OBJECTIVETo study the effects of Ginkgo biloba extract (GBE) on the pharmacokinetics and pharmacodynamics of warfarin and observe the anticoagulant activity of GBE.

METHODA randomized, double-blinded, placebo-controlled, two-way cross-over trial was conducted. Twelve healthy volunteers (sex ratio was 1: 1) were randomized into two groups and received GBE (three pill, tid) or placebo (three pill, tid) for 5 weeks respectively. the subjects received a single dose of warfarin (5 mg) on the day 29. Blood samples for pharmacokinetics and pharmacodynamics assessment were collectd.

RESULTCompared with placebo, BE had no significant pharmacodynamics effects on warfarin and had no effects on prothrombin time (PT) and activated partial thromboplastin time (APTT). GBE extract increased C(max), AUC(0-144 min), AUC(0-infinity), t1/2, of warfarin significantly and decreased CL(F) of warfarin significantly (P < 0.05), and there were no singnificant difference of V(d) (F).

CONCLUSIONGBE has limited effects on the pharmacokinetics but no effects on the pharmacodynamics of single dose warfain in health subjects. GBE has no effects on clotting process alone.

Adult ; Anticoagulants ; pharmacology ; Double-Blind Method ; Female ; Ginkgo biloba ; Herb-Drug Interactions ; Humans ; Male ; Plant Extracts ; pharmacology ; Warfarin ; blood ; pharmacology ; Young Adult

Objective To explore the feasibility of 3D printed individualized applicator for the intracavitary HDR-brachytherapy for nasopharyngeal carcinoma.Methods CT scan was performed in 1 case of recurrent rT1 nasopharyngeal carcinoma and 1 case of T2 residual nasopharyngeal carcinoma and the obtained images were transmitted to 3D image processing software.The geometric contour parameters of the nasopharyngeal cavity were obtained and a pipeline was designed to make it close to the recurrent gross tumor volume (rGTV).Individualized cavity applicators were created by using 3D printer.The applicator was inserted into the patient's nasopharyngeal cavity through oral cavity.The source tube and false source were inserted into the preset pipe of the applicator.CT scan was performed again and the images were transmitted to the 3D brachytherapy planning system.Mter delineating the target volume and organ at risk,treatment plan was optimized.After completing the first treatment,the applicator was removed.Before second treatment in a few days,CT scan was reviewed to confirm whether the position was correct.Results When the applicator was inserted into the nasopharyngeal cavity,it could be fully aligned with the nasopharyngeal wall and self-fixed without additional fixation measures.Comparing the location of false source in multiple reviews of CT scan,the error was ≤ 1 mm.No significant discomfort was reported throughout the treatment.In optimized three-dimensional treatment,100％ prescription dose curve included the full rGTV,maximum dose of the brain stem and spinal cord was＜30％ prescription dose.Recurrent patients were given with a prescription dose of DT 40Gy/8 fractions/4 weeks and patients with residual tumors were given with 12Gy/2 fractions/1 week.No tumor recurrence was observed at postoperative 3 months in two cases.Conclusions The 3D printed individualized nasopharyngeal intracavitary applicator has the advantages of self-fixation,accurate location,good repeatability and good patient tolerance.The short-term outcome is effective,whereas its long-term clinical effect and adverse reactions need to be further observed.

Objective: To explore the function of NLRP1 in noninfectious pulmonary injury (nonIPI) after allogeneic stem cell transplantation (allo-HSCT) . Methods: In this study, we established the model of allo-HSCT with C57BL/6 and NLRP^-/- mouse as recipients. Chimera rate was measured by flow cytometry. The HE staining was used to observe the pathology changes in the lungs. NLRP1 and relevant inflammatory proteins were measured by Western Blot. Results: On the day 14 after allo-HSCT, the chimera rate was more than 96%, HSCs of donors had been successfully transplanted into recipients. HE staining showed that nonIPI occurred after allo-HSCT. The degrees of injuries reached the peak on day 21. In addition, the expressions of MPO, NLRP1, p20, Mature-IL-1β and Mature-IL-18 had same tends with the degrees of nonIPI. When we knocked out NLRP1 gene of recipients, the degrees of nonIPI reduced and the expressions of MPO, p20, Mature-IL-1β and Mature-IL-18 were less than in non-knockout group. Conclusion allo-HSCT could cause nonIPI and high expressions of MPO, p20, IL-1β, IL-18, NLRP1. Knocking out NLRP1 gene could alleviate the degrees of nonIPI and reduce the expressions of relevant inflammatory proteins, indicating that NLRP1 might be one of factors contributed to nonIPI after allo-HSCT.

