The proliferation of Patu8988 cells pre-treated with metformin for 72h was measured by CCK-8 assay.Cell cycle was analyzed by flow cytometry.The expression of related genes was detected by RT-PCR.Metformin suppressed the proliferation of Patu8988 cells in a dose-dependent manner( r=0.994,P＜0.05 ).The proportion of cells at G0/G1 stage was increased while that of G2/M stage decreased (P＜0.05 ).The expressions of MMP-3,cyclinD1,p53 were down regulated and that of Bax was up regulated.The results show that metformin may inhibit the proliferation of Patu8988 cells,via blocking the cell cycle and affecting the expression of related genes.

Objective To investigate thermal degradation kinetic characteristics of Cefmenoxime Hydrochloride in infusion solutions, and predict its thermal stability. Methods The HPLC was applied to determine the contents of Cefmenoxime Hydrochloride. Classical isothermal kinetic method and multivariate linear model were used to predict the expiration date of the injection. Results It was found that the thermal degradation kinetics of Cefmenoxime Hydrochloride in two infusion solutions corresponded with the first-order kinetics. The expiration dates of Cefmenoxime Hydrochloride in 0. 9%sodium chloride injection calculated by two different methods were 2. 20 days and 1. 52 days,and in 5% glucose injection were 2. 09 days and 1. 53 days,respectively. Conclusion The thermal stability of Cefmenoxime Hydrochloride in infusion solutions is poor and its expiration dates are the same calculated by two different methods.

Objective To evaluate thetherapeutic effect of sodium deoxyribonucleotide injection at Zusanli point for chemotherapy-induced leukopenia in patients with lung cancer.MethodsA total of 116 chemotherapy-induced leukopenia patients with lung cancer were randomly divided into a therapy group and a control group, 60 in the treatment group and 56 in the control group. The patients in the treatment group were treated with sodium deoxyribonucleotide injection atZusnlipoint, and those in the control group were treated with vein injection of sodium deoxyribonucleotide.Results The total effective rate in the treatment group was significant higher than that in the control group (91.7%vs.76.8%;χ2=4.890,P=0.032). The effective rates on days 3,5,7 and 10 in the treatment group were also significant higher than those in the control group (on day 3: 51.7%vs. 32.1%,χ2=4.530,P=0.036; on day 5: 76.7%vs. 53.6%,χ2=6.840,P=0.018; on day 7: 85.0%vs. 67.9%,χ2=4.770,P=0.026; on day 10: 78.3%vs. 53.6%,χ2=7.960,P=0.011).Conclusion Sodium deoxyribonucleotide injection atZusanlipoint has definite efficacy for chemotherapy-induced leukopenia in patients with lung cancer.

Objective To determine the protective effect of isosorbidemononitrate (IM) on myocardial injury after restoration of spontaneous circulation (ROSC)in swine models of cardiac arrest induced by ventricular fibrillation.Methods The experiment was carried out in Animal Lab of Beijing Chao-Yang Hospital,Capital Medical University.Ventricular fibrillation was induced and untreated for 8 min in twenty WhuZhiShan piglets.CPR was performed until ROSC occurred.The animals were randomized (random number)into two groups:IMgroup (n =10)and control group (n =10).IM [2 μg/(kg· min)]or the equivalent volume in saline was administered respectively for 6 h after ROSC.Hemodynamics and post-resuscitation cardiac function were monitored until 24 h after ROSC. Echocardiography and transmission electron microscopy were useed at 72 h after ROSC.Results There was no significant difference in survival rate between the two groups.No significant differences in mean arterial pressures (mmHg)at ROSC 6 h (88.5 ±5.6 vs.87.8 ±6.0,P =0.790)and ROSC 24 h (89.3 ±3.8 vs.86.9 ± 5.0,P =0.245)between the two groups were found.Cardiac outputs (L/min)were significantly increased at ROSC 6 h (2.40 ±0.17 vs.1.60 ±0.14,P <0.01)and ROSC 24 h (2.49 ±0.17 vs.2.09 ±0.21,P<0.01);and ejection fraction at ROSC 72 h (0.67 ±0.08 vs.0.56 ±0.09,P =0.044)was improved too,and significant differences were found between the two groups.The ultra-structural myocardial injury was ameliorated in the MI group at 72 h after CPR observed by using electron microscopy.Conclusions IM can ameliorate post-resuscitation cardiac dysfunction in porcine models of cardiac arrest induced by ventricular fibrillation.

