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Objective To establish the diagnostic model based on detection of serum biomarkers in pancreatic cancer (PC) associated diabetes.Methods From June 2013 to July 2014, at Ruijin Hospital, School of Medicine , Shanghai Jiao Tong University , 30 patients diagnosed with PC companied with new onset diabetic mellitus and 30 patients with new onset type 2 diabetic mellitus , were enrolled .Serum samples were examined by liquid chromatography-mass spectrometry ( LC-MS) for metabolomics analysis .Orthogonal partial least square ( OPLS ) was performed for raw data analysis to obtain the differentially expressed metabolites between two groups .The first 15 cases of each group were taken as training samples and the left as validation samples.The model was established using logistic regression via stepwise differentially expressed metabolites and clinical data input in training samples .The diagnostic efficiency of the model was verified in validating samples . Results Ten differentially expressed metabolites were identified in PC companied with new onset diabetic mellitus group and new onset type 2 diabetic mellitus group .The differentially expressed metabolites identified in positive ion mode were 3-ketosphingosine , arachidonoyl dopamine , phosphatidylethanolamine ( 18 :2 ) , ubiquinone-1 and valine .The differentially expressed metabolites identified in negative ion mode were C 16 sphingosine-1-phosphate, keto palmitic acid, isoleucine, N-succinyl-L-diaminopimelic acid and uridine.The diagnostic model was established in training samples:p=e(Xβ)/(1+e(Xβ)), ( Xβ) =-158.975-1.891 (age) +0.309 ( phosphatidylethanolamine 18:2 ) +1.035 ( C16 sphingosine-1-phosphate ) +0.084 (isoleucine) +1.1145 ( N-succinyl-L-diaminopimelic acid ).The area under curve ( AUC) of receiver operating characteristic (ROC) of this model was 0.982 in validation samples, the sensitivity and specificity were both 93.3％.Conclusion Serum metabolomics-based diagnostic approach is a promising method for screening PC from new onset diabetic mellitus .
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Objective To detect and analyze the value of adipokines in the diagnosis and prognosis of patients with pancreatic cancer complicated with diabetes.Methods From July 2012 to June 2013,24 pancreatic ductal adenocarcinoma (PDAC) complicated with diabetes mellitus (DM) (study group),30 PDAC (control group A) and 31 DM (control group B) cases were collected.Serum levels of adiponectin,resistin,leptin and visfatin were tested and the differences were compared among different groups.Receiver operator characteristic (ROC) curves were used to analyze the diagnostic value of the above cytokines.The patients were followed up for two to 58 months.Kaplan-Meier survival curve was performed to analyze the prediction value of above cytokines in recurrence-free survivals (RFS) in patients with PDAC complicated with DM.Chi square test,t test and Mann-Whitney U test were used for statistical analysis.Results The median levels of serum adiponectin and resistin of study group were both higher than those of control group B (36.92 mg/L,15.80 mg/L to 101.57 mg/L vs 12.84 mg/L,5.64 mg/L to 21.39 mg/L;9.07 μg/L,6.39 μg/L to 12.19 μg/L vs 5.93 μg/L,4.22 μg/L to 7.68 μg/L,respectively),and the differences were statistically significant (Z=-3.462 and-2.868,P=0.001 and 0.004,respectively).However the serum levels of leptin and visfatin of study group were both lower than those of control group B (1.02 μg/L,0.11 μg/L to 2.06 μg/L vs 1.92 μg/L,0.96 μg/L to 2.72 μg/L;2.43 μg/L,0.48 μg/L to 4.28 μg/L vs 4.18 μg/L,2.43 μg/L to 7.28 μg/L),and the differences were statistically significant (Z=-1.986 and-2.336,both P＜0.05).The results of ROC curve analysis of adipokines in differential diagnosis of pancreatic cancer from diabetes indicated that the areas under the curve (95 ％ confidence interval) of serum adiponectin,resistin,leptin and visfatin in the diagnosis of PDAC were 0.774 (0.645,0.903),0.727 (0.593,0.861),0.657 (0.504,0.810) and 0.685 (0.543,0.826),respectively,with statistical significance (P=0.001,0.004,0.047 and 0.020,respectively).The sensitivity of combination of CA19-9 and adiponeetin in the diagnosis of PDAC complicated with DM was 0.917 and the negative predictive value was 0.940.The leptin level in advanced PDAC patients was lower than that in non advanced PDAC patients (0.61 μg/L,0.11 μg/L to 2.28 μg/L vs 1.86 μg/L,0.79 μg/L to 4.14 μg /L);and the difference was statistically significant (Z=-2.210,P=0.027).Higher serum adiponectin level was correlated with early recurrence after operation in PDAC patients complicated with DM (P=0.035).Conclusions Serum adipokines may be valuable in screening PDAC in patients with DM.And adipokines may be valuable in the prediction of recurrence after operation in PDAC patients complicated with DM.
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The prevalence of inflammatory bowel disease (IBD) in China is increasing year by year, however, the efficacy and safety of commonly used therapeutic methods are limited.Granulocyte and monocyte adsorptive apheresis (GMA) is one of the effective methods for treatment of IBD used abroad, however, there is still lacking of such research in China.Aims: To investigate the efficacy and safety of GMA in IBD patients.Methods: A retrospective study was conducted in 21 cases of IBD patients [13 cases with ulcerative colitis (UC) and 8 with Crohn's disease (CD)] who accepted GMA treatment from May 2013 to July 2014 at the Shanghai Rui Jin Hospital.All the cases were poor responders to 5-aminosalycylic acid (5-ASA) or steroid-refractory.The clinical data were collected, and the clinical activity index (CAI), endoscopic activity index (EAI), laboratory parameters including serum albumin (Alb), hemoglobin (Hb), erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), leukocyte count and percentage of neutrophils, as well as the adverse effects before and two weeks after the end of GMA treatment were analyzed.Results: After GMA treatment, both CAI and EAI were decreased significantly in UC and CD groups as compared with those before treatment (P all 0.05).The treatment was well tolerated with no severe adverse effects.Conclusions: GMA is safe and effective for ameliorating clinical symptoms, attenuating intestinal mucosal injury and controlling active inflammation in IBD patient that has not responded to 5-ASA or steroid treatment.Prospective clinical studies with large samples are needed to confirm these findings.
