Influencia de la NeuroEPO en el corazón fetal en un modelo de insuficiencia placentaria en ratas

Fundamento: la insuficiencia placentaria es la causa más común del retardo del crecimiento intrauterino, que puede provocar alteraciones cardiovasculares. Recientemente, se han desarrollado terapias con eritropoyetina que protegen los tejidos cardiacos con hipoxia. Objetivo: evaluar la influencia de la eritropoyetina recombinante humana con bajo contenido de ácido siálico (NeuroEPO) en el corazón fetal en un modelo de insuficiencia placentaria en ratas. Métodos: se utilizaron 14 ratas Wistar gestadas con ligadura unilateral de la arteria uterina derecha en el día 16 de la gestación. Ese mismo día, a siete ratas se le administró NeuroEPO (0,5 mg/kg/día subcutáneo por tres días) y al resto placebo. En el día 20 de la gestación los fetos se dividieron en cuatro grupos: un grupo control, un grupo con retardo del crecimiento intrauterino, un grupo control NeuroEPO y un grupo con retardo del crecimiento intrauterino y NeuroEPO. En los fetos se obtuvo el peso placentario, peso fetal y la eficacia placentaria. En el estudio histológico se cuantificó el número de cardiomiocitos, número de vasos sanguíneos y cantidad de las fibras de colágenos. Resultados: el grupo con retardo del crecimiento intrauterino presentó una disminución del peso fetal, del número de cardiomiocitos, del número de vasos sanguíneos y un aumento en la cantidad de fibras colágenas (p<0.05). Al tratar con NeuroEPO a los fetos con retardo en el crecimiento intrauterino, aumentó el peso fetal, aunque el peso no fue similar al control. El resto de las variables se comportaron semejantes al control. Conclusiones: la administración de esta molécula mejoró el peso fetal y permitió un equilibrio adecuado en el desarrollo del corazón fetal, quizás, debido a los efectos citoprotectores de esta molécula.

Foundation: placental insufficiency is the most common cause of intrauterine growth retardation, which can cause cardiovascular alterations. Recently, erythropoietin therapies have been developed that protect hypoxic cardiac tissues. Objective: To evaluate the influence of human recombinant erythropoietin with low sialic acid content (NeuroEPO) on the fetal heart in a rat model of placental insufficiency. Methods: 14 Wistar rats gestated with unilateral ligation of the right uterine artery on day 16 of gestation were used. That same day, seven rats were administered NeuroEPO (0.5 mg/kg/day subcutaneously for three days) and the rest received placebo. On day 20 of gestation, the fetuses were divided into four groups: a control group, a group with intrauterine growth retardation, a NeuroEPO control group, and a group with intrauterine growth retardation and NeuroEPO. In the fetuses, placental weight, fetal weight and placental efficiency were obtained. In the histological study, the number of cardiomyocytes, number of blood vessels and quantity of collagen fibers were quantified. Results: the group with intrauterine growth retardation presented a decrease in fetal weight, the number of cardiomyocytes, the number of blood vessels and an increase in the amount of collagen fibers (p<0.05). When fetuses with intrauterine growth retardation were treated with NeuroEPO, fetal weight increased, although the weight was not similar to the control. The rest of the variables behaved similar to the control. Conclusions: the administration of this molecule improved fetal weight and allowed an adequate balance in the development of the fetal heart, perhaps due to the cytoprotective effects of this molecule.

Functional effects of microRNA-211-5p-targeted inhibition of erythropoietin hepatocyte kinase receptor and ligand B2 signaling pathway on spinal cord nerve injury / 中国医师进修杂志

