Adult ; Gamma Rays ; Humans ; Male ; Radiation Protection ; instrumentation ; Space Suits

An HPLC method for the determination of 18alpha-glycyrrhetinic acid and 18beta-glycyrrhetinic acid in rat plasma was established, which was used subsequently to determine the pharmacokinetic profiles of both epimers of glycyrrhetinic acid in rats. alpha-glycyrrhetinic acid, beta-glycyrrhetinic acid, and a mixture of alpha-glycyrrhetinic and beta-glycyrrhetinic acids were administered to rats via gastric infusion. Blood samples were collected at different time intervals and extracted by liquid-liquid extraction. Separation was achieved by using a Kromasil C18 column (150 mm x 4.6 mm, 5 microm) with the mobile phase composed of acetonitrile--4 mmol x L(-1) ammonium acetate solution (46 : 54, v/v) at a flow rate of 1.0 mL x min(-1), and the detection wavelength was set at 250 nm. The pharmacokinetic parameters were calculated using the software DAS 2.0. In a combined administration, the main pharmacokinetic parameters of beta-glycyrrhetinic acid are significantly different from that of alpha-glycyrrhetinic acid (P < 0.05), while no significant difference was obtained when administrated individually. Compared to the single administration, significant differences (P < 0.05) on the values of AUC(0-t) and AUC(0-infinity) of beta-glycyrrhetinic acid were observed when this chemical was administrated together with alpha-glycyrrhetinic acid. In contrast, the pharmacokinetic parameters of alpha-glycyrrhetinic acid were not affected even under the co-administration. Here, a sensitive, specific, rapid and reproducible HPLC method was developed for the pharmacokinetic studies of alpha-glycyrrhetinic acid and beta-glycyrrhetinic acid in rat plasma.

Objective To observe the immunostaining of endothelin-1(ET-1) and von Willebrand factor(vWF) in pulmonary vascular of ventricular septal defect(VSD) with pulmonary hypertension(PH),and the possible roles of ET-1 and vWF in the development of PH and remodeling in pulmonary artery.Methods VSD with non-PH were choosed as control group,20 cases with VSD with PH were divided into Ⅰgroup and Ⅱgroup according to mean pulmonary artery pressure. The specimens from middle lobe of right lung was obtained and stained by immunohistochemical technique.The degree of immunoreaction was measured with light density.Results The light density of ET-1 and vWF in small pulmonary arteries had significant statistical difference between every group,and Ⅱgroup was higher than those of Ⅰgroup,but no difference in small pulmonary veins.In every group,the light density of ET-1 and vWF had significant difference between small pulmonary arteries and pulmonary veins.There were statistical correlation among mean pulmonary pressure,VSD/A,ET-1 and vWF.Conclusions ET-1 and vWF are concerned with the development of PH and mediate pulmonary vascular remodeling.The data of small pulmonary veins suggest that the main origin of ET-1 in pulmonary tissue is small pulmonary artery.

An HPLC method for the determination of 18alpha-glycyrrhetinic acid and 18beta-glycyrrhetinic acid in rat plasma was established, which was used subsequently to determine the pharmacokinetic profiles of both epimers of glycyrrhetinic acid in rats. alpha-glycyrrhetinic acid, beta-glycyrrhetinic acid, and a mixture of alpha-glycyrrhetinic and beta-glycyrrhetinic acids were administered to rats via gastric infusion. Blood samples were collected at different time intervals and extracted by liquid-liquid extraction. Separation was achieved by using a Kromasil C18 column (150 mm x 4.6 mm, 5 microm) with the mobile phase composed of acetonitrile--4 mmol x L(-1) ammonium acetate solution (46 : 54, v/v) at a flow rate of 1.0 mL x min(-1), and the detection wavelength was set at 250 nm. The pharmacokinetic parameters were calculated using the software DAS 2.0. In a combined administration, the main pharmacokinetic parameters of beta-glycyrrhetinic acid are significantly different from that of alpha-glycyrrhetinic acid (P < 0.05), while no significant difference was obtained when administrated individually. Compared to the single administration, significant differences (P < 0.05) on the values of AUC(0-t) and AUC(0-infinity) of beta-glycyrrhetinic acid were observed when this chemical was administrated together with alpha-glycyrrhetinic acid. In contrast, the pharmacokinetic parameters of alpha-glycyrrhetinic acid were not affected even under the co-administration. Here, a sensitive, specific, rapid and reproducible HPLC method was developed for the pharmacokinetic studies of alpha-glycyrrhetinic acid and beta-glycyrrhetinic acid in rat plasma.
Animals ; Area Under Curve ; Chromatography, High Pressure Liquid ; methods ; Glycyrrhetinic Acid ; analogs & derivatives ; blood ; pharmacokinetics ; Male ; Rats ; Rats, Sprague-Dawley ; Stereoisomerism

OBJECTIVETo investigate the relationship between the changes of the L-type calcium current (I(Ca, L)) and the calcium-activated transient outward chloride current (I(Cl, Ca)), and the repolarization characteristic of action potential in phase 1 under isoprenaline (ISO) stimulation in atrium myocytes of rabbit.

