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.

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

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.

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

OBJECTIVE To evaluate the cardiotoxicity of a widen-spectrum antineoplastic drug, gambogic acid, through quantitative multiple cellular phenotypic characterization. METHODS H9c2 cell line was used as a model with doxorubicin (Dox) and amiodarone (Ami) as positive controls, hypaconi?tine as negative control and 0.1% DMSO as normal control. An optimized protocol was established to identify the morphology and function of cell nuclei. The effect of drugs on cell viability, nuclear area (Hoechst33342), mitochondria mass (MitoTracker Deep Red) and cytoplasmic calcium ion mobilization (Rhod2 AM)was studied. EC50 and Z′values were calculated to evaluate the degree of toxicology and to estimate the precision and false-positive rate, respectively. RESULTS Dose-response analysis indicated that EC50 of Dox on cell viability, nuclear area, mitochondrial mass was 0.72, 0.014 and 1.21μmol · L-1, respectively. On the other hand, EC50 of Ami on the parameters of cell viability, nuclear area and mitochon?drial mass was 14.83, 6.72 and 4.54μmol·L-1, respectively with Z′value above 0.5. Hypaconitine decreased the SER ridge of mitochondria. Gambogic acid caused significant mortality of H9c2 cells and induced nuclear shrinkage as Ami did. The EC50 values of cell viability and nuclear area were 0.24 and 1.16 μmol · L- 1. Meanwhile,gambogic acid disturbed the mitochondrial function as indicated by the increased mitochondrial area (EC50=0.44 μmol · L-1), abnormal SER Ridge(EC50=0.99 μmol · L-1) and decreased mitochondrial mass(EC50=1.21 μmol · L- 1). Cellular calcium mobilization was lower than normal (EC50=0.41 μmol · L-1). CONCLUSION The EC50 values of positive controls calculated from our assessment are similar those reported in literature. A multi-parameter and simultaneous evaluation enables a comprehensive analysis of the morphology of nuclei and mitochondria of cardiomyocytes and a preliminary assessment of the mechanisms of toxicity.

The clinical characteristics, therapeutic effects and complications of 32 incipient patients with acute Vogt-Koyanagi-Harada ( VKH) syndrome admitted in Wuxi Second Hospital during October 2010 to September 2013 were retrospectively analyzed.There were 15 males and 17 females with a mean age of (41.3 ±14.1) years (22 -71 years), the time from the disease onset to treatment ranged from 3 to 20 days.Among 32 cases, 30 ( 94%) had premonitory symptoms. The multifocal bullous neurosensory detachment, optic disk hyperemia and edema in posterior pole of fundus were found in all cases, and exudative retinal detachment was found in 4 cases (6 eyes).The results of optical coherence tomography ( OCT) showed the macula neurosensory detachment, thick retinal neuroepithelial layer and wavy RPE layer in all patients.Fundus fluorescein angiography ( FFA) showed that scattered hyperfluorescence dots and cystic fluorescein reservoir was observed in early phase and later period respectively.Patients received intravenous methylprednisolone with the onset dose of 80 mg per day for 3-7 days and oral administration followed, which would gradually decrease later;the average treatment duration was (52.9 ±14.6) weeks. The visual acuity of 40 eyes (22 cases) was recovered to more than 0.8, and no blindness occurred after the treatment.During the treatment hair loss, depigmentation of skin and hair were found in 12 cases (38%) , and 2 cases showed short-term elevated intraocular pressure.These symptoms disappeared after drug therapy ceased.And no recurrence was found during the follow-up of 6 months.However, sunset glow fundus was found in 13 patients (26 eyes).The study shows that the diagnosis of VKH syndrome is based on the typical signs of the fundus presented on OCT and FFA.Early and systemic administration of glucocorticoids is important treatment for patients with VHK syndrome, which could decrease systemic and local complications effectively.

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 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.