Objective:To detect the expression of microRNA (miR)-211-5p, erythropoietin hepatocyte kinase receptor B2 (EphB2) and erythropoietin hepatocyte kinase ligand B2 (ephrin B2) in spinal cord tissues as well as nerve cells after spinal cord injury (SCI), and to explore their mechanisms and effects on neurological recovery in SCI rats.Methods:The study was conducted from May 2020 to June 2021 using Sprague Dawley (SD) rats and PC12 cells. SD rats were divided into sham-operated group and SCI group of 30 rats each, and Basso-Beattie-Bresnahan (BBB) score were performed at different postoperative time points (1, 3, 7, 14, 21 and 28 d), and the relative expression of miR-211-5p and Eph/ephrin B2 mRNA was measured by quantitative real-time polymerase chain reaction (qPCR); the SCI rats were divided into recombinant lentiviral vector LV-miR-211-5p group (group A), empty lentiviral vector LV-eGFP (group B) and saline group (group C), with 15 rats in each group, respectively. The recombinant lentiviral vector, empty lentiviral vector and saline were injected on the cephalic and caudal sides of the spinal cord injury, and the relative expression of miR-211-5p and Eph/ephrin B2 mRNA in the spinal cord tissue was measured at 1, 7 and 14 d after surgery. In addition, a PC12 injury cell line model was established with 150 μmol/L hydrogen peroxide (H 2O 2), and the apoptosis rate and apoptosis-related proteins and contents of different cell lines were detected by flow cytometry and Western blot, respectively. MiR-211-5p was verified to target EphB2 by dual luciferase reporter gene. Results:The results of the animal experiments showed that at different postoperative time points, the miR-211-5p levels in the SCI group were lower than those in the SHAM group: 0.70 ± 0.03 vs. 1.00 ± 0.10, 0.60 ± 0.04 vs. 1.00 ± 0.05, 0.45 ± 0.10 vs. 1.00 ± 0.12, 0.30 ± 0.06 vs. 1.00 ± 0.15, 0.20 ± 0.05 vs. 1.00 ± 0.13, 0.10 ± 0.02 vs. 1.00 ± 0.07. In contrast, levels of Eph/ephrin B2 were higher in the SCI group compared to the SHAM group: 1.10 ± 0.05 vs. 1.00 ± 0.01, 1.80 ± 0.01 vs. 1.00 ± 0.08, 2.30 ± 0.01 vs. 1.00 ± 0.10, 2.60 ± 0.01 vs. 1.00 ± 0.05, 2.80 ± 0.01 vs. 1.00 ± 0.06, 3.00 ± 0.01 vs. 1.00 ± 0.07 and 1.20 ± 0.05 vs. 1.00 ± 0.02, 1.60 ± 0.01 vs. 1.00 ± 0.03, 2.10 ± 0.10 vs. 1.00 ± 0.01, 2.40 ± 0.11 vs. 1.00 ± 0.09, 2.70 ± 0.13 vs. 1.00 ± 0.05, 2.90 ± 0.12 vs. 1.00 ± 0.03 ( P<0.05). At 14 d after surgery, Group A exhibited higher BBB scores than Groups B and C: (14.0 ± 1.1) points vs. (8.0 ± 1.1) and (8.2 ± 1.2) points, while miR-211-5p levels were higher than those in Groups B and C: 1.90 ± 0.10 vs. 0.40 ± 0.01 and 0.50 ± 0.02, and Eph/ephrin B2 levels were lower than those in Groups B and C: 0.70 ± 0.10 vs. 1.80 ± 0.04 and 1.90 ± 0.06, 0.60 ± 0.03 vs. 2.00 ± 0.04 and 2.10 ± 0.05 ( P<0.05). Immunofluorescence staining showed that the levels of GAP-43 and synaptophysin in group A were higher than those in groups B and C at 14 d after surgery ( P<0.05). Cellular assays showed that overexpression of miR-211-5p inhibited the apoptosis rate of H 2O 2-induced PC12 cells and the expression of the apoptosis-related gene Cleaved-caspase3 ( P<0.05). Knockdown of miR-211-5p increased the apoptosis rate of H 2O 2-induced PC12 cells and the expression of the apoptosis-related gene Cleaved-caspase3 ( P<0.05). Dual luciferase reporter gene assay confirmed that EphB2 was a target gene of miR-211-5p and overexpression of EphB2 antagonized the inhibitory apoptosis effect of miR-211-5p on H 2O 2-induced PC12 cells. Conclusions:This study showed that miR-211-5p could promote neurological repair in SCI by inhibiting the expression of Eph/ephrin B2 signaling pathway, suggesting that using miR-211-5p as a target to inhibit Eph/ephrin B2 signaling pathway may have a protective effect on SCI.

Correlation of ncRNA-mediated Up-regulation of EphB4 with Poor Prognosis and Tumor Immunoinfiltration in Low-grade Glioma / 医学研究杂志

Objective To investigate the expression of erythropoietin-producing human hepatocellular receptors B4(EphB4)and its upstream targets as well as correlation with prognosis in low-grade glioma(LGG),for analyzing its potential role as a therapeutic tar-get.Methods Firstly analyzed the expression of EphB4 in glioma and normal brain tissue by The Cancer Genome Atlas(TCGA)data-base.Then,Gene Expression Profiling Interactive Analysis(GEPIA)database was used to analyze the effects of EphB4 on various cancer survival.The possible upstream regulatory non-coding RNA(ncRNA)of EphB4 were analyzed by R and starBase database.The correla-tion of EphB4 with tumor immune cell infiltration,biomarkers of immune cells and immune checkpoint expression were analyzed using the Tumor Immune Estimation Resource(TIMER)database.Results UBA6-AS1/hsa-miR-346 axis was the most potential upstream non-coding RNA(ncRNA)related pathway to influence expression of EphB4 in LGG.At the same time,the level of EphB4 was posi-tively correlated with the tumor immune cell infiltration,immune cell biomarkers and immune checkpoint in LGG.Conclusion NcRNA-mediated up-regulation of EphB4 is associated with poor prognosis and tumor immunoinfiltration in LGG.

