Brain Stem/pathology* ; Death, Sudden/etiology* ; Fatal Outcome ; Humans ; Intracranial Hemorrhages/mortality* ; Leukemia/pathology*

Traditional Chinese ancient prescriptions have been used for treatment of liver cancer for a long history and the scientific and rational compatibility is a great wealth for modern research and development (R&D) of new drugs. The research and development of new drugs are often accompanied with a large investment, a long cycle and a high risk, especially for the anti-tumor drugs R&D which are facing more risks and lower successful rate. In this research, the regularity of compatibility of drugs was analyzed from 124 anti-hepatoma ancient prescriptions by computer program. The results can offer help to the R&D of anti-hepatoma new drugs and reduce the risk of drug screening. In addition, we surveyed 22 companies in this field from six provinces such as Beijing, Shanghai, Tianjin and so on and obtained 240 risk assessment questionaires. Then we used qualitative analysis method to interpret the greatest impacts for the risks in the process of R&D, production and sales of anti-hepatoma new drugs. The study provides a basis for anti-liver cancer drugs R&D researchers, who can take effective measures to reduce the R&D risks and improve successful rate.
Carcinoma, Hepatocellular ; drug therapy ; history ; China ; Drug Discovery ; history ; Drug Incompatibility ; Drug Prescriptions ; history ; Drugs, Chinese Herbal ; history ; therapeutic use ; History, Ancient ; Humans ; Liver Neoplasms ; drug therapy ; history ; Research ; history

BackgroundThe influence of glaucoma on the quality of life in patients is of increasing concern for ophthalmologists in recent years. However,some studies demonstrated that different types of questionnaires about quality of life have various disadvantages. Therefore, to accurately and fully assess the influencing factors of quality of life in glaucoma patients is very important. ObjectiveThe present study was to survey the self-reported visionrelated quality of life(QOL) in glaucoma patients by means of utility analysis and to tentatively analyze its influencing factors. Methods Patients with glaucoma were recruited from a single tertiary ophthalmic department. Standard face-to-face interviews were conducted. Utility values of linear rating scale ( RS ) and time trade-off ( TTO ) were calculated to evaluate the self-reported vision-related QOL of the patients. The correlations of the utility values with the patients' general and ophthalmologic characteristics were also analyzed. This survey was approved by the Ethic Committee of Beijing Tongren Hospital. Oral informed consent was obtained from the subjects before the study.ResultsA cross-sectional study was designed. A total of 86 glaucoma patients were enrolled in this study with 62 male and 24 female, with a mean age of 44. 67 years old. The mean utility values measured by RS and TTO were 0. 62± 0. 19 and 0. 77 ± 0. 12, respectively, and no evidential correlation was found between these two values ( r =0. 074, P=0. 499 ). The RS value was associated with daily visual acuity,mean deviation(MD) of visual field and the history of trabeculectomy. Neither daily visual acuity nor MD showed a significant correlation with the TTO value. Age, work status and educational background contributed to higher utility value for the TTO method. After adjusting for age, work status and educational level,patients with visual acuity in the worse-seeing eye better than 0. 3 showed a higher TTO value than those with less than 0. 3. Conclusions Utility analysis possesses the advantages of convenience and sensitivity. RS utility value is easily affected by the Objective visual status and surgery history in glaucomatous patients,which reflects the subjective assessment of patients'visual quality. However, TTO value is primarily associated with age,work status and education level rather than visual function in glaucoma patients,which is therefore subjective assessment of the disease-related quality of life. These Results indicate that visual function impairment is not a determining factor for the QOL of glaucoma patients.

AIMTo study the pharmacokinetics of genistein in Beagle dogs.

METHODSGenistein, suspended in 0.5% CMC-Na solution, was orally administered to Beagle dogs at the dose of 5.34 mg.kg-1. At various time intervals, 1.5 mL of blood was drawn from the vein of dogs in their front legs. At the same time, urine and feces were collected. After the collection, the feces were homogenized with physiological saline (to 1 g feces, 10 mL physiological saline were added). The genistein in plasma, urine and homogenized feces was extracted twice by vortexing with 2.0 mL mixture of methyl tert-butyl ether and pentane (8:2). The organic phase was transferred into tubes and evaporated in ventilation cabinet. The residue was dissolved in 50 microL of methanol and 20 microL of the solution was drawn and detected by high-performance liquid chromatography. The pharmacokinetic parameter was calculated by 3P97 software.

RESULTSThe plasma concentration-time curve was fitted to a one-open-compartment model. The peak time was 0.29 h, and the elimination half-life was 0.52 h. After genistein was administered, 10.79% of genistein were excreted from urine and 21.55% from feces within 24 h. It was also found that 13.00% genistein were excreted from urine and 52.46% from feces within 60 h.

CONCLUSIONIt showed that the speed of absorption and elimination of genistein was high in Beagle dog, and genistein was mainly excreted in the form of parent compound in urine and feces.

Animals ; Anticarcinogenic Agents ; blood ; pharmacokinetics ; urine ; Area Under Curve ; Chromatography, High Pressure Liquid ; Dogs ; Feces ; chemistry ; Genistein ; blood ; pharmacokinetics ; urine

AIMTo study the metabolic kinetics of MN9202 in Beagle dog liver microsome.

