Volume 21,Issue 3,2012 Table of Contents

1 Sequential drug combination schemes of regional intra-arterial infusion for severe acute pancreatitis

ZHANG Qingshun , SUN Hongwei , ZHU Yefan , JIN Yuepeng , SUN Yunpeng , ZHOU Mengtao ,

2012, 21(3):249-252. DOI: 10.7659/j.issn.1005-6947.2012.03.001

[Abstract](533) [HTML](0) [PDF 407.60 K](728)

Abstract:
Objective: To study the feasibility of sequential regional intra-arterial infusion (RAI) and drug combination schemes in treatment of severe acute pancreatitis (SAP). Methods: The clinical data of 45 patients with SAP undergoing early RAI treatment were retrospectively analyzed. Results: The drugs used in all cases included: ⑴ Disebrin saline (25 U/mL, used as the infusion vehicle for all drugs); ⑵ 5-FU (250 mg/12 h, used in the first week for 7 days); ⑶ Somatostatin or its analogue (0.4 mg sandostatin or 6 mg somatostatin, daily, for about 2 weeks); ⑷ Antibiotics (continuous infusion in 12 cases with secondary infection and prophylactic use for 2 weeks in 23 cases without secondary infection). The selectively used medications included: ⑴ Ulinastatin (10 000-20 000 U/12 h, in 5 cases complicated with MODS); ⑵ Prostaglandin E1 (10 μg/12 h, in 4 cases who had microcirculatory disturbance). Of the whole group, 2 cases died and 45 cases were cured. Conclusion: RAI is a feasible and effective modality for SAP patients, but care must be taken for drug selection and compatibility during infusion.

2 Minimally invasive catheter drainage lessens the early inflammatory response of severe acute pancreatitis

ZHANG Chunxia , WANG Min , LONG Guanbao , ZHANG Jun , ZHENG Jianwei , SHEN Ming

2012, 21(3):253-256. DOI: 10.7659/j.issn.1005-6947.2012.03.002

[Abstract](586) [HTML](0) [PDF 401.95 K](774)

Abstract:

Objective: To investigate the therapeutic effect of minimally invasive catheter drainage on early inflammatory response of severe acute pancreatitis (SAP). Methods: Fifty-seven SAP patients with peritoneal effusion were divided into the observation group (29 cases with minimally invasive catheter drainage) and control group (28 cases with conventional drainage) using a random number table. Both groups underwent the same basic regimen of treatment, and then the observation group received the minimally invasive drainage while the control group had conventional ultrasound-guided catheter drainage. The inflammatory indexes responding to acute inflammatory such as TNF-α, IL-6, IL-8 and CRP were detected before and after treatment. Meanwhile, the recovery time of bowel function, and duration of systemic inflammatory response syndrome (SIRS) and incidence of multiple organ dysfunction syndrome (MODS) were observed. Results: The acute inflammatory response occurred in the both groups, and all the serum inflammatory indexes detected in the both groups tended to gradually decrease with different degrees. The levels of TNF-α, IL-6 and CRP on day 3 and 7, and the level of IL-8 on day 7 after drainage in the observation group were significantly lower than those of the control group (all P<0.05). The recovery time of bowel function and the SIRS duration of the observation group were shorter than those of the control group (both P<0.05). Furthermore, the incidence of MODS of the observation group (13.8%) was also significantly lower than that of the control group (28.6%) (P<0.01). Conclusion: Minimally invasive catheter drainage for SAP can lessen the early inflammatory response, accelerate bowel function recovery, and reduce the incidence of MODS.

3 B ultrasound-guided percutaneous catheter drainage for local complications of severe acute pancreatitis

CHEN Xiutao , ZOU Deping , HE Tieying , LIN Hai , HAN Wei , CHEN Qilong

2012, 21(3):257-261. DOI: 10.7659/j.issn.1005-6947.2012.03.003

[Abstract](525) [HTML](0) [PDF 570.40 K](782)

Abstract:
Objective: To assess the clinical efficacy of B ultrasound-guided percutaneous catheter drainage (PCD) for local complications of severe acute pancreatitis (SAP). Methods: The clinical data of 42 SAP patients with local complications undergoing B ultrasound-guided PCD from January 2006 to October 2009 in our hospital were retrospectively analyzed. Of the patients, 14 cases were complicated with acute fluid collection, 12 cases with sterile pancreatic necrosis, 9 cases with infected pancreatic necrosis, 4 cases with pancreatic abscess, 1 case with encysted infected necrosis and 2 cases with pancreatic pseudocysts. Microbiological examination was performed to determine whether the puncture fluid was associated with infection or not, and the clinical symptoms, drainage effect and imaging changes after PCD were observed. Results: Of the 42 patients, the 14 cases with acute fluid collection were all cured, but 2 of them developed peripancreatic infection and one case had an enterocutaneous fistula, but no death occurred; in the 12 cases with sterile pancreatic necrosis, 9 cases were cured (75%), 3 cases developed pancreatic infection and then underwent operation, 1 of whom died; in the 9 cases with infected pancreatic necrosis, 2 cases were cured and 4 cases underwent operation due to poor drainage, 2 of whom died and 3 declined treatment; the single case with encysted infected necrosis developed intracystic bleeding after PCD and died after emergency surgery; in the 4 cases of pancreatic abscess, 1 case was cured, 3 cases were converted to operation and no death occurred; the 2 cases with pancreatic pseudocysts were successfully drained and the catheters were removed 1 and 2 months later, respectively. Conclusion: B ultrasound-guided PCD is a safe and easily handled procedure, and it plays various roles in treating different SAP local complications. It avoids conventional surgical intervention for certain patients.

