Podoplanin (PDPN), being mucin-like transmembrane sialoglycoprotein, is expressed on lymphatic endothelial cells, with its significant role in the development of inflammation, separation of blood and lymphatic circulation, platelet aggregation, integrity of the renal filtration barrier and alveolar. In recent years, many researches have demonstrated that PDPN is overexpressed on the surface of some tumor cells. The interaction between PDPN and CLEC-2 plays an important role in the development of tumor growth, migration and transfer, therefore, anti-PDPN antibody offers a new direction for the treatment of tumor patients. This paper aims at reviewing the progress and application prospect of PDPN.

Objective To study the expression of aquaporins-4 (AQP4) in the brain tissue of rats with pancreatic encephalopathy (PE) induced by phospholipase A2 and to explore the role of aquaporins-4 in PE.Methods Twenty five healthy Wistar rats were randomized into 3 groups:blank group ( n =5),PE group (n =10 ) and control group (n =10 ).The experimental model was established in rats by injecting phospholipase A2 into carotid artery (0.1 ml/100 g body weight).Same amount of normal saline was used in the control group and no treatment was used in the blank group.One day later,the rats were sacrificed,then the measurement of brain tissue wet/dry (W/D) weight ratio was performed,and brain tissue was routinely pathologically examined,immunohistochemistry and Western blotting were performed in each group to detect the expression of aquaporins-4.Results There was no obvious brain tissue pathological change in the control group and blank group.Neurons in the brain tissue of PE rats presented with significant edema and ballooning degeneration,infiltration of inflammatory cells,leukocyte aggregation around the microvessels.The water contents in the brain tissue in the blank group and control group,PE group were (61.44 ±0.36)％,(63.20±0.32)％ and (78.33 ±0.24)％,and it was significantly higher in PE group than that in the control and blank group (P＜0.05).The expressions of aquaporins-4 in the brain tissue were 0.41 ±0.27,0.49 ±0.13,0.98 ±0.21,respectively,and it was significantly increased in PE group than that in the control and blank group (P ＜ 0.05 ).Conclusions Aquaporins-4 may play important roles in the pathogenesis of pancreatic encephalopathy.

Objective To investigate the analgesic efficacy and spinal neurotoxicity of intrathecal (IT) different doses of dexmedetomidine in rats. Methods Sixty male SD rats weighing 180-220 g were randomly divided into 5 groups ( n = 12 each): groupnormal control (group C); group IT normal saline (group N); different doses of dexmedetomidine groups received IT dexmedetomidine 0.75, 1.50 and 3.00 μg/kg respectively (groups D1.3). Paw withdrawal threshold to mechanical stimulation (PWMT)with yon Frey filaments and tail flick latency (TFL) to a thermal nociceptive stimulus were measured before (To, baseline) and at 30 or60 rin after IT dexmedetomidine or normal saline administration (T1, T2 ) and the percentage of the maximum possible effect ( MPE ) was calculated. Lumbar segment of the spinal cord ( L4-6 ) was removed for microscopic examination and determination of c-Fos expression (by immuno-histochemistry) at 7, 24 and 48 h after IT dexmedetomidine or normal saline administration. Results PWMT, TFL and the percentage of MPE were significantly increased after IT dexmedetomidine as compared with the baseline values at T0 in groups D1-3 ( P ＜ 0.05). PWMT was significantly higher at T1 and TFL and the percentage of MPE were higher at T2 in groups D1-3 than in groups C and N,and in group D3 than in groups D1,2 ( P ＜ 0.05). At 7,24 h after IT dexmedetomidine c-Fos protein expression was significantly higher in group D3 than in groups C and N( P ＜ 0.05). There was no significant difference in c-Fos expression at 48 h after IT dexmedetomidine between group D3 and groups C and N ( P ＞ 0.05 ). At 24 h after IT dexmedetomidine c-Fos protein expression was significantly higher in group D3 than in other 4 groups( P ＜ 0.05). Slight spinal cord injury was observed at 24 h after IT dexmedetomidine in group D3. Conclusion IT dexmedetomidine has antinociceptive effect. High dose dexmedetomidine IT can produce transient reversible toxicity to the spinal cord.

Objective To establish an experimental animal model of hypertriglyceridemic(HTG)panereatitis by using special lipoprotein lipase(LPL)deficient HTG heterozygous mice.Methods LPL deficient HTG heterozygous mice and wild type mice were divided into experiment group and control group,then each group was subdivided into 12 h,24 h subgroup.Acute pancreatitis(AP)was induced by caerulein intra-abdominal injection for 7 times(50μg/kg)at the interval of 1 h;the mice in the control group received same amount of normal ssline.The serum level of TG,amylase was determined,and morphologic changes were scored.Results The serum level of TG in LPL deficient HTG heterozygous mice was(3.55±0.27)mmol/L,which was significantly higher than that of wild type mice[(0.94±0.18)mmol/L,P＜0.05].The serum level of TG and amylase in heterozygous mice at 12 h was(3.55±0.27)mmol/L and(3685±484)U/L,which was significantly higher than those in wild type mice[(0.92±0.11)mmol/L and(2501±410)U/L,P＜0.05].The pancreatic tissue edema,necrosis,bleeding and inflammatory cell infiltration score was 3.94 ±0.21,3.94±0.21,1.84±0.25 and 1.84±0.25 in heterozygous mice,which was significantly higher than that of wild type mice(3.06±0.01,2.52±0.51,0.46±0.22 and 0.58±0.38,P＜0.05).Conclusions The serum level of TG was moderately and stably elevated in heterozygous mice.The mice developed more severe panereatitis after caemlein induction.which was an ideal experimental model for study of mechanism of HTG pancreatitis.

