Modeling methodologies developed for studying pharmacokinetic(PK)/pharmacodynamic(PD) processes confront many challenges related in part to the severe restrictions on the number and type of measurements that are available from laboratory experiments and clinical trials, as well as the variability in the experiments and the uncertainty associated with the processes themselves. Bayesian methods have provided a framework for PK/PD modeling and drug development that can address some of the above-mentioned challenges. This paper presents two illustrations of the application of Bayesian methods: the first involves a population modeling study of the cellular kinetics of the antiretroviral compound Lamivudine in the PBMCs of HIV-1 infected adolescents; the second uses a population mixture modeling approach to identifying hidden subpopulations that can not be identified by available measured covariates.

11.0 for the pH of reaction solution,65℃～75℃for the reaction temperature,and 1:1.7 for the mass ratio of corn(dry weight)to FeCl_3?6H_2O.The corn polysaccharide-Fe(Ⅲ)complex synthesized with the optimized process was stable,with good solubility in water.The assay of Fe(Ⅲ)was 39.86%,40.20%and 40.17%,respectively for three batches of products.The RSD was

Facing current situation of integrative medicine (IM), authors put forward that clinical and diagnosis program of IM could be carried out from clinical path, pathogenesis, treatment theory and philosophy, and so on, but with different integration degrees. Meanwhile, formulation of concrete program should be disease-targetedly set up, and adjusted from person to person, from place to place, from time to time. As for settled IM program , authors could evaluate it from whether Chinese medicine and Western medicine have formed complementary, synergistic, excitatory actions, and toxicity attenuation; whether more problems could be solved in efficacy, safety, practicability, and economy than previous single mode.
Critical Pathways ; Integrative Medicine ; trends ; Medicine, Chinese Traditional ; trends

Hypoxia is a general characteristic of most solid malignancies and intimately related to cancer progression. Homeostatic response to hypoxia is primarily mediated by hypoxia inducible factor-1alpha (HIF-1alpha) that elicits transcriptional activity through recruitment P300 coactivator. Targeting the interaction of HIF- alpha and P300 would thus constitute a novel approach for cancer treatment by suppressing tumor angiogenesis and metastasis. Here, a screening assay was developed for inhibitors targeting the interaction between HIF-1alpha and P300. The nucleotide sequence of human HIF-1alpha and P300 were cloned into pBIND and pACT vectors, named pBIND-HIF1alpha and pACT-P300. The interaction of HIF-1alpha and P300 was identified in HEK293 cell using mammalian two-hybrid system. And compound chetomin decreased their interaction in this mammalian two-hybrid system. We further verified HIF-1 inhibition effect of chetomin in U251-HRE cells. Therefore, we established a screening assay combined HIF-1alpha and P300 mammalian two-hybrid system and U251-HRE reporter assay for HIF-1 selective inhibitors.
Cell Hypoxia ; Disulfides ; pharmacology ; Drug Screening Assays, Antitumor ; E1A-Associated p300 Protein ; antagonists & inhibitors ; HEK293 Cells ; Humans ; Hypoxia-Inducible Factor 1, alpha Subunit ; antagonists & inhibitors ; Indole Alkaloids ; pharmacology ; Two-Hybrid System Techniques

[Objective]To investigate the genetic polymorphisms of the CYP2C19 gene in the elderly Chinese Han populations of Guangzhou,and compare the frequencies of CYP2C19 gene polymorphisms in different populations,in order to provide accurate data for the appropriate prescription.[Methods]To detect the genetic polymorphisms of the CYP2C19 gene by the DNA microarray,and compare the frequencies of CYP2C19 gene polymorphisms in Chinese Han populations from different areas and the different races.[Results]There were 2312 case samples in our study. The allele frequencies of CYP2C19*1,CYP2C19*2 and CYP2C19*3 were 64.27%,30.75%,and 4.98%,respectively. As the genotype,EM(*1/*1)was 41.44%(n=958),IM(*1/*2,*1/*3)was 45.67%(n=1056),and PM(*2/*2,*2/*3 and*3/*3)was 12.89%(n=298). The ratios of EM and IM in Chinese Han populations from different areas and all the subtypes of the CYP2C19 genotype in different minority were statistically significant. As the races,there were difference in all the subtypes of the CYP2C19 genotype when Asian populations were compared with white races(P<1304.64)and black races(P<0.01),which was also statistically significant.[Conclusions]The distributions of the CYP2C19 gene polymorphisms were significantly different in Chinese han populations and in different races,and the main subtypes of the CYP2C19 genotype in the elderly of Chinese han populations were IM and EM,which is beneficial for prescribing appropriate in the elderly populations.

