1.Current progress of iron metabolism and tumor development
Journal of Medical Postgraduates 2017;30(9):998-1003
Iron is an essential nutrient that not only participates in cell oxidative phosphorylation, DNA synthesis and replication, but also regulates cancer associated genes through hypoxia-inducible factor (HIF).In the process of cancerization, cells change the way of iron metabolism resulting in a high consumption of iron.In this case, pathways of iron acquisition, efflux, storage and regulation are perturbed.Therefore, iron can significantly contribute to tumor growth, cell survival and metastasis.In this paper, we summarize the iron changes in cancer cells and the relationship between the changes and tumorigenesis.We also briefly state the potential problems of current clinical using iron chelating agents in oncotherapy.Targeting iron metabolic pathways may provide new tools for cancer prognosis and therapy.
2.Effect of Formula Granule of Siwu Drugs on Sex Hormone and Its Receptor in Bone Marrow Depressed Mice
Mingzhao JIA ; Qing XIA ; Zhiwei CHEN
Tianjin Medical Journal 2009;37(7):578-580
Objective: To investigate the effect of abstracted formula granule of Siwu drugs on the sex hormones and expressions of androgen receptor (AR)and estrogen receptor (ER) in bone marrow depressed mice. Methods: One hundred and eighty mice (90 male and 90 female) were randomly divided into 6 groups. The effects of the formula granule of Siwu on sex hormones and expressions of AR and ER were explored by SABC method in bone marrow of depressed mice. Results: For the male rats, the levels of androgen were increased in male of treatment groups compared with those of model groups (P<0.05), and the levels of estrogen were decreased in male of treatment groups compared with those of model groups (P<0.05).For the female rats, the levels of androgen were increased in female of treatment groups compared with those of model groups,but no significant differences (P>0.05), and the levels of estrogen were decreased in femal of treatment groups compared with those of model groups (P<0.05). There was a dose dependent manner between treatment groups. Conclusion: The results suggested that formula granule of Siwu drugs may play a role in the hematopoietic function to repair bone marrow depression by improving AR and the balance of estrogen / androgen in mice.
3.Effect of Restraint and Watered Stress of Different Durations on Gastric Empting in Rats
Dan ZHANG ; Zhiwei XIA ; Yajing HAN
Acta Laboratorium Animalis Scientia Sinica 2009;17(6):415-418
Objective To study the effect of restraint and watered stress of different durations on the gastric empting in rats. Methods 48 male SD rats (weight ±150 g) were divided randomly into 6 groups with 8 in each. The experimental rats were restrained and watered in 23℃ water box for 1 h/d, while the controls were free. The body weight, general conditions and behavioral indexes of the rats were observed and recorded. The gastric empting rate was measured in rats with semi-solid diet after 3 d,7 d and 28 d during the statistically significant differences among different groups of different stress groups,and between the 3 d test group and 3 d control group. The gastric empting rate was higer in the 7-day test than in 7 d controlled group, lower in the 28 d test group than 28 d control group. Conclusion Different chronic stress can cause changes of gastric empting rate. With the prolonging of stress time, the empting rate is rising and then decending.
4.A survey of nonsteroidal anti-inflammatory drugs and aspirin associated peptic ulcer bleeding in hospitals
Zhiwei XIA ; Linlin MA ; Wei YAO
Chinese Journal of Internal Medicine 2011;50(2):111-115
Objective To investigate the clinical characteristic and prognosis of nonsteroidal antiinflammatory drugs( NSAIDs)and aspirin associated peptic ulcer bleeding. Method All patients with peptic ulcer bleeding were studied by the same researcher after admission and discharge. Results Fifty-one cases with NSAIDs and aspirin medication of the total peptic ulcer bleeding patients ( 147 cases) were included (34. 7% ). Compared with patients not associated with NSAIDs and aspirin medication, they are older [(41.2 ± 1. 9 ) years vs ( 59.4 ± 2. 2 ) years, P < 0. 001], more commonly associated with hypertension ( 10. 4% vs 39. 2% ,P <0. 001 ), coronary heart disease ( 10. 4% vs 17.6% ,P <0. 001 ) ,diabetes (4. 2%vs 19. 6%, P = 0. 005 ); and had more severe anemia (7. 3% vs 23. 5%, P = 0. 008 ). Fewer patients in NSAIDs group had epigastric pain (61.5% vs 27.5%, P < 0. 001 ), while there was more re-bleeding (9.4% vs 15.7%, P = 0.034). In all bleeding patients, factors associated with re-bleeding, surgical intervention and death included NSAIDs and aspirin medication, and low platelet count. In patients with NSAIDs and aspirin medication, re-bleeding was associated with previous ulcer history ( P < 0. 05 ).Conclusion Peptic ulcer bleeding patients with NSAIDs and aspirin medication were more severe ill, and less likely to present with epigastric pain.
