Reassessing the six months prognosis of patients with severe or very severe aplastic anemia without hematological responses at three months after immunosuppressive therapy / 中华血液学杂志

Objective: To reassess the predictors for response at 6 months in patients with severe or very severe aplastic anemia (SAA/VSAA) who failed to respond to immunosuppressive therapy (IST) at 3 months. Methods: We retrospectively analyzed the clinical data of 173 patients with SAA/VSAA from 2017 to 2018 who received IST and were classified as nonresponders at 3 months. Univariate and multivariate logistic regression analysis were used to evaluate factors that could predict the response at 6 months. Results: Univariate analysis showed that the 3-month hemoglobin (HGB) level (P=0.017) , platelet (PLT) level (P=0.005) , absolute reticulocyte count (ARC) (P<0.001) , trough cyclosporine concentration (CsA-C0) (P=0.042) , soluble transferrin receptor (sTfR) level (P=0.003) , improved value of reticulocyte count (ARC(△)) (P<0.001) , and improved value of soluble transferrin receptor (sTfR(△)) level (P<0.001) were related to the 6-month response. The results of the multivariate analysis showed that the PLT level (P=0.020) and ARC(△) (P<0.001) were independent prognostic factors for response at 6 months. If the ARC(△) was less than 6.9×10(9)/L, the 6-month hematological response rate was low, regardless of the patient's PLT count. Survival analysis showed that both the 3-year overall survival (OS) [ (80.1±3.9) % vs (97.6±2.6) %, P=0.002] and 3-year event-free survival (EFS) [ (31.4±4.5) % vs (86.5±5.3) %, P<0.001] of the nonresponders at 6 months were significantly lower than those of the response group. Conclusion: Residual hematopoietic indicators at 3 months after IST are prognostic parameters. The improved value of the reticulocyte count could reflect whether the bone marrow hematopoiesis is recovering and the degree of recovery. A second treatment could be performed sooner for patients with a very low ARC(△).

Vitamin A deficiency regulates the expression of ferritin in young male Wistar rats / A deficiência de vitamina A regula a expressão de ferritina em ratos Wistar machos jovens

ABSTRACT Objective Iron deficiency and vitamin A deficiency are two of the main micronutrient deficiencies. Both micronutrients are essential for human life and children's development. This study aimed to investigate the effects of vitamin A deficiency on ferritin and transferrin receptors' expression and its relationship with iron deficiency. Methods Five diets with different vitamin A-to-iron ratios were given to thirty five 21-day-old male Wistar rats (separated in groups of seven animals each). The animals received the diet for six weeks before being euthanized. Serum iron and retinol levels were measured as biochemical parameters. Their duodenums, spleens, and livers were analyzed for the expression of ferritin and transferrin receptors by Western Blotting. Results Regarding biochemical parameters, the results show that when both vitamin A and iron are insufficient, the serum iron content (74.74µg/dL) is significantly lower than the control group (255.86µg/dL). The results also show that vitamin A deficiency does not influence the expression of the transferrin receptor, but only of the ferritin one. Conclusion Vitamin A deficiency regulates the expression of ferritin in young male Wistar rats.

RESUMO Objetivo A deficiência de ferro e de vitamina A são duas das principais deficiências de micronutrientes, sendo que ambos são essenciais para a vida humana e o desenvolvimento das crianças. O objetivo deste estudo foi investigar o efeito da deficiência de vitamina A na expressão de ferritina e o receptor de transferrina e sua relação com a deficiência de ferro. Métodos Cinco dietas com diferentes proporções de vitamina A para ferro foram administradas a 35 ratos Wistar machos de 21 dias de vida (sete animais por grupo). Os animais receberam a dieta por seis semanas antes de serem eutanasiados. Os níveis séricos de ferro e retinol foram medidos como parâmetros bioquímicos. Duodeno, baço e fígado foram analisados quanto à expressão de ferritina e o receptor de transferrina por Western Blotting. Resultados Em relação aos parâmetros bioquímicos, os resultados mostram que quando a vitamina A e o ferro são insuficientes, o teor de ferro sérico (74.74µg/dL) é significativamente menor do que no grupo controle (255.86µg/dL). Os resultados também mostram que a deficiência de vitamina A não influencia a expressão do receptor da transferrina, mas da ferritina. Conclusão A deficiência de vitamina A regula a expressão de ferritina em ratos Wistar machos jovens.

Progress on epigenetic regulation of iron homeostasis / 浙江大学学报·医学版

Iron homeostasis plays an important role for the maintenance of human health. It is known that iron metabolism is tightly regulated by several key genes, including divalent metal transport-1(), transferrin receptor 1(), transferrin receptor 2(), ferroportin(), hepcidin(), hemojuvelin() and . Recently, it is reported that DNA methylation, histone acetylation, and microRNA (miRNA) epigenetically regulated iron homeostasis. Among these epigenetic regulators, DNA hypermethylation of the promoter region of , and bone morphogenetic protein 6 () genes result in inhibitory effect on the expression of these iron-related gene. In addition, histone deacetylase (HADC) suppresses gene expression. On the contrary, HADC inhibitor upregulates gene expression. Additional reports showed that miRNA can also modulate iron absorption, transport, storage and utilization via downregulation of and other genes. It is noteworthy that some key epigenetic regulatory enzymes, such as DNA demethylase TET2 and histone lysine demethylase JmjC KDMs, require iron for the enzymatic activities. In this review, we summarize the recent progress of DNA methylation, histone acetylation and miRNA in regulating iron metabolism and also discuss the future research directions.