OBJECTIVETo investigate the hazards of aluminum dusts to the exposed workers and the clinical features of aluminosis.

METHODRetrospective investigation on 75 aluminosis patients from a certain factory diagnosed in Shanghai Occupational Diseases Hospital from 1972 to 2004 was carried out.

RESULTSThere were 27 cases of aluminosis I (36.0%), 28 cases of aluminosis II (37.3%) and 20 cases of aluminosis III (26.7%) among 75 cases. The shortest exposure duration was 3 years, and the longest 17 years, and 37 cases of aluminosis occurred after exposure less than 10 years. hest radiographic examination mainly showed irregular micro-shadows: t (22/75), s (4/75), t/u (1/75), t/s (2/75), or predominantly irregular mixed microshadows s/p (5/75), s/r (1/75), t/p (9/75), t/q (5/75); some showed round shape micro-shadows: p (6/75), q (1/75), p/q (3/75), q/p (1/75). 27 cases showed large shadows, 20 cases of them were diagnosed as pneumoconiosis III. A lot of irregular micro-shadows gathered and developed to form uneven, loose and border-irregular masses. Most massive fibrosis looked like stripe or plait, located mostly in middle and upper lung field. 8 patients suffered from aluminosis with single side of massive fibrosis and 12 with both sides of massive fibrosis, accounting for 40% and 60% respectively. Mediastinal and bronchopulmonary lymph nodes were enlarged and calcified, accompanied with pleural thickening.

CONCLUSIONSShort exposure to high concentration of black fused alumina may cause serious aluminosis to the exposes. The hazards of aluminum dusts should not be ignored.

Aluminum Oxide ; toxicity ; Female ; Humans ; Male ; Occupational Diseases ; etiology ; Occupational Exposure ; Pneumoconiosis ; etiology ; Retrospective Studies ; Workplace

Objective To conduct mutation screening of SCN1A 3′ untranslated region (UTR) on Dravet syndrome (DS) patients without mutations in the SCN1A coding region and promoter region, and functional analysis of the variant from DS patients.Methods Twenty-eight DS patients without mutations in the SCN1A coding region and promoter region were screened for SCN1A 3′ UTR mutations using PCR and direct sequencing.Functional analysis of the detected mutation was done via luciferase assay, mRNA stability analysis and RNA electrophoretic mobility shift assay (RNA-EMSA).Results A novo variant (c.*20A>G) in SCN1A 3′ UTR was found in one DS patient.The variant (c.*20A>G) reduced the luciferase gene xpression by 30% through increasing the affinity of pluripotent embryonal carcinoma cell line NT2/cytoplasmic protein binding and reducing luciferase gene mRNA stability (t=8.5,P<0.01).Conclusions A functional variant was detected from one patient with DS.This variant negatively regulated the gene expression by increasing the affinity of pluripotent embryonal carcinoma cell line NT2/cytoplasmic protein binding and reducing mRNA stability.

