1.Variation of long-chain 3-hydroxyacyl CoA dehydrogenase DNA methylated modification and corre-lation with gene mRNA expression of early- onset preeclampsia, HELLP syndrome and antiphospholipid syndrome in trophoblast cells of placenta
Ran MENG ; Zi YANG ; Hailing WANG ; Yiwei HAN ; Yanling WANG ; Huan YU
Chinese Journal of Obstetrics and Gynecology 2016;51(4):270-278
Objective By detecting the DNA methylation and gene expression of long-chain 3-hydroxyacyl CoA dehydrogenase (LCHAD) in trophoblast cells, analyze the correlation of DNA methylation and gene expression in early-onset preeclampsia (EPE), hemolysis, elevated liver enzymes, and low platelets (HELLP) syndrome and antiphospholipid syndrome (APS), to investigate the molecular basis of long-chain fatty acid oxidation changes in different preeclampsia and pathological pregnancy. Methods Primary human cytotrophoblast cells and HTR8/Svneo cells were treated with serum from patients with EPE (14 cases), HELLP (12 cases), APS (14 cases), and normal pregnant women (NP, 14 cases). The methylation level of LCHAD gene promoter region through the MassARRAY platform and mRNA expression level by real-time fluorescent quantitative PCR technique were conducted. Results (1) Cytosine-phosphate-guanine (CpG)sites in human LCHAD DNA promoter region:CpG sites were detected in the range of 558 bp before LCHAD gene transcription start site, the detected CpG sites were 11 sites including 8 single sites and 3 complex sites. The position of these sites were at-984,-960,-899,-853,-811,-796,-774,-727,-615,-595,-579 respectively. (2) The sites of-899,-853,-615 and-595 showed increased methylation level in EPE and HELLP groups. The methylation level at-899,-853 and-615 sites in EPE and HELLP groups were significantly higher than those in NP group(P<0.01). The methylation level at-853 site was higher in EPE group than that in HELLP group(P<0.05). The-595 site showed the unmethylated in EPE, HELLP and APS groups. There were significantly difference between the 3 groups and EPE group(P<0.01). (3) The gene expression of LCHAD mRNA in EPE(0.048±0.005), HELLP(0.045±0.006)and APS(0.044±0.004) groups were significantly lower than NP group(0.076 ± 0.009;P<0.01). (4) The correlation of methylation level and gene expression in all groups: the methylation level at-899,-853,-727,-615 and-579 sites were negatively correlated with gene mRNA expression in EPE group (P<0.05). The methylation level at-899,-853 and-615 sites were negatively correlated with gene mRNA expression in HELLP group(P<0.05). Conclusions The variation of LCHAD DNA methylation of trophoblast cells are found among EPE, HELLP syndrome and APS. The different correlation of LCHAD DNA methylation and gene expression are different in pathological groups. LCHAD DNA methylation of EPE and HELLP syndrome were significantly increased and negatively correlated with LCHAD gene mRNA expression. These results further revealed the molecular basis of long-chain fatty acid oxidation in different preeclampsia and pathological pregnancy.