Objective To investigate the dynamic expression of cluster of differentiation 47 (CD47) and its ligands signaling regulatory protein α (SIRPα) and thrombospondin-1 (TSP-1) in mice infected with Toxoplasma gondii in the second and third trimesters.. Methods C57BL/6J mice (6 to 8 weeks old) were used for modeling T. gondii infection in the first trimester, and the pregnant mice were randomly divided into the normal control and infection groups, of 10 mice in each group. Pregnant mice in the infection group were intraperitoneally injected with 150 T. gondii tachyzoites on gestational day (Gd) 6.5, while pregnant mice in the normal control group were intraperitoneally injected with the same volume of physiological saline at the same time. The uterine and placental specimens were collected from all pregnant mice on Gd12.5 and Gd18.5, and the pregnant outcomes were recorded. The pathological damages of mouse uterine and placental specimens were observed using hematoxylin-eosin (HE) staining on Gd12.5 and Gd18.5. The relative expression of CD47, SIRPα, TSP-1, surface antigen 1 (SAG1), interferon-γ (IFN-γ), interleukin-2 (IL-2), IL-4 and IL-13 mRNA was quantified in mouse uterine and placental specimens using real-time fluorescence quantitative PCR (qPCR) assay, and the CD47, SIRPα, TSP-1 expression was determined in mouse uterine and placental specimens using immunohistochemical staining. Results As compared with those in the normal control group, the pregnant mice in the infection group showed back arching, bristling, trembling and listlessness during pregnancy, and several mice presented virginal bleeding and abortion. Pathological examinations showed inflammatory cell infiltration, congestion and necrosis in uterine and placental specimens of pregnant mice in the infection group, a higher abortion rate of pregnant mice was seen in the infection group than in the normal control group on Gd12.5 (χ² = 20.405, P < 0.001) and Gd18.5 (χ² = 28.644, P < 0.001). qPCR assay showed significant differences in the expression of CD47, SIRPα, TSP-1, SAG1, INF-γ, IL-2, IL-4 and IL-13 genes in mouse placental specimens between the normal control and infection groups on Gd12.5 and Gd18.5 [F′ (F) = 37.511, 29.337, 97.343, 53.755, 67.188, 21.145, 8.658 and 13.930, all P values < 0.001]. Higher CD47, SIRPα and TSP-1 gene expression was quantified in mouse placental specimens in the infection group than in the normal control group on Gd12.5 (all P values < 0.01), and lower CD47, SIRPα and TSP-1 gene expression was quantified in the infection group than in the normal control group on Gd18.5 (all P values < 0.001), while higher SAG1 gene expression was detected in placental specimens of pregnant mice in the infection group than in the normal control group on Gd12.5 and Gd18.5 (both P values < 0.01). In addition, higher INF-γ and IL-2 expression and lower IL-4 and IL-13 expression was detected in mouse placental specimens in the infection group than in the normal control group on Gd12.5 and Gd18.5 (all P values < 0.001), and there were significant differences in the CD47, SIRPα, TSP-1, SAG1, INF-γ, IL-2, IL-4 and IL-13 gene expression in uterine specimens of pregnant mice between the normal control and infection groups on Gd12.5 and Gd18.5 [H(F′ and F) = 14.951, 25.977, 18.711, 48.595, 39.318, 14.248 and 15.468, all P values < 0.01], and higher CD47 and TSP-1 expression was detected in mouse uterine specimens in the infection group than in the control group on Gd12.5 and Gd18.5 (all P values < 0.01); however, no significant difference was found in the SIRPα expression (P > 0.05). Higher SAG1 expression was detected in uterine specimens of pregnant mice in the infection group than in the normal control group on Gd12.5 and Gd18.5 (both P values < 0.01), and higher INF-γ and IL-2 gene expression and lower IL-4 and IL-13 gene expression was found in the placental specimens of pregnant mice in the infection group than in the normal control group on Gd12.5 and Gd18.5 (all P values < 0.001). Spearman correlation analysis showed that the CD47 gene expression correlated positively with IFN-γ (r_s = 0.735, P < 0.05) and IL-2 (r_s = 0.655, P < 0.05) and negatively with IL-4 (r_s = −0.689, P < 0.05) and IL-13 expression (r_s = −0.795, P < 0.05) in the placental specimens of pregnant mice in the infection group on Gd12.5, and the CD47 gene expression correlated negatively with IFN-γ (r_s = −0.745, P < 0.05) and IL-2 expression (r_s = −0.816, P < 0.05) and positively with IL-4 (r_s = 0.704, P < 0.05) and IL-13 (r_s = 0.802, P < 0.05) in the placental specimens of pregnant mice in the infection group on Gd18.5. Immunohistochemical staining showed mild CD47, SIRPα and TSP-1 expression in uterine and placental specimens of pregnant mice in the normal control group on Gd12.5 and Gd18.5, strong CD47, SIRPα and TSP-1 expression in the placental specimens of pregnant mice in the infection group on Gd12.5 and strong CD47 and TSP-1 expression in the uterine specimens of pregnant mice in the infection group on Gd12.5. Conclusions T. gondii infection in the first trimester may cause abnormal expression of CD47 and its ligands SIRPα and TSP-1 in the maternal-fetal interface of pregnant mice in the second and third trimesters, which may be associated with the immune escape of T. gondii at the maternal-fetal interface.