Application and prospects of erythropoietin in bone tissue engineering / 中国组织工程研究

BACKGROUND:Bone defects are caused by many factors,such as inflammation,tumor,trauma or bone diseases.Erythropoietin can promote the differentiation of mesenchymal stem cells into osteoblasts and osteoclasts and act on vascular endothelial cells to induce angiogenesis and accelerate the repair of bone and cartilage defects.Erythropoietin is a growth factor with potential application in bone tissue engineering construction. OBJECTIVE:To expound the application and potential mechanism of erythropoietin in bone tissue engineering. METHODS:The first author searched the related articles published in CNKI,WanFang,VIP,and PubMed databases from 2004 to 2022 by computer.Search terms were"erythropoietin,bone defect,bone regeneration,angiogenesis,osteogenesis,osteoblast,osteoclast,bone tissue engineering"in Chinese and English.Finally,64 articles were included for review. RESULTS AND CONCLUSION:(1)Erythropoietin can directly act on osteoblasts and osteoclasts in the bone marrow microenvironment by promoting the differentiation of mesenchymal stem cells into osteoblasts,osteoclasts,adipocytes,nerve cells and stromal cells.The activation of Wnt/β-catenin,hypoxia-inducible factor 1α/vascular endothelial growth factor,p38 MAPK and EphrinB2/EphB4 signaling pathways mediates the osteogenic differentiation of mesenchymal stem cells.(2)Erythropoietin can not only regulate the production of erythrocytes to alter the oxygen-carrying capacity of blood but also stimulate vascular endothelial cells to promote angiogenesis.The new blood vessels can carry oxygen,nutrients,growth factors,and bone progenitor cells necessary for osteogenesis to the osteogenic site,thereby promoting bone formation and fracture healing.(3)Currently,erythropoietin is being used as a growth factor with osteogenic and angiogenic effects in various types of scaffold materials such as chitosan,polycaprolactone,bioceramics,and nanofibers through various drug delivery methods.Erythropoietin,along with other growth factors such as bone morphogenetic protein-2 and bone morphogenetic protein-9,has been applied to the surface of scaffold materials to participate in the repair of bone defects.Erythropoietin has demonstrated excellent practicality in the construction of new tissue-engineered bone and has potential clinical application value.

Effects of roxadustat versus recombination human erythropoietin on coronary artery calcification in maintenance hemodialysis patients / 中国药房

OBJECTIVE To compare the effects of roxadustat and recombination human erythropoietin （rHuEPO） on coronary artery calcification in maintenance hemodialysis （MHD） patients. METHODS In retrospective analysis， MHD patients prescribed roxadustat in the Blood Purification Center of the First Affiliated Hospital of Chongqing Medical University from April 2019 to June 2021 were selected as the ROX group （56 patients）， and MHD patients prescribed rHuEPO during the same period were selected as the EPO group （60 patients）， and follow-up observation was conducted for 12 months. The differences in laboratory index， coronary artery calcification score （CACS）， and cardiac ultrasound parameters before and after treatment as well as the occurrence of cardiac and cerebrovascular adverse events during follow-up period were compared between the two groups. RESULTS There was no statistical difference in CACS between the two groups before and after treatment （P＞0.05）； but the difference of CACS in the ROX group was significantly lower than the EPO group （P＜0.05）. There was no statistically significant difference in cardiac ultrasound parameters and laboratory indexes between the two groups before and after treatment （P＜0.05）. The incidence of apoplexy and myocardial infarction in the ROX group was lower than that in the EPO group （P＜0.05）， and there was no statistically significant difference in the incidence of hospitalization due to heart failure between the two groups （P＞0.05）. CONCLUSIONS Compared with rHuEPO， roxadustat may have a positive effect on delaying coronary artery calcification in MHD patients and may be beneficial in reducing the incidence of myocardial infarction and apoplexy in MHD patients.

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.

La obesidad como factor riesgo para eritrocitosis secundaria

Introducción. La obesidad es un problema de salud pública, está asociada exponencialmente al aumento del riesgo de desarrollar patologías como diabetes, cáncer, enfermedades cardiovasculares y pulmonares. En la altitud, la hipoxia hipobárica conllevaría una repercusión importante en personas con obesidad involucrando disminución de la funcionalidad pulmonar, incremento de HIF y de eritropoyetina que pueden condicionar el desarrollo de una eritrocitosis secundaria. Objetivo. Determinar el rol de la obesidad en la presentación de la eritrocitosis en un ambiente de hipoxia hipobárica. Material y métodos. Estudio descriptivo transversal con carácter retrospectivo que consideró 615 pacientes con eritrocitosis (EPA, ES) residentes a 3650 y 4150 m s. n. m., ciudades de La Paz y El Alto (Bolivia). Se analizó datos demográficos, clínicos y laboratoriales, considerando características del IMC según grados de obesidad. Resultados. Se observó que, el 7% que reflejaron IMC normal correlacionaron con EPA, mientras que el 93% distribuidos por grados de sobrepeso u obesidad correlacionaron con ES. Los eventos trombóticos estuvieron relacionados con el incremento eritropoyetina, no así con la obesidad. A mayor IMC, mayores fueron las concentraciones de eritropoyetina. La presentación de eritrocitosis fue representativa en varones (80 %), adicionalmente, la edad de presentación fue después de los 50 años de edad. Conclusiones. La obesidad constituye un factor de riesgo importante en la presentación de la eritrocitosis secundaria en grandes altitudes, su etiopatogenia está representada por el incremento de eritropoyetina sérica.

