Effect of cyclic hydraulic stimulation on pore structure and methane sorption characteristics of anthracite coal: A case study in the Qinshui Basin, China

The cyclic hydraulic stimulation(CHS) has proven as a prospective technology for enhancing the permeability of unconventional formations such as coalbeds. However, the effects of CHS on the microstructure and gas sorption behavior of coal remain unclear. In this study, laboratory tests including the nuclear magnetic resonance(NMR), low-temperature nitrogen sorption(LTNS), and methane sorption isotherm measurement were conducted to explore changes in the pore structure and methane sorption characteristics caused by CHS on an anthracite coal from Qinshui Basin, China. The NMR and LTNS tests show that after CHS treatment, meso- and macro-pores tend to be enlarged, whereas micropores with larger sizes and transition-pores may be converted into smaller-sized micro-pores. After the coal samples treated with 1, 3, 5 and 7 hydraulic stimulation cycles, the total specific surface area(TSSA)decreased from 0.636 to 0.538, 0.516, 0.505, and 0.491 m^(2)/g, respectively. Fractal analysis based on the NMR and LTNS results show that the surface fractal dimensions increase with the increase in the number of hydraulic stimulation cycles, while the volume fractal dimensions exhibit an opposite trend to the surface fractal dimensions, indicating that the pore surface roughness and pore structure connectivity are both increased after CHS treatment. Methane sorption isothermal measurements show that both the Langmuir volume and Langmuir pressure decrease significantly with the increase in the number of hydraulic stimulation cycles. The Langmuir volume and the Langmuir pressure decrease from 33.47 cm^(3)/g and 0.205 MPa to 24.18 cm^(3)/g and 0.176 MPa after the coal samples treated with 7 hydraulic stimulation cycles, respectively. The increments of Langmuir volume and Langmuir pressure are positively correlated with the increment of TSSA and negatively correlated with the increments of surface fractal dimensions.

Analysis of the autophagy gene expression profile of pancreatic cancer based on autophagy-related protein microtubule-associated protein 1A/1B-light chain 3

BACKGROUND Pancreatic cancer is a highly invasive malignant tumor. Expression levels of the autophagy-related protein microtubule-associated protein 1 A/1 B-light chain 3(LC3) and perineural invasion(PNI) are closely related to its occurrence and development. Our previous results showed that the high expression of LC3 was positively correlated with PNI in the patients with pancreatic cancer. In this study, we further searched for differential genes involved in autophagy of pancreatic cancer by gene expression profiling and analyzed their biological functions in pancreatic cancer, which provides a theoretical basis for elucidating the pathophysiological mechanism of autophagy in pancreatic cancer and PNI.AIM To identify differentially expressed genes involved in pancreatic cancer autophagy and explore the pathogenesis at the molecular level.METHODS Two sets of gene expression profiles of pancreatic cancer/normal tissue(GSE16515 and GSE15471) were collected from the Gene Expression Omnibus.Significance analysis of microarrays algorithm was used to screen differentially expressed genes related to pancreatic cancer. Gene Ontology(GO) analysis and Kyoto Encyclopedia of Genes and Genomes(KEGG) pathway analysis were used to analyze the functional enrichment of the differentially expressed genes. Protein interaction data containing only differentially expressed genes was downloaded from String database and screened. Module mining was carried out by Cytoscape software and ClusterOne plug-in. The interaction relationship between the modules was analyzed and the pivot nodes between the functional modules were determined according to the information of the functional modules and the data of reliable protein interaction network.RESULTS Based on the above two data sets of pancreatic tissue total gene expression, 6098 and 12928 differentially expressed genes were obtained by analysis of genes with higher phenotypic correlation. After extracting the intersection of the two differential gene sets, 4870 genes were determined. GO analysis showed that 14 significant functional items including negative regulation of protein ubiquitination were closely related to autophagy. A total of 986 differentially expressed genes were enriched in these functional items. After eliminating the autophagy related genes of human cancer cells which had been defined, 347 differentially expressed genes were obtained. KEGG pathway analysis showed that the pathways hsa04144 and hsa04020 were related to autophagy. In addition,65 clustering modules were screened after the protein interaction network was constructed based on String database, and module 32 contains the LC3 gene,which interacts with multiple autophagy-related genes. Moreover, ubiquitin C acts as a pivot node in functional modules to connect multiple modules related to pancreatic cancer and autophagy.CONCLUSION Three hundred and forty-seven genes associated with autophagy in human pancreatic cancer were concentrated, and a key gene ubiquitin C which is closely related to the occurrence of PNI was determined, suggesting that LC3 may influence the PNI and prognosis of pancreatic cancer through ubiquitin C.

