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There is increasing evidence that circular RNAs (circRNAs) can serve as microRNA (miRNA) sponges to regulate metastasis of multiple tumors, including pancreatic ductal adenocarcinoma (PDAC). However, the role of the circRNA/miRNA regulatory network in metastasis of PDAC has not been elucidated. The purpose of this study is to explore the role of circ_0047744/miR-21/SOCS5 in the metastasis of PDAC. We found that circRNA_0047744 was weakly expressed in PDAC tissues and cell lines. The expression of circ_0047744 was negatively correlated with lymph node metastasis and positively correlated with overall survival in PDAC patients. Functionally, the overexpression of circ_0047744 suppressed cell migration and invasion in vitro and in vivo. Mechanistically, circ_0047744 could regulate SOCS5 expression by acting as a sponge of miR-21 to inhibit migration and invasion of PDAC cells. Our study demonstrates that circ_0047744 acts as an anti-oncogene to inhibit PDAC metastasis by regulating the miR-21/SOCS5 axis, indicating that circ_0047744 may be a potential novel therapeutic target for PDAC patients.

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 cancer is a common malignant tumor with a dismal prognosis. Preoperative differentiation of extrapancreatic extension (EPE) based on radiomics will facilitate treatment decision-making.This research retrospectively recruited 156 patients from two medical centers. 122 patients from the center A were randomly divided into the training set and the internal test set in a 4:1 ratio. Additionally, 34 patients from the center B served as the external test set. Radiomics features were extracted from multiparametric MRI (MP-MRI), containing axial T2 weighted imaging (T2WI), diffusion weighted imaging (DWI), and dynamic contrast enhancement (DCE) sequences. The three-step method was used for feature extraction: SelecteKBest, least absolute shrinkage and selection operator (LASSO) algorithm, and recursive feature elimination based on random forest (RFE-RF). The model was constructed using six classifiers based on machine learning, and the classifier with the best performance was chosen. Finally, clinical factors associated with EPE were incorporated into the combined model.The classifier with the best performance was XGBoost, which obtained area under curve (AUC) values of 0.853 and 0.848 in the internal and external test sets, respectively. Through SelectKBest, the most relevant clinical factor for EPE was determined to be platelet, which was then added to the combined model, yielding AUC values of 0.880 and 0.848 in the internal and external test sets, respectively.Radiomics models had the potential to noninvasively and accurately predict EPE before surgery. Additionally, it would add value to personalized precision treatment.

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).

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%, P0.001). 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%, P0.01). 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], P0.001). Dual-modality drainage did not increase procedure-related complications compared with TMD only (13.0% vs 12.8%, P0.05). 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.

Background: For pregnant women who develop complications during the third trimester of pregnancy, or who have not given birth naturally after more than 41 weeks of pregnancy, artificial induction of labor is needed in order to obtain a healthy outcome for both the mother and the child. The 2014 edition of the Guidelines for Promoting Cervical Maturation and Delivery in Late Pregnancy point out that the use of COOK cervical ripening balloons to mechanically dilate the cervix can be used in the third trimester to promote cervical ripening and labor induction [1]. The disadvantage is the risk of infection, premature rupture of membranes, and umbilical cord prolapse [2]. The safety of balloon induction for pregnant women colonized by group B streptococcus (GBS) is currently lacking in multi-center clinical research data. This article will study the safety of COOK double balloon induction in pregnant women colonized by GBS.Methods: A total of 1,681 pregnant women who used COOK double balloons for cervical ripening in Changsha Maternity and Child Health Hospital from September 2018 to September 2020 were selected as the research subjects, from which 125 cases with colonization of group B streptococcus in the reproductive tract were selected as the observation group. Pregnant women without group B streptococcus colonization (N = 1556) served as the control group. This study compares the two groups’ delivery methods, postpartum complications, and neonatal conditions. Results: The rate of transition to cesarean section in the observation group was slightly higher, and the difference was statistically significant (p = 0.049). The rate of postpartum hemorrhage was higher than that of the control group (p < 0.05). Although chorioamnionitis increased compared to the control group, the difference was not significant (p > 0.05). The comparison of newborn birth indicators between the two groups showed no statistically significant difference (p > 0.05). Conclusion: When pregnant women with colonization of group B streptococcus of the genital tract use the COOK double balloon to promote cervical ripening, the success rate of labor induction is high. Use of the balloon does not increase the cesarean section rate and the incidence of chorioamnionitis, nor does it increase the risk of neonatal infection. However, the risk of postpartum hemorrhage increases, and it is necessary to take active measures to reduce this risk.

