OBJECTIVE: To investigate the protection of hepatocyte growth factor (HGF) on CML cell line K562 from apoptosis induced by etoposide (VP-16) and its molecular mechanism. METHODS: Quantitative and qualitative analyses on cell morphological change of apoptosis were performed through acridine orange (AO) staining and HE staining, and fluorescent flow cytometry.The test analyzes membrane on the surface of the PS evagination and integrity of cell membrane surface and mitochondrial membrane potential changes were performed through Annexin V-FITC/PI double dyeing and JC-1 cell dyeing tests, and apoptotic factors such as Bcl-2, Bax, Caspase-3 and Caspase-9 were measured by SYBR Green (Takara) qRT-PCR. RESULTS: The HE and AO staining revealed that apoptotic rates in HGF+VP-16 groups were significantly lower than those in VP-16 groups (P<0.05, P<0.05), HGF can inhibit the apoptosis of cells induced by VP-16; FCM (Annexin V-FITC/ PI and JC-1) tests showed that cells apoptotic rates in HGF+VP-16 groups were significantly lower than those in VP-16 groups (P<0.05, P<0.001), indicating that HGF has the anti-apoptosis function. Apoptosis related gene mRNA expression tests found that the Bcl-2 mRNA expression in HGF+VP group was obviously higher than that in the VP-16 group (P<0.001), while Bax mRNA, Caspase-3 mRNA, and Caspase-9 mRNA expressions were significantly lower than those in the VP-16 group (P<0.05, P<0.001, P<0.001), suggesting that HGF possesses antiapoptotic effect through inhibiting apoptosis gene expression and promoting the antiapoptotic gene expression simultaneously. CONCLUSION: HGF can significantly protect K562 cells from apoptosis induced by VP-16 through the HGF/c-Met way to regulate PI3K/AKT pathway.

OBJECTIVETo develop a new technique for assessing the risk of birth defects, which are a major cause of infant mortality and disability in many parts of the world.

METHODSThe region of interest in this study was Heshun County, the county in China with the highest rate of neural tube defects (NTDs). A hybrid particle swarm optimization/ant colony optimization (PSO/ACO) algorithm was used to quantify the probability of NTDs occurring at villages with no births. The hybrid PSO/ACO algorithm is a form of artificial intelligence adapted for hierarchical classification. It is a powerful technique for modeling complex problems involving impacts of causes.

RESULTSThe algorithm was easy to apply, with the accuracy of the results being 69.5%±7.02% at the 95% confidence level.

CONCLUSIONThe proposed method is simple to apply, has acceptable fault tolerance, and greatly enhances the accuracy of calculations.

Algorithms ; Artificial Intelligence ; China ; epidemiology ; Environmental Exposure ; adverse effects ; Humans ; Infant, Newborn ; Models, Biological ; Neural Tube Defects ; epidemiology ; Risk Factors

Objective To investigate the prevalence of voice disorder and voice fatigue mental state in the pri-mary school teachers in a district of Chengdu.Methods A random sampling survey included 389 teachers from a dis-trict of Chengdu after they filled out the throat symptoms questionnaire,carried out voice fatigue tests,and strobo-scopic laryngoscopy.Results The most common voice of discomfort symptoms was hoarseness,followed by sore throat,dry throat and vocal fatigue.There were 189 teachers,48.5%,with voice disorders as the voice disorder group)and 200 teachers without throat and voice disorders as the control group.The failure rate was significantly higher at 80 dB than 75 dB,and for the study group,the failure rate was higher than that of the control group.The difference was statistically significant in 1,2 and 10 minutes between the two groups(P <0.05).Conclusion Voice fatigue is very common in the primary school teachers and when high volumes are required,the voice fatigue is more serious.To reduce voice fatigue and the incidence of primary school teachers'voice disease,we should strengthen the teacher's voice health care.