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Objective To evaluate the efficacy and safety of rabeprazole sodium injection in the treatment of non-esophageal variceal upper gastrointestinal bleeding in comparison with the positive control,omeprazole.Methods From January 2010 to January 2011,231 patients with non-esophageal variceal upper gastrointestinal bleeding from 20 hospitals were divided into rabeprazole group and omeprazole group in this multicenter,randomized,blind,parallel-group,positive drug controlled clinical trial.Hemostasis rate in 72 hours was the primary endpoint.Hemostasis rate in 120 hours,time to hemostasis,blood transfusion volume and the rate of switching treatments were the secondary endpoint.And safety was also analyzed.Chi square test and Wilcoxon rank sum test were performed for statistical analysis.Results At 72 hours after treatment,the hemostasis rates of rabeprazole group and omeprazole group were 98.20％(109/111)and 98.25％(112/114), respectively, and the difference was not statistically significant (P＞0.05).The 95％ confidence interval (CI) of the rate difference between the two group was-3.50 ％ to 3.40 ％.The result of non-inferiority test indicated that the lower limit of the 95％CI of the rate difference between the two groups was-2.95％ (U=5.652,P＜0.01),and rabeprazole group was not inferior to omeprazole group.At 12 hours after treatment,the hemostatic rates of rabeprazole group and omeprazole group were 63.06％(70/111) and 53.51％(61/114),respectively,and there was no statistically significant difference (P＞0.05).At 120 hours after treatment,the hemostasis rates of rabeprazole group and omeprazole group were 99.10 ％ (110/111) and 98.25 ％ (112 /114),and there was no statistically significant difference (P＞0.05).The median time of hemostasis of two groups was 24 hours.During the treatment,there were two cases and seven cases of rabeprazole group and omeprazole group received blood transfusions,respectively;there were 0.90％ (1/111) and 2.63 ％ (3/114) patients switched to other treatment,and no statistically significant difference was found (P＞0.05).The rates of adverse event of rabeprazole group and omeprazole group were 11.61％ (13/112) and 5.26％ (6/114),respectively.The rates of adverse reaction were 6.25％ (7/112) and 4.39％ (5/114),respectively.The differences in the rates of adverse event and adverse reaction between two groups were not statistically significant(both P＞0.05).Conclusion Rabeprazole sodium injection is an effective and safe drug in the treatment of non-esophageal variceal upper gastrointestinal bleeding.
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Objective To investigate the role of mucosal mast cells infiltration and degranulation with nerve growth factor (NGF)in development of visceral hypersensitivity in Sprague-Dawley (SD)rats. Methods The model of visceral hypersensitivity of irritable bowel syndrome (IBS)was established in 19 neonate SD rats with intestinal stimulation (rectalballon distention)on 8th,10th and 12th postnatal days. The other 19 neonate SD rats without colonic distention were assigned to the control group.After rats grew up (six to eight weeks old),the visceral sensitivity was tested by abdominal withdrawal reflex (AWR)in 10 rats of each group.Mast cell infiltration and degranulation were observed with toluidine blue staining in colon tissue slides.The NGF level of intestinal tissues was detected by enzyme-linked immunosorbent assay (ELISA)methods in the left nine rats of each group.The culture system of dorsal root ganglias (DRG)from the neonatal rats was set up.The changes of electrophysilogical characters of DRG stimulated with NGF (100 ng/mL)for four days were recorded with patch-clamp.Paired t test was performed for comparison between groups.Results The results of AWR indicated that neonatal colonic stimulation could significantly increase visceral sensitivity after growing up.Under 20,40 and 60 mmHg (1 mmHg=0.133 kPa)distention pressure,visceral sensitivity scores of visceral hypersensitivity rats and rats of control group were 1 .00±0.50 vs 1 .67 ±0.50,1 .89 ±0.31 vs 2.89 ±0.34 and 2.89 ±0.33 vs 3.89±0.33,the differences were statistically significant (t=-2.83,-6.00 and -6.00,all P <0.05 ). The results of master cells staining in tissue slides showed colonic master cells infiltration was obvious in rats with visceral hypersensitivity,and part of mast cells were degranulation.The result of ELISA demonstrated that NGF level of visceral hypersensitivity rats was significantly higher than that of control group ((11.07±3.06)pg/mg vs (2.38 ±1.88)pg/mg,t =-6.93,P <0.05).The results of electrophysilogical tests of primary cultured DRG indicated that compared with blank control growp,the action potential threshold of neuron in NGF 100 ng/mL group significantly decreased ((-18.0±2.1 )mV vs (-29.0 ± 2.5 )mV,t = 12.26,P <0.05)and discharge frequency increased ((5 .0± 1 .4 )/800 ms vs (12.0 ± 3.2)/800 ms,t=-8.40,P <0.05 ).Meanwhile,neuron voltage-gated K+ current density remarkably decreased,most were sustained delayed rectifier K+ current (I K )decreasing ((279.0 ±48.0)pA/pF vs (203.0±39.0)pA/pF,t=6.18,P <0.05).Conclusion Colonic stimulation in neonatal rats could cause intestinal master cells infiltration and degranulation,which induced changes of neuron electrophysilogical characters and resulted in visceral hypersensitivity after growing up.
