PURPOSE: Studies suggest that regular use of metformin may decrease cancer mortality. We investigated the association between diabetes medication use and cancer survival. MATERIALS AND METHODS: The current study includes 633 breast, 890 colorectal, 824 lung, and 543 gastric cancer cases identified from participants of two population-based cohort studies in Shanghai. Information on diabetes medication use was obtained by linking to electronic medical records. The associations between diabetes medication use (metformin, sulfonylureas, and insulin) and overall and cancer-specific survival were evaluated using time-dependent Cox proportional hazards models. RESULTS: After adjustment for clinical characteristics and treatment factors, use of metformin was associated with better overall survival among colorectal cancer patients (hazards ratio [HR], 0.55; 95% confidence interval [CI], 0.34 to 0.88) and for all four types of cancer combined (HR, 0.75; 95% CI, 0.57 to 0.98). Ever use of insulin was associated with worse survival for all cancer types combined (HR, 1.89; 95% CI, 1.57 to 2.29) and for the four cancer types individually. Similar associations were seen for diabetic patients. Sulfonylureas use was associated with worse overall survival for breast or gastric cancer (HR, 2.87; 95% CI, 1.22 to 6.80 and HR, 2.05; 95% CI, 1.09 to 3.84, respectively) among diabetic patients. Similar association patterns were observed between diabetes medication use and cancer-specific survival. CONCLUSION: Metformin was associated with improved survival among colorectal cancer cases, while insulin use was associated with worse survival among patients of four major cancers. Further investigation on the topic is needed given the potential translational impact of these findings.
Breast ; Cohort Studies ; Colorectal Neoplasms ; Electronic Health Records ; Humans ; Insulin ; Lung ; Metformin ; Mortality ; Proportional Hazards Models ; Stomach Neoplasms

Objective To investigate the relationship between lipoprotein associated phospholipase A2 (Lp－PLA2)and atherosclerotic plaque instability in patients with acute coronary syndrome (ACS),and to provide theoretical basis for diagnosis and treatment of ACS.Methods From September 2015 to February 2016,80 patients with ACS in Shidao People's Hospital of Rongcheng were selected as the study group,including 38 cases in unstable angina group(UAP group),24 cases in non ST segment elevation myocardial infarction group (NSTEMI group), 18 cases in ST segment elevation myocardial infarction group(STEMI group).Forty patients with stable angina pectoris (SAP group)and 40 healthy subjects(healthy group)were selected as control group.Each group was collected 8 hours fasting morning blood sample,the levels of Lp－PLA2,C reactive protein(CRP),troponin Ⅰ,and low density lipoprotein were detected,in order to compare the differences among the groups and the correlation between Lp－PLA2 and ACS plaque instability was analyzed.Results The levels of Lp－PLA2,CRP,troponin Ⅰ and low density lipopro-tein in the ACS group were (312.63 ±11.14)ng/mL,(21.98 ±7.83)mg/L,(0.720 ±0.490)μg/L,(174.76 ± 30.82)mg/dL,respectively,which were significantly higher than those of the healthy group [(141.14 ±12.30)ng/mL, (2.38 ±1.68 )mg/L,(0.010 ±0.003 )μg/L,(79.24 ±17.80 )mg/Ml],and stable angina pectoris group [(176.42 ±12.44)ng/mL,(4.22 ±3.68)mg/L,(0.010 ±0.004)μg/L,(96.54 ±19.41)mg/mL].There were statistically significant differences among all groups(F＝3.07,1.99,2.43,3.25,all P＜0.01).The levels of CRP, Lp－PLA2 and cTnI in ACS patients with different types of the STEMI group,NSTEMI group,UAP group had statisti-cally significant differences,which of the STEMI group were higher than those of the NSTEMI group,which of the NSTEMI group were higher than those of the UAP group(F＝5.15,3.47,2.43,all P＜0.05).Correlation analysis showed that the level of Lp－PLA2 was positively correlated with low density lipoprotein(r＝0.625,P＜0.01)and lipoprotein a(r＝0.532,P＜0.01).logistic regression analysis showed that Lp －PLA2 and CRP were significant independent risk factors of ACS,Lp－PLA2(OR＝1.613,95%CI:1.292 －1.992,P＜0.01),CRP(OR＝1.452, 95%CI:1.210-1.782,P＜0.01).Conclusion Lp－PLA2 is independent risk factor of ACS.Lp－PLA2 is involved in the inflammatory reaction of ACS,and is strongly associated with the stability of atherosclerotic plaque.