Objective To investigate the expression of chemokine receptor (CXCR)4 in human pancreatic cancer cell lines,and its association with proliferation,adhesion and invasion of pancreatic cancer cells.Methods The CXCR4 mRNA and protein in three pancreatic cancer cell lines were detected by RT-PCR and Western blotting,respectively.Confocal microscopy was used to detect the fluorescence intensity induced by SDF-lα in AsPC-1 cells.MTT test was performed to study the proliferation of pancreatic cancer cells.The invasive ability of pancreatic cell lines was determined by transwell invasion assay kit and the adhesive ability was detected by cell adhesive test in vitro.Results There were expressions of CXCR4 mRNA and protein in different extent in three pancreatic cancer cell lines.The strong expression was seen in AsPC-1 cell line,but weak expression in SW1990 cell line.The CXCR4 was functional expressed on AsPC-1 ceils.SDF-1α improved the proliferation,adhesion and invasion of three pancreatic cancer cell lines,especially in AsPC-1 cell line,while the proliferation in SW1990 cell line was weak.But all above effects of the SDF-1α could be inhibited by AMD3100.Conclasions CXCR4 mRNA and protein were expressed in pancreatic cancer cell lines.The efficacy that SDF-1 can increase the invasive ability of pancreatic cancer ceils through SDF-1/CXCR4 axis is closely related to the expression of CXCR4.

Objective To investigate the expressions of stromal cell-derived factor1 (SDF-1) and its receptor CXCR4 in human pancreatic carcinoma tissues, cell lines and pancreatic stellate cells (PSCs). Methods SDF-1 /CXCR4 and α-SMA protein expression levels and SDF-1 and CXCR4 protein in AsPC-1 and PSCs were detected by immunohistochemical staining in 10 cases of peri-eareinoma tissues and 37 cases of pancreatic carcinoma tissues. The expression of SDF-1 and CXCR4 mRNA in pancreatic cell lines and PSCs were detected by RT-PCR. Results CXCR4 were positively expressed in all pancreatic carcinoma tissues [(+) 8 cases, (+ +) 20 cases, (+ + +) 9 cases]; and there were no CXCR4 expression in 2 cases of pori-careinoma tissues and CXCR4 were positively expressed in 8 cases [(+) 7 cases, (+ +) 1 cases]; with significant difference (P <0.01). And the expression of SDF-1 protein in carcinomatous stromal tissues was much higher than that in the stromal tissues of peri-carcinoma (P < 0.01), and it corresponded to the increase of α-SMA expression. The CXCR4 protein expression was found in AsPC-1, while SDF-1 protein expression was found in PSC. The CXCR4 mRNA expression was found in AsPC-1, BxPC3, SW1990, while there were no SDF-1 mRNA expression in the above mentioned cell lines. SDF-1 mRNA was expressed in PSC and CXCR4 mRNA was weakly expressed in PSC. Conclusions The expression of CXCR4 mRNA and protein were found in pancreatic carcinoma specimens and cell lines. PSCs expressed SDF-1 mRNA and protein. PSCs may promote the invasion and metastasis through SDF-1/CXCR4 axis.

Objective To examine the expression of CD9 protein in pancreatic cancer tissues and adjacent tissues,and to analyze its relation with the progress and prognosis of pancreatic cancer.Methods From September 2005 to December 2009,surgical resected cancer tissues and adjacent tissues of 90 patients with pancreatic cancer and their clinical data were collected.The expression of CD9 protein in pancreatic cancer tissues and adjacent tissues was detected by immunohistochemistry,and its relationship with clinicopathological features was analyzed.Chi-square test was performed for comparison of ratios between groups.Overall survival (OS) analysis of 90 patients after surgery was performed.Results The high expression rate of CD9 protein (64.4％,58/90) in cancer tissue was significantly higher than that in cancer adjacent tissue (45.6％,41/90),the difference has statistically significant (χ2 =6.847,P＜0.05).CD9 protein was highly expressed in most of pancreatic cancer tissue which was well differentiated or without lymph node metastasis (74.6％ (50/67) vs 39.1％ (9/23),χz =9.554,P＜0.01; 50.0％(17/34) vs 73.2％(41/56),χ2 =5.856,P＜0.05 respectively).However,the expression of CD9 was not correlated with gender and age (both P＞0.05).OS and progression-free survival (PFS) of the patients with CD9 highly expressed were significantly longer than those with low expression of CD9 (median OS:33.0 months vs 7.0 months,χ2 =15.400 P＜0.01.Median PFS:30.5 months vs 5.0 months,χ2 =13.750,P＜0.01).Conclusion CD9 protein is a kind of protein related with the invasive ability of pancreatic cancer,which may play a role in progression and metastasis of pancreatic cancer and can help to determine the prognosis to a certain extent.

