A novel experimental apparatus for single polycrystalline diamond compact cutter tests.

Polycrystalline diamond compact (PDC) bits are increasingly favored in the drilling field due to their high efficiency in rock breaking together with their longevity. To investigate the rock failure mechanism and further improve the performance of PDC bits, innovative experimental equipment is proposed in this paper. With its assistance, we can study the characteristics of rock-breaking using a PDC cutter under different conditions, e.g., high pressure and high temperature (HPHT), confining pressure, and jet impingement. The setup can be grouped into three parts: a rock cutting system, high-pressure jet generation system, and controlling system. A series of experiments was conducted to demonstrate the reliability of the setup. The results demonstrate the improvement in performance of PDC bits in the exploration of HPHT formations.

Design of experimental setup for liquid nitrogen assisted polycrystalline diamond compact bit drilling.

A liquid nitrogen assisted polycrystalline diamond compact (PDC) bit drilling method is expected to be suitable for hot dry rock (HDR) drilling because the huge thermal stress induced in the drilling process can help to break the rock and the low temperature liquid nitrogen can efficiently cool the drilling tools. However, there is no experimental research on liquid nitrogen assisted PDC bits breaking high temperature granite, and the rock breaking efficiency of this new drilling method is still unclear. To investigate the feasibility and efficiency of liquid nitrogen assisted PDC bit breaking HDR, a novel experimental setup was designed. This setup is composed of four units: the drilling fluid circulation system, drilling system, formation simulation system, and data acquisition and control system. It can also be used to research the effects of drilling parameters such as weight on bit, rotary speed, drilling fluid jet pressure, and feed speed on drilling efficiency. A series of drilling experiments using liquid nitrogen and water have been successfully carried out with this setup. The results indicate that liquid nitrogen assisted PDC bit drilling has excellent performance in breaking HDR, which can accelerate the application of this new technique in geothermal drilling.

[Experimental study on intervention effect of Grifola frondosa on nonalcoholic steatohepatitis].

To study the preventive effect of Grifola frondosa on nonalcoholic steatohepatitis (NASH). The rat model of NASH was established by feeding high-fat diets for 12 weeks and intervened with 0.5 g · kg(-1) · d(-1) and 1.0 g · kg(-1) · d(-1) of C. frondosa powder suspensions. The degrees of hepatocyte fatty degeneration and inflammation were observed under the optical microscope with routine HE staining. The NAFLD activity scores (NAS) were calculated. Serum ALT, AST and hepatic TG and CHOL were tested by the biochemical method. The hepatic MDA was examined by thiobarbituric acid method. The hepatic SOD was tested by the xanthine oxidase test. The hepatic GSH-PX activity was determined by the dithio-nitrobenzoic acid method. Hepatic TNF-α and IL-6 were detected by the enzyme-linked immunosorbent assay (ELISA). The NASH model group induced by high-fat diets showed higher hepatic NAS, ser- um ALT, AST, CHOL and hepatic TG, CHOL, MDA, TNF-α, IL-6 (P < 0.01 or P < 0.05) and lower serum TG and hepatic SOD, GSH-PX (P < 0.01, P < 0.05) than the normal control group. After being intervened with different doses of G. frondosa, the NASH group revealed significantly lower hepatic NAS, serum ALT and hepatic TG, CHOL, MDA, TNF-α and IL-6 (P < 0.05) and higher hepatic SOD, GSH-PX (P < 0.05) than the model group. G. frondosa may prevent the further development of NASH by improving the disorder of lipid metabolism in rats with NASH induced by high-fat diets, relieving the level of oxidative stress and reducing the generation of inflammatory cytokines.

Use of an autologous liver round ligament flap zeros postoperative bile leak after curative resection of hilar cholangiocarcinoma.

