Esophageal carcinoma is one of the most common malignancies with high cancer-related morbidity and mortality worldwide. MicroRNAs (miRNAs) are a class of small non-coding RNAs that regulate a wide variety of cellular processes, and also play an important role in the development and progression of cancers. In a previous microarray study, we demonstrated that miR-130b was upregulated in esophageal squamous cell carcinoma (ESCC) tissues. However, the biologic functions and the molecular mechanism of miR-130b in ESCC remain to be elucidated. qRT-PCR assays were used to quantify miR-130b expression levels in ESCC samples. Novel targets of miR-130b were identified via a bioinformatics search and confirmed using a dual-luciferase reporter system. Western blotting and qRT-PCR assays were used to quantify the expression of the target gene PTEN (phosphatase and tensin homolog) and the downstream effector, Akt. ESCC cells over- or underexpressing miR-130b were analyzed for in vitro biologic functions. High levels of miR-130b were identified in 20 ESCC samples following comparison with adjacent non-neoplastic tissues. We confirmed that miR-130b interacted with the 3′-untranslated region of PTEN, and that an increase in the expression level of miR-130b negatively affected the protein level of PTEN. However, the dysregulation of miR-130b had no obvious impact on PTEN mRNA. As Akt is a downstream effector of PTEN, we explored if miR-130b affected Akt expression, and found that miR-130b indirectly regulated the level of phosphorylated Akt, while total Akt protein remained unchanged. Overexpression of miR-130b increased the proliferation of ESCC cells and enhanced their ability to migrate and invade. In contrast, the proliferation, migration, and invasion of ESCC cells were weakened when miR-130b expression was suppressed, which was reversed by PTEN-targeted siRNA. The results indicate that miR-130b plays an oncogenic role in ESCC cells by repressing PTEN expression and Akt phosphorylation, which would be helpful in developing miRNA-based treatments for ESCC.

Pancreatic cancer (PC) is one of the most lethal malignances. Identification of biomarkers for early diagnosis of PC is a key imperative. MicroRNAs (miRNAs) have been shown to be valuable biomarkers in the context of several cancers. Exosomes refer to vesicles released by the tumor cells at the early stage of disease. Thus, detection of miRNA in exosomes can be used as a potential biomarker for PC. In this study, we profiled serum levels of miRNAs in patients with chronic pancreatitis (CP) and PC; the role of miR‑23b‑3p in PC progression was assessed in vitro. Additionally, we assessed, the expression of miR‑23b‑3p in exosomes isolated from serum samples and assessed the correlation between the expression of miR‑23b‑3p and carbohydrate antigen 19-9 (CA19-9). Three serum samples each were randomly selected from healthy controls (n=20), and patients with CP (n=18) and PC (n=16) for miRNA microarray profiling. The dysregulated miRNAs were confirmed using qRT‑PCR. Four dysregulated miRNAs common to patients with CP and PC were identified on miRNA microarray analysis and confirmed by qRT‑PCR. miR‑23b‑3p level was consistently higher in serum samples from PC patients as compared to those from healthy controls and CP patients (p<0.05). Overexpression of miR‑23b‑3p promoted proliferation, migration, and invasion capability of PC cells in vitro (p<0.05). Furthermore, miR‑23b‑3p was upregulated in exosomes of PC serum samples and the supernatant of pancreatic cancer cells (PANC‑1), and the expression levels of miR‑23b‑3p were associated with those of serum CA19-9 levels. This study provides insights into the potential role of miR‑23b‑3p as a novel biomarker and target for treatment of PC.

The present study was to evaluate the accuracy of bedside index for severity in acute pancreatitis (BISAP) in predicting the severity and prognoses of acute pancreatitis (AP) in Chinese patients. Clinical data for 497 patients with AP were analyzed retrospectively to compare BISAP with acute physiology and chronic health evaluation II, Ranson, and computed tomography severity index scores in predicting the severity of AP and the occurrence of pancreatic necrosis, mortality, and organ failure in patients with severe AP (SAP) using the area under the receiver-operating characteristic curve. Of the 497 patients, 396 had mild AP and 101 had SAP. There were significant correlations between the scores of any two systems. BISAP performed similarly to other scoring systems in predicting SAP, as well as pancreatic necrosis, mortality, and organ failure in SAP patients, in terms of the area under the receiver-operating characteristic curve. BISAP score is valuable in predicting the severity of AP and prognoses of SAP in Chinese patients.

