Application of machine learning model based on XGBoost algorithm in early prediction of patients with acute severe pancreatitis / 中华危重病急救医学

OBJECTIVE@#To establish a machine learning model based on extreme gradient boosting (XGBoost) algorithm for early prediction of severe acute pancreatitis (SAP), and explore its predictive efficiency.@*METHODS@#A retrospective cohort study was conducted. The patients with acute pancreatitis (AP) who admitted to the First Affiliated Hospital of Soochow University, the Second Affiliated Hospital of Soochow University and Changshu Hospital Affiliated to Soochow University from January 1, 2020 to December 31, 2021 were enrolled. Demography information, etiology, past history, and clinical indicators and imaging data within 48 hours of admission were collected according to the medical record system and image system, and the modified CT severity index (MCTSI), Ranson score, bedside index for severity in acute pancreatitis (BISAP) and acute pancreatitis risk score (SABP) were calculated. The data sets of the First Affiliated Hospital of Soochow University and Changshu Hospital Affiliated to Soochow University were randomly divided into training set and validation set according to 8 : 2. Based on XGBoost algorithm, the SAP prediction model was constructed on the basis of hyperparameter adjustment by 5-fold cross validation and loss function. The data set of the Second Affiliated Hospital of Soochow University was served as independent test set. The predictive efficacy of the XGBoost model was evaluated by drawing the receiver operator characteristic curve (ROC curve), and compared it with the traditional AP related severity score; variable importance ranking diagram and Shapley additive explanation (SHAP) diagram were drawn to visually explain the model.@*RESULTS@#A total of 1 183 AP patients were enrolled finally, of which 129 (10.9%) developed SAP. Among the patients from the First Affiliated Hospital of Soochow University and Changshu Hospital Affiliated to Soochow University, there were 786 patients in the training set and 197 in the validation set; 200 patients from the Second Affiliated Hospital of Soochow University were used as the test set. Analysis of all three datasets showed that patients who advanced to SAP exhibited pathological manifestation such as abnormal respiratory function, coagulation function, liver and kidney function, and lipid metabolism. Based on the XGBoost algorithm, an SAP prediction model was constructed, and ROC curve analysis showed that the accuracy for prediction of SAP reached 0.830, the area under the ROC curve (AUC) was 0.927, which was significantly improved compared with the traditional scoring systems including MCTSI, Ranson, BISAP and SABP, the accuracy was 0.610, 0.690, 0.763, 0.625, and the AUC was 0.689, 0.631, 0.875, and 0.770, respectively. The feature importance analysis based on the XGBoost model showed that the top ten items ranked by the importance of model features were admission pleural effusion (0.119), albumin (Alb, 0.049), triglycerides (TG, 0.036), Ca2+ (0.034), prothrombin time (PT, 0.031), systemic inflammatory response syndrome (SIRS, 0.031), C-reactive protein (CRP, 0.031), platelet count (PLT, 0.030), lactate dehydrogenase (LDH, 0.029), and alkaline phosphatase (ALP, 0.028). The above indicators were of great significance for the XGBoost model to predict SAP. The SHAP contribution analysis based on the XGBoost model showed that the risk of SAP increased significantly when patients had pleural effusion and decreased Alb.@*CONCLUSIONS@#A SAP prediction scoring system was established based on the machine automatic learning XGBoost algorithm, which can predict the SAP risk of patients within 48 hours of admission with good accuracy.

Research advances in machine learning models for acute pancreatitis / 临床肝胆病杂志

Acute pancreatitis （AP） is a gastrointestinal disease that requires early intervention， and when it progresses to moderate-severe AP （MSAP） or severe AP （SAP）， there will be a significant increase in the mortality rate of patients. Machine learning （ML） has achieved great success in the early prediction of AP using clinical data with the help of its powerful computational and learning capabilities. This article reviews the research advances in ML in predicting the severity， complications， and death of AP， so as to provide a theoretical basis and new insights for clinical diagnosis and treatment of AP through artificial intelligence.

Improvement of the quality standard for Kunxian capsules / 药学实践杂志

Objective To improve the quality standards of Kunxian capsules (KC) and effectively control the product quality. Methods Triptolide, icariin and hypericin were used as the indicator components, to increase or improve the thin layer chromatography (TLC) identification methods of Kunming begonia, epimedium and dodder. Agilent ZORBA SB-C18 (4.6 mm×250 mm, 5 μm) as a chromatographic column, the HPLC method for the determination of triptolide was improved with acetonitrile-0.1% formic acid solution as the mobile phase and 220 nm as the detection wavelength. Results The spots in the TLC method of Kunming begonia, epimedium and dodder has strong specificity, good and clear separation of characteristic spots, negative and no interference. The quantitative analysis of the content of triptolide in KC showed that there is a good linear relationship (r=0.9995) between the mass concentration of triptolide and the peak area in the range of 40.16-502.00 μg/ml, the average recovery was 98.12%, RSD was 8.25%, and the accuracy was good. Conclusion The TLC identification method and HPLC method established in this experiment have strong specificity and good reproducibility, and can effectively control the quality of KC.