BACKGROUND: Postoperative bile leak is a major surgical morbidity after curative resection with hepaticojejunostomy for hilar cholangiocarcinoma, especially in Bismuth-Corlette types III and IV. This retrospective study assessed the effectiveness and safety of an autologous hepatic round ligament flap (AHRLF) for reducing bile leak after hilar hepaticojejunostomy. METHODS: Nine type III and IV hilar cholangiocarcinoma patients were consecutively hospitalized for elective perihilar partial hepatectomy with hilar hepaticojejunostomy using an AHRLF between October 2009 and September 2013. The AHRLF was harvested to reinforce the perihilar hepaticojejunostomy. Main outcome measures included operative time, blood loss, postoperative recovery times, morbidity, bile leak, R0 resection rate, and overall survival. RESULTS: All patients underwent uneventful R0 resection with hilar hepaticojejunostomy. No patient experienced postoperative bile leak. CONCLUSIONS: The AHRLF was associated with lack of bile leak after curative perihilar hepatectomy with hepaticojejunostomy for hilar cholangiocarcinoma, without compromising oncologic safety, and is recommended in selected patients.

TRIM29 as a novel biomarker in pancreatic adenocarcinoma.

BACKGROUND AND AIM: Tripartite motif-containing 29 (TRIM29) is structurally a member of the tripartite motif family of proteins and is involved in diverse human cancers. However, its role in pancreatic cancer remains unclear. METHODS: The expression pattern of TRIM29 in pancreatic ductal adenocarcinoma was assessed by immunocytochemistry. Multivariate logistic regression analysis was used to investigate the association between TRIM29 and clinical characteristics. In vitro analyses by scratch wound healing assay and invasion assays were performed using the pancreatic cancer cell lines. RESULTS: Immunohistochemical analysis showed TRIM29 expression in pancreatic cancer tissues was significantly higher (n = 186) than that in matched adjacent nontumor tissues. TRIM29 protein expression was significantly correlated with lymph node metastasis (P = 0.019). Patients with positive TRIM29 expression showed both shorter overall survival and shorter recurrence-free survival than those with negative TRIM29 expression. Multivariate analysis revealed that TRIM29 was an independent factor for pancreatic cancer over survival (HR = 2.180, 95% CI: 1.324-4.198, P = 0.011). In vitro, TRIM29 knockdown resulted in inhibition of pancreatic cancer cell proliferation, migration, and invasion. CONCLUSIONS: Our results indicate that TRIM29 promotes tumor progression and may be a novel prognostic marker for pancreatic ductal adenocarcinoma.

Continuous irrigation around pancreatic remnant decreases pancreatic fistula-related intraabdominal complications after distal pancreatectomy.

PURPOSE: To evaluate whether the technique of irrigation around pancreatic remnant after distal pancreatectomy (DP) can reduce the incidence of postoperative pancreatic fistula (PF) and its related intraabdominal complications. METHODS: In the retrospective clinical trial, the technique of irrigation around pancreatic remnant after DP was introduced. The clinical data of 60 patients who underwent the irrigation technique (irrigation group) and the other 65 patients who did not undergo the technique (non-irrigation group) were recorded, respectively. Preoperative clinicopathological features, intraoperative parameters, postoperative morbidity, clinically significant PF, and its related intraabdominal complications were compared between the two groups. RESULTS: The patency of irrigation tubes and drains was maintained in 59 patients. The overall incidence of PF was 31.2 %. There was no significant difference in the rate of PF between the two groups (P = 0.781), but the rate of PF-related intraabdominal complications was significantly lower in the irrigation group than that in the non-irrigation group (5 vs. 18, P = 0.005). The overall incidence of intraabdominal complications was significantly lower in the irrigation group than that in the non-irrigation group (23 vs. 39, P = 0.025). CONCLUSION: The technique of irrigation around pancreatic remnant after DP is a simple method for prevention of clinically significant PF and its related intraabdominal complications.

Nanoparticle-mediated local delivery of an antisense TGF-ß1 construct inhibits intimal hyperplasia in autogenous vein grafts in rats.

