The abnormal glucose metabolism of tumor cells is associated with a variety of mechanisms.Hypoxia inducible factor (HIF) is able to activate the glycolytic enzymes,which is conducive to getting energy through glycolysis.The dysfunction or the depletion in numbers of mitochondria can inhibit the oxidative phosphorylation pathway of glucose to some extent.The activation of oncogenes and the inactivation of tumor suppressor genes are also involved in the regulation of mitochondrial respiratory chain and glycolytic enzymes,thus affecting the process of glucose metabolism.Compared with normal cells,the synthesis of oxidative phosphorylation enzymes is inhibited in cancer cells.In addition,the abnormal glucose metabolism plays an important role in the growth,invasion and metastasis of tumor cells.

Objective To explore the effects of dichloroacetate (DCA) combined with cisplatin on the apoptosis of HCT116 and possible mechanisms.Methods The inhibitory effects of DCA and cisplatin alone or in combination on colorectal carcinoma cell line HCT116 were examined by MTT and Hoechst 33342 staining,the mitochondrial membrane potential changes were measured by Rodanmine123 staining under fluorescent microscope.The expression of bcl-2 was checked by qPCR.The activity of caspase-3 was assayed.Results DCA or cisplatin alone could inhibit the growth of HCT116 in a time and dose dependent manner.Compared with single drug treatment,there was significantly synergistic effect after treatment of DCA combined with cisplatin for 48 hours.Compared with the single drug treatment,the nuclear morphological changes such as chromatin condensation and fragmentation were more severe,and the mitochondrial transmembrane potential declines were markedly apparent for DCA + cisplatin group.The expression of bcl-2 gene in combination group was inhibited (P ＜ 0.05),and the activity of caspase-3 significantly increased (P ＜ 0.01).Conclusions DCA could inhibit the proliferation and induce the apoptosis of HCT116 cells in a time and dose dependent manner.The combination use of DCA and cisplatin has a synergistic effect on the biological action of HCT116.This may be attributed to lowering of mitochondrial transmembrane potential and the suppressed expression of bcl-2 gene.

Animals ; Arthritis, Experimental ; metabolism ; pathology ; Breast Neoplasms ; pathology ; Cadherins ; metabolism ; physiology ; Cell Movement ; Female ; Fibroblasts ; cytology ; pathology ; Humans ; Macrophages ; cytology ; pathology ; Neoplasm Invasiveness ; Synovial Membrane ; cytology ; metabolism ; pathology

Objective:To determine the characteristics and differences in bleomycin-induced lung ifbrosis model by repeated low-dose intravenous injection and single dose intratracheal instillation of bleomycin.
Methods:Forty male ICR (Institute for Cancer Research) mice were randomly divided into a model group I, a model group II, and 2 control groups (10 mice in each group). In model group I, bleomycin was injected intravenously at 10 mg/(kg·d) for 14 consecutive days;and in model group II, bleomycin was instilled intratracheally at 5 mg/kg. The 2 control groups were given isotonic saline solution. At the 28th day, the mice were sacrificed and the bronchoalveolar lavage lfuid (BALF) was collected. The total cells and proteins in the BALF, pulmonary coeffcient, and hydroxyproline (HYP) content were determined. The pathological changes were observed by the eosin staining and Masson's trichrome staining.
Results:1) Both intravenous injection and intratracheal instillation of bleomycin resulted in severe and extensive inlfammation and ifbrosis in the lungs. The total cells and proteins in the BALF, HYP content, pulmonary coeffcient and the pathological score of pulmonary ifbrosis were all signiifcantly increased in the 2 model groups (P<0.01). 2) Fibrosis was mainly under the pleura or around the vessel in model group I, and it was located near the bronehia and bronchioles in model group II. 3) The death rate was higher in the model group II than that in the model group I. 4) Proteins in the BALF were significantly higher in model group II than that in model group I (P<0.05). There was no difference in the total cells in the BALF, the pulmonary coefficient, the HYP content, and the pathological score of pulmonary ifbrosis between the 2 groups (P>0.05).
Conclusion:The pulmonary fibrosis model can be successfully established by intravenous injection or intratracheal instillation of bleomycin, but the sites of pulmonary ifbrosis are different. The histological changes caused by the repeated low-dose intravenous injection of bleomycin is more similar to idiopathic pulmonary ifbrosis than that by the single dose intratracheal instillation.

