1.Clinical significance of hypoxia inducible factor-prolyl hydroxylase 1 and factor inhibiting hypoxia inducible factor-1 expression in placentas of women with severe pre-eclampsia
Nannan LUAN ; Chong QIAO ; Feng JIN ; Wenhui LIU ; Tao SHANG
Chinese Journal of Obstetrics and Gynecology 2008;43(12):913-917
Objective To investigate the role of hypoxia inducible factor(HIF)-prolyl hydroxylase 1 (HPHl)and factor inhibiting HIF-1(FIH-1)in placentas in the pathogenesis and development of severe pre-eclampsia.Methods RT-PCR and western blot analyses were used to detect the HPH1 and FIH-1expression levels in placentas of 34 patients with severe pre-eclampsia and 24 cases of term pregnancy (normal pregnancy group)and their correlations with symptoms were analyzed.Results (1)The HPHI mRNA and protein expression levels in placentas of severe pre-eclampsia group were 0.40±0.04 and 59.5±3.4 separately,significantly lower than those of normal pregnancy group,0.84±0.12 and 71.6±1.7(P<0.01).The FIH-1 mRNA and protein expression levels in placentas of severe pre-eclampsia group wereQ 31 ±0.05 and 45.6±2.4 separately,significantly lower than those of normal pregnancy group,0.43±0.04 and 54.9±2.1(P<0.01).(2)The mRNA and protein expression levels of HPH1 and FIH-1 in severe pre-eclampsia group were all negatively correlated with mean arterial pressure(MAP)[the Spearman correlation coefficient was-0.854(P<0.01)],urinary protein per 24 hours[the Spearman correlation coefficient was-0.936(P<0.01)1 and the occurrence of fundus oculi artery spasm[the Spearman correlation coefficient was-0.854(P<0.01)].(3)rrhe expression of HPHl mRNA in placentas of all the 58 cases WBB 0.58±0.27.higher than the expression of FIH-1 mRNA,which was 0.39±0.10.There was a positive correlation between them.The pearson correlation coefficient was 0.686(P<0.01).The expression of HPH1 protein in placentas of all the 58 cases was 64.5±6.7,higher than the expression of FIH-1,which was 49.4±5.2.There was a positive correlation between them.The Pearson correlation coefficient was 0.947(P<0.01).Conclusion The expression imbalance of HPH1 and FIH-1in palcenta may play an important role in the pathogenesis and development of severe pre-eclampsia through inhibiting HIF-1a.
2.Correlation between the expression of high mobility group box 1 and receptor for advanced glycation end products and the onset of pre-eclampsia
Lin GAO ; Wenhui LIU ; Nannan LUAN ; Chong FENG ; Tao SHANG
Chinese Journal of Obstetrics and Gynecology 2008;43(10):746-750
Objective To evaluate different expressions of high mobility group box 1(HMGB1)and receptor for advanced glycation end products(RAGE)in placentas and their relationship with preeclampsia.Methods Fifteen early-onset pre-eclaraptic women(early-onset pre-eclampsia group),22 late-onset pre-eclamptic women(late-onset pre-eclampsia group)and 12 normotensive women(control group)in the third trimester were recruited at the Shengjing Hospital of China Medical University from March 2006 to March 2007.The localization and levels of HMGB1 and RAGE in placentas of the three groups were detected by the strept avidin biotin-peroxidose method.Results (1)Immunoreactivities to HMGB1:positive immnnostaining for HMGB1 was observed in trophoblast,macrophages,decidual cells,vascular muscle cells,endothelial cells and placental mesenchymal cells in the placentas from the pre-eclamptic women,while a low level of immunoreactivities was observed in the placentas from healthy pregnancies;the staining was observed within both the nuclei and the cytoplasm,mainly in the cytoplasm.The cytotrophoblast,especially the nuclei was extensively positive for HMGB1 in early-onset pre-eclampsia. (2)Immunoreactivities to RAGE:positive immunostaining for HMGB1 was observed in syncytiotrophoblast,macrophages and endothelial cells in the placentas from the preeclamptic women,while a low level of immunoreactivities was observed in the placentas from healthy pregnancies:the staining was in the cytoplasm and(or)cell membrane.The trophoblast was extensively positive for RAGE in early-onset pre-eclampsia.(3)Positive rate of HMGB1 expression:the expression of HMGB1 in early-onset group(73%,11/15)and late-onset group(64%,14/22)was significantly higher than that in normal group(17%,2/12;P<0.05),but no significant difference was found in early-onset group and late-onset group(P>0.05).(4)Positive rate of RAGE expression:the expression of RAGE in early-onset group(80%,12/15)and late-onset group (82%,18/22)was significantly higher than that in normal group(25%,3/12;P<0.05),but no significant difference was found in early-onset group and late-onset group(P>0.05).Conclusions The increased expression of HMGB1 and RACE in the placenta may play an important role in the pathogenesis of pre-eclampsis.The different locations may be associated with the occurrence of different onset types of pre-eclampsia.