Phenotype changes of oral epithelial stem cells after in vitro culture

Abstract The aim of our study was to isolate populations of keratinocyte stem cells based on the expression of cell surface markers and to investigate whether the culture could affect their phenotype. keratinocytes from human oral mucosa were sorted based on the expression of the epithelial stem cell markers p75NTR and CD71. We also examined the co-expression of other epithelial stem markers such as integrins β1 and α6 and their stem cell-like proprieties in in vitro assays. Three passages after being sorted by MACS, more than 93% of the p75NTR+ve cells lost the expression of p75NTR, while 5.46% of the p75NTR-ve gained it. Within the small population of the p75NTR+ve cells, 88% co-expressed other epithelial stem cell markers such as integrins β1 and α6, while only 28% of p75NTR-ve cells co-expressed these markers. These results were confirmed by sorting cells by FACS. Additionally, when double staining was used for sorting cells, 99% of the p75NTR+veCD71-ve and 33% of the p75NTR-veCD71+ve cells expressed both integrins, but just one week after culture, only 1.74% of the p75NTR+veCD71-ve cells still expressed p75NTR and only 0.32% still expressed CD71. Similar results were obtained when co-culturing p75NTR+ve and p75NTR-ve populations before analysis. Our results suggest that phenotype changes may be part of an intrinsic cellular mechanism to conserve levels of protein expression as they may found in the human body. In addition, in vitro culture may not offer ideal conditions for epithelial stem cell maintenance due to phenotype changes under standard culture conditions.

Serum level of soluble transferrin receptor in children with hemoglobin H disease / 中国当代儿科杂志

OBJECTIVE@#To investigate the serum level of soluble transferrin receptor (sTfR) and its association with the degree of anemia in children with hemoglobin H (HbH) disease.@*METHODS@#A total of 55 children with HbH disease were enrolled as the HbH group, and 30 healthy children were enrolled as the control group. The HbH group was further divided into a deletional HbH disease group and a non-deletional HbH disease group. A retrospective analysis was performed for hematological parameters and serum sTfR level in all groups.@*RESULTS@#Of the 55 children with HbH disease, 39 had deletional HbH disease and 16 had non-deletional HbH disease. Compared with the control group, the deletional and non-deletional HbH disease groups had significantly lower hemoglobin (Hb), mean corpuscular volume (MCV), and mean corpuscular hemoglobin (MCH) and a significantly higher serum level of sTfR. Compared with the deletional HbH disease group, the non-deletional HbH disease group had significantly lower red blood cell count (RBC) and Hb level and significantly higher MCV, MCH, and serum sTfR level. In children with HbH disease, serum sTfR level was negatively correlated with RBC and Hb level (r=-0.739 and -0.667 respectively, P<0.05) and positively correlated with MCV and MCH (r=0.750 and 0.434 respectively, P<0.05).@*CONCLUSIONS@#Serum sTfR level is associated the degree of anemia in children with HbH disease, and sTfR may be a target for the treatment of HbH disease.

Expression Changes of Serum Transferrin Receptor and Its Mechanism in Children with Acute Leukemia / 中国实验血液学杂志

OBJECTIVE@#To investigate the expression changes of serum transferrin receptor（sTFR） and its related mechanism in children with acute leukemia（AL）.@*METHODS@#Forty-six children with acute leukemia treated in our hospital from June 2016 to June 2017 were selected and enrolled in the AL group, 40 healthy children were enrolled in the control group. The related clinical data were recorded, including age, sex and CNSL level. RNA interference technology was used to silence TFR genes of KG-1a and TCHu147 cells, MTT method and flow cytometry were used to analyze the effect of TFR gene on proliferation and cell cycle of KG-1a cells and TCHu147 cells. Western blot was used to detect the level of cyclin related to leukemic cells after siRNA interference.@*RESULTS@#The level of sTFR in AL patients was significantly higher than that of healthy people (P<0.05). The mRNA and protein expression levels of TFR in peripheral blood leukemic cells were all higher than those in healthy people (P<0.05). The level of sTFR closely related to the white blood cell（WBC） count, the proportion and absolute number of leukemic cells, hepcidin（Hepc） level, and risk grade in AL patients (P<0.05). The proliferation ability of KG-1a and TCHu147 cells after TFR siRNA interference was significantly inhibited (P<0.05). Fow cytometry showed that after the TFR siRNA interference, the ratio of KG-1a and TCHu147 cells in G/G phase was 62.51%±5.39% and 63.37%±4.27%, respectively, which increased significantly as compared with the blank and negative control group (P<0.05); the ratio of KG-1a and TCHu147 in G/M phase was 5.74%±1.34% and 7.37%±1.56%, respectively, which significantly decreased as compared with the blank control and the negative control group (P<0.05).@*CONCLUSION@#The peripheral blood leukemic cells of AL patients can synthesize more TFR protein, lead into the increase of sTFR level. It can effectively interfere the division of leukemia cells by downregulating the expression of TFR gene.