Objective To investigate the effects of rapid colloid and crystalloid infusions on the plasma concentration of propofol( Cp) during target-controlled infusion.Methods Thirty-six patients were randomly assigned to three interventions(12 patients per group).At least 30 min after the start of propofol infusion,the hydroxyethyl starch solution group(HES)received HES of 24 mL/(kg· h),on the former 20 min,the sodium acetate Ringer’s injection group(AR)received AR of 24 mL/(kg· h),while HES group and AR group of later 20 min and the control group of whole course received AR of 2 mL/(kg· h).The plasma concentrations of propofol were recorded per 2 min and a half.The cardiac outputting,blood volume and clearance of indocyanine green were measured by pulsed dye density analyzer,the effective hepatic blood flow( EHBF) were obtained.Results The varying of Cp with time showed a significant treatment factor(F[2,33] =14.14,P<0.001)and time factor(F[16,528] =10.37,P<0.001)and interaction between the above factors(F[32,528] =2.82,P <0.001) by ANOVA for repeated measurement;the difference of Cp among each group,Cp in HES group was significantly lower than AR group(5-40 min)or control group(10-40 min),with significant difference(P<0.05).The varying of EHBF with time showed a significant treatment factor(F[2,28] =3.68,P=0.038)and time factor(F[2,56] =5.37,P=0.007)and interaction between the above factors(F [4,56] =3.67,P=0.010);while there was no significant difference in other groups.Conclusion Rapid HES infusion increases the effective hepatic blood flow,resulting in a decrease of propofol concentration during target-controlled infusion.Rapid HES infusion should be used cautiously as it may decrease the depth of anesthesia.

Objective To study some sensitive electrophysiological parameters in surveillance of allograft rejection.Methods Forty rats underwent heterotopic heart transplantations.IMEG was re- corded by an epicardiac unipolar pacing lead fixed at the right ventricular outflow tract.QRS amplitude and heart rate were determed daily in 10 syngeneic and 30 allogeneic transplants.Syngeneic transplants were killed at 7 th postoperative day,and allogeneic transplants killed at 3 rd,5 th and 7 th postopera- tive day.Histopathologie studies were performed at every transplanted heart.Results In syngeneic group,QRS amplitude kept constant after the transplantation while no significant differences were ob- served at the 3 rd,5 th and 7 th postoperative day.QRS amplitude was dropped obviously in allogeneic group after the first two postoperative days whereas significant differences were observed at the rejec- ting and non-rejecting hearts.Conclusions IMEG is a valid method to monitor acute allograft rejec- tion.QRS amplitude is a more sensitive electrophysiological parameter to diagnose severe rejections than heart rate,while mild rejections were not detected by this method.

The pharmaceutical ethynylestradiol (EE) is a potent endocrine modulator. Application enlargement of ethynylestradiol in clinics and abuse in livestock farming and fishing make it important to explore ethynylestradiol toxicological action on vertebrate embryonic development and to establish an in vivo method for EE toxicity detection efficiently and conveniently. In the present study, using a model animal zebrafish and 17alpha-ethynylestradiol as a representative compound, we have investigated EE2 teratogenicity, target tissues and target genes on zebrafish embryo. The results show that median teratogenesis concentration (TC50) of EE2 is 0.8 microg x mL(-1), and median lethal dose (LD50) is 3.3 microg x mL(-1). Targets of EE2 action were implicated in brain, eyes, heart, muscle, skeleton, pigment and viscera. Embryonic cardiac arrhythmia caused by EE2 is probably resulted from heart abnormal structure. The embryonic stage sensitive to EE2 mainly started at cleavage and last up to the organogenesis with time-accumulating effect. RT-PCR results indicate that EE2 treatment disturbed gene expression pattern at the early period of zebrafish embryonic development by suppressing transcription of gene boz that promotes brain development, upregulating genes for trunk and tail, such as ntl, spt, shh, and perturbing Nodal signal expression of TGFbeta superfamily, for example, cyc, sqt and oep. Using zebrafish, an efficient in vivo method for quick evaluation of EE toxicity on embryonic development has been developed.

