Study on MRI of nude mice bearing nasopharyngeal carcinoma metastasis model by using molecular probe USPIO-PEG-sLeX / 实用放射学杂志

Objective To investigate the value of molecular probe USPIO-PEG-sLeX in metastasis model of nasopharyngeal carcinoma. Methods According to the pathological results of transplanted tumors of nude mice with nasopharyngeal carcinoma,the tumor-bearing mice were divided into metastatic group and non-metastatic group.T2 ? values of the transplanted tumors at four different time points were measured before and after the injection of USPIO-PEG-sLeX(t0＝plain scan,t1＝scan immediately after enhancement,t2＝1 hour post-enhancement scan,t3＝2 hours post-enhancement scan).ΔT2 ? and enhancing rates at t1 ,t2,t3 were calculated.Results The plain T2 ? values of the metastatic group and the non-metastatic group were 22.25±8.08 and 27.01±9.45,respectively.There was no significant difference between the two groups at t0 (P＞0.05).The T2 ? values at t1,t2 and t3 were 11.57±4.02 and 24.82±7.84,10.09±4.88 and 24.15±8.74,12.46±5.63,23.42±7.12 respectively in the metastatic and non-metastatic groups,differences were statistically significant (P values were 0.005,0.008 and 0.01 9,respectively).ΔT2 ? values at time t1 ,t2 and t3 in nude mice in the metastatic and non-metastatic groups were 10.69±6.23,3.86±2.20,12.1 7±8.67 and 2.87±1.37,9.80±3.03,4.32±2.28 respectively.The differences were statistically significant (P values were 0.027,0.048 and 0.043,respectively).The enhancement rates at t1,t2 and t3 in nude mice in metastatic and non-metastatic groups were 45.98±14.03,7.10±5.18,5 1.1 5±22.70 and 1 1.04±6.01 ,44.05 ±13.92,12.09 ±7.54,respectively,with statistically significant differences (P values were 0.001,0.005 and 0.007,respectively).After two-way repeated-measures analysis of variance,there was a statistically significant difference in T2 ? values between the metastatic and non-metastatic groups (P＝0.02＜0.05).There was a statistically significant difference in T2 ? values at different times (P＝0.001＜0.05).There was an interaction between the metastatic and non-metastatic groups and the scan time (P＝0.043＜0.05).Conclusion USPIO-PEG-sLeX molecular probe can non- invasively monitor E-selectin expression,and has a good application prospect in monitoring the metastasis of nasopharyngeal carcino-ma xenograft models.

Significance of ultrasound tissue characteristics of carotid atherosclerotic plaques in predicting cardiocerebrovascular events in patients with type 2 diabetes / 国际脑血管病杂志

Objective To investigate the predictive value of ultrasonic tissue charateristics of carotid atherosclerotic plaques in cardiocerebrovascular events in patients with type 2 diabetes mellitus (T2DM).Methods From January 2003 to December 2015,patients with T2DM treated in Xi'an Gaoxin Hospital were selected.Their carotid atherosclerotic plaques were examined by ultrasound.Intergrated backscatter (IBS) and thickness of carotid plaques of the patients were documented.The cardiocerebrovascular events were folbwed up prospectively.Kaplan-Meier curve,COX proportional risk regression model,and receiver operating characteristic (ROC) curve were used to compare and analyze the predictive values of calibratedIBS (C-IBS),Framingham Risk Score (FRS) and plaque thickness for the risk of cardiocerebrovascular events in patients with T2DM.Results There was significant difference in the risk of cardiovascular events between the low C-IBS group (n=48,C-IBS ＜17.1 dB) and the high C-IBS group (n=48,C-IBS ≥17.1 dB) (35.4％ vs.12.5％;P=0.015).There was no significant difference in the risk of cardiocerebrovascular events between the thin plaque group (n =48,plaque thickness ＜ 1.3 mm) and the thick plaque group (n=48,plaque thickness ＞1.3 mm) (14.6％ vs.33.3％;P=0.070).COX proportional risk regression model analysis showed that C-IBS (hazard ratio,1.505,95％ confidence interval 1.196-1.893,P=0.001) and plaque thickness (hazard ratio,4.794,95％ confidence interval 1.142-20.130,P =0.032) were the independent risk factors for the risk of cardiocerebrovascular events.ROC curve analysis found that the combination of C-IBS,FRS and plaque thickness could predict the risk of cardiocerebrovascular events in patients with T2DM.Conclusion Ultrasonic tissue characteristics of carotid atherosclerotic plaque (C-IBS and plaque thickness) in combination with FRS may predict cardiocerebrovascular events in patients with T2DM.

