Objective:This study aimed to investigate the effects and the molecular mechanism of JNJ-7706621 on cell cycle and apoptosis of breast cancer cell lines. Methods:Breast cancer cell lines T47D and MDA-MB-231 were cultured in vitro and treated with JNJ-7706621 at varying concentrations. MTT assay was used to measure cell proliferation. Flow cytometry was applied to analyze the distribution of cell cycle and apoptotic rates. Western blot was performed to analyze the expression of cyclin B1-CDK, the phosphoryla-tion levels of CDK1Thr161 and CDK1Tyr15, as well as the expression of p53, Bcl-2, caspase3 and poly(ADP-ribose) polymerase (PARP). Results:JNJ-7706621 inhibited the proliferation of the T47D and MDA-MB-231 cells in a dose-and time-dependent manner. Flow cytometry showed that the T47D and the MDA-MB-231 cells in the G2/M-phase significantly increased after treatment at varying concentrations (0, 1, 2, 4μM) of JNJ-7706621:the G2/M-phase rates at the corresponding concentrations were (12.66±1.55)%, (20.63± 1.32)%, (23.20±1.82)%, and (32.19±2.37)%, respectively, for the T47D cells (P<0.05), and the G2/M-phase rates were (16.22±1.48)%, (21.45±0.85)%, (25.25±1.26)%, and (31.08±1.16)%, respectively, for the MDA-MB-231 cells (P<0.05). The rates of apoptotic cells were also significantly increased (P<0.05). Western blot results indicated that JNJ-7706621 exerted a slight effect on the expression of CDK1 and p53 and that the phosphorylation level of CDK1 decreased at the Thr161 site but increased at the Tyr15 site. In addition, cleaved caspase3 and PARP increased, whereas Bcl-2 and cyclinB1 decreased significantly. Conclusion:JNJ-7706621 can significantly inhibit the proliferation of breast cancer cell lines T47D and MDA-MB-231 by inducing cell cycle arrest and apoptosis, which may be associated with the downregulation of the CDK1 phosphorylation at the Thr161 site.

Objective To investigate the alterations of outer membrane permeation of multiple-antibiotic-resistant Proteus mirabilis.Methods Laboratory-derived cefotaxime-resistant mutants were induced by serial passages of clinical isolated susceptible Proteus mirabilis on cefotaxime-containing agar.Thereafter,the outer membrane proteins(OMP)of the parental strains and mutants were analyzed by sodium dodeeyl sulfate-polyacrylamide gradient gel electrophresis(SDS-PAGE)and the uptake of ciprofloxacin (CPLX)was determined with high pressure liquid chromatography(HPLC).Lastly,morphological analysis was performed by scanning and transmission electron microscopy.Results Compared with the parental strains.the mutants wete resistant to quinolones,cephalosporins and penicillins;the content of OMP with relative molecular weight 40 000 was reduced and that of 37 000 0MP was increased.The uptake of CPLX was reduced and the ratios of peak concentration were decreased to 1:1.74,1:1.53 compared with that of suseeptible strains.CPLX concentration absorbed was lower than the break point 1 mg/L of resistance and the difference of CPLX intracellular concentration between resistant and susceptible strains was less than 2 times.which resulted in much more increase of minimum inhibitory concentrations(MICs).Meanwhile,it was observed under electronic microscopy that resistant strains lost the rodlike shape and had more distinctive membrane fold,wider periplasmic space and les8 nucleiods.Conclusion The multiple-antibiotic-resistant Proteus mirabilis shows decrease of drug uptake and changes of ultrastructure,which may be related to alterations of outer membrane permeation.

Inflammatory bowel disease (IBD) is a group of diseases characterized by recurrent episodes of chronic intestinal inflammation including ulcerative colitis (UC) and Crohn's disease (CD).The prevalence of IBD has shown a rapid growth in China.Malnutrition is often seen in IBD patients,especially in those with CD.Appropriate diets and supplementation of trace elements,calcium,vitamin D,and probiotics are beneficial for disease remission and control.Nutrition support therapy can improve the nutritional status and meanwhile may facilitate the induction and maintenance of remission in CD patients.

Evidence-Based Medicine ; Humans ; Medicine, Chinese Traditional

Objective:To investigate the effect of short-term intensive treatment with insulin on metabolic control,?-cell function and insulin resistance in newly diagnosed type 2 diabetic patients. Methods:Thirty-eight newly diagnosed type 2 diabetic patients were randomly divided into two groups and treated with continuous subcutaneous insulin infusion(CSII) or multiple daily insulin injection(MDI) for 1 month.Fasting blood glucose(FBG) and lipid profiles were measured,and oral glucose tolerance test(OGTT)was performed before and after the treatment.The second phase insulin and C peptide secretions were measured by calculating area under curve(AUC) in OGTT.HOMA model was used to evaluate ?-cell function((HOMA-?)) and insulin resistance. Results:Excellent control of FBG was achieved after 1 month intensive treatment.(HOMA-?) was improved significantly. Conclusion:The excellent metabolic control and ?-cell function improvement can be achieved by short-term intensive insulin therapies like CSII or MDI.