BACKGROUND: Intimal hyperplasia is one of the most important causes of vascular graft failure. Numerous studies have correlated transforming growth factor-ß1 (TGF-ß1) with extracellular matrix (ECM) deposition, a hallmark of intimal thickening. PRINCIPAL FINDINGS: In the present study, we performed immunohistochemistry, RT-PCR, and Western blot to examine the dynamic expression of TGF-ß1, TGF-ß1 receptor type I (TGF-ß RI), matrix metalloproteinase-1 (MMP-1) and tissue inhibitor of metalloproteinase-1 (TIMP-1) during intimal hyperplasia in grafted veins of a rat model generated by grafting a portion of the right internal jugular vein to the ipisiliary carotid artery. Additionally, we determined whether nanoparticle-mediated delivery of a TGF-ß1 antisense-expressing construct prevented TGF-ß1 expression and intimal hyperplasia in grafted veins. In grafted veins, the expression of TGF-ß1 significantly increased on day 3 after transplantation, peaked on day 7, slightly decreased on day 14, and returned to baseline levels on day 28. The positive expression of TGF-ß RI in grafted veins remarkably increased on day 7, peaked on day 14, and decreased thereafter. MMP-1 expression decreased significantly, while TIMP-1 expression increased, significantly on days 14 and 28. Nanoparticle-mediated delivery of a TGF-ß1 antisense-expressing construct down-regulated TGF-ß1 expression and inhibited intimal hyperplasia in grafted veins. CONCLUSIONS: Our findings provide further evidence that TGF-ß1 plays an integral role in the development of intimal hyperplasia after vascular injury. Nanoparticle-mediated delivery of a TGF-ß1 antisense-expressing construct is a feasible strategy to target TGF-ß1-induced intimal thickening.

Involvement of COX-2/PGE(2) Pathway in the Upregulation of MMP-9 Expression in Pancreatic Cancer.

COX-2 and MMP-9 have been reported to show an overexpression in pancreatic cancer, and thus an attempt to explore the correlation between them has become a target of this study. Besides, PGE(2), a product of COX-2, was also under research as to whether it is involved in the upregulation of MMP-9 expression by COX-2. Expression of COX-2 and MMP-9 mRNA varied in pancreatic adenocarcinomas, and the mRNA level of COX-2 was correlated positively with MMP-9. Both BxPC-3 and Capan-1 cells had strong expression of COX-2 and MMP-9. MMP-9 expression was downregulated significantly in BxPC-3 and Capan-1 cells after treatment with COX-2 inhibitors or COX-2 siRNA plasmids, and upregulated in BxPC-3 significantly by exogenous TNF-α, LPS or PGE(2). The upregulation of MMP-9 by TNF-α or LPS was inhibited by COX-2 inhibitor NS398. There was a significant increase in the migration of BxPC-3 cells with TNF-α, LPS, or PGE(2) treatment; however, the increase caused by TNF-α or LPS was also inhibited remarkably by NS398. Our findings demonstrated that COX-2 upregulates MMP-9 expression in pancreatic cancer, and PGE(2) may be involved in it.

Sphincter of Oddi manometry by choledochoscope in patients with duodenobiliary reflux.

BACKGROUND AND AIM: Previous research has confirmed that duodenobiliary reflux exists in patients with choledocholithiasis. The objective of this study was to investigate whether the motor activity of the sphincter of Oddi (SO) has an effect on duodenobiliary reflux. METHODS: A total of 51 patients orally ingested 1mL water containing technetium-99m diethylenetriaminepentaacetatic acid, and a 2-h bile collection was obtained from the T tube. Technetium counts in the collected bile were performed using an RM905 radioactivity meter. The patients were divided into two groups: reflux group (duodenobiliary reflux positive) and control group (duodenobiliary reflux negative). Next, 33 cases were randomly selected and double blinded to receive SO manometry by choledochoscope. RESULTS: Of the 51 total cases, 16 bile samples exhibited radioactivity. The average SO basal pressure and contraction pressure values were 7.2±3.9mmHg and 53.5±24.5mmHg, respectively, in the reflux group, and 14.7±11.0mmHg and 117.2±65.6mmHg, respectively, in the control group. The choledochus pressure values were 5.1±1.6mmHg and 11.5±7.4mmHg in the reflux group and the control group, respectively. The differences between the groups were statistically significant; however, the SO contraction frequency, SO contraction duration, and duodenum pressure values were not significantly different between the groups. CONCLUSION: The decreases in the SO basal pressure and SO contraction pressure, and the decrease in choledochus pressure, might play a role in duodenobiliary reflux.

