Physiologically based pharmacokinetic model (PBPK), a mechanistic mathematic model, which can simulate the absorption, distribution, metabolism and excretion of drugs, is being more widely used in pharmaceutical research and development areas. This article reviews primarily the recent advances in the procedure of establishing a PBPK model, including specifying of the PBPK model structure, specification of the tissue model, writing of equations, set of model parameters, simulation and evaluation. Application significance, major challenges and future developments of PBPK model in pharmaceutical areas are also discussed.
Animals ; Biological Transport ; Computer Simulation ; Humans ; Models, Biological ; Pharmaceutical Preparations ; chemistry ; metabolism ; Pharmacokinetics ; Software ; Tissue Distribution

Objective To investigate the radiographic characteristics of degenerative lumbar scoliosis (DLS) and its relationship to osteoporosis. Methods 229 cases (83 males, 146 females) of DLS from January 1998 to June 2005 were reviewed. The mean age was 56.8 years (ranged from 40 to 74 years). The Cobb angle and vertebral stability in coronal plane were measured in anteroposterior radiographs and the changes of lordosis in sagittal plane were observed in lateral radiographs. The bone mineral density(BMD) and T-Score of lumbar spine (L2-L4) were measured using Dual Energy X-ray Absorptiometry. Results The mean Cobb angle is 9.45??4.79?, 151 cases(66%) with the angle less than 10?, 60 cases (26%) with 10?-20?, and 18 cases (8%) with more than 20?. Right side scoliosis were found in 52% (120 cases), left side in 48% (109 cases). 159 cases (69%) companied with gradeⅠ(Nash-Moe) vertebra rotation, 54 cases (24%) with grade Ⅱ. And the vertebra rotation was most evident on scoliosis apex. There were 20 cases (9%) with more than 4 mm lateral translation between the lumbar vertebrae which were usually the apex vertebrae with the most degenerative changes. The physical lordosis decreased in most cases in which 16 cases (7%) developed lumbar or thoracolumbar kyphosis. And the kyphosis degree was not relevant to scoliosis Cobb angle. The mean T-Score of BMD measurement was -1.88?0.17, which was -1.49?0.14, -2.56?0.24, -2.89?0.50 for the groups of with Cobb angle 20? respectively. There were 153 cases (67%) with T10?), and 98 cases (43%) with T

Objective To evaluate the practicality of MAGE-1 and MAGE-3 genes encoding proteins used as a target for immunotherapy in renal cell carcinoma and urinary transitional cell carcinoma patients. Methods Reverse transcriptase-polymerase chain reaction (RT-PCR) was used for detection of MAGE-1 and MAGE-3 genes in the specimens from renal cell carcinoma (n=18) and urinary transitional cell carcinoma (n=26),and in 10 specimens taken from the tumor surrounding tissues. Results Positive expression of MAGE-1 and MAGE-3 genes at mRNA was detected in 10(56%) and 11(61%),respectively,of 18 cases of renal cell carcinoma;and expression of both MAGE-1 and MAGE-3 in 8(44%).Out of 26 cases of urinary transitional cell carcinomas,16 (62%) expressed MAGE-1 and 15 (58%) expressed MAGE-3;and 12 (46%) expressed both MAGE-1 and MAGE-3.No expression of MAGE-1 or MAGE-3 was detected in 10 specimens from tumor surrounding tissues. Conclusions The tumor-specific antigens MAGE-1,MAGE-3 genes might be used as molecular markers and specific targets of immunotherapy and gene therapy for renal cell carcinoma and urinary transitional cell carcinoma.