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BACKGROUND/AIMS: To investigate the effects of esomeprazole and rebamipide combination therapy on symptomatic improvement in patients with reflux esophagitis. METHODS: A total of 501 patients with reflux esophagitis were randomized into one of the following two treatment regimens: 40 mg esomeprazole plus 300 mg rebamipide daily (combination therapy group) or 40 mg esomeprazole daily (monotherapy group). We used a symptom questionnaire that evaluated heartburn, acid regurgitation, and four upper gastrointestinal symptoms. The primary efficacy end point was the mean decrease in the total symptom score. RESULTS: The mean decreases in the total symptom score at 4 weeks were estimated to be −18.1±13.8 in the combination therapy group and −15.1±11.9 in the monotherapy group (p=0.011). Changes in reflux symptoms from baseline after 4 weeks of treatment were −8.4±6.6 in the combination therapy group and −6.8±5.9 in the monotherapy group (p=0.009). CONCLUSIONS: Over a 4-week treatment course, esomeprazole and rebamipide combination therapy was more effective in decreasing the symptoms of reflux esophagitis than esomeprazole monotherapy.
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Humans , Esomeprazole , Esophagitis, Peptic , HeartburnABSTRACT
BACKGROUND/AIMS: To investigate the effects of esomeprazole and rebamipide combination therapy on symptomatic improvement in patients with reflux esophagitis. METHODS: A total of 501 patients with reflux esophagitis were randomized into one of the following two treatment regimens: 40 mg esomeprazole plus 300 mg rebamipide daily (combination therapy group) or 40 mg esomeprazole daily (monotherapy group). We used a symptom questionnaire that evaluated heartburn, acid regurgitation, and four upper gastrointestinal symptoms. The primary efficacy end point was the mean decrease in the total symptom score. RESULTS: The mean decreases in the total symptom score at 4 weeks were estimated to be −18.1±13.8 in the combination therapy group and −15.1±11.9 in the monotherapy group (p=0.011). Changes in reflux symptoms from baseline after 4 weeks of treatment were −8.4±6.6 in the combination therapy group and −6.8±5.9 in the monotherapy group (p=0.009). CONCLUSIONS: Over a 4-week treatment course, esomeprazole and rebamipide combination therapy was more effective in decreasing the symptoms of reflux esophagitis than esomeprazole monotherapy.
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Humans , Esomeprazole , Esophagitis, Peptic , HeartburnABSTRACT
Objective To explore the relationship between the severity of experimental acute pancreatitis (AP) and the expression of Myc interacting zinc finger protein 1 (MIZ1) in rat, to evaluate the value of MIZ1 for severity assessment .Methods Acute necrotizing pancreatitis ( ANP) model was induced by retrograde injection of sodium taurocholate into the pancreatic duct , and normal saline was used in control group.The rats were sacrificed at 6, 24, 48 h, and the blood and pancreas tissue was collected , and serum amylase level , C reactive protein ( CRP ) , TNF-α, IL-6 and MIZ1 were determined by ELISA .Pancreatic tissue was routinely examined by pathologist , and the MIZ1 protein expression in pancreatic tissue was measured by immunohistochemistry and Western blot .Results The serum amylase levels of control group and ANP group at 6, 24, 48 h were (449 ±40), (578 ±25), (1 021 ±205), (971 ±143)U/L, and the levels of CRP were (123 ±23), (169 ±25), (226 ±34), (229 ±24)mg/L;and the levels of IL-6 were (20.16 ± 4.11), (38.60 ±12.05), (52.33 ±6.77), (44.83 ±4.30)ng/L;and the levels of TNF-αwere (55.33 ±3.32), (82.8 ±5.26), (120.66 ±16.00), (108.33 ±12.17)ng/L;and the levels of MIZ1 were (5.51 ± 0.34), (3.44 ±0.56), (2.11 ±0.11), (2.41 ±0.43) ng/L.The pathologic scores of pancreas were (1.83 ±0.75), (6.00 ±1.67), (8.16 ±2.70), (9.33 ±1.50), and the expressions of MIZ1 in pancreatic tissue were 0.81 ±0.05, 0.53 ±0.07, 0.31 ±0.06, 0.21 ±0.08.Except for amylase level of ANP 6h group, other parameters of ANP group were significantly different with those of control group , and the parameters of ANP 24, 48 h group were significantly different with that of ANP 6 h group ( P<0.01), but there was no significantly different between ANP 24 and 48 h group.MIZ1 expression was negatively correlated with serum amylase level , CRP, TNF-α, IL-6 and pathologic scores of pancreas , and the difference was statistically signific ant (P<0.01).Conclusions The decreasing expression of MIZ1 is closely correlated with the severity of AP , and may be a potential marker for prognosis evaluation .
