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 explore changes of local renin-angiotensin system(RAS)in renal tissue of rat during short-and mid-term tail suspension,as well as their relations with humoral regulation and renal function induced by real or simulated weightlessness.Methods 1-and 4-week(wk)tail-suspended rat model were used to simulate short-and mid-term weightlessness,respectively.Reverse transcriptase polymerase chain reaction(RT-PCR)was carried out to examine the mRNA expression of components of local RAS in renal tissue.Results Except for angiotensin Ⅱ receptor type 2(AT2),all of the other components of local RAS,including angiotensinogen(AGT),renin,angiotensin converting enzyme(ACE),angiotensin Ⅱ receptor type 1a(AT1a)and angiotensin Ⅱ receptor type 1b(AT1b),were found their expression in renal tissue of Sprague-Dawley rats.After 1 wk of tail suspension,mRNA expression of renin in renal tissue increased significantly(P

Objective To determine the level of interleukin (IL)-10 in sera and culture supernatants of CD4+CD25+T cells from children with atopic dermatitis (AD),and to evaluate its relationship with clinical course and severity of AD.Methods Totally,46 children with AD and 31 healthy controls were included in the study.All the patients were divided into 3 groups,i.e.,mild (n =10),moderate (n =16) and severe (n =20) group,according to severity scoring of atopic dermatitis (SCORAD) score.Venous blood samples were obtained from the patients and healthy controls.CD4+CD25+ regulatory T cells were separated from the blood samples by magnetic cell sorting (MACS) system in two steps and cultured in vitro.Enzyme linked immunosorbent assay (ELISA) was conducted to quantify the level of IL-10 in sera and culture supernatants of CD4+CD25 + T cells from these subjects.Analysis of variance was carried out to compare the level of supematant and serum IL-10 between the patients and controls,and Pearson correlation analysis to assess the relationship between the level of IL-10 and SCORAD score.Results The patients with mild,moderate and severe AD showed a similar serum IL-10 level compared with the healthy controls ((43.10 ± 25.07) pg/ml,(68.40 ± 36.65) pg/ml and (55.55 ± 41.97) pg/ml vs.(58.27 ± 36.84) pg/ml,all P ＞ 0.05).The level of supernatant IL-10 secreted by CD4+CD25+ T cells from the controls was significantly higher than that from the patients with severe AD ((55.15 ± 11.15) pg/ml vs.(27.25 ± 7.01) pg/ml,P ＜ 0.05),but similar to that from the patients with mild and moderate AD ((52.96 ± 11.69) pg/ml and (49.86 ± 9.18) pg/ml,respectively,both P ＞ 0.05).The level of secreted IL-10 was negatively correlated with SCORAD score (r =－0.757,P ＜ 0.01),whereas the serum level of IL-10 showed no statistical correlation with SCORAD score.Conclusion CD4+CD25+ T cells and IL-10 may be implicated in the development of AD.

Objective To compare the efficacy of weight loss,metformin and rosiglitazone in women with polycystic ovary syndrome(PCOS).Methods A randomized controlled trial(RCT)was carried out in Peking Union Medical College Hospital(PUMCH),one hundred and six women with PCOS were assigned to three intervention groups:weight loss,weight loss and metformin,weight loss and rosiglitazone group.Patients were treated with weight loss(diet and exercise),weight loss and mefformin (500 mg three times daily),weight loss and rosiglitazone(4 mg once daily)for three months.Sixty patients completed treatments.Basal body temperature(BBT),total testosterone as well as fasting serum insulin levels and lipid were measured and compared in all patients before and after weight loss.Results No significant differences were found in the baseline characteristics among three groups.In weight loss group 51%(22/43)patients completed treatment,and 23%(5/22)patients resumed ovulation.In weight loss and mefformin group 58%(21/36)patients completed treatment,and 43%(9/21)patients resumed ovulation.In weight loss and rosiglitazone group 63%(17/27)patients completed treatment,and 59% (10/17)patients resumed ovulation.Ovulation rate was significantly higher in weight loss and rosiglitazone group than in weight loss group.There was no significant difference among three groups in body mass index (BMI),waist circumference,waist-hip ratio(WHR),sex hormone,serum fasting insulin and lipid level after treatment.Conclusion Weight loss,metformin and rosiglitazone all can improve ovulation each.