A novel technique for the management of pancreaticojejunal anastomosis dehiscence following pancreaticoduodenectomy.

BACKGROUND: To report a novel technique for management of pancreaticojejunal anastomosis dehiscence after pancreaticoduodenectomy. MATERIAL AND METHODS: The anastomosis is disconnected and the blind jejunal limb is shortened and closed. A silicon tube in the pancreatic duct introduced in the first operation is fixed at the pancreatic stump. If no tube was placed during pancreaticoduodenectomy, it is placed at reoperation. The transected edge of the pancreas is stitched, and the distal part of the silicon tube is inserted into the jejunal loop and fixed in the jejunal wall. Drains and a catheter for continuous irrigation are placed. RESULTS: All patients tolerated reoperation and experienced unremarkable postoperative courses. Follow-up ranged from 5 to 27 months, and all patients exhibited normal pancreatic function and no pseudocyst formation. CONCLUSION: This technique is an effective method for management of pancreaticojejunal anastomosis dehiscence that avoids complications associated with completion pancreatectomy and preserves pancreatic function.

Pancreaticojejunal bridge-anastomosis: a novel option for surgeon to preserve pancreatic body and tail in urgent reoperation for intra-abdominal massive hemorrhage after pancreaticoduodenectomy.

BACKGROUND: Postoperative intra-abdominal massive bleeding is a rare and life-threatening complication associated with pancreaticoduodenectomy. Completion pancreatectomy (CP) was usually performed during reexploration for the complication. The management could decrease the complications, such as the pancreatic leakage or intraluminal infection after reexploration, but could increase mortality during the perioperative period. It also could result in loss of pancreatic function forever. This study evaluated an alternative surgical management for intra-abdominal massive hemorrhage to prevent pancreas function, simplify the surgical processes, and decrease the mortality of relaparotomy. METHODS: Outcome after pancreaticojejunal bridge-anastomosis (PJBA) performed between January 2006 and June 2009 was compared with that after CP performed between February 1984 and December 2005. RESULTS: Between February 1984 and June 2009, 963 patients underwent the Whipple procedure (PD) or pylorus-preserving pancreaticoduodectomy (PPPD). Pancreatic leakage occurred in 103 patients (10.7%); 22 cases (21.4%) developed into intra-abdominal massive bleeding. Nonsurgical procedures of transarterial embolization (TAE) were performed in ten (45.45%) patients, of whom one died (10%). Twelve (54.55%) underwent reoperation. Five had CP with one death (20%). Pancreatic remnant was preserved by pancreaticojejunal bridge-anastomosis (PJBA) in seven patients with no deaths. The reexploration time was 340 +/- 48.2 min vs. 247.9 +/- 40.8 min (P < 0.01) for CP and PJBA group and the blood loss was 2,180 +/- 526.3 ml vs. 1,628.6 +/- 325.1 ml (P < 0.05). In-hospital time for CP was less than that for PJBA (P < 0.05). All patients with CP still developed endocrine insufficiency ("brittle" diabetes) and diarrhea (exocrine insufficiency). There were no evidences of exocrine and endocrine insufficiency in patients with PJBA. CONCLUSIONS: Pancreaticojejunal bridge-anastomosis is an easy, simple, and safe procedure for intra-abdominal massive hemorrhage associated with pancreaticoduodenectomy. It could decrease the mortality of reoperation and preserve the pancreatic function.

Abdominal separation in an adult male patient with acute abdominal pain.