5.Relationship of body mass index with hiatal hernia and reflux esophagitis
Bingxia GAO ; Liping DUAN ; Kun WANG ; Zhiwei XIA
Chinese Journal of Digestive Endoscopy 2011;28(6):316-319
Objective To investigate the relationship of body mass index with hiatal hernia (HH) and reflux esophagitis (RE).Methods Two hundreds and twenty seven gastroesophageal reflux disease (GERD) patients with typical acid regurgitation and heartburn were enrolled and categorized into three groups according to body mass index (BMI, kg/m2) as normal weight (18.5≤BMI <24), overweight (24≤BMI<28), and obesity (BMI≥28).RE, non-erosive reflux disease (NERD) and HH were diagnosed by gastroscopy.All the patients underwent ambulatory 24-hour pH monitoring and the pathological acid reflux was considered when the DeMeester score≥15.Effects of BMI on RE and HH were estimated by using logistic regression analysis.Results The percentages of RE and HH were 30.0%(68/227) and 5.7%(13/227), respectively.76.9% (10/13) HH patients had RE. Proportions of RE and HH increased significantly with increasing BMI (P<0.05), so was that of RE above grade B in three groups (6.4%, 16.9% and 31.6%,P=0.003).DeMeester scores of the three groups were 15.9, 19.8 and 36.9, respectively (P<0.05).The average 24-hour intra-esophagus pH value of overweight group, was significantly lower than that of normal weight patients in the afternoon and midnight (P<0.01).Multivariate analysis showed obesity was a risk factor for HH with OR 7.058 (95% CI: 1.294~38.488, P=0.024), male (OR: 2.537, 95% CI: 1.350~4.766, P=0.004), overweight (OR: 1.921, 95% CI: 1.005~3.670, P=0.048), obesity (OR: 3.305, 95% CI: 1.123~9.724, P=0.030) and HH (OR: 6.879, 95% CI: 1.695~27.913, P=0.007) were risk factors for RE.Conclusion BMI has a significant association with HH and RE, obesity is a common risk factor for both HH and RE, HH may induce the development of RE.
6.Quantitative assessment of iron load in myocardial overload rabbit model: preliminary study of MRI T2* map
Lu HUANG ; Rui HAN ; Zhiwei LI ; Sishu YUAN ; Liming XIA
Chinese Journal of Radiology 2014;48(3):236-240
Objective To preliminarily investigate the feasibility of MRI-T2* map in evaluating myocardial iron load of myocardial iron overload rabbit models.Methods Eleven rabbits were included in this study and divided into two groups,myocardial iron overload group (n =10) and the control group (n =1).Iron dextrin (dose of 50 mg/kg) was injected in muscles of thigh once a week,totally 12 weeks.Serum iron test and MRI examination were performed before iron injection,and 1 week to 12 weeks after iron injection.MRI scan protocol included short axial T2* map of the left ventricle and cross-section T2* map of the liver.T2* and R2* of the heart and the liver were measured.One rabbit was killed after MRI examination at pre-iron injection,1 week to 8 weeks,11 weeks and 12 weeks after iron injection,respectively.Heart and liver were avulsed to undergo in vitro MRI scan and then paraffin embedded for pathological slices.MRI scan protocol and measurements of the heart and the liver samples were the same to that of in vivo ones.Pearson correlation was used to calculate the relationships between the parameters.Results Myocardial T2* [(32.5 ± 8.3 ms)] and R2* values [(38.4 ± 7.9) Hz] had significant correlation with injecting iron content(1 033.2 ± 673.4 mg),the Pearson coefficients were-0.799 (P =0.001) and 0.770 (P =0.002),respectively.Myocardial T2 had no significant correlation with liver T2* values (r =0.556,P =0.070).T2* values of heart and liver in vivo [(32.5 ± 8.3) ms and (8.8 ± 5.4) ms],respectively had strong correlation with those in vitro [(19.4 ± 6.5) ms and (9.8 ± 5.0) ms],respectively (r =0.757,P =0.007 and r=0.861,P=0.001).T2* and R2* values of the heart and the liver in vivo and in vitro had no significant correlations with serum iron (P > 0.05).On Prussian blue staining slices,blue particles of myocardium,sinus hepaticus and hepatocyte increased with injecting iron content.Conclusions It is feasible for MRI-T2* map to evaluate the myocardial iron load noninvasively.It may provide reliable information for detecting myocardial iron overload in patients with iron overload at an early stage.