METHODSAtrium myocytes were obtained by enzymatic dissociation from a section of atrial free wall. The membrane currents and action potential were recorded by the whole-cell patch-clamp technique.

RESULTSAfter recording I(Ca, L), atrium myocytes were perfused with ISO (1 micromol/L) immediately. Five minutes later, a transient outward current (I(to)) was significantly induced, and the peak of I(to) was gradually increased while I(Ca, L) gradually decreased with increasing in clamp voltage. The I(to) was resistant to 4-AP (3 mmol/L) but sensitive to DIDS (150 micromol/L, Cl(-) channel blocker). This current was blocked by CdCl(2) (200 micromol/L, Ca(2+) channel blocker). The elicited rate of I(to) was 91.67% (P < 0.05). (2) The shape of AP was like an inverse triangle with no plateau in Phase 2 after ISO (1 micromol/L) perfusion. Moreover, compared to the parameters of control group, APD(50) and APD(90) were significantly shortened from (65.4 +/- 4.2) ms and (95.8 +/- 3.8) ms to (12.8 +/- 3.8) ms and (27.0 +/- 4.7) ms, and reduced to 80.46% and 71.87%, respectively (P < 0.01, n = 12). 4-AP (3 mmol/L) had on obvious effect on the shape of AP, however, the plateau of AP in phase 2 was recovered by DIDS (150 micromol/L) perfusion, APD(50) and APD(90) were (41.1 +/- 4.5) ms and (79.6 +/- 3.4) ms respectively. Compared to the parameters of control group, there were no significant differences (P > 0.05, n = 12). These results indicated that ionic transport were changed by ISO perfusion in atrium myocytes and I(to) played an important role in the phase 1 repolarization of AP.

CONCLUSIONSBefore ISO administration, we could only observe I(Ca, L) in atrium myocytes of rabbit. After isoproterenol intervention, certain intracellular ionic consistency and membrane ionic channels were changed. Calcium activated chloride channel and I(to2) revealed obvious predominance which shorten APD significantly. Action potential showed a triangle with no plateau, suggesting an electrical remodeling in atrium myocytes. The remodeling of ionic channel is related possibly with the opening of Ca(2+)-activated Cl(-) current, which maybe the electrophysiological base of reentrant atrial tachycardia.

Animals ; Calcium ; metabolism ; Calcium Channels, L-Type ; metabolism ; Calcium Signaling ; Cells, Cultured ; Chloride Channels ; metabolism ; Heart Atria ; cytology ; metabolism ; Ion Transport ; Isoproterenol ; pharmacology ; Myocytes, Cardiac ; drug effects ; metabolism ; Patch-Clamp Techniques ; Rabbits

OBJECTIVETo investigate the morphological features and immunophenotype of unspecified peripheral T cell lymphoma with distinct lymphoid follicular growth pattern.

METHODSThree cases of peripheral T cell lymphoma with special pathohistological features were collected. Morphologic analysis and immunohistochemical staining for CD3, CD45RO, CD43, CD20, CD79a, cyclinD1, bcl-2, CD4, CD8 and S-100 were performed. PCR was used to study TCR gamma gene rearrangements.

RESULTSThe main symptoms of all the three patients with the primary sites of cervix and lower jaw. There were intermittent fever and skin rashes in the course of the disease. Morphological study showed lymphoid follicular reactive hyperplasia, mantle zone disappear, prominent infiltration of marginal zones by medium-sized tumor cells with clear cytoplasm and significant nuclear atypia. The immunophenotypic profile confirmed that they were T cell lymphomas. TCR gamma gene rearrangements were found in all the three patients.

CONCLUSIONIn some unspecified peripheral T cell lymphomas, the distinct follicular growth pattern and incomplete effacement of the lymph node architecture make it necessary to differentiate them from reactive hyperplasia, marginal zone B cell lymphoma, follicular B cell lymphoma and mantle cell lymphoma.

