Comparative Study on Iron Content Detection by Energy Spectral CT and MRI in MDS Patients.

Objective: The purpose of this study was to identify the difference between dual energy spectral computed tomography (DECT) and magnetic resonance imaging (MRI) used to detect liver/cardiac iron content in Myelodysplastic syndrome (MDS) patients with differently adjusted serum ferritin (ASF) levels. Method: Liver and cardiac iron content were detected by DECT and MRI. Patients were divided into different subgroups according to the level of ASF. The receiver operating characteristic curve (ROC) analysis was applied in each subgroup. The correlation between iron content detected by DECT/MRI and ASF was analyzed in each subgroup. Result: ROC curves showed that liver virtual iron content (LVIC) Az was significantly less than liver iron concentration (LIC) Az in the subgroup with ASF < 1,000 ng/ml. There was no significant difference between LVIC Az and LIC Az in the subgroup with 1,000 ≤ ASF < 2,500 ng/ml and 2,500 ≤ ASF < 5,000 ng/ml. LVIC Az was significantly higher than LIC Az in the subgroup with ASF <5,000 and 5,000 ≤ ASF ng/ml. In patients undergoing DECT and MRI examination on the same day, ASF was significantly correlated with LVIC, whereas no significant correlation was observed between ASF and LIC. After removing the data of ASF > 5,000 mg/L in LIC, LIC became correlated with ASF. There was no significant difference between the subgroup with 2,500 ≤ ASF < 5,000 ng/ml and 5,000 ng/ml ≤ ASF in LIC expression. Furthermore, both LIC and liver VIC had significant correlations with ASF in patients with ASF < 2,500 ng/ml, while LVIC was still correlated with ASF, LIC was not correlated with ASF in patients with 2,500 ng/ml ≤ ASF. Moreover, neither cardiac VIC nor myocardial iron content (MIC) were correlated with ASF in these subgroups. Conclusion: MRI and DECT were complementary to each other in liver iron detection. In MDS patients with high iron content, such as ASF ≥ 5,000 ng/ml, DECT was more reliable than the MRI in the assessment of iron content. But in patients with low iron content, such as ASF < 1,000 ng/ml, MRI is more reliable than DECT. Therefore, for the sake of more accurately evaluating the iron content, the appropriate detection method can be selected according to ASF.

Analysis of the influencing factors related to liver and cardiac iron overload in MDS patients detected by MRI in the real world.

OBJECTIVES: We aim to explore and analyze the related influencing factors of liver and cardiac iron overload in MDS patients detected by magnetic resonance imaging (MRI). METHODS: We have detected cardiac T2* and liver T2* by MRI in 105 MDS patients. Among them, 20 patients accepted MRI examination before and after iron chelation therapy (ICT). Results: We found that adjusted ferritin (ASF) was significantly correlated with liver T2* and cardiac T2*. RBC transfusion volume, brain natriuretic peptide (BNP) and age were the related factors of cardiac T2*, while RBC transfusion volume and erythropoietin (EPO) were related factors of liver T2*. After ICT, the changes of ASF and liver T2* were earlier than cardiac T2*. Chronic hepatitis but virus copy normal's has no significant effect on liver iron deposition. CONCLUSION: These results showed special attention should be paid to these related influencing factors of liver and cardiac T2* expression when we evaluated iron overload and detected the efficacy of ICT in MDS patients.

The E3 protein ubiquitin ligase Itch is a potential target in myeloid malignancies with marrow fibrosis.

BACKGROUND: The underlying mechanism of myeloid malignancies like myelodysplastic syndrome (MDS) and acute myelocytic leukemia (AML) with bone marrow (BM) fibrosis (hereafter referred to as MDS-F and AML-F) is not fully understood. This study aimed to investigate the role of the E3 protein ubiquitin ligase Itch in the pathogenesis of these diseases preliminarily. METHODS: Through bioinformatic methods we found that the E3 protein ubiquitin ligase Itch might play a role in the pathogenesis of MDS-F and AML-F as well as the phosphatidylinositol 3-kinase (PI3K)/Akt pathway. We first investigated whether the PI3K/Akt pathway could regulate the expression Itch and its substrate p73 by using the myeloid neoplasm cell line K562 as a model. Then we assayed the Itch mRNA level of clinical samples in different subgroups to have a knowledge of its role in the myeloid diseases. RESULTS: Through the cellular experiments we got that the PI3K/Akt pathway might not regulate the expression of Itch and its substrate p73. In patients with high risk MDS, AML, fibrosis or higher white blood cells (WBC) count, Itch mRNA level significantly increased when compared with the control groups. But the mRNA level didn't show significant difference in the subgroups classified by karyotype. Through correlative analysis we found that the mRNA level had positive correlation with the WBC count of the patients. CONCLUSIONS: The PI3K/Akt pathway may not get involved in the regulation of the expression of Itch in K562 cells or myeloid tumors and Itch may play a role both in the proliferation and the generation of fibrosis in myeloid malignancies.

[Effects of Abnormal Iron Metabolism on EPO-STAT5 Signaling Pathway in Anemia Patients].