Objective: To explore the clinical value of 3D-DSA technology in the diagnosis and treatment guidance of hepatic artery chemoembolization. Methods: Liver cancer patients in the treatment groups were collected to receive 3D-DSA imaging guidance at the Affiliated Hospital of Xuzhou Medical University between March and May 2017. In addition, routine 2D-DSA imaging was selected for treatment-received group. Intra-operative blood vessels and tumor-like lesions were observed. The total exposure dose (CAK, unit mGy), cumulative irradiation intensity per unit area (DAP, unit mGy.cm2) and dosage of contrast agent (ml) were calculated separately for two groups of patients. The same senior physicians and technicians operated both groups of patients. Comparisons of measurement were analyzed by t-test and chi-square test was used for count data. Results: Data of twenty patients were collected from the two groups. Tumor location, target vessels structure and shape of development were clear in all patients in the treatment group. The control group had 17 cases of tumor development and the target vascular structure was clear in 16 cases. CAK mean treatment group was lower than control group (554.11 + 38.87) mGy and (644.53 + 26.70) mGy, and DAP mean treatment group was lower than the control group (125.25 + 7.54) mGy·cm² and (143.49 + 6.18) mGy·cm². The two groups were compared (P value < 0.05), and the differences were statistically significant. The mean dose of contrast agent in the two groups were lower than control group (64.42 + 3.92) ml, (70.79 + 4.47) ml, and the differences between the two groups were statistically significant (P < 0.05). Conclusion 3D-DSA imaging technology can provide effective diagnosis and guidance in the treatment of hepatic artery chemoembolization. It can effectively reduce the radiation exposure dose and radiation intensity, and it is of high clinical value for interventional embolization of liver cancer.

Objective: To investigate the combined impact of lifestyle factors on stomach cancer risk. Methods: We analyzed the data from the Shanghai Men's Health Study (SMHS) (2002-2013). The SMHS was conducted in eight neighborhood communities of urban Shanghai. From 2002 through June 2006, 61 480 residents aged 40 to 74 years old with no history of cancer were recruited. Failure time was the date of stomach cancer incidence, death or date of the last follow-up (December 31, 2013). The first two in-person follow-up surveys were conducted in 2004-2008, and 2008-2011, respectively. Using data on lifestyle, the healthy lifestyle index (HLI) was developed. The following lifestyle factors were included: smoking, alcohol consumption, diet habit, overweighted and physical activity. Cox proportional hazard models were used to evaluate the association of stomach cancer risk with lifestyle factors and HLI. Results: Over 9.28 years' follow-up, 477 incident cases of stomach cancer were identified from 59 503 study participants. Participants with zero, one, two, three, four, and five favorable lifestyle behaviors accounted for 3.44% (n=2 045), 18.14% (n=10 793), 33.68% (n=20 041), 29.43% (n=17 511), 12.82% (n=7 627), and 2.50% (n=1 486), respectively. Among all the five lifestyle factors, smoking and alcohol use were significantly related to stomach cancer risk. The relative risk of stomach cancer was 0.71 (95%CI: 0.57-0.87) for those who never smoked or quitted smoking for no less than 10 years and 0.70 (95%CI: 0.55-0.90) for those who consumed alcohol no more than 14 drinks per week. For each increment of healthy lifestyle index, the relative risk of stomach cancer was 0.86 (95%CI: 0.79-0.95). Compared to men with none or one healthy lifestyle factor, the relative risk for those with four or five was 0.62 (95%CI: 0.46-0.83). When we rebuilt HLI using more categories of each lifestyle factors, the HLI ranged from 0 to 11. For each point increase, the relative risk of stomach cancer was 0.93 (95%CI: 0.89-0.97). Compared those with 0 to 3 points, the relative risk of those with 8 to 11 points was 0.64 (95%CI: 0.47-0.87). Conclusion In the SMHS, only a small proportion of men adhered to all the five healthy lifestyle factors. Compared to those with none or one healthy lifestyle behaviors, those with five may prevent about 1/3 stomach cancer incidence and the HLI was inversely associated with stomach cancer risk.

Objective To study the effect of serum uric acid (UA) levels on kidney graft function as well as long-term graft survival after renal transplantation.Methods The clinical data of 859 kidney transplant recipients from Jan.2008 to May 2014 were investigated retrospectively.The differences in clinical indexes between normal UA group and hyperuricemia group were compared based on UA levels.Cox regression model was built to analyze the effect of elevated UA on overall graft loss,death censored graft failure and death of patients,respectively.Kaplan-Meier graft survival curve was used to compare the overall graft loss,death censored graft failure and death of patients between normal UA group and hyperuricemia group.Results The average follow-up time was 38.6 ± 17.3 months for 859 kidney transplant recipients.590 (68.7％) recipients were enrolled in normal UA group and 269 (31.3％) recipients were defined as hyperuricemia patients.The average eGFR in hyperuricemia group was significantly decreased as compared with normal UA group (79.4 ± 20.93 vs.94.7 ± 20.55,P＜0.001).Cox regression model showed that if UA level increased per 10 mol/L,the risk of overall graft lost increased 1.070 times (P＜0.001) and the risk of death censored graft failure increased 1.121 times (P＜0.001) accordingly.Kaplan-Meier analysis showed the overall graft loss was dramatically decreased (P =0.009),and the death censored graft failure was significantly decreased (P＜0.0001) in hyperuricemia group as compared with that in normal UA group.The death of patients showed no significant difference between two groups (P =0.638).Conclusion Serum UA levels after kidney transplantation affect graft function as well as long-term graft survival.

