characteristics, and its estimation results change with the change of function relationships. This paper describes the dynamic parameter design method in a linear relationship between response variables and signal factors, and provides a case for verification. The results of this study are applicable to engineers and academics who need to conduct product design, process development and process optimization through dynamic parameter design.

Inflammation is one of the inducing factors of pancreatic ductal adenocarcinoma (PDAC), and microRNAs have been confirmed to be involved in the occurrence and development of PDAC. However, whether RELA, an inflammatory regulator, is involved in the regulation of PDAC by miRNA remains to be further studied. In the present study miR-21 was characterized and its upstream regulatory mechanism was investigated, as well as its functional effects and target genes in pancreatic ductal adenocarcinoma (PDAC). In situ hybridization analysis confirmed increased miR-21 expression levels in PDAC tissues. The results of the chromatin immunoprecipitation and dual-luciferase reporter assays demonstrated that transcription factor RELA modulated miR-21 transcription in the PDAC, PANC-1 and MIA PaCa-2 cell lines. Subsequently, a cell viability assay, EdU staining assay and flow cytometry analysis, demonstrated that miR-21 promoted cell proliferation and cell cycle progression, but inhibited cell apoptosis in vitro. Furthermore, a xenograft assay demonstrated that miR-21 accelerated tumor growth in vivo. Mechanistically, miR-21 directly regulated the expression of Rho GTPase activating protein 24 (ARHGAP24), which was indicated to be a tumor suppressor gene. Moreover, both miR-21 and ARHGAP24 were strongly associated with clinical features and may therefore serve as valuable biomarkers in PDAC prognosis.

N7-Methylguanosine (m7G) modification holds significant importance in regulating posttranscriptional gene expression in epigenetics. Long non-coding RNAs (lncRNAs) have been demonstrated to play a crucial role in cancer progression. m7G-related lncRNA may be involved in the progression of pancreatic cancer (PC), although the underlying mechanism of regulation remains obscure. We obtained RNA sequence transcriptome data and relevant clinical information from the TCGA and GTEx databases. Univariate and multivariate Cox proportional risk analyses were performed to build a twelve-m7G-associated lncRNA risk model with prognostic value. The model was verified using receiver operating characteristic curve analysis and Kaplan–Meier analysis. The expression level of m7G-related lncRNAs in vitro was validated. Knockdown of SNHG8 increased the proliferation and migration of PC cells. Differentially expressed genes between high- and low-risk groups were identified for gene set enrichment analysis, immune infiltration, and potential drug exploration. We conducted an m7G-related lncRNA predictive risk model for PC patients. The model had independent prognostic significance and offered an exact survival prediction. The research provided us with better knowledge of the regulation of tumor-infiltrating lymphocytes in PC. The m7G-related lncRNA risk model may serve as a precise prognostic tool and indicate prospective therapeutic targets for PC patients.

Rapid progression and metastasis are the major causes of death in patients with pancreatic ductal adenocarcinoma (PDAC). ELK3, a member of the ternary complex factor (TCF), has been associated with the initiation and progression of various cancers. However, the role of ELK3 in PDAC is not yet fully understood. Online databases and immunohistochemistry were used to analyze the ELK3 levels in PDAC tissues. The function of ELK3 was confirmed by a series of in vivo and in vitro studies. Western blotting and immunofluorescence were used to detect the molecular mechanisms of PDAC. ChIP-qPCR was used to study the mechanism responsible for the elevation of ELK3 expression in PDAC. The ELK3 levels were higher in PDAC tissues than in adjacent normal tissues. Functionally, we demonstrated that ELK3 acted as an oncogene to promote PDAC tumorigenesis and metastasis. Further study suggested that ELK3 promoted PDAC cell migration and invasion by activating the Wnt/β-catenin pathway, and proved that ZEB1 could directly bind to the promoter of ELK3 to increase its transcription. Finally, both were associated with the patients’ clinicopathological features and worse overall survival. Conclusively, our findings enrich the role of ELK3 in PDAC, and provide potential avenues for exploring more effective biomarkers and therapeutic strategies for the treatment of PDAC.