Etiología y evolución de la anemia en pacientes sometidos a cirugía cardiovascular / Etiology and evolution of anemia in patients submitted to cardiovascular surgery

Resumen Objetivo: El objetivo del presente estudio es evaluar en nuestro medio la prevalencia de anemia en el preoperatorio de la cirugía cardiovascular, su incidencia postoperatoria y su evolución durante el primer mes. Métodos: Se realizó un estudio de cohorte prospectivo en el que se incluyeron todos los pacientes sometidos a cirugía cardiovascular central intervenidos durante el periodo del 01/09/2021 al 01/09/2022 en un hospital universitario. Se realizó seguimiento clínico y de laboratorio previo a la cirugía, al quinto y al día treinta del postoperatorio. Se comparó a los grupos con y sin anemia preoperatoria. Resultados: La prevalencia de anemia en el preoperatorio fue del 32.1%. La incidencia de anemia en el postoperatorio fue del 96% en el grupo de pacientes sin anemia previa. Al mes de la cirugía un 73 y un 90% de los pacientes, con y sin anemia preoperatoria respectivamente, persistían anémicos. Los pacientes con anemia preoperatoria tuvieron una menor recuperación de sus valores de hemoglobina al mes. Se observó una tendencia a mayor mortalidad y una mayor necesidad de derivación a centros de rehabilitación postegreso hospitalario en aquellos con anemia preoperatoria. Conclusiones: En este trabajo se evidenció una alta prevalencia e incidencia de anemia en el perioperatorio de las cirugías cardiovasculares. Así como su subtratamiento y elevada persistencia durante el mes posterior a la cirugía.

Abstract Objective: The aim of this study is to evaluate the prevalence of anemia in the preoperative period of cardiovascular surgery, its postoperative incidence and its evolution during the first month in our setting. Methods: A prospective cohort study was carried out in which all patients undergoing central cardiovascular surgery operated during the period 09/01/2021-09/01/2022 in a university hospital were included. Clinical and laboratory follow-up was carried out prior to surgery, on the fifth and on the 30th postoperative day. Groups with and without preoperative anemia were compared. Results: The prevalence of anemia in the preoperative period was 32.1%. The incidence of anemia in the postoperative period was 96% in the group of patients without previous anemia. One month after surgery, 73 and 90% of the patients, with and without preoperative anemia, respectively, remained anemic. Patients with preoperative anemia had less recovery of their hemoglobin values at one month. A trend towards higher mortality and a greater need for referral to post-hospital discharge rehabilitation centers was observed in those with preoperative anemia. Conclusions: In this work, a high prevalence and incidence of anemia in the perioperative period of cardiovascular surgeries was evidenced. As well as its subtreatment and high persistence during the month after surgery.

Hepcidin and inflammation associated with iron deficiency in childhood obesity - A systematic review

Abstract Objectives: This paper aims to review data on the association of obesity and iron deficiency in children and adolescents, exposing the possible involvement of hepcidin and interleukin-6 (IL-6), obesity's inflammation biomarkers. Data source: Articles from PUBMED and WEB OF SCIENCE database with no chronological limit were reviewed to write this systematic review. Keywords such as children, obesity, iron deficiency, and hepcidin were used. After deleting duplicated and review articles, 91 were screened, and 39 were selected as eligible. Sixteen articles were included because they involved serum hepcidin levels in obese children and adolescents as outcomes. Summary of findings: Finally, those 16 articles were organized in two tables: one includes therapeutic interventions, and the other does not. As hepcidin was discovered in 2000, the first articles that presented serum hepcidin's quantification in obese children and adolescents, homeostasis iron markers, and their possible association with obesity's inflammatory environment began to be published in 2008. Conclusions: Obesity's chronic inflammation state leads to the production of IL-6, which acts as a signaling molecule for hepcidin synthesis, resulting in iron deficiency, which is common in obese children and adolescents who respond inadequately to iron supplementation. On the other hand, that population responds adequately to therapeutic intervention programs that lead to weight loss, guaranteeing iron homeostasis improvement. Therefore, perhaps it is time to discuss serum hepcidin level quantification as part of evaluating children and adolescents with iron deficiency, which could guide clinical choices that might lead to better therapeutic outcomes.