Objective To study the therapeutic effect of IGF?1R inhibitor TAE226 on malignant pleural effusion ( MPE) in nude mice. Methods Human lung carcinoma A549 cells were injected into the pleural cavity of nude mice to establish MPE model. The mice were randomly divided into model group and treatment group, and were orally administered with distilled water and TAE226 ( 20 mg/kg ) in the same volume, respectively. The volume of pleural effusion and tumor weight of the two groups were observed. HE staining was used to reveal the histological changes and enzyme?linked immunosorbent assay ( ELISA) was used to detect the IGF?1R protein expression. IGF?1R mRNA level in the tumor tissue was determined by RT?PCR. Microvessel density (MVD) and cell proliferation index (PI) were assessed by immunohistochemical analysis. The protein expression levels of IGF?1R, p?IGF?1R, PI3K and p?PI3K in the tumor tissue were determined by Western blotting. Results The volumes of pleural effusion were ( 241. 4 ± 89. 7 ) μl and (121.7±78.8) μl in the model and treatment groups, respectively (P<0.05). The tumor weight of treatment group was (316.7±186.3) mg, significantly lower than that of the model group (671.4±281.4) mg (P<0.05) . RT?PCR analysis showed that IGF?1R mRNA level was 0. 914 ± 0. 029 in the treatment group, significantly lower than that of the model group (1.152±0.037, P<0.01). The ELISA data revealed that IGF?1R protein expression level of the model group was significantly higher than that of the treatment group [(41.0±4.7) μg/L vs. (24.0±3.1) μg/L, P<0.01]. Immunohistochemical analysis showed that there were significant differences between MVD and PI in the model and treatment groups [ MVD, 34. 75 ± 3. 49 vs. 22.25±3.63;PI, (75.25±7.15)% vs. (45.75±5.12)%;P<0.01 for both). Western blot data showed that IGF?1R and PI3K protein expression levels were not significantly different between the model and treatment groups (1.03±0.33 vs. 0.98±0.37 and 1.05±0.28 vs. 0.98±0.19), respectively (P>0.05), but p?IGF?1R and p?PI3K protein expression levels had significant differences between the two groups (1.08±0.10 vs. 0.51± 0.08 and 1.12±0.09 vs. 0.86±0.09), respectively (P<0.01 for both). Conclusions The IGF?1R inhibitor can effectively inhibit the formation of malignant pleural effusion. Its mechanism may be related to the suppression of tumor cell proliferation, invasion and angiogenesis through inhibition of PI3K signaling. TAE226 treatment may be a potential therapeutic regimen of treating malignant pleural effusion.

Objective To study the therapeutic effect of IGF?1R inhibitor TAE226 on malignant pleural effusion ( MPE) in nude mice. Methods Human lung carcinoma A549 cells were injected into the pleural cavity of nude mice to establish MPE model. The mice were randomly divided into model group and treatment group, and were orally administered with distilled water and TAE226 ( 20 mg/kg ) in the same volume, respectively. The volume of pleural effusion and tumor weight of the two groups were observed. HE staining was used to reveal the histological changes and enzyme?linked immunosorbent assay ( ELISA) was used to detect the IGF?1R protein expression. IGF?1R mRNA level in the tumor tissue was determined by RT?PCR. Microvessel density (MVD) and cell proliferation index (PI) were assessed by immunohistochemical analysis. The protein expression levels of IGF?1R, p?IGF?1R, PI3K and p?PI3K in the tumor tissue were determined by Western blotting. Results The volumes of pleural effusion were ( 241. 4 ± 89. 7 ) μl and (121.7±78.8) μl in the model and treatment groups, respectively (P<0.05). The tumor weight of treatment group was (316.7±186.3) mg, significantly lower than that of the model group (671.4±281.4) mg (P<0.05) . RT?PCR analysis showed that IGF?1R mRNA level was 0. 914 ± 0. 029 in the treatment group, significantly lower than that of the model group (1.152±0.037, P<0.01). The ELISA data revealed that IGF?1R protein expression level of the model group was significantly higher than that of the treatment group [(41.0±4.7) μg/L vs. (24.0±3.1) μg/L, P<0.01]. Immunohistochemical analysis showed that there were significant differences between MVD and PI in the model and treatment groups [ MVD, 34. 75 ± 3. 49 vs. 22.25±3.63;PI, (75.25±7.15)% vs. (45.75±5.12)%;P<0.01 for both). Western blot data showed that IGF?1R and PI3K protein expression levels were not significantly different between the model and treatment groups (1.03±0.33 vs. 0.98±0.37 and 1.05±0.28 vs. 0.98±0.19), respectively (P>0.05), but p?IGF?1R and p?PI3K protein expression levels had significant differences between the two groups (1.08±0.10 vs. 0.51± 0.08 and 1.12±0.09 vs. 0.86±0.09), respectively (P<0.01 for both). Conclusions The IGF?1R inhibitor can effectively inhibit the formation of malignant pleural effusion. Its mechanism may be related to the suppression of tumor cell proliferation, invasion and angiogenesis through inhibition of PI3K signaling. TAE226 treatment may be a potential therapeutic regimen of treating malignant pleural effusion.