BACKGROUND: Cell apoptosis and ventricle reconstitution following myocardial infarction are of mutual cause-effect, and they cause vicious cycle. How to reduce the apoptosis events following myocardial infarction is one of keys to saving heart function.OBJECTIVE: To observe the effect of umbilical cord blood mesenchymal stem cell (UCBSMC) transplantation on remaining myocardial tissue of dogs with acute myocardial infarction.DESIGN: A randomized controlled observation.SETTING: Department of Cardiothoracic Surgery, Xinhua Hospital.MATERIALS: This study was carried out in the Central Laboratory of Xinhua Hospital from October 2005 to May 2007.Thirty-six adult hybrid dogs, male and female in half, were provided by the Animal Experimental Center of Xinhua Hospital.METHODS: Thirty-six dogs were divided into cell transplantation group and control group, with 18 dogs in each according to table of random digit. Mesenchymal stem cells were isolated from the umbilical cord blood of full-term pregnant hybrid dogs, cultured and amplified. Then, they were labeled with Laz gene, in vitro induced with 5-azacytidine, and transplanted into the dogs with acute myocardial infarction in the cell transplantation group. Rats in the control group were injected with the same amount of normal saline. Each dog was euthanized by anesthesia for harvesting myocardial specimen 1,4 and 8 weeks after transplantation.MAIN OUTCOME MEASURES: ① Remaining and apoptosis index detected by TUNEL method. ② Myocardial cell volume and histomorphology detected by confocal microscopy. ③ Histological change of myocardial collagen network detected by haematoxylin-basic fuchsin-picric acid staining.RESULTS: Thirty-six involved experimental dogs all entered the stage of final analysis. ①The apoptosis index in the cell transplantation group was significantly lower than that in the control group 1, 4 and 8 weeks after cell transplantation (P ＜0.05). ② Myocardial cell volume in the cell transplantation group 1, 4 and 8 weeks after cell transplantation was significantly larger than that in the control group (P ＜ 0.05). ③ Collagen fiber in the myocardial tissue of dogs in the cell transplantation group was arranged in order and regularly, and in contrast that in the control group was not, and fibers in the control group fused partially.CONCLUSION: UCBSMC transplantation reduces the apoptosis of myocardial cells, promotes the hypertrophy of remaining myocardial cells, regulates myocardial collagen network and improves heart function.

Objective To report a case of Majocchi's granuloma induced by var. raubitschekii of Trichophyton rubrum, and to evaluate the relationship between deep and superficial fungal infection with genotyping technique. Methods The patient underwent physical, pathological and mycologic examination,which included microscopic observation, fungal culture, and urease reaction. The sequence of intertranscribed spacer (ITS) of rDNA was analysed by PCR and sequencing. Isolates from affected toes and tissue as well as one reference strain and six clinical strains of T. rubrum, were subjected to analysis of the tandem repeat subelement(TRS-1) in nontranscribed spacer(NTS)of rDNA by PCR. Results A 48-year-old female patient presented with a 2-month history of red papules and nodular lesions on the back, buttock and thigh,as well as a 3-year history of onychomycosis which had become more severe after a liver transplantation 9 months before. Pathological and mycologic examinations confirmed the diagnosis of Majocchi's granuloma. The pathogen was identified as var. raubitschekii of T. rubrum by microscopic examination, fungal culture, positive urease reaction and the sequence of ITS. As shown by the amplications of TRS-1 of NTS, the genotypes of strains from affected nails and tissue were identical, but differed from those of other clinical strains of T.rubrum. Conclusions There is a polymorphism in TRS-1 of rDNA NTS of T. rubrum, with the genotypes of isolates from affected nails and tissue being identical, which suggests they are of the same origin.

