This study was aimed to develop a maximum a posteriori Bayesian (MAPB) estimation method to estimate individual pharmacokinetic parameters based on D-optimal sampling strategy. Meanwhile, the performance of MAPB was compared with the multiple linear regression (MLR) method in terms of accuracy and precision. Pharmacokinetic study of pioglitazone was employed as the example case. The population pharmacokinetics was characterized by nonlinear mixed effects model (NONMEM). The sparse sampling strategy (1-4 points) was identified by D-optimal algorithm using WinPOPT software. The simulated data generated by Monte Carlo method were used to access the performance of MAPB and MLR. As the number of samples per subject decreased, the accuracy and precision of MAPB method tended to get worse. The estimation for CL and Vby MAPB using D-optimal two-point design had less bias with low inter-individual variability, and had more bias and imprecision with high residue variability. The estimation of AUC by MAPB using D-optimal 2 points design had similar accuracy and precision to MLR. However, MAPB estimation was better than MLR while adjusting the sampling time to one hour. Overall, the MAPB method had similar predictive performance as MLR, but MAPB could provide more pharmacokinetic information with higher sampling flexibility.

Purpose To study the expression of inhibitor of differentiation 2 (Id2) in Ewing sarcoma of bone as well as the correlation with cell cycle proteins. Methods The expression of Id2, c-Myc, Cyclin D1, p53, p16 and p27 in 45 cases of Ewing sarcoma were detected by immunohistochemical EnVision methods, the relationship between the expression of Id2 and clinicopathologic characteristics and the correlation with cell cycle proteins were analyzed. Results Total expression of Id2 was found in 88. 9% of Ewing sarcoma. Strong expression of Id2 was detected in 33. 3% cases. Higher frequencies of c-Myc and Cyclin D1 immunostaining were observed (66. 7% and 71. 1%, respectively), but lower frequencies of p53, p16 and p27 expression were present (20. 0%, 35. 6% and 28. 9%, respectively). Id2 overexpression displayed a negative relationship with p27 expression (P<0. 05). Among the follow-up of 24 cases, overexpression of Id2 was found more frequency in dead and metastases cases (41. 2%) when compared to that of progres-sion-free survival cases (14. 3%). Conclusions Id2 was extensively expressed in Ewing sarcoma of bone. Overexpression of Id2 and its correlation with p27 expression suggest that this is an important pathway involved in development of Ewing sarcoma. Moreover, Id2 overexpression may predict poor prognosis.

Objective:To study the expression of Survivin,VEGF,p53 and their correlation inbreast cancer, 22 cases of hyperplasia of mammary gland and 10 cases of paracainoma normal tissues by immunohistochemical technique (SP).Results: The positive rates of Survivin were 76.7%,18.2% and 0% in breast cancer, hyperplasia of mammary gland and paracacinoma normal tissues (P

Objective To investigate the levels and clinical significance of monocyte chemoattractant protein (MCP)-1 and tissue factor (TF) in patients with acute exacerbation of chronic obstructive pulmonary disease(AECOPD).Methods Forty-nine elderly patients with AECOPD(AECOPD group) and 30 healthy controls (control group) were selected,and AECOPD group was divided into procalcitonin (PCT) increased group (PCT ≥ 0.5 μ g/L,19 cases) and PCT normal group (PCT ＜ 0.5 μ g/L,30 cases) according to the level of serum PCT.The levels of plasma TF,serum MCP-1 and PCT were determined by enzyme linked immunosorbent assay.Results The levels of plasma TF and serum MCP-1 were (203.6 ± 92.9),(152.8 ±99.9) ng/L in AECOPD group,and (136.9 ±24.3),(87.5 ±41.5) ng/L in control group.There were significant differences in the levels of plasma TF and serum MCP-1 between AECOPD group and control group (P＜0.01).The level of plasma TF was positively correlated with serum MCP-1 (r =0.673,P=0.029).The levels of plasma TF and serum MCP-1 were (215.3 ±71.2),(181.1 ±61.6) ng/L in PCT increased group,and (192.4 ±79.7),(137.3 ±74.4) ng/L in PCT normal group.There were significant differences in the levels of plasma TF and serum MCP-1 between PCT increased group and PCT normal group (P＜0.05).Conclusions In patients with AECOPD,hypercoagulability state is activated,and it is more severe in the patients with increased PCT.The level of plasma TF is positively correlated with serum MCP-1 in patients with AECOPD.To monitor the levels of plasma TF and serum MCP-1 is particularly important for elderly patients of AECOPD with hypercoagulability state to prevent cardiovascular,lungs and cerebrovascular thrombotic disease.