Factores asociados a anemia ferropénica en lactantes y preescolares / Factors associated with iron deficiency anemia in infants and preschoolers

Introducción: La anemia se define como una afección en la cual el número de glóbulos rojos o la concentración de hemoglobina dentro de estos se encuentran por debajo del límite inferior, 11 gr/dl para menores entre 6 a 59 meses. La OMS calcula que a nivel mundial la anemia presenta una prevalencia del 42% en los niños menores de 5 años. Objetivos: Realizar una revisión panorámica de diversas publicaciones científicas acerca de los factores asociados a la anemia ferropénica en preescolares. Materiales y métodos: La revisión se realizó a través de la búsqueda electrónica de diversos artículos científicos relacionados con el tema. Se utilizó la pregunta PEO: ¿Cuáles son los factores asociados a anemia ferropénica en lactantes y preescolares? Se seleccionaron los artículos publicados desde el 2017 hasta el 2022. Resultados: De los 48 artículos encontrados en la revisión, 33 fueron descartados por no cumplir con nuestros criterios de selección, quedando 15 artículos para esta revisión. Basado en 12 artículos revisados, se halló que los factores que se asocian a anemia en menores de 5 años eran por problemas socioeconómicos, déficit de micronutrientes altos en hierro en dieta, madre con antecedente de anemia, la edad materna, falta de educación, entre otros. Conclusión: Los factores predisponentes para la presencia de anemia ferropénica en los menores de 5 años más importantes fueron los relacionados con la edad materna, el nivel socioeconómico y educativo de la madre que conllevan el déficit de hierro del menor.

Introduction: Anemia is defined as a condition in which the number of red blood cells or the hemoglobin concentration within red blood cells is below the lower limit, 11 g/dL for children aged 6-59 months. The WHO estimates that worldwide anemia has a prevalence of 42% in children under 5 years of age. Objectives: To perform an overview review of various scientific publications on the factors associated with iron deficiency anemia in preschoolers. Materials and methods: The review was carried out through an electronic search of various scientific articles related to the subject. The PEO question was used: What are the factors associated with iron deficiency anemia in infants and preschoolers? Articles published from 2017 to 2022 were selected. Results: Of the 48 articles found in the review, 33 were discarded for not meeting our selection criteria, leaving 15 articles for this review. Based on 12 articles reviewed, it was found that the factors associated with anemia in children under 5 years of age were socioeconomic problems, deficiency of micronutrients high in iron in the diet, mothers with a history of anemia, maternal age, lack of education, among others. Conclusion: The most important predisposing factors for the presence of iron deficiency anemia in children under 5 years of age were those related to maternal age, socioeconomic and educational level of the mother that lead to iron deficiency in the child.

Riesgos y beneficios de la profilaxis con sulfato ferroso en lactantes nacidos a término con niveles de hemoglobina y ferremia desconocidos / Risks and benefits of iron supplementation in full-term infants with unknown hemoglobin and ferritin levels

La seguridad y eficacia de los programas de suplementación con hierro a lactantes, está actualmente en discusión. El objetivo de esta revisión fue identificar estudios sobre riesgos y beneficios de la suplementación con hierro profiláctico en lactantes menores de un año, nacidos a término, con niveles de hemoglobina (Hb) y ferremia desconocidos. Se realizó una búsqueda en Pubmed y Cochrane, identificando 3 revisiones sistemáticas y metaanálisis. Estos estudios arrojaron resultados que indican mejoras en los niveles séricos de hierro y hemoglobina como resultado de la suplementación con hierro. Sin embargo, no se observó un beneficio significativo en el desarrollo cognitivo de los lactantes. Los efectos adversos más reportados son los gastrointestinales, efectos en el crecimiento (menor ganancia de talla y peso) y menor absorción de zinc. En resumen, la evidencia en cuanto a la profilaxis con hierro en lactantes es limitada, lo que nos lleva a recomendar un seguimiento cercano de los lactantes que reciben suplementos de hierro, con el objetivo de detectar posibles eventos adversos. Es fundamental evaluar cuidadosamente los riesgos y beneficios de esta intervención antes de su implementación (AU)

The safety and efficacy of iron supplementation programs for infants are currently under discussion. The objective of this review was to identify studies on the risks and benefits of prophylactic iron supplementation in infants under one year of age, born at term, with unknown hemoglobin (Hb) and serum iron levels. The search was conducted on Pubmed and Cochrane, identifying three systematic reviews and meta-analyses. The results indicate improvements in serum iron and hemoglobin levels as a result of iron supplementation. However, a significant benefit in infant cognitive development was not observed. The most reported adverse effects were gastrointestinal, effects on growth (reduced height and weight gain), and reduced zinc absorption. In summary, the evidence regarding iron prophylaxis in infants is limited, leading us to recommend close monitoring of infants receiving iron supplements to detect potential adverse events. It is crucial to carefully assess the risks and benefits of this intervention before implementation (AU)

Is Iron Overload Associated with Worse Outcomes in Patients with Chronic Liver Disease Undergoing Liver Transplantation?

