Establishment of Gemcitabine-resistant Human Pancreatic Cancer Cell Subclone and Preliminary Exploration of the Resistance Mechanism / 胃肠病学

Background:Gemcitabine is the first-line drug for chemotherapy of pancreatic cancer. However,owing to the inherent and acquired resistance,gemcitabine does not change obviously the prognosis of patients with pancreatic cancer. Exploration of the mechanism of acquired resistance to gemcitabine is of great clinical importance. Aims:To establish a gemcitabine-resistant human pancreatic cancer cell subclone and to explore preliminarily the resistance mechanism. Methods:Human pancreatic cancer cell line SW1990 was stimulated continuously with 0. 5 μmol/ L gemcitabine in vitro to establish the gemcitabine-resistant subclone SW1990-0. 5. The resistance index of SW1990-0. 5 cells was counted by CCK-8 assay. Proliferation and invasion of SW1990 and SW1990-0. 5 cells were detected by cell doubling time assay and scratch wound healing assay in vitro;cell cycle and cell apoptosis were detected by flow cytometry;expressions of multidrug-resistance related genes(MDR-1,MRP-1,and BRCP)and gemcitabine metabolic enzyme related genes(dCK,RRM1, and RRM2)were determined by real-time PCR. Results:The resistance index of SW1990-0. 5 cells was 9. 32. Compared with the parental SW1990 cells,the proliferation capacity but not the invasion capacity of SW1990-0. 5 cells in vitro was reduced. When treated with gemcitabine,the cell cycle of SW1990-0. 5 cells was similar to that of parental cells,whereas the cell apoptosis was significantly inhibited;expressions of MRP-1,BRCP and dCK mRNA were down-regulated,while expressions of MDR-1,RRM1 and RRM2 mRNA did not change. Conclusions:A stable gemcitabine-resistant human pancreatic cancer cell subclone SW1990-0. 5 was successfully established. Inhibition of cell apoptosis and down-regulation of dCK expression might contribute to the acquired resistance to gemcitabine of pancreatic cancer.

Gemcitabine-resistant Human Pancreatic Cancer Cell Line Overexpresses APE1/Ref-1 / 胃肠病学

Background:Gemcitabine is the main drug for chemotherapy of advanced pancreatic cancer,however,the prognosis of pancreatic cancer patients has not been changed obviously because of the high innate and acquired resistance of cancer cells to gemcitabine. Aims:To investigate the correlation of DNA repair and expression of human APE1 / Ref-1(apurinic/apyrimidinic endonuclease 1 / redox factor-1),the key enzyme in base excision repair pathway,with the resistance of pancreatic cancer to gemcitabine. Methods:A gemcitabine-resistant human pancreatic cancer cell line SW1990-0. 5 with a resistance index of 9. 32 and its parental cell line SW1990 were treated with gemcitabine. DNA injury was assessed by comet assay. Expressions of APE1 / Ref-1 mRNA and protein were determined by real-time PCR and Western blotting, respectively. Results:In comet assay,after treated with gemcitabine for 24 hours,OTM value of SW1990-0. 5 and SW1990 cells were 0. 32 ± 0. 13 and 26. 96 ± 6. 83,respectively. Expression level of APE1 / Ref-1 mRNA in SW1990-0. 5 cells was 2. 48 ± 0. 49;and expression levels of APE1 / Ref-1 protein in SW1990-0. 5 and SW1990 cells were 1. 57 ± 0. 08 and 0. 84 ± 0. 06,respectively. Statistically significant differences were existed in all these parameters between SW1990-0. 5 and SW1990 cells(P all < 0. 05). Conclusions:DNA repair might be correlated with the resistance of pancreatic cancer to gemcitabine,and up-regulation of APE1 / Ref-1 might contribute to this resistance by its function on DNA repair.