Introduction. Obesity is a public health problem, it is associated with an increased risk of developing pathologies such as diabetes, cancer, cardiovascular or lung diseases. At high-altitude, hypobaric hypoxia may imply a significant impact in people with obesity, it involves a decrease in lung functionality, an increase of HIF and erythropoietin conditioning the development of secondary erythrocytosis. Objective. To determine the role of obesity in the occurrence of erythrocytosis at a hypobaric hypoxia environment. Material and methods. Retrospective cross-sectional descriptive study that considered 615 patients with erythrocytosis (EPA, ES) residing at 3650 and 4150 m, La Paz and El Alto cities from Bolivia. Demographic, clinical and laboratory data by considering patients BMI characteristics as well as degrees of obesity were analyzed. Results. 7% corresponding to a normal BMI displayed correlation with CMS- erythrocytosis, while 93% distributed by degrees of overweight or obesity correlated with ES. Thrombotic events were related to increased erythropoietin, but not to obesity. The higher BMI, the higher erythropoietin concentrations were. Occurrence of erythrocytosis was representative in men (80%), likewise the occurrence age was after 50 years old. Conclusions. Obesity constitutes an important risk factor in the occurrence of secondary erythrocytosis at high altitude, its etiopathogenesis is represented by increased serum erythropoietin.

Consensus of the Brazilian association of hematology, hemotherapy and cellular therapy on patient blood management: Assessment and management of postoperative anemia

Abstract Postoperative anemia is a complex clinical issue that requires attention due to its ramifications on the patient's recovery and prognosis. Originating from multiple determinants, such as intraoperative blood loss, hemolysis, nutritional deficiencies, systemic inflammation and impact on the bone marrow, postoperative anemia has varied and often challenging presentations. Patients undergoing major surgical procedures, in particular, are susceptible to developing anemia due to the considerable associated blood loss. Accurate diagnosis plays a crucial role in the approach, requiring meticulous hematological analysis, including hemoglobin, hematocrit and reticulocyte count, as well as an in-depth investigation of the underlying causes. An additional challenge arises in the form of the excessive practice of phlebotomy during hospitalization for clinical monitoring. Although it is essential to assess the progression of anemia, frequent removal of blood may contribute to iatrogenic anemia, further delaying recovery and possibly increasing susceptibility to infection.

Efecto de la hemodiálisis de alto flujo en la dosis de eritropoyetina en pacientes con enfermedad renal crónica

Objetivo: Evaluar el requerimiento de eritropoyetina (EPO) tras el cambio de membrana de bajo a alto flujo en pacientes prevalentes en hemodiálisis. Secundariamente determinar la variación de β2-microglobulina, Proteína C reactiva (PCR) y ferritina. Material y métodos: Estudio retrospectivo observacional en pacientes prevalentes en hemodiálisis en dos centros de diálisis en Perú. Se determinaron las características clínicas y demográficas de los pacientes. Se determinó hemoglobina, porcentaje de saturación de transferrina, ferritina, Kt/V y dosis de EPO basal y cada 3 meses durante los 12 meses posteriores al cambio de dializador. Adicionalmente se determinó la PCR y β2-microglobulina a los 3, 6 y 12 meses. Resultados: Se incluyeron 58 pacientes que cumplieron con los criterios de inclusión y exclusión. La dosis de EPO basal fue 5 763,55 ± 3 000,69 UI/semana y a los 12 meses, 4031,18 ± 2 663,95 UI/semana (p=0,000) y la hemoglobina basal 11,10 ± 1,24 g/dl y a los 12 meses 11,69 ± 1,28 g/dl (p=0, 077). La β2-microglobulina disminuyó de 45,64 ± 11,39 mg/l a 26,26 ± 8,02 mg/l a los 12 meses (p=0,000). Conclusiones: En la población de estudio la dosis de EPO disminuyó 30% a los 12 meses sin cambios en la hemoglobina. La β2-microglobulina disminuyó 42,5% al año.

SUMMARY Objective: To evaluate the requirements of erythropoietin (EPO) after changing low membrane flow to high in patients on hemodialysis. Secondly, to evaluate changes in serum levels of beta 2 microglobulin, C-reactive protein (CRP) and ferritin. Methods: A retrospective-observational study was carried-out in patients on hemodialysis in two centers in Peru. Clinical and demographic characteristics of patients were reported. Levels of hemoglobin, ferritin saturation percentage, ferritin, Kt/V and EPO baseline doses and each three months for one year after changing the dialyzer were measured. Additionally, serum levels of C-reactive protein and beta 2 microglobulin at 3, 6 and 12 months were obtained. Results: A total of 58 were included; baseline EPO levels were 5 763.55 ± 3 000.69 UI/week and at 12 months were 4 031.18 ± 2663.95 UI/week (p=0.000); baseline hemoglobin was 11.10 ± 1.24 g/dl and 11.69 ± 1.28 g/dl (p=0.077) after 12 months. Serum levels of beta 2 microglobulin dropped from 45.64 ± 11.39 mg/l at baseline to 26.26 ± 8.02 mg/l at one year (p=0.000). Conclusions: EPO doses dropped 30% at 12 months with no changes in hemoglobin. Beta 2 microglobulin dropped 42.5% after one year.