Relationship between autophagy and perineural invasion, clinicopathological features, and prognosis in pancreatic cancer

AIM To investigate the relationship between autophagy and perineural invasion(PNI), clinical features, and prognosis in patients with pancreatic cancer. METHODS Clinical and pathological data were retrospectively collected from 109 patients with pancreatic ductal adenocarcinoma who underwent radical resection at the First Affiliated Hospital of Zhengzhou University from January 2011 to August 2016. Expression levels of the autophagy-related protein microtubuleassociated protein 1 A/1 B-light chain 3(LC3) and PNI marker ubiquitin carboxy-terminal hydrolase(UCH) in pancreatic cancer tissues were detected by immunohistochemistry. The correlations among LC3 expression, PNI, and clinical pathological features in pancreatic cancer were analyzed. The patients were followed for further survival analysis. RESULTS In 109 cases of pancreatic cancer, 68.8%(75/109) had evidence of PNI and 61.5%(67/109) had high LC3 expression. PNI was associated with lymph node metastasis, pancreatitis, and CA19-9 levels(P < 0.05). LC3 expression was related to lymph node metastasis(P < 0.05) and was positively correlated with neural invasion(P < 0.05, r = 0.227). Multivariate logistic regression analysis indicated that LC3 expression, lymph node metastasis, pancreatitis, and CA19-9 level were factors that influenced neural invasion, whereas only neural invasion itself was an independent factor for high LC3 expression. Univariate analysis showed that LC3 expression, neural invasion, and CA19-9 level were related to the overall survival of pancreatic cancer patients(P < 0.05). Multivariate COX regression analysis indicated that PNI and LC3 expression were independent risk factors for poor prognosis in pancreatic cancer(P < 0.05). CONCLUSION PNI in patients with pancreatic cancer is positively related to autophagy. Neural invasion and LC3 expression are independent risk factors for pancreatic cancer with a poor prognosis.

Perirenal space blocking restores gastrointestinal function in patients with severe acute pancreatitis

AIM:To investigate effects of perirenal space blocking(PSB)on gastrointestinal function in patients with severe acute pancreatitis(SAP).METHODS:Forty patients with SAP were randomly allocated to receive PSB or no PSB(NPSB).All the SAP patients received specialized medical therapy(SMT).Patients in the PSB group received PSB+SMT when hospitalized and after diagnosis,whereas patients in the NPSB group only received SMT.A modifed gastrointestinal failure(GIF)scoring system was used to assess the gastrointestinal function in SAP patients after admission.Pain severity(visual analog scale,0 to100)was monitored every 24 h for 72 h.RESULTS:Modified GIF score decreased in both groups during the 10-d study period.The median score decrease was initially significantly greater in the PSB group than in the NPSB group after PSB was per-formed.During the 72-h study period,pain intensity decreased in both groups.The median pain decrease was significantly greater in the PSB group than in the NPSB group at single time points.Patients in the PSB group had significantly lower incidences of hospital mortality,multiple organ dysfunction syndrome,systemic inflammatory response syndrome,and pancreatic infection,and stayed in the intensive care unit for a shorter duration.However,no difference in terms of operation incidence was found between the two groups.CONCLUSION:PSB could ameliorate gastrointestinal dysfunction or failure during the early stage of SAP.Moreover,PSB administration could improve prognosis and decrease the mortality of SAP patients.

Enzyme-mediated hydrolytic activation of prodrugs

Prodrug design is an important part of drug discovery.Prodrugs can offer many advantages over parent drugs such as increased solubility,enhanced stability,improved bioavailability,reduced side effects,and better selectivity.Many prodrugs have been used successfully in the clinic;examples include oseltamivir in anti-influenza therapy,enalapril in anti-hypertension therapy,capecitabine in cancer therapy,and omeprazole in the treatment of peptic ulcer.A key step in prodrug design is the incorporation of an activation mechanism that can convert the prodrug into the active species in an efficient and/or controlled manner to meet the needs of a given medical application.Prodrug activation can be achieved through enzyme-mediated hydrolytic or oxidoreductive processes while activation of some prodrugs may proceed through pure chemical nonenzymatic processes.This review focuses on the hydrolytic enzymes that have been used in prodrug activation,including transferases,hydrolases,and lyases.