Objective To evaluate the effect of transnasal optic nerve decompression for traumatic optic neuropathy in different surgery time. Methods The databases of the Cochrane library, Embase, PubMed, Wanfang Database, China Journal Full-text Database (CNKI), Weipu Database(VIP) were searched for retrospective studies and clinical controlled trials. The search words included traumatic optic neuropathy, TON, eye traumas, transnasal endoscopicoptic decompression, TEOND, decompression of optic canal and endoscopy. According to the inclusion and exclusion criteria, the data were extracted. The RevMan 5.3 was used to analyze the data. Results All of 1 087 studies were detected. Sixteen eligible studies were enrolled, including 803 eyes. Meta analysis showed that the recovery degree of visual acuity, curative effect in operation group within 7 d of trauma was obviously superior to the operation group 7 d after trauma (OR=2.78;95%CI:2.02-3.82;P<0.01). Conclusions Transnasal endoscopic optic nerve decompression in treatment of traumatic optic neuropathy should be operated as soon as possible, and it is better to operate within 7 d.

OBJECTIVE:To investigate the permeability of lomefloxacin through blood-pancreatic barrier in rats.METHO-DS:Lomefloxacin(20mg/kg body weight) was injected through caudal vein.At the given time points,the samples were collected.The concentrations of lomefloxacin in the serum,pancreatic tissue and liver tissue were measured by HPLC.RESULTS:The concentration-time profiles of lomefloxacin could be described as two-compartment model in rats.The peak concentrations in serum,pancreatic tissue and liver tissue were 65.550?g/ml,48.801?g/g and 84.121?g/g at 5 min post-injection respectively.Then the concentrations decreased quickly in all of them.Concentrations in pancreatic tissue were higher than those in serum at 10 min and even at 480 min post-injection.The permeation ratio (PR) through blood-pancreatic barrier was 0.744 at 5 min and rose to 3.817 at 480min.CONCLUSION:After intravenous injection,lomefloxacin can permeate blood-pancreatic barrier satisfactory,therefore it is worthy of being recommended for prevention and treatment of pancreatic infections.

Objective To analyze youth talents' scientific research projects in research oriented hospital for recent five years,provide scientific basis for hospitals to strengthen the youth talents' capacity building of research innovation.Methods Identify those youth talents who have been funded in the First Affiliated Hospital of Xinjiang Medical University,and statistically analyze the demographic information,granted scientific research projects and hospital funding situations.Results There are 140 young talents who have got scientific research projects from 2011 to 2015 in the hospital.The national project number and the trend of approval rate has no obvious change;the provincial level project number and approval rate showed a trend of a significant increase in the last two years;Setting up the hospital fund promoted the youth talents' scientific research ability,but there are still spaces for further improvement in the funding field and founded group.Conclusions There has been a group of youth talents to stand out from the crowd during the construction and the development of the researchoriented hospital,but youth talents remains scarce for the national key projects and talent projects,and that will put forward new requirements for the hospital in the future to strengthen the youth talents' capacity building of research innovation,which needs to gradually establish a suitable cultivation mode and mechanism for youth talents' growth.

Objective To observe the efficacy of breviscapine in the treatment of patients with acute cerebral infarction and its effect on serum neuron specific enolase(NSE), angiotensin-2(Ang-2) and interleukin-6(IL-6) levels.Methods 60 cases of acute cerebral infarction(ACI) patients from January 2014 to January 2015 in Sichuan Provincial People's Hospital were selected and randomly divided into two groups, 30 cases in each group.All patients were given conventional western medicine treatment , and the observation group were also treated with breviscapine.After 2 weeks, the degree of neural function defect scores and efficacy were compared and the serum levels of NSE , Ang-2 and IL-6 were detected by enzyme linked immunosorbent assay(ELISA) and compared pre-and post-treatment between two groups.Results The degree of neural function defect score post-treatment in observation group was significantly lower than that in control group ( P<0.05 ).The overall response in observation group was 27 cases (90.00%), which was significantly higher than 20 cases(66.67%) in control group(χ2 =4.81,P<0.05).The serum levels of Ang-2, IL-6 and NSE post-treatment in observation group were significantly lower than those in control group ( P<0.05 ) .Conclusion The curative effect of breviscapine in treatment of acute cerebral infarction is significantly, which could improve the cerebral microcirculation, protect the brain tissue, and its mechanism may be through reducing the serum levels of NSE, IL-6 and Ang-2.