OBJECTIVE: To compare the clinical efficacy and safety of oral administration of Buxue Yimu Pills (BYP, ), ferrous sulfate (FS), and the combination of BYP and FS on gynecological anemia, and investigate the mechanisms using network pharmacology. METHODS: A randomized, controlled, multi-center clinical trial was conducted. Totally 150 patients with hemoglobin of 70-110 g/L due to gynecological conditions were recruited and randomized (using the block randomization method) into Buxue Yimu Pills group (24 g/d), oral iron group (FS Tablets, 0.9 g/d), and combined treatment group (BYP, 24 g/d plus FS Tablets, 0.9 g/d), 50 patients in each group. At the enrollment and 4-week treatment, complete blood count, serum iron indexes were evaluated. Adverse events, liver and renal functions, as well as blood coagulation were observed. Network pharmacology was conducted to identify the active ingredients and explore the potential mechanisms of BYP. RESULTS: Ten (20%) and 7 (14%) participants discontinued the therapy due to gastrointestinal symptoms in oral iron and combination treatment groups. All 3 groups showed elevated hemoglobin. The patients in the iron group exhibited typically elevated in serum iron and ferritin and decreased in total iron-binding capacity. No change in iron indexes was observed in BYP group. The patients in the combination treatment group neither showed significant changes in serum ferritin nor total iron-binding capacity. No significant adverse reactions were observed in the BYP group. The network pharmacology identified 27 bioactive compounds and 145 targets of BYP on gynecological anemia. Biological processes and pathways including regulation of inflammation, hormone, angiogenesis and hemostasis, response to decreased oxygen levels, effects on myeloma cell, and response to metal ions were identified. CONCLUSION BYP contributes to the practical improvement on gynecological anemia potentially through multi-target mechanisms and optimized iron re-distribution. (Trial registration: No. NCT03232554).
Humans ; Anemia/drug therapy* ; Anemia, Iron-Deficiency/drug therapy* ; Ferritins/therapeutic use* ; Hemoglobins ; Iron/therapeutic use* ; Network Pharmacology ; Drugs, Chinese Herbal

OBJECTIVE: To observe and compare the therapeutic effects of hydroxypropyl chitosan ferrous ion complex solution and ferrous sulfate solution in iron deficiency anemia rats and their effects on gastric mucosa. METHODS: Seven rats were randomly selected from thirty five SPF grade SD rats as control group, and were fed with normal diet, distilled water (E). The rest of SD rats were fed with low iron feed and distilled water plus continuous tail vein bloodletting to establish the iron deficiency anemia model. After the model was established successfully, the rats were randomly divided into four groups: blank control group (A), iron deficiency anemia control group (B), ferrous sulfate group (C), hydroxypropyl chitosan ferrous ion complex (HPCTS-Fe RESULTS: After modeling, except the normal control group, the hair color of the rats in the four groups showed dark yellow and the belly of the toes became white gradually. HGB, HCT, Ret%, MCV, MCH, MCHC and SF decreased significantly (P < 0.05). After treatment, the rats with dark yellow hair in group C and D were improved, and the toe abdomen turned pink gradually. RBC, HGB, HCT, Ret%, MCV, MCH, MCHC and SF in rats in group C and D increased, which were higher than those in group B (P < 0.05). The HGB of the rats in group D was higher than that of group C in day 28th during treatment and the Ret% was higher than that in group C at day 10th (P<0.05).After treatment, the liver and spleen of the rats in group C and D were lighter than those in group B (P<0.05).The gastric mucosa in group A, B, D and E was not damaged obviously, while it was slightly irritated and damaged in group C. CONCLUSION Hydroxypropyl chitosan ferrous complex solution can improve the hemoglobin level of SD rats with iron deficiency anemia, which is stronger than ferrous sulfate solution and shows no damage to gastric mucosa.
Anemia, Iron-Deficiency/drug therapy* ; Animals ; Chitosan ; Ferrous Compounds ; Hemoglobins ; Iron ; Rats ; Rats, Sprague-Dawley