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Objective To evaluate the efficacy and safety of mesalazine modified-release tablets in the maintenance treatment of patients with ulcerative colitis (UC) in remission phase.Methods This study was a multi-center,single-blinded and randomized controlled study.From November 2010 to August 2012,251 patients with UC from 18 hospitals were enrolled.According to the randomization table,all patients were divided into the mesalazine modified-release tablets group (n 126) and the mesalazine enteric-coated tablets group (n=125).The course of treatment were both 48 weeks.The primary efficacy parameter of the two groups including the rate of non-recurrence of bloody stool,and the secondary efficacy parameter including period of non-recurrence of bloody stool,period of non-recurrence of UC,incidence of adverse events and adverse drug reactions were observed.The GENMOD model was applied to calculate 95％ confidence interval (CI) of the rate of non-recurrence of bloody stool of the two groups.If the lower limits was over-10％ of the setting,it indicated that the former was not inferior to the latter.Results In 48 weeks of maintenance treatment,the rate of non-recurrence of bloody stool of themesalazinemodified-release tablets group was 82.99％(95％CI 73.53％ to 92.45％) and 73.30％ (95％ CI 64.04％ to 82.56％) in the mesalazine enteric-coated tablets group,respectively,and the difference between the two groups was 9.69％(95％CI-1.15％ to 20.53％ (＞-10％)) which indicated the mesalazine modified-release tablets group was not inferior to the mesalazine enteric-coated tablets group.There was no significant difference in the period of non recurrence of bloody stool and period of non recurrence of UC between the two groups (both P＞0.05).The incidence of adverse events was 48.78％ (60/123) in the mesalazine modified-release tablets group and 48.00％ (60/125) in the mesalazine enteric-coated tablets group,and the difference was not statistically significant (P=0.902).The incidence of adverse reactions was 16.26 ％ (20/123) in the mesalazine modified release tablets group and 13.60 ％ (17/125) in the mesalazine enteric-coated tablets group.There was no statistically significant difference (P =0.556).Conclusion Mesalazine modified release tablets can help maintain long-term remission in patients with UC,and can be used as a safe and effective alternative medicine in the treatments of UC in remission phase.
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Objective To evaluate the efficacy and safety of mesalazine modified-release tablets in the treatment of mild and moderate active ulcerative colitis (UC).Methods This study was a multicenter,single-blinded and randomized controlled study.A total of 251 active UC patients in 18 hospitals were enrolled into this study from November 2010 to January 2012.The subjects were divided into the mesalazine modified-release tablets group (n=123) and the mesalazine enteric-coated tablets group (n=128),three times daily,each of which took mesalazine modified-release tablets or mesalazine enteric coated tablets 800 mg,respectively,and the course of treatment was eight weeks.The difference of UC disease activity index (UC-DAI),UC-DAI at the beginning minus UC-DAI at the final evaluation,was calculated at final evaluation.And this was the primary efficacy parameter.Complete remission rate and effective rate were considered as the secondary efficacy parameter.Adverse drug reactions rates of two groups were calculated and taken as safety evalution.If the lower limit of the 95 ％ confidence interval was more than-0.1 in the difference of the decrease in UC-DAI between the two groups,the non-inferiority of mesalazine modified release tablets to mesalazine enteric-coated tablets was demonstrated.The analysis of covariance model was used for the primary efficacy parameter and the sub-group analysis.And chisquare test was used for the comparison between the two groups in the secondary efficacy parameter and in the adverse drug reactions.Results At the final evaluation,the decrease in UC-DAI of mesalazine modified-release tablets group was 2.84 and that of mesalazine enteric-coated tablets group was 2.56.The reduction degree was 0.27.The lower limit of the 95 ％ confidence interval in the difference of the decrease in UC DAI between the two groups was-0.34,which demonstrated the non-inferiority of mesalazine modified release tablets to mesalazine enteric-coated tablets.The complete remission rates of mesalazine modified release tablets group and mesalazine enteric-coated tablets group were 48.33％ (58/120) and 55.65％ (69/124) and the effective rates were 63.33％ (76/120) and 66.94％ (83/124),and there was no statistically significant difference between the two groups (all P＞ 0.05).At final evaluation,the decrease in UC DAI of mild patients (UC DAI 3 to 5 at enrollment) of mesalazine modified-release tablets group and mesalazine enteric-coated tablets group were 2.16 and 2.05,respectively; the difference of mesalazine modified release tablets group and mesalazine enteric coated tablets group of reduction degree of UC-DAI was 0.11,that of moderate patients (UC-DAI 6 to 8 at enrollment) were 3.49 and 3.03,respectively,the difference of mesalazine modified-release tablets group and mesalazine enteric-coated tablets group of reduction degree of UC DAI was 0.46,and there was no statistically significant difference between the groups (all P＞0.05).The adverse drug reactions rates of mesalazine modified-release tablets group and mesalazine enteric coated tablets group were 6.61％ (8/121) and 10.24％ (13/127),and there was no statistically significant difference between the two groups (P＞ 0.05).No serious adverse drug reactions were found in two groups.Conclusion Mesalazine modified release tablets has good efficacy and high safety in the treatment of mild to moderate active UC.