4 Alteration of ATP level in CD4+ T lymphocytes during infection stage of severe acute pancreatitis

HOU Zhenyu , CUI Naiqiang , ZHANG Jing , ZHANG Hongtao , GU Kaikai

2012, 21(3):262-266. DOI: 10.7659/j.issn.1005-6947.2012.03.004

[Abstract](584) [HTML](0) [PDF 401.48 K](763)

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Objective: To investigate the relations of the ATP level in the CD4+ T lymphocytes during the infection stage of severe acute pancreatitis (SAP). Methods: Forty-two SAP patients (SAP group) admitted to Nankai Hospital and 36 healthy volunteers (control group) were enrolled in this study. The ATP value in the CD4+ T lymphocytes of the SAP group were measured by ImmuKnowTM assay on day 1, 4, 7, 14 and 21 after admission and the control subjects underwent the same assessment at matched intervals. Afterwards, according to whether the patients entered the infection stage or not, the SAP group was further divided into the infection group (18 cases) and non-infection group (24 cases). The ATP level variations among the 3 groups were analyzed and compared, and the receiver operating characteristic curve was used to assess the value of using the ATP level alteration to estimate the secondary infection of SAP. Results: The ATP in the CD4+ T lymphocytes of the control group maintained a consistent level. The ATP levels of the two SAP groups altered in a roughly parallel pattern, both which increased significantly compared to the control group on day 1 and 4 after their hospitalization (P<0.05), but declined significantly on day 7 and reached the lowest values on day 14, and then picked up gradually. The decreasing extent of the ATP level of the infection group was greater than that of the non-infection group (P<0.05), and the ATP level of the non-infection group was approximately close to that of the control group but the infection group was still significantly lower than the control group (P<0.05). ROC curve analysis showed that the SAP patients would experience an increased risk of secondary infection when their ATP level in the CD4+ T lymphocytes deceased (<151.55 ng/mL), and the sensitivity and specificity of using the ATP level alteration to estimate the secondary infection of SAP were 0.810 and 0.605, respectively. Conclusion: The ATP level in CD4+ cells can relatively reflect the overall cellular immunological competence and the risk to secondary infection for SAP patients.

5 Effect of GdCl3 pretreatment on CYLD and NF-κB in alveolar macrophages of rats with lung injury secondary to acute pancreatitis

LIU Limin , MA Ruiqing , YAN Wenmao , CHENG Shi

2012, 21(3):267-271. DOI: 10.7659/j.issn.1005-6947.2012.03.005

[Abstract](489) [HTML](0) [PDF 933.63 K](879)

Abstract:
Objective: To investigate the effect of GdCl3 pretreatment on the tumor suppressor CYLD and NF-κB in alveolar macrophages (AMs) of rats with acute lung injury induced by acute necrotizing pancreatitis (ANP), so as to explore the role of CYLD in acute lung injury secondary to ANP. Methods: Thirty-six SD rats were equally randomized into the normal control group, ANP group and GdCl3 pretreatment group. The ANP model was established by retrograde injection of 5% sodium taurocholate into the biliopancreatic duct and the GdCl3 pretreatment group were injected with GdCl3 (10 mg/kg) through tail vein 30 min prior to model establishment. Animals were sacrificed 6 h after ANP induction, and then the AMs were harvested via bronchoalveolar lavage. The contents of TNF-α and IL-1β in bronchoalveolar lavage fluid (BALF) were detected, and the activation levels of NF-κB and CYLD in AMs were determined by Western blot analysis. The myeloperoxidase (MPO) activity levels in the lung tissues were measured and pathological examination of the lung tissues was performed. Results: No pathological change was found in lung tissues of the normal control group, while the lung tissues of both the ANP and GdCl3 pretreatment group showed marked pathological changes such as congestion, edema and accumulation of inflammatory exudates, but these changes of the GdCl3 pretreatment group were relatively mild compared with the ANP group. The MPO activity level in the lung tissues, and the contents of TNF-α and IL-1β in the BALF were all significantly increased in the ANP group compared with the normal control group (all P<0.05). The relative expression levels of NF-κB in the normal control group, ANP group and GdCl3 pretreatment group were 0.08±0.03, 0.18±0.06 and 0.11±0.04, and the relative expression levels of CYLD of the three groups were 0.32±0.09, 0.15±0.05 and 0.27±0.07, respectively. There were negative correlations between the expression of NF-κB and CYLD in the AMs of the ANP group and GdCl3 pretreatment group (r=–0.708 and r=–0.571, both P<0.05). Conclusion: There is reduced CYLD expression and activated NF-κB expression in the impaired lung tissue associated with ANP. GdCl3 can up-regulate the CYLD expression and inhibit the NF-κB activation, thereby ameliorate the lung injury secondary to ANP.

