Dioscin has a wide range of biological effects and broad application prospects. However the studies concerning the toxicology and mechanism of dioscin is small. This article is to study the hepatotoxicity of dioscin and the effect of dioscin treatment on expression of aryl hydrocarbon receptor (AhR) mRNA and CYP1A mRNA and protein in HepG2 cells in vitro. Dioscin 0.5-32 µmol · L(-1) exposed to HepG2 cells for 12 h, cell viability was examined by CCK-8 assay and the release rate of lactate dehydrogenase (LDH) was to evaluate cell membrane damage. HepG2 cells morphologic changes were quantified by inverted Microscope, and the effect on production of reactive oxygen species (ROS) was detected by flow cytometry. The mRNA expression of CYP1A and AhR was evaluated by RT-RCR. The protein expression of CYP1A1 was detected by western blot. The cell viability was significantly inhibited after HepG2 cells were exposed to dioscin 0.5-32 µmol · L(-1). Compared with the control, the LDH release rate and ROS were significantly increased. The expression of CYPlA and AhR mRNA was increased. The expression of CYP1Al protein was increased after dioscin treatment, and resveratrol, an AhR antagonist, could downregulate the expression of CYP1A1. It follows that large doses dioscin has potential hepatotoxicity. The possible mechanism may be dioscin can active aryl hydrocarbon receptor (AhR) and induce the expression of CYP1A.
Cell Survival ; drug effects ; Chemical and Drug Induced Liver Injury ; etiology ; Cytochrome P-450 CYP1A1 ; genetics ; Diosgenin ; analogs & derivatives ; toxicity ; Hep G2 Cells ; Humans ; L-Lactate Dehydrogenase ; secretion ; RNA, Messenger ; analysis ; Reactive Oxygen Species ; metabolism ; Receptors, Aryl Hydrocarbon ; genetics

To research the effect of Ginseng Radix et Rhizoma and Aconiti Lateralis Radix Praeparata compatibility on cardiac toxicity in rats by UPLC-Q-TOF/MS, and explore the endogenous markers and molecule mechanism. Different compatibility of Shenfu decoction were given to male Wistar rats at dosage of 20 g · kg(-1) for 7 days, collected the serum, and analyze the endogenous metabolites effected by Shenfu formulation by principal component analysis and partial least-squares analysis. Results showed that content of glutathione, phosphatidylcholine and citric acid decreased in mixed-decoction group, while ascorbic acid, uric acid, D-galactose, tryptophan, L-phenylalanine increased. The results showed cardiac toxicity of Aconiti Lateralis Radix Praeparata in Shenfu mixed-decoction. Shenfu co-decoction group showed a similar or weaker trend compared with control group, but most of them do not have a statistically significant. The results indicated the scientific basis of Shenfu compatibility by comparison of co-decoction group with mixed-decoction group. Shenfu compatibility can reduce cardiac toxicity induced by Aconiti Lateralis Radix Praeparata, and citric acid, glutathione, phosphatidyl choline, uric acid might be regarded as potential markers of cardiotoxicity.
Animals ; Biomarkers ; Cardiotoxicity ; Drugs, Chinese Herbal ; toxicity ; Glutathione ; blood ; Least-Squares Analysis ; Male ; Metabolomics ; methods ; Principal Component Analysis ; Rats ; Rats, Wistar

To study the effect of Siwu decoction on the function and expression of P-glycoprotein (P-gp) in Caco-2 cells. The Real-time quantitative poly-merase chain reaction (Q-PCR) was used to analyze the mRNA expression of MDR1 gene in Caco-2 cells. Flow cytometer was used to study the effect of Siwu decoction on the uptake of Rhodamine 123 in Caco-2 cells, in order to evaluate the efflux function of P-gp. Western blotting method was used to detect the effect of Siwu decoction on the P-gp protein expression of Caco-2 cells. Compared with the blank control group, after Caco-2 incubation with Siwu decoction at concentrations of 3.3, 5.0, 10.0 g x L(-1) for 24, 48, 72 h, the mRNA expression of MDR1 was up-regulated, suggesting the effect of Siwu decoction in inducing the expression of MDR1. After the administration with Siwu decoction in Caco-2 cells for 48 h, the uptake of Rhodamine 123 in Caco-2 cells decreased by respectively 16.6%, 22.1% (P < 0.05) and 45.4% (P < 0.01), indicating that the long-term administration of Siwu decoction can enhance the P-gp efflux function of Caco-2 cells. After the incubation of Caco-2 cells with Siwu decoction for 48 h, the P-gp protein expression on Caco-2 cell emebranes, demonstrating the effect of Siwu decoction in inducing the protein expression of P-gp.
ATP Binding Cassette Transporter, Sub-Family B ; genetics ; metabolism ; ATP-Binding Cassette, Sub-Family B, Member 1 ; genetics ; metabolism ; Caco-2 Cells ; Drugs, Chinese Herbal ; pharmacology ; Humans ; Up-Regulation ; drug effects

OBJECTIVETo compare the short-term outcomes in patients with esophageal cancer after subtotal esophagectomy via thoracoscopy in prone position and in left lateral position.

