Expression of tissue factor in rabbit pulmonary artery in an acute pulmonary embolism model / 世界急诊医学杂志（英文）

BACKGROUND:Tissue factor (TF) is the initiation factor of the extrinsic coagulation pathway, and plays a critical role in the process of thrombosis. This study aimed to investigate the expression of TF and to explore their clinical effect on the pulmonary artery after acute pulmonary thromboembolism. METHODS:Thirty-four Japanese white rabbits (Level II animals) supplied by Tianjin Medical University were randomly assigned into:group A, specimens of the pulmonary artery taken 3 hours after pulmonary embolism (n=8); group B, specimens of the pulmonary artery taken 8 hours after pulmonary embolism (n=8); group C, specimens of the pulmonary artery taken 24 hours after pulmonary embolism (n=8); and control group, pseudo-operations performed without injection of autologous blood clots (n=10). The animal model of pulmonary thrombo-embolism was established by injection of autologous blood clots into the jugular vein through a 5F catheter, and was confirmed by digital subtraction angiography. The mRNA expression of TF in different parts of the pulmonary artery was accessed by RT-PCR. Theq test was used if there was a significant difference in a given continuous variable among the three groups assessed by ANOVA. The experiment equipment was supplied by the State Key Laboratory of Experimental Hematology, Institute of Hematology and Blood Diseases Hospital, the Chinese Academy of Medical Sciences and Peking Union Medical College. RESULTS:The TF expression in the specimen adjacent to emboli was stable at 3, 8 or 24 hours after embolism. The mRNA expression of TF at 3 and 8 hours after embolism was lower in the specimens taken from the distal end of the morbid pulmonary artery than those adjacent to emboli. While at 24 hours after embolism, there were similar mRNA levels in specimens either adjacent or distal to emboli. CONCLUSION:The high level of TF expression in pulmonary artery tissue adjacent to emboli could lead to locally increased coagulation activity, indicating the necessity of initiating anti-coagulation treatment as soon as possible after acute pulmonary embolism.

The association between polymorphism of transforming growth factor-β1 and radiochemotherapy response and survival in esophageal squamous cell carcinoma patients / 中华预防医学杂志

<p><b>OBJECTIVE</b>To evaluate the association between polymorphism of transforming growth factor-β1 (TGF-β1)-509C/T and radiochemotherapy response and survival in esophageal squamous cell carcinoma (ESCC) patients.</p><p><b>METHODS</b>The genotype of TGF-β1-509C/T was detected by polymerase chain reaction-based restriction fragment length polymorphism assay (PCR-RFLP) in 230 ESCC patients receiving radiotherapy alone or in combination with chemotherapy. Unconditional multivariate logistic regression analysis was done to estimate adjusted odds ratios (ORs) along with the corresponding 95% confidence intervals (CIs) for the polymorphism and radiochemotherapy response. The associations between overall survival time or hazard ratio (HR) of ESCC patients and genetic variation or the clinical data were estimated by applying univariate and multivariate Cox-regression analyses.</p><p><b>RESULTS</b>Among 208 patients with upper gastrointestinal contrast assessment, 87 cases were susceptible to radiochemotherapy treatment and the TGF-β1-509CC, CT and TT genotype patients were 17 (19.5%), 48 (55.2%) and 22 (25.3%), respectively. Among the patients who were insensitive to radiochemotherapy treatment (n = 121), the TGF-β1-509CC, CT and TT genotype patients were 39 (32.2%), 54 (44.6%) and 28 (23.2%), respectively. Compared with TGF-β1-509CC genotype, the CT and TT genotype carriers had a significantly better treatment response (adjusted OR = 2.07, 95%CI, 1.05 - 4.09, P = 0.036). The median survival time of CC genotype patients was 17.0 (95%CI, 12.0 - 23.0) months, CT genotype patients was 22.0 (95%CI, 16.0 - 33.0) months and TT genotype patients was 25.0 (95%CI, 15.0 - 41.0) months. Compared to CC genotype patients, the survival time difference of CT and TT group was close to the statistical break point (P = 0.063). Our data showed that the subjects with CT or TT genotype had an decreased HR respectively as compared with those with CC genotype (CT, adjusted HR = 0.81, 95%CI, 0.52 - 1.24; TT, adjusted HR = 0.86, 95%CI, 0.65 - 1.12), but the difference was not statistically significant (P > 0.05). However, tumor location, clinical stage and radiochemotherapy response affected the overall survival time of the patient significantly (adjusted HR = 1.28, 95%CI: 1.01 - 1.61, P = 0.040; 1.49, 95%CI, 1.17 - 1.88, P = 0.001; 1.55, 95%CI, 1.06 - 2.26, P = 0.023, respectively).</p><p><b>CONCLUSION</b>These results suggest that TGF-β1-509C/T polymorphisms were associated with radiochemotherapy for esophageal squamous cell carcinoma which might be genetic markers for prediction of the radiochemotherapy response in ESCC patients.</p>