METHODSBeagle dog liver microsomes were prepared by using ultracentrifuge method. After incubating 0.4 micromol x L(-1) MN9202 with 1 g x L(-1) microsomes for 30 min at 37 degrees C, the reaction was terminated by adding 0.5 mL alkalization. The RP-HPLC was used to determine the drug in the incubation mixture. The Michaelis-Menten parameters Km, and Vmax in Beagle dog liver microsomes were initially estimated by analyzing Lineweave-Brurk plot. Various selective CYP inhibitors were used to investigate their inhibitory effect on the metabolism of MN9202.

RESULTSThe Km, Vmax and CLint of MN9202 were (22.6 +/- 8.0) micromol x L(-1), (0.54 +/- 0.17) micromol x g(-1) x min(-1) and (0.0242 +/- 0.0009) L x g(-1) x min(-1), respectively. The metabolism of MN9202 was significantly inhibited by ketoconazole (Ket) and troleandomycin (Tro) in Beagle dog liver microsomes. Tranylcypromine (Tra) could inhibit the metabolism of drug as well. While other inhibitors showed little inhibitory effect on the metabolism of MN9202.

CONCLUSIONIt was shown that CYP3A and CYP2C19 were involved in MN9202 metabolism. The inhibitors of human CYP3A and CYP2C19 may have potential interaction with MN9202, and this can reduce the metabolism rate and increase the toxicity of MN9202.

Animals ; Aryl Hydrocarbon Hydroxylases ; antagonists & inhibitors ; Calcium Channel Blockers ; metabolism ; pharmacokinetics ; Cytochrome P-450 CYP2C19 ; Cytochrome P-450 CYP3A Inhibitors ; Dihydropyridines ; metabolism ; pharmacokinetics ; Dogs ; Ketoconazole ; pharmacology ; Microsomes, Liver ; metabolism ; Mixed Function Oxygenases ; antagonists & inhibitors ; Nitrobenzenes ; metabolism ; pharmacokinetics ; Tranylcypromine ; pharmacology ; Troleandomycin ; pharmacology

OBJECTIVETo construct a subtractive cDNA library of genes transactivated by PS1TP1 protein with suppression subtractive hybridization (SSH) technique.

METHODSSuppression subtractive hybridization technique and bioinformatics technique were used, the mRNA from HepG2 cells transfected with pcDNA3.1 (-) -PS1TP1 and pcDNA3. 1 (-) empty vector was isolated, respectively; cDNA underwent two times of nested PCR, amplified cDNA fragments were subcloned into pGEM-Teasy vectors to set up the subtractive library.

RESULTSThe subtractive library of genes transactivated by PS1TP1 was constructed successfully. Sequence analysis was performed in 43 clones randomly, and the full length sequences were obtained with bioinformatics method and searched for homologous DNA sequence from GenBank, altogether 12 coding sequences were gotten, which consisted of 10 known and 2 unknown ones.

CONCLUSIONThe obtained sequences may be target genes transactivated by PS1TP1 protein among which some genes coding proteins involved in cell cycle regulation, metabolism, immunity and cell apoptosis. This finding brought some clues for studying the biological functions of PS1T1.

Hepatitis B ; genetics ; Humans ; Nucleic Acid Hybridization ; methods ; Transcriptional Activation ; genetics ; Viral Proteins ; genetics

Objective To systematically review and synthesize the lived experience of family members caring for schizophrenia patients at home,in order to provide evidence for community and home nursing. Methods We searched databases including The Cochrane Library,PubMed,EMbase,ISI Web of Science,PsycINFO,CINAHL,CBM, CNKI,VIP and Wanfang from inception to April 2017,to collect qualitative studies in the experience of family members caring for schizophrenia patients at home. The quality of included studies was evaluated according to JBI Critical Appraisal Tool for qualitative studies in Australia. Results A total of 31 studies were included,and 141 complete findings were grouped according to their similarities to form 8 categories. These categories resulted in two synthesized findings:Integration Results 1:It brought family members a negative influence in care process because of excessive pressure and burden,but over time,they were slowly accepting the fact and trying to cope with dis-ease;Integration Results 2:Patients were unable to take care of themselves,and caregivers were helpless and wanted assistance from the government and the health care system. Conclusion The government and health system should pay more attention to the impact of schizophrenia on family members who take care of schizophrenia patients. In the process of care,patients should be given support,guidance and encouragement,which help family members to improve coping abilities of psychology and disease,and to promote physical and mental health of schizophrenia pa-tients and their family members.

OBJECTIVETo explore the risk factors of road traffic injury (RTI), and to provide evidence for stretagy development on the prevention and control of RTI.

METHODSCase-crossover study was used. 402 drivers were face to face interviewed by specially designed questionnaire including the items as drinking alcohol before driving, onset anger scale (OAS), anxiety/irritation, Stanford sleepiness scale (SSS), vehicle breakdown, carelessness, violating the rules on right of way and traffic signs when driving. Tables related to case-control study on 1:1 matching was used for single factor analysis, and conditional logistic regression was used for multifactor analysis.