METHODSBetween September 2008 and September 2010, thoraco-laparoscopic esophagectomy (TLE) with thoracoscopic mobilization of the esophagus and mediastinal esophagectomy was performed in 41 patients in prone position (group A) and other 41 patients (group B) performed by the same surgeon in left lateral position.

RESULTSPreoperatively, the endoscopic location of the tumor was in the upper third in 5 cases (2 vs. 3), the middle third in 21 cases (12 vs. 9), and the lower third in 56 cases (27 vs. 29). The median operative time was 230 (range 170-310) min in group A and 280 (range 190-380) min in group B (P=0.04). The median intraoperative blood loss was 275 (range 100-320) ml in group A and 360 (range 120-670) ml in group B (P=0.09). The median number of lymph nodes dissected was 8.4 (range 4-23) in group A and 6.9 (range 6-21) in group B (P=0.03). The postoperative complications totaled 6 (14.6%) in group A and 8 (17.1%) in group B (P=0.44). After a median follow-up period of 15.7 (range 2-28) months for group A and 16.3 (range 3-31) months for group B, 19 patients in group A died and 21 patients in group B.

CONCLUSIONSFor esophageal cancer under T3N1M0, surgical outcomes are similar between prone thoracoscopic esophageal mobilization and left lateral position. Prone position may be associated with better lymph node dissection.

Esophageal Neoplasms ; surgery ; Esophagectomy ; methods ; Female ; Follow-Up Studies ; Humans ; Male ; Middle Aged ; Prone Position ; Retrospective Studies ; Thoracoscopy ; methods ; Treatment Outcome

In order to study the value of sequential and quantitative analysis of chimerism in determination of optional time of donor lymphocyte infusion (DLI) and prediction of efficacy of DLI, six patients with leukemias who relapsed or failed of engraftment were treated with DLI. Serial and quantitative analyses of donor chimerism (DC) both prior to and following DLI were performed by multiplex PCR amplification of STR markers (STR-PCR) and capillary electrophoresis with fluorescence detection. The results showed that at the time of relapse or graft rejection, STR-PCR indicated the decreasing donor chimerism in all six patients, at levels ranging from 27.3% to 85.7%. The declining value of DC (<90%) was detected in four patients at 26 days before relapse or graft rejection diagnosed clinically. Therefore the decrease of value of DC can be identified the high risk of relapse or graft failure and can be used to guide DLI implementation at early stage. In this study the clinical response were seen in two patients, the value of DC in these patients increased with convertion to a predominant donor profile (>90%) or converted to stable FDC shortly after DLI, while in the patients without clinical response, the level of DC decreased persistently or declined after transient increase. Three patients without response received second DLI. It is concluded that the monitoring of chimerism is proved to be a valuable to determine the optional time point of DLI and to early evaluate the efficacy of DLI. Furthermore, it can present a rational basis for treatment of intensification in the patients who did not respond to first-line DLI treatment.
Adolescent ; Adult ; Hematopoietic Stem Cell Transplantation ; Humans ; Lymphocyte Transfusion ; Recurrence ; Tissue Donors ; Transplantation Chimera

OBJECTIVETo meet the need for instrument assessing the cognitive abilities of infants and young children as well as discriminating between global developmental delay and particular deficits in either language or problem-solving skills, we intended to introduce Cognitive Adaptive Test/Clinical Linguistic and Auditory Milestone Scale (CAT/CLAMS) into China.

METHODSCAT/CLAMS were administered to 1604 normative children aged 4-36 months (in 16 age groups, about 100 children per age group) in Shanghai during the period from December 2003 to June 2004. In the meantime, Gesell Developmental Diagnosis was applied for 100 of these children, respectively aged 4, 6, 12, 18 and 30 months (20 children per age group). Interclass correlation coefficients (ICC) were adopted to analyze data in terms of inter-rater reliability and re-test reliability of the scales of CAT/CLAMS. Cronbach alpha coefficients were calculated to assess the inter consistency of the scales. Pearson correlation coefficients(r) were adopted to analyze the concurrent validity of the scales. The normative percentile graphs of CAT/CLAMS in the children from 4 to 36 Months of age in Shanghai, China were adopted.