¿Puede usarse el receptor soluble de transferrina para diagnosticar anemia ferropénica y evaluar la respuesta al hierro en lactantes con desnutrición aguda moderada? / Can soluble transferrin receptor be used in diagnosing iron deficiency anemia and assessing iron response in infants with moderate acute malnutrition?

Objetivo. Evaluar la eficacia del receptor soluble de transferrina (RST) en el diagnóstico de la anemia ferropénica (AF) y en la evaluación de la respuesta al hierro en los lactantes con desnutrición aguda moderada (DAM). Población y métodos. Se reclutó a lactantes con valores de hemoglobina (Hb) inferiores a los valores umbrales de anemia para su edad y con anemia hipocrómica/microcítica observada en el frotis de sangre periférica. La DAM se definió como un puntaje Z de peso/estatura de entre < -2 y -3. Se compararon los valores del hemograma, los parámetros férricos y el RST entre 41 lactantes con DAM y anemia (grupo DA), 32 lactantes con anemia sin DAM (grupo A) y controles saludables (n= 30). Una vez completado el tratamiento de la anemia y la desnutrición, se repitieron las evaluaciones. Resultados. Además de los índices hematológicos compatibles con AF, los valores de hierro sérico (Fe) y saturación de transferrina (ST) eran significativamente menores, mientras que el valor de transferrina era significativamente mayor en los grupos DA y A en comparación con los controles (p < 0,001). Los valores de ferritina y proteína C-reactiva (PCR) eran significativamente más elevados en el grupo DA (p < 0,05 para la ferritina, p < 0,01 para la PCR). El valor medio del RST fue similar en ambos grupos (DA y A) (p > 0,05) y significativamente mayor que en los controles (p < 0,001). Después del tratamiento con hierro, el RST disminuyó en los grupos DA y A (p < 0,001) a valores similares a los observados en los controles. El RST se correlacionó negativamente con la Hb durante todo el estudio (grupo DA: r= -0,350, p < 0,05; grupo A: r= -0,683, p < 0,01). Conclusiones. Dado que los valores del RST en los grupos DA y A disminuyeron después del tratamiento con hierro, consideramos que este parámetro no estuvo afectado por la DAM ni la inflamación y puede usarse, por sí solo, para detectar la AF y supervisar la respuesta al tratamiento en los lactantes con DAM.

Objective. To evaluate the efficacy of soluble transferrin receptor (sTfR) in diagnosing iron deficiency anemia (IDA) and evaluating iron response in infants with moderate acute malnutrition (MAM). Population and methods. Infants withhemoglobin (Hb) levels lower than threshold values for anemia for their ages and hypochromic/ microcytic anemia on peripheral smear were recruited. MAM was defined as weight/height z score < -2 to -3. Complete blood count (CBC), iron parameters and sTfR were compared among 41 infants with MAM and anemia (MA group), 32 infants with anemia without MAM (group A), and healthy controls (n= 30). Following anemia and malnutrition treatment, tests were repeated. Results. Besides hematological indices compatible with IDA, serum iron (Fe) and transferrin saturation (TS) were significantly lower, while transferrin was significantly higher in MA and A groups compared to controls (p <0.001). Ferritin and C-reactive protein (CRP) were significantly higher in MA group (p <0.05 ferritin, p <0.01 for CRP). Mean sTfR was similar in both MA and A groups (p >0.05) and significantly higher than controls (p <0.001). Following iron treatment, sTfR decreased inboth MA and A groups (p <0.001) to similar values as controls. sTfR was negatively correlated to Hb throughout the study (for MA group, r= -0.350, p <0.05; for A group, r= -0.683, p <0.01). Conclusions. As sTfR values in both MA and A groups decreased following iron treatment, we believe that this parameter was not influenced by MAM or inflammation; and it alone can be used to detect IDA and monitor treatment response in infants with MAM.