Importance of assessing biomarkers and physiological parameters of anemia-induced tissue hypoxia in the perioperative period

Abstract Anemia is associated with increased risk of Acute Kidney Injury (AKI), stroke and mortality in perioperative patients. We sought to understand the mechanism(s) by assessing the integrative physiological responses to anemia (kidney, brain), the degrees of anemia-induced tissue hypoxia, and associated biomarkers and physiological parameters. Experimental measurements demonstrate a linear relationship between blood Oxygen Content (CaO2) and renal microvascular PO2 (y = 0.30x + 6.9, r2= 0.75), demonstrating that renal hypoxia is proportional to the degree of anemia. This defines the kidney as a potential oxygen sensor during anemia. Further evidence of renal oxygen sensing is demonstrated by proportional increase in serum Erythropoietin (EPO) during anemia (y = 93.806*10−0.02, r2= 0.82). This data implicates systemic EPO levels as a biomarker of anemia-induced renal tissue hypoxia. By contrast, cerebral Oxygen Delivery (DO2) is defended by a profound proportional increase in Cerebral Blood Flow (CBF), minimizing tissue hypoxia in the brain, until more severe levels of anemia occur. We hypothesize that the kidney experiences profound early anemia-induced tissue hypoxia which contributes to adaptive mechanisms to preserve cerebral perfusion. At severe levels of anemia, renal hypoxia intensifies, and cerebral hypoxia occurs, possibly contributing to the mechanism(s) of AKI and stroke when adaptive mechanisms to preserve organ perfusion are overwhelmed. Clinical methods to detect renal tissue hypoxia (an early warning signal) and cerebral hypoxia (a later consequence of severe anemia) may inform clinical practice and support the assessment of clinical biomarkers (i.e., EPO) and physiological parameters (i.e., urinary PO2) of anemia-induced tissue hypoxia. This information may direct targeted treatment strategies to prevent adverse outcomes associated with anemia.

Erythropoietin as a treatment option for indirect traumatic optic neuropathy: A pilot study

Purpose: Our study aims to evaluate the effectiveness of intravenous erythropoietin (EPO) in patients with indirect traumatic optic neuropathy (TON), assess the side effects, and compare the visual function results among three groups of patients who had received different treatment options – EPO, steroids, and observation. Methods: Patients with indirect TON presenting to the neuro?ophthalmology clinic from August 2019 to March 2020, were assigned to three groups, with six patients in each group. In group 1, patients were recruited prospectively and received recombinant human erythropoietin, whereas, in groups 2 and 3, patients were recruited retrospectively and received intravenous methylprednisolone followed by oral steroids and multivitamins, respectively. Groups 1 and 2 included patients presenting within 2 weeks of trauma, whereas group 3 included those presenting beyond that. Best?corrected visual acuity, pupillary reaction, color vision, and visual fields following treatment were measured. Results: Initial visual acuity in the EPO group ranged from 20/80 to no perception of light (No PL). The mean initial BCVA (1.82 logMAR, standard deviation [SD] = 0.847) improved to 1.32, SD = 0.93 logMAR after treatment recorded at the third month (P = 0.0375), with no significant adverse effects. The initial BCVA of group 2 ranged from 20/120 to No PL. The mean initial BCVA (1.95, SD = 0.77 logMAR) improved to 1.45 logMAR, SD = 0.97 after treatment (P = 0.0435) but three patients had side effects of steroids. Initial visual acuity in Group 3 ranged from 20/40 to no PL. The mean initial BCVA (1.09 logMAR, SD = 1.10) worsened to 1.19 logMAR, SD = 1.06 after treatment after treatment (P = 0.0193). The improvement in BCVA when compared between the three groups was not significant. Conclusion: Both erythropoietin and steroids are effective in the management of traumatic optic neuropathy. However, erythropoietin shows lesser or no side effects when compared to steroids

Pitiriasis liquenoide varioliforme aguda posterior al inicio de eritropoyetina / Acute varioliform lichenoid pityriasis following the initiation of erythropoietin

Resumen La pitiriasis liquenoide varioliforme aguda (PLEVA) pertenece a un grupo de enfermedades categorizadas como pitiriasis liquenoides, junto con la enfermedad febril úlcero-necrótica de Mucha-Habermann y la pitiriasis liquenoide crónica (PLC). Se caracteriza por la aparición aguda de múltiples pápulas eritemato-violáceas con posterior necrosis, discromía residual y cicatrices varioliformes. Dentro de las teorías patogénicas propuestas se encuentra el posible papel de agentes infecciosos, trastornos linfoproliferativos, complejos inmunes e incluso, asociación a medicamentos. Se presenta un casode una mujer adulta con un cuadro típico de PLEVA con confirmación histopatológica, cuyas lesiones aparecieron posteriormente al inicio de eritropoyetina.

Abstract Pityriasis lichenoides et varioliformes acuta (PLEVA) is part of a group of diseases clustered as pityriasis lichenoides, next to febrile ulceronecrotic Mucha-Habermann disease and pityriasis lichenoides chronica. It's characterized by a sudden onset of multiple erythematous and violaceous papules which develop necrosis, leaving residual dyschromia and varioliform scars. It's been hypothesized the possible role of infectious agents, lymphoproliferative diseases, immune complexes and drugs. We present the case of a woman with a typical PLEVA with histopathological confirmation, whose lesions appeared after therapy with erythropoietin.