Analysis of risk factors of major adverse kidney events within 30 days in patients with acute pancreatitis / 中华危重病急救医学

Objective:To analyze the risk factors of major adverse kidney events within 30 days (MAKE30) in patients with acute pancreatitis (AP).Methods:A retrospective cohort study was conducted. A total of 162 patients who were first diagnosed with AP in the First Affiliated Hospital of Soochow University from June 2019 to June 2021 and the onset time was less than 72 hours were enrolled. Patients were divided into MAKE30 group and non-MAKE30 group according to the occurrence of MAKE30 after hospitalization. MAKE30 was defined as death from any cause, new renal replacement therapy (RRT), and persistent renal insufficiency (PRD). The clinical data of the two groups at admission were compared. The independent risk factors of MAKE30 were analyzed by multivariate Logistic regression method, and a regression equation was established as a quantitative prediction model of MAKE30. Receiver operator characteristic curve (ROC curve) was drawn to analyze the prediction of the quantitative prediction model value.Results:All 162 patients were included in the final analysis, including 32 in the MAKE30 group and 130 in the non-MAKE30 group. Univariate analysis showed that compared with the non-MAKE30 group, the body mass index (BMI), the proportion of severe AP, and the acute physiology and chronic health evaluation Ⅱ (APACHEⅡ) score, the sequential organ failure assessment (SOFA) score, blood urea nitrogen (BUN), serum creatinine (SCr), C-reactive protein (CRP), HCO 3-, Cl - levels and the proportion of hyperchloremia at admission in the MAKE30 group were significantly increased. Multivariate Logistic regression analysis showed that APACHE Ⅱ score at admission [odds ratio ( OR) = 1.659, 95% confidence interval (95% CI) was 1.426-1.956, P = 0.009], SOFA score ( OR = 1.501, 95% CI was 1.236-1.840, P = 0.014) and hyperchloremia ( OR = 1.858, 95% CI was 1.564-2.231, P = 0.004) were independent risk factors for MAKE30 in AP patients. The MAKE30 regression equation was established by the above risk factors [Logit( P) = 0.063+0.525×APACHEⅡ score+0.328×SOFA score+0.895×hyperchloremia], which was used as the MAKE30 quantitative prediction model. ROC curve analysis showed that the area under the ROC curve (AUC) of the model for predicting MAKE30 was 0.846 (95% CI was 0.774-0.923, P = 0.001). The patients were divided into two subgroups with hyperchloremia (Cl -≥110 mmol/L, n = 19) and non-hyperchloremia (Cl - < 110 mmol/L, n = 143) according to the blood Cl - level at admission. The incidence of MAKE30 and acute kidney injury (AKI) in the hyperchloremia group was significantly increased (MAKE30: 68.4% vs. 13.3%, AKI: 89.5% vs. 43.4%), and the levels of BUN and SCr at admission were significantly increased [BUN (mmol/L): 9.3±2.5 vs. 5.9±1.1, SCr (μmol/L): 162.3±26.4 vs. 78.6±9.2], the total length of hospital stay and length of intensive care unit (ICU) stay were significantly longer [total length of hospital stay (days): 10.2±1.6 vs. 5.6±1.2, length of ICU stay (days): 6.2±1.0 vs. 3.1±0.6], the cumulative intravenous infusion volume increased significantly at 48 hours and 72 hours (mL: 7 235.9±1 025.3 vs. 5 659.6±956.7 at 48 hours, 11 052.6±1 659.8 vs. 7 156.9±1 052.4 at 72 hours), differences were statistically significant (all P < 0.01). Conclusions:MAKE30 can be used as an important indicator to evaluate the short-term clinical prognosis of AP patients. APACHEⅡ score, SOFA score and hyperchloremia at admission are the main risk factors. The risk model of MAKE30 based on these three indicators has good predictive performance. AP patients with hyperchloremia are at high risk of developing MAKE30, which should be highly regarded in clinical practice.

Operation timing of laparoscopic cholecystectomy in mild acute billiary pancreatitis / 中华胰腺病杂志

Objective To explore the operation timing of laparoscopic cholecystectomy ( LC ) for patients with first onset of mild acute biliary pancreatitis ( ABP) . Methods From January 2012 to December 2017, a total of 905 ABP patients who admitted to the First Affiliated Hospital of Soochow University were retrospectively assessed. Among them, 165 ABP patients underwent LC. According to the different operation time after hospitalization, the patients were divided into 5 groups: within 2 weeks surgery group, 2-4 weeks surgery group, 4 -8 weeks surgery group, 8 -24 weeks surgery group and 24 weeks later surgery group. Surgery difficulty, postoperative recovery, total hospitalization time and recurrence of acute biliopancreatic disease before surgery were compared between the 5 groups. Results LC was successfully completed in all 165 patients. There was no statistically significant difference on the surgical difficulty and postoperative recovery among the 5 groups (P>0. 05). The total hospitalization time of within 2 weeks surgery group and 2-4 weeks surgery group was significantly shortened compared with that in 4-8 weeks surgery group, 8-24 weeks surgery group and 24 weeks later surgery group [14.5(8.0-21.0)d, 14.0(7.0-23.0)d]vs [17.0 (6.0-42.0)d, 20.0(9.0-46.0)d, 21.5(7.0-42.0)d], and the difference was statistically significant (P<0. 05). Moreover, the recurrence rate of acute biliopancreatic disease was 0 in within 2 weeks surgery group while waiting for surgery, which was lower than those of other four groups [6. 1％(2/33),38. 5％(15/39),61.5％(24/39),77.3％(17/22)], and the difference was statistically significant (P<0.05). Conclusions For ABP patients with first onset, LC was safe and feasible within 2 weeks after conservative treatment, which can significantly shorten the total hospitalization time and reduce the recurrence rate of acute biliopancreatic diseases during the waiting period.