2.Correlation of free fatty acid and blood lipids in early second trimester and uterine artery notch in pre-eclampsia
Fengqiu LI ; Zi YANG ; Aiqing ZHANG ; Jialüe WANG ; Xiaole SUN ; Ran MENG
Chinese Journal of Perinatal Medicine 2014;17(3):180-185
Objective To analyze the heterogeneous variation of serum free fatty acid (FFA) and lipids during early second trimester in women with or without uterine artery notch in pre-eclampsia (PE).Methods This is a prospective cohort study of 4 000 women with singleton pregnancies registered in early pregnancy and in whom regular check-ups were performed in Haidian Maternal & Child Health Hospital.Blood specimens were collected at gestational age 14-18 weeks at the same time of screening for Down's syndrome.One hundred and one cases with early diastolic notch of the uterine artery were included in the N+ group,and 172 cases without notch but at high risk of PE were included in the N-group at 22-24 weeks.In addition,205 women who were selected randomly at a ratio of 1 ∶ 5,without notch or PE high-risk factors,were also included in the N group.Both groups were subgrouped according to the outcomes of pregnancy complications:early-onset PE group EPE,late-onset PE (LPE),gestational hypertension (GH) group,gestational diabetes mellitus (GDM) group with normal blood pressure,and no complications (NC) group.The variation in FFA and other lipid metabolism indicators in the PE subgroups were compared and analyzed by two independent-sample t-test,one-factor analysis of variance,Chi-square test (or Fisher's exact) and Logistic regression.Results History of PE and pre-hypertension at first visit differed significantly between the N+ and N-groups [3.9% (4/101) vs.0.8% (3/377),x2=5.52,P<0.05; pre-hypertension at first visit,42.2% (43/101) vs.25.7% (97/377),x2=10.91,P<0.05].In the N+ group,23.8% (n=24) of women had PE,of which 37.5% (n=8) were early onset.In the N group,2.1% (n=8) had PE,and all were late onset.The incidence of PE differed significantly between the N+ and N-groups (x2=59.72,P<0.05).In the N+ group,FFA gradually decreased among the ePE,IPE,GH and NC groups [(0.68±0.27),(0.58±0.21),(0.57±0.21) and (0.49±0.19) mmol/L,F=2.78,P<0.05]; Multivariate regression analysis showed that FFA (OR=135.68,95%CI:3.78-4 873.00) and PE history (OR=123.25,95%CI:9.27-i 638.00) were risk factors of ePE.Pre-hypertension at registration (OR=4.69,95%CI:2.08-10.58) and pre-pregnancy body mass index (BMI) 24-28 (OR=3.69,95%CI:1.26-10.83) were risk factors ofGH.FFA (OR=9.08,95%CI:2.49-33.01) and pre-pregnancy BMI ≥ 28 (OR=5.08,95%CI:2.16-11.92) were risk factors for GDM.Conclusions Serum FFA and TG levels in early second trimester are correlated with PE,especially the early-onset PE.The onset of PE is heterogeneous and affected by many factors,and occurs in patients with or without early diastolic notch of the uterine artery in the second trimester.Patients with notch are more likely to have early-onset PE,which is correlated with blood FFA and TG levels.
3.The changes of LCHAD in preeclampsia with different clinical features and the correlation with NADPH P47-phox, p38MAPK- α, COX-2 and serum FFA and TG
Fengqiu LI ; Zi YANG ; Aiqing ZHANG ; Xiaole SUN ; Jialüe WANG ; Ran MENG
Chinese Journal of Obstetrics and Gynecology 2015;(2):92-100
Objective To investigate the changes of fatty acid oxidase in the placenta of preeclampsia cases with different clinical features, and the relationship with oxidative stress and inflammatory response. To study the correlation of serum free fatty acid (FFA) and triglycerides (TG) level in early second trimester with the molecular changes of the long-chain fatty acid oxidase in the third trimester. Methods This was prospective cohort study, in which cases with singleton pregnancies who archived in Haidian Maternal and Children′s Hospital, Beijing, from January 1st 2012 to May 31st, with regular prenatal care were included. Doppler ultrasound was used for screening for the presence of early diastolic notch of uterine artery at 22-24 weeks of gestation. All the 101 cases with the early diastolic notch of uterine artery were included as the notch group, and 377 cases without the early diastolic notch of uterine artery were included as the non-notch group. The perinatal outcomes and the incidence of hypertensive disorders in pregnancy of the two groups were observed. The serum level of FFA and TG was tested, and the mRNA and protein expression of long-chain 3-hydroxyacyl-CoA dehydrogenase (LCHAD), P47-phox subunit of nicotinamide adenine dinucleotide phosphate (NADPH) oxidase, p38 mitogen-activated protein kinase α (p38MAPK-α) and cyclooxygenase-2 (COX-2) were detected using real-time quantitative PCR and western blot. The relationship between serum level of FFA and TG and the mRNA and protein expression of LCHAD, NADPH P47-phox,p38MAPK-α and COX-2 of the placental tissue specimens were analyzed. Results (1) In the notch group, there were 9 cases of early-onset preeclampsia,15 cases of late-onset preeclampsia and 10 cases of gestational hypertension;and there were 8 cases of late-onset preeclampsia and 18 cases of gestational hypertension in the non-notch group. 