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Objective To explore the efficacy and safety of compound azintamide enteric‐coated tablets in the treatment of patients with dyspepsia after gastrointestinal surgery .Methods Multicenter , randomized ,double blind ,placebo‐controlled ,parallel controlled method w as applied .From January 2011 to January 2013 , of 240 patients with dyspepsia after gastrointestinal surgery from 12 hospitals in Shanghai were enrolled and divided into medicine treatment group (n= 120) and placebo control group (n= 120 ) ,received compound azintamide enteric‐coated tablets or placebo , respectively . Compound azintamide enteric‐coated tablet (100 mg) or placebo was oral taken each time ,three times per day for four weeks .Total and respective score of dyspeptic symptoms (abdominal distension ,loss of appetite ,early satiety ,belching ,nausea ,abdominal pain or abdominal discomfort) were evaluated prior to study and on the 1st , 2nd , 3rd and 4th week after treatment . On the 4th week after treatment ,the efficacy of the improvement of dyspeptic symptoms was compared between the two groups ,and the safety was also evaluated .The score of the quality‐of‐life was compared between the two groups prior to study and on the 4thweek after treatment .The t‐test was performed for comparison between measurement data ,Chi‐square test was used for count data ,and rank sum test was used for rank data .Results At one week after treatment ,the scores of abdominal distension (4 .61 ± 0 .98 ) ,early satiety (2 .87 ± 0 .64 ) ,belching (3 .03 ± 0 .58) ,abdominal pain or abdominal discomfort (3 .13 ± 0 .79) and total score (18 .32 ± 3 .44) of patients in medicine treatment group were significantly lower than those of placebo control group (8 .83 ± 1 .28、4 .28 ± 0 .61、4 .87 ± 1 .07、5 .46 ± 0 .87、29 .63 ± 5 .50) ,and the differences were statistically significant (t=28 .524、17 .400、16 .453、21 .619 and 18 .983 ,all P 0 .05) .At 2nd ,3rd and 4th week after treatment ,respective score of dyspeptic symptoms and total score of medicine treatment group (2nd week:2.57±1.28,1.87±1.17,1.55±1.27,1.55±1.08,1.09±0.82,1.98±1.02,10.53±4.54,3rdweek:1 .42 ± 0 .60 ,1 .11 ± 0 .45 ,0 .94 ± 0 .37 ,0 .94 ± 0 .41 ,0 .79 ± 0 .31 ,1 .42 ± 0 .55 ,6 .52 ± 2 .41 ,4th w eek:1.13±0.51,0.46±0.12,0.58±0.13,0.38±0.16,0.30±0.07,0.81±0.33,3.65±1.06)wereall significantly lower than those of placebo control group (2nd week:8 .50 ± 2 .61 ,3 .78 ± 2 .01 ,4 .08 ± 2 .14 , 4.73±2.64,2.27±2.13,4.91±2.24,28.25±8.86,3rdweek:7.92±2.51,3.68±1.76,4.08±1.86, 4.71±1.77,2.14±0.83,5.01±1.31,27.54±8.09,4th week:7.63±2.37,3.67±1.63,3.92±2.08, 4 .66 ± 2 .95 ,2 .14 ± 1 .65 ,4 .67 ± 2 .34 ,and 26 .68 ± 7 .45) ,and the differences were statistically significant (all t=0 .000 ,all P<0 .01) .At 4th week after treatment ,the total efficacy of total score improvement of dyspepsia symptoms in medicine treatment group was 86 .21% (100/116) ,which was significantly better than that of placebo control group (39 .16% (47/120)) ,and the difference was statistically significant (Z=9 .464 ,P<0 .01) .The total score of quality of life in medicine treatment group was significantly lower than that of placebo control group (12 .24 ± 4 .30 and 22 .13 ± 6 .18) ,and the difference was statistically significant (t=14 .225 , P< 0 .01 ) .No adverse events was observed in both groups during treatment period . Conclusion Compound azintamide enteric‐coated tablets may effectively improve dyspeptic symptoms and quality of life in patients with dyspepsia after gastrointestinal surgery ,and with good safety .
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Objective To investigate the effect of antioxidants including PDTC on pancreatic fibrosis of rats with chronic pancreatitis.Methods The rats were randomly divided into 5 groups including control group, CP group, PDTC treatment group, vitamin E treatment group and vitamin C treatment group.The CP model was in ducad by using intraperitoneal injection of DETC (750 mg/kg), twice a week.The control group received no treatment.After DETC injection, the treatment groups received an intraperitoneal injection of PDTC (100 mg/kg), vitamin E (15 mg/kg), vitamin C (15 mg/kg), respectively.Rats were sacrificed at 90 min, 24 h, 48 h, 72 h, 2 w, 3 w, 4 w, 6 w after first injection of DETC.Pancreatic tissue was taken for routine pathological examination.The activity of SOD, GSH-PX and MDA content were detected by spectrophotometric ratio method.α-SMA, desmin collagen Ⅰ, Ⅲ, TGF-β1, FN were detected by immunohistochemical assay.The expression of TGF-β1, FN mRNA was measured by RT-PCR.Results At 6w, the fibrosis and the parameters for damage of the pancreas in the three treatment groups were significantly better than that in CP group (P ＜0.01), the vacuolar degeneration index in vitamin E group and vitamin C group was also better than that in CP group (P ＜0.01).From the 2nd week, the activity of SOD, GSH PX in PDTC group, Vit C group and Vit E group was higher than that in CP group, while the MDA activity was lower than that in CP group, and the difference was statistically significant (P ＜ 0.01 or P ＜ 0.05).No significant difference was found among the three treatment groups.The mRNA levels of TGF-β1 and FN of the treatment groups were lower than those of CP group (P ＜0.05 or P ＜0.01), but higher than those of the control group (P ＜ 0.05).There was no significant difference among the three treatment groups (P ＞ 0.05).Conclusions PDTC and the other antioxidants can reduce oxygen free radicals by increasing the activity of SOD,suppressing the activation of PSCs, reducing the secretion of TGF-β1, Collagen Ⅰ , Ⅲ, FN and eventually inhibit the progress of pancreatic fibrosis.