Autophagy plays key roles in the development of acute pancreatitis (AP) and the regulation of impaired autophagy has therapeutic potential. The objective of the present study was to investigate whether pharmacological inhibition of autophagy could ameliorate AP in mice and examine the underlying mechanisms. In current study, by imaging-based high-throughput screening, a novel spautin-1 derivative spautin-A41 was identified as a potent autophagy inhibitor. Mice treated with spautin-A41 were resistant to the cerulein-induced elevation of serum pancreatic enzyme activities and pancreatic apoptosis. Mechanistically, spautin-A41 effectively reduced the expression levels of Class III phosphatidylinositol 3 (PI3) kinase complexes and subsequently ameliorated pancreatitis by inhibiting the formation of autophagosome. Therefore, pharmacological inhibition of autophagy by spautin-A41 may serve as new target for treating or lessening the severity of AP.

To comprehensively compare the wet suction technique with the conventional dry suction technique for endoscopic ultrasound-guided fine-needle aspiration (EUS-FNA) in solid lesions.Optimal suction techniques for EUS-FNA remain uncertain when approaching solid lesions.We performed a retrospective study of EUS-FNA at 3 medical centers in China. A total of 203 patients were enrolled who received 2 passes of EUS-FNA with 22-G needles. If the first pass underwent dry suction, the second pass was wet suction. Otherwise, the order of suction technique is opposite. Diagnostic accuracy, sample quality (including cellularity and blood contamination), and sample quantity (including specimen adequacy, the maximum intact specimen length, and the total specimen length) were compared between wet-suction and dry-suction techniques.The patients included 143 pancreatic lesions and 60 nonpancreatic lesions. Compared with the dry suction technique, the wet suction technique yielded a significantly higher diagnostic accuracy (85.22% vs. 72.41%,P=0.002), better specimen adequacy score and cellularity score (P0.0001), and lower blood contamination score (P0.0001). In the subgroup analysis, wet suction provided significantly higher diagnostic accuracy in pancreatic cancer without chronic pancreatitis (P0.05), and better cellularity score and specimen adequacy score, lower blood contamination score, and longer maximum intact specimen length and total specimen length in various lesions than that in dry suction.The wet suction technique resulted in significantly higher diagnostic accuracy in pancreatic cancer without chronic pancreatitis, and better cellularity and histologic specimen in most of solid lesions.

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.

As globalization progresses, the global economy becomes closely related and more difficult to predict. Early Warning System (EWS) is a major tool to monitor and forecast economic risk. In order to improve the timeliness of EWS, indicators obtained through big data analysis are increasingly utilized. However, the uncertainties about the extracted indicators are also augmented when the big data sources are not directly related to concerned economic problem. In this paper, our aim is to build an early warning systems (EWS) with multi-dimensional indicators, combined with genetic algorithm (GA) and analytic hierarchy process (AHP) to monitor the operation of the system in real-time. In order to handle the uncertainties, we use interval-valued variables and propose dominant criteria for different decision makers to meet their preferences.

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.

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.

Background/Aims: Although endoscopic metal biliary endoprosthesis (EMBE) is widely accepted as the most suitable drainage method for patients with unresectable malignant obstruction, uncontrolled post-procedural cholangitis is still a problem. We aimed to validate a new treatment modality to prevent post-ERCP cholangitis in patients with unresectable cholangiocarcinoma. Patients and Methods: A total of 378 patients who were diagnosed with unresectable malignant biliary obstruction and underwent EMBE or temporary endoscopic nasobiliary drainage (ENBD) following EMBE placement, from January 2010 to July 2016, were enrolled in this retrospective study. Incidence of cholangitis, related infectious indicators, success rate of biliary drainage, and occurrence of complications were evaluated. Results: The risk of overall cholangitis and related infectious indicators was significantly lower in EMBE plus ENBD group than that in EMBE group. The occurrence of cholangitis was 2.4% versus 11.9% (P = 0.004). On further analysis of subgroups, although no difference was detected in nonhilar cholangiocarcinoma subgroup, the incidence of cholangitis and related infectious indicators in hilar cholangiocarcinoma subgroup with EMBE modality were distinctly higher than that with EMBE plus ENBD modality (type I + II was 18.5% vs 0%, P < 0.05; type III + IV was 19.8% vs 3.8%, P < 0.05). No significant difference was found in successful biliary drainage rate and procedure-related complications when all subgroups were compared. Conclusions: The temporary placement of ENBD following EMBE is a simple and effective treatment modality to prevent post-ERCP cholangitis, especially in patients with hilar cholangiocarcinoma.

Epidemiological 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. We 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. In 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, I 2 = 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). Results 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.

International audience; In reliability analysis, comparing system reliability is an essential task when designing safe systems. When the failure probabilities of the system components (assumed to be independent) are precisely known, this task is relatively simple to achieve, as system reliabilities are precise numbers. When failure probabilities are ill-known (known to lie in an interval) and we want to have guaranteed comparisons (i.e., declare a system more reliable than another when it is for any possible probability value), there are different ways to compare system reliabilities. We explore the computational problems posed by such extensions, providing first insights about their pros and cons.