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.

The main pharmacological constituents of Chinese traditional medicine herb Cnidium monnieri are coumarin compounds and volatile oil. In addition, it contains monoterpene polyols, glucides, as well as recently discovered sesquiterpene components. In recent years, rather active investigations of its anti-tumor were performed at home and abroad. C. monnieri possesses multi-aspect and comprehensive anti-tumor functions, involving directly tumor-inhibitory activity, anti-mutagenicity, reversing multi-drug tolerance of tumor, as well as improving immune functions and so on. In this review, chemical constituents, anti-tumor activities and relevant investigations of Fructus Cnidii were summarized recent decade.
Antineoplastic Agents, Phytogenic ; pharmacology ; Cnidium ; chemistry ; Coumarins ; chemistry ; isolation & purification ; pharmacology ; Drugs, Chinese Herbal ; pharmacology ; Furocoumarins ; chemistry ; isolation & purification ; pharmacology ; Molecular Structure

OBJECTIVETo investigate 18q21 LOH in human pancreatic ductal adenocarcinomas and chronic pancreatitis by fluorescence in-situ hybrydization (FISH) technique, and to analyze the relationship between 18q21 LOH and clinicopathologic characteristics.

METHODSRP11-729G3 and RP11-850A17, the regions on 18q21, were selected as the target fragments, the region RP11-621L6, close to the centromere of chromosome 18, was selected as the reference fragment. The specific BAC clones were used to isolate and purify the corresponding genomic DNA, which were labeled with biotin or DIG by nick translation into dual color probes. 18q21 LOH was assessed by dual-color FISH in 30 cases of pancreatic ductal adenocarcinoma and 10 cases of chronic pancreatitis. All samples were 10% formalin fixed and paraffin embedded. The relationship between 18q21 LOH and clinicopathologic characteristics was analyzed.

RESULTSAmong 30 cases of pancreatic ductal adenocarcinoma, 25 cases showed LOH at the region RP11-729G3 (83.3%), and 26 cases showed LOH at the region RP11-850A17 (86.6%). Among these, 25 cases with LOH at both regions, 1 case showed LOH only at the region of RP11-850A17. No LOH was found in 10 cases of chronic pancreatitis.

CONCLUSIONS18q21 LOH is a high-frequency event in human pancreatic ductal adenocarcinomas. LOH at the regions RP11-729G3 and RP11-850A17 demonstrates a high concordance. 18q21 may play an important role during pancreatic carcinogenesis and tumor progression. 18q21 LOH may be used as a diagnostic marker for pancreatic ductal adenocarcinoma.

Adenocarcinoma ; classification ; genetics ; Adult ; Aged ; Carcinoma, Pancreatic Ductal ; classification ; genetics ; Chromosome Mapping ; Chromosomes, Human, Pair 18 ; Female ; Humans ; In Situ Hybridization, Fluorescence ; methods ; Loss of Heterozygosity ; genetics ; Male ; Middle Aged ; Pancreatic Neoplasms ; classification ; genetics ; Pancreatitis, Chronic ; classification ; genetics

The steps for installation and withdrawal of WYD2000 field surgical lamp were introduced.The failures and causes of broken cross-arm connector of WYD2000 field surgical lamp were analyzed.The problems of WYD2000 field surgical lamp in vulnerability to breaking and difficulty in maintenance were solved by designing and manufacturing a special maintenance tool and optimizing the materials and fixing mode of cross-arm connection.References were provided for main-tenance and improvement of WYD2000 field surgical lamp.[Chinese Medical Equipment Journal,2024,45(4):116-118]

Glucagon-like peptide-1 (GLP-1) expression is shared by both intestinal cells and neurons of brainstem, which plays anorexigenic role on food intake. However, the exact source of physiological GLP-1 influencing food intake and pertinent mechanism of GLP-1 receptor agonists (GLP-1RA) remain unelucidated. In this study, the immediate early gene product c-Fos was chosen as the specific antigen for immunohistochemistry to show the certain areas of central nervous system (CNS) activation by the GLP-1RA. Thirty normal SD rats were randomly assigned to 3 groups, which were single intraperitoneally injected with Liraglutide (200 μg/kg), Exenatide (10 μg/kg) and saline, respectively. After injection, the amount of food intake and acute glycemic variation were assessed for comparison. The results showed that acute pharmacological dosage of GLP-1RA (Liraglutide or Exenatide) could significantly influence food intake. However, glycemic change indicated that the anorexic effect was dissociated with change in blood glucose in normal rats. Moreover, c-Fos was expressed significantly higher in major critical nuclei related to food intake in GLP-1RA groups when compared with the control group, and its expression was also found in spinal cord. The results suggested that acute administration of pharmacological doses of GLP-1 influences CNS via circulation and vagal pathways, especially on the arcuate nucleus (ARC) and the nucleus of solitary tract (NTS), and GLP-1 modulates autonomic nervous activities.
Animals ; Eating ; drug effects ; Exenatide ; pharmacology ; Glucagon-Like Peptide-1 Receptor ; agonists ; Liraglutide ; pharmacology ; Random Allocation ; Rats ; Rats, Sprague-Dawley