In vitro study on the role and mechanism of interferon α-1b in regulating the inhibition of protein kinase Cεand Cα on fibrosis of hepatic stellate cells / 中华传染病杂志

Objective To investigate the regulation of interferon α-1b (IFNα-1b) on protein kinase Cε(PKCε) and protein kinase Cα(PKCα) which inhibit the fibrosis of hepatic stellate cells (HSC) ,and to explore its mechanism .Methods HSC-T6 cells were treated with different levels of IFNα-1b (100 , 200 ,400 ,800 and 1000 U/mL) and the proliferation of HSC-T6 cells was analyzed by methyl thiazol tetrazolium (MTT) assay .Changes of hydroxyproline level were analyzed .The expressions of PKCεand PKCαwere detected by immunofluorescence staining . PKCε, PKCα,β-catenin and Survivin mRNA levels were detected by RT-PCR . PKCε, PKCα,β-catenin and Survivin protein levels were detected by Western blot . Variance analysis was conducted by using one-way ANOVA approach . Results The inhibition rates of 100 , 200 , 400 , 800 and 1000 U/mL IFNα-1b treatment after 24 hours of administration were (15 .85 ± 1 .05)％ ,(36 .59 ± 1 .03)％ ,(45 .12 ± 1 .05)％ ,(50 .00 ± 1 .01)％ and (62 .20 ± 1 .02)％ ,respectively ,with statistically significant differences among groups (F=27 .478 , P<0 .01) .The 48h inhibition rates were (20 .87 ± 1 .09)％ ,(43 .96 ± 1 .08)％ ,(53 .85 ± 1 .08)％ ,(64 .84 ± 1 .06)％ and (74 .72 ± 1 .07)％ ,respectively ,with statistically significant differences among groups (F=25 .321 , P< 0 .01 ) . half maximal inhibitory concentration at 48 h was 343 .47 U/mL . The levels of hydroxyproline in 100 ,200 and 400 U/mL IFNα-1b groups were (7 .48 ± 0 .28) ,(6 .26 ± 0 .17) and (3 .86 ± 0 .20) μg/mL ,respectively ,which were lower than that in control group (8 .47 ± 0 .32) μg/mL .The differences were all statistically significant (t=4 .033 ,10 .564 and 21 .160 ,respective ,all P<0 .05) .The fluorescence intensities of PKCεin 100 ,200 and 400 U/mL IFNα-1b groups were all lower than that of control group .The differences were statistically significant (t=1 .984 ,2 .457 and 7 .771 ,respectively ,all P<0 .05) .The fluorescence intensities of PKCαwere also significantly lower than that of control group (t=9 .232 ,15 .921 and 22 .222 ,respectively ,all P< 0 .01) .With the increase of IFNα-1b level ,the levels of HSC-T6 PKCε,PKCα,β-catenin and survivin were significantly lower than those of control group (t=7 .020 ,24 .562 ,45 .701 and 14 .241 ,respectively ,all P<0 .01) .With the increase of IFNα-1b ,the levels of HSC-T6 PKCε,PKCα,β-catenin and survivin were significantly lower than those of control group (t=9 .564 ,4 .409 ,10 .036 and 6 .794 ,respectively ,all P<0 .01) .Conclusions IFNα-1b can down-regulate the expression of collagen in hepatic stellate cells in a dose-dependent manner ,reduce the expressions of PKCε,PKCα,β-catenin and Survivin ,and inhibit the proliferation of HSC-T6 hepatic stellate cells .

Effects of angiotensin Ⅱ on protein kinase Cε and Cα expression in hepatic stellate cells / 中国医师杂志

Objective To investigate the effect of angiotensin Ⅱ on protein kinase Cε (PKCε) and protein kinase Cα (PKCα) expression in hepatic stellate cells.Methods Hepatic stellate cell (HSC)-T6 cells were treated with different concentrations of angiotensin Ⅱ and the proliferation of HSC-T6 cells was detected by methyl thiazolyl tetrazolium (MTT) assay.The expression of PKCε and PKCα was detected by immunofluorescence staining.PKCε and PKCα mRNA levels was detected by real time polymerase chain reaction (PCR).Results Angiotensin Ⅱ concentrated the proliferation of HSC-T6 cells and the level of hydroxyproline (F =25.321,13.283,P ＜ 0.001) and showed a dose-dependent effect.With the increase of angiotensin Ⅱ concentration,PKCε significantly increased and translocated in the cell membrane;PKCα increased significantly,especially in transplanted membrane and cytoplasm (F =21.387,19.431,P ＜0.01),and showed obvious dose effect.Meanwhile,Angiotensin Ⅱ increased the expression of PKCε and PKCα,and induced cell proliferation by up-regulating PKCε and PKCα mRNA levels (F =13.279,15.174,P ＜ 0.05).Conclusions Angiotensin Ⅱ can up-regulate the expression of collagen in hepatic stellate cells in a dose-dependent manner,increase the expression of protein kinase Cε and Cα,and promote the proliferation of hepatic stellate cells.

