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(△).
Anemia, Aplastic/drug therapy* ; Antilymphocyte Serum/therapeutic use* ; Cyclosporine/therapeutic use* ; Humans ; Immunosuppression Therapy ; Immunosuppressive Agents/therapeutic use* ; Prognosis ; Receptors, Transferrin/therapeutic use* ; Retrospective Studies ; Treatment Outcome

Iron metabolism is the process of absorption, transport, storage and conversion and excretion of the essential trace element iron in living organisms. Normal iron metabolism tightly regulates iron content at the systemic and cellular levels through a variety of related proteins to prevent excessive free radicals from being generated during the iron cycle that can damage the body. Various abnormalities in iron metabolism are found in a variety of lymphohaematopoietic tumours and an insidious link between iron metabolism and tumour development has been revealed. Serum ferritin levels and abnormalities of iron transport proteins, transferrin and their receptors can be used as prognostic indicators for lymphohematopoietic tumours and have opened up new directions of diagnosis and treatment, with a large number of novel drugs targeting tumours emerging to date. This article briefly describes the normal iron metabolism process and highlights the progress of research on abnormal iron metabolism in lymphohematopoietic tumors at the systemic and cellular levels.
Hematopoiesis ; Humans ; Iron/metabolism* ; Neoplasms ; Receptors, Transferrin/metabolism* ; Transferrin/metabolism*

Hemochromatosis/genetics* ; Histocompatibility Antigens Class I/genetics* ; Humans ; Mutation ; Receptors, Transferrin/genetics*

transferrin saturation (TSAT).CONCLUSION: Although the relationship was not cause-and-effect, increased RWT was independently associated with high serum hepcidin, particularly in women and patients with low TSAT. The relationship between cardiac geometry and serum hepcidin in CKD patients needs to be confirmed in future studies.]]>
Anemia ; Comorbidity ; Female ; Hepcidins ; Humans ; Inflammation ; Logistic Models ; Metabolism ; Miners ; Prospective Studies ; Renal Insufficiency, Chronic ; Transferrin

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.
Epigenesis, Genetic ; Gene Expression Regulation ; genetics ; Homeostasis ; Humans ; Iron ; metabolism ; Receptors, Transferrin

BACKGROUND: Microcytic anemia, the most common form of anemia in children and adolescents, is a heterogeneous group of diseases that is acquired or inherited. We assessed the frequency and causes of microcytosis in children and adolescents with the sickle cell trait (SCT). METHODS: This descriptive study included 95 subjects (49 males and 46 females) with SCT who attended Basra Center for Hereditary Blood Diseases for evaluation. Investigations included complete blood count, high performance liquid chromatography, capillary electrophoresis, and measurement of serum ferritin and transferrin levels. RESULTS: SCT subjects had a low hemoglobin (Hb) concentration (9.79±1.75 g/dL), low mean corpuscular volume (MCV, 67.43±9.22), low mean corpuscular Hb (21.15±3.64), and a normal red cell distribution width (RDW, 14.00±2.30). Among 95 SCT subjects, 81 (85.26%) had microcytosis, 12 (12.63%) had normal MCV, and 2 (2.11%) exhibited macrocytosis. Sixty-three (77.78%) SCT subjects with microcytosis were iron deficient, and 18 (22.22%) had normal iron levels. The mean serum ferritin and HbA2 levels were significantly lower, while the RDW, sickle Hb, and serum transferrin levels were significantly higher in patients with microcytosis and iron deficiency compared to non-iron deficient subjects (P<0.05). Correlation coefficients did not reveal a significant association between the MCV and iron status of SCT subjects (P>0.05). CONCLUSION: Despite the frequent occurrence of iron deficiency in SCT subjects, co-inheritance of alpha-thalassemia seemed to be the cause of low MCV in non-iron deficient individuals with microcytosis. Genetic analysis is required to understand the genetic basis of this phenomenon.
Adolescent ; alpha-Thalassemia ; Anemia ; Blood Cell Count ; Child ; Chromatography, Liquid ; Electrophoresis, Capillary ; Erythrocyte Indices ; Ferritins ; Hematologic Diseases ; Humans ; Iraq ; Iron ; Male ; Sickle Cell Trait ; Transferrin