Impact of obesity on long-term survival after aortic valve replacement with small prosthesis / 中华胸心血管外科杂志

Objective This study was designed to evaluate the effect of obesity on late survival after aortic valve replacement(AVR) in patients with implantation of small aortic prosthesis(size≤21).Methods From January 1998 through December 2008,307 patients in a single center in china underwent primary AVR with smaller prosthesis survive the 30 days of surgery.Patients were defined as normal if body mass index (BM1) ＜ 24.0 kg/m2,as overweight if BMI 24.0-27.9 kg/m2,and as obesity if BMI≥28.0 kg/m2.Data of New York Heart Association(NYHA) Functional class,effective orifice area index (EOAI),left ventricular mass index(LVMI),left ventricular ejection fraction(LVEF) were got at the 3rd month(M),6th M,1 st year(Y),3rd Y,5th Y,8th Y after operation respectively.Results At multivariable analysis,obesity was independent factor of later mortality [hazard ratio (HR):1.62 ; P =0.01].Obesity group and overweight group had poor survival (P ＜0.001)and higher proportion of NYHA Function Ⅲ/Ⅳ (P ＜ 0.01) in long-term compared to normal group.EOAI were lower and LVMI were higher in obesity group and overweight group,but LVEF have no significant difference.Conclusion Obesity is associated with increased late mortality after AVR in patients with implantation of small aortic prosthesis.Obesity and overweight may also affect the NYHA function in long term.EOAI should be improved where possible as it may reduce late mortality and improve life quality in such patients.

Doxycycline-based quadruple regimen versus routine quadruple regimen for rescue eradication of Helicobacter pylori: an open-label control study in Chinese patients

<p><b>INTRODUCTION</b>This study aimed to compare the efficacy and safety of quadruple therapy containing doxycycline and routine quadruple therapy for Helicobacter (H.) pylori rescue eradication in patients who had failed the one-week triple therapy.</p><p><b>METHODS</b>Patients who failed the first-line eradication therapy were allocated into two groups. Group A patients (n = 43) were administered esomeprazole 20 mg, bismuth potassium citrate 220 mg, amoxicillin 1 g and doxycycline 100 mg, all bid for ten days, while Group B patients (n = 42) were administered esomeprazole 20 mg bid, bismuth potassium citrate 220 mg bid, metronidazole 400 mg bid and tetracycline 750 mg q.6h, for ten days. The results of H. pylori eradication were assessed with 13C urea breath test four weeks after the therapy, and the side effects were recorded.</p><p><b>RESULTS</b>A total of 85 patients (average age 46.9 years) were enrolled in the study. Successful eradication rate for H. pylori was 72.5% in Group A and 64.1% in Group B, with no significant difference between the two groups. 11.6% (5/43) of patients from group A and 31.0% (13/42) from group B reported at least one adverse event. The adverse events of all 18 patients disappeared after the therapy ceased.</p><p><b>CONCLUSION</b>Quadruple therapy containing doxycycline is as effective as routine quadruple therapy for H. pylori rescue eradication. The regimen is well tolerated by most patients and causes fewer adverse events than routine quadruple therapy. Hence, it may be recommended as a suitable alternative H. pylori rescue regimen in China.</p>

A meta-analysis on the timing of parenteral nutrition and enteral nutrition in acute pancreatitis / 中华临床营养杂志

Objective To compare the effect of parenteral nutrition and enteral nutrition with different start time on acute pancreatitic patients.Methods Randomized controlled trials comparing enteral and parenteral nutrition in acute pancreatitic patients published from January 1996 to January 2011 were searched in MEDLINE,EMBASE,Cochrane databases,Wanfang science library,and China National Knowledge Infrastructure.The information about study design,patient characteristics,and outcomes were extracted by two independent analysers before processed with RevMan 4.2 software.Results Altogether 14 trials were included.When started after 24 hours of admission,enteral nutrition,in comparison with total parenteral nutrition,resulted in a statistically significant reduction in the risks of infections (P =0.0004),surgical intervention (P =0.0200),organ failure (P =0.0400),and morality (P =0.0002) in acute pancreatitic patient.When started within 48 hours of admission,enteral nutrition,in comparison with total parenteral nutrition,resulted in a statistically significant reduction in the risks of infections (P =0.0000),surgical intervention (P =0.0001),organ failure (P =0.0006),and mortality (P =0.0300) in acute pancreatitic patients.Conclusions The time of the commencement of nutriton has an influence on the benefits of enteral nutrition.Enteral nutrition started between 24 hours and 48 hours of admission is more effective than within 24 hours or after 48 hours of admission.