Expression of thioredoxin reductase 1 in liver and peripheral blood of human and rats exposed to airborne arsenic through coal-burning / 中华地方病学杂志

Objective To study the expression and enzyme activity of thioredoxin reductase 1 (TrxR1) in liver and peripheral blood of human and rats exposed to airborne arsenic through coal-burning as well as its role in liver injury of coal-burning-borne arsenic poisoning.Methods This study was divided into 2 parts.Part 1 was a population study:133 local residents exposed to airborne arsenic through coal-burning were selected as arsenic exposure groups including a non-patient group (25 cases),no obvious hepatopathy group (38 cases),mild (43 cases) and moderate to severe hepatopathy groups (27 cases) from areas affected by endemic arsenism in Guizhou Province.Thirty-four healthy residents from arsenic not affected areas were selected as controls.Peripheral blood samples were collected from all these people.The expression of TrxR1 mRNA was determined by real-time fluorescence quantitative PCR (qPCR),and enzyme activity of TrxR was tested by visible spectrophotometry.Part 2 was an animal experiment study:Thirty Wistar rats,weighing about 80-100 g,were divided into control group,drinking-waterborne arsenic poisoning group and coal-burning-borne arsenic poisoning group (including low,medium and high arsenic contaminated grain groups) by means of a table of random number according to body mass,6 rats in each group.The control group was fed with normal diet for 3 months; drinking-water-borne arsenic poisoning group and coal-burning-borne arsenic poisoning group were fed with 10 mg/kg As2O3 solution and different concentrations(25,50,100 mg/kg) of arsenic-containing feed,respectively,for 3 months.The expression of TrxR1 mRNA was determined by qPCR; protein expression level of TrxR1 in liver tissue was detected by immunohistochemistry,and enzyme activity of TrxR in serum and liver tissue was tested by visible spectrophotometry.Results The mRNA expressions of TrxR1 in peripheral blood were 1.599 8 (1.128 9-2.156 8),1.469 3 (1.146 1-1.976 3),1.203 6 (0.463 1-1.816 2) and 0.912 3(0.631 8-1.535 0),respectively,among non-patient group,no obvious hepatopathy group,mild and moderate to severe hepatopathy groups.Compared to the control group[1.649 7(1.161 1-2.380 2)],the differences were significant statistically in mild and moderate to severe hepatopathy groups (all P ＜ 0.05).The enzyme activity of TrxR in peripheral blood was (3.12 ± 0.76),(2.81 ± 0.84),(2.52 ± 0.73),(2.42 ± 0.76)U/ml,respectively,in those corresponding groups.Compared to the control group [(3.02 ± 0.70)U/ml],the differences were significant statistically in mild and moderate to severe hepatopathy groups (all P ＜ 0.05).The mRNA expressions of TrxR1 in peripheral blood were 1.05 ± 0.14,1.18 ± 0.18,1.04 ± 0.10 and 0.97 ± 0.13,respectively,among drinking-water-borne arsenic poisoning group,low,medium and high arsenic contaminated grain groups; all of which were lower than that in the control group (1.23 ± 0.15,all P ＜ 0.05) except that of the low arsenic contaminated grain group.The mRNA expressions of TrxR1 in liver tissue were 0.78± 0.10,0.83 ± 0.10,0.79 ± 0.09 and 0.77 ± 0.11,respectively; all of which were lower than that in the control group (0.94 ± 0.12,all P ＜ 0.05).The protein expression of TrxR1 in liver tissue was 310.33 ± 38.81,312.50 ± 23.36,305.67 ± 20.57 and 298.17 ± 23.52,respectively,among the arsenic poisoning groups; all of which were lower than that in the control group (348.50 ± 32.35,all P ＜ 0.05).The enzyme activity of TrxR in serum was (4.22 ± 0.73),(4.86 ± 0.63),(4.04 ± 0.57),(3.73 ± 0.64)U/ml,respectively; all of which were lower than that in the control group [(9.52 ± 1.08)U/ml,all P ＜ 0.05].The enzyme activity of TrxR in liver tissue was (14.82 ± 1.67),(18.76 ± 2.76),(14.90 ± 2.17),(11.55 ± 1.74) U/mg,respectively; all of which were lower than that in the control group [(23.71 ± 3.05)U/mg,all P ＜ 0.05].Conclusion Arsenic aggravates liver injury of coal-burning arsenic poisoning through down-regulating the expressions of TrxR1 mRNA and protein and reducing its enzyme activity as well.