Interferon ( IFN) kills tumor through:direct tumor killing, stimulating immune response to tumor cells by activating the immune system and inhibiting tumor angiogenesis.However, its clinical application has been restrained by the deficiencies such as short half-life and severe side effects.IFN-antibody fusion can bring IFN to the vicinity of tumors using tumor specific antibody, while reducing the concentration of IFN in the rest parts of the body.Thus, system toxicity caused by IFN can be significantly lessened.We herein summarized the research and development of preclinical antibody-interferon conjugates and provide new thought on the development of IFN or antibody based fusion proteins.

Objective To evaluate the role of spinal sigma-1 receptors in the maintenance of bone cancer pain (BCP) in rats and the relationship with extracellular signal-regulated kinase (ERK).Methods Part Ⅰ Twenty-four female Sprague-Dawley rats,weighing 180-220 g,were randomized into 2 groups using a random number table:sham operation group (S group,n =4) and BCP group (n =20).BCP was induced by inoculating Walker 256 mammary gland carcinoma cells into the medullary cavity of the right tibia.Four rats were sacrificed on day 10 after inoculation in S group or on day 3,5,7,10 and 14 after inoculation in BCP group,and the L4-6 segments of the spinal cord were removed to measure the expression of sigma-1 receptors by Western blot.Part Ⅱ Forty female Sprague-Dawley rats,weighing 180-220 g,were randomized into 4 groups (n =10 each) using a random number table:sham operation group (S group),sigma-1 receptor inhibitor BD1047 group (BD group),BCP group,and BCP + BD1047 group (BCP + BD group).On day 10 to 14 after inoculation,normal saline 20 μl was injected intrathecally once a day in S and BCP groups,or BD1047 120 nmol/20μl was injected intrathecally once a day in BD and BCP + BD groups.Mechanical paw withdrawal threshold (MWT) to yon Frey filament stimulation was measured one day before inoculation,on day 3,5 and 7 after inoculation,and on day 10,12 and 14 after administration.After measurement of MWT on day 14 after inoculation,the rats were sacrificed and the L4-6 segments of the spinal cord were removed to determine the expression of phosphorylated ERK (p-ERK) by Western blot.Results Part Ⅰ Compared with group S,the expression of sigma-1 was significantly up-regulated and peaked on day 10 after operation in group BCP.Part Ⅱ Compared with S group,no significant changes were found in MWT and p-ERK expression at each time point in BD group,and MWT was decreased and p-ERK expression was up-regulated in BCP and BCP + BD groups.Compared with group BCP,after intrathecal injection of BD1047,MWT was significantly increased and the expression of p-ERK was down-regulated in BCP + BD group.Conclusion Spinal sigma-1 receptors are involved in the maintenance of BCP in rats possibly through promoting phosphorylation of ERK.

Objective To detect the expressions of decoy receptor 3 (DcR3) in pancreatic cancer tissues and to analyze the significance of DcR3 in the diagnosis, treatment and prognosis of patients with pancreatic cancer.Methods The expressions of DcR3 in pancreatic cancer tissues (n =100), paracancer tissues (n =15) and normal tissues (n =15) were detected with immunohistochemical method (Envision method).Results The positive rate of DcR3 in pancreatic cancer tissues was significantly higher than that in adjacent-tumor pancreatic cancer tissues (86.0％ vs.46.6％, P ＜ 0.05).The positive rate of DcR3 in adjacent-tumor pancreatic cancer tissues was significantly higher than that in normal tissues (46.6％ vs.13.3％, P ＜ 0.05).In clinical stage Ⅲ, the positive rate of DcR3 was significantly higher than that in stage Ⅱ and stage Ⅰ (100％ vs.87.0％, P＜0.05;100％ vs.62.5％, P＜0.05).There were significant differences among the three groups (P ＜ 0.05).With lymph node metastasis, the DcR3 positive rate was significantly higher than that in the group without lymph node metastasis (93.4％ vs.79.6％, P ＜ 0.05).In poorly differentiated pancreatic cancer, the positive rate of DcR3 was significantly higher than that in the highly differentiated group (100％ vs.64.0％, P ＜0.05), the positive rate of DcR3 was significantly higher in the moderately differentiated group than that in the highly differentiated group (88.6％ vs.64.0％, P ＜ 0.05) , There were significant differences among the three groups (P ＜ 0.05).There was no significant difference in the positive rate of DcR3 between the different age groups or the different gender groups (P ＞ 0.05).Conclusions The expression levels of DcR3 in patients with pancreatic cancer gradually increased from normal tissues to paracancer tissues, to pancreas tissues.The expression level of DcR3 protein was closely related to clinical stage, degree of tissue differentiation and presence of lymph node metastasis, but not associated with age, sex, and tumor diameter size.