Iron deficiency anemia is one of the most common micronutrient deficient conditions around the globe with various consequences, including the weakened immune system. Quercetin is widely distributed bioflavonoid; it has been debated for its dual roles in iron regulation. Quercetin-iron interaction in the body is a complex mechanism which has not been completely understood. The present study aimed to investigate the effect of quercetin on iron supplementation in iron deficiency anemia and on iNOS expression in splenic macrophages. The rat model of iron deficiency anemia was induced by feeding low iron diet to weanling rats for 20 days. The animals were then administered with ferrous sulfate, quercetin, and their combination for 30 days. Blood parameters, histopathological analysis, iron storage, CD68, iNOS and SLC40 expression in rat spleen were investigated. Our results showed that quercetin regulated iron absorption, despite SLC40 down-expression, indicating possible alternate route of iron transport, and that quercetin modulated iNOS production in splenic macrophages.
Anemia, Iron-Deficiency ; drug therapy ; genetics ; metabolism ; Animals ; Dietary Supplements ; analysis ; Female ; Homeostasis ; drug effects ; Humans ; Iron ; deficiency ; Macrophages ; drug effects ; metabolism ; Nitric Oxide Synthase Type II ; genetics ; metabolism ; Quercetin ; administration & dosage ; Rats ; Rats, Sprague-Dawley ; Spleen ; drug effects ; enzymology

Ewing sarcoma/primitive neuroectodermal tumors (ES/PNET) are a group of malignant tumors with varying degrees of neuroectodermal differentiation. Although it may develop in any organs, ES/PNET originating from small intestine is exceedingly rare. We experienced a 9-year-old girl presenting with abdominal pain, melena, and iron deficiency anemia. Imaging work-up showed multiple masses in the small bowel and omentum with disseminated peritoneal seeding nodules, indicating lymphoma as the most likely diagnosis. Pathological reports from explorative diagnostic laparoscopic biopsy showed tumors comprising small round cells with CD99 expression and EWS-FLI1 translocation leading to the diagnosis of ES/PNET. Tumor burden decreased gradually during five consecutive cycles of systemic chemotherapy. The patient received segmental resection of jejunum, followed by adjuvant chemotherapy. This is the first pediatric case of ES/PNET found in small intestine in Korea.
Abdominal Pain ; Anemia, Iron-Deficiency ; Biopsy ; Chemotherapy, Adjuvant ; Child ; Diagnosis ; Drug Therapy ; Female ; Humans ; Intestine, Small ; Jejunum ; Korea ; Lymphoma ; Melena ; Neural Plate ; Neuroectodermal Tumors ; Neuroectodermal Tumors, Primitive ; Omentum ; Pediatrics ; Sarcoma, Ewing ; Tumor Burden

BACKGROUND/AIMS: There are few data on the effects of low hemoglobin levels on the left ventricle (LV) in patients without heart disease. The objective of this study was to document changes in the echocardiographic variables of LV structure and function after the correction of anemia without significant cardiovascular disease. METHODS: In total, 34 iron-deficiency anemia patients (35 +/- 11 years old, 32 females) without traditional cardiovascular risk factors or cardiovascular disease and 34 age- and gender-matched controls were studied. Assessments included history, physical examination, and echocardiography. Of the 34 patients with anemia enrolled, 20 were followed and underwent echocardiography after correction of the anemia. RESULTS: There were significant differences between the anemia and control groups in LV diameter, left ventricular mass index (LVMI), left atrial volume index (LAVI), peak mitral early diastolic (E) velocity, peak mitral late diastolic (A) velocity, E/A ratio, the ratio of mitral to mitral annular early diastolic velocity (E/E'), stroke volume, and cardiac index. Twenty patients underwent follow-up echocardiography after treatment of anemia. The follow-up results showed significant decreases in the LV end-diastolic and end-systolic diameters and LVMI, compared with baseline levels. LAVI, E velocity, and E/E' also decreased, suggesting a decrease in LV filling pressure. CONCLUSIONS: Low hemoglobin level was associated with larger cardiac chambers, increased LV, mass and higher LV filling pressure even in the subjects without cardiovascular risk factors or overt cardiovascular disease. Appropriate correction of anemia decreased LV mass, LA volume, and E/E'.
Adult ; Anemia, Iron-Deficiency/blood/diagnosis/*drug therapy/physiopathology ; Biological Markers/metabolism ; Case-Control Studies ; Echocardiography, Doppler ; Female ; Heart Ventricles/*physiopathology/ultrasonography ; Hematinics/*therapeutic use ; Hemoglobins/metabolism ; Humans ; Male ; Middle Aged ; Prospective Studies ; Recovery of Function ; Time Factors ; Treatment Outcome ; *Ventricular Function, Left ; *Ventricular Pressure ; *Ventricular Remodeling ; Young Adult