15 cases with normal blood pressure in each group were randomly selected as the control group.(2)The serum level of TG of cases of early-onset preeclampsia, late-onset preeclampsia and gestational hypertension in the notch group were(2.0±0.8),(1.8±0.6)and (1.9±0.7)mmol/L, and that of FFA were(0.68±0.26),(0.52±0.10)and(0.52±0.17)mmol/L, respectively. The serum level of TG of cases of late-onset preeclampsia and gestational hypertension in the non-notch group were(1.6±0.6)and(1.4±0.4)mmol/L, and that of FFA were(0.49±0.11)and(0.48±0.05)mmol/L, respectively. The serum level of TG and FFA in the control group were(1.4±0.5)and(0.52±0.06)mmol/L, respectively. The TG level of the notch group was higher than that of the control group, and the difference was statistically significant (P<0.05). The FFA level of the early-onset preeclampsia in the notch group was higher than that of late-onset preeclampsia in the notch group, late-onset preeclampsia in the non-notch group and the control group, and the difference was statistically significant (P<0.05).(3) The mRNA expression of LCHAD in the placenta of early-onset preeclampsia in the notch group was significantly lower than that of the late-onset preeclampsia in the notch group, late-onset preeclampsia in the non-notch group and the control group (P<0.01). The mRNA expression of NADPH P47-phox of the early-onset preeclampsia in the notch group were significantly higher than that of late-onset preeclampsia in the notch group, late-onset preeclampsia in the non-notch group and the control group(P<0.01). The mRNA expression of p38MAPK-α of the early-onset preeclampsia in the notch group were significantly higher than that of late-onset preeclampsia in the notch group, late-onset preeclampsia in the non-notch group and the control group (P<0.01). The mRNA expression of COX-2 of the early-onset preeclampsia in the notch group were significantly higher than that of late-onset preeclampsia in the notch group, late-onset preeclampsia in the non-notch group and the control group (P<0.01).(4)The protein expression of LCHAD in the placenta of early-onset preeclampsia in the notch group, late-onset preeclampsia in the notch group and gestational hypertension in the notch group were significantly lower than that of the control group (P<0.01); and the protein expression of LCHAD in the placenta of early-onset preeclampsia in the notch group was significantly lower than that of late-onset preeclampsia in the non-notch group (P<0.01). The protein expression of NADPH P47-phox in the placenta of early-onset preeclampsia in the notch group was significantly higher than that of late-onset preeclampsia in the non-notch group and control group (P<0.05). The protein expression of p38MAPK-α in the placenta of early-onset preeclampsia in the notch group was significantly higher than that of late-onset preeclampsia in the notch group, late-onset preeclampsia in the non-notch group and control group (P<0.01). The protein expression of COX-2 in the placenta of early-onset preeclampsia in the notch group, late-onset preeclampsia in the notch group, gestational hypertension in the notch group, late-onset preeclampsia in the non-notch group, and gestational hypertension in the non-notch group, were significantly higher than that of control group (P<0.01).(5)The blood concentration of maternal FFA in the early-onset preeclampsia in the notch group was significantly negatively correlated with the mRNA and protein expression of placental LCHAD (r=-0.810,-0.932,P<0.01). There was no correlation between maternal TG level and the mRNA and protein expression of placental LCHAD in each group(P> 0.05).(6)The mRNA expression of placental LCHAD in the early-onset preeclampsia in the notch group was significantly negatively correlated with the mRNA expression of placental NADPH P47-phox and COX-2 (r=- 0.877,-0.762, P<0.05). The mRNA expression of placental LCHAD in the control group was significantly negatively correlated with the mRNA expression of placental COX-2 (r=- 0.565, P<0.01). The protein expression of placental LCHAD in the early-onset preeclampsia in the notch group was significantly negatively correlated with the protein expression of NADPH P47-phox (r=- 0.818, P<0.01). The protein expression of placental LCHAD in the control group was significantly negatively correlated with the protein expression of COX-2 (r=- 0.502,P<0.01). Conclusions The placental mRNA and protein expression of long-chain fatty acid oxidation enzymes were different in different clinical features of preeclampsia, which were reduced more obviously in the early-onset preeclampsia in the notch group than that of the late-onset preeclampsia in the notch group, and were negatively correlated with the elevated serum FFA level, significantly enhanced oxidative stress and inflammatory response, but with no correlation with serum TG level.
