IntroductionThe development of drug resistance is the main obstacle for successful treatment in acute myeloid leukemia (AML). Noncoding RNAs have been implicated in biological function in AML drug resistance. Aberrant protein glycosylation is associated with AML progression. The aim of the study was to explore the potential regulatory mechanism of lncRNA MEG3/miR‐155/ALG9 axis in drug resistance of AML.MethodsQRT‐PCR and Western blot were used for comparison analyses of ALG9, MEG3, and miR‐155 levels. CCK‐8 and colony formation assays were determined for drug sensitivity and proliferative capability of AML cells. Luciferase reporter assay was used to confirm the targets of miR‐155.ResultsThe mannosyltransferase ALG9 and MEG3 was downregulated in peripheral blood mononuclear cells (PBMCs) of M5/multidrug resistance (MDR) AML patients and adriamycin (ADR)‐resistant AML cell lines, which determined a positive correlation in AML patients. Low expression of ALG9 and MEG3 predicted poor prognosis of AML patients. The altered level of ALG9 was found corresponding to the drug‐resistant phenotype and sphere formation of AML cells. MiR‐155 was overexpressed in M5/MDR patients and ADR‐resistant AML cells, as well as inversely correlated to ALG9 expression. MEG3 was a direct target of miR‐155 and could sponge miR‐155 in AML cells. MEG3 interacted with miR‐155 to regulate ALG9 expression, which reversed the effects of ALG9 regulation on proliferation and drug resistance in AML cells.ConclusionMEG3 sponged miR‐155 by competing endogenous RNA (ceRNA) mechanism, which further modulated ALG9 expression and AML procession, providing a novel therapeutic target for AML chemoresistance.

Cellular communication processes are highly dynamic and mediated, at least in part, by contacts between various membrane structures. The endoplasmic reticulum (ER), the major biosynthetic organelle of the cell, establishes an extensive network with other membrane structures to regulate the transport of intracellular molecules. Vacuole membrane protein 1 (VMP1), an ER-localized metazoan-specific protein, plays important roles in the formation of autophagosomes and communication between the ER and other organelles, including mitochondria, autophagosome precursor membranes, Golgi, lipid droplets, and endosomes. Increasing evidence has indicated that autophagy and ER-membrane communication at membrane contact sites are closely related to neurodegenerative disorders, such as Parkinson's disease, Alzheimer's disease, and amyotrophic lateral sclerosis. In this review, we summarize the roles of VMP1 in autophagy and ER-membrane contacts and discuss their potential implications in neurodegenerative disorders.

No abstract

Background: To evaluate the value of the 3-hour post-ERCP serum amylase level for early prediction of post-ERCP pancreatitis (PEP). Method: A study of 206 patients performed ERCP was analysed. The patients with PEP were recorded. ROC curves were used to statistically analyze the data. Results: PEP occurred in 21 patients (10.19%). The 3-hour post-ERCP pancreatic amylase level was used as the test variable, and the PEP occurrence as the state variable to plot ROC curve. The area under the curve (AUC) was 0.816 , and was statistically significant (P<0.001). The standard error (SE) was 0.0507, the 95% confidence interval (CI) was 0.756-0.866, and the optimal cut-off value was 351U/L (sensitivity 76.19%, specificity 83.24%, positive likelihood ratio 4.55, negative likelihood ratio 0.29, Youden index 59.43%). The ROC curves were plotted for both serum amylase and lipase respectively. The areas under the ROC curves were statistically significant(P<0.001). The area under the ROC curve for the 3-hour post-ERCP lipase was 0.778, the 95% confidence interval was 0.673-0.862, and optimal cut-off value was 1834 U/L. The area under the ROC curve for the 3-hour post-ERCP serum amylase was 0.780, and the 95% confidence interval was 0.676-0.864. The optimal cut-off is 380U/L, and there was no statistically significant difference between the two for diagnostic accuracy. According to gender, there was no statistically significant difference in the diagnostic accuracy. In the male group, 436 U/L serum amylase provided the greatest diagnostic accuracy with sensitivity(SE) of 70.5%, specificity(SP) of 89.2%, positive predictive value (PPV) 87.5%, and negative predictive value (NPV) 78.1%. Whereas, in the female group, 357U/L serum amylase provided the greatest diagnostic accuracy with sensitivity of 76.9%, specificity of 81.2%, positive predictive value of 80.4%, negative predictive value of 77.9%. Conclusions: 1. The 3-hour post-ERCP serum amylase level is a useful measurement for predicting post-ERCP pancreatitis. 2. There was no significant difference between serum amylase and lipase 3-hour post-ERCP for predicting PEP. 3. There was no statistically significant difference between male and female using the 3-hour post-ERCP serum amylase level to predict PEP. For female, the optimal cut-off value was 357 U/L, whereas male 436U/L .

Background: To evaluate the value of the 3-h post-ERCP serum amylase level for early prediction of post-ERCP pancreatitis (PEP). Method: A study of 206 patients performed ERCP (Encoscopic Retrograde Cholangio-Pancreatography) at a single centre was done from Jan. 2011 to Nov. 2016. The serum amylase or lipase level was measured at 3 h after ERCP. The patients with PEP were recorded. ROC curves were used to statistically analyze the data: The enrolled patients were divided into two groups according to gender, then we analyzed the data respectively. We comprehensively evaluated the predictive value of PEP by 3-h post-ERCP serum amylase level based on the results above. Results: Two hundred six patients (92 males, 114 females) were enrolled. PEP occurred in 21 patients (10.19%) among them. The median time to discharge was 7 days (min = 1d, max = 13d) after the procedure. In the 206 patients, the 3-h post-ERCP pancreatic amylase level was used as the test variable, and the PEP occurrence as the state variable to plot the ROC curve. The area under the curve (AUC) was 0.816, and was statistically significant (P < 0.001). The standard error (SE) was 0.0507, the 95% confidence interval (CI) was 0.756-0.866, and the optimal cutoff value was 351 U/L (sensitivity 76.19%, specificity 83.24%, positive likelihood ratio 4.55, negative likelihood ratio 0.29, Youden index 59.43%). Of the 206 patients, there were 83 patients with both 3-h post-ERCP amylase level and lipase level detected, and the ROC curves were plotted for both serum amylase and lipase respectively. The ROC curve matched-pair testing was carried out: The areas under the ROC curves were statistically significant. (P < 0.001) The area under the ROC curve for the 3-h post-ERCP lipase was 0.778, the 95% confidence interval was 0.673-0.862, and optimal cutoff value was 1834 U/L. The area under the ROC curve for the 3-h post-ERCP serum amylase was 0.780, and the 95% confidence interval was 0.676-0.864. The optimal cutoff is 380 U/L, and there was no statistically significant difference between the two for diagnostic accuracy. According to gender, 206 patients were divided into 2 groups, and the ROC curves were drawn respectively. Based on statistical analysis, there was no statistically significant difference in the diagnostic accuracy of the two groups. In the male group, 436 U/L serum amylase provided the greatest diagnostic accuracy with sensitivity (SE) of 70.5%, specificity (SP) of 89.2%, positive predictive value (PPV) 87.5%, and negative predictive value (NPV) 78.1%. Whereas, in the female group, 357 U/L