6 Effect of PDTC on acute lung injury secondary to acute necrotizing pancreatitis in rats

MA Ruiqing , LIU Limin , YAN Wenmao , CHENG Shi

2012, 21(3):272-276. DOI: 10.7659/j.issn.1005-6947.2012.03.006

[Abstract](551) [HTML](0) [PDF 1.04 M](983)

Abstract:
Objective: To investigate the effect of pyrrolidine dithiocarbamate (PDTC) on acute lung injury secondary to acute necrotizing pancreatitis (ANP) in rats. Methods: Thirty-six adult SD rats were equally randomized into the sham operation group, ANP group and ANP+PDTC pretreatment group. ANP model was induced by retrograde injection of 5% sodium taurocholate into biliopancreatic duct, and the animals of the PDTC pretreatment group were intraperitoneally injected with PDTC (30 mg/kg) l hour prior to ANP induction. All the animals were sacrificed 6 hours after model establishment, the alveolar macrophages (AMs) were harvested via bronchoalveolar lavage (BAL), and then the apoptosis of AMs was detected by flow cytometer and the activation levels of NF-κB and CYLD in AMs was determined by immunohistochemistry and Western blot method. The contents of TNF-α and IL-1β in the bronchoalveolar lavage fluid (BALF) were also detected. Meanwhile, the myeloperoxidase (MPO) levels of the lung tissues were measured, and pathological assessment of the lung tissues was performed. Results: No pathological change was noted in lung tissues of the sham operation group, while the lung tissues of both the ANP and PDTC pretreatment group showed marked pathological changes such as congestion, edema and accumulation of inflammatory exudates, but these changes of the PDTC pretreatment group were relatively mild compared with those of the ANP group. The MPO activity in the lung tissues, and the contents of TNF-α and IL-1β in the BALF were all significantly increased in the ANP group compared with the sham operation group (all P<0.05), while the elevations of the above parameters were markedly inhibited in the PDTC group and their differences with the ANP group had statistical significance (all P<0.05). The apoptosis rates of AMs of the sham operation group, ANP group and PDTC group were (3.47±1.45)%, (1.16±0.31)% and (1.80±0.60)% respectively, and the differences among the groups had statistical significance (all P<0.05). The immunohistochemical staining indicated that the NF-κB in the AMs of the sham operation group, ANP group and PDTC group presented weak positive, strong positive and moderate positive expression, respectively. The relative expression levels of NF-κB of the sham operation group, ANP group and PDTC pretreatment group were 0.08±0.03, 0.18±0.06 and 0.13±0.04 respectively, and the differences among the groups had statistical significance (all P<0.05). The relative expression levels of CYLD of the three groups were 0.32±0.09, 0.15±0.05 and 0.26±0.08 respectively, in which there was statistical significant difference between the sham operation group and ANP group (P<0.05) and no significant difference between the sham operation group and PDTC pretreatment group (P>0.05). There were negative correlations between the expression of NF-κB and CYLD in the AMs of the ANP group and PDTC pretreatment group (r=–0.708 and r=–0.481, both P<0.05). Conclusion: PDTC can induce the apoptosis of AMs by inhibiting NF-κB activation and enhancing the expression of NF-κB negative regulator CYLD, and thereby ameliorate the lung injury secondary to ANP.

7 Impact of PI3Kγ gene knockout on acinar cells in mice with acute pancreatitis

JIA Wenzhuo , SUN Jianhua , YU Tao , XIAO Gang

2012, 21(3):277-282. DOI: 10.7659/j.issn.1005-6947.2012.03.007

[Abstract](581) [HTML](0) [PDF 1.20 M](815)