RESULTSThe risk factors that were associated with RTI including high OAS (OAS = 5-7, OR = 114.88, 95% CI:4.29-3074.86), violating the rules on right of way (OR = 46.96, 95% CI:12.74-173.11), violating traffic signs when driving(OR = 24.57, 95% CI: 8.69-69.45), carelessness (OR = 14. 54,95% CI: 6.85-30.86), unsafe distance between vehicles( OR = 14.30,95% CI: 3.68-55.60), wrong judgement (OR = 14.67,95% CI:4.88-44.10), vehicle breakdown (OR = 8.57, 95% CI: 1.38- 53.27) and improper measure ( OR = 8.46, 95% CI: 2.46-29.14) etc.

CONCLUSIONImproper driving behaviors, abnormal psychological status and driving skills of drivers were related to RTI, suggesting that it was necessary to carry out continous traffic security education to the drivers.

Accidents, Traffic ; statistics & numerical data ; Adult ; Cross-Over Studies ; Demography ; Female ; Humans ; Logistic Models ; Male ; Multivariate Analysis ; Risk Factors ; Surveys and Questionnaires ; Wounds and Injuries ; epidemiology ; etiology ; prevention & control

BACKGROUNDThe ADRA2B gene insertion/deletion (I/D) polymorphism is associated with various cardiovascular and metabolic phenotypes. Large (C1) and small (C2) artery compliance, assessed by pulse wave analysis, is considered as sensitive markers or risk factors for cardiovascular disease. Therefore whether the ADRA2B I/D polymorphism is associated with C1 and C2 need to be investigated.

METHODSA total of 227 men and 243 women were enrolled in a Chinese family-based study. C1 and C2 were measured by pulse wave analysis. ADRA2B genotypes were determined by polymerase chain reaction. Statistical methods included generalized estimation equations and quantitative transmission disequilibrium test.

RESULTSThe II (31.9%), ID (46.8%) and DD (21.3%) genotype frequencies were in Hardy-Weinberg equilibrium (P = 0.73). The covariates selected by stepwise regression for C1 and C2 were age, systolic pressure and gender. The population based association analysis showed that C1 and C2 were not associated with ADRA2B genotype both before (C1: P = 0.28; C2: P = 0.27) and after (C1: P = 0.58; C2: P = 0.18) the adjustment. The family-based analyses of 128 informative offspring showed that transmission of the D-allele was not associated with C1 or C2, both before (C1: P = 0.42; C2: P = 0.85) and after (C1: P = 0.31; C2: P = 0.82) the adjustment.

CONCLUSIONThe study do not support that the ADRA2B gene I/D polymorphism has a major gene effect on C1 or C2 in the Chinese population of current sample size.

Adult ; Aged ; Arteries ; physiology ; Blood Pressure ; Compliance ; Female ; Humans ; Male ; Middle Aged ; Polymorphism, Genetic ; Receptors, Adrenergic, alpha-2 ; genetics

BACKGROUND AND OBJECTIVEIn Guangxi province, from 1970s to 1990s, the mortality of primary liver cancer (PLC) ranked the first among a variety of malignant tumors. Investigating the epidemiological characteristics of PLC is very important for developing reasonable and effective treatment strategy, allocating health resources rationally, and evaluating the quality of PLC prevention and control. This study was to analyze the mortality and epidemiological characteristics of PLC in Guangxi province between 2004 and 2005.

METHODSMulti stage stratified cluster random sampling method was used to select 9 counties (cities or urban areas) as sample points. The residents' death causes between 2004 and 2005 were analyzed, and the epidemiological characteristics of PLC were investigated.

RESULTSIn the period of 2004-2005, the crude mortality of PLC was 34.39/100,000 in Guangxi province population (55.30/100,000 in men and 13.21/100,000 in women). The national population standardized mortality in 1964 was 22.17/100,000. The man to woman ratio of mortality was 4.19:1. PLC ranked as the first death cause among a variety of malignant tumors, and PLC related death accounted for 30.70% of all tumor related death cases. Age specific mortality of PLC was increased with age, rising significantly from 30 year old (from 25 year old in men and from 40 year old in women), and reached a peak at 75 year old.

CONCLUSIONSThe mortality of PLC shows a decreasing trend in Guangxi province in the early 21st century, and the starting age of PLC death peak postpones about 10 years than that in 1990s. It shows that the comprehensive prevention and control measures of PLC implemented in Guangxi province are fruitful. However, the PLC mortality in Guangxi province is still significantly higher than the national average level, and it still ranks as the first death cause in a variety of malignant tumors in Guangxi province. PLC mainly occurs in middle aged and elderly people. The prevention and treatment research of PLC still has a long way to go.

Adolescent ; Adult ; Age Distribution ; Aged ; Aged, 80 and over ; Child ; Child, Preschool ; China ; epidemiology ; Female ; Humans ; Infant ; Liver Neoplasms ; epidemiology ; mortality ; Male ; Middle Aged ; Mortality ; trends ; Sex Distribution ; Young Adult