A exploration of the relation of NF-E2-related factor 2-antioxidant response element combining capacity and its downstream gene expression and hepatic injury of coal-burning-borne arsenism / 中华地方病学杂志

Objective To detect the combining capacity of peripheral blood NF-E2-related factor 2 (Nrf2)of arsenic-exposed residents in the coal-contaminated arsenism area in Guizhou with the sequence of downstream antioxidant response element (ARE) as well as antioxidase gene expression,and to provide a basis for in-depth revelation of arsenic oxidative damage mechanism to human body.Methods Jiaole and Changqing villages in coal-burning-borne arsenism areas in Xingren County of Guizhou were selected as the survey spots,and 161 cases of arsenic-exposed residents were selected as the arsenic exposed group on the basis of physical examination.They were divided into non-patient group (21 cases) and patient group (140 cases) according to the Diagnostic Criteria of Endemic Arsenism (WS/T 211-2001),and the patient group was further divided into mild hepatosis group (52 cases),moderately severe hepatosis group (36 cases) and non-apparent hepatosis group (52 cases) according to the Diagnostic Criteria of Occupational Chronic (GBZ 59-2010).Moreover,45 residents from one village neighboring to non-epidemic area were selected as controls.The hemocyte nucleoprotein was extracted from peripheral blood in the sampling subjects.The combining capacity of peripheral blood Nrf2-ARE was tested by electrophoretic mobility shift assay (EMSA),and the relative expression quantity of Cu/Zn superoxide dismutase (Cu/Zn-SOD) and glutathione peroxidase 1 (GSH-Pxl) mRNA was tested with real-time fluorescence quantification PCR (qPCR).Results The testing results of Nrf2-ARE combining capacity showed that the difference of Nrf2-ARE combining capacity between groups was statistically significant (F =116.033,P ＜ 0.05).Compared with the control group (3.14 ± 1.34),the Nrf2-ARE combining capacity was higher in the non-apparent hepatosis group (5.17 ± 2.06),mild hepatosis group (13.13 ± 4.84) and moderately severe hepatosis group (32.35 ± 14.76,all P ＜ 0.05);compared with the non-patient group (5.15 ± 3.23) and non-apparent hepatosis group,the Nrf2-ARE combining capacity of mild hepatosis group and moderately severe hepatosis group was higher (all P ＜ 0.05);compared with mild hepatosis group,the Nrf2-ARE combining capacity of moderately severe hepatosis group was higher (P ＜ 0.05).The results of Cu/Zn-SOD and GSH-Pxl mRNA expression showed the relative expression quantities of Cu/Zn-SOD [Median (M):1.127 8,1.257 8,1.632 0] and GSH-Pxl (M:1.334 5,1.940 9,2.062 6) mRNA of non-apparent hepatosis,mild hepatosis,moderately severe hepatosis groups were higher than those of the control groups (M:0.961 8,0.884 3),respectively,and their differences were statistically significant (x2 =13.065,19.934,all P ＜ 0.05).The relative expression quantities of GSH-Pxl mRNA of mild hepatosis group and moderately severe hepatosis group were higher than that of the non-patient group (M:1.248 4),and their differences were statistically significant (all P ＜ 0.05).The correlation analysis indicated the Nrf2-ARE combining capacity was positively related to the Cu/Zn-SOD and GSH-Px1 mRNA expression (r =0.271,0.292,all P ＜ 0.01).Conclusion The increase of Nrtf2-ARE combining capacity by arsenic participates is involved in the regulation of Nrf2 downstream antioxidase gene expression,and this process possibly participates in occurrence and development of coal-burning-borne arsenism and hepatic injury.