BACKGROUND: Iron deficiency anemia is the most common form of anemia in India. Hemoglobin A1c (HbA1c) is used in diabetic patients as an index of glycemic control reflecting glucose levels of the previous 3 months. Like blood sugar levels, HbA1c levels are also affected by the presence of variant hemoglobins, hemolytic anemias, nutritional anemias, uremia, pregnancy, and acute blood loss. However, reports on the effects of iron deficiency anemia on HbA1c levels are inconsistent. We conducted a study to analyze the effects of iron deficiency anemia on HbA1c levels and to assess whether treatment of iron deficiency anemia affects HbA1c levels. METHODS: Fifty patients confirmed to have iron deficiency anemia were enrolled in this study. HbA1c and absolute HbA1c levels were measured both at baseline and at 2 months after treatment, and these values were compared with those in the control population. RESULTS: The mean baseline HbA1c level in anemic patients (4.6%) was significantly lower than that in the control group (5.5%, p<0.05). A significant increase was observed in the patients' absolute HbA1c levels at 2 months after treatment (0.29 g/dL vs. 0.73 g/dL, p<0.01). There was a significant difference between the baseline values of patients and controls (0.29 g/dL vs. 0.74 g/dL, p<0.01). CONCLUSIONS: In contrast to the observations of previous studies, ours showed that HbA1c levels and absolute HbA1c levels increased with treatment of iron deficiency anemia. This could be attributable to nutritional deficiency and/or certain unknown variables. Further studies are warranted.
Adolescent ; Adult ; Anemia, Iron-Deficiency/*blood/drug therapy ; Child ; Female ; Ferritins/blood ; Hemoglobin A, Glycosylated/*analysis ; Hemoglobins/analysis ; Humans ; Iron/therapeutic use ; Male ; Time Factors

BACKGROUND/AIMS: Helicobacter pylori (H. pylori) infection appears to subvert the human iron regulatory mechanism and thus upregulates hepcidin, resulting in unexplained iron-deficiency anemia (IDA). We evaluated serum prohepcidin levels before and after eradication of H. pylori in IDA patients to assess whether it plays a role in IDA related to H. pylori infection. METHODS: Subjects diagnosed with unexplained IDA underwent upper gastrointestinal endoscopy and colonoscopy to confirm H. pylori infection and to exclude gastrointestinal bleeding. Blood was sampled before treatment to eradicate H. pylori and again 1 month later. Serum prohepcidin levels were measured using a commercial enzyme-linked immunosorbent assay kit. RESULTS: Serum prohepcidin levels decreased significantly after oral iron replacement combined with H. pylori eradication (p = 0.011). The reduction ratio of serum prohepcidin levels after the treatment did not differ among the combined oral iron replacement and H. pylori eradication groups, the H. pylori eradication only group, and the iron replacement only group (p = 0.894). CONCLUSIONS: Serum prohepcidin levels decrease after both H. pylori eradication and oral iron administration, with improvement in IDA. Serum concentration of prohepcidin is related to the anemia status, rather than to the current status of H. pylori infection, in IDA patients.
Administration, Oral ; Adult ; Aged ; Anemia, Iron-Deficiency/*blood/drug therapy/*microbiology ; Antimicrobial Cationic Peptides/*blood ; Endoscopy, Gastrointestinal ; Female ; Follow-Up Studies ; Helicobacter Infections/*blood/*complications/pathology ; *Helicobacter pylori ; Humans ; Iron/administration & dosage ; Male ; Middle Aged ; Prospective Studies ; Protein Precursors/*blood ; Severity of Illness Index

BACKGROUNDIron deficiency (ID) is still a great challenge to health care worldwide. Results of randomized controlled trials (RCTs) evaluating the effect of Helicobacter pylori (H. pylori) eradication on ID are contradictory. This study aimed to evaluate the effect of H. pylori eradication on ID with a meta-analysis of RCTs.

METHODSFive electronic databases were searched for RCTs evaluating the effect of H. pylori eradication on ID. Summary effects were assessed with the methods recommended by the Cochrane Collaboration.

