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

Cone-Beam Computed Tomography ; methods ; Humans ; Nasopharyngeal Neoplasms ; diagnostic imaging ; radiotherapy ; Radiotherapy Planning, Computer-Assisted ; Radiotherapy, Intensity-Modulated ; methods

Alimentary tract duplications are rare congenital anomalies that usually present in childhood and occasionally in adults. They are most common in the ileum, but can occur anywhere along the alimentary tract from the mouth to the anus. We report a 24-year-old woman who presented with a giant chylous ileum cyst duplication. To our knowledge, there is only one other report of a patient with a giant chylous cyst in the literature.
Abdominal Pain ; Adult ; Cysts ; diagnosis ; pathology ; surgery ; Female ; Humans ; Ileum ; surgery ; Magnetic Resonance Imaging ; Tomography, X-Ray Computed

Objective To explore the relationship between peripheral Th17 cell number and chronic gastritis in Helicobacter pylori(H.pylori)-infected children.Methods Children were diagnosed as chronic gastritis by endoscopy.The degree and activity of inflammation were graded by histopathology examinations.The patients with both 13C urea breath test and urease test positive were diagnosed as H.pylori infection.The peripheral Th17 cell number was measured by flow cytometry and expressed as a ratio to total T cell.Results The Th17 cell number in HP group (chronic gastritis with H.pylori infection,n =33),non-HP group (chronic gastritis without H.pylori infection,n =24) and normal controls (n =15) were (1.55 ±0.30)％,(1.06 ±0.33)％,and (1.04 ±0.35)％,respectively.HP group included a statistically higher Th17 cell number than the other groups (all P ＜ 0.05),while no obvious difference was found between non-HP group and controls (P ＞ 0.05).According to the degree of inflammation,the chronic gastritis with H.pylori infection was categorized into non-apparent (n =10),mild (n =8),moderate (n =9) and severe (n =6) subgroups.The Th17 cell number in each subgroup was (1.64 ± 0.21)％ (non-apparent),(1.61 ± 0.23)％(mild),(1.25 ± 0.29) ％ (moderate) and (1.75 ± 0.20) ％ (severe),respectively.The moderate group had a lowest Th17 cell number among 4 groups (P ＜ 0.05).And significant differences did not exit in the other 3 groups (P ＞ 0.05).The HP group patients with different inflammatory activity had a Th17 cell number of (1.23 ±0.25)％ in nonapparent (n=15),(1.53 ±0.15)％ in mild (n=6),(1.55 ±0.32)％ in moderate (n=6) and (1.71 ±0.35)％ in severe (n =6) subgroup,respectively.However,there were no significant differences among 4 subgroups (P ＞ 0.05).Conclusions In the progress of chronic gastritis with H.pylori infection,Th17 cells may play a role as a double-edged sword by protecting and fighting against H.pylori infection and immunopathologic insults.This would provide more insights into the treatment of H.pylori infection.

Objective To explore the diagnostic value of prothrombin time(PT),activated partial thromboplastin time(APTT),fibrinogen(FIB),D-Dimer(DD),antithrombin Ⅲ(ATⅢ),platelet(PLT)in activity and severity assessment of ulcerative colitis(UC),and to analyze whether they could evaluate the degree of activity UC in children.Methods The data of UC patients in the Department of Gastroenterology,Children's Hospital of Nanjing Medical University from January 2012 to September 2016 were analyzed,25 cases of remission and 36 cases of active UC patients were selected as the study subjects.Thirty healthy children were selected as healthy control group,combined with the coagulation function indicators for analysis.Results Receiver operating characteristic area under the curve(AUC)of PT,APTT,FIB,DD,ATⅢ and PLT in UC patients was 0.659,0.840,0.744,0.776,0.599 and 0.792,the activity of UC patients was 0.849,0.889,0.836,0.912,0.964 and 0.966,respectively.The results of PT,APTT,FIB,DD and PLT in children with active UC were significantly higher than those in the healthy control group,and ATⅢ was significantly lower than that in the healthy control group.Compared with the healthy controls,the levels in remission UC patients were not significantly different(P>0.05).The 3 subgroups of activity UC had no significant differences among PT and APTT(F=0.652,1.755,all P>0.05),However,there were significant differences among FIB,DD,ATⅢ and PLT(F=66.495,32.817,88.284,22.892,all P<0.05).FIB,DD and PLT were moderately positively correlated with severity of activity UC patients(r=0.857,0.648,0.654,all P<0.05),and ATⅢ had moderately negative correlation(r=-0.789,P<0.05).Progressive regression analysis showed that the severity of UC was associated with FIB,DD and ATⅢ(R2=0.830,F=39.962,P<0.05).Conclusion FIB,DD and ATⅢ can be used as index for the activity and evaluation of UC.