OBJECTIVE:To study the inhibitory effect of dihydrotanshinone(DTS)on human lung cancer GLC-82 cell and its mechanism. METHODS:After treated with 0(blank control),5,10,20,40,80 and 100 μg/ml DTS for 24 and 48 h,MTT as-say was used to measure the inhibition rates and IC50 of cells;cell apoptosis was detected by flow cytometry after treated with 17.85 μg/ml DTS for 12,24 and 48 h to calculate apoptotic rate;Western blot was used to detect the protein expressions of Bcl-2, Bax and Caspase-3. RESULTS:Compared with blank control group,different concentrations of DTS inhibited the proliferation of cells;24 and 48 h maximal inhibition rate were 54.48% and 64.95%,respectively;IC50 were 62.36 and 33.94 μg/ml. DTS could induce cell apoptosis in positive time dependent manner,and the range of inhibition rate was 5.6%-29.6%;Western blot showed DTS could down-regulate the expression of Bcl-2 protein and up-regulate the expression of Caspase-3 protein (P<0.01 or P<0.05). CONCLUSIONS:DTS have significant inhibitory effect on GLC-82 cells and also induce cell apoptosis,by a possible mech-anism of down-regulating the expression of Bcl-2 protein and up-regulating the expression of Caspase-3 protein.

Objective To improve the utilization ratio of operating room in Affiliated Hospital of Central South Uni-versity Xiangya Medical School by providing more comprehensive reference data for the design of surgical time pre-diction and dispatch system. Methods A questionnaire was designed according to the review of literature and consul-tation of experts for investigating the surgical time influencing factors. The surgical time influencing factors were ana-lyzed by stratified sampling. Results The surgeons-related factor was the highest influencing factor while the pa-tients themselves-related factor was the lowest influencing factor in the 2-dimensional factors. The selected 38 1-dimensional factors could affect the operating time with their mean influencing value>2 . 45 . The recognition of sur-gical time influencing factors was different in different operating rooms. Conclusion There are a variety of surgical time influencing factors. However, the surgeons-related factor is the highest influencing factor. The cognition of anesthesia-related factors and surgeons-related factors differs in different operating rooms.

Objective To investigate the safety of thalidomide in the treatment of immune-related bowel diseases for providing clinical reference.Methods Thirty-five patients with immune-related bowel diseases (31 Crohn's disease,2 ulcerative colitis and 2 Behcet's disease) treated with thalidomide were enrolled in this study.The incidence,type,severity,duration of thalidomide related adverse drug reaction (ADR) and the dose-effect relationship of neurotoxicity were analyzed.Results All the patients were treated with a mean dose of thalidomide (109.29 ± 30.37) mg/d for (18.8 ± 12.4) months,and 33 occurred ADR.The three most frequent ADR were numbness [51.4％ (18/35)],somnolence [48.6％ (17/35)] and dermatitis [37.1％ (13/35)].The median time to development of these three ADR were 6.50,0.25,and 1.00 months,respectively.Severe ADR leading to withdrawal accounted for 20.0％ (7/35),including reasons of peripheral neuritis (3/7),dermatitis (2/7) and myelosuppression (2/7).The incidence of peripheral neuritis was not significantly related to the maximal and initial dose of thalidomide (P ＞ 0.05).Conclusions Although the incidence of ADR was relatively high during the treatment of thalidomide,most of them were mild and well tolerated.Thalidomide can be safely used in patients with immune-related bowel diseases under close monitoring.

Objective To explore the correlation of minimal residual disease ( MRD) and ABC genes expression in acute myeloid leukemia ( AML) .Methods 52 de novo AML bone marrow samples were used to detect the expres-sion of ABCB1,ABCC1,ABCC4 andABCG2 by real-time PCR at diagnosis.Meanwhile, followed up these patients to monitor MRD with MFC at the points of finishing the first induction cause as well as the third ,the sixth and the ninth month after chemotherapy .Results The expression level of 4 ABC transporters among three MRD level de-tected after induction cause are correlated significantly with ABCB1(P<0.01), ABCC1(P<0.01), ABCC4(P<0.01) and ABCG2(P<0.01).Further more, after nine months follow-up, the patients whose MRD turned into positive again were detected a high ABC transports expression level , comparing with those MRD remained negative for nine months,which was of a statistically significance for ABCB1(P<0.05), ABCC1(P<0.05), ABCC4(P<0.01) and ABCG2(P<0.01).Conclusions A positive correlation of MRD and ABC transporters level in AML is found.

Purpose: To investigate the mechanism of acupuncture treatment of diabetic peripheral neuropathy. Methods: Acupuncture therapy was used to treat diabetic peripheral neuropathy, and compared with oral calcium antagonist and vitamin therapy by random control observation.Electromyography was performed for analysis at the same time. Results: Acupuncture treatment alleviated symptoms such as extremity numbness, pain and paresthesia in varying degrees in diabetic patients with peripheral neuropathy. The results of electromyography showed a marked improvement in motor and sensory conduction velocities. Conclusion: It is indicated that acupuncture therapy is markedly superior to oral calcium antagonist and vitamin therapy in clinical effect on diabetic peripheral neuropathy, and electromyographic recovery.