Gemcitabine induces Notch signaling pathway activation in pancreatic cancer cell lines SW1990 and BxPC3 / 中华胰腺病杂志

Objective To investigate the changes of Notch signaling pathway activity in human pancreatic cancer cell lines (SW1990, BxPC3 )after gemcitabine induction, and to study its relationship with pancreatic cancer resistant to gemcitabine chemotherapy. Methods The pancreatic cancer cell lines SW1990 and BxPC3 were cultured with different concentrations of gemcitabine for 48 hours. The Notch signaling pathway receptors ( Notch1, Notch2, Notch3, Notch4), ligands (Jagged1, Jagged2) and downstream target Hesl mRNAs expression were detected by quantitative real-time PCR (Q-PCR). Protein levels of Hes1 were determined by Western blotting. Results After treatment with 2 μmol/L gemcitabine for 48 hours, the expression of Notch1, Notch2, Notch3, Jagged1, Jagged2 and Hes1 mRNAs in SW1990 cells were 8.26 ±0.48, 39.12 ±4.87, 0.84 ±0.06, 105.8 ± 17.92, 6.59 ±0.32 and 17.30 ±2.96, which were significantly elevated when compared with those without gemcitabine treatment ( 1.02 ± 0. 15, 15.25 ± 1.28, 0. 12 ± 0.02,32.66 ± 1.98, 1.88 ± 0.29 and 5.02 ± 0.64, P < 0.05 or P < 0. 01 ); the expression in BxPC3 cells was 7.87 ±0.59, 109.4 ± 10.98, 0.74 ±0.19, 62.73 ± 13.50, 2.09 ±0.16 and 15.38 ± 1.06, which were significantly elevated when compared with those without gemcitabine treatment ( 1.14 ±0.43, 58.96 ±2.63,0.10 ± 0.02, 16.95 ± 3.79, 0.98 ± 0.02 and 2.04 ± 0.16, P < 0.05 or P < 0.01 ). The expressions of Hes1protein in SW1990 cells after 1, 2 μmol/L gemcitabine treatment for 48 h were 0.30 ±0.03, 0.42 ±0.03;and the expressions in BxPC3 cells were 0.33 ± 0.02, 0.45 ± 0.03, which were significantly increased when compared with those without gemcitabine treatment (0.13 ± 0.01, F = 33.71,0.09 ± 0.02, F = 38.54, P <0.01 ). Conclusions The Notch signaling pathway is significantly activated in pancreatic cancer cells SW1990 and BxPC3 by gemcitabine, which may be one of the mechanisms of chemoresistance.

Relationship between inflammatory response induced by cardiopulmonary bypass and postoperative cognitive dysfunction / 中华麻醉学杂志

Objective To examine the relationship between inflammatory response induced by cardiopulmonary bypass and postoperative cognitive dysfunction.Methods Twenty-five patients undergoing elective cardiac valve replacement under cardiopulmonary bypass were randomly divided into two groups:ulinastatin group(group U,n=13) and control group(group C,n=12).In group U,ulinastatin 12 000 U/kg Was given intravenously immediately after induction of anesthesia,6 000 U/kg ulinastatin Was added to the priming solution,and 6000 U/kg ulinastatin was given at 5 min before the aortic decamping.In group C,normal saline was given instead of ulinastatin.Venous blood samples were taken after induction of anesthesia,at the end of CPB,and 24 h after operation for determination of plasma IL-6 concentration and neutrophils NF-kB expression.The cognitive function of the patients was evaluated by Mini-Mental State Examination(MMSE) before and 3 d,7 d after operation.Results The concentraion of IL-6 and neutrophils NF-kB expression were lower in group U than in group C(P<0.05 or 0.01).There wag no significant difference in the incidence of postoperative cognitive dysfunction between group C and U.Conclusion Inflammatory response induced by cardiopulmonary bypass is not related to postoperative cognitive dysfunction.