Effects of recombinant human erythropoietin on cerebral blood flow in preterm infants: arterial spin labeling magnetic resonance imaging evaluation / 中国新生儿科杂志

Objective:To study the effects of recombinant human erythropoietin (rhEPO) on cerebral blood flow (CBF) in preterm infants using arterial spin labeling (ASL) magnetic resonance imaging (MRI).Methods:From September 2021 to June 2022, preterm infants (gestational age ≤32 weeks, birth weight ≤1 500 g) admitted to NICU of our hospital within 24 h after birth were randomly assigned into rhEPO group and control group for this prospective study. The rhEPO group was given rhEPO (500 IU/kg iv, once every other day for 2 weeks) within 72 h after birth plus symptomatic supportive treatment. The control group received same amount of normal saline injection. Both groups received brain MRI, diffusion-weighted imaging and ASL at adjusted gestational age of 35~37 weeks and CBF values of interested areas were measured.Results:A total of 85 infants were enrolled, including 40 in the rhEPO group and 45 in the control group. No significant differences existed in the incidences of periventricular-intraventricular hemorrhage, periventricular leukomalacia, focal white matter injury and extensive white matter injury between the two groups ( P>0.05). The CBF values [ml/(100 g·min)] of frontal cortex [left 15.1±3.9 vs. 17.9±3.1, right 15.9 (12.5, 17.8) vs. 18.1(16.1,20.2)], temporal cortex [left 15.8±4.3 vs. 18.6±3.8, right 16.3(13.2,19.4) vs. 18.1(15.7,19.7)], occipital cortex (left 15.8±6.1 vs. 18.8±3.3, right 16.8±5.5 vs. 19.3±4.8), basal ganglia (left 24.7±7.2 vs. 28.7±6.2, right 26.0±7.9 vs. 29.3±6.4) and thalamus (left 32.7±11.8 vs. 37.9±8.6, right 32.1±11.6 vs. 37.6±10.2) in the rhEPO group were significantly lower than the control group ( P<0.05). No significant differences existed of CBF value at the parietal cortex between the two groups ( P>0.05). Conclusions:Early application of rhEPO can reduce CBF in premature infants, which may be related to the neuro-protective effects of EPO.

Kidney xenotransplantation: status quo and development trend of physiological research / 器官移植

Organ transplantation is the most effective treatment for all categories of end-stage organ diseases. To resolve the shortage of donors in organ transplantation, widespread attention has been diverted to xenotransplantation. At present, clinicians mainly highlight the problems related to xenotransplantation rejection and viral infection. The physiology of xenotransplantation has been rarely studied. Kidney performs endocrine function by producing erythropoietin (EPO), renin and activating vitamin D. Although these pathways are usually well preserved in allogeneic transplantation, species-specific differences, especially those between pigs and non-human primates, may still affect the physiological function of transplant organs. In this article, the changes of EPO, renin-angiotensin-aldosterone system (RAAS) and active vitamin D3 of pig and human after xenotransplantation were illustrated, aiming to provide reference for subclinical research of xenotransplantation.

A retrospective study and value analysis of erythropoietin in improving postoperative anemia in renal transplant patients / 现代泌尿外科杂志

【Objective】 To explore the effects of early application of erythropoietin (EPO) in patients with anemia after renal transplantation. 【Methods】 Patients who underwent renal transplantation in the First Affiliated Hospital of Soochow University were retrospectively analyzed. According to whether EPO was applied after operation, the patients were divided into EPO group and routine group. Patients with delayed renal function recovery were excluded, and the remaining patients were further analyzed. The general, laboratory and follow-up data of the two groups were compared, and adverse drug reactions were observed. 【Results】 The hemoglobin (P=0.026), red blood cell count (P=0.038) and hematocrit (P=0.011) in EPO group were higher than those in the routine group 2 weeks after operation, while the postoperative serum creatinine level was lower (P=0.001). Since the first week after operation, the reticulocyte count in EPO group was significantly higher than that in routine group (P<0.01). There was a negative correlation between hemoglobin and serum creatinine in EPO group at week 1 (r=-0.375, P=0.010) and week 2 (r=-0.386, P=0.008). During the treatment, 6 patients showed transient elevation of serum potassium, which returned to normal after symptomatic treatment, and no obvious adverse drug reactions were observed. 【Conclusion】 Continuous application of erythropoietin in the early stage after renal transplantation can significantly improve anemia in renal transplant patients and promote the recovery of renal function.