The application and effect of PBL teaching method in Hebei Medical University / 中华医学教育探索杂志

In order to promote the integration between disciplines, the convergence between basic course and clinical teaching, increasing students ability including the active learning and life-long learning ability, finding problem and solving problem ability, teamwork spirit and so on. After nearly 3 years preparation, Hebei Medical University successfully carried out the PBL teaching in Seven-year Clinical Medicine Science. Combining with the teaching activities, formative assessment was carried out, and PBL teaching website was established. The reform has already achieved initial results, got good responds from teachers and students. Through the study, it has been confirmed that the PBL teaching method in Hebei Medical University is effective and worthy to reference.

Relationship between changes of genetic damage and development of disease in patients with arsenism caused by coal-burning / 中华预防医学杂志

<p><b>OBJECTIVE</b>To investigate the changes of genetic damage in patients with arsenism caused by coal-burning in 9 years. To analyze the relationship between the changes of genetic damage and disease progression and provide a basis for condition monitoring.</p><p><b>METHODS</b>Of 206 arsenism patients from the area with endemic arsenism in Guizhou province were tracking surveyed in February 1998 and divided into 4 groups, including suspicious, mild, moderate and severe poisoning group. Another 67 healthy residents from a neighbour township 12 km away where arsenic was not prevalent were surveyed. Over a 9-year follow-up, 131 arsenism patients and 45 controls with the complete biochemical indexes among them were selected as subjects in December 2006. Arsenic (As) concentration of urine and hair were detected by silver diethyldithiocarbamate spectrophotometry (Ag-DDC). Micronucleis (MN) and chromosome aberrations (CA) were analyzed by conventional methods. DNA single-strand breaks of peripheral blood were measured by single cell gel electrophoresis (SCGE), and the tail lengths of comet were used to measure DNA damage.</p><p><b>RESULTS</b>Among the control, suspicious, mild, moderate and severe arsenic poisoning group, the As contents of urine and hair were respectively (34.16 ± 10.25), (52.35 ± 22.41), (62.26 ± 31.13), (71.43 ± 49.92), (78.45 ± 50.64) µg/L and (1.37 ± 0.56), (3.69 ± 1.78), (4.88 ± 3.49), (5.21 ± 3.10), (6.25 ± 4.04) µg/g in 2006, which were lower than that 9 years before (urine as contents were (36.07 ± 20.70), (73.65 ± 41.33) , (90.92 ± 82.14) , (126.55 ± 107.31) and (139.44 ± 90.90) µg/L, and hair As contents were (1.41 ± 1.18), (4.85 ± 4.20), (5.72 ± 4.07) , (6.43 ± 4.32) and (7.19 ± 4.68) µg/g, respectively, F value was 10.63, 7.72, 14.66, 11.00 respectively, all P values were < 0.05). Except for suspicious poisoning group, the differences of urine As contents in the other groups all showed significance (P < 0.05). The incidences of MN were (0.238 ± 0.130) %, (0.268 ± 0.192) %, (0.283 ± 0.157) % and (0.391 ± 0.233)%; the incidences of CA were (14.36 ± 5.44) %, (18.09 ± 6.49) %, (19.38 ± 5.63)% and (19.83 ± 5.84) %; the tail lengths of comet were (29.88 ± 13.81) , (29.84 ± 12.80) , (34.50 ± 9.88) and (41.58 ± 12.98) µm respectively in 2006 for all poisoning groups; which were higher than that 9 years before(the incidences of MN were (0.163 ± 0.051) %, (0.186 ± 0.117) %, (0.196 ± 0.104) % and (0.273 ± 0.142) %; the incidences of CA were (13.18 ± 5.17)%, (14.48 ± 6.61)%, (15.67 ± 8.49) % and (16.90 ± 8.38) %; the tail lengths of comet were (15.07 ± 12.93) , (19.57 ± 8.80) , (27.03 ± 10.77) and (34.71 ± 14.95) µm) , except for the incidences of MN and CA in suspicious poisoning group and of MN in mild poisoning group , the differences of the three indexes in the other groups were significant (P < 0.05) . The state of illness of arsenic poisoning patients aggravated 9 years later. With the increase of urine and hair As contents and the development of arsenism, the incidences of MN, CA and the tail lengths of comet of all poisoning groups increased. There were positive correlations among them (r values were respectively 0.212, 0.316, 0.232, 0.263, 0.321, 0.654 and 0.760) (P < 0.05).</p><p><b>CONCLUSION</b>The exacerbation of genetic damage was related to constantly high arsenic loads. The accumulation of genetic damage and its irreversibility might be one of the important reasons of the development of arsenism and cancer.</p>