Surgical treatment of cardiac myxoma / 中国综合临床

Objective To review and sum up the experience of diagnosis and surgical treatment of cardiac myxoma. Methods 133 patients with cardiac myxoma of different locations from January 1990 to May 2007 admitted in Qilu Hospital of Shandong University and Department of Cardivovascular Affdiafed Zhong shan Hospital of Xiamen Unversity were clearly diagnosed by two dimensional echecardiography. The tumors of 109 patients were located in left atrium ,22 in right atrium and 2 in both cardiac atria. All the patients underwent tumor extirpation under extracor-poreal circulation. Atrioventricular valve plasty was performed when necessary. 11 underwent bicuspid valvuloplasty and 6 underwent tricuspid valvuloplasty at the same time. All the minors were sent to histopathology examination. Re-suits Two patients died of low cardiac output syndrome in early postoperative period. Cerebral embolism happened in 6 cases,left lower extremity embolism and pulmonary embolism in 1 ease respectively. Other patients' symptoms were improved and the physical sign disappeared. All the tumors were demonstrated to be benign cardiac myxoma. Conclusions Most cardiac myxoma is benign but its clinical consequence is severe. So tumor extirpation should be performed as soon as possible and the following-up is important after operation. Prevention of tumor defluvium is im-portant. Two dimensional echocardiography is preferred in the diagnosis of cardiac myxoma.

Effects of on-pump and off-pump coronary artery bypass grafting on plasma adrenomedullin and endothelin-1 levels in elderly patients / 中华老年医学杂志

Objective To investigate the effects of on-pump and off-pump coronary artery bypass grafting on plasma adrenomedullin (ADM) and endothelin-1 (ET-1) levels before and after operation in elderly patients. Methods Elderly patients aged 60 years and over with coronary artery bypass grafting were enrolled in the study and divided into off-pump group and on-pump group, each group had 20 cases. Blood samples were collected before surgery, immediately after operation and 6,24 hours, 3 days after operation. The plasma levels of ADM and ET-1 were dectecded by radio immunoassay. Results The levels of ADM and ET-1 were significantly increased immediately after operation in 2 groups of on-and off-pump. The levels of ET-1 in on-pump group and off-pump group were (67.59±10.18) ng/L and (58.73±9.64) ng/L respectively. The levels of ADM in on-and off-groups were (284.90±36.24) ng/L and (243.25±25.70) ng/L. This showed that in on-pump group, the plasma levels of ADM and ET-1 increased more significantly(P＜0.05). The plasma levels of ADM and ET-1 began to decline at 6 hours after operation, and continued to 24 hours after operation. On 3 days after operation, the plasma levels of ADM and ET-1 in off-pump group returned to the preoperative level, but they were still maintained at a high level in on-pump group.Conclusions For elderly patients, both on-pump and off-pump coronary artery bypass grafting can cause endothelial dysfunction, increasing plasma levels of ET-1 and ADM. But compared with the on-pump coronary artery bypass grafting, the off-pump coronary artery bypass grafting has less influence.

Meaning of Perioperative Plasma Concentration of NT-ProBNP in the Risk Assessment of Rheumatic Valve Disease / 中国循环杂志

0.05),but elevated markedly and acutely to a peak level at 24 h after operation (P

Keeping Characteristics in the 7-years Program / 中华医学教育探索杂志

The college has been keeping its characteristics in the 7-year medical students training program in the pastten years. It is emphasized that the cultivating target in this program is to make the students become creative medicalprofessionals with lifelong study capacity by applying the humanistic spirit as the forerunner, and placing emphasis onthe practical and advanced feature, The training mode should fully incarnate the consistent characteristics of the bach-elor-and-master courses and the three-phrase tutor system, which aims to improve the practical and research competenceof the students. And the training outcome has been approved to be identical with the target set in advance.[

A meta-analysis of total parenteral nutrition versus enteral nutrition in patients with acute pancreatitis / 中华消化杂志

Objective To analyze the effect of total parenteral nutrition (TPN) and enteral nutrition (EN) in patients with acute pancreatitis. Methods Randomized controlled trials of TPN and EN in patients with acute pancreatitis were searched in Medline and China Biological Medicine Disk from Jan 1966 to June 2004. Eight studies were enrolled into the analysis. The detail about the trial design, characters of the subjects, results of the studies were reviewed by two independent authors and analysed by using Revman 4.2 software. Results Compared with TPN, EN was associated with a significantly lower incidence of secondary infections (RR 0.45, 95% CI 0.29-0.68, P=0.0002) and other complications(RR 0.67, 95% CI 0.47-0.96, P=0.03), fewer surgical interventions (RR 0.47, 95%CI 0.24-0.94, P=0.03) and shorter hospitalization. However, there was no significant difference in mortality (RR 0.61, 95%CI 0.32-1.18, P=0.14) between patients with TPN and EN. Conclusion EN could be the preferred nutrition feeding method in patients with acute pancreatitis.