This paper is in order to discussion with the composition and characteristics of Tibetan medicine plant resources, and promote the reasonable protection and utilization of the resources of Tibetan materia medica. Statistical analysis of species, distributions, and others of Chinese endemic seed plant from Tibetan medicine plants and usually used in the clinic of Tibetan medicine. The results showed that there are 523 species (25%) of Chinese endemic seed plant, belonging to 65 families and 162 genera, in about 2 000 varieties of Tibetan medicine plants recorded in relevant literatures. There are 180 Chinese endemic seed plant species (28%) belonging to 42 families and 72 genera from 625 medicine plants usually used in the clinic of Tibetan medicine. Specifically, the most of these Chinese endemic seed plant species are characteristic crude drug used in Tibetan medicine, and mainly or only distributed in Qinghai-Tibet Plateau. And a few species of them were intersected with traditional Chinese medicines (TCM) and other ethnic medicines. In addition, about 10% are listed in China Species Red List. The Qinghai-Tibet Plateau is the most abundant areas of Areal-types of the Chinese endemic seed plant. This is the biological and ecological reason formation the characteristics of Tibetan medicine plant resources. Therefore, strengthen the research of Chinese endemic seed plants used in Tibetan medicine is great significance for the reasonable protection and utilization of Tibetan medicine plant resources.
Drugs, Chinese Herbal ; chemistry ; Medicine, Tibetan Traditional ; Plants, Medicinal ; chemistry ; classification ; growth & development ; Seeds ; chemistry ; classification ; Tibet

Histone lysine methyltransferase EZH2 has been reported to be frequently overexpressed in hepatocellular carcinoma (HCC) tissues and associated with hepatocarcinogenesis. However, the exact mechanism of EZH2 up-regulation in HCC has not been determined. In this study, we used murine hepatocyte AML12 cells to investigate the role of hepatitis B virus X protein (HBx) in regulating the expression of mEZH2. Western blot analysis demonstrated that the expression level of mEZH2 protein in AML12 cells was up-regulated by HBx in a dose-dependent manner. To further investigate the mechanism of mEZH2 overexpression, the 2500 bp regulatory sequence upstream from the first exon of the mEZH2 gene was amplified from AML12 genomic DNA and constructed into a luciferase reporter plasmid. The luciferase activity of the mEZH2 promoter significantly increased in AML12 cells co-transfected with HBx plasmid, and deleting the -486/-214 promoter region decreased HBx-induced mEZH2 promoter activation by nearly 50%. The -486/-214 region was then analyzed in the TRANSFAC 6.0 database and a typical E2F1-binding site was found. Mutation of this E2F1-binding site or knockdown of E2F1 expression by RNAi led to a dramatic decrease in HBx-induced activation of the mEZH2 promoter and mEZH2 overexpression in AML12 cells. These results provide evidence that HBx up-regulates mEZH2 expression by transactivating the mEZH2 promoter through E2F1 transcription factor, thereby providing new epigenetic evidence for the carcinogenic effect of HBx.
Animals ; Binding Sites ; Cell Line ; E2F1 Transcription Factor ; genetics ; Enhancer of Zeste Homolog 2 Protein ; Hepatocytes ; cytology ; metabolism ; virology ; Histone-Lysine N-Methyltransferase ; genetics ; metabolism ; Mice ; Plasmids ; Polycomb Repressive Complex 2 ; Promoter Regions, Genetic ; genetics ; RNA, Small Interfering ; genetics ; Trans-Activators ; genetics ; metabolism ; Transfection ; Up-Regulation

Professor GU Wei-chao is with great academic and clinical experience. He has thoughts in ZHANG Xi-chun's academic thoughts, especially his application of Zhang's theory. He added Rhodiolae Crenulatae Radix et Rhizoma, Agrimoniae Herba, Taxilli Herba, Nardostachyos Radix et Rhizoma, Corni Fructus, and Glycyrrhizae Radix et Rhizoma Praeparata cum Melle to Shengxian Decoction to make modified Shengxian Decoction to strengthen the efficacy of invigorating qi and ascending qi collapse, reinforcing heart and astringing qi, cultivating the essence and notifying kidney, and inducing resuscitation and allaying tiredness, with a purpose to treat sinking qi syndrome of heart and lung diseases and expand the application areas of Zhang's Shengxian Decoction. This article introduced experience of GU Wei-chao in treating heart and lung diseases by using modified Shengxian Decoction through three clinical cases of effusion after lung surgery, chest and heart pain and difficulties in breathing.