4.Clinical effect of Yisui decoction plus western medicine in treating multiple system atrophy.
Pei-Ran ZHANG ; Gai-Hui GUO ; Wei-Hong GU ; Zi-Yi ZHANG ; Kang WANG ; Miao JIN
China Journal of Chinese Materia Medica 2014;39(15):2968-2971
To observe the clinical effect of Yisui decoction plus western medicine in treating multiple system atrophy patients, totally 65 patients from China-Japan Friendship hospital during 2008-2012 with complete clinical data and received consecutive traditional Chinese medicine and western medicine treatment for more than 3 months were observed changes of traditional Chinese medicine symptom score, part 1 of unified multiple system atrophy rating scale, orthostatic hypotension before treatment and after 3 months treatment. After 3 months treatment, total effective rate of traditional Chinese medicine symptom was 70.8%. Compared with before treatment, score of part 1 of unified multiple system atrophy rating scale was obviously reduced after 3 month treatment (P < 0.001). Ex- cept swallow function without significant improvement, the remaining projects of unified multiple system atrophy rating scale were im- proved obviously (P < 0.05), of which the most obvious differences were orthostatic symptoms, falls and intestinal function (P < 0.001). Orthostatic hypotension after 1 month treatment and 3 month treatment was obviously better than before treatment (P < 0.001). There was no significant difference in orthostatic hypotension between 1 month treatment and 3 month treatment. The research results show that Yisui decoction plus western medicine has a certain effect on improving clinical symptoms of multiple system atrophy patients, especially has a significant effect on orthostatic hypotension, and can maintain a stable clinical effect in a certain period of time.
Adult
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Aged
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Humans
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Hypotension, Orthostatic
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drug therapy
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Male
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Medicine, Chinese Traditional
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adverse effects
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methods
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Middle Aged
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Multiple System Atrophy
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drug therapy
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Retrospective Studies
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Treatment Outcome
5.Assessment of the damage to visual function by optical coherence tomography in patients with multiple sclerosis or neuromyelitis optica spectrum disorders
Mei-Zi, WANG ; Shu-Ran, WANG ; Li-Na, WANG ; Yang, TANG ; Kun, LEI ; Min, FANG ; Liu, YANG ; Yuan-Zhen, QU
International Eye Science 2016;16(7):1253-1257
AIM:To evaluate the optic nerve and axon impairment of relapsing - remitting multiple sclerosis ( RRMS) and neuromyelitis optica spectrum disorders ( NMOSD ) via detecting the peripapillary retinal nerve fiber layer (pRNFL) and the ganglion cell complex( GCC) thickness by optic coherence tomography(OCT).
METHODS: Retrospective case control study. Two hundred three cases were collected from August 2014 to January 2016 in Beijing Tian Tan Hospital. They were divided into four groups, including the normal group (n=60), the RRMS group ( n = 60 ), the NMOSD anti -aquaporin- 4 autoantibody seropositive( NMOSD- AQP4 -Ab seropositive) group (n= 48), and the NMOSD-AQP4-Abseronegative group (n = 35). All people were detected for the average and four quadrants ( superior, inferior, nasal, temporal) of pRNFL thickness and the average and two quadrants (superior, inferior) of GCC thickness with OCT. One way analysis of variance or nonparametric tests was used to compare the differences of pRNFL and GCC thickness between groups.