Hepcidin and iron parameters in children with anemia of chronic disease and iron deficiency anemia

BACKGROUND: Anemia of chronic disease (ACD) and iron deficiency anemia (IDA) are the two most prevalent forms of anemia having interrelated characteristics. Hepcidin, a newly introduced biomarker for assessment of iron status, is a homeostatic regulator of iron metabolism. We investigated the role of hepcidin and other conventional iron parameters to assess iron status among children with ACD and IDA. We also identified children with ACD who developed iron deficiency (ID). METHODS: The study was undertaken in anemic children with 30 cases each of ACD and IDA along with 30 age and sex-matched controls. The ACD cases were subdivided into pure ACD and ACD with coexistent ID. All cases were subjected to following tests: complete blood count with peripheral smear, serum C-reactive protein, serum interleukin-6, iron studies, serum soluble transferrin receptor (sTfR), and serum hepcidin. RESULTS: The mean serum hepcidin concentration was significantly increased in pure ACD patients (143.85±42.76 ng/mL) as compared to those in IDA patients (6.01±2.83 ng/mL, P < 0.001) and controls (24.96±9.09 ng/mL, P <0.001). Also, compared to pure ACD patients [normal sTfR levels (<3 µg/mL)], the serum hepcidin concentration was reduced significantly in ACD patients with ID [high sTfR levels (≥3 µg/mL)] with a mean of 10.0±2.97 ng/mL. CONCLUSION: Hepcidin measurement can provide a useful tool for differentiating ACD from IDA and also help to identify an iron deficiency in ACD patients. This might aid in the appropriate selection of therapy for these patients.

Serum Protein Expression Level in 47 Patients with Megaloblastic Anemia and Its Clinical Significance / 中国实验血液学杂志

<p><b>OBJECTIVE</b>To study the clinical significance of serum protein expression level in patients with megaloblastic anemia(MA).</p><p><b>METHODS</b>A total of 47 patients with MA were enrolled in this study between November 2013 and November 2015, and 50 healthy people in the same period were selected as controls. The levels of total protein (TP), albumin (Alb), ferritin (FER), transferrin (TRF) and soluble transferrin receptor (sTfR) were compared between 2 groups, and the serum protein expression levels in different types of MA, varous anemia degrees of MA were analyzed.</p><p><b>RESULTS</b>The leves of TP, Alb and FER in MA patients were significantly lower than those in control group, the levels of TRF and sTfR were statistically significantly higher than those in control group(P<0.05); the levels of TP, Alb and FER in the patients with mild anemia were significantly higher than those in the patients with moderate and severe anemia, the levels of TRF and sTfR were statistically significantly lower(P<0.05), while the levels of TP, Alb and FER in patients with moderate anemia were significantly higher than those in the patients with severe anemia, the levels of TRF and sTfR were significantly lower(P<0.05). Compared with levels before treatment, the levels of TP, Alb and FER significantly increased after treatment, while the TRF and sTfR levels significantly decreased (P<0.05).</p><p><b>CONCLUSION</b>Serum levels of TP, Alb, FER, TRF and sTfR can provide a basis for the diagnosis of MA, and contribute to predict the disease to some extent.</p>

Influence of GATA-1 on Expression of EpoR in Bone Marrow CD71+ Cells of Rat Model with High Altitude Polycythemia / 中国实验血液学杂志

<p><b>OBJECTIVE</b>To explore the influence of GATA-1 on expression of EpoR in bone marrow CD71+ cells of rat model with high altitude polycythemia (HAPC).</p><p><b>METHODS</b>Forty-eight male SD rats were randomly divided into normal control and HAPC model group. HAPC model was established at the altitude of 4 300 meters in the natural environment, and verified by bone marrow cell counts and hematological parameters. Myeloid CD71+ cells were separated by the density gradient centrifugation combined with magnetic activated cell sorting. The expression of EpoR on cell membrane was detected by flow cytometry and cell immunofluorescence. The expression changes of GATA-1 and EpoR mRNA and protein were detected by Q-PCR and Western blot, respectively. CD71+ cells were cultured under normoxia and hypoxia, respectively. After transfection for 96 h, the optimal interference sequence GATA-1 shRNA1 was selected. And the mRNA and protein expression level of GATA-1 and EpoR were detected by Q-PCR and Western blot respectively.</p><p><b>RESULTS</b>The animal model with HAPC was established successfully and comfirmed by the bone marrow cell counting and the hematologic parameters in comparison with that of the normal control. EpoR expression on the myeloid CD71+ cell membrane in HAPC group was significantly higher than that in normal control (P<0.05). The expression of GATA-1 and EpoR in myeloid CD71+ cells of HAPC group was higher than that in control group (P<0.05). The mRNA and protein expression of GATA-1 and EpoR in two groups positively correlated (control group, r=0.929, P<0.01, r=0.802, P<0.05; HAPC group, r=0.822, P<0.05, r=0.839, P<0.01). However, the mRNA and protein expression of EpoR at normoxia and hypoxia was significantly lower than that in negative control group after interfernce with GATA-1 shRNA1 for 96 h (P<0.05). And the expression of GATA-1 and EpoR under hypoxia was higher than that in normoxia.</p><p><b>CONCLUSION</b>The effect of GATA-1 on EpoR expression may be correlated with the pathogenesis of HAPC.</p>

