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.

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 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.

Tumor cell plasticity, including epithelial to mesenchymal transition (EMT) and its reverse program, mesenchymal to epithe-lial transition (MET), regulates circulating tumor cells and carcinoma metastasis. Twist is overexpressed in rhabdomyosarcoma, breast cancer, gastric cancer, and other tumors. Twist, as a transcriptional factor, cross-talks with multiple signaling pathways, forming a com-plex network to participate in the regulation of EMT/MET in circulating tumor cells, which in turn promotes metastasis of tumor cells. Therefore, monitoring the level of Twist and epithelial–mesenchymal phenotypic molecules is important as it may be beneficial for in-creasing the detection ratio of circulating tumor cells as tumor biomarkers and for evaluating the effects of anticancer drugs.

Objective To investigate the detection of multidrug-resistant organisms (MDROs)in a hospital, evaluate the efficacy of multi-disciplinary team(MDT)on management of MDROs,and provide guidance for effective control on MDRO infection.Methods From October 2013 to September 2014,compliance to comprehensive inter-vention measures in clinical departments in different stages as well as detection of MDROs from patients were com-pared respectively.Results Compliance to comprehensive intervention measures showed an overall upward trend from the fourth quarter of 2013 to the first,second,and third quarters of 2014,difference was statistically signifi-cant (all P <0.001 ).From the fourth quarter of 2013 to the third quarter of 2014,the percentage of the major MDRO strains in the same species of bacteria were:methicillin-resistant Staphylococcus aureus (MRSA)52.34%, 45.45%,48.95%,and 26.25% respectively;carbapenem-resistant Acinetobacter baumannii (CRAB)64.42%, 63.07%,59.87%,and 43.09% respectively;multidrug-resistant Pseudomonas aeruginosa (MDRPA)42.11 %, 41 .82%,29.33%,and 17.52% respectively;the detection rate of MRSA,CRAB,and MDRPA showed an overall downward trend,difference among different stages were statistically significant (all P <0.001 ).Detection rates of carbapenem-resistant Enterobacteriaceae (CRE)and vancomycin-resistant Enterococcus (VRE)were both low (<5%),difference among different stages were not statistically significant (all P >0.05).Conclusion MDT on man-agement of MDROs is helpful for reducing the emergence and spread of MDROs.

Objective To detect left atrial (LA) function and left ventricular (LV)-LA coupling using vector flow mapping (VFM) and two-dimensional tissue tracking (2DTT) echocardiography in patients with diabetes.Methods A total of 51 patients with type 2 diabetes (DM group) and 38 healthy volunteers (control group) were studied.LA and LV strain were assessed by 2DTT.The energy loss (EL) of LA and LV during ventricular systole (ELs),early diastole (ELed),and atrial contraction (ELac) were measured by VFM.Results LVEL in DM group was significantly increased compared to that in control group (P<0.05).LAELs and LAELed in control group were higher than those in DM group (P<0.05);while LAELac decreased in control group (P<0.05).Multivariate regression analysis identified E and LVELed as independent predictors of LAELed;Peak torsion,LA peak systolic strain and LVELac were independent predictors of LAELac.Conclusions The reservoir and conduit function of LA are impaired in patients with DM,while the pump function increases as a compensation.Abnormal LA-LV coupling also appears in patients with DM.

Objectives To detect the loss of heterozygosity(LOH)frequencies of microsatellite loci D9S171and D9S1604in p16gene of psoriatic keratinocytes,and to study the correlation between mi-crosatellite LOH of p16gene and the development of psoriasis.Methods By the use of polymerase chain reaction(PCR)-denaturing polyacrylamide gel electrophoresis-silver staining,LOH was detected with23sam-ples of keratinocytes from psoriatic lesions and non-lesion skin.Results LOH was identified at loci D9S171and D9S1604in5and10out of23keratinocyte samples from LOH-exhibited psoriatic lesions,and in2and3of keratinocyte samples from psoriatic non-lesion skin,respectively.The frequency of LOH at D9S1604was significantly higher in psoriatic lesion samples than that in psoriatic non-lesion skin(P

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.

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.