Regulation of osteogenic differentiation under hypoxia by EphrinB2/EphB4 in MC3T3-E1 cells / 口腔疾病防治

Objective @# To investigate the effect of erythropoietin producing hepatocyte kinase receptor ligand B2-erythropoietin producing hepatocyte kinase receptor B4 (EphrinB2/EphB4) on the osteogenic differentiation of MC3T3-E1 cells in a hypoxic environment to provide experimental evidence for hypoxia regulation of osteoblast differentiation.@*Methods @# Control groups and cobalt chloride (CoCl2)-induced hypoxia groups were set up first. qRT-PCR was used to detect the mRNA expression of the osteogenic markers alkaline phosphatase (ALP), collogen1 (COL I), runt-related transcription factor 2 (RUNX2) and osteocalcin (OCN). ALP staining was used to detect the activity of cell alkaline phosphatase after osteogenic induction. The mRNA and protein expression levels of hypoxia inducible factor-1α (HIF-1α), EphrinB2 and EphB4 in the two groups were detected via qRT-PCR and Western blot. Then, the CoCl2 + inhibitor group was established. NVP-BHG712, an EphB4 phosphorylation inhibitor, was added to this group to prevent EphrinB2 from binding to EphB4 and producing signals. qRT-PCR and Western blot were used to detect the mRNA and protein expression of osteogenic markers, including ALP, RUNX2, COL I, and OCN. ALP staining and Alizarin red S staining were used to measure osteoblast differentiation and mineralization. @*Results @# Compared with the control group, the mRNA expression of the osteogenic differentiation markers ALP, RUNX2, COL-1, and OCN in MC3T3-E1 cells increased, and ALP activity and mineralization were enhanced under CoCl2-induced hypoxia in vitro (P<0.05). Additionally, the expression of HIF-1α, EphrinB2 and EphB4 was upregulated at the mRNA and protein levels under hypoxia (P<0.05). When NVP-BHG712 was used to block the connection between EphrinB2 and EphB4, the expression of osteogenic markers and ALP activity and mineralization were decreased (P<0.05).@*Conclusion@#EphrinB2/EphB4 can promote osteogenic differentiation of MC3T3-E1 cells and increase the expression of osteogenic markers and tissue mineralization in a hypoxic environment.

Clinical comparative study of roxadustat and recombinant human erythropoietin in the treatment of non-dialysis stage 3 to 5 chronic kidney disease and renal anemia / 中国医师进修杂志

Objective:To compare the clinical curative effect of roxadustat and recombinant human erythropoietin (rhEPO) on non-dialysis stage 3 to 5 chronic kidney disease (CKD) combined with renal anemia (RA).Methods:A total of 108 patients with non-dialysis stage 3 to 5 CKD and RA admitted to Jiangbei Branch of Zhongda Hospital Affiliated to Southeast University were prospectively enrolled between January 2020 and October 2022. According to random number table method, they were divided into group A and group B, 54 cases in each group. The group A was treated with roxadustat and polysaccharide-iron complex (PIC) for 3 months, while group B was treated with rhEPO and PIC for 3 months. The clinical curative effect, levels of hemoglobin (Hb), red blood cell count (RBC), hematocrit (Hct), serum ferritin (SF), transferrin saturation (TSAT), transferrin (TRF), blood urea nitrogen (BUN), serum creatinine (Scr) and β2-microglobulin (β2-MG) before and after treatment, and the incidence of adverse reactions during treatment in the two groups were compared.Results:The total response rate of treatment in group A was significantly higher than that in group B: 87.04% (47/54) vs. 70.37% (38/54), and the difference was statistically significant ( P<0.05). After treatment, levels of RBC, Hb and Hct in group A were significantly higher than those in group B: (3.47 ± 0.59) × 10 12/L vs. (2.60 ± 0.51) × 10 12/L, (110.45 ± 12.97) g/L vs. (93.64 ± 10.58) g/L, 0.358 ± 0.054 vs. 0.303 ± 0.043, and the difference was statistically significant ( P<0.05). The levels of TSAT, SF and TRF in group A were significantly higher than those in group B: (35.17 ± 3.65)% vs. (29.82 ± 3.10)%, (286.74 ± 17.23) μg/L vs. (243.16 ± 15.49) μg/L, (2.76 ± 0.45) g/L vs. (2.40 ± 0.32) g/L, and the difference was statistically significant ( P<0.05). The levels of BUN, Scr and β2-MG in group A were significantly lower than those in group B: (3.98 ± 0.41) mmol/L vs. (4.36 ± 0.54) mmol/L, (62.57 ± 7.89) μmol/L vs. (80.34 ± 9.65) μmol/L, (1.50 ± 0.42) μg/L vs. (1.99 ± 0.58) μg/L, and the difference was statistically significant ( P<0.05). During treatment, incidence of adverse reactions in group A was significantly lower than that in group B: 11.11% (6/54) vs. 25.93% (14/54), and the difference was statistically significant ( P<0.05). Conclusions:Compared with rhEPO, roxadustat has better curative effect, which can effectively relieve anemia and improve iron metabolism in patients with non-dialysis stage 3 to 5 CKD and RA, with good safety.