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Objective To explore the role of pancreatic cancer-derived microvesicles (MV) and their enclosed microRNAs (miRNA) in the pathogenesis of pancreatic cancer induced diabetes mellitus (DM).Methods The supernatants of three pancreatic cancer cell lines SW1990, BxPC3 and PANC1 were collected, and MV were isolated with gradient centrifugation.The entrance of MV into pancreatic islet cell line MIN6 was proved by Western blot assay and fluorescence-label method.The miRNA-19a levels were measured in MV and MV-free supernatants of three pancreatic cancer cells lines.The three experimental groups were MIN6 cells separately treated by MV derive from SW1990, BxPC3 and PANC1, and untreated MIN6 cells were assigned to the control group.The miRNA-19a levels as well as changes of glucose stimulated insulin secretion (GSIS) were measured.Afterward, pre-miRNA-19a and anti-miRNA-19a were transfected into MIN6 cells by liposome, and the effects of them on GSIS were observed.Results CD63 and AGO2 as the protein markers of MV and the entrance of MV from pancreatic cancer into pancreatic islet cell line MIN6 were detected by Western blotting.The miRNA-19a levels in MV and MV-free supernatants of SW1990, BxPC3 and PANC1 were (132.7±16.0), (32.8±4.3), (78.4±8.9),(22.6±3.3), (63.3±12.0) and (23.3±3.3) pmol/L, respectively, and the differences were statistically significant (t=10.44, 10.12 and 5.56,all P＜0.01).Compared to the MIN6 control group, the miRNA-19a levels of MIN6 treated by MV from SW1990, BxPC3 and PANC1 significantly increased, and the 2-△△Ctvalue was 2.02 ± 0.50, 1.80 ± 0.41 and 2.11 ± 0.59, respectively, and the differences were statistically significant (t=2.97, 2.77, 2.84;all P＜0.05).Stimulated with high glucose, the GSIS of pancreatic islet cells treated by SW1990, BxPC3 and PANC1 in three groups decreased, which were (103.73±16.49), (141.17±11.26), and (138.24±13.97) ng · mg protein-1 · h-1 MV, respectively, and that of control group was (256.24 ± 33.05) ng · mg protein-1 · h-1.The differences were statistically significant (t=4.13, 3.30 and 3.29, all P＜0.05).Compared with control group, GSIS of pre-miRNA-19a treated MIN6 remarkably decreased, which was (126.17± 62.87) ng · mg protein-1 ·h-1 and (316.72±91.87) ng · mg protein-1 · h-1 , and the difference was statistically significant (t=2.97, P＜0.05).GSIS of MIN6 cells transfected with anti-miRNA-19a was higher than that of control group, which was (697.47±77.62) ng · mg protein 1 · h-1 and (355.33 ±84.77) ng · mg protein-1 ·h-1 , and the difference was statistically significant (t=-2.97,P＜0.05).Conclusion The entrance of MV derived from pancreatic cancer into pancreatic islet cell line MIN6 may cause the dysfunction of insulin secretion an important signaling molecules, miRNA-19a.
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Pancreatic cancer (PC)is one of common malignant digestive diseases.It is mostly diagnosed at advanced stage,with an ex-tremely poor progression.The relationship between diabetes and PC was shown by numerous epidemiological studies for decades.Retrospec-tive clinical studies and research on molecular mechanisms in recent years have led to a new understanding of the relationship between diabe-tes,especially new-onset diabetes,and PC,the effect of antidiabetic medication on PC,and the molecular mechanisms underlying the con-nection between diabetes and PC.It is suggested by recent data that long-standing diabetes is one of the risk factors for PC development, new-onset diabetes may facilitate early diagnosis of PC,diabetes may have an impact on the prognosis of PC,the option of antidiabetic medication may influence the incidence of PC,and exploring the molecular mechanisms underlying the association between diabetes and PC may help to identify the new therapeutic target for PC.
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Objective To investigate the effects of acupuncture on the improvement of esophageal motility disorder in patients with refractory gastroesophageal reflux disease (GERD).Methods From September 2012 to March 2014,40 patients with refractory GERD were enrolled and evenly divided into the treatment group and the control group. High resolution esophageal impedance manometry was conducted in patients.After the first examination,patients of the control group lay down for 30 minutes, and patients of the treatment group received acupuncture treatment at Neiguan,Gongsun and Zusanli points for 30 minutes.Then all the patients underwent high resolution esophageal impedance manometry again.ManoView ESO 3.0 software was used for analysis.The parameters included swallowing peristalsis defect,lower esophageal sphincter (LES)pressure,LES residual pressure,LES length,upper esophageal sphincter (UES)pressure,distal wave amplitude,peristalsis duration time,starting speed of peristalsis wave,speed of edge contraction and integration of the peristaltic waves.Chi-square test or t test was performed for data analysis.Results The percentage of normal swallows of the treatment group before and after treatment was 56.0% (112/200)and 74.0% (148/200),the percentage of delayed esophageal emptying was 31 .5 % (63/200 )and 11 .5 % (23/200 ),and the differences were statistically significant (χ2 =14.242 and 23.700,both P 0.05 ).The LES resting pressure of the treatment group before and after treatment was (20.2 ±18.8)mmHg (1 mmHg=0.133 kPa)and (26.3±10.1)mmHg,the length of LES was (2.2 ±0.6 )cm and (3.3 ±0.8)cm,the distal esophageal peristaltic amplitude was (60.2 ± 21 .9)mmHg and (41 .1 ± 16.8 )mmHg,and the differences were statistically significant (t = 5 .519, 6.580 and 6.881 ,all P 0.05 ).There as no significant difference in LES resting pressure and LES residual pressure of the control group before and after lying down (both P >0.05 ).However,before and after lying down,there were significant differences in the length of LES ((2.3 ±0.6)cm vs (2.5 ±0.6)cm) and UES resting pressure ((67.4 ±21 .2 )mmHg vs (53.5 ±18.1 )mmHg)in the control group (t =2.530 and 6.652,both P 0.05).Before and after lying down,there was no significant difference in distal wave amplitude,duration of peristalsis,the beginning speed of the peristaltic wave and CFV of the control group (all P >0.05 ).Conclusion Acupuncture can help increase the LES resting pressure,extend the length of LES,improve the overall peristaltic pressure and completeness of esophageal somatic part,meanwhile,it increases the percentage of normal swallows of patients with refractory GERD.