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Objective: To observe the effect of PI3Kγ gene knockout on the extent of the pancreatic lesion, acinar cell function and HSP70 protein expression level of mice with acute pancreatitis (AP). Methods: The male wild-type (WT) C57BL/6 mice and PI3Kγ gene knockout (KO) mice were randomly divided into control group and AP group with 12 mice in each group. The in vivo AP model was induced by intraperitoneal injections of cerulean and mice of the control group were subjected to exactly the same regimen of saline injections. In addition, the pancreatic acini were isolated from another two different sets of mice (8 per set), and then the acinar cells were stimulated with CCK-8 to prepare an in vitro AP model. Control cells were treated with DMSO instead of CCK-8. Pathological changes of the pancreatic tissues were assessed, and the serum level of amylase, trypsin activity in pancreatic tissues and acinar cells, and level amylase release from the acinar cells were measured. The HSP70 protein expressions in pancreatic tissues and acinar cells were determined by Western blot analysis. Results: In pathological observation, the pancreatic tissues from the control groups of both types of mice showed no abnormality, while both AP groups presented varying degrees of edema, necrosis and hemorrhage. The quantitative analysis showed that the number of necrotic acinar cells and vacuoles of the KO mice were significantly less than those of the WT mice (both P<0.05). There were no significant differences in trypsin activity of the pancreatic tissues and isolated acinar cells between the two control groups (both P>0.05), but the trypsin activity of the pancreatic tissues and isolated acinar cells of the KO mice were significantly lower than those of the WT mice in the AP groups (in vivo and in vitro) (both P<0.05). No statistical differences were noted in serum amylase level and acinar cell amylase release curve between the two types of mice (both P>0.05). Compared with the control groups, the HSP70 protein expressions in both pancreatic tissues and acinar cells increased obviously in AP groups (in vivo and in vitro), in which the HSP70 expression levels of the KO mice were significantly higher than those of the WT mice (both P<0.05). Conclusion: PI3Kγ may promote acinar necrosis in acute pancreatitis by down-regulating HSP70 protein expressions and enhancing activation of trypsinogen, but it has no obvious effect on amylase secretion.

8 Protective effect of curcumin for severe acute pancreatitis in rats and its mechanism

LIU Jing , HUANG Li , HU Xiaosong , ZHANG You ju , PENG Lan , WANG Dong

2012, 21(3):283-289. DOI: 10.7659/j.issn.1005-6947.2012.03.008

[Abstract](690) [HTML](0) [PDF 2.21 M](925)

Abstract:
Objective: To invesigate the protective effect of curcumin for severe acute pancreatits and its possible mechanism. Methods: Fifty-four SD rats were equally randomized into the sham operation group, SAP model group (SAP group) and curcumin pretreatment + SAP group (curcumin pretreatment group). The SAP model was induced by retrograde cholangiopancreatic duct injection of 5% sodium taurocholate. At 3, 6 and 12 hours after surgery, the ascites volume and the following observation parameters of each group were determined: these included the serum levels of amylase (AMY), IL-6 and TNF-α, and the pathological impairment and scoring of the pancreatic tissues as well as the expression of NF-κB p65 and TLR4 in the pancreatic tissues. Results: The ascites volume and serum levels of AMY, IL-6 and TNF-α in both the SAP group and curcumin pretreatment group were markedly increased at each observation time point compared with the sham operation group, especially at 6 and 12 hours, and the differences between them had statistical significance (all P<0.01). Except for the sham operation group, both the SAP group and curcumin pretreatment group exhibited the typical pathological changes of SAP, while the pathological changes in the curcumin pretreatment group at each time point were all markedly milder than those in the SAP group and the Schmidt scores at the 6- and 12-h time points of the curcumin pretreatment group were all significantly lower than those of the SAP group (both P<0.05). The expression levels of NF-κB p65 and TLR4 in the SAP group and curcumin pretreatment group were markedly higher than those of the sham operation group but both expressions of the curcumin pretreatment group were lower than those of the SAP group. Conclusion: Curcumin has protective effect for SAP, and the possible mechanism may be associated with its inhibition of the activation of TLR4 and NF-κB, thereby alleviating the inflammatory response and pancreatic injury.

9 Local arterial infusion with low molecular weight heparin in treatment of severe acute pancreatitis: an experimental study

ZHANG Shilong , TU Qiaoli , SHI Bin

2012, 21(3):290-294. DOI: 10.7659/j.issn.1005-6947.2012.03.009

[Abstract](603) [HTML](0) [PDF 1003.74 K](806)

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Objective: To investigate the therapeutic effect of local arterial infusion (LAI) with low molecular weight heparin (LMWH) on severe acute pancreatitis in rabbits and its effect on the serum levels of TNF-α, IL-6 and IL-10. Methods: Twenty-four healthy adult rabbits were randomized into the sham operation group, SAP model group, SAP plus LMWH intravenous injection group (IV group) and SAP plus LMWH LAI group (LAI group). SAP model was established by injection with 5% sodium taurocholate under pancreatic capsule, and the rabbits of the two treatment groups were given LMWH (300 IU/kg) by intravenous injection or LAI, respectively. The serum levels of TNF-α, IL-6 and IL-10 in rabbits of each group were detected at 0.5, 3, 6 and 12 h after surgery and the pathological changes of pancreatic tissues were also assessed. Results: After surgery, the serum levels of TNF-α and IL-6 of the sham operation group were slowly elevated, while those of the remaining groups were markedly increased within 0.5 to 6 h, that all had statistical differences compared with the sham operation group (P<0.05 or P<0.01), and then gradually declined. The serum levels of TNF-α and IL-6 of the IV group and LAI group were all significantly lower than those of the SAP group at each observation time point (P<0.05 or P<0.01) and, further, the decreasing degrees of the two factors in the LAI group were more pronounced than those in the IV group (P<0.05 or P<0.01). The level of IL-10 of the sham operation group had no obvious alteration over the observation period after surgery, while it was markedly decreased in the SAP group at each time point after 6 h and all had statistical differences compared with the sham operation group (all P<0.01). The level of IL-10 of the IV and LAI group markedly increased with statistical differences compared with the SAP group (P<0.05 or P<0.01) and, furthermore, its increasing degree in the LAI group was more pronounced than that in the IV group (P<0.01). Except for the sham operation group, all the pancreatic tissues of the other groups exhibited pathological characteristics of SAP with varying degrees, among which the most severe was in the SAP group, less in the IV group, and least in the LAI group. Conclusion: LMWH can decrease the TNF-α and IL-6 levels, and increase the IL-10 level in rabbits with SAP. LMWH has therapeutic effect on SAP and its local arterial injection is more effective than intravenous injection.