7.Effects of chronic arsenic exposure on mRNA expression of estrogen receptor-binding fragment-associated gene 9 and estrogen-responsive finger protein in female rat's uterus and ovary tissue
Zhiwei GUO ; Weihong YANG ; Hongyu GUO ; Xiaohong HAN ; Yajuan XIA
Chinese Journal of Endemiology 2014;33(1):11-14
Objective To observe the effects of chronic arsenic exposure on mRNA expression of estrogen receptor-binding fragment-associated gene 9 (Ebag9) and estrogen-responsive finger protein (efp) in uterus and ovary of female rats.Methods Fifty female Wistar rats were randomly divided into five groups according to arsenic (As2O3) concentrations given through drinking-water:0.00 (control),0.05,0.10,0.20,0.40 mg/L arsenic exposure groups and real-time RCR (RT-PCR) was used to detect the mRNA expression of Ebag9 and efp in uterus and ovary tissue at the 31 weeks of experiment.Results The mRNA expression levels of Ebag9 and efp of the 0.00,0.05,0.10,0.20,0.40 mg/L arsenic exposure groups were respectively as follows:0.761 ± 0.178,0.521 ± 0.130,0.544 ± 0.035,0.525 ± 0.198,0.498 ± 0.240 and 0.795 ± 0.171,0.874 ± 0.077,0.797 ± 0.066,0.796 ± 0.040,0.832 ± 0.096.Compared with control group,a decreased tendency was observed in Ebag9 mRNA level(with P value 0.055 in 0.40 mg/L arsenic exposure group) and increased tendency in efp mRNA level in experimental groups (all P > 0.05).The mRNA expression levels of Ebag9 and efp in ovary of the five groups were by turns:0.702 ± 0.484,0.719 ± 0.336,0.693 ± 0.095,0.706 ± 0.055,0.728 ± 0.073 and 0.924 ± 0.061,1.009 ± 0.034,0.930 ± 0.085,0.929 ± 0.068,1.012 ± 0.101.Compared with control group,the expression level of Ebag9 mRNA showed a increased tendency in 0.05,0.20,0.40 mg/L arsenic exposure groups(all P > 0.05).The efp mRNA level increased in experimental groups,with significant difference in 0.05,0.40 mg/L groups (all P < 0.05).Conclusions The expression of efp mRNA has changed in ovary of female rats exposed to chronic arsenic.Arsenic may act as an environmental endocrine disruptor to exert its effect.
8.The characteristics of esophagogastric junction contractile index in patients with gastroesophageal reflux disease or functional heartburn
Kun WANG ; Liping DUAN ; Ying GE ; Zhiwei XIA ; Zhijie XU
Chinese Journal of Internal Medicine 2016;55(4):283-288
Objective To study the role of esophagogastric junction contractile index (EGJ-CI) in evaluating the function of anti-reflux barrier,and in differentiating patients with gastroesophageal reflux disease (GERD) from those with functional heartburn (FH).Methods A total of 115 patients presenting heartburn were enrolled in the study from January 2012 to June 2015.All subjects had completed Gerd-Q questionnaire and undergone gastroscopy,24-hour pH-impedance monitoring and esophageal high-resolution manometry.GERD patients were divided into as reflux esophagitis,acid-nonerosive reflux disease (NERD) and weakly acid-NERD groups.Patients with normal esophageal mucosa,normal acid exposure and negative proton pump inhibitor test were enrolled in FH group.EGJ-CI (mmHg · cm) as well as EGJ rest pressure and 4s integrated relaxation pressure (IRP 4s) were measured.Results Among the 115 patients,18 were reflux esophagitis [(49.0 ± 18.9) years,M ∶ F =10 ∶ 8],25 were acid-NERD [(48.7 ± 14.4) years,M∶F=13∶ 12],37 were weakly acid-NERD [(52.0 ±14.8) years,M∶F=15∶22] and 35 were FH [(53.6 ± 14.8),M∶ F =8∶27].No differences of Gerd-Q scores were noticed between the four groups.(1) Negative correlations were demonstrated between EGJ-CI and esophageal acid exposure time (r =-0.283,P =0.002),EGJ-CI and acid reflux events (r =-0.233,P =0.012),EGJ-CI and weakly acid reflux events (r =-0.213,P =0.022),EGJ-CI and non-acid reflux events (r =-0.200,P =0.032).(2)The value of EGJ-CI was significantly higher in FH patients than in the three subgroups of GERD(all P < 0.01).EGJ rest pressure of FH group was higher than that of acid-NERD (P < 0.01).IRP 4s in acid-NERD group was lower than that of FH and weakly acid-NERD (P < 0.05).(3) The area under curve (AUC) of EGJ-CI was higher than that of EGJ-CIT,EGJ rest pressure or IRP 4s (0.686 vs 0.678,0.641 and 0.578).The cut-off value of EGJ-CI to differentiate GERD from FH was 9.74 mmHg · cm with sensitivity 82.86% and specificity 51.52%.Conclusions The EGJ-CI values are negatively correlated with esophageal acid exposure time,weakly acid reflux events and non-acid reflux events.Thus it might be used as a metric to reflect the anti-reflux function of EGJ.According to the cut-off value of EGJ-CI 9.74 mmHg · cm,patients with GERD can be sensitively differentiated from patients with FH.
