AIM: To investigate the effect of endotoxin on rat hepatic mitochondria. METHODS: Rats were randomly divided into two groups:endotoxin group and the control. 8 cases of animals were included in each group. The effect of electron leak on the production of endogenous oxygen free radicals and the changes of mitochondria function were studied.RESULTS: Treated with endotoxin, a significant increase in O  2 and the rate of state 3,4 were observed in liver mitochondria; The rate of electron transfer to proton pump of mitochondria respiratory chain complex Ⅱ+Ⅲ( H +/2e -), respiratory control rate and ADP/O decreased significantly. CONCLUSION: A increase in production of endogenous oxygen free radicals induced by endotoxin plays an important role in the injury of rat liver mitochondria.

OBJECTIVE: To explore molecular etiology and clinical characteristics of two pedigrees affected with hereditary factor VII(FVII) deficiency. METHODS: The nine exons and flanking sequences of the F7 gene of the probands were amplified by PCR. The amplicons were analyzed by direct sequencing. Suspected mutations were subjected to SWISS-MODEL modeling and analysis of protein structure change by Pymol software and conservation of amino acids across various species. RESULTS: For proband of pedigree 1, the prothrombin time (PT), FVII activity (FVII:C) and FVII antigen (FVII:Ag) were 36.3 s, 3%, 53.56%, respectively. Sequencing revealed a compound heterozygous variants of c.80_81delCT and c.1371G>T(p.Arg439Ser). His son carried a heterozygous c.1371G>T (p.Arg439Ser) variant. For proband of pedigree 2, the PT, FVII:C and FVII:Ag were 22.3 s, 4%, 1.58%, respectively. Sequencing has revealed a compound heterozygous c.278G>T(p.Arg75Met) missense variant in exon 3 and c.1278T>G (p.His408Gln) in exon 9 of the F7 gene. His mother and son both carried a heterozygous c.278G>T(p.Arg75Met) variant. Three-dimensional simulation and homology analysis revealed that the p.Arg439Ser and p.Arg75Met can respectively alter part of hydrogen bonds and two highly conserved amino acids. CONCLUSION Two novel heterozygous missense variants of the F7 gene [c.1371G>T(p.Arg439Ser) and c.278G>T(p.Arg75Met)] probably account for the decrease of factor VII in the two pedigrees.
Asian Continental Ancestry Group ; Factor VII ; Factor VII Deficiency ; Genotype ; Heterozygote ; Humans ; Mutation ; Pedigree

OBJECTIVE: To carry out phenotypic and genotypic analysis for two Chinese pedigrees affected with coagulation factor XII (F XII) deficiency. METHODS: Plasma prothrombin time (PT), activated partial thromboplastin time (APTT), fibrinogen (FIB), thrombin time (TT), and blood coagulation factor VIII, IX, XI, XII activity (FVIII:C, FIX:C, FXI:C, FXII:C) were determined with one stage clotting assay on a STAGO coagulation analyzer. FXII antigen was determined with an enzyme linked immunosorbent assay (ELISA). The 14 exons and their flanking sequences of the F12 gene were subjected to PCR amplification and Sanger sequencing. The conservation and structure of mutant protein were analyzed with MegAlign software and PYMOL software. RESULTS: The APTT of the probands was significantly prolonged, while their FXII:C and FXII:Ag were significantly reduced. Genetic analysis of the proband has revealed three novel mutations in the F12 gene, including g.5972G>A splice site mutation in intron 5, g.8810_8814delGTCTA in exon 14, and g.6259G>A (p.Pro182Leu) in exon 7. In addition, a previously known mutation IVS13-1G>A has been found. CONCLUSION Four mutations have been identified in the two Chinese pedigrees, among which three were novel. Above mutations probably played a role in the defect of FXII in the two pedigrees.
Exons ; Factor XII ; genetics ; Factor XII Deficiency ; genetics ; Genetic Testing ; Humans ; Pedigree

OBJECTIVE: To analyze the phenotype and genotype of a patient affected with inherited antithrombin deficiency. METHODS: All exons and exon-intron boundaries of the AT genes were subjected to PCR amplification and Sanger sequencing. The influence of variants on the disease was predicted using bioinformatic software (MutationTaster). RESULTS: The results of all coagulation tests were normal, though the antithrombin activity and antigen content of the proband and his father have decreased significantly (34%, 48% and 12.97 mg/dL, 15.60 mg/dL, respectively). His mother was normal. Genetic analysis revealed that the proband and his father both carried a heterozygous g.2736dupT variant of the AT gene. Bioinformatic analysis suggested that the variant may be pathogenic. CONCLUSION The proband and his father both had type I hereditary antithrombin deficiency caused by a g.2736dupT variant of the AT gene. The variant was unreported previously.
Antithrombin III/genetics* ; Antithrombin III Deficiency/genetics* ; DNA Mutational Analysis ; Genetic Testing ; Heterozygote ; Humans ; Male ; Mutation ; Pedigree