3.Pandanus tectorius derived caffeoylquinic acids inhibit lipid accumulation in HepG2 hepatoma cells through regulation of gene expression involved in lipid metabolism.
Chong-ming WU ; Hong LUAN ; Shuai WANG ; Xiao-po ZHANG ; Hai-tao LIU ; Peng GUO
Acta Pharmaceutica Sinica 2015;50(3):278-283
The fruit of Pandanus tectorius (PTF) has a long history of use as a folk medicine to treat hyperlipidemia in Hainan province, South China. Our previous studies have shown that the n-butanol extract of PTF is rich in caffeoylquinic acids and has an adequate therapeutic effect on dyslipidemic animals induced by high-fat diet. In this work, seven caffeoylquinic acids isolated from PTF were screened for the lipid-lowering activity in HepG2 hepatoma cells. Oil-Red O staining, microscopy and intracellular triglyceride (TG) and total cholesterol (TC) quantification showed that 3-O-caffeoylquinic acid (3-CQA), 3, 5-di-O-caffeoylquinic acid (3,5-CQA), and 3,4,5-tri-O-caffeoylquinic acid (3,4,5-CQA) significantly inhibited lipid accumulation induced by oleic acid and decreased intracellular levels of TC and TG in a dose-dependent manner. These three caffeoylquinic acids showed no significant cytotoxicity at concentrations of 1 -50 μmol x L(-1) as determined by MTT assay. Realtime quantitative PCR revealed that 3-CQA and 3, 5-CQA significantly increased the expression of lipid oxidation-related genes PPARα, CPT-1 and ACOX1 while 3-CQA, 3, 5-CQA and 3,4,5-CQA decreased the expression of lipogenic genes SREBP-1c, SREBP-2, HMGR, ACC, FAS. Overall, 3-CQA, 3, 5-CQA and 3, 4, 5-CQA may be the principal hypolipidemic components in PTF which can decrease intracellular lipid accumulation through up-regulating the expression of lipid oxidative genes and down-regulating the expression of lipogenic genes.
Carcinoma, Hepatocellular
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metabolism
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China
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Cholesterol
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metabolism
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Gene Expression Regulation
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Hep G2 Cells
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Humans
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Lipid Metabolism
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Liver Neoplasms
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metabolism
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Oleic Acid
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Pandanaceae
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chemistry
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Quinic Acid
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analogs & derivatives
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chemistry
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Sterol Regulatory Element Binding Protein 1
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Triglycerides
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metabolism
4.Correlation between thyroid hormones and renal function in severe pre-eclampsia patients with hypothyroidism
Jiaren ZHOU ; Wei LI ; Juan DU ; Chong QIAO ; Tao SHANG ; Xuemin LIU
Chinese Journal of Obstetrics and Gynecology 2014;49(11):811-815
Objective To study effects of different degree of hypothyroidism in severe preeclampsia (S-PE) pregnant women on renal function and the correlation between them.Methods 46 S-PE patients with subclinical hypothyroidism (SCH) registered for treatment in the Shengjing Hospital of China Medical University from May 2011 to March 2013 were selected into SCH group,and 23 S-PE with overt hypothyroidism (OH) were selected into OH group,and 109 S-PE with normal thyroid stimulating hormone (TSH) levels were selected into simple group.Thyroid hormone and kidney function tests were analyzed in pregnant women with S-PE.We made an analysis of the relative risk of the detection rate of abnormal renal function and also the relationship between the levels of thyroid hormone and serum uric acid,serum urea and creatinine in patients with S-PE.Results (1) In SCH group serum TSH was (6.1±3.2) mU/L,free triiodothyronine (FT3) was (4.0±0.6) pmol/L,free thyroxine (FT4) was (11.8± 1.5) pmol/L; in OH group serum TSH was (5.2± 1.3) mU/L,FT3 was (3.7±0.6) pmol/L,FT4 was (9.3±0.5) pmol/L; in simple S-PE group serum TSH was (1.9±0.8) mU/L,FT3 was (4.0±0.8) pmol/L and FT4 was (11.9±1.9) pmol/L.TSH in SCH group was significantly higher than that in simple S-PE group (P>0.01),the difference of in SCH and OH group were not statistically significant (P>0.05).The difference of FT3 in three groups were not statistically significant (P<0.05) ;FT4 in OH group was significantly lower than thoes in SCH and simple groups (P<0.05).