Complications of therapeutic endoscopic retrograde cholangiopancreatography in patients with metabolic syndrome / 中华消化内镜杂志

Objective To investigate the complications of therapeutic endoscopic retrograde cholangiopancreatography(ERCP) in patients with metabolic syndrome and their prevention. Methods Clinical data of 300 patients who underwent therapeutic ERCP in the First Affiliated Hospital of Soochow University from March 2013 to January 2016 were analyzed retrospectively. Among these patients, 100 of them(group A)had metabolic syndrome and 200 others(group B)did not. Age, sex and post-operative hyperamylasemia,acute pancreatitis,infection of biliary tract and upper gastrointestinal bleeding of two groups were compared. In addition,effects of BMI,TG,BP and FPG on the occurrence of complications in group A were analyzed. Results No difference was found in age and sex between group A and B(P>0.05),but group A had higher incidences of post-operative hyperamylasemia[16.0%(16/100)VS 6.0% (12/200)],acute pancreatitis[14.0%(14/100)VS 4.0%(8/200)], infection of biliary tract[12.0% (12/100)VS 4.0%(8/200)]and upper gastrointestinal bleeding[8.0%(8/100)VS 1.0%(2/200)] (P<0.05). Meanwhile, patients had higher incidences of complications(post-operative hyperamylasemia, acute pancreatitis,infection of biliary tract and upper gastrointestinal bleeding)when BMI[56.10%(46/82) VS 22.22%(4/18)],TG[56.41%(44/78)VS 27.27%(6/22)],BP[64.29%(27/42)VS 39.66% (23/58)]or FPG[54.44%(49/90)VS 10.00%(1/10)]increased in group A(P < 0.05).Conclusion Patients with metabolic syndrome have a higher incidence of complications after therapeutic ERCP than patients without. Therefore,careful preparation, post-operative observation and intervention are essential when patients with metabolic syndrome undergo therapeutic ERCP.

Evaluation of Clinical Effect of Rabeprazole Combined with Teprenone Capsules in Treatment of Gastric Ulcer by Marking Targeting Biopsy and Leptin / 医药导报

Objective To evaluate clinical effect of rabeprazole combined with teprenone capsules in treatment of gastric ulcer by marking targeting biopsy and leptin.Methods A total of 118 patients with active gastric ulcer confirmed by endoscopy were randomly divided into two groups.Patients in the treatment group (n=60) were given rabeprazole 10 mg,bid,and teprenone capsules 50 mg,tid.Patients in the control group (n=58) were given rabeprazole 10 mg,bid.Both groups were treated continuously for 56 days.Before and after treatment,2 groups were labeled with biopsy,the clinical efficacy and the healing rate of two groups were recorded,the quality of healing and the expression of leptin were compared.The level of leptin was tested after treatment.Results After 10 days,the difference of clinical curative effect was not statistically significant (P>0.05).After 56 days,the difference of clinical curative effect was statistically significant (P<0.05);ulcer healing rate (93.33%)in treatment group was higher than that of control group (72.41%);ulcer healing quality (93.33%) in treatment group was higher than that of control group (58.62%);leptin level of treatment group was lower than that of the control group;gastric ulcer recurrence rate (3.8%) in treatment group was lower than that of the control group (24.0%) (all P<0.05).Conclusion Rabeprazole combined with teprenone in the treatment of gastric ulcer is better than rabeprazole.Marking targeting biopsy and leptin can be used to evaluate the healing quality of gastric ulcer more accurately,which can be an evaluation index of the quality of gastric ulcer healing and used as an indicator of the quality of gastric ulcer healing.

Effects of matriptase down regulation on invasion of human pancreatic cancer cells SW1990 / 中华胰腺病杂志