OBJECTIVE To investigate the antitumor effect of cadmium (Ⅱ) complex of pyrazolone derivatives 1-phenyl-3-methyl-4-propionyl-5-pyrazolone salicyloyl hydrazide-cadmium (Ⅱ) (Cd-PMPP-SAL) on the murine melanoma B16 cells in vitro and in vivo and its mechanisms. METHODS B16 cells were incubated with Cd-PMPP-SAL at 1.0, 1.5, 3.0, 5.0 and 10.0 mg·L-1 for 24, 48 or 72 h. The prolifera? tion rate of B16 cel s was evaluated by MTT assay. B16 cel s were incubated with Cd-PMPP-SAL at 6.25, 12.50 and 25.00 mg·L-1 for 24 h, while cell morphology was observed by Hoechst33258 staining. Apop?tosis of B16 cells was detected by Annexin Ⅴ-FITC/PI staining. The activity of caspases in B16 cells was detected by caspase activity assay. C57BL/6J mice were inoculated subcutaneously with B16 cells to establish a tumor-bearing model. Five days later, Cd-PMPP-SAL at 6.25, 12.50 and 25.00 mg·kg-1 was injected into tumors of C57BL/6J mice once a day for 12 d. The body mass was recorded daily. One day after the last administration, all the mice were killed and the tumor was harvested. Tumor volume and mass were measured, and the tumor inhibitory rates were calculated. Pathological changes of the tumor, liver and lung were observed under a microscope. The expressions of vascular endothelial growth factor (VEGF) and fibroblast growth factor 2 (FGF2) in tumor tissues were detected by immuno?histochemistry. The apoptotic cells in transplanted tumor tissues were detected by TUNEL. RESULTS Cd-PMPP-SAL inhibited the proliferation of B16 cells. The IC50 was 4.946 mg · L-1, and 95% confidence interval was 4.24-5.65 mg · L-1. The apoptosis rates(12.8 ± 1.4)% and (18.4 ± 0.4)% of Cd-PMPP-SAL 12.50 and 25.00 mg · L-1 groups were significantly higher than those of control group (1.7 ± 0.1)% (P<0.01). The activity of caspase 3 and 9 of Cd-PMPP-SAL 25.00 mg · L-1 group was significantly higher than that of control group (P<0.01), but there was no significant difference in caspases 3/7. The relative tumor volumes of Cd-PMPP-SAL 6.25, 12.50 and 25.00 mg · kg-1 treated groups from the 8th day of treatment were significantly decreased compared with the model group (P<0.01). The result of paraffin sections showed that the transplanted tumor tissues in Cd-PMPP-SAL 12.50 and 25.00 mg · kg- 1 groups exhibited different degrees of necrosis, but there was no significant pathological damage to the liver or lung tissues of mice. Compared with model group, expressions of VEGF and FGF2 in Cd-PMPP-SAL 12.50 and 25.00 mg · kg-1 treated groups were significantly inhibited (P<0.05), and apoptotic cell rates were significantly higher (P<0.05). CONCLUSION Cd-PMPP-SAL can inhibit growth of B16 cells in vivo and in vitro, which may be associated with induction of tumor cell apoptosis and inhibition of tumor angiogenesis.

Objective To investigate the relationship between the clinical features of patients with different cancer and their clin‐icalstage,lymphnodemetastasissituation.Methods 135cancerpatientsdiagnosedandtreatedinthehospitalfromJanuary2010to December 2014 were enrolled in the study ,in addition to that ,57 people who underwent healthy examination in the hospital and proved to be healthy were also recruited as control group .Prothrombin time(PT) ,thrombin clotting time(TT) ,activated partial thromboplastin time(APTT) ,D‐dimer ,fibrinogen(FIB) were tested for the people mentioned above .Results The level of routine coagulation indicators were statistically significant different between people with different types of cancers and control group(P<0 .05) .Compared with the control group ,PT ,APTT of the cancer patients significantly shortened ,FIB ,D‐dimer levels were signifi‐cantly increased(P<0 .05) .PT ,APTT was prolonged in lung cancer ,esophageal cancer ,breast cancer ,stomach cancer compared with lung cancer ,FIB ,D‐dimer decreased compared with other malignancies(P<0 .05) .PT ,APTT was decreased and D‐dimer ,FIB was significantly increased in cancer(lung ,esophagus ,breast ,stomach) with Ⅲ‐Ⅳ stage or lymph node metastasis than Ⅰ‐Ⅱstage or non‐lymph node metastasis ,the difference was statistically significant(P<0 .05) .Conclusion The malignant tumors were with hypercoagulable state ,there are differences in coagulation in different clinical stages ,lymph node metastasis .