(2)Serum uric acid,creatinine and urea levels in OH group was (436± 114),(75± 15) μmol/L and (6±3)mmol/L,in simple S-PE group they were (378± 114),(65 ±22) μmol/L and (5±3) mmol/L.In comparison,the differences was statistically significant(P<0.05).The differences were not statistically significant in SCH and OH groups (P>0.05).(3)The abnormal detection rate of uric acid was significantly higher in SCH than that in OH group [46% (21/46) versus 22% (5/23),OR=3.0,P<0.05].The comparison of remaining index has no statistical significance(P>0.05).(4)In SCH group there was a significant inverse correlation of serum FT3 with serum urea levels,serum creatinine and serum uric acid (r=-0.32,-0.58,-0.35,P<0.05).There was not a correlation of serum TSH,FT4 with indicators of renal function (P>0.05).In OH group there was a negative correlation between FT3 and serum creatinine concentrations (r=-0.40,P<0.05).In OH group there was not a correlation of FT3 with serum uric acid and urea (P>0.05).There was a positive correlation between TSH and serum creatinine in simple S-PE group (r=0.20,P=0.04).There was not a correlation between TSH and serum urea(r=0.04,P=0.65),and serum uric acid (r=0.12,P=0.20).Conclusions There was effect of different hypothyrosis state in pre-eclampsia patients on renal function.Serum uric acid,urea and creatinine concentrations in S-PE pregnant women with OH were significantly higher than those in simple S-PE group with normal TSH.There was a negative correlation between FT3 and serum creatinine in S-PE.Hence the thyroid function should be regularly monitored in S-PE patients to find damage of renal function and management hypothyrosis.
5.Preparation and preliminary utilization of monoclonal antibodies specifically against an immunogenic fragment in ectodomain of prostate-specific membrane antigen (PSMA)
Rong TAO ; Zhenhua NI ; Sheng YANG ; Chong LIU ; Min ZHU ; Jiangfan SHEN ; Shaohua TU
Chinese Journal of Immunology 2016;(2):205-209
Objective:To prepare monoclonal antibodies specifically against an immunogenic fragment in ectodomain of prostate-specific membrane antigen ( PSMA ).Methods: An polypeptide immunogenic fragment in the ectodomain of PSMA was predicted by biological information technology,and then it was expressed prokaryotically.BALB/c mice were immunized with the prokar-ytically expressed recombinant polypeptide antigen,to prepare the monoclonal antibodies specifically against an immunogenic fragment in ectodomain of PSMA by hybridoma technology,purification of monoclonal antibody by affinity chromatography,characterization of the monoclonal antibodies by Western blot.The radioimmunoimaging in prostate cancer model was performed by using the labeled McAb.Results:Throught the software analysis,we got the antigen fragment in the ectodomain of PSMA containing 310aa sequences higher specificity, artificially synthesized gene sequence of the region, and constructed a prokaryotic expression vector pET-32a-r-ectodomain-PSMA,by prokaryotic expression we obtained the 50 kD target antigen,after hybridization,the three positive hybridoma cell lines (5E6,4A5 and 4D7) were selected by ELISA using target antigen,the isotypes of 5E6 and 4A5 were IgG2a,the isotypes of 4D7 were IgG1,the titer of three monoclonal antibodies was above 1∶256 000.Western blot results showed that the prepared monoclonal anti-bodies could binding specifically to the antigen in the ectodomain of PSMA.Radioimmunoimaging in prostate cancer animal model results further confirm that the prepared monoclonal antibodies could combinate with the antigen in the ectodomain of PSMA in the animal body, and make the tumor imaging.Conclusion: The prepared monoclonal antibodies can specifically recognizes the PSMA antigen,which laid the foundation for the immunodiagnosis and immunotherapy of prostate cancer.
6.Application of MSCT's coronary artery calcification score in evaluation of sudden death caused by coronary artery disease.
Lei WAN ; Chong-Liang YING ; Ning-Guo LIU ; Wen-Tao XIA ; Ya-Hui WANG ; Hua WEI ; Guang-You ZHU
Journal of Forensic Medicine 2013;29(6):401-404
OBJECTIVE:
To access application value of multi-slice spiral computed tomography (MSCT) and coronary artery calcium scoring (CACS) in investigation the coronary artery disease (CAD), and to explore the effective way of virtual autopsy to evaluate the sudden death due to CAD.