RESULTSEight studies involving 800 participants were included in this meta-analysis. The overall analysis showed that H. pylori eradication accelerated the improvement of ferritin levels in ID people (mean difference (MD), 7.74 microg/L; 95%CI, 4.61 to 10.88; P < 0.00001). In a subgroup analysis, H. pylori eradication accelerated the improvement of ferritin levels one month (MD, 7.00 microg/L; 95%CI, 1.72 to 12.28; P = 0.009) and two months (MD, 9.80 microg/L; 95%CI, 2.22 to 17.40; P = 0.01) after the initiation of treatment. However, H. pylori eradication did not show a beneficial effect on the improvement of ferritin levels three months (MD, 7.20 microg/L; 95%CI, -3.25 to 17.65; P = 0.18), one year (MD, 10.17 microg/L; 95%CI, -1.00 to 21.34; P = 0.07) and forty months (MD, 1.00 microg/L; 95%CI, -0.57 to 2.57; P = 0.21) after the initiation of treatment. H. pylori eradication did not accelerate the improvement of hemoglobin concentrations in the overall analysis (MD, 0.38 g/dl; 95%CI, -0.45 to 1.22; P = 0.37). In a subgroup analysis, H. pylori eradication did not accelerate the improvement of hemoglobin concentrations one month (MD, -0.48 g/dl; 95%CI, -2.39 to 1.42; P = 0.62), three months (MD, -0.10 g/dl; 95%CI, -0.35 to 0.15; P = 0.44) and forty months (MD, 0.10 g/dl; 95%CI, -0.37 to 0.57; P = 0.68) after the initiation of treatment. However, H. pylori eradication accelerated the improvement of hemoglobin concentrations two months (MD, 1.96 g/dl; 95%CI, 1.48 to 2.44; P < 0.00001) and one year (MD, 0.37 g/dl; 95%CI, 0.08 to 0.65; P = 0.01) after the initiation of treatment.

CONCLUSIONSH. pylori eradication is likely to improve the absorption of oral ferrous. H. pylori infection may play some roles in the development of ID.

Anemia, Iron-Deficiency ; blood ; drug therapy ; etiology ; Animals ; Anti-Bacterial Agents ; therapeutic use ; Helicobacter Infections ; complications ; drug therapy ; microbiology ; Humans ; Randomized Controlled Trials as Topic

OBJECTIVETo observe the different impacts of electrolytic iron, FeSO4, and NaFeEDTA on body iron store of anemic school students.

METHODSFour hundreds anemic students at the age of 11-18 years were divided into four groups. Of which, three consumed different iron fortificants from wheat flour as food vehicle for six months and one consumed non-fortified flour (control). The fortification level of electrolytic iron, FeSO4, and NaFeEDTA was 60 mg Fe/kg, 30 mg Fe/kg, and 20 mg Fe/kg, respectively. Blood samples were collected at 0, 2, 4, and 6 months and hemoglobin (Hb), serum ferritin (SF), and transferrin receptor (TfR) were measured.

RESULTSThe hemoglobin levels in three intervention groups increased, the increments of Hb in the NaFeEDTA group were significantly higher than that in the other groups. SF and TfR levels increased in the tested groups and body iron store in the NaFeEDTA group was higher than that in the other groups. These parameters did not show any significant changes in the control group.

CONCLUSIONNaFeEDTA and FeSO4 fortified wheat flour has positive impacts on iron status in anemic students and NaFeEDTA is more effective than FeSO4, while electrolytic iron is less effective in improving iron store in anemic students.

Adolescent ; Anemia, Iron-Deficiency ; drug therapy ; Child ; Dietary Supplements ; Dose-Response Relationship, Drug ; Edetic Acid ; chemistry ; pharmacology ; Female ; Ferric Compounds ; chemistry ; pharmacology ; Flour ; analysis ; Food, Fortified ; Humans ; Iron ; chemistry ; pharmacology ; Iron, Dietary ; Male ; Nutritional Status ; Triticum

OBJECTIVETo evaluate the effect of NaFeEDTA on hemoglobin level in iron deficient population.

METHODSComprehensive literature retrieval was performed via searching electronic databases, hand searching bibliographies of books and relevant journals, collecting grey literatures, looking into conference abstracts, contacting fields experts and reviewing references and citations. Criteria from Cochrane EPOC review group were used to assess the quality of included studies. Generic inverse variance method was used to undertake meta-analysis.

RESULTSThe pooled estimate for hemoglobin level (weighted mean difference) was 12.14 g/L (95% CI: 5.60-18.69; P < 0.001). Subgroup analysis indicated that lower baseline hemoglobin level and higher dose for intervention were associated to greater increase in hemoglobin level.

CONCLUSIONThis systematic review indicated that NaFeEDTA improved hemoglobin significantly in iron deficient population.

Anemia, Iron-Deficiency ; blood ; drug therapy ; metabolism ; Edetic Acid ; therapeutic use ; Ferric Compounds ; therapeutic use ; Hemoglobins ; metabolism ; Humans ; Iron Chelating Agents ; therapeutic use