Arsenic exposure causes human 8-hydroxyguanine DNA glycosidase 1 gene methylation and DNA oxidative damage / 中国药理学与毒理学杂志

OBJECTIVE To investigate DNA hypermethylation of human 8-hydroxyguanine glycosy-lase(hOGG1 )gene and and the level of oxidative stress and DNA oxidative damage relations with arse-nic poisoning.METHODS In ende mic coal-pollution-borne arsenism area,Xinren county,Guizhou Province,according to the diagnostic criteria of ende mic arsenism(WS /T21 1 -2001 ),207 people with ende mic arsenism were selected and divided into four groups(The arsenic exposure group:46 cases, mild arsenism group:46 cases,moderate arsenism group:60 cases and severe arsenism group:55 cases).64 residents were selected as controls in a village about 12 km away fro m the ende mic arsenism area.With the informed consent principle,peripheral blood of all respondents was collected in order to analyze DNA methylation.Methylation-specific poly merase chain reaction were respectively performed to analyze hOGG1 Hypermethylation in arsenism respondents.Che mical methods were performed on the activity of super oxide dis mutase (SOD)and glutathione peroxidase (GSH-Px),while the contents of malondialdehyde (MDA)in the blood of patients were measured,and the contents of 8-hydroxy-2′-deox-yguanine(8-OHdG)urine of patients were measured and analysed.On the basis of methylation status are divided into hOGG1 gene methylation group (34 cases)and hOGG1 gene no methylation group (237cases).Analysis was performd on hOGG1 gene DNA methylation and the relationship between oxi-dative stress and arsenic poisoning.RESULTS The positive rates of hypermethylation of hOGG1 were associated with the degree of arsenic poisonin (co mpared with control group,χ2 =23.916,P 0.05).CONCLUSION Coal arsenic exposure can cause hOGG1 gene high methylation and oxidation and anti-oxidation system imbalance,causing DNA oxidative damage,it is one of the reasons to pro mote the develop ment of arsenic poisoning occurred.