METHODS:
Nine cases of sudden cardiac death were collected to analyze MSCT before the autopsy. The quantitative analysis of the degree of coronary artery calcium was made by Agatston's method. The CACS of all the subjects were calculated based on the diagnostic criteria for CAD, in which calcium scoring was more than 400. The results of CACS were compared with that of the autopsy.
RESULTS:
Only 2 cases got the high calcium scoring which were more than 400 in the 9 cases died of CAD confirmed by the autopsy. The prediction rate of CACS for CAD was only 22.2%. Pulmonary edema of different severity was found in both autopsy and MSCT. There was a higher morbidity rate in the left anterior descending of coronary artery than the other branches.
CONCLUSION
Obvious calcification of coronary artery can be detected by MSCT and calculating CACS. To detect subtle calcification needs other technologies such as postmortem angiography.
Autopsy
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Coronary Angiography
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Coronary Artery Disease/diagnostic imaging*
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Death, Sudden/pathology*
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Humans
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Multidetector Computed Tomography/methods*
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Predictive Value of Tests
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Vascular Calcification/diagnostic imaging*
7.Association between G894T mutation in endothelial nitric oxide synthase gene and premature coronary heart disease.
Chong-qi JIA ; Yan NING ; Tong-tao LIU ; Zhao-lan LIU
Chinese Journal of Epidemiology 2005;26(1):51-53
OBJECTIVETo assess the association between G894T (Glu298Asp) mutation in exon 7 of the endothelial nitric oxide synthase gene and premature coronary heart disease (P-CHD).
METHODSHospital-based case-control study was conducted. Newly-diagnosed CHD patients were recruited as study subjects. 132 CHD patients diagnosed at/before age 55 for males and 65 for females were assigned to P-CHD case group with other 172 CHD patients as the control group. Polymerase chain reaction with Ban II restriction enzyme digestion was performed to detect the G894T mutation.
RESULTSG894T mutant genotypes in P-CHD group (TT, GT and GG frequencies were 6.06%, 20.45% and 73.48%, respectively) were significant higher than those in control group (TT, GT and GG frequencies were 1.74%, 11.63% and 86.63%, respectively) (P = 0.01). Mutant T allele frequency in P-CHD group was also significantly higher than that in control group (16.29% versus 7.56%, P = 0.001, OR = 2.38, 95% CI: 1.38 - 4.16). Stepwise multiple logistic regression analysis at 0.05 significant level with sex, smoking, alcohol drinking, and overweight covariates indicated that G894T mutation also having significant effect on P-CHD (P = 0.01, OR = 2.25, 95% CI: 1.19 - 4.26).
CONCLUSIONThis study suggested that G894T mutation in endothelial nitric oxide synthase gene might serve as a major risk factor to the pathogenesis of P-CHD in this study population.
Age Factors ; Case-Control Studies ; Coronary Disease ; enzymology ; genetics ; Exons ; genetics ; Female ; Gene Frequency ; Humans ; Male ; Middle Aged ; Nitric Oxide Synthase Type III ; genetics ; Point Mutation ; Risk Factors
8.Eyeball structure changes in high myopic patients and their significance for forensic assessment.
Yi-Chang LIU ; Wen-Tao XIA ; Xing-Tao ZHOU ; Rui-Jue LIU ; Shi-Zhong BIAN ; Chong-Liang YING ; Guang-You ZHU
Journal of Forensic Medicine 2008;24(5):356-360
There are irreversible eyeball structural changes in high myopic patients. These changes include axial length, corneal radius, anterior chamber depth, fundus degeneration, macula thickness, etc. There is a close relationship between the damage degree of visual function and these changes. The incidence of complications, such as vitreous opacity, posterior vitreous detachment, cataract, glaucoma, posterior staphyloma and retina detachment, is also highly related to the myopia diopter. More and more researches have indicated that the myopia diopter and the level of visual function are affected by multiple factors. It is promising to detect all of these changes by different kinds of methods, and to assess visual function through these changes. By clarifying these changes, it is also useful to distinguish traumatic damage from disease to provide evidence for forensic assessment of eye injuries.
Eye/physiopathology*
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Forensic Medicine
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Humans
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Myopia/pathology*
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Vision, Ocular/physiology*
9.Selective neck dissection for node-positive necks (N1, N2) in patients with head and neck squamous cell carcinoma.