ABSTRACT Background: Iron overload is frequent in patients with chronic liver disease, associated with shorter survival after liver transplantation in patients with hereditary hemochromatosis. Its effect on patients without hereditary hemochromatosis is unclear. The aim of the study was to study the clinical impact of iron overload in patients who underwent liver transplantation at an academic tertiary referral center. Methods: We performed a retrospective cohort study including all patients without hereditary hemochromatosis who underwent liver transplantation from 2015 to 2017 at an academic tertiary referral center in Mexico City. Explant liver biopsies were reprocessed to obtain the histochemical hepatic iron index, considering a score ≥ 0.15 as iron overload. Baseline characteristics were compared between patients with and without iron overload. Survival was estimated using the Kaplan-Meier method, compared with the log-rank test and the Cox proportional hazards model. Results: Of 105 patients included, 45% had iron overload. Viral and metabolic etiologies, alcohol consumption, and obesity were more frequent in patients with iron overload than in those without iron overload (43% vs. 21%, 32% vs. 22%, p = 0.011; 34% vs. 9%, p = 0.001; and 32% vs. 12%, p = 0.013, respectively). Eight patients died within 90 days after liver transplantation (one with iron overload). Complication rate was higher in patients with iron overload versus those without iron overload (223 vs. 93 events/100 person-months; median time to any complication of 2 vs. 3 days, p = 0.043), without differences in complication type. Fatality rate was lower in patients with iron overload versus those without iron overload (0.7 vs. 4.5 deaths/100 person-months, p = 0.055). Conclusion: Detecting iron overload might identify patients at risk of early complications after liver transplantation. Further studies are required to understand the role of iron overload in survival.

Uso de hierro intravenoso en el tratamiento de la anemia ferropénica en niños. A propósito de un caso

Introducción: el déficit de hierro es la causa más común de anemia debido a carencia nutricional. Su tratamiento consiste en proporcionar alimentos ricos en hierro biodisponible junto con la administración de hierro oral. En circunstancias definidas puede utilizarse el hierro intravenoso. Objetivo: describir el abordaje diagnóstico y terapéutico de un niño portador de anemia ferropénica severa secundaria a mala adherencia al hierro oral en el que se utilizó hierro intravenoso. Caso clínico: niño de 21 meses, raza blanca. Antecedente de anemia ferropénica severa, con repercusión hemodinámica que a los 14 meses requirió transfusión de sangre desplasmatizada. Sin controles de hemoglobina posteriores. Sin adherencia a profilaxis con hierro vía oral. Alto consumo de leche de vaca y bajo consumo de alimentos ricos en hierro. En el contexto de infección respiratoria aguda baja se constata anemia clínica con marcado decaimiento y anorexia, sin repercusión hemodinámica. Se confirma la anemia microcítica, hipocrómica severa, con ancho de distribución eritrocitaria elevado, con metabolismo de hierro alterado. Recibe hierro sacarato, intravenoso, por seis días con buena tolerancia y evolución. Discusión: se identificaron múltiples factores de riesgo para anemia ferropénica. La pobre respuesta al tratamiento con hierro oral debido a efectos adversos y olvidos de administración, junto al antecedente de anemia ferropénica severa, que requirió transfusión de sangre desplasmatizada, motivaron la indicación de hierro intravenoso. Su administración fue programada y monitorizada, sin complicaciones. Es necesario fortalecer la prevención en todos los controles pediátricos y abordar este problema de salud desde una mirada interdisciplinaria.

Summary: Introduction: iron deficiency is the most common cause of anemia due to nutritional deficiency. Its treatment consists of providing bioavailable iron rich food together with oral iron. In specific circumstances, intravenous iron may be used. Objective: of this study is to describe the diagnostic and therapeutic approach used with a child with severe iron deficiency anemia secondary to poor adherence to oral iron, in which intravenous iron was used. Clinical case: 21 month-old white patient. History of severe iron deficiency anemia, with hemodynamic repercussions that at 14 months of age required transfusion of deplasmatized blood. Without subsequent hemoglobin controls. No adherence to oral iron prophylaxis. High consumption of cow's milk and low of iron-rich foods. Within the context of acute lower respiratory infection, a clinical anemia with marked decline and anorexia were observed, without hemodynamic repercussions. Severe hypochromic microcytic anemia was confirmed, with an elevated erythrocyte distribution width and altered iron metabolism. He received iron saccharate, intravenously for 6 days with good tolerance and evolution. Discussion: multiple risk factors for iron deficiency anemia were identified. The poor response to treatment with oral iron resulting from adverse effects and lack of proper administration, together with a history of severe iron deficiency anemia, which required transfusion of deplasmatized blood, led to the prescription of intravenous iron. This administration was scheduled and monitored, occurring without complications. It is necessary to strengthen prevention of this condition in all pediatric check-ups and address this health problem from an interdisciplinary perspective.