Adult ; Antigens, CD ; analysis ; Cyclin D1 ; analysis ; Female ; Gene Rearrangement ; Genes, T-Cell Receptor ; genetics ; Humans ; Immunohistochemistry ; Jurkat Cells ; Lymph Nodes ; metabolism ; pathology ; Lymphoma, T-Cell, Peripheral ; genetics ; metabolism ; pathology ; Male ; Proto-Oncogene Proteins c-bcl-2 ; analysis ; Retrospective Studies ; S100 Proteins ; analysis

OBJECTIVETo investigate the effects of bortezomib on the migration of endothelial cells and the expression of angiogenesis-related molecules, and explore the mechanism of its antiproliferation of tumor cells.

METHODSCell count kit CCK-8 was used to detect the relative proliferation activity of cells after treated by bortezomib at different concentrations for 12 h and 24 h, respectively. Transwell model was uesd to detect the migration rate of cells. Expression levels of VEGF and Annexin A2 genes were determined by real-time quantitative PCR. Annexin A2 protein was validated by Western blot.

RESULTSAfter treated with bortezomib at concentrations of 2.5, 5.0 and 10 nmol/L for 12h, respectively, the HMEC-1 cell proliferation activity was 1.004 ± 0.002, 0.793 ± 0.021 and 0.874 ± 0.062, respectively, being no statistical difference from that of control group (1.000) P < 0.05); while the migration rates of them were 0.697 ± 0.060, 0.597 ± 0.090 and 0.874 ± 0.062, respectively, being significantly lower than that of control group (1.000) (P < 0.05) and so did for the expression of VEGF and Annexin A2 genes. After treated with 5 nmol/L bortezomib for 12 h, the Annexin A2 and VEGF gene relative expression level of HMEC-1 cells was 0.540 ± 0.001 and 0.793 ± 0.153, respectively, being of statistical difference from that of control group (1.000) P < 0.05). The conspicuous downregulation of Annexin A2 protein was also confirmed by Western Blot.

CONCLUSIONSBortezomib can inhibit migration of endothelial cell HMEC-1 by downregulating the expression of VEGF and Annexin A2, displaying a new mechanism of bortezomib for inhibition of tumor proliferation.

Annexin A2 ; metabolism ; Bortezomib ; Cell Proliferation ; drug effects ; Endothelial Cells ; metabolism ; Humans ; RNA, Messenger ; genetics ; Vascular Endothelial Growth Factor A ; metabolism

Objective To investigate the value of diffusion weighted imaging(DWI)in predicting delayed encephalopathy of the rabbits brain after carbon monoxide(CO)poisoning.Methods Sixty healthy rabbits were put into self-made poisoning cabinet and were poisoned by inhalation of CO.Aeration of CO was stopped when the rabbits became comatous,and the cabinet was kept airpoof for 6 h.The rabbits underwent MRI before poisoning,at 1 h,3 d,5 d,7 d,15 d,30 d,45 d,and 60 d after poisoning respectively. Axial and sagittal T_2WI,axial T_1WI and DWI were performed.In the rabbits that did not show symptoms of delayed encephalopathy,the observation was discontinued on the 60~(th)day.In the rabbit that showed the symptoms,the observation was discontinued on the 30~(th)——45~(th)day.The changing pattern of cortical ADC values before and after CO poisoning was observed and its relationship with delayed encephalopathy was investigated.Results In the group without delayed encephalopathy(15 rabbits),the ADC value at 1 h after poisoning[(7.58?0.36)?10~(-4)mm~2/s]decreased significantly compared with the pre-poisoning value[(8.02?0.35)?10~(-4)mm~2/s](q=0.4441,P0.05).In the group with delayed encephalopathy(15 rabbits),the ADC value at 1 h after poisoning [(7.40?0.32)?10~(-4)mm~2/s]decreased significantly compared with the pre-poisoning value[(8.08? 0.32)?10~(-4)mm~2/s](q=0.6728,P

