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.

Objective Concluding the clinical feature and prognosis of primary testicular lymphoma to improve the understanding of this disease.Methods During 1995 and 2010,17 cases of primary testicular lymphoma treated in Beijing Friendship Hospital of Capital Medical University were retrospectively analyzed of its clinical features,diagnosis,treatment and prognosis.Results Seventeen patients with a mean age of 68 years complained the testicular sohd mass as their first symptoms.The mean tumor diameter was 4.7 cm,and all patients underwent orchidectomy,and testicular non- Hodgkin's lymphoma was confirmed by pathologic examination.Fourteen cases were diffuse large B cell type and 3 cases were anaplastic large cell type.The clinical stage of all the patients was IE.Fourteen cases were followed up (3 cases were lost)with mean follow-up time of 37.8 months by outpatient interview and telephone,all patients were treated with CHOP chemotherapy,and some of them were combined with rituximab and preventive lowdose pelvic radiotherapy.Five cases died of other chronic medical complications,1 case with contralateral testicular metastasis received surgery again.There were 9 tumor free survival cases in total.Conclusion Primary testicular lymphoma is rare and more common in older men.Postoperative pathologic diagnosis is gold standard.The systemic treatment and individual therapy is the first choice for primary testicular lymphoma.

This study is to investigate the protection effect of schisandrin B (Sch B) against oxidation stress of HK-2 cells induced by cisplatin and the mechanisms involved. HK-2 cells were cultured and divided into different groups: solvent control group, cisplatin exposure group, positive group, Sch B treatment group. Cell viability and toxicity were evaluated by MTT and LDH assay. GSH level and SOD enzymes activities were also measured. DCFH-DA as fluorescence probe was used to detect ROS level by fluorescence microplate reader. Nrf2 translocation was detected by Western blotting. Real time Q-PCR was used to detect expressions of NQO1, HO-1 and GCLC mRNA level. The results showed that Sch B could significantly inhibit the decline of cell viability induced by cisplatin treatment (P < 0.05) and the protective effect was in a dose dependent manner. Furthermore, Sch B treatment significantly inhibited the increase of ROS level induced by cisplatin and reversed the decrease of GSH level (P < 0.05). When Sch B concentration was up to 5 micromol x L(-1), SOD enzyme activities were also enhanced significantly compared with that of the cisplatin group (P < 0.05). It was shown that Sch B could cause nuclear accumulation of Nrf2 in association with downstream activation of Nrf2 mediated oxidative response genes such as GCLC, NQO1 and HO-1. These results suggested Sch B could protect against the oxidative damage of HK-2 cells induced by cisplatin via the activation of Nrf2/ARE signal pathway.

Objective To construct and identify over?expressing lentiviral vector of mSema3A. Methods Sema3A gene of mice was amplified by PCR,then the gene was inserted into plasmids pDown?mSema3A?IRES/EGFPby Gateway technology. The plasmids pLV/EXPNZ?puro?mSema3A?IRES/EGFP were produced by recombination. After sequencing identification,the vector pLV(Exp)?Puro?CMV?mSema3A?IRES/EGFP was packed and condensed. Finally the recombinant vectors were used to transfect 293T cells to obtain virus pools. Results The recombinant lentiviral vectors were 11 538 bp with EGFP marker,and Sema3Agenes were inserted into the lentiviral vector correctly,indicating the over?expressing vector of Sema3A gene in mice was successfully constructed. Conclusion The over?expressing lentiviral vector of mSema3A was constructed correctly, which lay a foundation of screening of over?expressing strains of such gene in specific cells.