OBJECTIVE: This study was designed to evaluate hematological disorders and the orchestrating roles of hepcidin and IL-6 in rat models of thioacetamide (TAA) and carbon tetrachloride (CCl4) hepatotoxicity. METHODS: Rats were intraperitoneally injected with TAA (10 mg/100 g rat weight dissolved in isosaline) or CCl4 (100 μL/100 g rat weight diluted as 1:4 in corn oil) twice weekly for eight consecutive weeks to induce subchronic liver fibrosis. Blood and tissue samples were collected and analyzed. RESULTS: CCl4 but not TAA significantly decreased the RBCs, Hb, PCV, and MCV values with minimal alterations in other erythrocytic indices. Both hepatotoxins showed leukocytosis, granulocytosis, and thrombocytopenia. By the end of the experiment, the erythropoietin level increased in the CCl4 model. The serum iron, UIBC, TIBC, transferrin saturation%, and serum transferrin concentration values significantly decreased, whereas that of ferritin increased in the CCl4 model. TAA increased the iron parameters toward iron overload. RT-PCR analysis revealed increased expression of hepatic hepcidin and IL-6 mRNAs in the CCl4 model and suppressed hepcidin expression without significant effect on IL-6 in the TAA model. CONCLUSION These data suggest differences driven by hepcidin and IL-6 expression between CCl4 and TAA liver fibrosis models and are of clinical importance for diagnosis and therapeutics of liver diseases.
Animals ; Blood Chemical Analysis ; Carbon Tetrachloride ; toxicity ; Hepcidins ; pharmacology ; Injections, Intraperitoneal ; Interleukin-6 ; pharmacology ; Iron ; blood ; metabolism ; Leukocytosis ; chemically induced ; therapy ; Liver Cirrhosis ; chemically induced ; therapy ; Male ; Rats ; Thioacetamide ; toxicity ; Thrombocytopenia ; chemically induced ; therapy ; Transferrin ; metabolism

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.
Child ; Erythrocyte Count ; Hemoglobin H ; Humans ; Receptors, Transferrin ; Retrospective Studies ; alpha-Thalassemia

This study investigated advantages and potential risks associated with drinking alcohol in Koreans based on the alcohol flush reaction. Our investigation reviewed published studies and examined moderate-drinking levels for Koreans based on modified National Institute on Alcohol Abuse and Alcoholism guidelines. Fourteen articles out of a total 198 publications were searched using PubMed, EMBASE, KoreaMed, and RISS (Research Information Sharing Service) databases and selected for review. Individuals without alcohol flush reaction (non-flushers) exhibited lower risks associated with insulin resistance, metabolic syndrome, and hyperhomocysteinemia and their 10-year cardiovascular disease risk when alcohol consumption was ≤8 drinks/wk. Conversely, risks associated with insulin resistance, metabolic syndrome, high blood pressure, prediabetes or type-2 diabetes, and high intraocular pressure and increases in carbohydrate-deficient transferrin, gamma glutamyl transferase, and blood glucose levels were present when >8 drinks were consumed. For individuals with flushing reaction (flushers), advantages were reported in relation to risks of hyperhomocysteinemia when alcohol consumption was ≤4 drinks/wk, whereas consumption of >4 drinks/wk increased the risk of insulin resistance, metabolic syndrome, high blood pressure, pre-diabetes or type-2 diabetes, high-risk colorectal adenoma, and high intraocular pressure and increased carbohydrate-deficient transferrin, gamma glutamyl transferase, and blood glucose levels. The moderate drinking level for Koreans is ≤8 drinks/wk for men aged ≤65 years and ≤4 drinks/wk for men aged over 65. For women, these limits should be half of those for men. Furthermore, individuals with flushing reaction should maintain an alcohol consumption level half of that for non-flushers.
Adenoma ; Alcohol Drinking ; Blood Glucose ; Cardiovascular Diseases ; Drinking ; Female ; Flushing ; Humans ; Hyperhomocysteinemia ; Hypertension ; Information Dissemination ; Insulin Resistance ; Intraocular Pressure ; Male ; National Institute on Alcohol Abuse and Alcoholism (U.S.) ; Prediabetic State ; Transferases ; Transferrin

PURPOSE: This study sought to examine whether near total gastrectomy (nTG) confers a long-term nutritional benefit when compared with total gastrectomy (TG) for the treatment of gastric cancer. MATERIALS AND METHODS: Patients who underwent nTG or TG for gastric cancer were included (n=570). Using the 1:2 matched propensity score, 25 patients from the nTG group and 50 patients from the TG group were compared retrospectively for oncologic outcomes, including long-term survival and nutritional status. RESULTS: The length of the proximal resection margin, number of retrieved lymph nodes and tumor nodes, metastasis stage, short-term postoperative outcomes, and long-term survival were not significantly different between the groups. The body mass index values, and serum total protein and hemoglobin levels of the patients decreased significantly until postoperative 6 months, and then recovered slightly over time (P < 0.05); however, there was no difference in the levels between the groups. The prognostic nutritional index values and serum albumin levels decreased significantly until postoperative 6 months and then recovered (P < 0.05); the levels decreased more in the nTG group than in the TG group (P < 0.05). The mean corpuscular volumes and serum transferrin levels increased significantly until postoperative 1 year and then recovered slightly over time (P < 0.05); however, there was no difference between the groups. Serum vitamin B12, iron, and ferritin levels of the patients did not change significantly over time, and no difference existed between the groups. CONCLUSIONS: A small remnant stomach after nTG conferred no significant nutritional benefits over TG.
Body Mass Index ; Erythrocyte Indices ; Ferritins ; Gastrectomy* ; Gastric Stump ; Humans ; Iron ; Lymph Nodes ; Neoplasm Metastasis ; Nutrition Assessment ; Nutritional Status ; Propensity Score* ; Retrospective Studies ; Serum Albumin ; Stomach Neoplasms* ; Transferrin ; Vitamin B 12