RESULTS: Comparing with the normal group, the average and all quadrants of pRNFL and GCC thickness in the RRMS, the NMOSD - AQP4 - Ab seropositive and the NMOSD-AQP4-Ab seronegative group were thinner (P<0. 01). Among them, the pRNFL and GCC thickness in the NMOSD- AQP4 - Ab seropositive group was the thinnest. Differences between groups in the pRNFL thickness:compared with the RRMS group, all quadrants of pRNFL and GCC thickness in the NMOSD-AQP4-Ab seropositive group were significantly thinner(P<0. 01); compared with the NMOSD- AQP4- Ab seronegative group, the inferior, nasal and temporal pRNFL thickness in the NMOSD-AQP4-Ab seropositive group were significantly thinner(P<0. 05), while the superior quadrant did not show significant differences( P > 0. 05); compared with the RRMS group, the superior pRNFL thickness in the NMOSD - AQP4 - Ab seronegative group was significantly thinner ( P < 0. 05), while the inferior, nasal and temporal quadrants did not show significant differences ( P > 0. 05 ). Differences between groups in the GCC thickness: compared with both the RRMS and the NMOSD- AQP4- Ab seronegative group, all quadrants of GCC thickness in the NMOSD -AQP4-Ab seropositive group were significantly thinner (P<0. 05); compared with the RRMS group, the superior GCC thickness in the NMOSD - AQP4 - Ab seronegative group was significantly thinner(P<0. 01), while the inferior quadrant did not show significant difference(P>0.05).
CONCLUSION: The optic nerve and axon impairment in NMOSD - AQP4 - Ab seropositive group was the most severe and the impairment in RRMS group was the least severe. The impairment in NMOSD - AQP4 - Ab seronegative group was between the former two, and could be more similar to that of RMMS.
6.Effect and mechanism of total flavonoids of bugloss on rats with myocardial ischemia and reperfusion injury.
Xiao-Na XU ; Zi-Ran NIU ; Shou-Bao WANG ; Yu-Cai CHEN ; Li GAO ; Lian-Hu FANG ; Guan-Hua DU
Acta Pharmaceutica Sinica 2014;49(6):875-881
This study is to investigate the effect of total flavonoids of Uygur medicine bugloss (BTF) on rats with myocardial ischemia/reperfusion injury, and to explore the mechanisms by which it acts. Left anterior descending (LAD) coronary artery in rats was occluded for 30 min followed by 4 h reperfusion. Meanwhile, BTF dissolved in saline was administered intraperitoneally at dosage of 10, 30 and 50 mg x kg(-1). Electrocardiograph, infarction index, serum myocardial enzymes and heart function were determined to evaluate the effect of BTF. Some other observations were carried out to explore whether inhibiting inflammation and apoptosis is involved in the mechanisms underlying BTF. Our results showed that in ischemia/reperfusion injured rats BTF could dose-dependently reduce myocardial infarction index and myocardial enzyme leakage, and enhance heart function, indicating that it possesses significant cardio protection. ELISA analysis showed that BTF could decrease the content of myocardial inflammatory cytokines such as IL-1beta, IL-6 and TNF-alpha. Western-blotting confirmed that BTF could increase the expression of anti-apoptotic protein Bcl-2 and reduce the expression of proapoptosis protein Bax. Further more, the phosphorylation level of PI3K and Akt was upregulated by BTF treatment. BTF can protect rat against myocardial ischemia/reperfusion injury. Anti-inflammation and inhibition of apoptosis through upregulating PI3K/Akt signal pathway may contribute to the protective effect of BTF.