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Objective To evaluate the efficacy and safety of compound azintamide enteric-coated tablet in the treatment of patients with post-cholecystectomy dyspepsia.Methods A multicentre,randomized,double-blinded,placebo-controlled trail was conducted.A total of 120 patients with post-cholecystectomy dyspepsia were divided into azintamide group (n=60) and placebo group (n＝60),taking compound azintamide enteric-coated tablet or placebo 100 mg each time,three times per day for 28 days.The score of each dyspeptic symptom (abdominal distension,loss of appetite,early satiety,belching,nausea,abdominal pain or abdominal discomfort) and total score of dyspepsia were evaluated prior to study and on the 7th,14th,21st and 28th day after treatment.The efficacy of the improvement of dyspeptic symptoms was compared between the two groups on the 28th day after treatment and the safety was evaluated.The score of the quality-of-life was compared between the two groups prior to study and on the 28th day after treatment.The t-test or chi-square test was performed for statistical analysis.Results The scores of abdominal distension,belching,nausea,abdominal pain or abdominal discomfort and the total score of azintamide group on the 7th day after treatment (5.7±3.1,3.5±2.1,0.3±0.1,3.3±1.7 and 17.9±9.6) were significantly lower than those prior to study (8.9±5.3,5.3±2.5,0.9±0.4,4.5±3.7,24.3±14.5;t=3.758,3.976,10.494,2.125 and 2.654,allP＜0.05).On the14th,21st and28thday after treatment in azintamide group,the score of each dyspeptic symptom and the total score were lower than those prior to study.The symptom of abdominal distension significantly improved on the 7th,14th,21st and 28th day after treatment in placebo group,and the score of early satiety and total score of dyspepsia were significantly lower on the 28th day after treatment compared with those before treatment.In azintamide group,the total efficacy rate was 66.7％ (40/60),which was higher than that of placebo group (38.3％,23/60) and the difference was statistically significant (x2 =9.653,P ＜ 0.01).On the 28th day after treatment,SF-NDI of azintamide group was 4.4±3.4,which was significantly lower than that of placebo group (9.6±6.0) and the difference was statistically significant (t=5.450,P＜0.01).In azintamide group there was one patient with rash on the 7th day after treatment,and in placebo group there was one patient with headache on the 14th day after treatment.The symptoms disappeared seven days after medicine withdrawal.Conclusion Compound azintamide enteric-coated tablet effectively improves dyspeptic symptoms and quality of life in patients with post-cholecysteetomy dyspepsia and has good safety.
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Objective To investigate the circulating microRNAs carrier in pancreatic cancer.Methods Pancreatic cancer cell lines SW1990 and BxPC3 were routinely cultured and serum of 6 patients with pancreatic cancer and 6 healthy subjects (control group) were collected.Serum and pancreatic cancer cell line supernatant microvesicles (MV) were obtained by gradient centrifugation.The expression of Ago2,CD63 was detected by Western blotting,the expression of microRNA in microvesicle section and microvesicle-free section in serum was detected by using quantitative PCR method.Results The supernatant MV of pancreatic cancer cell lines expressed Ago2,CD63 protein,and these MV carried different microRNAs in different cell lines.In the serum of pancreatic cancer and control group,miR-20a,miR-21,miR-24,miR-25,miR-191,miR-483-5p were detected,but the quantity was relatively higher in MV section,and the expression of microRNAs in pancreatic cancer's MV was inconsistent with that of control group.The expression of miR-20a,miR-24,miR-191 in pancreatic cancer group was (2.93 ± 0.29),(2.73 ± 0.46),(2.39 ± 0.51) times as much as those in control group,and the difference between the two groups was statistically significant (F =75.97,25.80,12.94,P ＜ 0.05 or ＜ 0.01).Conclusions The main circulating microRNAs carrier in pancreatic cancer is microvesicle.