9.Trend analysis of endemic arsenism in the monitored areas of the disease in 2010 - 2012 in Inner Mongolia
Yajuan XIA ; Kegong WU ; Kuiying FANG ; Zhiwei GUO ; Na CUI
Chinese Journal of Endemiology 2016;(1):32-34
Objectives To monitor the residents prevalence of endemic arsenism in the disease affected areas in Inner Mongolia, so as to provide feasible suggestions for control of arsenism in the future. Methods Monitoring data were obtained from the Project of Endemic Disease Prevention Granted by Central Government in 2010 - 2012, and the conditions of arsenism patients from 38 endemic arsenic villages were analyzed among different year, age and gender. Results The detection rate of arsenism of the 38 surveillance villages was 7.38%(517/7 004) in 2010, 7.10%(482/6 784) in 2011 and 6.62% (431/6 514) in 2012. The arsenism patients of mild;moderate and severe cases from 2010 to 2012, accounted for 74.47% (385/517), 74.27% (358/482), 75.17% (324/431); 16.83% (87/517), 16.60% (80/482), 15.78% (68/431) and 8.7% (45/517), 9.13% (44/482), 9.05% (39/431), respectively. For skin lesions, the detection rates of keratosis, pigmentation and depigmentation from 2010 to 2012, were 8.08%(566/7 004), 7.90%(536/6 784), 7.77%(506/6 514);3.27%(229/7 004), 3.29%(223/6 784), 2.87%(187/6 514) and 6.68% (468/7 004), 6.63% (450/6 784), 5.82% (379/6 514), respectively, showed a declining trend. It also showed a declining trend with age, and the patients were mainly 40 years old people and older, and the highest detection rate was in the 60- 70 years old group[15.54%(143/920)、14.72%(135/917)、13.36%(136/1 018)]. For gender distribution, the detection rate of the three years was higher in male than female [male 8.24%(300/3 639), 7.99%(283/3 542), 7.71%(260/3 372);female 6.45%(217/3 365), 6.14%(199/3 242), 5.44%(171/3 142),χ2=8.24, 8.77, 13.54, all P〈0.01]. Conclusion There is no big change of arsenism conditions in 2010-2012, with a slight declining trend.
10.Prevention and handling of missing data in clinical trials.
Zhiwei JIANG ; Chanjuan LI ; Ling WANG ; Jielai XIA
Acta Pharmaceutica Sinica 2015;50(11):1402-7
Missing data is a common but unavoidable issue in clinical trials. It not only lowers the trial power, but brings the bias to the trial results. Therefore, on one hand, the missing data handling methods are employed in data analysis. On the other hand, it is vital to prevent the missing data in the trials. Prevention of missing data should take the first place. From the perspective of data, firstly, some measures should be taken at the stages of protocol design, data collection and data check to enhance the patients' compliance and reduce the unnecessary missing data. Secondly, the causes of confirmed missing data in the trials should be notified and recorded in detail, which are very important to determine the mechanism of missing data and choose the suitable missing data handling methods, e.g., last observation carried forward (LOCF); multiple imputation (MI); mixed-effect model repeated measure (MMRM), etc.