Objective: To investigate the effects of early enteral nutrition (EEN) in the treatment of patients with severe burns. Methods: Medical records of 52 patients with severe burns hospitalized in the three affiliations of authors from August to September in 2014 were retrospectively analyzed and divided into EEN group (n=28) and non-early enteral nutrition (NEEN) group (n=24) according to the initiation time of enteral nutrition. On the basis of routine treatment, enteral nutrition was given to patients in group EEN within post injury day (POD) 3, while enteral nutrition was given to patients in group NEEN after POD 3. The following items were compared between patients of the two groups, such as the ratio of enteral nutrition intake to total energy intake, the ratio of parenteral nutrition intake to total energy intake, the ratio of total energy intake to energy target on POD 1, 2, 3, 4, 5, 6, 7, 14, 21, and 28, the levels of prealbumin, serum creatinine, blood urea nitrogen, total bilirubin, direct bilirubin, and Acute Physiology and Chronic Health Evaluation Ⅱ (APACHE Ⅱ) score on POD 1, 3, 7, 14, and 28, the first operation time, the number of operations, and the frequencies of abdominal distension, diarrhea, vomiting, aspiration, catheter blockage, and low blood sugar within POD 28. Data were processed with χ²test, ttest, Wilcoxon rank sum test, and Bonferroni correction. Results: (1) The ratio of parenteral nutrition intake to total energy intake of patients in group EEN on POD 1 was obviously lower than that in group NEEN (Z=2.078, P<0.05). The ratio of enteral nutrition intake to total energy intake and the ratio of total energy intake to energy target of patients in group EEN on POD 2 and 3 were obviously higher than those in group NEEN (Z=5.766, 6.404, t=4.907, 6.378, P<0.01). The ratio of total energy intake to energy target of patients in group EEN was obviously lower than that in group NEEN on POD 4, 5, 6, and 7 (t=4.635, 2.547, 3.751, 5.373, P<0.05 or P<0.01). On POD 2, 4, 5, 14, 21, and 28, the ratio of enteral nutrition intake to total energy intake of patients in group EEN was obviously higher than the ratio of parenteral nutrition intake to total energy intake within the same group (Z=5.326, 2.046, 2.129, 4.118, 3.174, 3.963, P<0.05 or P<0.01). In group NEEN, the ratio of enteral nutrition to total energy intake of patients on POD 1, 2, and 3 was obviously lower than the ratio of parenteral nutrition intake to total energy intake within the same group (Z=2.591, 2.591, 3.293, P<0.05 or P<0.01), while the ratio of enteral nutrition to total energy intake of patients on POD 14, 21, 28 was obviously higher than the ratio of parenteral nutrition intake to total energy intake within the same group (Z=2.529, 3.173, 3.133, P<0.05 or P<0.01). (2) The prealbumin levels of patients in the two groups were close on POD 1, 3, 7, and 14 (t=1.983, 0.093, 0.832, 1.475, P>0.05). On POD 28, the prealbumin level of patients in group EEN was obviously higher than that in group NEEN (t=3.163, P<0.05). The levels of serum creatinine, blood urea nitrogen, total bilirubin, and direct bilirubin of patients in the two groups at all time points post injury were close (Z=1.340, 0.547, 0.245, 0.387, 0.009, 1.170, 0.340, 1.491, 0.274, 1.953, 0.527, 0.789, 0.474, 1.156, 0.482, 0.268, 0.190, 0.116, 1.194, 0.431, P>0.05). (3) The APACHE Ⅱ scores of patients in group EEN were (22.5±3.1) and (15.6±3.8) points respectively on POD 1 and 3, which were close to (23.6±3.0) and (17.6±4.2) points of patients in group NEEN (t=1.352, 1.733, P>0.05). The APACHE Ⅱ scores of patients in group EEN on POD 7, 14, and 28 were (13.6±3.6), (13.8±4.1), and (15.5±4.1) points, respectively, which were obviously lower than (18.5±3.9), (19.5±4.2) and (20.8±3.8) points of patients in group NEEN (t=4.677, 4.843, 4.792, P<0.05). (4) Within POD 28, the time of the first operation, the number of operations, and the frequencies of abdominal distension, diarrhea, vomiting, aspiration, catheter blockage and hypoglycemia were similar between patients of the two groups (t=0.684, 0.782, Z=0.161, 1.751, 0.525, 0.764, 0.190, 0.199, P>0.05). Conclusions EEN in the treatment of patients with severe burns potentially increases the energy intake at early stage and improves APACHE Ⅱ score and prealbumin level on POD 28, without increasing frequencies of adverse reactions.