Introdução: a deficiência de ferro é a causa mais comum de anemia por deficiência nutricional. Seu tratamento consiste no fornecimento de alimentos ricos em ferro biodisponível, juntamente com a administração de ferro por via oral. Em circunstâncias especificas, pode ser utilizado ferro intravenoso. Objetivo: descrever a abordagem diagnóstica e terapêutica de uma criança com anemia ferropriva grave secundária a sua má adesão ao ferro oral, e o uso de ferro intravenoso. Caso clínico: 21 meses, raça branca. História de anemia ferropriva grave, com repercussão hemodinâmica que requiriu de transfusão de sangue desplasmatizada aos 14 meses. Não houve nenhum controle de hemoglobina subsequente. Nenhuma adesão à profilaxia oral com ferro. Alto consumo de leite de vaca e baixo consumo de alimentos ricos em ferro. No contexto de infecção respiratória inferior aguda, observa-se anemia clínica com acentuado emagrecimento e anorexia, sem repercussões hemodinâmicas. É confirmada anemia microcítica e hipocrômica grave, com largura de distribuição eritrocitária elevada e metabolismo alterado do ferro. Recebeu sacarose férrica intravenosa por 6 dias com boa tolerância e evolução. Discussão: foram identificados múltiplos fatores de risco para anemia ferropriva. A má resposta ao tratamento com ferro oral devido aos efeitos adversos e ao esquecimento da administração, aliás da história de anemia ferropriva grave, que exigiu transfusão de sangue desplasmatizada, motivaram a indicação do ferro intravenoso. Sua administração foi programada e monitorada, e aconteceu sem intercorrências. É preciso fortalecer a prevenção em todos os controles pediátricos e abordar este problema de saúde numa persectiva interdisciplinar.

Association between preoperative anemia optimization and major complications after non-cardiac surgery: a retrospective analysis

Abstract Background: Anemia is common in the preoperative setting and associated with increased postoperative complications and mortality. However, it is unclear if preoperative anemia optimization reduces postoperative complications. We aimed to assess the association between preoperative anemia optimization and a composite endpoint of major cardiovascular, renal, and pulmonary complications and all-cause mortality within 30 days after noncardiac surgery in adult patients. Methods: In this retrospective analysis preoperative anemia was defined as hemoglobin concentration below 12.0 g.dl−1 in women and 13.0 g.dl−1 in men within 6 months before surgery. A propensity score-based generalized estimating equation analysis was used to determine the association between preoperative anemia optimization and the primary outcome. Moreover, mediation analysis was conducted to investigate whether intraoperative red blood cell transfusion or duration of intraoperative hypotension were mediators of the relation between anemia optimization and the primary outcome. Results: Fifty-seven hundred anemia optimized, and 8721 non-optimized patients met study criteria. The proportion of patients having any component of the composite of major complications and all-cause mortality was 21.5% in the anemia-optimized versus 18.0% in the non-optimized, with confounder-adjusted odds ratio estimate of 0.99 (95% CI 0.86-1.15) for anemia optimization versus non-optimization, p = 0.90. Intraoperative red blood cell transfusion had a minor mediation effect on the relationship between preoperative anemia optimization and the primary outcome, whereas duration of intraoperative hypotension was not found to be a mediator. Conclusion: Preoperative anemia optimization did not appear to be associated with a composite outcome of major in-hospital postoperative cardiovascular, renal, and pulmonary complications and all-cause in-hospital mortality.

Reduced HDL-cholesterol in long COVID-19: A key metabolic risk factor tied to disease severity

Abstract This controlled study investigated metabolic changes in non-vaccinated individuals with Long-COVID-19, along with their connection to the severity of the disease. The study involved 88 patients who experienced varying levels of initial disease severity (mild, moderate, and severe), and a control group of 29 healthy individuals. Metabolic risk markers from fasting blood samples were analyzed, and data regarding disease severity indicators were collected. Findings indicated significant metabolic shifts in severe Long-COVID-19 cases, mainly a marked drop in HDL-C levels and a doubled increase in ferritin levels and insulin resistance compared to the mild cases and controls. HDL-C and ferritin were identified as the leading factors predicted by disease severity. In conclusion, the decline in HDL-C levels and rise in ferritin levels seen in Long-COVID-19 individuals, largely influenced by the severity of the initial infection, could potentially play a role in the persistence and progression of Long-COVID-19. Hence, these markers could be considered as possible therapeutic targets, and help shape preventive strategies to reduce the long-term impacts of the disease.