Brain Neoplasms ; diagnostic imaging ; radiotherapy ; Cranial Irradiation ; Dose Fractionation ; Glioblastoma ; diagnostic imaging ; radiotherapy ; Humans ; Magnetic Resonance Imaging ; Positron-Emission Tomography ; Radiotherapy Dosage ; Radiotherapy, Conformal ; methods ; Tomography, X-Ray Computed

Objective To find the effective therapeutic arrangement through investigating the clinical characteristics of chronic cardiac insufficiency with anaemia. Methods A total of 46 cases of anemia from 315patients who had been admitted to department of cardiology, the First Affiliated Hospital, Harbin Medical University for chronic cardiac insufficiency with anaemia were selected. They were divided into two groups. There were 22 patients in the first group who only accepted treatment to improve cardiac function (normal cardiac, diuretic,vasodilator therapy, etc.), and 24 patients in the second group who accepted treatment to improve cardiac function while receiving anti-anemia therapy treatment, oral ferrous sulfate tablets(0.3 g/tablet), 1 tablet each time, 3 times a day and(or) 2 times per week subcutaneous erythropoietin 3000 U. The hemoglobin(Hb), red blood cell(RBC) ,hematocrit (HCT), left ventricular ejection fraction (LVEF), fractional shortening (FS), stroke volume (SV) , cardiac output(CO) and E peak and A peak ratio(E/A) were observed before and after treatment. By logistic regression, grade grade Ⅱ , Ⅲ , Ⅳ, the incidence of anaemia were 7.9% (10/126), 19.2% (23/120) and 24.6% (17/69),respectively. Grade Ⅱ compared with grades Ⅲ, Ⅳ, the difference was statistically significant (x2 = 4.08, 3.12, all (3.49 ± 0.17) × 1012/L, (0.36 ± 0.08)%, (48.9 ± 3.11)%, (15.6 ± 1.8)%, (38.9 ± 3.7)%, (4.4 ± 1.6)% and (130.7 ±5.75)g/L, (4.12 ± 0.25) × 1012/L, (0.43 ± 0.02)%, (58.5 ± 2.65)%, (18.0 ± 2.5)%, (49.1 ± 7.7)%, (5.1 ± 1.2)%in the first and second groups, respectively. The difference between the two groups was statistically significant(t =value of Hb, RBC, HCT, LVEF, FS,SV, CO were (102.7 ± 6.93)g/L, (3.41 ± 0.12) × 1012/L, (0.35 ± 0.07)%,(47.5 ± 2.86)%, (16.0 ± 2.4)%, (38.2 ± 7.9)%, (3.7 ± 1.4)%, respectively. Compared with those after treatment,the difference was statistically significant (t = 15.632, 13.325, 5.569, 17.182, 3.186, 2.999, 3.074, all P ＜ 0.05);Ⅳ-level relative risk were 1.62, 3.14(P ＜ 0.05 or ＜ 0.01) . Conclusions Based on the standard treatment with treatment of anemia, cardiac contractile function can be improved.

OBJECTIVETo investigate the migration of fluorescent dye PKH26-labeled BM-MSC in the Alzheimer's model rats.