Objective: To explore the prognostic factors of patients with intrahepatic cholangiocarcinoma (ICC) after surgical resection and establish a nomogram for survival prediction. Methods: A total of 160 patients with ICC who underwent surgical resection in the First Affiliated Hospital of Xi′an Jiaotong University from January 2010 to December 2018 were retrospectively analyzed. Among them, 89 patients were males and 71 were females, aged from 29 to 81 years with a age of (57.41±10.35) years. Observation indicators included: (1) The result of follow-up: postoperative survival. (2) The univariate analysis and multivariate analysis affecting postoperative patients′ prognosis. (3) The establishment and validation of nomogram model. The follow-up using outpatient and telephone was performed once every 3 months within 1 year postoperatively and once every 3-6 months after 1 year postoperatively up to August 1, 2019. The follow-up included liver function, CA19-9, upper abdominal ultrasound, CT or MRI. The overall postoperative survival time, end point of observation, was the date from the operation date to the follow-up date, or the date of death due to tumor recurrence and metastasis. The patients′ clinicopathological data was included in the prognostic factor analysis, the Kaplan-meier method and Log-rank test were conducted for the univariate analysis, the Cox proportional risk regression model was used for the multivariate analysis. The independent risk factors based on Cox regression model were screened to establish a nomogram for postoperative survival prediction. The patients were divided into the model group (n=112) for the establishment of survival nomogram and the validation group (n=48) for the assessment of predictive ability at a ratio of 7∶3, and the accuracy of nomogram in postoperative survival prediction was assessed by c-index. Measurement data with normal distribution were expressed with (Mean±SD). Measurement data with skewed distribution were described as M (range). Count data were expressed as cases and percentage. Results: During the follow-up period, all patients with ICC after surgical resection were followed up for a survival time of 20 months (2-111 months). 100 patients died of multiple organ failure caused by tumor recurrence and metastasis and 60 patients survived. The 1-, 3- and 5-year overall survival rates of patients were 63.3%, 30.0% and 19.6%, respectively. Univariate analysis showed that CA19-9, hepatolithiasis, number of tumor, range of liver resection, tumor differentiation, pathology type, tumor diameter, vascular invasion, TNM stage, lymphatic metastasis, satellite foci and surgical margin were the prognostic factors of ICC patients after surgical resection (HR=1.78, 1.97, 2.91, 1.89, 3.06, 2.86, 2.07, 1.94, 2.24, 1.95, 2.68, 2.00, 95%CI: 1.12-2.85, 1.22-3.16, 1.85-4.56, 1.26-2.85, 1.38-6.82, 1.31-6.25, 1.37-3.14, 1.07-3.51, 1.24-4.06, 1.26-3.01, 1.28-5.60, 1.11-3.59, P<0.05). Multivariate analysis showed that hepatolithiasis, number of tumor, range of liver resection, tumor differentiation (low differentiation) and pathology type were independent risk factors of ICC patients after surgical resection (HR=2.47, 2.37, 2.06, 5.52, 5.72, 95%CI: 1.39-4.38, 1.44-3.91, 1.25-3.40, 1.24-24.49, 2.31-14.17, P<0.05). The nomogram was established based on above five independent risk factors, the c-index value for postoperative survival of the model group and validation group were 0.71 (95%CI: 0.64-0.79) and 0.71(95%CI: 0.61-0.81), respectively. Conclusion A nomogram based on hepatolithiasis, number of tumor, range of liver resection, tumor differentiation and pathology type has better accuracy in postoperative survival prediction for patients with ICC.

OBJECTIVETo analyze the allele frequencies of 7 short tandem repeat (STR) loci (D12S1718, D12S1675, D12S358, D12S367, D12S1638, D12S1646 and D12S1682) on chromosome 12 among Kashing-Beck disease (KBD) patients and the control population living in the KBD areas and non-KBD area.

METHODSEDTA-blood specimens were collected from 102 unrelated individuals of Chinese Han population in Shaanxi province including 29 KBD patients,30 controls living in the KBD area and 43 living in the non-KBD area. DNA samples were extracted using the Wizard Genomic DNA purification kit (http://www. Promega. com) and were amplified by polymerase chain reaction (PCR) technique. The PCR products were analyzed by ABI 3100 Genetic Analyzer.

RESULTS(1) In KBD patients group, the allele number for 7 STR loci were 4,7,7,8,5,5 and 7, the genotype number were 5,12,13,11,10,9 and 13; (2) In the control population living in KBD area, the allele number for 7 STR loci were 4,9,7,6,6,6 and 8,t he genotype number were 5,10,12,14,12,9 and 13;(3) In the control population living in the non-KBD area, the allele number for 7 STR loci were 7,9,7,7,5,8 and 11, the genotype number were 9,16, 17,16,12,15 and 20;(4) Compared with the allele frequencies among three groups, there were significant differences between KBD patients and the controls living in the KBD area (D12S367: P = 0.034; D12S1638: P = 0.041) and the controls living in the non-KBD area (D12S367: P = 0. 029; D12S1638: P= 0 .028) in the D12S367 and D12S1638 loci; (5) There were significant differences among KBD patients (P = 0.036), controls living in the KBD area (P = 0.039) and controls living in the non-KBD area in the D12S1646.

CONCLUSIONThere was significant difference between KBD patients and the controls in the D12S367 and D12S1638 loci.

Adult ; Case-Control Studies ; Child ; Chromosomes, Human, Pair 12 ; genetics ; Female ; Gene Frequency ; Genetic Loci ; genetics ; Genotype ; Humans ; Joint Diseases ; genetics ; Male ; Microsatellite Repeats ; genetics