Objective To investigate the diagnostic value of Enzymes linked immunosorbent assay(ELISA)detection of anti phospholipase A2 receptor antibody(anti-PLA2R)in idiopathic membranous nephropathy patients.Methods All articles published from January 2012 to April 2017 about ELISA test on anti phospholipase A2 recepeor antibody as a maker for IMN were collected, and the quality of the studies was evaluated by using the guidelines of the updated Quality Assessment of Diagnostic Accuracy Stud-ies(QUADAS-2)tool.According to the inclusion criteria and exclusion criteria,the research objects were selected and the data were extracted,and the analysis was carried out by Meta-Disc1.4 software.The results are summarized on the basis of sensitivity,speci-ficity,and summary receiver operating characteristic curve(ROC curve).Results Ten articles were selected according to inclusion criteria and 1517 cases were included in the study.The combined sensitivity was 0.68[95% CI(0.64,0.70)];the merge specificity was 0.92[95% CI(0.90,0.95)],and the subjects'working curve showed AUC 0.807 4.Conclusion The detection of anti-PLA2R by ELISA is effective in the diagnosis of idiopathic membranous nephropathy,which can be used as an effective supplement for the diagnosis of idiopathic membranous nephropathy.

Purpose To explore the value of Doppler ultrasound in the diagnosis of congenital hypertrophic pyloric stenosis (CHPS) by observing pylorus. Materials and Methods Sixyt-five children with CHPS diagnosed by ultrasound in Neonatology Department of Guangzhou First People's Hospital from 2006 to 2015 were retrospectively analyzed. CHPS group and 50 infants in control group were examined by Doppler ultrasound to observe the features of blood flow distribution and blood flow grading, and Doppler spectrum analysis was performed to observe contrast agent passing through pyloric canal. Results The difference of the thickness of muscular layer and mucous layer, and that of the long diameter and inner diameter of pyloric canal in CHPS group and control group all suggested marked statistical significance (P<0.01); the blood flow grading in muscular layer and mucous layer between the two groups showed statistical significance (t=13.33 and 18.77, all P<0.01). The blood flow velocity in muscular layer of CHPS group was (16.96±0.91) cm/s, resistance index (RI) 0.68±0.33, inner diameter of pyloric canal (1.98±0.33) mm. Conclusion Doppler ultrasound enables us to grasp the distribution and grading of blood flow of pylorus as well as the condition of contrast agent passing through pyloric canal, in which way the degree of pyloric stenosis can be evaluated by combining indexes such as Vmax and RI, and an objective basis for clinical choice of treatment can be provided, possessing high application value.

Objective To verify the feasibility and effectiveness of modified gastric bypass surgery in the treatment of non-obese type 2 diabetic mellitus(T2DM ) GK rats .Methods Forty male GK rats were randomly divided into four groups (n=10) ,the group A served as the modified gastric bypass ,group B as the Roux-en-Y gastric bypass ,group C as the sham operation and group D as the blank control group .Fasting blood glucose(FBG) ,glycosylated hemoglobin(HbA1c) and fasting serum insulin(FINS) in each group were detected at preoperative 1 week ,postoperative 1 ,2 ,4 ,8 ,12 weeks .Results The rat body mass at postoperative 1 week in the group A and B was significantly decreased compared with the group D ,and began to recover at postoperative 4 weeks , the rat body mass at the same time point had no statistical difference between the group A and B (P>0 .05) .FPG ,FINS and HbA1c at preoperative 1 week had no statistical difference among various groups (P>0 .05) .FPG and FINS at postoperative 1 week had no statistical difference among various groups (P>0 .05) .FPG and FINS at postoperative 2 ,4 ,8 ,12 weeks had no statistical difference between the group A and B(P>0 .05) ,which had no statistical difference between the group A with the group C and D (P>0 .05) . HbA1c at postoperative 4 weeks had no statistical difference among various groups (P>0 .05);which at postoperative 12 weeks had no statistical difference between the group A and B (P>0 .05) ,while which had no statistical difference between the group A with the group C and D(P>0 .05) .Conclusion The modified gastric bypass surgery has the improvement effect on glycometabolism of rat non-obese T2DM ,which is similar to that of Roux-en-Y gastric bypass surgery .