10 Therapeutic effect of glycyrrhizin for severe acute pancreatitis in rats

FAN Qinqiao , CHEN Xiaoxue , YANG Zheng , LIU Bo , YANG Genhui , CHEN Shuwei , ZHAO Ch

2012, 21(3):295-299. DOI: 10.7659/j.issn.1005-6947.2012.03.010

[Abstract](757) [HTML](0) [PDF 653.34 K](742)

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Objective: To investigete the therapeutic effect of glycyrrhizin on severe acute pancreatitis (SAP) in rats. Methods: Rats were equally randomized into sham operation group, SAP group and SAP plus glycyrrhizin treatment group (treatment group). The SAP model was induced by retrograde cholangiopancreatic duct injection of 5% sodium taurocholate. The postoperative survival time and the serum levels of amylase, IL-1β, IL-6 and TNF-α, as well as the pathological scores of pancreatic tissue of each group at the predefined time points after surgery were determined and compared. Results: No death occurred in the sham operation group during the observation period, while the average survival time of the SAP group and treatment group was (28.50±17.82) and (41.50±17.59) hours respectively, and the difference between them had statistical significance (P<0.05). Compared with the sham operation group, the serum levels of amylase, TNF-α, IL-1β and IL-6 of the SAP group and treatment group at each observation point were all significantly increased (all P<0.05), but the elevated levels of the above parameters in the treatment group were all significantly lower than those in the SAP group (all P<0.05). Except for the sham operation group, both the SAP group and treatment group presented the pathological features of SAP, but to a different extent; the pathological change in the treatment group was relatively mild and its pathological scores at each time points were also significantly lower than those of the SAP group (all P<0.05). Conclusion: Glycyrrhizin has a definite therapeutic effect on SAP in rats.

11 Protective effect of salvianolate on myocardial injury secondary to acute necrotizing pancreatitis in rats

CHEN Shu , HUANG Wukui , XIAOKAITI·Yibulayin , ZHU Gongbing , YANG Xinwen , PAER

2012, 21(3):300-303. DOI: 10.7659/j.issn.1005-6947.2012.03.011

[Abstract](604) [HTML](0) [PDF 578.80 K](702)

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Objective: To investigate the protective effect of salvianolate intravenous injection on the myocardial impairment secondary to acute necrotizing pancreatitis (ANP) in rats. Methods: Forty-two healthy male SD rats were equally randomized into the control group, ANP model group and salvianolate treatment group. The ANP model was induced by intraperitoneal injection of 20% L-Arginine solution and rats of the salvianolate treatment group were given salvianolate (100 mg/kg) injection through tail veil 10 min after ANP induction. All rats were killed 48 h after model establishment, and the serum amylase activity, contents of cardiac troponin I, and phospholipase A2 in myocardial tissues were detected. The pathological examination of the myocardial tissues was performed. Results: Compared with the control group, the activated serum amylase, and serum contents of cardiac troponin I and myocardial phospholipase A2 levels of both the ANP model group and salvianolate treatment group were significantly increased (all P<0.05), but these parameters of the salvianolate treatment group were all lower than those of the ANP model group (all P<0.05). No pathological change was noted in myocardial tissues of the control group, while the myocardial tissues of the ANP model group showed focal inflammatory infiltration with occasional myocyte rupture and hemorrhage, and the salvianolate treatment group exhibited slight inflammatory infiltration in interstitial tissue of myocardium. Conclusion: Salvianolate injection has protective effect on myocardial injury secondary to ANP.

12 Influence of stable inhibition of XIAP and survivin expression on biological characteristics of pancreatic cancer cells

ZAI Hongyan , JIANG Chun , YI Xiaoping , DENG Gongping , LI Yixiong

2012, 21(3):304-311. DOI: 10.7659/j.issn.1005-6947.2012.03.012

[Abstract](419) [HTML](0) [PDF 1.12 M](833)