RESULTSAdministrations of the CAT/CLAMS for each subject usually took 10-20 minutes. Individual scores (CLAMS, CAT, and CAT/CLAMS) increased with ages (Pearson correlation coefficients were 0.96, 0.98 and 0.98, respectively, P < 0.01 for all). ICCs (intraclass correlation coefficient) in terms of individual scores for the inter-rater reliability test and the re-test reliability test were respectively > or = 0.96 (P < 0.01) and > or = 0.95 (P < 0.01), all the Cronbach alpha coefficients were > or = 0.98; in 100 children of the 5 age groups, there was significantly positive correlation between CAT/CLAMS and Gesell Developmental Diagnosis in terms of language skill DQ and adaptive skill DQ, and Full Scale DQ (r = 0.517, 0.703, 0.613, respectively, P < 0.01 for all). Moreover, this significant positive correlation was observed in each of the 5 age groups (r = 0.455-0.827, P < 0.05).

CONCLUSIONCAT/CLAMS is suitable for discriminating between global developmental delay and particular deficits in either language or problem-solving skills. It is a quick, reliable, and valid instrument, with refined and quantified results. It is a good tool for developmental surveillance and screening of infants and young children.

Child Development ; Child, Preschool ; Humans ; Infant ; Language Tests ; standards ; Neuropsychological Tests ; standards

OBJECTIVETo compare the inhibitory effects of cytokine-induced killer (CIK) cells alone, chemotherapeutic drug alone, and CIK cells combined with chemotherapeutic drug on the growth of hepatocellular carcinoma (HCC) cells transplanted in nude mice.

METHODSPeripheral blood mononuclear cells (PBMC) collected from five healthy donors by blood cell separator were incubated in vitro to induce CIK cells in the presence of interferon-gamma (IFN-gamma), IL-2 and anti-CD3 monoclonal antibody (mAb). The phenotype of CIK cells was characterized by flow cytometric analysis. BEL-7402 HCC cells were inoculated subcutaneously to nude mice. On day 5, at the inoculation site were injected normal saline (group 1), CIK cells (3 x 10(7) and 6 x 10(7), group 2 and 3), mitomycin-C (MMC 80 microg in 0.2 ml, group 4), and CIK cells combined with MMC (group 5), respectively.

RESULTSThe percentage of CD3(+), CD3(+)CD8(+), CD3(+)CD56(+), CD25(+) cells increased from 64.0%, 28.0%, 7.8%, and 9.1% to 94.7%, 67.7%, 61.3%, and 84.0% respectively after cytokine induction. The percentage of CD3(+) and CD3(+)CD8(+) cells remained at high levels during incubation period, but that of CD25(+) and CD3(+)CD56(+) cells peaked respectively on day 7 and 13 and then declined. During the 90-day observation, the tumor formation rates were 100%, 70.0%, 80.0%, 70.0% and 66.7%; and the mouse survival rates were 10.0%, 60.0%, 40.0%, 50.0% and 75.0%, respectively from group 1 to group 5. Compared to the other groups, in the combined therapy group of mice, not only the tumor grew slowly and but also showed more marked tissue necrosis.

CONCLUSIONThe growth inhibitory effect on human HCC transplanted in nude mice of combined CIK cells and MMC treatment is more potent than that of CIK cells or MMC alone.

Animals ; Antibiotics, Antineoplastic ; therapeutic use ; Carcinoma, Hepatocellular ; immunology ; pathology ; therapy ; Cell Line, Tumor ; Cells, Cultured ; Combined Modality Therapy ; Cytokines ; metabolism ; pharmacology ; Female ; Humans ; Immunotherapy, Adoptive ; Killer Cells, Natural ; transplantation ; Liver Neoplasms ; immunology ; pathology ; therapy ; Male ; Mice ; Mice, Inbred BALB C ; Mice, Nude ; Mitomycin ; therapeutic use ; Neoplasm Transplantation

OBJECTIVETo investigate the effect of different operation time to percutaneous balloon pulmonic valvuloplasty (PBPV) to critical pulmonary valve stenosis (CPS).

METHODTwenty-one infants (age ≤ 60 days at operating day) suffered from CPS, diagnosed by fetal echocardiogram and confirmed by echocardiography after birth, were enrolled in this case-control-study with written informed consent during April 2007 to December 2011. Of the 21 cases, 7 had prenatal diagnosis in our prenatal diagnosis center (prenatal group, Pre) and 14 were referred from other hospitals, who were divided into postpartum group A (Post A, referred within 28 days after birth) and postpartum group B (Post B, referred 29 to 60 days after birth). To Pre-group, the integrative interventional protocol was cautiously made by the consultative specialists, including intrauterine diagnosis, perinatal care and urgent PBPV soon after birth. To Post-group, emergency PBPV was preformed after the referral. Tei index of right ventricular and pressure-gradient (PG) between right ventricular and pulmonary artery were measured before and at different time points one year after PBPV.