We report a male patient with prolonged post-prandial abdominal distension and a sudden onset of epigastric pain initially diagnosed as acute abdomen. The patient had no history of surgery. Physical examination revealed peritonitis and abdominal computed tomography scan showed upper abdominal mesentery intorsion. The patient then underwent surgical intervention. It was found that the descending mesocolon dorsal root was connected to the ascending colon and formed a membrane encapsulating the small intestine. The membrane also formed an orifice in the ileal pars caeca, from which a 30 cm herniated ileum formed a "C"-shaped loop which was strangulated by the orifice. An abdominal separation was diagnosed after surgery. We liberated the membranous peritoneum which incarcerated the intestinal canal from the root of ileocecal junction to Treitz ligament, and reduced the small intestinal malrotation. The patient had an uneventful recovery after operation with his abdominal distention disappeared during the follow-up. Abdominal separation is a rare situation, which may be related with embryo development. Surgery is a choice of treatment for it.

MEK1 and MEK2 isoforms regulate distinct functions in pancreatic cancer cells.

The mitogen-activated protein kinase kinase 1/2 (MEK1/2) signalling pathway plays a central role in tumour progression. Small molecules that inhibit MEK1/2 are therefore considered attractive candidates for anti-cancer drugs. However, the exact contributions of MEK1 and MEK2 to the development of pancreatic cancer remain to be established. To differentiate the functions of MEK1 and MEK2 in a cultured pancreatic cancer cell line, we utilised shRNA-mediated knockdown of their two mRNAs individually. We studied the effects of MEK1 and MEK2 knockdown on cell morphology, proliferation, mitotic arrest, and in vitro invasion capability in PC-1.0 cells. The results showed that inhibition of MEK1 expression was an effective and specific approach to inhibit cell proliferation and induce G0/G1 arrest. On the other hand, MEK2 knockdown specially altered cell morphology and inhibited the invasive ability of pancreatic cancer cells. Therefore, MEK1 and MEK2 mediate different biological responses in cultured pancreatic cancer cells. These proteins could become distinct targets for the inhibition of specific cellular functions in the treatment of pancreatic cancer.

Primary mesenchymal chondrosarcoma of the pancreas.

Extraskeletal chondrosarcomas are rare and there is only one reported case of primary pancreatic chondrosarcoma. We report the case of a 34-year-old woman with a 6-month history of abdominal pain and distention. Radiological studies indicated a mass in the pancreas, and exploratory laparotomy revealed a tumour of the pancreas extending to the hepatic vessels and hepatoduodenal ligament. The mass was completely excised, and the histopathological diagnosis was primary mesenchymal pancreatic chondrosarcoma. Tumour recurred at follow-up 52 months postoperatively.

Analysis of invasion-metastasis in pancreatic cancer: Correlation between the expression and arrangement of tight junction protein-2 and cell dissociation in pancreatic cancer cells.

High frequency of invasion and metastasis is one of the key characteristics of pancreatic cancer. In our recent study, tight junction protein-2 (Tjp-2) was identified as a differentially expressed gene related to invasion-metastasis in highly (PC-1.0) and weakly (PC-1) invasive and metastatic pancreatic cancer cells by cDNA microarray analysis. Changes in the structure and function of tight junctions are correlated with carcinogenesis and tumour development. In this study, RT-PCR, Western blotting and immunocytochemistry were used to study the correlation between the expression and localisation of Tjp-2 and cell dissociation in pancreatic cancer. Tjp-2 mRNA and protein were differentially expressed in PC-1.0 and PC-1 cells. Furthermore, the addition of dissociation factor (DF) or U0126 (a MEK inhibitor) significantly induced changes in the mRNA expression and protein intracellular localisation of Tjp-2, and in the simultaneous cell dissociation of PC-1.0 and PC-1 cells. However, protein expression of Tjp-2 was not affected by DF or U0126 treatment. The current results indicate that Tjp-2 is involved in the regulation of cell dissociation in pancreatic cancer cells through changes in gene expression and intracellular localisation. Tjp-2 may serve as a new target for molecular therapies that prevent the invasion and metastasis of pancreatic cancer.

Involvement of the expression and redistribution of claudin-23 in pancreatic cancer cell dissociation.