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Objective: To investigate the inhibitory effect of lentiviral vector-mediated RNA interference (RNAi) on XIAP (X-linked inhibitor of apoptosis protein) and survivin expression in human pancreatic cells and its effect on the proliferation, apoptosis and chemosensitivity of pancreatic cells. Methods: The pGCSIL-PUR and pGCSIL-NEO were used to construct the lentiviral vectors containing shRNA targeting XIAP and survivin gene, respectively, and the human pancreatic cancer SW1990 and Panc-1 cells were transfected with these lentiviruses. The cells were screened by puromycin and neomycin double selection and expanded to obtain the stably transfected cell lines. The XIAP and survivin expressions were determined by real-time PCR and Western blot, respectively. The proliferation and chemosensitivity of the cells were detected by MTT assay, and caspase-3/7 activity measurement and DAPI-staining were performed to assess cell apoptosis. Results: The stable SW1990 and Panc-1 cells with inhibition of XIAP and survivin expression were obtained after the effective interference targets of XIAP and survivin screening. MTT results showed that the proliferative abilities of both types of pancreatic cells significantly decreased after the suppression of XIAP or survivin expression, and the combination inhibition of the two genes exerted a strengthened effect. Although XIAP or survivin inhibition had no obvious effect on apoptosis of both types of pancreatic cells, they enhanced the sensitivities of both types of cells to the chemotherapy agents (5-FU and gemcitabine), and this effect was also strengthened by their combination. Conclusion: The lentiviral vector-mediated RNAi targeting XIAP and survivin can effectively inhibit XIAP and survivin expression, and also inhibit proliferation and enhance chemosensitivity of pancreatic cells. The combination inhibition of both genes can exert a synergistic effect.

13 Preliminary study of microRNA expression profiles in human pancreatic cancer

ZHENG Yansong , XIE Rongzhen , SHI Zheng

2012, 21(3):312-316. DOI: 10.7659/j.issn.1005-6947.2012.03.013

[Abstract](373) [HTML](0) [PDF 808.05 K](786)

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Objective: To investigate the microRNAs (miRNAs) expression profiles in human pancreatic cancer, so as to provide a basis for further exploring the role of miRNAs in the molecular mechanism that leads to the occurrence and development of pancreatic cancer. Methods: The differentially expressed miRNAs between the pancreatic cancer tissue and adjacent normal pancreatic tissue were analyzed by microRNA array, and then two of the differentially expressed miRNA were selected to perform quantitative real time PCR (qRT-PCR) assay, so as to validate the microRNA array results. Results: Compared with the normal pancreatic tissues, 15 miRNAs were more than 1.5-fold up-regulated, and 11 miRNAs were more than 1.5-fold down-regulated in pancreatic cancer tissues. The values of relative quantification (RQ) of miR-10b and miR-21 in pancreatic cancer tissues and their adjacent normal tissues from 8 cases detected by qRT-PCR were 0.0743±0.0222 vs. 0.0287±0.0129, and 0.3062±0.1117 vs. 0.0240±0.0137, respectively (both P<0.05), and these were consistent with the microRNA array results. Conclusion: The 26 differentially expressed miRNAs screened by microRNA array may contribute to the occurrence and development of pancreatic cancer, and their respective roles in this disease are worthy of further investigation.

14 Survivin gene inhibition in pancreatic cancer PANC-1 cells by RNAi vectors

CHEN Jianyun , CUI Haining

2012, 21(3):317-321. DOI: 10.7659/j.issn.1005-6947.2012.03.014

[Abstract](419) [HTML](0) [PDF 671.80 K](717)

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Objective: To observe the inhibitory effect of survivin specific RNA interference (RNAi) vectors on the survivin mRNA and protein expression of pancreatic cancer PANC-1 cells. Methods: The plasmid vectors encoding U6 promoter-driven siRNA against survivin and the negative control plasmid were transfected into the pancreatic carcinoma PANC-1 cells, respectively. The mRNA and protein expression of survivin were detected by RT-PCR and Western blot, respectively. Results: In the PANC-1 cells transfected with RNAi vectors against survivin, the 24 h and 48 h inhibitory ratios on survivin mRNA expression were (52.67± 3.51)% and (75.33±3.06)%, and those on protein expression were (58.00±3.61)% and (76.67±4.73)%, respectively. All the differences had statistical significance compared with the negative control cells (all P<0.05). Conclusion: The RNAi vectors with U6 promoter can effectively inhibit the survivin expression in pancreatic carcinoma PANC-1 cells.

15 Effect of gene silencing of DNMT1 and DNMT3b on the methylation in the promoter region of p16 and RASSF1A gene in pancreatic carcinoma BxPC-3 cells

XIAO Weidong , LI Yong , Zou Yeqing , LI Xueming , CAI Jun , ZENG Linshan , HU W

2012, 21(3):322-326. DOI: 10.7659/j.issn.1005-6947.2012.03.015

[Abstract](438) [HTML](0) [PDF 397.37 K](713)