Objective:To analyze the clinical features and the effects of different treatments on 5-year overall survival (OS) rate and 5-year disease free survival (DFS) rate of stage 0-Ⅲ triple-negative breast cancer (TNBC).Methods:The data of 209 patients diagnosed as stage 0-Ⅲ TNBC in Ward 2 of Department of General Surgery of the Fifth Medical Center of PLA General Hospital from January 2004 to December 2013 were selected. The relationships between the clinical features, treatments and 5-year OS rate, 5-year DFS rate were retrospectively analyzed. Kaplan-Meier method was used to draw survival curves, and Cox proportional risk model was used for multivariate analysis.Results:Univariate analysis found that clinical stage and methods of surgery were associated with 5-year OS rate ( χ2=52.615, P<0.001; χ2=17.329, P=0.001) and 5-year DFS rate ( χ2=55.112, P<0.001; χ2=18.816, P<0.001). Multivariate analysis showed that clinical stage was an independent prognostic factor of DFS ( HR=3.637, 95% CI: 2.146-6.164, P<0.001) and OS ( HR=3.545, 95% CI: 2.091-6.009, P<0.001). For the TNBC patients without axillary lymph node metastasis ( n=118), the 5-year OS rates of patients with breast conservation surgery + sentinel lymph node biopsy, total breast resection + sentinel lymph node biopsy, modified radical mastectomy and breast conserving surgery + axillary lymph node dissection were 97.6%, 97.7%, 91.4%, 100% respectively, the 5-year DFS rates were 97.3%, 94.3%, 85.8%, 100% respectively, and there were no significant differences among the four groups ( χ2=3.369, P=0.338; χ2=3.868, P=0.276). The 5-year OS rate (74.5% vs. 91.1%) and 5-year DFS rate (73.6% vs. 86.8%) were significantly different in patients receiving neoadjuvant chemotherapy ( n=106) compared with those receiving adjuvant chemotherapy ( n=80) ( χ2=4.504, P=0.034; χ2=4.683, P=0.030). The patients receiving neoadjuvant chemotherapy had later clinical stages than those receiving adjuvant chemotherapy ( χ2=35.314, P<0.001). There were no significant differences in 5-year OS rate and 5-year DFS rate between the patients receiving neoadjuvant chemotherapy and adjuvant chemotherapy with the same clinical stage (all P>0.05). The 5-year OS rates of patients with pathologic complete response (pCR), partial response (PR) and stable disease (SD) obtained by neoadjuvant chemotherapy were 100%, 75.8% and 57.1% respectively, and the 5-year DFS rates were 100%, 74.5% and 55.7% respectively, with statistically significant differences ( χ2=10.086, P=0.006; χ2=10.399, P=0.006). Between the pCR group and the PR group, the 5-year OS rate ( χ2=4.238, P=0.040) and 5-year DFS rate ( χ2=4.525, P=0.033) were significantly different. Between the pCR group and the SD group, the 5-year OS rate ( χ2=8.163, P=0.004) and 5-year DFS rate ( χ2=8.509, P=0.004) were significantly different. Between the PR group and the SD group, the 5-year OS rate ( χ2=3.931, P=0.047) and 5-year DFS rate ( χ2=3.896, P=0.048) were significantly different. Conclusion:For the patients with stage 0-Ⅲ TNBC, clinical stage is an independent prognostic factor. For the TNBC patients without axillary lymph node metastasis, breast conservation surgery + sentinel lymph node biopsy, total breast resection + sentinel lymph node biopsy, modified radical mastectomy and breast conserving surgery + axillary lymph node dissection have similar outcomes. There is no significant difference between neoadjuvant chemotherapy and adjuvant chemotherapy in the prognosis of patients with the same clinical stage, but patients with pCR or PR obtained by neoadjuvant chemotherapy can achieve better survival.

Objective To understand the situation and the influencing factors of life quality in diabetic patients in Shanghai， and to develop effective intervention measures. Methods A total of 212 diabetic patients in Baoshan District， Shanghai were selected as the research objects. Diabetes specific quality of life scale （DSQL） was used to investigate the basic situation and quality of life of patients. Combined with biochemical detection indexes and questionnaire survey， data were analyzed by variance analysis and multiple linear stepwise regression analysis. Blood glucose level was assessed according to the 1999 WHO diagnostic criteria for type 2 diabetes. Results The overall quality of life score in the patients was 4.31±7.82， which was higher than the domestic norm. The best quality of life was in the dimension of physiological function with the score of 1.84±6.00， which was lower than the domestic norm. The next was the dimension of social relationship， and the worst was the dimension of treatment. The single factor analysis and multivariate analysis identified the following influence factors of quality of life in the patients： family history， educational level， exercise habit， blood glucose control and diet control. There was a negative correlation with educational level and blood glucose control， and a positive correlation with diet control. Conclusion The quality of life in the middle-aged diabetic patients was affected by the education level， blood glucose control and diet control. We suggest to strengthen the community management， health education， and improve the living habits.