Anemia ferropénica en el embarazo: esquema de sulfato ferroso intermitente en comparación con el continuo / Iron deficiency anaemia in pregnancy: comparison of intermittent versus continuous ferrous sulphate regimen

Resumen OBJETIVO: Comparar las concentraciones de hemoglobina en embarazadas con anemia por deficiencia de hierro que recibieron un tratamiento intermitente en comparación con el continuo de 200 mg de sulfato ferroso por vía oral. Además, comparar la frecuencia de efectos secundarios del tratamiento intermitente con el continuo. MATERIALES Y MÉTODOS: Ensayo clínico, aleatorizado, no cegado, efectuado en la Unidad Médica de Alta Especialidad Hospital de Ginecoobstetricia 4 Luis Castelazo Ayala, IMSS, en pacientes de 18 a 35 años atendidas entre los meses de enero a marzo del 2023 con 30 o más semanas de embarazo, diagnóstico de anemia ferropénica (definida operativamente solo con una biometría hemática inferior a 11 g/dL, con hipocromía y microcitosis), sin antecedentes de enfermedad crónico-degenerativa. El análisis estadístico se procesó en el programa SPSS v21, la distribución y características de la muestra con análisis univariado, seguido de un análisis bivariado con t de Student y diferencia de medias. Se consideró con significación estadística el valor de p < 0.05. RESULTADOS: Se estudiaron 32 pacientes: 16 con esquema continuo y 16 con el intermitente. Ambos grupos con incremento de 1 g/dL entre la hemoglobina inicial y final (p < 0.01), con una diferencia de medias entre el aumento de los grupos con p = 0.4. Con disminución significativa de la epigastralgia y la náusea. CONCLUSIONES: El tratamiento intermitente con sulfato ferroso incrementa las concentraciones de hemoglobina igual que un esquema continuo, pero con menos efectos adversos.

Abstract OBJECTIVE: To compare hemoglobin concentrations in pregnant women with iron deficiency anemia who received intermittent versus continuous treatment with 200 mg oral ferrous sulfate. In addition, to compare the incidence of side effects of intermittent versus continuous treatment. MATERIALS AND METHODS: Randomized, non-blinded, clinical trial conducted at the Unidad Médica de Alta Especialidad Hospital de Ginecoobstetricia 4 Luis Castelazo Ayala, IMSS, in patients aged 18 to 35 years attended between January and March 2023 with 30 or more weeks of pregnancy, diagnosis of iron deficiency anemia (operationally defined only with a blood biometry lower than 11 g/dL, with hypochromia and microcytosis), without a history of chronic degenerative disease. Statistical analysis was performed in SPSS v21 program, distribution and characteristics of the sample with univariate analysis, followed by bivariate analysis with Student's t and mean difference. A value of p < 0.05 was considered statistically significant. RESULTS: Thirty-two patients were studied: 16 with continuous and 16 with intermittent regimen. Both groups with increase of 1 g/dL between initial and final hemoglobin (p < 0.01), with a mean difference between groups increase with p = 0.4. With significant reduction in epigastralgia and nausea. CONCLUSIONS: Intermittent treatment with ferrous sulfate increases hemoglobin concentrations.

Consensus of the Brazilian association of hematology, hemotherapy and cellular therapy on patient blood management: Preoperative Phase - Preoperative management of the patient's anemia

Abstract Managing anemia before surgery is extremely important as it is a clinical condition that can significantly increase surgical risk and affect patient outcomes. Anemia is characterized by a reduction in the number of red blood cells or hemoglobin levels leading to a lower oxygen-carrying capacity of the blood. Proper treatment requires a multifaceted approach to ensure patients are in the best possible condition for surgery and to minimize potential complications. The challenge is recognizing anemia early and implementing a timely intervention to correct it. Anemic patients are more susceptible to surgical complications such as increased infection rates, slower wound healing and increased risk of cardiovascular events during and after surgery. Additionally, anemia can exacerbate existing medical conditions, causing greater strain on organs and organ systems. To correct anemia and optimize patient outcomes, several essential measures must be taken with the most common being identifying and correcting iron deficiency.