Dissociation of pancreatic cancer cells from primary sites is the critical first step in tumour invasion and metastasis. Changes in the structure and function of tight junctions are reported to be correlated with carcinogenesis and tumour development. Using cDNA microarray analysis, we recently identified claudin-23 as a differentially expressed gene related to invasion-metastasis in highly (PC-1.0) and weakly (PC-1) invasive and metastatic pancreatic cancer cells. In this study, RT-PCR, Western blotting and immunocytochemistry were used to demonstrate the involvement of the expression and redistribution of claudin-23 in pancreatic cancer cell dissociation. Claudin-23 mRNA and protein were differentially expressed in PC-1.0 and PC-1 cells. Claudin-23 expression was induced in a PC-1.0 subclone expressing mitogen-activated protein kinase kinase (MEK)-1 short-hairpin RNA (shRNA) and claudin-23 was redistributed in a PC-1.0 subclone expressing MEK2 shRNA. Furthermore, these MEK2 shRNA-expressing PC-1.0 cells aggregated and formed island-like cell colonies. By contrast, the addition of dissociation factor-conditioned medium significantly reduced claudin-23 mRNA and protein expression in PC-1 cells. The present results indicate that claudin-23 is involved in the regulation of pancreatic cancer cell dissociation through changes in gene expression and intracellular localisation. In addition, claudin-23 expression is possibly correlated with the activation of the MEK signalling pathway during pancreatic cancer cell dissociation. Claudin-23 may thus serve as a new target for molecular therapies to prevent pancreatic cancer invasion and metastasis.

Genomic analysis of invasion-metastasis-related factors in pancreatic cancer cells.

Pancreatic cancer is known to be an extremely lethal neoplasm, one of the reasons being that pancreatic cancer itself has an extremely high potential of invasion-metastasis. In our previous study, two pancreatic cancer cell lines with a different potential for invasion-metastasis, PC-1 with a low potential and PC-1.0 with a high potential of invasion-metastasis after intrapancreatic transplantation, were established in a Syrian golden hamster. To determine the invasion-metastasis-related factors, a cDNA microarray that represented a set of 27,000 genes was hybridized with a labeled cDNA probe and screened for molecular profiling analysis. Furthermore, Gene Ontology and Pathway differential expression of candidate genes was further validated using RT-PCR. One hundred and forty-one differentially expressed genes (>3.0-fold change) were identified in the present study, including 46 up-regulated genes (e.g., nup107, tjp-2 and MMP-13) and 95 down-regulated genes (e.g., Spc21, plau and CD44) in the PC-1.0 cells. Our present results suggest that a highly organized and structured process of tumor invasion-metastasis exists in the pancreas. Analysis of gene expression profiles by cDNA microarray provides useful information for clarifying the mechanism underlying this invasion and metastasis. Furthermore, the identification of invasion-metastasis-specific genes may allow us to develop new therapeutic and diagnostic targets for the invasion-metastasis of pancreatic cancer.

Study of 5-Aza-CdR on transcription regulation of RASSF1A gene in the BIU87 cell line.

OBJECTIVES: To investigate the effect of 5-Aza-CdR on methylation and expression of RASSF1A gene in the human bladder cancer BIU87 cell line. METHODS: Cultured BIU87 cells were treated with increasing concentrations (0.1, 0.5, 1.0, 5.0 micromol/l) of 5-Aza-CdR. MTT was used to detect the proliferation of BIU87 cells. The methylation status and expression level of RASSF1A gene in BIU87 cells were analyzed by methylation-specific polymerase chain reaction and RT-PCR before and after treatment with 5-Aza-CdR. Meanwhile, Western blot was used to detect the changes of RASSF1A protein. RESULTS: In this study we found that the growth velocity of the BIU87 cell line was suppressed to various degrees after having been treated with different concentrations of 5-Aza-CdR, and the survival rate decreased with increasing 5- Aza-CdR concentrations. Besides, the methylation status of RASSF1A was obviously reversed and mRNA was re-expressed after treatment with 5-Aza-CdR. Expression of RASSF1A protein increased with increasing 5-Aza-CdR concentrations. CONCLUSIONS: Our results suggest that the tumor-suppressive effect of 5-Aza-CdR may result from reactivation of silenced RASSF1A through a demethylation function.