Ye TAO ; Ye-Hai LIU ; Chong-Xian YU ; Hong-Wu LI ; Yan ZANG
Chinese Journal of Otorhinolaryngology Head and Neck Surgery 2008;43(9):681-685
OBJECTIVETo evaluate therapeutic effect in a consecutive series of patients with node-positive of N1 and N2 head and neck squamous cell carcinoma (HNSCC) who underwent selective neck dissection as part of their treatment in a single institution.
METHODSRetrospectively analyzed 36 patients with node positive head and neck squamous cell carcinoma, which had undergone 40 selective neck dissection (SND) and 16 radical neck dissections (RND) and the therapeutic effects of the SND in HNSCC patients with node positive. Kaplan-Meier method was used to estimate the survival analysis among the different levels, and log-rank method for comparison of the different distribution of the several influential factors of the survival; the fisher's exact test was used to test the difference of the neck recurrence between the groups that with or without lymph node extracapsular spread. Cox proportional hazard model was applied to screen the potentially significant prognostic factors.
RESULTSThe 3 and 5 years survival rate of this group were 76.8% and 54.3% retrospectively. The 3 and 5 years' survival rate were both 100% in the N1 + N2a group, while 59.4% and 32.0% in the N2b + N2c group correspondingly. With log-rank test between the two groups above, significant statistical difference was revealed (P = 0.003) in the 5 years' survival rates. To the groups that with or without extracapsular spread (ECS), the recurrence rate were 36.4% and 3.4% respectively and significant statistical difference existed (P = 0.015). In the groups that with or without ECS, the 3 years' survival rate were 45.5% and 81.8% , and 5 years' survival rate were 39.7% and 65.5% respectively, also the significant statistical difference (P = 0.0148 and P = 0.0423 respectively) had presented.
CONCLUSIONSSND is appropriate for treatment of N1 neck of the patient with HNSCC; However, SND should be taken very cautious to the N2 neck and node-positive neck with extracapsular spread, MRND or RND might be a better choice to prevent the recurrence in the neck.
Adult ; Aged ; Carcinoma, Squamous Cell ; pathology ; surgery ; Female ; Head and Neck Neoplasms ; pathology ; surgery ; Humans ; Lymph Nodes ; pathology ; Lymphatic Metastasis ; Male ; Middle Aged ; Neck Dissection ; methods ; Neoplasm Recurrence, Local ; pathology ; Neoplasm Staging ; Prognosis ; Retrospective Studies ; Survival Rate ; Treatment Outcome
10.Association of nicotinamide adenine dinucleotide phosphate oxidase p22phox gene 549C>T polymorphism with coronary artery disease.
Tong-tao LIU ; Li-li WANG ; Sheng-xia FANG ; Chong-qi JIA
Chinese Medical Journal 2012;125(8):1416-1419
BACKGROUNDThe p22phox is a critical component of the superoxide-generating vascular nicotinamide adenine dinucleotide phosphate (NADPH) oxidase. Several polymorphisms in p22phox gene are studied for their association with cardiovascular diseases. However, no publication is available to assess the relation of 549C > T polymorphism in p22phox gene to coronary artery disease (CAD) risk. This study was to investigate the effect of the p22phox gene 549C > T polymorphism on CAD risk.
METHODSHospital-based case-control study was conducted with 297 CAD patients and 343 healthy persons as the control group. Polymerase chain reaction and pyrosequencing using PSQ 96 MA Pyrosequencer (Biotage AB) were used to detect the polymorphisms. Multiple Logistic regression model was used to adjust the potential confounders and to estimate odds ratio (OR) with 95% confidence intervals (CIs).
RESULTSThe observed genotype frequencies of this polymorphism obeyed the Hardy-Weinberg equilibrium in both cases (P = 0.439) and controls (P = 0.668). The frequency of mutant genotypes (TT + CT) in cases (41.08%) was higher than that in controls (36.73%) with an OR = 1.20 (95%CI = 0.87-1.65). After the adjustment of the potential confounders, there was a significant association of the mutant genotypes with increased risk of CAD (OR = 1.57, 95%CI = 1.01-2.46, P = 0.047).
CONCLUSIONSThe mutant genotypes of the p22phox gene 549C > T polymorphism had a significant effect on the increased risk of CAD in this studied population.
Case-Control Studies ; Coronary Artery Disease ; etiology ; genetics ; Female ; Genotype ; Humans ; Logistic Models ; Male ; Middle Aged ; NADPH Oxidases ; genetics ; Polymorphism, Single Nucleotide