Iron deficiency anemia as a risk factor for pulp disease in children from the central Peruvian jungle: a case‒control study

Abstract Aim To investigate iron-deficiency anemia as a risk factor for dental pulp disease in children from the central Peruvian jungle. Methodology A case-control study was carried out with 270 children, of which 90 referred to cases and 180, to controls. Patients with pulp disease were diagnosed according to the criteria of the Association of Endodontists and the American Board of Endodontics. A specific questionnaire was used to assess ferrous sulfate consumption, maternal education level, maternal age, occupation, and household income. Data were analyzed using Pearson's correlation coefficient and a binary logistic regression. Results Iron deficiency anemia offers a risk factor for pulp disease in children (OR 7.44, IC 95% 4.0-13.8). According to multivariate analysis using binary logistic regression, ferrous sulfate consumption (OR 13.8, IC 95% 5.6.33.9), maternal education level (OR 2.4, IC 95% 1.1-5.3), maternal age (OR 7.5, IC 95% 2.9-19.4), household income (OR 4.0, IC 95% 1.6-9.6), and caries (OR 10.7, IC 95% 4.5-25.7) configured independent factors that were statistically associated with pulp disease. Conclusion Iron deficiency anemia, ferrous sulfate consumption, maternal education level, maternal age, household income, and dental caries were positively associated with pulp disease in children

A meta-analysis of ferric carboxymaltose versus other intravenous iron preparations for the management of iron deficiency anemia during pregnancy

Abstract Objective: We conducted a meta-analysis of randomized clinical trials evaluating the clinical effects of ferric carboxymaltose therapy compared to other intravenous iron in improving hemoglobin and serum ferritin in pregnant women. We also assessed the safety of ferric carboxymaltose vs. other intravenous iron. Data source: EMBASE, PubMed, and Web of Science were searched for trials related to ferric carboxymaltose in pregnant women, published between 2005 and 2021. We also reviewed articles from google scholar. The keywords "ferric carboxymaltose," "FCM," "intravenous," "randomized," "pregnancy," "quality of life," and "neonatal outcomes" were used to search the literature. The search was limited to pregnant women. Selection of studies: Studies related to ferric carboxymaltose in pregnancy were scanned. Observational studies, review articles, and case reports were excluded. Randomized studies in pregnant women involving ferric carboxymaltose and other intravenous iron formulations were shortlisted. Of 256 studies, nine randomized control trials were selected. Data collection: Two reviewers independently extracted data from nine selected trials Data synthesis: The final effect size for increase in hemoglobin after treatment was significant for ferric carboxymaltose vs. iron sucrose/iron polymaltose (standard mean difference 0.89g/dl [95% confidence interval 0.27,1.51]). The final effect size for the increase in ferritin after treatment was more for ferric carboxymaltose vs. iron sucrose/iron polymaltose (standard mean difference 22.53µg/L [-7.26, 52.33]). No serious adverse events were reported with ferric carboxymaltose or other intravenous iron. Conclusion: Ferric carboxymaltose demonstrated better efficacy than other intravenous iron in increasing hemoglobin and ferritin levels in treating iron deficiency anemia in pregnant women.

Targeting ferroptosis for treatment of Alzheimer' s disease / 中国药理学通报

Alzheimer' s disease (AD) is a progressive neurodegenerative disorder histologically characterized by the presence of senile plaques and neurofibrillary tangles (NFTs) found in and around pyramidal neurons in cortical tissue. Mounting evidence suggests regional increased iron load and dyshomeostasis have been associated with oxidative stress, oxidation of proteins and lipids, and cell death, and appears to be a risk factor for more rapid cognitive decline, thereby involved in multiple aspects of the pathophysiology of AD. Ferroptosis is a newly identified iron-dependent lipid peroxidation-driven cell death and emerging evidences have demonstrated the involvement of ferroptosis in the pathological process of AD. Notably, some novel compounds targeting ferroptosis can relieve AD-related pathological symptoms in AD cells and animal model and exhibit potential clinical benefits in AD patients. This review systematically summarizes the growing molecular and clinical evidence implicating ferroptosis in the pathogenesis of AD, and then reviews the application of ferroptosis inhibitors in mouse/cell models to provide valuable information for future treatment and prevention of AD.

Research progress in ferroptosis pathways and ubiquitination modification of ferroptosis-related molecules / 中国药理学通报

Ferroptosis is an iron-dependent cell death caused by phospholipid peroxidation damage of polyunsaturated fatty acids on cell membranes and involves several pathways, including the iron homeostasis regulatory pathway, the cystine glutamate reverse transporter (system Xc) pathway and the voltage-dependent anion channel (VDAC) pathway. Ferroptosis is involved in the development of several diseases (e. g. myocardial infarction, stroke, cancer and degenerative diseases). The ubiquitination is an important post-translational modification of various protein molecules in the organism. Studies have shown that regulating the ubiquitination of ferroptosis pathway-related molecules can control cellular ferroptosis. Targeting the ubiquitination of ferroptosis pathway-related molecules can effectively promote or inhibit ferroptosis, which is expected to be a new strategy for the treatment of cancer or cardiovascular diseases. In this paper we review the progress of the ferroptosis pathways and the ubiquitination modification of ferroptosis-related molecules.