Animals
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Apoptosis
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Apoptosis Regulatory Proteins
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Boraginaceae
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chemistry
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Flavonoids
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pharmacology
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Heart
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Interleukin-6
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Myocardial Infarction
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Myocardial Reperfusion Injury
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drug therapy
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Myocardium
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Phosphatidylinositol 3-Kinases
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Phosphorylation
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Protective Agents
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Proto-Oncogene Proteins c-akt
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Rats
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Signal Transduction
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Tumor Necrosis Factor-alpha
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bcl-2-Associated X Protein
7.Investigation of soil-transmitted nematode infections in Xiding Township, Menghai County,Yunnan Province
Fangwei WU ; Libo WANG ; Ran CHEN ; Zunwei DU ; Xinliu YAN ; Benfu LI ; Jia PENG ; Jinrong ZI ; Long MA ; Zhijian NIE
Chinese Journal of Schistosomiasis Control 2017;29(1):93-95
Objective To understand the status of soil?transmitted nematode infections in Xiding Township,Menghai Coun?ty,Yunnan Province,so as to provide the reference for formulating the strategy of soil?transmitted nematodosis control. Meth?ods Soil?transmitted nematode eggs in feces were detected by the Kato?Katz method,and the eggs of Enterobius vermicularis were detected by the cellophane tape method in children. The soil samples were collected from vegetable ,fruit and other crop fields of 15 residents randomly to detect hookworm. Results The stool samples from 1 002 residents were examined and the soil?transmitted nematode infection rate was 20.06%(201/1 002). The infection rates of hookworm,Ascaris lumbricoides and Trichu?ris trichura were 18.96%(190 cases),1.70%(17 cases)and 0.90%(9 cases)respectively. The percentages of people with light infection of hookworm,A. lumbricoides and T. trichura were 97.37%(185/190),88.24%(15/17)and 100%(9/9)respec?tively. No infection of E. vermicularis was found. Fifteen soil samples were tested,and no hookworm was found in the soil. Con?clusion The infection rate of soil?transmitted nematode in Xiding Township,Menghai County is high,but the infectiosity is light. The control and monitoring of soil?transmitted nematodosis should be strengthened in this area.
8.Investigation on status of pollution of vibrio cholera in seafood and aquatic products in 12 provinces of China in 2005.
Jing ZHANG ; Zhao-rui CHANG ; Hao-jie ZHONG ; Duo-chun WANG ; Jin XU ; Biao KAN ; Lu RAN ; Zi-jun WANG
Chinese Journal of Preventive Medicine 2007;41(3):208-211
OBJECTIVETo understand the pollution rates of vibrio cholera (V. cholera) in different seafood, aquatic products and their circulatory processes, so as to help making measures for cholera control and prevention.
METHODSDifferent seafood, aquatic products and breed water specimen collected from 12 provinces of China were tested from July to September in 2005.
RESULTA total of 12 104 samples of seafood and aquatic products were tested and the average pollution rate of vibrio cholera was 0.52%. The positive isolate rate of turtle sample (1.72%) was the highest among all samples. The second higher isolated rate was 1.14% in water specimen of turtle breed pool. The positive rate of bullfrog was 0.50%. The percentage of toxin strains was 47.54% and 79.31% of them were isolated from turtle and water samples of turtle breed pool. The important sector of the pollution of vibrio cholera was in turtle breed pool (2.38%).
CONCLUSIONThe average pollution rate of vibrio cholera in seafood and aquatic products in 12 provinces of China was low. It should be very necessary to supervise the sanitation in turtle breed for controlling and preventing the vibrio cholera.
Animals ; China ; Female ; Fishes ; microbiology ; Food Contamination ; analysis ; prevention & control ; statistics & numerical data ; Male ; Seafood ; microbiology ; Seawater ; analysis ; Turtles ; microbiology ; Vibrio cholerae ; isolation & purification
9.Pitfalls in positron emission tomography/computed tomography imaging: causes and their classifications.
Tian-ran LI ; Jia-he TIAN ; Hui WANG ; Zi-qian CHEN ; Chun-lei ZHAO
Chinese Medical Sciences Journal 2009;24(1):12-19
OBJECTIVETo describe the pitfalls in positron emission tomography/computed tomography (PET/CT) imaging and classify them according to the principles of their generation.
METHODSWe summarized retrospectively the 18F-fluorodeoxyglucose (FDP) PET/CT imaging pitfalls through reviewing the PET/CT images of 872 patients. The pitfalls were divided into artifacts and infrequent physiological uptake, and the artifacts were further classified according to their causes. Meanwhile, we calculated the incidences of various pitfalls. Whether the PET/CT pitfalls influenced the diagnostic decision was analyzed. The appearances of pitfalls in PET were also described.