Progress on anti-tumor molecular mechanisms of dihydroartemisinin / 浙江大学学报·医学版

Artemisinin is an anti-malarial drug with poor water solubility and oral absorption; so a variety of derivatives based on the parent nucleus have been developed. Compared with artemisinin, dihydroartemisinin (DHA) has a stronger anti-malaria activity, and has the advantages of high metabolic rate and better water solubility. Recent studies have discovered that DHA has a good inhibitory effect on tumor cells, which is closely related to the peroxide bridge in its molecular structure. Since tumor cells need more Fethan normal cells, there are a large number of transferrin receptors on the tumor cell membrane. DHA can break the peroxide bridge in the presence of Fe, and the free radicals generated can play its lethal effect on tumor cells. In addition, DHA can promote endocytosis of transferrin receptor, and thus prevent cancer cells from taking Fefrom microenvironment. This article reviews the anti-tumor molecular mechanism of DHA, including accelerating oxidative damage, inducing apoptosis, inhibiting the growth, proliferation and invasion of tumor cells, reversing tumor multidrug resistance.

Iron Supplementation Reverses the Reduction of Hydroxymethylcytosine in Hepatic DNA Associated With Chronic Alcohol Consumption in Rats

BACKGROUND: Alcohol is known to affect two epigenetic phenomena, DNA methylation and DNA hydroxymethylation, and iron is a cofactor of ten-eleven translocation (TET) enzymes that catalyze the conversion from methylcytosine to hydroxymethylcytosine. In the present study we aimed to determine the effects of alcohol on DNA hydroxymethylation and further effects of iron on alcohol associated epigenetic changes. METHODS: Twenty-four male Sprague-Dawley rats were fed either Lieber-DeCarli alcohol diet (36% calories from ethanol) or Lieber-DeCarli control diet along with or without iron supplementation (0.6% carbonyl iron) for 8 weeks. Hepatic non-heme iron concentrations were measured by colorimetric assays. Protein levels of hepatic ferritin and transferrin receptor were determined by Western blotting. Methylcytosine, hydroxymethylcytosine and unmodified cytosine in DNA were simultaneously measured by liquid chromatography/mass spectrometry method. RESULTS: Iron supplementation significantly increased hepatic non-heme iron contents (P < 0.05) but alcohol alone did not. However, both alcohol and iron significantly increased hepatic ferritin levels and decreased hepatic transferrin receptor levels (P < 0.05). Alcohol reduced hepatic DNA hydroxymethylation (0.21% ± 0.04% vs. 0.33% ± 0.04%, P = 0.01) compared to control, while iron supplementation to alcohol diet did not change DNA hydroxymethylation. There was no significant difference in methylcytosine levels, while unmodified cytosine levels were significantly increased in alcohol-fed groups compared to control (95.61% ± 0.08% vs. 95.26% ± 0.12%, P = 0.03), suggesting that alcohol further increases the conversion from hydroxymethylcytosine to unmodified cytosine. CONCLUSIONS: Chronic alcohol consumption alters global DNA hydroxymethylation in the liver but iron supplementation reverses the epigenetic effect of alcohol.

Glicanos de la vellosidad trofoblástica en la anemia ferropénica y la preeclampsia grave / Glycans in villus trophoblast in iron deficiency anemia and early-onset severe preeclampsia

Glycoproteins attached to cell membrane of syncytiotrophoblast are in close contact with maternal blood, thus these molecules could participate in cell-to-cell communication and biological functions involving ligand-receptors in the maternal-fetal interphase. The attached glycans are involved in the stability, folding and exportation of the protein towards the cell membrane. The objective of this study was to characterize the glycan profile of third trimester placental villi obtained from pregnant women with early-onset severe preeclampsia and gestational anemia compared with normal pregnant women. Protein extracts from placental villi were used in lectin blot assays. -2,3 N- and O-linked sialic acid was over-expressed in villous of severe preeclamptic placentas measured by MAA lectin staining. High mannose glycans and Gal-GlcNAc patterns were also increased in severe preeclampsia compared with the other groups. These findings can explain changes in the cell membrane expression of glycoproteins.

Introducción: Las glicoproteínas de la membrana del sincitiotrofoblasto (STB) se encuentran en contacto con la sangre materna, por lo que pueden participar en la comunicación en la interface materno-fetal. Objetivo: caracterizar patrones de glicanos de la vellosidad trofoblástica de mujeres sanas, anémicas por deficiencia de hierro y preeclámpticas graves de inicio temprano. Materiales y métodos: se obtuvieron extractos proteínicos de vellosidad placentaria de tercer trimestre y se determinó la expresión de patrones de glicanos, usando lectinas. Para la comparación de los grupos se utilizó la prueba de Kruskal-Wallis. Resultados: Se encontró una sobreexpresión en los patrones de glicosilación Gal-GlcNAc, manosa y ácido siálico α2-3 en el grupo con preeclampsia. Conclusiones: El aumento en los patrones Gal-GlcNAc, alta manosilación y ácido siálico α2-3, en proteínas de vellosidad placentaria en los pesos moleculares encontrados, pudiera explicar cambios en la expresión de proteínas de membrana del STB.