Active Ingredients of Chinese Medicines Induce Ferroptosis in Tumor Cells： A Review / 中国实验方剂学杂志

Ferroptosis， a new form of programmed cell death different from apoptosis， necrosis， and autophagy， is closely associated with a variety of physiological and pathological processes. Iron-mediated accumulation of reactive oxygen species is the main inducement of ferroptosis， the mechanism of which is related to intracellular lipid metabolism， iron metabolism， and antioxidant defense pathways. Multiple signaling axes and regulators jointly regulate the occurrence and disruption of ferroptosis. Studies have demonstrated that ferroptosis regulates the growth and proliferation of tumor cells. Inducing ferroptosis in tumor cells can control the growth， metastasis， and multi-drug resistance of tumors. Therefore， the effect and mechanism of ferroptosis on tumor cells have become a hot topic in anti-cancer research. As the research advances， a variety of ferroptosis inducers has been used in the clinical chemotherapy for cancers and demonstrate significant efficacy. Accordingly， the development of ferroptosis-inducing anticancer drugs has become a new research direction for tumor treatment. Some active ingredients such as lycorine， oleanolic acid， dihydroartemisinin， pseudolaric acid B， and ophiopogonin B of Chinese medicines can induce ferroptosis in tumor cells via lipid metabolism， iron metabolism， system Xc-， and GPX4/GSH to regulate the development of tumors， demonstrating a promising prospect in clinical treatment. Based on the theory of the mechanism of ferroptosis， this paper reviews the research progress in ferroptosis induced by active ingredients of Chinese medicines in tumor cells and describes the metabolic regulatory network of ferroptosis from signaling pathways and regulatory factors， providing new strategies for applying active ingredients of Chinese medicines in the treatment of tumors.

Research status of ocular changes in beta-thalassemia major / 国际眼科杂志(Guoji Yanke Zazhi)

Beta-thalassemia major(β-TM)is an inherited disease caused by a defect in the synthesis of globin. The disease requires long-term blood transfusion and iron chelator treatment, which can cause various secondary changes in the body and eye tissues. Compared with normal peers, β-TM patients will show changes in the eye such as steeper corneal curvature, shallower anterior chamber, increased lens thickness, shorter axial length, and reduced tear secretion. At the same time, nutritional deficiencies and the use of iron chelator drugs will increase the risk of complicated cataract and retinal degeneration, thus affecting the quality of life of β-TM patients.This article combines relevant domestic and foreign literatures to explore and review the changes in the eye of β-TM patients, with a view to providing valuable insights for clinical practice.

Effect of Baihe Yuzi Prescription on CFTR， AQP， and ZIP Ion Channels and Oxidative Stress in Epididymis of Oligoasthenozoospermia Rats / 中国实验方剂学杂志

ObjectiveTo observe the effects of Baihe Yuzi prescription （BYP） on the cystic fibrosis transmembrane conductance regulator （CFTR）， aquaporin （AQP）， zinc/iron-regulated transporter-like protein （ZIP） and local oxidative stress in epididymis of oligoasthenozoospermia （OAS） rats， and to explore the mechanism of its intervention in OAS. MethodAfter 35 rats were acclimatized for 1 week， 7 rats were randomly selected as the normal group， and the remaining 28 rats were given tripterygium glycosides （TG） 30 mg·kg-1. After 4 weeks of modeling， they were randomly divided into 4 groups： model group， BYP low-dose group （LBYP）， BYP high-dose group （HBYP） and levocarnitine group， with 7 rats in each group. The rats in the normal group and model group were given normal saline at the same dosage. The levocarnitine group rats were given L-carnitine oral liquid （100 mg·kg-1） by gavage. The LBYP group rats were given BYP 6.3 g·kg-1， and the HBYP group rats were given BYP 12.6 g·kg-1 by gavage once a day for consecutive 4 weeks. After the end of the intervention， sperm count and motility of all rats were detected， the histopathological structure of epididymis was observed by hematoxylin-eosin （HE） staining， and the expressions of CFTR， AQP9， AQP3， ZIP8， ZIP12 and other proteins were detected by Western blot. The contents of α-glycosidase （α-GC）， sialic acid （SA）， carnitine， superoxide dismutase （SOD）， glutathione peroxidase （GSH-Px） and malondialdehyde （MDA） were detected by enzyme-linked immunosorbent assay （ELISA）. Total zinc content was measured using an inductively coupled plasma mass spectrometer. Free zinc ion content was detected by zinc ion probes. ResultCompared with those in the normal group， the sperm count and motility of rats were decreased and the epididymal structure was disordered in the model group. The contents of α-GC and carnitine were decreased in epididymis （P<0.05）. MDA levels were increased， while SOD， GSH-Px and zinc levels were decreased （P<0.05）. The expressions of CFTR and ZIP12 in the head and cauda of the epididymis were down-regulated， and AQP3 expression was up-regulated. The expression of ZIP8 in the cauda epididymis was up-regulated （P<0.05）. Compared with the model group， BYP can significantly improve the sperm count and motility， the epididymal structure of OAS rats and the levels of α-GC and carnitine （P<0.05）. The expressions of CFTR and ZIP12 in the head and cauda of the epididymis were up-regulated， while the expressions of ZIP8 in the cauda epididymis and AQP3 in the head of the epididymis were decreased （P<0.05）. The SOD and GSH-Px levels and total zinc content in epididymis were increased， and the MDA levels were decreased （P<0.05）. ConclusionBYP may improve the sperm quality and repair epididymal tissue structure and function of OAS rats， by regulating the expressions of CFTR， AQP3， and ZIP12 ion channels and local antioxidant mechanism.