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Objective: To investigate the effect of gene silencing of DNMT1 and DNMT3b on methylation in the promoter region of p16 and RASSF1A gene in pancreatic carcinoma BxPC-3 cells. Methods: The pancreatic carcinoma BxPC-3 cells were divided into five groups, which included the DNMT1 interference group (transfected with DNMT1-siRNA), DNMT3b interference group (transfected with DNMT3b-siRNA), double interference group (transfected with DNMT1+DNMT3b-siRNA), negative control group (transfected negative-siRNA) and blank control group (transfected with lipofectamine). Forty-eight hours after transfection, the mRNA and protein expression of DNMT1 and DNMT3b were analyzed by real-time RT-PCR and Western blot, and the methylation status in the promoter region of p16 and RASSF1A gene was detected with methylation-specific PCR (MSP). Results: Compared with the negative or blank control group, the mRNA and protein expression levels of the targeted genes were all markedly down-regulated in each interference group (all P<0.01). The methylation status of p16 and RASSF1A gene was positive in both the blank and negative control group; the p16 gene was unmethylated and RASSF1A gene was partially methylated in DNMT1 interference group and double interference group; the p16 gene was partially methylated and RASSF1A gene showed methylation-positive state in DNMT3b interference group. Conclusion: DNMT1 interference has better effect than DNMT3b interference on demethylation in BxPC-3 cells, and the double knockdown of DNMT1 and DNMT3b exerts no synergistic action. DNMT1 could serve as an effective target for the demethylation therapy of pancreatic carcinoma.

16 Relevance of different anastomosis patterns on incidence of pancreatic fistula after Partington operation

FENG Liushun , SUN Zhong , HE Xiangjun , LI Jie , LIU Qi

2012, 21(3):327-329. DOI: 10.7659/j.issn.1005-6947.2012.03.016

[Abstract](540) [HTML](0) [PDF 333.57 K](759)

Abstract:
Objective: To investigate the relevance of different anastomosis patterns to the incidence of pancreatic fistula after Roux-en-Y pancreaticojejunostomy (PJ). Methods: The clinical data of 47 patients with chronic pancreatitis and associated dilation of the main pancreatic duct undergoing Roux-en-Y PJ from Augest 1999 to June 2011 were retrospectively analyzed. According to the different anastomosis patterns (continuous or interrupted Prolene sutures), the patients were divided into two groups, and then the incidence of pancreatic fistula and clinical outcomes of the two groups after surgery were analyzed, respectively. Results: No pancreatic fistula occurred in the 25 cases with continuous sutures, while 4 of the 22 cases with interrupted sutures developed pancreatic fistula, and the difference between the two group had statistical significance (P<0.05). The postoperative follow-up ranged from 3 to 5 years, and the abdominal pain was completely relieved in 46 cases. Conclusion: Interrupted suture is prone to developing pancreatic fistula after Roux-en-Y PJ. However, the continuous Prolene suture technique may reduce the incidence of pancreatic fistula and this procedure is also simple and easy to perform.

17 Major postoperative complications of pancreaticoduodenal resection in 442 cases

ZHANG Qiuxue , WANG Tiegong , LIU Ruhai , LI Xuefeng , YANG Dongshan , CHEN Xin , ZHAN

2012, 21(3):330-334. DOI: 10.7659/j.issn.1005-6947.2012.03.017

[Abstract](366) [HTML](0) [PDF 418.59 K](769)

Abstract:
Objective: To investigate the incidence of major postoperative complications after pancreatoduodenectomy (PD) and their prevention and control measures. Methods: The incidence of postoperative complications in 442 cases undergoing PD from August 1994 to December 2010 in our hospital was retrospectively studied. The cases were grouped according to different historical periods and different types of pancreatic-enteric anastomosis performed. Thirty-two cases undergoing pancreatic-enteric anastomosis by the invagination method before December 1998 were designated as group A, 305 cases undergoing end-to-side duct-to-mucosa pancreatojejunostomy after that time were assigned as group B, and 105 cases with binding invagination anastomosis were group C. The direct or indirect operation-related postoperative complications and mortality of each group were analyzed. Results: The total incidence of complications and mortality of the whole group was 29.9% and 2.3%, respectively. Comparison among the three groups showed that all the studied postoperative parameters of groups B and C were better than those of group A (all P<0.01), but the differences between group B and C had no statistical significance (all P>0.05). The incidence of direct operation related complications of group A, B and C was 43.8%, 6.6% and 6.7% (in which the incidence of pancreatic fistula was 28.1%, 3.6% and 2.9%), while the incidence of indirect operation related complications was 59.4%, 17.0% and 19.0% and the mortality rate was 21.9%, 0.7% and 1.0%, respectively. Conclusion: The prevalence of postoperative pancreatic fistula is related to the pancreaticojejunal anastomosis procedure. Expert surgical skill, meticulous technique of anastomosis and enhanced pre- and postoperative control measures are important factors for reducing complications and mortality after PD.

