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:To provide evidence for rational use and clinical monitoring of Alprostadil lipid-micro injection (Li-po-PGE1). METHODS:Adult inpatients receiving Lipo-PGE1 from hospital information system(HIS)of 159 hospitals were select-ed as research subject. Based on frequency statistics,population,clinical diagnosis,and average daily dose of Lipo-PGE1 were all studied. RESULTS:A total of 71687 adult inpatients were included,and the male was more than female,mostly aged 61-75. The hospitalization duration was 8-14 d(45.01%),most of patients were recovered(68.20%). Lipo-PGE1 was wildly used in the clin-ic,and was used for 871 kinds of clinical diseases in total;top 3 diseases were cerebral infarction(9.06%),non-insulin dependent diabetes mellitus (8.65%) and chronic ischemic heart disease (8.08%). The average daily dose of different diseases and different hospitals were significantly different,mostly≤12.5μg. CONCLUSIONS:As adjuvant drug,medical institutions and related super-vision departments should formulate reasonable monitoring index and strengthen medication guidance and evaluation of Lipo-PGE1.

Objective To investigate the neuropathic pain (NP) accompanying spinal cord injury (SCI),and to analyze the related factors to provide references for its prevention and treatment.Methods Seventy SCI patients with NP were selected using the DN4 scale.Their age,gender,occupation,education level,monthly income,injury position,marital status and other data were surveyed using a general questionnaire.Their NP situation was surveyed using a simplified McGill pain questionnaire (SF-MPQ).Results The patients' average visual analogous scale (VAS) score was 4.37.Their average pain rating index (PRI) according to the SF-MPQ was 8.23,with the PRI-sensory and PRI-emotional components 5.23 and 3.00 respectively.The average degree of present pain intensity was 1.86,between mild pain and discomfort,and discomfort was the description most commonly used.The most common pain descriptor was prickling pain,followed by burning pain and bulge pain.85.7％ of the patients felt that their pain had an adverse effect on their affective state,and exhaustion occurred more often than any other descriptive words.Univariant analysis showed that the degree of injury,education level,marital status,monthly income,family support and medication history were all factors correlated with NP perceptions.Multi-variate logistic regression analysis showed that being unmarried and severity of injury were independent protective factors against NP.No family support,no medication and low income were independent risk factors for NP.Conclusion The type of neuropathic pain varies in patients with spinal cord injury.The intensity of the pain is mostly at a medium level.The emotional state of most patients was affected.Neuropathic pain involves many factors.Being unmarried and severely injured are independent protective factors,while lack of family support,no medication,and having low income were independent risk factors.

Objective: To study the influence of gallic acid (GA) on the migration of human gastric carcinoma SGC-7901 cells, and to explore its mechanism.Methods: The human gastric carcinoma SGC-7901 cells were cultured and divided into control group and 3.125, 6.250, 12.500, 25.000, 50.000,100.000 mg·L-1 GA groups. The inhibitory rates of proliferation of SGC-7901 cells in various groups were examined by MTT assay;the migration abilities of SGC-7901 cells in various groups were measured with scratch assay;the expression levels of vascular of endothelial growth factor (VEGF) in various groups were detected by immunocytochemistry.Results: Compared with control group, the inhibitory rates of proliferation of SGC-7901 cells in different doses of GA groups were significantly increased in a dose-dependent manner(F=59.451,P<0.01).Compared with control group, the wound healing rates in different doses of GA groups were significantly decreased (P<0.01).Compared with control group, the expression levels of VEGF protein in 12.500 and 25.000 mg· L-1 GA groups were decreased (P<0.05).Conclusion: GA could inhibit the proliferation and migration of SGC-7901 cells through down-regulating the expression levels of VEGF protein.

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.

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 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.