Relationships between the gene polymorphisms of drug metabolizing enzymes and the outcome of the first induction chemotherapy in patients with de novo acute myeloid leukemia / 中国实验血液学杂志

The objective of this study was to investigate the correlation between the gene polymorphisms of drug metabolizing enzymes and the outcome of the first induction chemotherapy in patients with de novo acute myeloid leukemia (AML). 113 de novo AML patients were enrolled in this study. The genotypes of 11 single nucleotide polymorphisms (SNP) in drug metabolizing enzymes were detected by the SNPstream(®) Genotyping System. The correlation between the distribution of genotypes and the complete remission rate of first induction chemotherapy was analyzed by logical regression. The results showed that patients with variant genotype of CYP2D6 (rs16947) had a lower complete remission (CR) rate, as compared to those with wild type (p = 0.033, OR = 0.32, 95%CI 0.112 - 0.915); meanwhile the patients with variant genotype of GSTO2 (rs156697) had a higher CR rate as compared to those with wild type (p = 0.011, OR = 3.023, 95%CI 1.289 - 7.089). Combined analysis of the above polymorphisms, showed that patients with variant genotype of CYP2D6 and wild genotype of GSTO2 (V + W) had lower CR rates in comparison to patients with wild genotypes of both polymorphisms (p = 0.017, OR = 0.183, 95%CI 0.045 - 0.735). It is concluded that CYP2D6 (rs16947) and GSTO2 (rs156697) polymorphisms are independent factors influencing CR rates of the first induction chemotherapy in de novo AML patients.

Analysis on promoter CpG methylation and expression of HOXB4 gene in cord blood CD34(+) cells and peripheral blood mononuclear cells / 中国实验血液学杂志

This study was aimed to examine the expression and promoter CpG island methylation of homeobox B4 (HOXB4) gene in CD34(+) cells from cord blood and peripheral blood mononuclear cells (PBMNCs) from health adult, and to investigate the expression level of HOXB4 in these two cells and its relationship with the promoter methylation. Semi-quantitative reverse transcription polymerase chain reaction (RT-PCR) was used to examine the expression of HOXB4 in CD34(+) cells and PBMNCs, and bisulfite sequencing technique was used to detect the methylation status of the promoter CpG sites of HOXB4 gene in CD34(+) cells and PBMNCs. The results indicated that highly expressed HOXB4 and unmethylation of HOXB4 promoter CpG island occurred in CD34(+) cells. However, loss of HOXB4 expression and the methylated CpG island of HOXB4 were observed in PBMNCs, and the methylated C residue was positioned at -129 bp in the upstream of ATG. It is concluded that the methylation status of HOXB4 gene promoter may be one negative regulatory mechanism for HOXB4 gene expression. The unmethylation of CpG island in the promoter region of HOXB4 gene may be correlated with the high expression of HOXB4 gene in CD34(+) cells, while the promoter methylation of HOXB4 gene may be associated with HOXB4 gene silencing in PBMNCs. The preliminary identification of HOXB4 promoter methylation site would provide a basis for further study and a novel approach to expand hematopoietic progenitor cells.

Effect of Recombinant N-segment of Thrombospondin-1 on the Proliferation of ECV304 / 中国生物工程杂志

Objective: To construct an expression system containing the N-terminal segment of Thrombospondin-1 (TSP-1) in E. coli. To investigate the activity of TSF. Methods: thbs1 gene fragment was amplified from human fetal cord vein endothelial cells and inserted into plasmid pET32c ( + ) which was then transfected and expressed in E. coli. Investigate the effect of recombinant TSF to the proliferation of ECV304 in vitro with MTT. The expression level of CD36 was assayed by FACS. Results: Recombinant TSF was purified. TSF could restrain the proliferation of ECV304 with CD36 low-expression. Conclusions:Low dose of rTSF was a latent assistant treatment of anti-cancer.