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Objective To investigate the pathologic changes in the pancreas of rats after intraperitoneal injection of DETC,a kind of superoxide dismutase (SOD) inhibitor,and to compared that with another model of chronic pancreatitis by pancreatic duct injection of TNBS.Methods The rats were randomly divided into DETC group,DETC control group,TNBS group,TNBS control group,normal control group.Rats in DETC group received an intra-peritoneal injection of DETC twice a week,and rats in DETC control group received an intra-peritoneal injection of same amount of normal saline.Rats in TNBS group was injected with 2％ TNBS ethanol phosphate buffer into the pancreatic duct,while rats in TNBS control group was treated with injection of same amount of ethanol phosphate buffer,and rats in normal control group received no treatment.The rats were sacrificed after 2 w,4 w,6 w and 8 w.The serum levels of amylase were determined,and pathological and ultrastructure changes of the pancreas were measured.The levels of SOD,GSH-PX activity and MDA content were detected.The expressions of α-SMA,Desmin,Collagen Ⅰ,Collagen Ⅲ,TGF-β1,FN in tissue were detected by immunohistochemical assay.The TGF-β1 mRNA expression was detected by RTPCR.Results No rat died in DETC group.The mortality rate of TNBS group was 15％.The serum levels of amylase were not statistically different between the 2 groups.The fibrosis scores of rat in DETC group at 4 w was 3.4 ± 1.l,which was significantly higher than that in TNBS group (3.0 ± 1.3,t =3.462,P ＜ 0.05).At 6 w,the damage scores of rat in DETC group was 9.1 ± 1.8,which was significantly higher than that in TNBS group (8.4 ± 1.8,t =2.943,P ＜ 0.05).Scores of vacuolar degeneration and fatty infiltration of rat in DETC group were higher than those in TNBS group,but the difference between the two groups was not statistically significant.Two weeks later,ultrastructure changes of pancreas could be observed,and large amounts of regenerative or mature collagen could be seen at 4 w.The SOD activity of DETC group was significantly decreased when compared with those in TNBS group (t =5.468,P ＜ 0.01).The GSH-PX activity of DETC group at 2 w,6w was significantly decreased when compared with those in TNBS group (t =6.497,10.125,P＜0.01).While the activity of MDA at 6 w,8 w was significantly increased when compared with those in TNBS group (t =3.350,5.407,P ＜0.05).The differences at other time points were not statistically significant.The expressions of (a)-SMA,Desmin,Collagen Ⅰ,Collagen Ⅲ,TGF-β1,FN,and TGF-β1 mRNA were not statistically significant between the 2 groups.Conclusions Sustained suppression of SOD activity can successfully induce chronic pancreatitis.Fatty infiltration and fibrosis in pancreas in DETC group occurs earlier with more severe presentation than that in TNBS group.Intraperitoneal injection of DETC is easy with low mortality rate,which is an ideal method for chronic pancreatitis model induction.
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Objective To investigate the diagnostic value of UL-16 binding protein 2 (ULBP-2,macrophage inhibitory cytokine-1 (MIC-1) for pancreatic cancer.Methods The serum samples of 152pancreatic cancer patients,20 precursors of pancreatic cancer,91 chronic pancreatitis patients and 96 age/sexmatched healthy persons were collected.The serum ULBP-2 and MIC-1 levels were determined by using the ELISA kit and were compared with level of CA19-9.A receiver operating characteristic (ROC) curve was constructed to evaluate their diagnostic values for pancreatic cancer.Results The serum levels of ULBP-2 in patients with pancreatic cancer,precursors of pancreatic cancer,chronic pancreatitis and healthy persons were (219.9 ± 182.5),(62.6 ± 11.4),(68.4 ± 36.8),(76.5 ± 40.9) μg/L,the corresponding values of MIC 1 were (3521.3±3903.4),(973.6±589.0),(959.6±879.0),(427.6±317.0) μg/L,while the corresponding values of CA19-9 were (1448.8 ± 3707.0),(12.0 ± 9.3),(38.2 ± 139.0),(7.7 ± 5.0)kU/L.The parameters in pancreatic cancer patients were significantly higher than those in control group (x2 =40.628,71.662,45.505,15.827,36.433,63.494,26.264,73.427,49.088,P ＜ 0.01).The area under ROC curves(AUC) of ULBP-2,MIC-1,CA19-9 were 0.909,0.864,0.818,and ULBP-2 was superior to CA19-9 and MIC-1,however the combined measurement of three markers produced the highest diagnostic yield(AUC =0.982).For early stage pancreatic diseases (precursors to pancreatic cancer and IA stage pancreatic cancer),AUC of ULBP-2,MIC-1,CA19-9 were 0.506,0.837,0.684,MIC-1 was superior to ULBP-2 and CA19-9,however the combined measurement of MIC-1 and CA19-9 produced the highest diagnostic yield(AUC =0.897).Conclusions Serum ULBP-2,MIC-1 levels are significantly elevated in pancreatic cancer patients.The combined measurement of ULBP-2,MIC-1 and CA 19-9 can increase the diagnostic yield for pancreatic cancer.
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Objective To evaluate the efficacy and safety of prucalopride two mg once daily in the treatment of chronic constipation (CC) in China.Methods In this multicentre,randomised,placebo controlled,parallel-group,phase Ⅲ study,patients with CC received either two mg prucalopride or placebo,once daily,for 12 weeks.The primary efficacy endpoint was the proportion of patients reaching an average of three or more spontaneous complete bowel movements (SCBM) per week during the 12 week treatment.The key secondary efficacy endpoint was the percentage of patients reaching three or more SCBM/week during the first four weeks of treatment.Other efficacy assessments included the average number of SCBM/week; the median time to onset of first SCBM after intake of the first dose of trial medication and the average number of bisacodyl tablets or enemas used per week.Furthermore,the symptoms of constipation were assessed by patient assessment of constipation symptom (PAC-SYM) questionnaire.The quality of life was evaluated by patient assessment of constipation-quality of life (PAC-QOL) questionnaire.Safety assessments included adverse events,laboratory values and cardiovascular events.Results Four hundred and forty-six patients from China were screened,313 were treated and 295 completed 12-week study treatment.Averaged over 12 weeks,significantly higher proportion of patients on prucalopride two mg (39.4％,P＜0.01) had three or more SCBM/week compared with placebo (12.7％,x2 =29.50,P＜0.01).Over four weeks,significantly higher proportion of responders was also found in patients on prucalopride (40.0 ％vs 13.3 ％,x2 =28.58,P＜0.01).Prucalopride also significantly improved associated symptoms and quality of life (QOL).The most frequent treatment emergent adverse events were diarrhoea,nausea,abdominal pain,and headache,which were mild to moderate and transient,spontaneously resolved in a few days.Conclusion Prucalopride two mg once daily significantly improved bowel function,associated symptoms and satisfaction in CC over a 12-week treatment period,and was safe and well tolerated in Chinese patients.