Expression of CD71 on cell proliferation in hematologic malignancy and its correlation with Ki-67 / 中国实验血液学杂志

<p><b>OBJECTIVE</b>This study was to explore the expression of CD71, as a proliferation indicator, on cell proliferaration in hematologic malignancy and its correlation with Ki-67, so as to assess the feasibility of CD71 instead of Ki-67 for assaying cell proliferation by flow cytometry (FCM).</p><p><b>METHODS</b>(1) Compared with mature B lymphoctyes during stationary phase in peripheral blood from healthy people, the cell cycle and the expression of CD71 and Ki-67 of cell lines from patients with leukemia and lymphoma were examined, the correlation among CD71, S-phase cell fraction (SPF) and Ki-67 were analyzed; (2) Compared with mature B lymphoctyes in bone marrow from non-hematologic disease patients, the expression and correlation of CD71 and Ki-67 of all kinds of leukemic cells and myeloma cells from bone marrow were analyzed by using Ki-67/CD71/CD45/CD123, Ki-67/CD71/CD45/CD20 or Ki-67/CD71/CD45/CD138.</p><p><b>RESULTS</b>(1) in respect to the expression rate of CD71 on tumor cell lines, the expression rate of CD71 on HL-60 cells was (99.77 ± 0.064)%, the expression rate of CD71 on NB4 cells was (99.23 ± 0.12)%, the expression rate on THP-1 cells was (98.90 ± 0.30)% and the expression rate on K562 cells was (97.03 ± 0.15)% in myelogenous leukemia cell lines, the expression rate of CD71 on Raji cells was (99.35 ± 0.21)% and the expression rate on Mino cell was (96.95 ± 0.42)% in lymphoma cell lines, which were also obviously higher than that on cells of the control group (P < 0.05); (2) in respect to the expression rate of CD71 on tumor cells in bone marrow, the expression rate of CD71 on poorly differentiated AML(M1 and M2) cells was (51.50 ± 19.31)%, the expression rate of CD71 on acute promyelocytic leukemia (AML-M3) cells was (35.71 ± 14.02) %, the expression rate of CD71 on acute monocytic leukemia (AML-M5) cells was (30.54 ± 14.38)%, the expression rate of CD71 on acute T lymphoblastic leukemia cells was (68.40 ± 20.83)%, the expression rate of CD71 on acute B lymphoblastic leukemia was (39.67 ± 18.27)%, the expression rate of CD71 on multiple myeloma (MM) cells was (55.49 ± 18.15%), the expression rate of CD71 on chronic lymphocytic leukemia(CLL) was (1.32 ± 0.33%), which were also higher than that on cells in the control group(P < 0.05) except for CLL cells (P > 0.05); (3) CD71 had a positive linear corrlation with SPF in cell lines (r = 0.914, P < 0.05), and also had a positive linear corrlation with Ki-67 in cell lines and carcinoma cells from bone marrow (r = 0.894,r = 0.904, P < 0.05).</p><p><b>CONCLUSION</b>The CD71 can take the place of Ki-67 as an indicator of cell proliferation activity of hematologic malignancies and the determination CD71 by FCM is simpler and better than that of Ki-67 in respest of methodology.</p>

The usefulness of soluble transferrin receptor in the diagnosis and treatment of iron deficiency anemia in children / 소아과

PURPOSE: Soluble transferrin receptor (sTfR) is a truncated extracellular form of the membrane transferrin receptor produced by proteolysis. Concentrations of serum sTfR are related to iron status and erythropoiesis in the body. We investigated whether serum sTfR levels can aid in diagnosis and treatment of iron deficiency anemia (IDA) in children. METHODS: Ninety-eight patients with IDA were enrolled and were classified according to age at diagnosis. Group 1 comprised 78 children, aged 6-59 months, and group 2 comprised 20 adolescents, aged 12-16 years. RESULTS: In group 1, patients' serum sTfR levels correlated negatively with mean corpuscular volume; hemoglobin (Hb), ferritin, and serum iron levels; and transferrin saturation and positively with total iron binding capacity (TIBC) and red cell distribution width. In group 2, patients' serum sTfR levels did not correlate with ferritin levels and TIBC, but had a significant relationship with other iron indices. Hb and serum sTfR levels had a significant inverse relationship in both groups; however, in group 1, there was no correlation between Hb and serum ferritin levels. In 30 patients of group 1, serum sTfR levels were significantly decreased with an increase in Hb levels after iron supplementation for 1 month. CONCLUSION: Serum sTfR levels significantly correlated with other diagnostic iron parameters of IDA and inversely correlated with an increase in Hb levels following iron supplementation. Therefore, serum sTfR levels can be a useful marker for the diagnosis and treatment of IDA in children.