Objective To investigate the spectrum,diagnosis,time of therapy and management of the congeni-tal heart disease(CHD)in patients with Down′s syndrome(DS).Methods A retrospective report was undertaken of 96 cases in children with DS accompanied by CHD in Department of Pediatric Cardiology,Beijing Anzhen Hospital Af-filiated to Capital Medical University.Data were collected and analyzed about their clinical characteristics,and types of cardiovascular abnormalities,and the important laboratory examinations such as echocardiography and catheterization as well as the procedures of diagnosis and treatments were summarized.Then the interventions,complications and prognosis of different patients were estimated.Results (1)Single congenital heart disease was found in 33 cases (34.38%),a-mong which ventricular septal defect was the most common (14 cases,14.58%),followed by atrioventricular septal de-fect and atrial septal defect (equally,7 cases,7.29%).Multi -cardiovascular abnormalities were discovered in 63 ca-ses,and patent ductus arteriosus turned out to be the most common (42 cases,66.67%).(2)Cat-heterization was car-ried out in 18 cases of serious pulmonary arterial hypertension,and 8 cases were proved resistant pulmonary arterial hy-pertension without operation opportunity.The other 8 cases were estimated as high pulmonary arterial hypertension and medical therapy was suggested before reassessment to reduce surgical risks.(3)Operations were undertaken in 61 ca-ses,among which percutaneous interventional occlusion was performed in 7 cases and surgical interventions were per-formed in 54 patients,in which perioperation complications and death were found in 5 cases and 4 cases,respectively. Conclusions Operation interventions are practicable and most cases recovered well with systematic examinations and assessment in patients with DS and cardiovascular malformations.Early diagnosis and timely interventions are highly suggested.Also close attentions should be paid to follow -up and re -estimation after medical therapy.

Antrodia cinnamomea, an edible and medicinal fungus with significant economic value and application prospects, is rich in terpenoids, benzenoids, lignans, polysaccharides, and benzoquinone, succinic and maleic derivatives. In this study, the transcriptome of A. cinnamomea cultured on the wood substrates of Cinnamomum glanduliferum (YZM), C. camphora (XZM), and C. kanehirae (NZM) was sequenced using the high-throughput sequencing technology Illumina HiSeq 2000, and the data were assembled by de novo strategy to obtain 78,729 Unigenes with an N50 of 4,463 bp. Compared with public databases, about 11,435, 6,947, and 5,994 Unigenes were annotated to the Non-Redundant (NR), Gene Ontology (GO), and Kyoto Encyclopedia of Genes and Genome (KEGG), respectively. The comprehensive analysis of the mycelium terpene biosynthesis-related genes in A. cinnamomea revealed that the expression of acetyl-CoA acetyltransferase (AACT), acyl-CoA dehydrogenase (MCAD), 3-hydroxy-3-methylglutaryl-coenzyme A (HMG-CoA), mevalonate pyrophosphate decarboxylase (MVD), and isopentenyl diphosphate isomerase (IDI) was significantly higher on NZM compared to the other two wood substrates. Similarly, the expression of geranylgeranyltransferase (GGT) was significantly higher on YZM compared to NZM and XZM, and the expression of farnesyl transferase (FTase) was significantly higher on XZM. Furthermore, the expressions of 2,3-oxidized squalene cyclase (OCS), squalene synthase (SQS), and squalene epoxidase (SE) were significantly higher on NZM. Overall, this study provides a potential approach to explore the molecular regulation mechanism of terpenoid biosynthesis in A. cinnamomea.

Meridians and Acupoints Science is a basic course and important component of acupuncture and Tuina science. This course contains considerable theoretical and basic knowledge to be memorized, which causes some difficulties for students to study and inevitably influences the learning effect. In view of that, the authors implemented reforms in interest teaching practice in teaching of Meridians and Acupoints Science. Reforms including the use of interesting memory method, string comparison of acupoints, interspersed discussion of cases, presentation of famous doctors' experience in acupoint application and development of the second class activities have achieved some success. That has aroused the students' enthusiasm for learning and improved the quality of teaching.

AIMTo know the effect of cysteamine on the pancreatic secretion and enzyme activity in geese.

METHODSEight adult geese fitted chronic pancreatic and duodenal cannulas were used to evaluate the effect of cysteamine (CS) on the pancreatic secretion and enzyme activity. The experiment was consist of control and treated phase. CS was added in the diet at the dosage of 100 mg/kg bw on the first day of treated phase. The birds were free fed at daytime (8:00-20:00) and fasted at nighttime (20:00-8:00). The pancreatic juice samples were collected continuously for three days in each phase.