INTRODUCTION: This study aims to construct a real-time deep convolutional neural networks (DCNNs) system to diagnose early esophageal squamous cell carcinoma (ESCC) with white light imaging endoscopy. METHODS: A total of 4,002 images from 1,078 patients were used to train and cross-validate the DCNN model for diagnosing early ESCC. The performance of the model was further tested with independent internal and external validation data sets containing 1,033 images from 243 patients. The performance of the model was then compared with endoscopists. The accuracy, sensitivity, specificity, positive predictive value, negative predictive value, and Cohen kappa coefficient were measured to assess performance. RESULTS: The DCNN model had excellent performance in diagnosing early ESCC with a sensitivity of 0.979, a specificity of 0.886, a positive predictive value of 0.777, a negative predictive value of 0.991, and an area under curve of 0.954 in the internal validation data set. The model also depicted a tremendously generalized performance in 2 external data sets and exhibited superior performance compared with endoscopists. The performance of the endoscopists was markedly elevated after referring to the predictions of the DCNN model. An open-accessed website of the DCNN system was established to facilitate associated research. DISCUSSION: A real-time DCNN system, which was constructed to diagnose early ESCC, showed good performance in validation data sets. However, more prospective validation is needed to understand its true clinical significance in the real world.

Background. Mesenchymal stem cells (MSCs), with the powerful metabolic and functional supporting abilities for inflammatory diseases, may be an effective therapeutic strategy for acute liver failure (ALF). However, the efficacy of MSCs can still be promoted if pretreatment is applied to enhance their poor migration towards the damaged liver. The purpose of this study is to determine the effect of IL-1β pretreatment on the efficacy and homing ability of MSCs in ALF. Methods. MSCs were isolated by the whole bone marrow adherence method and characterized. The efficacy and homing ability of IL-1β-pretreated MSCs (Pre-MSCs) were examined in a rat ALF model and compared with that of MSCs and normal saline. Then, Western blot was performed to detect the c-Met and CXCR4 expression of MSCs and Pre-MSCs and followed by flow cytometry to detect the meaningful indicators. Finally, the migration abilities of different cells and different conditions were tested by the Transwell migration assay. Results. MSCs of ideal purity were successfully isolated and cultured. Comparing with MSCs, Pre-MSCs had significantly better efficacy on improving the survival rate and liver function of ALF rats. Further analyses of damaged liver tissues showed that IL-1β pretreatment significantly enhanced the efficacy of MSCs on suppressing liver necrosis. Besides, Pre-MSCs exhibited better effects in inhibiting apoptosis and activating proliferation. The results of tracing experiments with CM-Dil-labeled cells confirmed that more cells migrated to the damaged liver in the Pre-MSC group. In terms of mechanism, the CXCR4 expression was significantly enhanced by IL-1β pretreatment, and an increased migration ability towards SDF-1 that could be reversed by AMD3100 was found in Pre-MSCs. Conclusion. IL-1β pretreatment could enhance the homing ability of MSCs at least partially by increasing the expression of CXCR4 and further improve the efficacy of MSCs on ALF.

Background: Immunotherapy is a novel hotspot for the treatment of pancreatic adenocarcinoma (PAAD). However, potential biomarkers which could identify the inflamed tumor microenvironment (TME) are urgently required. Methods: In the present study, we measured the levels of B7-H3, B7-H4, and major tumor-infiltrating immune cells (TIICs) using bioinformatics analyses and immunohistochemistry (IHC) staining on PAAD samples represented in the tissue microarray (TMA) format. Statistical analysis and figures exhibition were performed using R 4.1.0, SPSS 26.0, and GraphPad Prism 6.0. Results: B7-H3 and B7-H4 were up-regulated in PAAD compared with para-tumor tissues, and their expression exhibited no tight correlation in PAAD tissues. B7-H3 and B7-H4 were lowly expressed in well-differentiated PAAD tissues and correlated with poorly differentiated grades. Besides, single B7-H3 or B7-H4 expression exhibited limited prognostic value, but co-deficiency of B7-H3 and B7-H4 predicted a better prognosis in PAAD. Moreover, co-deficiency of B7-H3 and B7-H4 indicated immuno-hot tumors with high CD8 + T cell infiltration. Conclusions: Overall, combined B7-H3 and B7-H4 expression is a promising stratification strategy to assess prognosis and immunogenicity in PAAD, which could be used as a novel classifier in clinical practice.