RESULTSPitfalls could be found in PET/CT images of 684 (78.4%) patients. Artifacts were found in 664 (76.15%) patients, and could be classified into self-factor artifacts and equipment- or technology-related artifacts. Among self-factor artifacts, respiratory motion (57.5%), postprandial or hyperglycemia artifacts (2.41%), and metal or high density matter artifacts (1.38%) were frequent. As for equipment- or technology-related factors, injection point outleakage or radiotracer contamination (13.88%) and truncation artifacts (1.83%) were most common ones. Infrequent physiological FDG uptakes, including fatty uptake, endometrial uptake, and bilateral breast feeding period uptake, were found in 20 (2.29%) patients. Among all pitfalls, the artifacts in 92 (13.4%) patients and infrequent physiological uptakes in 6 (0.88%) patients affected the diagnostic results. Artifact images in PET could be described as hot or cold area and the images of infrequent physiological uptake were always shown as hot area.
CONCLUSIONSThe incidence of pitfall in PET/CT imaging was high and the causes of pitfalls are various. Among all causes that artifacts generated, respiratory motion is the most common. Some pitfalls may disturb clinical physicians' decision, so it is important to recognize artifacts and physiological uptake, and distinguish them from pathological uptakes.
Adolescent ; Adult ; Aged ; Aged, 80 and over ; Artifacts ; Breast Feeding ; Child ; Child, Preschool ; Diagnostic Errors ; statistics & numerical data ; Drug Contamination ; Endometrium ; metabolism ; Fatty Acids ; metabolism ; Female ; Fluorodeoxyglucose F18 ; Humans ; Hyperglycemia ; Image Interpretation, Computer-Assisted ; Infant ; Injections, Intravenous ; Male ; Middle Aged ; Movement ; Positron-Emission Tomography ; Respiration ; Young Adult
10.Disruption of blood brain-barrier by leukemic cells in central nervous system leukemia.
Sa-ran FENG ; Zi-xing CHEN ; Jian-nong CEN ; Hong-jie SHEN ; Yuan-yuan WANG ; Li YAO
Chinese Journal of Hematology 2011;32(5):289-293
OBJECTIVETo observe the effect of leukemic cells on blood-brain barrier (BBB) in mice with central nervous system leukemia (CNSL) by establishing mice CNSL model and an in vitro BBB model and explore the mechanism of leukemic cell infiltrating central nervous system (CNS).
METHODSAfter splenectomy, cytoxan intraperitoneal injection, and sublethal irradiation, 10 BALB/c nu/nu mice were transplanted intravenously with 1.2 × 10(7) of SHI-1 human monocytic leukemic cells. Mice were monitored for survival and clinical manifestation of nerve palsy. The leukemic cells engrafted were examined by RT-PCR, histopathology and bone marrow (BM) smears. Immunofluorescence analysis with laser scanning fluorescence confocal microscopy was used to determine the expression of fibrinogen and tight-junction protein ZO-1. An in vitro BBB model composed of human brain microvascular endothelial cells (BMVECs) was developed on a Matrigel-based insert. Different leukemic cell lines were seeded onto the upper compartment of transwell insert. After incubated for 24 h with BMVECs, cells that had migrated into the lower compartment were counted and analyzed.
RESULTS(1) Paralysis with or without sight loss was developed in half the mice 30-35 d after innoculated with SHI-1 cells. Leukemic cells infiltrates were observed in BM and in different part of brain tissues including brain parenchyma. The transcriptions of human MLL/AF6 fusion gene were also detected in BM and brain tissues in paralysis mice. The fibrinogen expression and ZO-1 disruption were detected in the infiltrated tissue. (2) After 24 h incubation with leukemic cells, the BMVECs sheets were disrupted and grew singly and ZO-1 expression was down-regulated markedly. SHI-1 cells showed more injurious to BMVECs and higher invasive rate \[(40.33 ± 1.53)% vs (11.83 ± 1.44)%, P < 0.05\] than HL-60 cells did.
CONCLUSIONOne of the mechanisms of leukemic cells infiltrates CNS in CNSL is injure to the BBB.
Animals ; Blood-Brain Barrier ; physiology ; Central Nervous System ; pathology ; Central Nervous System Neoplasms ; pathology ; HL-60 Cells ; Humans ; Leukemia ; pathology ; Mice ; Mice, Inbred BALB C ; Mice, Nude