Objective To investigate the detection of IMP andVIM metallo-β-lactamases (MβLs)genes in clinically iso-lated gram-negative bacteria as well as bacterial resistance toβ-lactam antimicrobial agents.Methods 113 clinically isolated bacteria were performed antimicrobial susceptibility testing by Kirby-Bauer method ,drug-resistant genes IMP and VIM were detected by polymerase chain reaction (PCR),PCR products were sequenced and aligned with BLAST software. Results VIM gene was detected in 1 Pseudomonas fluorescens strain ,IMP gene was detected in 15 strains ,they were Klebsiella pneumoniae (n=6),Acinetobacter baumannii (n=3),Escherichia coli (n=2),Ralstonia picket-tii (n=1),Pseudomonas aeruginosa (n=1 ),Citrobacter amalonaticua (n=1 ),and Enterobacter cloacae (n=1 ). BLAST results showed that VIM gene was VIM-2 subtype,similarity with gene bank was 99%;all IMP genes were IMP-1 subtype,which were highly homologous ,similarity was 98%-99%.Resistant rates of IMP positive strains to ceftriaxone,cefotaxime,cefoxitin,aztreonam and imipenem were all significantly higher than negative strains (all P <0.05).Conclusion IMP genes of different strains are highly homologous,all are IMP-1 type,indi-cating that IMP genes are highly transmissible and can spread among different species of bacteria.IMP genes are related with resistance ofβ-lactam antimicrobial agents.

Objective To construct cyclic clinical skill training system and to evaluate its application effect in clinical practice in department obstetrics and gynecology.Methods Cyclic clinical skill training system was established in department obstetrics and gynecology.Totally 104 eight-year program clinical medicine students of grade 2005 and 2006 in people's hospital of Peking university were enrolled as the research object and were divided into control group ( n =54,grade 2005) and experimental group (n =50,grade 2006 ).Students of control group were taught by normal teaching method and contacted with patients in clinical practice while those in experimental group were taught by cyclic clinical skill training system. (theoretical test before practice-simulated training-real practicetheoretical test after practice).Results of theoretical test after practice were compared between the two groups,using statistical t test.Results At the end of internship,students in experimental had higher scores in theoretical test than those in control group,with statistical differences (88.70 vs.85.02,P ＜0.05).Students' skill test scores were (77.04 ± 10.35 ) and (45.61 ± 14.42) before practice while (84.59 ± 10.10) and (68.78 ± 10.83) after practice,with statistical differences ( P ＜ 0.01 ).Conclusions Cyclic clinical skills training system can promote students' skills of obstetrics and gynecology,therefore worth promoting.

Objective To investigate the safety and clinical effect of renal hilum controlling during right retroperitoneal laparoscopic living donor nephrectomy (RPLDN).Methods From January 2009 to May 2012,62 cases of right RPLDN were performed in our department.The clinical data,including the general status of donors,operative time,blood loss,donor kidney warm ischemic time,hospital stays and complications,were analyzed retrospectively.Results Right RPLDN was performed successfully on all 62 cases without conversion to open procedure and apparent complications.The function of all the kidney grafts recovered well.Mean operative time was 73.5 ± 10.4 min,mean blood loss was 30.7 ± 10.4 ml,mean warm ischemic time was 107.2 ± 24.8 s,mean artery and vein lengths were 3.3 ± 0.5 cm and 2.0 ± 0.4 cm,vena cava incision suture time was 2.0 ± 0.5 min and mean hospital stay was 5.2 ± 1.6 days,respectively.Conclusion Right donor kidney with small part of vena cava can be harvested by using retroperitoneal laparoscopy plus open passage way.This technique of renal hilum controlling in RPLDN has good clinical effect and more advantages,including ensuring the safety of donors and kidney grafts,promoting the operation done smoothly,reducing the pain and financial burden of donors.