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Abstract Background Pancreatic cancer is one of the most lethal malignancies and has an extremely poor diagnosis and prognosis. The development of resistance to gemcitabine is still a major challenge. The long noncoding RNA PVT1 was reported to be involved in carcinogenesis and chemoresistance; however, the mechanism by which PVT1 regulates the sensitivity of pancreatic cancer to gemcitabine remains poorly understood. Methods The viability of pancreatic cancer cells was assessed by MTT assay in vitro and xenograft tumor formation assay in vivo. The expression levels of PVT1 and miR-619-5p were detected by quantitative real-time polymerase chain reaction (qRT-PCR). Western blotting analysis and qRT-PCR were performed to assess the protein and mRNA levels of Pygo2 and ATG14, respectively. Autophagy was explored via autophagic flux detection under confocal microscopy and autophagic vacuole investigation under transmission electron microscopy (TEM). The functional role and mechanism of PVT1 were further investigated by gain- and loss-of-function assays in vitro. Results In the present study, we demonstrated that PVT1 was up-regulated in gemcitabine-resistant pancreatic cancer cell lines. Gain- and loss-of-function assays revealed that PVT1 impaired sensitivity to gemcitabine in vitro and in vivo. We further found that PVT1 up-regulated the expression of both Pygo2 and ATG14 and thus regulated Wnt/β-catenin signaling and autophagic activity to overcome gemcitabine resistance through sponging miR-619-5p. Moreover, we discovered three TCF/LEF binding elements (TBEs) in the promoter region of PVT1, and activation of Wnt/β-catenin signaling mediated by the up-regulation of Pygo2 increased PVT1 expression by direct binding to the TBE region. Furthermore, PVT1 was discovered to interact with ATG14, thus promoting assembly of the autophagy specific complex I (PtdIns3K-C1) and ATG14-dependent class III PtdIns3K activity. Conclusions These data indicate that PVT1 plays a critical role in the sensitivity of pancreatic cancer to gemcitabine and highlight its potential as a valuable target for pancreatic cancer therapy.

Abstract Objectives To build a combined model based on the ultrasound radiomic and morphological features, and evaluate its diagnostic performance for preoperative prediction of central lymph node metastasis (CLNM) in patients with papillary thyroid carcinoma (PTC). Method A total of 295 eligible patients, who underwent preoperative ultrasound scan and were pathologically diagnosed with unifocal PTC were included at our hospital from October 2019 to July 2022. According to ultrasound scanners, patients were divided into the training set (115 with CLNM; 97 without CLNM) and validation set (45 with CLNM; 38 without CLNM). Ultrasound radiomic, morphological, and combined models were constructed using multivariate logistic regression. The diagnostic performance was assessed by the area under the curve (AUC) of the receiver operating characteristic curve, accuracy, sensitivity, and specificity. Results A combined model was built based on the morphology, boundary, length diameter, and radiomic score. The AUC was 0.960 (95% CI, 0.924–0.982) and 0.966 (95% CI, 0.901–0.993) in the training and validation set, respectively. Calibration curves showed good consistency between prediction and observation, and DCA demonstrated the clinical benefit of the combined model. Conclusion Based on ultrasound radiomic and morphological features, the combined model showed a good performance in predicting CLNM of patients with PTC preoperatively.

Abstract Background As an important component of accelerated rehabilitation surgery, goal-directed fluid therapy (GDT) is one of the optimized fluid therapy strategies and is closely related to perioperative complications and mortality. This article aimed to study the effect of combining plasma colloid osmotic pressure (COP) with stroke volume variation (SVV) as a target for intraoperative GDT for postoperative pulmonary complications in older patients undergoing major abdominal surgery. Methods In this study, older patients (n = 100) undergoing radical resection of gastroenteric tumors were randomized to three groups: Group C (n1 = 31) received a conventional infusion regimen, Group S1 (n2 = 34) received GDT based on SVV, and Group S2 (n3 = 35) received GDT based on SVV and COP. The results were recorded, including the lung injury score (LIS); PaO2/FiO2 ratio; lactic acid value at the times of beginning (T0) and 1 h (T1), 2 h (T2), and 3 h (T3) after liquid infusion in the operation room; the total liquid infusion volume; infusion volumes of crystalline and colloidal liquids; urine production rate; pulmonary complications 7 days after surgery; and the severity grading of postoperative pulmonary complications. Results The patients in the S2 group had fewer postoperative pulmonary complications than those in the C group (P

Abstract Objective To investigate the influences of exercise on the levels of chemerin and its receptor chemokine-like receptor (CMKLR1) in the peripheral metabolic organs of obesity and diabetes rats, and whether the mechanism is related to peroxisome proliferator activated receptor γ (PPARγ), a key modulator of glycolipid metabolism. Methods Obesity rats induced by 8-week high fat diet (HFD) were randomly divided into obesity group (OB) and exercised obesity group (EOB) with 8 rats each group, and 40 diabetes rats established by 8-week HFD plus low dose of streptozotocin were randomly divided into 4 groups: diabetes group (DM), exercised diabetes group (EDM), exercised diabetes plus PPARγ agonist pioglitazone group (EDP), and exercised diabetes plus PPARγ antagonist GW9662 group (EDG). The rats in EOB, EDM, EDG and EDP groups participated in a 4-week moderate-intensity aerobic exercise on a treadmill with gradually increasing intensity, once a day and 6 days/week, and 30 min before each exercise EDP and EDG were administrated to the rats in EDP and EDG groups, respectively. Before and after 4-week exercise, glycolipid metabolism indexes, serum chemerin and the levels of chemerin and CMKLR1 in metabolic organs such as liver and gastrocnemius were investigated (not detecting adipose for no available perirenal adipose from DM rats). Results (1) In addition to serum chemerin, the levels of chemerin and CMKLR1 in the liver and gastrocnemius of EOB and EDM rats were declined, accompanied with the improved glycolipid metabolism. (2) The decreased chemerin/CMKLR1 in the EDM rats were reversed by PPARγ antagonist GW9662 and further strengthened by PPARγ agonist pioglitazones. Conclusions Besides serum chemerin, the levels of chemerin/CMKLR1 in the metabolic organs of obesity and diabetes rats were alleviated by exercise, which were likely to be associated with the improvement of glycolipid metabolism. Exercise-induced decrements of chemerin/CMKLR1 in the diabetes rats were mediated by PPARγ.

Abstract Enhancer of zeste homolog 2 (EZH2), a histone methyltransferase and a catalytic component of PRC2, catalyzes tri-methylation of histone H3 at Lys 27 (H3K27me3) to regulate gene expression through epigenetic machinery. EZH2 also functions both as a transcriptional suppressor and a transcriptional co-activator, depending on H3K27me3 or not and on the different cellular contexts. Unsurprisingly, numerous studies have highlighted the role of EZH2 in cancer development and progression. Through modulating critical gene expression, EZH2 promotes cell survival, proliferation, epithelial to mesenchymal, invasion, and drug resistance of cancer cells. The tumor suppressive effects of EZH2 are also identified. What is more, EZH2 has decisive roles in immune cells (for example, T cells, NK cells, dendritic cells and macrophages), which are essential components in tumor microenvironment. In this review, we aim to discuss the molecular functions of EZH2, highlight recent findings regarding the physiological functions and related regulation of EZH2 in cancer pathogenesis. Furthermore, we summarized and updated the emerging roles of EZH2 in tumor immunity, and current pre-clinical and clinical trials of EZH2 inhibitors in cancer therapy.