OBJECTIVE: To study the effects of iron metabolism abnormality on EPO-STAT5 signaling pathway in anemia patients. METHODS: According to diseases, the patients were divided into 3 groups: lower risk myelodysplastic syndrome (MDS) group (30 cases) including 14 cases of non-iron over load and 16 cases of iron over load, 12 cases of them were treated by iron chelation therapy; anemia of chronic disease (ACD) group (12 cases) and iron deficiency anemia (IDA) group (12 cases). In addition, the healthy control group was selected. The iron metaloslism index (SF, SI, TIBC), serum level of EPO, plasma level of P-STAT5 and STAT-5 mRNA expression in peripheral blood cells were detected and compared in different groups. Moreover, the effects of iron metabolism abnormality on the expression of EPO and STAT5 in anemia patients were analyzed. RESULTS: compared with non-iron over load group, the EPO level in iron over load group significantly increased (P<0.05), the expression of STAT5 mRNA and P-STAT5 significantly decreased (P<0.05). After iron chelation therapy, the EPO level in serum significantly decreased (P<0.05), the expression of STAT5 mRNA and P-STAT5 was up-regulated significantly (P<0.05). Compared with healthy control group, the expression of EPO in ACD group was down-regulated significantly, while the expression of STAT5 mRNA was not different, but the P-STAT5 expression was down-regulated significantly (P<0.05). Compared with the healtly control group, the EPO expression in IDA group was enhanced significantly (P<0.05), the expression of STAT5 mRNA and P-STAT5 were also significantly enhanced (P<0.05). CONCLUSION: The excessive iron load or chronic inflammation may inhibit the activation of EPO-STAT5 signaling pathway and aggravate the anemia.

Comparative analysis of the survey results of iodine deficiency disorders between high-risk areas in Chongqing and in Linzhi of Tibet in 2007 / 中国地方病学杂志

Objective To investigate iodine deficiency disorders(IDD) in Chongqing and Linzhi, and to provide scientific basis for IDD control and prevention. Methods According to the national program developed in 2007, investigation was conducted in Chengkou and Wuxi county in Chongqing municipality, and Linzhi, Bomi,Milin and Langxian county in Linzhi prefecture. Five towns were sampled in Linzhi county, and 3 in other counties.In each town, one township primary school and two village primary schools were selected to inspect thyroid by B ultrasound and palpation, and urinary iodine of children aged 8 to 10 years was tested in these schools. Meanwhile,2 villages were selected in each town for test of salt iodine level and urinary iodine of childbearing age women and search cretin cases. Results Three hundred and forty families in Chongqing and 915 families in Linzhi were investigated. The coverage of iodized salt in Chongqing was 98.82%(336/340), which was significantly higher than that in Linzhi[66.34%(607/905), x2 = 139.56, P ＜ 0.01]. Goiter rate of children in Chongqing was 9.27%(89/960) by palpation and 8.34% (61/731) by B ultrasound, while goiter rate of children in Linzhi was 7.80%(102/1308) by palpation and 5.53% (69/1248) by B ultrasound. The difference of goiter rate by palpation between Chongqing and Linzhi was not statistically significant (x2 = 1.37, P ＞ 0.05 ). But goiter rate of children by B ultrasound in Chongqing was higher than that in Linzhi (x2= 5.51, P ＜ 0.05). In Chongqing, the median urinary iodine was 319.15 μg/L, and 345.75 μg/L in Chengkou county and 281.39 μg/L in Wuxi county. In Linzhi prefecture, the median urinary iodine was 189.81 μg/L, and 207.81 μg/L in Linzhi county, 161.12 μg/L in Bomi county, 131.83 μg/L in Milin county and 334.60 μg/L in Langxian county. The median urinary iodine in childbearing women were 248.42 μg/L in Chongqing and 121.25 μg/L in Linzhi. The median urinary iodine in Chongqing both in children and women were higher than those in Linzhi. No new cretin case was found in these two areas. Conclusions Goiter rate in high risk areas of IDD in Chongqing and Linzhi has decreased to less than 10%.No new cretin case is found in these areas. It can be concluded that the work of control and prevention is effective.There is excess iodine in Chongqing. In Linzhi county and Langxian county, iodine is excess in children and deficient in women. Further investigation should be conducted to find out the reason. Population iodine is excess in Bomi and Milin counties. The concentration of salt iodine should be decreased in Chongqing. In Linzhi prefecture,adding iodine measures should be adjusted based on further investigation.

[The effect of cyclin D2 shRNA on the proliferation and apoptosis of LP-1 cell].

OBJECTIVE: To construct cyclin D2 (CCND2) short hairpin RNA ( shRNA) plasmid for repressing the expression of CCND2 in human myeloma cell line LP-1,and to detect its effect on the proliferation and apoptosis of LP-1 cell. METHODS: A CCND2 shRNA model was constructed and cloned into plasmid pGensil-2, then the plasmid was transfected into LP-1 cell in vitro. The CCND2 expression cell proliferation, cell cycle and cell apoptosis of the transfected LP-1 cells were studied by RT-PCR, trypanosome staining, flow cytometry and annexin V assay. RESULTS: The transfection efficiency of LP-1 cell was 34. 2%. In the transfected LP-1 cell CCND2 mRNA expression was reduced significantly, the cell growth was inhibited significantly and the cell cycle was partly arrested in G, phase. The apoptosis rate of the transfected LP-1 cell after 72 h was (25.7+/-4.8)%. CONCLUSION: The inhibition of CCND2 in LP-1 cells could inhibit the cell growth and induce cell apoptosis. CCND2 maybe a new therapeutic target.

[Long distance vectorette PCR for detecting translocation of IgH gene in switch regions of patients with multiple myeloma].

Chromosomal translocations involving immunoglobulin heavy chain (IgH) locus at 14q32 are commonly seen in multiple myeloma (MM), which may involve in pathogenesis and associate with prognosis. To rapidly detect the occurrence of translocation involving IgH locus and the fellow chromosomes and isolate the break points, According to the break points occured in switch regions, patents and references, a long distance vectorette PCR method was developed. The results showed that using this method, a 3.5 kb PCR product from MM cell line U266 was gained, each ends aligned with 11q and IgHalpha 1 switch region, respectively. It is concluded that LDV-PCR is effective detection technique. Detecting China MM patients by using this method can interpret some specific clinic statues and pathogenesis mechanisms, and help to find new therapy targets and to assess the patient prognosis.