Deficiencia subclínica de hierro en niños menores de cuatro años de edad, ciudad de Valencia, Venezuela / Subclinical iron deficiency in children under four years of age, Valencia city, Venezuela / Deficiencia subclinica de ferro em changas menores de quatro anos de idade, cidade de Valencia, Venezuela

La deficiencia de hierro (DH) se considera un problema de salud pública y afecta principalmente a los niños en las etapas de crecimiento rápido y desarrollo psicomotor. El objetivo del estudio fue identificar la deficiencia subclínica de hierro en niños menores de 4 años, mediante el uso de ferritina sérica (FS), receptor soluble de transferrina (RsTf) e índice RsTf-FS como herramientas diagnósticas. El estudio fue descriptivo, transversal, y se realizó en Valencia, Venezuela, en 2006. Se determinaron en 541 niños las concentraciones de hemoglobina (método automatizado), FS (IRMA), RsTf (ELISA), Proteína C Reactiva y alfa glicoproteína (nefelometría). Se realizaron estadísticos descriptivos, prueba de Mann-Whitney y Fisher, con nivel de significancia de p<0,05. El 72,1% de los niños tenían depósitos de hierro agotados, 25,5% eritropoyesis deficiente de hierro y 27,0% anemia. El índice RsTf-FS identificó mayor porcentaje de niños con DH subclínica; mostrando mayor valor diagnóstico frente a la FS y el RsTf por separado. El índice RsTf-FS podría convertirse en una prueba invaluable para distinguir entre agotamiento de los depósitos corporales de hierro y eritropoyesis deficiente de hierro, fases subclínicas de la DH. Se propone una intervención nutricional con base en la suplementación y la educación como estrategia fundamental para disminuir la prevalencia de DH y anemia.

Iron deficiency is considered a public health problem, especially affecting children at ages of fast growth and psychomotor development. The study was aimed to identify subclinical iron deficiency in children below four years of age, through the use of serum ferritin (FS), soluble transferrin receptor (RsTf) and index RsTf-FS as diagnostic tools. It was a descriptive, transversal study performed at Valencia, Venezuela, 2006. Hemoglobin (Hb) by automated method, FS by IRMA, RsTf by ELISA, C Reactive Protein and alpha glycoprotein by nephelometry were assessed in 541 subjects. Descriptives values and Mann-Whitney and Fisher test results are presented. A p value <0.05 was considered significant. 72.1% of children had iron stores depletion, 25.5% had iron deficient erithropoyesis and prevalence of anemia was 27.0%. The index RsTf-FS allowed to identify a higher percentage of children with subclinical iron deficiency, which indicates that the index is better diagnostic indicator than FS or RsTf by separate. Index RsTf-FS could become a invaluable test in order to distinguish between iron body stores depletion and iron-deficient erythropoiesis, subclinical phases of iron deficiency. Nutritional intervention based on supplementation and education as fundamental tool to diminish anemia and iron deficiency prevalence should be initiated.

A deficiencia de ferro (DF) é considerada um problema de saúde pública e afeta principalmente changas em fases de crescimento rápido e desenvolvimento psicomotor. O objetivo do estudo foi identificar a deficiencia de ferro subclinica em criangas menores de 4 anos, através do uso de ferritina sérica (FS), receptor solúvel de transferrina (sTfR) e índice sTfR-FS como ferramentas de diagnóstico. O estudo foi descritivo, transversal, e foi feito em Valencia, Venezuela, em 2006. Foram determinadas em 541 criangas as con-centragoes de hemoglobina (método automatizado), FS (IRMA), sTfR (ELISA), Proteína C reativa e alfa-gli-coproteína (nefelometria). Foram realizados estatísticos descritivos, testes de Mann-Whitney e Fisher, com um nivel de significancia de p<0,05. 72,1% das criangas tinham os depósitos de ferro esgotados, 25,5% eritropoiese deficiente de ferro e 27,0% anemia. O índice sTfR-FS identificou maior percentagem de crian-gas com DF subclínica mostrando assim maior valor diagnóstico em relagáo a FS e sTfR separadamente. O índice sTfR-FS poderia tornar-se um teste de valor inestimável para a distingáo entre deplegáo de reservas corporais de ferro e eritropoiese deficiente de ferro, estágios subclínicos da deficiencia de ferro. Propoe-se uma intervengáo nutricional com base na suplementagáo e educagáo como estratégia fundamental para diminuir a prevalencia de deficiencia de ferro e anemia.

Study of serum soluble transferrin receptors and Reticulocyte Hemoglobin content in patients with Juvenile Rheumatoid Arthritis

Objectives: The present study was conducted to evaluate the levels of serum soluble transferrin receptors [sTfR] and reticulocyte hemoglobin content [CHr] in patients with juvenile idiopathic arthritis [JIA] attending the pediatric rheumatology outpatient clinic of Alexandria University Children's Hospital [AUCH]

Study design: Forty three JIA patients whose age ranged from 3 to 16 years were enrolled in the study as well as 20 healthy children of matched age and sex as a control group. Complete blood count with CHr, iron profile, acute phase response parameters and sTfR levels were done in all patients and controls