With the progress of information technology and intelligent technology,the intelligent development of urine testing instruments is facing new opportunities.Using the disease cybernetics theory model to analyze the business process and current urine testing instruments of clinical urine analyzer,a generational theoretical model of urine testing instruments has been constructed,which is conducive to guiding the intelligent development direction of urine testing instruments.The study divides urine testing instruments into one to four generations of products,with the first-generation of products being operated by doctors.The second-generation products are currently available for laboratory technicians to use various urine analyzers.The third-generation products further optimize the testing process and intelligence,without the need for inspectors to operate.The fourth-generation products are unmanned and do not require sampling.It can be seen that with the development of technology,urine analysis has indeed become more convenient,but after all,various instruments have their limitations.Therefore,the establishment of a theoretical model for the generation of urine testing instruments should be applied in clinical urine testing,which can not only improve the efficiency of urine analysis but also improve its quality.

Objective:To discuss the molecular association pattern of Shenling Baizhu Powder for type 2 diabetes (T2DM) and ulcerative colitis through network pharmacology method based on the theory of "treating different diseases with same method" in TCM.Methods:The TCMSP and ETCM Chinese medicine chemical composition databases were used to obtain the chemical composition and predict the targets of Shenling Baizhu Powder. The OMIM, GeneCards, DrugBank and TTD disease databases were used to obtain the disease targets of T2DM and ulcerative colitis. The intersection targets of chemical composition of Shenling Baizhu Powder, T2DM and ulcerative colitis were obtained by Bioinformatics platform. Cytoscape 3.8.2 software was used to map the "Chinese materia medica-component-target" network and "effective component- intersection target" network. The GO enrichment analysis and KEGG pathway analysis of the intersection targets were performed with the STRING platform. The intersection target protein-protein interaction network was constructed by STRING database, and core targets were obtained using the CytoNCA plugin of Cytoscape 3.8.2 software. AutodockTools software was applied to validate the molecular docking between the core chemical components and the core targets of Shenling Baizhu Powder.Results:Totally 176 chemical components of Shenling Baizhu Powder, 226 corresponding targets, 11 478 T2DM targets, 4 857 Ulcerative targets of ulcerative colitis, and 162 intersection targets of medicinal chemistry components and diseases were obtained. 1 789 related biological processes, 163 molecular functions, 92 cell constituents, and 192 signaling pathways were obtained by GO enrichment analysis and KEGG pathway analysis. The signaling pathways were mainly about AGE-RAGE, TNF, IL-17,MAPK, PI3K-Akt signaling pathways, etc. The core components of Shenling Baizhu Powder were mainly sitosterol, luteolin, kaempferol, naringenin, beta-carotene, etc. The core targets were EGFR, ALB, IL1B, CASP3, ESR1, VEGFA, PTGS2, TNF, IL6, MYC, AKT 1, JUN, TP53, etc. The core chemical components had tight correlation with the core targets by the molecular docking.Conclusions:By acting on core targets such as TNF, IL1B, IL6, AKT1, VRGFA, PTGS2, MYC, JUN, TP53, and regulating IL-17 signaling pathway, TNF signaling pathway, MAPK signaling pathway, AGE-RAGE signaling pathway, etc., Shenling Baizhu Powder improves tissue inflammation damage, mucosal barrier damage, immune regulation imbalance, intestinal flora dysbiosis, insulin resistance, apoptosis, oxidative stress and other biological processes. Therefore Shenling Baizhu Powder can treat T2DM and ulcerative colitis with the same method.