Relationship between genetic polymorphisms in nucleotide excision repair gene excision repair cross complement group 6, xeroderma pigmentosum group A and coal-burning-borne-arsenism / 中华地方病学杂志

Objective To investigate the relationship between genetic polymorphisms in nucleotide excision repair gene excision repair cross complementing group 6(ERCC6),xeroderma pigmentosum group A(XPA) and coal-burning-borne-arsenism in Guizhou Province.Method ERCC6 A3368G,ERCC6 C-6530G and XPA A23G gene polymorphisms were analyzed by polymerase chain reaction restriction fragment length polymorphism technique(PCR-RFLP) of 205 cases which were chosen as patients with arsenism and 187 residents as control group.Results The distributions of ERCC6 A3368G,ERCC6 C-6530G and XPA A23G in the case group were not statistically significant compared with those of the control group(x2 =3.209,2.963,3.335,all P ＞ 0.05); individuals carrying G allelomorphic gene(AG + GG) had a lower risk than individuals carring A allelomorphic gene(ORadj =0.282,95％CI:0.126-0.628,P =0.002); relationship was not found between single genetic polymorphisms of ERCC6 C-6530G,XPA A23G and coal-burning-borne-arsenism; the risk of arsenism was decreased for individuals carrying the following five genotypes combination:ERCC6 A3368G(AG + GG) genotype and ERCC6 C-6530G CC genotype(ORadj =0.287,95％CI:0.087-0.946,P=0.040); ERCC6 A3368G(AG + GG) genotype and ERCC6 C-6530G(CG + GG) genotype (ORadj =0.226,95％CI:0.077-0.661,P =0.007); ERCC6 A3368G(AG + GG) genotype and XPA A23G AA genotype (ORadj =0.150,95％CI:0.038-0.596,P =0.007); ERCC6 A3368G (AG + GG) genotype and XPA A23G(AG + GG) genotype(ORadj =0.325,95％CI:0.118-0.897,P =0.030) ; ERCC6 C6530G (CG + GG) genotype and XPA A23G AA genotype (ORadj =0.397,95％CI:0.162-0.975,P=0.036).Conclusions Individuals carring ERCC6 A3368G (AG + GG) genotype have a low risk of arsenism.There are five genotypes combination of three gene polymorphisms in two genes,ERCC6 and XPA,which may reduce the risk of coal-burning-borne-arsenism.

Value of BCL-2 and P53mt proteins in screening skin carcinoma caused by arseniasis / 中华流行病学杂志

<p><b>OBJECTIVE</b>To discuss the value of P53mt and BCL-2 proteins in screening skin carcinoma due to arseniasis.</p><p><b>METHODS</b>P53mt and BCL-2 proteins were detected by immunohistochemical staining. chi(2) test was used to analyze the difference of positive rate between two groups. Screening value of the two biomarkers was also evaluated through the analysis of relative indexes.</p><p><b>RESULTS</b>Positive percentages of P53mt and BCL-2 in carcinoma group were 88.89% and 94.44% respectively, both were higher than those of 36.0% and 66.0% in non-carcinoma group (for P53mt, P < 0.01; for BCL-2, P < 0.05). ORs of P53mt and BCL-2 were 14.22 (2.93 - 68.97) and 8.76 (1.07 - 71.51), respectively. Youden's Index and specificity of P53mt were 0.529 and 64.0%, which were much higher than those of BCL-2. Serial tests improved the value of screening with Youden's Index 0.569, but parallel test lowered it to 0.244.</p><p><b>CONCLUSIONS</b>P53mt and BCL-2 were practical biomarkers to screen skin carcinoma due to arseniasis, and the former was better than the latter. The value of screening can be improved by a series of tests.</p>

Hypermethylation and Transcription and Expression of O~6-methylguanine-DNA Methyltransferase Gene in Patients of Endemic Arsenism / 环境与健康杂志

0.05),but the average levels of DNMT1 mRNA of mild and moderate groups were significantly lower than that of the control group(P