18 Diagnosis and management of insulinoma: a report of 72 cases

ZHAO Xinyang , SHEN Ming , WANG Chao , ZHENG Jianwei , XUE Xinbo

2012, 21(3):335-339. DOI: 10.7659/j.issn.1005-6947.2012.03.018

[Abstract](565) [HTML](0) [PDF 419.74 K](664)

Abstract:
Objective: To investigate the diagnosis and surgical treatment of insulinoma. Methods: The clinical data of 72 patients with insulinoma admitted to our hospital spanning more than 31 years were retrospectively analyzed. Results: Of the 72 patients, 84.72% had a typical Whipple’s triad, and the ratio of plasma immunoreactive insulin to glucose (IRI/G) was greater than 0.3 in 80.56%. The positive rates of preoperative niveau diagnosis were 78.13% by transabdominal ultrasonography, 60.97% by CT, 100% by pancreatic perfusion imaging of multislice spiral CT, 37.50% by MRI, 72.73% by endoscopic ultrasound and 28.57% by DSA, respectively. The diagnostic positive detection rate of intraoperative ultrasonography (IOUS) plus palpation was 92.31%. The diameters of 88.75% of the tumors were less than 2 cm, and 37.5% of tumors were located in the head and neck of the pancreas, 27.5% in the body, and 35.0% in the tail, and 81.58% of the patients had indications for regional enucleation of insulinoma. All of the 72 cases were confirmed as insulinoma by final pathology, of whom 65 (90.28%) were functional insulinoma, 7 (9.72%) were nonfunctional insulinoma, 4 (5.56%) were multiple insulinoma, 2 (2.78%) had malignant tendency, and 1 (1.39%) was combined with multiple endocrine neoplasia type 1 (MEN-1). Conclusion: Whipple’s triad and IRI/G>0.3 can be the main basis for the defining diagnosis of insulinoma. A combination of multiple examinations such as ultrasonography, CT, pancreatic perfusion imaging of multislice spiral CT, MRI, endoscopic ultrasound and DSA may be recommended before operation, and IOUS plus palpation is a simple and effective way for intraoperative localization. Regional enucleation of insulinoma is the best surgical approach for most insulinoma.

19 Diagnosis and surgical management of pancreatic duct stones: a report of 43 cases

YANG Zhaoxu , SONG Wenjie , HE Yong , CHEN Yong , DOU Kefeng

2012, 21(3):340-344. DOI: 10.7659/j.issn.1005-6947.2012.03.019

[Abstract](1199) [HTML](0) [PDF 472.90 K](778)

Abstract:
Objective: To investigate the diagnosis and surgical treatment of pancreatic duct stones. Methods: The clinical data of 43 patients undergoing surgical procedure for pancreatic duct stones during the past 6 years in our hospital were retrospectively analyzed. Results: The male-to-female ratio among the patients was 2:1. The main symptom of the patients was upper abdominal pain and some of them had accompanied lower back pain. The diagnosis of all cases was confirmed by imaging examinations. Thirty-four cases underwent pancreatic lithotomy with a side-to-side Roux-en-Y pancreaticojejunostomy (two cases had a synchronous resection of the body and tail of the pancreas), five cases underwent duodenum-preserving pancreatic head resection, and pylorus-preserving pancreaticoduodenectomy, classical Whipple procedure and resection of the body and tail of the pancreas with splenectomy were performed in one case each, respectively, and unresectable tumor was found in one case during surgical exploration. The period of follow-up ranged from 5 months to 6 years. Of the 43 patients, 23 cases had their abdominal pain completely alleviated and 18 cases had varying degrees of improvement. Conclusion: Imaging examination is the main modality for diagnosis of pancreatic duct stones, and the surgical procedure for this condition should be individualized to the specific patient. Pancreatic lithotomy with a side-to-side Roux-en-Y pancreaticojejunostomy is the main operative procedure for pancreatic duct stones, and other procedures such as duodenum-preserving pancreatic head resection or distal pancreatectomy may be recommended depending on the patient's situation.

20 Diagnosis and treatment of pancreatic cystic tumors

CHEN Meifu , LIU Jianming , LU Xinsheng

2012, 21(3):345-349. DOI: 10.7659/j.issn.1005-6947.2012.03.020

[Abstract](463) [HTML](0) [PDF 380.71 K](857)

Abstract:
Cystic tumors of the pancreas are relatively rare, and are often misdiagnosed or neglected in clinical practice due to slow growth, deep location and the lack of typical symptoms and signs. With the development of pancreatic surgery and imaging techniques in recent years, as well as the continued investigation of pancreatic cystic tumors, considerable progress has been achieved in this field. These have promoted the early detection, treatment planning, and choice of surgical procedure and estimating the prognosis for pancreatic cystic tumors. This paper reviews the advances in clinical diagnosis and treatment of these diseases.

21 Mechanism of immediate blood-mediated inflammatory reaction following islet cell transplantation

WANG Shenggang , ZHAO Zhongxin

2012, 21(3):350-353. DOI: 10.7659/j.issn.1005-6947.2012.03.021

[Abstract](535) [HTML](0) [PDF 363.89 K](794)

Abstract:
The immediate blood-mediated inflammatory reaction (IBMIR) will be triggered when islets come in direct contact with the recipient’s blood during islet cell transplantation, which causes the rapid loss of insulin secretion function of the islet cells. This paper addresses the problems involved in the occurrence mechanism of IBMIR, including the activation of the coagulation system and complement system, and the antibodies impact, and the roles of the inflammatory mediators and inflammatory cells infiltration as well as the glucose toxicity.

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Volume 21,Issue 3,2012 Table of Contents

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