Objective To observe the effect of restrictive transfusion in colon cancer surgery in elderly patients on postoperative VAP (ventilator-associated pneumonia). Methods Forty cases of elderly patients with colon cancer intending to undertake surgery were randomly divided into restrictive transfusion group (group R) and standard transfusion group (group S) with 20 cases in each group. In group R, patients were administered one third of accumulative fluid loss in the first 60 minute, then the infusion rate were 4 mL/(kg·h) and central venous pressure was maintained at 5 ~ 7 cmH2O. In group S, rate of fluid administration = CVE + deficit +maintenance + loss + third space. Blood gas index including lactic acid and volumes of fluid administered, blood loss, urine volume and thoracic fluid count (TFC) were recorded in the operation. Clinical pulmonary infection score(CPIS) was recorded respectively before operation, 1 day, 3 day, 7 day after operation to evaluate the risk of VAP. Results Compare with those in group S, there were significantly less TFC and intraoperative volumes of fluid administration in group R. The CPIS was significant lower at day1, day3, day7 after operation in group R. There was no significant difference in MAP, HR, CO and urine volume between two groups. Conclusions In colon cancer surgery for elderly patients, restrictive transfusion can maintain hemodynamic stability, ensure the tissue oxygenation, reduce conjunction edema, shorten the recovery and hospital stay and reduce the incidence of VAP.

Objective To observe the effect of bloodletting cupping on the serum insulin level in patients with simple obesity. Methods Fifty simple obesity patients were randomized into a treatment group and a control group, 25 in each group. The treatment group was intervened by bloodletting cupping, while the control group was by oral administration of Sibutramine Hydrochloride. The efficacy for losing weight and the serum insulin level were evaluated and compared before intervention and after 2 treatment courses. Results The total effective rate was 88.0%in the treatment group versus 80.0%in the control group, and the difference was statistically insignificant (P>0.05). The serum insulin levels were changed significantly in both groups after intervention (P＜0.05). After intervention, there was a significant difference in comparing the serum insulin level between the two groups (P＜0.05). Conclusion Bloodletting cupping can significantly improve the serum insulin level in patients with simple obesity.

Objective To observe the clinical effect and safety of propranololand imiquimod therapy for infantile hemangiomas of proliferative phase.Methods A total of 53 infantile patients with hemangiomas of proliferative phase that were treated in our department were collected.According to patient's condition,the patients were classified into treatment group and observation group.The treatment group consisted of 34 patients received propranolol and imiquimod treatment,and 19 cases belonged to the observation group.The changes of tumor were compared between the treatment group and the observation group.Pre-therapeutic and post-therapeutic heart rate,blood pressure,blood glucose were monitored in the treatment group,so were in post-treatment.Results After 6 months,the effective rate was 97.1％ (33/34) in treatment group,and the effective rate was 57.9％ (11/19)in observation group.There was significant difference between treatment group and observation group in effective rate (P＜0.05),and so did blood pressure and heart rate after medication in the treatment group,but not in blood glucose,heart rate six hours after medication (P＞0.05).Conclusions Propranolol and imiquimod therapy has a certain inhibitory effect on infantile hemangiomas of proliferative phase.Propranolol and imiquimod are safe in patients with infantile hemangioma,and adverse reactions are mild.