1.MicroRNA profiles in pancreatic ductal adenocarcinoma
Jing ZHANG ; Chenyan ZHAO ; Qinghua LIU ; Danghui YU ; Ying CHEN ; Min SHI ; Canrong NI ; Minghua ZHU
Chinese Journal of Pancreatology 2012;12(5):313-316
Objective To study the differentially expressed microRNA (miRNA) between pancreatic ductal adenocarcinoma (PDAC) and para-cancerous tissues,and determine related target genes.Methods Nine fresh PDAC tumor tissues and 3 adjacent normal pancreatic tissues were collected,then Agilent miRNAmicroarray with 713 miRNA loci was used to identify the differentially expressed miRNA.Real-time PCR method was applied to verify the up-regulated miRNA.TargetScan 5.1 and miRandaV5 software were used to analyze the related target genes.Results miRNA microarray identified 11 PDAC related miRNAs,among them,the expressions of miR-194*,miR-192*,miR-602,miR-194 were up-regulated,while the expressions of miR-139-3p,miR-513a-5p,miR-630,miR-30c-1 *,miR-887,miR-508-5p,miR-516a-5p were down-regulated.The expressions of miR-192,miR-194 and their homolog were verified in 31 PDAC tumor tissues.After software analysis,it was found that target genes of miR-192 were ZEB2,CXCL-2,EEF1A1,ERCC3,and target genes of miR-192 * were DCC,SMAD4,FAS,and target genes of miR-194 included DACHI,IGSF11,PTPN2,RBBP4,while target genes of miR-194 * included CD40LG,CIDEB,FHL1.Conclusions Eleven differentially expressed miRNAs are present in PDC,and they may be involved in the occurrence and development of PDC.
2.Assay development for determination of DZ2002, a new reversible SAHH inhibitor, and its acid metabolite DZA in blood and application to rat pharmacokinetic study
Weiwei JIA ; Jing LI ; Feifei DU ; Yan SUN ; Fang XU ; Fengqing WANG ; Olajide-E. OLALEYE ; Danghui CHEN ; Wei TANG ; Jianping ZUO ; Chuan LI
Journal of Pharmaceutical Analysis 2019;9(1):25-33
Methyl (S)-4-(6-amino-9H-purin-9-yl)-2-hydroxybutanoate (DZ2002) is a potent reversible inhibitor of S-adenosyl-L-homocysteine hydrolase (SAHH). Due to its ester structure, DZ2002 is rapidly hydrolyzed in rat blood to 4-(6-amino-9H-purin-9-yl)-2-hydroxybutyric acid (DZA) during and after blood sampling from rats; this hampers accurate determination of the circulating DZ2002 and its acid metabolite DZA in rats. To this end, a method for determining the blood concentrations of DZ2002 and DZA in rats was developed by using methanol to immediately deactivate blood carboxylesterases during sampling. The newly developed bioanalytical assay possessed favorable accuracy and precision with lower limit of quantification of 31 nM for DZ2002 and DZA. This validated assay was applied to a rat pharmacokinetic study of DZ2002. After oral administration, DZ2002 was found to be extensively converted into DZA. The level of systemic exposure to DZ2002 was significantly lower than that of DZA. The apparent oral bioavailability of DZ2002 was 90%–159%. The mean terminal half-lives of DZ2002 and DZA were 0.3–0.9 and 1.3–5.1 h, respectively. The sample preparation method illustrated here may be adopted for de-termination of other circulating ester drugs and their acid metabolites in rodents.
3.Application of transmesenteric vein extrahepatic portosystemic shunt to treat extrahepatic portal vein obstructive disease
Weixiao LI ; Mingzhe CUI ; Deyang SONG ; Jiangbo CHEN ; Danghui LU ; Dongbin ZHANG ; Shuiting ZHAI
Chinese Journal of Radiology 2021;55(9):903-909
Objective:To explore the feasibility, safety and effectivity of applying transmesenteric vein extrahepatic portosystemic shunt (TEPS) to treat extrahepatic portal vein obstructive disease (EHPVOD).Methods:From December 2020 to April 2021, 12 patients with EHPVOD in the Vascular Surgery Department of Zhengzhou University People′s Hospital were prospectively enrolled in the study. The infra-umbilical median longitudinal minilaparotomy was performed to expose the branch of superior mesenteric vein (SMV). RUPS-100 was introduced into the trunk of SMV. A balloon with a diameter of 20 mm was introduced through right internal jugular vein (RIJV) into inferior vena cava (IVC). Under fluoroscopy, RUPS-100 was used to puncture the balloon in IVC. A stiff guide wire was used to establish the pathway between RIJV and SMV. Finally the portosystemic shunt between IVC and SMV was established with a covered stent-graft. The total operative time, the time of establishing portosystemic shunt alone, the dosage of contrast agent, the preoperative and postoperative pressure of SMV were recorded. Paired t test was used to compare the preoperative and postoperative pressure of SMV. Results:All 12 patients were successfully performed TEPS. The total operative time was (113±32) min, the time of establishing portosystemic shunt alone was (31±5) min, the dosage of contrast agent was (129±48) ml. The postoperative pressure of SMV [(14.3±2.1) mmHg] decreased significantly ( t=20.125, P<0.01) compared to baseline [(27.8±2.7) mmHg]. All portal hypertension symptoms released after the operations.There was 1 case of delayed incision healing, 1 case of bacteremia and 1 case of slight hepatic encephalopathy, but all of them were cured. There was no death case. Postoperative CT showed all portosystemic shunts were patent. Conclusion:TEPS is a new, safe, effective and feasible treatment method for patients of acute and chronic EHPVOD.