Objective To investigate the effect of the down regulation of matriptase expression on invasion of human pancreatic cancers cells SW1990.Methods Small interfering RNA targeting at matriptase (Ma-siRNA) was transfected into human pancreatic cancers SW1990 cells,and nonsense siRNA (NC-siRNA) group was used as control.Real time PCR assay and Western blot were used to detect the expression of matriptase mRNA and protein.Transwell assay was used to examine the invasion ability of cancer cells.The enzymatic activity of matriptase and MMP-9 was determined by gelatin zymography assay.Results The expression level of matriptase mRNA in NC-siRNA group,12.5,25,50 nmol/L Ma-siRNA group were 1.000,0.417 ± 0.006,0.233 ± 0.068,0.221 ± 0.092;and the protein expression of matriptase were 0.736 ± 0.066,0.498 ± 0.036,0.341 ± 0.118,0.239 ± 0.050,respectively.The matriptase mRNA and protein expression in Ma-siRNA groups was significantly lower than those in NC-siRNA group,and the difference between the two groups was statistically significant (P ＜ 0.05).The enzymatic activity of matriptase were 1.501 ±0.165,1.211 ±0.265,0.645 ±0.165,0.620 ±0.003,and the enzymatic activity of MMP-9 were 0.929 ± 0.260,0.484 ± 0.364,0.352 ± 0.113,0.346 ± 0.121,and the enzymatic activity of matriptase and MMP-9 in 25,50 nmol/L Ma-siRNA groups was significantly lower than that in NC-siRNA group,and the difference was statistically significant (P ＜ 0.05 or ＜ 0.01).The number of transmembrane cell was (256 ± 1)/per 200 power field,and it was (109 ± 3)/per 200 power field in 25 nmol/L Ma-siRNA group,and the invasion ability of the cells in 25 nmol/L Ma-siRNA group was decreased by (57.4 ± 5.4) ％ when compared with that of control group.Conclusions Down-regulation of matriptase inhibits invasion ability of pancreatic cancer SW1990 cells,and this result may be due to the down regulated enzymatic activity of matriptase and MMP-9.

Expression and its significance of receptor-interacting protein kinase 3 in ulcerative colitis / 中华消化杂志

Objective To explore the role of receptor‐interacting protein kinase 3 (RIP3)‐mediated necroptosis in ulcerative colitis (UC ) . Methods The colonic mucosa tissues of eighty‐five patients diagnosed with UC were collected .Disease staging and pathological classification of UC patients were evaluated according to Mayo standard and Truelove standard ,respectively .The expressions of RIP3 and tumor necrosis factor (TNF)‐α were detected by immunohistochemistry .The cell inflammation model in HT‐29 cells was induced by interferon (IFN)‐γ.The expression of RIP3 mRNA and interleukin (IL)‐1βmRNA was determined by real time polymerase chain reaction (RT‐PCR) .Twenty healthy individuals were studied as controls .A single factor analysis of variance was performed in the comparison among groups ,and Pearson correlation analysis was used for correlation analysis .Results Among 85 patients with UC , 27 cases were mild ,30 cases were moderate and 28 cases were severe;for pathological classification ,26 were gradeⅠ ,31 were gradeⅡ and 28 were grade Ⅲ .The Mayo score was positively correlated with pathological grade (r=0 .997 , P<0 .05) .The expression of RIP3 and TNF‐α in colonic mucosa tissues of UC group increased along with the pathological classification grade .The expression of RIP3 of gradeⅠto Ⅲ was 1 .81 ± 0 .98 ,2 .77 ± 1 .26 and 4 .86 ± 2 .77 ,respectively ,and the differences were statistically significant (F=26 .10 ,P<0 .05) .The expression of TNF‐αof gradeⅠto Ⅲ was 1 .35 ± 0 .69 ,2 .61 ± 1 .41 and 4 .43 ± 2 .17 ,respectively ,and the differences were statistically significant (F=31 .80 ,P<0 .05) .The expression of IL‐1β mRNA of IFN‐γ group ,IFN‐γ+ z‐VAD group and IFN‐γ+z‐VAD+ TNF‐αgroup was 0 .68 ± 0 .27 ,1 .47 ± 0 .12 and 1 .86 ± 0 .16 ,respectively ,and the differences were statistically significant (F=38 .45 , P<0 .05) .The expression of RIP3 mRNA of IFN‐γgroup ,IFN‐γ+z‐VAD group and IFN‐γ+z‐VAD+TNF‐αgroup was 0 .46 ± 0 .13 ,1 .21 ± 0 .29 and 2 .06 ± 0 .20 ,respectively , and the differences were statistically significant (F= 55 .15 , P< 0 .05) .Conclusions TNF‐α/RIP3 signal pathway is up‐regulated in UC .RIP3‐mediated necroptosis promotes the death of colonic epithelial cells and exacerbates inflammatory response .RIP3‐mediated necroptosis may be an important mechanism in UC .

Effect of cerulenin combined with gemcitabine on proliferation and apoptosis in human pancreatic cell line BxPC3 / 中华胰腺病杂志