Bilirubin ; Child ; Duodenogastric Reflux ; diagnosis ; Esophageal Diseases ; diagnosis ; Esophagus ; metabolism ; Gastroesophageal Reflux ; diagnosis ; Humans

Calcitonin ; blood ; Fluorine ; adverse effects ; Humans ; Occupational Exposure ; adverse effects ; Osteocalcin ; blood

Objective:To investigate the effects of Porhyromonas endodontalis(P.e)liopolysaccharide(LPS)on the expression of IL-23mRNA and protein in mouse osteoblasts MC3T3-E1 and the role of phosphatidylinositol 3-Kinases (PI3K)signaling pathway in this process.Methods:MC3T3-E1 cells were treated with different concentrations of P.e LPS for different hours,or pretreated with LY294002,a special PI3K inhibitor.The IL-23 mRNA and protein expression levels were detected by real-time PCR and Western blot respectively.Results:The level of IL-23 mRNA increased in MC3T3-E1 cells with the increase of concentration and the treatment time of P.e LPS(P <0.05).The IL-23 protein expression was increased by P.e LPS in a time dependent manner(P <0.05).The mRNA and protein of IL-23 decreased(P <0.05)after pretreatment with LY294002.Conclusion:P.e LPS can induce the expression of IL-23 mRNA and protein in MC3T3-E1 cells,and the PI3K signaling pathway may play a part in this process.

Objective Curcumin and MS-275,an inhibitor of histone deacetylase (HDAC),are promising anti-tumor agents. The aim of present study was to investigate the mechanisms of apoptosis induced by combined use of MS-275 in low dosage and curcumin in prostate cancer cell line DU145. Methods MTT assay was used to evaluate the lethal effect on DU145 cells by solitary use of MS-275 and or combined with curcumin. The changes in cell life cycle was detected by flow cytometry. The expressions of the survival signaling pathways were determined by Western blotting. Results Solitary application of MS-275 or curcumin may inhibit the growth of DU145 cells in a time and dose-dependent manner. The combination of MS-275 (1?mol/L) and curcumin (20?mol/L) exhibited obvious cytotoxic effect on cell viability,which was only 45.9% 48h after the combined treatment. Cell cycle assay showed that the combination of MS-275 and curcumin resulted in obvious appearance of sub-G1 phase in DU145 cells,implying that the cell apoptosis had been induced. The results of Western blotting showed that after treatment of MS-275 or curcumin singly,the phosphorylation level of Akt and ERK kinase declined slightly,however,when MS-275 and curcumin were used together,there appeared a prominent inhibitory effect on Akt and ERK kinase,indicated by a sharp decline of their phosphorylation level,and at the same time,the level of cleaved PARP,a hallmark of apoptosis,was increased in DU145 cells. Conclusion Combined use of MS-275 and curcumin may exert a synergistic cytotoxic effect on the viability of DU145 cells,and exhibit an inhibitory activity on Akt and ERK kinases to induce apoptosis.

The publication of the scientific theses and their management are significant for the development of technology and science in the hospital.Therefore.they play an important role iU the hospital management.The retrospective analysis on the theses that published in the last 5 years and embodied by SCI was conducted using the statistics method and analyzed the first 10 departments in the published theses in this paper.The specialty of our hospital and the shortcoming in the scientific research was concluded from the analysis result.The amount of the theses increased steadily,and the research capability of the key subjects and key departments were promoted.The amount and the quality of the theses reflected an important indicator of the development strategy that means to develop the hospital through science.technology and education.Therefore,these conclusions could offer some valuable information to the manage department of t}le hospital.