Results: From the total 43 patients with JIA, 22 patients [51.2%] were anemic and 21 [48.8%] were non anemic. Hemoglobin level had negative correlation with illness duration in the anemic group [p=0.007]. No significant difference was found between these 2 groups as regards to any of the medications taken, The anemic group had significantly higher levels of CBC parameters of inflammation, acute phase response parameters and disease activity score than the non-anemic group [p=<0.001]. In the non-anemic group, these parameters showed no significant difference from the controls. Anemic group had significantly higher ferritin level and sTfR. than the non anemic and the controls [p.0.001]. CHr was significantly lower in anemic group than the other 2 groups [p=0.001]

Conclusion: Anemia in JIA is associated with high levels of ferritin and sTfR. with lower CHr. Serum ferritin, being an acute phase reactant, is not reliable in diagnosing anemia in case of chronic disease necessitating the use of other markers as: sTfR. and CHr

Iron Deficiency Anemia in Infants and Young Children / 임상소아혈액종양

The etiology of iron deficiency anemia (IDA) in infancy (9-24 months) are diet, parasite, blood loss and Helicobacter pylori. Diet is the most common etiology of IDA in infancy. If infant with breastfeeding beyond 6 months of life is premature, low birth weight and twin, the risk of IDA will increase. Hookworm infestation could be an etiology in some underdeveloped countries. Blood loss could be caused by hospitalization (blood sampling especially in premature newborn), diet-related (exposure to a heat-labile protein in whole cow's milk), and lesion of gastrointestinal tract. The diagnosis of IDA is simple (a hemoglobin level <11 g/dL and serum ferritin <12 microg/L). But most of the patients we encounter have acute infections (respiratory infections, urinary tract infection and acute otitis media etc) at sampling time. Because ferritin is an acute phase reactant, the level of ferritin cannot stand true iron status in an acutely infected infant. We recommend two methods to help differentiate pure IDA and anemia of inflammation. One is to check ratio of transferrin receptor and ferritin. The other is to check ferritin after CRP is normalized. Because the international marriage increases, thalassemia is also included in differential diagnosis of microcytic anemia of infant.

Iron Deficiency Anemia in Infants and Young Children / 임상소아혈액종양

The etiology of iron deficiency anemia (IDA) in infancy (9-24 months) are diet, parasite, blood loss and Helicobacter pylori. Diet is the most common etiology of IDA in infancy. If infant with breastfeeding beyond 6 months of life is premature, low birth weight and twin, the risk of IDA will increase. Hookworm infestation could be an etiology in some underdeveloped countries. Blood loss could be caused by hospitalization (blood sampling especially in premature newborn), diet-related (exposure to a heat-labile protein in whole cow's milk), and lesion of gastrointestinal tract. The diagnosis of IDA is simple (a hemoglobin level <11 g/dL and serum ferritin <12 microg/L). But most of the patients we encounter have acute infections (respiratory infections, urinary tract infection and acute otitis media etc) at sampling time. Because ferritin is an acute phase reactant, the level of ferritin cannot stand true iron status in an acutely infected infant. We recommend two methods to help differentiate pure IDA and anemia of inflammation. One is to check ratio of transferrin receptor and ferritin. The other is to check ferritin after CRP is normalized. Because the international marriage increases, thalassemia is also included in differential diagnosis of microcytic anemia of infant.

Changes of CD34(+) and CD71(+)CD45(-) cell levels in bone marrow of MDS and AA patients / 中国实验血液学杂志

This study was aimed to investigate the changes of CD34(+) and CD71(+)CD45(-) cell levels in MDS and AA patients. A total of 25 cases MDS and 43 cases of AA (18 cases SAA and 25 cases of NSAA) from January 2010 to October 2013 in the Department of Hematology, affiliated hospital of Hebei United University were enrolled in this study. The complete blood count, bone marrow smears, bone marrow biopsy, karyotype analysis and bone marrow blood cell immune genotyping (mainly the proportion of CD34(+) cells, CD71(+)CD45(-) cells in nucleated cells) were carried out for all patients; the changes of CD34(+) and CD71(+)CD45(-) cell levels in patients with MDS and AA (SAA NSAA) were compared; the differences of white blood cell count, platelet count and hemoglobin concentration in patients with count of CD71(+)CD45(-) ≥ 15% or <15% were analyzed. The results showed that the count of CD34(+) in MDS group was higher than that in AA (NSAA and SAA) group (P < 0.05). The count of CD71(+)CD45(-) cells in MDS group was higher than that in SAA (P < 0.05), there was no significant difference between NSAA group and MDS group. In MDS group with CD71(+)CD45(-) ≥ 15%, the platelet count was significantly higher than that in NSAA group (P < 0.05); and there was no statistical difference for leukocyte, platelet count and hemoglobin level between MDS and NSAA group with CD71(+)CD45(-) <15% (P > 0.05). It is concluded that the count of CD34(+) cells in MDS patients is significantly higher than that in AA and SAA patients. The count of CD71(+)CD45(-) cells in MDS group is significantly higher than that of SAA group. The platelet count in MDS patients with CD71(+)CD45(-) cells ≥ 15% is significantly higher than that of the NSAA group.