Objective To investigate the effect and mechanism of action in pancreatic cancer BxPC3 cell treated by cerulenin in combination with gemcitabine.Methods BxPC3 cells were cultivated with 10 μg/ml cerulenin,20 μmol/L gemcitabine or 10 μg/ml cerulenin + 20 μmol/L gemcitabine for 48 h,and cells without treatment were control.Cell proliferation was detected by CCK-8 assay,and early apoptosis was detected by AnnexinV/PI double staining method.The expression of Bcl-2 mRNA and Bax mRNA were detected by RT-PCR,and the protein level of Bcl-2,Bax were detected by Western Blot.Results The inhibition rate of BxPC3 cells were 0,(51.28 ± 1.84) ％,(53.59 ± 1.62) ％,(84.57 ± 1.01) ％ in control,cerulenin group,gemcitabine group,combination group; and the rate of early apoptosis was (0.83 ± 0.31) ％,(31.37 ± 1.04) ％,(38.33 ± 0.75) ％,(69.43 ± 0.83) ％,and the expression of Bcl-2 mRNA was 0.67 ± 0.01,0.44 ±0.01,0.36 ±0.08,0.27 ±0.07,and the expression of Bax mRNA was 0.14 ±0.01,0.31 ± 0.02,0.32 ± 0.03,0.91 ± 0.06 ; while the ratio of Bcl-2 mRNA/Bax mRNA was 4.78 ± 0.13,1.39 ± 0.04,1.15 ± 0.02,0.30 ± 0.02 ; the expression of Bcl-2 protein was 1.24 ± 0.04,0.51 ± 0.02,0.42 ± 0.02,0.13 ±0.01 ; and the expression of Bax protein was 0.20 ± 0.05,0.47 ± 0.01,0.54 ± 0.01,1.21 ± 0.03 ; while the ratio of Bcl-2/Bax was 6.00 ± 0.11,1.11 ± 0.01,0.77 ± 0.03,0.10 ± 0.06.And the difference among the groups was statistically significant (P ＜ 0.01).Conclusions Cerulenin combined with gemcitabin has synergistic effect on the inhibition of BxPC cells proliferation.Its mechanisms may be up-regulation of Bax,down-regulation of Bcl-2,and promoting apoptosis of cells through the decrease of Bcl-2/Bax ratio.

Effect of metformin on proliferation and apoptosis in human pancreatic cancer cell line CFPAC-1 / 中华胰腺病杂志

Objective To investigate the effect of metformin on the proliferation and apoptosis in human pancreatic cancer cell line CFPAC-1,and to explore the potential mechanism.Methods Human pancreatic cancer CFPAC-1 cells were cultured in vitro,and were treated with metformin at different concentrations (1,2.5,5,10,20,40,60 mmol/L) for different durations (24 h,48 h and 72 h),and cells without treatment were considered as control group.Cell proliferation was evaluated by CCK-8,cell cycle was determined by flow cytometry,apoptosis was determined by Annexin V/PI double staining method,and Western blot was used to detect the protein expression of p-AMPK,FAS,cyclin D1,Bcl-xl,Bax,caspase-3 and survivin.Results Metformin could inhibit the proliferation of CFPAC-1 cells in a time and dose dependent manner.Forty-eight hours after 40 mmol/L metformin treatment,the proportion of CFPAC-1 cells in phase G0/G1 was significantly increased [(65.93 ± 0.27)％ vs (42.89± 1.02)％],and the proportion of CFPAC-1 cells in phase G2/M,S was significantly decreased [(22.01 ± 2.95) ％ vs (38.28 ± 4.93) ％,(13.58±0.43)％ vs (20.12 ± 3.38)％],and the difference between the two groups was statistically significant (P ＜0.05).The apoptosis rate was increased from (3.01 ± 0.49) ％ to (32.97 ± 3.19) ％,(P ＜ 0.05) ; and the expression of p-AMPK,Bax,and caspase-3 was increased,while the expression of FAS,cyclin D1,Bcl-xl,survivin were decreased.Conclusions Metformin can inhibit proliferation and promote apoptosis of CFPAC-1 cells mainly by activation of AMPK pathway,and down-regulation of FAS,cyclin D1,survivin and Bcl xl/Bax ratio,as well as up-regulation of caspase-3.

Effect of probiotics on patients with severe acute pancreatitis: A Meta analysis / 中华消化杂志

Objective To explore the effect of probiotics on patients with severe acute pancreatitis.Methods Randomized controlled trials of probiotics in patients with severe acute pancreatitis were searched in Cochrane Library(2010),Medline(1966 to September 2010),China Academic Literature Full-text Database,Chinese Science and Technology Journal Database and WanFang Database between 1966 and September 2010.Evaluation of literature quality and data extraction were independently completed by two researchers.Data were analyzed with RevMan4.3 software.Results A total of 313 papers had been searched.After excluded duplicated and low-level paper,six articles were included in this study.The result showed that the infection rate(OR=0.88,95％CI[0.56,1.38])and mortality rate(OR=1.44,95％CI[0.78,2.64])of patients with severe acute pancreatitis in intervention group were not lower than control group,however the length of stay in hospital was shorter in intervention group than control group(WMD=-4.69,95％ CI[-7.73,-1.65]).There was no significant difference between intervention group and control group in systemic inflammatory response syndrome(OR =1.33,95 ％ CI[0.63,2.83]),multiple organ failure (OR=1.50,95 ％ CI[0.89,2.52])and transfering to surgery department for further treatment(OR=0.92,95％CI[0.56,1.51]).Conclusion So far the studies indicated that probiotics could not lower the infection rate and mortality rate in patients with severe acute pancreatitis.Large sample and highquality randomized controlled trials are needed for further evaluation.