Effects of protease inhibitor gabexate mesilate on motility of human Oddi's sphincter / 中华消化杂志

0.05).②Gabexate mesilate significantly reduced the frequency of contraction (P0.05).③High dose gabexate mesilate could markedly reduce the motility index ( P

NSAIDs induced apoptosis of gastric cancer cell lines and the mechanism / 中国癌症杂志

Purpose:To investigate whether NSAIDs can induce apoptosis of gastric cancer cell lines,to observe the effect of different p53 genotype on NSAIDs induced apoptosis,to elucidate the regulation of NSAIDs on expression of apoptosis related genes. Methods:The anti-proliferative effect of NSAIDs was measured by MTT assay.Apoptosis was determined by acridine orange(AO) staining,Annexin-V/PI double staining,laser scanning cytometry(LSC) and flow cytometry (FCM).Alteration of bcl-2 and bax genes was detected by reverse transcription polymerase chain reaction (RT-PCR).Protein expression was determined by Western-blotting.Results: Indomethacin (Indo) and Aspirin (Asp) inhibited both AGS(wild-type p53)and MKN28(mutant p53) gastric cancer cell lines growth in a time/dose dependent manner.AGS cell line was more sensitive to NSAIDs,which apoptosis percentage was significantly higher than MKN28 under the same condition. The percentages of apoptosis of MKN28 were somewhat higher among NSAIDs treated groups compared with the normal control group,but these slight differences were not statistically significant. The bax mRNA kept increasing since NSAIDs treatment accompanied by a decrease of bcl-2 gene.The Bax protein increased after treatment while the Bcl-2 protein was undetectable, which tendency was more obvious during 6-24hs.Conclusion: Both Indo and Asp could induce apoptosis in gastric cancer cell lines,which adds further theoretical foundation to the anti-cancer use of NSAIDs.NSAIDs could not induce notable apoptosis of MKN28,which indicated the mutant p53 gene perhaps blocked NSAIDs induced apoptosis.One of the major pathways that mediated the anti-tumour response of NSAIDs in gastric cancer cells was through up-regulation of bax and down-regulation of bcl-2 genes and/or proteins.[

Effects of Helicobacter pylori and non-steroidal anti-inflammatory drugs on proliferation of gastric epithelial cells / 中华消化杂志

Objective To investigate the interactions and effects of Helicobacter pylori (H.pylori) and non steroidal anti inflammatory drugs (NSAID) on the proliferation of gastric epithelial cells in vitro. Methods After co culturing of gastric cancer cell line AGS cells with H.pylori and/or NSAID (indomethacin and aspirin) for 48 hours, the cell proliferation and proliferating cell nuclear antigen (PCNA) were examined by MTT assay and Western blot. Results cagA positive H.pylori strain NCTC11637, but not cagA negative H.pylori strain NCTC12908, had the effect of enhancing gastric epithelium cell proliferation. However, the effect of proliferation was dependent on the density of H.pylori . It was demonstrated that low density (range from 3.2?10 4 CFU/ml to 4?10 6 CFU/ml) of bacteria suspensions resulted in proliferative effect, while high density (more than 2?10 7 CFU/ml) resulted in inhibition. Besides, indomethacin and aspirin inhibited cell proliferation in a dose dependent manner. Moreover, when AGS cells were incubated with cagA positive H.pylori and NSAID, inhibition rather than proliferation was observed. cagA positive H.pylori strains up regulated the expression of PCNA while indomethacin and aspirin down regulated the level of PCNA expression. Meanwhile, the expression of PCNA was also reduced significantly when AGS was co cultured with H.pylori and NSAID. Conclusions The results indicated that gastric epithelium cell proliferation was associated with different H.pylori strains and its density. cagA positive H.pylori strain is prone to increase cell proliferation, but cagA negative H.pylori strain has no such effect. NSAID can inhibit gastric epithelial cell proliferation and reverse such effect caused by H.pylori.