RESULTThe values of SpO2 in Pre-group ranged from 82%-92% (86.57% ± 5.34%) under the state of continuous intravenous infusion of alprostadil. PBPV was successfully preformed within 3-6 days after birth. The values of SpO2 increased to 97.33% ± 1.15% post procedure. The values of PG pre- and post- procedure were (86.34 ± 11.77) mm Hg and (31.43 ± 8.46) mm Hg respectively. Preoperative RV Tei-index was 0.68 ± 0.05, it decreased rapidly after procedure, and recovered to normal one month after procedure. Only one case showed restenosis seven months after procedure and repeated PBPV. Fourteen referral cases (6 cases in Post A group and 8 cases in Post B group, accompanied in 1 and 3 cases with heart failure), the values of SpO2 ranged from 83%-91% under state of continuous intravenous infusion of alprostadil. And the operating time was 10-57 days after birth. The values of SpO2 recovered to normal post procedure, and heart failure alleviated. Increased preoperative RV pressure obviously decreased significantly post-procedure. And increased Tei-index declined gradually, at one-year follow-up, the value of Tei-index in Post A group recovered to normal, whereas that of Post B was (0.51 ± 0.06), compared to Pre and Post A groups, the difference was significant (P < 0.05) . One case showed restenosis nine months after procedure and repeated PBPV was performed. The hypoxic exposure durations were (4.43 ± 0.68) , (16.33 ± 4.46) , (41.25 ± 9.19) , respectively, and the difference among the three groups was significant (P < 0.05).

CONCLUSIONTo the fetuses with definite prenatal diagnosis of critical pulmonary valve stenosis, preoperative general condition can be adjusted to more suitable for emergency operation. Early PBPV can achieve shorter hypoxic exposure and better recovery of right ventricular function post procedure. Perinatal integrated intervention for CPS can significantly improve the prognosis and quality of life in this patient population.

Catheterization ; instrumentation ; methods ; Dilatation ; methods ; Echocardiography ; Female ; Humans ; Infant ; Infant, Newborn ; Pregnancy ; Prenatal Diagnosis ; methods ; Pulmonary Artery ; physiopathology ; surgery ; Pulmonary Valve Stenosis ; congenital ; diagnosis ; physiopathology ; surgery ; Time Factors ; Treatment Outcome ; Ventricular Function, Right

BACKGROUNDThe optimal endpoint for catheter ablation of persistent atrial fibrillation (AF) remains ambiguous. This study investigated the impact of AF termination as a procedural endpoint and the termination mode on long-term clinical outcome.

METHODSTwo hundred and ninety-three patients who underwent stepwise ablation for persistent AF were categorized into the AF termination by ablation group and into the electrical cardioversion (CV) group. Subgroups were also analyzed based on different termination modes. Follow-up assessment included early recurrence and sinus rhythm (SR) maintenance.

RESULTSDuring initial ablation, 33 patients (11.3%) were directly converted to SR, 166 patients (56.7%) were converted to atrial tachycardia (AT) that subsequently restored SR with further ablation in 98 patients (33.4%), and a total of 162 patients (55.3%) underwent cardioversion due to persistent atrial arrhythmias. Comparison between termination by ablation and termination by cardioversion in patients exhibiting AF or AT revealed that no significant difference was observed in early recurrence (38.2% vs. 43.8%, P = 0.328) and SR maintenance (67.2% vs. 59.8%, P = 0.198) during the (23 ± 7) months follow-up. Even after repeat ablation, the SR maintenance continued to exhibit no statistical difference in above two groups (72.5% vs. 70.4%, P = 0.686). Further analysis of subgroups, however, demonstrated that patients with AF terminated directly to SR experienced better clinical outcomes than other subgroups (P < 0.05). Furthermore, atrial arrhythmias present during ablation have been implicated in prediction of recurrence mode: AF or AT (P < 0.05).

CONCLUSIONSTermination as a procedural endpoint is not associated with favorable long-term SR maintenance in persistent AF. AF methods that convert arrhythmia directly to SR have, however, been linked with improved clinical outcomes, although conversions to AT may not be correlated. Atrial arrhythmias observed during the ablation may be used to predict the recurrence mode.

Adult ; Aged ; Atrial Fibrillation ; physiopathology ; therapy ; Catheter Ablation ; methods ; Electrophysiologic Techniques, Cardiac ; Female ; Humans ; Male ; Middle Aged

Catheter Ablation ; methods ; Heart Atria ; surgery ; Heart Defects, Congenital ; surgery ; Humans ; Postoperative Complications ; prevention & control ; Tachycardia, Supraventricular ; prevention & control