Effects of thalidomide on proliferation and apoptosis in human pancreatic cancer cell line SW1990 / 中华胰腺病杂志

ObjectiveTo investigate the effect of thalidomide on the proliferation and apoptosis in human pancreatic cancer cell SW1990 in vitro.MethodsSW1990 cell line was treated with thalidomide at different concentrations (3.125,6.25,12.5,25,50,100,200 and 400 μg/ml) for 24,48,72 h,and then cell proliferation were evaluated by MTT.Cell cycle was determined by flow cytometry,apoptosis was determined by annexin V/PI fluos staining,Bcl-2,Bax protein expression and Bcl-2/Bax ratios were measured by Western Blot in vitro.ResultsThalidomide inhibited the proliferation of SW1990 cells in a time and dosedependant manner.The proportion of G0/G1 phase of SW1990 cells with 200 μg/ml thalidomide treatment increased from (41.15 ± 2.23 ) ％ to (58.83 ± 2.33 ) ％,apoptosis rate increased from 2.6％ to 28.0％,the expression of Bax protein up-regulated from 0.17 ± 0.03 to 0.33 ± 0.04,the expression of Bcl-2 protein downregulated from 0.35 ± 0.02 to 0.17± 0.01,the ration of Bcl-2/Bax decreased from 2.17 ± 0.44 to 0.52 ±0.07.ConclusionsThalidomide can inhibit the proliferation of pancreatic cancer SW1990 cells by upregulating Bax,down-regulating Bcl-2,inducing cell apoptosis and cell Go/G1 phase arrest.

The effects of enteral nutrition versus total parenteral nutrition on gut barrier function in severe acute pancreatitis / 中华内科杂志

Objective To evaluate the effect of enteral nutrition (EN) versus total parenteral nutrition(TPN) on gut barrier function in patients with severe acute pancreatitis (SAP). Methods Sixtythree patients with SAP enrolled from 4 hospitals were randomly assigned into EN group(29 cases) and TPN group(34 cases). EN group patients were fed via a spiral nasojejunal feeding tube placed routinely by endoscopy or fluoroscopy, and TPN group patients were nourished intravenously with TPN during the same period. The changes of serum endotoxin, diamine oxidase, and urinary excretion of lactulose and mannitol ratio (L/M) were observed. Results Plasma concentration of endotoxin were markedly decreased in EN group as compared with that in TPN group at the 7th,14th ,21th day of entry trial [(39. 30 ± 15. 82) EU/L vs (73.05 ±21.16) EU/L,(22.64 ±14.31) EU/L vs (49.34 ±24.54) EU/L,(14.81 ± 10.93)EU/L vs ( 30. 08 ± 14. 10 ) EU/L, P ＜ 0. 05]. Plasma concentration of diamine oxidase were markedly decreased in EN group as compared with that in TPN group at the 7th, 14th day of entry trial [(9. 97 ± 3. 84)U/Lvs (19.89±9.89)U/L,(5.42±1. 84) U/Lvs (8.79 ±4.08) U/L, both P ＜ 0. 05]. The urinary L/M decreased significantly in EN group than those in TPN group at the 7th, 14th,21th day of entry trial (0.28 ±0.25 vs 0. 65 ±0.45,0.21 ±0. 18 vs 0.54 ±0.41,0.08 ±0.04 vs 0.29 ±0.06, all P＜0.05).Conclusion EN has better effect on improving intestinal barrier function than TPN in treatment of patients with SAP.

Effect of melatonin on the pancreatic cancer in mice subcutaneous xenograft / 中华胰腺病杂志

Objective To investigate the therapeutic effects of melatonin (MT) on human pancreatic cancer in Balb/c nude mice subcutaneous xenograft model. Methods Pancreatic cancer model was established high dose MT(20 mg· kg -1 · d-1 ) , gemcitabine( GEM,50 mg· kg -1 · d-1 ) and high dose MT combination with GEM. Tumor size was measured regularly. The tumor growth curve was drawn. The activity of mice spleen natural killer cell was determined by MTT. Results Compared with the controls [ ( 1. 476 ± 0.075) cm3 ], tumor volumes in low dose MT group[ (0.998 ±0.112)cm3], high dose MT group[ (0.756 ±0.128) cm3], GEM group [ (0. 746 ± 0. 115 ) cm3 ], combination group [ (0. 305 ± 0. 111 ) cm3 ] were significantly decreased ( P <0.01), and the tumor size in high dose MT group was smaller than that in low dose MT group, while the tumor size in combination group was the smallest. The activity of mice spleen natural killer cell was ( 18.07 ± 1.23) %in control group, and they were (44.27 ±3.19)% ,(45.16 ±3.20)% and (30.29 ±2.91)% in low dose MT group, high dose MT group, combination group, which were significantly higher than those in the control group;the activity of natural killer cell in GEM group was ( 14.24 ± 2.70) %, which was significantly lower than that in the control group (P <0.05), but the activity of natural killer cell in combination group was significantly higher than that in the GEM group (P < 0.01 ). Conclusions MT could improve the immune function of mice,inhibit the growth of tumor, and MT combination with GEM may have more potent antitumor effect.

