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

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.

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 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.

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.

Mycoepoxydiene is a novel antitumor agent extracted from marine lignicolous fungi HLY-2, which is Diaporthe phaseolorum by molecule identification. The medium optimization for mycoepoxydiene by orthogonal design and the comparison of submerged fermentation and solid state fermentation were studied. The rusult is that the maximal yield of the compound is 543mg/L, which is 43 times compared to the customary half-seawater PD medium and 15 times to the best submerged condition. This optimum culture medium included potato 250g/L, seawater 300mL/L, glucose 30g/L, lactose 50g/L, KH_ 2 PO_ 4 0.65mmol/L and (NH_ 4 )_ 2 SO_ 4 1g/L in the solid state condition. Differentiation analysis between submerged and solid state fermentation, and antitumor activity of these ferment products were also studied. The antitumor activity of products of the optimum medium approached the pure compound.

In traditional Chinese medicine(TCM),abnormal and diseased conditions have been defined as Zheng Hou, a unique disease definition system in the context of holism. For over 3000 years the main clinical treatment method for TCM therapeutics has been so called Fang-ji, a TCM medicinal formula usually composed of several herbs and medical materials. The compositions of Fang-ji are based on the clinical practice under the guidelines of "bian-zheng-lun-zhi" and the principles of "Jun-chen-zuo-shi". Each Zheng is treated with a correspondingly-individualized Fang-ji.The modern approach to the study of Fang-ji pharmacology,however,has been focusing on the isolation and identification of individual active components for cellular and molecular targets. Although this approach has led to the development of many new monomers purified from Fang-ji as new drugs widely used in clinical practice such as the an-timalarial artemsinin,which has earned a Nobel Prize,the pharmacological bases of these purified effective monomers or active components have lost the TCM characteristics and are far different from the phar-macological theory and clinical applications of Fang-ji,in terms of the principles of"bian-zheng-lun-zhi"and "Jun-chen-zuo-shi". Here we introduce the emerging pharmacophenophenics as a systematical paradigm for the pharmacological study of Fang-ji.Pharmacophenomics studies the orchestrated multi-target pharmacology of combination therapy.With well-defined molecular mechanisms of Zheng Hou at the level of multi-omics and a suite of new phenomics technologies and platforms, the pharmacophe-nomics may be used to characterize the drug-response phenome of Fang-ji and to identify the corre-sponding multiple therapeutic targets according to the TCM theory of Jun-chen-zuo-shi.Pharmacophe-nomic study of Fang-ji will also lay a theoretical foundation for the new science of precision medicine.