Intermittent Theta Burst Stimulation Attenuates Cognitive Deficits and Alzheimer's Disease-Type Pathologies via ISCA1-Mediated Mitochondrial Modulation in APP/PS1 Mice / 神经科学通报·英文版

Intermittent theta burst stimulation (iTBS), a time-saving and cost-effective repetitive transcranial magnetic stimulation regime, has been shown to improve cognition in patients with Alzheimer's disease (AD). However, the specific mechanism underlying iTBS-induced cognitive enhancement remains unknown. Previous studies suggested that mitochondrial functions are modulated by magnetic stimulation. Here, we showed that iTBS upregulates the expression of iron-sulfur cluster assembly 1 (ISCA1, an essential regulatory factor for mitochondrial respiration) in the brain of APP/PS1 mice. In vivo and in vitro studies revealed that iTBS modulates mitochondrial iron-sulfur cluster assembly to facilitate mitochondrial respiration and function, which is required for ISCA1. Moreover, iTBS rescues cognitive decline and attenuates AD-type pathologies in APP/PS1 mice. The present study uncovers a novel mechanism by which iTBS modulates mitochondrial respiration and function via ISCA1-mediated iron-sulfur cluster assembly to alleviate cognitive impairments and pathologies in AD. We provide the mechanistic target of iTBS that warrants its therapeutic potential for AD patients.

Targeting ferroptosis and ferritinophagy: new targets for cardiovascular diseases / 浙江大学学报（英文版）（B辑：生物医学和生物技术）

Cardiovascular diseases (CVDs) are a leading factor driving mortality worldwide. Iron, an essential trace mineral, is important in numerous biological processes, and its role in CVDs has raised broad discussion for decades. Iron-mediated cell death, namely ferroptosis, has attracted much attention due to its critical role in cardiomyocyte damage and CVDs. Furthermore, ferritinophagy is the upstream mechanism that induces ferroptosis, and is closely related to CVDs. This review aims to delineate the processes and mechanisms of ferroptosis and ferritinophagy, and the regulatory pathways and molecular targets involved in ferritinophagy, and to determine their roles in CVDs. Furthermore, we discuss the possibility of targeting ferritinophagy-induced ferroptosis modulators for treating CVDs. Collectively, this review offers some new insights into the pathology of CVDs and identifies possible therapeutic targets.

The role of iron-uptake factor PiuB in pathogenicity of soybean pathogen Xanthomonas axonopodis pv. glycines / 生物工程学报

Iron is an essential element for living organisms that plays critical roles in the process of bacterial growth and metabolism. However, it remains to be elucidated whether piuB encoding iron-uptake factor is involved in iron uptake and pathogenicity of Xanthomonas axonopodis pv. glycines (Xag). To investigate the function of piuB, we firstly generated a piuB deletion mutant (ΔpiuB) by homologous recombination. Compared with the wild-type, the piuB mutant exhibited significantly reduced growth and virulence in host soybean. The mutant displayed markedly increased siderophore secretory volume, and its sensitivity to Fe3+, Cu2+, Zn2+ and Mn2+ was significantly enhanced. Additionally, the H2O2 resistance, exopolysaccharide yield, biofilm formation, and cell mobility of ΔpiuB were significantly diminished compared to that of the wild-type. The addition of exogenous Fe3+ cannot effectively restore the above characteristics of ΔpiuB. However, expressing piuB in trans rescued the properties lost by ΔpiuB to the levels in the wild-type. Taken together, our results demonstrated that PiuB is a potential factor for Xag to assimilate Fe3+, and is necessary for Xag to be pathogenic in host soybean.