Effects of melatonin on proliferation and apoptosis in human pancreatic cancer cell line SW1990 / 中华胰腺病杂志

Objective To investigate the effect of melatonin (MT) on the proliferation and apoptosis in human pancreatic cancer cell SW1990 in vitro.Methods SW1990 cell line were treated with MT at different concentrations (0.1,0.5,1.0,2.5 and 5.0 mmol/L) and at different time points (24 h,48 h and 72 h).Cell proliferation was evaluated by MTT and apoptosis was determined by AnnexinV/Pl,cell cycle was determined by flow cytometry,and Western Blot was used to detect the expression of Bcl-2 and Bax.Results MT could inhibit the proliferation of SW1990 cell in a time and dose dependent manner.48 h after 0.1～5.0 mmol/L MT treatment,the proliferation inhibitory rate was 7.4%～85.8%,the proportion of SW1990 cell in phase G0/G1 was 72.6%～85.33%.48 h after 1～5.0 mmol/L MT treatment,the apoptosis rate was 21.5% ～41.7%,and the expression of Bcl-2 was down-regulated and the ratio of Bcl-2/Bax decreased.Conclusions MT could inhibit the proliferation of SW1990 pancreatic cancer cells by up-regulating the expression of Bax and down-regulating the expression of Bcl-2,as well as enhancing apoptosis and blocking SW1990 cell in phase G0/G1.

Effect of early continuous enteral nutrition combined with interstinal mucosal protective agents on gut barrier in patients with severe acute pancreatitis:A multicenter prospective randomized controlled trial / 中华消化杂志

Objective To assess the effect of continuous early enteral nutrition(EEN)combined with intestinal mucosal protective agents on gut barrier function in patients with severe acute pancreatitis.Methods A total of 79 patients with severe acute pancreatitis selected from four centers between May 2004 to June 2006 were enrolled and divided into EEN combined with intestinal mucosal protective agents group(combined group,n=39)and total parenteral nutrition(TPN)group(n=40).The patients were received either EEN or TPN when homeostasis were achieved within 72 hours after onset.The patients in combined group were administered pepti-2000 variant combined with glutamine,arginine and intestinal mucosal protective agents.The patients in TPN group were administered through a central vein.APACHE-Ⅱ score was recorded every week;The concentration of serum amylase,plasmic diamine oxi dase(DAO)and endotoxin were mesured on day 1,7,14 and 21 as well as urinary excretion of lactulose (L)and mannitol(M).Complications,lenth and charges of hospital stay were recorded.Results There was no death in both groups.The APACHE-Ⅱ score decreased on day 7,but lower in combined group (6.00±1.60)than that in TPN group(7.08±2.34)(P＜0.05).On day 7,14 and 21,the concentrations of endotoxin in combined group was(39.30±15.82),(22.64±14.31),(14.81±10.93)Eu/L,respectively,urinary L/M ratio was 0.28±0.25,0.21±0.18 and 0.08±0.04,respectively,IFABP-c was 15.62±5.26),(5.46±1.18)and(3.26±0.94)pg/ml,respectively.All of these parameters were significantly lower than those in TPN group(P＜0.05).The infectious rates including pancreatic,peritoneal and respiratory infection in TPN group were much higher than that in combined group(26.47% vs 3.44%,P＜0.01).The composition of flora fecal remained unchange in combined group rather than TPN group.The mean hospital stay was shorter in combined group[(20.0±5.7)days]compared to TPN groups[(34.5±12.9)days].The charges were also significantly lower in combined group,with average cost of RMB 25,900±14,200,while it was 46,800±4,030 in TPN group.Conclusions EEN combined with intestinal mucosal protective agents can improve gut barrier function via reducing the gut permeability,improving the hypoperfusion,maintaining the integrity and gut fecal flora.It might reduce the course and charges of hospital stay.

Magnetic iron oxide nanoparticles mediated gene therapy for breast cancer--an in vitro study / 华中科技大学学报（医学）（英德文版）

The aim of this study was to evaluate the feasibility and efficacy of using TRAIL gene to treat breast cancer mediated with a novel carrier - magnetic iron oxide nanoparticles (poly-MAG-1000) coated with PEI. The magnetic iron oxide nanoparticles were used as gene carrier to transfect TRAIL gene into MCF-7 cells. The polyMAG-1000 without TRAIL gene was transfected into the tumor cells as negative control. TRAIL gene transfection with liposome as carrier served as positive control. The apoptosis of cells was detected with TUNEL method. The apoptosis ratio of tumor cells was measured with flow cytometry (FCM). It was found that the apoptosis occurred in the tumor cells after transfection of TRAIL gene mediated by both polyMAG-1000 and liposome. The apoptosis ratio in the group with polyMAG-1000 as gene carrier was (25.11+/-2.85) %, whereas it was (5.06+/- 1.05) % in the control group with polyMAG-1000 (P<0.01). The apoptosis ratio was as low as (18.31+/-2.44) % in the group with liposome as gene carrier (P<0.05, as compared with the group with polyMAG-1000 as gene carrier). It is suggested that TRAIL gene may induce apoptosis in MCF-7 breast cancer cells. The magnetic iron oxide nanoparticles coated with PEI may be a potential gene carrier with high transfection efficacy for cancer gene therapy..