Purpose To investigate the effect and mechanism of norcantharidin(NCTD)on invasion of human breast cancer cell line MCF-7 in vitro.Methods MTT assay Was used to determine MCF-7 cell proliferation,Transwell kit was used to determine cell migration,treated with NCTD on 200,400,600 μmol/L,to detect the expression of CXCR4 and CXCL12 in the control and treatment groups by real time PCR and Western blot.Results NCTD had inhibitive effects on proliferation and invasion of human breast cancer cell line MCF-7 in a dose-dependent manner,with the IC_(50) value of 582 μmol/L at 24 h,and the expression of CXCR4 Was deCreased in NCTD groups in vitro.Conclusion NCTD in vitro inhibits invasion and metastasis of human beast cancer cell line MCF-7 throush the down regulation to the expression of CXCR4.

Objective NKT cells are very important as a kind of non-specific immune cells. Much attention in antitumor significance has been received in the study of its effect on malignant diseases. The aim of this study was to detect the expression of NKT cells and its CD+8 NKT subsets in peripheral blood of esophageal patients and normal person, and to analyze the changes in the expression of NKG2D and NKG2A receptorsand its clinical pathological factors. Methods By flow cytometric analysis, 53 patients with esophageal carcinoma and 39 normal controls were analysed for peripheral blood of NKT cells and CD+8 NKT subsets, and the expression of NKT cells NKG2A and expression of NKG2D receptor. The clinical pathological factors were collected for the comparative analysis. Results Compared with the normal control group, the expression of NKT cells in peripheral blood of esophageal patients increased [(4.32±0.73) %, (5.97±1.29) %] (t =3.562, P <0.01), and the expression level of its surface receptor NKG2D reduced [(17.56±5.92) %, (15.12±1.56) %] (t =3.892, P <0.05), but the express levels of NKG2A [(4.02±1.41) %, (5.99±4.59) %] in creased (r = 4.015, P <0.05), those expression change with the development of the esophageal cancer. Conclusion The increased expression of NKT cells and CD+8 NKT subsets in the peripheral blood of patients with esophageal carcinoma refletcs that the immune feedback of patients' antineoplastic effect is strengthened. The decresed expression of the active receptor NKG2D and the increased expression of the inhibitory receptor NKG2A on NKT cells might be one of mechanisms leading to the reduction of NKT cell activity and immune escape of patients with esophageal carcinoma. The changes of surface receptors of NKT cells may be associated with the development of the esophageal cancer.

Two patients underwent liver transplantation of blood type incompatibility were collected from Fuzhou General Hospital of Nanjing Military Area Command of Chinese PLA. Case 1: A male who had primary hepatic carcinoma underwent classic orthotopic liver transplantation; the blood of donor was type A, and the blood of recipient was type O. Case 2: A female having history of type B hepatitis underwent classic orthotopic liver transplantation due to pregnancy combining with severe liver disease and coagulation disorder; the blood of donor was type B, and the blood of recipient was type O. Immunohistochemistry staining was used to observe pathological changes and deposition of various immunoglobulin and complement in two cases following liver transplantation of blood type incompatibility under optic microscope and to investigate diagnostic standard of humoral rejection. The results showed that linear or granular depositions of IgG, IgM, IgA, C4c, C4d, and Clq were found in endothelial cells of hepatic sinusoid, suggesting that IgG and other immunoglobulin exhibited a strongly positively diffused deposition on the endothelial cells of hepatic sinusoid, while expression of C4d and other complements was also found. All those mentioned above could be considered as evidences to prove onset of humoral rejection in transplanted liver tissue.