RESULTSCS increased the average rate of pancreatic secretion by 240.16% (P < 0.01), in which that of daytime was elevated by 234.45% (P < 0.01), while that of nighttime elevated by 253.70% (P < 0.01). The secretion volume at daytime was more than that of night. CS increased trypsin activity by 49.05% (P < 0.01), whereas lipase and amylase activity was reduced by 25.44% (P < 0.01) and 21.95% (P < 0.01) separately. The one hour total activity of trypsin, lipase and amylase were elevated by 406.88% (P < 0.01), 153.58% (P < 0.01) and 166.59% (P < 0.01) respectively. Ratios of pancreatic secretion were different between day and night.

CONCLUSIONThese results indicate that CS can affect the pancreatic juice secretion and pancreatic enzyme activity by depleting the somatostatin, so that benefits to improve the digestive foundation and supply more nutrition for quickly growing in geese.

Animals ; Cysteamine ; pharmacology ; Geese ; physiology ; Pancreas ; drug effects ; enzymology ; secretion ; Pancreatic Juice ; secretion ; Pancreatin ; metabolism

To develop a parent-metabolite pharmacokinetic model for risperidone (RIP) and its major active metabolite (9-hydroxyrisperidone) and investigate their pharmacokinetics characteristics in healthy male volunteers, twenty-two healthy volunteers were orally given a single dose of 2 mg RIP. Plasma samples were collected in the period of 96 hours and concentrations of RIP and 9-hydroxyrisperidone were measured by a validated HPLC/MS method. CYP2D6 phenotypes were identified by the T1/2 of RIP and 9-hydroxyrisperidone according to the literature. Model structure identifiability analysis was performed by the similarity transformation approach to investigate whether the unknown parameters of the proposed model could be estimated from the designed experiment. Pharmacokinetics parameters were estimated using weighted least squares method, and the final pharmacokinetics model were tested and evaluated by Monte Carlo simulation. Eighteen volunteers were phenotyped as extensive metabolizers (EM) and four volunteers were identified as intermediate metabolizers (IM). The final model included central and peripheral compartment for both parent (RIP) and metabolite (9-hydroxyrisperidone) respectively. Model structure identifiability analysis indicated that the proposed model was local identifiable. However, if the ratio of RIP converted to 9-hydroxyrisperidone was assumed to be 32% in EM, and 22% in IM, the model could be globally identifiable. The predicted time-concentration curve and AUC(0-t), C(max), T(max) of RIP and 9-hydroxyrisperidone estimated by the established model were in agreement with the observations and noncompartment analysis. Rate constant of RIP conversion to 9-hydroxyrisperidone was (0.12 +/- 0.08) h(-1) and (0.014 +/- 0.007) h(-1) for EM and IM, respectively. Elimination rate constants of RIP were (0.25 +/- 0.18) and (0.05 +/- 0.23) h(-1) for EM and IM, respectively. Model validation result showed that all parameters derived from the concentration data fitted well with the theoretical value, with mean prediction error of most PK parameter within +/- 15%. The established model well defined the disposition of RIP and 9-hydroxyrisperidone simultaneously and showed large inter-individual pharmacokinetics variation in different CYP2D6 phenotype. The model also provide a useful approach to characterize pharmacokinetics of other parent-metabolite drugs.
Adult ; Cytochrome P-450 CYP2D6 ; physiology ; Humans ; Isoxazoles ; pharmacokinetics ; Male ; Models, Biological ; Monte Carlo Method ; Paliperidone Palmitate ; Pyrimidines ; pharmacokinetics ; Risperidone ; pharmacokinetics

AIMTo develop limited sampling strategy (LSS) for estimation of C(max) and AUC(0-t) and assessing the bioequivalence of two pioglitazone hydrochloride (PGT) preparations.