METHODSNormal human bone marrow extracted for isolation of BM-MSC was cultured in vitro. The 5th passaged BM-MSC was labeled with PKH26, and observed under a fluorescence microscope for PKH26 labeling efficiency, and using flow cytometry BM-MSC surface markers was checked. The PKH26 labeled BM-MSC injected into the tail vein of the normal control group and AD animal model group, 14 days after finding the PKH26-labeled BM-MSC cells in the rat hippocampus using fluorescence microscopy. Using the Morris water maze experiment comparison of AD model and BM-MSC transplantation group of spatial learning and memory ability.

RESULTSTFlow cytometry showed BM-MSC surface markers CD73 and CD105 were positive. In vitro, PKH26-labeled rate of BM-MSC was 100 %. The Morris water maze experiment comparison of BM-MSC transplantation group and AD group of animals, BM-MSC transplantation group at 13, 14 days of spatial learning and memory ability than AD animal group had significantly improved. 14 days after BM-MSCs in rat hippocampus could be found which were PKH26-positive, consistent with DAPI staining. PKH26-positive cells in animal models of AD were significantly more than those in the normal control group.

CONCLUSIONBM-MSC in AD rats not only migrates through the blood-brain barrier, but also mainly survives in the hippocampus of AD rats, and it can improve AD rat model of learning disabilities.

Alzheimer Disease ; pathology ; Animals ; Bone Marrow Cells ; cytology ; Cell Movement ; Cells, Cultured ; Disease Models, Animal ; Humans ; Injections, Intravenous ; Male ; Mesenchymal Stromal Cells ; cytology ; Organic Chemicals ; Rats ; Rats, Sprague-Dawley

The objectives of this study are to prepare resveratrol loaded mixed micelles composed of poloxamer 403 and poloxamer 407, and optimize the formulation in order to achieve higher drug solubility and sustained drug release. Firstly, a thin-film hydration method was utilized to prepare the micelles. By using drug-loading, encapsulation yield and particle size of the micelles as criteria, influence of three variables, namely poloxamer 407 mass fraction, amount of water and feeding of resveratrol, on the quality of the micelles was optimized with a central composite design method. Steady fluorescence measurement was carried out to evaluate the critical micelle concentration of the carriers. Micelle stability upon dilution with simulated gastric fluid and simulated intestinal fluid was investigated. The in vitro release of resveratrol from the mixed micelles was monitored by dialysis method. It was observed that the particle size of the optimized micelle formulation was 24 nm, with drug-loading 11.78%, and encapsulation yield 82.51%. The mixed micelles increased the solubility of resveratrol for about 197 times. Moreover, the mixed micelles had a low critical micelle concentration of 0.05 mg · mL(-1) in water and no apparent changes in particle size and drug content were observed upon micelles dilution, indicating improved kinetic stability. Resveratrol was released from the micelles in a controlled manner for over 20 h, and the release process can be well described by Higuchi equation. Therefore, resveratrol-loaded poloxamer 403/407 mixed micelles could improve the solubility of resveratrol significantly and sustained drug release behavior can be achieved.
Drug Carriers ; chemistry ; Fluorescence ; Kinetics ; Micelles ; Particle Size ; Poloxamer ; chemistry ; Solubility ; Stilbenes ; chemistry ; Water

Purpose:It is the authors' intention to improve the diagnostic and differential diagnostic accuracy of ultrasound for acute tes-tis diseases by analyzing the sonographic features.Materials and Methods:The sonographic features of 78 acute testis diseasess were analyzed.The results were compared with the clinical,surgical and pathological results.Results:78 patients had obviously different sonographic features between different types of acute testis diseases.12 testicular tumors were big mass with uneven internal echoes and often with calcification.The distributions of the vessels in the lesions were irregular or branch-like.26 cases of testicular contusion had scrotal wall edema and thickening,with low echo and liquid collection in the lesions.21 cases of acute orchitis usually intumesced with color ball-shaped rich blood flow signals.18 cases with testicular torsion had blood flow on the affected side decreased or disappeared,lcase of tuberculocele showed extremely uneven and various echoes mixed in testis.Conclusion: A fast and exact diagnosis or differential diagnosis of acute testis diseases can be obtained with ultrasound.