Objective To investigate the clinical characteristic and the predicting value of plasma Apelin in elderly patients with sepsis.Methods A retrospective analysis was conducted in 26 sepsis patients aged (72.9±9.7) years in average and 30 healthy controls.Serum Apelin level was measured by ELISA.Body mass index (BMI) and C-reaction protein (CRP) were detected.Patients were divided into survival group (n=18) and death group (n 8).According to acute physiology and chronic health evaluation (APACHE) Ⅱ,patients were divided into subgroup A (n=14,APACHE Ⅱ score≤20) and subgroup B (n=12,APACHE Ⅱ score＞20).Results The Apelin concentration was higher in sepsis patients than in healthy controls [(0.38±0.15)ng/L vs.(0.19±0.12)ng/L,t=2.011,P＜0.05].The Apelin concentration was lower in survival group than in death group[(0.21 ± 0.29)ng/L vs.(0.49 ± 0.32) ng/L,t =2.094,P＜0.05].The Apelin level was increased with APACHE Ⅱ scores increment in sepsis patients (P＜0.05).Multivariable logistic analysis showed that when taking survival/death as the dependent variable and Apelin as the independent variable,the ()R value was 4.162 with 95％ CI:1.115-15.535(P＜0.05).Conclusions Increased serum Apelin level reflects the severity of illness in patients with sepsis,which is a risk factor for death in prognosis of sepsis.

Objective To summarize the expression of CK19, HBME-land 34βE12 in papillary carcinoma of the thyroid (PCT) and their differential diagnostic value. Methods Clinical data of papillary carcinoma of the thyroid,nodular goiter and paraeareinoma were reviewed. All HE slides were reexamined and immunostains for CK19, HBME-land 34βEI2 were performed in selected case. Staining results were evaluated. Results Those cases typically showed complex papillary structures and interstitial fibrosis, while nuclear features included ground class appearance, grooves and nuclear pseudoinelusion. The positive rates for CKI9, HBME-1 and 34βE12 in PCT were 100.0 %, 89.4 % and 42.6 % respectively, the differences were statistically significant(P <0.01). Conclusion PCT occurs preferentially in the group of middle-aged women. The diagnosis of PCT should be distinguished from other plesiomorphous benign papillary lesions. Combined detection of CK19, HBME-1, 34βE12 can be most helpful for diagnosis for of PCT.

Objective To analyze CD+4 CDHi25 CDLo127 regulatory T cells (Treg) in peripheral blood of patients with thyroid nodules and differentiated thyroid cancer and their change regularity, and to investigate the immunosuppression mechanism. Methods The peripheral blood was collected from 175 patients with thyroid nodules, including 43 patients with differentiated thyroid cancer and 132 patients with nodular goiter.By using monoclonal antibodies, the blood samples were evaluated with the flow cytomertry for lymphocyte subsets and Treg cells. Results The results showed the prevalence of the CD+4 CDHi25 CDLo127 Treg in differentiated thyroid cancer group [(6.48±1.49) %] and nodular goiter group [(6.23+1.67) %] was higher than those in the healthy group [(5.62±1.48) %], and the difference was significant(P < 0.005), but there was no significant difference between the nodular goiter group and differentiated thyroid cancer group (P >0.005).Conclusion It is concluded that the relative increase of CD+4 CDHi25 CDLo127 Treg in peripheral blood of patients with nodular goiter and differentiated thyroid cancer may be related to immunosuppression and tumor progression.