Objective To investigate the role of pancreatic β cell on pancreatic regeneration following experimental acute pancreatitis.Methods Eighty-seven SD male rats were randomly divided into four groups:control group ( n =15 ),STZ group ( n =24),L-Arg group ( n =24 ),STZ + Arg group ( n =24).60 mg/kg of STZ was administrated by intraperitoneal injection to induce the diabetes model.2.5 g/kg body weight of LArg was administrated by intraperitoneal injection to induce the acute pancreatitis model.The rats were sacrificed 1,3,5,7 d later and the serum levels of amylase and glucose were measured.Relative pancreatic weight (pancreatic weight/body weight) were measured.Pancreatic tissue underwent routine pathologic examination,and the percentage of area of necrosis and tissue transformation was calculated.The expression of Reg4 and insulin was performed by immunofluorescence.Results Serum level of glucose significantly increased after STZ injection.After L-Arg injection,serum level of amylase significantly increased,and there was pancreatic tissue edema,necrosis,infiltration of inflammatory cells,which suggested the successful model induction.The percentage of area of necrosis in STZ + L-Arg group was (71.6 ± 6.0) ％ at the 3rd day,which were significantly higher than (42.3 ± 4.0 ) ％ in L-Arg group; the percentage of area of transformation was (45.6 ± 5.4) ％,which were significantly lower than (78.5 ± 6.4) ％ in L-Arg group.Expression of Reg4 in pancreatic islets of STZ + L-Arg group was significantly lower than those in L-Arg group.Conclusions STZ impairs pancreatic β cells,aggravates pancreatic damage following L-arginine induced pancreatitis and inhibits pancreatic regeneration.

Objective Metabonomics method based gas chromatography-mass spectrometry (GC/MS)were used to analyze the urine samples of patients with hyperlipidemic pancreatitis (HLP) to describe the characteristics of metabolism changes of HLP,identify potential biomarkers,and investigate the role of metabonomics study in the management of AP.Methods 24 patients of HLP and 40 age,sex matched volunteers were enrolled and their urine samples were collected.The urine samples underwent preparation,derivation and GC/MS analysis,Orthogonal-Projection to Latent Structures-Discriminant Analysis (OPLS-DA)were performed to detect the metabolic profile difference between the HLP and control group.Results HLP patients can be precisely distinguished from healthy controls.21 metabolites (credibility ＞ 700 ) were identified using the reference compounds available in the libraries of NIST and Wiley.It was identified that levels of nicotinic acid,aconitie acid,citric acid,hippurie acid,hydroxyphenylacetic acid,hydroxyphenylpropionicacid were decreased,while the levels of tryptophan,tyrosine,tyramine,16-hexadecanoic acid,18octadecanoie acid were increased.It was also suggested that there was change in tricarboxylic acid cycle and gut bacterial flora,as well as fat metabolism and metabolism of amino acid.Conclusions There are differences between healthy controls and HLP patients in the term of GC/MS metabolic profiling,and the biomarkers in the metabolites could be found through metabonomics analysis,and the mechanisms of the metabolic changes could be explored.It was noted that the research of metabolites in the urine samples may be a useful tool to help diagnose and understand the pathogenesis of HLP.Metabonomics analysis is a promising research method.

Objective To compare the value of bedside index for severity in acute pancreatitis (BISAP),Ranson score and Balthazar computed tomography severity index (CTSI) in predicting the severity and prognosis of acute pancreatitis (AP).Methods From 2005 to 2011 in Shanghai,the clinical data of 1004 AP cases from seven hospitals was collected and retrospectively analyzed.The value of BISAP score,Ranson score and Balthazar CTSI in predicting the severity and prognosis of AP were assessed with receiver operator characteristic (ROC) curve.Results Among 1004 patients,the main cause of AP was biliary disease (580 cases),about 57.77％.The incidence of pancreatic necrosis,mortality and SAP increased along with BISAP score.The risk of pancreatic necrosis in patients with CTSI ≥ three was significantly higher than that of ＜ three.The risk of pancreatic necrosis and SAP in patients with BISAP score ≥ two was significantly higher than that of ＜ two (OR:4.93,95％CI 3.62-6.70; OR 2.62,95％CI 1.59-4.31,respectively).There was no significant difference in the accuracy of predicting the progression and mortality of AP among these three score systems.However the sensitivity of BISAP score (OR:61.54,95％CI 35.09-87.99) in predicting the progression and mortality of AP was better than that of Ranson (OR:46.15,95 ％ CI 19.05-73.25) and CTSI (OR:46.15,95％CI 19.05-73.25).Conclusions BISAP score is easy to perform and when combined with CTSI,it helps to make the diagnosis and classification of AP in time,predict the prognosis accurately.Compared with Ranson score,BISAP score has higher clinical value.