METHODSHealthy subjects (n = 20), enrolled in a bioequivalence study, were received 30 mg PGT po of reference or test formulation. The plasma concentration of PGT was determined by the validated HPLC method. A multiple linear regression analysis of the Cmax and AUC(0-t) against the PGT concentration for the reference formulation was carried out to develop LSS models to estimate these parameters. The models were internally validated by the Jackknife method and externally validated using simulated sets generated by Monte Carlo method. The best model was employed to assess bioequivalence of the two PGT formulations.

RESULTSThe linear relationship between pharmacokinetics parameters and single concentration point was poor. Several models for these parameters estimation met the predefined criteria (r2 > 0.9). The Jackknife validation procedure revealed that LSS models based on two sampling times (C1, C2.5 and C1.5, C2.5 for C(max); C1.5, C9 and C2.5, C9 for AUC(0-t) predict accurately. Mean prediction errors (MPE) were less than 3%, and mean absolute prediction error (MAE) were less than 9%. The prediction error (PE) beyond 20% was less than 5% of total samples. Model external validation by Monte Carlo simulated data indicated that the most informative sampling combinations were C1.5, C2.5 for C(max), and C1.5, C9 for AUC(0-t), respectively. MPE and MAE of the proposed models were less than 5% , and 9% respectively. The PE beyond 20% was less than 5% of the total. Bioequivalence assessment of the two PGT formulations, based on the best LSS models, provided results similar to those obtained using all the observed concentration-time data points, and indicated that the two PGT formulations were bioequivalent.

CONCLUSIONThe LSS method for bioequivalence assessment of PGT formulations was established and proved to be applicable and accurate. Thus, it could be considered appropriate for PGT bioequivalence study with inexpensive cost of sampling acquisition and analysis. Key words: pioglitazone hydrochloride; limited sampling strategy; Monte Carlo simulation; bioequivalence

Administration, Oral ; Adult ; Area Under Curve ; Chromatography, High Pressure Liquid ; Humans ; Hypoglycemic Agents ; administration & dosage ; blood ; pharmacokinetics ; Male ; Models, Biological ; Monte Carlo Method ; Sample Size ; Therapeutic Equivalency ; Thiazolidinediones ; administration & dosage ; blood ; pharmacokinetics

AIMTo know the effect of cysteamine (CS) on the plasma levels of somatostatin (SS) and some metabolic hormones in adult geese.

METHODSFourteen adult crossbred geese (Chuan white x Tai lake) fitted with chronic wing vein cannulas were used in this study to evaluate the effect of CS on SS, TSH, T3 and T4 levels. The experiment was consisted of control and treated phase. The diet was added CS at dosage of 100 mg/kg bw on the first day of the treated phase. The blood samples were collected from the cannulas and analyzed by radioimmunoassay.

RESULTSThe plasma SS concentration was (1.87 +/- 0.10) microg/L in control phase. Whereas SS concentrations on day 1, 3, 5, 7 of treated phase were decreased markedly (P < 0.05 or P < 0.01). Thereafter it was rose on the seventh day, however it was still lower than that of control. The thyroid stimulating hormone (TSH) content (2.45 +/- 0.31 mIU/L) was significantly decreased by 21.63% (P < 0.01) on day 1, and 18.37% (P > 0.05) on day 3 and day 5. Comparing with control phase (5.41 +/- 0.98 microg/L), T4 contents were elevated by 60.26% (P < 0.01), 43.25% (P < 0.01), 37.15% (P < 0.01) and 16. 82% (P < 0.01) respectively on day 1, 3, 5, 7. T3 level was (1.05 +/- 0.06) microg/L in control phase, whereas the levels was significantly increased by 36.19% (P < 0.01) on day 3. Also, the insulin concentration was higher than that of control (4.43 +/- 0.41 mU/ L) by 18.28% (P < 0.05) on the day 5.

CONCLUSIONThese results indicate that CS can decrease the plasma SS and TSH levels, whereas increase the levels of T4, T3 and insulin, therefore change metabolism, improve the nutrition transform and accelerate the growth in geese.

Animals ; Cysteamine ; pharmacology ; Diet ; Geese ; Insulin ; blood ; Somatostatin ; blood ; Thyrotropin ; blood ; Thyroxine ; blood ; Triiodothyronine ; blood