OBJECTIVE:To investigate general regularity and characteristics of adverse drug reactions/events(ADR/ADE)in-duced by Dezocine injection,and to provide reference for safe and rational drug use in clinic. METHODS:Retrieved from Jiangsu Province ADR Database during Jan. 2009-Aug. 2016,ADR/ADE induced by Dezocine injection was analyzed statistically in re-spects of patient's gender and age,usage and dosage,organs/systems involved in ADR,clinical manifestations and outcome. RE-SULTS:Among 1290 ADR/ADE induced by Dezocine injection,there were 40 cases of severe ADR/ADE(3.10％);medical insti-tutions were main reporting units (1276 cases,98.81％). In ADR/ADE cases,female was more male,with ratio of male to fe-male was 1:1.45. ADR/ADE mostly occurred in 45-65 age group(43.49％). Intravenous medication was main route of administra-tion (1137 cases,88.14％). Initial dose of 577 cases was excessive dose (50.75％). ADR/ADE mainly involved gastrointestinal system (54.99％),central and peripheral nervous system (24.72％) and systemic lesions (5.20％). Severe ADR/ADE manifested as anaphylactic shock,palpitation and dyspnea,etc. But anaphylactic shock was not mentioned in drug package inserts. 1283 ADR/ADE(99.46％)were cured or improved . CONCLUSIONS:It is necessary to strengthen drug safety reevaluation of Dezocine injec-tion after being on the market,improve drug package inserts and enhance patients education as so as to reduce and avoid the occur-rence of ADR/ADE.

Background The rejection following keratoplasty still is a leading cause of corneal transplantation failure.Studies showed that the interleukin-22 (IL-22) ,one of the effector molecules of T helper cell 17 (Th17) participated on the rejection after heart,liver and bone marrow transplantation.However,the effect of IL-22 on corneal graft rejection is not well understood.Objective This study was to investigate the expression of IL-22 mRNA in the corneal grafts and the role of IL-22 in the immune rejection after corneal transplantation in rats.Methods Seventy-two Wistar rats were randomized into autologous keratoplasty group,allograft keratoplasty group and anti-rejection group,and other 4 normal Wistar rats served as normal control group.Autologous keratoplasty was operated on the Wistar rats of the autologous keratoplasty group,and allograft keratoplasty were carried out with the 24 SD rats as donors and 48 Wistar rats as recipients.Tobramycin and dexamethasone eye drops were topically administrated after autologous keratoplasty for 2 weeks in the anti-rejection group.The experimental eyes were examined by slit lamp microscope after surgery and graft survival was evaluated based on the rejection scoring criteria of Larkin.Intergroup accumulated survival rates of grafts were compared using Kaplan-Meier analysis.Histopathological examination of grafts was carried out in 5 and 14 days after operation respectively,and the related expression levels of IL-22 mRNA and aryl hydrocar-bon receptor (AhR) mRNA were carried out by real-time fluorescence quantitative PCR.The feeding and use of the experimental animals followed the Guangdong provincial regulations on the management of experimental animals.The experimental design was approved by the ethics committee of Southern Medical University.Results The median survival time of grafts in the allograft keratoplasty group was 10 days,and that in the anti-rejection group was 17 days,showing a significant survival extention in the anti-rejection group (x2=16.442,P =0.000).Significant differences were found among the 4 groups in the related expression levels of IL-22 mRNA in both 5 days and 14 days after surgery (postoperative 5 days : F=2.44,P =0.00;postoperative 14 days: F=267.92, P =0.00), and the related expression levels of IL-22 mRNA were remarkably higher in the allograft keratoplasty group than those in the anti-rejection group at different time points (postoperative 5 days :9.70±0.35 vs.0.46±0.21;postoperative 14 days : 23.12 ± 1.89 vs.3.14±0.94) (both at P＜0.05).The related expression levels of AhR mRNA in the grafts were considerably different among the 4 groups (postoperative 5 days : F =395.73, P =0.00;postoperative 14 days : F =942.37, P =0.00) , and the expression levels were significantly elevated in the allograft keratoplasty group compared with the anti-rejection group at various time points (postoperative 5 days:2.52±0.32 vs.1.89±0.10;postoperative 14 days:7.20±0.25 vs.2.60±0.17) (both at P＜0.05).Conclusions The expression level of IL-22 RNA up-regulates in the grafts with immuno-rejection.Topical administration of tobramycin and dexamethasone eye drops inhibits the rejection after keratoplasty.AhR plays a regulative role to the expression of IL-22 in rats after keratoplasty.