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.

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.

Safety assessment in clinical trials is dependent on an in-depth analysis of the adverse events to a great extent. However, there are difficulties in summary classification, data management and statistical analysis of the adverse events because of the different expressions on the same adverse events caused by regional, linguistic, ethnic, cultural and other differences. In order to ensure the normative expressions, it's necessary to standardize the terms in recording the adverse events. MedDRA (medical dictionary for regulatory activities) has been widely recommended and applied in the world as a powerful support for the adverse events reporting in clinical trials. In this paper, the development history, applicable scope, hierarchy structure, encoding term selection and standardized query strategies of the MedDRA is introduced. Furthermore, the practical process of adverse events encoding with MedDRA is proposed. Finally, the framework of statistical analysis about adverse events is discussed.
Adverse Drug Reaction Reporting Systems ; standards ; statistics & numerical data ; Databases, Pharmaceutical ; standards ; Humans

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 sum up the experience of perioperative management of patients with heart transplantation.Methods In recent 3 years 24 cases of dilated cardiomyopathy,4 cases of(serious) valve disease,1 case of serious ischemic cardiomyopathy and 1 case of bi-ventricular assist(received) heart transplantation surgery.The mean by pass time was 75?24 min and the mean aortic clamp time was 72?8 min.Cyclosporine,MMF and prenisodone were adopted as anti-immune(response) strategy and the dose of cyclosporine was adjusted according to the serum concentration.(Intramyocardial) electrograms and tissue Doppler ultrasound technique were used to monitor the(immune) response situation.The myocardial biopsy was performed in case of the suspect of acute(rejection).Results In 5 postoperative deaths,3 cases died of low cardiac output,1 died of infection-(induced) multiple organ failure and 1 case died of serious bleeding.The postoperative complications(included) right heart failure in 6 cases,renal failure in 13 cases,and acute rejection in 4 cases.(Conclusion) The effective prevention and management of complications is the key point of success of heart transplantation.Application of comprehensive monitoring techniques is beneficial to the management of the immune rejection after transplantation.

Objective To discuss the therapy modalities and their efficacy for Cobb's syndrome Methods Data from 14 cases of Cobb's syndrome were retrospectively reviewed of which diagnosis, management and follow-up were discussend. Results Follow-up period of the 14 cases was 4 months to 3 years, of them, no complete cure occurred, 12 cases improved, 2 cases deteriorated. Conclusions Early diagnosis and early treatment using in terventional and surgical method are the key point for this kind of in curable diseases.

Objective To observe the influence of N-acetylcysteine(NAC)on the formation of Pseudomonas aeruginosa biofilm(BF),and to study the synergism of bactericidal activities of NAC combined with levofloxacinon to the mature Pseudomonas aeruginosa biofilm.Methods The experiment was done in experiment centre of Xiangya Hospital.Scanning electronic microcopy(SEM)were utilized to demonstrate the effect of NAC on the formation of biofilm.Then biofilm cultured without NAC were detected by optical microscopy after being stained with AgNO3.The minimal inhibitory concentration were detected by double test tube diluted method.The mature biofilm was treated by NAC and/or different concentrations of levofloxacin for 24 hours.The influence of levofloxacin combined with NAC were examined by MTT method on the bacterial quantity in biofilms.Results Biofilm was achieved on the silicon slides in all groups 7 days after the incubation of Pseudomonas aeruginosa.Scanning electronic microcopy showed that the mucoid materials among bacteria was significantly reduced and the thickness of biofilm was decreased in NAC groups.Levofloxacin beyond 1 MIC could significantly decline the viable cells on biofilms(P

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.

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 determine the characterization of mucA gene mutation in clinically isolated Pseudomonas aeruginosa (P.aeruginosa), and the relation between mucA mutation and the mucoid phenotype.Methods A total of 58 strains of P.aeruginosa were collected. Of them,8 were nonmucoid phenotype and 50 were mucoid phenotype.We detected mucA mutations with PCR-SSCP and sequencing analysis. Alginate was examined by colorimetry. Results All strrains had mucA mutations (100%), 16 of the 50 (32%) isolates contained mucA mutations that could alter the encoding sequence of amino acids, and the rate in nonmucoid isolates was 0. Fourteen mutation sites were found, 5 of which could alter the encoding sequence of amino acids, and the others were silent mutations. The alginate concentration of mucoid P.aeruginosa was higher than the nonmucoid P.aeruginos(P＜0.01). The alginate concentration of the isolates which contained mucA mutations that could alter the encoding sequence of amino acid was higher than the strains only with silent mutations (P＜0.01).Conclusion mucA mutation correlates with the alginate production and phenotype of bacterial colonies.