Related factors of endogenous erythropoietin and its association with 10-year risks of cardiovascular disease in a community-based Chinese study / 北京大学学报(医学版)

OBJECTIVE@#To investigate the associated factors of endogenous erythropoietin (EPO) and its association with 10-year risks of atherosclerotic cardiovascular disease in a Chinese community-based general population.@*METHODS@#The participants of this study were from an atherosclerosis cohort survey which was established by the Department of Cardiology, Peking University First Hospital in 2011. The cohort survey was performed in the Gucheng and Pingguoyuan communities of Shijingshan district in Beijing, China. The inclusion criteria of this study were: (1) endogenous EPO was measured; (2) health questionnaire data and other clinical data were complete; (3) participatants who had cardiovascular or cerebrovascular diseases (defined as self-reported coronary heart disease, stroke or transient ischemic attack) or anemia or estimated glomerular filtration rate (eGFR) < 60 mL/(min·1.73 m2) at baseline were excluded. Multivariate linear regression model was used to examine the associated factors of endogenous EPO. The participants were grouped into low (< 5%), moderate (5%-10%) and high risk (≥10%) groups, based on predicted 10-year cardiovascular disease risk using the prediction for atherosclerotic cardiovascular disease risk in China (China-PAR) equations.@*RESULTS@#A total of 4 013 participants were included. Mean age of them was (55.9±8.2) years, 62.2% (n=2 496) of them were female, and 46.3% (n=1 859), 70.9% (n=2 845), 21.9% (n=879) had hypertension, dyslipidemia and diabetes, individually. The average body mass index was (26.1±3.3) kg/m2. The median of EPO level was 12.8 (9.3-17.4) IU/L and 25.1% (n=998) were at high 10-years risk of cardiovascular disease. Hemoglobin (β=-0.05, 95%CI: -0.07 to -0.04) and eGFR ≥90 mL/(min·1.73 m2) (β=-0.05, 95%CI: -0.07 to -0.04) were associated with lower in transformed EPO levels while hypertension (β=0.08, 95%CI: 0.05 to 0.12) and obesity (β=0.14, 95%CI: 0.09 to 0.18) were associated with higher in transformed EPO levels in multivariate linear regression analyses. Ten-year cardiovascular disease risks were positively associated with in transformed EPO levels (β=0.07, 95%CI: 0.05 to 0.09). The participants at moderate and high cardiovascular disease risks had significant higher EPO levels than the low risk group (all P < 0.05).@*CONCLUSION@#In community-based Beijing populations, endogenous EPO was associated with hemoglobin, renal function, obesity and hypertension. Individuals at high 10-years cardiovascular disease risks have higher endogenous EPO levels. Endogenous EPO may be a potential risk marker of cardiovascular disease.

Prevalence and factors associated with the severity of anaemia among patients on chronic haemodialysis in Lagos, Nigeria

Anaemia is a global public health problem with high mortality and morbidity. It is also a common consequence of chronic kidney disease (CKD). There is a paucity of data on the actual burden of anaemia among patients on chronic haemodialysis (CHD) in Lagos, Nigeria. Objectives: To determine the prevalence and factors associated with the severity of anaemia among Nigerian patients undergoing chronic haemodialysis. Methods: This was a retrospective analysis of adult patients with end-stage renal disease (ESRD) on maintenance haemodialysis at the Lagos State University Teaching Hospital, Ikeja, Lagos. The data extracted from the clinical case files included the bio-demographic and clinical parameters, including the treatment modalities. Results: A total of 92 patients comprising 69 (75%) males and 23 (25.0%) females with the overall mean age of 48.2±14.0 years were included. Hypertension was the commonest aetiology of CKD and the average duration of haemodialysis was 16.6 months. The commonest access route for haemodialysis was a central line while 96.7% and 81.5% received erythropoietin and intravenous iron sucrose respectively. Seventy-three (79.3%) patients have had intra-dialysis blood transfusions in the past. Mild, moderate, and severe anaemia were recorded in 17%, 67%, and 16% respectively. The use of erythropoietin, iron sucrose, and increased frequency of blood transfusions correlated with the severity of anaemia. Conclusion: Anaemia is highly prevalent among patients with CKD on chronic haemodialysis. Increased frequency of blood transfusions, inadequate utilization of erythropoietin, and iron sucrose administration are associated with anaemia severity.

Risk of induction of corneal neovascularization with topical erythropoietin: an animal safety study

Purpose: To evaluate the pro-angiogenic effect of topical erythropoietin on cornea in chemical burn-injured rabbit eyes. Methods: The corneal alkali-burn injury was induced in 10 eyes of 10 rabbits using filter paper saturated with 1.0 mol sodium hydroxide. The eyes were categorized into the treatment group (n = 5) that received topical erythropoietin (3000 IU/mL) every 8 hr for one month versus the control group (n = 5) that received normal saline every 8 hr for one month. All eyes were treated with topical ciprofloxacin every 8 hr until corneal re-epithelialization was complete. Corneal epithelial defects, stromal opacity, and neovascularization were evaluated after the injury. At the conclusion of the study, the rabbits were euthanized and their corneas were submitted to histopathological examination. Results: Baseline characteristics including the rabbits' weight and the severity of corneal injury were comparable in two groups. Time to complete corneal re-epithelialization was 37 days in the treatment group and 45 days in the control group (P = 0.83). There was no significant difference between the groups in the rate of epithelial healing or corneal opacification. Clinical and microscopic corneal neovascularization was observed in one eye (20%) in the treatment group and two eyes (40%) in the control group (P = 0.49). Conclusion: Recombinant human erythropoietin administered topically did not induce vessel formation in rabbit corneas after chemical burn.